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[ [ "the reasons for that may be related to factors such as rejection to the use of two hearing aids , financial issues , aesthetic reasons , problems with manual dexterity , very asymmetric losses , and central processing issues.19 \n given such reality , this work intends to analyze the effects of unilateral adaptation of hearing aids on the symptoms of depression and the social activity constraints of elderly subjects with hearing impairment .", "aging is part of the natural process of human development , and it brings multiple biopsychosocial changes that cause a slow and progressive deterioration of body functions that are essential to life . among these functions that undergo important mostly irreversible changes is hearing.1 hearing loss is considered one of the three most common conditions in the elderly,2 with occurrence of 5 to 20% in 60-year - olds , increasing to 60% in people over 65 years old.1 \n 3 in brazil , 60% of the elderly have some degree of hearing loss.4 \n the term used to describe hearing loss associated with aging is presbycusis , which causes a decrease in hearing sensitivity and a reduction in the ability to understand speech .", "thus , recommended intervention by hearing aid adaptation contributes to the prevention of emotional disorders such as depression.12 \n depression is defined as a mental disorder that causes feelings of sadness , pessimism , hopelessness , difficulty concentrating , and difficulty making decisions and initiating tasks , among other symptoms.13 despite being very common in the elderly , it can not be attributed solely to aging ." ], [ "this is a prospective interventional study of elderly individuals of both sexes with recommended use of hearing aids at a hearing center in porto alegre .", "the questionnaire was prepared in 198222 and translated and adapted to brazilian portuguese.23 it contains 10 questions that aim to assess the impact of hearing loss on the emotional and social status of elderly people .", "the presence and degree of hearing loss were classified according to the world health organization by analyzing mean airway tone threshold in the frequencies of 500 , 1,000 , 2,000 , and 4,000 hz.20 \n after that , seniors were asked to answer two questionnaires individually , without the intervention of third parties : the geriatric depression scale ( gds ) and the hearing handicap inventory for elderly short version ( hhie - s ) .", "the study was divided into two phases . in phase 1 , subjects responded to an interview with questions on demographics and health ( general and hearing ) .", "thirty days after purchasing the device , they returned to the hearing center to participate in the second phase of the research . in phase 2", "all 10 questions provide three choices of answers : for each yes answer , 4 points is assigned ; each sometimes , 2 points ; and each no , 0 points . the total score ranges from 0 to 40 points , and the higher the score , the greater subjects ' self - perception of social activity constraints : 0 to 8 points indicate no social activity constraints ; 10 to 23 points , mild to moderate social activity constraint ; and 24 to 40 points , significant social activity constraints.8 \n 22 \n after testing , the participants were subjected to the selection and unilaterally hearing aid adaptation processes", "the gds , an instrument validated for portuguese and composed of 15 yes - or - no questions , is used to detect depression symptoms in the elderly ." ], [ "the sample consisted of 13 elderly patients with hearing loss , ages from 60 to 90 years ( mean 72.85 11.05 years ) , 10 women ( 76.9% ) and 3 men ( 23.1% ) .", "abbreviations : gds , geriatric depression scale ; hhie - s , hearing handicap inventory for elderly short version . \n", "the lack of association between the classification of the gds and hhie on the two phases is an important point , because it shows that there were different results in both assessments ( before and after hearing aid adaptation)that is , on the sample studied , unilateral prosthetization resulted in benefits for patients . \n", "there was significant difference between the gds ( p = 0.031 ) and hhie ( p < ", "no significant association was found for these variables in the periods before and after the adaptation ( p > 0.999 ) .", "table 2 depicts an association analysis between the gds classification of phases 1 and 2 , indicating that there was no significant association between the variables in the periods before and after the adaptation ( p = 0.615 ) ." ], [ "the findings reinforce the importance of hearing aid use in elderly patients , because many times family and social relationships are affected by the hearing impairment .", "thus , the adaptation of a single amplifying device can also generate benefit for elderly patients , which is important for the reduction of one of the most prevalent problems in the aging population , depression .", "the adaptation to amplification devices , albeit unilaterally , has proved to be effective in reducing symptoms of depression and social activity constraints .", "results show evidence of the positive effects of hearing aid use , even if unilateral , helping to reduce the impact that hearing loss has on social relationships and on the quality of life of the elderly.9 results are consistent with another study that examined the short - term benefits of amplification in new users.29 \n the data also show a significant difference in scores obtained in phases 1 and 2 of the gds ( p = 0.031 ) and hhie - s ( p < 0.001 ) , confirming a reduction or elimination of depression symptoms and social activity constraints in elderly patients , agreeing with other published studies ( table 4).2 \n 8 \n 11 \n 29 \n 30 again , it is important to highlight that in the studied group , unilateral prosthesis resulted in substantial benefits not only regarding hearing but also in other matters essential for the well - being and quality of life of individuals .", "thus , a hearing aid , even when unilateral , promoted elimination or reduction of symptoms of depression in the sample studied ." ], [ "results show that unilateral hearing aid contributed to the elimination or reduction of depression symptoms and of social activity constraints in elderly participants in this research sample group ." ] ]

[ [ "ameloblastomas are rare benign odontogenic tumours , most commonly found in a patient s lower jaw .", ", i describe a woman who underwent a repair of her mandibular defect by a combination of innovative techniques , in order to reduce the risk of complications and get her back to an aesthetically pleasing level .", "the surgical approach for correction of this mandibular defect is often reconstruction of the mandible in view of inserting dental implants at a later date . despite surgical advancements ,", "although rarely metastatic , the growth of these lesions can result in defects in the jaw easily destroying surrounding bony tissues .", ", bone grafting with non - vascularized bone remains a good option where facilities for soft tissue flaps are not readily accessible .", "for this reason , the treatment is often excision of the lesion , with wide excision margins , resulting in the absence of a part , or all , of the mandible .", "creating an effective wound closure and reducing the incidence of infection is an important stage in the success of the operation , and has been combated here by tissue expanding the submucosa , using osmed pellets , prior to surgery ." ], [ "this resulted in an absence of teeth from the canines back and removal of bone down to the inferior alveolar nerve .", "a 35-year - old lady presented to the craniofacial surgeons looking for a permanent fixture to the bony defect in her lower - right mandible . in 1991", "( a ) radiolocal image of patient 's jaw . ( b ) ct scan of head the patient was initially given the option between a bone graft or vascularized tissue ( free fibular flap ) and informed of the complications a bone graft carries a risk of rejection and vascularized tissue needs an increased amount of post - operative care to ensure that the tissue remains vascularized .", "there is clear absence of teeth on the lower - right side from the canines back ( to include the premolar , molar and wisdom teeth ) and presence of healthy oral mucosa with laxity to move the submucosa medially ." ], [ "often patients suffering from ameloblastomas undergo resection as treatment and are left with bony defects that require reconstruction . in this case , the intention was to realize an aesthetically pleasing appearance for the patient and it has been shown that bone grafting with subsequent dental implants is a successful method . as in this case , it is recommended that non - vascularized autogenous bone grafting can be used when a two - layer watertight closure is attainable .", "although the insertion of dental implants is the end goal for this surgery , the importance of this case report is to highlight the novel techniques involved in making this surgery a success . the use of small osmed pellets in the submucosa of the mouth to cause sufficient tissue expansion and create a tension - free closure , combined with the titanium construct packed with grafted iliac bone to rebuild the jaw was an approach recommended by the doctors for the repair of bony defects of < 5 cm .", "sources of bone could have been harvested from either local or distant sites but in this case , an extra - oral site ( iliac bone ) was used as a moderate amount of bone was needed .", "i suggest prudent management of future cases post - operatively to ensure a continued success of the graft .", "the use of osmed pellets was innovative , as pellets of this size have only recently been experimented on goats maxilla ." ] ]

[ [ "therefore , dpp4 inhibitor might be more effective in increasing circulating glp1 levels in patients with type 2 diabetes if they have low glp1 levels . based on these lines of evidence , we hypothesized that dpp4 inhibitor would be effective in patients with type 2 diabetes with high serum 3 pufa concentrations . in the present study , therefore , we investigated the relationship between serum epa or dha concentrations and a decrease in hemoglobin a1c in patients with type 2 diabetes prescribed dpp4 inhibitors .", "however , the direct effects of epa or dha consumption on glycemic control in patients with type 2 diabetes have remained uncertain .", "a recent study has shown a significant inverse correlation between serum epa or dha concentrations and cardiovascular risk .", "these reports show that 3 polyunsaturated fatty acids ( pufa ) , including la , epa and dha , increase glp1 secretion in mice .", "glucagonlike peptide1 ( glp1 ) , the most potent incretin hormone , stimulates glucoseinduced insulin secretion and inhibits glucagon secretion , which consequently leads to a decrease in hepatic glucose production and blood glucose levels ." ], [ "serum epa and dha concentrations were measured in 62 consecutive patients with type 2 diabetes recruited from the outpatient clinic at kyoto prefectural university of medicine , kyoto , japan , who were newly given dpp4 inhibitor as a monotherapy or as an addon therapy to oral hypoglycemic agents ( oha ) .", "after 24 weeks of treatment with dpp4 inhibitor , we evaluated the relationships between a decrease in hemoglobin a1c from baseline and serum epa or dha concentrations , as well as age , sex , body mass index ( bmi ) , hemoglobin a1c at baseline and usage of antidiabetic concomitant drugs .", "the prior diet , exercise program and dosage of oha in the study patients were maintained during the observation period .", "sitagliptin at a daily dose of 50 mg , which was the standard dose in japanese patients , was continuously given once daily during the observation period .", "paired ttest was carried out to assess the statistical significance of difference in hemoglobin a1c between baseline and after dpp4 inhibitor treatment , and unpaired ttest was carried out to assess the statistical significance of difference in a decrease in hemoglobin a1c between groups using stat view software ( version 5.0 ; sas institute , cary , nc , usa ) . because epa and dha showed skewed distributions , logarithm ( log ) transformation was carried out before performing correlation and regression analysis . the relationship between log epa , log dha or log ( epa + dha ) and a decrease in hemoglobin a1c", "serum total cholesterol , highdensity lipoprotein cholesterol and triglyceride concentrations were assessed using standard enzymatic methods ." ], [ "serum epa and dha concentrations were measured in 62 consecutive patients with type 2 diabetes recruited from the outpatient clinic at kyoto prefectural university of medicine , kyoto , japan , who were newly given dpp4 inhibitor as a monotherapy or as an addon therapy to oral hypoglycemic agents ( oha ) .", "sitagliptin at a daily dose of 50 mg , which was the standard dose in japanese patients , was continuously given once daily during the observation period .", "patients with advanced renal dysfunction ( serum creatinine concentration was equal to or more than 2.0 mg / dl ) were excluded from the present study .", "after 24 weeks of treatment with dpp4 inhibitor , we evaluated the relationships between a decrease in hemoglobin a1c from baseline and serum epa or dha concentrations , as well as age , sex , body mass index ( bmi ) , hemoglobin a1c at baseline and usage of antidiabetic concomitant drugs .", "the prior diet , exercise program and dosage of oha in the study patients were maintained during the observation period .", "type 2 diabetes was diagnosed according to the report of the expert committee on the diagnosis and classification of diabetes mellitus ." ], [ "serum total cholesterol , highdensity lipoprotein cholesterol and triglyceride concentrations were assessed using standard enzymatic methods .", "hemoglobin a1c was assayed using highperformance liquid chromatography and was expressed as a national glycohemoglobin standardization program unit as recommended by the japan diabetes society ." ], [ "paired ttest was carried out to assess the statistical significance of difference in hemoglobin a1c between baseline and after dpp4 inhibitor treatment , and unpaired ttest was carried out to assess the statistical significance of difference in a decrease in hemoglobin a1c between groups using stat view software ( version 5.0 ; sas institute , cary , nc , usa ) . because epa and dha showed skewed distributions , logarithm ( log ) transformation was carried out before performing correlation and regression analysis . the relationship between log epa , log dha or log ( epa + dha ) and a decrease in hemoglobin a1c", "means , medians or frequencies of potential confounding variables were calculated . skewed variables , such as epa and dha ,", ", we included independent variables that were significantly correlated with a decrease in hemoglobin a1c in the univariate analyses .", "was examined by linear regression analysis . in multiple regression analysis to assess the effects of various factors on decrease in hemoglobin a1c", "are presented as the median ( interquartile range ) , and continuous variables are presented as the mean standard deviation ( sd ) ." ], [ "characteristics of the 62 patients with type 2 diabetes enrolled in the present study are shown in table 1 .", "presence of antidiabetic concomitant drugs ( no = 0 , yes = 1 ) .", "dha , docosahexaenoic acid ; epa , eicosapentaenoic acid . a decrease in hemoglobin a1c correlated with bmi ( r = 0.396 , p = 0.0013 ) , age ( r = 0.275 p = 0.0032 ) , hemoglobin a1c at baseline ( r = 0.490 , p < 0.0001 ) , log epa ( r = 0.285 , p = 0.0246 ) and log ( epa + dha ) ( r = 0.260 , p = 0.0411 ) . there were no significant differences in decrease in hemoglobin a1c between male and female patients ( 1.0 0.8% vs 1.0 0.9% , p = 0.9758 ) . decrease in hemoglobin a1c was greater in patients treated with antidiabetic concomitant drugs compared with that in patients without those ( 1.1 0.9% vs 0.6 0.4% , p = 0.0342 ) . in the multiple regression analysis to examine the effects of variables on the decrease in hemoglobin a1c , we included the following independent variables , which were significantly correlated with a decrease in hemoglobin a1c in the univariate analyses : age , bmi , hemoglobin a1c at baseline , usage of antidiabetic concomitant drugs and log epa .", "multiple regression analysis showed that bmi , hemoglobin a1c at baseline and log epa were independent determinants of a decrease in hemoglobin a1c ( table 3 ) .", "log epa and log ( epa + dha ) correlated with a decrease in hemoglobin a1c .", "mean hemoglobin a1c was significantly decreased from 8.1 1.1% at baseline to 7.2 1.0% at 24 weeks after administration of dpp4 inhibitor ." ], [ "dpp4 inhibitor is effective in patients with type 2 diabetes with high serum epa concentrations .", "we analyzed the correlations between serum epa concentrations and a decrease in hemoglobin a1c in patients with dpp4 inhibitor monotherapy , dpp4 inhibitor addon therapy to sulfonylurea , to metformin , and to sulfonylurea and metformin .", "in the present study , serum epa concentrations correlated with a decrease in hemoglobin a1c .", "dpp4 inhibitor increases endogenous active glp1 levels through prevention of glp1 degradation , leading to an increase in circulating insulin levels and a decrease in blood glucose levels . because of the pharmacological action of dpp4 inhibitor on insulin secretion , dpp4 inhibitor is effective in type 2 diabetic patients with impaired insulin secretion , which is a characteristic of japanese patients with type 2 diabetes . indeed , as compared with american and european patients with type 2 diabetes , japanese patients with type 2 diabetes might be higher responders to dpp4 inhibitor .", "serum epa concentrations increase with age in apparently healthy japanese . in the present study , however , there was no significant correlation between log epa and age in patients with type 2 diabetes ." ] ]

[ [ "pregnancy course was regular , except for maternal consumption of mebendazol at 5 weeks ' gestation to treat a pinworm infection .", "maternal history was negative for consumption of any known teratogenic class drug during the whole pregnancy .", "final diagnosis was that of a sporadic co. x - ray showing absence of left middle finger distal phalanx .", "clinical examination at birth was normal , except for complete congenital anonychia of left middle finger ( fig.1 ) .", "parents were not consanguineous and have normal fingernails and toenails . the baby was discharged on the third day of life , and was found healthy and thriving at three - month follow - up visit ." ], [ "more recently , several pathogenetic mechanisms have been proposed for this condition : \n\n selective abnormal fetal vascular supply from palmar digital artery causing in utero ischemic injury : the ischemic damage would mainly be seen on the radial side of the affected finger due to the smaller caliber of the artery on that side 15 , which should be more protected than the ulnar one;16 \n\n in utero dysplastic change in the crescent - shaped cap of the distal phalanx , a theory that would account for the frequent y shape of the dysplastic distal phalanx , when present;17 \n\n genetic mutations causing impairment of the wnt signaling pathway , an evolutionarily conserved signal transduction pathway that plays a pivotal role in embryonic development , growth regulation of multiple tissues , and cancer development;18 \n\n fetal exposure to teratogens , particularly antiepilectic drugs : phenytoin 19 , valproate , and carbamazepine20 \n \n selective abnormal fetal vascular supply from palmar digital artery causing in utero ischemic injury : the ischemic damage would mainly be seen on the radial side of the affected finger due to the smaller caliber of the artery on that side 15 , which should be more protected than the ulnar one;16 \n \n in utero dysplastic change in the crescent - shaped cap of the distal phalanx , a theory that would account for the frequent y shape of the dysplastic distal phalanx , when present;17 \n \n genetic mutations causing impairment of the wnt signaling pathway , an evolutionarily conserved signal transduction pathway that plays a pivotal role in embryonic development , growth regulation of multiple tissues , and cancer development;18 \n \n fetal exposure to teratogens , particularly antiepilectic drugs : phenytoin 19 , valproate , and carbamazepine20 \n a literature research showed no proven association between the use of mebendazole during pregnancy and co. conversely , helminth infection during pregnancy is associated with poor cognitive and gross motor outcomes in infants , so that measures to prevent helminth infection during pregnancy should be reinforced;21 anthelminthic therapy is actually recommended in infected pregnant women , and it has been associated to a decreased rate of maternal anemia and low birth weight 22 .", "congenital onychodystrophy ( co ) , also called as iso kikuchi syndrome , was first described by iso in 1969 1 and later by kikuchi in 1974 2 as a clinical syndrome involving dysplasia / absence of fingernails with underlying bone abnormalities . since these first observations", "acquired isolated nail disorders 8 several heterogeneous multisystem pathologies may also come with ungueal abnormalities ; these are summarized in table2 \n 813 ." ], [ "nevertheless , clinical follow - up is needed in order to exclude other conditions associated with multisystem pathology ; a complete family history may also be warranted to determine sporadic or hereditary transmission of such a condition ." ], [] ]

[ [ "glycogen synthase kinase-3 ( gsk-3 ) , an evolutionarily conserved ubiquitous serine threonine kinase consisting of and isoforms , is a multifaceted protein with diverse cellular and neurophysiological functions .", "this article reviews the findings supporting the role of gsk-3 inhibition in mediating lithium s neuroprotective effects against excitotoxicity in both cultured neurons and animal models of ischemic stroke .", "gsk-3 inhibition has attracted widespread attention as one of the critical therapeutic targets whereby lithium exerts its effects on mood stabilization , neurogenesis , neurotrophicity , neuroprotection , anti - inflammation , and others ( for review , rowe and chuang , 2004 ; rowe et al .", "lithium , a competitive inhibitor of magnesium , directly inhibits atp magnesium - dependent catalytic activity of gsk-3 ." ], [ "we have designed isoform - specific small interfering rnas ( sirnas ) to distinguish the functional and regulatory differences between the two gsk-3 isoforms in rat cerebral cortical neuronal cultures ( liang and chuang , 2007 ) .", "these results strongly suggest that both gsk-3 and are involved in glutamate - induced neuronal death and that both isoforms are the initial targets of lithium - elicited neuroprotection .", "transfection with sirna for gsk-3 or gsk-3 or with dominant - negative mutants specific for either isoform produced almost complete protection against glutamate - induced , n - methyl - d - aspartate ( nmda ) receptor - mediated excitotoxicity .", "enhanced gene transcription triggered by bdnf , via sequestration of transcriptional co - activator p300 , suppresses smad3/4-dependent transactivation and subsequently decreases the expression of tgf--responsive genes , pai-1 , and p21 .", "the sirna - induced neuroprotection was associated with enhanced n - terminal phosphorylation in both gsk-3 isoforms ." ], [ "these results demonstrate that gsk-3 is the initial target of lithium to selectively activate bdnf promoter iv and that bdnf induction by lithium involves a novel responsive region in promoter iv of the bdnf gene .", "lithium - induced , gsk-3-dependent bdnf promoter iv activation could be a part of the molecular mechanisms underlying its neuroprotective effects and as such , possibly accounts for the therapeutic actions in bipolar patients .", "although glutamate - induced excitotoxicity in cultured cortical neurons was blocked by treatment with either lithium or mk-801 ( an nmda receptor antagonist ) , the src kinase inhibitor su6656 only partially diminished this toxicity ( hashimoto et al . , 2003 ) , suggesting that other components are involved . in cgcs , lithium - induced neuroprotection against glutamate excitotoxicity was associated with up - regulation of the anti - apoptotic protein bcl-2 , down - regulation of the pro - apoptotic proteins p53 and bax , and suppressed release of cytochrome c from mitochondria ( chen and chuang , 1999 ) , whereas the involvement of gsk-3 in the regulation of nmda signaling by lithium treatment is currently unclear and requires further investigations .", "we hypothesized that this bdnf up - regulation and subsequent activation of its receptor trkb might play a critical role in mediating the neuroprotective effects of lithium . in confirmation of this hypothesis", "as one of the major neurotrophins , bdnf is essential for cortical development , synaptic plasticity , and neural survival , and is likely a key mediator of the clinical efficacy of anti - depressants and anxiolytic drugs ( for review , woo and lu , 2006 ) ." ], [ "when systematically administrated to permanent mcao mice , sb216763 decreased infarct volume and restored the loss of mitochondrial dna , thus supporting a novel role of gsk-3 inhibitors in stimulating the renewal of functional mitochondria following ischemic stroke .", "together , these findings raise the potential utility of using mscs primed with inhibitors of gsk-3 and hdac to enhance the migration and homing capacity for transplantation into stroke victims .", "gsk-3 is also negatively regulated by the wnt/-catenin signaling pathway and , accordingly , activating the canonical wnt pathway has been shown to contribute to adult hippocampal neural progenitor cell proliferation triggered by lithium treatment ( wexler et al . , 2008 ) . in a collaborative study ,", "in fact , chronic lithium treatment has been demonstrated to increase activity in the mek / erk pathway in vivo , and lithium s neuroprotection has been suggested to depend on the induction of this signaling pathway ( einat et al .", "since vegf has been linked to angiogenesis , neurogenesis , and neuroprotection ( for review , fan and yang , 2007 ) , vegf over - expression may contribute to lithium s ability to promote neurovascular remodeling and to induce functional recovery after ischemic stroke .", "post - ischemic inflammation is a dynamic process involving a complicated set of interactions between inflammatory cells and molecules ( iadecola and alexander , 2001 ) . a recent study documented the anti - inflammatory effects of lithium in a neonatal rat hypoxic ischemic model ." ], [ "taken together , these effects of lithium in reducing apoptosis , suppressing inflammation , enhancing angiogenesis and neurogenesis , contribute to behavioral improvement and functional recovery after ischemia . lines with solid arrows represent stimulatory connections ; lines with flattened ends represent inhibitory connections .", "a growing body of evidence supports that lithium , a mood stabilizer used to treat bipolar disorder , has neuroprotective properties in both cellular and in vivo experimental settings .", "lithium has been used as a prototype drug to seek evidence for the involvement of gsk-3 inhibition in lithium - induced protection against excitotoxicity in cultured neurons and animal models of cerebral ischemic stroke .", "up - regulation of hsp70 and bcl-2 as well as down - regulation of p53 likely contributed to the protective effects of lithium in the ischemic conditions , thus supporting similar underlying neuroprotective mechanisms in the excitotoxic cellular models and animal models of ischemic stroke .", "induction of bdnf is an early and essential step for neuroprotection and is involved in lithium - induced neurogenesis .", "in addition , superinduction of hsp70 by lithium treatment not only inhibits brain ischemia - induced apoptosis , but also contributes to the anti - inflammatory effects of lithium through inactivation of nf-b .", "counteraction of gsk-3 inhibition of vegf and mmp-9 by lithium enhances angiogenesis and neurovascular remodeling ." ], [ "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 ." ] ]

[ [ "studies have shown the incidence of injury from squash to range from 35.5 to 80.9 per 100,000 players .", "this is the first case reported of a patient sustaining such extensive head , neck and spinal injuries from a squash - related injury .", "craniofacial and spinal fractures typically result from high - energy blunt force to the skeleton , as seen in motor vehicle accidents .", "trauma to the head ( including the eyes ) is the most common cause of squas - related hospital presentation , comprising 48.7% of all emergency department presentations ." ], [ "imaging of the facial bones [ figure 1 ] showed a le fort type ii fracture , with comminuted fractures of the roofs of the orbit bilaterally and a depressed fracture of the left orbital floor .", "the patient underwent craniotomy , obliteration of the frontal sinus and open reduction internal fixation ( orif ) of the frontal bone .", "there was also fracture of the right maxilla at the junction of the maxilla and zygomatic arch , extending towards but not involve the right orbital floor . on the left , there was fracture of the anterior part of the left zygomatic arch which extended into the anterolateral wall of the left maxillary sinus .", "orif of the maxilla bilaterally , orif of the infra - orbital rim and supra - orbital rim bilaterally and inter - maxillary screw fixation was also performed .", "imaging of the cervical spine [ figure 2 ] showed an undisplaced fracture of the posterior arch of c1 on the right side and a type 3 dens fracture with posterior displacement of 4 mm but no contact with the spinal cord .", "post - operative ct scans demonstrated complete bony union in the c2 fracture site [ figure 3 ] and uncomplicated fixation of the facial bone fractures [ figure 4 ] ." ], [ "the thinnest and weakest segment of the orbit is the floor , which is the most common site of fracture .", "our patient suffered injuries to multiple sites in the cranium , facial bones and the vertebrae that have previously not reported in the literature .", "our patient had a fracture of the posterior arch of c1 on the right side and a type 3 dens fracture , which required cervical fusion ." ], [ "we report the first case of extensive head and spinal injury resulting from collision with the wall of a squash court .", "the injuries ranged from the frontal bone to the thoracic vertebra and are usually seen in high velocity trauma ." ] ]

[ [ "cdh1 expression is frequently absent in a variety of epithelial tumors , and loss of normal intercellular junctions results in promotion of cancer invasion and metastasis and is correlated with several types of cancers.1517 however , the association between and clinicopathological significance of cdh1 promoter hypermethylation and lung cancer remains unclear . in this study , we systematically investigate studies of cdh1 promoter hypermethylation and lung cancer , and validate the association between cdh1 promoter hypermethylation and lung cancer using meta - analysis methods .", "in addition , we summarize these findings and discuss tumor suppressor function , as well as the clinicopathological significance of cdh1 in lung cancer .", "currently , an enormous amount of research is aimed at understanding the molecular and cellular biology of lung cancer ; however , much more work is needed to better understand the correlation between gene regulation and lung cancer .", "lung cancer is a leading cause of cancer mortality in the usa and other developed countries.1 the two major forms of the disease are non - small cell lung cancer and small cell lung cancer , which account for 85% and 15% of all lung cancers , respectively.2 despite advances in preliminary detection and standard treatment with combination chemotherapy and radiotherapy , the prognosis for patients with lung cancer has not improved significantly in the last 20 years,3,4 and survival rates have changed little over the past 2 decades ." ], [ "two researchers independently collected the information and extracted the data regarding authorship , year , source of publication , inclusion criteria , cdh1 methylation frequency , sex status , smoking history , pathological type , clinical staging , degree of differentiation , lymph node metastasis , epidermal growth factor receptor status , and prognosis in patients and controls .", "a study included for meta - analysis needed to have : evaluated the correlation between cdh1 methylation and lung cancer ; included a clinical cohort and controls ; included at least three patients and controls ; used methylation - specific polymerase chain reaction or quantitative methylation - specific polymerase chain reaction to examine cdh1 methylation and expression ; and used tissue data rather than blood data .", "a systematic literature searching was performed using pubmed , embase , and the web of science up to august 13 , 2014 without any language restrictions .", "the following keywords and terms were used : [ methylation or dna methylation or hypermethylation or de - methylation ] and [ cdh1 or cadherin-1 or cam 120/80 or epithelial cadherin ( e - cadherin ) or uvomorulin ] and [ lung cancer or lung carcinoma or lung tumor ] .", "methodological evaluation was assessed by the researchers according to the remark ( reporting recommendations for tumor marker prognostic studies ) guidelines and elcwp ( european lung cancer working party ) score.18,19 the meta - analysis was performed using reviewer manager 5 ( cochrane collaboration , oxford , uk ) . pooled odds ratios ( ors ) and confidence intervals ( cis ) were calculated to assess the correlation between cdh1 methylation and lung cancer .", "titles , abstracts , and key words in the articles were initially evaluated for inclusion criteria .", "studies that did not meet our inclusion criteria were excluded . when the same groups of patients were reported in multiple papers ,", "cochran s q test and i \n 2 were used to assess heterogeneity among the studies.20 a q test showing p<0.05 or an i \n 2 test > 50% indicated significant heterogeneity and a fixed - effects model was used to calculate the parameters .", "details and additional information were identified and collected from the full text of these articles ." ], [ "the following keywords and terms were used : [ methylation or dna methylation or hypermethylation or de - methylation ] and [ cdh1 or cadherin-1 or cam 120/80 or epithelial cadherin ( e - cadherin ) or uvomorulin ] and [ lung cancer or lung carcinoma or lung tumor ] .", "a systematic literature searching was performed using pubmed , embase , and the web of science up to august 13 , 2014 without any language restrictions .", "the published scientific articles were restricted to english language , and conference abstracts were excluded due to lack of sufficient data .", "details and additional information were identified and collected from the full text of these articles .", "titles , abstracts , and key words in the articles were initially evaluated for inclusion criteria ." ], [ "a study included for meta - analysis needed to have : evaluated the correlation between cdh1 methylation and lung cancer ; included a clinical cohort and controls ; included at least three patients and controls ; used methylation - specific polymerase chain reaction or quantitative methylation - specific polymerase chain reaction to examine cdh1 methylation and expression ; and used tissue data rather than blood data .", "studies that did not meet our inclusion criteria were excluded . when the same groups of patients were reported in multiple papers , only the most recent and complete paper was selected to avoid overlap ." ], [ "two researchers independently collected the information and extracted the data regarding authorship , year , source of publication , inclusion criteria , cdh1 methylation frequency , sex status , smoking history , pathological type , clinical staging , degree of differentiation , lymph node metastasis , epidermal growth factor receptor status , and prognosis in patients and controls .", "methodological evaluation was assessed by the researchers according to the remark ( reporting recommendations for tumor marker prognostic studies ) guidelines and elcwp ( european lung cancer working party ) score.18,19" ], [ "pooled odds ratios ( ors ) and confidence intervals ( cis ) were calculated to assess the correlation between cdh1 methylation and lung cancer .", "cochran s q test and i \n 2 were used to assess heterogeneity among the studies.20 a q test showing p<0.05 or an i \n 2 test > 50% indicated significant heterogeneity and a fixed - effects model was used to calculate the parameters .", "otherwise , a random - effects model was used to pool data and attempt to identify potential sources of heterogeneity based on subgroup analyses.21,22 publication bias was assessed by begg s test and use of funnel plots.23 the analysis of meta - regression and publication bias was performed using stata version 10.0 ( statacorp , college station , tx , usa ) .", "the meta - analysis was performed using reviewer manager 5 ( cochrane collaboration , oxford , uk ) ." ], [ "these findings indicate that cdh1 methylation is a key molecular event in tumor tissue but not in normal tissue .", "the results also show heterogeneity across the included studies ( i \n 2 is 61% , ie , more than 50% ) . given this significant heterogeneity , a subgroup analysis was performed to investigate sex status , smoking history , pathological type , clinical stage , differentiation degree , and lymph node metastasis to observe the relationship between cdh1 methylation and clinical characteristics ( see figure 3 ) .", "this result indicates that the occurrence of cdh1 methylation is higher in tumor tissue than in normal tissue . using the fixed model , meta - analysis showed that 657 cases and 593 controls from 12 studies were pooled or as shown in figure 2 ( or 3.89 , 95% ci 2.875.27 , p<0.00001 ) .", "the characteristics of the studies are shown in table 1.2436 six papers were used to study the correlation between cdh1 methylation and sex status .", "the funnel plot shown in figure 4 is partially symmetric , indicating low publication bias regarding cdh1 methylation in lung cancer .", "five papers provided smoking history data , allowing an investigation of the influence of smoking on cdh1 methylation ." ], [ "we further determined the clinicopathological significance of cdh1 promoter hypermethylation in patients with lung cancer . for smoking history ,", "the results show that the cdh1 methylation level in the cancer group was significantly higher than in the control group . the pooled or using the fixed - effect model was 3.89 ( 95% ci 2.875.27 versus the control group ) .", "although a large number of studies have demonstrated a possible relationship between cdh1 methylation and lung cancer , a meta - analysis can summarize the relevant studies and compare different subgroup characteristics . in this meta - analysis", "cdh1 methylation plays a key role in the induction of lung cancer due to silencing of the tumor suppressor gene cdh1 .", "demonstrate that loss of expression or function of cdh1 can activate transcription factors associated with epithelial - mesenchymal transition , leading to metastasis of cancer cells.37 \n cdh1 methylation has been detected in several types of carcinoma , including breast cancer , gastric cancer , and lung cancer.3840 a comprehensive evaluation of markers of methylation in lung cancer is needed to better understand the relationship between cdh1 methylation and lung cancer .", "hypermethylation of tumor suppressor genes and hypomethylation of oncogenes are two essential components of the molecular mechanism involved in the epigenomic regulation of initiation and progression of cancer . as a tumor suppressor gene ," ], [ "cdh1 methylation might be a biomarker of lung cancer , with potential value in predicting the prognosis of the disease , and warrants further studies involving more clinical cases for meta - analysis in the future .", "in addition , the potential variables on cdh1 methylation from different group database are still not clear due to the limitation of the statistical power of meta - analysis ." ] ]

[ [ "the objective of this study is to quantify ncs repeatability utilizing the nc - stat ( neurometrix , inc . , waltham , massachusetts ) , an automated ncs system [ 810 ] .", "we hypothesized that use of the nc - stat system would yield highly reproducible ncs results .", "inter - tester variability refers to variability of a test parameter measured on a single individual when repeat test measurements are made by two or more examiners .", "potential sources of variation include the use of different emg instruments at different test sessions or sites , inconsistent placement of recording and stimulating electrodes , use of non - standardized distance measurements , use of sub - maximal electrical stimuli , poor skin preparation resulting in high skin impedance , and failure to maintain limb temperature within an acceptable range or to compensate for temperature .", "all these factors may compromise the repeatability of ncs measurement and lead to erroneous diagnostic conclusions . aside from true physiological changes , factors that influence repeatability of ncs measurements", "intra - tester variability refers to variability of a test parameter when repeat test measurements are made by a single examiner . in the absence of physiological changes ,", "nerve conduction studies ( ncs ) are an objective , quantitative , and reproducible measure of peripheral nerve function and are widely used in the diagnosis of neuropathies [ 1 , 2 ] ." ], [ "2sample motor and sensory responses acquired by the nc - stat nerve conduction instrument during the repeatability study for one subject .", ". sample motor and sensory responses acquired by the nc - stat nerve conduction instrument during the repeatability study for one subject .", "the device automatically checked skin impedance and determined the minimum stimulator current needed to deliver a supramaximal stimulus with amplitude ranging from 10 to 100 ma and duration between 100 and 500 s . the evoked compound muscle ( cmap ) or compound sensory nerve ( snap ) action potentials were recorded following a series of supramaximal stimuli .", "waltham , ma , usa ) , an automated ncs instrument . shown in figure 1 is a photograph of the nc - stat system components : pre - fabricated electrode arrays specific to peroneal nerve motor testing ; an electronic monitor to be connected to the electrode arrays for nerve stimulation and waveform acquisition and analysis ; a communication port to transmit data for report generation .", "it consists of three components : pre - fabricated electrode arrays ( biosensor , left panel ) for a peroneal motor nerve conduction study , an electronic monitor ( connected to a biosensor during testing ) , a report generation system ( not shown ) based on electrophysiological data collected and processed by the monitor and transmitted via docking station ( a telecommunication port for secure data transfer via telephone line ) .", "the nc - stat system is fda 510(k ) cleared for the performance of motor studies of the median , ulnar , peroneal and tibial nerves , and sensory studies of the median , ulnar and sural nerves .", "it consists of three components : pre - fabricated electrode arrays ( biosensor , left panel ) for a peroneal motor nerve conduction study , an electronic monitor ( connected to a biosensor during testing ) , a report generation system ( not shown ) based on electrophysiological data collected and processed by the monitor and transmitted via docking station ( a telecommunication port for secure data transfer via telephone line ) .", "the temperature correction factor corrcoef was previously determined in an independent study population ( 150 subjects , data on file ) , which also found dependence of cmap and snap amplitude on temperature to be not statistically significant .", "each study lasted for about 2 weeks to complete the 7-day interval test - retest protocol for 15 subjects . a technician applied pre - fabricated electrode arrays specific to each nerve based on readily identifiable anatomic landmarks .", "top left panel shows the ulnar sensory nerve action potential ( snap ) with distal sensory latency ( dsl ) marked by an open circle .", "top left panel shows the ulnar sensory nerve action potential ( snap ) with distal sensory latency ( dsl ) marked by an open circle .", "the distal sensory latency ( dsl ) was measured from stimulus onset to the initial negative peak ( upward deflection ) of the snap ( open circle in the upper left panel of figure 2 ) .", "distal motor latency ( dml ) was the time difference between stimulus onset and initial negative deflection ( marked as + in the lower left panel of figure 2 ) .", "up to 20 peroneal and tibial f - wave responses ( with 40 traces as a maximum for personal , and 24 traces as a maximum for tibial ) were acquired for lower extremity tests . \n", "bottom left panel shows the ulnar compound muscle action potential ( cmap ) with distal motor latency ( dml ) marked with a plus and negative peak marked with a triangle for peak - to - base amplitude calculation ." ], [ "all were healthy office workers who lacked neurological complaints or known causes of peripheral neuropathy .", "the study was approved and monitored by an independent review board ( copernicus group , cary , nc , usa ) ." ], [ "the nc - stat system is fda 510(k ) cleared for the performance of motor studies of the median , ulnar , peroneal and tibial nerves , and sensory studies of the median , ulnar and sural nerves .", "waltham , ma , usa ) , an automated ncs instrument . shown in figure 1 is a photograph of the nc - stat system components : pre - fabricated electrode arrays specific to peroneal nerve motor testing ; an electronic monitor to be connected to the electrode arrays for nerve stimulation and waveform acquisition and analysis ; a communication port to transmit data for report generation .", "it consists of three components : pre - fabricated electrode arrays ( biosensor , left panel ) for a peroneal motor nerve conduction study , an electronic monitor ( connected to a biosensor during testing ) , a report generation system ( not shown ) based on electrophysiological data collected and processed by the monitor and transmitted via docking station ( a telecommunication port for secure data transfer via telephone line ) .", "2sample motor and sensory responses acquired by the nc - stat nerve conduction instrument during the repeatability study for one subject .", "sample motor and sensory responses acquired by the nc - stat nerve conduction instrument during the repeatability study for one subject .", "it consists of three components : pre - fabricated electrode arrays ( biosensor , left panel ) for a peroneal motor nerve conduction study , an electronic monitor ( connected to a biosensor during testing ) , a report generation system ( not shown ) based on electrophysiological data collected and processed by the monitor and transmitted via docking station ( a telecommunication port for secure data transfer via telephone line ) .", "the device automatically checked skin impedance and determined the minimum stimulator current needed to deliver a supramaximal stimulus with amplitude ranging from 10 to 100 ma and duration between 100 and 500 s . the evoked compound muscle ( cmap ) or compound sensory nerve ( snap ) action potentials were recorded following a series of supramaximal stimuli .", "each study lasted for about 2 weeks to complete the 7-day interval test - retest protocol for 15 subjects . a technician applied pre - fabricated electrode arrays specific to each nerve based on readily identifiable anatomic landmarks .", "up to 20 peroneal and tibial f - wave responses ( with 40 traces as a maximum for personal , and 24 traces as a maximum for tibial ) were acquired for lower extremity tests . \n", "top left panel shows the ulnar sensory nerve action potential ( snap ) with distal sensory latency ( dsl ) marked by an open circle .", "top left panel shows the ulnar sensory nerve action potential ( snap ) with distal sensory latency ( dsl ) marked by an open circle .", "responses were recorded using detector pairs placed along a line between the lateral malleolus and the 3rd toe , over the vicinity of the extensor digitorum brevis muscle ( see figure 1 ) . for tibial nerve testing , stimulating cathode was placed over the posterior tibial nerve just posterior to the medial malleolus . both the active and inactive electrodes were located just distal to the medial malleolus .", "bottom left panel shows the ulnar compound muscle action potential ( cmap ) with distal motor latency ( dml ) marked with a plus and negative peak marked with a triangle for peak - to - base amplitude calculation ." ], [ "the temperature correction factor corrcoef was previously determined in an independent study population ( 150 subjects , data on file ) , which also found dependence of cmap and snap amplitude on temperature to be not statistically significant .", "all ncs parameters were determined by automated computer algorithms [ 7 , 9 , 10 ] . for motor studies , distal motor latency ( dml ) was the time difference between stimulus onset and initial negative deflection ( marked as + in the lower left panel of figure 2 ) .", "the distal sensory latency ( dsl ) was measured from stimulus onset to the initial negative peak ( upward deflection ) of the snap ( open circle in the upper left panel of figure 2 ) .", "all motor and sensory latencies were adjusted for deviation of skin surface temperature from reference values ( 32 c upper extremity , 30 c lower extremity ) with a linear correction formula : latency(corrected ) = latency ( raw))corrcoef(temperature - reference ) .", "f - wave onset latency was identified for each trace with an identified f - wave response ( traces with ", "+ , right panel of figure 2 ) , and their average was reported as the mean f - wave latency ( vertical dotted line ) .", "cmap amplitude was measured baseline to negative peak ( upward deflection , identified by the upper triangle ) based on the averaged cmap .", "the snap amplitude was measured peak to peak ( negative - positive , or vertical distance between open and closed circles ) ." ], [ "the riv is the difference between two tests as a percentage of the average of the two tests . because of the small sample size", ", 10th and 90th percentiles of riv were calculated for all parameters to minimize the impact of outliers . to facilitate comparison , the 5th and 95th percentile values , as reported by others ,", "statistical measures used to quantify ncs repeatability mirrored those used in prior studies [ 2 , 4 , 5 ] . the pearson product - moment correlation ( cc )", "coefficient of variation ( cov ) of test - retest ncs parameters was calculated and the average over all nerves was reported . relative intertrial variation ( riv )", "intraclass correlation coefficient ( icc ) was used to determine the agreement between the two tests .", "the mean and standard deviation of the difference between the test and retest results were also reported .", "paired t - tests were carried out to ensure that two tests yielded ncs parameters with the same mean ." ], [ "dml is the onset of initial deflection and cmap is negative peak to baseline amplitude difference .", "dml is the onset of initial deflection and cmap is negative peak to baseline amplitude difference .", "statistical measures of nerve conduction study parameter repeatability cc : pearson product moment correlation to assess the association between test - retest results .", "dsl is the negative peak latency and snap amplitude is the peak - to - peak amplitude difference .", "dsl is the negative peak latency and snap amplitude is the peak - to - peak amplitude difference .", "fwl is the arithmetic mean of individual f - wave latencies in an f - wave set ." ], [ "several studies ( summarized in table 2 ) have examined ncs parameter repeatability [ 2 , 4 , 5 ] . in , the repeatability of ncs was evaluated for 60 sites participating in a clinical trial , with ncs oversight performed by an experienced , insightful and knowledgeable core lab .", "further studies with longer test - retest intervals and a higher subject count would be valuable in confirming the high reproducibility of ncs parameters measured in this study . extending the study to pathologic nerves and validating the equivalent or superior performance of automated ncs instrument should increase the adoption rate of the automated ncs technology in patient management", "our study yielded similar results , though our study demonstrated a higher cov for peroneal cmap amplitude ( 9% vs. 29.8% ) . in", "it would be valuable to quantify repeatability of the automated ncs instrument in neuropathic nerves . at the time of this study ,", "dml repeatability was less affected by electrode size in both our study and the study of ." ] ]

