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[ "recent findings suggest that high adiponectin concentration is an independent predictor of mortality in chronic heart failure patients , chronic kidney patients , and elderly patients , who are at high risk for cardiovascular events ( 8 - 12 ) . obesity has been proven to be an independent risk factor for cad in both genders , and is a growing health problem in most developed and some developing countries ( 13 - 15 ) . body weight , body mass index ( bmi ) , waist circumference ( wc ) and whr are primary methods to determine obesity . while bmi reflects general obesity , waist circumference and waist hip ratio are related to central - type obesity , where body fat is primarily located in the abdomen . prospective epidemiological studies have revealed that central obesity ( determined by wc and whr ) is more relevant in cad risk compared to general obesity ( determined by bmi ) ( 16 - 18 ) . while whr is commonly used in reflecting central obesity , waist circumference is shown to have a better correlation with abdominal fat localization ( 19 - 22 ) . to our best knowledge , this is the first study performed in kosovo focusing on this particular issue . adiponectin has gained particular interest on account of its relation with insulin sensitivity , atherosclerosis , and inflammation ( 6 ) .", "the study population consisted of 82 consecutive patients who underwent coronary angiography for suspected or known coronary atherosclerosis at the university clinical center of kosovo . with the exception of acute coronary syndromes , the patients had to present in a stable clinical condition without major concomitant non - cardiovascular disease . gensini score assesses the severity of coronary artery disease : it grades narrowing of the lumen of the coronary artery and scores it as 1 for 1 - 25% narrowing , 2 for 26 - 50% narrowing , 4 for 51 - 75% , 8 for 76 - 90% , 16 for 91 - 99% and 32 for a completely occluded artery . cad was defined as more than 50% luminal stenosis identified in a minimum of two views , in the case of single - vessel involvement . gensini score was expressed as the sum of the scores for all three coronary arteries to evaluate the entire extent of coronary artery disease ( 23 ) . the primary predictor variable was serum adiponectin level as determined by immunoassay of thawed fasting serum samples . the multiplication factor for a left main stem ( lms ) lesion is 5 , it is 2.5 for proximal left anterior descending artery ( lad ) and proximal circumflex artery ( cx ) lesions , 1.5 for a mid - lad lesion , and 1 for distal lad , mid / distal cx and right coronary artery lesions . this score is then multiplied by a factor , according to the importance of the coronary artery .", "the study population consisted of 82 consecutive patients who underwent coronary angiography for suspected or known coronary atherosclerosis at the university clinical center of kosovo . with the exception of acute coronary syndromes , the patients had to present in a stable clinical condition without major concomitant non - cardiovascular disease . the study protocol was approved by the ethical committee of the faculty of medicine , university of prishtina , and research was conducted in accordance with declaration of helsinki guidelines . written informed consent", "gensini score assesses the severity of coronary artery disease : it grades narrowing of the lumen of the coronary artery and scores it as 1 for 1 - 25% narrowing , 2 for 26 - 50% narrowing , 4 for 51 - 75% , 8 for 76 - 90% , 16 for 91 - 99% and 32 for a completely occluded artery . this score is then multiplied by a factor , according to the importance of the coronary artery . cad was defined as more than 50% luminal stenosis identified in a minimum of two views , in the case of single - vessel involvement . gensini score was expressed as the sum of the scores for all three coronary arteries to evaluate the entire extent of coronary artery disease ( 23 ) . the multiplication factor for a left main stem ( lms ) lesion is 5 , it is 2.5 for proximal left anterior descending artery ( lad ) and proximal circumflex artery ( cx ) lesions , 1.5 for a mid - lad lesion , and 1 for distal lad , mid / distal cx and right coronary artery lesions .", "the who defines the ratios of > 9.0 in men and > 8.5 in women as one of the decisive benchmarks for metabolic syndrome . the waist is measured at the narrowest part of the waist , between the lowest rib and iliac crest , and the hip circumference is taken at the widest area of the hips at the greatest protuberance of the buttocks . the wc was measured by tape in cm and was also categorized according to the world health organization ( who ) criteria ( 24 ) . waist height ratio ( whtr ) is measured by division of weight circumference by their height , always expressed in same units . blood pressure was measured by european society of hypertension - international protocol 2 ( esh - ip2 ) . with the whr ,", "the primary predictor variable was serum adiponectin level as determined by immunoassay of thawed fasting serum samples . the laboratory was monitored for the precision and accuracy of glucose and lipid measurements by the surveillance program . each sample was assayed in duplicate , and adiponectin level was calculated as the average of the two measurements . the 12-h fasting blood samples were taken in the morning and the sera were stored at -70 c immediately after centrifugation until being assayed .", "adiponectin as the focusing variable of this study was included in the model regardless of its statistical significance . additionally , single ( unadjusted ) and multiple ( adjusted ) binary logistic regressions were carried out with cad group as the dependent variable , and the other significant variables as independent predictors . the cut p value of 0.1 was used as a criterion to identify the variables which need to be included in the binary logistic regression models . the continuous variables were primarily analyzed using a t - test , while the binary data were primary analyzed using a chi - squared test .", "of the eighty - two study patients , 41 patients comprised the cad group ( study subject ) and 41 patients were classified as the non - cad group ( control subject ) . cad patients had higher mean gensini scores than non - cad patients ( 53.16 33.46 vs. 1.21 5.66 , p<0.0001 ) , but there was no statistically significant difference detected between cad and non cad for plasma adiponectin levels , presented in table 2 . adiponectin levels show a non - significantly progressive decline as the angiographic severity of coronary artery stenosis increases ( value=0.335 ) as shown in table 4 distribution of gensini in different bmi categories significant differences were seen in binary logistic regression models for cad analysis for adiponectin , whr , lvef , dbp , male gender and for smoker . bmi did not correlate with gensini score by severity of coronary arteries , as seen in table 5 .", "the present study found that there was a strong association between adiponectin and coronary artery disease . these findings provide further evidence for an adiponectin paradox in which higher levels of adiponectin may be secreted as a protective or a compensatory response to worsening cardiovascular disease . in our study , we found medium significant positive correlation between gensini and adiponectin ( r= 0.272 , p=0.01 ) . as a consequence of their findings they suggested that unstable plaque may stabilize as the patient grows older or that accumulation of adiponectin in atherosclerotic vascular walls may suppress its elimination half - life from plasma , resulting in an increase in plasma concentrations of adiponectin in older patients with cad . although a significant relation between serum adiponectin levels and age was not found in our study , it is known that age has an effect on serum adiponectin levels and that there is a positive relationship between age and serum adiponectin level ( 32 ) . other experimental studies have demonstrated a beneficial , protective effect of adiponectin on myocardium . elevated plasma levels of adiponectin among patients with heart failure high serum adiponectin levels , instead of being protective , have been shown to be associated with increased mortality and adverse event rates .", "there is a significant positive correlation between waist - hip ratio and severity of coronary artery disease . also , there is a significant positive correlation between adiponectin and gensini score among kosovar patients ." ]
background : this study aimed to investigate correlation between adiponectin and waist - hip - ratio with severity of coronary artery disease ( cad ) . there is uncertainty about the association between circulating concentrations of adiponectin and cad.methods:we enrolled eighty - two consecutive patients undergoing non - urgent coronary angiography for cad survey . according to the angiography results , the patients were divided into two groups in 1:1 ratio patients admitted with a diagnosis of cad and non - cad . we conducted hospital based research , involving study group with documented angiographically cad , and control group without evidence of cad . angiograms were also quantified for the extent and severity of cad by the gensini scoring system . we measured baseline adiponectin levels in stored serum samples of all patients , anthropometric and biochemical risk factors were assessed in both groups.results:the presence of cad was associated with current smoking , male gender , waist hip ratio ( whr ) and left ventricular ejection fraction ( lvef ) . baseline adiponectin concentrations correlated significantly in terms of the lipid parameters , positively with hdl cholesterol concentrations ( r=0.327 , p=0.028 , p<0.05 ) and serum triglyceride concentrations were correlated negatively ( r=-0.513 , p<0.001 ) . no significant difference between median adiponectin levels at baseline was observed between cases and controls.conclusion:there is a significant positive correlation between waist hip ratio and presence and severity of coronary artery disease . in conclusion , there is a significant positive correlation between adiponectin and gensini score among kosovar patients .
[ "the localized form of neurofibromatosis type - i , first described by gammel in 1931 , is very rare . neurofibromatosis ( nf ) is an autosomal dominant disease , discovered in 1882 , by the german pathologist friedrich daniel von recklinghausen , characterized by disordered growth of ectodermal tissues , and is part of a group of disorders called phakomatoses ( neurocutaneous syndrome ) . it is characterized by spots of increased skin pigmentation ( caf au lait spots ) , combined with peripheral nerve tumors and a variety of other dysplastic abnormalities of the skin , nervous system , bones , endocrine organs , and blood vessels .", "a 26-year - old female patient reported to the dental department complaining about the unesthetic appearance of her face , since eight years [ figure 1 ] . the histopathological slide revealed a non - encapsulated tumor of the dermis with a normal overlying epidermis . soft tissue growths with sessile bases on right buccal mucosa soft tissue growths with sessile bases on the tongue laboratory findings revealed a raised erythrocyte sedimentation rate ( esr ) ( 70 mm in the first hour ) , a decreased hemoglobin level ( 7.5 gm% ) , and the enzyme - linked immunosorbent assay ( elisa ) was found to be nonreactive . a panoramic radiograph disclosed asymmetric enlargement of the right side of the mandible , with loss of cortication of the lower border in the midline area , expansion of the body of the mandible causing displacement of the teeth , seen on right side , expansion of the right inferior alveolar nerve canal , enlarged mental foramen , resorption of the roots of the mandibular right teeth , and loss of the right antegonial notch .", "plastic surgeons may be included in the correction of deformities , especially those of the face . considering the autosomal dominant inheritance pattern of neurofibromatosis , genetic counseling acoustic neuromas and tumors that cause tinnitus and vertigo must be excised with great caution . treatment of neurofibromatosis is predominantly surgical . when neurofibromas increase in size or cause pain , malignant transformation must be suspected , and excision or biopsy must be performed . bone involvement includes pseudoarthrosis of the tibia , bowing of the long bones , and orbital defects . less than 1% of the healthy children have three or more such spots , although one or two caf au lait macules are commonly encountered in healthy individuals without disease . most individuals with neurofibromatosis have six or more spots that are 1.5 cm or greater in diameter . in young children ," ]
segmental neurofibromatosis is a rare disorder , characterized by neurofibromas or caf-au - lait macules limited to one region of the body . its occurrence on the face is extremely rare and only few cases of segmental neurofibromatosis over the face have been described so far . we present a case of segmental neurofibromatosis involving the buccal mucosa , tongue , cheek , ear , and neck on the right side of the face .
[ "the zygomaticomaxillary complex is an important functional and aesthetic landmark of the midface , and it provides prominent cheek structure . however , unfortunately it is very vulnerable to injury because of its intrinsically prominent convexity . closed reduction without surgical incisions has virtually been abandoned because judgment on the adequate reduction of fracture could not been made and it often resulted in disappointing cosmetic results . open reduction with surgical incisions has been accomplished through keen 's approach , gillies ' approach , bicoronal scalp flap approach or the more popular dingman 's approach ( 1 ) .", "between march 2002 and january 2006 , a total of 53 patients with zygomatic complex fractures , which were not severely comminuted , were treated with this surgical method . all patients were treated with two - point fixation through a single transconjunctival approach with a lateral canthal extension . if the reduction of zygoma was not complete , an additional small gingivobuccal incision ( less than 2 cm ) follow - up radiographs ( waters ' view and zygomatic arch view ) were routinely used to evaluate the adequacy of reduction . under general endotracheal anesthesia , a lateral canthal incision , about 1.0 - 2.0 cm , preoperative and postoperative clinical examinations were performed with special attention paid to features such as symmetry of zygoma and canthal ligaments , enophthalmos , diplopia , limited ocular function , scarring and ectropion . the periosteum is closed with a 4 - 0 absorbable suture , and the conjunctiva is closed by a 7 - 0 absorbable suture . in case of old patient with lid laxity , the canthopexy is accomplished by a 5 - 0 absorbable suture fixation in the direction of posterior - superiorly to the periosteum of lateral orbital rim to prevent the postoperative ectropion . in other cases , was made and subperiosteal dissection was performed to expose zygomaticomaxillary buttress and posterior surface of zygoma . through the small gingivobuccal incision ,", "all patients were treated with two - point fixation through a single transconjunctival approach with a lateral canthal extension . if the reduction of zygoma was not complete , an additional small gingivobuccal incision ( less than 2 cm ) between march 2002 and january 2006 , a total of 53 patients with zygomatic complex fractures , which were not severely comminuted , were treated with this surgical method . knight and north classification , four patients ( 7.5% ) belonged to group i , twenty one patients ( 39.6% ) belonged to group ii , eight patients ( 15% ) belonged to group iv , eleven patients ( 20.7% ) belonged to group v , and nine patients ( 16.9% ) belonged to group vi . follow - up radiographs ( waters ' view and zygomatic arch view ) were routinely used to evaluate the adequacy of reduction . preoperative and postoperative clinical examinations were performed with special attention paid to features such as symmetry of zygoma and canthal ligaments , enophthalmos , diplopia , limited ocular function , scarring and ectropion . the follow - up period ranged from 8 to 46 months ( average 24.8 months ) . was made and subperiosteal dissection was performed to expose zygomaticomaxillary buttress and posterior surface of zygoma . through the small gingivobuccal incision ,", "the periosteum is closed with a 4 - 0 absorbable suture , and the conjunctiva is closed by a 7 - 0 absorbable suture . in case of old patient with lid laxity , the canthopexy is accomplished by a 5 - 0 absorbable suture fixation in the direction of posterior - superiorly to the periosteum of lateral orbital rim to prevent the postoperative ectropion . in other cases , the periosteum is incised and a subperiosteal dissection is done to expose the orbital floor , the inferior orbital rim , and the lateral orbital rim including the zygomaticofrontal suture area ( fig . the lateral aspect of the upper lid is retracted superiorly , and the periosteum of lateral orbital rim is exposed . , the dingman 's elevator is placed posteriorly to the body of the zygoma along the zygomatic arch and a reduction of zygoma is done . dingman 's elevator is inserted through the small gingivobuccal incision and an accurate reduction can be accomplished . in all cases ,", "during the average 24.8 months of follow up , most patients had functionally and esthetically satisfactory results . this case was 78 yr - old patient who had lid laxity preoperatively and showed ectropion postoperatively , which may be due to scar contracture . and none of them had persistent diplopia , enophthalmos or alteration of visual acuity . upon postoperative radiography ( skull waters view and zygomatic arch view ) , all patients showed satisfactory facial symmetry , no lateral canthal displacement , and no functional impairment .", "although subciliary incision with lateral eyebrow incision ( dingman 's approach ) is the most common approach to the zygomatic complex ( 7 , 10 ) , it can leave a visible scar and ectropion of the lower eyelid . , we believe that the proposed technique is very useful for the treatment of zygomatic complex fracture which is not severely comminuted , because it provides excellent exposure and postoperative stability of the zygoma with a lower incidence of complications , including visible scarring and ectropion . factors predisposing to an eyelid retraction and ectropion include hematoma , eyelid edema , adhesions of the orbital septum , scar contracture , horizontal laxity of the eyelid margin , weakening of the pretarsal muscle , and wide dissection of the anterior periosteum ( 11 ) . to decrease the complication rates of the subciliary approach , many authors have tried to treat zygoma complex fracture repair using the transconjunctival approach ( 1 , 6 - 9 ) . they emphasized the advantage of this approach over the dingman 's approach , in terms of minimal ectropion , hidden scars , and minimal lid lymphedema . in the transconjunctival approach" ]
the ultimate goal in treating zygomatic complex fracture is to obtain an accurate , stable reduction while minimizing external scars and functional deformity . the present authors present our experiences with a single transconjunctival incision and two - point ( inferior orbital rim and frontozygomatic suture ) fixation in 53 patients with zygomatic complex fracture which were not comminuted . all patients had transconjunctival approaches with lateral canthal extensions , and six out of 53 patients also had an additional small ( about less than 2 cm ) gingivobuccal incision to achieve an accurate reduction . there were 3 minor complications , and the overall esthetics and functional results were satisfactory with a long term follow - up . our method has the following advantages in the reduction of zygomatic complex fracture ; it leaves only an inconspicuous lateral canthal scar . in addition , it provides excellent simultaneous visualization of the inferior orbital rim and frontozygomatic suture area . hence , two - point fixation through a single incision can be performed with a satisfactory stability .
[ "we herein report a case in which a pet owner developed p. multocida endocarditis and was subsequently treated via opat ( outpatient parenteral antimicrobial therapy ) service with an excellent clinical outcome . species identification of p. multocida was performed using traditional microbiological methods and confirmed with 16s rrna sequencing and matrix - assisted laser desorption / ionization time - of - flight mass spectrometry ( maldi - tof ) . the gram - negative coccobacillus pasteurella multocida is normally found in the oral cavity of dogs and cats . it is a recognised cause of wound infection as a result of bites , licking or scratching . bacteraemia and endocarditis are uncommon complications and , from literature reviews , are found to be associated with prior animal trauma , a second source of infection ( e.g. cellulitis ) and high mortality rates .", "a 38-year - old man was admitted to our hospital with a 2 days history of fever , malaise and cellulitis around a mitrofanoff abdominal catheter . multiple comorbidities included marfan syndrome ( with metallic aortic valve inserted sixteen years before ) and congenital urological abnormalities that led to the mitrofanoff appendicovesicostomy and a recent renal transplant , five years and six months before admission respectively . therefore , the patient was treated following our local protocol for infective endocarditis : he was switched to ceftriaxone iv 2 gr / od , a picc line was inserted in the right arm and he was discharged under the opat ( outpatient parenteral antimicrobial therapy ) service to complete six weeks iv antibiotics as an outpatient . on follow - up , two repeat ttes showed clear aortic valve . the patient was documented to be penicillin allergic ( previous skin rash ) , so was initiated on ertapenem iv 1 gr / od . the cellulitis improved and the patient was clinically well within 48 hours of commencing antibiotics .", "we reviewed all the previous reported cases of p. multocida endocarditis in the literature through pubmed and cross - references search . to our knowledge this is the twenty - first reported case of endocarditis but the first to be reported in a penicillin allergic patient . as with previous cases , a fluoroquinolone , doxycycline , or co - trimoxazole should be considered for skin and soft tissue infections as an alternative for patients with intolerance to -lactams . there are no clear guidelines about the treatment of p. multocida endocarditis in penicillin - allergic patients .", "we propose that maldi - tof is a rapid , accurate method for the identification of p. multocida from bacterial cultures and can significantly reduce the time to diagnosis of p. multocida bacteraemia . furthermore we have shown that cephalosporins and carbapenems are probably good substitutes for penicillin in case of allergy . clinicians may face various challenges , from achieving the correct species identification to chosing treatment regimens in penicillin - allergic patients . in our case new diagnostic techniques such as 16s rrna sequencing and maldi - tof were demonstrated to be invaluable tools for species confirmation ." ]
pasteurella multocida is a rare cause of infective endocarditis with only a few cases described . this report involves a 38-year - old penicillin - allergic patient in an immunocompromised state with several co - morbidities . two molecular microbiological techniques , 16s rrna sequencing and matrix - assisted laser desorption / ionization time - of - flight mass spectrometry were used to confirm the species identification as p. multocida . previous reports in the literature are also reviewed .
[ "patient aged 64 was admitted to the county hospital urology ward in september 2010 and diagnosed with tumor of the left kidney . ct showed a solid focal lesion of the left kidney ( 30 x 40 x 32 mm ) located below the renal stalk and covering the renal pelvis and the paranephric section of the left ureter , apart from that no changes were observed ( figure 1 ) . ultrasonographic exam revealed the structure with a diameter of 45 mm in the central field of the left kidney . sided ureterorenoscopy was conducted and a urine sample was taken for cytology to exclude epithelial nature of the tumor . after undergoing the above mentioned test , the patient was qualified for transperitoneal radical nephrectomy . with general anesthesia applied , the left kidney was removed through an incision below the left costal margin . during the operation , a significant peripheral infiltration was discovered which hindered access to the renal stalk of the left kidney . radiological image of the chest did not reveal any pathological changes . in order to make the results of pre operational diagnosis", "the case presented in the report illustrates diagnostic and therapeutic difficulties that a urologist might encounter during treatment of patients with possible renal tumor . medical records and literature mention several cases of malignant kidney lymphoma [ 1 , 2 ] . some authors claim that this entity accounts for 3% of all solid renal tumors among adults . lymphomatous renal involvement can have three different causes : most commonly it appears along with the generalized disease and enlarged lymph nodes . renal involvement develops without any symptoms then.it may be related to organ transplantation and infection with epstein such cases are rare and difficult to diagnose which may lead to mistakes in treatment . such cases are rare and difficult to diagnose which may lead to mistakes in treatment . \n " ]
we present a 64year old patient suffering from extranodal malignant lymphoma . the patient was admitted to the county hospital urology ward with suspicion of the left kidney tumor . as part of pre operational diagnosis , ultrasonographic examination and computed tomography of kidneys were conducted . the results confirmed the initial diagnosis . after undergoing radical surgical treatment , the patient is currently under the care of hematology ward of oncology centre .
[ "assessment of myocardial viability in patients with coronary artery disease is of great clinical importance , as dysfunctional but viable myocardium has the ability to regain contractility after coronary revascularization with subsequent improvements in cardiac function and prognosis . the perfusable tissue index ( pti ) however , pti has never been used in clinical practice , primarily due to the complex imaging protocol consisting of dynamic [ o]h2o and [ o]co scans , together with a transmission scan , and the lack of high - quality , clinically usable parametric images . the purpose of this study was to compare these novel parametric pti images with late gadolinium - enhanced cardiovascular magnetic resonance ( lge - cmr ) imaging , an established method for quantifying scar size and a marker of viability . can be used as a marker of myocardial viability , having been validated in patients with ischaemic heart disease [ 27 ] . recently , however , a method was developed to derive the pti from a single [ o]h2o pet / ct scan . given the current potential of clinical [ o]h2o - based perfusion imaging and the rapid growth in the availability of cardiac pet / ct systems , pti viability measurements could become incorporated into clinical practice [ 9 , 10 ] . parametric pti images derived from [ o]h2o pet / ct scans , however , have not yet been validated .", "the study population comprised 46 patients with documented or suspected coronary artery disease who had been studied using both pet / ct and cmr within a 2-month period . ( b ) atf ( g ml ) , ( c ) ptf ( g ml ) , and ( d ) pti in a patient without coronary artery disease example of short axis images of ( a ) blood volume , ( b ) atf ( g ml ) , ( c ) ptf ( g ml ) , and ( d ) pti in a patient without coronary artery disease cmr studies were performed on a 1.5-t whole - body scanner ( magnetom sonata or avanto ; siemens , erlangen , germany ) , using a six - channel phased - array body coil . after survey scans , patients with contraindications for pet / ct or cmr ( e.g. pacemaker , claustrophobia , atrial fibrillation ) were excluded . parametric pti images were calculated as previously described . in brief , parametric images of myocardial blood flow ( mbf ) , perfusable tissue fraction ( ptf ) , and arterial and venous blood volume fractions were calculated using a basis function implementation of the standard single - tissue compartment model for [ o]h2o [ 1114 ] . parametric images of arterial and venous blood volume fractions were subtracted from normalized ct transmission images , resulting in parametric anatomic tissue fraction ( atf ) images . finally , parametric pti images were calculated as the ratio of ptf and atf images ( fig . 1 ) .", "the study population comprised 46 patients with documented or suspected coronary artery disease who had been studied using both pet / ct and cmr within a 2-month period . all patients were in a stable clinical condition and no ischaemic events or revascularizations had occurred during the period between the two examinations . patients with contraindications for pet / ct or cmr ( e.g. pacemaker , claustrophobia , atrial fibrillation ) were excluded . the study was approved by the institutional medical ethics review committee , and all participants gave written informed consent prior to inclusion .", "a second set of rois were placed over the right ventricle ( rv ) cavity in at least five transaxial planes , with roi boundaries at least 1 cm from the rv wall to avoid spill - in from myocardial activity . these rois were combined into one volume of interest ( voi ) for the ascending aorta . both vois were then projected onto all dynamic [ o]h2o images , thereby generating arterial ( ca(t ) ) and rv ( crv(t ) ) time activity curves . dynamic [ o]h2o images were reconstructed into 22 frames ( 1 10 , 8 5 , 4 10 , 2 15 , 3 20 , 2 30 , 2 60 s ) using the three - dimensional row action maximum likelihood algorithm and applying all appropriate corrections for the scanner , normalization , dead time , decay , scatter , randoms and attenuation based on the corresponding ld ct scan . using capp software ( siemens / cti , knoxville , tn ) , regions of interest ( rois ) of 1 cm diameter were placed over the ascending aorta in at least ten transaxial image planes of the frame showing the first pass of the injected bolus . all scans were checked for misalignment between the ld ct scan and the [ o]h2o scan ; in none of the patients were corrections needed .", "( b ) atf ( g ml ) , ( c ) ptf ( g ml ) , and ( d ) pti in a patient without coronary artery disease example of short axis images of ( a ) blood volume , ( b ) atf ( g ml ) , ( c ) ptf ( g ml ) , and ( d ) pti in a patient without coronary artery disease parametric pti images were calculated as previously described . in brief , parametric images of myocardial blood flow ( mbf ) , perfusable tissue fraction ( ptf ) , and arterial and venous blood volume fractions were calculated using a basis function implementation of the standard single - tissue compartment model for [ o]h2o [ 1114 ] . finally , 16 myocardial vois were defined manually on parametric ptf images , according to the 16 segments model of the american heart association , after which this voi template was projected onto the parametric pti images.fig . parametric images of arterial and venous blood volume fractions were subtracted from normalized ct transmission images , resulting in parametric anatomic tissue fraction ( atf ) images . finally , parametric pti images were calculated as the ratio of ptf and atf images ( fig . 1 ) .", "contrast images were acquired 10 to 15 min after administration of 0.2 mmol kg gadolinium - dtpa in the same views as in the cine images , using a two - dimensional segmented inversion - recovery prepared gradient echo sequence ( te 4.4 ms , tr 9.8 ms , inversion time 250 to 300 ms , typical voxel size 1.3 1.6 5.0 mm ) . stacks of 10 to 12 short - axis slices were acquired to fully cover the left ventricle ( lv ) . cmr studies were performed on a 1.5-t whole - body scanner ( magnetom sonata or avanto ; siemens , erlangen , germany ) , using a six - channel phased - array body coil . after survey scans , a retrotriggered , balanced steady - state free precession gradient - echo sequence was used for cine imaging . the cardiac cycle consisted of 20 phases . after obtaining four- , three- and two - chamber view cines ,", "all areas of enhancement were quantified by computer - assisted planimetry on each of the short - axis images and the segmental extent of enhancement was expressed as a percentage of the segmental area . the amount of fibrosis was calculated using the full - width at half - maximum method , which defines fibrosis as myocardial tissue with a signal intensity 50 % of the maximum hyperenhancement intensity . the endocardial and epicardial borders of the lv were outlined manually in both end - diastolic and end - systolic phases of all short - axis images . finally , myocardial segments were graded as viable or nonviable using the previously defined cut - off value of 50 % lge per segment [ 15 , 17 ] . cmr images were analysed according to the same 16-segment model as used for the parametric pet images . if no enhancement was found in a slice , the maximum signal of the nearest slice with enhancement was used .", "the area under the curve ( auc ) was considered a measure of accuracy to discriminate between viable and nonviable myocardium . a p value of < 0.05 was considered statistically significant . receiver operating characteristic curves were generated for ptf , pti and mbf for the prediction of myocardial viability assessed by lge cmr . continuous variables are presented as means sd , and categorical data are summarized as frequencies and percentages . multiple datasets were compared using analysis of variance ( anova ) , and specific differences were identified using student s t - test with bonferroni inequality adjustment .", "lge was seen in the cmr images of 34 patients ( 74 % ) . of the 736 myocardial segments , 4receiver operator characteristics curves for the abilities of ptf , pti and mbf to differentiate between viable and nonviable segments based on late gadolinium enhancement receiver operator characteristics curves for the abilities of ptf , pti and mbf to differentiate between viable and nonviable segments based on late gadolinium enhancement figure 2 shows a concordant pattern between parametric ptf , pti and lge cmr images in a patient with ischaemic cardiomyopathy after an anterior myocardial infarction.fig . 3long axis images in a patient with a nontransmural anterior myocardial infarction : a cmr with lge ; b pti long axis images ( a d ) and polar maps ( e h ) in a patient with an anterior myocardial infarction : a , e cmr with lge ( arrow , % transmurality ) ; b , f ptf ( g ml ) ; c , g pti ; d , h mbf ( ml g min ) long axis images in a patient with a nontransmural anterior myocardial infarction : a cmr with lge ; b pti using cmr as a reference , 91 of 364 ( 25 % ) segments showing some degree of lge were judged to be nonviable ( lge > 50 % ) . as shown in fig . 4 ,", "lge was seen in the cmr images of 34 patients ( 74 % ) . of the 736 myocardial segments , 364 ( 49 % ) showed some degree of lge.table 1patient characteristics ( n = 46)characteristicvalueage ( years)65 10gender ( male)36 ( 78 % ) previous myocardial infarction34 ( 74 % ) lv end - diastolic volume ( ml)226 65lv end - systolic volume ( ml)135 71lv ejection fraction ( % ) 42 16lv mass ( g)132 39 patient characteristics ( n = 46 )", "pet / ct and cmr data are summarized in table 2 . there was a gradual decrease in ptf , pti and mbf values with increasing degree of lge on cmr images ( p < 0.001 by anova ) . atf values remained relatively constant , except for a significant decrease in the ( near ) transmurally enhanced segments ( p < 0.001 by anova).table 2segmental pet / ct and lge dataextent of lge ( % ) control", "figure 2 shows a concordant pattern between parametric ptf , pti and lge cmr images in a patient with ischaemic cardiomyopathy after an anterior myocardial infarction.fig . 4receiver operator characteristics curves for the abilities of ptf , pti and mbf to differentiate between viable and nonviable segments based on late gadolinium enhancement receiver operator characteristics curves for the abilities of ptf , pti and mbf to differentiate between viable and nonviable segments based on late gadolinium enhancement 3long axis images in a patient with a nontransmural anterior myocardial infarction : a cmr with lge ; b pti long axis images ( a d ) and polar maps ( e h ) in a patient with an anterior myocardial infarction : a , e cmr with lge ( arrow , % transmurality ) ; b , f ptf ( g ml ) ; c , g pti ; d , h mbf ( ml g min ) long axis images in a patient with a nontransmural anterior myocardial infarction : a cmr with lge ; b pti using cmr as a reference , 91 of 364 ( 25 % ) segments showing some degree of lge were judged to be nonviable ( lge > 50 % ) . as shown in fig . 4 ,", "furthermore , these images and myocardial perfusion imaging are obtained simultaneously allowing both myocardial viability and ischaemia to be evaluated in a single scanning session . the present study was conducted to validate the use of a parametric myocardial viability imaging technique using [ o]h2o pet / ct in patients with ischaemic heart disease . viability assessed using parametric ptf and pti imaging was in good agreement with that assessed using lge cmr .", "ptf and pti , obtained from a single [ o]h2o pet / ct scan , can be used as markers of myocardial viability in patients with coronary artery disease .", "this article is distributed under the terms of the creative commons attribution license which permits any use , distribution , and reproduction in any medium , provided the original author(s ) and the source are credited ." ]
purposethe perfusable tissue index ( pti ) is a marker of myocardial viability . recent technological advances have made it possible to generate parametric pti images from a single [ 15o]h2o pet / ct scan . the purpose of this study was to validate these parametric pti images.methodsthe study population comprised 46 patients with documented or suspected coronary artery disease who were studied with [ 15o]h2o pet and late gadolinium - enhanced ( lge ) cardiac magnetic resonance imaging ( cmr).resultsof the 736 myocardial segments included , 364 showed some degree of lge . pti and perfusable tissue fraction ( ptf ) diminished with increasing lge . the areas under the curve of the pti and ptf , used to predict ( near ) transmural lge on cmr , were 0.86 and 0.87 , respectively . optimal sensitivity and specificity were 91 % and 73 % for pti and 69 % and 87 % for ptf , respectively.conclusionpti and ptf assessed with a single [ 15o]h2o scan can be utilized as markers of myocardial viability in patients with coronary artery disease .
[ ", we present evidence for the enhanced potential for growth and spread of a small introduced population of organisms faced with allee effects when adaptation occurs . we model the growth and spread of this population according to a reaction - diffusion equation , and allow evolution to influence inverse density dependent effects through a genetic subsystem that provides the opportunity for successful invasion when otherwise ( under the current , ecological paradigm ) the population would go extinct . our purpose here is to explore the feasibility of small populations that may adaptively respond to overcome allee effects in order to establish , given any amount of genetic variation . in this paper nevertheless , we focus our attention on population level demographic allee effects with the underlying assumption that a component allee effect led to the demographic allee effect . essentially , it is the case that introduced individuals may be maladapted to small population sizes where their survival and reproductive ability are significantly impacted , and these impacts on individual fitness combine to produce an overall decrease in abundance ( i.e. , demographic allee effects ) . as allee effects impact individual fitness , the underlying traits that influence these effects (", "the deterministic model that we explore in this paper broadly describes population dynamics with density - mediated growth ( i.e. , an allee effect ) and diffusive dispersal . the framework that is used to link evolutionary change with ecological processes involves developing a relationship between the fast , ecological and slow , evolutionary timescales in order to make these rates comparable ( kondrashov and khibnik 1996 ) . in the coupled evolutionary ecology model , the reaction - diffusion eqn . , we consider populations that are introduced below the invasion risk threshold , but nonetheless succeed if evolutionary dynamics are considered in conjunction with the ecological system . the results reveal the possibility that an introduced population that would fail to persist in the ecological context of this model has the potential to succeed through evolutionary means . including evolution within the context of ecological invasions can serve to provide more robust predictions for management strategies .", "the growth and spread of an introduced population of organisms is represented by a reaction - diffusion equation described by ( lewis and kareiva 1993 ) : which determines the rate of change in the local population density relative to the carrying capacity [ u which denotes u(x , t ) ] over time , at a point in space . growth dynamics of the model population ( a ) , and the solution of eqn . the inclusion of diffusion in the model provides a spatially explicit understanding of how all of the components interact to affect invasion / establishment success . there are many variations of single - species models of population dynamics that exhibit allee effects ( see table 1 of boukal and berec 2002 ) , however the growth function of eqn . there are two critical elements that emerge based on the solution to the partial differential equation ( pde ) .", "the framework that is used to link evolutionary change with ecological processes involves developing a relationship between the fast , ecological and slow , evolutionary timescales in order to make these rates comparable ( kondrashov and khibnik 1996 ) . in the coupled evolutionary ecology model , the reaction - diffusion eqn . the results reveal the possibility that an introduced population that would fail to persist in the ecological context of this model has the potential to succeed through evolutionary means . including evolution within the context of ecological invasions can serve to provide more robust predictions for management strategies . this genetic subsystem is coupled to the ecological model to explore the effects of selection and genetic variance on traits that may increase a population 's likelihood of survival . in order to incorporate evolutionary factors that may influence invasion success , we develop a quantitative genetic subsystem .", "earlier , we assumed that the genetic variation ( ) was small ( to use mean fitness as a proxy for individual fitness ) , which can subsequently be taken advantage of for our analysis of the coupled evolutionary ecological dynamics . when = 0 , the situation without evolution , the genetic subsystem is frozen and the population moves towards a stable equilibrium of the ecological subsystem ( carrying capacity or extinction ) depending on its initial density ( greater than or less than the allee threshold respectively ; fig . thus , in addition to the initial density of the introduced population and the genetic variance , the initial radius or patch size of the initial invasion area , the ratio of diffusion to reproduction , and gene flow will factor into successful establishment and give rise to a wider range of interactions between the ecology and evolution of this system . the trait distribution over time , figs 4c and 5c , therefore reflect the population density distribution , but are also influenced by the trait values of the migrants . as individuals disperse out to new locations and push the boundaries of the species range , their trait values are averaged to determine the demographic allee threshold for that spatial coordinate . this demographic allee threshold combines with their local population density to influence individual fitness and population growth ( where the distance between the density and mean trait value is the initial degree of maladaptation ) . if the rate of evolution is fast enough , the allee threshold can fall below the population density , causing the rate of change of population density to become positive ( where u > a ) and the population grows and can successfully invade .", "additionally , we can draw several general insights about how dispersal impacts selection and evolution of allee effects in an invasion context . although there is still much more work to be done to elucidate the factors that determine establishment success of founder populations , this theoretical approach has the promise to provide evidence in support of our working hypothesis that adaptive evolution can mitigate allee effects and be an important driver of biological invasions . current management strategies ( e.g. , reducing population density or size ) are based on ecological theory ( e.g. drake et al . 2005 ) , but this evolutionary ecology model suggests that adaptive evolution can enable successful establishment and that ecological considerations alone may not be sufficient . under the assumptions of an allee effect and diffusive dispersal , the idea of ecological size thresholds fits well with the ecological evidence that a large founding population is a primary cause of successful establishment ( lockwood et al . because bottlenecks during founding events do not always result in highly reduced genetic variability , even small founding populations may have sufficient genetic variation to evolve to overcome allee effects and establish , contrary to solely ecologically based predictions ." ]
the mechanisms that facilitate success of an invasive species include both ecological and evolutionary processes . investigating the evolutionary dynamics of founder populations can enhance our understanding of patterns of invasiveness and provide insight into management strategies for controlling further establishment of introduced populations . our aim is to analyze the evolutionary consequences of ecological processes ( i.e. , propagule pressure and threshold density effects ) that impact successful colonization . we address our questions using a spatially - explicit modeling approach that incorporates dispersal , density dependent population growth , and selection . our results show that adaptive evolution may occur in small or sparse populations , providing a means of mitigating or avoiding inverse density dependent effects ( i.e. , allee effects ) . the rate at which this adaptation occurs is proportional to the amount of genetic variance and is a crucial component in assessing whether natural selection can rescue a population from extinction . we provide theoretical evidence for the importance of recognizing evolution in predicting and explaining successful biological invasions .
[ "the primary objective of this study was to establish the need for screening hiv seropositive women for cti . real - time pcr has increasingly been used and is easier to perform and faster , and since it is performed in a closed system it is less prone to contamination than the conventional pcr . keeping the above background in mind this study was undertaken to generate reliable data regarding prevalence of cti in hiv - infected and hiv - uninfected women by real - time pcr , the most sensitive and specific test available currently for diagnosing genital chlamydia infection . genital infection due to chlamydia trachomatis is one of the most prevalent bacterial sexually transmitted infections ( stis ) . according to the who estimates , globally 92 million new cases of c. trachomatis infection thus , screening for cti in hiv seropositive women is highly recommended to prevent morbidity associated with the disease and devastating clinical consequences . however , it is important to document laboratory - confirmed incidence and prevalence of cti from the developing world as well .", "study subjects were recruited as follows : thirty adult hiv seropositive women with symptoms suggestive of rtis ( study group a1),thirty adult hiv seropositive women without symptoms suggestive of rtis ( study group a2),thirty age and sex matched adult hiv seronegative women with symptoms suggestive of rtis ( control group b1),thirty age and sex matched adult hiv seronegative women without symptoms suggestive of rtis ( control group b2 ) . thirty adult hiv seropositive women with symptoms suggestive of rtis ( study group a1 ) , thirty adult hiv seropositive women without symptoms suggestive of rtis ( study group a2 ) , thirty age and sex matched adult hiv seronegative women with symptoms suggestive of rtis ( control group b1 ) , thirty age and sex matched adult hiv seronegative women without symptoms suggestive of rtis ( control group b2 ) . this was a cross - sectional analysis to determine the prevalence of chlamydia trachomatis infection by using real - time pcr in hiv seropositive and seronegative , symptomatic , and asymptomatic women visiting the ictc of our department . genital c. trachomatis infection was diagnosed by using cobas taqman ct test , v2.0 , an in vitro nucleic acid amplification test for the qualitative detection of chlamydia trachomatis dna in female endocervical swab specimens . this study was conducted prospectively between july 2010 and january 2011 at the hiv molecular laboratory of the department of microbiology , maulana azad medical college .", "the prevalence of cti was higher in hiv seropositive women as compared to hiv seronegative women ( or 4.214 ; 95% ci 0.45738.865 ) and among the hiv positive asymptomatic as compared to the hiv negative asymptomatic ( or 2.111 ; 95% ci 1.6062.776 ) , although the differences were not found to be statistically significant ( table 6 ) . chlamydia trachomatis infection was more commonly diagnosed in the asymptomatic hiv seropositive study subjects as compared to the symptomatic hiv seropositive study subjects . in our study vaginitis was the most common syndrome diagnosed in both the study and the control groups . \n the age and gender profile of all the participants is shown in table 2 . in both the hiv seropositive study group and the hiv seronegative control group the mean age of hiv - infected cases was found to be 30.92 5.7 years and in hiv - uninfected controls 28.52 6.9 years . \n", "our study presents an insight into the prevalence data of genital chlamydia infections in hiv - infected and hiv - uninfected women visiting the ictc of new delhi 's largest tertiary care hospital . the present study also validates the fact that chlamydia infections are usually asymptomatic as 10% of the asymptomatic women were diagnosed with cti while only 3.3% of symptomatic women had lab - confirmed cti in the hiv positive study group . this association of chlamydia infection with younger age is consistent with studies from other developing countries [ 32 , 33 ] . it is meaningful to have genuine laboratory - confirmed data on the incidence / prevalence of rtis / stis in india . as the asymptomatic nature of stis in india stis / rtis and hiv / aids are major public health problems . incidence and prevalence data have a key role in control strategies for hiv and stis .", "this study clearly shows that cti is more prevalent among hiv - infected females ( with or without symptoms of rti ) as compared to hiv - uninfected females . our study also stresses the usefulness of screening asymptomatic hiv - infected and hiv - uninfected females for cti by risk assessment and diagnostic testing periodically to prevent the occurrence of adverse outcomes associated with the disease and also to check further spread of infection in the community . for countries like india that still do not currently have an active chlamydia screening program in place , however , since use of real - time pcr is not feasible in most hospitals in developing countries efforts should be made to develop a simple , cost - effective , sensitive , and specific point of care test to identify and treat women with cti for prevention of sequelae and hiv transmission . it is also important that any test adopted in a national screening program be used in the primary care setting by practitioners without the need for expensive training and equipment . randomized controlled trials are required to delineate the benefits of screening in the sexually active population as our study participants represent a high risk group ." ]
reproductive tract infection ( rtis)/sexually transmitted infections ( stis ) are recognized as a major public health problem , particularly due to their relationship with hiv infection . early detection and treatment of chlamydia trachomatis infection ( cti ) among hiv - infected and hiv - uninfected women may impact heterosexual hiv transmission . a total of 120 participants were enrolled : 30 hiv seropositive women with symptoms of rtis , 30 hiv seropositive women without symptoms of rtis , 30 hiv seronegative women with symptoms of rtis , and 30 hiv seronegative women without symptoms of rtis . one endocervical swab was collected from all participants and cti was detected by real - time pcr ( cobas taqman ct test , v2.0 ) . cti was detected in 4 ( 6.67% ) hiv - infected women and in 1 ( 1.67% ) hiv - uninfected woman ( or 4.214 ; 95% ci 0.45738.865 ) . vaginal discharge was present in almost half of hiv - infected and hiv - uninfected women ; lower abdominal pain was present in 11 ( 18.3% ) of hiv - infected and in 9 ( 15% ) of hiv - uninfected women . this study showed that cti is more prevalent among hiv - infected females as compared to hiv - uninfected females . as the use of real - time pcr is not feasible in most hospitals , efforts should be made to develop a simple , sensitive , and specific test to identify women with cti for prevention of sequelae and hiv transmission .
[ "although some authors suggest that laminoplasty is superior to laminectomy with lateral mass screw fixation and bone grafting regarding preserved range of motion , indications for the use of clf are broader than that of laminoplasty and recent studies showed good outcomes for clf . thus , the aim of this study is to evaluate the efficacy and safety of txa in controlling blood loss during clf for the treatment of mcsm . multilevel cervical spondylotic myelopathy ( mcsm ) is a serious disease which can lead to spinal cord dysfunction and a substantial decrease in quality of life . in addition , mcsm requiring multilevel cervical spine surgery can be accompanied by extensive blood loss . as spinal surgery has become increasingly complex , so control of perioperative bleeding has become an important clinical issue for spine surgeons . clf has been widely used for many years for treating mcsm caused by multilevel cervical spinal cord compression . it has been widely used in various medical fields such as cardiac surgery , gynecology , dentistry , urological surgery , and liver transplantation to reduce the perioperative blood loss , as it is relatively inexpensive and has not been cited in the literature as causing any significant untoward side effects . in addition , txa has been reported to reduce blood loss and transfusion requirements during orthopedic surgery , most commonly in knee and hip joint replacement . although the benefits of txa in spinal surgery have been reported", "a retrospective comparative analysis was performed in patients with mcsm undergoing clf of vertebrae c3 to c6 . the control group consisted of 46 patients who underwent clf for the treatment of mcsm in our institution without being given txa . in both groups the quantity of intraoperative and postoperative blood loss and the preoperative and day 1 postoperative hematological data for each patient were obtained in the 2 groups . patients with cirrhosis of the liver , serious cardiac disease , chronic renal failure , cancer , allergy to txa , a history of thromboembolic disease ( deep vein thrombosis , ischemic heart disease , pulmonary embolism , transient ischemic attack , strokes , or subarachnoid hemorrhage ) , bleeding disorders , hypercoagulation status , disseminated intravascular coagulation , pregnancy , combined anterior and posterior spinal fusions , patients receiving antiplatelet and/or anticoagulant therapy at the time of the study , and treatments of vertebrae outside of c3 to c6 were excluded from the study . between november 2014 and april 2016 , 119 clfs fitting the inclusion criteria were performed in our center . each surgeon ( hao , liu , he , wu , wang , zheng , and zhao ) in this study had more than 20 years of experience in spinal surgery . , we analyzed patient demographic trait ( age at surgery , gender , body weight , height , and body mass index ) and duration of surgery which was defined as the time from the initial incision to the completion of wound closure . all patients in the txa group were given a dose of 15 mg / kg of txa ( transamin ; daiichi pharmaceutical , tokyo , japan ) before a skin incision was made , followed immediately with a maintenance dose of 100 mg / hour , and continued until wound closure .", "laminectomy was performed using a high speed matchstick burr to drill troughs in the bone at the lateral edge of the lamina on each side , prior to complete removal of the entire lamina and associated ligamentum flavum of the target vertebrae ( c3c6 ) . the spinous processes , lamina , and lateral mass facet complexes were exposed using a standard posterior midline opening after longitudinally dividing the nuchal fascia in line with a midline skin incision . lateral mass screws were placed bilaterally on vertebrae c3 to c6 then fixed with rods using the margerl technique . the excised lamina and spinous processes were cleaned of soft tissue and cut into pieces for use as autograft material .", "all patients in the txa group were given a dose of 15 mg / kg of txa ( transamin ; daiichi pharmaceutical , tokyo , japan ) before a skin incision was made , followed immediately with a maintenance dose of 100 mg / hour , and continued until wound closure . no patient in the control group received intraoperative administration of txa or any other antifibrinolytic drug .", "continuous variable data were presented as mean and standard deviation while categorical variable data were presented as a number and its specific value . statistical differences between the 2 experimental groups were compared using a chi - square test or fisher exact test for categorical variables and student t test for continuous variables . all analyses were performed using ibm spss statistics for windows , version 19.0 ( ibm corp . , united states of america ) .", "the txa ( tranexamic acid ) group had significantly less intraoperative , postoperative , and total blood loss compared to the control group . there were no significantly different in blood hgb hct between the control and txa groups . there was significantly less intraoperative blood loss in the txa group compared to the control ( fig . hgb = hemoglobin , hct = content and hematocrit , txa = tranexamic acid . although the hgb and hct values in the txa group were all higher than those of the control group , the differences were not statistically significant ( fig . no statistically significant difference in duration of surgery was observed between the 2 groups , with a mean time of 155.72 15.59 and 153.52 11.91 minutes in the control and txa groups , respectively ( p = 0.387 ) . the txa group had significantly less postoperative blood loss during the 1st 16 hours compared to the control group ( 108.08 44.31 vs 132.83 49.39 ml , p = 0.005 ) .", ", we evaluated the effects of txa with a dose of 15 mg / kg followed by a maintenance dose of 100 mg / hour . a prospective randomized controlled study would better determine the safety and efficacy of txa during laminectomy with lateral mass screw fixation and bone grafting . numerous studies have supported the use of txa in orthopedic surgery . although it has been evaluated in many studies , the safety and efficacy of txa for blood loss reduction in spinal surgery has not been clearly demonstrated , especially for clf . clf for the treatment of mcsm has proved to be a successful technique for restoring normal cervical lordotic alignment , recovering neurological function , and decreasing the morbidity of c5 palsy and axial pain . thus , the use of txa in patients undergoing clf should be regarded as safe .", "in this study , blood loss ( both intra- and postoperative ) in the txa group was significantly lower than that in the control group , and no major intraoperative complications occurred . our results indicate that the use of intravenous txa is both safe and effective in reducing blood loss in clf . prophylactic txa may provide the benefit of limiting excessive blood loss in posterior approach cervical spinal surgery . a future prospective randomized controlled trial will provide superior evidence of the efficacy and safety of txa ." ]
abstractto assess the safety and efficacy of tranexamic acid ( txa ) for decreasing perioperative blood loss in cervical laminectomy with lateral mass screw fixation and bone grafting ( clf ) , in which all surgical procedures are identical.from november 2014 to april 2016 , we performed a retrospective comparative analysis of 119 patients with multilevel cervical spondylotic myelopathy who had undergone a clf from c3 to c6 in our center . all surgeries were performed on the patients using a consistent , standard procedure . patients were divided into control ( 46 ) and txa ( 73 ) groups according to whether or not they had received txa treatment before and during surgery . demographic profiles of patients such as gender , age , body weight , height , and body mass index were collated and differences between the 2 groups compared . preoperative and postoperative hematological data in addition to intraoperative and postoperative blood loss were compared between the 2 groups . additionally , any complications of txa were also evaluated to assess safety.there was no statistically significant difference in demographic traits between the 2 groups . intraoperative blood loss in the txa group ( 179.66 81.45 ml ) was significantly lower than that of the control group ( 269.13 94.68 ml , p < 0.001 ) , as was postoperative blood loss ( 108.08 44.31 and 132.83 49.39 ml , respectively ; p = 0.005 ) . total blood loss in the txa group ( 287.74 115.40 ml ) was also significantly lower than that of the control group ( 401.96 127.88 , p < 0.01 ) . no major intraoperative complications occurred in any of the cases.txa significantly reduced perioperative blood loss in clf with no major side effects .
[ "high plasma troponin levels have been associated with severe adverse outcomes and increased mortality [ 7 , 1215 ] . in this study we wanted to test the hypothesis that fatal outcome following hip fracture hip fracture is a moderate musculoskeletal trauma that mainly affects the older population with comorbid conditions . myocardial injury may be difficult to diagnose because of impaired communication , limitations of clinical manifestation and non - specific electrocardiographic ( ecg ) changes [ 6 , 7 ] . comorbidity and the double trauma may dispose them to serious postoperative adverse outcomes and a high mortality dominated by cardiovascular events [ 25 ] . the isoenzyme myocardium - specific creatine kinase ( ck - mb ) is expressed in the myocardium and ck in the skeletal muscle cells .", "a total of 302 consecutive patients over 75 years of age with dislocated hip fractures were enrolled in the study at elverum ( ech ) and buskerud ( bch ) central hospitals during the period 20052009 . blood samples were obtained from an antecubital vein , collected preoperatively ( 1 ) and postoperatively [ within 24 hours ( 0 ) ] and on days one [ 2448 h ( + 1 ) ] and four ( + 4 ) . univariate and stepwise multivariate logistic regression analyses were used to estimate unadjusted and adjusted odds ratios with respect to survival at the three month follow - up . non - parametric mann - whitney tests were done for tnt due to skewed distribution . a linear mixed model for repeated measurements with a random intercept and bonferroni adjusted pairwise post hoc comparisons were used to analyse the biochemical markers with respect to mortality and repeated venous blood analyses . troponin t ( tnt ) and ck - mb were measured by electrochemiluminescence immunoassay ( elica , roche , basel , switzerland and abbott , abbott park , il , usa ) . values for tnt were only measured at the ech study centre ( n = 146 ) .", "we found that our hypothesis , stating no predictive value from cardio - muscular plasma enzymes with regard to early mortality in patients with hip fracture , was false . \n high tnt plasma concentration was associated with increased mortality ( or 6.1 95% ci 623.1 , p = 0.008 ) at day four after surgery . missing data are assumed to be completely at random asa , male sex and age were significantly associated with mortality within three months ( table 1 ) . within one day after surgery , the plasma levels of ck and ck - mb increased nearly threefold ( inverse for the ratio ) . on days 1 and + 1 , ck and ck - mb values were significantly higher among those who died compared to those who survived ( p = 0.001 and p = 0.031 , respectively ) ( fig . 1 ) . / l before surgery correlated with three month mortality [ odds ratio ( or ) 10.9 , 95% confidence interval ( ci ) 2.254.0 , p = 0.003 ] ( table 2 ) . on the fourth postoperative day , tnt plasma levels rose twofold in the mortality group and remained unchanged in the alive group .", "this prospective study on 302 elderly patients with hip fracture disclosed that 19.5% had died within three months . / l are robust predictors of three month postoperative mortality in the elderly undergoing hip fracture surgery . , this study showed that basic clinical information on sex , age and comorbidity ( asa score ) and a high postoperative plasma concentration of tnt > 0.04 g potential heart muscle damage was investigated in this study with ck - mb and tnt analyses . this analysis suggests that ck and ck - mb are unspecific enzymes that are not distinct for skeletal and cardiac muscle damage following a hip fracture and are not feasible as prognostic markers of mortality , a finding consistent with other investigators . this information may be of importance for therapeutic and post - hospital health care intervention ." ]
hip fracture , a moderate musculoskeletal trauma , is associated with a high postoperative mortality . most patients are elderly , with comorbid conditions and often with heart disease . the objective of this study was to find out if clinical parameters and analyses of specific muscle enzymes could predict three month postoperative mortality . a total of 302 patients above 75 years of age with hip fracture were consecutively enrolled . baseline information on age , sex and comorbidity assessed with the american society of anesthesiologists ( asa ) score was obtained before surgery . creatine kinase ( ck ) , myocardium - specific creatine kinase ( ck - mb ) and troponin t ( tnt ) were analysed from venous blood , collected the day before surgery ( 1 ) and postoperatively , within 24 hours ( 0 ) and on days one ( + 1 ) and four ( + 4 ) . the overall three month mortality was 19.5% . multivariate analyses showed that age , male sex and comorbidity ( asa ) correlated with mortality ( p = 0.027 , p = 0.002 , p < 0.001 , respectively ) . surgery induced a two- to threefold increase of ck and ck - mb but without any correlation with mortality . however , high tnt levels > 0.04 g / l correlated significantly with death ( days 1 , + 1 and + 4 , p = 0.003 , p = 0.005 and p = 0.003 , respectively ) . multivariate analyses , adjusted for age , sex and asa category , confirmed this correlation ( day + 4 , p = 0.008 ) . thus , in elderly patients with comorbidities undergoing hip fracture surgery information on sex , age , asa category and postoperative laboratory analyses on tnt provide the clinicians with useful information on patients at risk of fatal outcome .
[ "", "the impression of acute retinal necrosis was confirmed by polymerase chain reaction of aqueous humor by detecting herpes simplex virus type 2 ; therefore , the patient received intravenous acyclovir . a young man was referred with a chief complaint of blurred vision and pain of the left eye 1 month after herpetic encephalitis in the left frontotemporal lobe . the patient had multiple foci of retinitis in the retinal periphery associated with vitritis , blot retinal hemorrhage and retinal arteriolitis .", "herpetic encephalitis may be a risk factor for acute retinal necrosis . the virus may reach the eye by the trans - axonal route .", "acute retinal necrosis ( arn ) is one of the clinical presentations of herpes simplex virus ( hsv ) . patients with arn due to hsv-1 and varicella zoster virus tend to be older , whereas those with arn due to hsv-2 tend to be younger [ 3 , 4 ] . in this article , we report one case of unilateral arn 1 month after the herpetic encephalitis . pcr is very helpful in the detection of the varicella zoster , hsv type 1 and 2 . polymerase chain reaction ( pcr ) analysis of the aqueous humor can detect the cause of arn specifically .", "the patient is a 25-year - old man who was admitted with a chief complaint of decreased vision and pain in left eye for the previous 4 days . the patient also received aspirin to treat an associated hypercoagulable state . with this treatment , no new lesion developed and opacity of the media decreased ; so prophylactic barrier laser photocoagulation in the areas of healthy retina at the posterior borders of the necrotic lesion prevented retinal detachment . the patient also complained of perception of floating objects in the visual field of the left eye . the patient had no past medical history indicating an immunocompromised state ; he had been admitted to the neurology ward due to herpetic encephalitis 1 month previous to the occurrence of visual symptoms . the inflammation decreased and the patient had no vitreous traction or retinal detachment or other eye involvement . intravitreal antiviral agents such as ganciclovir and foscarnet were not used in this patient because the disease was controlled by intravenous acyclovir .", "some of the studies report arn several years after neonatal and infantile herpetic encephalitis [ 5 , 6 ] ; therefore , herpetic encephalitis may be a risk factor for arn development . other articles report that the virus accesses the retina from the brain by the trans - axonal route ; consequently , this virus can cause recurrent episodes of arn [ 8 , 9 ] . these reports may necessitate a prophylaxis with antiviral agents after herpetic encephalitis to prevent arn . in a study by pavsio et al . , the role of long - term prophylaxis with acyclovir in children who had herpetic encephalitis is an important issue . we reemphasize the correlation between these two diseases . on the other hand , arn may be an indication of possible central nervous system involvement and neuroimaging may be necessary in all cases of arn to rule out herpetic encephalitis . prophylaxis could be considered after hsv encephalitis to prevent arn or after arn to prevent second eye involvement ." ]
purposeto report a case of unilateral acute retinal necrosis after herpetic encephalitiscase reporta young man was referred with a chief complaint of blurred vision and pain of the left eye 1 month after herpetic encephalitis in the left frontotemporal lobe . the patient had multiple foci of retinitis in the retinal periphery associated with vitritis , blot retinal hemorrhage and retinal arteriolitis . the impression of acute retinal necrosis was confirmed by polymerase chain reaction of aqueous humor by detecting herpes simplex virus type 2 ; therefore , the patient received intravenous acyclovir.conclusionherpetic encephalitis may be a risk factor for acute retinal necrosis . the virus may reach the eye by the trans - axonal route . prophylaxis with acyclovir may be necessary after herpetic encephalitis to prevent acute retinal necrosis .
[ "inspection of the database of clusters of orthologous groups of proteins ( cogs ) revealed only one family of such proteins that is represented in most of the sequenced bacterial , archaeal and eukaryotic genomes . the near ubiquity of the rhomboid family among bacteria , archaea and eukaryotes , along with the remarkable functional conservation , suggests that a signaling mechanism mediated by rhomboids might have functioned already in the last common ancestor of all extant life forms , with subsequent loss in several lineages . to address this possibility the prototype of this family is the rhomboid ( rho ) protein from drosophila melanogaster , a developmental regulator involved in epidermal growth factor ( egf)-dependent signaling pathways [ 2 - 4 ] .", "the parsimonious interpretation of the rhomboid family tree seems to be that the evolutionary history of this family had been replete with horizontal gene transfer ( hgt ) and lineage - specific gene loss events . in particular , in spite of the presence of rhomboids in the majority of modern life forms from all three primary superkingdoms , phylogenetic analysis suggests that this family has not been inherited from the last universal common ancestor ( luca ) . the concordance of the results obtained with several independent methods for phylogenetic tree construction and statistical analysis specifically aimed at testing the alternative hypothesis of monophyletic origin of eukaryotic rhomboids shows strong support for the major aspects of the tree topology in figure 2 and , in particular , for the polyphyly of eukaryotic rhomboids . the phylogenetic tree of the rhomboid family shown in figure 2 and supported by the additional tests described above follows neither the ' standard model ' scenario , with the major split between the archaeo - eukaryotic and bacterial lineages nor the ' mitochondrial ' scenario , which postulates acquisition of a gene by eukaryotes from the pro - mitochondrial endosymbiont . the alternative phylogenies reflected two distinct hypotheses : first , clustering of the rho and parl subfamilies of eukaryotic rhomboids with the prokaryotic rhomboid families as suggested by the tree topology in figure 2 ; and second , monophyly of the eukaryotic rhomboids ( figure 3 ) . in particular , at least two hgt events seem to have contributed to the origin of eukaryotic rhomboids , one of them yielding the rho subfamily and the other one the parl subfamily , with a possible additional hgt in plants ( figures 2,3 ) . given the broad phyletic representation of both subfamilies of eukaryotic rhomboids , both the rho subfamily and the parl subfamily", "although the sequence similarity between eukaryotic and prokaryotic rhomboid family proteins is relatively low ( around 10 - 15% identity in the conserved region ) , the entire superfamily could be retrieved from the protein sequence databases within three iterations of the psi - blast program with a high statistical significance and without any false positives . the conserved core of the rhomboid family consists of six conserved tmhs ( figure 1 ) . the predicted catalytic serine is located in tmh5 , whereas the predicted catalytic histidine is in tmh7 ; tmh3 contains two additional histidines and an asparagine , which are conserved in the great majority of the rhomboid - family proteins ( figure 1 ) .", "the concordance of the results obtained with several independent methods for phylogenetic tree construction and statistical analysis specifically aimed at testing the alternative hypothesis of monophyletic origin of eukaryotic rhomboids shows strong support for the major aspects of the tree topology in figure 2 and , in particular , for the polyphyly of eukaryotic rhomboids . theoretical analysis of evolutionary scenarios constructed on the basis of the phyletic patterns of cogs by applying the parsimony principle shows that the complexity of the inferred gene set of luca critically depends on the relative rates of gene loss and hgt at the early stages of evolution . a complex luca with around 2,000 genes the parsimonious interpretation of the rhomboid family tree seems to be that the evolutionary history of this family had been replete with horizontal gene transfer ( hgt ) and lineage - specific gene loss events . the phylogenetic tree of the rhomboid family shown in figure 2 and supported by the additional tests described above follows neither the ' standard model ' scenario , with the major split between the archaeo - eukaryotic and bacterial lineages nor the ' mitochondrial ' scenario , which postulates acquisition of a gene by eukaryotes from the pro - mitochondrial endosymbiont . the alternative phylogenies reflected two distinct hypotheses : first , clustering of the rho and parl subfamilies of eukaryotic rhomboids with the prokaryotic rhomboid families as suggested by the tree topology in figure 2 ; and second , monophyly of the eukaryotic rhomboids ( figure 3 ) . in particular , in spite of the presence of rhomboids in the majority of modern life forms from all three primary superkingdoms , phylogenetic analysis suggests that this family has not been inherited from the last universal common ancestor ( luca ) . in particular , at least two hgt events seem to have contributed to the origin of eukaryotic rhomboids , one of them yielding the rho subfamily and the other one the parl subfamily , with a possible additional hgt in plants ( figures 2,3 ) . given the broad phyletic representation of both subfamilies of eukaryotic rhomboids , both the rho subfamily and the parl subfamily several lineage - specific expansions of paralogs are noticeable , in insects , mammals and plants ( figure 2 ) . thus , the existence of two distinct subfamilies of eukaryotic rhomboids is supported by features of domain architectures that appear to comprise shared derived characters . within these two major eukaryotic subfamilies ,", "although most of the ( nearly ) ubiquitous protein families probably do derive from luca , explicit phylogenetic analysis is required to ascertain this in each case . phylogenetic analysis of the rhomboid family described here carries a general message for studies aimed at the reconstruction of ancestral life forms , particularly luca . the rhomboid family might be the most widespread and conserved group of integral membrane proteins . in and by itself , this would suggest that this family is part of the gene repertoire of luca . these events , which might have introduced rip as a means of intercellular communication , could have been pivotal in the evolution of eukaryotic multicellularity along the lines discussed previously with regard to the apparent bacterial origin of key components of eukaryotic programmed cell death machinery . are involved , the multiple - hgt scenario seemed to be supported by several methods of tree analysis and statistical tests . however , phylogenetic analysis suggests a different scenario , one of emergence in a bacterial lineage with subsequent multiple , independent hgt events and gene losses . although caution is due in the evolutionary interpretation of phylogenetic trees for large families , particularly when membrane proteins with a relatively small number of conserved positions , such as the rhomboids , subsequent evolution of rhomboids in eukaryotes proceeded by lineage - specific expansion of paralogs followed by diversification through the addition of an extra tmh in different positions relative to the catalytic core , some limited domain accretion ( see figure 2 ) and sequence divergence .", "multiple alignments of protein sequences were constructed using the clustalw program and manually adjusted on the basis of the examination of psi - blast search outputs and the superposition of the predicted tmhs , which were identified using the programs tmpred and tmap . maximum parsimony trees were constructed using the heuristic search option of paup * . in addition , trees were constructed by bayesian inference using the markov chain monte carlo method as implemented in the mrbayes package . the reliability of the tree topology was assessed using the rell ( resampling of estimated log - likelihoods ) bootstrap method of molphy , with 10,000 replications . alternative placements of selected clades in maximum - likelihood trees were compared by using the rearrangement optimization method ( kishino - hasegawa test ) as implemented in the protml program [ 43 - 45 ] . phylogenetic trees were built using the least - squares method implemented in the fitch program of the phylip package , with subsequent local rearrangement using the protml program of the molphy package to obtain the maximum likelihood tree . the nonredundant ( nr ) protein sequence database at the national center for biotechnology information ( nih , bethesda ) was searched iteratively using the psi - blast program with multiple starting queries . constraint trees were imported into paup * and subjected to neighbor - joining search to generate the phylogenies corresponding to alternative hypotheses . these phylogenies were compared using the kh , templeton ( wilcoxon signed - ranks ) and winning - sites ( sign ) tests implemented in paup*. psi - blast was normally run with expectation ( e ) value of 0.01 as the cut - off for inclusion of sequences into the position - specific scoring matrix . the complete alignment information , including columns with gaps , was used for the mrbayes analysis .", "l.p . is supported by a grant from the natural sciences and engineering research council of canada .", "the figure schematically shows the proposed three stages of evolution of the rhomboid family . in ( a ) , the progenitor of the rhomboid family functions as a transporter for a regulatory peptide in some bacterial lineage . in ( b ) , the catalytic site of the intramembrane protease evolves , allowing the switch to rip as the mechanism of the regulatory peptide release . in ( c ) , the emergence of rip is followed by a burst of hgt . the alignment includes the majority of the detected rhomboid family proteins ; some closely related sequences were omitted . only the six conserved ( predicted ) transmembrane helices ( tmh ) and short surrounding regions are shown . the two major eukaryotic subfamilies are denoted as rho and parl ( see text ) and four clusters containing unexpected ( from a phylogenetic viewpoint ) sets of species are denoted 1 - 4 . the proteins are identified with the gene identification ( gi ) number from the nonredundant database and an abbreviated species name . bacterial species are color - coded green , eukaryotic species blue and archaeal species yellow . the transmembrane helices of rhomboid are designated as in figure 1 ; their topology in the membrane is based on that proposed in ." ]
the near - universal presence of the rhomboid family in bacteria , archaea and eukaryotes appears to suggest that this protein is part of the heritage of the last universal common ancestor , phylogenetic tree analysis indicates a likely bacterial origin with subsequent dissemination by horizontal gene transfer .