[ [ "this study was conducted within the north central cancer treatment group , a national cancer cooperative group that is funded in part by the national cancer institute . questionnaire and clinical trial data from two separate cancer therapeutic trials , n9921 and", "a cox proportional hazards model , which adjusted for cancer treatment , performance score , age , gender , and sum of target lesions at baseline , was used to evaluate whether social support scores were related to time - to - cancer progression or overall survival . in order to illustrate the influence of social support on overall survival , we divided the cohort by social support score quartiles .", "nonetheless , for the current study , we conducted a retrospective power calculation for the comparisons of two independent means to evaluate the power available for comparing the lubben social support score by the dichotomous factors of gender , performance score , and severe adverse events .", "these two trials recruited patients between february 2000 and february 2001 and between december 2004 and february 2006 , respectively . the present study s design was formulated prior to the initiation of the first trial and entailed merging and analyzing data from both of these prospectively conducted clinical trials .", "these criteria are described in greater detail elsewhere,14,15 but relevant factors consistent between both trials included the following : 1 ) patient aged 65 years or older ; 2 ) eastern cooperative group performance score ( an often - utilized score that describes the level of function of cancer patients ) of 0 , 1 , or 2 ; 3 ) histologic or cytologic confirmation of non - small cell lung cancer ; 4 ) unresectable cancer ; 5 ) no prior chemotherapy ; 6 ) physician - anticipated life expectancy of 12 weeks or longer ; and 7 ) absence of a major medical illness that would preclude participation in a therapeutic cancer clinical trial .", "a logistic regression model , which adjusted for the same baseline factors mentioned above , was used to assess relationships between social support and adverse events ." ], [ "this study was conducted within the north central cancer treatment group , a national cancer cooperative group that is funded in part by the national cancer institute . questionnaire and clinical trial data from two separate cancer therapeutic trials , n9921 and", "these two trials recruited patients between february 2000 and february 2001 and between december 2004 and february 2006 , respectively . the present study s design was formulated prior to the initiation of the first trial and entailed merging and analyzing data from both of these prospectively conducted clinical trials ." ], [ "these criteria are described in greater detail elsewhere,14,15 but relevant factors consistent between both trials included the following : 1 ) patient aged 65 years or older ; 2 ) eastern cooperative group performance score ( an often - utilized score that describes the level of function of cancer patients ) of 0 , 1 , or 2 ; 3 ) histologic or cytologic confirmation of non - small cell lung cancer ; 4 ) unresectable cancer ; 5 ) no prior chemotherapy ; 6 ) physician - anticipated life expectancy of 12 weeks or longer ; and 7 ) absence of a major medical illness that would preclude participation in a therapeutic cancer clinical trial .", "eligibility criteria for these two trials focused on selecting patients who could tolerate the chemotherapy agents , gefitinib , paclitaxel , and carboplatin , which were used in one or both of the trials mentioned above .", "in addition , all patients had to have had adequate organ function , as demonstrated by an acceptable hemogram , liver function tests , and serum creatinine at the time of study enrollment .", "other eligibility criteria were more specific to each chemotherapy regimen patients were about to receive , such as , for example , an exclusion of patients with severe neuropathy in the event they were to receive paclitaxel ." ], [ "this 12-item instrument has been previously validated , has been tested in a variety of settings , and includes questionnaire items that are highly germane to defining extent of social support.16 thereafter patients were treated with one of the following chemotherapy regimens : 1 ) weekly carboplatin and paclitaxel ( intravenous ) ; 2 ) weekly carboplatin and paclitaxel ( intravenous ) potentially for four months followed by daily gefitinib ( oral ) ; or 3 ) daily gefitinib ( oral ) .", "all eligible patients completed the lubben social network scale within 14 days of trial registration and prior to receiving any chemotherapy .", "patients were to continue cancer therapy until evidence of cancer progression , until unacceptable side effects occurred , or , for a maximum of four months , if they were receiving conventional chemotherapy .", "they were monitored indefinitely for cancer therapy - related side effects by means of the common terminology criteria , version 2 from the national cancer institute.17 tumor response as assessed by the recist criteria,18 and overall survival was assessed ." ], [ "nonetheless , for the current study , we conducted a retrospective power calculation for the comparisons of two independent means to evaluate the power available for comparing the lubben social support score by the dichotomous factors of gender , performance score , and severe adverse events .", "a cox proportional hazards model , which adjusted for cancer treatment , performance score , age , gender , and sum of target lesions at baseline , was used to evaluate whether social support scores were related to time - to - cancer progression or overall survival . in order to illustrate the influence of social support on overall survival , we divided the cohort by social support score quartiles .", "the sample sizes for the two individual trials were calculated to obtain adequate statistical power for the primary aims of these clinical trials , not for the social support aims .", "a logistic regression model , which adjusted for the same baseline factors mentioned above , was used to assess relationships between social support and adverse events .", "a rank sum test was used to evaluate whether social support scores differed based on the characteristics of gender , age ( > = 70 ) , and performance status .", "was based on the computation that the overall conventional alpha level is 0.05 and that seven multiple comparisons were made with a bonferroni adjustment .", "the sample size of 113 ( 56 in each group ) with an observed standard score deviation of 17 and an observed median social support score of 72 yields 84% power to detect a difference of 12 points ( 60 versus 72 ) using a two - sided alpha of 0.007 ." ], [ "a total of 113 patients met the eligibility criteria , received chemotherapy on a clinical trial , and therefore participated in the current study .", "although there was a trend to suggest that higher social support scores ironically predicted a shorter time - to - cancer - progression ( p = 0.02 ; hazard ratio [ hr ] = 1.02 ; 95% confidence interval [ ci ] : 1.001.03 ) , these scores did not predict overall survival ( p = 0.34 ; hr = 1.01 ; 95% ci : 0.991.02 ) ( figure 2 ) .", "it should be noted that , although normative reference data are not readily available , a community - based study among a group of 7,524 older individuals observed a similarly - derived , average social support score of 63.19 among women and men in the present study , the average score was not statistically different : 72 in both ( rank sum , p = 0.87 ) ( figure 1 ) .", "forty - two percent of the cohort consisted of women , and the median age ( range ) was 74 years ( 65 , 91 ) . at the time of study entry , a performance score of 0 , 1 , or 2 was observed in 29% , 55% , and 16% of the cohort , respectively .", "the median transformed social support score for the entire cohort ( range ) was 72 ( 30100 ) ." ], [ "a total of 113 patients met the eligibility criteria , received chemotherapy on a clinical trial , and therefore participated in the current study .", "forty - two percent of the cohort consisted of women , and the median age ( range ) was 74 years ( 65 , 91 ) . at the time of study entry , a performance score of 0 , 1 , or 2 was observed in 29% , 55% , and 16% of the cohort , respectively .", "one patient did not receive chemotherapy , and two did not meet the eligibility criteria described earlier ; thus , these three patients are not included in the analyses ." ], [ "it should be noted that , although normative reference data are not readily available , a community - based study among a group of 7,524 older individuals observed a similarly - derived , average social support score of 63.19 among women and men in the present study , the average score was not statistically different : 72 in both ( rank sum , p = 0.87 ) ( figure 1 ) .", "always have someone who can take them to their medical appointments , and 71% reported that they always have someone from whom they can seek help if they have medication side effects .", "lubben social network scale data are summarized in table 2 . of note , 44% of patients reported that they see nine or more relatives at least once a month , and 27% reported that they see five to eight .", "in addition , 73% reported that when they have an important decision to make , they always have someone to talk with .", "although there was a trend to suggest that higher social support scores ironically predicted a shorter time - to - cancer - progression ( p = 0.02 ; hazard ratio [ hr ] = 1.02 ; 95% confidence interval [ ci ] : 1.001.03 ) , these scores did not predict overall survival ( p = 0.34 ; hr = 1.01 ; 95% ci : 0.991.02 ) ( figure 2 ) .", "additionally , there was no statistically significant difference in social support scores among patients with an eastern cooperative oncology group performance score of 0 versus 1 and 2 : median score 74 and 70 ( rank sum , p = 0.06 ) ." ], [ "the present study was designed to assess and evaluate the role of social support in a group of geriatric non - small cell lung cancer patients who were enrolled in two different cancer therapeutic clinical trials .", "this study found that this cohort of geriatric patients had high levels of social support , as suggested by the fact that 81% reported that they ", "however , social support was not associated with improved survival or diminished side effects from chemotherapy . moreover , no differences were observed between men and women in terms of baseline social support .", "second , although this study found that social support is not associated with clinical outcomes among elderly lung cancer patients , there remains no question that these patients have major needs that are likely exacerbated by a lack of social support ." ] ]

[ [ "we hereby report a case of 41-year - old male patient who acquired pws about a year ago .", "acquired pwss are an uncommon entity developing later in life , but morphologically and histologically similar to the congenital lesions .", "port - wine stains ( pwss ) are congenital vascular malformations comprised of ectatic dermal capillaries and affecting 0.3 - 1% of newborn infants ." ], [ "a 41-year - old male presented to the outpatient department of dermatology of our tertiary care hospital with complaint of asymptomatic reddish patches involving the lower part of right leg for 10 months .", "a diffuse partially blanchable erythema extending from the right ankle and involving the medial aspect of right leg up to the knee discrete irregularly shaped partially blanchable reddish - purple macules present on the anterior aspect of right leg on the basis of the clinical examination , a provisional diagnosis of acquired pws was made and the patient investigated .", "dermatological examination revealed a diffuse partially blanchable erythema extending from the right ankle and involving chiefly the medial aspect of right leg up to the knee [ figure 1 ] .", "the patch started from near the ankle and gradually spread to involve whole of the medial aspect of right leg over a period of 10 months ." ], [ "the case report demonstrates a rare occurrence of a vascular malformation in an adult patient .", "this is the first report of an acquired port - wine stain from india and previous reports of such cases have also been reviewed .", "pwss are congenital vascular malformations usually presenting at birth in the form of pink - red to purple macules , which become darker , raised , and nodular as the person ages .", "although no definite cause could be appreciated for the development of lesion in our patient , further reports and future insights into the pathogenesis of such cases would broaden our knowledge regarding this infrequently reported phenomenon .", "various factors have been proposed for the occurrence of acquired pwss . of these , trauma has been found to be the most important causative factor in majority of the cases ." ] ]

[ [ "of the total 1338 lncrnas identified to be differentially expressed after ldir in either balb / c or spret / eij , 1337 had a significantly correlated expression pattern with at least one mrna that was also differentially expressed after ldir .", "however , the relevance of lncrnas in the cell and tissue response to ionizing radiation has not yet been characterized . in this study , we used agilent sureprint g3 microarrays to profile lncrna and mrna from mammary glands of balb / c mice 2 , 4 , and 8 weeks after irradiation and of spret / eij mice 4 weeks after irradiation with 10 cgy of x - radiation .", "our results indicate lncrnas may exert a partial or key role in the regulation of coding rna expression induced by radiation .", "we identified lncrna and mrna expression signatures for each time point after irradiation in comparison to sham .", "ionizing radiation is a well - known carcinogen in humans , and breast is one of the most sensitive organs to radiogenic cancer .", "we know remarkably little of molecular mechanisms that may be protective or risky for breast cancer after exposure to low - dose ionizing radiation ( ldir ) ." ], [ "mammary tissues were collected for gene expression profile at 2 , 4 , and 8 weeks after irradiation .", "genes that were differentially expressed between sham and irradiated were identified by the unpaired student 's t - test with a p value cut - off of 0.05 ( p value < 0.001 for baseline strain comparison ) and a fold - change criteria of more than 1.5 . for each of the 8 experimental treatment groups , the average expression values of the 3 biological replicates", "significantly correlated pairs of mrna and lncrna were calculated using a standard permutation test . in brief , for each potential mrna and lncrna pair , the 8 mrna values were randomly rearranged and a correlation coefficient was calculated between the 8 mrnas and 8 lncrnas values .", "the p value reported in this work represents the percentage of permutations leading to a higher correlation than the original correlation between the 8 mrnas and 8 lncrnas values . in other words ,", "the lower the p value is , the more likely the mrna and lncrna pair is not randomly associated .", "agilent sureprint g3 mouse ge 8x60k microarrays were used according to the manufacturer 's protocol ( arrays contained 39,430 entrez gene rnas and 16,251 lncrnas ) ." ], [ "to identify potential lncrnas and mrnas that may determine susceptibility to radiation - induced breast cancer , we profiled two inbred strains of mice with differing genetic susceptibilities : balb / c mice as more sensitive and spret / eij as more resistant .", "taken together these data show that ldir induces coordinated changes in lncrna and mrnas and suggests a critical role for lncrnas in mediating the low - dose radiation response .", "we found significant differences in the expression of a number of chemokines including cxcl10 , ccl6 , and ccl25 , which were expressed at higher levels in mammary tissues of the more sensitive and susceptible balb / c mice and which have previously been associated with breast cancer progression when over expressed . to identify lncrna and mrna expression changes induced by low - dose ionizing radiation ( ldir ) , we profiled lncrna and mrna expression from mammary glands of balb / c mice 2 , 4 , and 8 weeks after irradiation and of spret / eij mice 4 weeks after irradiation with 10 cgy of x - radiation . for balb / c mice ,", "our analyses identified significant strain differences in gene expression between balb / c and spret / eij mammary tissues ." ], [ "however , the specific regulatory mechanism of this control requires further investigation , and knock - out and overexpression of the lncrna genes in mice and other model systems should be performed to increase our understanding of the regulatory mechanisms in response to ldir .", "in this study , we demonstrate that genetic background strongly influences the expression of lncrnas and their response to low - dose radiation by transcriptomic analysis of mouse mammary glands using microarrays that contain both lncrnas and coding rnas .", "moreover , the changes in the expression of lncrnas are significantly correlated with the expression of coding rnas , suggesting that lncrnas may coordinate the tissue response to radiation via regulation of coding mrnas .", "we have identified a number of lncrnas that are significantly changed after exposure to ldir at three different timepoints after radiation exposure ." ] ]

[ [ "\n women with psychiatric diseases are treated with antipsychotic medication(s ) with limited evidence to support the safety of their use during pregnancy.olanzapine , a second - generation antipsychotic , is a us food and drug administration pregnancy category c drug with no unequivocal evidence of harm to the fetus.we report the first case of tracheo - esophageal fistula as a possible teratogenic effect of olanzapine exposure . \n" ], [ "there have been reports of congenital anomalies in newborns of mothers exposed to antipsychotic medications during pregnancy [ 14 ] .", "are rarely included in clinical trials , leading to a dearth of data available on the safety of antipsychotic drugs in this population .", "women with psychiatric diseases may become pregnant and are treated with antipsychotics without any proven evidence of safety . due to ethical issues , pregnant women", "olanzapine , a second - generation antipsychotic , is a us food and drug administration ( fda ) pregnancy category c drug [ 3 , 5 ] with no unequivocal evidence of harm to the fetus .", "the possibility of further teratogenic effects of olanzapine can not be ruled out . in this case report , we report the first case of tracheo - esophageal fistula ( tef ) as a possible teratogenic effect of olanzapine exposure ." ], [ "we report the case of a 29-year - old married woman with bipolar disorder with mixed episodes who had been treated with olanzapine in the psychiatric outpatient department of our institute ( lady hardinge medical college , new delhi , india ) for the last 7 years who delivered a full - term female baby with tef in september 2013 .", "1chest x - ray posteroanterior view of the newborn baby , who was born to a mother with antenatal exposure to olanzapine , suggestive of tracheo - esophageal fistula \n chest x - ray posteroanterior view of the newborn baby , who was born to a mother with antenatal exposure to olanzapine , suggestive of tracheo - esophageal fistula" ], [ "we tried to establish the causality between the adverse outcome ( tef ) and use of olanzapine during pregnancy according to the who - umc ( world health organization ", "the current case report of tef associated with antenatal olanzapine exposure demonstrates the need for large clinical studies to generate more conclusive data concerning use of this drug during pregnancy .", "a number of drugs are clearly known to be associated with teratogenicity , such as thalidomide and isotretinoin , but the majority of drugs do not have conclusive data concerning their effect on fetal development and growth . due to strict ethical constraints , at - risk populations ( including pregnant women ) are not included in most clinical trials , limiting the availability of data on the use of drugs ( including antipsychotics ) in these populations , and thus spontaneous reporting of suspected adverse drug effects constitutes an essential tool for generating data on the safety of drugs , especially in the population of pregnant women . according to a retrospective analysis of data from the lilly safety database , of the 610 prospectively identified pregnancies exposed to olanzapine with an available outcome", "uppsala monitoring centre ) adverse drug reaction causality assessment scale and the naranjo causality assessment scale .", "however , a careful literature search revealed a paucity of data on the incidence of tef in children born to women with psychiatric disease and the problem of confounding by indication can not be ruled out .", "it has been proposed that antipsychotics interfere with the action of calmodulin , which has an important role in organogenesis ." ], [ "on the basis of the present case and the literature , it is suggested that antenatal olanzapine exposure may be related to the development of tef in newborns .", "such post - marketing reports are effective tools to disclose the adverse effects of drugs , which are difficult to detect in clinical trials and may factually change the safety status of a drug .", "however , the present case report can only be considered as preliminary evidence and further observational prospective studies of women with antenatal exposure to olanzapine should be conducted to explore the strength of association between tef and olanzapine .", "knowledge of the teratogenic potential of a drug is essential to prevent / reduce the morbidity and mortality associated with a congenital anomaly ( tef in this case ) ." ], [], [], [ "written informed consent was obtained from the infant s father for publication of this case report ." ] ]

[ [ "\n\t\t\t\t olfactory neuroblastoma ( onb ) is a rare malignant tumor arising from the olfactory epithelium of the nasal cavity and the paranasal sinuses .", "additional information regarding the clinical course and outcome was collected from the patients ' charts and phone calls to the patients , their relatives , and their general practitioners . in this study , we have reviewed 19 cases of olfactory neuroblastomas treated over 24-year period and analyzed the clinical features , treatment outcomes , and prognostic factors .", "however most authors believe that craniofacial resection followed by rt offers the gold standard treatment in this disease . despite aggressive therapies , local , regional relapse , and distant metastasis occur frequently and often after extended periods of follow - up .", "the anatomic origin in the superior nasal cavity leads to nonspecific symptoms that make early diagnosis difficult .", "data for this case series were acquired retrospectively from the files of division of medical oncology , cerrahpasa medical faculty , istanbul university .", "onb is mostly a locally aggressive tumor that can spread to lymph nodes but metastatic involvement of bone , bone marrow , and other organs was also reported ." ], [ "the data of nineteen patients of olfactory neuroblastomas treated and followed up between 1986 and 2010 at division of medical oncology , cerrahpasa medical faculty , istanbul university , were analyzed retrospectively .", "patient characteristics , initial symptoms , tumor extent , histologic features , primary therapy , tumor recurrence , and treatments of recurrent disease were determined .", "patients were staged according to the kadish staging system . a single pathologist with expertise in head and neck neoplasms reviewed the histological specimens .", "local ethics committee 's approval and patients ' or their next of kin 's informed consent were taken before the study ." ], [ "survival rates were calculated from diagnosis to the death of the patient using the kaplan - meier life table method .", "treatment response was assessed by clinical examinations and computed tomography ( ct ) or magnetic resonance imaging ( mri ) ." ], [ "as a treatment for recurrence and metastasis , reoperation of primary site plus radiation therapy in 4 patients and radiation therapy alone in 4 patients were offered .", "locoregional recurrence developed in 6 and distant metastasis in 6 patients . during the follow - up period , these groups exhibited distant metastasis to the brain , spinal cord , bone , bone marrow , meninges , and lungs .", "as a part of primary treatment modality 8 patients received ctx , so did the three relapsed patients . ", "the madian age at diagnosis was 46 ( range : 19 to 68 years ) .", "nasal tumor resection in 2 patients , maxillectomy plus orbital exenteration in 1 , and external ethmoidectomy ( ee ) in 1 were also used as surgical treatments . of these 14 patients who underwent surgical tumor resection ," ], [ "onb is a rare malignant tumor that comprises 4,65% of malignant nasal and paranasal tumors .", "the initial histopathologic grade of iii / iv , and involvement of orbita , brain , or bone marrow metastasis were the statistically significant poor prognostic factors , whereas age , sex , and treatment modality were not prognostic factors .", "the reasons for that might be including low number of patients in the study , being 5 distant site metastasis , 4 cervical lymph node metastasis at the time of diagnosis , only one orbital exentration ( although there were 8 orbital involvement ) , and 12 patients exhibiting high grade histology and inability to evaluate surgical margins in resected tumors . in conclusion , advanced tumor stage ,", "the most common symptoms at the initial diagnosis were defined as unilateral nasal obstruction and epistaxis in the literature .", "the cause of this poor result was presentation of 5 patients with distant metastases ( 26% ; 2 brain , 1 bone marrow , 2 other sites ) , 4 patients ( 21% ) with cervical lymph node metastasis , 12 patients ( 63% ) with high - grade histology at the time of diagnosis , and inability to evaluate the surgical margins of the resected tumors .", "there is evidence that histological grade of onb influences biologic behavior , particularly because it relates to disease progression , local recurrence , and metastasis . for the well - differentiated tumors a slower disease progression and less tendency for local recurrence have been described . in our study , the 2-year survival rate of this grade i / ii - iii / iv disease was 16 versus 50% , respectively ." ] ]

[ [ "our results suggest that bir either does not occur or is so infrequent that its role within the concert of dsb repair mechanisms can at best be a minor one in organisms with a large dna content ( > 1 mb ) per chromosome arm .", "unrepaired dsbs are usually lethal for dividing cells due to the subsequent loss of the acentric fragment and the unstable break - end of the centric fragment .", "bir during s phase without resolution of the holiday junction circumvents the dsb , yielding a conservative replication pattern with regard to the broken chromatid distal to the breakpoint . to test whether bir may occur within chromosomes of higher plants after dsb induction" ], [ "only complete metaphase cells were scored for chromatid aberrations : chromatid and isochromatid breaks ( one or both sister chromatids with terminal deletion ) , interstitial deletions , duplication deletion ( the deleted part of one chromatid is inserted into a break of the sister chromatid ) , and reciprocal chromatid translocations .", "the field bean , vicia faba l. , karyotype acb with six large and individually distinguishable chromosome pairs ( dbel et al . , 1978 ) is much more comfortable for aberration scoring than for instance a. thaliana with smaller chromosomes and less mitoses per root meristem .", "about 12 cm long primary roots were incubated for 18 h in aerated hoagland solution , ph 5.5 , containing 1.25 mm hydroxyurea which synchronizes cells by blocking the cell cycle in early s phase . for mutagen treatment during s phase , the roots were incubated for 1.5 h in hoagland solution containing 10 g / ml bleomycin with or without 20 m edu ( invitrogen ) followed by incubation in hoagland solution for 4.5 h and then 0.05% colchicine for 2.5 h ( to arrest metaphases ) before fixation in ethanol : acetic acid ( 3:1 ) overnight .", "alternatively , the root tips were fixed in 4% formaldehyde for 20 min for isolation of metaphase chromosomes ( schubert et al . , 1993 ) and subsequent detection of edu incorporation using the click.it edu imaging kit from invitrogen according to manufacturer 's instruction .", "for scoring of chromatid aberrations , roots were washed for 10 min in distilled water , hydrolyzed for 11 min in 1 " ], [ "none of these chromosomes showed asymmetric labeling up to an arm end as to be expected if the replication fork is stalled at a single - strand break and the 3-break - end recurrently invaded the unreplicated double helix , or if it replicated till the end of the template by unidirectional fork migration ( figure 2a and hastings et al . , 2009 ) .", "the s phase - independent clastogen bleomycin induces dna breaks directly . a dose of 10 g / ml was previously shown to yield chromatid aberrations in up to 30% of the first post - treatment metaphases of field bean root tip meristems ( heindorff et al . , 1987 ) .", "chromatid - type aberrations induced by edu , bleomycin , or both during g2 or s phase in field bean root tip meristems ( summary of two independent experiments ) .", "( c ) interstitial asymmetric chromatid labeling ( arrows ) after bleomycin treatment in the presence of edu during g2 .", "b ) interstitial asymmetric chromatid labeling ( arrows ) after bleomycin treatment in the presence of edu during s phase .", "t = reciprocal translocation , i = isochromatid break , d = interstitial deletion , b = chromatid break , see figure 3a ." ], [ "the s phase - independent clastogen bleomycin induces dna breaks directly . a dose of 10 g / ml was previously shown to yield chromatid aberrations in up to 30% of the first post - treatment metaphases of field bean root tip meristems ( heindorff et al . , 1987 ) .", "t = reciprocal translocation , i = isochromatid break , d = interstitial deletion , b = chromatid break , see figure 3a .", "chromatid - type aberrations induced by edu , bleomycin , or both during g2 or s phase in field bean root tip meristems ( summary of two independent experiments ) .", "the same bleomycin concentration applied for 1.5 h to ( mainly ) g2 cells of root tip meristems , in two independent experiments yielded on an average of 14.8% of metaphases with chromatid aberrations ." ], [ "none of these chromosomes showed asymmetric labeling up to an arm end as to be expected if the replication fork is stalled at a single - strand break and the 3-break - end recurrently invaded the unreplicated double helix , or if it replicated till the end of the template by unidirectional fork migration ( figure 2a and hastings et al . , 2009 ) .", "right cell : interstitial deletion ( arrow ) , the deleted fragment remains attached to the undamaged sister chromatid , the chromosome involved is surrounded by black dots . ( b ) interstitial asymmetric chromatid labeling ( arrows ) after bleomycin treatment in the presence of edu during s phase .", "no chromosome showed asymmetric labeling up to the chromosome end , i.e. , an unlabeled terminal region of one of the sister chromatids .", "no chromosome showed asymmetric labeling of one chromatid up to the arm end , as expected in the case of a conservative bir ( figure 2b ) .", "also symmetric terminal labeling of sister chromatids , as expected in the case of semiconservative bir ( figure 2c ) was not observed .", "( c ) interstitial asymmetric chromatid labeling ( arrows ) after bleomycin treatment in the presence of edu during g2 ." ], [ "if bir occurs in higher plants in the same way as postulated for yeast ( i.e. , as replication extending from the break position up to the corresponding chromosome arm end ) conservative replication in s or g2 ( figures 2a , b ) or semiconservative replication in g2 ( figure 2c ) should be detectable .", "however , in a number of chromosomes corresponding to 308 s and g2 cells , treated simultaneously with the chromosome - breaking agent bleomycin and the base analog edu , not a single chromosome showed a labeling pattern indicative of bir . in budding yeast , more than half of diploid cells repair ho - endonuclease - induced dsbs by bir using the homologous chromosome as template ( bosco and haber , 1998 ) ; meaning more than half of the dsbs", "are repaired via bir if the endonuclease ho causes one dsb per diploid yeast cell .", "taken together these arguments imply that the existence of a bir pathway in higher eukaryotes is unlikely ." ], [ "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 experimental approaches used in the \n identification of the pacemaker , key enzymes , bottlenecks .", "thus , any metabolic pathway can be a potential \n therapeutic target . in the absence of a solid \n theoretical background that may build a strategy for the rational design of \n drugs ,", "the \n answer to this question seems obvious when three broad areas of research and \n development are identified in which manipulation of metabolic pathways is \n relevant : ( a ) drug design to treat diseases , ( b ) genetic engineering of \n organisms of biotechnological interest , and ( c ) genetic syndromes therapy ." ], [ "for example , inspection of the glycolytic pathway ( teleological approach ) suggests that \n hexokinase ( hk ) and phosphofructokinase-1 ( pfk-1 ) ( which are at the beginning \n and after a branch of the pathway ) are the key steps of glycolysis .", "both gapdh activity and flux showed \n identical titration curves , leading to the conclusion that gapdh was the \n rate - limiting step of glycolysis in streptococcus lactis and s. cremoris ( see , \n however , section 3.2 ; glycolysis in lactobacteria below ) . all together , these results constitute \n the main reason why many intermediary metabolism researchers , including the \n authors of biochemistry text books , have proposed hk , pfk-1 , and pyk as the \n rate - limiting steps of glycolysis . in \n consequence , to vary the glycolytic flux , one of these enzymes has to be \n modified .", "the use of the enzyme cooperativity approach has established that the regulatory \n steps of glycolysis are ( i ) pfk-1 and pyk because they are allosteric enzymes \n and ( ii ) hk because it is inhibited by its products ( g6p and adp , or amp as an adp - analogue ) . \n the application of the crossover theorem \n ( approach no .", "v ) to glycolysis has shown a consistent variation in the pfk-1 substrate \n ( f6p ) and product ( f1,6bp ) ." ], [ ". however , \n when the methodological development of genetic engineering allowed modulating the \n expression of enzymes within cells , researchers turned to the rate - limiting \n step concept to manipulate a metabolic pathway to increase flux and/or its \n intermediates , hypothesizing that the overexpression of only one , or of a few \n key glycolytic genes , should increase the flux .", "metabolic modeling has shown that only with \n the incorporation of the consuming reactions of the pathway end products , a true \n steady state can be established . in \n conclusion , without a solid theoretical framework , the overexpression of only \n one enzyme ( the rate - limiting step ) , or of many arbitrarily selected enzymes \n ( tables 1 and 2 ) , the problem of increasing the flux or metabolite \n concentrations can not be solved .", "the feedback inhibition of -ecs has led several researchers to propose \n that this enzyme is the rate - limiting step of gsh synthesis [ 3335 ] .", "there are some successful examples of the genetic engineering approach to manipulate \n metabolism : overexpression \n ( approx .", "gsh is \n involved in the oxidative stress processing , xenobiotic detoxification , and , in \n some plants and yeasts , in the inactivation of toxic heavy metals ( for a recent \n revision see ) ." ], [ "the kinetoplastid parasites trypanosoma \n cruzi , trypanosoma brucei , and leishmania are the causative agents of \n chagas disease , african trypanosomiasis , and leishmaniasis , respectively . the \n available drugs to treat these diseases are highly toxic for humans .", "several glycolytic enzymes are overexpressed in \n at least 70% of human cancers . except \n for glucose transporter 1 ( glut-1 ) , the other 11 glycolytic enzymes ( hk to ldh ) \n are overexpressed in brain and nervous system cancers .", "prostate and lymphatic nodule cancers ( hodgkin \n and non - hodgkin lymphomas ; myelomas ) overexpress 10 glycolytic enzymes ( except \n for hk ; in prostate cancer glut1 is also overexpressed ) .", "in \n fact , most of the antioxidant metabolism of these parasites depend on tsh2 ( figure 3 ) [ 69 , 70 ] . thus , the enzymes of this metabolic pathway have been \n proposed as drug targets for killing the parasites ." ], [ "this analysis establishes a \n theoretical framework that explains the results observed with the enzyme \n overexpression and downregulation experiments . in addition , it helps to identify and design \n experimental strategies for the manipulation of a given process in an organism \n ( heavy metal hyperaccumulation ; increased production of ethanol , co2 , \n lactate or acetate ; or inhibition of a metabolic pathway flux with therapeutic \n purposes ) .", "several experimental strategies have been \n developed to determine cvi : \n formation of heterokarionts and heterocygots ( classical genetics),titration of flux with specific inhibitors , elasticity analysis , mathematical modeling ( in \n silico biology),in vitro reconstitution of metabolic pathways , genetic engineering to manipulate in vivo protein levels . \n ", "formation of heterokarionts and heterocygots ( classical genetics ) , titration of flux with specific inhibitors , mathematical modeling ( in \n silico biology ) , in vitro reconstitution of metabolic pathways , genetic engineering to manipulate in vivo protein levels .", "modeling requires the consideration of all \n reported experimental data and interactions that have been described for the \n components of a specific pathway , thus allowing for the integration of disperse \n data , discarding irrelevant facts . although all models are oversimplifications of complex cellular \n processes , they are useful for the deduction of essential relationships , for \n the design of experimental strategies that evaluate the control of a metabolic \n pathway , and for the detection of incompatibilities in the kinetic parameters \n of the participating enzymes and transporters , which may prompt the \n experimental revision of the most critical uncertainties . with \n", "different \n experimental approaches have been developed to detect and direct what has to be \n done and measured , in order to identify and understand why an enzyme exerts a \n significant or a negligible control on flux and metabolite concentration in a \n metabolic pathway ." ] ]

[ [ "the present review focuses on spindle burst activity in the cerebral cortex of the developing rat during the first postnatal week and summarizes our current understanding ( i ) on the functional properties of spindle bursts , ( ii ) the mechanisms underlying their generation , ( iii ) the synchronous patterns and cerebral networks associated with spindle bursts , and ( iv ) the physiological and pathophysiological role of spindle bursts during early cortical development .", "network - driven spindle - like oscillations are a functional hallmark of the developing cerebral cortex . during late prenatal and early postnatal stages of development ,", "spontaneous spindle - like oscillations have been identified as physiological activity patterns in various neocortical areas of different mammalian species [ 14 ] . in humans ," ], [ "two distinct activity patterns can be observed in the neonatal rat cerebral cortex in vivo : gamma oscillations and spindles bursts ( figures 1 and 2 ) [ 1419 ] .", "these data further support the hypothesis that spindle bursts in developing cerebral cortex fulfill an important role in the maturation of the neocortical architecture . in the next section we will discuss the network and molecular mechanisms underlying the generation of spindle bursts in neonatal cerebral cortex .", "selective removal of the subplate in s1 in vivo causes a significant decline in the occurrence of spontaneous spindle bursts and disturbances in the development of the cortical architecture in the barrel cortex ." ], [ "is in contrast to previous observations , which demonstrated that dissection of neocortical inputs fails to suppress muscle twitches in rat pups . in summary , these data indicate that neocortical spindle bursts in newborn rodents ( and delta brushes in human fetus during the third trimester or in preterms ) are generated by central pattern generator ( cpg ) circuits in spinal cord , brainstem , and motor cortex ( for cpg circuits in mature brain see [ 4244 ] ) .", "simultaneous multielectrode recordings in the barrel cortex and in the ventral posteromedial nucleus ( vpm ) of the somatosensory thalamus of p0-p1 rats in vivo have demonstrated that the majority of spontaneous cortical spindle bursts and also gamma oscillations are not generated within s1 , but rather in subcortical structures or outside of s1 ( figures 4(a ) and 4(b ) ) . at this age a local , functionally defined lesion in the vpm blocks the whisker stimulation - induced cortical responses and also profoundly reduces the spontaneously occurring cortical burst activity , further demonstrating that the majority of the spontaneous spindle bursts in p0-p1 rat barrel cortex are generated in subcortical structures of the whisker - to - barrel cortex pathway ( for further information see ) . silencing the sensory periphery by injection of lidocaine into the whisker pad causes a significant reduction in the occurrence of spontaneous spindle bursts and gamma oscillations by ~50% ( figure 4(c ) ) , indicating that during this developmental period at least half of the spontaneous burst activity in s1 is related to activity in the sensory periphery .", "spindle bursts in the cerebral cortex of newborn rats can be elicited [ 34 , 35 ] and modulated by cholinergic mechanisms . in vitro , spindle burst - like oscillations can be reliably induced by activation of muscarinic acetylcholine receptors , predominantly of the m1 and m5 type . in vivo ,", "neuropharmacological studies provided insights into the molecular mechanisms underlying the generation and modulation of neocortical spindle bursts . in vivo and in vitro data suggest that gabaergic synapses are not crucial for the generation of spindle bursts or spindle burst - like activity , respectively , but are essential for their spatial confinement to a cortical ( pre- ) column ." ], [ "as discussed above , spatially confined spindle bursts in newborn rat cortex synchronize a local neuronal network resembling a neocortical ( pre- ) column ( figure 3 ) . beside these intra - areal synchronization", "in unanesthetized newborn rats callosotomy doubled the occurrence of spontaneous spindle bursts , suggesting that the corpus callosum modulates functionally inhibitory interactions between homotopic regions in both hemispheres during the occurrence of spindle burst activity .", "the same authors demonstrate that the hippocampus drives this early activity in the prefrontal cortex . beside this intrahemispheric synchronization between different cortical regions , spindle bursts", "this interhemispheric communication of spindle burst activity depends on an intact corpus callosum . in this regard ," ], [ "an increasing amount of experimental and clinical data strongly indicate that spindle bursts play an important role in the physiological development of the cerebral cortex .", "experimental evidence indicates that spindle bursts may be particularly suited to interfere with early neurodevelopmental processes , and thus disturbances in spindle burst activity may cause long - term structural and functional disorders . at early stages of development spontaneous and sensory - evoked activity patterns", "influence a variety of developmental processes , such as neurogenesis , apoptosis , neuronal migration , cellular differentiation , network formation , and myelination ( for review , see ) .", ", these experimental data suggest that any disturbances in the spontaneous activity of the developing cerebral cortex ( including spontaneous spindle bursts ) induce acute dysfunctions , which may cause long - term disorders ." ], [ "while it is generally accepted that early electrical activity shapes the maturation of neocortical circuits , it remains an open question whether the specific properties of spindle burst are required or fulfill a distinct role in development . in this regard , it is possible that the spatiotemporal patterns of spindle bursts translate into a local molecular signal which fulfills an important developmental role . in particular", "thus , one reason for the coexistence of spindle bursts and gamma oscillations during early postnatal development might be a distinct role in neocortical maturation .", "another unresolved issue is that both spindle bursts and gamma oscillations can be observed during the same period of early development .", "they can be observed in early postnatal rodent brain from the day of birth (; also see ) and occur spontaneously as well as after sensory stimulation . moreover ," ], [ "spatially confined spindle bursts and delta brushes represent the most prominent physiological activity patterns in the developing cerebral cortex of newborn rodents and preterm human infants , respectively .", "however , it remains to be studied in more detail how exactly spindle bursts influence the maturation of the cortex and how a potential long - term dysfunction due to disturbances in spindle burst activity can be prevented by early intervention .", "spontaneous and stimulus - evoked spindle bursts can be observed in various neocortical areas of different mammalian species and play important roles in the early development of cortical networks .", "since this important type of brain activity is already present in the human fetus in utero ( either spontaneously occurring or related to sensory inputs from the uterine environment ) , a better understanding of the physiological relevance of spindle burst oscillations is of major clinical relevance ." ] ]