[ "an infliction in the life expectancy figure of patients with sickle cell disease ( scd ) occurred around the middle of the 1970s ( fig . this minimal increase in life expectancy coincided with my appointment at thomas jefferson university as the associate director of the newly created adult sickle cell center . the steady stream of admissions of patients with acute painful vaso - occlusive crises ( vocs ) to the emergency department ( ed ) and hospital were not welcome by most providers , hospital administration , the house and nursing staffs . stripped from the protective sphere of the pediatric world and the empathy of their pediatric hematologists and the pediatric ancillary staff , they were in a state of fear , anxiety , depression and , worst of all , severe pain . listening to and believing the patients and keeping detailed records of ed and hospital admissions and the analgesics prescribed , revealed that most patients genuinely do not respond to a certain analgesic or a certain dose . increasing the doses of an analgesic or switching to another drug solved the problem in most patients . the trickle of patients increased gradually and we were faced with adolescent and young adult african american patients who were in a state of confusion .", "the cyp3a4 enzyme metabolizes more than 50% of all drugs ; consequently , opioids metabolized by this enzyme have a high risk of drug - drug interactions . ( a ) morphine - like molecule ( yellow ) in the deep pocket ( blue ) of the -opioid receptor . ( b ) phase i involves the cyp enzymes and phase ii metabolism conjugates the drug to hydrophilic substances , such as glucuronic acid , sulfate , glycine , or glutathione . parallel to the progress in the pharmacodynamics of opioids mentioned above , a concomitant advance in the pharmacokinetics of opioids was bubbling to the surface . patients who are ums of fentanyl would rapidly convert it into inactive metabolites with minimal or absent analgesic effect requiring increasing the dose of fentanyl . on the other hand , patients who are pms of fentanyl would experience prompt relief with relatively small doses of fentanyl but higher doses could be toxic due to the accumulation of unmetabolized fentanyl . -opioid receptors from an intimate pair when crystallized with a ligand ( yellow ) such as morphine . knowing how an opioid molecule ( yellow ) sticks in the pocket of its receptor ( blue ) in the 1970s , it was hypothesized that opioids have receptors to bind to and activate in order to relieve pain by blocking or minimizing the transmission of painful stimuli and raising the pain threshold .", "together , current data on the pharmacodynamics and pharmacokinetics of opioids show great variability of genotypes among patients and extreme variability in individual responses to opioids . determining the pharmacogenetics profile of each patient facilitates the choice of drugs that would be efficacious for that patient and avoid those drugs associated with harmful drug - drug interaction . this approach in diagnostics and therapeutics ushers in the dawn of a new field for the management of individual patients based on their unique pharmacogenetics , phenotypic and biomarker characteristics . we hope that this methodology would be approved and sponsored by the insurance companies for patients with scd . in the meantime , listening , believing and respecting the patient with sickle cell pain should be maintained for now as the approach to individualized therapy . this future approach is referred to as personalized medicine or , more recently , precision medicine .", "" ]
in the 1970s , sickle cell pain was treated with trial and error approach by increasing or decreasing the dose of an opioid or switching from one analgesic to another . this approach was controversial with criticism and doubt about its usefulness . since then , advances in determining the structure of opioid receptors and the role of the cyp450 enzymes in metabolizing opioids revealed that these anatomic and metabolic findings are not the same in all persons , thus explaining the variability in response to opioids among patients . thus , the trial and error approach has a scientific basis after all .
[ "overall , our study demonstrates the functionality of lnps modified for receptor targeting for sirna delivery to dcs . , we reasoned that this lnp platform could be a useful foundation for the delivery of sirnas to dcs to modulate immune responses . to achieve this dec205 dcs mediate cross - presentation of antigen resulting in modulation of cd8 t - cell responses . therefore , inhibition of gene expression by dec205 dcs is a potentially powerful approach for regulating cd8 t - cell activation . using this approach , we assessed the ability of dec - lnps ( lnps coated with scfv specific for murine dec205 , containing sirnas specific for costimulatory molecules ) to inhibit immune responses . together with a complementary study , this work demonstrates the feasibility of gene silencing in immune cells using lnp technology . clearly additionally our results suggest that specific cell targeting can mediate immunological responses to sirna formulations . although designed for hepatic gene silencing , the efficacy of these lnps and their derivatives has been assessed for rnai - mediated gene silencing in macrophages ( mos ) and dcs in vitro and in vivo .", "having demonstrated dec205-mediated uptake of dec - lnps in vitro , we investigated their localization in vivo . conversely , dec - lnp injection was useful for the identification of sirnas with immune - activating potential . from these results consistent with our previous results ( figure 4a ) , animals treated with dec - lnps containing 2f modified sirnas also upregulated these costimulatory molecules . importantly , and similar to work by other groups , we found that 2ome modified sirnas induced minimal immune activation . to attempt to circumvent the need for a time and resource intensive in vivo assay , we wanted to determine whether an in vitro assay could be used to detect immunostimulatory sirnas . , we used sirnas containing selective 2ome substitutions for all subsequent studies . to target autoimmune diseases , reducing the expression of several costimulatory molecules we confirmed that gene knockdown was rnai - mediated using 5 race to detect sirna - directed mrna cleavage products ( figure 4c ) . this observation was surprising considering these experiments were performed using sirnas containing 2f modified rna , previously reported to have reduced immunostimulatory activity . to better assess this effect , we synthesized a series of luciferase - specific control sirnas ( luc ) containing 2oh rna ( unmodified ) , 2f pyrimidines or selected 2ome modifications ( see methods for modification strategy ; based on refs .", ", we have shown that a clinically relevant lnp can be modified for cell - specific delivery of sirnas . in vivo administration currently , the most advanced lnp platforms use the ionizable cationic lipid dlindma , or its dlin - kc2-dma and dlin - mc3-dma derivatives . we achieve significant reduction in expression of cd40 , cd80 , and cd86 on splenic dcs using our dec - lnps following systemic delivery , and ongoing studies are addressing the durability of gene knockdown and the potential use of these dec - lnps for treating autoimmune diseases . in summary we have shown that conjugation of a scfv , specific for the dc receptor dec205 , is sufficient to direct delivery of dlindma - formulated dec - lnps to splenic dcs . coated lnps formulated with the cationic lipid ddab with full - length dec205 antibody for sirna delivery and demonstrated the ability to reduce expression of the costimulatory molecule cd40 in dec205 dcs . while some gene knockdown was achieved , this lipid is known for its adjuvant qualities , and is being developed for applications that require immune response stimulation . importantly , we demonstrated that targeted delivery resulted in effective rnai - mediated gene silencing of one , or several genes , to essentially basal expression levels ( figures 4 and 5a c ) .", "cho cells , cho cells that stably express dec205 ( cho - dec ) , a dec205 b lymphoma line ( a20 cells ) and bmdcs , derived from b6 and dec205 mice , were used to assess lnp binding and uptake . the pbmc fraction was used directly or following purification of cd14 cells ( stemcell technologies , vancouver , british columbia , canada ) , monocytes were cultured for 5 days in the presence of granulocyte - macrophage colony - stimulating factor and il4 to generate modcs . cd11ccd8 splenic dcs were isolated by flow cytometry from b6 mice injected the previous day with dec - lnps containing either a 1:1:1 mix of cd40 , cd80 , and cd86 sirnas or control sirnas . splenic t cells from balb / c mice were isolated by macs using a pan t cell isolation kit ii ( miltenyi , san diego , ca ) . the primers and oligonucleotide sequences used : adapter rna : 5-cgacuggagcacgaggacacugacauggacugaaggaguagaaa-3 ; gsp forward : 5-cgactggagcacgaggacactga-3 ; cd80 gsp reverse : 5-tgcgccgaatcctgccccaa-3 ; cd80 reverse nested : 5-atcaggagggtcttctgggg-3 ; cd86 gsp reverse : 5-agtaactgaagctgtaatctccttccaata-3 ; cd86 reverse nested : 5-ctgtgacattatcttgtgatatctgcatgt-3. analysis of immune stimulation . pcr amplification using an adapter - specific primer and a nested gsp primer will amplify the cleavage product and identify the cut site which corresponds to position 10/11 of the sirna guide strand if mediated via rnai . sirna synthesis . modified and unmodified individual sirna sequences were synthesized on an expedite 8909 dna synthesizer ( biolytic , fremont , ca ) and purified by standard protocols , as described . total rna was isolated from cd11ccd8 splenocytes that had taken up lnps , i.e. , sirna - dy547 ( as for gene knockdown by qpcr ) , ligated at the 5 end to an adapter rna oligonucleotide and first strand cdna was synthesized using a gene - specific primer ( gsp ) . a cholesterol quantification kit ( abcam , cambridge , ma ) was use to determine the total lipid concentration . based on lipid concentration , the surface area per lipid head group ( ~0.6 nm ) , lnp diameter and their unilamellar structure , ~5060 scfvs are conjugated to each lnp under the conditions outlined above . cd11c murine bmdcs ( day 6 ; macs purified , miltenyi biotec , san diego , ca ) were cultured with dec - lnps and monitored for activation ( cd40 , cd80 , cd86 ) 1 day later by flow cytometry . in vivo stimulation", "" ]
due to their ability to knock down the expression of any gene , sirnas have been heralded as ideal candidates for treating a wide variety of diseases , including those involving undruggable targets . however , the therapeutic potential of sirnas remains severely limited by a lack of effective delivery vehicles . recently , lipid nanoparticles ( lnps ) containing ionizable cationic lipids have been developed for hepatic sirna delivery . however , their suitability for delivery to other cell types has not been determined . we have modified lnps for preferential targeting to dendritic cells ( dcs ) , central regulators of immune responses . to achieve directed delivery , we coated lnps with a single - chain antibody ( scfv ; dec - lnps ) , specific to murine dec205 , which is highly expressed on distinct dc subsets . here we show that injection of sirnas encapsulated in dec - lnps are preferentially delivered to dec205 + dcs . gene knockdown following uptake of dec - lnps containing sirnas specific for the costimulatory molecules cd40 , cd80 , and cd86 dramatically decreases gene expression levels . we demonstrate the functionality of this knockdown with a mixed lymphocyte response ( mlr ) . overall , we report that injection of lnps modified to restrict their uptake to a distinct cell population can confer profound gene knockdown , sufficient to inhibit powerful immune responses like the mlr .
[ "despite all the research demonstrating its safety , adverse cardiac arrhythmias such as nodal rhythm with bradycardia , prolongation of qtc interval , precipitation of torsade de pointes and isorhythmic atrioventricular dissociation ( isravd ) have been reported with sevoflurane anaesthesia . sevoflurane does not sensitise the myocardium to arrhythmogenic effects of catecholamines and has the least effect on cardiac conduction system .", "a 60-year - old woman weighing 60 kg with carcinoma in the right breast was scheduled for elective modified radical mastectomy . real - time picture from the monitor shows the inspired and expired concentration of sevoflurane a 5-year - old boy weighing 15 kg was scheduled for left inguinal hernia repair . the difference in heart rate ( ecg trace ) and pulse rate ( pulse oximetry trace ) is seen due to electrical alternans . real - time picture from the monitor shows electrical alternans with absent p waves in ecg trace . sevoflurane concentration was reduced to 5% and satisfactory proseal laryngeal mask airway insertion ( size 3 ) was accomplished with suxamethonium 100 mg .", "a 60-year - old woman weighing 60 kg with carcinoma in the right breast was scheduled for elective modified radical mastectomy . real - time picture from the monitor shows electrical alternans with absent p waves in ecg trace . the difference in heart rate ( ecg trace ) and pulse rate ( pulse oximetry trace ) is seen due to electrical alternans . sevoflurane concentration was reduced to 5% and satisfactory proseal laryngeal mask airway insertion ( size 3 ) was accomplished with suxamethonium 100 mg .", "a 5-year - old boy weighing 15 kg was scheduled for left inguinal hernia repair . sudden drop in hr to 56/min was noticed and the ecg revealed the presence of junctional rhythm with absent p waves and regular narrow qrs complexes . at that moment , spo2 was 99% and bp was 66/36 mmhg . the etco2 was between 31 and 33 mmhg , as measured through the angle piece interfaced between the face mask and the breathing circuit . inhalation induction of anaesthesia was performed with sevoflurane in 100% oxygen ( fresh gas flow 5 l / min ) through t piece circuit with child breathing spontaneously at a rate of 20 to 24/min . intravenous fentanyl ( 30 g ) was administered and anaesthesia was maintained with 1.5% isoflurane in a mixture of 50% nitrous oxide in oxygen ( fresh gas flow rate 5 l / min ) . after breathing 8% sevoflurane for 2 minutes , the child did not show any motor response to jaw thrust .", "american college of cardiology / american heart association recommends using volatile agents during non - cardiac surgery for the maintenance of general anaesthesia in haemodynamically stable patients at risk for myocardial ischemia . anticipating a difficult airway and considering the patient 's cardiac status , and associated hypertension , rarely , sevoflurane - induced suppression of baroreceptor reflex activity might result in desynchronisation between the atria and ventricle causing haemodynamic instability which may require electrical pacing . caution should also be exercised with its use in patients on ca channel and b blocker therapy . to conclude , sevoflurane in high concentration ( 8% ) should be used with caution in children and in conditions where primary pacemaker activity is suppressed , as in elderly . it is therefore wise to rely on the pr rather than the hr in such cases to treat bradycardia ." ]
when inhalational induction is indicated , sevoflurane is the most popular choice in both children and adults . higher inspired concentrations of sevoflurane can cause adverse cardiac arrhythmias that are seen to disappear once the agent is discontinued . we report the occurrence of isorhythmic atrioventricular dissociation and junctional rhythm with absent p waves during sevoflurane anaesthesia in an adult and a child , respectively .
[ "according to the mca , only a compromised ability to make a decision in accordance with certain procedural norms , loosely defined with reference to the ability to understand , this law aims to protect the individual 's right to pursue their own ends by adopting a capacity test that focuses on the decision - making process rather than the substance of the patient 's decision . ; for a full description of the case , see halpern , 2012 ) one problem with adopting a diachronic perspective in assessments of mental capacity is that whether questions of procedural rationality are properly understood in diachronic terms remains a contested issue in the fields of economics , psychology and philosophy . retain and use or weigh relevant information , or an inability to communicate a decision , properly grounds judgments of incapacity ( s. 3(1 ) ) .", "much of the normative and descriptive work on a diachronic perspective in personal decision - making has taken place in the fields of economics and psychology , but these fields have tended to adopt contrasting positions on the normative question . prudence to refer to taking a diachronic perspective in decision - making:prudence can not on this view be explained merely by the perception that something is in one 's future interest ; there must be a desire to further one 's future interests if the perception is to have an effect economists often treat a person 's weighting of the future as a preference like any other , in a framework that assumes that preferences are not available to rational criticism . there seems little doubt that most people have the desire that makes prudence possible [ however , according to this view we are not ] in any sense required to possess the desires in question : consequently we are not required to act on the specified considerations . if one lacks the relevant desire , there is nothing more to be said . i now turn back to questions of mental capacity and what implications a diachronic perspective such as bratman 's would have . however , all of the theorists canvassed thus far reason from premises about the extension of self over a lifetime , to conclusions about what reasons individuals have , and it will be argued here that this conception of the relationship between the requirements of practical rationality and the metaphysics of self is the wrong way around . as described above , the kind of requirement in question is often defended by nagel and others on the grounds that not giving weight to the future undermines one 's own interests . however , at times a different kind of argument is suggested in nagel 's work .", "the arguments above suggest that a diachronic perspective on questions of mental capacity is consistent with a procedural understanding of the functional element of the mca 's incapacity test . the motivation for investigating these theoretical questions about procedural rationality was the idea that a diachronic perspective might enable a mental capacity test such as that adopted in the mca to deal with certain hard cases , particularly in the context of mental disorder , without undermining its value - neutral approach . given this , could a diachronic understanding of what it is to have mental capacity help by justifying the inclusion of a requirement such as the ability to consider the future as a part of what it means to be able to understand , retain , use or weigh information in assessments of mental capacity ? this perspective allows us to reconcile the ideas that mental capacity requires that we care about the future personal consequences of our choices , and that life - ending decisions can be made with mental capacity . however , it does not follow from the view offered here , even given the sure knowledge that a patient 's future self would retrospectively endorse a medical intervention , that their present self is irrational in refusing it . in the imagined case there is an unambiguous conflict between what the patient currently wants ( no treatment ) and what the future self will want in retrospect ( treatment ) . using this conflict to doubt the patient 's current capacity to make the treatment decision assumes that the future self 's perspective should be given greater weight in the current self 's decision - making . however , if the ability to care about the future is included as part of what it means to have mental capacity , then consideration of a patient 's commitments from a diachronic perspective will also be central to this prior decision .", "it has been argued here that a diachronic perspective on mental capacity is relevant to questions about when an infringement on treatment decision - making liberty is justified . however , including considerations derived from a diachronic perspective in assessments of capacity comes into conflict with central patient autonomy - preserving features of the mca . this suggests that in some cases , especially in the context of mental illness , the importance placed on patient autonomy in contemporary medical ethics presents the law with a dilemma . on the one hand i will suggest that the answer lies in a common view about what makes patient autonomy valuable what makes it the case that for the most part , people 's treatment decisions , especially their refusals , ought to be respected . the importance of allowing patients to be self - determining in relation to their own medical care is often justified along lines that it", "however , in practice , appeal to these considerations in assessments of mental capacity undermines the role played by the functional element of the test in preserving patient autonomy . while involuntary treatment without reference to mental capacity is often assumed to undermine the principle of respecting patient autonomy , it was argued here that this is not necessarily so . in this article my focus was requirements of rationality derived from a diachronic perspective , and the question of what kinds of consideration this perspective would enable mental capacity assessments to include . it was an attempt to explore the limits of the mca 's incapacity test , given its value - neutral approach . it was argued that considerations derived from a diachronic perspective are relevant to questions of treatment decision - making liberty , and are consistent with a procedural understanding of the functional element of the test . when human agency is seriously compromised , preserving patient autonomy may sometimes require overriding a treatment decision to restore selfhood , on grounds that are not easily accounted for under the mca without compromising the value - neutral aspirations of this area of law . the inclusion of these considerations seems necessary for adequately caring for those with a mental disorder under universal capacity legislation . yet including these factors in assessments of mental capacity undermines the protections of patient autonomy that supporters of a shift to universal capacity legislation hope to gain . in considering a move to abandon dedicated mental health law , legislators must therefore resolve a bind . the central motivation for such a move is concern about unjustified infringements on liberty in the context of psychiatric diagnoses ." ]
calls for the adoption of a universal capacity approach to replace dedicated mental health law are motivated by the idea that the measures designed to protect patient autonomy in legislation such as the mental capacity act 2005 should apply to everyone , including people with a psychiatric diagnosis . in this article it is argued that a diachronic perspective on questions of mental capacity is necessary if capacity law is to play this broader role , but that employing this perspective in assessments of capacity undermines central patient autonomy preserving features of the legislation , which presents a moral dilemma .
[ "type iii dysbetalipoproteinaemia is a kind of lipid metabolism disorders , caused by apo - e deficiency , which leads to accumulation of chylomicrons and very low density lipoprotein remnants in the plasma.123 lipid metabolism disorders are mostly manifested by xanthomas , which are known as yellowish cholesterol - rich material in large foam cells accumulating in the skins and tendons.14 these yellowish lesions may appear all over the body , on the palm of the hands , sole of the foot , tendons , and even on the eyelids.5 these lesions firstly described with or without hyperlipidaemia in association with monoclonal immunoglobulin . based on this fact , there are three forms of xanthoma : hyperlipaemic xanthoma , normolipaemic xanthoma and necrobiotic xanthogranuloma.6 xanthomatosis is usually associated with hyperlipidaemia , and morbidity and mortality of this condition are related to atherosclerosis and pancreatitis.7 hyperlipaemic xanthoma lesions are more polymorphic and can include tuberous , tendinous , palmar or eruptive xanthoma . the epidermal - mucosal changes of hyperparakeratosis , neutrophilic infiltrate and dermal - submucosal foam cell reaction are distinctive features of these xanthomas.8 hereby , we present a rare type of xanthomas calling cauliflower xanthoma in a 43-year - old man with dysbetalipoproteinaemia . verruciform xanthoma usually presents as a hyperkeratotic , cauliflower like , verrucous or papillomatous lesion.6 it initially was described as a unique clinicopathologic lesion of the oral mucosa and was subsequently reported in the skin .", ", the patient diagnosed as familial dysbetalipoproteinaemia ( fdl ) and the unique lesions on the lower limb called cauliflower xanthoma . xanthomas on the shoulder and back of the neck xanthomas on the extensor side of the hand by searching in the medical data bases , we can not find a previous such a lesion . therefore , we decided to present this case without revealing patient 's name , after taking his consent . considering the fact that the treatment with high dose statin was effective in correction of lipid abnormality and regression of skin lesions in his three siblings , we wanted to try the treatment procedure in this patient but he refused any intervention . although siblings of this case had the same disorder , they did nt develop such lesions .", "fdl , also known as hyperlipoproteinemia type - iii or broad beta disease , is a rare inherited disorder characterised by improper metabolism of certain lipids , specially plasma cholesterol , triglyceride rich chylomicron and very low density lipoproteins ( vldl ) remnants.1 presence or absence of the symptoms of this disease depends on two major risk factors : genetic and diet.910 mutations in the gene for apolipoprotein e ( apo e ) are the main cause of this disease . , cauliflower xanthomas could be a symptom of fdl , and it should be considered as a differential diagnosis while approaching to these lesions . this means that with standard cholesterol diet , symptoms of fdl will not appear , even in the genetically susceptible person.10 xanthomas can be a symptom of fdl . there should be distinctive monitoring of fdl patients including regular checking of their serum lipids . controlling underlying disorders , and reducing excess calories , saturated fat and cholesterol , is the main aim of treating these patients . according to this article" ]
familial dysbetalipoproteinaemia ( fdl ) is an inherited disorder in which both cholesterol and triglycerides are elevated in the plasma , pre - disposing the people to coronary artery disease and peripheral vascular disease . the disease is mostly manifested by xanthomas , which have variable forms according to lipid amounts in the plasma of the blood . hereby , we report a 43-year - old man with fdl , presenting with a rare form of xanthomas calling cauliflower xanthoma all over the body .
[ "exacerbation is an important life - threatening event for patients with copd , and can lead to hospitalization and death.14 patients who suffer frequent and repeated exacerbations within 1 year have a poor prognosis,5 characterized by worsening of health - related quality of life ( hrqol),6,7 a rapid decline in lung function,810 and high mortality.11 frequent exacerbators also carry a high risk of further exacerbation and hospitalization.11,12 however , it has been suggested that japanese patients with copd may have fewer exacerbations , and they also may have a higher proportion of elderly patients , those with emphysema , and those with a lower body mass index in comparison to westerners.1215 the prognosis of japanese patients with copd who suffer frequent and repeated exacerbations is unclear . we conducted a 1-year prospective observational trial in a daily - life setting involving 90 japanese patients with copd to investigate whether previous moderate - to - severe exacerbations are associated with future exacerbations in this patient population .", "copd patients were divided into three groups , based on the total number of moderate and severe exacerbations within the last year before enrollment in the study , ie , non- ( previous moderate and severe exacerbations , 0/year ) , infrequent ( one exacerbation / year ) , and frequent ( two or more exacerbations / year ) exacerbator groups , in accordance with a previous report.16 in addition , patients with previous hospitalizations were classified as having a subphenotype with severe exacerbation ( severe exacerbators ) . consecutive patients for whom medical records were available covering a period of at least 1 year since provision of informed consent were selected for the study ; information on previous annual copd - related exacerbations and hospitalizations was collected on the basis of those medical records . we conducted a 1-year prospective observational trial in accordance with good clinical practice ( gcp ) guidelines and approved by the ethics committee of kurume university and chikugo city hospital ( gcp 11 - 127 , september 2012august 2014 ) . subsequent moderate and severe exacerbation events during 1 year of prospective observation were recognized as future risk indicators , and baseline parameters were chosen and modified in accordance with a previous report.16 kaplan meier analyses and log - rank tests for subsequent moderate and severe exacerbations were performed in all three groups of patients . for patients who were observed throughout the study period , the odds ratio ( 95% confidence interval [ ci ] ) of baseline parameters was determined to predict factors for future risk ( subsequent exacerbations once or more and twice or more ) using univariate and logistic multivariate regression analyses .", "copd patients were divided into three groups , based on the total number of moderate and severe exacerbations within the last year before enrollment in the study , ie , non- ( previous moderate and severe exacerbations , 0/year ) , infrequent ( one exacerbation / year ) , and frequent ( two or more exacerbations / year ) exacerbator groups , in accordance with a previous report.16 in addition , patients with previous hospitalizations were classified as having a subphenotype with severe exacerbation ( severe exacerbators ) . we conducted a 1-year prospective observational trial in accordance with good clinical practice ( gcp ) guidelines and approved by the ethics committee of kurume university and chikugo city hospital ( gcp 11 - 127 , september 2012august 2014 ) . consecutive patients for whom medical records were available covering a period of at least 1 year since provision of informed consent were selected for the study ; information on previous annual copd - related exacerbations and hospitalizations was collected on the basis of those medical records . duration of copd was defined as the period ( years ) since the patient had been diagnosed by a physician as having copd , emphysema , and/or chronic bronchitis.22,23 after stable status for at least 4 weeks had been confirmed , each patient was required to regularly visit the hospital every 2 months , and to request emergency admission when the symptoms worsened . regular respiratory medications were not changed during the period of the study , which was conducted in a daily - life setting . the data collected for each patient included baseline data for previous moderate and severe exacerbations and hospitalizations ; clinical parameters included age , sex , body mass index , smoking habits , smoking index , comorbidities , duration of copd , 5-grade modified medical research council ( mmrc ) dyspnea scale score,17 total copd assessment test ( cat ) score,18,19 frequency scale for symptoms of gastroesophageal reflux disease ( gerd ) ( fssg),20 center for epidemiologic studies depression ( cesd ) scale score,21 medications , blood pressure and heart rate , lung function and blood parameters , and chest computed tomography .", "copd overlap syndrome ( acos ) was made on the basis of a history of dyspnea and wheezing attacks at rest , large variations in daily symptoms , a fixed fev1/fvc ratio of < 0.7 , marked reversibility of fev1 after administration of bronchodilators ( > 15% and > 400 ml ) , and a peripheral eosinophil count of > 600/mm , in accordance with a previous report.25 to exclude any patients with asthma , patients who had past symptoms of repeated spasmodic wheezes and medications for asthma and a classification of fev1 > 200 ml or > 12% after bronchodilation were excluded.24 diagnosis of asthma ", "baseline data for the mmrc scale , total cat , fssg scale , and cesd scale scores were obtained only once , based on a self - report completed by each patient after written informed consent had been obtained.1721", "information about comorbidities was obtained from the patients by interview , and the diagnoses were confirmed by physicians . however , patients who had moderate - to - severe comorbidities associated with poor prognosis , such as active malignancies , depression ( cesd scale > 16 points),21 liver cirrhosis , digestive ulcers , persistent arrhythmia , congestive heart disease , coronary artery disease , lung fibrosis and bronchiectasis , chronic renal failure requiring dialysis , and central nervous system disorders , including palsy and dementia , were excluded , in accordance with previous studies.26,27 hypertension ( systolic > 140 mmhg or diastolic > 90 mmhg blood pressure or use of medications ) , dyslipidemia ( serum low-[14 ] or high- [ < 4 ] 15 mg / l , or use of medications ) , diabetes ( blood hemoglobin a1c 6.5% national glycohemoglobin standardization program value or use of medications)28 without triopathy ( neuropathy , retinopathy , and nephropathy ) , and gerd ( fssg scale > 7 points)20 were accepted as comorbidities .", "previous and prospective exacerbations documented in the medical records made by physicians were accepted as moderate and severe events . moderate exacerbations that required a prescription for antibiotics and/or systemic corticosteroids were defined on the basis of symptom - based diagnosis , such as increased cough and sputum production , a change in sputum color , and worsening of dyspnea from a stable state and beyond normal day - to - day variations , ie , showing acute onset and necessitating a change in regular medication , in accordance with previous reports.1,29,30 copd - related and other causes of death and hospitalization were prospectively followed for 1 year . unreported exacerbations were considered to be those to which patients had been insensitive , or those that had been self - controlled in spite of worsening of respiratory symptoms . mild and unreported exacerbations were not considered to have been equal in severity to previous and prospective exacerbations . however , mild exacerbations were defined as those that improved naturally without any medication or administration of inhaled short - acting bronchodilators .", "subsequent moderate and severe exacerbation events during 1 year of prospective observation were recognized as future risk indicators , and baseline parameters were chosen and modified in accordance with a previous report.16 kaplan meier analyses and log - rank tests for subsequent moderate and severe exacerbations were performed in all three groups of patients . for patients who were observed throughout the study period , the odds ratio ( 95% confidence interval [ ci ] ) of baseline parameters was determined to predict factors for future risk ( subsequent exacerbations once or more and twice or more ) using univariate and logistic multivariate regression analyses . medians of age , body mass index , smoking index , and duration of copd were 68 years , 21.4 kg / m , 53.5 pack - years , and 4 years , respectively , and each median was used as the cutoff value for the analysis . characteristics were compared using analysis of variance , fisher s exact test , -test for trend , and tukey data are expressed as mean standard deviation ( sd ) and number ( percentage ) of non- , infrequent , and frequent exacerbators at baseline .", "the independent risk factors for both one or more and two or more future exacerbations were low fev1 predicted , presence of gerd , and regular use of ics , whereas a low body mass index was an independent risk factor for one or more but not for two or more future exacerbations ( table 3 ) . univariate analysis revealed that a low fev1 ( < 50% ) had the highest odds ratio for risk of future exacerbation ( one or more exacerbations / year ) , followed in order by regular use of ics , two or more previous exacerbations in the last year , presence of gerd , pneumococcal vaccination , one or more previous exacerbations in the last year , low body mass index ( 21.4 kg / m ) , a high total cat score ( 10 points ) , a high mmrc scale grade ( 2 ) and older age ( 68 years ) , whereas in patients who suffered two or more exacerbations , the highest odds ratio was observed due to the presence of gerd , followed in order by regular use of ics , low fev1 predicted , pneumococcal vaccination , older age , a high mmrc - scale grade , long duration of copd ( 4 years ) , and two or more and one or more previous exacerbations in the last year ( table 2 ) . ninety of 110 patients who provided informed consent were finally analyzed ; 32 ( 35.6% ) patients had suffered previous moderate and/or severe exacerbations during the last year . however , 13 ( 86.7% ) of 15 patients who had received ics had also received pneumococcal vaccination .", "ninety of 110 patients who provided informed consent were finally analyzed ; 32 ( 35.6% ) patients had suffered previous moderate and/or severe exacerbations during the last year . the numbers of patients with non- , infrequent , and frequent exacerbations were 58 ( 64.4% ) , 12 ( 13.3% ) , and 20 ( 22.2% ) , respectively ( figure 1 ) .", "at baseline , frequent exacerbators had a significantly lower body mass index , were less likely to be male or current smokers , had higher mmrc - scale grades and higher total cat score , had a higher proportion of spirometric stages iii and iv , gerd , and use of inhaled corticosteroid ( ics)/long - acting muscarinic antagonist or ics / long - acting 2-agonist combination therapy , and lower lung - function parameters , including fev1 , fvc , and fev1/fvc ratio before and after bronchodilator use compared with nonexacerbators , but not in comparison with infrequent exacerbators ( table 1 ) . frequent and infrequent exacerbators had significantly higher mmrc - scale grades and total cat scores compared with nonexacerbators ( table 1 ) . there was no change in the frequency of previous annual hospitalizations per patient between those with frequent and infrequent exacerbations ( table 1 ) .", "during the 1-year prospective observation period , one frequent exacerbator , one infrequent exacerbator , and two nonexacerbators died , with causes of death respiratory failure with copd exacerbation , cerebrovascular attack , and malignancies ( small - cell lung cancer and colon cancer ) , respectively , whereas one frequent exacerbator and six nonexacerbators dropped out for private reasons . as a result , 78 patients ( 17 frequent , eleven infrequent , and 50 nonexacerbators ) completed the study ( figure 1 ) . figure 2 also shows that among the frequent exacerbators , the number of patients who subsequently suffered severe exacerbations ( requiring one or more hospitalizations ) was two ( 11.8% ) , and frequent ( two or more exacerbations / year ) , infrequent ( one exacerbation / year ) , and no moderate or severe exacerbations were seven ( 42.1% ) , six ( 35.3% ) , and four ( 23.5% ) , respectively , whereas seven ( 63.6% ) of eleven infrequent and 37 ( 74.0% ) of 50 nonexacerbators experienced no further exacerbation . patients who regularly used ics had higher but not significant contraction of pneumonia than those who did not use ics ( p>0.05 ) . in addition , one severe exacerbator died due to copd - related respiratory failure during the 1-year prospective observation period .", "figure 3a shows that the mean annual frequencies ( sd , exacerbations / year ) of future total ( 1.41.2 , p=0.0020 ) and moderate ( 1.31.1 , p=0.0057 ) exacerbations in frequent exacerbators were significantly higher than those in nonexacerbators ( 0.40.8 and 0.40.7 , respectively ) , but not in infrequent exacerbators ( 0.91.4 and 0.81.4 , respectively ) . the median ( mean sd ) periods ( days ) until the first moderate and severe exacerbations for frequent , infrequent , and nonexacerbators were 266 ( 23528 ) , 365 ( 29330 ) , and 365 ( 32313 ) days , respectively ( log - rank test , p=0.0012 ) . there was no significant difference in the annual frequencies of severe exacerbation ( hospitalization ) among non- ( 0.00.3 ) , infrequent ( 0.10.39 ) , and frequent ( 0.10.3 ) exacerbators ( p>0.05 ) . figure 3b shows the kaplan meier analysis of the period until the first moderate and severe exacerbations . the median ( mean sd ) periods until the first severe exacerbation were 365 ( 3632 ) , 365 ( 3650 ) , and 365 ( 3605 ) days , respectively ( p>0.05 ; data not shown ) .", "univariate analysis revealed that a low fev1 ( < 50% ) had the highest odds ratio for risk of future exacerbation ( one or more exacerbations / year ) , followed in order by regular use of ics , two or more previous exacerbations in the last year , presence of gerd , pneumococcal vaccination , one or more previous exacerbations in the last year , low body mass index ( 21.4 kg / m ) , a high total cat score ( 10 points ) , a high mmrc scale grade ( 2 ) and older age ( 68 years ) , whereas in patients who suffered two or more exacerbations , the highest odds ratio was observed due to the presence of gerd , followed in order by regular use of ics , low fev1 predicted , pneumococcal vaccination , older age , a high mmrc - scale grade , long duration of copd ( 4 years ) , and two or more and one or more previous exacerbations in the last year ( table 2 ) . however , 13 ( 86.7% ) of 15 patients who had received ics had also received pneumococcal vaccination . the independent risk factors for both one or more and two or more future exacerbations were low fev1 predicted , presence of gerd , and regular use of ics , whereas a low body mass index was an independent risk factor for one or more but not for two or more future exacerbations ( table 3 ) .", "the frequent - exacerbator phenotype is important to consider in the management of copd patients , who require future exacerbation - related hospitalization associated with high mortality.16 a previous western study suggested that frequent exacerbators tend to have had exacerbations during the previous year , a lower fev1 , more severe hrqol , a history of gerd , and a higher peripheral white blood - cell count in comparison with infrequent exacerbators and nonexacerbators.12 another western study demonstrated that the characteristics of frequent exacerbators include a more severe mmrc - scale grade , lower fev1 predicted , comorbid cardiovascular disease , depression or osteoporosis , and female sex as independent risk factors.32,33 we conducted the present study to observe moderate and severe exacerbations 1 year before and after baseline to investigate the characteristics of japanese copd patients who were frequent exacerbators . based on exacerbations during the previous year , we found that frequent exacerbators were more likely to be female , have a lower body mass index , have a significantly lower fev1 predicted , have a higher mmrc - scale grade ( lower exercise tolerance ) , and have a lower total cat score ( lower hrqol ) . the guidelines1,43 recommend long - term treatment with ics and pneumococcal vaccination for patients with severe and very severe copd , and frequent exacerbations may not be adequately controlled by long - acting bronchodilators . in our study regular use of ics , but not pneumococcal vaccination , was an independent risk factor for future frequent exacerbations . gerd was an independent , and the highest , risk factor for future frequent exacerbations , although all patients with gerd were receiving proton - pump inhibitors . our results confirmed previous reports.12,42 a low fev1 predicted was an independent risk factor for future exacerbations .", "the presence of gerd , regular use of ics , and low fev1 may be associated with frequent exacerbations ." ]
backgroundthe prognosis of japanese patients with copd who suffer repeated exacerbations is unclear , although westerners with such episodes have a poor prognosis.materials and methodswe conducted a 1-year prospective observational trial involving 90 japanese patients with copd : 58 nonexacerbators , 12 infrequent exacerbators , and 20 frequent exacerbators classified on the basis of exacerbation frequency ( zero , one , and two or more exacerbations / year ) , respectively , during the previous year were observed prospectively for 1 year . the characteristics of frequent exacerbators , the frequency of exacerbation , and the period until the first event were then compared among the groups.resultsa total of 78 patients completed the study . frequent exacerbators had a significantly higher risk of frequent exacerbation in the following year than the case for nonexacerbators ( odds ratio [ 95% confidence interval ] 2.94 [ 1.217.17 ] , p=0.0340 ) , but not in comparison with infrequent exacerbators ( 1.51 [ 0.494.63 ] , p>0.05 ) . the mean annual frequency of exacerbations in the following year was significantly ( p=0.0020 ) higher in the frequent exacerbators ( 1.4 exacerbations / year ) than in the nonexacerbators ( 0.4 ) , but not in the infrequent exacerbators ( 0.9 , p>0.05 ) . the mean period until the first exacerbation was significantly shorter in the frequent exacerbators than in the infrequent or nonexacerbators ( p=0.0012 ) . independent risk factors for future frequent exacerbation included the presence of gastroesophageal reflux disease , more severe airflow obstruction , and use of inhaled corticosteroids.conclusionour present results indicate that japanese copd patients suffering frequent exacerbation have a poor prognosis . the characteristics of japanese and western copd patients suffering frequent exacerbation are similar .
[ "\n lipoma is a rare tumor but can be found at various sites in the abdominal cavity ( fig . lipoma is a rare tumor but can be found at various sites in the abdominal cavity ( fig . imaging is incapable of distinguishing it from liposarcoma.lipoblastoma is a type of a benign tumor with embryonic fat . lipoblastomatosis is a form of this tumor characterized by aggressive localized growth.hibernoma is a benign tumor , mainly composed of brown fat , in whose cells the numbers of mitochondria responsible for enhanced metabolic activity are impressive . it is usually found in the extremities and torso whereas abdominal cavity belongs to its rather rare sites . in us , such tumors are echogenic .", "liposarcoma is the only malignancy deriving from adipose tissue that is relatively frequently encountered in the retroperitoneal space ( it constitutes nearly 1/3 of sarcomas at this site and 1015% of all neoplasms of this type ) . according to the who , these tumors can be divided into five histological subtypes depending on the grade of their differentiation ( well - differentiated , dedifferentiated , myxoid , round cell , pleomorphic ) , which is relevant in prognosis . they are characterized by the predominance of a solid component , and the only sign suggesting a malignancy is poorly circumscribed margins . a chance for malignant transformation myxoid liposarcoma is characterized by a cystic structure and should be distinguished e.g. from lymphangioma , teratoma or cystic mesothelioma . it is a primary germinal tumor that can contain adipose tissue and occurs at similar sites . poorly differentiated subtypes account for even 40% of local relapses , and metastases are observed in 17% of cases . as has already been mentioned , well - differentiated liposarcoma is difficult to distinguish from lipoma also in sonography .", "mesenteric lymphangioma as a multilocular lesion without flow ( arrow ) retroperitoneal neuroblastoma in a 13-year - old ( arrows ) . cystic lesions can correspond to mesenteric cysts , lymphatic or vascular angiomatosis and even a cystic form of peritoneal mesothelioma , which is considered a benign lesion ( fig . desmoid tumors , also called fibromatosis , are an interesting group of benign tumors that exhibit local aggressiveness and have considerable tendency to recur ( in approximately 50% of cases ) .", "these changes are rarely encountered but they represent a rich spectrum of mainly mesenchymal neoplasms : fibrosarcoma , malignant fibrous histiocytoma , hemangiopericytoma , leiomyosarcoma , rhabdomyosarcoma and gastrointestinal stromal tumors ( fig . an epithelioid malignant neoplasm encountered at this site is malignant peritoneal mesothelioma , a lesion that almost exclusively develops in males in the fifth and sixth decade of life .", "sandwich sign in the small bowel mesentery ( arrows ) created by enlarged lymph nodes surrounding the superior mesenteric vessels a manifestation of non - hodgkin lymphoma extranodal location of follicular lymphoma in the small bowel mesentery ( arrow ) lesions in the lymph nodes , which are relatively frequently affected by various neoplastic and non - neoplastic processes , have been presented only briefly since these issues are too broad to be included in this review . this is the most numerous group with prevailing carcinoma foci , mainly deriving from abdominal organs , such as pancreas , stomach , large bowel or ovaries . well - designed prospective studies have proven ultrasound imaging to be highly useful in detecting abdominal carcinomatosis . moreover , ultrasound guidance enables one to obtain diagnostically valuable material for cytological and histological analysis in the vast majority of such cases .", "authors do not report any financial or personal connections with other persons or organizations , which might negatively affect the contents of this publication and/or claim authorship rights to this publication ." ]
this article focuses on various cancerous lesions that are found beyond organs in the intra - abdominal fat and can be visualized with ultrasonography . these lesions are divided into five groups . the first group includes primary benign tumors containing adipocytes , such as lipoma , lipoblastoma , hibernoma and other lesions with an adipose tissue component , such as myolipoma , angiomyolipoma , myelolipoma and teratoma . the second group comprises primary malignant adipocytecontaining tumors , including liposarcoma and immature teratoma . the third group contains primary benign tumors without an adipocyte component that are located in intra - abdominal fat . this is a numerous group of lesions represented by cystic and solid tumors . the fourth group encompasses primary malignant tumors without an adipocyte component that are located in intra - abdominal fat . these are rare lesions associated mainly with sarcomas : fibrosarcoma , malignant fibrous histiocytoma , hemangiopericytoma and leiomyosarcoma . an epithelioid tumor at this site is mesothelioma . the last but not least group includes secondary malignant tumors without an adipocyte component located in intra - abdominal fat . this is the most numerous group with prevailing carcinoma foci . for each of these groups , the authors present ultrasound features of individual lesions and discuss their differential diagnosis . in the vast majority of cases , the material for cytological and histological analysis can be obtained during ultrasound - guided procedures . this is the advantage of this imaging modality .
[ "the national cancer institute ( nci ) of the united states of america has proposed a reporting system for thyroid fine needle aspiration ( fna ) cytology , so - called bethesda system , which became an international standard of thyroid cytology [ 1 , 2 ] . following this recommendation , the uk royal college of pathologists ( the uk system ) [ 3 , 4 ] and italian societies of endocrinology and the italian society for anatomic pathology and cytology joint with the italian division of the international academy of pathology ( the italian system ) [ 5 , 6 ] updated their diagnostic schema comparable with the bethesda system . in 2013 , the japan thyroid association ( jta ) published guidelines for clinical practice for the management of thyroid nodules , including its diagnostic system for reporting thyroid fna cytology as shown in table 1 [ 79 ] , using criteria similar to those used in the papanicolaou society recommendation , the bethesda system [ 1 , 2 ] , the uk system [ 3 , 4 ] , and the italian system [ 5 , 6 ] . this study examined observer variation in the subclassification of fn among 4 thyroid experts to validate the usefulness and limitations of this characteristic risk stratification of fn recommended in the jta guidelines . the jta reporting system of thyroid cytology further recommends risk stratification of follicular neoplasms ( fn ) into favor benign ( low risk : lr ) , borderline ( moderate risk : mr ) , and favor malignant ( high risk : hr ) , which was adopted from the practice of high - volume thyroid centers in japan . it is not our purpose to address in detail all the morphological issues of thyroid cytology .", "twenty cases of cytological smear samples with follicular patterned lesions were randomly selected by one ( k. kameyama ) of the authors and they were further analyzed for subclassification of fn and diagnoses by 4 reviewers , as shown in table 2 . those 20 cases of smear samples ( one representative smear sample each stained by the papanicolaou method ) were circulated among the 4 reviewers without clinical information . informed consent of all 4 reviewers was obtained for this study protocol . for statistical analysis of observer concordance , was first introduced as a measure of the level of agreement between pairs of raters and extended to multiple raters , known as composite [ 11 , 12 ] . they were requested to subclassify fn following the new jta reporting system of thyroid cytology as shown in table 1 . the present study is a reproducibility study undertaken by 4 reviewers ( kennichi kakudo , kaori kameyama , mitsuyoshi hirokawa , and ryohei katoh ) who have special interest in thyroid pathology , all of whom are members of the clinical guideline committee of the jta . the 4 reviewers examined cytological samples independently without exchanging opinions and were unaware of the original cytological diagnoses and final histologic diagnoses . because this study was conceived as an audit of cytology performance and the results are anonymized , institutional ethical committee permission was not required for its conduct . conventional smear samples of indeterminate diagnosis ( n = 389 ) were selected from files ( n = 3843 ) from the year 2005 at ito hospital , tokyo , japan , by one ( k. kameyama ) of the authors .", "although the risks of malignancy in the subcategories of fn differed among the 4 reviewers , it is of note that hr cytological diagnosis was significantly correlated with malignant histological diagnosis , and the risk of malignancy ( 6075% ) was significantly higher than that in the other 2 subcategories ( 035.7% ) in our study ( p = 0.002 ) . composite statistical analysis clearly demonstrated good concordance for the hr diagnosis in malignant cases ( = 0.7714 ) ( table 3 ) , while this was not found for the other subcategories in both benign and malignant lesions ( < 0.4 ) . there were 8 malignant cases ( 2 ftcs , widely invasive ; 4 ftcs , minimally invasive ; and 2 ptcs ) and 12 benign cases ( 1 an and 11 fas ) .", ", thyroid fna cytology remains a main stay in the management of patients with thyroid nodules integrated with other clinical tests , such as ultrasound image diagnosis . as a conclusion we believe that patients with cytological diagnosis of hr subcategory of fn in the jta system should be surgically treated especially if other risk factors coexisted . on the other hand , patients with lr or mr category the hr subcategory has a high predictive value of malignancy and good agreement among the 4 reviewers which is clinically helpful to triage patients for surgery . therefore , surgical resection rate of indeterminate category is low in japan usually less than 50% , particularly in cases with fn . we propose that future thyroid cytology classification schemes should reconsider clinical managements of indeterminate categories and how to reduce unnecessary surgeries for patients with benign thyroid nodules [ 79 ] ." ]
background . the japan thyroid association recently published guidelines for clinical practice for the management of thyroid nodules , which include a diagnostic system for reporting thyroid fine needle aspiration cytology . it is characterized by the subclassification of follicular neoplasms , which is different from other internationally accepted reporting systems . materials and methods . this study examined observer variability in the subclassification of follicular neoplasms among 4 reviewers using papanicolaou - stained smear samples from 20 surgically treated patients with indeterminate cytology . results . the favor malignant subcategory had high predictive value of malignancy ( risk of malignancy : 6075% ) and good agreement among the 4 reviewers ( = 0.7714 ) . conclusion . these results clearly confirmed that the risk stratification of follicular neoplasms , which was adapted from cytology practice of high - volume thyroid centers in japan , can provide clinically helpful information to estimate the risk of malignancy and to triage patients for surgery .
[ "results were evaluated across specialties to determine any specialty - specific practice trends that might hinder effective recognition and management of an actively bleeding patient with coagulopathy , including acquired hemophilia . the survey , based on an actual case found to be the result of acquired hemophilia , focused on participants stepwise evaluation and management of a case patient who presented to the hospital with recent - onset bleeding . the survey also assessed participants history with regard to consulting hematologists , discovering or diagnosing underlying bleeding disorders , and encountering acquired hemophilia in clinical practice . findings pertaining to the interpretation and follow - up of abnormal coagulation studies , enlistment of hematology consultation , and the diagnostic decision process in an actively bleeding case patient were the primary areas assessed in this analysis . a survey was conducted of physicians across a number of specialties to identify potential barriers to the effective recognition and management of this rare but important cause of serious bleeding . severe bleeds occur in up to 90% of patients with acquired hemophilia,11 and the reported overall mortality rate in these patients ranges from 8% to 22%.1517 given the rarity of acquired hemophilia , combined with the general lack of familiarity of nonhematologists with this condition , the diagnosis of acquired hemophilia poses a clinical challenge , even in patients presenting with straightforward bleeding and an isolated , prolonged aptt . acquired hemophilia - related bleeding does not respond to the typical management algorithms used for hemorrhaging in a patient and , therefore , is associated with high morbidity and mortality .", "survey questions focused on the diagnostic and general therapeutic approach to the management of a case patient ( figure 1 ) whose presentation and clinical course were based on those of a real patient who experienced significant delays in diagnosis despite the involvement of multiple specialists . at each juncture in the case , participants were given lists of actions that included diagnostic tests ( laboratory , radiology , other ) , consultations , and potential treatments addressing bleeding or anemia ( local hemostasis , transfusion ) . since familiarity with the upper limits of normal of the pt / aptt tests was being tested in this study , upper limits of normal were not specified , and aptts were 25% to 30% above the upper limits of normal and set at a value that respective specialties would recognize as abnormal based on their experience with ordering and interpreting this laboratory test . physicians within the specialties of hematology , hematology / oncology , emergency medicine , geriatrics , internal medicine , rheumatology , obstetrics and gynecology , critical care medicine , and general surgery were randomly sampled from the american medical association physician masterfile . hematology / oncology respondents were given the option of ordering additional specialty coagulation laboratory tests ( eg , mixing studies ) . participants were additionally questioned about their experiences diagnosing underlying bleeding disorders and , in the case of nonhematologist specialists , consulting hematologist colleagues . findings from the surveys completed by the physicians specializing in hematology , hematology / oncology , emergency medicine , geriatrics , internal medicine , rheumatology , and critical care medicine are presented herein . in particular , hematologists , hematologist / oncologists , general surgeons , and emergency medicine and critical care physicians were required to be practicing at an acute care hospital . for internists and geriatricians , obstetricians / gynecologists were required to have an active obstetrics practice . upon confirmation of eligibility , participants completed the online survey , the average duration of which was approximately 10 minutes .", "the majority ( 57% ) of hematologists had been consulted a minimum of 5 times by their colleagues in emergency medicine . the difference was most noticeable for physicians in emergency medicine ( 35%73% ) , the specialty most likely to refer the patient to an inpatient medical / hospitalist or critical care service . more than 85% of emergency medicine and critical care physicians reported having ever discovered an underlying bleeding disorder , while 100% of hematologists and hematologist / oncologists reported having ever diagnosed one ( figure 6a ) . requests for gastroenterology consultations ranged from 10% to 43% and were highest for the internal medicine group , which also had the highest proportion of physicians recommending endoscopy ( 16% each for upper gastrointestinal endoscopy and colonoscopy ) . for the purposes of assessing multiple specialties , the next 12 hours of observation in the case patient s clinical course were described as having occurred in the emergency department . by the end of this observation period , a total of 302 physicians ( 5051 per specialty ) participated in the case - based survey reported herein . the distribution of reasons for which respondents would have consulted a hematologist is also shown in table 2 . in the majority of specialties ( emergency medicine , geriatrics , and internal medicine ) ,", "faced with an older adult female patient with recurrent epistaxis , nearly 90% of physicians in each of the surveyed specialties indicated they would have ordered a complete blood count and coagulation studies ( pt / inr and aptt ) as part of the initial evaluation ( figure 2a ) . despite abnormal results of the aptt at 42 seconds ( with an upper limit of normal typically ranging from 35 to 39 seconds , although not specified in the case ) , less than half the physicians in most specialties would have chosen to repeat the coagulation studies as one of the next steps ( figure 2b ) . in contrast , 67% of hematologists would have repeated these studies . less than 45% of surveyed physicians in all nonhematology specialties would have consulted a hematologist after reviewing the initial coagulation study results ( figure 2b ) . rheumatologists were most likely to obtain a consult ( 43% ) , although they were presented with an initial aptt that was more abnormal ( 50 seconds ) than the aptt initially presented to the other specialists .", "emergency medicine physicians were given the additional option of consulting general surgery practitioners ; 2% would have done so after the first set of laboratory results at the second presentation , and 20% would have done so in response to the second set of laboratory results . requests for gastroenterology consultations ranged from 10% to 43% and were highest for the internal medicine group , which also had the highest proportion of physicians recommending endoscopy ( 16% each for upper gastrointestinal endoscopy and colonoscopy ) . for the purposes of assessing multiple specialties , the next 12 hours of observation in the case patient s clinical course were described as having occurred in the emergency department . by the end of this observation period , in contrast with previous time points , by this point in the patient s clinical presentation , 73% to 94% of respondents would have consulted a hematologist . the majority of hematologists would have ordered 1:1 mixing studies of patient and normal plasma to rule out coagulation inhibitors ( 97% ) and fibrinogen / fibrin split products testing ( 75% ) in response to the laboratory results obtained after 12 hours of observation , as part of a diagnostic evaluation of the prolonged aptt . after the patient s second presentation several weeks later with bruising and abdominal / back pain , again nearly 90% or more of respondents ( including critical care specialists , who began their case review at this juncture in the patient s clinical course ) would have ordered both a complete blood and coagulation studies as part of their initial evaluation ( figure 2c ) . emergency medicine physicians demonstrated the greatest breadth of testing , with 82% additionally recommending urinalysis and 92% recommending a stool guaiac test .", "the percentages of physicians in each specialty who would have recommended admission of this case patient to a general hospital floor or back to a skilled nursing facility or nursing home after initial presentation with subsequent abnormal aptt of 42 seconds are shown in figure 5a . across the majority of specialties , less than 20% of physicians would have recommended overnight admission to a general hospital floor , while more than 50% of physicians in these specialties would have recommended discharge to a skilled nursing facility or a nursing home . in contrast with respondents from other specialties , a slightly higher proportion of hematologists and hematologist / oncologists would have endorsed a higher level of care at this point ; 36% of physicians in this group indicated they would have favored overnight hospital admission over discharge to a skilled nursing facility . the majority of physicians faced with the second presentation would have recommended that the patient be admitted to the hospital . the differences among specialties were most noticeable in allocation to a general hospital floor versus an intensive care unit after review of initial laboratory results or the second set of laboratory results obtained after 12 hours of observation ( figure 5b ) . while approximately 80% or more of physicians in each specialty would have recommended hospital admission in response to both sets of laboratory results , the proportion recommending admission specifically to the intensive care unit increased as the laboratory values deteriorated ( worsening anemia and coagulopathy ) . based on the laboratory results obtained after 12 hours of observation , nearly 50% or more of physicians in each specialty would have recommended admission to the intensive care unit in lieu of a general hospital floor , compared with approximately 40% or less across specialties after the initial laboratory results obtained during the patient s second presentation . the difference was most noticeable for physicians in emergency medicine ( 35%73% ) , the specialty most likely to refer the patient to an inpatient medical / hospitalist or critical care service .", "more than 85% of emergency medicine and critical care physicians reported having ever discovered an underlying bleeding disorder , while 100% of hematologists and hematologist / oncologists reported having ever diagnosed one ( figure 6a ) . the percentage of physicians in other specialties who had ever discovered an underlying bleeding diathesis ranged from 47% to 65% . among those physicians who had previously diagnosed or discovered a bleeding disorder , 14% to 77% had specifically encountered acquired hemophilia ( figure 6b ) , although this quantitative survey did not assess whether they understood this disorder . hematologists and hematologists / oncologists accounted for the highest percentage in this group , while internal medicine specialists accounted for the lowest percentage .", "table 2 shows the frequencies with which various specialties had ever consulted a hematologist when they encountered a patient with an abnormal pt / inr and aptt and no history of a bleeding diathesis or medications that affect coagulation . the majority ( 57% ) of hematologists had been consulted a minimum of 5 times by their colleagues in emergency medicine . the distribution of reasons for which respondents would have consulted a hematologist is also shown in table 2 . in the majority of specialties ( emergency medicine , geriatrics , and internal medicine ) , the highest percentage of physicians had consulted a hematologist 1 to 2 times for a patient with an unexplained prolonged pt / inr or aptt . the majority of these consults pertained to significantly abnormal coagulation studies with or without clinical bleeding ( table 2 ) . conversely , the frequency with which hematologists had ever been consulted by an emergency medicine provider for an abnormal pt / inr or aptt in a patient with no history of bleeding diathesis or medications that affect coagulation is outlined in table 2 . the most common reason for consulting a hematologist was abnormal coagulation study results in the setting of clinical bleeding ( table 2 ) , which was parallel to the findings for the 100 additional surgeons and obstetricians surveyed ( data not shown ) . the most common response among critical care specialists to the open - ended question , what are the circumstances around which you would call for a hematology consult ? was an unexplained abnormal lab or bleeding ( 33 like or similar mentions ) , followed by any unexplained bleeding disorder the highest percentage ( 39% ) of critical care physicians had consulted a hematologist at least 5 times for such a patient .", "this represents yet another barrier to the effective diagnosis and management of this rare yet serious bleeding diathesis . given the survey findings reflecting the infrequency with which most physicians have encountered these conditions , consultation with a hematologist may facilitate the diagnostic evaluation and proper management of a hemorrhaging patient suspected of having an underlying bleeding diathesis , particularly acquired hemophilia . however , this requires a level of familiarity and expertise in treating acquired hemophilia and other rare bleeding disorders that is not often seen outside of an academic hematology practice . while bleeding may be relatively common , most acquired and congenital bleeding disorders are uncommon , and some , such as acquired hemophilia , are rare . nevertheless , the consequences of failure to recognize promptly and treat properly a bleeding disorder may be significant.18 in the case of acquired hemophilia , morbidity and mortality rates are particularly high : severe bleeding is experienced by up to 90% of affected patients , and mortality rates the consulting hematologist can provide specific guidance , leading to the prompt diagnosis and optimal management of an actively bleeding patient with acquired hemophilia , including initiation of immunosuppression , which is usually necessary to eradicate the inhibitor and to prevent additional bleeding episodes .", "for the hospitalist or intensivist charged with the care of a bleeding patient , immediate stabilization is the initial priority and should take precedence over determination of a specific etiology of bleeding . the insights from this survey highlights knowledge and practice gaps that could be the focus of targeted educational initiatives , including diagnostic algorithms , to ensure proper and efficient workup of the abnormal laboratory studies that characterize acquired hemophilia . however , in the presence of underlying coagulopathy , particularly acquired hemophilia or other rare disorders , traditional measures of stabilization may not be as effective as expected . , physicians must harbor a high index of suspicion to diagnose this condition promptly in patients who present with recent - onset or acute bleeding . given the high morbidity and mortality while hospitalists and intensivists should be able to conduct a thorough differential of bleeding and eliminate most common etiologies , consultation with a hematologist ( particularly one with specific expertise in coagulation disorders ) may facilitate the evaluation of coagulopathic patients and subsequent interpretation of diagnostic findings , as well as initiation of appropriate treatment . given the rarity of acquired hemophilia , as exemplified by the findings of this survey" ]
background : bleeding symptoms commonly seen by multiple physician specialties may belie undiagnosed congenital or acquired bleeding disorders . acquired hemophilia is a potentially life - threatening cause of unexplained acute bleeding manifested by an abnormal activated partial thromboplastin time ( aptt ) that does not correct with 1:1 mixing with normal plasma.methods:practicing physicians ( hematology / oncology , emergency medicine , geriatrics , internal medicine , rheumatology , obstetrics and gynecology , critical care medicine , and general surgery ) completed an online survey based on a hypothetical case scenario.results:excluding surgeons and obstetrician / gynecologist respondents , 302 physicians ( about 50 per specialty ) were presented with an older adult woman complaining of recurrent epistaxis . nearly 90% ordered a complete blood count and coagulation studies ( aptt , prothrombin time [ pt]/international normalized ratio [ inr ] ) . despite a prolonged aptt of 42 seconds , < 50% of nonhematologists would repeat the aptt , and < 45% would consult a hematologist ; emergency medicine physicians were least likely ( 10% ) and rheumatologists were most likely ( 43% ) to consult . after presentation weeks later with bruising and abdominal / back pain , 90% of physicians within each specialty ordered a complete blood count or pt / inr / aptt . despite an aptt of 63 seconds , the majority did not repeat the aptt . at this point , approximately 75% of internal medicine and geriatric physicians indicated they would consult a hematologist , versus 47% in emergency medicine and 50% in critical care . all participants preferred abdominal computed tomography ( 80%84% ) . after 12 hours of additional observation , 73% to 94% of respondents consulted a hematologist . complete blood count revealed anemia and an aptt twice the upper limit of normal ; emergency medicine physicians remained least likely to request a consult.conclusion:determining the cause of an abnormal coagulation study result should carry equal weight as looking for the site of bleeding and could be facilitated by consultation with a hematologist . insight from this survey highlights knowledge and practice gaps that could be the target of focused educational initiatives .
[ "a recently published review focuses on cwi maintenance during plant cell wall morphogenesis ( wolf et al . , 2011 ) . this review will focus on recent developments regarding the role of cwi maintenance during biotic stress responses . therefore , the available knowledge regarding cwi maintenance during plant development and in yeast will be covered here only briefly to provide a conceptual framework regarding cellular processes involved and to illustrate the degree of functional conservation between species . it will discuss how cwi maintenance could have a previously unrecognized role in the perception of and response to biotic stress . the available evidence suggests that a dedicated plant cell wall integrity ( cwi ) maintenance mechanism exists ( wolf et al . , 2011 ) . while our understanding of the mechanisms regulating stress responses and morphogenesis has increased significantly , our knowledge regarding the processes maintaining cwi is still limited . in the last years similarities between the yeast and plant cwi maintenance mechanisms have also been reviewed ( hamann and denness , 2011 ) .", "the available data suggest both organizational and functional similarities between the yeast and plant cwi maintenance mechanism while also highlighting how signals from mechanical and chemical sensors regulate jointly the cwd response . while both plant and yeast cells are enveloped by cell walls , certain important differences exist that affect the biological role and function of the plant cwi maintenance mechanism . the response can involve activation of genes required for cell wall biosynthetic processes , remodeling of the cytoskeleton , and cell cycle progression . this means that in plant cells the sheer number of cell wall - related signaling events during development and plant environment interaction could disguise the activity of a dedicated plant cwi maintenance mechanism .", "this highlights the ability of the cell to adapt to changes in cell wall composition and provides evidence for the existence of a cwi maintenance mechanism . the plant cell wall is comparable to an exoskeleton surrounding the plant cell and providing both structural support and protection from biotic as well as abiotic stresses . this process reinforces the wall against pathogen infection , waterproofs it , and increases structural integrity ( tronchet et al . , 2010 ; it consists of cellulose microfibrils , pectin , hemicelluloses , proteins , and in certain cases lignin ( somerville et al . , 2004 ) .", "to summarize , these results suggest distinct resistance signaling cascades are induced by defects in primary and secondary cell wall formation as well as for different secondary cell wall components . three of the powdery mildew resistance ( pmr ) mutants that have been identified on the molecular level affect genes involved in cell wall biosynthetic processes . plant cell walls are capable of adjusting their composition and structure in response to pathogen infection ( dong et al . , 2008 ) . a mutation in ( cellulose synthasea3 , cesa3 ) a subunit of the cellulose synthase complex leads to ectopic production of lignin , i.e. , replacement of a missing load bearing cell wall component by another one ( cano - delgado et al they also highlight the direct impact of changes in cell wall composition / structure on the response to pathogen infection .", "the mode of action of the plant cell wall maintenance mechanism is not well understood . the available evidence supports the notion that the plant cell wall is an integral component contributing to pathogen response mechanisms and illustrates the influence of cell wall defects on infection . i will focus here on several kinases that have been implicated in cwd perception and/or pathogen response . therefore , studies focusing on the effects of particular cell wall defects on pathogen resistance and the mode of action of the cwi maintenance mechanism could facilitate research into biotic stress response . based on the knowledge from yeast , chemical and physical signals could act as indicators for the functional integrity of the plant cell wall either individually or jointly . by combining these different types of signal", "the author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest ." ]
plant cell walls provide structural support during development and represent together with the cuticle the first line of defense against biotic and abiotic stress . in recent years , evidence has accumulated that a dedicated plant cell wall integrity ( cwi ) maintenance mechanism exists . this mechanism monitors and maintains functional integrity of the cell wall during different biological processes . the available data suggest that it may represent a component of the stress response mechanisms underlying biotic and abiotic stress responses , which has not been identified previously as a distinct mechanism . here i will review the available evidence regarding the mode of action of the cwi maintenance mechanism and discuss its role in the context of biotic plant stress response mechanisms .
[ "genes , such as dab2ip , dlc-1 , h - cadherin , id4 , integrin 4 , runx3 , sfrp1 , and shp1 , has been identified as being implicated in aberrant dna methylation during development of human malignancy ( 11 - 18 ) . in order to gain insight into the differential epigenetic alterations in leukemia , we investigated the methylation statuses at selected locus of these genes in aml and cml patients using a methylation - specific polymerase chain reaction ( msp ) . genomic dna hypomethylation has been observed in the peripheral blood mononuclear cells of leukemia patients and in tumor cells of patients with b - cell lymphoproliferative diseases ( 1 ) . cml is a clonal disease of stem cell origin that is characterized by the presence of the philadelphia chromosome ( ph+ ) , which has been named t(9,22)(q34:q11 ) . dna methylation may affect karyotypic stability , may influence euchromatin - heterochromatin interactions , and has been correlated with disease progression ( 2 ) . on the other hand , for example , some patients with lymphomas do not express tumor suppressor genes because the promoters of these genes are methylated .", "diagnostic bone marrow samples were obtained from 23 patients with aml and 21 patients with cml . we performed polymerase chain reaction ( pcr ) using specific pcr primers capable of distinguishing between methylated and unmethylated dna sequences . the primers for the unmethylated and methylated dna sequences , pcr product size , and annealing temperature are shown in table 1 . the msp primer sets were selected at the 5'-cpg island regions of genes using the methprimer software ( www.urogene.org ) . msp results were analyzed as a dichotomous variable based on the presence or absence of gene methylation .", "the samples were gathered by the division of hematology / oncology ( department of internal medicine , korea university medical center , seoul , republic of korea ) and analyzed by pathologist . institutional review board approval and informed consent were obtained ( kumc - irb-2006011-p-1 , kumcirb-2006012-p-2 ) . of the aml patients , 17 males and 6 females were included , with ages ranging from 26 to 78 yr , at a median age of 45.61 ( sd , 15.56 ) yr . of the cml patients , diagnostic bone marrow samples were obtained from 23 patients with aml and 21 patients with cml . 22 normal peripheral bloods were obtained from healthy volunteers ( 11 males and 10 females ) ranging from 20 to 78 yr of age ( meansd , 45.3620.64 ) . 11 males and 10 females were included , with ages ranging from 18 to 75 yr ( meansd , 49.9116.53 ) . as controls ,", "we performed polymerase chain reaction ( pcr ) using specific pcr primers capable of distinguishing between methylated and unmethylated dna sequences . the primers for the unmethylated and methylated dna sequences , pcr product size , and annealing temperature are shown in table 1 . the msp primer sets were selected at the 5'-cpg island regions of genes using the methprimer software ( www.urogene.org ) . the pcr conditions were as follows : initial denaturation and hot start at 95 for 5 min , and cycles consisting of 30 sec at 95 , 30 sec at the annealing temperature , and 30 sec at 72. in addition , sck , a human cholangiocarcinoma cell line , was used as positive control for integrin 4 gene ( 20 ) . chemical modification was performed as described previously , with minor modifications ( 19 ) . in brief", "msp results were analyzed as a dichotomous variable based on the presence or absence of gene methylation . the msp results of tumor and normal samples were compared and analyzed with the pearson chi - square test ( version 12 ; spss inc . ,", "the multiple genes were found to be methylated in bone marrow from patients with aml or cml . specifically , the frequencies of promoter hypermethylation at selected locus in the 23 aml samples were : 78.3% ( 18/23 ) for shp1 , 65.2% ( 15/23 ) for id4 and sfrp1 , 26.1% ( 6/23 ) for h - cadherin , 8.7% ( 2/23 ) for dlc-1 , and 4.3% ( 1/23 ) for dab2ip and runx3 . . furthermore , there was a statistically significant difference between the dna methylation frequencies of aml patients and cml patients . the frequencies of dna methylation of id4 , sfrp1 , and shp1 were higher in aml compared to those in cml ( p=0.001 , p<0.0001 , and p=0.001 , respectively ) ( table 2 ) . in contrast , no statistical differences between aml and cml were detected in other genes such as dlc-1 , dab2ip , h - cadherin , integrin 4 , and runx3 . promoter methylation results at selected locus of eight genes with msp method were shown in fig .", "the results of the present study demonstrate the substantially increased frequency of promoter hypermethylation in id4 , sfrp1 , and shp1 genes in aml compared to cml . our results suggest that aberrant dna methylation of shp1 may be related to the tumorigenicity of aml and cml and hypermethylation of id4 , sfrp1 , and shp1 genes may contribute to the pathogenesis mechanism of aml specifically . methylation frequencies of shp1 gene were the high detected in cml as well as aml ." ]
to gain insight into the differential mechanism of gene promoter hypermethylation in acute and chronic leukemia , we identified the methylation status on one part of 5'cpg rich region of 8 genes , dab2ip , dlc-1 , h - cadherin , id4 , integrin 4 , runx3 , sfrp1 , and shp1 in bone marrows from acute myeloid leukemia ( aml ) and chronic myeloid leukemia ( cml ) patients . also , we compared the methylation status of genes in aml and cml using methylation - specific pcr ( msp ) . the frequencies of dna methylation of id4 , sfrp1 , and shp1 were higher in aml patients compared to those in cml patients . in contrast , no statistical difference between aml and cml was detected for other genes such as dlc-1 , dab2ip , h - cadherin , integrin 4 , and runx3 . taken together , these results suggest that these methylation - controlled genes may have different roles in aml and cml , and thus , may act as a biological marker of aml .
[ "vertical axis rotation following dislocation is a rare variant of this type of injury and can prevent closed reduction in the acute setting . acute patellar dislocation is a common injury usually associated with a significant traumatic mechanism resulting in lateral displacement .", "a 32-year old gentleman presented with an irreducible patella dislocation following an unusual atraumatic mechanism . following attempts at closed reduction under sedation and regional nerve block , eventual open reduction and soft tissue reconstruction was required under general anesthetic . during the open reduction procedure , it was noted that the patella had dislocated into a lateral extra - articular position and rotated around its vertical axis .", "a review of the literature suggests dislocations such as the current presentation , are extremely rare and although have been described to occur with minor trauma , have never been described to occur following a largely atraumatic event . in such cases , closed reduction may be impossible even with adequate analgesia due to patella position and soft tissue obstruction .", "patellar dislocation is a relatively common occurrence and is usually managed in the emergency department with closed manipulation under sedation . acute patellar dislocation is defined as the abrupt disruption in the relationship of the patella within the femoral groove . however , when the patella itself rotates around its vertical axis during dislocation , surgical intervention is usually required .", "a 32-year old gentleman was admitted to our trauma department with a painful , immobile right knee . , there was an obvious deformity suggesting lateral displacement of the patella with a sulcus in the skin evident over the femoral groove . lateral radiograph of the right knee demonstrating rotation of patella our patient was subsequently taken to theatre where one final attempt of closed reduction was carried out under general anaesthetic and muscle relaxation . ultimately , this failed and an open reduction was performed . intraoperative antero - posterior florous copy image following successful reduction lateral radiograph of the right knee following surgery in knee splint", "since then , only a handful of case reports describing vertical axis rotation of the patella have been published with the majority describing the location of the patella within the femoral trochlea ( intra - articular ) [ 2 - 11 ] . our case is rare as our patient had a less common variant of extra - articular patellar dislocation complicated by vertical axis rotation and by the fact , that the causative mechanism was largely atraumatic . patellar dislocations can vary widely in their pattern of presentation however vertical axis rotation complicates only a small number of these cases . in 1844 , cooper described the earliest case of patellar dislocation with vertical axis rotation . we feel this may be an indication of the chronic deficiency in the mpfl likely contributing to cases of extra - articular dislocation . on reviewing the previous cases of extra - articular dislocation in the literature", "from our experience with this case , difficulty in reducing a dislocated patella should alert surgeons to the possibility of an extra - articular dislocation with possible vertical axis rotation . in these scenarios , multiple attempts at reduction we were able to achieve adequate analgesia and sedation using local and regional anaesthesia , without successful reduction of the dislocation . although some authors have demonstrated successful closed reduction with the use of local anaesthetic and muscle relaxants , this is not always effective . furthermore , attempted closed reduction under general anaesthesia in our case was also unsuccessful , demonstrating how closed reduction can be futile in certain cases . we would recommend a low threshold for open reduction in such cases by a specialist knee surgeon who may assess and reconstruct damaged soft tissue damage in one operation vertical axis rotation is a rare entity complicating patella dislocations . in this rare event emergency physicians should be aware of this complication and refer to the relevant specialist for open reduction under general anaesthesia in order to minimize patient discomfort and potential articular surface damage ." ]
introduction : acute patellar dislocation is a common injury usually associated with a significant traumatic mechanism resulting in lateral displacement . vertical axis rotation following dislocation is a rare variant of this type of injury and can prevent closed reduction in the acute setting.case presentation : a 32-year old gentleman presented with an irreducible patella dislocation following an unusual atraumatic mechanism . following attempts at closed reduction under sedation and regional nerve block , eventual open reduction and soft tissue reconstruction was required under general anesthetic . during the open reduction procedure , it was noted that the patella had dislocated into a lateral extra - articular position and rotated around its vertical axis . following patella reduction , the medial patellar retinaculum was repaired . examination under anesthetic revealed satisfactory tracking of patella following repair.conclusion:a review of the literature suggests dislocations such as the current presentation , are extremely rare and although have been described to occur with minor trauma , have never been described to occur following a largely atraumatic event . in such cases , closed reduction may be impossible even with adequate analgesia due to patella position and soft tissue obstruction . open reduction is essential in these situations .
[ "graphene oxide ( go ) solution was synthesized from natural graphite powder by a modification of hummers method.45 cu2o / rgo composites were fabricated by a microwave - assisted hydrothermal reaction . the catalyst colloid ( 100 l ) was deposited onto an area of approximately 1 cm of the fto conductive glass to form the working electrode . the reaction product was monitored by periodical sampling of the gas phase from the glass chamber by using a gas - tight syringe and analyzed by gc ( varian gc-450 ) with a thermal conductivity detector ( tcd , connected to a molecular sieve column ) to detect h2 , o2 , and n2 and a flame ionization detector ( fid , connected to a cp - sil 5cb capillary column ) to detect hydrocarbons . a methanizer was installed to enable the fid to detect co with 1000 higher sensitivity . for the isotope - tracer experiment , the morphologies of the products were characterized by field - emission scanning electron microscopy ( fesem , jeol-6701f ) and tem ( jeol-2010f ) .", "graphene oxide ( go ) solution was synthesized from natural graphite powder by a modification of hummers method.45 cu2o / rgo composites were fabricated by a microwave - assisted hydrothermal reaction . were also synthesized , which include cu2o/0.25 % rgo , cu2o/0.5 % rgo , and cu2o/1 % rgo , in which x % represents the calculated weight ratio of the go added to cu2o . after stirring for 2 h , firstly , cu(no3)2 was added to a mixture of ethanol and water in the ratio of 64:36 . then , a calculated amount of go solution and formic acid ( 3 ml ) were added . for optimization , cu2o / rgo composites with different amounts of rgo the homogeneous solution was heated with stirring in the microwave system at 150 c for 3 h. after the product was cooled to rt , the final product was collected by centrifugation , washed with water five times , and dried at 70 c . blank cu2o was synthesized through the same procedure , except for the addition of go solution .", "the morphologies of the products were characterized by field - emission scanning electron microscopy ( fesem , jeol-6701f ) and tem ( jeol-2010f ) . xrd was performed by using a rigaku rint 2100 diffractometer at a voltage of 40 kv . uv / vis spectra were recorded by using a shimadu uv / vis 2550 spectrophotometer . pl emission spectra were measured at rt by using a fluorescence spectrophotometer ( f-4500 , hitachi ) .", "the potential ranged from 1.0 to 0 v with a potential step of 10 mv at a frequency of 1 khz . the catalyst colloid ( 100 l ) was deposited onto an area of approximately 1 cm of the fto conductive glass to form the working electrode . a pt wire was used as a counter electrode , and an ag / agcl electrode was the reference electrode in the three - electrode photo - electrochemical system . eis were recorded under an alternating current perturbation signal of 10 mv over the frequency range of 1 mhz to 100 mhz . photocatalyst ( 5 mg ) and nafion solution ( 10 l , 5 wt % ) were dispersed in a water / isopropanol mixture ( 1 ml , 3:1 v / v ) by at least 30 min sonication to form a homogeneous catalyst colloid . for the measurements ,", "photocatalysts were treated at 200 c for 3 h in a tubular furnace under the protection of ar or in air ( denoted cu2o treated in ar or air ) . after the addition of cu2o / rgo ( 0.5 g ) into co2-saturated water ( 10 ml ) , the septum - sealed reactor was purged by ar gas for 10 min . the reaction product was monitored by periodical sampling of the gas phase from the glass chamber by using a gas - tight syringe and analyzed by gc ( varian gc-450 ) with a thermal conductivity detector ( tcd , connected to a molecular sieve column ) to detect h2 , o2 , and n2 and a flame ionization detector ( fid , connected to a cp - sil 5cb capillary column ) to detect hydrocarbons . a methanizer was installed to enable the fid to detect co with 1000 higher sensitivity . the co2 reduction reaction was performed in batches by using a septum - sealed glass chamber with a volume of 120 ml , which was heated at 160 for 1 h prior to measurement . to remove possible trace organic contaminants ,", "as a service to our authors and readers , this journal provides supporting information supplied by the authors . such materials are peer reviewed and may be re - organized for online delivery , but are not copy - edited or typeset . technical support issues arising from supporting information ( other than missing files ) should be addressed to the authors" ]
a facile one - step microwave - assisted chemical method has been successfully used for the synthesis of cu2o / reduced graphene oxide ( rgo ) composites . photocatalytic co2 reduction was then investigated on the junction under ambient conditions . the rgo coating dramatically increases cu2o activity for co2 photoreduction to result in a nearly six times higher activity than the optimized cu2o and 50 times higher activity than the cu2o / ruox junction in the 20th hour . furthermore , an apparent initial quantum yield of approximately 0.34 % at 400 nm has been achieved by the cu2o / rgo junction for co2 photoreduction . the photocurrent of the junction is nearly double that of the blank cu2o photocathode . the improved activity together with the enhanced stability of cu2o is attributed to the efficient charge separation and transfer to rgo as well as the protection function of rgo , which was proved by xrd , sem , tem , x - ray photoelectron spectroscopy , photo - electrochemical , photoluminescence , and impedance characterizations . this study further presents useful information for other photocatalyst modification for efficient co2 reduction without the need for a noble - metal co - catalyst .
[ "the authors of this paper have previously shown that the fractal dimension and proportion of the area of pit - and - fissure discoloration to the area of occlusal surface obtained by digital imaging were significantly correlated with the depth of the caries and the diagnodent values in extracted teeth . the aim of this study was to assess the possibility of the clinical application of the diagnosis of occlusal caries using digital imaging by examining the sensitivity , the specificity , and the accuracy in comparison with the diagnodent values and the dentists ' diagnoses . for assessment of the method as a diagnostic system , the ability of the diagnosis , such as the sensitivity , the specificity , and the accuracy , should be researched in clinical situation . the laser fluorescence - based caries detection device diagnodent ( kavo , germany ) has been introduced as an alternative . however , no single detection method for caries is sufficient ; therefore , the combination of some detection methods has been recommended [ 57 ] . if the shape of caries can be quantified , and the relationship between the numerical value and the condition of the lesion can be demonstrated , this information would be helpful to diagnose dental caries . the diagnosis of caries has mainly consisted of visual inspection and tactile assessment with probing .", "five dentists ranging from 3 to 15 years of professional experience examined the teeth after calibration of the criteria of the caries assessment conducted before the study ; the calibration was done as follows ; first , the five dentists examined 30 extracted teeth and decide which treatment plan would be appropriate ( preventive or operative ) . at that time one hundred teeth ( 36 premolars and 64 molars ) with pit - and - fissure discoloration from 19 outpatients were examined at the clinic of oral diagnosis and general dentistry , dental hospital , tokyo medical and dental university . a dentist preliminarily diagnosed each tooth using visual inspection and tactile examination to decide which treatment plan would be appropriate ( preventive or operative ) . the clinical diagnosis of preventive treatment for teeth was classified as co. on the other hand , carious lesions requiring operative treatment were removed in a conventional clinical way . if the resulting cavity preparation was limited in the enamel , then the clinical diagnosis was classified as c1 . if the resulting cavity preparation reached the dentin , and sound tissue still remained between the cavity and the pulp chamber , then the clinical diagnosis was classified as c2 . at last , the dentists discussed to accord the treatment planning for each tooth referring the depth of the lesion . differences in fd , pa , and dd between each clinical diagnosis were analyzed using two - way anova and games - howell test to reveal the clinical diagnosis and the effect of the examining dentists .", "the accuracy of the combination of fd and pa was greater than that of fd , pa , and dd . the specificity of pa was greater than that of fd , dd , and the combination of fd and pa . the sensitivity of fd was greater than that of pa , dd , and the combination of fd and pa . based on the discriminant formula of each explanatory variable , the thresholds of fd , pa , and dd between preventive and operative treatments were 1.20 , 0.012 , and 28.8 , respectively . the two - way anova revealed that the fd , pa , and dd were different among the clinical diagnosis ( p < .01 ) . there were also significant correlations among fd , pa , and dd ( p < .01 ) . \n", "previously , it was reported that the fractal dimension and the proportion of the area of pit - and - fissure discoloration to the area of occlusal surface were significantly correlated with the depth of the caries and the diagnodent values in extracted teeth . in this study , these results indicate that image analysis of molar pit - and - fissure discoloration was clinically useful for the diagnosis of caries . therefore , we considered that difference of the diagnosis among the dentists would be small . in the present study , to examine the possibility of digital imaging in the diagnosis of occlusal caries , diagnodent was used as a comparative pre - existing dental caries detection tool . thus , the accuracy of the diagnosis of occlusal caries using digital images of discolored areas was comparable to that of diagnodent ; therefore , its clinical application as a diagnostic tool is possible . diagnosis using digital images of pit - and - fissure discoloration depended on the statistical relationship between the shape of discoloration and the depth of caries . further research is needed to determine the discriminant formulas to diagnose caries using the image analysis of molar pit - and - fissure discoloration ." ]
the aim of this study was to assess the possibility of digital image analysis of pit - and - fissure discoloration in order to diagnose caries . digital images showing pit - and - fissure discoloration in 100 teeth of 19 patients were analyzed to obtain the fractal dimension ( fd ) and the proportion of the area of pit - and - fissure discoloration to the area of occlusal surface ( pa ) . diagnodent values were measured ( dd ) , and dentists ' diagnoses were also obtained . the sensitivity and specificity of fd , pa , dd , and the combination of fd and pa compared to the dentists ' diagnoses were calculated . the sensitivities of fd , pa , dd , and the combination of fd and pa were 0.89 , 0.47 , 0.69 , and 0.86 , respectively , and the specificities were 0.84 , 0.95 , 0.91 , and 0.86 , respectively . although further research is needed for the practical use , it is possible to use the analysis of digital images of pit - and - fissure molar discoloration as a diagnostic tool .
[ "we report using a pfeifer incision to correct a moderate true median cleft of the upper lip . craniofacial clefts may be caused by failure of the maxillary processes to fuse , external pressure , amniotic bands , oligohydramnios , central disorganization of the neural crest , and hematomas . in 1973 , craniofacial defects are rare , disfiguring facial anomalies , with an incidence of about 1.4 to 4.9 cases per 100,000 live births .", "a five - year - old boy with a facial cleft presented to our clinic . on examination , there was a median cleft of the upper lip involving the white roll , with no bony involvements . vermilion form was satisfactory and the fullness and continuity of the orbicularis oris were maintained . subsequently , a wavy incision line was made starting from the deepest point and extending over the philtrum just above the cleft ( fig . a diamond incision was made over the vermilion and the labial mucosa , intra - orally extending just beyond the cleft margin . undermining of the orbicularis oris muscle was performed and it was approximated using 4 - 0 vicryl .", "the postoperative results were excellent and proper approximation of the orbicularis oris muscle and the vermilion was achieved with a symmetrical cupid 's bow and philtrum . we were able to achieve adequate symmetry of the philtrum and the cupid 's bow , which is important in cases like this . the only disadvantage of this technique is that the final closure line is placed directly over the philtrum . a median cleft can also be called midline cleft or vertical cleft through the centre of the upper lip , and is a rare anomaly , the exact developmental origin of which is not clear . the above - mentioned studies prove the versatility of the pfeifer incision . in our case", "since the presentation of midline cleft deformities varies widely , each case should be individually considered and treated . pfeifer incisions can successfully provide mucosal length , vermilion fullness , and lip symmetry in patients with moderate median cleft lip ." ]
median cleft is the midline cleft of the lip . it develops due to incomplete or failed fusion of the median nasal prominence . it can present with minimal deformities such as involvement of the vermilion border , or complex clefting of the midline structures and brain . median clefts are broadly classified as true and false clefts . this case report describes a rare case of median cleft of the upper lip involving the white roll , which was not associated with any other deformities . treatment included reconstruction of the philtrum and the cupid 's bow while maintaining vermilion fullness and continuity , and minimizing scar formation . various techniques have been advocated for treatment of this type of median upper lip cleft . here we describe a technique using pfeifer incision to correct our patient 's defect . pfeifer incision consists of wavy lines and its use has been advocated for correction of various craniofacial abnormalities .
[ "rapd - pcr has the advantage of being fast , reproducible , simple , and low - cost , thus , it is an appropriate approach for primary screening of epidemic strains in large number of isolates ( 23 , 24 ) . pseudomonas aeruginosa is an important gram - negative opportunistic pathogen that has the capability to create variable clinical infections , including , but not limited to , wound infections , urinary tract infections ( utis ) , and blood stream infections ( bsi ) , particularly in hospitalized and immunocompromised patients ( 1 , 2 ) . although mlst and pfge have more discriminatory power , they are expensive , especially in developing countries ( 22 ) . since determining bacterial isolates relatedness is essential for understanding the transmission routes , different typing methods that can be divided into two major categories , phenotypic and genotypic methods , have been established ( 14 ) . phenotypic methods such as serotyping , pyocin typing , and antimicrobial susceptibility typing depend on the environmental factors , therefore , have low discriminatory power ( 14 , 15 ) .", "to our knowledge , limited data are available about genetic diversity of p. aeruginosa recovered from different clinical specimens in isfahan ; the purpose of the current study was to determine the antibiotic susceptibility profiles and genetic relatedness in p. aeruginosa isolated from patients admitted to a referral hospital in isfahan , iran .", ", a total of 150 non - duplicate samples ( urine , sputum , wound , blood , and eye discharge ) taken from hospitalized - patients admitted to different wards of hospital were analyzed . this study was conducted at a teaching referral hospital of isfahan , iran , from february 2013 to november 2013 . during the mentioned period primary identification of p. aeruginosa was done based on the standard conventional biochemical tests , including gram staining , catalase , oxidase , oxidative - fermentative ( of ) tests , pigment production and growth at 42c . then , primary identification was further confirmed with species - specific pcr using its ( 16s-23s rrna internal transcribed spacer ) primer ( 25 , 26 ) . we also used 100 bp dna ladder ( cinnagen , iran ) as the standard molecular size ( 100 bp-3000 bp ) . we used cut - off value of 80% for determination of potential clonal relatedness ( 31 - 33 ) . resistance to antibiotics was evaluated by kirby - bauer s disk diffusion method according to clsi ( clinical laboratory standard institute ) recommendation ( 27 ) . p. aeruginosa standard strain ( atcc 27853 ) was used as the quality control . ", ", a total of 150 non - duplicate samples ( urine , sputum , wound , blood , and eye discharge ) taken from hospitalized - patients admitted to different wards of hospital were analyzed . this study was conducted at a teaching referral hospital of isfahan , iran , from february 2013 to november 2013 . during the mentioned period primary identification of p. aeruginosa was done based on the standard conventional biochemical tests , including gram staining , catalase , oxidase , oxidative - fermentative ( of ) tests , pigment production and growth at 42c . then , primary identification was further confirmed with species - specific pcr using its ( 16s-23s rrna internal transcribed spacer ) primer ( 25 , 26 ) . the study was approved by the ethics committee of isfahan university of medical sciences ( no . 392063 ) .", "resistance to antibiotics was evaluated by kirby - bauer s disk diffusion method according to clsi ( clinical laboratory standard institute ) recommendation ( 27 ) . the following disks ( mast , uk ) were applied : ceftazidime ( caz , 30 g ) , imipenem ( imp , 10 g ) , meropenem ( mem , 10 g ) , ciprofloxacin ( cip , 5 g ) , aztreonam ( atm , 30 g ) , polymyxin b ( pb , 300 units ) , and amikacin ( amk , 30 g ) .", "we also used 100 bp dna ladder ( cinnagen , iran ) as the standard molecular size ( 100 bp-3000 bp ) . we used cut - off value of 80% for determination of potential clonal relatedness ( 31 - 33 ) . dice similarity coefficient and unweighted average pair group method ( upgma ) were used for similarity matrix calculation and cluster analysis , respectively ( 28 , 29 ) . only major reproducible bands rapd - fingerprints were recorded as present ( 1 ) or absent ( 0 ) for each band . by means of freetree and treeview softwares , dna amplification was carried out using biometra thermocycler ( germany ) and following a two - step program , 1 ) denaturation 5 min at 95c , annealing 5 min at 36c , elongation 5 min at 72c , for 4 cycles , and 2 ) 31 cycles consisted of 94c for 1 min , 45c for 1 min , 72c for 2 min , followed by a final extension at 72c for 10 min ( 21 ) .", "based on 65% similarity level , eight main cluster , with most of the strains belonging to cluster 1 were detected ( figure 3 ) . out of 150 samples , 54 ( 36% ) were positive for p. aeruginosa culture . rapd fingerprinting results of p. aeruginosa based on 80% showed 39 different groups ( figure 3 ) . although the majority of isolates had unique fingerprint , group one composed of 3 isolates ( patients s48 , s29 , s31 ) . genetic relatedness of clinical isolates of the detected p. aeruginosa has been carried out using rapd - pcr assay , which showed 55% to 100% similarity ( figure 3 ) . the highest percentage ( 55.6% ) of resistance was observed against ceftazidime and imipenem with 30 of the isolates being resistant ; all isolates were sensitive to polymyxin b ( figure 1 ) .", "constant monitoring of antibiotic susceptibility profiles and genetic relatedness among bacterial infectious agents are essential steps for infection control ( 34 ) . to improve our understanding about p. aeruginosa antibiotic resistance and their distribution , 54 non - duplicate isolates of p. aeruginosa by using kirby - bauer s disk diffusion and rapd - pcr methods p. aeruginosa involved in this study were highly resistant to different antibiotic families like , monobactams , cephalosporins , quinolones , and carbapenems ( figure 1 ) . prescription of common antibiotics ( imipenem and amikacin ) in our hospital due to high resistance rate must be restricted . according to our data , considerable genetic diversity exists among isolated p. aeruginosa although , in our investigated hospital , carbapenems ( imipenem , meropenem ) along with amikacin are the most currently used antibiotics for the treatment of p. aeruginosa infections , results of this study revealed that prescription of them should be limited . in order to optimize treatment of p. aeruginosa infections in our hospital ( ; it is possible that different sources of p. aeruginosa be involved in our hospital that can lead to host colonization . in order to accurately control the infection , other p. aeruginosa isolated from hospital environment" ]
background : pseudomonas aeruginosa is a well - known opportunistic pathogen , which affects hospitalized patients in different wards due to its natural resistance to drugs.objectives:the purpose of the current study was to determine the antibiotic susceptibility profiles and genetic relatedness in p. aeruginosa isolated from patients admitted to a referral hospital in isfahan , iran.materials and methods : out of 150 analyzed samples , 54 p. aeruginosa isolates were recovered and were subjected to antibiotic resistance patterns and genetic diversity determination by kirby - bauer s disk diffusion method and rapd - pcr , respectively.results:the highest percentage of resistance was observed against ceftazidime and imipenem with 30 ( 55.6% ) isolates ; meanwhile all isolates were sensitive to polymyxin b. twenty - eight ( 51.8% ) isolates revealed resistance to all applied antibiotics . rapd - pcr ( random amplified polymorphic dna- polymerase chain reaction ) results showed 54 unique genotypes , which were divided into 39 clusters.conclusions:although different source of p. aeruginosa may involve in patient colonization , genetically related strains were isolated from different wards and or the same ward of the hospital . our results pointed to the restriction of currently used antibiotics in studied hospital . we hope that our results cast light on the control and transmission of the infection in the investigated hospital .
[ "we hypothesize that the combination of acylation \n and cyclization of short polyarginine peptides having less than six \n arginine residues will increase the intracellular uptake and can generate \n peptides with molecular transporter properties . for convenience , square \n brackets [ ] and parentheses ( ) we compared acpps with a corresponding \n acylated linear polyarginine peptide ( alpp ) and a nonacylated cyclic \n polyarginine as controls . phosphopeptide ptyr - glu - glu - ile ( pyeei ) \n is an optimal peptide ligand for binding to the src tyrosine kinase \n sh2 domain . in this study , we used negatively charged fluorescein - labeled \n phosphopeptide f-gpyeei as a model cell - impermeable compound .", "cytotoxicity \n of peptides was examined \n by mts proliferation assay in two human cancer cell lines ( sk - ov-3 \n and ccrf - cem ) and one human normal cell line ( hek 293 t ) . fluorescein - labeled \n peptides were synthesized with the same protocol \n before the attachment of fatty acid . , the assay was carried out at 4 c \n to inhibit the energy - dependent cellular uptake pathways . 5(6)-carboxyfluorescein ( fam ) was used as a negative control . for examination \n of the cellular uptake mechanism of f-dodecanoyl-[r5 ] at low temperature however , in the synthesis of cyclic peptides , the \n side chain protected linear peptides were first cleaved from the resin \n by using a cleavage cocktail , containing 2,2,2-trifluoroethanol ( tfe)/acetic \n acid / dichloromethane ( dcm ) ( 2:1:7 , v / v / v ) . fmoc - l - amino acid building blocks , fatty acids , and preloaded \n h - arg(pbf)-2-chlorotrityl resin were used as starting materials .", "the presence of \n the peptide possibly improved the cellular uptake of dox and enhanced \n the antiproliferative activity . the results showed that the cellular uptake of f-acpp \n was inhibited in the presence of sodium azide and 2-deoxy - d - glucose , suggesting that receptor - mediated endocytosis is involved \n for the cellular uptake of f-acpp . in atp depletion assay , \n these results showed that the cell proliferation of mcf-7 cells was \n inhibited in a time - dependent manner suggesting a sustained drug release \n by peptide leading to a higher inhibitory effect . time - dependent antiproliferative activity \n of dox ( 5 m ) in \n the presence and absence of [ r6]-c12 ( 5 m ) . the intracellular uptake of f-gpyeei in the presence \n of dodecanoyl-[r5 ] and dodecanoyl-[r6 ] was enhanced \n by 3.4- and 5.5-fold higher than the uptake in the absence of acpps . \n however , this is evident that the intracellular uptake \n of f-dodecanoyl-[r5 ] was inhibited , and there was \n no significant difference between the cells treated with fam compared \n to those treated with f-dodecanoyl-[r5 ] in temperature \n control and atp depletion assays , suggesting that endocytosis is the \n major pathway for the cellular uptake of f-dodecanoyl-[r5 ] . however , the intracellular uptake \n of the phosphopeptide did not improve significantly in the presence \n of either acylated linear polyarginine peptide or cyclic [ r5 ] . w4-[r5 ] enhanced intracellular delivery of f-gpyeei by 4.1-fold \n higher compared to that of dodecanoyl-[r5 ] in sk - ov-3 . \n however , w - dodecanoyl-[r5 ] improved the uptake of f-gpyeei \n by 1.3-fold higher compared to that of w4-[r5 ] in ccrf - cem cells ( figure 9 ) . the antiproliferative \n potency of dox ( 5 m ) was enhanced by 7% , 11% , and 14% in the \n presence of [ r6]-c12 ( 5 m ) when compared \n with that of the drug alone after 24 , 48 , and 72 h incubation , respectively . \n", "cyclization and acylation reactions on the structure \n of the peptide enhanced the intracellular uptake of polyarginine peptides \n although they carry a short length of sequence . this intracellular \n delivery property of acpps can be optimized by modifying the length \n of fatty acid chain . to the best of our knowledge , acpps showed \n higher potency as molecular transporter compared to the corresponding \n linear counterpart and cyclic polyarginine without fatty acid . this is the first \n report of cyclic fatty acylated polyarginine peptide as molecular \n transporter of a cell - impermeable phosphopeptide . the \n mechanism of the peptide internalization was found to be energy - dependent \n endocytosis . in \n conclusion , acylated cyclic polyarginine peptides were synthesized \n and examined as cpps and potential molecular transporters ." ]
many of the reported arginine - rich cell - penetrating peptides ( cpps ) for the enhanced delivery of drugs are linear peptides composed of more than seven arginine residues to retain the cell penetration properties . herein , we synthesized a class of nine polyarginine peptides containing 5 and 6 arginines , namely , r5 and r6 . we further explored the effect of acylation with long chain fatty acids ( i.e. , octanoic acid , dodecanoic acid , and hexadecanoic acid ) and cyclization on the cell penetrating properties of the peptides . the fluorescence - labeled acylated cyclic peptide dodecanoyl-[r5 ] and linear peptide dodecanoyl-(r5 ) showed approximately 13.7- and 10.2-fold higher cellular uptake than that of control 5,6-carboxyfluorescein , respectively . the mechanism of the peptide internalization into cells was found to be energy - dependent endocytosis . dodecanoyl-[r5 ] and dodecanoyl-[r6 ] enhanced the intracellular uptake of a fluorescence - labeled cell - impermeable negatively charged phosphopeptide ( f-gpyeei ) in human ovarian cancer cells ( sk - ov-3 ) by 3.4-fold and 5.5-fold , respectively , as shown by flow cytometry . the cellular uptake of f-gpyeei in the presence of hexadecanoyl-[r5 ] was 9.3- and 6.0-fold higher than that in the presence of octanoyl-[r5 ] and dodecanoyl-[r5 ] , respectively . dodecanoyl-[r5 ] enhanced the cellular uptake of the phosphopeptide by 1.42.5-fold higher than the corresponding linear peptide dodecanoyl-(r5 ) and those of representative cpps , such as hepta - arginine ( cr7 ) and tat peptide . these results showed that a combination of acylation by long chain fatty acids and cyclization on short arginine - containing peptides can improve their cell - penetrating property , possibly through efficient interaction of rigid positively charged r and hydrophobic dodecanoyl moiety with the corresponding residues in the cell membrane phospholipids .
[ ", this work benefited from two large - scale population - based surveys : the first one , representative at the national level , was used to develop the score , and the second one , a cohort study , was utilized for external validation . consequently , we aimed to develop a simple laboratory - free risk score to identify people with undiagnosed diabetes and incident diabetes in peru , a latin american country that spans coastal , andean , and rainforest settings . in order to do so however , fasting glucose is not always available in primary care settings , especially in semiurban and rural areas . as a result , a major challenge to be overcome in many countries is the implementation of a simple , fast , and laboratory - free based screening method . most of the available algorithms for diabetes screening have been developed in caucasian [ 79 ] and asian populations [ 1013 ] and very few in other ethnic groups [ 14 , 15 ] . to date , one diabetes risk score has been developed and validated in latin america so far which was derived from one urban area in brazil , thus bearing limited generalizability to the wider region . furthermore , it is well established that before adopting existing risk scores as screening tools in different populations and ethnic groups , their performance needs to be evaluated , calibrated , or validated in local settings . as the american diabetes association , the peruvian ministry of health recommends diabetes screening in general population with fasting glucose in adults aged 40 to 70 years with risk factors . as of 2014 , the worldwide prevalence of type 2 diabetes mellitus ( t2 dm ) was estimated to be 9% among adults aged 18 years with great impact on mortality , particularly in low- and middle - income countries ( lmic ) [ 1 , 2 ] . moreover , globally , approximately 25% to 75% of diabetes cases remain undiagnosed [ 3 , 4 ] , until further complications , especially at the macro- and micro - vascular level , manifest clinically . in latin america , the american diabetes association recommends the use of glucose test as t2 dm screening in people with overweight and obesity as well as in those with other risk factors . as a result", "the national survey of nutritional and biochemical indicators for noncommunicable diseases ( eninbsc in spanish ) , conducted by the peruvian national institute of health , was used to develop our predictive model . the peruvian risk score was compared to previously published models for undiagnosed diabetes including the brazilian risk score , the qingdao score , the indian risk score , the kuwaiti risk score , the patient self - assessment score , and the rotterdam risk score using the c - statistic . finally , using the follow - up data of the cronicas cohort study , the risk score was also evaluated to detect incident cases of t2 dm by excluding those with diabetes diagnosis at baseline . data collected comprised risk factors for cardiovascular disease based on a modified version of the who step approach questionnaire for surveillance of noncommunicable disease . the eninbsc is a national population - based survey carried out in peru between august 2004 and april 2005 , designed to estimate the prevalence of hypertension , type 2 diabetes mellitus , and other risk factors for noncommunicable diseases at the national and regional level . then , the prevalence and 95% confidence intervals ( 95% ci ) of total diabetes and undiagnosed diabetes were estimated in each study . as one of the main aims of a nonlaboratory risk score is to identify people who warrant having a blood test ( i.e. , fasting glucose , glycated haemoglobin , etc . ) , the cut - point with the highest sensitivity was also estimated and described . this was complemented with the cronicas cohort study , whose baseline and longitudinal information was used to validate the risk score .", "the performance of this risk score was also assessed to predict incident cases of diabetes using the longitudinal data from the cronicas cohort study . in addition , when the risk score was evaluated by applying the score to the cronicas cohort study 's population , the auc for undiagnosed diabetes was 0.68 ( 95% ci : 0.620.73 ) . at the suggested cut - point of 2 , one hundred twenty - one new cases of diabetes were found accounting for 6,207 person - years at risk , with an overall incidence of 1.95 ( 95% ci : 1.632.33 ) cases per 100 person - years of risk . 80% would be categorized as undiagnosed diabetes with sensitivity , specificity , ppv , and npv of 94.0% , 20.0% , 3.3% , and 99.1% , respectively . when previous published algorithms for undiagnosed diabetes the overall prevalence of diabetes was 5.1% ( 129/2538 ; 95% ci : 4.2%5.9% ) in the eninbsc survey and 8.7% ( 272/3135 ; 95% ci : 7.7%9.7% ) in the cronicas cohort study 's baseline .", "using a national population - based survey , a simple nonblood based risk score based on age , history of diabetes in first - degree relatives , and waist circumference was built and shown to perform moderately in detecting undiagnosed diabetes when externally validated . moreover , our idea was to develop a simple and easily applicable score instead of a complex algorithm for predicting undiagnosed and incident diabetes . moreover , the performance of the score was almost similar for detecting incident cases of diabetes in the peruvian population . moreover , two of these variables are easily evaluable during medical appointment or through individual 's self - assessment , and only a measuring tape and no calculations are required to be implemented in clinical practice or at the population level . from a cross - sectional point of view , with a cut - point 2 , from 1000 participants assessed by the peruvian diabetes risk score , a total of 420 would be classified as undiagnosed diabetes with the detection of 20 cases and only 6 will be missing . on the other hand , with a cut - point 1 , from 1000 screened individuals , a total of 804 would be categorized as having undiagnosed diabetes with the detection of 27 cases and only 7 will be missing . finally , as other diabetes risk scores , the model warrants further scrutiny before it can be used in other populations . in addition , and not included in the aforementioned review , only one risk score was developed in latin america using brazilian urban population . our findings also demonstrate that approximately 35% of cases of t2 dm ( 39% in the eninbsc survey and 33% in the baseline of the cronicas cohort study ) are not aware of their disease .", "this experience in generating such simple , easy - to - use approaches for the identification of t2 dm can serve to inform other similar lmic efforts who are on early stages of diabetes prevention . the peruvian diabetes risk score , built using age , self - reported diabetes in first - degree relatives , and waist circumference , proves to be a simple pragmatic screening tool for undiagnosed and incident cases of diabetes in peru . this tool , due to its simplicity , can facilitate various initiatives oriented to introduce and scale up early preventative and management strategies on a wider scale ." ]
objective . to develop and validate a risk score for detecting cases of undiagnosed diabetes in a resource - constrained country . methods . two population - based studies in peruvian population aged 35 years were used in the analysis : the eninbsc survey ( n = 2,472 ) and the cronicas cohort study ( n = 2,945 ) . fasting plasma glucose 7.0 mmol / l was used to diagnose diabetes in both studies . coefficients for risk score were derived from the eninbsc data and then the performance was validated using both baseline and follow - up data of the cronicas cohort study . results . the prevalence of undiagnosed diabetes was 2.0% in the eninbsc survey and 2.9% in the cronicas cohort study . predictors of undiagnosed diabetes were age , diabetes in first - degree relatives , and waist circumference . score values ranged from 0 to 4 , with an optimal cutoff 2 and had a moderate performance when applied in the cronicas baseline data ( auc = 0.68 ; 95% ci : 0.620.73 ; sensitivity 70% ; specificity 59% ) . when predicting incident cases , the auc was 0.66 ( 95% ci : 0.610.71 ) , with a sensitivity of 69% and specificity of 59% . conclusions . a simple nonblood based risk score based on age , diabetes in first - degree relatives , and waist circumference can be used as a simple screening tool for undiagnosed and incident cases of diabetes in peru .
[ "the present study was designed to investigate the potential use of p53 rnai to block p53 expression , as well as the subsequent effect on cell invasion and gene expression on the human cervical cancer cell . rnai ( rna interference ) is a natural mechanism able to specific inhibit a target gene . many recent investigations have shown that sirna can efficiently inhibit oncogene expression in cancer cells . various investigations demonstrated clearly that the deactivation of p53 constitutes a crucial step in carcinogenesis . rnai has been demonstrated as a relevant investigation device for particular target genes by using exogenous sirnas . sirnas represent an encouraging novel type of medicaments for cancer therapy , as a result of targeting the mutated tumour suppressor genes or activated oncogenes . the prospective exploitation as a therapeutic has lately been strengthened by the small interfering rna ( sirna ) delivery to human tumours .", "we performed the invasion assays on hela cells to evaluate the impact of p53sirna treatment using the cim - plate 16 with the xcelligence rtca dp instrument ( roche applied science ) according to the described protocol by . hela is a human cervical carcinoma cell line ; this was incubated in a 5% co2 incubator at 37c . for maintenance the evaluation of the vegf protein expression at 48 hours post treatment was done using human vegf quantikine elisa kit ( r&d , catalog no . the data analysis was carried out to compare the gene expression values for the treated and untreated groups using ct method . as housekeeping gene siport neofx 0.25% concentration was able to achieve the maximum inhibition of target gene with no effects on cell viability . a validated p53sirna pool ( sc-29435 , santa cruz ) was used at a concentration of 50 nm in serum starvation condition using optimem medium ( gibco , invitrogen , romania ) , in accordance with the producer recommendations .", "siport neofx 0.25% concentration was able to achieve the maximum inhibition of target gene with no effects on cell viability . a validated p53sirna pool ( sc-29435 , santa cruz ) was used at a concentration of 50 nm in serum starvation condition using optimem medium ( gibco , invitrogen , romania ) , in accordance with the producer recommendations . hela is a human cervical carcinoma cell line ; this was incubated in a 5% co2 incubator at 37c . for maintenance / well were used for reverse - transfection , based on a preliminary optimised protocol for p53sirna , using siport neofx as transfection agent ( ambion , usa ) .", "we performed the invasion assays on hela cells to evaluate the impact of p53sirna treatment using the cim - plate 16 with the xcelligence rtca dp instrument ( roche applied science ) according to the described protocol by .", "the total rna for the cells treated with 50 nm p53sirna andthe control group respectively at 24 hours post treatment was extracted using trireagent ( sigma - aldrich , bucharest romania ) based on the producer recommended protocol for each triplicate specimen . the rna concentrations and quality were assessed by the nanodrop-1100 agilent 2100 bioanalyzer spectrophotometer . all of the samples had a rin ( rna integrity number ) higher than 7.5 . the total rna ( 500 ng ) from all the samples was reverse transcribed using the first strand cdna synthesis kit for rt - pcr ( roche , bucharest romania ) . for the gene amplification we used taqman universal pcr master mix , in a 20 l volume in a 96-well plate using the roche lightcycler 480 system . the 8 genes selected were assessed using specific primer and upl based on in silico design .", "the data analysis was carried out to compare the gene expression values for the treated and untreated groups using ct method . as housekeeping gene", "the evaluation of the vegf protein expression at 48 hours post treatment was done using human vegf quantikine elisa kit ( r&d , catalog no .", "after 48h post transfection with p53 sirna inhibition in hela cell line , vegf protein was found dowregulated in the culture medium than in the control group ( figure 3 ) . the cim - plate 16 furnishes a kinetic cell - response profile to p53sirna throughout an investigation , specifying the commencement and ratio of invasion and migration of hela cells . xcelligence system is an innovative device that allows the scanning of cellular response via an impedance - based technology in real time , lacking any exogenous labels . we can observe a delay and a reduction of the cell migration after the p53sirna treatment . relative gene expression quantification using ct method leads to the downregulation of the selected gene , presented in the figure 2 . taqman qrt - pcr assay was used to examine the effect of p53sirna on a panel of 8 genes related to apoptosis and angiogenesis . this data can facilitate to comprehend the response to treatment in dynamic . in figure 1", "the cim - plate 16 furnishes a kinetic cell - response profile to p53sirna throughout an investigation , specifying the commencement and ratio of invasion and migration of hela cells . xcelligence system is an innovative device that allows the scanning of cellular response via an impedance - based technology in real time , lacking any exogenous labels . we can observe a delay and a reduction of the cell migration after the p53sirna treatment . this data can facilitate to comprehend the response to treatment in dynamic . in figure 1", "taqman qrt - pcr assay was used to examine the effect of p53sirna on a panel of 8 genes related to apoptosis and angiogenesis . relative gene expression quantification using ct method leads to the downregulation of the selected gene , presented in the figure 2 .", "after 48h post transfection with p53 sirna inhibition in hela cell line , vegf protein was found dowregulated in the culture medium than in the control group ( figure 3 ) .", "the complete comprehension of the cross - talk between p53 and angiogenic pathways represents a challenge in cancer therapy [ 2426 ] . the inhibition of mutant p53 represents a significant therapeutic target , a fact emphasized by walerych as rebel angel . the role of the present study is to emphasize the cooperation between oncogenic mechanisms , confirming the crosstalk between apoptotic and angiogenic mechanisms . this has a significant therapeutic relevance based on the fact that mutated p53 is related to cancer aggressiveness or to promoting metastasis . in a similar study was observed that , by using sirna targeting p53/p73 , tumoral cells were sensitized to chemotherapy . in a recent study , pinx1 was displayed as a novel target gene of p53 , proposing the suppression of p53/pinx1 pathway as a novel mechanism to enhance the telomerase activity in cervical cancer cells , and leading to reduction of cell proliferation .", "may also have an important significance outside the context of cervical cancer , by using specific inhibitors for p53 for increasing therapeutic response in a wide range of tumoral pathology . therefore , p53 inhibitions become dependent and rely on angiogenesis for growth and metastasis . the results in the current research the angiogenic phenotype related to p53 targeted by sirna in human cancers is frequently associated with resistance to conventional genotoxic anticancer agents . p53 gene knockdown in hela cells plays an important role not only in apoptosis but also in angiogenesis through various mechanisms that regulate tumour cell development and migration ." ]
background and aimssirnas represent an encouraging novel alternative in cancer therapy as a result of targeting the mutated tumour suppressor genes or activated oncogenes . targeting oncogenic signals , as the mutated p53 gene that gains oncogenic role , we observed inhibition of migration , a downregulation of specific genes involved in apoptosis but also in angiogenesis , connected with a reduction in invasion rate in the case of p53sirna therapy.methodsthe study was designed to assess the role of p53 by using rnai ( rna interference ) in hela in vitro cell culture model . therefore cell migration rate was assessed by using xcelligence systems , gene expression for a panel of genes involved in apoptosis and angiogenesis , and validation of gene expression data at protein level.resultson the selected in vitro model p53 sirna therapy was correlated with the reduction of cell migration . the downregulation of p53 , pten , tnf , nfkb , bcl-2 , icam-2 , vegf , and fgfb was evidenced as response to p53 inhibition.conclusionrnai may be a valuable technology in order to restore the normal cellular phenotype . the results in the current research may also have an important significance outside the context of cervical cancer , by using specific inhibitors for p53 for increasing the therapeutic response in a wide range of tumoral pathology .
[ "the aim of this study was to demonstrate whether there is any difference between two group of patients with coronary atherosclerotic plaque and subjects without coronary atherosclerosis for the presence of c. pneumoniae dna by polymerase chain reaction ( pcr ) method . this controversy about the role c. pneumoniae in the pathogenesis of atherosclerosis emphasizes the importance of more research works . atherosclerosis is a coronary heart disease ( chd ) , and is the most common cause of death in the industrialized world . high blood pressure ( bp ) , hypercholesterolemia , diabetes mellitus ( dm ) and smoking are considered as the major risk factors for the development of atherosclerosis . in addition , increasing age , male sex , family history and genetic factors predispose patients to chd.1 there is some data that have suggested the possible potential role of some infectious agents in the pathogenesis of atherosclerosis.26 the possibility of infectious agents may trigger the process of atherosclerosis by direct or indirect inflammatory effects , especially at younger ages.5 although different studies have been carried out to prove this hypothesis some infections may contribute in the pathogenesis of atherosclerosis ; nothing has ever been conclusively proven . the possible role of some agents such as chlamydophila pneumoniae,6 \n hepatitis c. virus,7 \n human immunodeficiency virus,7 \n hepatitis b virus,8 \n cytomegalovirus,9 \n herpes virus,9 \n epstein - barr virus,10 \n mycobacterium tuberculosis,11 and helicobacter pylori,3 have been considered in the pathogenesis of atherosclerosis . among these pathogens , c. pneumoniae is important , because it could be effectively treated by antibiotics.12 \n c. pneumoniae is an obligatory intracellular organism , and is responsible for at least 10% of community - acquired pneumonias . this bacterium has also been associated with pharyngitis , bronchitis , otitis , influenza - like illness , sinusitis and myocarditis.1214 conflicting results have been reported about the relationship between c. pneumonia and atherosclerosis .", "coronary artery tissues were selected from another study that was performed previously by our colleagues for determining prevalence of atherosclerotic plaques in autopsy cases with non - cardiac death in northeast iran . in this study , left coronary artery ( lca ) , right coronary artery ( rca ) and left circumflex artery ( lcx ) had been evaluated grossly and microscopically . this case - control study was carried out on 60 formalin - fixed paraffin - embedded ( ffpe ) coronary artery biopsies in the molecular pathology laboratory , ghaem hospital , mashhad , iran in 2010 . our materials included 30 coronary artery tissues with atherosclerotic plaques that were defined as study group , and 30 coronary artery tissues without atherosclerotic plaques that served as the control group . archived slides of the two groups were reviewed by two pathologists for confirmation of diagnosis , tissue adequacy and selection of the best paraffin blocks for dna extraction . five to seven , 5-m - thick sectionswere cut from each ffpe specimen under sterile conditions , and then the dna was extracted by using proteinase k and non - heating dna extraction method.20 dna concentration was determined by using the thermo scientific nanodrop 2000 spectrophotometer , and specimens with low dna content ( < 20 ng/l ) were excluded from the study . pcr was performed for detecting c. pneumoniae dna by using the pcr kits ( dna technology ( jsc ) , pcr kit , moscow , russia ) .", "fisher 's exact test showed no significant difference for detection of c. pneumoniae between samples of coronary artery with and without atherosclerotic plaque ( p = 1 ) . the age range in the control group was 20 - 46 years with a mean ( standard deviation ) age of 26.0 ( 6.41 ) years . in the study group , the mean bmi of the patients in the study and control groups were 24.4 ( 3.77 ) and 23.9 ( 2.62 ) kg / m respectively [ table 1 ] . the frequency of atherosclerotic plaques in the different vessels of heart of the patients in the study is as shown in table 2 . as a result , the possibility of the appearance of advanced atherosclerotic plaques s in lca was higher than the two other vessels . it ranges from 18 to 50 years with a mean ( sd ) age of 32.0 ( 9.46 ) years and the t - test showed no significant difference between the ages of patients in the study and control groups ( p=0.97 ) . comparisons between patients with coronary atherosclerosis and controls for weight , height and body mass index the frequency of atherosclerotic plaques in different vessels of the heart in the study group positive pcr result for c. pneumonia was seen in one ( 3.3% ) sample among the 30 coronary artery tissues with atherosclerosis ( advanced plaque ) , while all the control samples were negative . concurrent occurrences of different stages of atherosclerosis were seen in our patients . only one vessel involvement with fibro - fatty morphology ( mild )", "inflammatory cells are seen during all steps of atherogenesis , and some infectious agents may trigger this inflammation.113 although some studies showed that c. pneumoniae can increase the risk of atherosclerosis , 61819 but we did not find any significant difference in the frequency of c. pneumoniae dna isolation in the coronary arteries with and without atherosclerosis by pcr method . they examined coronary artery samples with two different methods , and both revealed a high rate of reactivity to this bacterium in severe atherosclerosis and a much lower rate in mild atherosclerosis ; therefore , they concluded that severity ( stage ) of atherosclerosis can be presumed as an important factor in diagnosis of c. pneumoniae infection . we believe that the lack of standardized methods for the detection of c. pnuemoniae infection used in the aforementioned studies is probably one of the important reasons for the discrepancies in their results . c. pnuemoniae is a common human pathogen ; the majority of infected subjects have few or no symptoms . further studies involving a greater number of patients and also using more specific methods for detecting living c. pneumonia organisms by culture can be helpful . ischemic heart disease could be observed in the absence of its major risk factors such as increasing age , male gender , hypertension , hyperlipidemia , smoking and dm ." ]
background : atherosclerosis is a coronary heart disease , andis the most common cause of death in the industrialized world . some studies suggested that atherosclerosis may be triggered by infectious agents , mostly chlamydophila pneumoniae . however , the role of c. pneumoniae in the pathogenesis of coronary atherosclerosis is still controversial.objectives:this study was performed to evaluate whether there is a significant association between coronary artery atherosclerosis and c. pneumoniae by the polymerase chain reaction ( pcr ) method.materials and methods : this case - control study was carried out on formalin - fixed paraffin - embedded tissue biopsies of the coronary arteries obtained from 30 patients with coronary atherosclerosis and 30 subjects without atherosclerosis living in northeast of iran . all subjects ' weight and height were determined , and the body mass index was calculated . we also reviewed the medical history and previous laboratory reports of patients . deoxyribonucleic acid ( dna ) was extracted , and c. pneumonia dna was amplified and detected using pcr assay.results:the age of the patients in the study group was from 18 to 50 years , and the male to female ratio was 5:1 . only oneout of the 30 coronary tissue samples had positive pcr for c. pneumoniae ( 3.3% ) , while it was negative for patients in the control group.conclusions:this study showed that c. pneumoniae infection is not strongly associated with coronary artery atherosclerosis in northeast of iran .
[ "confrontation with the consequences of diabetes causes a crisis in physical , mental , and spiritual dimensions . sometimes the spiritual crisis can be tremendous . since spiritual health coordinates different aspects of human life , this study aimed to identify the spiritual health of patients with defects caused by diabetes", "this was a qualitative - phenomenological and descriptive study and the participants were selected from rehabilitation centers in isfahan and valiasr hospital in zanjan .", "outcome of this phase of the study was 173 codes and 2 groups that included hindering factors in spiritual health and the promotion of the relation with god . the concepts that patients had experienced as hindering factors of the treatment process were disappointment and hopelessness , guilt , feeling distant from god , quitting obligatory acts and knowing god as cruel . the concepts that patients had experienced as contributing factors to the healing process were resorting to imams , god s ordering the disease as a reward , fear of god s punishment , believing in miracles , being closer to god , believing in the mercy of god , returning to religious practice , feeling of enjoying life and knowing that the disease is the atonement of sins .", "with regard to the importance of spiritual and religious care as one of the tasks of nurses , as the key members of health team , they should respect the patients beliefs and values in addition to considering their physical and mental conditions .", "this study was conducted to understand the spiritual experiences of the patients with organ amputation due to diabetes . the increasing interest of medical scientists to the impact of praying in the treatment of other diseases can be indicative of treatment of some diseases in case of modern medicine failure . on the other hand , medical researchers also acknowledge the importance of medical procedures of traditional and complementary therapies including prayer to treat the diseases . even the western scientific community has recently published articles showing that doctors can not be indifferent to the religious beliefs of patients for treatment . organ amputation due to diabetes causes crisis in the physical , mental , and spiritual life of the patients . in this case in which science is unable to help a person , this issue is of vital importance especially in serious cases . , the spiritual health is the unique element that can harmonize physical , mental and social aspects of the human life and is necessary for coping with the disease . as a matter of fact , although the mortality rate in diabetic patients due to ketoacidosis and infection is declining , deaths from diabetes complications including diabetic foot complications has increased dramatically . according to some reports , its rate in the first year after amputation is 1340 percent , in the third year", "the study population consisted of patients with defects , caused by diabetes , who had referred to rehabilitation centers in esfahan and zanjan provinces . in this study , the researcher tried to be cautious with the information collected to be free from any kind of bias and to avoid persons with poor memory and those who could not provide the correct information . in the interviews , the researcher attempted to withdraw his assumptions about the phenomenon under study and thus help to strengthen the data . the aim of phenomenological studies is to understand the phenomena of human experience through the analysis of participants verbal explanations of experiences . sampling was purposive and the inclusion criteria for participants were the injury caused by diabetes and the willingness to participate in the interview . the participants and the research partners also reviewed all the data . to achieve reliability and objectivity of the research data , the account access was used . to increase the portability of the present study , the complete research project was introduced . the criteria for validity and reliability of data were lincoln and guba . in order to make the study believable , there were 15 participants entered the study ( 8 men and 7 women at 5070 years of age ) .", "length of diabetes was between 530 years and the length of organ amputation caused by diabetes also varied from 2 weeks to 11 years with mean of 4.2 years . the education level comprised of uneducated to junior high school . the concepts derived from patients experiences as factors interfering spiritual health in the treatment process were disappointment and hopelessness , guilt , feeling distant from god , quitting obligatory acts and considering god cruel . factors promoting the healing process were deemed by god , fear of god punishment , belief in miracles , being closer to god , believing god to be merciful , returning to religious practice , enjoying life and indicating the disease as the atonement of sins . regarding employment , 53.3 percent of the participants ( 8 people ) lost their jobs and were unemployed due to organ amputation caused by diabetes . most of the participants , encounteringdiabetes - related organ amputatio , said that in such circumstances , intellectual protections , religious sources , and having a strong relationship with a higher power could improve the quality of life , and support the individuals and reduce the severity of symptoms . the age range of participants was between 50 - 75 years with mean age of 59.7 years . there were 15 patients participating in this study , comprised of 7 women and 8 men .", "nowadays , some of the organizations that evaluate health care systems and are responsible for granting accreditation to them , suggest that the spiritual needs of the patients in health care should be also evaluated . nurses should pay close attention in the implementation of these provisions , and if the patients are upset , they should leave them alone . in this regard , a research by tracy et al . finally , the importance of spiritual and religious care , which is today considered as one of nurses tasks , urges them as the key members of health teams to respect patients beliefs and values as well as their physical and mental aspects . was conducted on two thousand nurses in critical care units in which 55% of nurses reported that patients and families were asking them to pray . the results of this study showed a significant difference between the duration of fever and length of patients stay that was lower in the intervention group compared to the control group . therefore , the appeal to the imams in patients with organ amputation due to diabetes is high ." ]
background : confrontation with the consequences of diabetes causes a crisis in physical , mental , and spiritual dimensions . sometimes the spiritual crisis can be tremendous . since spiritual health coordinates different aspects of human life , this study aimed to identify the spiritual health of patients with defects caused by diabetes.materials and methods : this was a qualitative - phenomenological and descriptive study and the participants were selected from rehabilitation centers in isfahan and valiasr hospital in zanjan . a purposive sample of 15 participants underwent deep interviews . colaizzi s method of analysis was used to analyze the data.findings:outcome of this phase of the study was 173 codes and 2 groups that included hindering factors in spiritual health and the promotion of the relation with god . the concepts that patients had experienced as hindering factors of the treatment process were disappointment and hopelessness , guilt , feeling distant from god , quitting obligatory acts and knowing god as cruel . the concepts that patients had experienced as contributing factors to the healing process were resorting to imams , god s ordering the disease as a reward , fear of god s punishment , believing in miracles , being closer to god , believing in the mercy of god , returning to religious practice , feeling of enjoying life and knowing that the disease is the atonement of sins.conclusions:with regard to the importance of spiritual and religious care as one of the tasks of nurses , as the key members of health team , they should respect the patients beliefs and values in addition to considering their physical and mental conditions .
[ "insulin resistance and vitamin d deficiency in asian - indian children and adolescents , we sought to examine the relationship between vitamin d status and insulin resistance . we also sought to determine if puberty affected the relationship of vitamin d status and parameters of insulin resistance and sensitivity in asian - indian children and adolescents . vitamin d deficiency was once thought to exclusively affect bone metabolism , but now there is ample evidence of its role in many other conditions including metabolic syndrome , autoimmune diseases , and cancer . several observational studies in adults , including the framingham heart study , have reported an inverse association between vitamin d status and insulin resistance .", "blood samples were collected in fasting state ( minimum 9 hours fasting ) , followed by oral glucose tolerance test ( anhydrous glucose = 1.75 gm / kg bodyweight , maximum of 75 gram , dissolved in 250 ml of water , ingested over 5 minutes ) with sample collection at 60 and 120 minutes after glucose ingestion . was calculated by computer - based model called homeostasis assessment model ( homa - ir ) utilizing fasting blood glucose and fasting serum insulin levels .the whole body insulin sensitivity index ( wbisi ) or matsuda index was calculated by the formula suggested by matsuda and defronzo .area under curve ( auc ) was calculated for blood glucose ( 0 , 60 , and 120 minutes ) and serum insulin ( 0 , 60 , and 120 minutes ) by using trapezoidal rule . \n insulin resistance ( ir ) pubertal stage was assessed by a single endocrinologist , based on breast stage and pubic hair development in girls and genitalia development in boys . subjects were selected from the children and adolescents attending the endocrinology outdoor services at aiims for evaluation of obesity . vitamin d deficiency was defined as a serum 25(oh)d levels less than 20 ng / ml . this was further subdivided to severe , moderate , and mild vitamin d deficiency if serum 25(oh)d levels were < 5 ng / ml , 5<10 ng / ml , and 10<20 ng / ml respectively . fat mass index ( fmi , fat mass in kg / height in meter ) and fat - free mass index ( ffmi , lean body mass+ bmc)/(height in meter ) were calculated .", "pearson 's correlation was used to assess association between continuous variables and partial correlations were used to determine relationship after adjusting for relevant covariates . student 's t - test was used to determine statistical difference between subjects with serum 25(oh)d < 10 ng / ml or more . stepwise linear regression analysis was used with serum 25(oh)d as dependent variable in the model . values for serum 25(oh)d , serum insulin , homa - ir , and matsuda isi were not normally distributed ; therefore , they were logarithmically transformed which yielded normal distribution . continuous variables not showing normal distribution were treated with appropriate log transformations before any parametric analysis .", "no statistical significant difference was seen in blood glucose , serum insulin , and auc for both , glucose and insulin between group 1 and group 2 . trends for higher insulin resistance ( homa - ir ) and lower insulin sensitivity ( wbisi ) were seen in subjects with lower serum 25(oh)d concentrations but not statistically significant . similarly , when prepubertal subjects were compared with all other subjects ( subjects in group 2 and 3 combined ) , significantly higher insulin sensitivity ( wbisi , mean sd 6.07 5.7 versus 3.42 2.7 , p < 0.01 ) and lower insulin resistance ( homa - ir , mean sd 3.68 2.7 versus 5.22 4.0 , p = 0.04 ) were seen in prepubertal subjects . when prepubertal subjects ( group 1 ) were compared with the prepubescent subjects ( group 2 ) , no significant difference was seen in any of the parameters including blood glucose , serum insulin , homa - ir , and wbisi . no significant correlation was seen between vitamin d status and any other parameters including total body fat percentage , fmi and parameters of insulin resistance and sensitivity in the prepubertal ( group 1 ) or peripubertal groups ( group 2 ) . subjects were divided into two groups , group a with serum 25(oh)d level < 10 ng / ml ( n = 41 ) and group b with serum 25(oh)d level 10 ng / ml ( n = 21 ) ( an arbitrary cutoff to compare subjects with mild vitamin d deficiency with moderate and severe vitamin d deficiency , 25 ) . total body fat percentage and fmi were significantly higher in group 1 in comparison to group 2 ( p = 0.015 and 0.007 , resp . ) .", "when subjects were stratified by pubertal stage , only subjects in tanner stage 5 exhibited a significant correlation between serum 25(oh)d and homa - ir , while prepubertal subjects did not show statistically significant correlation . this is the first study examining the relationship between serum 25(oh)d levels and parameters of insulin resistance in obese asian - indian children . the association between serum 25(oh)d and parameters of insulin sensitivity and resistance is influenced by puberty as a significant association was found between these two variables in postpubertal subjects ( tanner stage 5 ) only which remained significant even after adjustment for covariates . as association is not equal to causation , future longitudinal research studies are required in determining role of puberty on association between serum 25(oh)d and insulin resistance in both , obese as well as subjects with normal bmi . we demonstrated trends for that higher serum 25(oh)d levels are associated with better insulin sensitivity and less insulin resistance though this correlation did not reach statistical significance . , our study demonstrates a significant inverse relationship in obese asian - indian children between body fat indices and serum 25(oh)d concentrations which persists even after adjustment of covariates . we also show , for the first time , that the association between serum 25(oh)d and insulin resistance and sensitivity is influenced by pubertal staging ." ]
to study the effect of puberty on the relationship between serum 25-hydroxyvitamin d ( 25(oh)d ) and parameters of insulin kinetics in obese asian - indian children . material and methods . the study population included 62 obese asian - indian children and adolescents in the age group of 617 years . blood glucose , serum insulin , and serum 25(oh)d were measured . total body fat was measured by dual energy x - ray absorptiometry . indices of insulin resistance ( homa - ir , auc for insulin ) and sensitivity ( wbisi ) were calculated after oral glucose tolerance test . result . a total of 62 subjects ( 35 boys ; mean age = 13.0 3 years ; bmi = 29.3 4.8 kg / sq m ; 19 subjects in tanner stage 1 , 11 in stage 2 , 6 in stage 3 , 3 in stage 4 , and 23 subjects in tanner stage 5 ) were studied . all study subjects were vitamin d deficient with a mean serum 25(oh)d of 8.5 4.2 ng / ml . no significant relationship was observed between serum 25(oh)d and parameters of insulin kinetics in prepubertal children . however , a significant inverse correlation was seen between serum 25(oh)d and homair ( r = 0.41 , p = 0.03 ) in postpubertal subjects . conclusion . the relationship between vitamin d status and parameters of insulin kinetics are affected by puberty .
[ "a decision by surgeon was made to perform angiography of the left external carotid artery with subsequent embolization of the bleeding vessel . after a diagnosis of obstructive sleep apnea was made , a bilateral tonsillectomy and uvulopalatopharyngoplasty was planned for treatment . therefore , we injected a bolus of iv sugammadex 200 mg to reverse the residual nmb . a 21-year - old man ( height = 180 cm , weight = 95 kg , body mass index = 29.3 kg / m ) presented to the outpatient department with a long history of frequent and severe snoring . on physical exam ,", "the endovascular embolization due to refractory bleeding after tonsillectomy proved to be a valuable treatment method as an effective alternative to surgical intervention . sugammadex resolved the residual nmb within 2 min , even after reversal with anticholinesterase agents , and is a safe alternative to reversal of nmb induced by steroidal non - depolarizing agents . in this case , deep rocuronium - induced nmb can be reversed successfully with sugammadex at doses of 2 mg / kg and in as little as 2 min . to control bleeding , electrocauterization , packing of the pharynx , or angiographic embolization of the feeding artery may become necessary . the most common anesthetic used for rsi during the management of children with pth is succinylcholine . since the introduction of sugammadex , rsi with rocuronium followed by reversal with sugammadex allowed for earlier establishment of spontaneous ventilation than with succinylcholine , which has many adverse side events . during the second round of anesthesia , rocuronium 100 mg ( 1 mg / kg ) aberrant arterial blood supply to the tonsillar region derived from the internal carotid artery or the carotid bulb may be present ." ]
post - tonsillectomy hemorrhage ( pth ) is the most frequent complication of tonsillectomy , and occasionally results in a lethal outcome . a 21-year - old man ( height 180 cm , weight 95 kg ) was scheduled for a bilateral tonsillectomy and uvulopalatopharyngoplasty for treatment of obstructive sleep apnea . he required 5 rounds of general anesthesia due to recurrent pth . the anesthesiologist used sugammadex a total of 3 times to achieve the successful reversal of the deep neuromuscular blockade ( nmb ) induced by rocuronium . after sugammadex 2 mg / kg was administered , the nmb was reversed in 2 minutes each time . re - administration of rocuronium within a short time interval after sugammadex may result in unpredictable effects of neuromuscular blocking agents . sugammadex made it possible to perform a rapid , complete reverse when the residual block was maintained by an incomplete reversal of anticholinesterase .
[ "infertility has been recognized as a public health issue worldwide ( 1 ) leading to an increasing need to the use of assisted reproductive technologies ( art ) , including in vitro fertilization ( ivf ) . after the first reported case of ivf in 1978(2 ) art enabled millions of people to have their own children in cases when pregnancy did not occur under natural circumstances . the biggest issue with pre - implantation viability assessment is that due to ethical reasons any assay should be completely non - invasive because no one can predict what kind of interference would be the unwanted result in the later embryonic development . it is imperative , however , that accurate and economical methods should be developed to ensure that the most viable euploid embryo is selected for transfer . ideally , such tests would be noninvasive , lessening the risks to the embryo and reducing costs and workload in the embryology laboratory ( 19 ) . earlier clinical protocols preferred multiple embryo transfer , but multiple gestations can result in the increased risk of preterm delivery ( 10 - 16 ) .", "the most apparent and routinely applied - way of the assessment of viability is the morphological evaluation of in vitro fertilized embryos using microscopy . , we aimed to improve the success rate of implantation by adopting and further optimizing the istanbul consensus . there are several morphological features described which could be used for viability assessment purposes , these are dependent on the time spent after fertilization . right after fertilization in the 1-cell embryo the size and symmetry of the two pronuclei can be examined . the time of the first cell division is also a good predictor of later implantation potential , as zygotes that divide early tend to develop more frequently to the blastocyst stage . the reason is partly due to the fact that the final decision is made by a clinician , and not by an objective test result , and secondly it is does matter how important are the individual morphological features in the final conclusion ( 24 - 26 ) . to overcome the different practice of laboratories worldwide in 2011 an international consensus ( istanbul consensus ) has been reached on embryo viability assessment ( 27 )", "another possibility for non - invasive embryo viability assessment is the metabolomic examination of the culture medium surrounding the in vitro fertilized embryo . metabolomic , ( proteomic ) profiling of spent embryo culture ( sec ) offers an exceptional , non - invasive opportunity for the assessment of embryo viability ( 30,31 ) . mass spectrometry ( ms ) has the potential of specific and sensitive quantification in a wide spectrum of molecular mass ranges and therefore suites well the needs of metabolomic or proteomic fingerprinting and quantification . in parallel to the spreading of mass spectrometry , proteomics is also an emerging field in the understanding of embryo development ( 39,40 ) . the analysis of the embryonic secretome ( 41,42 ) provides information of the total transcriptome of the developing embryos . mass spectrometry can be used both in targeted and discovery analysis with accurate quantification of identified biomarkers after molecular identification by bottom - up or top - down proteomics using tandem or multiple ms ( 43 - 46 ) . in a recent publication from our laboratory ( 47 ) using liquid chromatography coupled mass spectrometry ( lc - ms ) , a fragment of the human haptoglobin molecule was identified in the culture medium . rather than analyzing the embryonic secretome , the aim this experiment was to use preexisting molecules present in the cell culture media as biomarkers ." ]
human reproduction is a relatively inefficient process and therefore the number of infertile couples is high . assisted reproductive technologies ( art ) have facilitated the birth of over five million children worldwide . art , however , superimposes its own relative inefficiency on the preexisting inefficiency of normal reproduction . the efficiency ( expressed as pregnancy rate ) is generally not more than 30% . modern reproductive medicine is gradually moving from multiple embryo transfer to the transfer of a single embryo , mainly because of obvious and unwanted side effects of multiple embryo transfer ( e.g. epidemic multiple pregnancies ) . this concept , however , requires a fast , professional selection of the most viable embryo during the first few days of art . thus the aim of a modern art is the safe transfer of a healthy , viable , single embryo . accurate and rapid methods of quantifying embryo viability are needed to reach this goal . methodological advances have the potential to make an important contribution , and there has been a drive to develop alternative non - invasive methods to better meet clinical needs . metabolic and genetic profiling of spent embryo culture ( sec ) media should offer an exceptional opportunity for the assessment of embryo viability . the current review focuses on the latest non - invasive diagnostic approaches for pre - implantation viability assessment of in vitro fertilized embryos .