[ [ "the high incidence of atrazine to contaminate water resources and the increasing concern about the toxicological properties of atrazine has made researches directed toward bioremediation of atrazine in polluted sites . therefore , the main objectives of this research are evaluating the effects of carbon and nitrogen sources on atrazine biodegradation using mixed bacterial consortium isolated from corn field soil located in south of shiraz ( kavar ) and determining the efficiency of atrazine biodegradation process in soil culture .", "kavar corn field soil with a long history of atrazine application in fars province of iran has been explored for their potential of atrazine biodegradation .", "since fars is an agricultural province and enjoys the top rank in wheat and corn production in the country in recent years , atrazine has been widely used as a selective herbicide to control broad - leaf and grassy weeds in agricultural corn fields .", "therefore , several applications of atrazine on soil resulted in an enhancement of atrazine degradation .", "atrazine has long - term reproductive and endocrine - disrupting effects and a probable human carcinogen ." ], [ "soil samples for liquid cultures were taken from south of shiraz ( kavar ) corn field with a long history of atrazine application ( more than 10 years ) in fars province .", "atrazine recovery percent from soil with this method of extraction was 98% . in order to isolate mixed bacterial consortiums capable of growth on atrazine as a carbon source ,", "after 10 days , the remained atrazine was measured . to measure the influence of nitrogen sources on the efficiency of atrazine biodegradation by the bacterial consortium in liquid culture , nitrogen sources as routine fertilizers were added to atrazine mineral salt broth containing sucrose and sodium citrate .", "after one day of incubation to allow herbicide sorption to the soil , inoculation with 300 l phosphate buffer containing the selected bacterial consortium was added to soil to yield 7.5 10 bacterial cell g soils as determined by plating on soil extract agar .", "a laboratory experiment was arranged to measure the influence of ph on the efficiency of atrazine biodegradation by the bacterial consortium in liquid culture ." ], [ "the rate of atrazine biodegradation for ammonium nitrate decreased quickly when the concentration of ammonium nitrate increased from zero to 600 kg ha soil , after that the reduction rate of atrazine degradation was getting slower .", "by using a mixed bacterial consortium with a high capability of atrazine degradation isolated from kavar corn field soil , the effect of different carbon sources on atrazine biodegradation was studied ( figure 1 ) . according to this figure ,", "the percent of atrazine biodegradation rate decreased from 87.72% to 29.58% as the ammonium nitrate concentration increased from 0.0 to 900 kg ha soil ." ], [ "results of this study suggested that atrazine bioremediation in soil utilizing atrazine - degrading bacterial consortium could be accomplished across a wide range of atrazine concentration if the soil moistures swere enough and also nutrient availability was balanced , too .", "carbon sources of sodium citrate and sucrose had the highest atrazine biodegradation rate . according to data ,", "enhanced atrazine biodegradation rates occurred with an increase in soil moisture from 7% to 25% .", "atrazine degradation exhibited a half - life of approximately 21.13 d. in conclusion , our results confirmed that atrazine biodegradation was higher in liquid cultures than soil .", "therefore , it is highly recommended that the feasibility of atrazine degradation to be studied by the bioaugmentation of mixed bacterial isolates to the real contaminated soil .", "the bacterial consortium with the ability to degrade atrazine provided a good opportunity for increasing the degradation rate of this herbicide through bioaugmentation ." ] ]

[ [ "therefore , in this study , we determined the expression pattern of olig1 in neural cells during rat spinal cord development .", "exploring temporal and spatial expression and distribution of olig1 will contribute to our understanding of the role of olig1 in specialization of neural cells during development .", "although it is widely known that olig1 promotes the differentiation and maturation of ols , it is unclear how these occur during development .", "however , studies investigating the expression and function of olig1 in development and disease are limited ." ], [ "eighty rats were randomized to eight groups and subgroups : embryonic day 14.5 ( e14.5 ) ( n=10 ) , e18.5 ( n=10 ) , postnatal day 0 ( p0 ) ( n=10 ) , p3 ( n=10 ) , p7 ( n=10 ) , postnatal 2 weeks ( p2w ) ( n=10 ) , p4w ( n=10 ) , and adults ( n=10 ) .", "western blot was used to detect the expression of olig1 in rat spinal cord tissues at different developmental stages .", "spinal cords from embryos ( e14.5 and e18.5 ) were dissected following cervical dislocation of the pregnant rats .", "was designated as day 0.5 ( when vaginal plugs in female rat were observed ) .", "the spinal cords were immunohistochemically stained , and in the second subgroup ( n=5 ) , the spinal cords were subjected to western blot .", "each group was randomized into two subgroups equally . in the first subgroup ( n=5 ) ,", "at least five randomly selected fields with a total of more than 500 cells were counted . in all experiments ," ], [ "eighty rats were randomized to eight groups and subgroups : embryonic day 14.5 ( e14.5 ) ( n=10 ) , e18.5 ( n=10 ) , postnatal day 0 ( p0 ) ( n=10 ) , p3 ( n=10 ) , p7 ( n=10 ) , postnatal 2 weeks ( p2w ) ( n=10 ) , p4w ( n=10 ) , and adults ( n=10 ) .", "spinal cords from embryos ( e14.5 and e18.5 ) were dissected following cervical dislocation of the pregnant rats .", "was designated as day 0.5 ( when vaginal plugs in female rat were observed ) .", "the spinal cords were immunohistochemically stained , and in the second subgroup ( n=5 ) , the spinal cords were subjected to western blot .", "each group was randomized into two subgroups equally . in the first subgroup ( n=5 ) ,", "all experimental protocols involving animals and their care were approved by the ethics committee of laboratory animal services center of bengbu medical college . to produce embryonic and newborn rats , one female was cohabited with two males , and gestational age ( embryo , e )" ], [ "at least five randomly selected fields with a total of more than 500 cells were counted . in all experiments ,", "the next day , the slides were washed in pbs three times and incubated with rhodamine - conjugated goat anti - mouse igm , igg or goat anti - rabbit igm , igg ( all 1:200 ; jackson immunoresearch lab , west grove , pa , usa ) for 1 hour at 37c .", "the slides were washed three times with pbs and coverslipped with gel aqueous mounting media ( biomeda , foster city , ca , usa ) containing hoechst 33342 ( sigma - aldrich ) to counterstain the nuclei .", "for immunohistochemistry staining , the frozen slides were air - dried at room temperature ( rt ) for 10 minutes and rinsed with pbs for 10 minutes .", "they were blocked with 10% donkey serum in tris - buffered saline ( tbs ) containing 0.3% triton x-100 ( tbst ) for 1 hour at rt .", "the following primary antibodies were used : monoclonal mouse anti - olig1 ( igg , 1:100 , millipore , billerica , ma , usa ) , monoclonal rabbit anti - myelin basic protein ( anti - mbp ; 1:300 , millipore ) , rabbit anti - glial fibrillary acidic protein ( anti - gfap ; 1:100 , millipore ) , monoclonal mouse anti - o4 ( igm , 1:100 , millipore ) , and rabbit anti--tubulin ( 1:100 , millipore ) ." ], [ "western blot was used to detect the expression of olig1 in rat spinal cord tissues at different developmental stages . briefly , tissue selected from the same segment of spinal cord was immediately transferred to a homogenizer containing 1 ml lysis buffer and 10 l phenylmethanesulfonyl fluoride ( pmsf ) ( 10 mg / ml ) and thoroughly homogenized for 5 minutes on ice , and then centrifuged at 12,000 g for 30 minutes at 4c to collect the supernatant .", "the intensity of immunoreactive bands for olig1 protein was normalized by the intensity of -actin .", "the protein concentration was determined using the bio - rad dc protein assay ( every 10 l sample contain 120 g protein ) .", "the protein concentrations of the supernatant were determined using a bca protein assay kit ( pierce , rockford , il , usa ) .", "films were digitized , and densitometry was performed using gel - pro analyzer ( media cybernetics , silver spring , md , usa ) ." ], [ "the data with three or more groups were analyzed by one - way analysis of variance ( anova ) followed by post hoc tukey s t - test to determine whether there were significant differences between individual groups .", "the data were analyzed using spss16.0 ( ibm , armonk , ny , usa ) software ." ], [ "western blot was used to determine olig1 expression in the rat spinal cord from e14.5 to adulthood .", "our results showed a significant change in the expression of olig1 protein in rat spinal cord at different developmental time points .", "we also analyzed subcellular localization of olig1 in neural cells and found that olig1 was localized in the cytoplasm of coexpressed cells at all time points during rat spinal cord development .", "furthermore , we failed to observe expression of mbp in the spinal cord during the embryonic period ( data not shown ) .", "our results showed that olig1 was expressed in both o4-positive oligodendrocyte progenitor cells ( opcs ; figure 2 ) and -tubulin - positive neurons ( figure 3 ) at all time points .", "however , interestingly , the expression of olig1 increased again from p2w to a high level until adulthood ( figure 1 ) .", "to determine the expression and localization of olig1 in different types of neural cells , we performed double immunostaining using the antibody against olig1 and another antibody against o4 , mbp , -tubulin , and gfap , respectively ." ], [ "western blot was used to determine olig1 expression in the rat spinal cord from e14.5 to adulthood .", "however , interestingly , the expression of olig1 increased again from p2w to a high level until adulthood ( figure 1 ) .", "our results showed a significant change in the expression of olig1 protein in rat spinal cord at different developmental time points ." ], [ "our results showed that olig1 was expressed in both o4-positive oligodendrocyte progenitor cells ( opcs ; figure 2 ) and -tubulin - positive neurons ( figure 3 ) at all time points .", "to determine the expression and localization of olig1 in different types of neural cells , we performed double immunostaining using the antibody against olig1 and another antibody against o4 , mbp , -tubulin , and gfap , respectively .", "furthermore , we failed to observe expression of mbp in the spinal cord during the embryonic period ( data not shown ) .", "we also analyzed subcellular localization of olig1 in neural cells and found that olig1 was localized in the cytoplasm of coexpressed cells at all time points during rat spinal cord development .", "mbp expression was not observed prior to p3 , and no cellular coexpression of mbp and olig1 was observed ( figure 4 ) .", "the coexpression of gfap and olig1 was observed at e14.5 but absent from day e18.5 to adulthood ." ], [ ", we systematically investigated the expression pattern of olig1 in neural cells during rat spinal cord development .", "first , using the western blot , we demonstrated the differential expression of olig1 in rat spinal cord development .", "however , the distribution and expression of olig1 in neural cells during development is unclear . in this study", "olig1 expression increased and peaked at e18.5 , which may contribute to the differentiation of a large number of neural cells into opcs and mn precursors at this stage .", "recently , it has been reported that olig1 protein expression was significantly decreased during mouse ol progenitor differentiation.18 however , the expression of olig1 increased again from p2w , which was consistent with a recent report that olig1 was expressed in human ols during process outgrowth and maintained at a high level prior to myelination.19 next , we identified the expression of olig1 in neural cells at several time points during spinal cord development ." ], [ "olig1 was localized in the cytoplasm of o4- or -tubulin - positive cells during the transition from e14.5 to adult .", "our results contribute to understanding the mechanism of developmental regulation of neural cells by olig1 .", "in conclusion , we systematically explored the expression pattern of olig1 in neural cells during rat spinal cord development .", "our results showed that olig1 was coexpressed with o4-positive opcs and -tubulin - positive neurons at all time points during development ." ] ]

[ [ "the purpose of \n this study was to apply joint mobilization and therapeutic exercise to the cervical spine \n and upper spine , investigate the effects on functional impairments caused by the neck pain , \n and examine differences between groups by comparing the intervention group with the group to \n which only therapeutic exercises were applied .", "neck pain is a common musculoskeletal disorder in modern society that can produce severe \n pain .", "recent evidence - based studies report that treatment combining \n therapeutic exercise and manual therapy is more effective18 , but research of combined interventions is sparse .", "neck pain occurs in the upper thoracic \n spine area including the shoulder , and it is mechanical pain caused by bad postures and \n habits in most cases3 . according to \n sharon , the upper thoracic spine is involved in the physiologic motion of the neck4 ." ], [ "after the pretest , group i performed therapeutic \n exercise and group ii performed both therapeutic exercise and joint mobilization for 60 \n minutes a day , three times a week for two weeks under the guidance of a physical therapist . \n", "group i ( therapeautic exercise ) , group ii ( mobilization & therapeautic \n exercise ) therapeutic exercises involved enhancing mobility , stability and muscular strength of the \n neck , improving proprioception , and performing reeducation of movement , and the intensity of \n exercises was adjusted according to the physical abilities of the individuals . for the joint \n mobilization ,", "group i was the therapeutic \n exercise group , and group ii was the group to which joint mobilization was applied in \n combination with therapeutic exercise ( table \n 1table 1.general characteristics of the subjects ( n=18)group igroup iigender ( female)99age ( years)58.0 1.659.0 2.4height ( cm)158.0 3.9157.0 4.7weight ( kg)58.0 4.659.0 6.6values are expressed as mean sd . * significant difference between pre - post test ( p<0.05 ) .", "the pretest included the visual analog scale ( vas ) , neck disability index \n ( ndi ) , active cervical range of motion ( acrom ) , static balance ability , muscle tone of the \n upper trapezius , and respiratory function .", "group i ( therapeautic exercise ) , group ii ( mobilization & therapeautic \n exercise ) ) .", "the subjects were \n randomly assigned to one of two groups of nine people each .", "afterwards , passive physiological intervertebral movement ( ppivm ) testing and \n passive intervertebral accessory movement ( paivm ) test were conducted to find which joints \n had restricted or excessive movement , and determine where joint mobilization would be \n applied . the vas was employed to measure the intensity of pain19 , the ndi was used to measure neck pain disability20 , and crom instrument to assess the \n cervical range of motion21 . in order to \n check static balance ," ], [ "the acrom increased significantly in both groups , and group ii \n improved significantly more on the right lateral flexion and rightward rotation than group i \n ( table 4table 4.active cervical range of motion of the subjects ( )group igroup iiflexionpre49.2 8.748.9 4.7post54.2 4.5 56.1 6.8*extensionpre54.9 4.356.4 4.9post 64.3 3.2 * 67.6 3.9*rt .", "vas and ndi led to significant changes in both groups , and group ii improved significantly \n more than group i ( tables 2table 2.visual analog scale of the subjectsgroup igroup iipre4.8 0.44.9 0.3post2.7 0.5 * 1.4 05**significant difference between pre - post test ( p<0.05 ) .", "muscle tone in the left and right upper trapezius muscle improved \n significantly in both groups , and there was no difference between groups ( table 7table 7.muscle tone of the subjectsgroup igroup iirt ." ], [ "joint mobilization and therapeutic exercise for functional impairments \n caused by chronic neck pain significantly improved several types of functional impairment . \n", "research related to neck pain suggests \n that there are more efficient interventions based on evidence through systematic reviews , \n and the interventions combining manual therapy and therapeutic exercise are described as \n more effective in recent literature18 . in \n this study , therapeutic exercises were conducted that are reported to be effective for \n patients with mechanical neck pain , namely , stretching exercise for the neck and upper \n limbs , static and dynamic stability exercise , strengthening exercise , and exercise \n reeducation14 .", "chronic neck pain patients suffer diverse functional impairments , including a deterioration \n of balance ability , respiratory function , range of joint motion , and proprioception11 .", "in addition , in the group to which both joint mobilization and therapeutic exercise were \n applied , significantly more improvement in the pain index , neck disability levels , and acrom \n was seen than in the group that received only therapeutic exercise ." ] ]

[ [ "adss obtained de - identified data for the entire population of alberta from alberta health and wellness administrative databases ( discharge abstract database , alberta physician claims data , ambulatory care classification system and vital statistics ) .", "odds ratios ( or ) and 95% confidence intervals were calculated and used to compare the likelihood of being a prevalent case and incident case of diabetes for the 2 populations in 2007 . or 95% confidence intervals that did not include the null value of 1.00 were considered statistically significant with a 5% error . to examine trends over time , average annual percent changes ( aapc ) in prevalence and incidence from 1995 to 2007 were determined and compared using joinpoint version 3.4.2 ( rockville , md ) for crude values .", "incidence was determined using the following formula : total number of youth with a diabetes incident date for in calendar year/(total population count for calendar year)(prevalent diabetes cases)+(incident diabetes cases ) .", "prevalence was determined using the following group - specific formula : total number of youth with diabetes in the calendar year / the total population for the calendar year .", "the first year in which an individual met the criteria for diabetes ( with no diabetes claims in the preceding 2 years ) was considered an incident year , and considered a prevalent case in subsequent years ." ], [ "the denominators were based on the health insurance registry ( which provincial law requires all residents and dependants to register ) for the entire population as of june 30 in each year . the first year in which an individual met the criteria for diabetes ( with no diabetes claims in the preceding 2 years )", "odds ratios ( or ) and 95% confidence intervals were calculated and used to compare the likelihood of being a prevalent case and incident case of diabetes for the 2 populations in 2007 . or 95% confidence intervals that did not include the null value of 1.00 were considered statistically significant with a 5% error . to examine trends over time , average annual percent changes ( aapc ) in prevalence and incidence from 1995 to 2007 were determined and compared using joinpoint version 3.4.2 ( rockville ,", "prevalence was determined using the following group - specific formula : total number of youth with diabetes in the calendar year / the total population for the calendar year .", "incidence was determined using the following formula : total number of youth with a diabetes incident date for in calendar year/(total population count for calendar year)(prevalent diabetes cases)+(incident diabetes cases ) .", "the aapc provides a relative summary measure of the trend over a pre - specified fixed interval .", "tests of parallelism were then performed to determine if trends over time differed by group or sex ." ], [ "crude rates of diabetes among status aboriginal and general population youth in alberta , 19952007 ( adss ) . a = prevalence ; b = incidence .", "based on alberta health and wellness administrative databases , 853,733 youth ( 51.2% male ) were living in the province as of 2007 , of which 50,930 were status aboriginal ( 51.2% male ) . among these youth", "the 2007 crude prevalence rate of diabetes was 0.27 and 0.31% in the status aboriginal and general population youth populations respectively ( fig . 1 , table i ) .", "crude diabetes prevalence and incidence among status aboriginal and general population youth , 2007 crude rates of both diabetes prevalence and incidence increased in status aboriginal and general population youth over the observation period ( fig . 1 , table ii ) .", "a total of 2,589 prevalent diabetes cases were apparent in 2007 , with 140 cases occurring amongst status aboriginal youth ." ], [ "status aboriginal youth , males in particular , experienced a disproportionate growth in diabetes . if unabated , increasing diabetes in youth will likely only further perpetuate the diabetes epidemic in the status aboriginal population .", "we report that youth - onset diabetes is an increasing problem in alberta , especially among status aboriginals .", "the observed accelerated increase in diabetes among status aboriginal youth is consistent with reports of a decrease in the age of diagnosis of diabetes among aboriginal adults . in saskatchewan", "reasons for the accelerated rise of diabetes among status aboriginal males have not been explored , but may be due in - part to escalating childhood overweight and obesity ( 31 ) with a possible gender - based lag in the obesity epidemic where it may have occurred earlier in time amongst females . in countries with universal healthcare , administrative data have become common and invaluable sources for the population - based surveillance of many chronic diseases .", ", diabetes prevalence and incidence has increased among all alberta youth from 1995 to 2007 .", "ethnic comparisons have remained largely unexplored in youth , despite numerous studies documenting the divergence in diabetes epidemiology in adult populations . in the beginning of adss observation 1995 , incidence and prevalence of diabetes were distinctly higher among general population . by 2007", "we are unable to distinguish the type of diabetes in our administrative data . however , our clinical experience suggest that the majority of the diabetes in aboriginal youth is type 2 diabetes , whereas in the non - aboriginal population it is heavily dominated by type 1 diabetes ." ], [ "this work was supported in part by a team grant to the alliance for canadian health outcomes research in diabetes ( achord ; reference # : otg-88588 ) , sponsored by the canadian institutes for health research institute of nutrition , metabolism and diabetes .", "this study is based in part on de - identified data provided by the alberta health and wellness ." ] ]

[ [ "tmc1 mrna is specifically expressed in neurosensory hair cells of the inner ear , and it is required for normal function of cochlear hair cells , although the molecular and cellular functions of the tmc1 protein are unknown ( 8) .", "mutations in the tmc1 gene have been associated with profound prelingual deafness ( dfnb7/b11 ) and progressive postlingual hearing loss ( dfna36 ) ; thy have been reported in different populations ( 9 ) .", "one disability that can sufficient to interfere with activities of daily living is non - syndromic hearing loss ( nshl ) ( 1 , 2 ) . people with even mild nshl have problems hearing speech when there is background noise and identifying the sounds sources ( 3 , 4 ) .", "nshl is the most common sensory deficit in humans , with an incidence of about 1 in 1,000 newborns ." ], [ "since no report has yet determined the frequency of tmc1 gene mutations in the iranian population , the present study was performed to screen and identify the mutations of this gene associated with nshl using polymerase chain reaction ", "single - stranded conformation polymorphism ( pcr - sscp ) and heteroduplex analysis ( ha ) ." ], [ "this experimental study was conducted at the cellular and molecular research center of shahrekord university of medical sciences from february 2011 to january 2012 . in the present study , we investigated the mutations of the tmc1 gene , locus dfnb7/11 , in a cohort of 100 patients with nshl in iran .", "the 890 blood samples of families with iranian origin was obtained in ethylene diamine tetra - acetic acid ( edta)-containing tubes ( sarstedt ) from 10 provinces of iran , namely semnan , sistan & baloochestan , fars , khozestan , kohgilooye va boyer ahmad , kordestan , chaharmahal & bakhtiari , booshehr , golestan , and gilan .", "after ha were subjected to direct dna sequencing of exons 7 and 13 of the tmc1 gene in an abi 3730xl automated sequencer ( applied biosystems ) by macrogen inc .", "total genomic dna was extracted from peripheral blood samples of patients using the phenol and chloroform standard procedure ( 11 ) . the quality of extracted genomic dna was quantified by nano - drop 1000 spectrophotometer ( thermo scientific inc . , wilmington , de , usa ) at a wavelength of 260/280", "for this study , the regional research ethical committee of shahrekord university of medical sciences ( grant number 91 - 3 - 2 , january 2011 ) approved the protocol and informed consent forms .", "site - directed mutagenesis ( sdm ) after gene amplification using the designed specific primers with changes in one nucleotide was used to generate positive control samples ." ], [ "this experimental study was conducted at the cellular and molecular research center of shahrekord university of medical sciences from february 2011 to january 2012 . in the present study , we investigated the mutations of the tmc1 gene , locus dfnb7/11 , in a cohort of 100 patients with nshl in iran .", "known environmental risk factors such as head trauma and use of ototoxic drugs could affect the study , so families with the possibility of exposure to these factors were excluded from the research .", "nshl informational questionnaires were filled out for all families . in previous work , these patients had no mutations in the cx26 gene ( 10 ) .", "the 890 blood samples of families with iranian origin was obtained in ethylene diamine tetra - acetic acid ( edta)-containing tubes ( sarstedt ) from 10 provinces of iran , namely semnan , sistan & baloochestan , fars , khozestan , kohgilooye va boyer ahmad , kordestan , chaharmahal & bakhtiari , booshehr , golestan , and gilan .", "finally , 100 patients ( one proband from each family ) were selected ( table 1 ) ." ], [ "total genomic dna was extracted from peripheral blood samples of patients using the phenol and chloroform standard procedure ( 11 ) . the quality of extracted genomic dna was quantified by nano - drop 1000 spectrophotometer ( thermo scientific inc . , wilmington , de , usa ) at a wavelength of 260/280 nm according to the method described by sambrook and russell ( 12 )" ], [ "site - directed mutagenesis ( sdm ) after gene amplification using the designed specific primers with changes in one nucleotide was used to generate positive control samples .", "for gene amplification of exons 7 and 13 of the tmc1 gene by pcr , two sets of overlapping primers were designed due to their length using the gene runner software version 3.0 ( hastings software , inc . , hastings , ny ) , and primer sequences were blasted in the national center for biotechnology information s ( ncbi s ) genbank . the details of the designed primers are shown in table 2 .", "mutant primers created by site - directed mutagenesis ( sdm ) as positive control , tmc1-m ( tmc1 mutant primer ) .", "standard pcr optimization was carried out in a total volume of 50 l reaction in 0.5 ml tubes for each amplicon in a gradient palm cycler ( corbett research , australia ) ." ], [ "for sscp , microtubes containing pcr products were mixed with an equal volume of formamide loading dye , heated to 96c for 15 minutes , and chilled on ice for 5 minutes before loading on the polyacrylamide gel .", "the electrophoresis tank was filled by tbe buffer 0.6 x , and tbe 1 x was used in the gel ; electrophoresis was performed with 2.5 - 5% glycerol at 20 w at 4c for 6 - 8 hours ." ], [ ", the pcr products were loaded on page with 10% urea and electrophoresis were performed at 320 v at 10 - 12c for 6 - 8 hours ( table 3 ) .", ". then , the pcr products were heated at 95c for 3 minutes and slowly cooled to 37c over 40 minutes . after mixing with 6 x triple dye loading buffer at a volume ratio of 1:5", "first , 3 l of edta ( 0.5 m ) was added to 2 l of pcr products" ], [ "the samples containing shift bands on the sscp gel and after ha were subjected to direct dna sequencing of exons 7 and 13 of the tmc1 gene in an abi 3730xl automated sequencer ( applied biosystems ) by macrogen inc ." ], [ "for this study , the regional research ethical committee of shahrekord university of medical sciences ( grant number 91 - 3 - 2 , january 2011 ) approved the protocol and informed consent forms .", "informed consent was obtained from all hearing loss patients before enrollment in the study based on the declaration of helsinki ( doh ) ." ], [ "the mean difference between groups was calculated using a t test . in this study ,", "all data were collected in the statistical program for the social sciences software ( spss , inc . ," ], [ "in this study , blood samples of 100 patients with hearing loss ( mean age 16.5 2.01 years , 49.2% men and 50.8% women , 74.15% married ) were collected from 10 provinces in iran .", "the connexin 26 gene is responsible for a large proportion of deafness ( about 14.6% ) , and these patients had no mutations in this gene ( 10 , 13 ) .", "only a number of suspected fragments in exon 7 showed a different banding pattern , but after sequencing , the mutations were not confirmed ( figure 3 ) .", "line m is a 100 bp dna ladder ( fermentas , germany ) , line 1 is positive control , line 3 is a suspected sample containing different bands compared to other samples , and lines 2 and 4 - 15 are samples from deaf patients . in the present study , to increase the accuracy of the sscp reaction , ha and mutant control ( positive control created by sdm ) were performed .", "neither pcr - sscp nor ha showed mutations in exons 7 and 13 of the tmc1 gene ( figures 1 and 2 ) .", "after page , fragments with a length of 187 and 250 bp were revealed for exons 7 and 13 , respectively , of the tmc1 gene .", "pcr products were used for sscp and ha for investigation of mutations in the sequences ." ], [ "2002 ) detected a 1.6 kb genomic deletion encompassing exon 14 of tmc1 in a recessive deafness mouse mutant , which lacks auditory responses and has hair - cell degeneration ( 7 ) . in the present study , the association of exons 7 and 13 mutations of tmc1 gene locus dfnb7/11 in deaf patients", "the findings of the current study indicate that mutations in exons 7 and 13 of tmc1 gene are not related to hearing loss in the iranian population .", "the prevalence of non - syndromic hearing impairment due to tmc1 in the pakistani population is 4.4% , and one study has indicated that the tmc1 protein might have an important function in the k channels of the inner hair cells ( 16 ) .", "the tmc1 gene is an autosomal recessive gene and a common cause of hearing loss in many countries , such as india , pakistan , algeria , iraq , lebanon , sudan , tunisia , and turkey ( 15 , 17 - 19 ) .", "one study showed that this gene was not the cause of nshl in the korean population ( 20 ) . in our study , as in the research in korea , a relation between the tmc1 gene and nshl in the iranian population was not observed ." ] ]

[ [ "microleakage between the root canal filling and root - canal walls may adversely affects the results of root - canal treatment.1 apical leakage is considered to be common cause of endodontic failure.2 hence , different endodontic filling materials , sealers and techniques have been introduced to the dental community in an attempt to improve apical seal.1 various materials have been used in root canal treatment in an attempt to achieve success .", "however , many studies showed no significant difference between these techniques.1 the aim of this in vitro study was to quantitatively evaluate the sealing properties of three different root - canal sealers ; tubliseal , sealapex and ah26 using a spectrophotometric method .", "but , a combination of gutta - percha and a sealer are used most commonly .", "is used to estimate the sealing ability which is corresponding to in vivo amount of micro leakage with particular sealer.2 many techniques were used to evaluate the leakage of sealers such as ; colored dye penetration radio labeled tracer penetration dissolution of hard tissue clearing of teeth , spectrometry of radioisotopes electrochemical and gas chromatography ." ], [ "thirty - six extracted sound mandibular molar natural teeth specimens with complete root and free from caries or cracks were collected , stored , disinfected and handled as per the recommendations and guidelines laid down by occupational safety and health administration and centers for disease control and prevention.4 the teeth were then placed in 0.9% physiologic saline solution for ten days prior to access cavity preparation .", "the samples were divided into three experimental groups ; group i : sealapex , group ii : tubliseal and group iii : ah26 with 12 samples in each group .", "the samples were then coated with nail varnish all over the root surface except 2 mm around the apical foramen . 2 ml of freshly prepared 2% methylene blue dye was taken in each vial and the apical third of the root was suspended in the dye for 72 h. samples were washed with distilled water , nail varnish removed and then placed in 20 ml of 35% nitric acid for 72 h. standard solutions of 1% , 0.5% , 0.2% , 0.05% , 0.02% and 0.01% of methylene blue in 35% nitric acid were prepared and stored for 72 h. the standard solutions and the nitric acid solutions were filtered and centrifuged for 1 min after 72 h. the supernatant was subjected to spectrophotometric analysis using a filter of 670 nm .", "the amount of leakage was extrapolated from a standard linear regression curve constructed from stock standard methylene blue dye solutions .", "obtained data were statistical analyzed with kruskal wallis and mann whitney u - tests using spss software version 20 ( ibm ) ." ], [ "the results of the quantitative evaluation of the sealing properties of the three root - canal sealers are shown in table 1 .", ", tubliseal showed a significant difference ( p > 0.005 ) . in comparison to sealapex", "comparisons made between tubliseal and ah26 showed no significant difference ( table 2 , chart 1 ) . mean and standard deviation values of volumetric dye penetration in groups with reference to transmission ." ], [ "three - dimensional obturation of the root canal system with a fluid impervious seal is an important factor for successful endodontic therapy .", "sealers based on zinc oxide - eugenol ( tubliseal ) , calcium hydroxide ( sealapex ) , epoxy resins ( ah26 ) were included in the present study . in present quantitative dye leakage study ,", "( 2006 ) observed sealapex with better apical sealing than the other sealers ( ah plus and rc sealer ) at 7 , 14 , and 21 days.3 ah26 is an epoxy resin based sealer that provides easy handling characteristics , good flow , good sealing to dentin and prominent antimicrobial activity.6 kumar et al . observed more micro leakage with zinc oxide - based sealer and least with resin based sealers , this is contradictory to our study.8 in our study , there was no statistical significant difference between tubliseal and ah26 in micro leakage .", "ah26 , resin based sealer provided a better apical seal when compared with sealapex even though the results were statistically not significant .", "tubliseal demonstrated least dye leakage in comparison with other experimental groups ( table 1 ) ." ], [ "in the present study , tubliseal sealer showed least microleage compared with sealapex and ah26 sealer .", "it is important to remember before declaring any root canal sealer as most acceptable that the results of the dye penetration studies indicate only the relative sealing ability of root canal fillings in vitro and they do not indicate their ability to prevent the penetration of bacteria into filled root canals in vivo ." ] ]

[ [ "the early clinical trial data for the second - generation pde4 inhibitors cilomilast ( ariflo , glaxosmithkline , usa ) and roflumilast ( daxas , altana , germany ) all pointed to a successful introduction of a novel non - steroid anti - inflammatory therapy to clinicians in combating severe copd ( gamble et al 2003 ; rabe et al 2005 ) nevertheless , while the progression of developing cilomilast has idled at the approvable stage for more than two years , the announcement of the termination of the agreement to develop roflumilast between altana and pfizer has raised concerns about the therapeutic efficacy of selectively inhibiting one or two isoenzymes in the pde4 family for copd management ( pharmiweb 2005 ) . in the early six - month", "in addition , the new trial data confirmed that the pde4 inhibitor roflumilast s efficacy was considerably lower than the approved therapies such as fluticasone / salmeterol ( a combination therapy of glucocorticosteroid and long - acting 2-agonist ) and tiotropium bromide ( long - acting anticholinergic ) .", "this holdup no doubt sets back the r&d of the most promising pde4 inhibitor in development for copd .", "the unexpectedly low long - term efficacy on exacerbation rate from roflumilast therapy made the r&d community re - examine the role of targeting pde4 in copd because one of the highest unmet needs in treating the disease is to reduce or eliminate exacerbations ( pharmiweb 2005 ) . in november of 2005", " record phase iii trial , roflumilast ( 500 mg daily ) clearly improved lung function ( ie , increased fev1 by + 97 ml ) and significantly reduced exacerbations ( acute worsening of symptoms ) compared with placebo ( rabe et al 2005 ) .", "however , in the follow - up one - year phase iii trials using exacerbations as one of the key endpoints , the results from the european copd ratio study that included 1513 patients with severe and very severe copd have failed to repeat the previously claimed efficacy .", ", altana announced the withdrawal of the european marketing authorization application ( maa ) for roflumilast and decided to wait for more clinical trial data for submission of a future maa ( altana 2005a ) ." ], [ "inhibition of pde4 has been established as an effective and reliable approach to increasing intracellular camp ( conti et al 2003 ) that underlines the signaling mechanisms for the treatment of copd . in recent years", "with all these preferred outcomes , it seems that the pde4 inhibitors in development ( cilomilast and roflumilast ) would be an ideal armory for the healthcare community to combat copd .", "the progressive loss of lung function leads to reductions in patients quality of life and results in exacerbations , cor pulmonale , and death .", "the pathological changes in the patients with copd are not fully reversible and it often takes many years for a patient at risk ( cough , sputum production ) to progress into suffering from mild airflow limitation , to moderate , severe , and very severe copd ( with chronic respiratory failure ) . in the absence of a magical therapy that can stop the disease progression and reverse the abnormalities of pulmonary function , the management , including drug therapy , for copd is long - term care .", "copd is a complex disease with pathophysiological features including inflammation ( neutrophils , macrophages , cd8 + lymphocytes infiltration , and inflammatory mediator tnf- and il-8 release ) , airway obstruction ( smooth muscle contraction , elevated cholinergic tone ) , respiratory bronchiolar " ], [ "enhancement of isoenzyme selectivity is critical for reducing side - effects of the pde4 inhibitors .", "the scaffold of individual pde4 isoenzyme and the structure of a given selective inhibitor govern isoenzyme - selective inhibition , depict the binding affinity , and determine the therapeutic window and rank order of potency in clinical use for the treatment of copd .", "an agent without 4d inhibition may end up lacking sufficient therapeutic efficacy for controlling copd ( spina 2004 ) .", "developing pde4 inhibitor as a therapy for copd is based on the fact that theophylline dilates airway smooth muscles and improves pulmonary function by inhibition of pde activity ( barnes 2003 ; spina 2004 ) the dose - limiting adverse reactions ( nausea , emesis , cardiac arrhythmias ) with the non - selective pde inhibitor theophylline and the first - generation pde4 inhibitor rolipram ( huang et al 2001 ; lagente et al 2005 ) directed the r&d of pde inhibitors to discover the second - generation of pde4 inhibitors cilomilast and roflumilast that have been successfully brought to the final stage for administration approval ( spina 2003 , 2004 ; lipworth 2005 ) based on the fact that the emetogenic reaction to pde4 inhibition is due to reticence of the pde4d isoenzyme ( lamontagne et al 2001 ; robichaud et al 2002 ) , several researchers in the field proposed to develop isoform - specific pde4 inhibitors that reduce or completely avoid disturbing pde4d activity and therefore do not trigger the emetic responses in the nervous system ( giembycz 2002 ; robichaud et al 2002 ; card et al 2004 ) ." ], [ "how , then , is the dose - limiting dilemma ( nausea , vomiting , diarrhea , and arteritis ) ( giembycz 2005 ; spina 2004 ; lipworth 2005 ) associated with the wide - spectrum pde4 inhibition overcome ?", "the beneficial effects on copd via relaxing airway smooth muscles and anti - inflammation mediated by pde4 inhibition with cilomilast and roflumilast have been emphasized and reviewed extensively ( spina 2004 ; lagente et al 2005 ; lipworth 2005 ; soto 2005 ) . improving pulmonary circulation has not been considered as an important therapeutic approach for managing patients with copd .", "the preference reduction in pulmonary arterial pressure by inhibition of pde4 suggests that administration of pde4 inhibitors may benefit copd patients by increasing ventilation ( airway relaxation ) and improving alveolar perfusion ( vasodilation ) , therefore improving blood gas exchange capacity and patients pulmonary function .", "although inhaling nitric oxide vasodilator can worsen gas exchange because of altered hypoxic regulation of ventilation - balance ( barbera 1996 ) in patients with stable copd , and vasodilators are considered as contraindications for copd patients , in their preliminary clinical trial , alp et al ( 2006 ) demonstrated that reduction of pulmonary vasculature resistance using the pde5 inhibitor sildenafil was able to significantly improve the exercise capacity ( 6-minute walk test ) of patients suffering from severe copd . a double - blinded , placebo - controlled , crossover clinical trial of sildenafil in patients ( n=10 ) with copd is going on to evaluate the effect of pde5 inhibition on patients exercise function , pulmonary function , and quality of life ( national institutes of health ) ." ], [ "noticing the low therapeutic ratio and insufficient clinical efficacy of the current generation of pde4 inhibitors ( cilomilast and roflumilast ) , giembycz ( 2005 ) assumed that one potential means of improving the therapeutic ratio and safety of pde4 inhibitors may lie in the development of compounds that have broader phosphodiesterase specificity and suggested dually targeting pde4 and pde1 , pde3 , or pde7 to enhance clinical efficacy .", "we believe that it is worthwhile to carry out a randomized clinical trial to evaluate the safety and efficacy of dually targeting pde4 and ca channels in managing the patients with severe copd .", ", there is a remark about pfizer s development of an inhaled dual - action pde4/spiriva ( long - lasting muscarinic antagonist tiotropium ) combination product for copd ( pharmiweb 2005 ) .", "this combined dual action modality is a favorable approach for managing patients with severe copd considering the presence of bronchoconstricting and inflammatory pathologies in the disease . in general , moderately targeting two mechanisms to reach the therapeutic goal should be more effective and safer than exploiting a single mechanism to its extended degree ." ], [ "the extensive in vitro , in vivo , and clinical trial study data and the established clinical beneficial effects ( anti - inflammation , bronchorelaxation , pulmonary vasodilation ) associated with pde4 inhibition strongly validate targeting pde4 for controlling copd .", "the unsatisfied efficacy of using pde4 inhibitor roflumilast in treatment of severe and very severe copd has raised concerns in the r&d community about the administrative approvability for the highly expected novel therapeutic modality in combating copd .", "development of an inhaled dual - action therapy such as pde4 inhibitor and muscarinic antagonist may be a correct approach to bringing a pde4 inhibitor to the demanding market .", "the other approach is using cca to overcome pde4 inhibitor - caused adverse effects , especially emetic responses and simultaneously enhance pde4 inhibitor s anti - inflammatory and bronchorelaxation , pulmonary vasodilation effects . of course , development of a dual agent that has with two pharmacophores in one chemical structure , therefore being able to target pde4 and l - type ca channels should also be able to improve the therapeutic window of pde4 inhibition and may make available a new therapeutic approach to managing copd ." ] ]