[ "in addition , we examined the association between vitamin d status and risk of having 1 ) newly diagnosed type 2 diabetes or 2 ) a known diagnosis of type 2 diabetes using the same models separately . finally , the same approach was used to estimate the influence of fish intake on risk of having type 2 diabetes using subjects reporting fish intake less than or equal to two times per week as a reference group . in the models , we further tested whether there was evidence of an interaction effect between vitamin d status and sex and vitamin d status and obesity . were included , i.e. , bmi , serum triacylglycerides , serum hdl , pcb exposure ( sum of major pcb congeners cb-138 , cb-153 , and cb-180 multiplied by 2 ) , smoking , and month of blood sampling . a logistic regression model was used to assess the association between serum 25(oh)d3 concentration and the risk of having type 2 diabetes . insulin resistance was estimated by the homeostasis model assessment ( homa - ir ) and calculated as fpi fpg / 22.5 ( 10 ) , where fpi is fasting plasma insulin and fpg is fasting plasma glucose . this study is part of a larger project examining the possible health effects of lifetime exposure to marine food and pollutants .", "insulin resistance was estimated by the homeostasis model assessment ( homa - ir ) and calculated as fpi fpg / 22.5 ( 10 ) , where fpi is fasting plasma insulin and fpg is fasting plasma glucose . a fasting capillary blood sample was used to determine blood glucose concentration using a direct - reading glucose biosensor ( precision xceed and abbott precision xtra plus strips ; abbott diabetes care , copenhagen , denmark ) . because plasma has higher water content than whole blood , the blood values diabetic subjects were identified from self - reported doctor s diagnosis and the reported use of hypoglycemic medication ; subjects were also classified as diabetic if they reported use of diabetes medication without reporting a diagnosis of diabetes . in participants -cell dysfunction was determined by calculating the homa -index of ( 20 fpi)/(fpg 3.5 ) ( 10 ) . not previously diagnosed , type 2 diabetes was considered to be present if the fasting plasma glucose was 7.0 were transformed to plasma glucose concentration by multiplying by 1.12 as recommended by the manufacturer .", "after storage at 80c , serum 25(oh)d3 concentrations were assessed using liquid chromatography - tandem mass spectrometry ( lc - ms / ms ) as described previously ( 11 ) . nmol / l , and the coefficient of variation was 9.6% at 20 nmol / l and 6.7% at 60 nmol / l .", "in addition , we examined the association between vitamin d status and risk of having 1 ) newly diagnosed type 2 diabetes or 2 ) a known diagnosis of type 2 diabetes using the same models separately . finally , the same approach was used to estimate the influence of fish intake on risk of having type 2 diabetes using subjects reporting fish intake less than or equal to two times per week as a reference group . in the models a logistic regression model was used to assess the association between serum 25(oh)d3 concentration and the risk of having type 2 diabetes . , we further tested whether there was evidence of an interaction effect between vitamin d status and sex and vitamin d status and obesity . a value of p < 0.05 ( two - tailed ) was taken to indicate statistical significance . vitamin d status was used as a binary exposure variable , i.e. , dichotomized at above ( sufficient ) or below 50 nmol / l ( deficient ) , and in the simple model , sex was used as an obligate covariate . in the adjusted model , additional covariates were included , i.e. , bmi , serum triacylglycerides , serum hdl , pcb exposure ( sum of major pcb congeners cb-138 , cb-153 , and cb-180 multiplied by 2 ) , smoking , and month of blood sampling . control subjects were nondiabetic subjects , i.e. , subjects with fasting blood glucose 6 mmol / l .", "mmol / l ; the crude model is adjusted for sex and compares the odds of either overall type 2 diabetes ( all type 2 diabetic subjects ) , newly diagnosed type 2 diabetes ( new subjects ) , or known type 2 diabetes in subjects ( previously known subjects ) with 25(oh)d < 50 after further adjustment for bmi , serum triacylglycerides , serum hdl , pcb exposure , smoking , and month of blood sampling , the association between vitamin d deficiency and type 2 diabetes remained , and the or was only marginally affected ( or 1.67 [ 1.112.50 ] ; p = 0.013 ) . in the separate analyses of previously undiagnosed and diagnosed subjects , we found that the sex - adjusted or for having newly diagnosed type 2 diabetes in the presence of vitamin d deficiency had more than doubled ( or 2.25 [ 95% ci 1.313.85 ] ; p = 0.003 ) . after further adjustment for bmi , serum triacylglycerides , serum hdl , pcb exposure , smoking , and month of blood sampling , the association between vitamin d deficiency and newly diagnosed type 2 diabetes remained unchanged ( or 1.99 [ 1.143.48 ] ; p = 0.022 ) , whereas the adjusted or for pre - existing diabetes in vitamin d deficiency was reduced considerably by similar adjustment ( or 1.48 ; p = 0.132 ) ( table 2 ) . obesity is a risk factor for vitamin d deficiency , and obese subjects had a lower serum 25(oh)d3 concentration than nonobese subjects ( 11 ) . nmol / l , was associated with an 80% increase in the sex - adjusted odds of having diabetes ( newly diagnosed and previously diagnosed subjects ) compared with sufficient vitamin d status ( odds ratio [ or ] 1.80 [ 95% ci 1.232.64 ] ; p = 0.002 ) .", "in this cross - sectional analysis of a population - based sample of septuagenarians , we found that the 25(oh)d3 concentration was inversely associated with the risk of newly diagnosed type 2 diabetes after adjustment for bmi and other established risk factors for type 2 diabetes . our study extends previous findings that a high vitamin d status protects against type 2 diabetes in younger subjects to subjects older than 70 years . subjects with 25(oh)d3 concentration below 50 nmol / l had the doubled risk of newly diagnosed diabetes compared with those having higher serum concentrations . therefore , our data suggest an inverse association between the serum concentration of 25(oh)d3 and the odds of newly diagnosed type 2 diabetes , thereby suggesting a protective role of vitamin d against the development of the disease , as suggested previously ( 13 ) . in further support of this association , we observed an increasing concentration of hba1c with decreasing 25(oh)d3 concentration , and this association was independent of bmi , serum triacylglycerides , smoking status , and sex . the results suggest that the negative impact of vitamin d deficiency on hba1c and newly diagnosed type 2 diabetes risk is independent of increased fat mass ." ]
objectivevitamin d deficiency is thought to be a risk factor for development of type 2 diabetes , and elderly subjects at northern latitudes may therefore be at particular risk.research design and methodsvitamin d status was assessed from serum concentrations of 25-hydroxyvitamin d3 [ 25(oh)d3 ] in 668 faroese residents aged 7074 years ( 64% of eligible population ) . we determined type 2 diabetes prevalence from past medical histories , fasting plasma concentrations of glucose , and/or glycosylated hemoglobin ( hba1c).resultswe observed 70 ( 11% ) new type 2 diabetic subjects , whereas 88 ( 13% ) were previously diagnosed . having vitamin d status < 50 nmol / l doubled the risk of newly diagnosed type 2 diabetes after adjustment for bmi , sex , exposure to polychlorinated biphenyls , serum triacylglyceride concentration , serum hdl concentration , smoking status , and month of blood sampling . furthermore , the hba1c concentration decreased at higher serum 25(oh)d3 concentrations independent of covariates.conclusionsin elderly subjects , vitamin d sufficiency may provide protection against type 2 diabetes . because the study is cross - sectional , intervention studies are needed to elucidate whether vitamin d could be used to prevent development of type 2 diabetes .
[ "we have developed a leaf senescence database ( lsd ) ( http://www.eplantsenescence.org/ ) by retrieving and integrating information from research papers and public databases . at present users can browse the entries in the database to obtain information including literatures , mutants , phenotypes , expression profiles , mirna interactions , orthologs in other plants and cross links to protein domain and family databases . we have implemented the blast tool kit for sequence similarity search against nucleotide or protein sequences of these sags in the lsd . a major feature of the lsd is the integration of a bioinformatics platform weblab we had developed previously ( 6 ) , which allows users to perform extensive sequence analysis of the sags they are interested in . we plan to identify putative sags from completely sequenced genomes and add them into the database in the near future , and improve the user interface based on user feedback , provide more help documents with case studies , add more links to other useful sites , and update the database in time with more leaf senescence related data available . 1145 sags from 21 species were manually curated and categorized into several groups according to their function . we hope that lsd could be a useful resource for the leaf senescence research community , as well as a gateway for the collaborative project we are working with both domestic and international colleagues . sennet brings together various community information including meetings , laboratories , websites and useful links related to plant senescence , while senwiki provides general information and knowledge of senescence with texts and images .", "we made an extensive literature survey and collected approximately 200 leaf senescence related papers published before october 2010 on major plant biology journals including plant cell , plant physiology , plant journal , new phytologist , journal of experimental botany , among others . a total of 1145 sags from 21 species including arabidopsis , rice and so on , were identified and manually verified based on genetic , genomic , proteomic , physiological and other experimental evidence . among them , sativaalfalfa101rosa hybridrose100triticum turgidumwheat101triticum aestivumwheat100total2111459658 number of sags and mutants in 21 species the information of 154 leaf senescence related mutants such as name , ecotype and mutagenesis method were also retrieved from literatures . 96 and 58 genes were supported by mutational investigation or transgenic over - expression study , respectively ( table 1 ) . \n the orthologs of each sag in other plants were retrieved from the online database orthomcl - db ( 8) . finally , putative function domains of sags - encoding proteins were identified with interproscan ( 9 ) . we predicted the potential mirna targets for the sags using the rnahybrid method ( 7 ) . in addition to manual curation , computational approaches were also employed to annotate these sags .", "users may retrieve sequence data and submit to weblab directly to perform extensive analysis for dna , mrna and protein sequences of the sags they are interested in . to meet the general requirement of data analysis , we integrated the sequence similarity search tool blast ( 10 ) and the sequence analysis platform weblab ( 6 ) into our leaf senescence database . weblab is a web - based bioinformatics platform developed by our center and publicly available worldwide ( http://www.weblab.org.cn/ ) ( 6 ) . users can either retrieve the sequence from lsd , or upload their own sequences to search homologs against different divisions ( gene , mrna , cds and protein ) in the lsd . a user space is provided to save input data and analysis results for registered users .", "the lsd database enables users to retrieve and analyze sags through the browse or search page . a tree - like structure was designed for both species and phenotypes , and a table was created for mutants . currently , the major source of sags was from the two model organisms a. thaliana ( 949 entries ) and oryza sativa ( 104 entries ) . the text search interface allows users to make queries with three types of data : ( i ) locus name , genbank i d , alias , species and description of genes ; ( ii ) name , type and ecotype of mutants ; and ( iii ) title , author , journal and date of literature papers . we predicted potential mirna targets for some sags and added links to mirbase ( 12 ) for these mirnas ( figure 2a ) . ( a ) mirna targets , ( b ) ortholog groups and ( c ) cross links to other databases . ( a ) mirna targets , ( b ) ortholog groups and ( c ) cross links to other databases . a typical entry in lsd , the arabidopsis nac transcription factor .", "users can click these links to bring up the corresponding sequence and submit it to weblab for further analysis , such as predicting gene structures , making pairwise or multiple sequence alignment , generating sequence logos , constructing phylogenetic trees , finding sequence motifs , etc . in addition to sequence similarity search with the blast tool kit implanted in the database , users may also perform extensive analysis for sequence data retrieved from the lsd . for each entry , links to different sequence types ( genomic , mrna , cds and protein ) are provided .", "we will update the database regularly with more leaf senescence related data available , and predict putative sags from completely sequenced plant genomes in the near future . we will improve the user interface with comments and suggestions from the user community and add more documents including case studies to help user to make thorough analysis of sags . we hope that lsd can be a platform not only for the domestic and international collaborators we are working with , but also for the research community of leaf senescence worldwide .", "national natural science foundation of china ( 31071160 to j.l . , 30625003 and 30730011 to h.g . ) ; ministry of science and technology of china ( 2009cb119101 to h.g . ) ; ministry of education of china ( ngi2008 - 108 - 3 to j.l . , ed20060047 to h.g . ) . funding for open access charge : national laboratory of protein engineering and plant genetic engineering ." ]
by broad literature survey , we have developed a leaf senescence database ( lsd , http://www.eplantsenescence.org/ ) that contains a total of 1145 senescence associated genes ( sags ) from 21 species . these sags were retrieved based on genetic , genomic , proteomic , physiological or other experimental evidence , and were classified into different categories according to their functions in leaf senescence or morphological phenotypes when mutated . we made extensive annotations for these sags by both manual and computational approaches , and users can either browse or search the database to obtain information including literatures , mutants , phenotypes , expression profiles , mirna interactions , orthologs in other plants and cross links to other databases . we have also integrated a bioinformatics analysis platform weblab into lsd , which allows users to perform extensive sequence analysis of their interested sags . the sag sequences in lsd can also be downloaded readily for bulk analysis . we believe that the lsd contains the largest number of sags to date and represents the most comprehensive and informative plant senescence - related database , which would facilitate the systems biology research and comparative studies on plant aging .
[ "female study participants were recruited from participants in a cross - sectional study assessing bmd in young women with type 1 diabetes and age - matched community control subjects ( 7 ) . post hoc power analysis of follow - up total hip bmd ( adjusted for age , bmi , and oc use ) indicated that our dataset of 63 case subjects ( n = 37 , < 20 years of age ) and 85 control subjects ( n = 36 , < 20 years of age ) gave our study 80% power to detect a difference between case and control subjects with an of 0.05 and a target effect size of 0.45 in women < 20 years of age and 0.63 in those > 20 years of age . , study participants completed questionnaires relating to personal and family health , lifestyle habits , dietary intake ( food frequency questionnaire ) , and medication intake including use of calcium supplements . all type 1 diabetic case subjects and nondiabetic control subjects who participated in the baseline study were recruited 2 years later to assess change in bmd over time . cases for the cross - sectional study ( baseline ) were recruited from a regional tertiary hospital pediatric diabetes center and from endocrinology practices in western new york . at the time of the initial study , the diabetes center followed over 600 patients aged 221 years with type 1 diabetes . the baseline study enrolled 72 case subjects ( diabetes duration > 2 years ) and 91 control subjects aged 1337 years who were at least 2 years postmenarchal ( 7 ) . female patients aged 1321 years in that clinical center were offered the opportunity to participate in the baseline study ( n = 138 ) . recruitment of older women involved contacting former center patients ( aged > 21 years ) , patients from regional endocrinology practices , and affected relatives of subjects screened by our diabetes center for the diabetes prevention trial .", "as in our previous study , there was no association found between bmd and diabetes duration , baseline a1c , or years since menarche . in addition , the percent change in osteocalcin level from baseline to follow - up was significantly different in diabetic women 20 years of age compared with control subjects after adjustment ( p < 0.03 ) . markers of bone formation did not correlate with bmd in our subjects . significant differences in bmd were identified at the total hip , femoral neck , and whole body in the case subjects 20 years of age compared with the control subjects . as in the previous report , no differences in bmd were seen between groups in the younger cohort . in the adjusted model ( for age , bmi , and oc use ) , bmd values at the total hip ( baseline , p = 0.003 ; follow - up , p = 0.007 ) and femoral neck ( baseline and follow - up , p < 0.001 ) were significantly lower in older women with diabetes compared with control subjects . after adjustment , the whole - body bmd was no longer significantly different between case and control subjects ; however , both age - groups showed a trend toward lower whole - body bmd in the case subjects . the follow - up group included 63 women with type 1 diabetes ( 58.7% < 20 years of age ) and 85 control subjects without diabetes ( 42.4% < 20 years of age ) at ages 1539 years at enrollment .", "while longitudinal studies have examined the effect of insulin therapy on bmd in patients with long - standing type 1 diabetes ( 12 ) , few have reported on the natural history of metabolic bone disease in younger women . here our findings demonstrate lower bmd in young women with type 1 diabetes compared with control subjects . we present bmd data for a well - characterized cohort of young women with type 1 diabetes at baseline and 2 years later . although bone density testing is not routinely performed in young women , these data suggest that screening may be important in young women with type 1 diabetes . the data presented here demonstrate that case subjects in the older cohort had persistently lower bmd than age - matched healthy control subjects . in this cohort ," ]
objective individuals with type 1 diabetes have decreased bone mineral density ( bmd ) , yet the natural history and pathogenesis of osteopenia are unclear . we have previously shown that women with type 1 diabetes ( aged 1335 years ) have lower bmd than community age - matched nondiabetic control subjects . we here report 2-year follow - up bmd data in this cohort to determine the natural history of bmd in young women with and without diabetes.research design and methods bmd was measured by dual - energy x - ray absorptiometry at baseline and 2 years later in 63 women with type 1 diabetes and in 85 age - matched community control subjects . a1c , igf-1 , igf binding protein-3 , serum osteocalcin , and urine n - teleopeptide were measured at follow-up.resultsafter adjusting for age , bmi , and oral contraceptive use , bmd at year 2 continued to be lower in women 20 years of age with type 1 diabetes compared with control subjects at the total hip , femoral neck , and whole body . lower bmd values were observed in cases < 20 years of age compared with control subjects ; however , the differences were not statistically significant . lower bmd did not correlate with diabetes control , growth factors , or metabolic bone markers.conclusionsthis study confirms our previous findings that young women with type 1 diabetes have lower bmd than control subjects and that these differences persist over time , particularly in women 20 years of age . persistence of low bmd as well as failure to accrue bone density after age 20 years may contribute to the increased incidence of osteoporotic hip fractures seen in postmenopausal women with type 1 diabetes .
[ "the aim of the current study was to assess the enamel cracks after debonding of brackets bonded with two different adhesive systems and also to evaluate enamel cracks after removing adhesive remnants and enamel polishing . acid - etching , rinsing , drying and applying resin and bonding agents are the routine steps of conventional orthodontic bracket bonding . traditional methods of bonding orthodontic brackets to teeth rely on acid etching to achieve adequate retention . many studies have shown that bracket debonding can cause enamel loss , particularly when the fracture occurs at the enamel - adhesive interface", "the adhesive remnants on each tooth were then assessed with the ari in a 03 scale : 0 indciates no composite left on the tooth ; 1 indicates less than half of the composite left on the tooth , 2 indicates that more than half of the composite is left on the tooth surface and 3 shows that all the composite is left on the tooth surface with a distinct impression of the bracket base . a standard edgewise twin metal bracket ( dentaurum , pforzheim , germany ) was bonded with transbond xt ( 3 m , usa ) to the center of the labial surface of each tooth . in the second group , the present method of force application was modified from a diametric compression test for tension that indirectly measures tensile strength . the teeth were then randomly divided into two equal groups . in the first group , the buccal surface of each central incisor after debonding , the buccal surfaces of the teeth in each group were examined by the same stereomicroscope and the magnified images ( 23.9 x ) were taken with the same digital camera . the number of enamel cracks and the length and the direction of each crack were assessed with the aid of the same software . the enamel cracks in each group were compared before bonding , after debonding and after polishing using repeated measures anova .", "the result of the independent t - test indicated that the mean shear bond strength of maxcem elite ( the self - adhesive composite cement ) was significantly lower than that of transbond xt ( the adhesive composite ) ( p<0.001 ) . there were significantly more enamel cracks in the transbond xt group after debonding and polishing compared to the maxcem elite group . in the maxcem elite group , the difference in the number of enamel cracks before and after debonding was statistically significant ( p<0.001 ) . ( 0 , no composite left on the tooth ; 1 , less than half of the composite left on the tooth ; 2 , more than half of the composite left on the tooth ; 3 , all the composite left on the tooth with a distinct impression of the bracket base ) there were no significant inter - group differences in the number of enamel cracks before debonding . sd : standard deviation significant difference significant difference between a and b ( wilcoxon test ) there was no significant difference in the length of enamel cracks between the two groups . in each group , however , a significant increase in the length of enamel cracks was obvious after debonding . the difference , however , was not significant after debonding and after polishing ( p=0.06 ) . the mean sbs of maxcem elite and transbond xt was 10.291.14 and 11.481.09 , respectively .", "the result of the independent t - test indicated that the mean shear bond strength of maxcem elite ( the self - adhesive composite cement ) was significantly lower than that of transbond xt ( the adhesive composite ) ( p<0.001 ) . the mean sbs of maxcem elite and transbond xt was 10.291.14 and 11.481.09 , respectively .", "there were significantly more enamel cracks in the transbond xt group after debonding and polishing compared to the maxcem elite group . in the maxcem elite group , the difference in the number of enamel cracks before and after debonding was statistically significant ( p<0.001 ) . the number of visible enamel cracks followed a similar pattern . in each group , before and after debonding , a significant intra the difference , however , was not significant after debonding and after polishing ( p=0.06 ) . there were no significant inter - group differences in the number of enamel cracks before debonding . sd : standard deviation significant difference significant difference between a and b ( wilcoxon test ) however , before and after polishing , the difference was not significant ( table 2 ) .", "there was no significant difference in the length of enamel cracks between the two groups . in each group , however , a significant increase in the length of enamel cracks was obvious after debonding . repeated measures test sd : standard deviation significant difference significant difference between a and b ( wilcoxon test )", "the mann - whitney - u test showed that the differences were statistically significant among the groups ( p=0.0001 ) ( table 4 ) . the adhesive remnant index ( ari ) ( 0 , no composite left on the tooth ; 1 , less than half of the composite left on the tooth ; 2 , more than half of the composite left on the tooth ; 3 , all the composite left on the tooth with a distinct impression of the bracket base )", "the main objective of this study was to evaluate the enamel cracks after debonding brackets , bonded with two different bonding systems followed by polishing . the sbs of maxcem elite , a self - adhesive cement , and transbond xt , a conventional adhesive composite , was also compared . the number and length of enamel cracks before bonding , after debonding and after polishing were also compared as well as the ari following the removal of orthodontic brackets . before bonding", "debonding brackets bonded with maxcem elite resulted in less enamel cracks . removing remnants of adhesives and polishing with a 12-blade tungsten carbide bur did not increase enamel cracks . maxcem elite has clinically acceptable bond strength and can be used as a routine adhesive for orthodontic purposes ." ]
objectives : the objective of this study was to assess the effect of new bonding techniques on enamel surface.materials and methods : sixty upper central incisors were randomly divided into two equal groups . in the first group , metal brackets were bonded using transbondxt and , in the second group , the same brackets were bonded with maxcem elite . the shear bond strength ( sbs ) of both agents to enamel was measured and the number and length of enamel cracks before bonding , after debonding and after polishing were compared . the number of visible cracks and the adhesive remnant index ( ari ) scores in each group were also measured.results:there were significantly more enamel cracks in the transbond xt group after debonding and polishing compared to the maxcem elite group . there was no significant difference in the length of enamel cracks between the two groups ; but , in each group , a significant increase in the length of enamel cracks was noticeable after debonding . polishing did not cause any statistically significant change in crack length . the sbs of maxcem elite was significantly lower than that of transbond xt ( 95% confidence interval).conclusion : maxcem elite offers clinically acceptable bond strength and can thus be used as a routine adhesive for orthodontic purposes since it is less likely to damage the enamel .
[ "sensitive skin is a common term used by patients and clinicians , as well as the cosmetic industry , and represents a complex clinical challenge faced by dermatologists and other skin care professionals . sensitive skin syndrome is a common and challenging condition , yet little is known about its underlying pathophysiology . fisher is credited with coining the term status cosmeticus to describe one extreme of the natural history of the cis in which the patient gradually becomes completely intolerant to the application of any cosmetic product . patients with sensitive skin often present with subjective complaints that are out of proportion to the objective clinical findings . the patients complain of severe facial irritation , burning , and/or stinging after application of cosmetic products and toiletries such as sunscreens and soaps , yet they do not demonstrate the clinical stigmata of scaling , induration , and/or erythema that would be expected in known inflammatory or allergic processes . fundamentally , sss is a state of hyperreactivity to environmental stimuli , presenting with a clear clinical picture and resulting from a single underlying pathology or a combination of pathologies . maibach described the cosmetic intolerance syndrome ( cis ) , which probably covers the bulk of the clinical presentation of the sensitive skin syndrome ( sss ) .", "some of the contradictions between investigators could be explained by flawed methodologies since the scientific community has yet to identify an acceptable objective screening test for sensitive skin . he therefore deduced that it is inappropriate to define a subject 's reaction to a chemical based on his or her response to another irritant . robinson , by performing patch testing with sodium dodecyl sulfate ( sds ) and looking for intra - individual response patterns , found that there is significant positive correlation between sds and other irritants but noted overall low correlation coefficients . this data resonate the idea that even the reference irritants commonly used in studies of this topic do not correlate with each other and with hyperreactivity tendencies . sds- or lactic acid - positive group , a reaction to one irritant could not predict a reaction with another . to further complicate matters there is evidence to suggest that no correlation exists between the lactic acid stinging test and the response to sds . she skin - tested 58 subjects with history of strong positive sds or lactic acid response . this complexityreinforces the need for a thorough diagnostic algorithm and , specifically , the need to test patients with multiple , repeated and complete ( i.e. all cosmetics applied by the patient at home ) patch testing before making a diagnosis .", "lacking an objective screening test , investigators resorted to epidemiological studies using patient surveys . in a large epidemiological study in the uk ( these findings were supported in a critical literature review , which showed that the evidence supporting the ethnic difference hypothesis using objective tests rarely reaches statistical significance and is often biased by subjective endpoints . in order to formulate a systematic clinical approach , the medical and cosmetic communities have attempted to characterize the condition . recent data looking into age - related differences in hyperreactivity are showing more consistent results .", "there is a known inverse relationship between corneocyte size and stratum corneum thickness and the permeability of the skin , and changes in this mechanical barrier result in abnormal skin penetration by irritants . the mechanism leading to the sss has been debated in the literature , but the leading hypothesis relates to increased stratum corneum permeability . increased erythema was objectively measured in hyperreacting subjects suggesting involvement of some baseline vascular component , and leading more recent investigators to propose the involvement of cutaneus sensory innervation in the pathogenesis of sss . in addition , low levels of ceramides in the stratum corneum have been linked to increased severity of sls - induced irritant contact dermatitis , pointing toward barrier compromise in sensitive skin . seidenari linked self - reported hyperreactivity to decreased skin capacitance ( indicating decreased water content ) , objectively suggesting increased absorption of irritants by the sensitive - skin population . in the same study ,", "eczema , atopic dermatitis , and rosacea are likely the three most common causes of sss related to barrier defect . maibach notes that patients suspected of having bdd often require a detailed diagnostic process in order to build the trust needed to safely refer them to the mental health professional . table 2 summarizes the steps in the evaluation of a patient suspected to have sss . the main reason why nicu is often a missed diagnosis in patients presenting with the sss is the transient nature of the reaction . , dermatologists should be aware that facial irritation complaints without any findings on exam are a common presentation in the dysmorphic patients and therefore extra caution is warranted . following specific treatment to halt the acute pathological process , preventing recurrence with a proper skin care regimen is indicated . in eczema and atopic dermatitis , the careful clinician may resort to short - term ( 2-week ) use of corticosteroids to stop the inflammatory process . finally , body dysmorphic disorder ( bdd ) should always be considered by the dermatologist when assessing skin complaints without objective findings .", "the next step in management is slow re - introduction of the minimally necessary skin care products . for females , specific algorithms have been developed for the management of sss but they are the result of accumulated clinical experience and lack experimental evidence to support their use . nonetheless , algorithmic thinking may aid in ensuring complete assessment . discontinuation of all topical medication and/or products , as well as elimination of activities and clothing resulting in skin friction , should be initiated and may need to last up to 12 months . the patient should then be assessed ( as described above ) for the occurrence of any visible dermatoses . if no clear pathology has emerged , rigorous testing is the next step . this exhausting process is not only a rational solution from a clinical management standpoint but may also aid in diagnosing the specific culprit in cases of invisible sss . testing should include patch and photopatch testing of routine allergens as well as of all of the patient 's skin care items . specific testing for contact urticaria should be a part of the testing protocol . finally , these algorithms include four basic steps : discontinuation , assessment , testing , and slow re - introduction .", "female self - perception of sensitivity is consistently increased compared to that of males , yet when put through objective reactivity testing the trend is unclear . this will allow clinical studies to rely on objective findings rather than self - reports and this , in turn , may result in more comprehensive and efficient management strategies . understanding the underlying mechanisms may lead to the development of a well - standardized screening test . it is reasonable to organize the differential diagnosis by dividing sss into visible and invisible sss ." ]
sensitive skin syndrome ( sss ) is a common and challenging condition , yet little is known about its underlying pathophysiology . patients with sss often present with subjective complaints of severe facial irritation , burning , and/or stinging after application of cosmetic products . these complaints are out of proportion to the objective clinical findings . defined as a self - diagnosed condition lacking any specific objective findings , sss is by definition difficult to quantify and , therefore , the scientific community has yet to identify an acceptable objective screening test . in this overview we review recent epidemiological studies , present current thinking on the pathophysiology leading to sss , discuss the challenges sss presents , and recommend a commonsense approach to management .
[ "although , sp is a relatively common condition , bilateral primary spontaneous pneumothorax ( bpsp ) is a very rare clinical condition with an occurrence ranging from 1.3 to 1.9% of all cases of sp . herein , we present a case of bpsp in an overweight young male patient , which is an exceptionally rare event . spontaneous pneumothorax ( sp ) comprises the largest group and is classified into primary spontaneous ( psp ) and secondary spontaneous pneumothorax . psp usually occurs in young , tall , thin men , especially smokers , in the absence of an underlying lung disease .", "three years after , no recurrence of pneumothorax took place and the patient remains healthy . \n recurrence of pneumothorax on the left side after removing the chest tube . during hospitalization a chest computed tomography ( ct ) was performed and revealed the presence of blebs at the apices of both upper lungs ( fig . the patient was referred to a tertiary center for an elective video - assisted thoracoscopic surgery intervention ( vats ) . plain chest x - rays on admission revealing bilateral pneumothorax . on emergency basis , the patient was managed with bilateral tube thoracostomy through the fifth intercostal spaces . during hospitalization", "the patient was successfully managed initially with a bilateral tube thoracostomy and finally with an elective bilateral vats procedure . in conclusion , bpsp is a rare clinical condition and usually develops in patients with low bmi and bilateral blebs / bullae . the present report describes a case of bpsp in an overweight patient showing that psp is an existing condition in patients with bmi value higher than the normal . diagnosis of bilateral pneumothorax presents difficulties ; while unilateral pneumothorax is relatively easily suspected from the patient 's medical history , physical and radiological findings , the diagnosis of bilateral pneumothorax is usually delayed . bpsp in overweight - obese patients is an existing condition and its early diagnosis requires high suspicion index .", "" ]
bilateral primary spontaneous pneumothorax ( bpsp ) is a rare condition , accounting for 1.6% of spontaneous pneumothoraces . patients with primary spontaneous pneumothorax have typically low body weight . bpsp in overweight / obese patients is an exceptionally rare event . the present report describes a case of an otherwise - healthy 20-year - old male patient with bmi 29.8 kg / m2 presented to our hospital owing to low - intensity chest pain and shortness of breath 7 days after the onset of symptoms . plain chest x - ray revealed the presence of bilateral pneumothorax . chest tubes were inserted on both sides . during hospitalization , a computed tomography demonstrated multiple blebs on the surface of the upper lobes of both lungs . hereupon , the patient referred to a tertiary center and underwent elective single - stage minimally invasive bilateral video - assisted thoracoscopic surgery . the present case report shows that bpsp in overweight / obese patients is an existing condition .
[ "previous familial adenomatous polyposis studies have focused upon faecal sterols and bile acids [ 1517 ] , but none has to the best of our knowledge analysed the content of fatty acids in feces , including very long chained fatty acids . colorectal cancers arising in patients with familial adenomatous polyposis can be largely prevented by polyp surveillance and prophylactic colectomy . the results describe the content of fatty acids in feces , and relate this to the proportions of fatty acids and levels of cyclooxygenase mrna expression in duodenal biopsies , diet , and levels of serum lipoproteins . because the effects of ileostomy construction may differ from that of ileal - pouch - anal anastomosis because of scarcity of the bacterial flora and different surface area of the terminal ileum , we did separate analyses for these two groups . hypothetically , ileal - pouch - anal anastomosis and ileostomy patients might differ with regard to the presence of various fatty acids in feces and their relationship to other reflections of lipoprotein metabolism , but we found no previous study focusing upon this issue . familial adenomatous polyposis account for 1% of colorectal cancers , and provides a model of apc inactivation as an early genetic event for the approximately 80%85% of cancers that develop from sporadic polyps .", "the present study comprises data from baseline for only the patients operated with ileal - pouch - anal anastomosis and ileostomy ( 77% of total study group ) . the main aim was to compare the effect of rofecoxib treatment on duodenal lesions ( data in preparation ) . data from the present study are taken from a randomized double - blind placebo - controlled intervention study with a cyclooxygenase-2 inhibitor [ 12 , 14 , 18 ] . all of them had been colectomized , and duodenal lesions had been verified by endoscopy and histology . they were asked to identify their habitual choices of edible fats by pointing at specially prepared pictures , in order to increase the validity of the estimate of dietary fat . dietary intake was assessed by a validated food frequency questionnaire , designed to cover as much of the total habitual diet as possible .", "age and fecal content of palmitolic acid , linoleic acid , and arachidonic acid differed between the ileostomy and the ileal - pouch - anal anastomosis patients ( table 1 ) . no significant correlations were found between the content of different fatty acids in feces and the levels of cyclooxygenase mrna expression in duodenal biopsies ( data not shown ) . several different fatty acids in feces correlated positively to dietary intake of fatty acids , most predominantly monounsaturated fatty acids ( table 2 ) . the content of linoleic acid in feces correlated negatively to the proportion of eicosaenoic acid in duodenal biopsies ( r = 0.6 , p < .05 ) . moreover , the content of linoleic acid in feces correlated significantly to the proportion of myristic acid ( r = 0.8 , p < .001 ) in duodenal biopsies , whereas the content of alpha - linolenic acid in feces correlated inversely to eicosaenoic acid ( r = 0.6 , p < no significant correlations were found between the content of different fatty acids in feces and the fatty acid dietary intake ( data not shown ) . with the exception of the palmitoleic acid / palmitic acid ratio and levels of cyclooxygenase-2 expression in duodenal biopsies ( r = 0.8 , p = .003 ) , no relationships were found between fatty acids in feces and the levels of cyclooxygenase mrna expression ( figure 1 ) . the content of arachidonic acid in feces was correlated negatively to the proportions of eicosapentaenoic acid ( r = 0.7 , p = .02 ) and docosahexaenoic acid ( r = 0.7 , p = .008 ) in duodenal biopsies .", "we may suggest that fatty acid content in feces is related to dietary intake , serum lipids , and fatty acid composition in duodenal biopsies , even in colectomized familial adenomatous polyposis patients . nevertheless , we suggest that these data are compelling enough to suggest that future familial adenomatous polyposis studies should investigate overall fatty acid metabolism , molecular mechanisms relevant to fatty acid metabolism , inflammation , and angiogenesis , in addition to nutrition requirements . in conclusion , we found a difference between ileal - pouch - anal anastomosis and ileostomy patients concerning associations between fecal fatty acid composition and other variables involved in lipoprotein metabolism . as expected , we found a difference between ileal - pouch - anal anastomosis and ileostomy patients concerning associations between fecal fatty acid composition and other variables involved in lipoprotein metabolism . we found no significant relationships between the levels of cyclooxygenase mrna expression in duodenal biopsies and the content of fatty acids in feces , except for the estimates of the content of delta-9-desaturase ( stearoyl - coa desaturase , scd ) activity , namely the ratio of palmitolic acid / palmitic acid [ 19 , 20 ] in the ileostomy group ." ]
a few familial adenomatous polyposis studies have focused upon faecal sterols and bile acids but none has analysed the fecal content of fatty acids . we report here findings of an observational study on 29 colectomized familial adenomatous polyposis patients that describe the fecal content of fatty acids , and relate this to the proportions of fatty acids and levels of cyclooxygenase mrna expression in duodenal biopsies , levels of serum lipoproteins , and diet . in the ileostomy group separately ( n = 12 ) , the fecal content of arachidonic acid was correlated negatively to the proportions of eicosapentaenoic acid and docosahexaenoic acid in duodenal biopsies . total serum - cholesterol was negatively correlated to the fecal content of saturates and monounsaturates . the fecal palmitoleic acid / palmitic acid ratio was positively correlated to the levels of cyclooxygease-2 expression in duodenal biopsies.in the ileal - pouch - anal anastomosis group separately ( n = 17 ) , significant correlations were found between the fecal contents of oleic acid , linoleic acid , and alpha - linolenic acid , and the proportions of myristic acid , oleic acid and eicosaenoic acid in duodenal biopsies . dietary monounsaturates were positively correlated to different fecal fatty acids . future studies should focus on molecular mechanisms relevant to fatty acid metabolism , inflammation , and angiogenesis , in addition to nutrition .
[ "transcutaneous electrical nerve stimulation ( tens)24 , use of intraoral lidocaine patch11 and computerized local anesthesia7 ( the wand ) are newly developed methods to alleviate the pain and anxiety of dental patients , as alternatives to conventional local anesthesia . the hypothesis of the present study was that the wand anesthesia technique reduces the pain at different phases ( needle insertion , delivery of local anesthetic and tooth preparation ) versus conventional buccal anesthesia with conventional plastic syringe . therefore , the study compared pain levels at needle insertion , during delivery of local anesthetic solution and during tooth preparation , for the conventional syringe technique on the buccal or labial aspect on one side , and the amsa technique with wand local anesthesia application on the other side of the maxilla . a 5-point verbal pain rating scale ( vrs)12,17 was used on 16 patients who were under prosthodontic treatment in the ondokuz mayis university clinic local anesthesia and pain control is one of the most important elements of dentistry , and particularly prosthetic dentistry .", "sixteen adult patients who had partially edentulous states of both left and right maxillary arch , and were to undergo fixed prosthodontic treatment , participated in this study . groups were labelled as follows : group ( c ) , pain perception scores at needle insertion for the conventional technique ; group ( c ) , pain perception scores for local anesthetic delivery by the conventional technique ; group ( c ) , pain perception scores at tooth preparation for the conventional technique ; group ( w ) , pain perception scores at needle insertion by the wand technique ; group ( w ) , pain perception scores for local anesthetic delivery for the wand technique ; and group ( w ) , pain perception scores at tooth preparation for the wand technique . the amsa technique with the wand for half the maxillary arch and conventional plastic syringe anesthesia on mucobuccal fold ( control group ) for opposite maxillary arch were administered by the same operator . the amsa technique with single wand injection was used on one side for central incisors , lateral incisors , upper canine , first and second premolars , and the traditional plastic aspirating syringe injection was used on the mucobuccal fold of the related tooth on the opposite side differences in pain rating were analyzed at needle insertion , delivery of local anesthetic and during tooth preparation for conventional versus the wand techniques . patients were asked to remove mask and rate the pain for both conventional and wand injection techniques .", "the wand technique registered a highly significantly lower pain level during the needle insertion phase ( z = - 4.064 , p<0.01 ) , with the wand technique having a lower pain level compared to the conventional . during the anesthetic solution delivery phase , the pain level for the wand technique was again highly significantly lower than for the conventional technique ( z = - 3.897 , p<0.01 ) . median scores , minimum and maximum pain rating values after needle insertion , and delivery of anesthetic and tooth preparation time for both conventional and wand techniques , are shown in table 3 . sixteen adult patients aged from 27 to 64 ( 12 women and 4 men ) participated in this study . however , there was no difference between the wand and conventional techniques for pain level during tooth preparation ( z = - 0.671 , p>0.05 ) .", "the research hypothesis stated that the wand anesthesia technique reduces the pain at different phases ( needle insertion , delivery of local anesthetic and tooth preparation ) versus conventional buccal anesthesia with conventional plastic syringe . the wand anesthesia technique reduces the pain compared the conventional anesthesia for needle insertion and anesthetic solution delivery phases ( p<0.01 ) , with the exception of tooth preparation phase ( p>0.05 ) . the same efficacy of anesthesia was achieved with conventional buccal anesthesia and the palatal approach amsa technique with the wand device25 . another benefit of palatal amsa injection using the wand is that it reduces the number of injections , and also the amount of anesthetic solution compared to conventional buccal infiltration anesthesia that applies multiple injections to each tooth .", "the amsa technique administered using the wand in a prosthodontic treatment reduced pain highly significantly more than conventional buccal anesthesia , both in inserting the needle and in the of delivery of local anesthetic . when comparing the anesthesia efficiency of amsa using the wand injection and conventional buccal infiltration techniques , no statistical difference was found . although the slow anesthetic flow rate proved superior in pain control , the pain score was not zero for the wand , contrary to the manufacturer 's claim . computer - controlled anesthesia using the wand appears advantageous for restorative procedures because more teeth are anesthetized with one palatal injection , and without numbness of lips and face , in contrast to multiple conventional buccal anesthetic injections for each tooth ." ]
objective : the objective of this study was to compare the pain levels on opposite sides of the maxilla at needle insertion during delivery of local anesthetic solution and tooth preparation for both conventional and anterior middle superior alveolar ( amsa ) technique with the wand computer - controlled local anesthesia application.material and methods : pain scores of 16 patients were evaluated with a 5-point verbal rating scale ( vrs ) and data were analyzed nonparametrically . pain differences at needle insertion , during delivery of local anesthetic , and at tooth preparation , for conventional versus the wand technique , were analyzed using the mann - whitney u test ( p=0.01).results : the wand technique had a lower pain level compared to conventional injection for needle insertion ( p<0.01 ) . in the anesthetic delivery phase , pain level for the wand technique was lower ( p<0.01 ) . however , there was no difference between the wand and conventional technique for pain level during tooth preparation ( p>0.05).conclusions;the amsa technique using the wand is recommended for prosthodontic treatment because it reduces pain during needle insertion and during delivery of local anaesthetic . however , these two techniques have the same pain levels for tooth preparation .
[ "this study aimed to develop and verify the use of a remote pulse oximetry system on healthy individuals . specifically , it aimed to establish the technical feasibility of transmitting pulse oximetry data remotely , to determine the validity of remote measurements when compared to conventional face to face measurements , and to evaluate the participants ' perception on the usability of the technology . a favourable result will enable the development of remote pulmonary rehabilitation programs for people living in rural or remote areas . pr is a multidisciplinary approach which incorporates self - management education with exercise training , psychosocial and nutritional support [ 11 , 12 ] . chronic obstructive pulmonary disease ( copd ) is a progressive lung disease which is characterized by airway obstruction and lung parenchyma destruction . it is a fundamental part of managing people with copd and has been shown to be effective in improving exercise tolerance , reducing dyspnoea , improving , quality of life and reducing the severity of acute exacerbations [ 1 , 1117 ] . although pr has been shown to be effective in managing symptoms and reducing hospital admissions , poor participation and adherence are a current problem among outpatient programs .", "thirty - seven healthy individuals were recruited to participate in a single remote cardiopulmonary exercise session . the satisfaction questionnaire rated the comfort , quality , and usability of the ehab device and remote pulse oximetry module . the validity of remote pulse oximetry was assessed by comparing the remote measurements ( therapist data ) with conventional face - to - face measurements ( participant data ) . , participants completed a questionnaire about their experience with the remote pulse oximeter module and ehab device by marking on a 100 mm visual analogue scale ( vas ) and providing any open - ended comments . during each session , participants were given an information sheet with instructions on how to affix the pulse oximeter module to the index finger of their nondominant hand and how to establish a connection with a therapist in another room via the ehab device . the data was subsequently stored in a mysql database on the server . a therapist device retrieved this data via an asp web service to produce a graph of the participant 's heart rate and spo2 recordings in near real time . for this study", "overall , participants rated their experience with the remote pulse oximeter and ehab device highly . ( n = 4 ) and [ the ehab was ] simple and easy to use the mean ( sd ) transmission latency of the pulse oximetry data ( not the videoconference ) between the computers was 2.94 ( 0.59 ) seconds . there were 34 successfully completed sessions on first attempt confirming the feasibility of the method , while three had to be repeated due to technical difficulties with the bluetooth or wifi connection . the mad and limits of agreement between participant and therapist data are shown in table 1 . ", "this study demonstrated the feasibility of a remote pulse oximeter for use during a pr program . remote measurements of spo2 and hr were valid when compared to conventional face - to - face measurements . however , inconvenience , distance , or availability of pr programs can lead to lack of participation and poor compliance . a therapist questionnaire is therefore required to assess their satisfaction and confidence in safely conducting a remote exercise session . furthermore , it has been shown that patients demonstrate more positive views of telecare encounters than their healthcare providers .", "our pilot study demonstrated that remote pulse oximetry was feasible , and the data transmission method produced valid data at the remote end when compared with conventional face - to - face measures . although this study was performed on healthy individuals , participants found the ehab device easy to operate and were confident it could be used at home . further studies are needed to address the technical feasibility and validity in a home environment and the therapist 's confidence in conducting a safe exercise program ." ]
pulmonary rehabilitation is an effective treatment for people with chronic obstructive pulmonary disease . however , access to these services is limited especially in rural and remote areas . telerehabilitation has the potential to deliver pulmonary rehabilitation programs to these communities . the aim of this study was threefold : to establish the technical feasibility of transmitting real - time pulse oximetry data , determine the validity of remote measurements compared to conventional face - to - face measures , and evaluate the participants ' perception of the usability of the technology . thirty - seven healthy individuals participated in a single remote pulmonary rehabilitation exercise session , conducted using the ehab telerehabilitation system . validity was assessed by comparing the participant 's oxygen saturation and heart rate with the data set received at the therapist 's remote location . there was an 80% exact agreement between participant and therapist data sets . the mean absolute difference and bland and altman 's limits of agreement fell within the minimum clinically important difference for both oxygen saturation and heart rate values . participants found the system easy to use and felt confident that they would be able to use it at home . remote measurement of pulse oximetry data for a pulmonary rehabilitation exercise session was feasible and valid when compared to conventional face - to - face methods .
[ "we therefore studied a combined cohort of trekkers from 2 expeditions to ha . in order to clarify the relative contribution of ams , hypoxia or exercise to ngal levels the potential role of inflammation in stimulating ngal was assessed by the measurement of highly sensitive c - reactive protein ( hscrp ) in a subset of participants . , we also studied a cohort pre- and postexercise at near sea level , and a further cohort exposed to acute normobaric hypoxia . we therefore hypothesised that ngal would increase at ha secondary to these various stimuli and that the magnitude of any increase might relate to the presence of ams . \n acute mountain sickness ( ams ) occurs during exposure to high altitude ( ha ) and is a clinical syndrome characterised by headache , insomnia , malaise , and gastrointestinal symptoms .", "a group of 22 subjects had ngal assayed at rest and after exercise at sl in the uk following ascent from sea level to 1085 m over 6 hours ( an equivalent gain in altitude and duration of exercise similar to that experienced on a trekking day in nepal ) . a within - subjects anova was performed to investigate any serial changes in ngal with ascent at rest and post - trek . a two - way mixed anova with either resting or after trek ngal at each study altitude as the within - subjects factor and the presence of ams ( according to the ll score at multiple altitudes ) as the between - subjects factor thirty - two subjects participating in a defence medical services ( dms ) trekking expedition ( trek 1 ) in the khumbu region of nepal were studied . fourteen subjects underwent a 3-hour exposure to normobaric hypoxia ( fio2 11.6% , equivalent to 4800 m altitude ) in a hypoxic chamber . twenty subjects from a further dms expedition ( trek 2 ) to nepal were also studied . ngal was analysed in the field on a biosite triage point of care monitor ( alere ltd , stockport , uk ) using a triage ngal test kit . twice - daily ams scores were assessed using the lake louise score ( lls ) questionnaire .", "demographic data for the field study ( trek 1 + 2 ) , the controls , and the hypoxic chamber study are shown in table 1 . in the 22 subjects ascending to 1085 m in the uk there was a significant difference between ngal depending on the presence or absence of ams at 5150 m ( figure 3 ) with higher values in those with ams and severe ams . a two - way mixed anova revealed a significant change ( p = 0.003 ) in resting ngal with ascent and an interaction with ams at 4270 m ( p = 0.017 ) and 4910 m ( p = 0.002 for change in ngal , p = 0.027 for interaction with ams ) . according to their ll scores at the highest study altitude ( 5150 m ) , there were 23 subjects with no ams , 16 subjects with mild ams , and 7 subjects with severe ams . within the subjects , anova demonstrated a significant change in ngal with ascent both at rest ( p = 0.007 ) and after trek ( p = 0.001 ) ( figure 2 ) .", "this is the first report to describe an association between ngal and both the presence and severity of ams at ha . the significant novel findings are that ngal rises in response to sustained hypobaric hypoxia but not acute normobaric hypoxia or near sl exercise and that this rise is related to ams at 5150 m. the rise in ngal following trekking ( by day 2 at 3400 m ) was to the levels normally associated with the subsequent development of arf ( > 150 ng / ml ) , but this did not occur . in addition to renal hypoxia , we suspect that other factors may also contribute to the rise in ngal at ha . the significantly greater ngal in those with severe or mild ams versus those without at 5150 ", "ngal rises in response to prolonged hypobaric hypoxia ; marked increases in ngal may occur without concomitant arf and the degree of ngal rise at ha is associated with the presence or absence of ams . the fact that ngal does not appear to rise secondary to acute normobaric hypoxia or exercise in isolation suggests that the rise at ha and relation with ams may have common pathways , perhaps related to prolonged hypoxia and an inflammatory response . with the huge and increasing popularity of recreational sports undertaken at both moderate and high altitude in conclusion , there are several interesting and novel findings that are worthy of further exploration . assessment of ngal takes a matter of minutes using poc testing , and its use in identifying ams requires further evaluation ." ]
acute mountain sickness ( ams ) is a common clinical challenge at high altitude ( ha ) . a point - of - care biochemical marker for ams could have widespread utility . neutrophil gelatinase - associated lipocalin ( ngal ) rises in response to renal injury , inflammation and oxidative stress . we investigated whether ngal rises with ha and if this rise was related to ams , hypoxia or exercise . ngal was assayed in a cohort ( n = 22 ) undertaking 6 hours exercise at near sea - level ( sl ) ; a cohort ( n = 14 ) during 3 hours of normobaric hypoxia ( fio2 11.6% ) and on two trekking expeditions ( n = 52 ) to over 5000 m. ngal did not change with exercise at sl or following normobaric hypoxia . during the trekking expeditions ngal levels ( ng / ml , mean sd , range ) rose significantly ( p < 0.001 ) from 68 14 ( 60102 ) at 1300 m to 183 107 ( 65519 ) ; 143 66 ( 60315 ) and 150 71 ( 60357 ) at 3400 m , 4270 m and 5150 m respectively . at 5150 m there was a significant difference in ngal between those with severe ams ( n = 7 ) , mild ams ( n = 16 ) or no ams ( n = 23 ) : 201 34 versus 171 19 versus 124 12 respectively ( p = 0.009 for severe versus no ams ; p = 0.026 for mild versus no ams ) . in summary , ngal rises in response to prolonged hypobaric hypoxia and demonstrates a relationship to the presence and severity of ams .
[ "when deposited on various \n substrate surfaces , rod - like , -conjugated , \n small organic molecules are well - known for their tendency to form \n highly anisotropic crystal shapes , which are frequently called fibers \n or needles . whereas the epitaxial growth has been studied on various substrates , \n in particular anisotropic surfaces seem favorable to conserve the \n highly anistropic morphology and optical properties , for example , \n polarized emission or adsorption provided by a parallel molecular \n orientation obtained by self - assembly . consequently , \n cu(110 ) , tio2(110 ) and muscovite mica(001 ) are frequently chosen as a proper fundament to study the epitaxial \n growth of rod - like small molecules . in this paper , the epitaxial \n growth of 2,2:6,2-ternaphthalene \n ( nnn ) on muscovite mica(001 ) is reported . as indicated in figure 1a , both crystal \n configurations provide a well - defined azimuthal alignment , which is \n discussed based on force field simulations and a recently reported \n growth model . the coexistence of needle - like structures \n and island - like crystallites is verified . the molecule is built from three naphthalene \n units , which are linked together by c structural analysis reveals \n two different crystal orientations . whereas island - like structures \n are built up by upright standing molecules orientated with a ( 001 ) \n contact plane relative to the muscovite mica substrate ( see figure 1b ) ,", "for the \n simulation of the 7 2 nnn stack , the molecular packing has \n been deduced from the crystal structure of a ( 111 ) orientated nnn crystallite . due to the presence of flat \n and edge - on molecules , , \n and z - positions of the molecular center of mass and \n the angle . the angle defines the azimuthal molecular \n alignment and is probed by rotating the nnn molecule around the z - axis ( surface normal ) . we perform a grid - based optimization \n to search for the best molecular adsorption geometry using a grid \n of 81 81 points for the lateral position . the adsorption distance has been optimized , \n yielding a distance of 1.6 of the lowest h atom of edge - on \n nnn molecules to the substrate surface . because energetic minima are \n significantly narrow for the molecular stack , an angular resolution \n of = 0.5 has been chosen for the calculations . the hwe technique was applied for the deposition \n of the organic material , which allows us to perform the growth process \n close to thermodynamic equilibrium , and in further consequence relatively \n high vapor pressure of the organic deposit in the substrate region \n can be achieved . therefore , the requirements concerning vacuum conditions \n are reduced compared with , for example , molecular beam epitaxy . the molecules and substrates are assumed to be \n rigid where the internal structure of an isolated nnn molecules is \n determined from the crystal structure .", "ledge \n directed epitaxy . based on the latter \n analysis together with xrd - pf data presented in figure 4 ( lna ) , it can be concluded that the minor fraction of s23 crystallites has most likely nucleated at b - type \n fibers , which are orientated approximately 30 tilted relative \n to [ 110]mica of the muscovite mica substrate . \n the lna of b * type crystallites is defined by their [ 110 ] orientation \n and consequently all crystallographic planes (11n ) are aligned parallel to it . because the angular tilt of 13.8 \n between the low index planes ( 110 ) and ( 111 ) \n perfectly correlates with the observed sfm analysis , the theoretically \n expected cross - section of a b1 * fiber has been modeled and is depicted below \n the experimental data . although , the observed steep height decrease \n at the fiber side walls is below the resolution limit of the sfm , \n a termination of the fibers by ( 001 ) and ( 001 ) facets can be \n assumed . based on the simulated xrd - pf diffraction peaks , the long needle \n axis ( lna ) and long molecular axis ( lma ) orientations of b orientated \n fibers have been deduced and are presented in figure 4 by solid filled arrows . whereas the lna coincides with the \n [ 110 ] orientation , the lma can be approximated by the alignment \n of [ 101 ] relative to the muscovite mica substrate . xrd - pf patterns of \n the organic crystallites can be constructed by mirror operation from \n the top hemisphere , sketched by a gray shaded sector . moreover , the \n xrd - pf patterns reveal a 2-fold rotational symmetry , which can be \n understood by an approximately equivalent adsorption energy for 180 \n turned organic crystallites . it is visualized that \n the [ 110 ] crystallographic direction of s1 crystallites \n provides the same azimuthal orientation as the lna of b1 fibers . such epitaxial alignment \n based on a geometrical fit between nucleating crystallites and already \n existing topographic features on the substrate is called ", "the epitaxial growth of ternaphtalene \n ( nnn ) on muscovite mica(001 ) has been investigated by combining structural \n ( xrd - pf ) and morphological ( sfm ) methods . the epitaxial \n growth of sexithiophene ( 6 t ) on muscovite mica showed the formation \n of four well - defined fiber orientations , which can be explained by \n mirror symmetry of the muscovite mica substrate and two differently \n stacked 6 t crystallites , which can nucleate at a molecular adsorption \n position . contrarily , experimental investigations \n indicate that nnn crystallites tend to stack in a single configuration , \n which explains the dominant formation of only two fiber orientations . \n based on force field simulations , based on this growth model , it can be understood \n that both crystal types provide a well - defined azimuthal orientation \n relative to the muscovite mica substrate . by use of force field \n simulations , the growth of the fibers is further analyzed . consistently , both methods \n reveal the formation of s ( 001 ) orientated nnn island - like structures \n which have nucleated at the sidewalls of b ( 111 ) orientated fibers . \n the optimal adsorption \n energy of a single nnn \n molecule has been deduced based on force - field simulations by selecting \n the most favorable adsorption site for each angle . the angle \n characterizes the azimuthal alignment of the lma relative \n to mirror symmetry plane of the muscovite mica substrate surface . \n" ]
the morphology and structure of 2,2:6,2-ternaphthalene ( nnn ) deposited on muscovite mica(001 ) substrates was investigated by scanning force microscopy ( sfm ) and specular x - ray diffraction measurements . consistently , both methods reveal the coexistence of needle - like structures with a { 111 } contact plane and { 001 } orientated island - like crystallites , which are built up by almost upright standing nnn molecules . both orientations are characterized by a well - defined azimuthal alignment relative to the substrate surface , which is analyzed by x - ray diffraction pole figure ( xrd - pf ) measurements . based on xrd - pf and sfm analysis , the azimuthal alignment of { 001 } orientated crystallites is explained by ledge - directed epitaxy along the fibers sidewalls . these fibers are found to orient along two dominant directions , which is verified and explained by a doubling of the energetically preferred molecular adsorption site by mirror symmetry of the substrate surface . the experimental findings are confirmed by force - field simulations and are discussed based on a recently reported growth model .
[ "a-38-year - old female patient consulted to our emergency outpatient clinic with complaints of fever , sore throat , coughing , shivering , chills , joint , and muscle pain , headache , chest pain continuing for nearly 2 weeks and she was hospitalized to investigate the etiology of fever . on thoracal imagings , bilateral hilar lymph nodes of which the largest being 2 cm in diameter , bilateral pleural effusion , and atelectasic areas in the parenchyma surrounding the pleural effusion were observed ( figure 1 , 2 ) . on abdominal tomograms , the patient whose pleural effusion completely regressed with steroid therapy discharged to be further followed up by rheumatology outpatient clinic ( figure 3 ) . however her hyperfebrile state persisted , echocardiograms obtained for the differential diagnosis of infective endocarditis .", "adult onset still s disease is a disease whose diagnosis can be made by excluding infectious , malign , autoimmune , and autoinflammatory diseases , and in consideration of its characteristic clinical , and laboratory findings . for definitive diagnosis , yamaguchi criteria can be used . still many characteristic features of aosd are not known , and a standard follow - up or a treatment protocol of the disease is not available . in patients who met diagnostic criteria , pleural effusion which may be seen in the clinical course of the disease should be presumably associated with the disease . besides regression of pleural effusion can be expected with the treatment of underlying desease , additional locally invasive diagnostic , and/or therapeutic interventions should be avoided . s disease pleural effusion , transient pulmonary infiltration , and pericarditis can be seen in 3040% of the patients . myocarditis , and ards are more frequently seen especially in patients with mas . in the differential diagnosis , infectious diseases ( ebv , cmv , hbv , rubella , parvovirus , coxsackie , hiv , subacute bacterial endocarditis , meningococcemia , tuberculosis , syphilis ) ; vasculites ( takayasu arteritis , polyarteritis nodosa , serum disease , thrombotic thrombocytopenic purpura ) ; malign diseases ( leukemia , lymphoma ) , connective tissue diseases ( ra , sle , mixed connective tissue disease ) , granulomatous diseases ( sarcoidosis , crohn disease ) ; autoinflammatory diseases ( kikuchi disease , sweet syndrome ) , and drug hypersensitivity reactions should be considered . in our patient" ]
adult onset still s disease is a rare systemic inflammatory disorder . at the onset of the disease sore throat , pharyngitis ; which does not respond to antibiotics , one or two times peaking febrile episodes , marked salmon - colored rash on the trunk and extremities , arthralgia , arthritis , myalgia , fatigue , loss of appetite with nausea and weight loss ; hepatosplenomegaly and lymphadenopathy can be seen . among laboratory examinations levels of ferritin and other acute phase reactants distinctly rise , and neutrophilic leukocytosis ; ana and rf negativity are detected . pleural and pericardial effusions , transient pulmonary infiltration , and rarely myocarditis can be seen during the course of the disease . here we report a patient who was examined for fever of unknown origin and diagnosed with adult onset still s disease which is a rare etiology of pleural effusion .
[ "thus , the purpose of this study was to measure the dc of two commercially dual - cured resin cements in different viscosities ( low and high ) when they were light - activated or when the materials were allowed to self - cure solely , after 5 minutes and 24 hours from the mixture of pastes ( base and catalyst ) . the hypothesis tested was that curing mode , evaluation time and viscosity would affect the dc of the resin cements . , the self - cure mode should ensure the high level of conversion , especially in the cervical proximal areas , the root canal and in the internal and deep areas of the cavity preparations.1214 several methodologies have been used to analyze the dc of resin - based materials ; however , most of them use fourier transform infrared spectroscopy ( ftir ) . although many researchers have evaluated the polymerization effectiveness to determine the physical and mechanical properties of dental materials,9,15,16 little information is known about the influence of different viscosities of dual - cured resin cements on their physical properties , such as the degree of conversion in situations of self - and dual - polymerization .", "two commercial dual - cure resin cements in high and low viscosities were evaluated : variolink ii ( ivoclar vivadent , schaan , liechtenstein ) and nexus 2 ( kerr corp . , orange , ca , usa ) . the resin cements consist of two paste components that were equally dispensed and mixed together according to manufacturers instructions . after mixing , resin cements ( n=5 ) monomer conversion was calculated ( % ) according to the changes in the ratio between the absorbance peaks corresponding to the aliphatic ( cc ) ( 1638 cm ) and aromatic ( 1608 cm ) carbon double bonds prior to and 5 minutes and 24 hours after polymerization initiation for both curing modes.10 the aromatic peak is used as an internal reference because the intensity does not change during the polymerization reaction.9,11 the effect of curing mode , viscosity and time intervals on the dc were evaluated for each material . the spectrum of unpolymerized material was obtained and the cements were either light - cured ( dual - polymerizing mode ) or allowed to self - cure only ( autopolymerizing mode ) . three - way repeated measure analysis of variance ( anova ) ( curing mode , viscosities and evaluation time ) was performed and tukey s post - hoc test was used to detect pair wise differences among experimental groups .", "the statistical analysis of the data showed significant differences in curing mode , viscosity and evaluation time factors for both resin cements ( p=.01 ) . the dc of resin cements was higher when the materials were light - cured and when the low - viscosity versions were used than when self - curing mode and the high - viscosity resin cements were tested , respectively ( p<.05 ) . other double - interactions and the triple - interaction ( curing mode x viscosity x evaluation time ) were not significant ( p>.05 ) . there was significant interaction between factors : the curing mode x evaluation time ( p=.01 ) .", "the results of this study showed that the curing mode ( auto- and dual - polymerization ) , the viscosity ( low or high ) and the evaluation time ( 5 minutes or 24 hours ) influenced the dc of resin cements . the low viscosity monomer allows better mobility and distribution of free radicals inside the resin material , which can increase the polymerization reaction and the monomer conversion.9 the increase of dc promoted by the low viscosity versions in percentage , following the polymerization mode ranged from 0.9 to 3.1% for the dual - polymerizing groups and ranged from 1.5 to 3.9% for the auto - polymerizing mode , which was the highest percentage among the groups from nexus 2 resin cement . for the variolink ii thus , the polymerization reaction for both resin cements continued after 5 minutes of the mixing of the base and catalyst pastes .", "the direct light - activation and the low viscosity version were important to provide higher dc for the dual - polymerizing resin cements . twenty - four hours after seating the indirect restoration is appropriate for final oclusal adjustments , finishing , and polishing procedures , which are capable of generating stress to the resin cement layer ." ]
objective : the purpose of this study was to evaluate the effects of the viscosities and curing modes on the degree of conversion ( dc ) of two resin cements.methods:eight experimental groups were evaluated ( n=5 ) , according to the dual - cured resin cements ( nexus 2/variolink ii ) , viscosity ( low and high ) and evaluation time ( 5 minutes and 24 hours ) . the resin cements were applied to surface of a horizontal attenuated - total - reflectance unit and were polymerized either with self - cure ( sc ) or light exposure ( xl3000/3 m espe ) for 40 seconds . infrared spectra were obtained after 5 minutes and 24 hours ( nicolet 520 ft - ir / thermo scientific inc . ) . dc was calculated according to changes in aliphatic - to - aromatic peak ratios pre- and post - curing . data ( % ) were analyzed by 3-way repeated measure anova ( curing mode , viscosity and time interval ) and tukey s post - hoc test ( p<.05).results : the dual - polymerizing mode provided higher dc than auto - polymerization . the dc mean values increased for both resin cements after 24 hours . the low - viscosity resin cements from light - activated or self - cured groups exhibited higher dc than high viscosity version.conclusion:the dc of resin cements was higher for the low viscosity version , following the light - polymerization and when were tested after 24 hours .
[ "one emerging policy is the role of preconception care as a complement to prenatal care . maternal and child health is connected to social , economic , and environmental conditions . in resource - poor countries , aside from pre - existing risks for poor maternal and child health outcomes , global changes have introduced new risks to the health of women and pregnancy , including alcohol and tobacco use , over nutrition , and micronutrient malnutrition [ 5 , 6 ] . because not all the deficits in achieving adequate prenatal care are likely to be solved in the near future , and global factors that lead to increases in risk can not be reversed , new strategies and policies to improve pregnancy outcome remain a high priority . transforming health systems for women and children . while the technology and interventions exist to prevent or treat the vast majority of adverse health conditions that affect children and women of reproductive age , many continue to die and even more suffer from ill health [ 2 , 3 ] . the central challenge to achieving these goals is to provide known interventions to the full population and at the right time when most known adverse outcomes can be prevented . despite 15 years of the global safe motherhood the early phase of implementation of preconception care in primary care settings in belgium was a challenge , as it highlighted the need for a strong partnership of all institutions involved in maternal and child health care .", "the family planning association of hong kong ( fpahk ) was founded in 1950 with an objective to reduce family size . the pre - pregnancy preparation service was launched in 1998 , in response to public demand for preconception care . the service integrates medical , counseling , and education services for couples planning conception to achieve the following outcomes : \n prevent and treat infections to safeguard the health of both partners and the fetus . the continuous flow of clients for the preconception service reflects public support and trust for the service . this low service fee is achieved through cost sharing with other sexual and reproductive health programs offered by the fpahk . is included in the package.help couples prepare for parenthood.help women with pre - existing medical illness understand the best timing for pregnancy , the effect of their illness on their pregnancy , the effect of pregnancy on their illness , the effect on her offspring , the need to adjust medication , and to avoid drugs with known or uncertain teratogenic effects.help women with gynecological diseases understand the impact of their diseases on conception and pregnancy . having achieved a low birth rate , a number of sexual and reproductive health programs have been launched with the objective of improving reproductive outcomes .", "the current challenge is to market it to all women who plan pregnancy , and to assure that the health care system has the capacity to match the demand and expansion of the service to other parts of the country . service delivery is clinic - based preconceptional counseling , medical protocol examination by a physician , and follow - up of women who want to have a baby . education includes lectures for obstetricians and gynecologists as well as for child - bearing age women attending maternity services . the women served , 40% reported no history of adverse reproductive outcomes , about 30% had history of spontaneous abortion , 13% had maternal disease , 15% had a baby with birth defect , and 2% had family history of genetic disease . however , careful review of medical and behavioral history indicated that 92% of preconception care attendees have at least one risk factor for adverse outcomes . the preconception counseling clinic , based at the korean motherisk program at samsung cheil hospital , an affiliated university hospital , includes teratogen information service for pregnant and breast feeding women , as well as preconception counseling . the preconception care medical protocol is composed of a physical examination , laboratory tests , and a questionnaire . of patients with specific problems such as a previous child with a birth defect are transferred to the department of maternal and fetal medicine . the goals are to enhance primary prevention of birth defects and preterm birth , increase in intended pregnancy , decrease in unnecessary pregnancy termination , and recovery of a higher birth rate in korea to maintain population replacement levels .", "the early phase of implementation of preconception care in primary care settings in belgium was a challenge , as it highlighted the need for a strong partnership of all institutions involved in maternal and child health care . an ad - hoc committee was formed to propose strategies , activities , financing options , and evaluation methods , starting with the development of evidence - based guidelines based on belgian epidemiological data . the o.n.e ( office de la naissance et de lenfance = organization for birth and childhood ) , is a belgian governmental organization charged with the protection and promotion of health of women and children . this activity will be implemented through prenatal care , pediatric and gynecology clinics , as well as general practitioners , in partnership with genetic and counselling centers .", "our pilot efforts indicate that screening for hiv in the preconception period is feasible and acceptable in this rural community . the unique premarital medical examination system prevalent in china and late onset of hiv transmission in china provided an opportunity to pilot implementation of the three - pronged strategy in guangxi province . a three - pronged approach to reducing mother - to - child transmission of hiv has long been advocated by global initiatives to reduce the burden of hiv / aids , but to our knowledge , never been implemented anywhere . given that the community is aware of the concept of premarital medical examination , social marketing techniques using family health enhancement as a core benefit , and efforts to regain the conceptual interest of population in preconception care are needed . a combination of testing strategies implemented at various stages before and during pregnancy would help identify all women at risk for hiv - exposed pregnancies .", "the major obstacles to preconception care included the following : a ) lack of systematic organization of these services within the health care system ; b ) poor coordination between governmental organizations involved in marriage , family planning and health care ; c ) unclear media messages ; and d ) the perception of the term voluntary by women to mean unnecessary . in october 2003 , the longstanding mandatory chinese requirement for couples planning marriage to obtain a premarital health check , a routine physical examination , laboratory tests , and reproductive health education , was removed , and this visit became voluntary . we used a three - stage process : 1 ) ascertain the nature of the problem regarding delivery of preconception care through the use of a series of questionnaires and interviews , 2 ) develop a test plan to promote preconception care , and 3 ) evaluate and refine the plan . overall , 91% of 10,000 questionnaires were completed , and 140 subjects were interviewed , including women of reproductive age , maternal and child health workers , and local government officials . reported rates of premarital examinations plummeted , and health officials voiced concern that women were not receiving adequate risk assessment and pre - pregnancy education , particularly regarding the benefit of folic acid in preventing neural tube defects . to assess the feasibility of increasing the rate of preconception care uptake , we conducted a pilot social marketing effort in a northern county ( mancheng , in hebei province ) during february and march , 2004 . following the workshop , 95% of women reported that they would be willing to pay up to rmb 100 ( us$12 ) for preconception health care services , and half indicated that more and better health messages were needed . improving coordination among government agencies , developing training materials targeted to different groups , and promulgating clear , consistent messages concerning the importance of preconception care that are delivered in all settings where women may have contact with the system before pregnancy can create demand for preconception services . the implementation plan included the use of social marketing to solicit government support , coordinate with various government organizations , train maternal child health ( mch ) workers at all levels , and to market the concept of preconception health care to women of childbearing age . to solicit government support , we established a project coordination committee , including high - level officials from the county project office , the county women 's office , the bureaus of health , family planning , and civil administration , and the women 's federation .", "as illustrated by the six examples highlighted above , it is evident that preconception care is not just a conceptual debate but a primary approach used to address various health issues and emerging national challenges . as noted so cogently by atrash et al . consistent with the conceptual framework of the 2005 bangkok charter on health promotion , preconception care should be seen as a program for the future , a development agenda that is aimed at overall health of the family . although adequate prenatal , obstetric , and primary care services can reduce the infant and maternal mortality in high - mortality - developing countries , such countries are not free from emerging risks to maternal and child outcomes . making preconception care available can have transgenerational impact on some women ; those who are aware of such opportunities and can access such services . our responsibility is to provide that opportunity . in fact , introduction to preconception care can complement the efforts to improve prenatal care uptake . further , in the countries such as south korea and hong kong , and others in similar demographic transition , this a healthy baby and a healthy mother are valued hopes and dreams of families and cultural heritages across the world . similar to the arguments in 1990s for and against hiv voluntary counseling services amidst the lack of availability of antiretroviral treatment , or against the attempts to market cell phones where land phones services are inadequate , advocating preconception care as a component of maternal child care services will remain controversial . as such , establishment of preconception care services tobacco and alcohol use rates among women in many developing countries have increased . however , as more women than before have access to education and information , are employed , have personal income and decision making power , and delay pregnancy , there are many opportunities to inform them about the need for preconception care and a healthy reproductive life . indeed , even a perfectly organized preconception care system is not likely to address other deficits in the reproductive health care system or in an inadequate prenatal care system in developing countries ; neither will it lead to rapid positive changes in related indicators ." ]
globally , maternal and child health faces diverse challenges depending on the status of the development of the country . some countries have introduced or explored preconception care for various reasons . falling birth rates and increasing knowledge about risk factors for adverse pregnancy outcomes led to the introduction of preconception care in hong kong in 1998 , and south korea in 2004 . in hong kong , comprehensive preconception care including laboratory tests are provided to over 4000 women each year at a cost of $ 75 per person . in korea , about 60% of the women served have known medical risk history , and the challenge is to expand the program capacity to all women who plan pregnancy , and conducting social marketing . belgium has established an ad hoc - committee to develop a comprehensive social marketing and professional training strategy for pilot testing preconception care models in the french speaking part of belgium , an area that represents 5 million people and 50,000 births per year using prenatal care and pediatric clinics , gynecological departments , and the genetic centers . in china , guangxi province piloted preconceptional hiv testing and counseling among couples who sought the then mandatory premarital medical examination as a component of the three - pronged approach to reduce mother to child transmission of hiv . hiv testing rates among couples increased from 38% to 62% over one year period . in october 2003 , china changed the legal requirement of premarital medical examination from mandatory to voluntary . this change was interpreted by most women that the premarital health examination was unnecessary and overall premarital health examination rates dropped . social marketing efforts piloted in 2004 indicated that 95% of women were willing to pay up to rmb 100 ( us$12 ) for preconception health care services . these case studies illustrate programmatic feasibility of preconception care services to address maternal and child health and other public health challenges in developed and emerging economies .
[ "the aim of this study \n is to compare il levels in exudative and transudative pleural \n fluids by measuring il levels in pleural effusions developed \n owing to various etiological factors in childhood . we aimed to \n examine whether the changes in pleural fluid protein , glucose , \n and lactate dehydrogenase ( ldh ) parameters , as well as in \n il-1 , il-2 , il-6 , and il-8 levels , were significant in \n differential diagnosis of childhood pleural effusions . although il levels in serum and various body fluids \n have been studied in various diseases , very few researches \n involving il levels in pleural effusions of children have been \n conducted [ 3 , 4 ] . when pleural effusion is \n detected , the characteristics of the fluid ( exudate or \n transudate ) must be revealed using thoracocentesis . fluid \n collection within the pleural cavity can be assessed with \n clinical and radiological means .", "the study group consisted of 26 patients admitted in the \n department of pediatrics , medical faculty , firat university with a \n diagnosis of pleural effusions . pleural effusions were categorized as exudates and transudates \n according to the clinical and laboratory findings . thoracal ultrasonograms were \n obtained from patients thought to have pleural effusions in \n consideration of medical history , physical examination , and chest \n x - rays . the presence and the amount of pleural fluids were \n determined and then thoracocentesis was performed . the patients whose pleural fluid smears revealed afb \n which could be cultured in lwenstein - jensen media and also \n responded favorably to the antituberculostatic treatment were \n acknowledged as cases with tuberculous pleurisy [ 5 , \n 6 , 7 ] . the cutoff values for the differentiation \n between the pleural transudates and exudates were determined as \n follows : protein , 3 g / dl ; ldh , 200 iu / l ; pleural \n fluid / serum protein ratio , 0.5 ; and pleural fluid / serum ldh \n ratio , 0.6 . empyematous effusions were characterised by \n the presence of gram - positive bacteria in pleural fluid smears , \n attendant pneumonia with or without bacterial growth in the \n cultures of pleural fluid samples , and typical glucose \n ( < 40 mg / dl ) and/or protein ( > 5 g / dl ) and/or ldh \n ( > 1000 ", "in our study group pleural effusions were of exudative ( n = 27 , \n 75% ) and transudative ( n = 9 , 25% ) type . the ages of the study \n subjects ranged between 9 months and 14 years . twelve \n parapneumonic ( 44% ) , 12 empyematous ( 44% ) , and 3 ( 12% ) \n tuberculous pleural effusions were detected in the exudate group ( table 1 ) . pg / ml in the \n empyematous effusion group and 919.0 9454.5 pg / ml in the \n tuberculous pleural effusion group . pg / ml in the tuberculous pleural \n effusion group . in the empyematous group , statistically significantly higher values were \n found in the empyematous group when compared with the \n parapneumonic and tuberculous pleural effusion groups ( p < .001 ) . statistically \n significantly higher values were obtained when compared with \n those of the parapneumonic effusion \n group , while the corresponding values detected in the tuberculous \n pleural effusion group were also significantly higher than those \n found in the parapneumonic effusion group ( p < .001 ) .", "this study have shown that for the differentiation between the \n exudative and transudative pleural effusions , in addition to the \n parametres such as protein , glucose and ldh , pleural fluid \n il-1 , il-2 , il-6 , and il-8 levels could be used . \n although many studies investigating the \n alterations in levels of il according to the exudative or \n transudative nature of pleural effusions in adults have been \n performed , similar studies pertaining to children are relatively \n few [ 16 , 17 , \n 18 ] . for that reason many studies have analysed \n il-1 levels in patients with meningitis , sepsis , urinary \n tract infections , and empyema . il-8 concentrations in \n the empyematous group were reported to be higher than those \n measured in the parapneumonic group . in accordance with this \n study , in our study the highest levels of il-8 were detected in \n the empyematous , parapneumonic , and tuberculous pleural effusions \n in decreasing order . il-1 levels of cerebrospinal fluids were found \n to be significantly higher than those with aseptic meningitis and \n in the control group . il-6 levels of cerebrospinal fluid in the patients with \n bacterial meningitis were reported to be significantly higher \n than the aseptic meningitis and in the control groups ." ]
the aim is to examine whether the changes in pleural fluid interleukin ( il)-1 , il-2 , il-6 , and il-8 levels were significant in differential diagnosis of childhood pleural effusions . il-1 , il-2 , il-6 , and il-8 levels in pleural fluids of all 36 patients were measured . the levels of il-1 , il-2 , il-6 , and il-8 in pleural fluids were statistically significantly higher in the transudate group compared with those of the exudate group . the levels of il-1 , il-6 , and il-8 were also found to be statistically significantly higher in the empyema group compared with both the parapneumonic and the tuberculous pleural effusion groups . the levels of il-2 and il-6 were detected to be statistically significantly higher in the tuberculous pleural effusion group in comparison with those of the parapneumonic effusion group . the results showed that pleural fluids il-1 , il-2 , il-6 , and il-8 could be used in pleural fluids exudate and transudate distinction .
[ "literature analysis showed few articles about this complication , but no publication has described the management of open patella fracture around total knee arthroplasty .", "we report a unique case of an open patellar fracture above a total knee arthroplasty , sustained by a 56-year - old female patient .", "despite the poor outcome of operative management in patellar periprosthetic fracture , this approach should be considered for acute and post traumatic fractures in young patients with a good remaining bone stock .", "the demographic changes with a high rate of aging and active population , as well as the improved life expectancy during the last decades have led to an increase in the number of total knee arthroplasties ( tka ) [ 1 , 2 , 3 , 4 ] , and consequently a raise of post - operative complications . among these complications , , we report a unique case of an open periprosthetic patellar fracture that was managed with operative treatment . periprosthetic fracture after tka is the most frequent cause of post - operative pain , and revision surgery . it also involves a literature analysis with description of the risk factors and treatment options of this uncommon entity .", "a 56-year - old female underwent a cemented postero - stabilized condylar tka with fixed tibial plateau through an antero - medial approach , in our department . she underwent wound irrigation , debridement of non - viable soft tissue from the wound , open reduction and fixation with a figure - eight cerclage wiring , without any revision of the implants . complementary immobilization with a removable knee pad at full extension , for six weeks was prescribed . fig 3 . a clinical picture showing the open patellar fracture a clinical picture showing the open patellar fracture . the knee radiographs showed a short oblique fracture at the inferior pole of the patella without any loosening of the implants or dislocation of the knee : this fracture is classified as type i according to ortigueraet d.j .", "the patient achieved union of the fracture : knee radiographs showed a healed patellar fracture , with hardware in place . at 6 months follow - up , physical examination did not reveal any signs of local or deep infection . clinical pictures at last follow - up showing a clean and dry wound ( 7 ) , and knee range of motion ( 8 , 9 ) clinical pictures at last follow - up showing a clean and dry wound ( 7 ) , and knee range of motion ( 8 , 9 ) . her knee was pain free and she was able to walk without crutches , but she had a mild stiffness : the knee range of motion was 0/60. no antero - posterior or frontal laxities were noted .", "since the late 1960s , total knee arthroplasty has been the most effective treatment for knee osteoarthritis , providing good functional outcomes and improvement in the patient s quality of life . nevertheless , the high failure rate of the operative treatment in the patellar peri - prosthetic fracture can be explained by : \n the high proportion of stress , atraumatic fracture ( 88% ) due to osteonecrosis which suggests a poor remaining bone stock.the stress fracture , unlike the acute and post traumatic ones , has a higher risk of non-union.the poor outcome of partial or complete patellectomy , which is a type of operative treatment.in our point of view , the post traumatic fractures in young patients are more likely to heal than stress fractures in the elderly . \n the high proportion of stress , atraumatic fracture ( 88% ) due to osteonecrosis which suggests a poor remaining bone stock . literature analysis showed that conservative or non - operative treatment was more successful for the management of non - displaced patella fracture with stable implant and an intact extension mechanism . reported a unique case of patellar fracture associated with open knee dislocation after a total knee arthroplasty .", "peri - prosthetic patella fracture is a very uncommon entity , and challenging to treat , especially the open ones , because of the high risk of infectious complications . although several previous studies report a high rate of failure and unpredictable results of open reduction for periprosthetic patellar fracture , this approach ( especially the internal fixation with a strong and dynamic construct ) should be considered in young patients with a good remaining bone stock , who sustained an open or a displaced fracture after a high energy trauma . orthopaedic surgeons should consider open reduction and internal fixation as a good management alternative for periprosthetic patellar fracture , in case of a post traumatic and acute fracture in young patients with a good bone stock ." ]
introduction : periprosthetic patellar fracture after total knee arthroplasty ( tka ) is a rare complication . their management can be very challenging with unpredictable results . literature analysis showed few articles about this complication , but no publication has described the management of open patella fracture around total knee arthroplasty.case presentation : we report a unique case of an open patellar fracture above a total knee arthroplasty , sustained by a 56-year - old female patient.conclusion:despite the poor outcome of operative management in patellar periprosthetic fracture , this approach should be considered for acute and post traumatic fractures in young patients with a good remaining bone stock .
[ "corneal epithelium - like structure was used to simulate the human eye , and we evaluated dna microarray and real - time polymerase chain reaction ( pcr ) analysis results from normal human corneal epithelial cells exposed to water - filtered broad - spectrum nir irradiation to simulate solar nir radiation that reaches the eye . we hypothesized that nir irradiation simulating solar nir radiation that reaches human tissues can induce changes in gene expression . to test this hypothesis , a three - dimensional reconstructed human corneal epithelial model with multilayered , since the epithelial layer of the cornea provides the first line of defense against environmental insults , the structural integrity of this layer is a key component of corneal function.10 although uv - induced corneal damage has been described in many previous studies,1115 the effects induced by nir radiation on the cornea have not been thoroughly investigated . near - infrared ( nir ) radiation can penetrate the skin and the sclera of the eye .", "corneal cells were cultivated between the air and liquid interface to form a multilayered , corneal epithelium - like structure . the three - dimensional reconstructed human corneal epithelial model ( labcyte cornea - model ) prepared from enzymatically digested normal human corneal epithelial tissues was purchased from japan tissue engineering corporation , aichi , japan as an in vitro model of corneal tissue.16 cells were cultured in media ( assay medium ; japan tissue engineering corporation ) , which was changed every 2 days until the cultures reached subconfluence.16 the subconfluent corneal cells were then subcultured with trypsin and seeded on a cell culture insert containing a microporous membrane with a 0.4 m pore size . the rna was extracted from control and irradiated groups , which consisted of six whole individual three - dimensional reconstructed human corneal epithelial models . after normalization and filtering of the raw data output files , log - fold changes in gene expression in the nir - irradiated group compared with the control group were analyzed using the genespring gx 11.0 software ( agilent technologies ) to determine the upregulated and downregulated genes , using a twofold change as the cutoff . upregulated and downregulated genes were further clustered into functional gene groups using the ontology analysis function with the genespring gx 11.0 software . the variant - specific primer sequences for the four egfr variants are given in table 2 . the primer sequences of epidermal growth factor receptor ( egfr ) , tubulin tyrosine ligase - like family member 5 ( ttll5 ) , and pq loop repeat containing 2 ( pqlc2 ) are given in table 1 .", "the nir device emits an nir spectrum between 1,100 nm and 1,800 nm , with water filtering to remove wavelengths between 1,400 nm and 1,500 nm , and simulates solar nir radiation that reaches the skin of humans on the earth s surface . to avoid thermal effects , the sapphire contact cooling tip was set to a fixed temperature of 20c . in our previous in vitro study , ten rounds at 10 j / cm using continuous energy single irradiation pulses of 4.3 seconds achieved drastic reduction in cell count . nir irradiation was performed with a broadband nir source ( titan ; cutera , brisbane , ca , usa ) .", "corneal cells were cultivated between the air and liquid interface to form a multilayered , corneal epithelium - like structure . the three - dimensional reconstructed human corneal epithelial model ( labcyte cornea - model ) prepared from enzymatically digested normal human corneal epithelial tissues was purchased from japan tissue engineering corporation , aichi , japan as an in vitro model of corneal tissue.16 cells were cultured in media ( assay medium ; japan tissue engineering corporation ) , which was changed every 2 days until the cultures reached subconfluence.16 the subconfluent corneal cells were then subcultured with trypsin and seeded on a cell culture insert containing a microporous membrane with a 0.4 m pore size .", "total rna from the corneal epithelial cells was extracted in qiazol reagent ( qiagen nv , venlo , the netherlands ) and spin - column purified using a rneasy mini spin column ( qiagen nv ) . the rna was extracted from control and irradiated groups , which consisted of six whole individual three - dimensional reconstructed human corneal epithelial models . the quantity and quality of the rna samples were then measured using uv absorbance ( nanodrop technologies , wilmington , de , usa ) , and the quality was also assessed using an agilent 2100 bioanalyzer series ii ( agilent technologies , santa clara , ca , usa ) .", "cy3-labeled crna samples were synthesized using the low input quick amp labeling kit ( agilent technologies ) according to the manufacturer s instructions . for each time point , 50 ng of total rna was used to generate first - strand cdna . after the denaturation ( 10 minutes at 65c ) and crna synthesis ( 2 hours at 40c ) steps , the reactions were incubated at 70c for 15 minutes to inactivate the affinity - script enzyme ( agilent technologies ) . for labeling reactions , crna samples were each mixed with 6 l of transcription master mix cocktail containing cy3-ctp and incubated at 40c for 2 hours . labeled crna was quantified on a nanodrop nd-1000 ( nanodrop technologies ) , and quality was also checked by agilent 2100 bioanalyzer series ii .", "after normalization and filtering of the raw data output files , log - fold changes in gene expression in the nir - irradiated group compared with the control group were analyzed using the genespring gx 11.0 software ( agilent technologies ) to determine the upregulated and downregulated genes , using a twofold change as the cutoff . upregulated and downregulated genes were further clustered into functional gene groups using the ontology analysis function with the genespring gx 11.0 software . microarray data were deposited into the minimum information about a microarray experiment ( miame)-compliant gene expression omnibus ( geo ) database ( accession number : gse76500 , http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse76500 ) . slides were scanned using the microarray scanner ( agilent technologies ) , and images were processed by the feature extraction software ( agilent technologies ) with background correction . data were imported into genespring , and normalization was performed with a 75 percentile shift .", "the primer sequences of epidermal growth factor receptor ( egfr ) , tubulin tyrosine ligase - like family member 5 ( ttll5 ) , and pq loop repeat containing 2 ( pqlc2 ) are given in table 1 . the variant - specific primer sequences for the four egfr variants are given in table 2 . all six whole individual three - dimensional reconstructed human corneal epithelial tissue culture models were used for quantitative real - time pcr analysis . since pqlc was ubiqitously and highly expressed in all samples , pqlc2 was used for normalization . quantitative real - time pcr analysis was achieved using the dna engine opticon 2 system ( bio - rad laboratories inc .", "all statistical data are presented as the mean sem , and a p - value of < 0.05 was considered to be statistically significant .", "to elucidate changes in genetic expression induced by exposure to nir irradiation that simulates solar nir radiation that reaches human eye tissues , dna microarray analysis was carried out using rna isolated from control and nir - irradiated corneal epithelial cells . using ~6.310 probes , we identified 52 upregulated genes and 98 downregulated genes in the nir - irradiated group compared with the control group . egfr showed a high degree of upregulation ( 19.4-fold ) relative to control cells , although statistically significant upregulation of egfr and ttll5 was not observed ( p=0.5127 and p=0.8273 , respectively ) ( figure 1 ) using the primer sequences listed in table 1 . gene ontology analysis of these 150 genes identified 41 upregulated genes that encode proteins with receptor - binding properties ( table 3 ) . meanwhile , when the expression of egfr variants was assessed in a dna microarray analysis , expression increased by 1.0-fold and 1.3-fold for egfr variants 1 and 3 , respectively . upon inclusion of variant - specific primer sequences for egfr ( table 2 ) , quantitative real - time pcr analysis revealed that statistically significant upregulation of variants 1 and 3 was observed ( p<0.05 ) , whereas there was no statistically significant upregulation of variants 2 and 4 ( p=0.1266 and p=0.5127 , respectively ) ( figure 2 ) . quantitative real - time pcr analysis was then performed for the two genes showing the highest degree of upregulation in the dna microarray analysis : egfr and ttll5 .", "to the best of our knowledge , this is the first study that examines changes in genetic expression in three - dimensional reconstructed corneal epithelial tissue after nir irradiation to simulate solar nir radiation that reaches human eye tissues . the findings here that egfr expression is significantly upregulated following exposure of corneal epithelial cells to nir irradiation support that solar nir radiation that reaches human tissues can induce corneal cell injury . the biological effects of sun and uv exposure have been extensively investigated . however , over half of the solar energy is in the nir range , and most of the uv - blocking materials can not block nir radiation .", "nir irradiation simulating solar nir radiation that reaches human tissues induced upregulated expression of egfr in human corneal cells . nir radiation represents more than half of solar energy and can not be sufficiently blocked by eyewear . moreover , thus , the results of this study indicate that enhanced protection from and avoidance of both uv and nir radiation should be considered to prevent eye damage ." ]
background and objectivehumans are increasingly exposed to near - infrared ( nir ) radiation from both natural ( eg , solar ) and artificial ( eg , electrical appliances ) sources . although the biological effects of sun and ultraviolet ( uv ) exposure have been extensively investigated , the biological effect of nir radiation is still unclear . we previously reported that nir as well as uv induces photoaging and standard uv - blocking materials , such as sunglasses , do not sufficiently block nir . the objective of this study was to investigate changes in gene expression in three - dimensional reconstructed corneal epithelial tissue culture exposed to broad - spectrum nir irradiation to simulate solar nir radiation that reaches human tissues.materials and methodsdna microarray and quantitative real - time polymerase chain reaction analysis were used to assess gene expression levels in a three - dimensional reconstructed corneal epithelial model composed of normal human corneal epithelial cells exposed to water - filtered broad - spectrum nir irradiation with a contact cooling ( 20c ) . the water - filter allowed 1,0001,800 nm wavelengths and excluded 1,4001,500 nm wavelengths.resultsa dna microarray with > 62,000 different probes showed 25 and 150 genes that were up- or downregulated by at least fourfold and twofold , respectively , after nir irradiation . in particular , epidermal growth factor receptor ( egfr ) was upregulated by 19.4-fold relative to control cells . quantitative real - time polymerase chain reaction analysis revealed that two variants of egfr in human corneal epithelial tissue were also significantly upregulated after five rounds of 10 j / cm2 irradiation ( p<0.05).conclusionwe found that nir irradiation induced the upregulated expression of egfr in human corneal cells . since over half of the solar energy reaching the earth is in the nir region , which can not be adequately blocked by eyewear and thus can induce eye damage with intensive or long - term exposure , protection from both uv and nir radiation may prevent changes in gene expression and in turn eye damage .
[ "hence , it is essential to have figures on prevalence and clinical presentation from our setup . therefore , we conducted this study to determine the prevalence of hypertensive crisis , its management , and its outcome in patients presenting to a tertiary care center in karachi . the reason for uncontrolled hypertension in pakistan is high due to lack of awareness , knowledge , adherence , and attitudes of pakistani patients with hypertension . however there is no data on patients with hypertensive crisis from tertiary care hospitals in pakistan . hypertension is a common chronic medical condition affecting people in pakistan and the rest of the world . additionally the number of patients who complicate towards stroke , myocardial infarction , and chronic kidney disease is also not known . it is an important modifiable risk factor for cardiovascular morbidity and mortality , particularly for stroke ( accounting for 51% of all stroke deaths worldwide ) , ischemic heart disease ( 45% of all deaths ) , chronic kidney disease , congestive heart failure , aortic aneurysm , and peripheral arterial disease .", "a minimum sample size of 237 patients was required to estimate a proportion of 19% of patients with hypertensive crises presenting to er , with bound on error of 5% and alpha of 5% . data over a period of 5 years , from year 2005 till year 2010 , was used . a sample of 1336 consecutive patients fulfilling the inclusion criterion was selected . various complications like myocardial infarction , stroke , aortic dissection , acute renal failure , and pulmonary edema developed during the hospital stay were recorded using the discharge summary notes filled by the primary consultant . patients admitted with primary diagnosis of hypertension crisis , uncontrolled hypertension , hypertensive emergency , and hypertensive urgency were selected through the icd-9-cm ( i-10 : essential ( primary ) hypertension , i-11 : hypertensive heart disease , i-12 : hypertensive renal disease , i-13 : hypertensive heart and renal disease , and i-15 : secondary hypertension ) . a history of physician - diagnosed diabetes mellitus ( dm ) , chronic kidney disease ( ckd ) , ischemic heart disease ( ihd ) , and stroke was noted from the patient 's medical record file . myocardial infarction was diagnosed when blood levels of sensitive and specific biomarkers such as cardiac troponin or ckmb are increased in the clinical setting of acute myocardial ischemia with electrocardiographic changes . according to who definition , this was a retrospective study conducted at the aga khan university , karachi , pakistan .", "a total of 73,063 hypertensive patients presented to the er between years 2005 and 2010 out of which a sample of 1336 ( 1.8% ) patients was taken for this study . the prevalence ( % ) of uncontrolled hypertension was 28.9% ( 387 ) . overall prevalence ( % ) of complications was 47.7% ( 104 ) in patients with hypertensive crisis . on further categorization of patients with hypertensive crisis who received intravenous antihypertensive in er versus not receiving intravenous medication , there was no significant difference in the complications in both groups .", "the strength of this study is that it is the first study from this region to report figures on prevalence of hypertensive crisis , as well as prevalence of complications as a result of hypertensive crisis among patients . we have shown in this study on patients presenting to er with hypertensive crisis that the prevalence of hypertensive crisis is high ( 56.3% ) . mean length of stay was longer in patients with hypertensive crisis and acute renal failure was the most common complication in these patients . this indicates that the use of intravenous nitrate as the most common antihypertensive for management of hypertensive crisis ( apart from use in patients with cardiac cause ) is not completely in accordance with the recommendations . intravenous labetalol was reported as the most frequently used antihypertensive medication for emergency department patients presenting with hypertensive urgency . the most common intravenous medication used to control hypertensive crisis in this study was nitrates .", "the prevalence of hypertensive crisis is high in our subjects . per oral calcium channel blocker and intravenous nitrate are the most commonly administered medications in the er and ward ." ]
objectives . hypertension , if uncontrolled , can lead to hypertensive crisis . we aim to determine the prevalence of hypertensive crisis , its management , and outcome in patients presenting to a tertiary care center in karachi . methods . this was a cross - sectional study conducted at the aga khan university , karachi , pakistan . adult inpatients ( > 18 yrs ) presenting to the er who were known hypertensive and had uncontrolled hypertension were included . results . out of 1336 patients , 28.6% ( 387 ) had uncontrolled hypertension . the prevalence of hypertensive crisis among uncontrolled hypertensive was 56.3% ( 218 ) . per oral calcium channel blocker ; 35.4% ( 137 ) and intravenous nitrate ; 22.7% ( 88 ) were the most commonly administered medication in the er . the mean ( sd ) drop in sbp in patients with hypertensive crisis on intravenous treatment was 53.1 ( 29 ) mm hg and on per oral treatment was 43 ( 27 ) mm hg . the maximum mean ( sd ) drop in blood pressure was seen by intravenous sodium nitroprusside ; 80 ( 51 ) mm hg in sbp . acute renal failure was the most common complication with a prevalence of 11.5% ( 24 ) . conclusion . the prevalence of hypertensive crisis is high . per oral calcium channel blocker and intravenous nitrate are the most commonly administered medications in our setup .
[ "p2y12 expression in primary microglia is variable with postnatal development and shows sexually dimorphic behavior . through the use of all the available p2y12-immunoreactive antibodies recognizing the c - terminus or the second intracellular loop of the receptor , the aim of the present work is to provide comparative evidence about p2y12 cell specificity in microglia versus oligodendrocytes particularly from the healthy and diseased cns under neuroinflammatory conditions as those sustained during amyotrophic lateral sclerosis ( als ) and multiple sclerosis ( ms ) . since neuroinflammation accompanies a large variety of neurodegenerative diseases , there is increasing interest in determining how the different cell phenotypes and cellular interconnectivity might contribute to reduce inflammation and reverse neurodegeneration . microglia actively participate to the context - dependent , neuroprotective / neurotoxic molecular network that is triggered during neuroinflammation . among the molecular cues having a key role in this process , a basic set of proteins and mrnas are differentially expressed among cell types , temporally and spatially , generating a vast assortment of cell phenotypes and/or activation states within a single tissue .", "microglia primary cultures prepared from mouse cortex as previously described were about 98% pure , as verified by immunofluorescence with cd11b ( for microglia ) , glial fibrillary acidic protein ( gfap , for astrocytes ) , neuronal nuclei ( neun , for neurons ) , and smi94 ( for oligodendrocytes ) . the obtained cdna was then cloned into the xhoi and xbai sites of the eukaryotic expression vector cs2 + mt to provide n - terminal 6x c - myc epitope - tagged mammalian expression plasmids , which has been validated by dna sequencing . mixed glial cultures were then shaken at 200 rpm at 37c for 1 h and 98% pure microglia collected from the supernatant of each flask , as verified by immunofluorescence with gfap , neun , neural / glial antigen 2 ( ng2 , for oligodendroglial precursor cells ) , myelin basic protein ( mbp , for mature oligodendrocytes ) , and cd11b . primary rat microglial and oligodendrocyte cells were lysed with trizol ( life technologies ) and total rna was extracted following the manufacturer 's instructions . a 98% pure population of oligodendrocytes was thus obtained , as verified by immunofluorescence with ng2 , mbp , gfap , neun , and cd11b antibodies . adult b6.cg-tg ( sod1-g93a)1gur / j mice expressing high copy number of mutant human sod1 with a gly93ala substitution ( sod1-g93a ) were originally obtained from jackson laboratories ( bar harbor , me , usa ) and housed in our indoor animal facility as described in apolloni and collaborators , .", "in order to provide wide ranging comparative analysis of p2y12 expression particularly in microglia and oligodendrocytes under neuroinflammatory conditions , we performed immunofluorescence and confocal analysis of receptor expression in primary cortical and organotypic cerebellar cultures , in tissue slices from rat striatum and cerebellum , in spinal cord sections from symptomatic and end stage sod1-g93a als mouse model , finally in autoptic cortical tissue from progressive ms donors . if p2y12 recognized by c - ter antibody exclusively in microglia from rat brain slices could be used as specific microglia marker during neuroinflammation , we validated its use in a typical neuroinflammatory disease such as als and for the first time characterized the presence of p2y12 receptor in sod1-g93a mouse model ( figure 4 ) . by immunofluorescence and confocal analysis on lumbar spinal cord sections ( l3l5 ) of wild - type ( wt ) mice , we first compared the immunoreactive signals obtained with c - ter and specific microglia markers cd11b ( red , recognizing ramified microglia ) and cd68 ( red , recognizing roundish activated microglia ) . in wt mice p2y12 protein is specifically recognized in extracts from human cerebral cortex snap frozen tissue , rat and mouse brain , mouse primary microglia ( mmg ) and ol ( figure 1(c ) ) . importantly , c - ter , intra1 ( red , insets a - f2 ) and intra2 , and intra fl ( data not shown ) antibodies all recognize the presence of p2y12 receptor in integrin ii/3-positive platelets ( green ) contained in the blood vessels of the analyzed tissues . as observed in als mouse spinal cord where p2y12 receptor detected by c - ter antibody is shown to temporally and regionally decrease in microglia as a function of increasing inflammatory damage ( figure 4 ) , we notice that microglia gradually lose immunoreactivity for c - ter antibody ( figure 6 ) in proximity to the demyelinating active cortical lesions of ms expressing augmented positivity for mhc ii [ 3335 ] .", "that both down - regulate the harmful responses and up - regulate the beneficial responses may hopefully slow pathological progression and provide meaningful hope for treatment . at the same time , the identification of clear markers involved in the m2/m1 microglia transition becomes mandatory for presymptomatic diagnosis , monitoring of disease progression , and efficacy of therapies . under this perspective , and consistently with previous findings establishing the role of purinergic receptors in the pathogenesis of both als and ms [ 14 , 43 ] , our present work serves this aim , by highlighting the gradual loss of p2y12 immunoreactivity as an early marker of neuroinflammation and microglia metamorphosis . anyhow , we can assert that the distinctive recognition of multibranched microglia renders the c - ter antibody a novel and useful tool to discriminate among microglia morphological states , thus making p2y12 receptor a selective and early marker for the ramified phase . we have indeed demonstrated here that p2y12 receptor protein identified in primary cultures of both microglia ( figure 2(a ) ) [ 18 , 44 ] and oligodendrocytes ( figure 2(b ) ) by different but p2y12-selective antibodies can be instead recognized in branched microglia exclusively by the use of c - ter antibody ( figures 36 ) .", "by comparative analysis of all the available p2y12-immunoreactive antibodies recognizing the c - terminus or the second intracellular loop of the receptor , we have established here that , under experimental conditions of well - preserved cytoarchitecture and tissue integrity , p2y12 receptor expressed by both ramified microglia or oligodendrocytes / myelinated fibers might serve a dual function as specific marker , respectively , of branched / surveillant microglia as well as demyelinating lesions . we believe that p2y12 identification and modulation might potentially acquire an important predictive value under neuroinflammatory conditions , as those found in als and ms . p2y12 is likely to deserve a key role in the verge of a neuroinflammatory breakdown ." ]
in the cns , neuroinflammation occurring during pathologies as amyotrophic lateral sclerosis ( als ) and multiple sclerosis ( ms ) is the consequence of an intricate interplay orchestrated by various cell phenotypes . among the molecular cues having a role in this process , extracellular nucleotides are responsible for intercellular communication and propagation of inflammatory stimuli . this occurs by binding to several receptor subtypes , defined p2x / p2y , which are widespread in different tissues and simultaneously localized on multiple cells . for instance , the metabotropic p2y12 subtype is found in the cns on microglia , affecting activation and chemotaxis , on oligodendrocytes , possessing a hypothesized role in myelination , and on astrocytes . by comparative analysis , we have established here that p2y12 receptor immunolabelled by antibodies against c - terminus or second intracellular loop , is , respectively , distributed and modulated under neuroinflammatory conditions on ramified microglia or myelinated fibers , in primary organotypic cerebellar cultures , tissue slices from rat striatum and cerebellum , spinal cord sections from symptomatic / end stage sod1-g93a als mice , and finally autoptic cortical tissue from progressive ms donors . we suggest that modulation of p2y12 expression might play a dual role as analytic marker of branched / surveillant microglia and demyelinating lesions , thus potentially acquiring a predictive value under neuroinflammatory conditions as those found in als and ms .
[ ", we characterized the spectrum of severity of kidney injury in a cohort of icu patients with aki who required dialysis . we specifically tested the association of creatinine elevation during icu stay , starting with icu admission and prior to dialysis initiation , with the risk of hospital mortality . acute kidney injury ( aki ) requiring dialysis is a serious complication in critically ill patients , bringing increased morbidity , mortality , and costs of care [ 14 ] . the consensus panel also proposed that the examination of natural history of severe aki in icu to be one of the high - priority research areas , with a goal that new information may improve our ability in conducting prospective trials of intervention aki [ 14 , 15 ] . to date , there are limited studies that have examined the course or progression of aki after icu admission until the point of dialysis initiation . whether the degree of severity of kidney injury prior to dialysis requirement independently influences mortality risk in aki is not known . in order to facilitate risk stratification that may be useful for the development of prospective studies , which are geared towards early diagnosis or intervention in severe aki we also examined the impact of severity of illness upon icu admission on the mortality risk in these patients . it is well recognized that small changes in creatinine ( mild - to - moderate aki ) independently predict mortality [ 10 , 11 ] ; we also recently reported that patients with aki requiring dialysis represent a wider spectrum of severity of kidney injury , contrary to the prevalent notion . thus , it can be hypothesized that the degree of elevation of creatinine prior to initiating dialysis may discriminate risk - adjusted mortality , similar to the observations in nondialysis requiring aki . ", "for this analysis , we specifically focused on examining characteristics and outcomes of those aki patients who progressed to new requirement of dialysis ( aki - d ) during icu stay ( part of stage iii aki according to the akin classification system ) . we categorized aki - d into four groups based on the change in creatinine level after icu admission but prior to initiation of dialysis : group i had an increase in creatinine ranging from 0.3 mg / dl to < 2-fold increase , group ii an increase in creatinine 2 times baseline but <3 times , group iii 3-fold increase in creatinine , and group iv included those patients with new dialysis requirement in icu but who experienced a creatinine elevation of < 0.3 mg / dl . independent predictors in the second step included the predicted mortality ( determined from the first step ) and the patient group based on creatinine elevation before dialysis . we examined a cohort derived from the veterans affairs ( va ) inpatient evaluation center ( ipec ) ; a national quality improvement program which reports risk - adjusted mortality , length of stay , and adherence to evidence - based practices in all va icus , by collecting data electronically from va computer databases . the study accounts for differences in patient characteristics using a previously validated logistic regression model that predicts mortality risk for each patient from independent predictors ( age , thirty - one comorbid disease groups ( by icd-9-cm codes ) , eighty - four mutually exclusive admission diagnoses determined from the icd-9-cm codes denoting the reason for admission to the icu , source of admission ( emergency room , outpatient clinics , ward , hospital , operating room , or nursing home ) , and the worst value of each of the 11 laboratory tests measured within 24 hours of icu admission ( sodium , urea , creatinine , bilirubin , albumin , glucose , hematocrit , white blood cell count , pao2 , paco2 , and ph ) .", "dialysis patients in groups ii and iii had a significantly higher smr than those patients in groups i and iv , when predicted mortality was < 10% or 1030% ; smr was not significantly different across all four groups in patients admitted with > 30% predicted mortality on icu admission . the frequencies of patients admitted with primary icu admission diagnoses of kidney disorders or electrolyte and metabolic disorders significantly varied across four groups and were 24% and 21% , respectively , in group iv ( < 0.3 mg / dl increase in creatinine before dialysis ) compared with only 1.9% and 2.1% in group iii ( > 3 times increase in creatinine before dialysis ) . overall , 21.9% of patients developed aki ( 71,090/324,999 ) of whom 2,744 patients experienced severe aki requiring dialysis . in contrast patients in other groups , who sustained only milder or no elevation in creatinine before dialysis initiation , had significantly higher creatinine and bun levels on icu admission . \n group iii patients ( those with > 3 times increase in creatinine prior to dialysis ) had the lowest levels of creatinine or bun on icu admission .", "the present study advances our understanding of natural history of progression of acute kidney injury during icu stay , in those patients who require dialysis . the present study is one of the first reports to show that in patients who developed aki requiring dialysis , the degree of kidney injury prior to dialysis initiation determines mortality risk , after accounting other major predictors of hospital mortality . the study finds that , in patients with aki requiring dialysis , the risk of mortality is independently associated with the degree of severity of kidney injury sustained during icu stay prior to dialysis initiation and that severity of illness further influences this relationship . somewhat indirect evidence comes from the studies that have reported the impact of baseline chronic kidney disease ( ckd ) in patients with aki requiring dialysis ." ]
in a multicenter observational cohort of patients - admitted to intensive care units ( icu ) , we assessed whether creatinine elevation prior to dialysis initiation in acute kidney injury ( aki - d ) further discriminates risk - adjusted mortality . aki - d was categorized into four groups ( grp ) based on creatinine elevation after icu admission but before dialysis initiation : grp i > 0.3 mg / dl to < 2-fold increase , grp ii 2 times but <3 times increase , grp iii 3-fold increase in creatinine , and grp iv none or < 0.3 mg / dl increase . standardized mortality rates ( smr ) were calculated by using a validated risk - adjusted mortality model and expressed with 95% confidence intervals ( ci ) . 2,744 patients developed aki - d during icu stay ; 36.7% , 20.9% , 31.2% , and 11.2% belonged to groups i , ii , iii , and iv , respectively . smr showed a graded increase in grp i , ii , and iii ( 1.40 ( 95% ci , 1.291.42 ) , 1.84 ( 1.662.04 ) , and 2.25 ( 2.072.45 ) ) and was 0.98 ( 0.781.20 ) in grp iv . in icu patients with aki - d , degree of creatinine elevation prior to dialysis initiation is independently associated with hospital mortality . it is the lowest in those experiencing minor or no elevations in creatinine and may represent reversible fluid - electrolyte disturbances .
[ "many previous studies have revealed that parents , especially mothers , of children with developmental disabilities such as intellectual disabilities ( ids ) , developmental delay , and physical and sensory handicaps are more likely to show signs of psychological distress or depressive symptoms and to exhibit lower well - being than parents of typically developing children [ 15 ] . so far , the major portion of resources has been directed to the treatment of and services connected with the children , and not enough attention has been paid to the actual mental condition and needs of the parents . to our knowledge , there have been no reports on a nationwide scale on the mental health and distress of parents having children with developmental disabilities in japan . since the understanding of the parents ' . evidently , the current psychiatric services in japan are not adequate to meet the complex mental health needs of people with i d appropriately , sensitively , and effectively . specialist psychiatric services for people with i d are available in some countries such as the uk and the usa ; however , the provision of high - quality psychiatric services remains a major concern in many countries . the paucity of trained psychiatrists and other allied professionals is a major barrier to the development of this subspecialty in many countries . in japan , high - quality psychiatric services for the parents of children with i d are assumed to be not well established . mental health may be essential for providing more appropriate support , we aimed to obtain a clear perspective on the situation facing the parents through this facility - based nationwide study .", "the first section sought information about the characteristics of the facility , such as staff adequacy , the scale of the facility , the health promotion services provided , the ages of their clients , and the clients ' main disabilities , namely , i d , pervasive developmental disorder ( pdd ) , profound intellectual and multiple disabilities ( pimd ) , physical disabilities , and others . the current survey included 1,102 institutions and consultation centers for children with developmental disabilities distributing in all prefectures in japan , which were listed in the national register of agencies , organizations , and institutions related to intellectual disabilities and the directory of support centers for individuals with developmental disabilities . professional workers in these facilities come into contact with children as their clients , and also with the children 's guardians , mainly with the mothers , on a daily basis . the second section sought information about the clients ' parents , such as signs of mental health distress and their needs , from the professional caregivers ' point of view . in japan , these institutions and centers play a key role in social support networks . also measures taken by the professional caregivers when encountering distressed parents were asked in detail . the questionnaire was written in japanese and was divided into two sections with a total of 47 multiple choice questions .", "practical use ( or not ) of social support networks , whether the child 's level of disability was severe or not , and parent participation in face - to - face family support groups or not were also thought to be influential factors . in all groups , regardless of the child 's disability , more direct welfare support for the child was considered to be helpful and thus requested to be improved , in order to meet the mental health needs of the parent . besides this , in the physical disability group , family support groups , in the pimd group , support ( including financial support ) for other family members , and in the i d and pdd groups , support for other family members ( mainly siblings and the other parent ) and medical treatment of the parent 's psychiatric disturbance were also emphasized . to fulfill the demanded future role of their facility signs of depression or a depressive state were the most common psychiatric disturbances seen in the parents . among the four groups , the pdd group most commonly experienced cases which showed signs of depression or a depressive state in parents . the parent 's poor socio - economic status and heavy care - giving burden , reflecting the child 's level of disability , were considered to be major factors in approximately one - third of the cases . many factors were reported to affect the mental health of parents . the presence or absence of support from other family members (", "in the present study , we surveyed institutions and consultation centers for children with developmental disabilities in japan , which play a central role in the social support networks . overall , the present study is the first nationwide survey that examined the professional caregivers ' perspective on the mental health of parents of children with developmental disabilities , and it underscores the importance of understanding and supporting the parents ' mental health needs , which leads to more appropriate support for children with developmental disabilities . almost all of the facilities experienced difficulties in keeping good relations with the clients ' parents , regardless of the children 's disabilities , and the majority of service providers noted that the proportion of such parents , out of the total , was roughly between 5 and 25% , and still increasing . this facility - based nationwide survey revealed the situation facing the parents of children with i d and other developmental disabilities from the professional caregivers ' point of view . these results suggested that thorough consideration of the parents ' mental health needs , especially prevention of depressive conditions and support for parents suffering from them , is urgent - demanded task for facilities ." ]
parents of children with intellectual disabilities and/or physical disabilities are supposed to have an increased risk for parenting stress and psychological distress . we as professional caregivers sometimes experience difficulties in keeping good relations or communicating with the parents . professional workers in 460 institutions and consultation centers throughout japan answered a questionnaire on their clinical experiences . about 90% of the facilities experienced distressed parents , and the parents ' condition such as mental health seemed to influence this . signs of a depressive state were the most common psychiatric disturbances detected , and it was notable in the pervasive developmental disorder group . more welfare support , presence of support groups , support from other family members , and medical treatment of the parents ' problems were considered to be helpful and thus requested to be improved . training more professionals who can properly deal with the parents ' mental health needs is an urgent matter that must be tackled .
[ "a case - control study and environmental investigation were undertaken to identify the vehicle of infection and source of the outbreak . in may 2001 , 24 cases of s. typhimurium dt160 salmonellosis were reported in the auckland region compared with an average of four sporadic cases each month with this serotype in the previous 7 months . four of the five patients who had eaten raw eggs could identify the retail brand and outlet of purchase .", "the source of this incursion of s. typhimurium dt160 into new zealand remains unknown : bird isolates have been exclusively from nonmigratory birds , s. typhimurium dt160 has not been identified in neighboring countries in the pacific basin , and early case - patients did not have a history of overseas travel . epidemiologic investigation of an outbreak of s. typhimurium dt160 infection in new from may to august 2001 found that contact with dead wild birds , contact with other persons with gastrointestinal illness , and consumption of fast food were all significantly associated with illness . consumption of undisinfected water has previously been identified as a risk factor for salmonellosis linked to bird transmission ( 14 ) ." ]
an outbreak of human salmonella enterica serotype typhimurium dt160 infection in new zealand was investigated from may to august 2001 . handling of dead wild birds , contact with persons with diarrheal illness , and consumption of fast food were associated with infection . contaminated roof - collected rainwater was also detected .
[ "we present an approach to finding non - crystallographic symmetry by directly searching for patterns of density that are present in more than one place in a map . we find that this is a rapid and accurate way to identify ncs , even in a case where the map is poor and the correlation of ncs - related density is low . non - crystallographic symmetry ( ncs ) is common in macromolecular crystals , occurring in about 1/3 or more of structures in the protein data bank [ 2 , 3 , 24 ] . though non - crystallographic symmetry increases the complexity of structure determination , in most cases it yields a distinct advantage in this process because it brings with it information on relationships between density in different parts of the crystal and between coordinates in different parts of the structure [ 4 , 1214 ] . this approach uses superposition of a cut - out region of the map with the remainder of the map , and therefore can make use of all the local features in a map , not just rotation - invariant ones . in this approach , an fft - based convolution search [ 5 , 16 ] is used to find orientations and translations that relate parts of a map to other parts of a map . one is simple examination of a model that has more than one copy of a chain .", "once a set of candidate ncs operators is obtained , the correlation of ncs - related density is examined in the original map , and the ncs operators are refined . then the ncs operators are refined to maximize the correlation of density among these ncs - related regions . the approach used here to identify non - crystallographic symmetry from an electron density map has three basic parts . the method used to identify such a location in the map is similar to a method commonly used to distinguish macromolecule from solvent in a map . for each grid point in the electron density map , the local rms variation in electron density is calculated . the density is transformed to the new orientation , and an fft - based convolution search [ 5 , 16 ] is used to identify non - crystallographic translations that yield a high correlation of density .", "the method used to identify such a location in the map is similar to a method commonly used to distinguish macromolecule from solvent in a map . for each grid point in the electron density map , the local rms variation in electron density is calculated . the approach used here to identify non - crystallographic symmetry from an electron density map has three basic parts . first , a location in the map is found that is likely to be inside the molecule . this is done by simply calculating the standard deviation of the density in the map inside a sphere with radius r ( typically 10 ) , centered at the grid point in question . then the grid point in the map with the highest local standard deviation of density is considered the best candidate for a position inside the macromolecule . additional points likely to be inside the macromolecule can optionally be found by choosing additional grid points with high local variation in density that are well separated ( typically at least 15 ) from previously chosen locations . this is important as it is the local symmetry of the molecule or molecules in the crystal that are of interest , so considering a region inside the molecule is essential for success .", "these rotation / translation pairs that yield high correlation ( typically all those at or above 75 % of the highest value found ) represent a possible set of ncs operators relating the various copies of the molecule in the asymmetric unit of the unit cell . additionally , the candidate point used to identify ncs and the ncs - related points in the map may be considered approximate centers of regions where ncs applies . next , a search for ncs relating the density near the candidate point inside the macromolecule with density elsewhere in the asymmetric unit of the crystal is carried out . to make the calculation rapid , they are used below as the starting point for identification of the region where ncs operators apply . the density is transformed to the new orientation , and an fft - based convolution search [ 5 , 16 ] is used to identify non - crystallographic translations that yield a high correlation of density . the resolution of the map used for this calculation may be chosen to be lower than the resolution of the original map ( typically a resolution of 4 is used ) . this sphere of density is the object that is to be compared with density everywhere in the map .", "once a set of candidate ncs operators is obtained , the correlation of ncs - related density is examined in the original map , and the ncs operators are refined . then the ncs operators are refined to maximize the correlation of density among these ncs - related regions . a region with arbitrary shape surrounding this point is then chosen by sequential addition of new boundary points such that the local correlation of ncs - related density at each point in the region is above a threshold ( typically 1/4 of the maximum correlation in the region ) . the local correlation of density is calculated using map grid points within a sphere ( normally with the radius used for identification of the solvent boundary , terwilliger 2000b ) , centered at the point in question . if the final correlation of ncs - related density ( averaged over all pairs of ncs - related points ) is above a threshold ( typically 0.4 ) then the ncs operators are considered to represent actual ncs in the crystal and are used in later stages of structure determination . in cases where the starting map is very poor , this is done using the same approach as has been applied to ncs operators obtained from heavy - atom positions . first the shape and position of the local region that is repeated by ncs ( the asymmetric unit of ncs ) is found . this threshold may be decreased , increasing the sensitivity of the procedure but also increasing the probability of finding ncs where none is present .", "we applied our procedure to finding non - crystallographic symmetry to a structure where an electron density map of moderate quality could be obtained using mad phasing . 1c and the other 4 locations within the asymmetric unit of the density in this crystal were then refined to identify the region over which correlation of density existed and to optimize the correlation of density among all copies of this repeated density . the density map was examined to find locations where the local variation of density was highest using the method phenix.guess_molecular_centers . it can be seen that this density has features even more like those expected of a density map of a protein than the individual regions of density ( the tubes of density are better - connected ) . it can be seen that this point is well within the region of the map with protein - like characteristics ( relatively connected and high density ) .", "the approach described here could also be used to find density that is similar in two different electron density maps . the approach described here for finding ncs in a map can be used in a number of situations . in the phenix crystallographic software , this last application could be useful in automatically finding relationships between molecules in different crystals when carrying out cross - crystal averaging . the method phenix.find_ncs_from_density is used during structure solution with phenix.autosol if ncs is expected but can not be found from heavy - atom sites , and it is used during iterative model - building with phenix.autobuild any time it is expected and has not been identified by any other means . the maps to be analyzed for ncs can be crystallographic maps , maps from electron microscopy , or maps from other sources . the ncs relationships identified in this way can be used as a powerful addition to the information available for density modification [ 4 , 1214 ] . these relationships can also be used in model - building , where an incompletely built chain can be built using a more complete ncs - related copy of the same chain as a template [ 9 , 15 , 20 ] ." ]
the internal symmetry of a macromolecule is both an important aspect of its function and a useful feature in obtaining a structure by x - ray crystallography and other techniques . a method is presented for finding internal symmetry and other non - crystallographic symmetry in a structure based on patterns of density in a density map for that structure . regions in map that are similar are identified by cutting out a sphere of density from a region that has high local variation and using an fft - based correlation search to find other regions that match . the relationships among correlated regions are then refined to maximize their correlations and are found to accurately represent non - crystallographic symmetry in the map .
[ "the aim of this study was to identify specific behavioral risk factors for overweight in young children and to assess their quantitative contribution to the prevalence of overweight in the general population and in high risk sub groups . in a large population - based birth cohort , we prospectively investigated associations between dietary habits , screen time and physical activity when the children were 5 and 7 years old and overweight at the age of 8 years . we also assessed the role of these behavioral factors separately in high risk sub groups : children of mothers with overweight and children of mothers with low education . it is well established that children from families with a low socio - economic status and children with overweight parents are at increased risk to develop overweight [ 39 ] . it is therefore particularly important to assess the role of behavioral risk factors specifically in these children , since they are the priority target groups for interventions to prevent and reduce overweight . we estimated the reduction of overweight prevalence that could be achieved if the prevalence of risk factors would be reduced . prevention , preferably starting at an early age , is considered as the key strategy to achieve this goal , and considerable effort is put into the design of preventive measures . whereas we know in general terms that overweight is the result of an unbalance between energy intake and energy expenditure , development of effective preventive measures requires a much more specific understanding . specific dietary habits and ( in)activities associated with overweight risk in specific age groups need to be identified and their quantitative contribution to the overweight prevalence in the population needs to be assessed . putting a halt to the rising trend in overweight prevalence has high priority in public health policy all over the developed world .", "the study population consisted of children who participated in the dutch prevention and incidence of asthma and mite allergy ( piama ) birth cohort study . in addition , the analyses were repeated , stratified for maternal education , maternal overweight and gender . the number of obese children was too small for analyses with fully adjusted regression models , and obesity was therefore not used as outcome measure in these analyses . in previous studies in the piama cohort , breast feeding was investigated in relation to overweight risk and was found to be associated with reduced overweight risk [ 12 , 13 ] . although breastfeeding is not the subject of this study , results on breast feeding are shown in the tables for completeness . in additional analyses , complete data on overweight and risk factors were available for 1871 children ( 47% of the 3963 children in the study at birth ) . during the medical examination of the 8-year - old children , the associations of physical activity and diet with overweight were also assessed separately for the exposures at age 5 and at age 7 . the associations between the exposure variables and overweight at the age of 8 years were analysed by logistic regression , adjusted for gender and birth weight .", "the association between maternal overweight and overweight in the child weakened only marginally in the model including behavioral risk factors ( 5% change in regression coefficient from 1.07 to 1.02 ) , indicating that the association between maternal overweight and overweight of the child is only to a limited extent mediated by the behavioral factors studied ( see table 2 , model 4 ) . the analyses were repeated after stratification for low maternal education , maternal overweight and gender , respectively . in the sub groups with low maternal education and with maternal overweight low maternal education and especially maternal overweight were strong predictors of childhood overweight ( see table 2 , model 1 ) . the association between low maternal education and overweight weakened substantially in the model including the behavioral risk factors ( an almost 25% change in the regression coefficient from 0.50 to 0.38 ) , indicating that these specific factors explain at least part of the excess overweight prevalence in children of mothers with low education ( see table 2 , model 3 ) . the results suggest that the associations between screen time and overweight were weaker in children of mothers with overweight or low education than in children of mothers with a normal weight or higher level of education ( table 4 ) .", "low maternal education and maternal overweight were found to be strongly associated with overweight in the child . we repeated the regression analyses in sub groups stratified by maternal weight status and maternal education . whereas in the high risk sub groups , screen time was higher than in low risk sub groups , the associations between screen time and overweight were weaker ( although not statistically significantly ) in these groups , and the population attributable risk percentage was lower than in the low risk sub groups . as the children of mothers with overweight and/or low education are the children at highest risk to develop overweight , this observation is potentially important for the development of preventive strategies and needs to be clarified in future observational as well as intervention studies . of 8 different potential behavioral risk factors , only screen time showed consistent and significant associations with overweight . in high risk sub groups of the population , the association between low maternal education and overweight weakened substantially when the behavioral risk factors were included in the model , indicating that these factors explain part of the association . our results thus suggest that , among the indicators of active and sedentary behavior that we studied , screen time is the most important risk factor for overweight in the age group studied .", "reduction of screen time should be part of interventions to prevent or reduce overweight in young children and could result in a reduction of overweight prevalence in the order of 2 percentage points in both high and low risk sub groups . our results also suggest however that interventions aimed to promote sports club membership , active transport to school , and playing outside may have little impact on the prevalence of overweight in this age group . the possibility that , due to reverse causation , associations between food intake and overweight can not be assessed in observational studies , needs further study ." ]
objective . to prospectively identify behavioral risk factors for childhood overweight and to assess their relevance in high risk sub groups ( children of mothers with overweight or low education ) . methods . in the piama birth cohort ( n = 3963 ) , questionnaire data were obtained at ages 5 and 7 on screen time , walking or cycling to school , playing outside , sports club membership , fast food consumption , snack consumption and soft drink consumption . weight and height were measured at age 8 years . results . screen time , but none of the other hypothesized behavioral factors , was associated with overweight ( aor 1.4 ( ci : 1.21.6 ) ) . the adjusted population attributable risk fraction for screen time > 1 hr / day was 10% in the high risk and 17% in the low risk sub groups . conclusion . reduction of screen time to < 1 hr / day could result in a reduction of overweight prevalence in the order of 2 percentage points in both high and low risks sub groups .
[ "these minimal health effect levels were derived using the tri service standards for field water and based on an average consumption of 10 liters per day for seven days for a 70 kg service member . therefore , detection of ricin and seb in water at or below the suggested health effect level is desired . the ability of the hhas to detect seb and ricin in four different water matrices , representative of waters used by different branches of the armed forces , was evaluated . the hhas were not modified in any way to optimize for the detection of toxins within water supplies despite the fact that they were initially developed to test for concentrated agent collected from high - efficiency aerosol collectors and impinged into a phosphate buffered saline ( pbs ) solution rather than to test unbuffered water supplies . the effectiveness of hhas in detecting biological agents in the air and in powders has resulted in a desire to test these assays to gauge their effectiveness to protect drinking water supplies used by us warfighters . in the present study , hhas from multiple manufacturers were evaluated for their effectiveness at detecting two specific targets , seb and ricin , in multiple water matrices . civilian first responders use similar versions of these antibody - based hhas for testing suspicious powder samples suspected to contain bwas . depending on which manufacturer of hha", "both singleplex ( one - line ) and multiplex ( two - line and two - dot ) hha models produced by two manufacturers were evaluated in the present study for the detection of ricin toxin and seb [ 5 , 6 ] . limits of detection ( lod ) were determined for each hha type in each water matrix and defined as the minimum concentration of toxin that could be detected by eye . active seb ( toxin technologies , sarasota , fla , usa ) and active ricin whole toxin ( vector laboratories , burlington , on , canada ) were obtained from the dod 's critical reagents program ( crp ) for use in the present study . the rapid staining protocol with sypro ruby protein stain ( invitrogen ) was used for the detection of seb . samples for circular dichroism ( cd ) were prepared by spiking ro water containing 1 mg / l fac with seb to a final concentration of 2 g / ml . control samples received no chlorine .", "due to the increased detection limits observed in chlorinated and brominated water , cd spectroscopy , which assesses the three - dimensional fold of a protein , was performed on samples of untreated seb and seb exposed to chlorine in an effort to evaluate the basis for increased lods ( figure 1 ) . for each sample all hhas were evaluated for their performance in formulated tap water , formulated tap water with chlorine , ro water with chlorine , and ro water with bromine for the detection of ricin and seb . detection below the suggested health effect level was desired ; however , seb was not detected below the suggested health effect level in chlorinated and brominated water and ricin was not detected below that level in brominated water . it was determined that ricin could be detected down to approximately 1 ng / ml for most hha models in both formulated tap water and formulated tap with chlorine , while exhibiting only slightly higher lods in ro with chlorine for most models . however , in ro with bromine , the lod for ricin increased to 3,000 ng / ml for all models tested . for seb , lods in formulated tap water were low , ranging from 0.9 ng / ml to 12.5 ng / ml . however , in both chlorinated and brominated water , lods increased to 2,500 ng / ml for singleplex hhas and even higher to 5,000 or 10,000 ng / ml for multiplex models . in all cases", "performance of hhas for air and surfaces is well known ; however , the use of hhas for detection of agents in water is less recognized . therefore , the application of hhas for detection in water was assessed in this study . in formulated tap water , detection of seb and ricin however , detection of both agents in water is still a concern and technologies capable of detection in water must be investigated . seb could potentially be used to attack low - volume water supplies ; however , due to the fact that ricin is less toxic by oral ingestion , it may be a less likely threat to drinking water ." ]
development of a rapid field test is needed capable of determining if field supplies of water are safe to drink by the warfighter during a military operation . the present study sought to assess the effectiveness of handheld assays ( hhas ) in detecting ricin and staphylococcal enterotoxin b ( seb ) in water . performance of hhas was evaluated in formulated tap water with and without chlorine , reverse osmosis water ( ro ) with chlorine , and ro with bromine . each matrix was prepared , spiked with ricin or seb at multiple concentrations , and then loaded onto hhas . hhas were allowed to develop and then read visually . limits of detection ( lod ) were determined for all hhas in each water type . both ricin and seb were detected by hhas in formulated tap water at or below the suggested health effect levels of 455 ng / ml and 4.55 ng / ml , respectively . however , in brominated or chlorinated waters , lods for seb increased to approximately 2,500 ng / ml . lods for ricin increased in chlorinated water , but still remained below the suggested health effect level . in brominated water , the lod for ricin increased to approximately 2,500 ng / ml . in conclusion , the hhas tested were less effective at detecting ricin and seb in disinfected water , as currently configured .
[ "previous studies have been performed on the pathogenesis and related mechanisms of pulmonary metastasis of osteosarcoma , but the involvement of p15 gene has not been reported . as it is of critical importance for early diagnosis of osteosarcoma to discover a simple but effective biological tumor marker , this study aimed to describe the mechanism of p15 gene mutation in the occurrence and lung metastasis of osteosarcoma in a rat model , as previously described . osteosarcoma is a common primary malignant bone tumor with complicated pathogenesis and frequent distal metastasis , thus causing higher mortality rates , especially in the teenagers . current studies have revealed the role of gene mutation in the proliferation of tumor cells . therefore , it is of critical importance to find a simple and effective biological marker for osteosarcoma , in order to make early diagnosis . this study may provide further evidence for developing methods in clinical diagnosis of malignant osteosarcoma . p15 , a novel tumor - suppressor gene , has been reported to play an important regulatory role in the progression of various malignant tumors , such as pulmonary cancer , nasopharynx cancer , and kidney cancer .", "after 0 , 1 , 2 , 4 , and 6 weeks of the inoculation , 5 rats from model or control groups were sacrificed to separate osteosarcoma and pulmonary tissues . the osteosarcoma model was prepared as previously reported . in brief , after general anesthesia , 0.5 ml umr-106 cell suspensions ( atcc , us , 110 per ml ) , which were cultivated in dmed containing 10% fetal bovine serum ( gibco , usa ) , were subcutaneously injected into the right forelimb of each rat in the model group . sp - ihc staining was used to show the positive expression of tumors cells and metastatic conditions . for a quantitative analysis , 10 randomly selected fields a total of 60 sd rats ( both males and females , ages 4~5 weeks , body weight 150~170 g ) from the laboratory animal center of harbin medical university , were randomly divided into control and model groups ( n=30 each ) . total rna were then extracted from blood cells for further synthesis of cdna , which was then used as the template in pcr assay for the analysis of 2 exon of p15 gene . using specific designed primers ( p15-f , 5-tggct ctgac cactc tgc-3 ; p15-r , 5-agcga attcg ggtgg gaa-3 ) and internal reference gene -actin ( forward , 5-gaaac tacgt tcaag cgatc-3 ; reverse , 5-ctaga agcat ttgcg gtgga-3 ) , the tumor volume was approximated as : ( short diameter long diameter)/2 , as reported elsewhere . the isolated pulmonary tissue was fixed in 10% neutral buffered formalin , followed by xylene dewaxing and gradient ethanol ( 100% , 95% , 80% , and 70% ) hydration .", "a total of 60 sd rats ( both males and females , ages 4~5 weeks , body weight 150~170 g ) from the laboratory animal center of harbin medical university , were randomly divided into control and model groups ( n=30 each ) . the osteosarcoma model was prepared as previously reported . in brief , after general anesthesia , 0.5 ml umr-106 cell suspensions ( atcc , us , 110 per ml ) , which were cultivated in dmed containing 10% fetal bovine serum ( gibco , usa ) , were subcutaneously injected into the right forelimb of each rat in the model group . rats were used for all experiments , and all procedures were approved by the animal ethics committee of harbin medical university .", "after 0 , 1 , 2 , 4 , and 6 weeks of the inoculation , 5 rats from model or control groups were sacrificed to separate osteosarcoma and pulmonary tissues . sp - ihc staining was used to show the positive expression of tumors cells and metastatic conditions . for a quantitative analysis , 10 randomly selected fields morphological changes were observed , along with the measurement of tumor size . the tumor volume was approximated as : ( short diameter long diameter)/2 , as reported elsewhere . the isolated pulmonary tissue was fixed in 10% neutral buffered formalin , followed by xylene dewaxing and gradient ethanol ( 100% , 95% , 80% , and 70% ) hydration . after being washed with pbs for 3 times , secondary antibody containing 1% labeled biotin was applied for incubation at 37c for 15 min . after being washed with pbs for 3 times , 3% horseradish peroxidase - labeled avidin working solution was used for incubation at 37c for15 min . pbs containing 5% normal goat sera was used to block at 37 for 10 min , then the sera was decanted and added to primary antibody . we added 20 g / ml protease k without dnase to incubate at 37c for 15 min , and then it was boiled in citric acid buffer ( 0.01 m , ph = 6.0 ) for 20 min after being washed 3 times ( 5 min each time ) with pbs until naturally cooling down to room temperature . we carefully followed the instructions in the sp - ihc detection kit ( shanghai yanhui bio - tech , china ) .", "total rna were then extracted from blood cells for further synthesis of cdna , which was then used as the template in pcr assay for the analysis of 2 exon of p15 gene . using specific designed primers ( p15-f , 5-tggct ctgac cactc tgc-3 ; p15-r , 5-agcga attcg ggtgg gaa-3 ) and internal reference gene -actin ( forward , 5-gaaac tacgt tcaag cgatc-3 ; reverse , 5-ctaga agcat ttgcg gtgga-3 ) , peripheral blood samples ( 0.5 ml ) were collected from all animals at the same time points , as detailed above . the reaction parameter was : pre - nature at 95c for 5 min , followed by 40 repeating cycles each containing 95c denature for 30 s , 60c annealing for 30 s , and 72c elongation for 30 s. the reaction was ended by final elongation at 72c for 8 min . agarose gel ( 1% ) electrophoresis was used to visualize pcr fragments lengths , along with -actin - controlled fragments ( 232 bp ) . pcr was performed in the following mixture : 1 l 10 reaction buffer , 70 m dntps ( 4 ) , 100 ng dna templates , 30 ng primers , 100 ng taq dna polymerase , plus ddh2o ( up to 10 l ) .", "spss 20.0 software package was used to analyze all collected data , which are presented as meanstandard deviation ( sd ) . between - group comparison", "in a total of 25 peripheral blood samples in osteosarcoma rats , 18 of them ( 72% ) showed mutation in the 2 exon of p15 gene , while control rats had normal gene isoforms ( table 3 , figure 2 ) . in examining rats from different time points further studies also revealed significant correlation between p15 gene mutation and occurrence of osteosarcoma ( r=0.998 , p<0.05 ) . after the injection of osteosarcoma cells , model rats had significantly elevated tumor cell percentage with the elongation of time . on the first week , most of osteosarcoma and pulmonary tissues showed negative staining for tumor cells . from week 2 , positive staining cells began to occur in model rats but not in control rats . on week 6 , the tumor positive rates were as high as 85% and 72% in primary and pulmonary tissues , respectively ( table 2 , figure 1 ) . one week after the inoculation of tumor cells , there were small tumor lesions underneath the skin around the injection sites .", "abnormally enlarged microvessels can be observed on the surface and in the peripheral muscles of the tumor , even by the naked eye . on the second week as shown in table 1 , the average size of these tumors was 4.000.18 ( in mm ) . , the tumor size increased to 4.000.25 ( in mm ) , with severe edema on the surface and in peripheral tissues . one week after the inoculation of tumor cells , there were small tumor lesions underneath the skin around the injection sites . on the fourth and sixth weeks after injection , tumor size continued to grow ( 17.000.23 and 21.000.31 , in mm respectively ) but more slowly .", "after the injection of osteosarcoma cells , model rats had significantly elevated tumor cell percentage with the elongation of time . on the first week , most of osteosarcoma and pulmonary tissues showed negative staining for tumor cells . from week 2 , positive staining cells began to occur in model rats but not in control rats . on week 6 , the tumor positive rates were as high as 85% and 72% in primary and pulmonary tissues , respectively ( table 2 , figure 1 ) .", "in a total of 25 peripheral blood samples in osteosarcoma rats , 18 of them ( 72% ) showed mutation in the 2 exon of p15 gene , while control rats had normal gene isoforms ( table 3 , figure 2 ) . in examining rats from different time points further studies also revealed significant correlation between p15 gene mutation and occurrence of osteosarcoma ( r=0.998 , p<0.05 ) .", "investigation of the mechanisms underlying the progression and metastasis of osteosarcoma is a popular research topic . recent evidence suggests the complexity of the abnormal regulation of p15 gene involved in bone tumor metastasis . however , the relationship between p15 gene and lung metastasis of osteosarcoma remains to be determined . the clinical features of osteosarcoma mainly include bone pain , hypercalcinemia , and osteolysis metastasis . all these studies point to the importance of p15 gene in inhibiting tumor growth and invasion , both of which are consistent with our results in osteosarcoma .", "our results indicate the close correlation between p15 gene mutation and growth of osteosarcoma , and the potentially direct involvement of p15 gene in pulmonary metastasis . our results suggest the potency of p15 mutant genes as a novel biological marker in early diagnosis of osteosarcoma in clinics , although its detailed molecular mechanism in progression and pulmonary metastasis require further study . molecular biology research is still required to elucidate the mechanism of mutation location of p15 gene , as well as its role in the metastasis of osteosarcoma to the lung ." ]
backgroundas a type of primary malignant bone tumor , osteosarcoma has high incidence and poor prognosis , and is predisposed for pulmonary metastasis . the abnormal expression of p15 gene directly participates in the invasion of various cancers . therefore , this study investigated the gene mutation of p15 in both primary lesion and pulmonary metastasis lesion of osteosarcoma in a rat model , in an attempt to elucidate the value of p15 gene as a biological marker.material/methodsa total of 60 sd rats were randomly divided into 2 groups . model rats had injection of osteosarcoma umr-106 cells ( 5106 ) inoculated underneath the right forelimb skin , while control rats received saline injection instead . six rats were sacrificed after 0 , 1 , 2 , 4 , and 6 weeks of the inoculation . tissue samples from inoculation sites and lungs were extracted for measuring the tumor size . sp immunohistochemical ( ihc ) staining was used to detect the positive expression rate , while p15 gene mutation was detected by pcr method.resultswith the elongation of inoculation time , tumor size was significantly increased ( p<0.05 ) . the positive expression rates in both primary and pulmonary metastasis lesions were also significantly elevated ( p<0.05 ) . the occurrence rate of p15 gene mutation in model rats was significantly elevated and showed a correlation with the tumor formation ( r=0.998 , p<0.05).conclusionsthe p15 gene mutation was significantly correlated with osteosarcoma formation and metastasis towards the pulmonary tissue , suggesting its potency as a novel biological marker for early diagnosis of osteosarcoma .