[ [ "long - acting beta-2 agonists such as salmeterol and formoterol are important controller medications in the maintenance therapy of chronic stable asthma , used as an add - on drug to inhaled corticosteroid . however , their usefulness in the management of acute attacks of asthma has recently been recognized , and they are approved for use as reliever medication in europe .", "short - acting 2 agonists are the preferred drugs as the initial bronchodilator for acute asthma because of their rapid onset of action . however , due to short duration of action they require frequent administration .", "formoterol is a unique bronchodilator having rapid onset and long duration of action with a favorable safety profile .", "so it can be an ideal alternative to short - acting 2 agonists in the management of acute asthma exacerbation by providing rapid bronchodilatation and reducing the need for frequent administration .", "this study compares the efficacy and safety of arformoterol and salbutamol delivered by nebulization in the management of acute non - severe asthma ." ], [ "a total of 50 patients attending the emergency room or chest opd of a tertiary care hospital with acute non - severe asthma over a 6-month period from january 2010 to june 2010 were selected for this study .", "the inclusion criteria were as follows : ( a ) age > 18 years ; ( b ) british thoracic society definition of acute non - severe asthma ; and ( c ) ability to perform forced expiratory maneuver .", "the following patients were excluded from the study : ( a ) patients presenting with acute severe / acute life - threatening / near - fatal asthma ; ( b ) patients with a previous diagnosis of chronic obstructive pulmonary disease ( copd ) ; ( c ) history of hypersensitivity to 2 agonists ; and ( d ) pregnant or lactating women .", "patients were then assigned by random number allocation to either of the two groups , that is , salbutamol or arformoterol group according to the medication given to them . in the salbutamol group , 5-mg salbutamol respules were administered through oxygen driven ( 6 l / min ) nebulizer ( pulmo mist ii nebuliser , nidek medical , kolkata , india ) at 20-min intervals for 1 h amounting to a total of 15 mg . in the arformoterol group ,", "baseline peak expiratory flow rate ( pefr ) was measured with a peak flow meter ( peak flow master , cipla ltd . ,", "the pulse rate , respiratory rate , and spo2 ( measured with fingertip pulse oximeter , model 6500 , nidek medical , kolkata , india ) were also recorded at the time of initial assessment .", "the age , sex , duration of asthma symptoms , and present controller medications were recorded .", "the drugs were administered in a double - blind manner . to eliminate the effects of other drugs on the treatment outcome" ], [ "among 50 patients satisfying the inclusion criteria , 25 patients received salbutamol and 25 patients received arformoterol therapy .", "the increases in pefr after the first and the second dose were significantly more with arformoterol than with salbutamol , but the increase in pefr after the third dose was similar in these two groups . the comparison of improvement following the therapy with salbutamol and arformoterol is shown in table 2 .", "baseline characteristics of the patients ( n = 50 ) receiving salbutamol and arformoterol therapy from the table , it is evident that the demographic profile and baseline pefr in the two groups were comparable .", "in both the groups , pefr showed significant increase over the baseline values and the increase was evident after each dose of the drug .", "improvement in pefr after each dose of bronchodilator when compared with the baseline both drugs were well tolerated ; no major adverse effect was noted in either group ." ], [ "our study has shown that both salbutamol and arformoterol are equally effective as a reliever medication as nebulizing solution in acute non - severe asthma .", "further studies are thus needed to clarify the efficacy , actual dose , dose frequency , cost - effectiveness , and long - term safety of arformoterol in acute exacerbations of asthma and copd with different levels of severity .", "several studies have shown the efficacy of formoterol in acute non - severe asthma , acute severe asthma , exercise induced bronchospasm , childhood asthma , and copd.[1317 ] most of the studies have used formoterol with terbuhaler , aerolizer , or metered dose inhaler . however , studies using formoterol nebulization are lacking ." ] ]

[ [ "hepatic angiomyolipoma ( haml ) is a rare benign mesenchymal liver tumor first described by ishak in 1976 ; it belongs to a group of perivascular epithelioid cell tumors called pecoma . until date ,", ", we have focused on the characteristic features of this tumor shown in imaging studies and by histological analysis , summarized these cases showing aggressive patterns , and discussed management of the patients and indications for surgical treatment .", "approximately 300 cases have been reported [ 310 ] ; however , its natural history has not been clarified .", "the majority of these tumors are believed to be clinically benign during a mean follow - up period of 6.8 years ; however , an increasing number of cases and aggressive changes including growth in size , recurrence after surgical resection , metastasis , and invasive growth pattern into the parenchyma and along the vessels have been reported . in this paper" ], [ "most cases were found as incidental liver tumors upon health screening or imaging examinations for other diseases .", "it usually follows a benign clinical course while some patients visited hospitals with unspecific symptoms of abdominal discomfort , fullness , and other such complaints .", "more than half of the renal aml are considered to be associated with tuberous sclerosis which features the loss of heterozygosity at tsc1 ( 9q34 ) and tsc2 ( 16p13 ) , while it is estimated to be 515% in the liver .", "thus the etiology of most of these tumors in the liver is unknown ; most cases have no history of liver diseases or specific symptoms , and no changes in laboratory data are seen .", "moreover , serum levels of the tumor markers alpha - fetoprotein , protein induced by vitamin k absence or antagonist ii , carcinoembryonic antigen , and carbohydrate antigen 19 - 9 were normal ." ], [ "contrast - enhanced dynamic mri using gadolinium or the hepatocyte - specific contrast agent gadolinium - ethoxybenzyl - diethylenetriamine pentaacetic acid showed early enhancement in the arterial phase followed by the prolonged enhancement in the portal phase and defective lesions in the hepatobiliary phase .", "if the tumor has predominance of lipomatous tissue , the differential diagnosis with hepatic hemangioma is difficult by sonography alone .", "mri is considered to be the best modality to determine the components of the tumor .", "color doppler sonography shows punctiform or filiform vascular distribution pattern if the tumor has predominance of angiomatous tissue ." ], [ "these results indicate that the hmb-45 staining , mitotic analysis by mib-1 ( ki67 ) , and p53 reactivity following the fine - needle biopsy of the tumor might be useful for the diagnosis of the tumor and its malignant potential .", "this variation of mixture levels in one tumor reflected the differences in imaging studies and made accurate diagnosis difficult .", "it is believed that majority of the hamls behave in a benign fashion and even if some cases showed invasive growth pattern into the adjacent hepatic parenchyma , portal triad ( figure 2(c ) ) , and hepatic vein ." ], [ "since haml usually follows benign clinical courses , the majority of the cases can be conservatively treated .", "therefore , once haml has been diagnosed by imaging studies , a fine - needle biopsy should be performed to make an accurate diagnosis and to confirm the predominance of the tissue components , the existence of pleomorphic nuclei with high proliferation activity , p53 immunoreactivity , and mutation in p53 if possible . if the aggressive patterns such as vascular invasion , high proliferation of the tumor cells , p53 immunoreactivity were marked , or when the imaging findings and biopsy can not provide a definitive diagnosis , or if the patients have abdominal symptoms , surgical resection should be considered .", "however , as not a few cases showed aggressive pattern in their courses [ 3 , 5 , 8 , 9 , 12 , 1624 ] and because of the low level of accurate diagnoses by imaging studies , and because of the possibility of dissemination of tumor cells into the peritoneal cavity if a tumor is malignant , tumor biopsy has been avoided , and many hamls have been surgically resected [ 3 , 8 , 9 ] . with the increasing number of resected samples , careful comparisons of imaging studies and pathological findings" ], [ "the majority of hamls behave as a benign tumors and conservative follow - up may be recommended ; however , with increasing number of the reports showing potentially malignant behavior , prompt surgical resection is essential for better prognosis of this tumor .", "haml is considered to be a benign mesenchymal tumor , and nonsurgical treatment with conservative management involving close followup is therefore suggested for patients with asymptomatic tumors smaller than 5 cm , which have been proved to be a typical haml by fine - needle aspiration biopsy . as a fact the renal angiomyolipoma often showed perirenal invasion , involvement of the renal vein , and the inferior vena cava , that are not considered as signs of malignant behavior and the angiomatous", "long - term follow - up of haml is necessary after its diagnosis by imaging studies and biopsy specimens and curative surgical treatment .", "this finding might be able to be detected by imaging studies as similar to hcc ." ], [ "we have reviewed noninvasive imaging studies and the role of histological diagnosis showing distinctive characteristics of haml to increase the rate of accurate diagnoses .", "we propose that tumor resection is indicated in the following scenarios : ( 1 ) the patients show symptoms ; ( 2 ) the tumor shows an aggressive growth ; ( 3 ) the tumor shows invasive growth into the vessels evidenced by fine - needle biopsy or imaging studies ; ( 4 ) the component of the tumor shows atypical epithelioid pattern , high proliferation activity , and/or p53 immunoreactivity ; and ( 5 ) a definitive diagnosis can not be made by imaging and pathological studies from malignant tumors .", "in addition , we summarized the cases that showed progressive patterns of the tumor and concluded that a careful followup of the tumor even after the final diagnosis is necessary ." ] ]

[ [ "the sentinel node is defined as the first tumour - draining lymphatic filter , and its involvement by metastatic disease should predict the global nodal status of the specific patient . skip metastasis in the context of a normal sentinel node is described as a very rare event . in patients with clinically node - negative disease , sentinel lymph node biopsy ( slnb ) had become the gold standard staging procedure , followed by axillary lymph node dissection ( alnd ) performed selectively in patients with previously proven ( by slnb ) sentinel node metastases .", "considering the therapeutic consequences , involvement of the sentinel node by metastatic disease in breast cancer patients is of great interest to the breast surgeon in order to plan the surgical approach .", "the purpose of this pilot study was to assess this new pre - operative diagnostic approach .", "using gamma probe combined with ultrasound- ( us ) guided percutaneous core needle biopsy ( cnb ) could increase the accuracy of identifying the sentinel node and allow a proper histopathologic diagnosis in order to avoid further slnb .", "unfortunately , the physical examination of the axillae can be inaccurate in identifying pathologic lymph nodes .", "the same is also true for the pre - treatment imaging ( with or without interventional procedures on the axillary node ) , characterized by a poor negative predictive value [ 48 ] ." ], [ "the accuracy of percutaneous biopsy guided by us and gamma probe over the skin in the pre - operative staging was correlated with final pathologic reports of slnb .", "the surgeon was able to recognize the sentinel lymph node biopsy marked by the radiologist with the skin mark and correlate with the results of the standard slnb ( validate the ability of the preoperative diagnostic method to correctly identify the sentinel node ) . because the most frequent tumor site is the upper - outer quadrant of the breast , the surgeon generally used the same type of incision of the breast to identify the sentinel node using the gamma probe guide when the conservative surgery was performed .", "information on histological type and grade and biological characteristics ( eg , receptor status or peritumoral vascular invasion of the primary carcinoma ) were obtained from the pathology report of the breast specimen . for the pathological staging of the axillae", "the final histopathological diagnosis of slnb was compared with the results of the cnb of the sentinel node .", "after injection , antero - posterior and lateral lymphoscintigraphic projections were obtained to identify the presence of a sentinel node and to define whether the radiocolloid has shifted to other possible sites of drainage , such as the internal mammary , intramammary , contralateral axillary or supraclavicular nodes ." ], [ "the definitive histopathological report of slnb expressed the presence of 1 micrometastasis that was not observed in the frozen section at the extemporary analysis . in the second patient , micrometastases were observed in the para - sentinel node at slnb , but no macrometastasis in the sentinel node were found .", "the hot spot was detected over the skin by gamma probe in all 10 patients , and was examined using us - guided cnb in all patients .", "main patient characteristics are shown in table 1 and include age , type of surgery , location of primary breast cancer , nodal stage at percutaneous biopsy , pathological nodal stage , and biological features of the breast tumor .", "in all the surgically excised sentinel lymph nodes , the pathologist documented the sign of the previous core needle biopsy , verifying that the biopsied lymph node was really the sentinel node .", "multiple sentinel nodes were not detected and no patient had the sentinel node draining to different possible sites .", "there were no major complications ( eg , clinically important bleeding , nerve injury , or infection ) related to the cnb procedure . one patient experienced a small amount of bleeding , which was stopped by simple local compression ; this was considered a minor complication . in all patients ," ], [ "the aim of this study was to verify the feasibility of this innovative method to detect and to biopsy the sentinel node in order to improve confidence in identification of the metastatic lymph node in the preoperative phase . in our opinion", "however , the concepts presented could improve the quality of lymph node sampling , particularly in early breast cancer patients", "in fact , in cases with positive preoperative lymph node cnb , a complete alnd can be performed directly as a primary procedure .", "pre - operative knowledge of an axillary metastatic sentinel lymph node could avoid the intraoperative slnb .", "sever et al10 proposed the use of intradermal peritumoral microbubble us contrast agents injection and lymphatic imaging to identify and localize the sentinel node in the preoperative stage . many studies report a moderate diagnostic sensitivity of the percutaneous biopsy of a morphologically abnormal axillary lymph node and an even lower sensitivity in cases where the biopsied lymph node has an unaltered appearance and the procedure is performed randomly . but how can you differentiate the sentinel node from a regular lymph node especially when the pathological sentinel node is not always the largest one or the morphologically abnormal one ?", "had avoided slnb in 30% of patients with a final pathology of metastatic lymph node by performing fine needle aspiration cytology ( fnac ) of the abnormal sonographic axillary node ." ], [ "in conclusion , gamma probe - assisted sonographic localization associated with cnb of the sentinel node in early breast cancer patients could be a feasible and accurate new method .", "further studies should investigate the definitive role of this method in pre - treatment breast cancer staging .", "particularly , it is necessary to investigate the clinical impact of this method in avoiding slnb , especially in cases when percutaneous sentinel node cnb is negative , without primary carcinoma peritumoral vascular invasion , in clinically node - negative breast disease patients ." ] ]

[ [ "since the first fontan procedure was introduced by fontan in 1971 , the surgical technique has evolved and the survival rate has shown dramatic improvement . recently ,", "several studies8,9,10,11,12 ) reported the pulmonary vasodilating therapy had an effective influence on fontan patients so we want to determine whether inhaled iloprost as a pulmonary vasodilator might have a role in the clinical symptoms , hemodynamics and exercise capacity of fontan patients .", "fontan surgery has been performed as an operation of the final stage for congenital heart disease with single ventricle physiology1 ) . in fontan circulation", "therefore , the pulmonary vascular resistance ( pvr ) must be lower than the antegrade transpulmonary flow resistance2 ) ." ], [ "an 18-year - old female with pulmonary atresia with intact ventricular septum status post fontan surgery at age of three years complained of aggravated dyspnea on exertion ( doe ) .", "the results are shown in table 1 . a 22-year - old male with double outlet right ventricle", "recently , she felt more difficult to climb the stairs due to shortness of breath .", ", the cardiac index and stroke volume were increased without significant change of pulmonary pressure and pvr ." ], [ "an 18-year - old female with pulmonary atresia with intact ventricular septum status post fontan surgery at age of three years complained of aggravated dyspnea on exertion ( doe ) .", "recently , she felt more difficult to climb the stairs due to shortness of breath .", ", the cardiac index and stroke volume were increased without significant change of pulmonary pressure and pvr .", "six - minute walking distance was increased from 380 to 395 m and nyha class changed from iii to ii .", "the inhaled iloprost was administered at 60 microgram / day divided by six times for 12 weeks .", "a physical examination showed regular heart beat without murmur and mild pitting edema on the pretibial area , liver and spleen were not palpable .", "after 12 weeks , the patient 's systemic blood pressure and o2 saturation were increased ." ], [ "a 22-year - old male with double outlet right ventricle status post fontan surgery at age of five years complained of mild doe only .", "after 12 weeks , the patient 's systemic blood pressure , o2 saturation , and nyha class were not changed significantly .", ", the cardiac index and stroke volume were also increased without significant change of pulmonary pressure and pvr ." ], [ "despite the increased survival rate of patients who has congenital heart disease with single ventricular physiology due to advanced surgical technique , the fontan surgery is still a palliative procedure .", "although more advanced curable treatments of fontan physiology have not been developed , pulmonary vasodilator therapy on fontan circulation is one of good suggestion for symptomatic treatment of fontan failure and improvement of the cardiac output .", "experiences with sildenafil therapy on fontan patients have also been reported11,12 ) . in a recent study , rhodes", "et al.15 ) reported on the effect of inhaled iloprost on exercise function of fontan patients . in this article", "the lowering of pvr may increase pulmonary blood flow and preload reserve in fontan physiology , and for this reason the selective pulmonary vasodilating therapy is interesting as a means to improve the fontan circulation8 ) .", "most studies were based on high level of endothelin-1 in fontan patients9,10 ) , the endothelin receptor antagonist induced improvement of clinical , hemodynamic parameters and exercise capacity .", "the loss of pulsatile blood flow of pulmonary circulation of fontan patients is positively correlated with high pvr ." ] ]

[ [ "only two instances of this tumor arising in the tongue have previously been reported [ 1 , 2 ] .", "angiomyolipoma is a benign tumor that is histologically composed of groups of mature adipose tissue intermixed with convoluted thick - walled blood vessels , interlacing bundles , and irregularly arranged sheets of smooth muscle , with the kidney as the most frequent site of involvement .", "extrarenal angiomyolipoma can occur in organs such as the liver , lung , uterus , and skin ." ], [ "a 61-year - old woman was referred to our hospital with a mass in the left proglossis that was painless , but had enlarged slowly for 5 years .", "histopathological examination showed an encapsulated lesion composed of a proliferation of an intricate mixture of mature adipose tissue , blood vessels , and smooth muscle ( figure 3(a ) ) .", "the patient 's postoperative course was uneventful , and there were no signs of recurrence at followup at 18 months ( figure 4 ) .", "the mass was well - demarcated and easily dissected with an ultrasonic surgical aspirator ( figure 2 ) ." ], [ "described a case of a angiomyolipomatous hamartoma arising in the left lateral border of the tongue . in the present case ,", "koizumi et al . reported a case of angiomyolipoma in the centre of the tongue .", "angiomyolipoma arose in the proglossis and it had a diagnosis of hemangioma because of its hardness and color ." ] ]

[ [ "bone and immune system are functionally integrated through complex homeostatic networks and , in all respects , osteoporosis could be considered a chronic immune mediated inflammatory disease which shares clinical and biological features with many other inflammatory conditions , as well as of other immune mediated diseases . in this context immune and bone systems appear to be integrated and sharing signaling pathways and regulatory mechanisms whose understanding provides a framework for obtaining new insights for the discovery of novel treatments for diseases related to both systems .", "purpose of this review is to outline a new panorama of osteoimmunology that is not limited to immune mediated bone turnover but also consider , in the light of the latest findings in this field , interesting connections with other systems and regulatory functions over bone remodeling .", "researchers recently hav - egained better understanding of the dialogue between immune and bone cells and a new reading register of bone remodeling is emerging , in which the various phases of bone formation and resorption , that coexist in a dynamic equilibrium , are under strict immunological control .", "thus osteoimmunology appears definitely as an interdisciplinary research and clinical field which also allowed new pathogenetic and clinical interpretations of well - known and common diseases , such as osteoporosis .", "its fields of interest are constantly expanding , thus enriching with an increasing number of translational implications , even in clinical practice and in various branches of medicine . here , the most important concepts in osteoimmunology are addressed in the context of physiopatological states bridging these two organ systems , including osteoporosis , ageing , menopause , inflammatory arthritis , cancer , dysmetabolism and neurological disorders .", "recently , extensive reciprocal interactions between the immune and skeletal systems have been demonstrated , resulting in the establishment of a new interdisciplinary research field , named osteoimmunology , which is focused on the understanding of the crosstalk between the immune and bone systems [ 1 - 3 ] .", "in particular , osteoimmunology investigates how the immune system impacts on bone turnover in physiological and pathological conditions through the immunoskeletal interface ." ], [ "an anti - sclerostin moab has recently been produced as a new osteoanabolic drug useful in the therapy of osteoporosis .", "antagonistic signaling between skeletal stem cell - derived subsets is a key mechanism in skeletal subset lineage commitment .", "other potential osteoanabolic drugs acting on the wnt pathway are also dkk inhibitor molecules , now in the experimental stage .", "bone tissue undergoes continuous adaptation during lifetime to preserve the structure of the skeleton and to control the mineral homeostasis ." ], [ "antagonistic signaling between skeletal stem cell - derived subsets is a key mechanism in skeletal subset lineage commitment .", "bone is a dynamic tissue formed by a protein and mineral salt matrix in which are embedded the bone cells , osteocytes ( ocy ) , osteoblasts ( ob ) and osteoclasts ( oc ) . in addition , many other types of cells take part in bone composition , including cartilage , stromal , hematopoietic and mesenchimal stem cells , all linked by a dense network of signals .", "the stem cells that maintain and repair the postnatal skeleton is an osteochondroreticular ( ocr ) stem cell that generate ob , chondrocytes , and reticular marrow stromal cells , but not adipocytes .", "bone tissue undergoes continuous adaptation during lifetime to preserve the structure of the skeleton and to control the mineral homeostasis ." ], [ "an anti - sclerostin moab has recently been produced as a new osteoanabolic drug useful in the therapy of osteoporosis .", "other potential osteoanabolic drugs acting on the wnt pathway are also dkk inhibitor molecules , now in the experimental stage .", "the binding of rank receptor on oc and their precursors by its ligand rankl , expressed by ob and stromal cells , is the main activation signal for bone resorption ." ], [ "msc express active tlr , through which they sense bone microenvironment , recognizing exogenous ( bacterial products ) and endogenous ( heat shock proteins , rna ) danger signals . the common tlr signaling feature is the activation of the nf- b transcription factors implicated in controlling the expression of inflammatory cytokines and cell maturation molecules .", "t helper ( th17 ) cells are capable of stimulating bone resorption and play a pivotal role in the bone loss of inflammatory conditions such as psoriasis , rheumatoid arthritis , periodontal disease , and inflammatory bowel disease .", "t lymphocytes resident in the bone marrow are the key immune cells that regulate bone remodeling and responsiveness of bone cells to parathyroid hormone ( pth ) , in physiological and pathological conditions . during inflammatory diseases or in conditions characterized by low - grade systemic inflammation , such as menopause and aging , oc bone resorption is driven by inflammatory cytokines produced by activated t lymphocytes .", "a central function of macrophages is their phagocytic ability . in particular , efferocytosis ( phagocytosis of apoptotic cells ) is a critical process in both clearing dead cells and replacement of progenitor cells to maintain bone homeostasis .", "cytokines secreted by bone cells drive naive t cell differentiation into several lineages , leading to expansion of mature t cell populations that further regulate bone homeostasis ." ], [ "t helper ( th17 ) cells are capable of stimulating bone resorption and play a pivotal role in the bone loss of inflammatory conditions such as psoriasis , rheumatoid arthritis , periodontal disease , and inflammatory bowel disease .", "t lymphocytes resident in the bone marrow are the key immune cells that regulate bone remodeling and responsiveness of bone cells to parathyroid hormone ( pth ) , in physiological and pathological conditions . during inflammatory diseases or in conditions characterized by low - grade systemic inflammation , such as menopause and aging , oc bone resorption is driven by inflammatory cytokines produced by activated t lymphocytes .", "cd40/cd40l signaling promotes macrophage activation and differentiation , antibody isotype switching , and the development of b cell memory .", "eph receptors and their associated ligands , expressed by cells found within the bone marrow microenvironment , including ob and oc , are implicated in the regulation of physiological and pathological bone remodeling , but also are central in many other different cellular processes including , in addition to immune regulation , angiogenesis , neuronal development and neoplastic metastatization .", "however , bone marrow t cells also support bone homeostasis by inducing bone formation via direct interactions with bone cells .", "the matrix glycoprotein osteopontin ( opn ) , produced by different types of cells , including immune cells , oc , endothelial and epithelial cells , increases bone resorption by inducing the expression of the osteoclastic immune receptor cd44 , essential for cell migration , and by directly enhancing oc attachment to bone extracellular matrix ( ecm ) , required for ocp activation . as a consequence of bone resorption , more opn", "the prevailing bone marrow t cells are activated central memory cd8 + lymphocytes , secreting relatively high levels of effector cytokines , mainy tnf-. these cells are abundant in postmenopausal women with osteoporotic fractures ." ], [ "therapy with teriparatide , a form of ipth treatment , increases the bone marrow levels of wnt10. bone marrow cd8 + t cells potentiate the anabolic activity of pth by providing wnt10 .", "bone marrow t cells provide cell surface signals and secrete cytokines that direct the differentiation of mesenchimal progenitors towards ob characterized by a high sensitivity to pth .", "moreover , tnf- upregulates the expression of cd40 in ob and stromal cells , increasing their sensitivity to cpth and suppressing opg .", "the catabolic effect of cpth is mostly mediated by enhanced production of rankl and decreased production of opg by ob and stromal cells ." ], [ "the common tlr signaling feature is the activation of the nf- b transcription factors implicated in controlling the expression of inflammatory cytokines and cell maturation molecules .", "inflammation results in disturbances in the immunoskeletal interface , i.e. the convergence of cells and cytokines that regulate both the immunity that the bone , causing osteoporosis .", "finally , not only the immune system regulates bone remodeling , but also the bone is able to influence the immune system , actively interacting with immune cells . the same bone cells would then be able to influence or even also perform many immune functions , such as cytokine production and antigen presentation [ 46 - 48 ] . in this sense , the bone would be regarded as a sort of expanded immune system .", "cytokines secreted by bone cells drive naive t cell differentiation into several lineages , leading to expansion of mature t cell populations that further regulate bone homeostasis ." ], [ "osteoporosis is a systemic disease of the skeleton , whose main features are loss of bone mass , bone mineral density ( bmd ) decrease and disruption of bone microarchitecture , so the skeleton becomes fragile , exposing patients to increased risk of fractures . aside from senile and postmenopausal osteoporosis , the first recognized types of primary osteoporosis , many other causes of secondary osteoporosis", "paradigmatic examples of the link between inflammation and osteoporosis are inflammatory arthritis , mainly ra ( fig .", "1 ) . ra is an autoimmune disease that is characterized by inflammation of the synovial joint , leading to severe structural damage and bone destruction .", "an increased bone resorption is the main pathogenetic mechanism in both disease progression leading to juxta - articular bone erosions and irreversible joint damage and systemic osteoporosis .", "could be therefore regarded as an immune mediated disease in which immune activation , through the induction of cytokine production and inflammation , leads to a remodeling of oc and ob activity and dysregulation of bone turnover with consequent increased bone resorption and osteoporosis .", "thus , the interaction of immune and mesenchymal cells plays a key role in both the chronic inflammation and bone destruction in ra ." ], [ "interestingly , this immunological pattern ( accumulation of activated cells and memory / effector lymphocytes secreting proinflammatory cytokines ) characterizing immunosenescence , is also peculiar of other immunological conditions associated with osteoporosis , such as ra , aids , chronic viral infections , etc . .", "teoimmunology , suggesting that immune cells take part in the bone changes typical of menopause , has led to a shift in the concept of osteoporosis , that is currently considered an inflammatory condition .", "osteoporosis has long been regarded as simply the consequence of the menopausal estrogen decline . os- the progression of articular erosions is clearly driven by proinflammatory and osteoclastogenic cytokines produced by immune cells in the inflamed joint .", "many of the biological mechanisms implicated in the aging process , such as cell senescence , proinflammatory immune profile , apoptosis and metabolism imbalance , are also implicated in bone remodeling .", "post - menopausal osteoporosis is a clear example of the mutual influences between immune system , bone and endocrine system . like many other hormones , in addition to specific target organs ( breast and reproductive system )", "these are senescent cells with proinflammatory properties , secreting several inflammatory cytokines able to influence bone remodeling ." ], [ ", bone cells may represent potential therapeutic targets in the treatment of both secondary neoplastic osteoporosis and the underlying neoplasia .", "small molecules able to specifically inhibit the intestinal tryptophane - hydroxylase and do not cross the blood brain barrier , have recently been proposed for the treatment of osteoporosis . in alzheimer s disease ( ad ) , a neurodegenerative disorder characterized by cortical and cerebrovascular amyloid peptide ( a ) deposits , neurofibrillary tangles , chronic inflammation , and neuronal loss , increased bone fracture rates and reduced bmd are commonly observed , suggesting common denominators between both disorders .", "the crosstalk between skeletal and bone marrow is crucial to hematopoietic stem cell ( hsc ) function and throughout the hemopoiesis .", "therefore , leptin receptors on skeletal msc function as a sensor of systemic energy homeostasis . various cell populations within the fat tissue can exacerbate the development of the chronic , low - grade inflammation associated with obesity and metabolic dysfunction .", "visceral fat tissue infiltrating macrophages in the setting of diet - induced obesity , have a pro - inflammatory phenotype which initiates and/or exacerbates the chronic inflammation that contributes to adipocyte dysfunction in obesity .", "fetuin - a , produced by the liver , is involved in the regulation of bone metabolism and insulin action , vascular calcification , neurodegenerative diseases and cancer cell proliferative signaling ." ], [ "the crosstalk between skeletal and bone marrow is crucial to hematopoietic stem cell ( hsc ) function and throughout the hemopoiesis .", "hematopoietic and skeletal stem cell homeostasis are closely related : msc progeny express numerous cytokines necessary for hsc maintenance and hematopoiesis , including kit ligand and stromal - derived factor , but also stem and progenitor cells of the hematopoietic system may reciprocally regulate skeletal progenitors by expressing myriad factors associated with skeletogenesis , whose cognate receptors are highly expressed by skeletal stem cells .", "cells of the immune system and bone cells derive from bone marrow precursors and develop in the same bone marrow microenvironment .", "the bone marrow microenvironment can also act as a niche for the onset and progression of neoplastic diseases , including both hematologic malignancies and metastases of solid tumors , mainly breast and prostatic cancer . in multiple myeloma , an osteolytic hematological malignancy characterized by an important skeletal involvement", "interestingly , these latter exhibit receptors to circulating hormones , such as leptin and thyroid - stymulating hormone , suggesting that skeletal stem cells and their progeny may link systemic exocrine regulation to both skeletal and hematopoietic system ." ], [ "as for bone , adipose tissue is a kind of immune tissue and produces immunoregulatory factors .", "therefore , these new clinical and experimental evidences definitively connect obesity and other related pathological conditions , such as metabolic syndrome , nonalcoholic fatty liver disease ( nafld ) and diabetes , to impaired bone health and fragility fractures [ 90 - 93 ] . in conclusion , it is currently emerging that adipose tissue , liver , bone and immune system modulate each other through a complex network of interconnected signals .", "various cell populations within the fat tissue can exacerbate the development of the chronic , low - grade inflammation associated with obesity and metabolic dysfunction .", "age / rage interaction is involved in the pathophysiological processes of many inflammatory and dysmetabolic diseases .", "the development and progression of diabetes - associated osteoporosis are mediated by the interaction between advanced glycation end products ( age ) and receptor of age ( rage ) ." ], [ "it is well eatablished that several neuroendocrine pathways modulate both immune responses and bone remodeling . in turn", "serotonin is synthesized in serotonergic neurons of the central nervous system , exerting various functions in the brain ; it is also synthesized in the gut , mediating different peripheral functions .", "it acts on bone cells using three different receptors : through 5ht1b receptors , it negatively regulates bone mass , while it enhances bone formation through 5ht2b and 5ht2c receptors .", "the neurological mechanism of action of serotonin on bone implicates also the interaction with the adipokine leptin , in an integrated homeostatic network with fat tissue and metabolism ( fig .", "small molecules able to specifically inhibit the intestinal tryptophane - hydroxylase and do not cross the blood brain barrier , have recently been proposed for the treatment of osteoporosis . in alzheimer s disease ( ad ) , a neurodegenerative disorder characterized by cortical and cerebrovascular amyloid peptide ( a ) deposits , neurofibrillary tangles , chronic inflammation , and neuronal loss , increased bone fracture rates and reduced bmd are commonly observed , suggesting common denominators between both disorders .", ", bone cells may represent potential therapeutic targets in the treatment of both secondary neoplastic osteoporosis and the underlying neoplasia ." ], [ "further important research horizons are opened with the extension of the discoveries of osteoimmunology and the disclosure of the immunoskeletal interface , whose practical implications may provide novel therapies for diseases other than osteoporosis , by targeting specific transcription factors , cytokines and their receptors . the correct understanding and decoding of the complex language", "through which immune system and bone communicate , although still in its dawn , is the essential requirement for the identification of such potentially useful therapeutic targets for both osteoporosis and other correlated inflammatory conditions , which share same mediators and signaling pathways .", "moreover , the discoveries of the existence of the immunoskeletal interface has also highlighted interesting repercussions for a wide range of pathological conditions beyond osteoporosis , including infections , autoimmune diseases , and neoplasia , in which same pathogenetic pathways are shared .", "considerable progress has been made in clarifying the crosstalk between bone and immune system that occurs in a complex and dynamic bone microenvironment . a central role in this crosstalk", "osteoporosis could be therefore considered as a systemic model of integrated signaling pathways and cytokines working in a cooperative fashion .", "osteoimmunology therefore represents a new approach to studying osteoporosis that in the past was not considered an inflammatory condition ." ], [] ]

[ [ "lam involvement of the uterus is extremely rare and there have been only a few such reported cases ( 2 - 7 ) , and the imaging findings of uterine lam have only been briefly mentioned in two reports ( 2 , 5 ) . in this article , we report the cross - sectional imaging findings of extensive lam involving the uterus and pelvic cavity in a 29-year - old woman with tuberous sclerosis complex ( tsc ) and we propose that certain imaging features and the clinical history may suggest the diagnosis . to the best of our knowledge ,", "lymphangioleiomyomatosis ( lam ) is a rare idiopathic disease that exclusively occurs in women of childbearing age , and this disease is characterized by the proliferation of abnormal smooth muscle cells in the lungs and along the thoracic and abdominal lymphatics ( 1 - 3 ) .", "the disease primarily affects the lungs in the majority of cases , but extrapulmonary lam occasionally occurs with or without subsequent involvement of the lungs .", "this is the first report of the imaging findings of lam involvement of female pelvic organs ." ], [ "when she was ten years old , she was diagnosed with tsc based on her history of seizure and mental retardation .", "five years previously , she underwent a pelvic magnetic resonance imaging ( mri ) study for the evaluation of menometrorrhagia and dysmenorrhea .", "markedly enlarged lam involving the uterus with extension to the pelvic cavity was suggested as the most probable diagnosis based on the follow - up imaging and clinical findings .", "the intraoperative findings revealed that the uterus was enlarged and distorted by multiple subserosal and intramural hemorrhagic cystic masses .", "adenomyotic cysts and uterine leiomyomas with red degeneration were considered in the differential diagnosis based on the imaging at that time .", "the cystic masses also involved both adnexae , the pelvic side wall and the omentum ." ], [ ", we report here on the extraordinary radiological findings of lam involving the uterus and pelvic cavity in a young woman with tsc .", "although uterine lam is rare , radiologists should consider the possibility of this disease when they see multiple cystic uterine or parauterine masses with or without internal hemorrhage in a patient with a history of tsc or pulmonary lam .", "uterine involvement of lam is extremely rare , and to the best of our knowledge , only eight cases of pathologically proven uterine lam have currently been reported ( 2 - 7 ) ." ] ]

[ [ "we performed the ts - dna gene sequence in 68 cancer samples from patients of different dukes ' stages ( a , b , and c ) and histological grade but we did not find any change in the ts - dna structure .", "this variant form presents a replacement of an evolutionary conserved tyrosine by a histidine at residue 33 of the ts polypeptide [ 17 , 18 ] ; this mutation represents the only difference between the two ts forms and must account for the structural and functional differences between them . in an our previous paper we performed the analysis of the ts structure in patients bearing crc to try to demonstrate the presence of that specific mutation , but we did not find it in any patient . here , we intend to proceed on the use of sequencing techniques to see if any ts variant form could be present in human cancer samples from patients who underwent surgery for primary colorectal cancer and previously untreated and try to find relationship between any hypothetical ts variant form with the 5-fu treatment . ", "ts is a key enzyme in the de novo synthesis of dtmp , an essential precursor of dna , which catalyses the methylation of dump to dtmp . ", "so , an association between drug response and altered ts structure could suggest that the novel ts form , which is encoded by a variant structural ts gene , confers relative resistance to fdurd ; this was supported by preliminary kinetic data indicating that this novel form has a reduced affinity for fdump .", "the critical role of ts in the nucleotide metabolism has made it an important target of a variety of chemotherapeutic agents including 5-fu , 5-fu prodrugs as capecitabine , and novel folate - based ts inhibitor such as raltitrexed and pemetrexed , used in the treatment of colorectal and other solid tumours ." ], [ "ts structure was assessed in a series of 68 patients who underwent surgery for primary colorectal carcinoma confirmed histologically and previously untreated .", "genomic dna was extracted from tumour and mucosa samples with a commercial kit purchased from qiagen ( kjvenlo , the netherlands ) and stored at 20. the ts gene of tumour and mucosa samples was amplified in seven different pcr reactions using dna primers of 1620 bases in length placed in the adjacent intronic regions of exons 1 , 2 , 3 , 4 , 5 , 6 , and 7 and listed in table 4 .", "the samples at surgery were divided in two parts : one was frozen at 80 until analysis , and the other portion was embedded in paraffin to confirm histologically the absence of contamination by normal and necrotic tissue and lymphocytes .", "the tumours were staged and graded according dukes ' system and their clinicopathological features were summarised in tables 1 , 2 , and 3 .", "the following exclusion criteria were applied : history of other neoplasias apart of crc and death occurring within 30 days following surgery and due to postoperative complications ." ], [ "7 patients had g1 histological grade , 36 had g2 , and 25 had g3 histological grade ; 10 patients had dukes ' a tumours , 27 patients had dukes ' b , and 31 patients had dukes c cancers .", "primary tumours and corresponding colonic mucosa were obtained from each patient and the ts genomic structure was performed on each of them , after histological control .", "the enzyme structure obtained by sequencing the ts genomic dna of each sample was performed in 68 patients with operable crc , untreated with previous chemotherapy .", "the median age of patients was 67 years ; 30 patients were male and 38 female .", "in all the tumour samples evaluated we did not find any ts - dna variant structure in tumour : all a , b , and c dukes ' patients showed stable ts - dna , and also in the germline genome no ts - dna variants have been observed ." ], [ "the conclusions that could be drown are that in dukes ' a , b , and c crcs there are no changes in the ts - dna gene structure and that the evaluation of the ts expression is the main crc prognostic and drug response marker .", "we performed the ts - dna gene sequence in 68 cancer samples from patients of different dukes ' stages ( a , b , and c ) and histological grade , but we did not find any mutation in the ts - dna structure .", "we intend to proceed on the use of sequencing techniques to see if any ts variant form could be present in human cancer samples from patients who underwent surgery for primary colorectal cancer ( crc ) and previously untreated and try to find a relationship between any hypothetical ts variant form with the 5-fu treatment and prognosis . ", "what remains is to evaluate the ts gene structure of the d metastatic dukes ' crcs : in these tumours it might be possible to find ts - dna structural changes related with their higher genomic instability and this fact could give an explanation of the 5-fu drug resistance and worse prognosis ." ] ]