[ "trichoscopy , dermoscopy hair and scalp , is a noninvasive technique for differential diagnosis of various hair and scalp diseases . here the term was used by hallopeau in 1889 and is derived from the greek ; thrix - hair , tillein - pull out and mania - madness . authors evaluated trichoscopic patterns in ttm and authors believe that these patterns are specific to ttm , which can aide in early diagnosis of this chronic condition . diagnosis is mainly by history and clinical examination , nevertheless , sometimes it is very difficult to differentiate it from other causes of noncicatricial alopecia . scalp is the most common site for pulling hair although other hair bearing areas may be involved . in less severe forms", "initially , ultrasound gel was applied either on the faceplate of dermoscopy or on the skin lesions and then lesions were observed through the eyepiece of dermoscopy . sony camera ( digital , 14 mega pixels ) was attached to save the images . although polarized dermoscopy was employed , ultrasound gel was applied for clarity of images and to lessen distortions associated with light . this study was carried out on 10 patients attending department of dermatology in a tertiary hospital attached to s. nijalingappa medical college at bagalkot , south india between january 2014 and july 2014 . dermlite 3 dermoscope ( 10 magnifications ) with both polarized and nonpolarized lights was employed in the study . ten patients with clinical features of ttm were subjected for a complete history and dermatological examination . demographic data such as age and gender and clinical variables in terms of site of lesions and disease duration were documented .", "this study was carried out on 10 patients attending department of dermatology in a tertiary hospital attached to s. nijalingappa medical college at bagalkot , south india between january 2014 and july 2014 . ten patients with clinical features of ttm were subjected for a complete history and dermatological examination . demographic data such as age and gender and clinical variables in terms of site of lesions and disease duration were documented .", "dermlite 3 dermoscope ( 10 magnifications ) with both polarized and nonpolarized lights was employed in the study . however , only polarized light version was used in our study . initially , ultrasound gel was applied either on the faceplate of dermoscopy or on the skin lesions and then lesions were observed through the eyepiece of dermoscopy . sony camera ( digital , 14 mega pixels ) was attached to save the images . although polarized dermoscopy was employed , ultrasound gel was applied for clarity of images and to lessen distortions associated with light .", "mean age of the patients was 34 years ( minimum age 13 years and maximum age 55 years ) . the most common trichoscopic pattern observed in all patients was decreased hair density and hairs broken at different lengths ( 100% ) [ figure 2 ] . most common symptom was patchy loss of hair over the scalp ( 100% ) especially in the frontal area [ figure 1 ] and one patient ( 10% ) had tonsure pattern of hair loss . the novel diagnostic signs like black dots and flame hair [ figure 4 ] , v - sign [ figure 3 ] , follicular hemorrhages [ figure 5 ] were observed in 3 patients ( 30% ) each . mean duration of disease was 19 months ( minimum 2 months and maximum 36 months ) . all patients ( 100% ) had the noninflammatory alopecia with follicles having distorted and collapsed inner root sheath [ figure 7 ] in histopathology .", "a hairball , trichobezoar , is a rare accompaniment of ttm in those who also eat the plucked hair ( trichophagia ) . in our study , trichotillomania is a chronic impulse control disorder characterized by repetitive hair pulling resulting in alopecia . in young children , it is usually a habit that resolves spontaneously or with minimal treatment . in older age groups , adolescents and adults , the favorite site is the easily reached fronto - parietal region of the scalp followed by eyelashes , eyebrows , pubic hair , body hair and facial hair . the diagnosis of ttm is often difficult as other hair loss diseases appear similar in clinical manifestations .", "trichoscopy , being a noninvasive and in vivo diagnostic technique , can be utilized in this condition as it plays a vital role in the diagnosis of this condition by demonstrating specific trichoscopic patterns . trichotillomania is often chronic and difficult to treat . patients may attempt to disguise the condition due to its social implications . hence further studies on trichoscopic patterns correlating with duration of disease and histopathology of ttm are suggested ." ]
introduction : trichotillomania ( ttm ) is characterized by patchy alopecia of hair bearing areas . this is because of compulsive urge to pull the hair . scalp is the most common site for pulling hair . usually , patients may have only small areas of baldness , in severe forms , tonsure pattern of baldness is observed . diagnosis is by history and clinical examination . however , it is difficult to differentiate from other causes of noncicatricial alopecia . here , authors observed trichoscopic patterns and evaluated their importance in the diagnosis of ttm.materials and methods : this study was conducted in s. nijalingappa medical college , bagalkot , from january 2014 to july 2014 . ten patients with clinically suspected ttm were included in the study . informed consent was taken and ethical clearance was obtained . dermlite3 dermoscope was used with sony camera attachment to save the images . histopathological examination was conducted in all the patients to confirm the diagnosis.results:ten patients were included in the study . mean age of the patients was 34 years . most common symptom was patchy loss of hair in the frontal area ( 100% ) . common trichoscopic feature was decreased hair density and broken hairs . trichoptilosis ( split ends ) and irregular coiled hairs were seen in 80% patients . novel diagnostic signs like black dots , flame hair , v - sign , follicular hemorrhages , were seen in 30% each . tulip hair and hair powder were observed in 10% of patients . all patients had the noninflammatory alopecia with distorted and collapsed inner root sheath in histopathology.conclusion:trichotillomania is often chronic and difficult to treat . hence , early diagnosis and treatment is necessary . authors believe that the trichoscopy plays a vital role in the diagnosis of this condition by demonstrating specific trichoscopic patterns .
[ "we describe a case of primary rectal syphilis which was suspected to be rectal cancer . sexual activity has become more acceptable in our culture recently , initiating various forms of sex , and as a result , many different clinical conditions of sexually transmitted disease ( std ) have appeared . in western countries the incidence of syphilis has risen , mainly in the 20 - 24 age group and its clinical manifestations have been various ( 3 ) . the prevalence of syphilis in the normal population has decreased significantly since 1977 in korea ( 1 , 2 ) . however , therefore , it is difficult to diagnose and physicians occasionally might prescribe inappropriate treatments ( 5 , 6 ) . in this paper it is usually asymptomatic and less frequently presents as proctitis , ulcer and pseudotumors ( 3 , 4 ) .", "the vdrl quantitative test was 1:64 and the fta - abs igm and igg test was positive . a human immunodeficiency virus ( hiv ) a repeat biopsy was done and the histologic result showed focal lymphoid hyperplasia . a vdrl quantitative test after 3 months was 1:1 . he complained of bowel habit change with tenesmus , mucous discharge , anal pain and intermittent presence of blood in stool . follow - up sigmoidoscopy after 1 month showed nearly complete regression of the chancre ( fig . the patient was treated with intramuscular penicillin g benzathine ( 2,400,000 iu im/1 week , thrice ) .", "most physicians have a tendency to consider rectal ulceration as a neoplasm ( 7 , 8) . similarly in our case symptoms and signs suggested rectal neoplasia and the clinical history did not reveal homosexuality . we believe when a positive serologic syphilis test is associated with ulcerative lesion , additional laboratory tests are not necessary . inguinal lymphadenopathy need not require an initial biopsy when evidence of regional infection is present . usually after antibiotic therapy of at least 4 weeks however , after the vdrl test the patient confessed that he had been raped by a homosexual male . therefore , when rectal syphilis is suspected ( i.e. , perianal condyloma acuminatum associated with inguinal lymphadenopathy ) the history of sexual intercourse , especially rectal intercourse , has to be taken ." ]
a 30-yr - old man was referred for suspicious rectal cancer because of ulcerated lesions in the rectum and a palpable mass in left inguinal area . sigmoidoscopy showed two indurated masses and histologic evaluation of biopsy revealed obliterative endarteritis with heavy plasma cell infiltration . both venereal disease research laboratories ( vdrl ) and fluorescent treponemal antibody absorption ( fta - abs ) tests were positive . after injection of penicillin g benzathine for 3 weeks , the rectal chancre and the palpable mass disappeared .
[ "the protective effects of vagus nerve during ischemia / reperfusion ( i / r ) have been suggested ( 1 ) . the role of sensory neurons in protective effects of melatonin in the healing of acute gastric injury and peptic ulcer has been reported . there is no study about the combined effects of melatonin administration and intervention of vagus nerve during gastric i / r injury . probably , vagus nerve and melatonin have interactions in their protective effects during gastric i / r events both protective and harmful effects of the stimulation of vagus nerve in digestive system have been reported . it has been shown that sensory nerve fibers are involved in protective effects of melatonin in the healing of acute gastric injury and peptic ulcer ( 16 ) . it is probable that vagus nerve exerts its gastric protective effects through releasing the aforementioned mediators .", "experimental groups were : 1 ) base+i / r+vehicle ; 2 ) base+i / r+melatonin ; 3 ) vagotomy+i / r+vehicle ; 4 ) vagotomy+i / r+melatonin ; 5)vagus nerve stimulation+i / r+vehicle ; 6)vagus nerve stimulation+i / r+ melatonin . base , means condition that neither vagus nerve was stimulated nor vagotomy was performed . after dissection of vagus nerve , distal end was covered with mineral oil and stimulated with bipolar electrode of a stimulator using 10 volt / msec pulses at the frequencies of 0.625 , 1.25 , 2.5 , 5 or 7.5hz for 30 sec . gastric i / r injury was induced by dissecting celiac artery from the surrounding tissues in rats anesthetized with 50 mg / kg pentobarbital , 30 minutes after dissection of vagus nerve . animals underwent tracheostomy and were cannulated ( in order to prevent probable airway occultation ) under anesthesia induced by intraperitoneal pentobarbital ( 50 mg / kg ) . after local shaving , a small incision was made in cervical area and branches of cervical vagus nerve were carefully dissected from carotid artery and cut ( 1 ) . stimulations were performed with 2-min intervals ( 23 ) . in order to ensure the stimulation of vagus nerve , electrocardiogram mda level was measured according to hiroshi ohkawa method via reaction with thiobarbituric acid and color formation . glutathione peroxides activity was determined by the method described by valentine and paglia method ( 20 ) , and enzyme activity was reported as u / mg protein . superoxide dismutase activity was determined using ransod kit ( randox , uk ) and enzyme activity was reported as u / mg protein ( 19 ) . catalase activity was determined by the method described by mari and reported as u / mg protein ( 20 ) . one part was kept in 10% formalin solution for histopathological assessment and the rest was kept at -70 c for evaluation of oxidant and antioxidant factors ( 18 , 25 ) .", "after dissection of vagus nerve , distal end was covered with mineral oil and stimulated with bipolar electrode of a stimulator using 10 volt / msec pulses at the frequencies of 0.625 , 1.25 , 2.5 , 5 or 7.5hz for 30 sec . animals underwent tracheostomy and were cannulated ( in order to prevent probable airway occultation ) under anesthesia induced by intraperitoneal pentobarbital ( 50 mg / kg ) . after local shaving , a small incision was made in cervical area and branches of cervical vagus nerve were carefully dissected from carotid artery and cut ( 1 ) . stimulations were performed with 2-min intervals ( 23 ) . in order to ensure the stimulation of vagus nerve , electrocardiogram", "gastric i / r injury was induced by dissecting celiac artery from the surrounding tissues in rats anesthetized with 50 mg / kg pentobarbital , 30 minutes after dissection of vagus nerve . melatonin was dissolved in 1% ethanol , diluted with 0.9% saline , and injected at a final volume of 0.3 ml ( 18 ) . melatonin ( 10 mg / kg ) was injected intraperitoneally before reperfusion in groups 5 , 6 and 7 ( 18 , 25 ) . then , celiac artery was closed with a microvascular clamp and returned to its place and the area was sutured using 4 - 0 silk . occlusion was continued for 30 min ( 18 ) followed by a 3-h circulation ( reperfusion ) .", "catalase activity was determined by the method described by mari and reported as u / mg protein ( 20 ) . glutathione peroxides activity was determined by the method described by valentine and paglia method ( 20 ) , and enzyme activity was reported as u / mg protein . superoxide dismutase activity was determined using ransod kit ( randox , uk ) and enzyme activity was reported as u / mg protein ( 19 ) . one part was kept in 10% formalin solution for histopathological assessment and the rest was kept at -70 c for evaluation of oxidant and antioxidant factors ( 18 , 25 ) . mda level was measured according to hiroshi ohkawa method via reaction with thiobarbituric acid and color formation . optical absorbance was determined at 532 nm and mda level was reported as nmol / mg protein ( 26 ) .", "the h & e stained sections were examined under low power ( 40x ) to identify the areas of neutrophil aggregates within all tissue blocks . the number of neutrophils was calculated in a semiquantitative manner using the mean value of 20 non - overlapping high power fields ( hpf ; magnification of 400x ; 0.08 mm ) by using a 40x objective and a square grid mounted in a 10x microscopic eyepiece .", "comparisons among different groups were made by one - way and two - way anova followed by post hoc tukey s test .", "base : condition that neither vagus was stimulated nor vagotomy was performed ; i / r : ischemia / reperfusion ; mel : melatonin ; veh : vehicle sod activity ( u / mg protein ) in gastric tissue of studied groups has been shown in figure 5 . base : condition that neither vagus was stimulated nor vagotomy was performed ; i / r : ischemia / reperfusion ; mel : melatonin ; veh : vehicle base : condition that neither vagus was stimulated nor vagotomy was performed ; i / r : ischemia / reperfusion ; mel : melatonin ; veh : vehicle mda level in the study groups is presented in figure 2 . base : condition that neither vagus was stimulated nor vagotomy was performed ; i / r : ischemia / reperfusion ; mel : melatonin ; veh : vehicle catalase activity in the study groups are shown in figure 3 . base : condition that neither vagus was stimulated nor vagotomy was performed ; i / r : ischemia / reperfusion ; mel : melatonin ; veh : vehicle figure 4 shows glutathione peroxidase activity in the studied groups . a significant increase in neutrophils count was shown in vagotomy+i / r+melatonin group ( 260.32 ) as compared to base+i / r+melatonin group ( p<0.05 ) . the number of neutrophils in gastric tissue of the study groups ( n=7 ) . as it is seen , mda level in gastric tissue was lower in base+i / r+melatonin group ( 4.090.15 nmol / mg protein ) in comparison with base+i / r+vehicle group ( 5.530.11 nmol / mg protein ) ( p<0.05 ) .", "mean number of neutrophils in base+ i / r+ melatonin group ( 23.80.37 ) was lower than that in base+ i / r+ vehicle group ( 27.20.37 ) ( p<0.01 ) . also , this parameter in vagus stimulation + i / r+ vehicle group ( 450.32 ) was higher than that in base+ i / r+ vehicle and vagotomy+ i / r+ vehicle groups ( 27.20.36 ) ( p<0.001 ) . a significant increase in neutrophils count was shown in vagotomy+i / r+melatonin group ( 260.32 ) as compared to base+i / r+melatonin group ( p<0.05 ) . the number of neutrophils in gastric tissue of the study groups ( n=7 ) . / r+ melatonin group as compared to base+i / r+ melatonin group ( p<0.01 ) . / r+melatonin group ( 20.6 0.4 ) in comparison to vagus stimulation+i / r+vehicle group ( p<0.001 ) . base : condition that neither vagus was stimulated nor vagotomy was performed ; i / r : ischemia / reperfusion ; mel : melatonin ; veh : vehicle # # # p<0.001 : vagus stimulation+i / r+veh group vs. vagotomy+i / r+veh group .", "as it is seen , mda level in gastric tissue was lower in base+i / r+melatonin group ( 4.090.15 nmol / mg protein ) in comparison with base+i / r+vehicle group ( 5.530.11 nmol / mg protein ) ( p<0.05 ) . moreover , a significant increase in mda level was shown in vagus stimulation+i/-r+vehicle group ( 7.310.25 nmol / mg protein ) in comparison with base+i / r+vehicle and vagotomy+i/- r+vehicle ( 5.570.14 nmol / mg protein ) groups ( p<0.01 ) . mda level was higher in vagotomy+i / r+melatonin group ( 5.75 0.63 nmol / mg protein ) in comparison with base+ i / r+melatonin group ( p<0.05 ) . base : condition that neither vagus was stimulated nor vagotomy was performed ; i / r : ischemia / reperfusion ; mel : melatonin ; veh : vehicle / r+vehicle group ( p<0.001 ) . also , mda level was lower in vagus stimulation+i", "base : condition that neither vagus was stimulated nor vagotomy was performed ; i / r : ischemia / reperfusion ; mel : melatonin ; veh : vehicle catalase activity was increased in base+i / r+melatonin group ( 0.060.003 u / mg protein ) in comparison with base+i / r+vehicle group ( 0.040.003 u / mg protein ) ( p<0.001 ) . a significant increase in catalase activity was shown in vagus stimulation+ i / r+vehicle group ( 0.07 0.004 u / mg protein ) in comparison with base+i / r+vehicle and vagotomy+i / r+vehicle groups ( 0.0420.002 u / mg protein ) ( p<0.001 ) . catalase activity was lower in vagotomy+i / r+melatonin group ( 0.040.003 u / mg protein ) in comparison with base+i / r+melatonin group ( p<0.05 ) . catalase activity ( u / mg protein ) in gastric tissue of the study groups ( n=7).***p<0.001 : base+i / r+mel group vs. base+i / r+veh group . / r+melatonin group ( 0.070.004 u / mg protein ) in comparison with base+i / r+melatonin group ( p<0.05 ) .", "a significant increase in gpx activity was shown in gastric tissue of basal+i / r+melatonin group ( 10.310.37 ) ( p<0.001 ) in comparison with that in basal+i / r+vehicle group ( 4.420.57 ) . / r+vehicle group ( 7.120.31 ) as compared to that observed in basal+i / r+vehicle and vagotomy+i / r+vehicle groups ( 4.430.38 ) ( p<0.001 ) . also , a significant increase in gpx activity was indicated in vagus stimulated+i base : condition that neither vagus was stimulated nor vagotomy was performed ; i / r : ischemia / reperfusion ; mel : melatonin ; veh : vehicle this parameter was significantly lower in vagotomy+ i / r+melatonin group ( 4.610.4 ) as compared to that in basal+i / r+melatonin group ( p<0.01 ) . level of gpx activity ( u / mg protein ) in gastric tissue of the study groups ( n=7 ) * * * p<0.001 : base+i / r+mel group vs. base+i / r+veh group . # # p<0.01 : vagus stimulation+i / r+veh group vs. vagotomy+i / r+veh group .", "sod activity ( u / mg protein ) in gastric tissue of studied groups has been shown in figure 5 . base : condition that neither vagus was stimulated nor vagotomy was performed ; i / r : ischemia / reperfusion ; mel : melatonin ; veh : vehicle as it is seen , this parameter in basal+i / r+melatonin group ( 0.310.004 ) was significantly higher ( p<0.05 ) than that in basal+i / r+vehicle group ( 0.230.016 ) . a significant decrease in sod activity superoxide dismutase activity ( u / mg protein ) in gastric tissue of the study groups ( n=7 ) * p<0.05 : base+i / r+mel group vs. base+i / r+veh group . # # p<0.01 : vagus stimulation+i / r+veh group vs. vagotomy+i / r+veh group . this parameter in vagotomy+i / r+melatonin group ( 0.170.04 ) was lower than that in basal+i/-r+melatonin group ( p<0.05 ) . / r+ vehicle group ( 0.310.004 ) in comparison with that in vagotomy+i / r+vehicle group ( 0.360.003 ) ( p<0.05 ) , but it was higher than that in basal+ i / r+vehicle group .", "the results of this study showed that melatonin administration decreased neutrophils infiltration and mda level and increased sod , cat and gpx activities in gastric tissue . also , vagus stimulation increased neutrophils infiltration and mda level in gastric tissue while melatonin administration along with vagus stimulation decreased the effect of vagus stimulation in gastric tissue . the present study was performed to investigate the protective effect of interaction between melatonin and vagus nerve during gastric i / r . melatonin increases the release of bicarbonate from gastric mucosa ( 39 ) and decreases the release of inflammatory cytokines of gi through increasing vagus activity ( 16 ) . it is probable that the stimulation of vagus nerve following gastric i / r aggravated the condition and increased the activity of oxidant enzymes .", "it is suggested that melatonin is neuroprotective in gastric i / r probably by decreasing gastritis and mda and increasing the activities of cat , sod and gpx . it is suggested that further studies are required to find the mechanisms involved in this interaction . these effects of melatonin are probably mediated by vagus nerve . moreover , in gastric i / r , melatonin can reverse harmful effects of vagus stimulation .", "" ]
objectives : vagal pathways in gastrointestinal tract are the most important pathways that regulate ischemia / reperfusion ( i / r ) . gastrointestinal tract is one of the important sources of melatonin production . the aim of this study was to investigate probable protective effect of the interaction between vagus nerve and melatonin after i / r.materials and methods : this study was performed in male rats that were divided into six groups . cervical vagus nerve was cut bilaterally after induction of i / r and the right one was stimulated by stimulator . melatonin or vehicle was injected intraperitoneally . the stomach was removed for histopathological and biochemical investigations.results:a significant decrease in infiltration of gastric neutrophils and malondialdehyde ( mda ) level after i / r was induced by melatonin and was disappeared after vagotomy . the stimulation of vagus nerve significantly enhanced these effects of melatonin . however , a stimulation of vagus nerve alone increased neutrophils infiltration and mda level . melatonin significantly increased the activities of catalase , glutathione peroxidase ( gpx ) , superoxide dismutases ( sod ) . unlike stimulation of vagus nerve , vagotomy decreased these effects of melatonin.conclusion:according to these results , it is probable that protective effects of melatonin after i / r may be mediated by vagus nerve . therefore , there is an interaction between melatonin and vagus nerve in their protective effects .
[ "risks of hyperglycemia and type 2 diabetes among fetal and childhood - exposed subjects , compared with nonexposed subject , were examined with the method of maximum likelihood by using the survey logistic regression model . interaction between famine exposure cohort ( fetal- or childhood - exposed vs. nonexposed ) and area ( severely affected and less severely affected ) was tested by adding a multiplicative factor in the survey logistic regression model . subjects were categorized into five exposure cohorts : nonexposed cohort , fetal - exposed cohort , early childhood exposed cohort , mid childhood exposed cohort , and late childhood exposed cohort . mean ages for subjects in nonexposed cohort , fetal - exposed cohort , early childhood exposed cohort , mid childhood exposed cohort , and late childhood dietary patterns , economic status , and bmi measured in 2002 were used as measures of the nutritional environment in adulthood and to examine the mismatch between fetal nutrition and adult nutrition . analyses were adjusted for sex , family history of diabetes , educational level , current smoking , alcohol use , and physical activity level , all assessed in 2002 . to explore whether the associations between fetal exposure to severe famine and hyperglycemia were affected by an improved nutritional environment in later life , we subsequently stratified the analyses by dietary patterns , economic status and bmi in adulthood . in addition , subjects who had been previously diagnosed with type 2 diabetes were added as cases of hyperglycemia and type 2 diabetes .", "subjects were categorized into five exposure cohorts : nonexposed cohort , fetal - exposed cohort , early childhood exposed cohort , mid childhood exposed cohort , and late childhood exposed cohort . this enabled us to test the hypothesis that the famine effect is stronger in the severely affected famine areas than that in the less severely affected famine areas and to consider both birth cohort effects and regional differences . . an excess death rate of 50% was used as the threshold : regions that had an equal or higher rate than this cutoff were categorized as severely affected famine areas , and otherwise as less severely affected famine areas . mean ages for subjects in nonexposed cohort , fetal - exposed cohort , early childhood exposed cohort , mid childhood exposed cohort , and late childhood exposed cohort were 39 , 42 , 45 , 47 , and 49 years , respectively . the excess death rate was calculated as the percentage change in mortality rate from the mean level in 19561958 to the highest value during the period 19591961 ( 7 ) the chinese famine affected the entire mainland of china , but the severity varied across regions due to different weather conditions , population density , and local policies regarding food shortage ( 7 ) . as previously described , we used the excess death rate of each province to determine the severity of the famine ( 7 ) .", "in addition , subjects who had been previously diagnosed with type 2 diabetes were added as cases of hyperglycemia and type 2 diabetes . mmol / l , including impaired fasting glucose , impaired glucose tolerance , and type 2 diabetes . fasting plasma glucose ( fpg ) concentration was measured using the glucose oxidize enzymatic method within 3 h of plasma preparation . we used criteria proposed by the who expert committee on diabetes mellitus ( 14 ) . all subjects were invited for blood collection after an 10 to 14 h overnight fast . the plasma was separated by centrifugation at 3,200 rpm for 1015 min within 1 h of collection , and kept at room temperature without sunshine .", "patterns represent the traditional chinese diets in the south and the north , respectively , whereas the other two represent westernized dietary patterns . in this study , we combined the clusters of green water and yellow earth as the traditional dietary pattern , and we combined the clusters of new affluence and western adopter as the affluent / western pattern . dietary patterns , economic status , and bmi measured in 2002 were used as measures of the nutritional environment in adulthood and to examine the mismatch between fetal nutrition and adult nutrition . briefly , four dietary patterns were derived through cluster analysis , which were labeled as green water , yellow earth , new affluence , and western adopter . green water and yellow earth current economic status was assessed by the mean annual income in the year prior to the 2002 cnnhs , which was treated as a dichotomous variable . the mean level of the current sample ( 2,000 chinese yuan per person per year ) was used as a cutoff point for economic status . we used the criteria recommended for chinese adults and classified subjects as overweight if bmi 24 kg / m , or otherwise normal ( 16 ) . the method for assessing dietary patterns has been described in detail elsewhere ( 15 ) .", "risks of hyperglycemia and type 2 diabetes among fetal and childhood - exposed subjects , compared with nonexposed subject , were examined with the method of maximum likelihood by using the survey logistic regression model . analyses were adjusted for sex , family history of diabetes , educational level , current smoking , alcohol use , and physical activity level , all assessed in 2002 . to explore whether the associations between fetal exposure to severe famine and hyperglycemia were affected by an improved nutritional environment in later life , we subsequently stratified the analyses by dietary patterns , economic status and bmi in adulthood . interaction between famine exposure cohort ( fetal- or childhood - exposed vs. nonexposed ) and area ( severely affected and less severely affected ) was tested by adding a multiplicative factor in the survey logistic regression model . the odds ratio of hyperglycemia in the fetal - exposed cohort compared with the nonexposed cohort was calculated within each category of the stratified factor . to distinguish severely and less severely affected famine areas more appropriately , we performed sensitivity analysis by using a more stringent cutoff point , i.e. , we used an excess death rate 100% to define the severity of famine . in addition , we performed analyses by using the cohort born during october 1 , 1962 , to september 30 , 1968 , as a nonexposed cohort for association analyses , or by excluding participants with a family history of diabetes . mean fpg differences between the exposed cohorts and the nonexposed cohort were tested by generalized least squares estimation ( 17 ) .", "concentrations of fasting plasma glucose and prevalence rates of hyperglycemia and type 2 diabetes by birth cohort and severity of the chinese famine area * data are adjusted means ( se ) for fasting plasma glucose , sex standard prevalence , and odds ratio for hyperglycemia and diabetes . . prevalence rate of hyperglycemia by birth cohorts and severity of famine areas : sensitivity analyses all odds ratios used the nonexposed cohort as the reference cohort . adjusted factors include sex , educational level , family history of diabetes , and current smoking , alcohol use , and physical activity level in 2002 . subjects exposed to famine during fetal life in severely affected famine areas had a higher prevalence of hyperglycemia than the nonexposed cohort . compared with nonexposed subjects , fpg was higher in the late childhood exposed cohort in both the severely affected famine areas and less severely affected famine areas .", ", we found that exposure to severe famine in fetal life increased the risk of hyperglycemia in adulthood . in this study of a large sample of chinese adults , we found a significant association between severe famine exposure during the fetal period and an increased risk of hyperglycemia in adulthood . the mismatched nutrition postnatal environment represented by a western dietary pattern and improved economic status further increased susceptibility to hyperglycemia in those who experienced fetal exposure to famine . together with previous studies , our study emphasizes that early life environment is critical for the risk of hyperglycemia in adult life . the association between fetal famine exposure and hyperglycemia was stronger in participants with an affluent / western dietary pattern ." ]
objectiveearly developmental adaptations in response to undernutrition may play an essential role in susceptibility to type 2 diabetes , particularly for those experiencing a mismatched rich nutritional environment in later life . we examined the associations of exposure to the chinese famine ( 19591961 ) during fetal life and childhood with the risk of hyperglycemia and type 2 diabetes in adulthood.research design and methodswe used the data for 7,874 rural adults born between 1954 and 1964 in selected communities from the cross - sectional 2002 china national nutrition and health survey . hyperglycemia was defined as fasting plasma glucose 6.1 mmol / l and/or 2-h plasma glucose 7.8 mmol / l and/or a previous clinical diagnosis of type 2 diabetes.resultsprevalences of hyperglycemia among adults in nonexposed , fetal exposed , early - childhood , mid - childhood , and late - childhood exposed cohorts were 2.4% , 5.7% , 3.9% , 3.4% , and 5.9% , respectively . in severely affected famine areas , fetal - exposed subjects had an increased risk of hyperglycemia compared with nonexposed subjects ( odds ratio = 3.92 ; 95% ci : 1.649.39 ; p = 0.002 ) ; this difference was not observed in less severely affected famine areas ( odds ratio = 0.57 ; 95% ci : 0.251.31 ; p = 0.185 ) . the odds ratios were significantly different between groups from the severe and less severe famine areas ( p for interaction = 0.001 ) . in severely affected famine areas , fetal - exposed subjects who followed an affluent / western dietary pattern ( odds ratios = 7.63 ; 95% ci : 2.4124.1 ; p = 0.0005 ) or who had a higher economic status in later life experienced a substantially elevated risk of hyperglycemia ( odds ratios = 6.20 ; 95% ci : 2.0818.5 ; p = 0.001).conclusionsfetal exposure to the severe chinese famine increases the risk of hyperglycemia in adulthood . this association appears to be exacerbated by a nutritionally rich environment in later life .
[ "other analyses inferred pleiotropy with triglyceride in the chromosome 2p region and pleiotropy with obesity in the chromosome 13 region . herein we present linkage and association analyses on the aa subset of the gennid sample using genotypes on 9,203 fine - mapping snps added to the genome scan snps used previously . our first goal was to more precisely localize the t2d susceptibility genes in each of the five chromosomal regions identified in the genome scan ( chromosome 2 at 6895 and 95121 mb , chromosome 7 at 5079 mb , chromosome 13 at 1930 mb , and chromosome 18 at 3165 mb ) . our second goal was to test for association of the gene - based fine - mapping snps with t2d and aod in order to identify genes related to t2d in aas . genome - wide linkage analysis using genotypes on 5,914 snps identified chromosomal regions that potentially harbor risk genes for t2d and age of t2d diagnosis ( aod ) . we have used this resource to increase understanding of the genetics of t2d by applying linkage and family - based association analysis to the african american ( aa ) subset of the gennid sample .", "we tested for an independent effect of each secondary associated snp , conditional on the snp within the same gene that attained the highest significance , by comparing the maximized likelihood estimating t2d and aod covariate effects for both snps simultaneously to the maximized likelihood estimating t2d and aod covariate effects for the most significant snp alone . we assessed each fine - mapping snp for association with ut2d and aod by coding the snp genotype as an additive covariate and testing its effect on both traits in a bivariate model . we applied variance components linkage analysis using the univariate model for each trait in conjunction with the ibd probabilities . at each cm across the 5 regions , all parameters were estimated for aod while only heritability and qtl effect were estimated for ut2d and bt2d with all other parameters for those traits fixed at estimates obtained upon maximizing the likelihood while correcting the likelihood for the ascertainment of each pedigree through an affected sib pair . power to produce a p - value of 0.00001 was estimated from simulation of 1000 replicates of a snp with minor allele frequency 0.4 and heterozygous effect a 10% increase in penetrance at age 50 for t2d or 3 year increase in aod . for fine - map genotyping , we used snagger ( http://snagger.sourceforge.net/ ) to select tagsnps within genes in the linkage regions on chromosomes 2 , 7 , 13 , and 18 . using hapmap phase 1 and 2 ( http://hapmap.ncbi.nlm.nih.gov ) , p < 0.05 after bonferroni correction for the number of secondary snps in the gene supported the independence of the secondary snp . the lod score at each cm was computed as the common logarithm of the ratio of the maximized likelihoods with the qtl effect estimated to the maximized likelihood with the qtl effect set to zero . likelihood analysis , as implemented in jpap , was used for univariate linkage analysis of unadjusted t2d ( ut2d ) , t2d adjusted for bmi ( bt2d ) , and aod and for bivariate association analysis of ut2d and aod .", "although 20 of the 27 associated genes were identified through a single snp , 5 genes were identified through 2 or 3 snps and arhgap25 and dpp10 were identified by 8 and 10 , respectively we genotyped 9,203 snps within five regions encompassing a total of 133 cm and 128 mb ( table 1 ) and merged them with 244 ( 36 duplicates ) genome scan snps . we previously identified 5 linkage peaks within four chromosomal regions from autosomal scans of t2d and aod ; the chromosome 2 region contained 2 peaks separated by 30 mb and the centromere . the number of associated snps ranged from 4 on chromosome 13 to 17 on chromosome 2q ; the number of associated genes ranged from 2 on chromosome 13 to 9 on chromosome 7 .", "we propose that each haplotype harbors a distinct causal variant , despite sharing associations with the same risk alleles , demonstrating the complexity of disease associations . , we nevertheless expect that the susceptibility genes residing in all regions both increase t2d risk and decrease aod . the fine - mapping of five chromosomal regions allowed us not only to confirm our genome scan linkages , but also to infer the presence of multiple t2d susceptibility genes in each of the regions . two types of evidence supported the presence of multiple susceptibility genes underlying the linkage peaks . the advantages include the opportunity to exploit information on local ancestry to localize disease susceptibility genes .", "" ]
we previously localized type 2 diabetes ( t2d ) susceptibility genes to five chromosomal regions through a genome - wide linkage scan of t2d and age of diagnosis ( aod ) in the african american subset of the gennid sample . to follow up these findings , we repeated the linkage and association analysis using genotypes on an additional 9,203 fine - mapping snps selected to tag genes under the linkage peaks . in each of the five regions , we confirmed linkage and inferred the presence two or more susceptibility genes . the evidence of multiple susceptibility genes comprised : 1 ) multiple linkage peaks in four of the five regions ; 2 ) association of t2d and aod with snps within 2 or more genes in every region . the associated genes included 3 previously reported to associate with t2d or related traits ( grb10 , nedd4l , lipg ) , and 24 novel candidate genes including genes in lipid metabolism ( acoxl ) and cell - cell and cell - matrix adhesion ( magi2 , cldn4 , ctnna2 ) .
[ "this review will primarily focus on the hypothesis which states that the variation of genetic components of the circadian system , similar to environmental changes , can affect several physiological systems and produce an elevation of the risk of developing a disease . in recent years this present research reports the last single nucleotide polymorphism ( snp ) associated with an elevated risk of developing principal pathologies worldwide such as mood disorder , infertility , cancer , metabolism and diabetes and addictions , and a description of usefulness for a more detailed study in other pathologies . different reports showed that the alterations of the circadian system increased the risks of cancer [ 2123 ] , preeclampsia , diabetes [ 3 , 25 ] , and mood disorder . the circadian system organizes the different biological functions in 24 h , such as sleep / activity , temperature , heart rate , glucose level , cortisol production , and oxidative stress . in mammals , mood disorder and psychosis are the principal causer of hospital stay during 2014 and represent the third cause of morbidity worldwide .", "this is an antecedent which , bearing in mind the ideas above , suggests the genetic components of the circadian system as a critical factor in the development of metabolic diseases . polymorphic variations of clock genes can be incrementing the risks of developing a disease similar to chronodisruption by environmental changes as it has been detected in human metabolic disorders ( see table 1 ) . today there are several metabolic problems affecting the population , such as obesity , hyperglycemia , dyslipidemia , and hypertension . the cooccurrence of three or more metabolic disorders , including obesity , is defined as metabolic syndrome , showing a prevalence in the united states during 2009 - 2010 of about 22% of adults ( 21.4626.15 ) . the insulin resistance or type", "the circadian system is important during reproduction and development [ 89 , 90 ] ; for example , it is involved in the timing of the lh surge [ 90 , 91 ] , stimulation of ovulation [ 90 , 92 ] , and regulating the level of steroidogenic acute regulatory protein ( star ) expression and is critical for cholesterol translocation inside mitochondria and sperm count . the genotyping of male partners detected a correlation between single nucleotide polymorphism of clock rs11932595 , rs6811520 , and 6850524 , with infertility ( p < 0.05 and or ranged between 1.4 and 1.9 ) . in humans , infertility affects about 9% of couples , and about one - third of infertility cases associated with idiopathic male infertility are multifactorial , with 50% due to genetic abnormalities . similarly , the analysis of bmal1 polymorphism rs4757144 in slovenian and serbian caucasian men showed a significant correlation with infertility ( p = 0.047 ) , suggesting that clock genes clock and bmal1 contribute to successful fertilization . the genetic factors of clock genes are implicated in the pathogenesis of infertility ( see table 2 ) , as it occurs in male partners of infertile couples .", "for this reason , we can say that the circadian system may contribute to the risk of developing a mood disorder and the genetic component of clock genes can be involved in the development of mood pathologies ( see table 2 ) . mood or affective disorders are important causes of morbidity , where we can highlight depressive pathologies and hypomaniac and maniac disorders as major diseases affecting the population [ 29 , 66 ] , and it can be highlighted that depressive pathologies are the third largest source of morbidity in the world . curiously , a potent correlation has been detected between mood disorders , sleep / activity , and the circadian system suggesting that the circadian system can be modulating the neuronal activity . during pregnancy , moreover , gene variants of positive regulator clock have also been associated with mood disorders .", "non - hodgkin 's lymphoma is characterized by lymphoproliferation and advanced clinical stages , invasion to other tissues , and death . these precedents reinforce the idea that clock genes can be modulators of cellular cycle and that modulates the risk of cancer . , different studies reveal the importance of the polymorphic variant of clock genes ( see table 3 ) and how the chrono - type modulates the risk of cancer , such as observed in breast cancer , in which the risk is more elevated in premenopausal women ( or , 2.43 and 2.55 ; resp . ) . the silencing of clock gene lowered when women carry polymorphisms associated with cancer such as rs10448004 and rs7698022 , which suggests that clock gene is a critical protagonist of cancer development . at level of colorectal cancer , a soft risk is associated with breast cancer in premenopausal women from india , which suggests there is a relation between per3 and cellular proliferation .", "but it has been described that the genetic component in the population predisposes the development of different pathologies such as diabetes , dyslipidemias , obesity , mood disorders , and addiction , all of which suggest the importance of this system to our health . however , other factors can be contributing on a minor scale , such as mealtimes or a genetic component . however , it is also necessary to say that the genetic component could be protecting our health such as in the case of polymorphisms associated with per2 and cry2 genes in diabetes , alcohol intake , and cancer . these findings will need to be implemented and evaluated at the genetic interaction level and also the way in which the environment factors trigger the expression of these pathologies will be examined . different chronodisruptors have been described in literature such as light / dark pattern and inhibition of melatonin production as occurs in shifts work . finally , prospective studies are necessary to assess the predictive potential of these markers and to implement early treatment with consequent cost reduction for the health system . the relevance of the genetic variation of clock genes and how it can interact with the environment is unknown . the circadian system is a supraphysiological system which modulates different physiological systems , and any alteration of this can have a negative impact on human health ." ]
the circadian system is a supraphysiological system that modulates different biological functions such as metabolism , sleep - wake , cellular proliferation , and body temperature . different chronodisruptors have been identified , such as shift work , feeding time , long days , and stress . the environmental changes and our modern lifestyle can alter the circadian system and increase the risk of developing pathologies such as cancer , preeclampsia , diabetes , and mood disorder . this system is organized by transcriptional / tranductional feedback loops of clock genes clock , bmal1 , per13 , and cry1 - 2 . how molecular components of the clock are able to influence the development of diseases and their risk relation with genetic components of polymorphism of clock genes is unknown . this research describes different genetic variations in the population and how these are associated with risk of cancer , metabolic diseases such as diabetes , obesity , and dyslipidemias , and also mood disorders such as depression , bipolar disease , excessive alcohol intake , and infertility . finally , these findings will need to be implemented and evaluated at the level of genetic interaction and how the environment factors trigger the expression of these pathologies will be examined .
[ "the ubiquitously expressed protein phosphatase 2a ( pp2a ) has been proposed as a target for the treatment of a number of pathologies ranging from neurodegenerative diseases such as alzheimer disease to a variety of neoplasias [ 79 ] . this review will focus on our emerging understanding of pp2a substrate specificity , which appears to involve additive effects of multiple discrete interactions . this paper will provide a summary of these studies and how the understanding of the determinants of pp2a substrate specificity has advanced .", "the heterotrimeric holoenzyme is targeted to discrete subcellular locales dictated in part by which b - regulatory subunit is incorporated . the localization imparted by the b - regulatory subunit dictates the spatial sphere of influence of the holoenzyme complex for potential substrates . while assembly of the many trimeric pp2a holoenzymes directs cellular localization and substrate specificity , further regulation is afforded through binding of specific protein inhibitors of pp2a . pp2a / b negatively regulates the erk map kinase signal transduction pathway . through formation of a ternary complex of the early response gene product iex-1 , b1 , and erk ,", "pp2a is a ubiquitous protein phosphatase responsible for the dephosphorylation of many different intracellular targets . the diverse repertoire of potential substrates for pp2a is imparted by the incorporation of one of fifteen unique b - regulatory subunits . a clearer understanding of the pp2a substrate specificity mechanisms will serve as the foundation for rational drug design of selective inhibitors and activators of specific pp2a holoenzyme complexes . , interactions between the regulatory subunit and phosphosubstrate may mediate multiple nearby dephosphorylation events . with the current structural information available for recent studies have increased our understanding of the mechanisms by which the b subunit imparts specificity to the holoenzyme complex . through selective incorporation of the b secondly , interactions between endogenous inhibitors and specific pp2a heterotrimers further restrict phosphatase activity . as shown for the b family , regulatory subunits mediate low - affinity interactions with substrates to increase the local concentration of substrates . through a flexible substrate selectivity loop which contacts the catalytic subunit the pp2a complexes , future high - resolution studies will further define the molecular mechanism of pp2a substrate specificity . as general , inhibitors of pp2a are either clinically irrelevant or toxic , as in the case of the small molecule inhibitor microcystin , novel methods to increase the specificity of pp2a inhibition or activation must be developed ." ]
protein phosphatase 2a- ( pp2a- ) catalyzed dephosphorylation of target substrate proteins is widespread and critical for cellular function . pp2a is predominantly found as a heterotrimeric complex of a catalytic subunit ( c ) , a scaffolding subunit ( a ) , and one member of 4 families of regulatory subunits ( b ) . substrate specificity of the holoenzyme complex is determined by the subcellular locale the complex is confined to , selective incorporation of the b subunit , interactions with endogenous inhibitory proteins , and specific intermolecular interactions between pp2a and target substrates . here , we discuss recent studies that have advanced our understanding of the molecular determinants for pp2a substrate specificity .
[ "network connectivity in science and in engineering fields as diverse as mechanics , communication technology , public health , geography and town planning , is studied mathematically using the concepts of graph theory ( bollobas , 1998 ) . connectivity is key to understanding activity in neural systems ( sporns et al . , 2000 ) . applying graph - theoretic concepts to the brain sheds new light on the basic principles of integration and segregation underlying adaptive cognitive processes , and on their disruption in maladaptive states . we will propose as an alternative theoretical possibility that , instead , brain pathologies are associated with a breakdown in the local organization . in schizophrenia patients , here we show by numerical simulations that in neural activity networks , with loss of connectivity a self - organizing small - world neural network can not sustain its local clustering , well before global connectivity breaks down .", "the iterated logistic map f(x)= 1 ax is unimodal on [ 1;1 ] [ 1;1 ] and capable of both periodic and chaotic behavior depending on its control parameter a. in this study , we construct networks of coupled logistic maps , all with parameter a = 1.7 such that the dynamics of a single unit are chaotic under iteration of a randomly chosen initial activation value . a unit x is coupled with coupling strength = 0.4 to any number mi of other units in the network such that its activation value xn + 1 at iteration n + 1 depends on the activation value of itself and all adjacent units at iteration n : \n\n in this equation , b(i ) is the set of units adjacent to unit i , mi is the number of units adjacent to unit i. the coupling strength is divided by mi , and has a compensation term ( 1 ) to make sure that logistic map of an individual unit retains its mapping [ 1:1 ] [ 1:1 ] , and thus functions properly for any numbers of adjacent units . a network of this type can be used to study the buildup and breakdown of modularity resulting from hebbian adaptive structural self - organization . the influence of these numbers shows a close relationship to the percolation function of random graphs . it implements a simple rewiring rule based on synchronization of chaotic activity and rewires at most one connection per iteration , carefully keeping the network 's total number of connections constant throughout the process . but as it turns out , both the consistent build - up of connective modularity on one hand , or the loss of structural coherence due to functional fragmentation on the other , are a result of changing dynamic activity depending critically on the number of connections in the network .", "a common principle for neural network evolution is preferential attachment ( barabsi and albert , 1999 ) . attractors in the space of possible systems ( gong and van leeuwen , 2004 ) , which offers a potential explanation for their ubiquity in biological neural networks at different scales , including the entire brain ( barabsi and albert , 1999 ) . in this scenario , connectivity constitutes a critical limit for the evolution to small - world structure ( figure 2 ) . self - organization from random to small - world critically in a network of 700 vertices . this mechanism leads to networks that are scale - free , but not modular small - worlds . only by combining preferential attachment with adaptive , hebbian rewiring , we compared the critical limit on the evolution to small - world structures to percolation thresholds of random networks with the same numbers of edges and vertices .", "attractors in the space of possible systems ( gong and van leeuwen , 2004 ) , which offers a potential explanation for their ubiquity in biological neural networks at different scales , including the entire brain ( barabsi and albert , 1999 ) . in this scenario , connectivity constitutes a critical limit for the evolution to small - world structure ( figure 2 ) . a common principle for neural network evolution is preferential attachment ( barabsi and albert , 1999 ) . this mechanism leads to networks that are scale - free , but not modular small - worlds . only by combining preferential attachment with adaptive , hebbian rewiring , self - organization from random to small - world critically in a network of 700 vertices . adaptive rewiring operates on this activity according to the general hebbian principle of what fires together wires together ( paulsen and sejnowski , 2000 ) . at successive points during the systems ongoing spontaneous activity", "we compared the critical limit on the evolution to small - world structures to percolation thresholds of random networks with the same numbers of edges and vertices . parameter k2 however , the horizontal position of the anchor point , showed a universal scaling law to the anchor point in the percolation function of random graphs , namely ( table 1 ) : aswn(n ) = arand(n ) . figure 4 shows that the observed minimum cc can be modeled as a linear function of cp(n ) , with k3 for offset and k4 for amplitude : ccpred = k3 + k4 \n cp(n ) . marquardt algorithm implemented in fityk . scaling power : the value of h in the equation aswn(n ) = arand(n ) . aswn(n ) : anchor point for the small - world networks fitted according to figure 4 . the behavior of these parameters across network sizes was not monotonic ( figure 4 ) .", "we propose that important insights into cortical activity and architecture can be obtained by modeling the activity - dependent rewiring of neural connections during development ( gong and van leeuwen , 2003 ; rubinov et al . , 2009b ) . in our model , network connections evolve in accordance with the principle that the structure rewires in adaptation to spontaneous , on - going activity . based on our results , however , we argue that fragmentation in brain pathologies such as schizophrenia may be considered theoretically as a breakdown in the local connectivity structure , prior to the loss of global coherence . the number minimally needed to secure local modularity , and hence to prevent it from shifting toward randomness in structure , is systematically related to , and greater than , that needed to secure global connectivity , even if the system has fallen into entirely random connectivity . , we propose that fragmentation is to be understood as a failure to organize the functional connectivity of the brain into a modular small - world structure . we observed universal scaling behavior in adaptive self - organization of clustered small - world networks : the connectivity needed for these network properties to emerge under hebbian rewiring scales with a universal power = 1.17 to the percolation function in random networks .", "we then start a new quintuple of simulations , increasing the number of connections e by 20 , generating five networks with v = 300 units and e = 2420 connections , and calculate the maximum , minimum , and average cc and cpl values from these five new simulations . one simulation consists of one network of v units and e connections , which is randomly initialized and then iterated exactly 4,000,000 times , simultaneously rearranging its connections and activity patterns , according to the adaptive rewiring scenario . evolution under adaptive rewiring of maximum , minimum , and average cluster coefficient and characteristic path length . even more reliable estimates could , in principle , be obtained by scaling up the network size to 2000 , 5000 , and 10,000 vertices , resources permitting , as computation time and data grow nonlinearly with network size . we continue doing this for batches of networks with 500 , 600 , 700 , 800 , 900 , and 1000 units , with connections increasing by 20 , showing asymptotic clustering and path - length behavior depending on connectivity for networks of different sizes ( figure 4 ) . we , therefore , considered reliable the estimates of the scaling power and other model parameters .", "the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest ." ]
psychiatric illnesses characterized by disorganized cognition , such as schizophrenia , have been described in terms of fragmentation and hence understood as reduction in functional brain connectivity , particularly in prefrontal and parietal areas . however , as graph theory shows , relatively small numbers of nonlocal connections are sufficient to ensure global coherence in the modular small - world network structure of the brain . we reconsider fragmentation in this perspective . computational studies have shown that for a given level of connectivity in a model of coupled nonlinear oscillators , modular small - world networks evolve from an initially random organization . here we demonstrate that with decreasing connectivity , the probability of evolving into a modular small - world network breaks down at a critical point , which scales to the percolation function of random networks with a universal exponent of = 1.17 . thus , according to the model , local modularity systematically breaks down before there is loss of global coherence in network connectivity . we , therefore , propose that fragmentation may involve , at least in its initial stages , the inability of a dynamically evolving network to sustain a modular small - world structure . the result is in a shift in the balance in schizophrenia from local to global functional connectivity .
[ "dysphagia can be classified into an oropharyngeal or an esophageal location , and it is caused by neuromuscular motility disorders and mechanical obstruction.1 ) mechanical dysphagia is associated with intrinsic or extrinsic compression , resulting in progressive intolerance to solids . the term , dysphagia aortica , has been used to describe difficulty in swallowing caused by external compression from an ectatic , tortuous , or aneurysmal aorta as a result of age - related degeneration.2 ) dysphagia aortica is classically seen in elderly women with short stature who have hypertension and kyphosis.3 ) we report herein a patient with dysphagia associated with an aortic aneurysm . dysphagia is the subjective awareness of difficulty in the passage of solids or liquids from the oropharynx to the stomach .", "we concluded that the symptoms and the results of the imaging studies were consistent with dysphagia aortica . an 86-year - old woman presented with worsening nausea and vomiting . because of her progressive dysphagia to solids for the last 6 months , she had ingested only semisolids and liquids . although we recommended surgical correction of the aortic aneurysm or percutaneous endoscopic gastrostomy , the patient declined any invasive procedures and she was transferred to a nursing home on the 12 hospital day .", "dysphagia aortica is an uncommon type of dysphagia that is caused by extrinsic mechanical compression . the association of suggestive symptoms , such as progressive intolerance to solids with concomitant weight loss along with the results of imaging and other diagnostic studies provide a high index of suspicion.6 ) the diagnostic work - up includes radiologic , endoscopic , and manometric studies . on a standard chest radiography and ct scan , the enlargement of the aortic arch and the tortuous dilated aorta can be observed . the radiographic findings are often inconclusive because a dilated , tortuous thoracic aorta is frequently encountered in elderly patients with dysphagia . it should be differentiated from other causes of dysphagia , such as gastroesophageal reflux disease or motility disorders , because dysphagia aortica often requires surgical intervention that can significantly reduce the morbidity and these interventions can be curative in some situations ." ]
dysphagia aortica is difficulty in swallowing caused by extrinsic compression of the esophagus due to an ectatic , tortuous , or aneurysmatic atherosclerotic thoracic aorta . this condition is very uncommon , and it is usually associated with old age , women with short stature , hypertension , and kyphosis . we report herein a case involving a patient with dysphagia who had an aortic aneurysm .
[ "from now on , molecular study regarding female sexuality has focused on female sexual hormone , like estrogen receptor ( er ) and er derivatives.12 but flibanserin is an agent of 5-hydroxytryptamin ( 5-ht ) type 1a receptor and an antagonist of 5-ht type 2a and thus a new molecular entity.3 flibanserin was originally developed as antidepressant drug . in clinical stage 2a as antidepressant , flibanserin could not prove its effectiveness , but almost no sexual function disorder was reported in subjects . for this reason , the arizona sexual experiences scale ( asex ) was used for making a comparison of the sexual function effectiveness of flibanserin on antidepressant vs. placebo proven in stage 2b studies among four depression programs.4 stage 2b studies have failed to prove its general effectiveness on depression , but in answering this question \" how intense is your sexual desire ? \" in the asex , flibanserin turned out to be more excellent in both placebo and active - comparator . since then , drug development has changed its directivity toward being a potential medicine for treating hypoactive sexual desire disorder ( hsdd ) .", "hsdd is chara or absence of sexual fantasy and sexual desire associated with personal pain in the 4th edition of the diagnostic and statistical manual - text revision ( dsm - iv - tr).5 determining lack or absence is done by clinicians by considering the factors influencing sexual activitie such as age and contexts of personal life . sexual function disorder is not explained well by other axis 1 disorders ( except other sexual function disorders ) and also it is not that it is caused only by direct physiological effects of materials ( i.e. , drug overuse , drug ) or overall medical status . the dsm-5 completed in 2013 addresses new illness called as female sexual interest / arousal disorder ( fsiad ) , which has both properties of hsdd and another illness of dsm - iv known as female sexual arousal disorder .", "postmenopausal women and sexual desire decline disorder male patients are not adapted during use and i t is not intended for reinforcing sexuality.1415 flibanserin underwent new drug application ( nda ) as original drug in 2009 . the two central phase 3 studies ( violet6 , daisy7 ) all used e - diary and did not show big statistical improvement compared to placebo in the pre - specified co - primary efficacy endpoint that assessed daily sexual desire . in both violet6 and daisy7 studies , flibanserin showed an increase in satisfying sexual events ( sse ) and female sexual function index ( fsfi ) and reduction in female sexual distress scale - revised ( fsds - r ) , but did not show a meaningful increase in e - diary scores compared to placebo . in both studies , applicants told that the effectiveness of flibanserin against sexual desire is better explained with fsfi , but most advisory committees did not agree to alteration in the e - diary evaluation method set as the one designed to evaluate sexual desire . fda finally approved it under the condition that risk evaluation and mitigation strategies ( rems ) should be enforced for flibanserin . in the future the effectiveness was not so big in general , and considering these concerns , fda refused to approve it again and recommended that additional safety studies are required . according to the latest fda review , there is no data indicating new efficacy . instead , flibanserin sponsors submitted additional safety data next day including research data proving that there is no obstacle to driving , data comparing the commercialized products and the side effects profile of these products , and analysis clarifying the potential effects of alcohol on side effects.9 despite the trustfulness of highly influential studies , fda product review is not a fundamental comparison , in fact , and so comparison of safety between individual products may be misunderstood . in particular ,", "in addition , if flibanserin is administered to patients with decline in liver failure , increase in concentration of drug in blood is observed and thus it 's considered that adverse effects are likely to occur . besides , taking it with herb extracts and digesters and gastroprotective drugs requiring no doctor prescription is likely to cause the risk of adverse effects and the use of flibanserin to women who are breast - feeding is contraindication . the adverse effects most common in prescribing flibanserin are reported as vertigo , fatigue , vomiting , insomnia , and mouth dryness . triptans is used for treating migraine as agonist of 5-ht type 1b and 1d receptor and may cause side effects of drowsiness if administered with flibanserin . hormonal contraceptives are known as weak cyp3a4 inhibitors , and likely to cause side effects such as vertigo , drowsiness , and fatigue if coadministered with flibanserin . alcohol is contraindication because if administered with alcohol , it is highly likely to cause central nervous system depression ( fatigue , drowsiness , and vertigo ) , low blood pressure , and swoon .", "as we discussed above , flibanserin was refused to approve by fda in 2009 for its adverse effects and discordance of its efficacy from different evaluation methods . ddis with fluconazole , ethanol , and many other drugs were mainly discussed and fda refused to approve it again recommending additional safety data . with the additional profile and analysis which can prove their safety compared with other products , on june 4 , 2015 , fda finally approved it on the grounds that rems should be enforced , and soon we can get flibanserin on - label under the strict prescription . we are waiting for patients ' reaction , considering the cost and effectiveness , in countries where flibanserin will be on sale , and more agents like unicenta ( uncnt ) and melsmon , which proved as having a efficacy of menopausal symptoms , have to be studied as treating for female sexual dysfunction.16 most common side effects were central nervous system depression , like fatigue , drowsiness , and vertigo . also , its administration with fluconazole , ketoconazole , ssri / snri , triptans , hormonal contraceptives , herb extracts , and several other drugs requiring no doctor prescription is prohibited because it is likely to increase the risk of adverse effects ." ]
there have been several products developed for male sexual dysfunction . however , developing agents for female sexual dysfunction is lagging behind for various reasons . sildenafil citrate ( viagra ) and tadalafil ( cialis ) , which have been prescribed for male sexual function disorders , are known to act on vessels.[1 ] on the other hand , flibanserin is thought to act on brain . flibanserin has been approved by u. s. food and drug administration ( fda ) for treatment of hypoactive sexual desire disorder ( hsdd ) of premenopausal women in 2015 , and is expected to be released in south korea soon . authors wrote this article to acknowledge flibanserin to sexologists for females or physicians for menopausal medicine , so that this agent can be safely used for females who have hsdd .
[ "we report a rare case of kcm occurring on the scalp which is an unusual site . kcm is itself very rare and distinct type of keratoacanthoma which usually occurs over extremities and scalp is unusual site for development of lesion . treatment is difficult as lesion of kcm present with large raised , rolled borders with peripheral extension .", "complete surgical excision with grafting was done successfully with dramatic improvement with no recurrence at 9 months [ figure 5 ] . lesion had developed de novo , as a pea sized lesion with gradual increase to cover entire vertex . a 62-year - old male , watchman by occupation presented with asymptomatic raised lesion on scalp since one year . . marked epidermal proliferation with crater formation with horn pearls and inflammatory infiltrate at the base of the lesion was suggestive of a fully developed lesion of kcm .", "first time from india we are reporting case of kcm presenting over scalp which is successfully treated with surgical excision without any recurrence . it can be localized to any region of the body but is more frequently seen on dorsum of hands and legs . progressive peripheral extension with a raised rolled - out margin and atrophy at the centre is a characteristic feature of kcm . the etiology is multifactorial that includes chronic ultraviolet ray exposure , smoking , contact with chemical carcinogens like pitch , mineral oil , tar , trauma and vaccination ." ]
keratoacanthoma ( ka ) is a rapidly evolving tumor , composed of keratinizing squamous cells originating in pilosebaceous follicles and resolving spontaneously if left untreated . it is relatively uncommon in dark - skinned and occurs in middle aged individuals . males are three times more affected than females . it presents as firm , rounded , flesh - colored or reddish papule ; with a rapid growth phase followed by spontaneous healing over three months . two types of ka exist i.e. , solitary and multiple . there are three rare clinical variants of solitary ka , namely giant ka , keratoacanthoma centrifugum marginatum ( kcm ) and subungual ka . in kcm , lesions are large , reaching upto 20cms . there is peripheral extension with raised , rolled border and atrophy in the center . there is no tendency toward spontaneous involution . the most common locations are dorsa of hands and legs , lesions on scalp being rare . a rare case of kcm occurring on scalp which is an unusual site is reported .
[ "however , the carbonate apatite heating at a temperature of 700900c for 25 hours , followed by washing using distilled water , the carbonate apatite can be hydroxyapatite [ 1113 ] . the instrument were used in this research were glass apparatus , ohaus analytical balance , petri dish , porcelain cup , buchner flask , buchner funnel , vacuum pump sargent - welch co. model 1400 , magnetic stirrer , magnetic bar , hotplate idealife , ph meter , furnace thermolyse 6000-barnstead , dessicator , thermometers , spnisosfd oven , stopwatch , shimadzu x - ray diffractometer ( xrd ) model 6000 , x - ray fluorescence ( xrf ) shimadzu , fourier transform infra - red ( ftir ) prestige-21 shimadzu , scanning electron microscopy combined with the ability to generate localized chemical information ( sem - edxa ) variant , and uv - vis shimadzu model 6105 . this suggests the existence of crab shells is abundant in indonesia , including in makassar . the raw material for the production of hydroxyapatite biomaterial is very easily available and abundant in indonesia . crabs shells containing calcium carbonate ( caco3 ) are very abundant ; amount 4070% , varies according to the species . the crystals structure of hydroxyapatite will be better by using cao as a precursor of calcium . hydroxyapatite is a calcium phosphate ceramic that is totally biocompatible and nontoxic and becomes an integral part of living bone and teeth tissue [ 18 ] .", "waste of crabs shells portunus pelagicus species was taken from an exporter crabs company in industry areal , makassar city , south sulawesi province , indonesia . the effectiveness of hydroxyapatite to protection against teeth demineralization was tested in acetate buffer ph 5.0 solutions , with 1 m of acetic acid concentration with the addition of hydroxyapatite in varying concentrations and immersion time . the proven in vitro demineralization of teeth was conducted through evaluating the concentration of phosphate in solution by using the uv - vis spectroscopy . the characterization of the compounds was performed by using x - ray diffraction ( xrd ) , ftir , and sem - edxa .", "this proves that the ca10(po4)6(oh)2 were synthesized from the crab shell effective for protection against tooth demineralization . . the greater concentrations of ca10(po4)6(oh)2 in the acetate buffer solution were teeth immersed exhibit the smaller mass of teeth in the solution . \n the decrease in the rate of tooth demineralization with the addition of ca10(po4)6(oh)2 can also be observed through analyzing the tooth mass reduction in the fifth variation of acetate buffer solution as shown in table 1 demineralization of teeth is a process of decomposition of the crystal of ca10(po4)6(oh)2 due to the acidic conditions by releasing ca and po4 ions .", "based on these results it is concluded as follows.waste of shells crabs ( portunus pelagicus ) proved to be used as raw material for the synthesis of ca10(po4)6(oh)2 due to high calcium levels which amounted to 66.62% in addition to the abundant existence as waste.the optimum temperature formation of ca10(po4)6(oh)2 is at 800c.ca10(po4)6(oh)2 were synthesized from waste of shell crabs ( portunus pelagicus ) in vitro effectively inhibiting the rate of demineralization of the tooth where the greater the addition of ca10(po4)6(oh)2 in the solution , the more the inhibiting demineralization of the tooth or the smaller the rate of tooth demineralization in solution . waste of shells crabs ( portunus pelagicus ) proved to be used as raw material for the synthesis of ca10(po4)6(oh)2 due to high calcium levels which amounted to 66.62% in addition to the abundant existence as waste ." ]
crab 's shells of portunus pelagicus species were used as raw materials for synthesis of hydroxyapatite were used for protection against demineralization of teeth . calcination was conducted to crab 's shells of portunus pelagicus at temperature of 1000c for 5 hours . the results of calcination was reacted with ( nh4)2hpo4 , then dried at 110c for 5 hours . sintering was conducted to results of precipitated dried with temperature variations 4001000c for a hour each variation of temperature then characterized by x - ray diffractometer and ftir in order to obtain the optimum formation temperature of hydroxyapatite is 800c . the hydroxyapatite is then tested its effectiveness in protection against tooth demineralization using acetate buffer ph 5.0 with 1 m acetic acid concentration with the addition of hydroxyapatite and time variation of immersion . the results showed that the rate of tooth demineralization in acetate buffer decreased significantly with the provision of hydroxyapatite into a solution where the addition of the magnitude of hydroxyapatite is greater decrease in the rate of tooth demineralization .