[ [ "however , because the number of japanese individuals enrolled in the global clinical trials was relatively limited ( 13 ) , the japanese ministry of health , labour and welfare required the market authorization holders to conduct a post - marketing surveillance study , called all cases surveillance ( 18 ) , as a condition of its approval to evaluate the safety and effectiveness of all japanese patients treated with panitumumab . the main purpose of this study was to collect detailed information , particularly with regard to safety issues , on all panitumumab - treated patients ; additionally , by evaluating a large number of patients , the study aimed to identify rare adverse drug reactions ( adrs ) , which are often undetectable in smaller clinical trials .", "panitumumab was first approved in the usa ( september 2006 ) and european union ( eu ) ( december 2007 ) as monotherapy and for use in combination therapy in the eu ( november 2011 ) . in japan ,", "panitumumab was approved ( april 2010 ) for the treatment of wild - type kras gene unresectable , advanced and recurrent colorectal cancer as monotherapy , and for use in combination therapy in the first- , second- and third - line , or later , settings based on global clinical trials ( 1012,1417 ) .", "the introduction of monoclonal antibody - based therapy targeting epidermal growth factor receptor ( egfr ) has provided new alternative treatment options for various types of malignancy , including colorectal cancer ( 58 ) .", "the approval of panitumumab in japan for use in combination therapy represents the first such approval in the world .", "colorectal cancer is one of the most common cancers , representing the second ( males ; 9% ) and third ( females ; 8% ) most prevalent cancer in the usa ( 1 ) , and the third overall leading cause of cancer - related death in the western world ( 2 ) .", "panitumumab is a high - affinity , fully human igg2 monoclonal antibody specific to the extracellular domain of egfr ( 5,9 ) ." ], [ "this post - marketing surveillance study was planned to include all patients treated with panitumumab from the start date ( 15 june 2010 ) of its launch in japan . to promote the appropriate use and evaluate safety information , a vectibix appropriate use committee , a vectibix safety evaluation committee and a vectibix interstitial lung disease ( ild ) review subcommittee", "overall survival time was defined as the time from the date of first administration of panitumumab to the date of death ( regardless of the cause of death ) or censored on the last date of survival ( date of confirmation of survival as recorded in the crf or , if there was no information regarding the date of confirmation of survival , the last date of panitumumab administration was used for calculation purposes ) .", ". patients were carefully observed , and information during their clinical courses for 10 months ( 42 weeks ) , or until discontinuation of panitumumab for any reason , was collected through the pre - specified case report forms ( crfs ) . at the time of registration , a recommendation letter to stop initiating treatment with panitumumab", "completion of a specific registration form ( fig . 1 ) , which reported patient characteristics and treatment information , was mandatory before panitumumab treatment was initiated . the registration period of this post - marketing surveillance was june 2010 to november 2010", "all reported ild - like events were assessed individually by an ild review subcommittee , comprising external experts in the field of radiology , pulmonology and medical oncology .", "subsequently , the following information relating to clinical course was collected using crfs : ( 1 ) patient background including prior chemotherapy and reason for its discontinuation / termination ; ( 2 ) administration of panitumumab including its dose and date , premedication to prevent infusion reaction , concurrent medications and combined therapy ; ( 3 ) laboratory tests including serum magnesium , calcium and potassium ; ( 4 ) adverse events including time to onset , grade according to national cancer institute common terminology criteria for adverse events ( ctcae ) ver . 4.0 , treatment , causality of panitumumab and recovery and ( 5 ) outcomes including disease progression , survival or death . \n figure 1.patient registration form excerpt .", "evaluation of ild - like events was performed using computed tomography ( ct ) and x - ray imaging , and by assessment of clinical information ." ], [ "overall survival ( n= 1062 ) in patients receiving third - line , or later , therapy with panitumumab monotherapy .", "during the registration period from june to november 2010 , a total of 3091 patients were registered ( completion of mandatory patient registration forms ) from 1031 clinical institutes and departments in japan . of the 3091 registered patients ,", "the median overall survival time ( 95% confidence interval ) was 10.3 months ( 9.011.8 months ) , with 56.6% censored cases .", "the overall incidence of adrs in all grades was 84.1% ( 2595/3085 patients ) ( table 2 ) ." ], [ "during the registration period from june to november 2010 , a total of 3091 patients were registered ( completion of mandatory patient registration forms ) from 1031 clinical institutes and departments in japan . of the 3091 registered patients ,", "the majority ( 86.5% ) received combination therapy , of which 193 patients received concomitant folfox ( 62.3% ) . with regard to the use of panitumumab monotherapy in the first - line setting , primary physicians did not select combination chemotherapy considering various patient factors , such as age and general condition , because there is no limitation in the indication of panitumumab for combination or monotherapy in japan .", "1254 ( 40.7% ) patients received monotherapy and 1831 ( 59.4% ) patients received combination chemotherapy .", "( 47.6% ) of the 2232 patients receiving third - line , or later , treatment were in the monotherapy group . \n" ], [ "the median period of treatment with panitumumab was 113.0 days ( range : 1559 days ) , with 14.6% of patients receiving panitumumab for > 10 months .", "the main reasons for discontinuation ( with some duplicate counting ) were as follows : disease progression in 1903 ( 61.7% ) patients , of which 1484 patients ( 78.0% ) had confirmed disease progression by diagnostic imaging ; occurrence of adverse events in 431 ( 14.0% ) patients ; patient refusal ( 190 patients ; 6.2% ) ; lack of patient hospital visits ( 30 patients ; 1.0% ) and other reasons ( 185 patients ; 6.0% ) .", "panitumumab was discontinued in 2592 ( 84.0% ) patients in the safety analysis set ( n = 3085 ) ." ], [ "the most common cause of death was ild ( 20 patients , according to the evaluation of the ild subcommittee ) .", "summary of safety data based on the evaluation of the ild review subcommittee . including grade-2 serious cases .", "the overall incidence of adrs in all grades was 84.1% ( 2595/3085 patients ) ( table 2 ) .", "a summary of safety data from the post - marketing surveillance study and panitumumab clinical trials ( 19 ) is presented in table 3 . \n" ], [ "the overall incidence rate of major skin disorders ' ( which includes all related events ) was 78.4% ( grade 3 , 14.7% ) .", "dermatitis acneiform occurred in 69.9% of patients ( grade 3 , 10.5% ) , paronychia in 24.2% ( grade 3 , 4.3% ) , dry skin in 21.7% ( grade 3 , 2.1% ) and pruritus in 4.8% ( grade 3 , 0.4% ) .", "the median time from the first day of treatment to the onset of each of the major skin disorders was as follows : 15 days for dermatitis acneiform , 43 days for paronychia , 29 days for dry skin and 21 days for pruritus .", "the prevalence of skin disorders was similar with panitumumab monotherapy ( 74.7% ; 937/1254 ) and panitumumab plus chemotherapy ( 80.9% ; 1482/1831 ) ." ], [ "the incidence rate of hypomagnesemia in the overall population was 16.9% ( 520/3085 ) , with that of grade 3 hypomagnesemia being 4.0% ( 123/3085 ) .", "the incidence rate of electrolyte abnormalities was 19.3% ( 596/3085 ) , with that of grade 3 cases being 4.8% ( 149/3085 ) .", "the respective incidence rates of hypomagnesemia , hypocalcemia and hypokalemia in patients for whom laboratory data for these three electrolytes were available were 36.5% ( 520/1425 ) , 6.7% ( 136/2016 ) and 2.3% ( 67/2855 ) .", "of 30 patients with grade 3 hypomagnesemia and hypocalcemia , 5 patients experienced relevant clinical symptoms accompanying electrolyte abnormalities : qtc prolongation ( 3 cases ) , rhabdomyolysis , paralysis , tetany and convulsion ( 1 case of each ) .", "the median time to hypomagnesemia onset after panitumumab treatment initiation was 63 days in all cases : 39.5 days in patients who were treated with cetuximab immediately before panitumumab and 71 days in patients who were not .", "the incidence of hypomagnesemia and hypocalcemia peaked at 34 months after the start of panitumumab administration .", "of 105 patients who experienced both hypomagnesemia and hypocalcemia , 42 patients had the same grade of hypomagnesemia and hypocalcemia ; 42 and 21 patients compared to each other had higher grades of hypomagnesemia and hypocalcemia , respectively ." ], [ "infusion reaction occurred in 1.5% ( 47/3085 ) of patients , with an incidence rate of grade 3 or serious cases of 0.2% ( 6/3085 ) . no grade 4 cases , or deaths due to infusion reaction ,", "infusion reaction occurred at initial administration in 61.7% ( 29/47 ) of patients and in 14.9% ( 7/47 ) of patients at second administration , while the first infusion reaction occurred at the time of the third or later administration in the remaining 11 patients ( with the latest infusion reaction occurring at the 21st administration ) .", "panitumumab was administered to 70 patients who had past histories of infusion reaction due to cetuximab , following premedication and at reduced speed of infusion in almost all cases .", "two of these patients ( 2.9% ) experienced grade 1 infusion reaction , while infusion reaction occurred in 9/847 ( 1.1% ) patients without a history of infusion reaction to cetuximab administration ." ], [ "overall , the incidence rate of ild was 1.3% ( 39/3085 ) : 1.3% in monotherapy and 1.3% in combination therapy , resulting in a mortality rate of 0.6% ( 20/3085 ) . of the total ild cases , 51.3% ( 20/39 )", "diffuse alveolar damage ( dad ) was observed in 46.2% ( 18/39 ) of patients and 15 of the 18 dad cases were fatal .", "the remaining ild cases were diagnosed as hypersensitivity pneumonia ( 9 cases ) or organizing pneumonia ( 8 cases ) , with 4 unevaluable cases . \n", "the time to onset of ild varied ( table 4 ) . as determined by ct imaging ,", "table 4.time to onset of interstitial lung disease ( ild)time ( months)all12345678910>10ild cases84111450320139fatal cases(6)(2)(4)(0)(2)(2)(0)(1)(2)(0)(1)(20 ) time to onset of interstitial lung disease ( ild )" ], [ "the incidence of cardiac disorders was 0.2% ( 7/3085 ) , with death due to heart failure ( grade 5 ) reported in one patient . in this patient ,", "treated with panitumumab and folfiri , pancytopenia ( not related to panitumumab ) appeared on day 23 , followed by pneumonia ( day 28 ) and heart failure ( day 32 ) ." ], [ "in total , 1135 deaths were recorded , and most of them were related to progression of colorectal cancer . however , in 25 ( 2.2% ) patients , a relationship to panitumumab treatment could not be ruled out . among these ,", "the most common cause of death was ild ( 20 patients , according to the evaluation of the ild subcommittee ) ." ], [ "meier curve for overall survival based on 1062 patients in the safety analysis set who were receiving panitumumab monotherapy in the third - line , or later , setting . \n", "figure 4.overall survival ( n= 1062 ) in patients receiving third - line , or later , therapy with panitumumab monotherapy .", "overall survival ( n= 1062 ) in patients receiving third - line , or later , therapy with panitumumab monotherapy .", "the median overall survival time ( 95% confidence interval ) was 10.3 months ( 9.011.8 months ) , with 56.6% censored cases ." ], [ "the main objective of the current post - marketing surveillance study was to evaluate the safety of panitumumab in japanese patients with unresectable colorectal cancer ( and with the majority of patients possessing wild - type kras tumors ) in clinical practice .", "the current post - marketing surveillance study in japanese patients with unresectable colorectal cancer confirmed the safety profile and effectiveness of panitumumab that has been reported previously in clinical trials .", "it is considered that the benefit / risk balance for the use of panitumumab in patients with unresectable colorectal cancer remains favorable also in japan .", "the egfr - signaling pathway potentially plays a pivotal role in regulating magnesium homeostasis , and , indeed , hypomagnesemia / magnesium has been shown in patients with colorectal cancer receiving egfr - targeting antibodies ( 24 ) . in the current study ," ], [ "this work was supported by takeda pharmaceutical company limited . funding to pay the open access publication charges for this article was provided by takeda pharmaceutical company ." ], [ "has received a consultancy fee from takeda , speaker honoraria from takeda , taiho and yakult , and research funding from takeda , bristol - myers squibb , merck serono and chugai .", "t.y . has received a consulting fee from takeda , speaker honoraria from chugai , takeda and merck serono , and research grants from taiho , daiichi - sankyo , lily , pfizer and yakult .", "t.h . has received a consultancy fee from takeda and speaker honoraria from takeda , chugai , taiho , pfizer , yakult and daiichi - sankyo .", "k.m . has received a consultancy fee from takeda , speaker honoraria from takeda , taiho , yakult , chugai , merck serono and bristol - myers squibb , and research funding from taiho , pfizer and merck serono .", "has received consultancy fees from taiho , chugai , takeda and merck serono , speaker honoraria from taiho , chugai , yakult , bristol - myers squibb , merck serono , kyowa hakko kirin , takeda , kaken , johnson & johnson , toray , aska and bayer , a manuscript fee from chugai , and a donation from taiho , chugai , yakult , bristol - myers squibb , merck serono , kyowa hakko kirin , takeda , daiichi - sankyo , ono , eisai , kaken and tori .", "y.k . has received a consultancy fee , speaker honoraria and non - specific research support from takeda ." ] ]

[ [ "it is classified into two clinical variants : the classical form , usually composed of multiple and grouped skin - colored , pedunculated and cerebriform nodules that often coalesce to form a plaque and a second more rare form , presenting as a solitary dome - shaped sessile papule or nodule.24 we report here eight cases of nlcs in order to assess the epidemiologic , clinical , and pathological features , as well as the management of this uncommon neoplasm .", "nevus lipomatosus cutaneous superficialis ( nlcs ) was first described by hoffman and zuhrelle in 1921.1 it s a rare idiopathic hamartomatous benign condition characterized by the presence of an ectopic mature adipose tissue within the dermis ." ], [ "this study was a retrospective case series including all patients with histopathologically documented nlcs , who attended the dermatology department of charles nicolle hospital in tunisia during the last 14 years ; between january 1997 and december 2010 . for each patient , we recorded the following data : age , sex , duration of the lesions , their localizations , number , and size as well as their management and evolution . ethical approval and informed consent" ], [ "epidemiologic , clinical and pathological features , and management of nevus lipomatosus cutaneous superficialis ( nlcs ) in all eight patients .", "eight patients with nlcs were observed , three males and five females , aged between 7 and 41 years . in patients number 4 , 5 , 7 , and 8 , lesions had begun during childhood ( at 1 , 4 , 5 , and 6 years respectively ) . for the other four patients ( number 1 , 2 , 3 , and 6 ) lesions had begun in the third to fourth decade of life .", "clinical presentation was that of the classical form in seven patients and of the solitary form in one patient ( patient number 3 ) . in four patients it was one of the limbs which had the lesion , and in the other four patients it was the trunk ( figure 1 : patient 8 ; figure 2 : patient 5 ) .", "table 1 summarizes the main epidemiologic , clinical and pathological features , and management of nlcs in all eight patients . \n" ], [ "patients unwilling for surgery may undergo cryotherapy which yields partial but satisfactory results.8 recently , a case of classic nlcs successfully treated with co2 laser was reported with no recurrence during a follow - up period of 12 months.23 in this retrospective study , we did nt investigate chromosomal abnormalities to identify the genetic biomarkers of this congenital pathology , since cytogenetic analysis was reported in only one previous study.20", "nlcs is more commonly present from birth , but can appear later in life ; there is neither sex predilection nor familial trend in this disorder.1 in this study , there were five cases in which the lesion appeared in the first three decades , and in three cases nlcs appeared after 35 years .", "the genetic background of nlcs is still unknown , only one cytogenetic study was reported recently showing a 2p24 deletion.20 the pathogenesis of nlcs remains unknown .", "two clinical patterns of nlcs exist ; a multiple form or classical type , and the solitary form . in the classical type ," ], [ "nlcs is a rare skin malformation ; we report herein a large case series of eight patients where the classical form is predominant", "physicians should be aware of this rare condition because early recognition enables more conservative resection of the tumor and less invasive reconstruction of the defect .", ". our study may give additional data about epidemiological and clinical pattern of this hamartoma .", "further studies are needed , especially prospective studies , by using chromosomal analysis to reach conclusions about the role of the genetic abnormalities in the development of this hamartoma ." ] ]

[ [ "hence , this study was carried out to investigate and compare the protective effect of administration of both tannic and gallic acids on normal and cisplatin induced nephrotoxicity in rats .", "extensive studies have been carried out on the protective effect of cotreatment and posttreatment of phenolic acids against cisplatin induced nephrotoxicity .", "the use of chemotherapy in the treatment of cancer has opened new possibilities for improvement of the quality of life of cancer patients . despite its success , treatment with some of the most effective anticancer drugs", "a number of strategies have been proposed for the prevention / management of cisplatin induced nephrotoxicity , since there is no specific treatment , with the use of some synthetic drugs which have been popular . however , these drugs have some associated risks and side - effects , hence , the need for natural alternatives of plant origin ( plant foods / extracts ) with little or no side - effect .", ", the mechanism of cisplatin ( cis - diamminedichloroplatinum ( ii ) or cddp ) induced nephrotoxicity has gradually been elucidated ." ], [ "dose of cisplatin ( 7.5 mg / kg bwt ) after oral treatment of ga and ta was given to the animals in groups ii , iii , iv , vi , and vii .", "also , ta was orally administered at two doses , 20 and 40 mg / kg body weight ( bwt ) , to groups vi and vii , respectively , for 7 consecutive days . on the 7th day of pretreatment , a single i.p .", "after two ( 2 ) weeks of acclimatization , 80 male rats were randomly divided into eight ( 8) groups of ten animals each : group i served as a normal control and received saline ( 0.85 w / v% ) orally for 7 consecutive days and on the 7th day , 1 hr after receiving the oral saline dose , the rats received a single i.p .", "ga was orally administered at two doses , 20 and 40 mg / kg body weight ( bwt ) , to groups iii and iv , respectively , for 7 consecutive days .", "groups v and viii received only higher dose ( 40 mg / kg ) of ga and ta orally for 7 consecutive days , respectively , and on the 7th day 1 hr ga and ta treatment received a single i.p .", "group ii served as toxicant group and received saline ( 0.85% ) orally for 7 consecutive days .", "injection of saline ( 0.85% ) to ensure that groups v and viii received only the higher dose of ga and ta ; this was done in order to test that the higher dose did not produce any kind of toxic effects ." ], [ "as evident from table 1 , administration of a single dose of cisplatin ( 7.5 mg / kg bwt ) caused a significant increase in the biomarkers of renal function ( creatinine , urea , and uric acid ) when compared with the control group that received only saline ( 0.85% w / v ) .", "however , pretreatment with gallic and tannic acids orally at two doses , 20 and 40 mg / kg body weight , respectively , shows a significant ( p < 0.05 ) improvement of renal function due to a decrease in the creatinine , urea , and uric acid levels when compared with the induced group ( group 2 ) . also , administration of a single i.p dose of cisplatin ( 7.5 mg / kg bwt ) caused a significant decrease in the biomarkers of oxidative stress [ superoxide dismutase ( sod ) , catalase ( cat ) , glutathione peroxidase ( gpx ) , and reduced glutathione ( gsh ) ] when compared with the control group that received only saline ( 0.85% w / v ) ( table 2 ) .", "however , pretreatment with gallic and tannic acids orally at two doses , 20 and 40 mg / kg body weight , respectively , shows a significant ( p < 0.05 ) improvement in the body 's antioxidant status by an increase in the activities of superoxide dismutase ( sod ) , catalase ( cat ) , glutathione peroxidase ( gpx ) , and reduced glutathione ( gsh ) when compared with the induced group ( table 2 ) . likewise , there was a significant ( p < 0.05 ) increase in the malondialdehyde ( mda ) content in rat kidney administered a single i.p dose of cisplatin ( 7.5 mg / kg bwt ) ." ], [ ", we compare the protective effect of administration of gallic and tannic acids ( two commonly phenolic acids that are structurally related ) of the same dosage against normal and cisplatin induced renal injury in rats for the first time by attenuating renal oxidative stress .", "however , the reduced kidney and plasma mda content ( figure 1 ) and restoration of sod , gsh , and cat activities ( table 2 ) in pretreated rats suggest an improvement in the in vivo antioxidant status , which may be a function of the antioxidant properties of the phenolic acids ( gallic and tannic acids )", "however , restoration of gsh levels in the pretreated rats suggests the antioxidant and nephroprotective properties of the phenolic acids ( table 2 ) .", "however , the restoration of the plasma creatinine , urea , and uric acid level in rats treated with both gallic and tannic acids ( table 1 ) suggests that both phenolic acids have the ability to prevent kidney damage and protect the kidney against nephrotoxicity ." ], [ "these results indicated that both gallic and tannic acids exhibit nephroprotective effect and the possible mechanism of action by which they exert this effect could be due to their antioxidant properties and inhibition of arginase activity .", "furthermore , they suppressed the generation of ros , lipid peroxidation , and oxidative stress in kidney tissues .", "the results of the present study revealed that oxidative stress and apoptosis / necrosis play an important role in pathogenesis of cisplatin nephrotoxicity .", "gallic and tannic acids , two important pharmacologically active phenolic compounds , reduced cisplatin induced functional and histological renal damage .", "however , tannic acid exhibited better nephroprotective potential than gallic acid which may be due to the glycosidation with a glucose moiety ." ] ]

[ [ "although both orbital cavernous haemangiomas and schwannomas share many similar clinical and radiological characteristics [ 58 ] , it is important to distinguish between the tumours because they demonstrate important different features and the treatments of choice for the two are different [ 3 , 79 ] .", "consequently , this study aims to assess mr imaging findings distinguishing orbital cavernous haemangiomas from schwannomas and to elaborate on specific differences between the two tumours .", "cavernous haemangioma is the most common primary orbital tumour in adults , accounting for 6% of all orbital lesions [ 13 ] .", "orbital cavernous haemangiomas and schwannomas present as slow progressive enlargement and the most common presenting sign and symptom is painless proptosis [ 48 ] .", "the spread pattern of the contrast enhancement on dynamic contrast - enhanced mr imaging is considered the most important finding distinguishing the two tumours [ 1014 ] . however , the literature on mr imaging findings in the differentiation of these two tumours is based on small patient populations .", "magnetic resonance imaging , especially dynamic mr imaging , plays a crucial role in the differentiation of orbital cavernous haemangiomas and schwannomas [ 7 , 8 , 1014 ] .", "orbital schwannomas are benign peripheral nerve sheath tumours and constitute 1% of all orbital tumours [ 1 , 3 ] ." ], [ "most patients presented with painless insidious proptosis . some patients demonstrated a limitation of extraocular motion , diplopia and strabismus .", "mr imaging including t1- and t2-weighted imaging and contrast - enhanced mr imaging was performed in all 59 patients .", "on contrast - enhanced mr imaging including dce mr imaging , the spread pattern of the contrast enhancement , enhancement pattern , ci and type of tic were evaluated .", "between june 2004 and february 2009 , 43 patients with cavernous haemangiomas and 16 patients with schwannomas confirmed by pathological results were enrolled in the protocol .", "c e dynamic mr images obtained at 25 , 75 and 225 s , respectively , after administration of gadopentetate dimeglumine , showed enhancement starting from one point of peripheral portion of the tumour ( arrowhead ) . f post - contrast t1-weighted imaging with fat saturation showed further enlargement of enhancement regions ( arrowhead ) frequency distribution of individual mr imaging features in cavernous haemangiomas was compared with that in schwannomas with chi - squared tests .", "progressive enhancement means that on early imaging after the injection , one small point or portion of enhancement was initially noted , then contrast media progressively filled up the tumour and eventually the mass showed total and homogeneous enhancement ( fig . 1 ) ." ], [ "mr imaging including t1- and t2-weighted imaging and contrast - enhanced mr imaging was performed in all 59 patients .", "between june 2004 and february 2009 , 43 patients with cavernous haemangiomas and 16 patients with schwannomas confirmed by pathological results were enrolled in the protocol .", "most patients presented with painless insidious proptosis . some patients demonstrated a limitation of extraocular motion , diplopia and strabismus .", "informed consent was obtained from all patients for anonymous performance of radiological studies and analysis of clinical data ." ], [ "we chose the area that demonstrated the greatest degree of early enhancement so that the time intensity curve ( tic ) could be generated .", "a region of interest ( roi ) was drawn manually on the dynamic images for assessment of the enhancement kinetics .", "the acquisition of the dynamic images began concurrently with the initiation of the injection of 0.1 mmol of gadopentetate dimeglumine ( magnevist , schering , berlin , germany ) per kilogram .", "dynamic contrast - enhanced ( dce ) mr imaging was performed by using a fast spoiled gradient recalled ( fspgr ) sequence with 8.4/4 ms , a flip angle of 15 , one excitation , a matrix of 256 160 , a field of view of 220 220 mm , and a section thickness of 3.2 mm at 0 interval .", "the contrast index ( ci ) was calculated from : ci = [ ( signal intensity post - contrast ) ( signal intensity pre - contrast)]/(signal intensity pre - contrast ) .", "the tics were analysed qualitatively as wash - out , persistent or plateau - shaped curves .", "dce mr imaging was evaluated by using a ge aw 4.2 workstation ( ge healthcare ) ." ], [ "the spread pattern of the contrast enhancement was divided into two groups : one starting from a small point or portion and the other starting from a wide area . ", "progressive enhancement means that on early imaging after the injection , one small point or portion of enhancement was initially noted , then contrast media progressively filled up the tumour and eventually the mass showed total and homogeneous enhancement ( fig . 1 ) .", "f post - contrast t1-weighted imaging with fat saturation showed further enlargement of enhancement regions ( arrowhead ) a 54-year - old woman with a cavernous haemangioma .", "c e dynamic mr images obtained at 25 , 75 and 225 s , respectively , after administration of gadopentetate dimeglumine , showed enhancement starting from one point of peripheral portion of the tumour ( arrowhead ) .", "c e dynamic mr images obtained at 25 , 75 and 225 s , respectively , after administration of gadopentetate dimeglumine , showed enhancement starting from one point of peripheral portion of the tumour ( arrowhead ) .", "on contrast - enhanced mr imaging including dce mr imaging , the spread pattern of the contrast enhancement , enhancement pattern , ci and type of tic were evaluated .", "b the tumour appeared hyperintense ( arrowhead ) relative to muscle on axial t2-weighted imaging ." ], [ "frequency distribution of individual mr imaging features in cavernous haemangiomas was compared with that in schwannomas with chi - squared tests .", "fisher s exact test was performed when the sample size in the subgroups was deemed too small ." ], [ "there was a significant difference between cavernous haemangiomas and schwannomas regarding the location ( including anterior orbit , posterior orbit , or both anterior and posterior orbit ; extraconal or intraconal space ) , configuration and margins of the mass , signal intensity and homogeneity on t1- and t2-weighted imaging , the spread pattern of the contrast enhancement , enhancement pattern and type of time ", "tables 1 and 2 describe the frequency distribution of non - enhanced mr imaging features ( table 1 ) and contrast - enhanced mr imaging features ( table 2 ) .", "a obliquely sagittal t1-weighted imaging identified an irregular extraconal tumour with isointensity of the anterior portion of the tumour ( arrow ) and slight hypointensity of the posterior portion ( arrowhead ) relative to muscle ." ], [ "thus , surgical excision is the treatment of choice for orbital schwannomas , different from orbital cavernous haemangiomas [ 3 , 79 ] .", "therefore , recent literature supports observation as an alternative to surgical excision for asymptomatic orbital cavernous haemangiomas and surgery can be withheld until vision is threatened or cosmetic appearance resulting from proptosis is unacceptable [ 3 , 9 ] .", "the most common presenting sign and symptom of the orbital cavernous haemangioma is painless proptosis . in the past", "capillary haemangiomas are a different sort of haemangiomatous tumour that are more common in children , often regress and have a different imaging appearance [ 5 , 7 ] .", "however , orbital cavernous haemangiomas have recently been classified as type 3 low - flow arteriovenous malformations with a direct arterial in - flow and venous out - flow mechanism ( arterial low - flow type ) rather than as true neoplasms or proliferating hamartomas , and , to our knowledge , there is no evidence of malignant transformation in the literature ." ], [ "cavernous haemangiomas and schwannomas have different mr imaging features including the location , configuration and margins of the mass , signal intensity and homogeneity on t1- and t2-weighted imaging , the spread pattern of contrast enhancement , the enhancement pattern and tic type , which could be helpful in the differentiation of the two tumours .", "mr imaging , especially dynamic contrast - enhanced mr imaging , plays a vital role in the differential diagnosis of cavernous haemangiomas and schwannomas .", "the spread pattern of the contrast enhancement on dynamic contrast - enhanced mr imaging is the most reliable finding distinguishing cavernous haemangiomas and schwannomas .", "markedly homogeneous hyperintensity signal on t2-weighted imaging is another reliable finding distinguishing the two tumours ." ] ]

[ [ "gingival enlargement is a common observation in clinical practice that may occur as a result of a response to varied stimuli and/or interactions with the host and the environment .", "such cases should be treated in a methodical manner , involving a detailed medical history followed by conventional nonsurgical therapy .", "these lesions could be either localized to certain aspect of the oral cavity or generalized affecting larger areas .", "these excessive gingival distensions may adversely affect speech , mastication , tooth eruption , esthetics along with major hindrance to the maintenance of routine oral hygiene .", "the possible reasons for this condition may be related to plaque , hormonal imbalances , or systemic - induced manifestation .", "however , in order to maintain successful therapeutic outcome , it is crucial to create patient awareness and motivation , along with a timely recall visits ." ], [ "previously , a case of amlodipine - induced gingival enlargement associated with fibroepithelial hyperplasia has been reported ; however , there has not been any report of amlodipine - induced gingival enlargement associated with pg , to the author 's knowledge .", "thus , the biopsy picture revealed a combination of drug - induced gingival overgrowth associated with pg .", "the present case reports a 23-year - old male patient who reported to the department of periodontology with the chief complaint of growth in the lower right front region of mouth since 1 year .", "thus , based on clinical and histopathological findings , the final diagnosis was determined as pof .", "a tentative diagnosis of fibroma was made and patient was informed about the treatment plan .", ". a differential diagnosis of pg , peripheral fibroma , and hyperplastic gingival overgrowth was suggested ." ], [ "the present case reports a 23-year - old male patient who reported to the department of periodontology with the chief complaint of growth in the lower right front region of mouth since 1 year .", "pyogenic granuloma ( pg ) may occur in all ages and is predominant in the second decade of life in females .", "it is a common nonneoplastic , exophytic vascular growth often associated with the history of trauma or chronic irritation .", "however , literature has reported about 16% of pg recur after excision in spite of being reactive hyperplasias ." ], [ "peripheral ossifying fibroma ( pof ) is usually an isolated nonneoplastic growth on gingiva that is categorized as a hyperplastic inflammatory lesion . a common gingival growth , it is typically seen on the interdental papilla and is believed to comprise about", "the elimination of causative factors , excision of the lesion is the choice of treatment .", "females are more commonly affected , and anterior maxilla is the most prevalent location of involvement .", "the etiology of pof is uncertain and have been attributed to trauma or local irritants such as plaque , calculus , microorganisms , masticatory forces , ill - fitting dentures , and poor - quality restorations . following" ], [ "previously , a case of amlodipine - induced gingival enlargement associated with fibroepithelial hyperplasia has been reported ; however , there has not been any report of amlodipine - induced gingival enlargement associated with pg , to the author 's knowledge .", "gingival enlargement has most frequently been described as an adverse effect following administration of nifedipine ; however , the incidence with amlodipine is rare . in the present case , a 40-year - old female patient reported with the chief complaint of swelling in the lower front region of gums , which had been progressively increasing in size over the previous 6 months .", "gingival enlargement is a known adverse effect of calcium channel blockers , especially the dihydropyridine group ." ], [ "the patient will reduce local microflora that will help in eliminating the major focus of infection . a critical factor that assists successful therapeutic outcome", "the patient should be placed on a regular dental visit , in which a complete description of the existing dental condition should be informed . creating awareness and educating patients regarding the influence of poor oral hygiene and habits to these gingival lesions are essential to avoid further recurrence .", "clinical differential diagnosis for localized gingival overgrowths includes fibroma , peripheral giant cell granuloma , pg , peripheral odontogenic fibroma , and peripheral ossifying fibroma . a relatively healthy oral environment provided by the dentist and maintained by", "it is possible to misdiagnose reactive lesions arising from the gingiva . a detailed case history to determine the etiology and histopathological examination is essential for an accurate diagnosis and for proper management ." ], [], [] ]

[ [ "it is obvious that more the concentration of epinephrine , the better the control of bleeding , but there will be more cardiovascular changes . in spite of the effect of local anesthetics on vital signs , their accurate application is able to dramatically reduce stress . given the above bodies of evidence and the importance of monitoring patients hemodynamic changes during oral surgery , the present study has been conducted to investigate these alterations during periodontal surgery outside the operating room with local anesthesia .", "successful management and treatment of periodontal disease depends upon simple medical procedures such as health education , prophylaxis , scaling and root - planing , gingivectomy , gingival grafts , and different types of gingival flaps .", "elimination of pathological changes of the pocket wall is among the objectives of surgical treatment for periodontal pockets , so that a stable and sustainable situation can be achieved .", "currently , several flap techniques have been applied for the treatment of pocket , among which modified widman flap is worth mentioning .", "periodontal pocket refers to the pathological increase in the depth of gingival sulcus , and is one of the main clinical features of periodontal disease ." ], [ "the equipments used in the study included ( 1 ) finger pulse oximeter ( soor afarinesh company ) , and ( 2 ) automatic sphygmomanometer ( omron company ) according to the following inclusion criteria , 50 patients ranging from 30 to 50 years participated in this study . in all patients , changes in heart rate , blood pressure , and also pulse oximetry", "this practical clinical trial study was carried out on patients with gingival disease referred to the clinic of dental faculty of babol university of medical sciences , and underwent modified widman flap surgery on anterior maxillary region in periodontology department .", "were examined during five steps ; the first step before injecting the anesthetic , the second step after the anesthetic injection and before the incision , the third step after the incision , the forth step after debridement , and the fifth step following stitching and the end of the operation .", "it should be noted that all the operations were performed by one surgeon , and all patients received two anesthetic cartridges containing lidocaine ( 2% ) and epinephrine ( 1:80000 ) ( darou pakhsh company ) , using the infiltration technique into the vestibular depth and interdental papilla and also hard palate mucosa , in anterior 1/6 region and incisive canal ; no additional anesthetic cartridge was used during surgery , and those in need of re - injection were excluded from the study .", "spo2 and hemodynamic alterations were assessed using the automatic sphygmomanometer and pulse oximeter attached to the patient 's finger during surgery . \n having no systemic disease to be considered as contraindication of periodontal surgery or affecting the heart rate and blood pressurehaving no sensitivity to anestheticsnot being in pregnancy or lactation period . \n ", "having no systemic disease to be considered as contraindication of periodontal surgery or affecting the heart rate and blood pressure having no sensitivity to anesthetics not being in pregnancy or lactation period .", "data were analyzed by spss statistical software using anova repeated measure test , and p < 0.05 was considered as statistically significant level ." ], [ "according to the following inclusion criteria , 50 patients ranging from 30 to 50 years participated in this study . in all patients , changes in heart rate , blood pressure , and also pulse oximetry", "were examined during five steps ; the first step before injecting the anesthetic , the second step after the anesthetic injection and before the incision , the third step after the incision , the forth step after debridement , and the fifth step following stitching and the end of the operation .", "it should be noted that all the operations were performed by one surgeon , and all patients received two anesthetic cartridges containing lidocaine ( 2% ) and epinephrine ( 1:80000 ) ( darou pakhsh company ) , using the infiltration technique into the vestibular depth and interdental papilla and also hard palate mucosa , in anterior 1/6 region and incisive canal ; no additional anesthetic cartridge was used during surgery , and those in need of re - injection were excluded from the study .", "spo2 and hemodynamic alterations were assessed using the automatic sphygmomanometer and pulse oximeter attached to the patient 's finger during surgery ." ], [ "\n having no systemic disease to be considered as contraindication of periodontal surgery or affecting the heart rate and blood pressurehaving no sensitivity to anestheticsnot being in pregnancy or lactation period . \n having no systemic disease to be considered as contraindication of periodontal surgery or affecting the heart rate and blood pressure having no sensitivity to anesthetics not being in pregnancy or lactation period ." ], [ "data were analyzed by spss statistical software using anova repeated measure test , and p < 0.05 was considered as statistically significant level ." ], [ "the present research has been implemented on 50 patients referring to periodontology department of dental faculty for periodontal surgery . among the study participants with the mean age of 42.58", "comparison of the meansd spo2 during the five stages of modified widman flap surgery spo2 variability during the five stages of modified widman flap surgery", "comparison of the meansd sb * during the five stages of modified widman flap surgery sbp changes during the five stages of modified widman flap surgery the maximum and the minimum diastolic blood pressures were , respectively , obtained in the second and the first stage ." ], [ "there was a significant difference between the first step and the second ( p < 0.0001 ) and the third ( p = 0.001 ) , the second step and the first ( p = 0.001 ) and the fourth and the fifth ( p < 0.0001 ) , the third step and the first ( p = 0.001 ) and the fourth ( p = 0.010 ) , the fourth step and the second ( p < 0.0001 ) and the third ( p = 0.010 ) , and also the fifth step and the second ( p < 0.0001 ) [ table 1 and figure 1 ] .", "the mean systolic blood pressure was highest in the second stage and lowest in the first one . in the five steps studied ,", "comparison of the meansd sb * during the five stages of modified widman flap surgery sbp changes during the five stages of modified widman flap surgery" ], [ "statistical analysis showed significant difference between the first stage and the second ( p = 0.001 ) , the second stage and the first ( p = 0.001 ) and the third ( p < 0.0001 ) and the fourth ( p = 0.003 ) , the third stage and the second ( p < 0.0001 ) , and the fourth step and the second ( p = 0.003 ) ; however , no meaningful relationship was found between the fifth step and the other stages [ table 2 and figure 2 ] .", "the maximum and the minimum diastolic blood pressures were , respectively , obtained in the second and the first stage .", "comparison of the meansd dbp * during the five stages of modified widman flap surgery dbp changes during the five stages of modified widman flap surgery" ], [ "significant differences were found between the first step and the second and the third ( p < 0.0001 ) , the second and the third steps and the other stages , the fourth step and the second and the third ( p < 0.0001 ) and the fifth ( p = 0.001 ) , and also the fifth step with the second and the third ( p < 0.0001 ) and the fourth ( p = 0.001 ) steps [ table 3 and figure 3 ] .", "according to statistical analysis , the maximum and the minimum heart rate was respectively observed in the second and the fifth stage .", "comparison of the meansd hr * during the five stages of modified widman flap surgery changes in hr during the five stages of modified widman flap surgery" ], [ "comparison of the meansd spo2 during the five stages of modified widman flap surgery spo2 variability during the five stages of modified widman flap surgery", "similarly , based on statistical analysis , no significant difference has been achieved in the mean spo2 during the five stages studied ( p > 0.05 ) [ table 4 and figure 4 ] ." ], [ "this study illustrates remarkable sedative effect of midazolam on anxious patient prior to the surgery ; nonetheless , this effect does not sustain during the operation .", "a meaningful difference has been found in the second step and following the anesthetic injection containing lidocaine and epinephrine ( 1:80000 ) ( p < 0.0001 ) in systolic and diastolic blood pressure and heart rate , on which the result was almost predictable .", "blood pressure and heart rate were remarkably increased after injection of anesthesia ( p < 0.05 ) . according to figures 1 , 2 , and 3 ,", "investigating changes in blood pressure and heart rate during dental surgery , the results revealed an increase in both parameters after anesthesia with lidocaine ( 2% ) and epinephrine ( 1:80000 ) , which is compatible to findings of the present research . in faraco", "have addressed to pulse oximetry during oral surgery with and without intravenous sedation and found out a significant reduction in arterial blood oxygen levels in the group receiving midazolam .", "heart rate and temperature variability during periodontal surgery , patients were divided into four groups according to types of surgery , and blood pressure and heart rate were measured after anesthetic injection and the end of the operation ; blood pressure and heart rate were decreased in patients undergoing gingivectomy and periodontal flap , which is in consistence with the results obtained in the present research . however , no changes in heart rate and blood pressure have been observed following frenectomy and curettage , indicating that the difficulty in treatment process is an effective factor in blood pressure ." ], [ "different surgical stages will be accompanied by diverse effects on hemodynamic variability and pulse oximetry . according to the present study , blood pressure and heart rate are significantly increased after anesthetic injection and are decreased in the following stages by the elimination of adrenaline stimulatory effect . moreover", ", no significant alteration has been observed in spo2 during the operational steps in this research ." ] ]

[ [ "this study was therefore designed to investigate the prevalence of ckd in the korean population using knhanes samples , based on the definition and classification by kdigo 2012 guidelines , as well as the impact of changes through a comparison of the ckd - epi and mdrd study equations for the estimation of gfr , and the associations between ckd and major risk factors , including dm , hypertension , age , and gender .", "the number of patients treated with renal replacement therapy ( rrt ) including dialysis and transplantation has increased dramatically in korea , from 28,046 in 2000 to 75,042 in 2013 .", "the prevalence of rrt was 1,446 patients per million population ( pmp ) , with an incidence of 234 pmp in 2013 .", "the ckd prevalence calculated from the mdrd study equation alone was 8.8% in 2005 and 7.2% in 2007 in korea national health and nutrition examination survey ( knhanes ) subjects aged 20 ; the prevalence calculated using the mdrd study equation with the dipstick proteinuria method has tended to decrease since 2001 in men and since 2005 in women among knhanes i to iv ( 1998 to 2009 ) subjects aged 20 . since there are no reports on ckd prevalence using the ckd - epi equations to estimate gfr and acr to measure albuminuria for koreans , a new analysis of ckd prevalence is necessary .", "chronic kidney disease ( ckd ) is defined as a structural or functional kidney abnormality lasting for 3 or more months .", "glomerular filtration rate ( gfr ) is considered the index of kidney function , and for convenience" ], [ "knhanes , composed of a health questionnaire survey , physical examination , and nutrition survey , has been conducted periodically since 1998 to assess the health and nutritional status of the non - institutionalized korean population by the korea centers for disease control and prevention ( kcdc ) .", "this retrospective , population - based study was performed using data acquired by the knhanes v from 2010 to 2012 .", "knhanes v was a cross - sectional , nationally representative survey with a multistage , stratified , and probability sampling design based on sex , age , and geographical area using household registries .", "the complex samples chi - square test was used to analyze prevalence of ckd by gfr with acr categories , and gfr comparison between mdrd and ckd - epi equations was expressed as a weighted percentage .", "associations of ckd , gfr , and acr categories with various risk factors , including gender , age , bmi , dm , hypertension , and dyslipidemia were expressed as an odds ratio ( or ) , which was calculated using complex samples multivariate logistic regression analyses .", "ckd was defined and classified based on kdigo guidelines using both gfr and urinary acr .", "individuals aged 19 were classified as adults in the study due to the kdigo guideline s classification of children as birth to 18 . the health examination was performed in a mobile health examination center ." ], [ "knhanes , composed of a health questionnaire survey , physical examination , and nutrition survey , has been conducted periodically since 1998 to assess the health and nutritional status of the non - institutionalized korean population by the korea centers for disease control and prevention ( kcdc ) .", "individuals aged 19 were classified as adults in the study due to the kdigo guideline s classification of children as birth to 18 .", "knhanes v was a cross - sectional , nationally representative survey with a multistage , stratified , and probability sampling design based on sex , age , and geographical area using household registries .", "this retrospective , population - based study was performed using data acquired by the knhanes v from 2010 to 2012 .", "the study protocol was approved by the institutional review board of kcdc ( 2010 - 02con-21-c ) , and written informed consents were obtained from all subjects or their guardians .", "the inclusion criteria were ( 1 ) adults aged 19 , and ( 2 ) available serum creatinine ( scr ) , urine albumin , and urine creatinine test results .", "knhanes v data of 2010 were excluded as urine albumin was not measured until 2011 ." ], [ "blood pressure ( bp ) was measured by a trained nurse following a standard protocol in accordance with the recommendations of the american heart association .", "blood samples were collected from the median cubital or cephalic veins by a skilled nurse after an overnight fast . a random urine sample ( first urine in the morning , if possible )", "the urine and pretreated blood samples were refrigerated and transported to the central laboratory within the day ( neodin medical institute , seoul , korea ) .", "three readings were obtained via mercury sphygmomanometer ( baumanometer , baum , copiague , ny , usa ) , and the mean of the second and third reading was reported as the final bp for individual participants .", "body mass index ( bmi ) was calculated as body weight divided by the square of the height , and expressed in units of kg / m .", "serum creatinine and urine creatinine were assayed by colorimetry using creatinine - hr l - type wako ( wako , osaka , japan ) following the jaffe method ; fasting glucose concentration ( fasting blood glucose , fbg ) by an enzymatic method using pureauto s glu ( sekisui , osaka , japan ) ; total cholesterol , high density lipoprotein cholesterol ( hdl - c ) , and triglycerides by an enzymatic method ; and urine albumin by turbidimetric assay using albumin ( roche , mannheim , germany ) , all performed using a hitachi automatic analyzer 7600 ( hitachi high - technologies co. , tokyo , japan ) , which was calibrated using calibrator for automated systems ( roche diagnostics , indianapolis , in , usa ) ." ], [ "individuals with gfr < 60 ml / min/1.73 m or acr 30 mg / g were classified as ckd patients .", "hypertension was defined as having a systolic blood pressure ( sbp ) of 140 mmhg or a diastolic blood pressure ( dbp ) of 90 mmhg , or having received a physician s diagnosis .", "gfr was estimated using ckd - epi equations , taking into account gender and serum creatinine .", "dm was defined as having a1c 6.5% , fbg of 126 mg / dl , or having received a physician s diagnosis .", "ckd was defined and classified based on kdigo guidelines using both gfr and urinary acr .", "dyslipidemia was defined as having total cholesterol 240 mg / dl , ldl - c 160 mg / dl , hdl - c < 40 mg / dl , triglycerides 200 mg / dl , or having received a physician s diagnosis ." ], [ "the study population was separated as a subpopulation , and the analysis was carried out on the entire knhanes samples for 2011 and 2012 to represent all korean adults without bias .", "the complex samples chi - square test was used to analyze prevalence of ckd by gfr with acr categories , and gfr comparison between mdrd and ckd - epi equations was expressed as a weighted percentage .", "associations of ckd , gfr , and acr categories with various risk factors , including gender , age , bmi , dm , hypertension , and dyslipidemia were expressed as an odds ratio ( or ) , which was calculated using complex samples multivariate logistic regression analyses .", "analyses were performed incorporating the sampling weights to obtain unbiased estimates from the complex knhanes sampling design following the knhanes recommendations .", "the demographic and biochemical characteristics of the study population were summarized and compared using the complex samples general linear model for continuous variables and the complex samples chi - square test for categorical variables ." ], [ "increasing age and obesity ( bmi 25 ) showed a positive correlation with ckd .", "dyslipidemia showed a significant association with ckd in women ( or , 1.324 ; p = 0.023 ) , but not in men ( or , 1.175 ; p = 0.243 ) .", "hypertensive patients showed a higher risk of ckd than the normotensive population ( or , 3.394 for men ; or , 2.935 for women ; both p < 0.0001 ) .", "diabetic patients showed a higher risk of ckd than the nondiabetic population ( or , 3.145 for men ; or , 1.983 for women ; both p < 0.001 ) .", "the ors of covariates to the prevalence of ckd , gfr < 60 ml / min/1.73 m , and acr 30 mg / g , after adjusting for age , bmi , hypertension , dm , and dyslipidemia in men and women are listed in table 6 ." ], [ "the anthropometric and biochemical characteristics of the study population in 2011 and 2012 were comparable , except for hdl - c , ldl - c , and prevalence of dyslipidemia ( table 1 ) .", "among the total sample size of 16,576 from 2011 and 2012 , 64.7% satisfied the inclusion criteria ( 10,636 individuals : 5,388 and 5,248 from 2011 and 2012 , respectively ) as shown in fig .", "the percentage of men was 52.6% , and the mean age was 45.8 years ( 95% ci , 45.2 to 46.3 ) .", "the composition of neither the total adults nor the study population was statistically different between 2011 and 2012 ( p = 0.232 and p = 0.087 , respectively ) . the study population comprised 81.8% of total adults ( 81.0% and 82.7% from 2011 and 2012 , respectively ,", "mean sbp was 118 mmhg ( 95% ci , 117 to 119 ) , and dbp 76 mmhg ( 95% ci , 76 to 77 ) .", "mean fbg was 97 mg / dl ( 95% ci , 97 to 98 ) , and a1c 5.7% ( 95% ci , 5.67 to 5.71 ) .", "mean serum creatinine was 0.86 mg / dl ( 95% ci , 0.85 to 0.86 ) , with an estimated gfr of 96 ml / min/1.73 m ( 95% ci , 96 to 97 ) ." ], [ "the ckd prevalence in korean adults was estimated as 7.9% ( 7.8% in 2011 and 8.0% in 2012 , p = 0.770 ) ( table 1 ) .", "the prevalence of low , moderately increased , high , and very high ckd risk prognosis was 92.0% , 6.3% , 1.1% , and 0.6% , respectively .", "the prevalence of hypertension , dm , and dyslipidemia was 27.8% ( 27.2% in 2011 and 28.4% in 2012 , p = 0.380 ) , 9.3% ( 9.7% in 2011 and 9.0% in 2012 , p = 0.306 ) , and 32.8% ( 34.6% in 2011 and 31.0% in 2012 , p = 0.004 ) , respectively .", "the prevalence of acr 30 mg / g in individuals with gfr 60 ml / min/1.73", "the distribution of ckd prevalence classified by the gfr and acr categories is shown in table 2 .", "the prevalence of gfr < 60 ml / min/1.73 m was 2.2% , whereas acr 30 mg / g was 6.5% ( a2 of 5.6% and a3 of 0.9% ) ." ], [ "2 . the prevalence of g1 was 67.9% and 59.4% by ckd - epi equations and the mdrd study equation , and g2 was 29.8% and 38.7% , respectively .", "the prevalence of gfr < 60 ml / min/1.73 m by the mdrd study equation was 2.0% , which was significantly less than the 2.2% by ckd - epi equations ( p < 0.001 ) .", "the prevalence of each estimated gfr category using ckd - epi equations and the mdrd study equation is shown in fig ." ], [ "the prevalence of at least 1 + proteinuria in a1 , expected to be fully negative , was 0.1% whereas or proteinuria in a2 and a3 , expected to be fully positive , were 5.3% and 0.3% , respectively ." ], [ "dyslipidemia showed a significant association with ckd in women ( or , 1.324 ; p = 0.023 ) , but not in men ( or , 1.175 ; p = 0.243 ) . increasing age and obesity ( bmi 25 ) showed a positive correlation with ckd .", "hypertensive patients showed a higher risk of ckd than the normotensive population ( or , 3.394 for men ; or , 2.935 for women ; both p < 0.0001 ) .", "the frequency of women among ckd patients was 54.3% , which was significantly higher than that for men ( p < 0.001 ) . among individuals with acr 30 mg / g ,", "diabetic patients showed a higher risk of ckd than the nondiabetic population ( or , 3.145 for men ; or , 1.983 for women ; both p < 0.001 ) ." ], [ "this study is the first to report ckd prevalence using gfr estimated by using ckd - epi equations together with acr for albuminuria in the korean population .", "the prevalence of ckd using estimated gfr by the ckd - epi equation and acr for albuminuria measurement was 7.9% in the knhanes samples of 2011 and 2012 in korean adults aged 19 .", "thus , urinalysis to detect albumin should be strongly recommended for patients with higher risk of ckd and cvd . as there is a consensus about the risk of ckd with dm and hypertension , regular albuminuria testing for at least these patients to detect kidney disease at an early stage" ], [ "1 . the prevalence of chronic kidney disease ( ckd ) was estimated to be 7.9% in the korea national health and nutrition examination survey samples of 2011 and 2012 in korean adults aged 19 .", "early identification of ckd paired with appropriate management and earlier referral to specialty kidney services results in economic and clinical benefits .", "4 . regular laboratory tests for albuminuria in the high - risk group , especially for hypertensive or diabetes mellitus patients , should contribute to early detection of ckd .", "the majority of ckd patients have albuminuria prior to a decrease in glomerular filtration rate ." ] ]

[ [ "while it is true that not all patients are able to dialyse themselves at home , it is a sad fact that many are never given the chance , despite the fact that patient choice has never been more discussed as an answer to almost any health care problem . although studies suggest that renal physicians and nurses regard home dialysis as the best treatment , it is in decline in most european countries , yet in - centre hospital - based dialysis is the most expensive and most disempowering option available .", "the practical barriers to home therapy vary from unit to unit but need to be identified and overcome if patients are to benefit from self - management", "patient pathway to ( relative ) freedom a step which can be made much easier if staff are familiar with the stages of change model and have a basic understanding of motivational interviewing .", ". however , it can be difficult to convince both staff and patients if they have no direct experience or training in this aspect of renal replacement therapy ." ], [ "pre - emptive living donor transplantation should always be promoted as the first - line treatment for kidney failure . however , where that is not possible , patients must receive timely , adequate and unbiased information and advice regarding the complete array of dialysis options available , including home - based peritoneal dialysis ( pd ) and haemodialysis ( hd ) .", "interestingly , a comparison of survival in canadian patients treated with nocturnal hd or deceased donor kidney transplantation showed no difference between the two treatments , suggesting that this intensive dialysis modality may be a bridge to transplantation , or even a suitable alternative , in the absence of an available living donor .", "ideally , every patient should learn about every dialysis modality , accepting that it is probably pointless to discuss pd with a patient who has previously had major abdominal surgery .", "understandably , a patient may never be adequately informed about home hd or assisted automated peritoneal dialysis if these modalities are not operating in the unit concerned .", "experience within our own service suggests that where a dialysis unit enables and actively encourages self - management , patients will tend to select themselves , and if well motivated may overcome significant difficulties , such as needle phobia , housing problems and literacy issues , to exceed the expectations or predictions of even quite experienced dialysis staff ." ], [ "there is much in our health care culture that expects care and treatment to be administered by caring and expert professionals , and this expectation is present in the providers of health care as much as it is in the recipients .", "visiting patients in their home environment is an essential part of training for both medical and nursing staff .", "interestingly , the general consensus among nephrologists in canada , usa and uk in 2006 was that 45% of patients are suitable for a home therapy , and if you question the staff in your local hd unit , very few would wish themselves to be dialysed in - centre if the need arose . despite this", "selection to medical and nursing staff simply does not work and that many capable patients are not finding their way through ", "there are of course individual differences in both staff and patients willingness to embrace self - care , but if we assume that cultures and individual preferences are not fixed , then we may find ways to move people along the self - care continuum .", "collaboration with another unit may enable staff to gain the training and experience required to be able to talk with authority and instill confidence in the patient ." ], [ "it is known that patients who start dialysis after adequate preparation tend to select a home therapy [ 5 , 6 ] .", "the stages of change model suggests that , for most people , a change in behaviour occurs gradually , with the patient moving from being uninterested , unaware or unwilling to make a change ( pre - contemplation ) , to considering a change ( contemplation ) , to deciding and preparing to make a change ( preparation then action ) .", "quit is much more likely to be successful than someone who has not , despite both being aware of the future health benefits .", "yet , we all know from our own educational experiences that this approach alone is insufficient . on the face of it , it seems plausible that suitable patients would accept the benefits of a home therapy , once they have been educated as to the reasons for the recommendation , and staff may be bemused when they do not do so .", "therefore , before a patient is able to begin to engage in discussion about any dialysis therapy , they must have reached a point of acceptance that dialysis is necessary . if they are not at this point , then any attempt at ", "this aspect of everyday human behaviour has been most extensively studied in the field of smoking cessation , where it is recognized that someone who has accepted the need to " ], [ "the uk national institute for health and clinical excellence ( nice ) produced guidance on home compared to hospital hd for patients with end - stage renal failure in 2002 .", "suitable for home hd should be offered the choice of having hd in the home or in a renal unit . the definition of ", "practical characteristics of patients suitable for home hd according to nice guidance 2002 although these guidelines are entirely clear and sensible , the manchester experience is that the definition of ", "enthusiastic and determined patients who might initially have been deemed unsuitable are found to be not only capable but successful home dialysers .", "indeed , the current feeling is that very few physical disabilities preclude home treatment if the patient is keen to proceed , and level of enthusiasm is a more reliable guide ." ], [ "the experience and confidence of the staff is crucial so that even if the patient is unsure of the process , they feel fully able to trust the team around them and to know who to turn to for reassurance or answers .", "many patients commitment at this stage is fragile and if the path is too rough or steep , or not well signposted , they may understandably decide to turn back .", "this requires some resources and infrastructure to be already in place , and if they are not , then all but the most determined patient is likely to be put off .", "therefore , from this point on , communication , planning and action must be slick and efficient in order to build the patient s confidence .", "it requires staff to engage with patients in conversations about what is important to them and what they value in more general terms ( e.g. freedom , independence , safety , quality and quantity of life ) and about what the complex hindrances to self - care may be so that an individualized response to these sorts of questions can move patients along the self - care continuum .", "once a patient has arrived at the point of choosing a home therapy , the pathway to their first dialysis at home must be as smooth and pot - hole free as possible ." ], [ "traditional methods of patient selection have not prevented a steady decline in home therapies over the past two decades , yet most dialysis unit staff say they would opt for a home therapy for themselves .", "the stages of change model coupled with basic motivational interviewing techniques can enable staff and patients to engage with each other in a more meaningful way such that many patients will be better able to understand the benefits of self - management and treatment at home .", "when faced with the spectre of dialysis treatment , most of us would not naturally opt for a home therapy .", "practical infrastructure barriers must also be tackled in order to smooth the pathway to home dialysis ." ] ]

[ [ "ebv is a double stranded dna virus of the herpes virus family and is the most common virus affecting humans .", "ebv is mainly a b - lymphotropic and epitheliotropic virus and rarely infects t cells and nk cells .", "the epstein barr virus ( ebv ) was described by michael anthony epstein and yvonne barr , who isolated ebv virus particles from endemic burkitt lymphoma specimens .", "the life cycle of ebv is composed of a lytic state and a latency state , the latter allowing lifelong persistence of the virus in the host ." ], [ "if the infection occurs in young adults and adolescents , it can manifest as mononucleosis ( glandular fever ) .", "most humans become infected with ebv during childhood , when the infection usually proceeds asymptomatically or with mild symptoms that are undistinguishable from other viral infections .", "might be observed . the histomorphological picture of primary ebv infection shares histomorphological features with other ebv - driven lymphoproliferative diseases ( lpd , table 2 ) ." ], [ "ebv reactivation in adults occurs primarily in the form of ebv - lpd presenting with a polymorphic histological and clinical picture .", "f 400 histomorphology of ebv - associated lymphoproliferative diseases . a and d illustrates the features of a primary ebv infection in the oral mucosa of a child . as examples of ebv reactivation , an ebv - associated mucocutaneous ulcer in the anal mucosa in a patient treated with azathioprin for myastenia ( b and e ) and a lymphomatoid granulomatosis in the lung of a patient ( c and f ) are shown .", "since the vast majority of humans have been infected by ebv in childhood and adolescence , ebv - associated lpds in adults usually arise from reactivation of the virus from ebv - infected memory cells ." ], [ "ebv - positive lymphomas occur in immunocompetent patients , but are much more frequent in immunocompromised patients . in the latter patient group ,", "nevertheless , in certain lymphoma entities , e.g. , nasal and extranasal nk t cell lymphoma , angioimmunoblastic t cell lymphoma , primary effusion lymphoma , and plasmablastic lymphoma , ebv association remains an important clue towards the correct diagnosis .", "of further relevance might be the identification of ebv - positive diffuse large b cell lymphoma ( dlbcl ) of the elderly ." ], [ "mucosa differential diagnostic of polymorphic ebv - positive lymphoproliferative disease ( lpd ) compared to hodgkin lymphoma", "the diagnostic criteria for ebv - positive lymphomas are described in the current who classification . however , distinguishing polymorphic ebv - lpd and a fully developed ebv - positive lymphoma can be challenging .", "a specifically difficult task is the differentiation of a polymorphic ebv - lpd from a fully developed classical hodgkin lymphoma , because the latter may be composed of a similarly polymorphic cellular infiltrate to that of the polymorphic ebv - lpd ." ], [ "if pathologists are confronted with lymphoid tissue histologically resembling inflammatory ( reactive ) tissue in immunocompetent patients , the decision whether or not to test for ebv is primarily based on histological features ( table 3 ) . in immunocompromised patients ,", "original magnification a d 400 recommendations for selecting tissue specimen and methods for ebv testing \n ptld posttransplantation lymphoproliferative disease , aitl angioimmunoblastic t cell lymphoma", "since indolent ( low grade ) b cell lymphomas are virtually never associated with ebv , testing can not be recommended . for other entities , which are listed in tables 3 and 5 , testing should be part of the standard diagnostic work - up .", "the method of testing should be eber in situ hybridization , which is most sensitive for detecting ebv , especially in lesions that can not necessarily be expected to express other viral antigens such as lmp1 ( table 3 ) .", "the question as to which specimen should be tested for ebv depends on the histopathological findings on the one hand and on the clinical context on the other hand ." ], [ "this is due on the one hand to the aging of many populations , with an increase in age - associated ebv reactivation . on the other hand , widespread access to commercial assays and", "although epidemiologic data are lacking , ebv - lpd distinct from overt lymphoma will be increasingly recognized .", "additionally , newly recognized subgroups of lymphomas , such as the ebv - positive dlbcl of the elderly , require the detection of ebv in more lymphoma entities as part of the diagnostic process .", "automatization leads to an increasing use of in situ hybridization for eber by diagnostic pathologists ." ] ]

[ [ "the purpose of this study was to determine the effects of abz and mbz on the activity of the gst , alp and proteases in the protoscoleces of hydatid cyst and to evaluate their inhibitory effects on enzyme activity .", "echinococcosis or cystic hydatid disease is an endemic parasitic disease in human populations in iran and some parts of the world .", "it is caused by larvae stage of echinococcus granulosus ( 1 ) . in the life cycle of e. granulosus ,", "glutathione - s - transferase ( gst ) is an enzyme , which has a significant role in the detoxification of parasite metabolites ( endogeous ) , host metabolites ( xenobiotics ) and drugs through their conjugation to glutathione ( 5 ) .", "alkaline phosphates ( alp ) is an enzyme that plays an important role in dampening host immune responses and also plays a role in feeding parasites ( 7 ) .", "the activities of protease described in e. granulosus ( 9 ) , has been detected in hydatid cyst fluid , cyst wall and in protoscoleces ." ], [ "protoscoleces were obtained by aseptic puncture from fertile liver hydatid cysts of ovine origin collected from an abattoir in rey city in tehran ( center of iran ) .", "a standard curve was prepared by using the standard solutions absorbance and the protein concentration of the samples were estimated ( 15 , 16 ) . in order to measure the activity of gst in e / s samples , reagent stock including potassium phosphate buffer 0.1 m , 100 mm reduced glutathione ( gsh ) and 100 mm 1-chloro-2,4- dinitrobenzene ( cdnb ) substrates were prepared in a microtube .", "viability was determined by eosin 0.01 exclusion analysis and only protoscoleces samples with viability higher than 95% were selected for the assays ( 13 ) .", "finally , total gst activity ( u / ml ) , of samples was calculated . to calculate the specific activity of gst enzyme , the rate of enzyme activity was divided by the mg protein concentration ( 17 ) .", "the precipitates were discarded and the total protein and enzyme activities were measured as follows : the concentrations of total proteins of e / s samples were measured by bradford method , which involves reacting the e / s samples with a dye that binds to protein . to measure" ], [ "protoscoleces were obtained by aseptic puncture from fertile liver hydatid cysts of ovine origin collected from an abattoir in rey city in tehran ( center of iran ) .", "protoscoleces were allowed to settle in a 50 ml falcon tube , and then washed several times in phosphate - buffered saline ( pbs ph , 7.2 ) .", "viability was determined by eosin 0.01 exclusion analysis and only protoscoleces samples with viability higher than 95% were selected for the assays ( 13 ) .", "mbz used in this study was obtained from rouzdarou pharmaceutical company ( iran ) and abz was purchased from tolide daruhai dami iran company ." ], [ "no : k4111 - 500 ) , 100u / ml of penicillin and 100g / ml of streptomycin as 1 ml for each ] containing 500l protoscoleces and 1 g / ml abz and/ mbz [ stock solution 1 mg / ml of dimethyl sulphoxide ( dmso ) ] were considered as test groups and 10 culture medium [ five culture containing 500 l protoscoleces with 0.6 l dmso , and five culture medium without dmso ] regarded as control groups and were incubated at 37 c in 5% co2 ( 14 ) ." ], [ "the culture supernatants containing the parasite e / s products were collected at time interval , every 12 h. at the end of each time interval , the entire 1 ml of culture medium ( culture supernatants ) was removed and replaced with the same volume of fresh medium ( 13 ) .", "the precipitates were discarded and the total protein and enzyme activities were measured as follows :" ], [ "the concentrations of total proteins of e / s samples were measured by bradford method , which involves reacting the e / s samples with a dye that binds to protein . to measure the protein concentration , standard solutions ( bovine serum albumin ) and e / s products", "a standard curve was prepared by using the standard solutions absorbance and the protein concentration of the samples were estimated ( 15 , 16 ) .", "the absorbance of e / s products and standard solutions were measured at 595 nm after 5 min incubation at room temperature .", "were prepared and the bradford reagent ( 100 mg coomassie brilliant blue g-250 , 50 ml 95% ethanol , 100 ml 85% phosphoric acid ) was added ." ], [ "the same method was performed for the control groups and absorbances of gst activities were measured at 340 nm for 5 min . finally , total gst activity ( u / ml ) , of samples was calculated . to calculate the specific activity of gst enzyme , the rate of enzyme activity was divided by the mg protein concentration ( 17 ) .", "in order to measure the activity of gst in e / s samples , reagent stock including potassium phosphate buffer 0.1 m , 100 mm reduced glutathione ( gsh ) and 100 mm 1-chloro-2,4- dinitrobenzene ( cdnb ) substrates were prepared in a microtube . to each test , from the mentioned mixture 1.8 ml and 200ul of abz and mbz treated protoscoleces e / s sample were added and mixed well ." ], [ "then 20 l of treated or control samples were added and mixed well and measured absorbance of sample for 5 min by every 1 min at 405 nm and enzyme activity were calculated according to the kit procedure .", "eight hundred l of buffer reagent ( r1 ) and 200 l of substrate reagent ( r2 ) were poured into cuvette and mixed ." ], [ "folin & ciocalteus phenol reagent primarily react with free tyrosine and produce a blue color .", "solution l - tyrosin 1.1 mm , dw , na2co3 , phenol ) and reported as units /ml enzyme ( 16 ) .", "the reaction was stopped using trichloroacetic acid ( 110 mm tca , prepared by diluting a 6.1n stock 1:55 with purified water ) .", "sasein solution 0.65% ( 6.5 mg / ml of casein in the 50 mm potassium phosphate buffer 50 mm , ph7.5 ) prepared and incubated at 37 c for 5 min , and then e / s samples were added to test tubes and were incubated 37 c for 10 min .", "the supernatant was poured into the test tube ; 1cc sodium carbonate solution ( 500 mm sodium carbonate solution , prepared using 53 mg / ml of anhydrous sodium carbonate in purified water ) and 200 l folin & ciocalteus phenol reagent were added and incubated for 30 min at 37 c ." ], [ "in order to determine the statistically significant difference between protein concentrations , gst , alp and protease activities of e / s samples of treated and control groups , t - test was used .", "a duplicate set of samples were taken for each test and at the end , their average was taken in to account ." ], [ "gst specific activity level of protoscoleces in abz group was 69.44 and in mbz treated group was 132.82 u / mg protein / ml .", "the mean protein concentration in the control group was 6.06 g / ml . protein concentration of e / s products of protoscoleces treated and control groups \n p<0.05 ; between control and treated groups \n \n p>0.05 ; between treated groups \n the results of gst , alp and protease activity are shown in table 2 .", "a significant difference was observed between specific activity of gst and alp enzymes in e / s products of protoscoleces treated with abz in comparison with the group treated with mbz ( p<0.05 ) .", "the mean protein concentrations in e / s samples of protoseoleces exposed to abz and mb were measured 3.55 and 4.58 g/ ml , respectively .", "released)(total volume of assay)volume of enzymetime of assayvolume of filtratespecific activity = units / ml enzymemg solid \n statistical analysis using t - test showed the significant difference between protein concentrations and specific activities of the enzymes in e / s products of protoscoleces treated with abz and mbz in comparison with control group ( p<0.05 ) .", "alp specific activity in abz and mbz treated protoscoleces were estimated as 19.22 and 22.27 u / mg protein / ml , receptively ." ], [ "the mean protein concentration in the control group was 6.06 g / ml . protein concentration of e / s products of protoscoleces treated and control groups \n p<0.05 ; between control and treated groups \n \n p>0.05 ; between treated groups \n", "the mean protein concentrations in e / s samples of protoseoleces exposed to abz and mb were measured 3.55 and 4.58 g/ ml , respectively ." ], [ "alp specific activity in abz and mbz treated protoscoleces were estimated as 19.22 and 22.27 u / mg protein / ml , receptively .", "gst specific activity level of protoscoleces in abz group was 69.44 and in mbz treated group was 132.82 u / mg protein / ml .", "protease specific activity in abz and mbz treated protoscoleces e / s products was not detected , while protease specific activity of control group e / s products calculated 7.61 u / mg protein / ml .", "gst , alp and protease activity in e / s products of protoscoleces treated and control groups p<0/005 , t = test or sample n / d = not detected \n gst activity = od / min0.0096total voluesample voluedilution factor \n alp activity = od 2764 \n protease activity=(umole tyrosine equivalents released)(total volume of assay)volume of enzymetime of assayvolume of filtratespecific activity = units / ml enzymemg solid \n", "alp specific activity of control group of e / s products was 27.85 u / mg protein/ ml ." ], [ "a significant difference was observed between specific activity of gst and alp enzymes in e / s products of protoscoleces treated with abz in comparison with the group treated with mbz ( p<0.05 ) .", "statistical analysis using t - test showed the significant difference between protein concentrations and specific activities of the enzymes in e / s products of protoscoleces treated with abz and mbz in comparison with control group ( p<0.05 ) .", "meanwhile there is no significant difference between protein concentration in e / s products of protoscoleces treated with abz compared with the group treated with mbz ( p>0.05 )" ], [ "the effect of abz and mbz on protein content and some enzymatic activities of e / s products were examined .", ", the study indicates that both anti hydatid benzimidazoles ( abz and mbz ) have an inhibitory effect on the activity of gst , alp and protease enzymes in e / s products of e. granulosus protoscoleces in vitro .", "based on these findings we can expect the decreasing of total protein in treated parasite culture media , which correlates our study that shows an average protein of test group is less than control group . in this study , a significant decrease observed in the activity of gst , alp and protease enzymes of the e / s products of treated groups in comparison with the control group .", "the results showed that the effect of abz on the activity of gst and alp is more than mbz and this may be due to the different structures of these drugs .", "based on the results obtained in this study , the reduction or inhibition of the enzymes ( gst and alp ) caused by abz and mbz could lead to alteration of metabolism in helminthes parasites . therefore", "gst is one of the major detoxification system component found in helminthes , particularly at high levels in cestodes and digeneas . in the tissue extracts of parasites gst activity" ], [ "the results of the two drugs indicated that abz is more effective on the enzymes activities ( gst and alp ) as compared with mbz .", "this may by attrirbuted tothe different structures of the two drug and might account for at least in part , differencein antihydatid mechanism of these benzimidazole derivation .", "both drugs have an inhibitory effect on the activity of gst , alp and protease enzymes ." ] ]

[ [ "phased - array mri is recommended as the preferred imaging modality for regional staging . ", "an established association exists with human papillomavirus ( hpv ) infection and premalignant intra - epithelial dysplasia . ", " anal carcinoma is increasingly diagnosed in patients with human immunodeficiency virus ( hiv ) , anoreceptive intercourse , chronic inflammatory bowel disease . ", " anal carcinoma is increasingly diagnosed in patients with human immunodeficiency virus ( hiv ) , anoreceptive intercourse , chronic inflammatory bowel disease. an established association exists with human papillomavirus ( hpv ) infection and premalignant intra - epithelial dysplasia. phased - array mri is recommended as the preferred imaging modality for regional staging. imaging allows detection of infectious complications , planning of radiotherapy or salvage surgery. follow - up mri allows reliable assessment of therapeutic response after chemo - radiotherapy ." ], [ "currently , at least half of scacs occur in relatively young ( 4060 years ) hiv - positive individuals , most often men who have sex with men ( msm ) [ 35 ] .", "furthermore , the incidence of scac is steadily increasing , particularly in patients with risk factors such as human immunodeficiency virus ( hiv ) infection , history of anoreceptive intercourse , coexistent cervical dysplasia or cancer , immunosuppression , inflammatory bowel diseases ( ibd ) and cigarette smoking .", "an uncommon malignancy in the general population , squamocellular anal carcinoma ( scac ) accounts for approximately 1 % of all gastrointestinal neoplasms and less than 5 % of anorectal tumours . in past decades", ", scac was usually diagnosed at a relatively advanced age with a significant female predominance , and believed to be an indolent disease secondary to chronic irritation . in recent years , similarly to uterine cervix dysplastic changes , oncogenic human papillomavirus ( hpv ) has been detected in the vast majority ( up to 90 % ) of invasive scacs , and linked to the development of low- and high - grade premalignant anal intra - epithelial neoplasms ( ain ) , particularly with high - risk or multiple hpv serotypes infection [ 1 , 2 ] ." ], [ "the surgical anus is about 4 cm long from the anorectal junction to the perianal skin on the external anal margin ( verge ) .", "following physical examination including digital rectal and vaginal examination , ano - proctoscopy and biopsy , imaging is required to evaluate the local extent of the lesion , lymph node involvement , possible invasion of adjacent organs and distant metastases [ 6 , 9 ] .", "unfortunately , in patients with anal lesions , positioning of endoanal sonography probes and mri coils is hampered by pain and stricture .", "because of its anatomical location , in most cases scac is diagnosed clinically in patients with rectal bleeding , pain , discharge or palpable masses .", "imaging the anal canal and perianal structures may prove technically challenging to perform and interpret ." ], [ "sensitivity of trus and mri for the identification of scac has been reported to approach 90100 % , with high concordance regarding tumour size , although on a limited number of patients , and more precise results with ultrasound for smaller , superficial tumours .", "ct may alter staging of anal scac in 20 % of patients , leading to inclusion of involved pelvic or inguinal lymph nodes in the radiation field [ 6 , 7 ] .", "axial t2-weighted ( a , b ) and post - contrast fat - suppressed t1-weighted ( c ) images show inguinal nodal metastases , larger on left side ( arrowheads ) plus bilateral enhancing perirectal adenopathies ( arrows ) as suggested by ecco guidelines , search for distant spread is usually performed by means of contrast - enhanced body mdct , with conventional imaging appearances of liver and lung metastases . dissemination is very uncommon ( less than 5 % of patients at initial diagnosis , and is usually encountered in association with post - treatment recurrence . alternatively , in immunocompetent patients f - fluorodeoxygluocose positron emission tomography ( fdg - pet / ct ) has high specificity for nodal and visceral dissemination . at diagnosis , fdg - pet /" ], [ "resolution of associated inflammatory changes during treatment is easily monitored by cross - sectional imaging ( figs . ", "in our experience , not infrequently anal tumours coexist with inflammatory conditions such as proctitis and abscesses . in such instances , mdct and mri provide confident detection of perirectal inflammatory changes and purulent collections that are differentiated from solid neoplastic tissue , thus allowing a correct therapeutic choice including surgical drainage as necessary ( figs . 5 , 8 , 9 , 10 ) .", "8a 60-year - old man with aids and clinical finding of ulcero - fungating anal mass ." ], [ "in the past , scac was treated with abdomino - perineal resection and permanent colostomy . currently , anal margin and small canal tumours without evidence of nodal spread may be successfully excised . in all other cases ,", "salvage surgery with abdomino - perineal resection is reserved for persistent or recurrent tumours [ 3 , 6 , 2325 ] .", "after radio - chemotherapy , imaging follow - up with mri represents a useful complement to clinical evaluation in the assessment of therapeutic response . shortly after treatment completion , interpretation of mri is usually challenging due to the superimposition of inflammatory changes resulting from radiotherapy . performed at least 68 weeks after treatment completion , mri provides confident , reproducible assessment of post - treatment modifications .", "stability in size and signal intensity of any residual abnormality visible at mri in the site of the treated lesion 1 year after therapy has been reported to be strongly associated with a favourable outcome ." ], [ "after the introduction of highly active anti - retroviral treatment ( haart ) , people with hiv infection or acquired immunodeficiency syndrome ( aids ) gained a greatly improved life expectancy with better immune conditions , at the price of an increased tendency to develop tumours .", "despite initial discouraging reports , in the haart era hiv - positive patients are likewise treated with standard chemo - radiation regimens , reaching satisfactory results in terms of local control and survival rates , although with increased toxicity and frequent local recurrences [ 4 , 5 , 26 , 27 , 32 ] .", "a high prevalence ( at least 30 % ) of anorectal complaints is characteristic of hiv - positive patients , particularly those practicing anoreceptive intercourse .", "screening procedures including high - resolution anoscopy and cytology smears are increasingly adopted at hiv care centres , to allow detection of scac precursors and early - stage tumours amenable to limited excision and topical therapies .", "prevention should limit the occurrence of advanced stages at diagnosis in the future [ 4 , 2629 ] ." ], [ "radiologists should be aware of the increased risk for anorectal cancer in middle - aged ibd patients , and clearly report any solid tissue as suspicious for neoplasm and suggest biopsy ( figs . ", "some literature reports have highlighted the increased risk of anus and lower rectum carcinomas associated with long - standing , severe perianal fistulising crohn s disease ( cd ) ( fig . ", "however , anal tumours may occasionally develop in patients with ulcerative colitis ( uc)-related ( fig . ", "ibd - associated anal cancers are often advanced at presentation , may require extensive surgery plus chemotherapy and radiotherapy , and are associated with a severe prognosis ." ], [ "state - of - the - art cross - sectional imaging with high - resolution mri using external phased - array coils and multiplanar mdct allow detailed , comprehensive visualisation of abnormalities involving the anus and perineal region .", "currently , mri represents the modality of choice for primary regional staging of scac , assessment of complications , of therapeutic response following chemo - radiotherapy , and of possible recurrences [ 9 , 10 , 13 ] .", "the established association with hpv infection and premalignant intra - epithelial dysplastic changes provides insight into the pathogenesis of hiv- and ibd - related anal cancers , and the possibility of prevention or early diagnosis through screening of high - risk individuals [ 1 , 2 ] ." ] ]