[ "although the use of vr in cognitive \n rehabilitation has been increasing , few systematic reviews have investigated the use of vr \n programs in cognitive rehabilitation and the overall effect of these programs on cognition . \n therefore , this systematic review investigated the different types of vr programs used for \n cognitive evaluation and interventions for patients with brain injury . in addition , vr tools can be used to record accurate measurements \n of the subject s performance9 and to \n deliver greater therapeutic stimulation to users5 . studies using vr \n programs for cognitive intervention were reviewed according to pico ( patient , intervention , \n comparison , and outcome ) methods . the virtual environment offered via vr technology makes it possible for patients to \n participate in activities in settings and environments similar to those encountered in real \n life7 , 8 . vr has been used as a \n tool to diagnose cognitive impairment and as a vehicle to provide new treatments5 . therefore , for successful rehabilitation , accurate and comprehensive cognitive \n assessment and treatment are required4 . for cognitive rehabilitation of patients with brain injury , traditional treatment and \n computer - based cognitive therapy vr systems allow users \n to interact in various sensory environments and to obtain real - time feedback on their \n performance using computer technology6 . \n", " inclusion criteria were : ( 1 ) subjects over the age of 19 years with brain \n injury ; ( 2 ) articles written in english ; and ( 3 ) studies that used vr in cognitive \n rehabilitation . ( virtual reality or virtual or game based virtual reality or computer based virtual \n reality ) and ( stroke or cerebral vascular accident or hemiplegia or brain injury or \n traumatic brain injury ) and ( cognition or cognitive or memory or attention or executive \n function ) . exclusion criteria were : ( 1 ) subjects who were animals or children ; ( 2 ) \n review articles ; and ( 3 ) 2d computer - based cognitive rehabilitation . randomized controlled trials ( rcts ) and crossover studies were scored on the physiotherapy \n evidence database ( pedro ) scale12 . two \n authors independently assessed the methodological quality of the included studies , and \n disagreements were resolved by reaching consensus .", "memory \n assessment was the most common study topic , followed by assessments of executive function \n and attention . a variety of vr programs were used ( table 1table 1.analysis of studies of cognitive assessment using vrauthor , yearassessment areatype of vrbrooks et al . table 2table 2.analysis of studies with cognitive interventions using vrstudypatientinterventioncomparisonoutcomenmean agetype of vrintensityoutcome measure(s)findingsakinwuntan et al . , 20132512eg 27.83 cg 30.67irex45 min / day , 34 times / week , total 3 weeksconventional otmet - sv , efpteg showed significant improvements in all outcome measures \n compared to the cgkim et al . , 20112628eg 66.5 cg 62.0irex30 min / day , 5 times / week , total 4 weekscomputer based cognitive therapyk - mmse , tol , vcpt , acpt , word - color test , fdst , bdst , fvst , bvst , \n vilt , velt , tmt - asignificant difference between experimental group and control \n group in vcpt and bvsteg : experimental group , cg : control group , met - sv : multiple errands test - simplified \n version , efpt : executive function performance test , fdst : forward digit span test , \n bdst : backward digit span test , tmt - a : trail making test - type a , tmt - b : trail making \n test - type b , velt : verbal learning test , vilt : visual learning test , ufov : useful \n field of view test , k - mmse : korean version of the mini - mental status examination , tol : \n tower of london test , vcpt : visual continuous performance test , acpt : auditory \n continuous performance test , fvst : forward visual span test , bvst : backward visual \n span test , ravlt : rey auditory verbal learning test , ir : immediate recall , dr : delayed \n recall , rbmt - the rivermead behavioural memory test , adas : alzheimer s disease \n assessment scale presents the characteristics of the five studies . three were rcts24,25,26 , one was a crossover \n study27 , and one was a case report28 . excepting the case report , four studies \n were assessed using the pedro scale . 1999271332.38nonimm - ersive vr exercise bicycle25 min / day , 3 times / week , total 4 weeksno treatmentfdst , bdst , digit symbol test , tmt - a & b , auditory learning \n test , velt , vilt , logical memory , complex figure testeg showed significant improvements in digit symbol test , velt , \n vilt compared to cgjacoby et al .", "in this review , the types of vr programs that have been used in cognitive evaluations of \n patients with brain injury were identified and studies of cognitive interventions were \n reviewed according to pico methods . in the included studies , the vr programs could \n distinguish the cognitive disability of patients in comparisons with healthy subjects . the results of this systematic review suggest that vr is an effective cognitive therapy for \n patients with brain injury compared to control therapy . thus , \n vr could be used as a new assessment method of the cognitive function of patients with brain \n injury . well - designed rcts and blind studies will be needed to provide evidence of the benefits of \n vr on cognitive function . the \n results of this systematic review indicate that the cognitive improvement of attention using \n vr programs will have a positive impact on the recovery of general cognitive function ." ]
[ purpose ] the purpose of this review was to investigate various types of vr programs and their use in cognitive evaluations and interventions for patients with brain injury . [ subjects and methods ] pubmed , cochrane , and otseeker electronic databases were searched with the search terms . at of 350 titles and abstracts were retrieved , and 17 articles were selected for this review . selected articles were assessed on the level of evidence using the physiotherapy evidence database ( pedro ) scale . [ results ] articles assessing the impact of cognitive impairments in memory were most commonly found , and vr interventions elicited positive effects in patients with brain injury . [ conclusion ] vr can be considered a new tool for cognitive rehabilitation after brain injury . vr interventions also have a number of advantages , e.g. cost - effectiveness , compared to other interventions .
[ "the aim of this study was to evaluate cytochrome oxidase i ( coi ) gene alongside 28s - d3 as a diagnostic tool for identification of an . anopheline mosquitoes ( krzywinski and besansky 2003 ) . variations in this fragment have been exploited as dna barcodes for identifications of culicidae mosquitoes including an . coi gene sequences have been extensively used for population studies and resolving evolutionary relationship among closely related species groups of insects ( lunt et al . 1996 ) and biology , variation in behaviors , and role of this species in malaria transmission in different geographical areas of iran has been extensively reviewed by others ( eshghi et al . despite a considerable progress in malaria control in iran over the past few years that led to significant reduction of cases , the disease still remains a major health problem in south and southeastern parts of the country .", "fluviatilis mosquitoes originated from different localities in south and southeastern areas of iran including fars , hormozgan , kerman , and sistan va baluchestan provinces . the extraction method and identity of some mosquitoes based on its2 and/or 28-d3 genes were described previously ( naddaf et al . all the dna samples were initially subjected to allele specific ( as)-pcr based on 28s - d3 gene as described by singh et al . the sequence data for the coi gene sequences were submitted to genbank with the accession numbers jx020706-jx020729 . the distances between groups and between individual sequences were calculated , and phylogenetic tree for iranian sequences was generated using the kimura two parameter ( k2p ) model of neighbor - joining method in a complete deletion procedure using mega 4 software ( tamura et al .", "fluviatilis mosquitoes originated from different localities in south and southeastern areas of iran including fars , hormozgan , kerman , and sistan va baluchestan provinces . the extraction method and identity of some mosquitoes based on its2 and/or 28-d3 genes were described previously ( naddaf et al .", "the sequence data for the coi gene sequences were submitted to genbank with the accession numbers jx020706-jx020729 . all the dna samples were initially subjected to allele specific ( as)-pcr based on 28s - d3 gene as described by singh et al . the distances between groups and between individual sequences were calculated , and phylogenetic tree for iranian sequences was generated using the kimura two parameter ( k2p ) model of neighbor - joining method in a complete deletion procedure using mega 4 software ( tamura et al . the sequences were manually edited and corrected using bioedit software , version 7.1.3.0 ( hall 1999 ) and fragments of 474 bp length were selected for analysis . pcr products were purified using a gel band purification kit ( pharmacia , piscataway , nj , usa ) according to manufacturer s recommendations and later sequenced using the same primers as used for amplification at seqlab laboratory in germany .", "the indian group exhibited the same distance ( 2.06% ) with fars group . the highest distance ( 3.09% ) among iranian individuals was between specimens 930 from fars province and 398 from sistan va baluchestan province . the mean distance between iranian and indian groups was 1.66% , while the value between fars group and the group comprising other iranian members was 2.06% . in addition , ten individuals from other geographical areas including four from koveh ( 170 , 172 , 173 , and 186 ) and one from minab ( 121 ) in hormozgan province , two from abchekan ( 392393 ) in sistan va baluchestan province , and three from kahnouj in kerman province ( 815 , 836 , and 839 ) were 100% identical . all the dna specimens from fars province yield only a product of approximately 375 bp length indicative of species u , whereas specimens from hormozgan , kerman and sistan va baluchestan provinces amplified two bands of 375 bp and 128 bp length . phylogenetic analysis using coi gene grouped individuals from fars province in two distinct clades separate from other iranian individuals representing populations of hormozgan , kerman , and sistan va baluchestan ( fig . six individuals belonging to two clades ( 87 , 97 , 655 , and 928 ) and ( 92 ) from fars province showed 100% identity .", "we report further evidence for the occurrence of these two sibling species by coi analysis of mitochondrial dna from the same specimens . this study shows that coi gene can be used as a useful tool along other dna markers like 28-d3 gene for dissolving closely related taxa of an . fluviatilis mosquitoes ( by its2 and 28s - d3 genes ) from india , iran , and other geographical areas by this genetic marker can bring more insight into taxonomy of this sibling species . accurate identification of malaria vectors is not only one of the most basic requisite for success of malaria control programs , but also has become an intriguing issue for understanding speciation process and evolution of anopheles mosquitoes . in absence of cytotaxonomic evidence , rapd - pcr methodology and variation in 28s - d3 gene have resolved two potential sibling species in an .", "this study shows that coi gene can be used as a useful tool along other dna markers like 28-d3 gene for dissolving closely related taxa of an . fluviatilis mosquitoes ( by its2 and 28s - d3 genes ) from india , iran , and other geographical areas by this genetic marker can bring more insight into taxonomy of this sibling species ." ]
background : anopheles fluviatilis , one of the major malaria vectors in iran , is assumed to be a complex of sibling species . the aim of this study was to evaluate cytochrome oxidase i ( coi ) gene alongside 28s - d3 as a diagnostic tool for identification of an . fluviatilis sibling species in iran.methods:dna sample belonging to 24 an . fluviatilis mosquitoes from different geographical areas in south and southeastern iran were used for amplification of coi gene followed by sequencing . the 474475 bp coi sequences obtained in this study were aligned with 59 similar sequences of an . fluviatilis and a sequence of anopheles minimus , as out group , from genbank database . the distances between group and individual sequences were calculated and phylogenetic tree for obtained sequences was generated by using kimura two parameter ( k2p ) model of neighbor - joining method.results:phylogenetic analysis using coi gene grouped members of fars province ( central iran ) in two distinct clades separate from other iranian members representing hormozgan , kerman , and sistan va baluchestan provinces . the mean distance between iranian and indian individuals was 1.66% , whereas the value between fars province individuals and the group comprising individuals from other areas of iran was 2.06%.conclusion : presence of 2.06% mean distance between individuals from fars province and those from other areas of iran is indicative of at least two sibling species in an . fluviatilis mosquitoes of iran . this finding confirms earlier results based on rapd - pcr and 28s - d3 analysis .
[ "we presented a case of schwannoma originating from the great omentum , including histological and immunohistological studies . they are found most commonly in the cranial and peripheral nerves , and occurrence in the omentum is very rare . however , there have been some cases reported to develop serious complications and , if there was malignancy , to cause metastasis or recurrence .", ", we performed laparoscopic resection with vessel sealing system , which revealed a 2.0 cm mass arising from the great omentum , not adherent to other organs . laboratory tests , including tumor makers , were normal . under a perioperative diagnosis of cystic tumor in the abdomen and cholelithiasis a 55-year - old man was referred to our department for the treatment of a tumor detected close to the stomach by ultrasound . medical examination including abdominal and endoscopic ultrasound showed a 2.0 1.3 cm cystic mass lateral to the wall of the stomach . computed tomography scan of the abdomen and pelvis showed a 2.6 1.9 cm cystic mass , which was slightly enhanced , and a gallbladder stone ( fig .", "they are seldom found in the abdomen , especially the extragastrointestinal tract , of which solitaly schwannoma of the great omentum is an extremely rare tumor . in 303 schwannomas reported by das gupta schwannomas are known to mainly arise from the peripheral and caranial nerves , the extremities and the retroperitoneum . , one case originated from the retroperitoneum , others from the central nervous system and peripheral nerve . in another review of the literature , stout and schwannomas are classified as one kind of the peripheral nerve sheath tumors , of which schwannnoma and neurofibroma are the most frequent . currently , the most precise determination of the tumor 's cell type is established by its immunohistochemical profile , ultrastructural features , or both . a tumor composed of cells with distinctly schwannian characteristics there are no case reports documenting other treatments , including chemotherapy for schwannomas in the abdominal cavity . therefore laparoscopic resection seemed to be the most adequate method to diagnose and rule out malignant tumor as a minimally invasive surgery ." ]
schwannoma in the abdomen is an uncommon neoplasm that occurs most frequently in the cranial and peripheral nerves ; it is extremely rare in the great omentum and only 6 cases of schwannoma of the great omentum have been observed previously . we report the case of a schwannoma found in the great omentum of a 55-year - old man who was treated with laparoscopic surgery . though it was difficult to diagnose preoperatively , the tumor showed malignant potential by rapidly increasing in size . histologically it was configured by a well - encapsulated round mass measuring 30 18 15 mm in diameter . immunohistochemically most of the neoplastic cells reacted moderately to nse , ncam and s-100 protein . we document the clinicopathological study of a schwannoma of the great omentum , followed by a review of the literature .
[ "we performed an initial exploratory microarray analysis in 5 cases and controls and then further examined the most highly expressed mirnas in an additional 15 cases and controls . , we sought to compare mirna expression in whole blood of patients with angiographically significant cad to that of healthy aged - matched controls . thus , mirna expression signatures in tissues and blood have a potential role in the diagnosis , prognosis , and assessment of therapy . in this study several recent studies have suggested that circulating micrornas could be useful as biomarkers for various human disease states , including cancer , acute myocardial infarction [ 47 ] , heart failure , and chronic vascular disease [ 8 , 9 ] . cad is caused by atherosclerosis , which is an inflammatory disease that involves multiple cell types , including circulating cells and cells in the vessel wall . despite advances in risk factor management on an epidemiological level , although the biological function of mirna is yet to be fully understood , tissue levels of specific mirnas have been shown to correlate with pathological development of different diseases .", "coronary angiograms were evaluated independently by two operators , who made visual estimation of luminal narrowing in multiple segments based on a modified form of the aha / acc classification of the coronary tree . using these data , significant cad was defined as at least one major epicardial vessel with > 50% stenosis , assessed by quantitative coronary angiography . additionally , we collected whole blood samples from patients with 2 risk factors for cad , but did not have angiographically significant cad . study participants were recruited as part of the emory cardiology biobank , consisting of 3492 consecutive patients enrolled prior to undergoing elective or emergent cardiac catheterization across three emory healthcare sites , between 2003 and 2008 . patients aged 2090 years were interviewed to collect demographic characteristics , medical history , and lifestyle habits . risk factor prevalence was determined by physician diagnosis and/or treatment for hypertension , hyperlipidemia , and diabetes . mirna was isolated using the preanalytix paxgene mirna isolation kit ( qiagen ) according to the manufacturer 's protocol .", "although we were able to detect some differences in whole blood mirna levels between healthy subjects and cad patients ( mir-584 , in particular ) , our microarray data suggest that , similar to other reports , levels of mirnas in the blood are low and microarrays may lack the sensitivity to adequately identify mirnas that might serve as vascular disease biomarkers . interestingly , among the mirnas that tended to show consistent differences between healthy and cad blood , mirna expression was generally higher in the blood of healthy subjects , a finding previously observed by others . we found that there was no difference in whole blood mirna expression of this latter group compared to that in patients with significant cad ( not shown ) , suggesting that these mirnas are markers for vascular inflammation rather than markers specific for significant cad . next , we performed qrt - pcr on rna isolated from whole blood of another 10 patients with angiographically significant cad and 15 healthy subjects . we compared the mirna expression levels in the blood of patients with angiographically significant cad or 2 risk factors for cad but not on acei or arb to that in blood of similar patients who were taking at least one of medications . ", "several recent studies have indicated that there is a potential role for circulating mirna levels as valuable biomarkers for different disease processes , including cancer , cardiomyopathy , and acute myocardial infarction . in this study , we wanted to address the hypothesis that mirna expression levels in blood could predict the presence of significant coronary artery disease in human subjects . the present study provides insight into whole blood levels of mirnas in patients with cad compared to healthy subjects and demonstrates their potential utility as biomarkers for vascular disease . we identified 11 mirnas whose expression was significantly downregulated in patients with angiographic evidence of significant atherosclerosis compared to healthy subjects that were matched for age and gender . in addition , our data suggest that inhibition of the renin angiotensin system by acei or arb use further influences mirna expression in blood ." ]
coronary artery disease ( cad ) is the largest killer of males and females in the united states . there is a need to develop innovative diagnostic markers for this disease . micrornas ( mirnas ) are a class of noncoding rnas that posttranscriptionally regulate the expression of genes involved in important cellular processes , and we hypothesized that the mirna expression profile would be altered in whole blood samples of patients with cad . we performed a microarray analysis on rna from the blood of 5 male subjects with cad and 5 healthy subjects ( mean age 53 years ) . subsequently , we performed qrt - pcr analysis of mirna expression in whole blood of another 10 patients with cad and 15 healthy subjects . we identified 11 mirnas that were significantly downregulated in cad subjects ( p < .05 ) . furthermore , we found an association between acei / arb use and downregulation of several mirnas that was independent of the presence of significant cad . in conclusion , we have identified a distinct mirna signature in whole blood that discriminates cad patients from healthy subjects . importantly , medication use may significantly alter mirna expression . these findings may have significant implications for identifying and managing individuals that either have cad or are at risk of developing the disease .
[ "we predicted that the nests ' protective properties reduced the need for behavioral defenses by p. emaciata workers , relative to paper - nesting polybia species with similar colony and nest sizes . we tested this prediction by disturbing p. emaciata colonies , and comparing the workers ' responses to those of simultaneously observed paper - nesting p. occidentalis colonies in the same location . we discuss the possible adaptive significance of deviations from the typical nest exit that have been documented in several paper wasp species , including p. emaciata . if so , we hypothesized that the wasps ' defensive responses to vertebrate attacks have changed to take advantage of nest durability .", "we disturbed the polybia nests by first tapping on the side of the outer envelope near the middle of the nest for 30 sec while wearing a full bee suit , and we noted the responses of on - nest and in - nest workers . we disturbed p. emaciata and p. occidentalis colonies in an effort to evoke defensive behavior , using stimuli that elicited nest exit and attack responses in costa rican p. occidentalis ( s.o'd . and this study was conducted in and near the town of gamboa , panama province , republic of panama ( 0907n 7942w ; 50 m elevation ) . surveys of eusocial wasp colonies during these periods indicated that p. emaciata was among the most abundant swarm - founding wasps in terms of nest density ( s.o'd . , unpublished data ) .", "all observation and in situ polybia colonies contained brood ( larvae and/or pupae were visible in the lower combs ) when they were tested . based on forager traffic and on the numbers of wasps exiting the nests during attacks in contrast , all 50 nest - tapping trials with p. occidentalis resulted in immediate ( within 1 sec ) exit - nest and attack responses . several dozen individuals rapidly exited the nest , took flight , and struck and attempted to sting the observer 's bee veil . the species difference in the per - colony probability of nest exit and attack within 30 sec of disturbance was significant ( fig .", "predation on swarm - founding wasp nests by bats ( jeanne , 1970a ) , birds ( skutch , 1971 ; windsor , 1976 ) , and primates ( vecht , 1967 ) has been documented . of special value to our understanding of the evolutionary significance of the mud - nesting habit will be field studies on the defensive behaviors of the other mud - nesting polybia species . we hypothesize that the unusual defensive response of p. emaciata is a behavioral adaptation to its use of mud in nest construction , which may make the nest more resistant than paper to entry by vertebrate predators . we suggest that this represents a special type of architectural defense ( hermann and blum , 1981 ) , where the defensive behavior of a species has been modified to exploit the properties of its nest material these patterns suggest that retreat behavior has evolved convergently in several lineages of epiponini , perhaps in response to particular types of predators .", "photograph of a mud nest of polybia emaciata collected july 1998 in gamboa , panama . box plots showing the range of probabilities of response to nest disturbance with attack within 30 sec by polybia emaciata and p. occidentalis colonies ." ]
the swarm - founding wasp polybia emaciata is unusual among eusocial vespidae because it uses mud , rather than wood pulp , as its primary nest construction material . polybia emaciata nests are more durable than similarly sized paper nests . we tested the hypothesis that the defensive behavior of this wasp may have been modified to take advantage of their strong nests in defense against vertebrate attacks . we simulated vertebrate disturbances by tapping on , and breathing in , p. emaciata nests and similarly sized p. occidentalis paper nests in the same location at the same time . polybia emaciata responses to disturbance were qualitatively different from those of p. occidentalis . the latter exit the nest and attack , while p. emaciata workers typically fled or entered the nest , attacking only after repeated and extended disturbances . we conclude that durable nest material may permit predator avoidance behavior in p. emaciata . we compare the defensive responses of p. emaciata workers with those of other swarm - founding vespidae , and discuss several selective forces that could cause the evolution of species variation in nest defense behavior .
[ ", we used quantitative real - time pcr , immunohistochemistry assay , and western blot analysis to investigate the expression pattern of mpg gene and protein in glioma specimens and normal control brain tissues . next , we analyzed the relationship between mpg expression and the glioma stage as well as the survival of patients . breast cancer cells are significantly more sensitive to the clinical chemotherapeutic agents , suggesting that the overexpression of mpg may be a possible gene therapy approach to sensitize tumor cells to the cell - killing effects of chemotherapeutic alkylating agents . the biological mechanism behind the increase of sensitivity to the chemotherapeutic agents in mpg overexpressing cell lines may be that the balance between glycosylase activity , leading to apurinic sites and formation of strand breaks , and subsequent excision repair processes may play an important role in determining cellular cytotoxicity and resistance to alkylating agents . of our interests , we focus on the involvement of mpg in human gliomas . thus , there is an urgent need to further investigate the molecular mechanisms of glioma and to identify the effective prognostic indicators for survival prediction.the dna - base excision repair ( ber ) pathway is responsible for the repair of exogenous and endogenous alkylating and oxidative dna damage , which may lead to carcinogenesis , cell death , and aging if left unrepaired however , little is known about the expression level of mpg in human gliomas with different clinical grades and its prognostic significance . to address this problem early diagnosis and prolonging survival in glioma patients remains a great challenge for clinicians in the field of neurooncology .", "in addition , 20 glioma specimens [ 5 pilocytic astrocytomas ( who i ) , 3 diffuse astrocytomas ( who ii ) , 3 anaplasia astrocytomas ( who iii ) , and 9 primary glioblastomas ( who iv ) ] were snap - frozen in liquid nitrogen and stored at 80c following surgery for mrna and protein isolation . total rna purified from all 20 glioma tissues and 10 control brain tissues a total of 128 formalin - fixed , paraffin - embedded specimens of gliomas resected between 2000 and 2010 were retrieved from the archives of the pathology department of tangdu hospital , fourth military medical university , p.r . paraffin and snap - frozen sections of nonneoplastic brain tissues from 10 patients with intractable epilepsy were also included as controls . thirty - two of the 128 gliomas were classified as low - grade [ 18 pilocytic astrocytomas ( who i ) and 14 diffuse astrocytomas ( who ii ) ] , and 96 were classified as high - grade gliomas [ 38 anaplasia astrocytomas ( who iii ) , and 58 primary glioblastomas ( who iv ) ] . randomized block design anova was used to analyze the statistical difference among different tissue types . in the analysis of glioma morbidity for all patients a total of 76 males and 52 females ( 1.46 : 1 ) were enrolled in this study , and the median age was 42 years ( range , 1271 ) . five - year followup was performed , and all patients had complete followup until death .", "the loss of mpg expression was a significant ( p < 0.001 ) and independent prognostic indicator for patients with glioma besides age , who grade and kps . the cox - proportional hazards model showed that mpg over - expression was associated with poor overall survival . furthermore , figure 5(b ) shows the postoperative survival curve of patients with glioma and mpg expression after adjusting for age , gender , who grade , and kps . by multivariate analysis ( table 2 ) , the median survival time of patients with negative expression of mpg could not be estimated by statistical analysis because all patients survived better than the overall median level , and those patients with strong positive ( + + + ) , moderate positive ( + + ) , and weak positive ( + ) of mpg were 9.1 1.5 months , 12.3 1.1 months , and 22.6 2.2 months ( log - rank test : p < 0.001 ) . the gene expression of mpg normalized to -actin in 20 glioma and 10 control brain tissues was detected by real - time pcr . as shown in figure 2 , the expression levels of mpg gene in human glioma tissues were conspicuously higher than those in control brain tissues ( p < 0.001 ) .", ", we investigated the expression of mpg in 128 cases of human glioma and compared the expression with tumor grade and survival rates of patients . these results suggest that the transcriptional and translational activation of human mpg might participate in the tumorigenesis and progression of glioma . because of the dismal survival in the patients with glioma , especially in gbm patients , there is an urgent need to find novel specific and effective prognostic markers in order to apply individualized treatments to specifically target the pathophysiologic and molecular properties of glioma patients . in the current study our data demonstrated that mpg gene and protein were both increased in glioma compared to nonneoplastic brain tissue . our data showed the over - expression of mpg gene and protein in human gliomas and also suggested for the first time that mpg be an unfavorable independent prognostic indicator for glioma patients ." ]
aim . to examine the expression of n - methylpurine - dna glycosylase ( mpg ) gene and protein in glioma samples with different who grades and its association with patients ' survival . methods . immunohistochemistry assay , quantitative real - time pcr and western blot analysis were carried out to investigate the expression of mpg gene and protein in 128 glioma and 10 non - neoplastic brain tissues . results . mpg gene expression level in glioma tissues was significantly higher than that in non - neoplastic brain tissues ( p < 0.001 ) . immunohistochemistry also showed that mpg protein was over - expressed in glioma tissues , which was consistent with the resutls of western blot analysis . additionally , the expression levels of mpg gene and protein both increase from grade i to grade iv glioma according to the results of real - time pcr , immunohistochemistry and western blot analysis . moreover , the survival rate of mpg - positive patients was significantly lower than that of mpg - negative patients ( p < 0.001 ) . we further confirmed that the over - expression of mpg was a significant and independent prognostic indicator in glioma by multivariate analysis ( p < 0.001 ) . conclusions . our data showed the over - expression of mpg gene and protein in human gliomas , and also suggested for the first time that mpg be an unfavorable independent prognostic indicator for glioma patients .
[ "thus , the objective of this study was to systematically review the literature regarding the prevalence of overweight and obesity in adolescents ( 1019 years old ) of both sexes published in the past 12 academic years ( 19992011 ) . the most widely used growth charts are the centers for disease control and prevention ( cdc-2000 ) , the international task force ( iotf ) , and the 2007 growth references for 5 to 19 year olds produced by the world health organization ( who-2007 ) . the cdc-2000 growth charts were developed to evaluate the nutritional status of us children and were originated from five cross - sectional representative surveys carried out in the us between 1963 and 1994 . these growth charts are routinely applied to identify children and adolescents with a bmi greater than the 85th or 95th percentiles following the advice of the us expert committee on childhood obesity . this reference was constructed using data from the 1977 nchs / who growth reference ( 1 to 24 years old ) merged with data from the 2006 who child growth standards for preschool children ( under 5 years of age ) using state - of - the - art statistical methods . the iotf reference also uses age - sex - specific bmi percentiles , and overweight and obesity definition corresponds to an adult bmi of 25 and 30 kg / m , respectively , and reflects values in children tracking to overweight and obesity in adults . although valuable information has been appearing in the literature or online , such as works from the health behaviour of school - aged children study which is mainly related to social determinants of health and well - being among young people , no systematic review has been conducted to understand the worldwide magnitude of the overweight and obesity problem among the adolescent population . the who-2007 growth references were created to replace the national center for health statistics ( nchs ) references [ 10 , 11 ] .", "we also reviewed the data on the prevalence of childhood overweight and obesity on the international obesity task force website at http://www.iaso.org / iotf/. to find the articles included in this review , the following inclusion criteria were used : ( 1 ) cross - sectional studies conducted in the last 12 years ( 19992011)when the original study did not report the survey year , it was not included ; ( 2 ) national and regional representative samples , but articles published on the prevalence of overweight in towns , urban , or rural areas in a country were excluded ; ( 3 ) weight and height objectively measured ; ( 4 ) results presented by sex ; ( 5 ) and for both overweight and obesity prevalence ; ( 6 ) the definition of overweight and obesity using the ( i ) cdc-2000 , ( ii ) iotf , and ( iii ) who-2007 growth references ; and ( 7 ) studies written in english , spanish , italian , or portuguese . the literature search was conducted in medline and scopus using the following mesh terms : overweight ; obesity ; prevalence ; adolescent . in total , 2537 articles were selected . moreover , if there were more than one national or regional study in the same country , the most recent one was included in the prevalence tables ( except for usa and canada , countries in which the most recent data was not included in the tables due to differences in the representativeness of the samples and the impossibility to calculate a single prevalence of overweight and obesity for adolescents ' boys and girls ; however , no differences in prevalence were observed between studies as it has been indicated in the discussion ) . the final number of articles included in this review was 39 articles related to overweight and obesity and also a study on the latest statistics on the prevalence of overweight and obesity in south africa . a systematic literature search was performed which ended on june 7 , 2012 ( see figure 1 ) . any matter of doubt was discussed by at least two of the reviewers ( m. m. bibiloni , a. pons , and j. a. tur ) . potentially relevant papers were selected by ( 1 ) screening the titles ; ( 2 ) screening the abstracts , and ( 3 ) if abstracts were not available or did not provide sufficient data , the entire article was retrieved and screened to determine whether it met the inclusion criteria .", "the obesity prevalence was 10% higher among boys in seventeen countries ( canada , usa , china , iran , israel , qatar , saudi arabia , taiwan , cyprus , czech republic , germany , greece , italy , portugal , sweden , australia , new zealand , denmark , and hungary ) and 10% higher among girls in four of the twenty - five countries ( south africa , seychelles , tunisia , and bahrain ) . in general , the prevalence of overweight plus obesity was higher in america [ 1820 ] , oceania [ 38 , 39 ] and europe [ 3037 ] and lower in africa [ 1517 ] and certain parts of asia [ 2129 ] ( in china and iran the total prevalence was less than 10% by the iotf cut - offs ) . the prevalence of overweight and obesity in southern italy and italian islands was higher among boys . table 1 presents a description of the forty studies selected for this review including the continent and the country where it was performed ( and region for not national studies ) , year of publishing , total number of participants in the study , number of adolescents , age range , proportion of girls , and number and definition for overweight and obesity classification used . a total of thirty - nine articles and a national health report were eligible according to the inclusion criteria established for this review . ", "the aim of this study was to review systematically the literature on overweight and obesity prevalence among adolescents worldwide . thirty - nine articles and one national health report that met the inclusion criteria were considered . the overweight and obesity prevalence in the included studies ranged widely . in sixteen of the twenty - three countries with national representative data using the iotf cut - off , overweight and obesity prevalence regarding national data , when prevalence was analysed according to sex , it was observed that boys showed a higher prevalence of overweight in almost half of the countries and a higher prevalence of obesity in almost all countries .", "the comparisons of overweight and obesity prevalence need interpretation with caution due to the difference in survey sampling methods , sample sizes , age range of subjects , quality of data in terms of height and weight measurement , and whether national programmes or strategies to tackle overweight and obesity are in place . even within the same country , the prevalence and trends of overweight and obesity may not be homogenous in view of different ethnicities , geographic regions , and socioeconomic status . only articles in english , spanish , italian , and portuguese were included in this review .", "the results of this review allow the following conclusions : ( 1 ) overweight and obesity prevalence is high ; ( 2 ) obesity is higher among boys , although it is not clear which sex has a higher proportion of adolescents with overweight ; ( 3 ) despite that there is no consensus about criteria to be used to classify adolescents as overweighed or obese , the most frequently used was the iotf reference . however , the international reference charts for monitoring the secular trends in childhood obesity need to be continually refined and evaluated . the results of this study would contribute to guiding health planners and administrators to develop proper tools for adolescent obesity management ." ]
objective . to review the extant literature on the prevalence of overweight and obesity in adolescents ( 1019 years old ) of both sexes . design . the search was carried out using medline and scopus considering articles published from the establishment of the databanks until june 7 , 2012 . data on the prevalence of children being overweight and obese from the international obesity task force ( iotf ) website was also reviewed . only original articles and one national health report were considered . forty studies met the inclusion criteria . results . twenty - five of these studies were nationally representative , and ten countries were represented only by regional data . conclusions . the prevalence of overweight and obesity among adolescents worldwide is high , and obesity is higher among boys . the iotf criterion is the most frequently used method to classify adolescents as overweighed or obese in public health research .
[ "\n sacubitril / valsartan is a combination of a neprilysin inhibitor and an angiotensin ii receptor blocker , indicated to decrease the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure.a patient previously stable on atorvastatin developed severe rhabdomyolysis and an elevation of transaminases within 26 days of initiation of sacubitril / valsartan . \n", "rhabdomyolysis is a syndrome characterized by skeletal muscle cell damage , leading to elevated creatine kinase ( ck ) , lactate dehydrogenase ( ldh ) , and aspartate aminotranferase ( ast ) , which can result in severe sequelae , including renal failure , cardiac arrhythmia , hyperthermia and death . sacubitril / valsartan has not been associated with rhabdomyolysis and is commonly used in patients who are also receiving statin therapy . entresto is a combination of sacubitril , a neprilysin inhibitor , and valsartan , an angiotensin ii receptor blocker ( arb ) , indicated to decrease the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure ( new york heart association [ nyha ] class ii ", "barr virus , hepatitis a , herpes simplex virus , hiv , and cytomegalovirus ( cmv ) . a 63-year - old guyanese woman with hypertension , hyperlipidemia , congestive heart failure ( chf ) , atrial fibrillation , and peripheral vascular disease presented to her primary care provider s office with a complaint of an episode of weakness at home associated with general malaise . barr virus , and herpes simplex virus , and had negative hepatitis a and b , hiv , hsv . and cmv tests.fig . ", "iv heart failure as there is insufficient information on which to base recommendations for or against statin treatment . in these patients , the choice of statin dose , and using a statin for cardiovascular risk reduction benefit , must be weighed against adverse effects , drug drug interactions , precautions and contraindications to statin therapy . a literature search regarding a drug interaction between sacubitril and statins yielded no reports of rhabdomyolysis with statins . because of the above - stated pharmacodynamics , we believe that the more likely mechanism is the increased serum concentration of atorvastatin . currently , there is no recommendation regarding the initiation or continuation of statins in patients with nyha class ii this patient had been on a variety of statins for more than 7 years , including atorvastatin , simvastatin , and rosuvastatin . of note , one of the concurrent medications , carvedilol , is a p - glycoprotein inhibitor that may increase the serum concentration of atorvastatin , a p - glycoprotein substrate ; however , the patient was stable on this combination for 7 years before sacubitril / valsartan was initiated .", "this case of severe rhabdomyolysis should stimulate further investigation of the potential negative effects of the initiation of sacubitril / valsartan in patients receiving statin therapy . since sacubitril / valsartan is targeted for patients with heart failure , we predict that this would comprise a large number of the candidates for treatment . we recommend consideration of obtaining baseline ck levels and lfts and close observation of patients . in this case future reports of this reaction may help to define high - risk patients , but it should be noted that our patient had no known high - risk characteristics for the development of rhabdomyolysis , except for prior mild elevations of ck during hospitalizations for chf exacerbations . , rhabdomyolysis developed within 3 weeks of initiation of sacubitril / valsartan and evaluation within a shorter time frame may be appropriate . we encourage the reporting of any similar reactions to the us fda , the manufacturer , and the medical community .", "", "eve s. faber , madhavi gavini , ronald ramirez and richard sadovsky declare that they have no conflicts of interest that are directly relevant to the content of this report .", "a copy of the written consent may be requested for review from the corresponding author ." ]
a 63-year - old woman previously stable on a regimen of atorvastatin 40 mg daily , carvedilol 25 mg twice daily , digoxin 0.125 mg daily , furosemide 40 mg daily , spironolactone 25 mg daily , rivaroxaban 15 mg daily , and enalapril 20 mg twice daily for heart failure developed rhabdomyolysis 26 days after enalapril was stopped and sacubitril / valsartan ( entresto ) started . the patient received sacubitril / valsartan at 24/26 mg twice daily for heart failure ; however , after 26 days she developed muscle and skin pain . investigations revealed elevated creatine kinase and liver function tests , and rhabdomyolysis with raised transaminases was diagnosed . sacubitril / valsartan and atorvastatin were discontinued and the patient was hydrated . she returned to baseline in 23 days and has not had any reoccurrence of rhabdomyolysis and elevated transaminases for 46 days . a naranjo assessment score of 5 was obtained , indicating a probable relationship between the patient s rhabdomyolysis and her use of sacubitril / valsartan . the drug interaction probability scale score was 3 , consistent with a possible interaction as a cause for the reaction , with sacubitril / valsartan as the precipitant drug and atorvastatin as the object drug .
[ ", we investigated the association of p2x7r rs3751142 and card8 rs2043211 polymorphisms with the susceptibility and clinical manifestations of gout in the male korean population . the nlrp3 inflammasome , a member of the nlr family , is a key player in the production of uric acid - mediated il-1 and is an important cytoplasmic protein complex involved in gouty inflammation ( 12 ) . recent single - nucleotide polymorphism ( snp ) studies suggested that genetic alternations of several target molecules such as card8 and p2x7r contribute to the process of nlrp3 inflammasome activation . genetic variants of card8 were identified to play a role in the pathogenesis of a variety of inflammatory diseases , such as rheumatoid arthritis ( ra ) ( 8) and inflammatory bowel disease ( ibd ) ( 9 ) . although the precise pathogenic mechanism of gout has not been clearly determined , several crucial proteins such as the purinergic receptor p2x ligand - gated ion channel 7 ( p2x7r ) ( 345 ) and caspase activation and recruitment domain 8 ( card8 ) ( 67 ) proteins are known to be responsible for the pathogenesis of gout .", "a total of 242 male gout patients fulfilled the preliminary criteria for classification of primary gout proposed by the american college of rheumatology ( 14 ) and a total of 280 healthy male controls were consecutively enrolled in this study . clinical and laboratory variables , including age at the time of study , disease onset age , body mass index ( bmi ) , disease duration , and serum uric acid level were identified by individual interviews with each patient and medical record review . the reference sequence was based on the sequence of human chromosome 12 , 12q24 for the p2rx7 gene , and human chromosome 19 , 19q13.33 for the card8 gene . the kruskal - wallis test was used to compare parametric parameters such as age , onset age , disease duration , bmi , and serum uric acid among the three genotypes of each gene . logistic regression analysis adjusted with age was applied to test whether the combined p2x7r rs3751142 and card8 rs2043211 genotype influenced the risk of gout development compared to those in controls . snp , single nucleotide polymorphism ; p2x7r , purinergic receptor p2x ligand - gated ion channel 7 ; card8 , caspase activation and recruitment domain 8 .", "a total of 242 male gout patients fulfilled the preliminary criteria for classification of primary gout proposed by the american college of rheumatology ( 14 ) and a total of 280 healthy male controls were consecutively enrolled in this study . clinical and laboratory variables , including age at the time of study , disease onset age , body mass index ( bmi ) , disease duration , and serum uric acid level were identified by individual interviews with each patient and medical record review . medications including corticosteroids , non - steroidal anti - inflammatory drugs ( nsaids ) , colchicine , allopurinol , and benzbromarone that were used for gout treatment within one month of the study onset were evaluated through medical record reviews . the study protocol was reviewed and approved by the institutional review board / ethics committee at each medical center that participated in this study .", "the reference sequence was based on the sequence of human chromosome 12 , 12q24 for the p2rx7 gene , and human chromosome 19 , 19q13.33 for the card8 gene . snp , single nucleotide polymorphism ; p2x7r , purinergic receptor p2x ligand - gated ion channel 7 ; card8 , caspase activation and recruitment domain 8 . assay reagents for rs3751142(c > a ) in the p2x7r gene and rs2043211(a > t ) in the card8 gene were designed by applied biosystems ( applied biosystems , foster city , ca , usa ) . the pcr was performed using the abi plus ( applied biosystems ) system and the samples were read and analyzed using abi plus ( applied biosystems ) software .", "clinical parameters are described as the median with interquartile range ( iqr ) or the number with percent ( % ) . the hardy - weinberg equilibrium for gout patients and controls adjusted with age was applied to test whether the combined p2x7r rs3751142 and card8 rs2043211 genotype influenced the risk of gout development compared to those in controls . the kruskal - wallis test was used to compare parametric parameters such as age , onset age , disease duration , bmi , and serum uric acid among the three genotypes of each gene . logistic regression analysis the genotypic frequency of each gene was calculated and assessed using the chi - square and fisher s exact tests , if appropriate . both kolmogorov - smirnov and shapiro - wilk analyses were tested to identify normality of data distribution , which did not show a normal distribution . the results are described as the odds ratio ( or ) with a 95% confidence interval ( ci ) .", "the authors assert that all procedures contributing to this work comply with the helsinki declaration of 1975 and its later amendments . all patients provided written informed consent , and the protocol of this study was approved by the institutional review board ( irb ) of daegu catholic university medical center ( irb no .", "rs3751142 ( c > a ) in p2x7r gene and rs2043211(a > t ) in card8 gene . a pair - wise comparison of p2x7r rs3751142 and card8 rs2043211 genotype combinations showed that a trend toward higher risk of gout development was identified in subjects who were heterozygous for the ca p2x7r rs3751142 genotype and recessive homozygous for the tt card8 rs2043211 genotype compared to the cc / aa combination ( p = 0.056 , or = 2.618 , 95% ci 0.975 - 7.031 ) ( table 5 ) . no genotypic deviations of rs3751142(c > a ) in the p2x7r gene and rs2043211(a > t ) in card8 based on the hardy - weinberg equilibrium were noted for gout or control patients ( p > 0.05 ) . there were no differences of clinical variables according to genotypic distribution of p2x7r rs3751142 and card8 rs2043211 . in a comparison model sub - analysis for onset age the statistical analysis was performed using logistic regression analysis after adjustment with age . or , odds ratio ; ci , confidence interval . the mean age was 55.0 ( iqr 45.063.0 ) years for gout patients and 45.0 ( iqr 41.053.0 ) for controls , which was significantly different between two groups ( p < 0.001 ) .", "the main objective of this study was to investigate whether genetic variability in the p2x7r rs3751142 and card8 rs2043211 genes was involved in the process of nlrp3 inflammasome activation , which might influence susceptibility for the development of gout . however , we found that in a pair - wise comparison of the ca / tt p2x7r and card8 genotype combination was shown to have an increased trend for the risk of gout ( or = 2.618 , p = 0.056 ) . in conclusion , this study provides evidence that the interaction of msu crystal - mediated p2x7r with card8 may be at least in part responsible for the pathogenesis of gout . this study identified that card8 rs2043211 was not associated with increased gout risk , which is in contrast to the known difference of genetic distribution of this snp in the chinese and european gout population ( 67 ) . as far as we know , this study is the first to determine genetic association between the p2x7r snp and gout patients , revealing that p2x7r polymorphism did not increase the risk of gout in our study population . our study demonstrated that the p2x7r rs3751142 and card8 rs2043211 genetic variants were not implicated in the development of gout in the male korean population . this study found that p2x7r rs3751142 was not a genetic risk factor associated with gout susceptibility ." ]
the aim of this study was to determine the association between p2x7r rs3751142 and card8 rs2043211 polymorphisms and gout susceptibility in male korean subjects . this study enrolled a total of 242 male patients with gout and 280 healthy controls . the polymorphisms of two individual genes including rs3751142(c > a ) in the p2x7r gene and rs2043211(a > t ) in the card8 gene were assessed using taq - man analysis . statistical analyses were performed using the chi - square test , kruskal - wallis test , and logistic regression analyses . a difference in genotypic frequency of the p2x7r rs3751142 and card8 rs2043211 genes was not detected between gout and control patients . clinical parameters including age , onset age , disease duration , body mass index , and serum uric acid levels were not different among the three genotypes for either p2x7r or card8 ( p > 0.05 for all ) . a pair - wise comparison of p2x7r rs3751142 and card8 rs2043211 genotype combinations revealed that subjects with the ca p2x7r rs3751142 genotype and the tt card8 rs2043211 genotype had a trend toward a higher risk of gout compared to the cc / aa combination ( p = 0.056 , or = 2.618 , 95% ci 0.975 - 7.031 ) . in conclusion , this study revealed that genetic variability of the p2x7r rs3751142 and card8 rs2043211 genes might , in part , be associated with susceptibility for gout .
[ "isolated involvement of the appendix in crohn 's disease is reported to be 0.2% to 1.8% , and is usually associated with ileocaecal crohn 's disease in 25% of ileal and 50% of caecal disease . while appendicitis in a patient who was previously diagnosed to have ileocaecal crohn 's may be managed with appendicectomy and ileocaecal resection , appendicectomy alone when performed for appendicitis in a patient with unsuspected ileocaecal crohn 's disease could lead to postoperative complications including enterocutaneous fistula .", "a young female patient who underwent appendicectomy elsewhere for acute appendicitis presented to us with a persistent enterocutaneous fistula of 6 weeks duration . she had complained of general ill health and occasional altered bowel habits for 6 months prior to the acute appendicitis presentation . our investigations , including a ct scan , suggested the possibility of ileocaecal crohn 's disease . when last seen 2 years later during her regular follow - up , she was found to be in good health . she underwent excision of the enterocutaneous fistula and ileocaecal resection , and histopathology of the resected specimen confirmed crohn 's disease . in the postoperative period she received mesasalazine .", "a high index of clinical suspicion is required to make a prompt diagnosis and institute appropriate further treatment in form of ileocaecal resection . the possibility of ileocaecal crohn 's disease should be considered in patients presenting with unexplained postoperative enterocutaneous fistula following appendicectomy .", "crohn 's disease is a chronic inflammatory condition that may involve the entire gi tract . operations described in the literature for crohn 's disease of the appendix include appendicectomy with caecectomy and ileocaecal resection . crohn 's disease has been reported to be the cause of acute appendicitis in 0.2% to 1.8% of all the appendicectomies in some series . however , patients who undergo appendectomy alone are at the risk of complications including enterocutaneous fistula in 34% to 58% of the cases", "a 24-year - old unmarried female patient presented to us with a persistent fistula in the right iliac fossa following an appendicectomy done in another hospital 6 weeks previously . on further questioning , she informed us that she had presented to this hospital with a 2-week history of abdominal pain , confined to the right lower abdomen . a specimen of the resected caecum revealed the cobblestone appearance of the mucosa , strongly suggesting the possibility of underlying caecal crohn 's disease ( fig . the histology was reported as inflammatory bowel disease ( ibd ) consistent with crohn 's disease ( fig . a diagnosis of pelvic peritonitis secondary to acute appendicitis was made by the physicians , and she was taken up for surgery after adequate resuscitation .", "when the preoperative diagnosis is acute appendicitis , crohn 's disease should be suspected when an atypical or protracted clinical course is present in a patient prior to the appendicitis , particularly in areas where crohn 's disease is prevalent . crohn 's disease is diagnosed by a combination of clinical manifestations and radiological findings including barium studies , showing string strictures , fissures , and fistula in the ileum and caecum . the diagnostic difficulty arises when a patient undergoes an appendicectomy for suspected acute appendicitis and the surgeon unexpectedly encounters ileocaecal pathology whose nature is difficult to ascertain in an emergency situation . in view of this , a definitive treatment in the form of ileocaecal resection for conditions like crohn 's disease may be difficult to carry out . while a frozen section may be helpful to differentiate some of these conditions it may not always be feasible in an emergency situation . if crohn 's disease of the appendix is suspected and is limited to the appendix then appendicectomy alone is a routine surgical procedure with very low intraoperative or postoperative mortality and a low rate of fistula formation.the postoperative enterocutaneous fistula incidence rate in crohn 's disease restricted to appendix alone has been reported to be 3.5% , whereas in patients with crohn 's disease of the ileocaecal segment , as in our patient , the postoperative enterocutaneous rate rises to 34% to 58% . crohn 's disease may involve the appendix by extension from the terminal ileum or the caecum and present as an acute or sub - acute appendicitis[15 ] . differential diagnosis includes the presence of foreign bodies and diverticulitis of the appendix , which also give rise to chronic granulomatous inflammation with induration and fibrosis of the appendiceal wall , and granulomatous disease of unknown aetiology such as appendiceal sarcoidosis , which is rare and often accompanies systemic disease .", "crohn 's disease of the appendix is usually associated with crohn 's disease of the ileum and caecum . appendicectomy will suffice in those who present subacutely , are diagnosed preoperatively by clinical signs , and radiographic evidence shows that the disease is restricted to the appendix alone . however , in the presence of ileocaecal involvement , resection of the ileocaecal segment may be required to prevent postoperative complications of enterocutaneous fistula . while patients who develop enterocutaneous fistula post - appendicectomy in an unsuspected crohn 's disease case have been treated with infliximab with some success , the majority of the patients required ileocaecal resection . moreover ," ]
context : isolated involvement of the appendix in crohn 's disease is reported to be 0.2% to 1.8% , and is usually associated with ileocaecal crohn 's disease in 25% of ileal and 50% of caecal disease . while appendicitis in a patient who was previously diagnosed to have ileocaecal crohn 's may be managed with appendicectomy and ileocaecal resection , appendicectomy alone when performed for appendicitis in a patient with unsuspected ileocaecal crohn 's disease could lead to postoperative complications including enterocutaneous fistula.case report : a young female patient who underwent appendicectomy elsewhere for acute appendicitis presented to us with a persistent enterocutaneous fistula of 6 weeks duration . she had complained of general ill health and occasional altered bowel habits for 6 months prior to the acute appendicitis presentation . our investigations , including a ct scan , suggested the possibility of ileocaecal crohn 's disease . she underwent excision of the enterocutaneous fistula and ileocaecal resection , and histopathology of the resected specimen confirmed crohn 's disease . in the postoperative period she received mesasalazine . when last seen 2 years later during her regular follow - up , she was found to be in good health.conclusion:the possibility of ileocaecal crohn 's disease should be considered in patients presenting with unexplained postoperative enterocutaneous fistula following appendicectomy . a high index of clinical suspicion is required to make a prompt diagnosis and institute appropriate further treatment in form of ileocaecal resection .
[ "the random sample comprises 267 caucasian preadolescents ( 121 girls , 146 boys ) and 330 caucasian adolescents ( 164 girls , 166 boys ) of a population belonging to the swedish part of the european youth heart study ( eyhs ) . the eyhs is a cross - sectional school - based study of risk factors for future cardiovascular disease among preadolescents ( 910 years old ) and adolescents ( 1516 years old ) . dietary data were processed by stormats ( version 4.02 , rudans lttdata , sweden ) and analysed using the swedish national food database ( version 99.1 ) . as part of a broad - ranging questionnaire , parents of the participants were asked if their child had a chronic illness or adhered to a special diet . since under - nourishment is practically non - existent in a nutritionally replete population such as sweden and milk intake accounts in part for daily energy intake , the bmi was taken as proxy for energy intake . fifty subjects did therefore not participate in this assessment ( 3 preadolescent girls , 7 preadolescent boys , 25 adolescent girls , and 15 adolescent boys ) . milk intake ( g / d ) was somewhat skewed to the right and therefore split in quintiles of milk intake . the consumption of milk was assessed by an interviewer - mediated 24-hour recall . in preadolescents , stepwise backward multiple linear regression analysis was performed in order to study the relationship between milk intake in quintiles and body height ( cm ) after adjustments for sex , birth weight ( g ) , father 's and mother 's height ( cm ) , bmi , tanner stage ( 15 ) , and ses .", "basic characteristics of covariates to body height in the study population of swedish preadolescents and adolescents variables associated to body height by quintiles of milk intake fifty - six ( 9% ) of the subjects of the whole sample were lnp . where lnp may restrict the intake of milk in these subjects and the variables included in the backward multivariate regression model were : milk intake , lct c > t-13910 polymorphism ( lp = ct , tt vs. lnp = cc ) , sex , birth weight , father 's and mother 's height , bmi , tanner stage , and ses . model 1 included the variables : milk intake in quintiles , lct-13910 c > t polymorphism , sex , birth weight , parents height , tanner stage , bmi , and ses . in a first step the studied exposure variables in this model were milk intake in quintiles and the lct c > t-13910 polymorphism , and the outcome variable was body height . characteristics of preadolescents and adolescents by quintile of milk intake are given in table 2 . milk intake tended to be lower in lnp compared to lp but the difference did not reach statistical significance ( p=0.067 ) .", "we found that milk intake and lct c > t-13910 polymorphism , known to modulate milk consumption , were significant contributors to the observed variance of body height in the studied population . we conclude that actual milk intake and the genetic lp trait is positively associated with body height in preadolescents and adolescents . increasing evidence suggests that cow 's milk consumption exerts a positive effect on longitudinal growth in preadolescents and adolescents , for instance , by affecting the igf - i - axis ( 8 , 11 , 2730 ) . nevertheless , higher milk consumption in childhood might exert both negative and positive effects , since greater height has been associated with higher risk of some cancers ( 29 , 3841 ) . our study accounts for parental height as regards milk intake and its potential effects on body height and growth in preadolescents and adolescents .", "this study was supported by grants from rebro lns landstings forskningskommitt and by nyckelfonden , rebro , sweden ." ]
backgroundbody height is a classic polygenic trait . about 80%90% of height is inherited and 10%20% owed to environmental factors , of which the most important ones are nutrition and diseases in preadolescents and adolescents.objectivethe aim of this study was to explore potential relations between the lct ( lactase ) c > t-13910 polymorphism , milk consumption , and body height in a sample of swedish preadolescents and adolescents.designin a cross - sectional study , using a random sample of preadolescents and adolescents ( n = 597 ) , dietary intakes were determined . anthropometric measurements including sexual maturity ( tanner stage ) and birth weight were assessed . parental body height and socio - economic status ( ses ) were obtained by questionnaires . genotyping for the lct c > t-13910 polymorphism that renders individuals lactase persistent ( lp ) or lactase non - persistent ( lnp ) was performed by dna sequencing . stepwise backward multivariate linear regression was used.resultsmilk consumption was significantly and positively associated with body height ( = 0.45 ; 95% ci : 0.040 , 0.87 , p = 0.032 ) . adjustments were performed for sex , parental height , birth weight , body mass index ( bmi ) , ses , and tanner stage . this model explains 90% of the observed variance of body height ( adjusted r2 = 0.89 ) . the presence of the -13910 t allele was positively associated with body height ( = 2.05 ; 95% ci : 0.18 , 3.92 , p = 0.032).conclusionsmilk consumption is positively associated with body height in preadolescents and adolescents . we show for the first time that a nutrigenetic variant might be able to explain in part phenotypic variation of body height in preadolescents and adolescents . due to the small sample size further studies are needed .
[ "the aim of the present study was to evaluate our 10-year experience in employing a rapid intraoperative pth assay for php . a curative drop in pth allows the surgeon to terminate the operation and obviate additional exploration , whereas failure of the pth levels to demonstrate an adequate decrement asks for additional exploration because of the presence of presumed additional hypersecreting gland(s ) . success rates for surgical treatment depend on the skill and experience of the surgeon in finding and recognizing the pathologic changes and excising the correct amount of hyperfunctioning parathyroid tissue . it is now expected that the vast majority of patients will be cured during initial surgical exploration at a low probability of morbidity . the conventional time - honored operation employing general endotracheal anesthesia and bilateral cervical exploration is safe and effective when performed by experienced surgeons . the goal of parathyroidectomy is the excision of the abnormal parathyroid gland(s ) , preserving the normal ones in order to achieve and maintain a postoperative normocalcemic state . primary hyperparathyroidism ( php ) is a hypercalcemic disease stemming from an abnormal increase in parathyroid hormone ( pth ) secretion by one or more parathyroid glands .", "a series of 91 consecutive patients with primary hyperparathyroidism underwent parathyroidectomy guided by intraoperative pth at federal university of so paulo , brazil , from june 2000 to april 2011 . focused parathyroidectomy guided by intraoperative pth was the initial procedure when preoperative localization tests were positive and when there were no suspicion of malignant disease . the iopth accuracy calculation was based on the following definitions : a true - positive ( tp ) result of iopth was defined as the correct prediction of postoperative normal calcium levels for at least 6 months ; true negative ( tn ) was the correct prediction of incomplete excision by either resection of an additional gland(s ) or operative failure ; false positive ( fp ) was the incorrect prediction of normocalcemia with subsequent postoperative persistent hypercalcemia and high pth levels ; false negative ( fn ) was the incorrect prediction of incomplete excision followed by postoperative normocalcemia . the intraoperative criterion used to predict successful parathyroidectomy was a decrease in the intact pth levels exceeding 50% from the preincision hormone level . recurrence was defined when , after reaching normocalcemic levels , serum calcium and intact pth measurements start to rise to abnormal values at least 6 months after surgery . a bilateral cervical exploration guided by intraoperative pth was performed when preoperative localization tests were negative . persistent disease was considered when serum calcium and pth levels remained above normal range just after surgery . all patients had their age , gender , symptoms ( bone and kidney ) , preoperative localization tests , serum ionized calcium ( ica ) , serum total calcium and intact pth recorded before parathyroidectomy , as well as iopth dosages . these 96 procedures were performed in 91 previous unexplored patients who had at least 6 months of postoperative follow - up with enough reported data to be eligible for the study .", "the demographic , clinical , and biochemical aspects of 91 patients with php are shown in table 1 . among all cohort of 91 patients , 69 ( 75.8% ) had solitary adenoma , 10 ( 11.0% ) had multiple endocrine neoplasia type 1 ( men1 ) , 6 ( 6.6% ) had double adenomas , 4 ( 4.4% ) had carcinomas , and 2 ( 2.2% ) patients are still waiting for remedial surgery for multiglandular disease ( mgd ) , 1 of whom had recurrence disease after 10 years of follow - up and the other persistent disease after a false positive iopth ( table 2 ) . there was only one case in the operative failure patients ; the iopth had an fp result ( table 4 ) . the other patient was first operated as a solitary adenoma and men1 diagnosis surfaced just in the follow - up . we had 85 ( 93.4% ) successful parathyroidectomies 6 ( 6.6% ) failed parathyroidectomies in 91 previous unexplored patients , and 5 ( 100% ) successful remedial surgeries . among the 85 successful patients , the mean decay of iopth in the successful group of patients was 80.5% ( 34.3% to 96.0% ) . in these 85 patients , we had 80 tp results ( 67 adenomas , 3 carcinomas , 8 men1 and 2 recurrences ", "one of our series limitations is the absence of vitamin d dosages , one important factor that should be related to the genesis of php recurrence . we get an inferior number of successful parathyroidectomy ( 93.4% ) in previous unexplored patients compared to some large series [ 9 , 32 ] , but it can be considered a satisfactory result , taking into account the high number of patients with carcinoma and men1 in our series . on the other hand , we have obtained good results ( 100% ) in 5 successful second surgical explorations so far : first , we removed a second adenoma in three patients ( two persistent and one recurrent disease ) ; second , we were able to remove a not found fourth gland in a men1 patient , and finally , we removed three glands in a men1 patient previous operated as an sporadic php . in our series of 91 patients , several studies have demonstrated the utility of iopth monitoring in the treatment of single - gland primary hyperparathyroidism [ 3 , 8 , 2127 ] . the surgical treatment for primary php has undergone some changes in recent years , evolving from the standard bilateral neck exploration technique to a less time - consuming procedure of unilateral neck exploration . taking into account the increasing number of asymptomatic and/or oligosymptomatic primary hyperparathyroidism diagnosis in the recent years , the need for a safe and less time - consuming procedure with low perioperative morbidity is clear . by resorting to those criteria , high accuracy in intraoperative prediction of cure is achieved . most experts agree that iopth assay is the most useful intraoperative adjunct to assist the surgeon in php surgical treatment [ 28 , 29 ] .", "the iopth revealed to be an important technological adjunct in the current parathyroid surgery for php ." ]
introduction . primary hyperparathyroidism ( php ) is characteristically determined by high levels of calcium and high or inappropriate levels of parathyroid hormone ( pth ) . technological advances have dramatically changed the surgical technique over the years once intraoperative parathyroid hormone ( iopth ) assay had allowed for focused approaches . objective . to evaluate our 10-year experience in employing a rapid intraoperative pth assay for php . methods . a prospective cohort of 91 php - operated patients in a tertiary institution in so paulo , brazil , from june 2000 to april 2011 . results . we had 85 ( 93.4% ) successful parathyroidectomies , 6 ( 6.6% ) failed parathyroidectomies in 91 previous unexplored patients , and 5 ( 100% ) successful remedial surgeries . the iopth was true - positive in 88.5% , true - negative in 7.3% , false - positive in 2.1% , and false - negative in 2.1% of the procedures . iopth was able to obviate additional exploration or to ask for additional exploration in 92 ( 95.8% ) procedures . conclusion . the iopth revealed to be an important technological adjunct in the current parathyroid surgery for php .
[ "the objective of the present report was to examine the association between the presence of depressive symptoms and/or increased levels of perceived stress , determined at baseline , and risk of incident cv events over 5 years of follow - up in a major national cohort study that used population - based sampling methods , collecting data in the home both in subjects with and without diabetes . the prevalence of diabetes in the u.s . has increased ( 1 ) , and cardiovascular ( cv ) complications remain the major cause of morbidity and mortality in persons with type 2 diabetes , contributing substantially to increased health care costs ( 2 ) . as individuals attempt to manage their diabetes , there is increasing recognition that comorbid behavioral problems , including both depressive symptoms and stress , are associated with poor glycemic control , poor lifestyle behaviors , and increased health services utilization ( 310 ) . likewise , there has not been adequate comparison of individuals with and without diabetes who have concurrent depressive symptoms and/or elevated levels of perceived stress to examine the unique consequences of behavioral and medical comorbidity . similarly , poor meta - bolic control may worsen depressive symptoms ( 5 ) , and the relationship appears to be bidirectional ( 8) . the prevalence of these comorbidities and their potential to worsen disease management have led some to develop interventions designed to address comorbid depressive symptoms or stress in persons with diabetes ( 1214 ) . we ( 11 ) and others ( 3,4 ) have shown that these behavioral challenges are associated with inadequate medication adherence , which may be associated with adverse outcomes . while many studies have documented the cross - sectional presence of these comorbidities and the effect on glycemic control in subjects with diabetes , only a limited number of studies have examined the potential impact on cv outcomes . most of these studies have been limited to patients with depression recruited from established health care settings , and the true population - level impact is unknown .", "the current study examined the relationship between comorbid depressive symptoms and/or elevated levels of perceived stress , both measured at baseline , in subjects with and without diabetes and the adjudicated incidence of stroke , acute chd , and cvd death for events occurring through 30 december 2010 . the primary outcomes of interest were physician - adjudicated cv events including stroke , myocardial infarction ( mi)/acute coronary heart disease ( chd ) , and cv death . the analysis cohort for this report was 22,003 after exclusion of participants with a history of stroke or heart disease at baseline ( n = 7,164 ) , missing diabetes status at baseline ( n = 845 ) , or missing follow - up data ( n = 171 ) . the initial analysis compared the demographic , socioeconomic , and cv risk characteristics of subjects with and without diabetes in three groups : 1 ) those reporting no comorbid depressive symptoms and without elevated levels of perceived stress , 2 ) those reporting either depressive symptoms or elevated levels of perceived stress , and 3 ) those reporting both depressive symptoms and elevated levels of perceived stress . the regards study included relevant measures for perceived stress and depressive symptoms and provides a unique opportunity to examine the impact of these behavioral comorbidities in individuals with and without diabetes and the incidence of adverse cv outcomes in a national sample of black and white adults . it was designed to examine factors associated with the geographic and racial differences in stroke incidence as well as excess stroke mortality in the southeastern u.s .", "the reasons for geographic and racial differences in stroke ( regards ) study is a population - based , prospective , longitudinal cohort study of 30,239 subjects aged > 45 years , 45% of whom are male , 55% female , 41% black , 59% white , 55% from the stroke belt the initial recruitment call was used to obtain verbal consent and collect cv history , risk factors , and demographic characteristics , including age , sex , and race ( each subject self - reported race , and by design , the study compared only non - hispanic black and white subjects , excluding other racial / ethnic groups ) . the description of the population for this analysis has previously been reported ( 15 ) . in short , the regards study included relevant measures for perceived stress and depressive symptoms and provides a unique opportunity to examine the impact of these behavioral comorbidities in individuals with and without diabetes and the incidence of adverse cv outcomes in a national sample of black and white adults . it was designed to examine factors associated with the geographic and racial differences in stroke incidence as well as excess stroke mortality in the southeastern u.s . ( i.e. , stroke belt ) relative to the rest of the nation and among blacks relative to whites . the regards cohort was recruited between january 2003 and october 2007 and is evaluated by computer - assisted telephone interview every 6 months .", "a brief physical exam including blood pressure ( assessed as the average of two measurements obtained with an aneroid sphygmomanometer after the subject was in the seated position for at least 3 min with both feet on the floor ) and blood and urine samples , and an electrocardiogram ( ecg ) was conducted during an in - home visit by a trained health professional 34 weeks after the telephone interview . atrial fibrillation was determined to be present if there was a self - reported history ( asked as has a doctor or other health professional ever told you that you had atrial fibrillation ? ) or if characteristic findings were present on the ecg as defined in the protocol . left ventricular hypertrophy was defined to be present or absent based on ecg findings using the sokolow - lyon limb lead criteria ( 17 ) as specified in the protocol . all ecgs were read by a trained cardiologist in a centralized ecg reading laboratory at the wake forest university / baptist medical center in winston - salem , nc , using a predefined interpretation protocol ( 16 ) . hs - crp was determined by particle - enhanced immunonephelometry using the bnii nephelometer ( n high sensitivity crp ; dade behring , deerfield , il ) , while total and hdl cholesterol and glucose were measured by colorimetric reflectance spectrophotometry using the ortho clinical vitros 950/irc chemistry system ( johnson & johnson clinical diagnostics , new brunswick , nj ) in accordance with the national cholesterol education program guidelines ( 18 ) . height and weight was measured via standard procedures , and bmi was computed as the body weight in kilograms divided by the square of height in meters ( 2 ) .", "these questions included responses that ranged from 0 to 12 based on the number of days the subject reported experiencing those feelings in the prior week , with higher scores indicating more depressive symptoms . perceived level of stress was measured using a four - item version of the cohen perceived stress scale ( 21 ) , a validated and previously used ( 22 ) instrument for measuring the perception of personal stress . the primary exposure of interest was the presence , at baseline , of depressive symptoms and/or elevated levels of perceived stress among individuals with diabetes at baseline compared with those without diabetes . diabetes was defined as self - reported diabetes obtained during the telephone interview or a fasting glucose 126 mg / dl , a nonfasting glucose 200 mg / dl , or the presence of oral hypoglycemic medication or insulin each obtained during the home visit . subjects with cohen perceived stress scale scores > 4 were determined to have high levels of psychological stress , corresponding to the highest quartile of scores . the presence of depressive symptoms was assessed using the previously validated four - item center for epidemiologic studies depression ( cesd ) questionnaire ( 19 ) . it measures the extent to which respondents perceive their lives as unpredictable , uncontrollable , and/or overloaded .", "the primary outcomes of interest were physician - adjudicated cv events including stroke , myocardial infarction ( mi)/acute coronary heart disease ( chd ) , and cv death . living participants or their proxies were contacted every 6 months via telephone to assess new - onset stroke , chd events , and cv mortality . participant deaths were detected by report of next of kin , online sources ( e.g. , the social security death index ) , and the national death index . for information surrounding the circumstances of participant death , proxies or next of kin additionally , following published guidelines , medical records in the last year of life , death certificates , and autopsy reports were collected and reviewed by the physician - led adjudicators to determine whether the death was a cvd death ( 24,25 ) . a trained interviewer administered a standardized questionnaire that specifically asks whether , since the last follow - up , they had been hospitalized for stroke or heart disease . for each positive response , the date and time of each event were recorded . after a report of a hospitalization or death that potentially could be related to cvd , medical records were retrieved , and the event was adjudicated by a physician - led medical review team , following published guidelines ( 24,25 ) . medical records were retrieved for all potential stroke- and chd - related hospitalizations and deaths . for suspected stroke ,", "data on traditional cv risk factors and socioeconomic factors were also collected in order to adjust for potential confounding in our analyses of the relationship between the presence of comorbid behavioral problems , diabetes , and adverse cv outcomes . additional data collected included the following : annual household income ( < $ 20,000/year , $ 20,000$35,000/year , $ 35,000$75,000/year , and > $ 75,000/year ) , education level ( less than high school education , high school graduate , some college , and college graduate or higher ) , and health insurance ( yes or no ) . also collected was a health history including a history of stroke or heart disease ( self - reported mi , coronary artery bypass grafting , bypass , angioplasty , stenting , or evidence of myocardial infarction on the study ecg ) . smoking behavior was collected and categorized as nonsmoker , past smoker , or current smoker .", "the initial analysis compared the demographic , socioeconomic , and cv risk characteristics of subjects with and without diabetes in three groups : 1 ) those reporting no comorbid depressive symptoms and without elevated levels of perceived stress , 2 ) those reporting either depressive symptoms or elevated levels of perceived stress , and 3 ) those reporting both depressive symptoms and elevated levels of perceived stress . the current study examined the relationship between comorbid depressive symptoms and/or elevated levels of perceived stress , both measured at baseline , in subjects with and without diabetes and the adjudicated incidence of stroke , acute chd , and cvd death for events occurring through 30 december 2010 . the analysis cohort for this report was 22,003 after exclusion of participants with a history of stroke or heart disease at baseline ( n = 7,164 ) , missing diabetes status at baseline ( n = 845 ) , or missing follow - up data ( n = 171 ) . age - adjusted incidence rates were then compared for each type of cv event in individuals with and without diabetes in the same three comparison groups . the longitudinal relationship between baseline behavioral morbidity ( i.e. , the three comparison groups ) , in both those with and without diabetes , and follow - up time for each participant was calculated from the date of the in - home visit to date of first stroke , acute chd , death , or last telephone follow - up . these models examined the relationships first in an unadjusted ( crude ) model and then in additional models that incrementally added the following groups of variables : 1 ) demographic characteristics ( race , age , sex , and region [ stroke belt vs. non stroke belt ] ) , 2 ) socioeconomic factors ( income , education , and health insurance ) , and , finally , 3 ) cv risk factors ( current smoking , history of heart disease , left ventricular hypertrophy , atrial fibrillation , bmi , systolic blood pressure , total cholesterol , hs - crp , and statin use ) . subsequent adjudicated cv events during follow - up was then examined in a series of cox proportional hazards models .", "the current study included a total of 22,003 subjects , of whom 42% were black , 58% female , and 56% living in the southeastern u.s . stroke belt . among all subjects at baseline , 18.6% subjects ( n = 4,090 ) had diabetes , 10% ( n = 2,202 ) reported increased depressive symptoms , and 28% ( n = 6,132 ) reported elevated levels of stress . table 2 also provides the results of a series of crude and progressively adjusted hazard ratio ( hr ) models for each of the three independent cv outcomes , demonstrating the progressive impact of comorbidity on acute chd and cv death among subjects with diabetes , relative to those without diabetes , even in fully adjusted models that accounted for demographic , socioeconomic , and cv risk factors . unlike the pattern for acute chd and cv death , event numbers , age - adjusted incidence rates per 1,000 person - years , and crude and adjusted hrs for stroke , acute chd , and cv disease death for individuals with stress or depressive symptoms and with stress and depressive symptoms compared with those with neither , for individuals with and without diabetes crude model adjusted for depressive symptom and stress category . consequences of comorbid diabetes and elevated depressive symptoms and/or stress on cv death during follow - up among participants in the regards study .", "the presence of elevated stress or depressive symptoms in community - dwelling subjects with diabetes was associated with an increased risk for acute chd or cv death . moreover , subjects with diabetes who reported both stress and depressive symptoms together had the greatest risk for acute chd and cv death . elevated levels of stress and depressive symptoms , alone and together , were associated with a pattern of increased hrs for acute coronary disease and cv death in adjusted models both in subjects with and in subjects without diabetes , achieving statistical significance in those with diabetes . while several studies have shown that formally diagnosed depression and/or depressive symptoms in subjects who are patients in an existing health care system are associated with incident chd , this is among the first studies to compare the impact of these behavioral comorbidities on cv outcomes and mortality in a population - based sample of subjects with versus without diabetes in the same study . the presence of either or both behavioral comorbidities in subjects with diabetes was also associated with increased hrs for stroke . these findings demonstrate the persistent disparities and negative cv impact of these comorbidities at the population level and suggest the need for more careful integration of behavioral screening and management in primary care settings , where most patients with type 2 diabetes are managed ." ]
objectiveto evaluate the impact of comorbid depressive symptoms and/or stress on adverse cardiovascular ( cv ) outcomes in individuals with diabetes compared with those without diabetes.research design and methodsinvestigators examined the relationship between baseline depressive symptoms and/or stress in adults with and without diabetes and physician - adjudicated incident cv outcomes including stroke , myocardial infarction / acute coronary heart disease , and cv death over a median follow - up of 5.95 years in the national regards cohort study.resultssubjects included 22,003 adults ( 4,090 with diabetes ) ( mean age 64 years , 58% female , 42% black , and 56% living in the southeastern stroke belt ) . elevated stress and/or depressive symptoms were more common in subjects with diabetes ( 36.8% vs. 29.5% ; p < 0.001 ) . in fully adjusted models , reporting either elevated stress or depressive symptoms was associated with a significantly increased incidence of stroke ( hr 1.57 [ 95% ci 1.05 , 2.33 ] vs. 1.01 [ 0.79 , 1.30 ] ) and cv death ( 1.53 [ 1.08 , 2.17 ] vs. 1.12 [ 0.90 , 1.38 ] ) in subjects with diabetes but not in those without diabetes . the combination of both elevated stress and depressive symptoms in subjects with diabetes was associated with a higher incidence of cv death ( 2.15 [ 1.33 , 3.47 ] ) than either behavioral comorbidity alone ( 1.53 [ 1.08 , 2.17 ] ) and higher than in those with both elevated stress and depressive symptoms but without diabetes ( 1.27 [ 0.86 , 1.88]).conclusionscomorbid stress and/or depressive symptoms are common in individuals with diabetes and together are associated with progressively increased risks for adverse cv outcomes .