[ [ "the aim of the present work is to apply a specific isolation method based on the enrichment of black yeasts by simulating in batch solid state - like cultures the environmental conditions that are found in gas biofilters for the treatment of volatile aromatic hydrocarbons .", "despite the medical and environmental relevance of herpotrichiellaceous black yeasts , little is understood on their biodiversity and natural occurrence . in order to address questions on niche shifts and environmental prevalence in relation to virulence factors and routes of transmission ,", "different environmental samples related to the life cycle of e. dermatitidis were used as inocula .", "black yeasts from the family herpotrichiellaceae ( order chaetothyriales ) are fungi with a remarkable dual ecology . on the one hand , they have a unique ability to adapt to extreme environments ( exposure to toxic chemicals , high temperature , scarcity of nutrients , acidic , and/or dry conditions ) , while on the other hand , they exhibit a significant human pathogenic potential . unlike common opportunistic fungi , herpotrichiellaceous black yeasts frequently cause infections in individuals without known underlying disease and only occasionally in immunocompromised patients . also , more often than any other fungal group , these organisms have been reported from environments that are rich in aromatic compounds ." ], [ "these samples were collected around utrecht ( the netherlands ) and concerned wild berries from different plants , guano - rich soil , as well as samples from creosote - treated oak railway ties , which might contain both fecal pollution and contamination with aromatic hydrocarbons .", "the list of sampled sites that were used as source of inoculum for the subsequent enrichment cultures is presented in table 1 .", "the same locations had previously been sampled for black yeasts , but without enrichment on volatile aromatic hydrocarbons . \n", "a solution of 140 g l of nacl was also added at the bottom of the desiccators to maintain an internal water activity value of 0.9 , and the whole set was incubated at 30c for at least 3 months . after this time", "the inoculated flasks were then closed with a cotton wool plug covered with aluminum foil and placed inside four desiccators where they were exposed , respectively , to a gaseous phase of benzene , toluene , xylene , or naphthalene .", "one milliliter of 1- , 10- , or 100-fold dilutions from each soil suspension were plated in duplicate on 2% malt extract agar containing penicillin and streptomycin and incubated at 30c ." ], [ "these samples were collected around utrecht ( the netherlands ) and concerned wild berries from different plants , guano - rich soil , as well as samples from creosote - treated oak railway ties , which might contain both fecal pollution and contamination with aromatic hydrocarbons .", "the list of sampled sites that were used as source of inoculum for the subsequent enrichment cultures is presented in table 1 .", "the same locations had previously been sampled for black yeasts , but without enrichment on volatile aromatic hydrocarbons . \n", "environmental samples were collected with sterile lab tools , placed in plastic bags and plates , then stored at 4c , and processed in the laboratory within 7 to 14 days .", "table 1samples and sampling sites in the utrecht area ( the netherlands ) used as source of inocula for the enrichment with volatile aromatic hydrocarbonscodesamplesampling locationgeographic coordinates ( wgs84)a1oak railway tie , outside railsnear station , hollandsche rading521041.95 n , 51045.96 ea2oak railway tie , between railsnear station , hollandsche rading521041.95 n , 51045.96 ea3oak railway tie , outside railsforest area , hilversum521220.68 n , 5119.66 ea4oak railway tie , between railsforest area , hilversum521220.68 n , 5119.66 ea5concrete railway tie , between railsforest area , hilversum521220.68 n , 5119.66 ec1berry , sorbus aucupariaroadside , de bilt52 717.18 n , 5 948.13 ec2berry , sorbus aucuparialight forest , voordaansepad , groenekan52 749.19 n , 5 931.42 ec3berry , sorbus aucuparialight hedge , oostveensepad , maartensdijk52 833.70 n , 5 951.98 ec4berry , sorbus aucuparialapersveld park , hilversum521254.74 n , 51110.25 ec5berry , viburnum opuluslight hedge , oostveensepad , maartensdijk52 833.70 n , 5 951.98 ec6berry , crataegus monogynahedge , vuursche pad , hollandsche rading521010.52 n , 51051.99 ed1guano - rich soil of jackdaw and starlinglapersveld park , hilversum , roosting under thuja521254.74 n , 51110.25 ed2guano - rich soil covered with hedera sp.lapersveld park , hilversum , roosting under thuja521254.74 n , 51110.25 ed3guano - tic soil of jackdaw and starlinglapersveld park , hilversum , roosting under thuja521254.74 n , 51110.25 ed4fresh goose feceslapersveld park , hilversum521254.74 n , 51110.25 ed5old goose feceslapersveld park , hilversum521254.74 n , 51110.25 e samples and sampling sites in the utrecht area ( the netherlands ) used as source of inocula for the enrichment with volatile aromatic hydrocarbons" ], [ "the solid state - like batch culture technique on a hydrocarbon atmosphere was employed to select for fungi that are able to grow on volatile aromatic hydrocarbons as the sole carbon and energy source .", "a solution of 140 g l of nacl was also added at the bottom of the desiccators to maintain an internal water activity value of 0.9 , and the whole set was incubated at 30c for at least 3 months . after this time ,", "one milliliter of 1- , 10- , or 100-fold dilutions from each soil suspension were plated in duplicate on 2% malt extract agar containing penicillin and streptomycin and incubated at 30c .", "colony growth was observed daily , and black yeast - like colonies were transferred to fresh potato dextrose agar plates for purification and provisional identification upon morphological characters .", "this gas phase was generated by placing 10 ml of a 5% ( v / v ) solution of the aromatic substrate in dibutyl - phthalate .", "the inoculated flasks were then closed with a cotton wool plug covered with aluminum foil and placed inside four desiccators where they were exposed , respectively , to a gaseous phase of benzene , toluene , xylene , or naphthalene .", "serum flasks of 100 ml were filled with approximately 25 ml of perlite granules , saturated with mineral medium . each environmental sample ( 13 g ) was washed with phosphate - buffered saline , and the suspension ( 40 ml ) was used to inoculate four different batches ( 10 ml each batch ) . as a control", ", these suspensions were also plated on sabouraud s glucose agar ( sga ) amended with antibiotics in order to prevent bacterial growth ." ], [ "a sterile blade was used to scrape off the mycelium from the surface of agar plate cultures of previously isolated fungi .", "the internal transcribed spacer ( its ) regions and the small subunit ( its1 - 5.8s - its2 ) of the rrna genes were amplified by using the primer set its1 ( 5-tcc gta ggt gaa cct gcg g-3 ) and its4 ( 5-tcc tcc gct tat tga tat gc-3 ) .", "the obtained dna sequences were compared against reference sequences by using the blastn algorithm on local cbs - knaw and public genbank databases ( ncbi , usa ) .", "phylogenetic analyses were conducted using mega version 4 ( center for evolutionary functional genomics , the biodesign institute , usa ) .", "dna was extracted using an ultra clean microbial dna isolation kit ( mobio , carlsbad , ca 92010 , usa ) according to the manufacturer s instructions ." ], [ "a single mold ( aspergillus fumigatus ) other than black yeasts was isolated from berries of sorbus aucuparia ( sample c1 ) .", "a total of 71 fungal strains were isolated upon enrichment of environmental samples on atmospheres of different volatile aromatic hydrocarbons ( table 2 ) . of those ,", "table 2number of fungal isolates obtained from solid state - like enrichment cultures incubated at 30c and a water activity of 0.9 , under an atmosphere rich in specific volatile aromatic hydrocarbonssample codebenzenetoluenexylenenaphthalenetotal strainsa10411015a203003a31086024a40110011c105005c207007d206006total strains104317071one isolated strain within this treatment was identified as aspergillus fumigatus ; this was the only non - black yeast strain from the whole obtained strain collection number of fungal isolates obtained from solid state - like enrichment cultures incubated at 30c and a water activity of 0.9 , under an atmosphere rich in specific volatile aromatic hydrocarbons one isolated strain within this treatment was identified as aspergillus fumigatus ; this was the only non - black yeast strain from the whole obtained strain collection from the natural sampled environments , black yeasts were isolated in two out of four berries from s. aucuparia ( 12 isolates , samples c1 and c2 ) , but no fungi were obtained from berry samples of viburnum opulus and crataegus monogyna ( samples c5 and c6 , respectively ) . soil mixed with bird feces ( guano ) also yielded melanized fungi in one out of five tested samples ( six isolates , sample d2 ) ." ], [ "the application of the enrichment method used in the present paper contributes to the isolation of fungi that have a potential for bioremediation of sites polluted with monoaromatic hydrocarbons .", "it should be noted though that neither of these enrichment conditions might represent the natural niche for these fungi , and they are therefore classified with difficulty in any of the known ecological categories . \n table 3overview of selective methods used for environmental isolation of black yeasts and related melanized fungi , with approximate resultsmethodprevalent genusorderecologyreferenceanimal baitexophiala , fonsecaea , cladophialophorachaetothyrialesopportunists[2 , 8]erythritolexophialachaetothyrialesopportunistsmineral oilexophiala , fonsecaeachaetothyrialesopportunistsraulin 40cexophialachaetothyrialesopportunistsneedleconiosporiumchaetothyrialesrock fungialkylbenzene vaporscladophialophora , exophialachaetothyrialesxenobioticsacidicexophialachaetothyrialesacidophileshortaeadothidealescrushconiosporiumchaetothyrialesrock fungihormonemadothidealeslow strengthexophialachaetothyrialesoligotrophssarcinomycesdothidealesrock fungicadophoraleotialesoligotrophshigh saltaureobasidium , hortaeadothidealeshalophiles[31 , 32]suspendcryomyces , friedmanniomycesdothidealespsychrophilesethanolbaudoiniadothidealesethanophiles overview of selective methods used for environmental isolation of black yeasts and related melanized fungi , with approximate results the present study demonstrates that enrichment on inert solid media incubated under a controlled atmosphere rich on volatile aromatic hydrocarbons compounds displays an extraordinary selectiveness toward chaetothyrialian fungi from the herpotrichiellaceae family .", "indeed , enrichment on volatile aromatic hydrocarbons in gas biofilters and similar systems thus far has never yielded pathogenic species of the higher fungal biohazard risk categories , such as cladophialophora bantiana or e. dermatitidis .", "this suggests that a certain degree of speciation between pathogenic and aromatic hydrocarbon metabolizing species has occurred in evolutionary terms . yet", "the presence of aromatic compounds and exposure to fluctuating and/or extreme environmental conditions , wood treated with creosote can be regarded as a paradigmatic environmental niche for black yeasts .", "several methods are based on osmotolerant and oligotrophic abilities of target fungi . with these regimens ," ] ]

[ [ "the aim of our study was to perform a comparative validation of wc , bmi , whr , and whtr for defining the metabolic syndrome in indian population living in the urban and rural areas of rohtak district , haryana , india .", "we used the idf definition of metabolic syndrome , excluding the measure of obesity , to determine which obesity measure among wc , bmi , whr , and whtr , and what appropriate cut - off value are most closely predictive of the non - adipose components of the idf 's definition of metabolic syndrome .", "the metabolic syndrome ( mets ) is a clustering of metabolic and cardiovascular risk factors that have been widely discussed for at least 20 years .", "although some have questioned the clinical utility of metabolic syndrome , there are many reasons to believe that this entity is useful . identification of metabolic syndrome is a simple measure of finding people with a clustering of risk factors that put them at increased risk of diabetes and cardiovascular disease ( cvd ) .", "since the first official definition of the metabolic syndrome put forward by a working group of the world health organization ( who ) in 1998 , a number of different definitions have been proposed .", "also , the identification of metabolic syndrome will attract attention to various other related conditions such as fatty liver , polycystic ovary syndrome , and obstructive sleep apnea ." ], [ "plasma glucose , total cholesterol , triglycerides , and hdl - cholesterol were measured . according to the idf definition for the indian population , for an individual to be defined as having the metabolic syndrome ,", "anthropometric indices including height ( without shoes and socks ) , weight , wc , and hip circumference were recorded for the subjects .", "of these two rural blocks , 85 anganwadi centers ( awc ) were selected by the random selection method . from the population survey", "it measures the effectiveness of a diagnostic marker and enables the selection of an optimal threshold value ( cut - off point ) for the marker .", "register of awc , male and female patients were randomly selected and called at the awc on a specified date and time after an overnight fast . in urban areas ,", "the area under the roc curve ( aurc ) was used as a measure of discrimination of a predictor .", "two out of total six urban health centers were selected randomly , and from the survey registers of these two health centers , male and female patients were selected randomly . a day before the study ,", "continuous data were expressed as mean sd . the optimal cut - off points for bmi , wc , whr , and whtr were obtained by selecting a point on the roc curve , which represented the largest sum of sensitivity and specificity .", "waist circumference was measured to the nearest 0.1 cm at the midpoint between the subcostal margin and the margin of the supracristal plane according to the idf diagnostic criteria .", "hip circumference was measured to the nearest 0.1 cm around the thighs , at the height of the greater trochanter , with the patients in the standing position ." ], [ "according to the idf definition for the indian population , for an individual to be defined as having the metabolic syndrome , he / she must be diagnosed as having central obesity defined as waist circumference 90 cm in males or 80 cm in females plus any two of the following four factors : ( 1 ) triglycerides 150 mg / dl or specific treatment for this lipid abnormality ; ( 2 ) hdl - cholesterol < 40 mg / dl in males or < 50 mg / dl in females or specific treatment for this lipid abnormality ; ( 3 ) sbp 130 mmhg , or dbp 85 mmhg or treatment for previously diagnosed hypertension ; ( 4 ) fasting plasma glucose 100 mg / dl or previously diagnosed type 2 diabetes .", "all analyses were done separately for men and women and according to their place of residence .", "it measures the effectiveness of a diagnostic marker and enables the selection of an optimal threshold value ( cut - off point ) for the marker .", "the area under the roc curve ( aurc ) was used as a measure of discrimination of a predictor .", "continuous data were expressed as mean sd . the optimal cut - off points for bmi , wc , whr , and whtr were obtained by selecting a point on the roc curve , which represented the largest sum of sensitivity and specificity .", "the statistical program for social sciences , version 17.0 ( spss inc . , chicago il ) , was used for all statistical analyses ." ], [ "roc curves of bmi , wc , whr , and whtr to predict the presence of two or more non - adipose components of metabolic syndrome in the entire study population irrespective of gender and place of living areas under the roc curve , cut offs , sensitivity , specificity of wc , bmi , whr and whtr when we compared these anthropometric variables as a predictor of metabolic syndrome irrespective of the place of living and gender , whtr was found to have the best aurc as a predictor of metabolic syndrome at a cut - off value of 0.52 [ table 2 ] , and it scored over wc as a predictor of metabolic syndrome ( p = 0.001 ) .", "( a ) roc curves of bmi , wc , whr , and whtr to predict the presence of two or more non - adipose components of metabolic syndrome in urban females .", "( c ) roc curves of bmi , wc , whr , and whtr to predict the presence of two or more non - adipose components of metabolic syndrome in rural females .", "( d ) roc curves of bmi , wc , whr , and whtr to predict the presence of two or more non - adipose components of metabolic syndrome in rural males . ( e )", "( b ) roc curves of bmi , wc , whr , and whtr to predict the presence of two or more non - adipose components of metabolic syndrome in urban males ." ], [ "we evaluated and compared the extent to which four different anthropometric variables of adiposity ( bmi , wc , whr , and whtr ) are able to predict two or more non - adipose components of metabolic syndrome using the idf criteria .", "it was observed that in both urban and rural men and women , wc is a better predictor of metabolic syndrome than the other three anthropometric variables ( bmi , whr , and whtr ) .", "the roc and aurc values for wc are better than that for whtr in case of men and women in both urban and rural areas ( p = 0.0054 ) , but if one has to use a single value for the ease and simplicity of prediction of metabolic syndrome , irrespective of gender and place of residence , then at a value of 0.52 , whtr is a good predictor of metabolic syndrome in comparison to wc where one has to use different values for different gender and place of residence . also , for disease with a high prevalence in population , such as metabolic syndrome , there is the need for a test with high specificity to ensure all true negative cases are picked up and the test will have a high positive predictive value .", "varying degree of prevalence of metabolic syndrome is reported from various regions of the world and the indian subcontinent , but very few data is available regarding the prevalence of metabolic syndrome separately in the urban and rural population of haryana and also regarding which anthropometric parameter of adiposity is best suited for urban and rural population .", "the comparison of roc of bmi with that of wc showed that bmi is inferior to wc in predicting metabolic syndrome ( p = 0.0001 ) ." ], [ "to conclude , although the predictive value of different gender - specific wc values is clearly superior to other anthropometric measures for the diagnosis of metabolic syndrome in both urban and rural population of both genders , a single value of whtr > 0.52 irrespective of gender and area of residence can be used as a universal screening tool for the identification of individuals at high risk to the development of metabolic complications ." ] ]

[ [ ", we also demonstrated that gfp and a small water - soluble fluorescent molecule ( uranine ) could be encapsulated in the gvs .", "establishment of a method for preparation of gvs in which materials are densely packed is an important step for creating artificial cells . to confirm the utility of our protocol for various types of inner materials", "we prepared gvs encapsulating 1.0 m microspheres , which are similar in size to intracellular organelles .", ", we used the w / o emulsion centrifugation protocol developed by the yomo group2337 , in which precipitated gvs are collected through a hole opened at the bottom of the centrifuge tube in which they are prepared .", "these five features make w / o emulsion centrifugation an indispensable method for generating cell - mimicking gvs . in previous work ,", "for example , the yomo group used this method to study the in vitro synthesis and pore - forming activity of the membrane protein -hemolysin32 ." ], [ "obtain the precipitated gvs by piercing the bottom of the microtube with a pushpin and collecting one droplet in a sterilized 1.5 ml microtube.dilute the precipitated gv droplet 10 - 100 fold by volume with the outer aqueous solution if the obtained gvs are obtained in quantities large enough to make observation difficult . \n immediately after chilling the microtube ,", "obtain the precipitated gvs by piercing the bottom of the microtube with a pushpin and collecting one droplet in a sterilized 1.5 ml microtube .", "dilute the precipitated gv droplet 10 - 100 fold by volume with the outer aqueous solution if the obtained gvs are obtained in quantities large enough to make observation difficult . \n", "form a lipid film on the inside surface of a 5 ml glass vial by evaporating a mixture of the dopc stock solution ( 51.0 l and the texas red dhpe stock solution ( 19.2 l ) under flowing nitrogen gas .", "mix 1 ml of the oil solution ( liquid paraffin containing dopc and texas red dhpe ) with 300 l of the inner aqueous solution in a 1.5 ml microtube.emulsify the two components in the microtube by using a mechanical homogenizer ( an agitator with blades that rotate at high speed ) operated at 10,000 rpm for 2 min at rt . \n " ], [ "obtain the precipitated gvs by piercing the bottom of the microtube with a pushpin and collecting one droplet in a sterilized 1.5 ml microtube.dilute the precipitated gv droplet 10 - 100 fold by volume with the outer aqueous solution if the obtained gvs are obtained in quantities large enough to make observation difficult . \n immediately after chilling the microtube ,", "obtain the precipitated gvs by piercing the bottom of the microtube with a pushpin and collecting one droplet in a sterilized 1.5 ml microtube .", "dilute the precipitated gv droplet 10 - 100 fold by volume with the outer aqueous solution if the obtained gvs are obtained in quantities large enough to make observation difficult .", "the final volume fraction of microspheres is 0.5 vol% , and the final concentrations of tris - hcl ( ph 7.5 ) and sucrose are 0.1 and 0.15 m , respectively.vortex the microtube for 30 sec and then sonicate it for 10 min . \n in a 1.5 ml" ], [ "place an adhesive incubation chamber for in situ polymerase chain reaction and hybridization ( chamber size 9 mm x 9 mm x 0.3 mm thick ) on top of a microscope cover glass.using a micropipette , deposit 25 l of the diluted precipitated gvs on the specimen area and immediately place another cover glass ( approximately 0.15 mm thick ) on top of the incubation chamber . \n ", "record microscopy images of the vesicles with a microscope ( 10x , 20x , and 40x objectives ) equipped with a 12v100whal - l halogen lamp . \n conduct fluorescence microscopy observations . \n", "record microscopy images of the vesicles with a microscope ( 10x , 20x , and 40x objectives ) equipped with a 12v100whal - l halogen lamp . \n ", "place an adhesive incubation chamber for in situ polymerase chain reaction and hybridization ( chamber size 9 mm x 9 mm x 0.3 mm thick ) on top of a microscope cover glass . using a micropipette , deposit 25 l of the diluted", "fit the units with 470 - 495 nm and 565 - 585 nm excitation filters , respectively , and with emission filters that transmit 510 - 550 nm and 600 - 690 nm light , respectively . \n ", "fit the units with 470 - 495 nm and 565 - 585 nm excitation filters , respectively , and with emission filters that transmit 510 - 550 nm and 600 - 690 nm light , respectively .", "precipitated gvs on the specimen area and immediately place another cover glass ( approximately 0.15 mm thick ) on top of the incubation chamber . \n" ], [ "our results indicate that we successfully encapsulated 1 m microspheres in gvs at a high volume fraction .", "the obtained vesicular dispersion often contained encapsulated materials outside of the gvs because the gvs often rupture during centrifugation . to obtain only gvs , a sorting method such as dialysis , gel filtration , or fluorescence - activated cell sorting", "if necessary for the purpose for which the precipitated gvs are to be used , they can be diluted with the outer aqueous solution . in some cases , the intermediate phase extended to the bottom of the tube , suggesting that any vesicles that formed were held together by the oil .", "we were also able to encapsulate other materials into 100 mol % dopc gvs using the same outer aqueous solution and the same protocol ( figure 4 ) .", "because the gvs form by transfer of emulsion droplets across the w / o interface , the osmotic pressures in the inner and outer aqueous layers must be the same . as a control experiment , we also prepared gvs containing no microspheres by means of the process shown in figure 1 and step 1.3 , except that the inner aqueous solution was prepared without microspheres . collection of the precipitated gvs after centrifugation is shown in figure 2 ." ], [ "the w / o emulsion centrifugation method is commonly used for the formation of gvs containing encapsulated materials .", "gvs with compartments are the first choice for these kinds of applications ; therefore , techniques , such as ours , that could be used for encapsulating magnetic microspheres and microspheres with diverse surface functionalization can be expected to be useful44 .", "although we were able to encapsulate microspheres in the gvs at a volume fraction high enough for microscopy observation , this method is not suitable for the preparation of gvs with a uniform volume fraction distribution .", ", we estimated that the volume fractions of microspheres in the gvs ranged from 4 - 30 vol% ; the volume fractions were not identical to the volume fraction of the inner aqueous solution used for gv preparation .", "the specific gravities of the inner aqueous dispersion medium and the outer aqueous solution must be chosen carefully . for the w / o emulsion to precipitate into the outer aqueous solution during centrifugation" ], [] ]

[ [ "right sided valvular involvement in infective endocarditis has been well - described , but lesions affecting eustachian valve are distinctly rare . in 1986 , edwards et al .", "first described the entity of eustachian valve endocarditis ( eve ) in an autopsy study of a patient with overwhelming streptococcal sepsis . in the literature only few cases have been reported so far .", "herein , we review the literature and describe 2 new cases in which the causative organisms were determined to be vancomycin resistant staphylococcus aureus ( vrsa ) , which is reported for the first time , and staphylococcus hominis ." ], [ "transesophageal echocardiographic image of vegetation attached to the right ventricular wall ( case 1 ) pulmonary ary : pulmonary artery .", "transesophageal echocardiography ( tee ) revealed a 6-cm , echogenic mass attached to the eustachian valve , [ figures 1 and 2 ] along with pulmonary valve and right ventricular wall . during the next 2 days , the patient 's condition was complicated by hemoptysis , renal failure and hypoxic respiratory failure requiring mechanical ventilation .", "suboptimal images by transthoracic echocardiography ( tte ) showed mobile vegetation on the tricuspid valve , along with severe tricuspid regurgitation ." ], [ "transesophageal echocardiographic image of vegetation attached to the right ventricular wall ( case 1 ) pulmonary ary : pulmonary artery .", "transesophageal echocardiography ( tee ) revealed a 6-cm , echogenic mass attached to the eustachian valve , [ figures 1 and 2 ] along with pulmonary valve and right ventricular wall . during the next 2 days , the patient 's condition was complicated by hemoptysis , renal failure and hypoxic respiratory failure requiring mechanical ventilation .", "suboptimal images by transthoracic echocardiography ( tte ) showed mobile vegetation on the tricuspid valve , along with severe tricuspid regurgitation .", "transesophageal echocardiography image demonstrating a large vegetation ( 6 cm ) attached to the eustachian valve ( case 1 ) vege : vegetation , ivc : inferior vena cava ." ], [ "a 86-year - old nursing home female with a history of dementia , severe aortic stenosis , congestive heart failure , chronic anemia secondary to gastrointestinal bleeding requiring implantable venous catheter insertion , presented with high grade temperature of 103f ( reference range 96.8 - 100.4 f ) rectally , pulse rate of 124bpm ( reference range 55 - 90 bpm ) , respiration rate of 23 breaths / min ( reference range 12 - 20 breaths / min ) and blood pressure of 128/69 mm hg ( reference range 100 - 139/55 - 84 mm hg ) .", "tte revealed moderate concentric left ventricular hypertrophy with ejection fraction of 70% , a heavily calcified aortic valve with severe aortic stenosis and moderate pulmonary hypertension ; however , no vegetations were identified ." ], [ "eustachian valve is an embryological remnant of the sinus venosus , directing oxygenated fetal blood from inferior vena cava across foramen ovale , and into the left atrium . in adults , it is non - functional and is considered a benign rudimentary structure .", "this is the first case of vrsa eve reported in the literature . in the second case , staphylococcus hominis ,", "we present 2 new cases of eve with a review of literature [ table 1 ] . in the previously reported cases , the age of patients ranged from 22 years to 76 years with a median age of 44.2 years , with a male to female ratio of 5:3 ." ], [ "it should be strongly considered when a patient has the clinical syndrome of right - sided endocarditis , but no vegetations are identified on tte .", "we found the incidence of eve to be highest in young intra - venous drug users , and staphylococcus aureus to be the most common microbial agent .", "although eve is rare , it may be unwise to rule out this diagnosis based solely on tte , especially in the setting of persistent bacteremia or pulmonary emboli .", "however , over the past 6 years eve has been seen more frequently in the elderly population with culture positivity for diverse microbial agents ." ] ]

[ [ "the \n hypothesis tested was that there are significant differences in the surface area , volume \n and specific surface area among the different sizes of endodontic files .", "the aim of this study was to determine , for the first time , the surface area , volume and \n specific surface area of successive file sizes of a commercially available ni - ti system . \n additionally , we tested the hypothesis that mxct is capable of discriminating the \n quantitative differences in the aforementioned geometrical properties between the \n successive sizes of endodontic files .", "these differences exist by definition due to the \n progressively increased size of the successive files used in root canal therapy .", "the technique is \n constantly being improved through hardware and software developments and the subsequent increase in \n resolution provides researchers with new information and approaches for the \n investigation of the material properties . in the dental field , mxct has been extensively used to quantify the geometrical changes \n in the root canal anatomy during endodontic therapy , comparing pre and post \n instrumentation analyses ." ], [ "three sets of flex - master ni - ti files ( vdw ; munich , germany ) , 6 files each ( iso sizes \n n 20/lot 0411310306 , n 25/lot 0410310302 and n 30/lot \n 0406310290 ) all of 0.04 taper , were utilized in this study . to avoid any inclination \n from the vertical axis ,", "the surface area ( sa ) and \n volume ( v ) of each file were determined by the embedded software ( ctan , skyscan , \n aartselaar , belgium ) employing the following formulas : with n = number of slices , s = slice thickness , pi = measured periphery in slice i \n and ai = measure area in slice i the specific surface area ( the surface to volume ratio ) was also calculated .", "the \n percentage differences between the successive file sizes for the aforementioned \n properties were calculated based on the formula : horizontal slices of all scanned files were also inspected for the presence of internal \n defects such as cracks or pores .", "a fixed threshold was applied to discriminate the crosssection from the air , \n providing high contrast images of the horizontal cross - sections .", "the surface area and volume of all files \n were determined from the tip up to the 16 mm level , taking 6,782 horizontal slices .", "the files were placed on the stage , employing a custom made \n attachment and then scanned by a mxct scanner ( skyscan model 1072 ; aartselaar , belgium ) \n operated under the following conditions : wo ka source ( 100 kv , 98 a ) , 2.36 \n m pixel size , 180 rotation , 0.9 rotation step , 1.9 sec exposure time \n averaging by two frames , and 1 mm al filter .", "the \n files were successively scanned using the automated routine of oversize mode , for 16 h \n each ." ], [ "all data were statistically analyzed using oneway anova and snk multiple comparison \n tests at a 95% significance level , employing the file size as the discriminating \n variable .", "linearity of the surface area and volume data versus iso size was analyzed \n employing linear regression analysis ." ], [ "figure 2 demonstrates two representative \n horizontal sections ( perpendicular to the longitudinal file axis ) from the mxct . the \n left image has been taken from a region near the handle and the right from a region near \n the cutting tip of a ni - ti file , demonstrating the difference in the cross - sectional \n surface area .", "the right image has a smaller cross- \n sectional surface , as it is closer to the cutting tip the quantitative results for the surface area , volume and specific surface area of \n successive file sizes are presented in table 1 . \n", "the raw \n data , the fitted line , the 95% confidence intervals , the yielded analytical formula , and \n the regression coefficient ( r ) are all presented in figures 3a and 3b for the \n surface area and volume , respectively . ", "mean values and standard deviations for the surface area ( sa ) , volume ( v ) , and \n specific surface area ( ssa ) of flexmaster ni - ti files .", "similar results were found for \n the volume of the ni - ti files tested . however , the increase in volume declined towards \n the larger file sizes .", "the surface area of the n 30 files showed the highest value followed by \n n 25 and n 20 .", "the file n 20 \n showed a significantly higher specific surface area followed by n 25 and \n n 30 ." ], [ "the estimation of the surface area and volume \n of endodontic files might provide a new approach for the characterization of \n clinically - related properties such as cutting efficiency , loading of dentin debris etc . \n", "this study demonstrates that mxct is a powerful tool with interesting applications for \n endodontic research .", "the results of the current study showed significant differences for the surface area and \n volume between the files tested , thus the original hypothesis is accepted .", "it is \n noteworthy that this analysis provided significant differences for the endodontic files \n with different iso sizes , demonstrating the ability of this analysis to discriminate the \n quantitative differences of the geometrical characteristics among the different \n endodontic file sizes .", "continuing technological advancements allowing development of more \n powerful mxct scanners should accelerate the applications of this methodology in the \n near future ." ], [ "this type of analysis should be used to investigate the unexplored correlations of the \n various clinical properties of the geometrical characteristics of the endodontic files , \n opening new avenues for research in the field of endodontics .", "the surface area and volume demonstrated an almost linear increase , while the specific \n surface area demonstrated an abrupt decrease towards the higher file sizes .", "for the \n first time , we have shown that mxct is capable of discriminating the quantitative \n differences in the geometrical properties of the successive sizes of endodontic files . \n" ], [ "this study has been funded by a research grant ( # rgp - vpp-206 ) from the \n research group program , deanship of scientific research , king saud university , \n riyadh , saudi arabia .", "the authors would like to thank the research group program for funding this research \n project ." ] ]

[ [ "a 2.15-kb fragment of human gip promoter with the a allele at rs3895874 , rs3809770 , rs3848460 , and rs937301 ( 2073 bp to + 77 bp ) was chemically synthesized ( genescript inc . ,", "promoter fragments with ancestral haplotypes were obtained using the site - directed mutagenesis . in the promoter reporter study , each experiment was conducted at least three times with three or four replicates for each treatment .", "the screening glucose challenge test for gestational diabetes was performed as previously described ( 24 ) .", "total gip , insulin , and c - peptide levels in human serum were measured using sandwich elisa kits ( millipore , billerica , ma ; mercodia , uppsala , sweden ; and calbiotech , spring valley , ca ) .", "blood samples were collected from patients for hormone measurement 1 h after administration of the oral glucose tolerance test .", "patients glucose challenge responses and serum hormone profiles were compared with the test or the student t test with welch correction ." ], [ "we recruited 123 patients , and all patients gave written informed consent to participate in the study .", "the screening glucose challenge test for gestational diabetes was performed as previously described ( 24 ) .", "this study was approved by the institutional ethics committee review boards of chang gung memorial hospital linkou medical center and chang gung university ." ], [ "genotyping of snps was performed using the taqman validated snp genotyping assays ( applied biosystems , foster city , ca ) .", "genomic dna samples of participants were extracted and purified from anticoagulated blood with the dneasy blood & tissue kit ( qiagen , venlo , netherlands ) ." ], [ "blood samples were collected from patients for hormone measurement 1 h after administration of the oral glucose tolerance test .", "total gip , insulin , and c - peptide levels in human serum were measured using sandwich elisa kits ( millipore , billerica , ma ; mercodia , uppsala , sweden ; and calbiotech , spring valley , ca ) ." ], [ "promoter fragments with ancestral haplotypes were obtained using the site - directed mutagenesis . in the promoter reporter study , each experiment was conducted at least three times with three or four replicates for each treatment .", "a 2.15-kb fragment of human gip promoter with the a allele at rs3895874 , rs3809770 , rs3848460 , and rs937301 ( 2073 bp to + 77 bp ) was chemically synthesized ( genescript inc . ,", "piscataway , nj ) and subcloned into the pgl4.2 luciferase reporter vector ( promega corp . , madison , wi ) ." ], [], [ "patients glucose challenge responses and serum hormone profiles were compared with the test or the student t test with welch correction . ratios of patients with glucose levels exceeding the threshold were analyzed with the test .", "all data were presented as mean sem , and the statistical significance cutoff value was 0.05 ." ], [ "because the three gip variants ( rs3895874 , rs3848460 , and rs937301 ) are highly linked compared with those that appeared alone in other candidate genes ( 32 ) , and because these gip variants are partially linked with a nonsynonymous gip snp ( rs2291725 ) ( 22 ) , these gip variants have a low likelihood of being false positive ( table 1 ) .", "select variants in cdkal1 , cyb5r4 , gad2 , and pparg were associated with type 2 diabetes - related or obesity - related traits ( 2831 ) . by contrast , there has been no report of linkage of gip variants in gwa studies .", "on the basis of the presence of highly divergent allele frequencies between eurasians and africans , the presence of ld and extended haplotypes in eurasians , and a > 30% minor allele frequency in the overall eurasian population , we identified seven snps in the 5 gene region of cdkal1 , cyb5r4 , gad2 , gip , and pparg as potential common metabolic modifiers ( table 1 ) . in earlier gwa studies ,", "to systematically identify putative metabolic modifiers , we curated and screened snps in 207 gene loci that have previously been implicated in the regulation of diabetes - related and/or obesity - related traits using fst ( supplementary table 1 ) .", "we genotyped a panel of 123 unrelated han - chinese women who underwent a screening glucose challenge test for gestational diabetes during the 23rd to the 29th weeks of pregnancy , and these patients were assigned to three genotype groups ( gip , gip , or gip ) based on alleles at rs3895874 , rs3848460 , and rs937301 ." ], [ "on the basis of the presence of highly divergent allele frequencies between eurasians and africans , the presence of ld and extended haplotypes in eurasians , and a > 30% minor allele frequency in the overall eurasian population , we identified seven snps in the 5 gene region of cdkal1 , cyb5r4 , gad2 , gip , and pparg as potential common metabolic modifiers ( table 1 ) . in earlier gwa studies ,", "to systematically identify putative metabolic modifiers , we curated and screened snps in 207 gene loci that have previously been implicated in the regulation of diabetes - related and/or obesity - related traits using fst ( supplementary table 1 ) .", "select variants in cdkal1 , cyb5r4 , gad2 , and pparg were associated with type 2 diabetes - related or obesity - related traits ( 2831 ) . by contrast , there has been no report of linkage of gip variants in gwa studies ." ], [ "we constructed and tested gip promoter reporters with each of the three major haplotypes in transfected human embryonic kidney ( hek ) 293 t cells ( fig .", "importantly , we found that reporters with an ancestral haplotype consistently exhibited significantly higher activities than those containing the derived haplotype in the presence of pax6 or gata4 ( p < 0.01 ) .", "together , these results suggested that derived alleles at rs3895874 , rs3848460 , and rs937301but not rs3809770represent functional mutations .", "the reporter activity is haplotype - dependent in the absence or presence of select transcription factors . to compare gip promoter reporter activities , hek293 t cells in 6-well" ], [ "we genotyped a panel of 123 unrelated han - chinese women who underwent a screening glucose challenge test for gestational diabetes during the 23rd to the 29th weeks of pregnancy , and these patients were assigned to three genotype groups ( gip , gip , or gip ) based on alleles at rs3895874 , rs3848460 , and rs937301 .", "given that earlier genome studies have not reported an association between gip variants and any trait , we speculated that the partial selection of gip variants in eurasian populations could be associated with adaptation at a life stage that is vulnerable to environmental changes and that has not been specifically studied . because pregnancy represents a critical life stage that subjects individuals to excessive metabolic load , and because its success has a major impact on reproductive fitness , we hypothesized that studies of phenotypic variation during pregnancy may provide a sensitive model to investigate the role of gip haplotypes . to test for an allelic effect of gip variants , we studied east asian patients for proof - of - concept testing because selection pressures are most likely ongoing in populations that exhibit the most significant evidence .", "therefore , the homozygous gip genotype could be associated with a reduced gip response and reduced capability of maintaining glucose homeostasis .", "association between gip haplotypes and gip response after glucose challenge tests in 123 pregnant han - chinese women gip , glucose - dependent insulinotropic polypeptide ; or , odds ratio . *" ], [ ", our data demonstrated a strong association between regulatory gip variants , and gip response and glucose metabolism , reinforcing the indication of an important role of gip signaling in diabetes - related traits from earlier gwa studies of gipr .", "specifically , we demonstrated that gip variants at the 5 gene region represent metabolic modifiers that contribute to phenotypic variation in gip response and glucose metabolism .", "on the basis of studies of signatures of selection , in vitro promoter assays , and glucose challenge tests in humans , we show that it is possible to identify causal variants related to energy - balance regulation by focusing on genic snps that were subject to environmental selection in a subset of candidate genes .", "thus , the gip signaling pathway could represent a hotspot for selection in recent human history and play an important role in the manifestation of phenotypic variation in energy - balance regulation among individuals ." ], [] ]