[ "membranous nephropathy ( mn ) is characterized by the formation of subepithelial immune deposit with resultant changes in glomerular basement membrane ( gbm ) , most notably spike formation . antineutrophil cytoplasmic antibodies ( anca)-associated glomerulonephritis ( gn ) is characterized by necrotizing and crescentic gn with paucity of immunoglobulin ( ig ) and complement deposition , which is also known as pauci - immune crescentic gn .", "a 48-year - old man presented with marked proteinuria , hypoalbuminemia , and renal dysfunction with positive results for myeloperoxidase ( mpo ) and anca . after one - month follow - up , antibody level and renal function did not improve . renal biopsy revealed crescents and thick gbm with subepithelial spikes along with igg deposition on immunofluorescent staining .", "coexistence of mn with mpo - anca crescentic gn is very rare and should be managed aggressively .", "we report a rare case of mn with myeloperoxidase ( mpo)-anca - associated crescentic gn in a 48 year - old - man who was admitted to our institute . membranous nephropathy ( mn ) is characterized by the formation of subepithelial immune deposit with resultant changes in glomerular basement membrane ( gbm ) , most notably spike formation . approximately 75% of mn represent as primary disease and the rest results from secondary causes , most commonly systemic lupus nephritis ( sle ) , infections such as hepatitis b or c viruses , malignancy , or drugs .", "he was diagnosed as a case of mpo - anca - associated crescentic gn with mn . a 48-year - old man presented with intermittent puffiness of face and edema of the feet for two months . results of viral screening for human immunodeficiency virus , hepatitis b and hepatitis c viruses were negative . serum anti - nuclear antibody ( ana ) , the levels of serum complements c3 and c4 were in normal limits .", "coexistence of anca - gn with mn is very rare ( 1 , 4 - 7 ) . when patient presents as rapidly progressive glomerulonephritis with marked proteinuria , further investigations to rule out possibility of mn with anca associated crescentic gn should be performed and the patient should be managed aggressively . ram et al . reported mn superimposed on churg - strauss syndrome ( 10 ) . the combination of anti gbm - gn and mn are also reported ( 11 , 12 ) . morizane et al . have reported a case of mpo - anca - associated gn , which was superimposed on type-3 mpgn . anca - associated gn is also associated with environmental triggers such as drugs and infections ( 9 ) ." ]
introduction : antineutrophil cytoplasmic antibodies ( anca)-associated glomerulonephritis ( gn ) is characterized by necrotizing and crescentic gn with paucity of immunoglobulin ( ig ) and complement deposition , which is also known as pauci - immune crescentic gn . membranous nephropathy ( mn ) is characterized by the formation of subepithelial immune deposit with resultant changes in glomerular basement membrane ( gbm ) , most notably spike formation.case presentation : a 48-year - old man presented with marked proteinuria , hypoalbuminemia , and renal dysfunction with positive results for myeloperoxidase ( mpo ) and anca . renal biopsy revealed crescents and thick gbm with subepithelial spikes along with igg deposition on immunofluorescent staining . the condition was diagnosed as mn with mpo - anca - associated crescentic gn . he was treated with intravenous methylprednisolone and cyclophosphamide . after one - month follow - up , antibody level and renal function did not improve.conclusions:coexistence of mn with mpo - anca crescentic gn is very rare and should be managed aggressively .
[ "consequently , inaccurate assessment of increased reactivity due to the interaction of anxiety with acute stressors may explain the inconsistent reports of increased risk of hypertension with increased reactivity . this study sought to investigate whether ( 1 ) anxiety determined the blood pressure response to stress tests and ( 2 ) anxiety differentially influenced blood pressure response to anger recall and cold pressor stress tests in african americans . we report that state ( in the moment ) anxiety was significantly associated with blood pressure response to both stressors ( anger recall and cold pressor stress tests ) in this population . these results support the idea that identification of hyperresponders to acute stress tests among african americans must take into account anxiety levels before determining whether an individual has increased reactivity to acute stress and/or that anxiety may play an important role along with reactivity response in hypertension development . although enhanced cardiovascular reactivity is generally associated with future development of hypertension and other cardiovascular events [ 15 ] , there are studies that have failed to show any relationship between reactivity to stress and future elevation of blood pressure [ 1 , 612 ] . however , our results do not support the idea that anxiety differentially impacts reactivity response to psychological , psychophysical , and physical stressors .", "the state anxiety subscale has an alpha coefficient of .87 , and the trait anxiety has an alpha coefficient of .88 , indicating good ( since .80 or greater ) internal consistency in this sample . higher scores on the state anxiety subscale indicate greater anxiety at the present time ; higher scores on the trait anxiety subscale indicate greater anxiety , in general . cardiovascular reactivity was calculated as the difference between the average baseline prestressor blood pressure and the average change in blood pressure over the 5-minute stress period . the study protocol consisted of state anxiety assessment , resting bp measurement , second resting bp measurement , cold pressor stressor , third resting bp measurement , anger recall stressor , trait anxiety assessment , recording medical history , body mass index measurement , and completing a demographics questionnaire . a psychological stressor , anger recall , was given only after blood pressures and heart rate returned to baseline resting values . the 50 participants reported here met the following criteria : ( 1 ) completed both the trait anxiety scale and the state anxiety scale , and ( 2 ) were between the ages of 18 and 40 years old . a sample of 179 ( 116 males , 63 females ) participants of african descent were recruited to the study .", "two participants did not complete the cold pressor stressor ; thus , the sample size is 48 for the cold pressor cardiovascular reactivity and 50 for the anger recall cardiovascular reactivity . scoring of the psychosocial scales spielberger state trait anxiety inventory utilized scoring protocols documented in prior research as indicated above and were confirmed with factor analysis . mean , standard deviation , standard error , median , and quartile calculations provide data reductions for sbp , dbp , and other clinical measures with multiple measurements . regression models , goodness of fit , multivariate parameter estimates , and confidence intervals were evaluated for each stressors impact on sbp , and dbp .", "cardiovascular reactivity was defined as the change in cardiovascular parameters ( sbp , dbp , mean arterial pressure ( map ) , and heart rate ( hr ) ) following the induction of a stress stimulus compared to baseline cardiovascular parameters . we examined pearson 's correlations of state anxiety , trait anxiety , age , bmi , and resting cardiovascular measures with the cardiovascular reactivity parameters . the variable selection results of the stepwise algorithm suggested the use of state anxiety for a parsimonious model of both cold pressor cardiovascular reactivity as well as anger recall cardiovascular reactivity . our next step was to evaluate regression models to predict cardiovascular reactivity with state anxiety as the independent variable . similar results were found with the model for predicting the change in cardiovascular reactivity for the ar stressor as shown in table 4 .", "this study investigated whether anxiety differentially affects cardiovascular reactivity to cold pressor and anger recall stress tests in a sample of young , healthy , community dwelling african american adults , a population prone to develop cardiovascular disease . importantly , we show that the state ( at the moment ) anxiety was significantly associated sbp and dbp responses to both cold pressor and anger recall laboratory stress tests in this population . this study shows that the current state of anxiety was significantly associated with blood pressure response to laboratory stress tests . consequently , anxiety levels should be assessed when using acute laboratory stress tests for identification of those with increased cardiovascular reactivity . in contrast to blood pressure , state anxiety differentially predicted hr response to cp but not ar . on the other hand ,", "additionally , our study design did not allow us to determine whether the impact of anxiety on blood pressure response to acute stressor is unique to anxiety or whether other psychosocial factors similarly influence blood pressure response to acute stress in our cohort . these findings need to be validated in a larger cross sectional population of african americans . another limitation of the study is that adrenergic system activation was not measured ; consequently , it could not be determined if the two stressors differentially activated the beta or alpha - adrenergic receptor pathways . this information would be helpful in future longitudinal studies that will address how activation of the alpha and beta adrenergic receptors pathways ultimately leads to hypertension development and the attending cardiovascular disease . a longitudinal study design will also help to address the question of whether inclusion of anxiety enhances the ability of increased reactivity to predict future elevations of blood pressure ." ]
although several studies have shown that enhanced cardiovascular reactivity can predict hypertension development in african americans , these findings have not been consistent among all studies examining reactivity and hypertension susceptibility . this inconsistency may be explained by the influence of anxiety ( state and trait ) on the blood pressure response to stress . therefore , this study sought to determine whether anxiety is associated with blood pressure response to cold pressor ( cp ) and anger recall ( ar ) stress tests in young healthy african americans . modeling using state and trait anxiety revealed that state anxiety predicts systolic ( sbp ) and diastolic blood pressure dbp response to cp and ar ( p 0.02 ) . interestingly , state anxiety predicted heart rate changes only to cp ( p < 0.01 ; p = 0.3 for ar ) . although trait anxiety was associated with sbp response to ar and not cp , it was not a significant predictor of reactivity in our models . we conclude that anxiety levels may contribute to the variable blood pressure response to acute stressors and , therefore , should be assessed when performing cardiovascular reactivity measures .
[ "sweet 's syndrome ( ss ) presenting in a localized and symmetric pattern is a very rare phenomenon . there have , however , been , a few case reports for the same . , ss may demonstrate numerous topographic variations , which could be quite confusing for the diagnosing dermatologist . ss per se was first reported in 1964 by robert douglas sweet . though classically presenting as tender pseudovesicles", "a 45-year - old farmer from nepal presented to the department of dermatology with complaints of an abrupt onset of an asymptomatic cutaneous eruption involving the neck and both the forearms since the past 5 days . fleshy pseudovesicles with central umbilication seen on the right forearm of our patient over the left forearm , a plaque with the characteristic central umbilication seen , closely mimicking the lesions encountered in molluscum contagiosum . furthermore , to note here is the symmetric pattern of lesion arrangement molluscoid pseudovesicles over the nape of the neck juicy plaques with a central depression and an overlying crust seen on the right side of the neck similar lesions on the left side of the neck as seen in figure 4 . to note here again , some of the lesions over the neck had a crust overlying the depressed center [ figures 4 and 5 ] . , papules and plaques of varying sizes with a striking central umbilication were identified involving the forearms and neck that gave an illusion of vesiculation [ figures 13 ] .", "sweet 's syndrome is the prototypical neutrophilic dermatosis , generally characterized by fever , an increase in the neutrophilic count along with tender pseudovesicles distributed over the body in an asymmetric manner . a variant of ss referred to as neutrophilic dermatosis of the dorsal hands ( nddh ) is a specific entity confined only to the dorsa of the hands and has been extensively reviewed in literature by galaria et al . , takahama and kanbe , cook et al . there have , however , been reports of the occurrence of ss localized to specific sites of the body though , some of which have presented with very unusual morphologic patterns , as shown by sommer et al . who described palmoplantar pustulosis as the sole finding in a ss patient , verma et al . demonstrating the occurrence of ss confined to the photo exposed sites alone , verma who elucidated a rare recurrent bullous eruption localized to the flexural aspect of both the forearms in a ss patient and brechtel et al . who reported a localized facial presentation of ss manifesting as an inflammatory lesion with a central depression superimposed with several pustules on the surface of the plaque . molluscoid lesions seen in ss is a very rare morphologic pattern encountered and to the best of our knowledge is being reported for the 1 time in literature localized patterns of ss are not so rare as previously thought ." ]
sweet 's syndrome is a well - known entity in the field of dermatology . it has presented itself in myriad forms , well - recorded in literature . our patient presented with a sudden eruption of nontender molluscoid pseudovesicles distributed over the neck and forearms alone . a complete diagnostic work up for the same did not give any clue regarding an underlying systemic ailment , responsible for the dermatosis . this case is being presented because of this extremely rare morphology of gomm - button disease .
[ "ha ) on the antimicrobial activity of two qacs ( benzalkonium chloride and cetyltrimethyl ammonium bromide ) against bacillus cereus and pseudomonas fluorescens , as they are two major contaminants in the food industry , particularly the dairy industry , and are a known cause of produce spoilage and foodborne illnesses [ 2 , 2226 ] . some of the interfering substances used throughout the experiments are proposed in the european standard en-1276 as potential interfering agents in disinfection while the others are extracellular polymeric substances ( eps ) from the biofilm matrix that have an important role in antimicrobial resistance . evaluated the bactericidal activity of disinfectants referred in the german veterinary society guidelines as references for testing disinfectants used in dairy and food industries . in order to simulate the conditions found in practice , they used low fat milk as an organic load and reported the significance in choosing an appropriate disinfectant since the inclusion of a challenging substance ( organic material ) is important to access the proper bactericidal activity . this work provides information on the influence of potential interfering substances ( bovine serum albumin quaternary ammonium compounds ( qacs ) are cationic surfactants that are commonly used because of their hard - surface cleaning , odor removal and antimicrobial properties . besides killing bacteria , the chemical nature of qacs can cause modifications on the properties of abiotic surfaces , decreasing their tension and therefore preventing attachment of microorganisms .", "the inactivation was calculated using metabolic activities according to the following equation : \n ( 1)% inactivation=(mcmt)mc100 , \n where mc is the metabolic activity of the control experiments ( without antimicrobial exposure ) and mt is the metabolic activity of the bacterial solutions exposed to the antimicrobial . to investigate the influence of interfering substances on the antimicrobial efficacy , the same procedure was followed with the addition of 300 mgl of bsa , alg , ye , or ha to the bacterial suspension , simulating low concentrations of interfering substances according to the european standard en-1276 . three independent experiments , each with duplicate samples , were performed for each condition tested . demonstrated that this procedure is more adequate and rapid than the assessment of colony forming units to characterize the antimicrobial activity of biocides against heterotrophic aerobic bacteria . the respiratory activity was ascertained by measuring oxygen uptake rates in a biological oxygen monitor ( yellow springs instruments 5300a ) . control experiments were performed to ascertain the effects of the 10-minute exposure to the neutralization solution , and no effects were detected on the respiratory activity of b. cereus and p. fluorescens ( data not shown ) .", "alg also reduced the antimicrobial activity of the combination of qacs against the bacterial consortium ( 35 to 20 mgl ) . the antibacterial activity of bac , ctab , and their combination was investigated in the absence and in the presence of four selected interfering substances . in the absence of interfering substances bac caused the inactivation of b. cereus at 10 mgl , p. fluorescens at 35 mgl , and the consortium at 20 mgl . the presence of bsa increased the mbc of the combination of qacs for b. cereus ( 3 to 5 mgl ) and the consortium .", "the interfering substances tested are commonly found as residuals in the food industry ( from food products and from microbial contaminants , biofilms ) [ 18 , 27 ] . in this study the present work shows that increasing qacs concentrations lead to an increase in antimicrobial effectiveness . therefore , it is necessary to know the role of each potential interfering substance in the antimicrobial activity in order to develop effective disinfection strategies . this result evidences that the mathematical modelling of disinfection strategies requires a case - to - case analysis when interfering substances are present . this is valid mainly when the qacs were applied in the absence of interfering substances . it is assumed that the organic material can potentially interfere with the antimicrobial agents by chemical and/or ionic interactions [ 15 , 33 ] . this means that disinfection was concentration dependent , as found for most of the antimicrobial chemicals .", "the tested interfering substances , referred in the european standard 1276 ( bsa and ye ) , and known eps constituents related with biofilm resistance ( alg ) resulted in mild interferences on the activity of the qacs . the bacteria were inactivated equally by all qacs , although in the absence of interfering substances ctab was the most efficient solution . the overall results demonstrate that a disinfection process in the presence of the selected interfering substances can reduce the effectiveness of bac , ctab , and their combination . p. fluorescens was the bacterium with the highest resistance to inactivation , followed by the bacterial consortium . ha were the interfering substance that resulted in the most severe effect by reducing the activity of qacs , causing , in some circumstances , significant respiratory activity potentiation ." ]
standard cleaning processes may not remove all the soiling typically found in food industry , such as carbohydrates , fats , or proteins . contaminants have a high impact in disinfection as their presence may reduce the activity of disinfectants . the influence of alginic acid , bovine serum albumin , yeast extract , and humic acids was assessed on the antimicrobial activities of benzalkonium chloride and cetyltrimethyl ammonium bromide against bacillus cereus vegetative cells and pseudomonas fluorescens . the bacteria ( single and consortium ) were exposed to surfactants ( single and combined ) in the absence and presence of potential disinfection interfering substances . the antimicrobial effects of the surfactants were assessed based on the bacterial respiratory activity measured by oxygen uptake rate due to glucose oxidation . the tested surfactants were efficient against both bacteria ( single and consortium ) with minimum bactericidal concentrations ranging from 3 to 35 mgl1 . the strongest effect was caused by humic acids that severely quenched antimicrobial action , increasing the minimum bactericidal concentration of the surfactants on p. fluorescens and the consortium . the inclusion of the other interfering substances resulted in mild interferences in the antibacterial activity . this study clearly demonstrates that humic acids should be considered as an antimicrobial interfering substance in the development of disinfection strategies .
[ "this paper focuses on coping with the fallout from one type of macrolevel social stressor : the recent great recession . however , macrolevel social conditions can affect the magnitude of stressors experienced in people 's lives and the extent to which they experience cumulative adversity . a key issue involving the effectiveness of alternative modes of coping with stressors derived from macrolevel social forces and protecting against deleterious drinking outcomes is the question of whether individual modes of coping outside of the political realm emphasized in the overall coping literature are most efficacious . or , alternatively , do stressors engendered by macrolevel social forces require unique forms of coping , that encompass the political realm ? social scientists who explore factors mediating and moderating the relationships between social stressors and mental health , including drinking outcomes , have highlighted modes of coping [ 1 , 2 ] . these studies have explored behaviors which protect people from being psychologically harmed and cognitive appraisals which influence behaviors such as problem - focused coping or using alcohol to self - medicate distress .", "non - hispanic whites serve as the reference category . after examining bivariate correlations in order to assess the basic patterns of association among key study variables , we performed structural equation modeling ( sem ) using mplus software to examine the predictive significance of economy - related stressors for coping outside of the political realm and politically oriented coping tactics and the two drinking outcomes considered ( i.e. , past - month drinking and problematic drinking ) , net of the sociodemographic control variables . the first model tested for associations between economic stressors and the drinking - related outcomes . separate equations include the interaction term for gender by each coping strategy in the path models linking coping with drinking outcomes . three dimensions of nonpolitical modes of coping are assessed : active coping , support coping , and avoidant coping . we considered the potential for nonpolitical coping and politically oriented coping tactics to mediate the associations between economy - related stressors and each of the outcomes assessed in two models . finally , because the associations between social stress and drinking are found to vary by gender [ 33 , 39 ] , we examined whether any observed mediating effects of the coping strategies investigated vary by gender . for these tests ,", "thus , the observation that economic strain is associated with greater problematic drinking in the extent to which it is associated with avoidant coping strategies appears to be more pronounced among men than among women . the lack of correlation between active coping and support coping and each of the drinking outcomes , respectively , provides some indication that not all of the coping strategies may be useful in understanding the associations between economic stressors and drinking - related outcomes . additionally , the possibility that coping resources may vary by gender is not strongly supported by the pattern of correlations reported , with the exception that women reported significantly more emotional support than men . however , and consistent with previous research , women are found to drink less and less problematically . it is noteworthy that stressors related to the economy are associated with each of the alcohol - related outcomes and all of the coping resources considered : economy - related stressors are associated with more alcohol consumption and problematic drinking , as well as higher levels of active coping , support coping , avoidant coping , and politically oriented coping . avoidant coping and politically oriented coping are associated with both alcohol consumption and problematic drinking , but in opposite directions . taken together , these findings indicate that both adaptive and maladaptive coping strategies come to bear on drinking patterns associated with economic strain . on the one hand , economic strain appears to be associated with drinking more and more problematically , in the extent to which it is associated with a tendency to engage in avoidant coping strategies . that is , greater economic strain appears to predict a greater propensity to use both maladaptive coping tactics ( i.e. , avoidant coping ) and adaptive coping tactics ( i.e. , active coping , support coping , and politically oriented coping ) . that is , greater avoidant coping is associated with greater alcohol consumption and problematic drinking , whereas greater politically oriented coping is associated with less alcohol consumption and problematic drinking .", "the findings from this study support a broadened conceptualization of modes of coping in stress paradigm - oriented research to encompass politically oriented coping , in addition to modes of coping outside of the political realm which have predominated in studies of the coping - related moderators or mediators of the associations between social stressors and drinking outcomes . however , our data showed that male but not female avoidant coping significantly predicted problem drinking . thus , with regard to nonpolitically oriented coping with economic stressors , males clearly utilized a coping mode that was maladaptive . further longitudinal studies are necessary to more clearly delineate the causal directions of the relationships between economic stressors , modes of coping , and drinking outcomes .", "in particular , considerations of more adaptive modes of coping might go beyond recommending individual behaviors such as job seeking by unemployed individuals to also suggest politically oriented coping to collectively try to influence the social conditions such as unemployment levels that may give rise to the propensity to self - medicate distress through the use of alcohol . despite the noted limitations , this study extends prior research on the moderators and mediators of the social stressor - drinking outcome relationships to broaden notions of coping to include politically oriented coping . future studies incorporating this mode of coping may more clearly elucidate the political dynamics involved in both the macrolevel production of social stressors and the deleterious alcohol - related consequences of these stressors . this line of research would also have implications for the treatment of alcohol - related problems ." ]
research derived from the stress paradigm suggests that certain types of coping ( e.g. , problem - focused coping instead of behavioral disengagement ) are protective against problem - related drinking to deal with social stressors . going beyond the typical focus in the coping literature , we hypothesize that stressors engendered by macrolevel social forces may require coping actions within the political realm in contrast to modes of coping focused outside of the political realm . a united states sample of 663 respondents completed a mail survey in 2010 , including measures of stressful consequences of the great recession , drinking patterns and problems , modes of coping encompassed in the brief cope instrument , and politically oriented coping . structural equation modeling examined whether modes of coping mediated the links between stressors and drinking outcomes . a substantial portion of the associations between stressors and drinking was explained by modes of coping . politically oriented coping was protective against problem drinking for both genders . future studies should further explore politically oriented coping in addition to modes of coping outside of the political realm when studying the relationships between macrolevel social stressors and deleterious drinking outcomes .
[ "the purpose of this study was to evaluate by strain gauges the preload and torque removal values on three abutment screws ( gold , titanium , and titanium with surface treatment screws ) applying an equivalent torque force ( 30.070.28 ncm ) . the rotation of gold - coated abutment screws placed with torque forces of 12 , 20 , and 32 ncm increased 73 , 76 , and 62% , respectively , when compared to titanium abutment screws2 . thus , decreasing of friction between metallic surfaces may increase the screw rotation and , consequently , the preload .", "therefore , when the abutment was fixed to the fixture by the abutment screw , tensions generated by this fixation pulled the unit against the abutment , producing a deformation in the lower plate connected to the strain gauges . after this evaluation , the abutment screw was removed using a digital torquemeter and the maximum value of reverse torque force required for screw removal was recorded in ncm . , the gold screw was then attached to the fixture with an applied torque force of 30.070.28 ncm , being repeated afterwards for groups b and c. then , the initial preload value for the abutment screws was determined ( in volts ) and all screws were kept in their positions for 5 minutes for preload stabilization , according to the literature9 . during this the preload stabilization period , the aforementioned sample was arranged into 3 different groups according to the characteristics of each abutment screw : group a was formed by gold screws , group b was formed by titanium screws , and group c was formed by surface - treated titanium screws . to determine fixation and removal torques , this load cell presented a central void for fixture fixation in its upper portion and a horizontal plate for fixation of four strain gauges on its lower portion ( figure 1 b ) . next , the force ( preload ) generated on the abutment screws was captured by the strain gauges in volts ( v ) and later converted to newton ( n ) . comparison of preload values within groups was possible using the mean of 6 measurements ( 0 to 5 minutes ) obtained at the first abutment fixation , using two - way anova .", "the mean fixation torque force when all screws were considered was 30.070.28 ncm ( c.i . titanium screws presented a mean removal torque of 18.751.89 ncm , and showed statistically significant differences ( p<0.001 ) . the highest preload value was obtained for screw # 7 ( 49.68 n ) , while screw # 3 presented the lowest value ( 25.30 n ) . in the group of surface - treated titanium screws , the gold screws presented the highest preload values and the titanium screws the lowest values ( figure 2 ) . the mean preload values of the gold screws was 131.728.98 n , and presented statistically significant differences ( p<0.01 ) compared to groups the gold screws presented a mean removal torque of 17.641.12 ncm , i.e. they did not shown statistically significant differences ( p=0.3713 ) . there were no statistically significant differences ( p=0.1244 ) among the groups regarding the fixation torque .", "although the results of this study showed that gold screws have a clear superiority of the produced preload , application of cyclic loads would be required for a closer simulation of the masticatory function on implanted - supported restorations . in addition , the finds of the present study suggest that the evaluated surface treatment of titanium screws was effective , since these screws presented higher preload values than conventional titanium screws . a maximum preload value of 666.4 n for gold screws and 458.2 n for titanium screws was reported8 . the findings of the present study suggest a trend for greater preload values verified for gold screws , followed by surface - treated titanium screws and titanium screws , confirming the outcomes of previous investigations4,8 . finite element analysis has been used to evaluate preloading through elongation of the abutment screw .", "it may be concluded : 1 . gold should be the material of choice for abutment fixation screws , since it produced the highest preload values , followed by surface - treated titanium screws and conventional titanium screws ; 2 . titanium screws presented the highest torque removal values , followed by gold screws , and surface - treated titanium screws ." ]
several authors still consider the mechanical problems of fracture and component loosening as the main causes of failure of implant - supported restorations . the purpose of this in vitro study was to compare the preload of three types of screw for transmucosal abutment attachment used in single implant - supported prosthesis through strain gauge and removal torque measurements . three external hex fixtures were used , and each received a transmucosal abutment ( cera one ) , which was fixed to the implant with its respective screw : group a- gold screw , group b- titanium screw and group c- surface - treated titanium screw ( ti - tite ) . ten screws of each type were attached applying a 30.070.28 ncm torque force and maintained in position for 5 minutes . after this , the preload values were measured using strain gauges and a measurement cell . gold screws presented higher preload values ( 131.728.98 n ) , followed by surface - treated titanium screws ( 97.784.68 n ) and titanium screws ( 37.035.69 n ) . anova ( p<0.05 ) and tukey 's test ( p<0.05 ) were applied . statistically significant differences were found among the groups for both preload and removal torque values . in conclusion , gold screws may be indicated to achieve superior longevity of the abutment - implant connection and , consequently , prosthetic restoration due to greater preload values yielded .
[ "the principal challenges in drug development for cns hiv infections are : ( 1 ) understanding the pathways for viral entry , replication , reservoirs , and glial activation in order to identify new targets for treatment , ( 2 ) developing selective therapeutics agents for those targets , or shaping effective strategies to deliver them within the cns , and finally but not to underestimate ( 3 ) collaborating with pharmaceutical companies to test promising drugs in clinical trials , and eventually exploit them in clinical practice . haart currently in use in the clinical practice . among the limits of the current treatments although haart has reduced the incidence of clinical signs of neurological disease in hiv - infected individuals , autopsy studies suggest that there has been no corresponding decline in the incidence of inflammatory lesions in the cns . highly active antiretroviral therapy ( haart ) , a combination of drugs that inhibits enzymes essential for hiv replication , can reduce the viremia and the onset of opportunistic infections in most patients , and prolong the survival ( see table 1 ) .", "the dynamic signaling pathways that are activated by virus replication and active / infiltrating macrophages and lymphocytes and the cytokines , chemokines , and neurotoxic products they elaborate may interfere with the homeostatic signaling pathways that maintain normal quiescent brain function . to understand the correlates in terms of neuroprotection , neuroinflammation , and neurodegeneration processes when there is resurgent virus replication , the balance favors neuronal death ( i.e. , via activation of jnk and p38 ) reflecting a failure to maintain homeostasis in the cns ( barber et al . , 2004 ) with the consequent motor and cognitive impairments . hiv is known to productively replicate in macrophages and microglia of the cns , but it also infects , via a cd4-independent pathway , macroglial cells such as astrocytes and most - importantly brain microvascular endothelial cells , which represent the major component of the blood brain barrier ( bbb ; bissel and wiley , 2004 ) . although it is generally accepted that neurons do not become infected by hiv , recent reports have shown that neuronal progenitor brain cells can be infected by various viral strains ( i.e. , hiv-1 ) , eventually playing a role as viral reservoirs ( lawrence et al . , 2004 ) . moreover , one of the important features of cns infection is that its viral populations can diverge from those of plasma : indeed , genetic compartmentalization of csf hiv-1 infection has been nicely demonstrated in a series of studies using the heteroduplex tracking essay to compare blood and csf viral populations cross - sectionally and longitudinally ( ritola et al . , 2005 ) ; therefore even if during acute infection the two population are identical , during chronic infection and especially in cases of hiv encephalitis they genetically and functionally diverge , and may justify the failure of antiretroviral therapy ( strain et al . , 2005 ) . identification of viral and cellular mechanisms in the cns that control virus replication after acute infection , maintain latency during the asymptomatic stage , and mediate resurgence of virus replication and development of hiv - associated encephalitis during late infection , is critical .", "herein are a couple of examples picturing how researches , initially conducted for neoplastic , neurodegenerative , or epileptic disorders , on specific pathways and delivery systems , might be adapted and applied to the field of cns hiv infection ( see figure 1 ) . many strategies are currently under evaluation to improve hiv treatment , but a relatively small number are primarily dedicated to the alleviation of neurological complaints or the control of neuroaids , and unfortunately more than 98% of drug candidates for cns disorders never make it to the clinic ( pardridge , 2003 ) . nanoformulated haart essentially manipulates the immune system for therapeutic purposes by using synthetic or biological nanoengineered drug carriers .", "discovered in 1898 , mitoguazone ( mgbm ) had been investigated but abandoned as an anti - cancer drug , recently it was found to cause selective loss of cd16 + hiv - infected cells , specifically by blocking osteopontin needed to transform a circulating macrophage into a cns / resident one . the manipulation of ifn and ifn apobec pathways could prevent hiv invasion of cns because of the potent intrinsic immunity exerted by the expression of apobec3 g gene in microvascular endothelial cells ( argyris et al . , 2007 ) . initially recognized , and extensively studied as a promising target for anti - cancer therapies because of its role during tumorigenesis , the pi3k / akt cell survival pathway became a target for anti - hiv treatment after the observation that pi3k inhibitors ( such as wortmannin and ly294002 ) or akt inhibitors ( such as miltefosine ) , both able to cross the bbb , contrast the cytoprotective effect exerted by tat proteins over macrophage / microglial cells , and make them again susceptible to cell death following an apoptotic stimulus ( chugh et al . most interestingly pi3k / akt inhibitors proved to be effective without harming uninfected cells and therefore experimental data as far available support their possible use for hiv - therapy and targeting of long - lived viral reservoirs .", "those nanoformulated drugs have been proven to be efficient delivery vehicles for a wide range of therapeutic agents , and can be easily injected in the blood circulation or virtually into any site of the brain with minimal invasiveness . nanoformulated haart essentially manipulates the immune system for therapeutic purposes by using synthetic or biological nanoengineered drug carriers . major concerns to this therapeutic approach are the choice of drug administration ( systemic or local ) and consequently the residence in the systemic blood circulation , or in the brain tissue adjacent to topic injection , the drug loading efficiency , and the burst release effect . furthermore , many other question marks are still to be answered , or even formulated . concerning synthetic carriers , hyaluronic acid , a linear polysaccharide composed of alternating d - glucuronic acid and n - acetyl - d - glucosamine units , because of its immunoneutrality , has been proposed as a biocompatible and biodegradable biomaterial for tissue engineering , and in drug delivery systems into the cns : particularly appealing would seem the opportunity to produce drug - incorporated hyaluronic acid nanoparticles ( jeong et al . , 2008 ) . as well monocytes , because of their abilities to move drugs inside the cells have advantages as a depot for haart , but also they might improve compliance as drugs can be released from cells for periods up to weeks or longer . nevertheless , further application of biological nanoengineered drug carriers will require optimization of nanoparticles uptake , deeper knowledge of their kinetics across the bbbs , and more sophisticated imaging systems to track migration of monocyte macrophages to the brain and target the delivery of specific therapeutics ( jeymohan et al . , 2009 ) .", "beside compounds aimed at control the virus , others try to treat the effects of the underlying neuroinflammation and neurodegeneration mechanisms , and might provide a beneficial supplement to haart . those insights support the hypothesis that inhibition of glutamate production by blocking mitochondrial glutaminase activity may clinically prevent neurotoxicity during hiv-1 infection . taken together the gsk3 , cdk5 , jnk , and p38 signaling pathways are important regulators of neurotoxicity , being responsible for synaptic and dendritic damage to pyramidal neurons , loss of immunoreactive neurons , and demyelinization . gsk3 inhibitors ( i.e. , lithium , valproic acid ) as well as cdk5 inhibitors ( i.e. , roscovitine ) seems to protect neuronal integrity and plasticity ( crews et al . , 2009 ) , while jnk- and p38-inhibitors ( i.e. , minocycline ) may prevent neuronal death ( lin et al . , 2001 ; bozyczko - coyne et al . , 2002 ) each of those target holds promise for the development of treatment strategies to ameliorated the neuropathological effects exerted by hiv proteins ( tat , vif , etc . ) neurotoxicity is mainly mediated through glutamate production , which is triggered by nmda subtypes of glutamate receptors , and correlated to caspase activation and subsequent neuronal apoptosis ( erdmann et al . , 2006 ) ; accordingly , pharmacologic inhibition of glutaminase directly correlate to neuronal survival ( tian et al . , 2008 ) .", "combinations of drugs work better and longer than seen previously , patients benefit demonstrably from the magnitude and duration of viral suppression , and require more and more symptomatic treatment of neuroaids cognitive impairment . however haart is very demanding for patients , non - adherence can lead to therapeutic failure , and in addition drug resistance is a continuing problem ; therefore , the need for improved drug and delivery systems , but also an interest for adaptive treatment strategies and mathematical modeling to manage structured treatment interruptions ( rosenberg et al . , 2007 ) , have been outlined by many researchers . to this regard a thigh collaboration with industry is strictly required and introduces a new set of challenges such as : ( 1 ) circulation of promising ideas , often just developed with university grants , ( 2 ) protection of intellectual property and patent rights , ( 3 ) fund - raising opportunities for start - ups during preclinical researches on novel compounds , until ( 4 ) identification of potential blockbusters appealing to big pharma companies for introduction in the market and their clinical exploitation . ( 2009 ) on behalf of the neuroaids research participants these priorities should be seen as a template for future growth of the field and its long - term impact . finally , current criteria for initiation of haart do not consider cns outcomes as a benchmark of efficacy , thus establishing cns - based criteria for initiation of protocols should be the ultimate goal not only for therapeutic but also for neuroprotection strategies ; as recently stated by jeymohan et al .", "the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest ." ]
the central nervous system ( cns ) represents an important target for hiv infection during multiple stages of the disease : early , after invasion of the host , acting as a viral reservoir ; lately , subverting its function and causing peripheral neuropathies and neurocognitive disorders ; and lastly , during the final stage of neuroaids , triggering opportunistic infections , cancers , and dementia . highly active antiretroviral therapy , a combination of drugs that inhibits enzymes essential for hiv replication , can reduce the viremia and the onset of opportunistic infections in most patients , and prolong the survival . among the limits of the current treatments the most noticeable is the inability to eradicate hiv - infected cells , both , limiting the time frame in which antiretroviral therapies initiated after exposure to hiv can prevent infection , and allowing replication - competent virus that persists in infected cells to emerge rapidly after the cessation of treatments . many strategies are currently under evaluation to improve hiv treatment , unfortunately more than 98% of drug candidates for cns disorders never make it to the clinic ; here in we report how nanoformulated strategies might be adapted and applied to the field of cns hiv infection .
[ "colorectal adenocarcinoma is the fourth most frequently diagnosed malignancy in korea , accounting for 12% of newly diagnosed cancer cases . according to the ministry of health and welfare , the incidence of colorectal cancer has increased in both males and females during the past 2 decades . although surgery is potentially curative , approximately one third of all newly diagnosed patients present with inoperable metastatic disease . palliative chemotherapy is more effective than the best supportive care for improving overall survival ( os ) as well as quality of life in advanced colorectal cancer . while significant advances have been made in recent years , cure is rarely possible in advanced colorectal cancer ( acc ) , making further improvements in therapy imperative . for more than three decades , in korea , capecitabine was approved in january 2006 as a partner with oxaliplatin or irinotecan for the treatment of acc . a decision regarding chemotherapy regimens for we therefore decided to evaluate various combination chemotherapy regimens as first - line chemotherapy for acc . have been used for acc treatment , the efficacy of palliative chemotherapy for acc has considerably improved . the recent integration of oxaliplatin and irinotecan for the management of acc patients has extended median os in a meaningful way . both drugs have been shown to have synergistic effects with 5-fu and fa in colorectal cancer cell lines . since irinotecan and oxaliplatin", "the primary endpoint of this retrospective study was progression - free survival ( pfs ) . a total of 537 acc patients were treated with first - line chemotherapy for advanced disease at samsung medical center ( seoul , korea ) . we attempted to exclude patients who were enrolled in clinical trials to ensure the choice of chemotherapy regimen was solely at the discretion of the treating physician . fifty - nine patients were excluded because they were treated with single - agent chemotherapy . multivariate models were used for exploratory purposes to examine the impact of each regimen on the outcomes of chemotherapy . the prophylactic use of hematopoietic growth factors was not allowed during treatment , except for patients with febrile neutropenia or grade 4 myelosuppression at the treating physician 's discretion .", "between january 2006 and december 2007 , a total of 478 acc patients were treated with combination chemotherapy in a first - line setting : folfox ( n=172 ) , folfiri ( n=95 ) , xelox ( n=155 ) , and xeliri ( n=56 ) . in 29 patients , chemotherapy involved bevacizumab . we found no relevant difference in the occurrence of overall grade 3 or 4 toxicities among regimens ( table 2 ) . in brief , the main difference in grade 3 or 4 toxicities with folfiri or xeliri was diarrhea ( 21% for folfiri and 27% for xeliri vs. 11% for folfox and 9% for xelox ; p=0.02 ) , and with folfox or xelox the difference involved peripheral neuropathy ( 9% for folfox and 7% for xelox vs. 2% for folfiri and xeliri ; p<0.01 ) . patients who had a poor performance status ( 2 in ecog scale ) were significantly less likely to respond to first - line chemotherapy ( 24% vs. 50% ; p<0.01 ) compared to those with an ecog performance status of 0 or 1 . . sixty percent of patients were male , and 33 patients ( 7% ) had an ecog performance status of 2 or more . the most common reason for discontinuation of treatment was disease progression . in 172 patients receiving folfox , two - thirds of patients more than half of the patients ( n=263 ) had received surgery for curative intent , and 206 patients received adjuvant chemotherapy or chemoradiotherapy .", "despite recent advances in the treatment of acc , patients treated with first - line chemotherapy have a median os rarely exceeding 24 months . in the current analysis , the evolution of treatment using irinotecan and oxaliplatin in combination with 5-fu regimens has resulted in a significant prolongation of life in patients with acc . because bevacizumab was only recently made available in korea as first - line chemotherapy , only 29 patients received bevacizumab . data from the current retrospective study suggest that patients are highly compliant with capecitabine , when given in combination with either oxaliplatin or irinotecan . since both drugs have demonstrated similar activity in first- and second - line settings , the optimal chemotherapy regimen and dosing schedule in patients with acc remains undecided . randomized trials comparing first - line folfox with folfiri indicated equivalent activity and moderate toxicity differences between these two regimens , suggesting that use of either oxaliplatin or irinotecan is reasonable . in another phase iii study in which patients crossed over to the alternative regimen upon progression while on their first - line regimen , the overall pfs on first - line therapy was 8.1 months for folfox and 8.5 months for folfiri . in a combined analysis of seven phase iii trials in acc , grothey et al . ", "this study confirms that both oxaliplatin- and irinotecan - containing combination chemotherapy are effective for the first - line treatment of acc . capecitabine clearly represents an effective and well - tolerated oral alternative to 5-fu . while the current study was primarily focused on cytotoxic therapies , the integration of targeted agents , including bevacizumab , is a novel standard option to further improve outcomes for patients with acc ." ]
purposefluoropyrimidine - based combination chemotherapy , in combination with either oxaliplatin or irinotecan , has demonstrated efficacy and tolerability in treatment of advanced colorectal cancer ( acc).materials and methodsbetween january 2006 and december 2007 , a total of 478 acc patients were treated with combination chemotherapy in first - line settings . combination therapies included : 5-fluorouracil , folinic acid plus oxaliplatin ( folfox , n=172 ) , 5-fluorouracil , folinic acid plus irinotecan ( folfiri , n=95 ) , capecitabine plus oxaliplatin ( xelox , n=155 ) , and capecitabine plus irinotecan ( xeliri , n=56 ) . folfox and folfiri were repeated every 2 weeks , whereas xelox and xeliri were repeated every 3 weeks until occurrence of disease progression or unacceptable toxicity , or until a patient chose to discontinue treatment.resultsthe median age was 58 years ( range , 19 to 84 years ) and the median chemotherapy durations for folfox , folfiri , xelox , and xeliri were 4.9 , 4.5 , 5.7 , and 5.4 months , respectively . combination chemotherapy regimens were generally well tolerated . the estimated median progression - free - survival ( pfs ) for all patients was 6.8 months ( 95% confidence interval , 6.3 to 7.3 months ) . no statistically significant difference in pfs was found among regimens used as first - line chemotherapy . sixty percent ( n=290 ) of patients received second or further lines of therapy after failure.conclusionfluoropyrimidine-based combination chemotherapy regimens appear to be equally active and tolerable as first - line therapy for acc .
[ "lymphomatoid granulomatosis ( lyg ) is a rare angiocentric and angiodestructive lymphoproliferative disease with granulomatous reaction involving the lungs most frequently , however , it may also involve the kidneys , skin and especially the central nervous system4,6,9,11 ) . therefore the purpose of this study is to submit the first report about the case with thoracic spinal lyg after diagnosis with b - precursor childhood acute lymphoblastic leukemia ( all ) . after surgical decompression with biopsy on the spinal lesion , diagnosis of grade ii lyg was made and rituximab was administered . the patient is in good neurological condition without recurrence at the 6-year follow - up . lyg is characterized by an infiltration of atypical lymphocytoid and plasmocytoid cells , with granulomatous inflammation in an angiocentric and angiodestructive polymorphic cellular infiltrate6,8 ) .", "a 4-year - old girl was diagnosed with b - precursor all with the involvement of kidneys and pancreas in november , 2004 . on april 12 , 2006 , the patient was admitted to pediatric clinic with a complaint of intermittent fever for 3 days . on april 19 , 2006 , 7 days after the admission , the patient developed a gait disturbance . the condition was suspected to be an acute inflammatory demyelinating polyneuropathy and was treated with intravenous immunoglobulin ( 400 mg / kg / day ) for 5 days . t2 weighted mri demonstrated heterogeneous high signal intensity infiltration on t4 vertebral body and subligamental spreading soft tissue mass on t3 - 5 epidural space from t4 posterior vertebral body , causing spinal cord compression ( fig . two weeks after , chest and abdomen ct revealed multiple low density nodular mass on the liver and the lower lobe of the left lung . however , her paraparesis was aggravated to grade 1 on mrc muscle strength grading scale from april 26 , 2006 , 14 days after the admission , and spinal mri was performed . one - week post - operative neurologic examination showed paraparesis grade 3 on mrc scale , and bare independent walking but as she still had gait impairment , she received rehabilitation .", "involvement of the spine has been rarely reported . to my best knowledge , this is the first report of thoracic spinal lyg presenting with unique progressive myelopathy . lyg is a rare lymphoproliferative disease characterized by angiocentric and angiodestructive ebv - positive b - cell proliferation of uncertain malignant potential , which might be associated with exuberant reactive t cell infiltration2,9 ) . its occurrence in children is quite rare4 ) . there were three cases of lymphomatoid granulomatosis with onset after all . lyg usually affects lungs primarily , and it may also present several significant extrapulmonary manifestations , affecting skin , kidney , spleen , and the central nervous system .", "childhood lyg is a rare disease but should be considered in the nodular pulmonary infiltrates and central nervous system manifestations , especially in the past diagnosis of childhood acute lymphoblastic leukemia . awareness of the features of lyg can lead to earlier diagnosis and prompt appropriate therapy . this case described an unusual occurrence of thoracic spinal lyg in a 4-year - old girl ." ]
lymphomatoid granulomatosis ( lyg ) is a lymphoproliferative disease involving the lungs most frequently ; however , it may also involve the kidneys , skin and especially the central nervous system . unique initial presentation of spinal involvement is extremely rare and epidural lesion of thoracic spine has not been reported . the prognosis for lyg has been reported to be poor , and there currently exists no satisfactory established treatment protocol . the purpose of this study is to report a case of successful treatment with surgery and rituximab combination therapy in thoracic spinal lyg .
[ "the surgical management of colorectal cancer is risky to the patient in terms of the surgical procedure and the interruption of immunosuppression . in general , these patients are more susceptible to perioperative complications . although open colorectal resection has been practiced for many years in kidney recipient patients , the minimally invasive procedure has been developed and is gaining popularity . kidney transplant recipients not only have numerous comorbidities associated with renal failure , but also often have additional problems due to chronic immunosuppression [ 13 ] . multiple randomized controlled trials have proven that minimally invasive surgery yields better short - term outcomes than open colorectal surgery in terms of reduced intraoperative bleeding , postoperative pain , and hospital stay , as well as a lower incidence of infection and respiratory complications , with equivalent long - term outcomes [ 4 , 5 ] . however , selected high - risk patients may benefit from minimally invasive colorectal resection due to reduced morbidity .", "the aim of this study was to prove the safety and feasibility of laparoscopic and robotic colorectal resection in kidney transplant recipients by evaluating the technical protocol and the short- and long - term outcomes .", "this retrospective review of all kidney transplant recipients diagnosed with colon or rectal cancer who received laparoscopic or robotic resection was conducted between may 2007 and august 2012 at yonsei university college of medicine , south korea . a main concern in laparoscopic and robotic colorectal resection is accurate and safe port placement to avoid injury to the transplanted kidney . , we used a hybrid technique by which the colon was mobilized laparoscopically and the robot was docked between the legs of the patients and used mainly for pelvic dissection . our preferred method is applying complete mesocolic principles where vessel ligation is performed at its origin . all patients received 4 liters of golytely ( peg-3350 and electrolytes for oral solution , braintree laboratories , inc . , antibiotics and a stress dose of steroids of 100 mg were given on induction of anesthesia and continued postoperatively with tapering dose of steroid .", "ten of these recipients were diagnosed with colon or rectal cancer and underwent minimally invasive surgical resection . the 3-year disease - free rate was 83.3% and the 3-year overall survival rate was 100% ( table 3 ) . five ( 50% ) patients were males ; the mean patient age was 56.8 ( range , 4772 ) years , and the mean body mass index was 22.4 ( range 20.526.4 ) kg / m . postoperative stages were i in 20% of the patients , ii in 50% of the patients , and iii in 30% of the patients ( table 3 ) . the mean estimated blood loss was 30 53.74 ( range 0150 ) ml . the mean interval between kidney transplantation and surgery was 11.7 ( range 1.322 ) years . preoperative stages were i and ii in 40% of the patients and iii in 10% of the patients . no tumor invasion or extension beyond the mesorectal fat with a maximum stage three ( 30% ) patients were anemic , with a mean hematocrit of 34.65 7.72% ( range 26.753.4% ) and a mean hemoglobin concentration of 11.38 2.54 ( range 8.917.4 ) g / dl . the american society of anesthesiologists scores were ii in 60% of patients and i and iii in 20% of patients each .", "no mortality occurred ; the 3-year disease - free rate was 83.3% , and the 3-year overall survival rate was 100% . in conclusion , minimally invasive surgery is feasible in kidney transplant recipients , who can benefit from fewer wound - related problems . our hospital is one of the leading hospitals in robotic surgery in korea . as we reported in our results , that one case was performed by robotic method . in that case therefore , minimally invasive colorectal procedures could be considered safe alternatives to open colorectal resection in selected kidney transplant patients . technical proficiency , experience , and the use of a multidisciplinary team approach including an oncologist and transplant team can result in a successful procedure and ensure the safety of the transplanted kidney . laparoscopic colorectal resection is less physically stressful and offers short - term advantages compared with open resection . technically , selection of the port insertion site is the most important step in a laparoscopic or robotic procedure . , we used a hybrid technique where the colonic mobilization was completed laparoscopically and the da vinci robot was used only for pelvic dissection ." ]
aim . to prove the safety and feasibility of minimally invasive ( laparoscopic and robotic ) colorectal resection in kidney recipients by evaluating the technical protocol and reviewing short- and long - term outcomes . methods . between may 2007 and august 2012 , a retrospective review of ten kidney transplant patients diagnosed with colorectal cancer was evaluated for technical tips , short- and long - term outcomes . results . the mean patients ' age was 56.8 9.91 years and 50% of them were male . anterior and low anterior resections were performed in 40% of the patients each ; 20% and 10% of the patients underwent right and left hemicolectomy , respectively . most ( 90% ) procedures were performed laparoscopically and 10% were performed robotically . no open conversions . mean operating time was 192.5 15 min , blood loss was 30 50 ml , and mean hospital stay was 9.7 5.5 days . two ( 20% ) patients had postoperative complications : wound seroma and chyloperitoneum . over a mean follow - up period of 31.4 21.57 months , no mortality or kidney rejection occurred . among the six patients followed up for a mean of 43.5 9.84 months , 83.3% were 3-year disease - free and the overall survival rate was 100% . conclusion . minimally invasive colorectal resection is likely to be safe and feasible , with fewer complications and acceptable short- and long - term outcomes , in kidney transplant recipients .
[ "recent reports indicate that selective thrombolytic therapy with intraarterial infusion of urokinase is effective for acute sma occlusion diagnosed early after onset . acute occlusion of the superior mesenteric artery ( sma ) causes extensive intestinal necrosis due to the difficulty of early diagnosis , resulting in poor prognosis , with a high postoperative mortality rate of 65.2% . early thrombolytic therapy can not always induce complete thrombolysis , and even if intestinal necrosis is avoided by administration of initial thrombolytic therapy , indications for additional thrombolytic therapy or the method for monitoring intestinal viability during subsequent follow - up have not been established . in this report , we present a case of acute sma occlusion diagnosed early after onset that was successfully treated by sequential and intermittent thrombolytic therapy by intraarterial urokinase infusion with angiographic evaluation of blood flow , thereby avoiding intestinal resection .", "abdominal enhanced ct showed a filling defect in the proximal portion of the sma main trunk , which led to the diagnosis of acute sma occlusion ( fig . the operation was completed without intestinal resection or direct removal of the thrombus from the sma . an 82-year - old woman with a past history of atrial fibrillation was admitted to our hospital , complaining of acute epigastric pain and stool with fresh blood . 24 h after the laparotomy , a second angiography was performed via the catheter that remained in place after first angiography , because clinical signs such as abdominal pain suggested the progression of intestinal ischemia . follow - up carefully monitored the possible onset of shower embolism by the residual thrombus .", "sequential and intermittent thrombolytic therapy with meticulous angiographic evaluation of blood flow is effective in the early stage of acute sma . in particular , it is much less invasive than strategies described in previous reports and enables accurate evaluation of intestinal blood flow or viability over the time course . , reports that support the usefulness of selective thrombolytic therapy via a catheter for angiography have increased . recent reports indicate that enhanced ct is feasible for early diagnosis of acute sma occlusion . early thrombolytic therapy is effective for acute sma occlusion in avoiding extensive intestinal resection . since the first report by jamieson et al ." ]
acute occlusion of the superior mesenteric artery ( sma ) causes extensive bowel necrosis , resulting in a poor prognosis with an extremely high mortality rate . an 82-year - old woman was admitted to our hospital with the complaint of abdominal pain . she was diagnosed as having acute sma occlusion by enhanced ct . five hours from onset , the first thrombolytic therapy with urokinase was performed , but failed to complete thrombolysis and recanalization of peripheral blood flow . an exploratory laparotomy following the first thrombolytic therapy showed a mild ischemic change in the affected intestine and mesentery , but no sign of necrosis . after the laparotomy , local thrombolytic therapy with angiographic evaluation of blood flow at 24 , 36 and 48 h from the first thrombolysis was performed . as a result , the residual thrombus disappeared and all branches of the sma became well visualized . the patient was discharged well without a second - look operation or major bowel resection . sequential intermittent thrombolytic therapy with meticulous angiographic evaluation of blood flow is effective for early - stage acute sma occlusion .
[ "the purpose of this study is to evaluate the correlation and reliability of cervical sagittal alignment parameters measured from lateral cervical xrs compared with lateral whole - body eos srs ( eos imaging , paris , france ) . we hypothesized that the difference in arm position and in the trajectory of the radiation beam between standard cervical xr and sr would result in a difference for all cervical sagittal alignment parameters . previous studies have demonstrated that arm positioning is an important factor during xr imaging , changing sagittal alignment parameters of the thoracic and lumbar spine.3 \n 4 \n 5 \n 6 \n 7 \n 8 in fact , park et al found that lateral whole - spine xrs with hands positioned touching the clavicle were associated with a decrease in t1 slope ( t1-s ) , posterior translation of the head , hypolordotic cervical spine , and downward gazing when compared with standing lateral cervical xrs with arms relaxed on either side of the body.9 \n to our knowledge , no study to date has compared cervical sagittal alignment parameters obtained from standing lateral cervical xrs versus lateral whole - body srs .", "we retrospectively evaluated adult patients with a primary diagnosis of cervical deformity treated by a single surgeon between january 2010 and december 2014 with both lateral cervical xrs and lateral srs obtained within 1 week of each other . at our institution , the intrarater reliability was quantified by intraclass correlation coefficient ( icc ) ( 3 , 1 ) , termed by shrout and fleiss.13 this type of icc is appropriate when study patients are a random sample of the underlying patient population , and a test and retest are only two occasions of interest . lateral cervical xrs are routinely obtained with the patient standing , with the arms in a relaxed neutral position , hanging at the side of the body ; this image is compared with srs obtained with eos imaging , which are acquired with patients standing and arms forward flexed at the shoulders . cervical sagittal alignment measurements were performed using a picture archiving and communications system , with each xr measured side by side on the same computer monitor to allow equal magnification / resolution of the cervical region from the lateral whole - body sr compared with the lateral cervical xr ( fig . icc values of more than 0.75 represent excellent reliability , values between 0.4 and 0.75 represent fair to good reliability , and value less than 0.4 represent poor reliability.14 the relationships between the parameters obtained from xrs and those from srs were compared by correlation analysis ( pearson correlation coefficient ) and paired t test . tia was then calculated by the formula tia = t1 slope + nt.12 \n the measuring parameters from cervical xr and sr were analyzed using r package irr . ", "icc values of cervical alignment parameters between lateral cervical radiograph and lateral whole - body stereoradiography . intrarater reliability was excellent for all cervical sagittal alignment parameters in both the xr and sr groups , with icc ranging from 0.799 to 0.994 for xr and 0.791 to 0.995 for sr . we found excellent correlations between xr and sr measurements for most cervical sagittal alignment parameters , with sca , sva , and c1c7 having r > 0.90 . abbreviations : icc , intraclass correlation coefficient ; nt , neck tilt ; sca , sagittal cobb angle ; sva , sagittal vertical axis ; td , translational distance ; tia , thoracic inlet angle . interrater reliability was excellent for all cervical sagittal alignment parameters in both the xr and sr groups , except nt and tia parameters , which had fair reliability .", "intrarater reliability was excellent for all cervical sagittal alignment parameters in both the xr and sr groups , with icc ranging from 0.799 to 0.994 for xr and 0.791 to 0.995 for sr . c1c7 demonstrated the highest intrarater icc in both groups ( 0.994 xr , 0.995 sr ) , with nt having the lowest intrarater icc in both groups ( 0.799 xr , 0.791 sr ; table 1 ) . abbreviations : ci , confidence interval ; icc , intraclass correlation coefficient ; nt , neck tilt ; sva , sagittal vertical axis ; t1-s , t1 slope ; tia , thoracic inlet angle . note : 95% ci is the 95% upper and lower boundaries for the confidence interval of icc .", "interrater icc was highest for sva ( 0.990 ) in the xr group and c1c7 ( 0.978 ) in the sr group , with nt having the lowest interrater icc in both groups ( 0.465 xr , 0.414 sr ; table 2 ) . interrater reliability was excellent for all cervical sagittal alignment parameters in both the xr and sr groups , except nt and tia parameters , which had fair reliability . abbreviations : ci , confidence interval ; icc , intraclass correlation coefficient ; nt , neck tilt ; sva , sagittal vertical axis ; t1-s , t1 slope ; tia , thoracic inlet angle . note : 95% ci is 95% upper and lower boundaries for the confidence interval of icc .", "icc values of cervical alignment parameters between lateral cervical radiograph and lateral whole - body stereoradiography . we found excellent correlations between xr and sr measurements for most cervical sagittal alignment parameters , with sca , sva , and c1c7 having r > 0.90 . abbreviations : icc , intraclass correlation coefficient ; nt , neck tilt ; sca , sagittal cobb angle ; sva , sagittal vertical axis ; td , translational distance ; tia , thoracic inlet angle . t1-s and tia were between 0.75 and 0.90 , and only nt had an r < 0.70 . we found a significant difference between the groups , with sr having lower measurements compared with xr for both sva ( 0.68 cm lower , p < 0.001 ) and c1c7 ( 1.02 cm lower , p < 0.001 ) .", "recent advances in imaging techniques include full - body sr , which allows low - dose , high - quality imaging of the entire spinal column and pelvis , as well as assessing for concomitant length discrepancy / deformity of the lower extremities and joints ( hips , knees , ankles).16 despite the purported advantages of sr , the difference in arm positioning compared with the standing lateral cervical xr and the effect on cervical sagittal alignment parameters is not completely understood . our study found most cervical sagittal alignment parameters ( sca , sva , and c1c7 ) measured from lateral cervical xrs and lateral whole - body eos srs had excellent correlation , with excellent intra- and interrater reliability in both groups . cervical sagittal imbalance remains a complex problem,9 \n 15 and optimal imaging to assess cervical sagittal alignment parameters is important during patient evaluation and particularly preoperative planning . we postulate that patients with symptomatic cervical deformity have degenerative changes with less flexibility of the subaxial spine . also", "based on the findings of our study , we believe sr is a reliable method for determining most cervical sagittal alignment parameters and a viable alternative to lateral cervical xr despite differences in arm position during imaging . however , measurements requiring visualization of the sternum such as nt and tia may not be reliable and do not appear to be optimal cervical sagittal alignment parameters . also , sr results in slight posterior head translation and subsequently lower sva and c17 translational distance compared with lateral cervical xr and may underestimate regional cervical sagittal alignment parameters in patients with cervical deformity or sagittal imbalance . the lower radiation exposure using single sr has to be weighed against its higher cost compared with xr ." ]
study design retrospective analysis.objective to evaluate the correlation and reliability of cervical sagittal alignment parameters obtained from lateral cervical radiographs ( xrs ) compared with lateral whole - body stereoradiographs ( srs).methods we evaluated adults with cervical deformity using both lateral xrs and lateral srs obtained within 1 week of each other between 2010 and 2014 . xr and sr images were measured by two independent spine surgeons using the following sagittal alignment parameters : c2c7 sagittal cobb angle ( sca ) , c2c7 sagittal vertical axis ( sva ) , c1c7 translational distance ( c17 ) , t1 slope ( t1-s ) , neck tilt ( nt ) , and thoracic inlet angle ( tia ) . pearson correlation and paired t test were used for statistical analysis , with intra- and interrater reliability analyzed using intraclass correlation coefficient ( icc).results a total of 35 patients were included in the study . we found excellent intrarater reliability for all sagittal alignment parameters in both the xr and sr groups with icc ranging from 0.799 to 0.994 for xr and 0.791 to 0.995 for sr . interrater reliability was also excellent for all parameters except nt and tia , which had fair reliability . we also found excellent correlations between xr and sr measurements for most sagittal alignment parameters ; sca , sva , and c1c7 had r > 0.90 , and only nt had r < 0.70 . there was a significant difference between groups , with sr having lower measurements compared with xr for both sva ( 0.68 cm lower , p < 0.001 ) and c1c7 ( 1.02 cm lower , p < 0.001 ) . there were no differences between groups for sca , t1-s , nt , and tia.conclusion whole - body stereoradiography appears to be a viable alternative for measuring cervical sagittal alignment parameters compared with standard radiography . xr and sr demonstrated excellent correlation for most sagittal alignment parameters except nt . however , sr had significantly lower average sva and c1c7 measurements than xr . the lower radiation exposure using single sr has to be weighed against its higher cost compared with xr .
[ "nucleotide excision repair ( ner ) plays a central role in preserving the genome of prokaryotes and eukaryotes . recent findings reveal that polymorphisms in human ner repair genes have an impact on the repair of dna lesions and cancer susceptibility [ 6 , 7 ] , as well as on chemotherapeutic efficacy . a better understanding of the mechanisms of recognition of dna lesions by the ner system may lead to the design of improved chemotherapeutic drugs that can modulate the repair response . however , the differences in the structural and thermodynamic properties of the lesions that control the diverse ner efficiencies have remained elusive . it has been suggested that the ner factors do not recognize the lesion itself , but rather the local distortions and destabilizations in the dna that are associated with it [ 2430 ] . a number of different properties of damaged dna that elicit the ner response have been proposed . ", "consistent with the conformational heterogeneity observed in the nmr studies , it was found that the 5- t[g*]t - ii duplex is much more dynamic than the 5- c[g*]c - ii duplex : the highly dynamic base pair on the 5-side of the lesion exhibits episodic denaturation of one of the two watson - crick hydrogen bonds , in agreement with the partial rupturing of this base pair observed by the nmr methods ; also , the 5- t[g*]t - ii duplex shows somewhat increased and more dynamic roll and untwisting compared to the 5- c[g*]c - ii case is consistent with the overall enhanced dynamics manifested in various structural properties , notably watson - crick hydrogen bonding and bending . the nmr data showed conformational heterogeneity in minor groove conformations , and the md simulations showed episodic denaturation of one of the two hydrogen bonds at the i : c base pair , explaining the heterogeneity . duplex , which is a manifestation of a kink that is highly flexible . ", "duplex is explained by its greater bending with enhanced flexibility : the intrinsic minor groove enlargement caused by both the guanine amino groups [ 55 , 68 ] and the great flexibility of pyrimidine - purine steps , including the c - a step [ 57 , 6972 ] allow the b[a]p moiety ( figure 5 ) to more favorably position itself , but at the expense of the greater bend that makes it more repair - susceptible . the ner efficiencies are 1.6 0.2 times greater in the 5- c[g*]c - ii than in the 5- c[g*]c - i sequence context showing that distant neighbors to [ g * ] modulate the ner susceptibility . the greater ner susceptibility for the 5- c[g*]c - ii the key role is played by the unique -c3-a4-c5- segment in the 5- c[g*]c - ii duplex . since different sequence steps are known to be differentially flexible [ 57 , 65 ] , we hypothesized that the same minor groove lesion [ 50 , 64 ] with different distant neighbors would be differentially repaired . this produces a yet more enlarged minor groove which is coupled with more local untwisting and more enlarged and flexible roll , causing the greater bend in 5- c[g*]c - ii ( figure 5 ) . duplex is more bent and suggested that it has more torsional flexibility than the 5- c[g*]c - i duplex . ", "we have carried out a series of studies with the same 10s ( + ) -trans - anti - b[a]p - n - dg lesion in a number of sequence contexts that differ in how the lesion is positioned in relation to nearby guanine amino groups . additionally , we have considered differences in intrinsic flexibility of sequences flanking the lesion . these are model systems for gaining understanding of ner lesion recognition factors . figure 4 summarizes our key findings and enables us to infer a hierarchy of ner recognition signals for the series of sequences and the single lesion we explored . we point out here that a variety of structural disturbances are found in each case , which are correlated ." ]
nucleotide excision repair ( ner ) plays a critical role in maintaining the integrity of the genome when damaged by bulky dna lesions , since inefficient repair can cause mutations and human diseases notably cancer . the structural properties of dna lesions that determine their relative susceptibilities to ner are therefore of great interest . as a model system , we have investigated the major mutagenic lesion derived from the environmental carcinogen benzo[a]pyrene ( b[a]p ) , 10s ( + ) -trans - anti - b[a]p - n2-dg in six different sequence contexts that differ in how the lesion is positioned in relation to nearby guanine amino groups . we have obtained molecular structural data by nmr and md simulations , bending properties from gel electrophoresis studies , and ner data obtained from human hela cell extracts for our six investigated sequence contexts . this model system suggests that disturbed watson - crick base pairing is a better recognition signal than a flexible bend , and that these can act in concert to provide an enhanced signal . steric hinderance between the minor groove - aligned lesion and nearby guanine amino groups determines the exact nature of the disturbances . both nearest neighbor and more distant neighbor sequence contexts have an impact . regardless of the exact distortions , we hypothesize that they provide a local thermodynamic destabilization signal for repair .