[ [ "the conventional definitions of pediatric adiposity depend on a measured body mass index ( bmi , kg / m ) interpreted relative to a reference distribution ( bmi normative growth charts ) for sex and age [ 13 ] .", ", we examined the performance of bmi z - score ( bmiz , referenced to cdc 2000 growth charts for the united states ) and whtr for the purpose of cardiometabolic risk assessment .", "thus , waist circumference also requires interpretation relative to its own reference distribution for sex and age .", "comparisons of risk assessments in youth have generally found little difference between bmi and waist circumference in the ability of these indicators to identify cardiometabolic risk [ 6 , 7 ] . the waist - to - height ratio ( whtr ) is an adiposity indicator with waist circumference in the numerator and a simplified correction ( as height ) for skeletal size .", "because it has body weight in its numerator , bmi reflects generalized ( total - body ) enlargement with a simplified correction ( as height ) for skeletal size .", "waist circumference is a regional measurement , it reflects specifically only abdominal or central enlargement .", "whtr does not depend on sex- or age - specific reference criteria [ 810 ] . in a large sample of us sixth - graders" ], [ "participants came from the baseline enrollment ( sixth - grade students in 2006 ) of the healthy study , a cluster - randomized , controlled , primary prevention trial designed to improve indicators of adiposity and glycemic dysregulation among us middle - school children [ 12 , 13 ] .", "seven research centers recruited 42 middle schools with at least 50% of students eligible to participate in the federally subsidized national school lunch program or belonging to an ancestral minority group at increased risk of type 2 diabetes ( hispanic , non - hispanic black , or native american ) .", "we calculated the total - to - hdl cholesterol ratio ( tc / hdlc ) , a variable that strongly predicts cardiovascular disease in adults and may be more strongly associated than ldl - cholesterol or hdl - cholesterol concentrations with pediatric adiposity [ 22 , 23 ] .", "in addition to stratification by sex , we chose a priori to stratify our analyses by high fatness or lower fatness because the ability of adiposity indicators to identify adipose tissue mass , ectopic fat , and cardiometabolic risk variables may be stronger among children in a higher fatness category [ 2326 ] . as defined for this report , the high - fatness level included students who were above the sex - specific median value for both bmiz and whtr ; any student below the median for either adiposity indicator was designated lower fatness . for each fatness level , we prepared sex - specific , linear - regression models adjusted for ancestry ( 4 categories ) and pubarche ( yes / no ) to estimate the associations of continuous adiposity indicators with the continuous cardiometabolic risk factors ( outcomes ) . since blood pressure varies with height in children [ 27 , 28 ] our models for blood pressure outcomes included an additional adjustment for height which was entered as a continuous variable .", "a detailed protocol and background details about the healthy study are available for download at http://www.healthystudy.org/. we restricted a priori our analytic sample to students with integer ages of 11 or 12 years who were able to participate in physical education and did not have known diabetes . from 5950 eligible enrollees , we excluded 13 students due to missing or invalid data for the adiposity indicators ( height , weight , and waist circumference ) ." ], [ "systolic blood pressure was not significantly associated with bmiz or whtr for high - fatness blacks of either sex , but the association was present for high - fatness students who were hispanic or white .", "similarly , both adiposity indicators were associated with diastolic blood pressure more strongly among high - fatness students ( 0.230.32 ; p < 0.001 for each of 4 beta coefficients ) than among lower - fatness students ( 0.030.05 ; p > 0.05 for each of four beta coefficients ) . for identification of lipid outcomes , however , we found steeper beta coefficients only among high - fatness boys ( compared to lower - fatness boys ) whose adiposity was assessed by bmiz . for both sexes assessed by whtr ,", "however , for high - fatness girls who were hispanic or white , bmiz and whtr had significant associations ( p < 0.05 ) with diastolic pressure . among high - fatness boys", "adiposity indicators explained < 3% of the variations in systolic blood pressure and fasting glucose . for each outcome variable in these high - fatness subpopulations , the effect sizes ( standardized beta coefficients ) associated with bmiz were similar to those associated with whtr . within the lower - fatness subpopulations of either sex ( table 4 ) ,", "an ancestral contrast ( blacks compared to whites ) related to systolic blood pressure was significant , however , only among the high - fatness girls assessed by bmiz ( figure 1 ; p < 0.01 ) .", "adiposity indicators in these lower - fatness subpopulations explained < 1% of the variations in systolic blood pressure , diastolic blood pressure , and fasting glucose ." ], [ "in this large sample of middle - school students at increased risk of obesity and type 2 diabetes , we found that adiposity indicators bmiz ( with reference to cdc 2000 growth charts ) and whtr ( without reference to sex and age ) had similar utility for identifying adverse levels of cardiometabolic variables .", "although high - fatness hispanic and white girls in our study demonstrated the expected associations between adiposity and blood pressure , we found among the high - fatness black girls ( but not black boys ) that neither bmiz nor whtr had a significant association with blood pressure outcomes ( figure 1 ) . in comparison to young hispanics and whites ,", "since both the bmiz and whtr indicators demonstrated similar patterns of nonassociation with black girls ' blood pressure , it may be that this absence of a correlation with blood pressure is due to factors operating primarily outside the abdominal region .", "perhaps black girls benefit from an increased capacity to expand their lower - body ( gluteofemoral ) , subcutaneous , adipose - tissue stores in a manner that would increase their total body weight yet protect them from cardiometabolic risk [ 7073 ] .", "if this protective characteristic of black girls extends into their later years , it could help explain why adult black women in the us experience no increased cardiometabolic risk or mortality until their bmi reaches approximately 33 kg / m ." ], [ "the whtr allows a simpler calculation without the necessity of squaring the child 's height . of interest to those concerned with child adiposity and", "cardiometabolic risk observed in different cultures or distinct time periods , the whtr will facilitate comparisons based directly on anthropometric observations without using normative reference tables that may not be suitable to all populations [ 7779 ] .", "adoption of the whtr could optimize both patient education and the tracking of risk . compared to bmi ,", "pediatric health care providers , too , may find it more useful to recognize risk associated with a waist increment ( corrected for height ) than with a weight increment ( corrected for height squared ) .", "if a well - standardized waist measurement comes into widespread use for clinical assessments of pediatric adiposity , patients and their families may improve their intuitive understanding of how excess adiposity contributes to adverse health risk ." ] ]

[ [ "the bucky shuttle being the combination of nanosize carbon structures fullerene and nanotube , has many possible applications : nanoscale storage cells , devices for directed medicine transfer and containers for effective and safe gas storage [ 7 - 13 ] .", "the nanocapsule - specific structure defines its adsorption qualities : at the storage stage under normal conditions , the nanocapsule contains the amount of methane that was adsorbed at normal temperature and under 40 mpa .", "the nanocapsule desorption takes place at the temperature elevation up to 350 k. there is no need to apply electric field during storage and desorption .", ", the processes of methane molecule adsorption , storage and desorption by the nanocapsule are investigated with molecular - dynamic modeling method .", "nanosize containers and capsules of various shapes that allow reaching a higher safety level and mass content of gas stored have been investigated for a number of years [ 11 - 13 ] .", "the engineering of nanostructured carbon opens the ways for the production of nanocapsules of complex structural shapes [ 14 - 16 ] . in this work" ], [ "methane adsorption , storage and desorption processes were modeled with the method of molecular dynamics .", "the values of hydrogen and carbon atom charges in methane molecule were obtained using the combination of hartree fock and becke exchange with lee yang ", "the motion of charged fullerene in the nanotube with the help of electric field is described in detail in .", "the following atom charge values in methane molecule were obtained : carbon atom 0.628204 mulliken and hydrogen atom + 0.157051 mulliken .", "the charged endohedral complex k@c60 moves in the blocking chamber and junction under the action of external electric field .", "the holes in the nanotube can exist at the temperatures up to 400 k ; when the temperature elevates , the hole diameter in the nanotubes considerably decreases due to the motion and fusion of single vacancies [ 8 - 10 ] . during modeling" ], [ "the change in the k@c60 ion kinetic energy as a function of time the methane molecules desorption process is shown in fig .", "the change in the k@c60 ion kinetic energy as a function of time in the time period from t = 16.5 ps to t = 26.5 ps , the considerable attenuating oscillations of the kinetic energy conditioned by the k@c60 motion along the blocking chamber walls adjacent to the junction entrance are observed . in this time period , each peak of the k@c60 kinetic energy corresponds to the time moments after passing the pentagonal rings in the structure of the blocking chamber . under the electric field action", "2 ) , the k@c60 endohedral complex is retained at the end of the blocking chamber under the action of van der waals forces . the methane molecules from the environment", "the value of the k@c60 kinetic energy does not exceed 0.033 ev . in the process of methane molecules adsorption ,", "the availability of even insignificant number of methane molecules in the blocking chamber considerably decreases the velocity of the k@c60 motion , and , respectively , the kinetic energy of the k@c60 impact against the blocking chamber wall ." ], [ "an obvious advantage of the nanocapsule is its operation cycle : methane is adsorbed under the elevated pressure ( 40 mpa ) and at normal temperature with further blocking of methane molecules by the k@c60 endohedral complex in the nanocapsule with the external electric field , the storage is performed in normal external conditions , and methane desorption is performed at temperature elevation up to 350 k , at which methane molecules push out the k@c60 and are desorbed from the nanocapsule .", "we demonstrated the functioning of the nanocapsule of complex structural shape for methane storage using the method of molecular dynamics .", "the electric field is not used , this significantly simplifies the use of nanocapsules in automobile applications .", "methane content in the nanocapsule at the storage stage is ~11.09 mass% . at the storage and desorption stages ,", "the multiple techniques of nanostructural engineering developed are the prerequisites for the creation of similar nanocapsules ." ], [ "calculations are made in interdepartmental supercomputer center of the russian academy of science ( moscow ) ." ] ]

[ [ "we describe a young male who developed mania while on amisulpride , a newer antipsychotic drug introduced in india .", "it is an unusual \" atypical \" antipsychotic , as the \" atypical \" profile of the new antipsychotics clozapine , olanzapine , quetiapine , and risperidone has been linked to combined antagonism of serotonin 2 ( 5-ht2 ) and dopamine 2 ( d2 ) receptors , whereas amisulpride has negligible affinity for 5 ht2 receptors and is specific for dopamine d2 and d3 receptors in the limbic rather than striatal structures .", "there are reports of amisulpride being used for the management of bipolar disorders . however , there are very few reports of mania induced by amisulpride . here" ], [ "a 18-year - old unmarried hindu male presented with a history suggestive of schizophrenia for the last 2 years .", "the patient was followed up after 1 week and during this time there was substantial improvement in his manic symptoms with ymrs score of 17 .", "after 10 days of 100 mg dose , the patient developed a manic episode , characterized by decreased need for sleep , over talkativeness , hyperactivity , persistent elevated mood , disinhibited behavior , over - grooming , and distractibility .", "it was initiated at 50 mg per day and was increased to 100 mg per day after 4 days of initiation it .", "he was prescribed amisulpride for the negative symptoms along with risperidone 4 mg that was continued ." ], [ "to the best of our knowledge of mania due to first amisulpride was reported by murphy in 2003 . however , in the case described by murphy , the patient was also on citalopram , an antidepressant , though its discontinuation did not led to improvement in manic symptoms .", "this case report highlights the fact that close monitoring of patients on amisulpiride should be done for manic symptoms .", "this is also important because of the fact that atypical antipsychotic drugs ( including amisulpride ) are used for the treatment for bipolar disorder .", "open label studies have shown that amisulpride may be useful for patients with bipolar disorder .", "also , as low doses enhance dopamine transmission , and high doses reduce dopamine transmission , it might be prudent to start amisulpride at the recommended target dose at the initiation of therapy ." ] ]

[ [ "this study attempted to evaluate the regional metabolic disorders using h mrs within the frontal , external and medial temporal lobes in patients with mci , as a predictor of clinical deterioration to dementia based on clinical follow - up .", "we observe the lowering of perfusion and metabolism of glucose and oxygen in temporal and parietal areas in patients with possible ad , as well as in those with mci .", "atrophy of the medial temporal lobe in mci patients with a positive correlation of atrophy level and a risk of conversion to ad , inadequate for age and observed in imaging examinations ( ct , mri ) , has been clearly demonstrated [ 813 ] .", "there have been several reports on such dysfunctions in the limbic system in patients with alzheimer disease .", "thus , when disorders of memory and other cognitive functions go beyond the standards of age and educational level , but have not yet reached the standards of dementia , we diagnose mild cognitive impairment ( mci ) , which includes several states that either match the standard in its wide meaning , for example age - associated memory impairment ( aami ) , age - related cognitive decline ( arcd ) , or we diagnose pathology like mci , which , although clinically similar , has a different prognosis than aami and arcd [ 14 ] . currently , base on criteria established by the mayo clinic group , mci is define as a transitional state between normal aging and alzheimer s disease , in which memory impairment is greater than expected for age , but general cognitive function and daily living activities are preserved ." ], [ "this study attempted to evaluate the regional metabolic disorders using h mrs within the frontal , external and medial temporal lobes in patients with mci , as a predictor of clinical deterioration to dementia based on clinical follow - up ." ], [ "we investigated the extent of cerebral atrophy , especially in medial and external temporal lobes and in frontal structures , as well as the presence of cortical - subcortical hyperintensive focuses ( which equal angiogenic lesions ) in t2-weighted images and flair sequence .", "it was divided into 2 areas the anterior ( the topographical point of reference in the coronal plane / layer was the level of dens ) and the posterior ( the point of reference was the output of the middle cerebellar peduncles from the pons ) . both areas were then added , and final average data sets were used in further analysis . in cases of reduced volume of the hippocampal formation , the adjacent fluid spaces ( eg , the temporal horn of the lateral ventricle and the lateral part of the transverse fissure ) were also included into the voi .", "morphological mri examination of the brain was carried out in transverse planes , parallel to the longitudinal axis of the temporal lobe in se , fse and flair sequences , in t1- and t2-weighted images , and in the frontal plane perpendicular to the longitudinal axis of the temporal lobe in flair sequence .", "the voi ( volume of interest ) was located in the frontal , medial and external temporal lobe regions , separately on each side . in case of medial temporal lobe covering the hippocampal formation ,", "evaluation of relative concentration ratios of metabolites from all vois , localized within frontal , medial and external temporal lobes , symmetrical on both sides , were performed in each case .", "a comparison of some metabolic ratios of mrs in patients with mci , who on follow - up has stable disease ( sd ) , disease progression ( dp ) and conversion to ad , was performed .", "results analysis of clinical and biochemical data age , mini - mental score ( mm - score ) , folic acid , vitamin b12 and homocysteine level was performed including initial data of all subjects enrolled into the study ." ], [ "the examination was performed on a group of 31 randomly selected subjects ( 19 females and 12 males ) with mci diagnosed under the care of the department of neurodegenerative disorders , medical research centre , polish academy of science .", "mci diagnosis was established by a team of specialists after analyzing all available information and test results .", "all subjects underwent neurological and psychiatric tests , routine laboratory investigations and standard neuropsychological examinations .", "patients with serious cns injuries , alcoholic abuse , diabetes , and serious hepatic and renal dysfunctions were excluded ." ], [ "we investigated the extent of cerebral atrophy , especially in medial and external temporal lobes and in frontal structures , as well as the presence of cortical - subcortical hyperintensive focuses ( which equal angiogenic lesions ) in t2-weighted images and flair sequence .", "it was divided into 2 areas the anterior ( the topographical point of reference in the coronal plane / layer was the level of dens ) and the posterior ( the point of reference was the output of the middle cerebellar peduncles from the pons ) . both areas were then added , and final average data sets were used in further analysis . in cases of reduced volume of the hippocampal formation , the adjacent fluid spaces ( eg , the temporal horn of the lateral ventricle and the lateral part of the transverse fissure ) were also included into the voi .", "the voi ( volume of interest ) was located in the frontal , medial and external temporal lobe regions , separately on each side . in case of medial temporal lobe covering the hippocampal formation ,", "morphological mri examination of the brain was carried out in transverse planes , parallel to the longitudinal axis of the temporal lobe in se , fse and flair sequences , in t1- and t2-weighted images , and in the frontal plane perpendicular to the longitudinal axis of the temporal lobe in flair sequence .", "n - acetylaspartate ( naa ) , choline ( cho ) , myoinositol ( mi ) , glutamine and glutamate ( glx ) were analyzed in reference to the signal of unsuppressed water signal , and also to the signal of creatine , considering its level as an inner standard ." ], [ "a comparison of some metabolic ratios of mrs in patients with mci , who on follow - up has stable disease ( sd ) , disease progression ( dp ) and conversion to ad , was performed .", "results analysis of clinical and biochemical data age , mini - mental score ( mm - score ) , folic acid , vitamin b12 and homocysteine level was performed including initial data of all subjects enrolled into the study .", "evaluation of relative concentration ratios of metabolites from all vois , localized within frontal , medial and external temporal lobes , symmetrical on both sides , were performed in each case .", "the statistical analysis was carried out using the statistica for windows 7.0 ( statsoft , ok , usa ) software package ." ], [ "all patients had annual clinical follow - up at least twice . at the beginning of the study , subjects were divided into 2 groups 9 subjects who had amnestic mci , and the others who had multidomain mci .", "there were no statistical differences between groups of patients with multidomain mci and amnestic mci , including age , m - m score , level of vitamin b12 , folic acid and homocysteine ( p>0.05 ) .", "statistical analyses of baseline metabolic ratios measurement using h mrs between the final 3 groups of patients , ( sd , dp and ad ) found significant difference in frontal lobes in mi / h20 ratio on left , between patients with stable disease ( 0.27 ) and those with progression ( 0.22 ) ( p=0.03 ) ( figure 1 ) . in the groups of patients with dp and those with conversion to ad", "( median 3 years ) 8 subjects had stable disease ( sd ) , 13 had progression of disease ( dp ) and 10 developed ad ." ], [ "it also seems clear that there is a lowering of the naa concentration in atrophic structures of the limbic system in patients with ad , and a reverse correlation of the level of this metabolite with the level of dementia .", "proton magnetic resonance spectroscopy h mrs enables an in vivo noninvasive assessment of the degree of biochemical disorders in a specified voi of the examined tissue , as well as monitoring the progress of those changes in the course of the disease and its treatment [ 5,1725 ] .", "in our study , we found a significant difference between the ratio of naa / cr between patients with ds vs. dp in the left frontal lobe .", "we also found significant difference in naa / h2o between patients with ds and dp in the left external temporal lobe ." ], [ "it also seems clear that there is a lowering of the naa concentration in atrophic structures of the limbic system in patients with ad , and a reverse correlation of the level of this metabolite with the level of dementia .", ", we found a significant difference between the ratio of naa / cr between patients with ds vs. dp in the left frontal lobe .", "however , the h mrs examinations of the posterior part of the cingulate gyrus ( frontal lobe ) in patients with mci , carried out by the rochester group , did not prove statistically significant differences of the naa ratios as compared to the control group . in our study", "we also found significant difference in naa / h2o between patients with ds and dp in the left external temporal lobe ." ], [ "some studies have found an elevated level of mi / cr , with good correlation of disease progression and increase of neurofibrillary tangles in patients with conversion into ad . in our study", "the authors associated this with an elevated activity of sodium - myoinositol transporter/ transmitter , which results from the existence of the additional 21 chromosome in down syndrome adults , which includes the gene - encoding protein of the transmitter . in our study , significant differences in mi / cr and mi / h2o were found in frontal and external temporal lobes , but not in the medial temporal lobe .", "we found the same tendency in mi / h2o ratio on the left frontal lobe between patients with disease stability and disease progression .", "we did not find any of these findings ; on the contrary , we detected some depletion of mi / cr in patients with conversion to ad compared to those with stable disease , with a significant difference on the left external temporal lobe ( 1.09 vs. 0.62 ) .", "some reports indicated that an elevated level of this metabolite in structures of the limbic system in patients with mci or dementia is connected with regional gliosis ." ], [ "our h mrs study shows a significant difference between chol / cr ratio only in the external temporal lobe on the left side , with a significant drop in the chol / cr ratio between patients with stable disease and ad .", "impairment of mitochondrial activity seen in elderly patients , and more obviously in patients with ad , could be related to increase of mitochondrial membrane damage and evaluated level of membrane phospholipid and decrease in phosphatidyl - choline and phosphatidylethanolamine described previously .", "this result agrees with metastasio et al . , who showed a decreased , but not significant , depletion of chol / cr in mci patients with disease progression compare to those with stable disease in both hemispheres .", "this could be related to cholinergic neuronal damage , which is indirectly confirmed by increased activity of choline acetyltransferase ( chat ) , and which probably represents a compensatory ( but insufficient ) response in ad ." ], [ "in our study , significant difference in glutamine and glutamate ( glx ) ratio was noted only on the medial temporal lobe on the right side , which indicates disturbance of glx .", "detailed analysis of glutamine and glutamate in mci and ad could be explored using the new 3 t system , which currently is commercially available . in the medial temporal lobe h mrs", "this theory was not corroborated in comparative studies of both of the methods used on a group of patients with temporal lobe epilepsy .", "has several limitations that could influence our results and our interpretation . in view of the complicated spatial shape of the medial temporal - hippocampal formation ( which is considered to be the region first changed by the progression of dementia pathology ) and its relatively small size , our volume of interest also covered other tissue structures outside the target structure , which could have caused partial falsification of the results as to its volume effect on the other hand , these structures belong to the limbic system , and show pathological changes in the subsequent stages of the disease ." ], [ "h mrs seems to be a very sensitive method that provides biochemical information using an in vivo approach in patients with initial mci , who in significant numbers developed disease progression and/or converted to ad .", "a potential advantage could be achieved by using 3 t systems , which can better discriminate quantization of glu + gln / cr and gln / cr ratios ." ] ]

[ [ "intraocular pressure ( iop ) is one the most important modifiable risk factors for glaucoma progression.13 iop measurements in the ophthalmology clinic are often limited to office hours , which do not fully represent the nychthemeral iop peaks and fluctuations.4,5 previously , 24-hour iop monitoring studies have reported fluctuation as high as 8.21.4 mmhg , but many of these studies measured iop in the sitting position , overnight in a hospital environment , and over a few sampling periods , which does not truly reflect the physiological and normal setting of one s daily living , especially when the subjects are awakened at night for iop measurements.610 various studies have reported the significance of iop fluctuation on glaucoma progression.11,12 while there are studies that report otherwise,13,14 much of the existing literature has only documented inter - visit or daytime iop variability over a limited number of hours .", "this is at least partly due to limitations of how frequently repeated tonometric iop measurements can be taken . a contact lens - based sensor ( cls )", "is nowadays available for the recording of ocular dimensional profiles for up to 24 hours.15 this device has been shown to be safe and tolerable in healthy subjects and glaucoma patients as well as to provide reproducible recording of 24-hour profiles.1618 the aim of this study was to analyze the 24-hour ocular dimensional profile in normal - tension glaucoma ( ntg ) patients on medical treatment ." ], [ "nocturnal versus diurnal mean variability from mean ; wake - to - sleep versus sleep - to - wake slopes ; number of nocturnal versus diurnal peaks ; and 24-hour , diurnal , and nocturnal variability among prostaglandin users and nonusers .", "whitney u - test : \n nocturnal versus diurnal mean variability from mean;wake - to - sleep versus sleep - to - wake slopes;number of nocturnal versus diurnal peaks ; and24-hour , diurnal , and nocturnal variability among prostaglandin users and nonusers .", "the device was ce - marked and thus approved for clinical use in 2009 . in healthy volunteers and glaucoma patients , the cls was found to be tolerable in normal activities of daily living and during sleep . a contact lens with base curve 8.7 mm was also found to be well adapted in most eyes , although the device also exists in steeper ( 8.4 mm ) and flatter ( 9.0 mm ) base curves.1618 the cls was placed on the subject s eye by an ophthalmologist in the outpatient clinic after a slit - lamp examination of the anterior segment and goldmann applanation tonometry ( gat ) by a single investigator . for those with unilateral disease , the cls was placed on the eye with ntg . for those with bilateral disease , a random eye assignment by card shuffling was used to determine the eye for the cls placement .", "the sensimed triggerfish ( sensimed ag , lausanne , switzerland ) is a soft silicone cls that enables recording of the ocular dimensional profile over a 24-hour period with minimal disturbance to one s daily routines and sleep cycles .", "diurnal / nocturnal variability : same as above but only during the awake and asleep periods , respectively , where the sleep cycle is determined from recorded sleep times in each individual s logbook and verified by the eye - blinking frequency ( present during waking ) and the presence of rhythmic ocular pulsation waves ( present during sleep ) .", "sleep - to - wake and wake - to - sleep slopes : calculated with a generalized linear model on raw measurements in units of mveq / hour from 1 hour before sleep or wake time to 1 hour after sleep or wake time , respectively .", "ntg was defined as open angle on gonioscopy ; progressive thinning of the retinal nerve fiber layer ( rnfl ) on optical coherence tomography , with corresponding glaucomatous visual field changes on the humphrey visual field analyzer ; and an iop 21 mmhg on all clinical visits based on previous medical records ." ], [ "sleep - to - wake and wake - to - sleep slopes : calculated with a generalized linear model on raw measurements in units of mveq / hour from 1 hour before sleep or wake time to 1 hour after sleep or wake time , respectively .", "diurnal / nocturnal variability : same as above but only during the awake and asleep periods , respectively , where the sleep cycle is determined from recorded sleep times in each individual s logbook and verified by the eye - blinking frequency ( present during waking ) and the presence of rhythmic ocular pulsation waves ( present during sleep ) .", "number of peaks : a peak is defined as a local maximum point in the smoothed curve .", "cls variability from mean : this variable reflects variability around the mean value of all raw ( not smoothed ) cls measurements in the respective period ( 24-hour , diurnal , or nocturnal ) .", "the calculation of the number of peaks occurs as follows : each trough is noted as the start of a peak ." ], [ "nocturnal versus diurnal mean variability from mean ; wake - to - sleep versus sleep - to - wake slopes ; number of nocturnal versus diurnal peaks ; and 24-hour , diurnal , and nocturnal variability among prostaglandin users and nonusers .", "fisher s exact test was used to compare the differences in the number of nocturnal peaks between those using a prostaglandin antiglaucoma medication versus those using other , non - prostaglandin antiglaucoma medications .", "whitney u - test : \n nocturnal versus diurnal mean variability from mean;wake - to - sleep versus sleep - to - wake slopes;number of nocturnal versus diurnal peaks ; and24-hour , diurnal , and nocturnal variability among prostaglandin users and nonusers .", "the pre- and post - cls gat iops were compared using the wilcoxon signed - rank test ." ], [ "similarly , the population had a mean negative linear slope from sleep - to - wake with a mean of 42.547.6 mveq / hour , signifying a decrease in the ocular dimensional profile upon waking . on comparing the two slopes , the rate of increase when going to sleep was significantly greater than the rate of decrease upon waking ( p<0.001 ) ( table 3 ) .", "the study population had a mean positive linear slope on their cls profile from wake - to - sleep with a mean of 53.242.9 mveq / hour , signifying an increase in the ocular dimensional profile when going to sleep .", "there were no statistically significant differences in the mean diurnal , nocturnal , or 24-hour variability between those with and without prostaglandin analog treatment ( all p>0.1 ) ( table 1 ) .", "in the 18 subjects enrolled in the study , there were seven males and eleven females .", "gat iops before and after the cls wear were 15.32.2 and 13.81.7 mmhg , respectively , while on the same antiglaucoma medications ( p=0.05 ) ." ], [ "the ocular dimensional profiles of all 18 ntg subjects were unique , with individual peaks occurring at different time intervals throughout the day and night ; no two tracings were identical .", "nevertheless , this is one of the few publications in the literature analyzing the 24-hour ocular dimensional profile on a continuous basis in ntg subjects receiving medical treatment .", "additional clinical research needs to be done before we can state ( based on evidence ) that the cls can be useful in optimizing the timing of medical therapy for individual patients .", "we are inclined to agree with previous postulations , wherein the increase in nocturnal iop was thought to be related to the gravitational pull of fluids to the eye and an increase in episcleral venous pressure during the supine sleep posture.19 through the use of the 24-hour cls , we affirm that the phenomenon of increased iop with supine posturing was consistent among ntg subjects under medical treatment ." ], [ "there was a 50% reduction in both the variability from the mean and number of peaks during sleep as compared to daytime .", "continuous 24-hour ocular dimensional profiles recorded in ntg patients on medical treatment revealed that the profile increased during sleep and decreased upon waking ." ] ]

[ [ "we share a novel , simple surgical approach to management of a case of chronic traumatic cyclodialysis cleft with a successful outcome .", "cyclodialysis cleft is a rare clinical finding , but one that can have significant ocular complications , including decreased vision , shallowing of the anterior chamber , corneal edema , hypotony , choroidal effusions , maculopathy , vascular tortuosity , and optic disc edema .", "while it can be caused by surgical manipulation of the eye , it is more frequently a consequence of trauma.1 traumatic injury to the eye results in separation of the ciliary body from the scleral spur , which creates an aberrant outflow pathway for aqueous humor through the suprachoroidal space and often leads to hypotony ." ], [ "a 70-year - old caucasian male followed at the martinsburg veterans affair hospital ophthalmology clinic , martinsburg , west virginia , usa , since 2002 was found consistently to have intraocular pressure ( iop ) asymmetry , with the right eye iop ranging from 615 mmhg and usually having an iop 04 mmhg lower than the left eye .", "postoperatively , the choroidal effusion resolved , but the patient s iop did not improve . on repeat gonioscopy", "therefore , the patient was taken for additional surgical repair of the persistent cleft by the same technique , this time with successful closure .", "he was monitored for primary open - angle glaucoma and was on latanoprost eye drops in the left eye for field defects in that eye . in april 2008 ,", "on postoperative day 1 following the second surgery , the patient complained of severe eye pain and nausea , and was found to have an lop of 58 mmhg ." ], [ "we found the needle type to have a curvature and size that was very helpful for the angle and length of the pass required .", "interrupted 10 - 0 nylon sutures were radially passed through the corneal side of the limbus , then through the iris root and ciliary body , and carried out through the sclera on the opposite side of the limbus ( figure 3 ) . to ensure that ciliary body was incorporated into each pass ,", "a nasal conjunctival peritomy was performed , and dissection down to bare sclera was carried out and continued superotemporally to encompass the region of the cyclodialysis cleft .", "additionally , as more sutures were placed , the eye appeared to become more firm .", "the sutures were tugged on intraoperatively and the iris root was evaluated for movement with mechanical pull ." ], [ "multiple approaches to cleft closure have been described in the literature , including medical management , laser photocoagulation , cryotherapy , trans - scleral diathermy , gas tamponade , and anterior scleral buckle , along with various surgical repair techniques.6 while different surgical approaches have been described , many are technically challenging , particularly in the hypotonous eye . in this case report", "additionally , we demonstrate clinical success with cleft closure in an eye with chronic hypotony .", "we present a simple , less - invasive approach to surgical cleft closure that was successful anatomically and functionally .", ", we discuss the repair of a chronic traumatic cyclodialysis with indirect surgical cyclopexy , which we found to be technically easier and less invasive than other reported techniques , but equally successful ." ] ]

[ [ "after concentration of the filtrate under reduced pressure , the resulting oil was purified by flash column chromatography ( etoac in hexane ) to afford alcohol 21 ( from 20 ) or 26 ( from 13 ) as a colorless oil .", "concentration under reduced pressure followed by purification of the residue by flash column chromatography ( etoac in hexane ) afforded azide 22 ( from 21 ) or 25 ( from 26 ) as a colorless oil .", "the resulting colorless oil was used in the next step without further purification ( 96 mg , quant . ) .", "the resulting colorless oil was used in the next step without further purification ( 192 mg , quant . ) .", "after 8 h , the reaction was quenched by the addition of nahco3 ( 5.95 mmol ) and then filtered ." ] ]

[ [ "we report a rare case of acute mastitis caused by enteric organisms passing through a cp shunt catheter , which had penetrated the transverse colon , and was related to a previous failed attempt to remove the shunt resulting in a divided catheter .", "ventriculoperitoneal and cystoperitoneal ( cp ) shunts are commonly used for the treatment of hydrocephalus and symptomatic intracranial cysts .", "abdominal complications , including intestinal volvulus , pseudocyst formation and migration into the gastrointestinal tract have been reported , accounting for 25% of shunt - related complications .", "bowel perforation by the shunt catheter is uncommon and accounts for 0.010.07% of all abdominal complications [ 13 ] .", "breast - related complications represent a class of thoracic shunt complication and are characterized by breast cerebrospinal fluid ( csf ) pseudocyst formation , csf galactorrhoea and shunt obstruction ." ], [ "the patient is a 56-year - old woman who underwent a surgical treatment of a lateral ventricle meningioma at the age of 29 .", "she developed a brain abscess related to the shunt catheter at the age of 55 .", "acute mastitis caused by enteric organisms which had migrated through the shunt catheter after penetration into the transverse colon was the presumptive diagnosis , and the catheter removed under general anesthesia .", "the diagnosis of acute mastitis was made and she was referred to our institution for further examination . on presentation ," ], [ "this is the first report of case with acute mastitis caused by enteric organisms migrating through a cp shunt catheter that had penetrated the transverse colon .", "csf leakage and retrograde flow from the peritoneal cavity to the breast may cause breast - related complications .", "the penetration of shunt catheters into the intestine at the distal end is rare with a reported incidence between 0.01 and 0.07% .", "a patient who presents with acute mastitis and has previously undergone shunt placement should undergo assessment of the abdominal segment of the catheter .", "the diagnosis of bowel perforation by a shunt may not be easy to make , unless the shunt protrudes from the anus [ 5 , 6 ] ." ] ]

[ [ "we explore , in mice , the possibility of diagnosing an early - melanoma tumor and following its growth by analyzing the changes that occur throughout the pathological process in vocs excreted in urine and feces .", "this study will contribute to the development of a noninvasive and reliable diagnostic procedure to detect melanoma in the urine of patients .", "we report here total of 29 potential biomarker candidates of melanoma ; 25 of these are novel , and 4 have been previously reported by other research groups in relation to vocs detected from cultures of human melanoma cells .", "the chemical identity of only 24 of the 29 possible biomarker candidates was revealed with high confidence ." ], [ "benzaldehyde levels in feces were 132% higher in the tumor - bearing mice than in the healthy group ( p = 0.004 ) , but it is important to notice that the increases were from the early - melanoma stage to the late melanoma stage ( p = 0.002 ) , and not from the healthy group to the early - melanoma stage . in other words , benzaldehyde could be a useful possible biomarker candidate for predicting melanoma , but not in its early stage .", "it is important to note that eight out of nine mice were correctly predicted with an early - melanoma by using the urine model , whereas the feces model did not clearly discriminate between healthy and early - melanoma mice .", "three compounds were detected only in the tumor - bearing mice ( table 2 ) , three vocs were detected only in the healthy and early - melanoma - bearing mice ( table 3 ) , and 13 vocs were detected in markedly higher concentrations in the tumor - bearing mice as compared with the healthy group ( table 4 ) .", "therefore , the samples were classified into three groups : healthy , early - melanoma , and late melanoma .", "as shown earlier , significantly higher amounts of this compound were found in metastatic melanoma cells , as compared with normal cells ." ], [ "the present study constitutes a novel proof - of - concept for the detection and monitoring of melanoma in urine and feces samples of mice at an early stage .", "our urine statistical model correctly predicted eight out of the 9 mice bearing an early - melanoma , indicating that mice at that stage can be detected and distinguished from healthy mice and from mice bearing a late melanoma . while other research groups [ 6 , 7 ] focused on comparing human melanoma to normal and nevus skin biopsies , we attempted to distinguish between mice with an early - melanoma and healthy mice .", "if the possible biomarker candidates were formed in biochemical processes related to the activity of cancer cells , we can expect to find some overlap between biomarkers found in human and mice .", "this finding suggests that isopropyl myristate is a valid direct product of melanoma cell metabolism for further study ." ], [ "urine and feces samples from nine mice were collected , twice before ( healthy group , n = 18 ) and four times after ( cancer group ,", "comparison between vocs content of the two first samples of each mouse , collected before b16 melanoma cell injection , showed high repetition of peaks in the chromatograms of each mouse .", "n = 35 , one mouse died before the last sample was obtained ) subcutaneous injection of b16 melanoma cells .", "consequently , we did not use a control group but compared the chromatograms of each mouse after b16 melanoma cell injection to those obtained before injection .", "each chromatogram vector was defined as a member in one of three classes , healthy , early - melanoma , and late melanoma in urine samples , and in one of two classes , healthy and melanoma in the feces samples .", "in addition , vocs above a culture of b16 melanoma cells were also collected and analyzed ." ] ]

[ [ "using these approaches , we demonstrate a role for clec12a in antibacterial autophagy and pinpoint a functionally relevant interaction node of clec12a with an e3 ligase complex that is important for this function .", "the autophagy pathway targets only a subpopulation of bacteria within a cell , and little is known about the molecules involved in the selective recognition and targeting of bacteria for autophagosomal degradation , despite the important pathological consequences of this process . in this study , we approached the question of the impact of the atg16l1 t300a risk variant by searching for associated responsiveness quantitative trait loci ( reqtls ) , which are defined as the effects of genetic variation on transcriptional responses of cells ( barreiro et al . , 2012 ) .", ", we perform stimulus - specific perturbational profiling in pbmcs , quantitative mass - spectrometry - based ( ms ) proteomics , and genome - wide rna expression analysis to identify antibacterial genes that are functionally related to atg16l1 .", "these studies have highlighted the contribution of multiple immune and cellular pathways to crohn s disease pathogenesis , particularly those involved in microbial defense ( jostins et al .", "genome - wide association studies ( gwass ) have emerged as a powerful non - biased technique for identifying pathways related to human diseases with complex genetic architecture ." ], [ "to identify molecules involved in the atg16l1-t300a - dependent antibacterial autophagy pathway , we used perturbational profiling to measure differential gene regulation in the setting of stimulation with pathogen - associated molecular patterns and bacterial challenge .", "other notable transcriptional regulators identified in our analysis that are known to be important for pathogen response include rela , nfe2 , hif1a , and arnt2 . taken together , this analysis suggests that deletion of clec12a results in an alteration of the response to pathogens at the transcriptional level and identifies key regulators involved in this response . to further understand the role of clec12a in antibacterial autophagy , we next applied an integrated systems approach using quantitative ms - based proteomics and coupled these results with our transcriptomic profiling analysis to uncover functional clec12a interactions relevant to bacterial defense ( figure 6c ) .", "given that mounting evidence indicates an important role for the involvement of host - microbiota interactions and bacterial defense pathways in crohn s disease ( knights et al . , 2013 ;", "we focused additional analysis on the autophagy pathway , the cellular degradation system that has been implicated in risk of crohn s disease by gwass , which identified predisposing alleles in atg16l1 and irgm ( immunity - related gtpase family m ) ( rioux et al . ,", ", these data suggest that clec12a functions selectively in the antibacterial autophagy pathway for multiple pathogens in both mouse and human cells .", "these results highlight the central role of clec12a in pathogen - induced defense pathways and suggest how deficiencies in clec12a could result in impaired bacterial defense ." ], [ "using this strategy , we uncovered bacteria- and bacterial - ligand - specific programs affected in healthy individuals homozygous for the t300a polymorphism in the autophagy gene atg16l1 .", ", we identified a role for clec12a in antibacterial autophagy and demonstrated that clec12a controls microbial replication in vitro and in vivo . using cells engineered to express the crohn s disease non - risk or risk allele of atg16l1", "this study highlights how perturbational profiling can be used to study pathways underlying immunity and pathogen defense and illustrates the potential of combining whole - genome experimental data sets to understand functional gene interactions within a relevant pathway .", "interestingly , 15% of the t300a - dependent response genes were found to play a role in autophagy pathways , highlighting important snp - pathway interactions .", "these results highlight how non - redundant genes in the same pathway can be identified through ligand - specific transcriptional regulation ." ], [ "the second exon of atg16l1 was targeted in hela cells using the px330 plasmid crispr system as described ( ran et al . , 2013 ) .", "s. typhimurium infections of hela cells and gentamicin protection assays were performed as previously described ( huett et al . , 2012 ) .", "microarray hybridization and genotyping of volunteers was performed as previously described ( smeekens et al . , 2013 ) .", "for entry assays , cells were infected for 20 min , washed , fixed in 4% paraformaldehyde for 15 min at room temperature , and stained as described below . for antibacterial autophagy assays in sirna - treated cells , rnai knockdown for 48 hr was performed as described above on hela cells plated on glass coverslips and infected as above .", "autophagy was induced in hela cells by treatment for 4 hr with 100 nm torin-1 , 10 g ml of e64d - pepstatin a ( sigma - aldrich ) , or mock treatment with dmso .", "clec12a mice were produced by conventional gene targeting of exons 14 on a c57bl/6 background ( p. redelinghuys , a. augello , r.a .", "cells were treated with sirna for 48 hr as described above and then autophagy was induced followed by cell lysis ( 25 mm tris [ ph 7.5 ] , 0.5% np-40 , 150 mm nacl , and protease inhibitors [ roche ] ) ." ], [] ]

[ [ "niv was implemented as an add - on modality in an acute medical ward and a respiratory ward at odense university hospital , odense , denmark , in 2004,4 based on local instructions and national recommendations,5 and the modality has since been used as a standard additional treatment primarily for patients with hypercapnic acute respiratory failure and verified or presumed copd .", "exclusion criteria for niv treatment in the ward are untreated pneumothorax , unstable hemodynamics , and affected alertness , indicating need of intensified monitoring and intubation capability when required .", "there are few reports on long - term survival after receiving niv in a clinical setting,6 and the issue of whether there is an advantage by implementing niv in patients with severe prognosis and expected high mortality rates has not been addressed .", "randomized controlled studies have shown that noninvasive ventilation ( niv ) reduces short - term mortality , risk of intubation and complication rate when given as an additional treatment to selected patients with an acute exacerbation in chronic obstructive pulmonary disease ( copd ) complicated by hypercapnic acute respiratory failure.1,2 plant et al2 showed a decrease of the in - hospital mortality rate from 20% to 10% when niv was given to patients with mild acidosis and in a stationary or intermediary ward in a multicenter setting .", "the aim of this study was to analyze long - term all - cause mortality following the first years of implementing niv in a real - life acute medical ward at a university hospital in denmark , with the null hypothesis that niv has no impact on long - term survival .", "specifically , patients with arterial measures of ph < 7.35 and paco2 > 6.0 kpa and mono - organic symptoms of dyspnea , respiratory rate > 25 and pao2 < 7.0 kpa without oxygen therapy are eligible for niv .", "as with most other treatment modalities , there is likely to be a less noticeable effect when comparing real - life and clinical trial efficacy ." ], [ "all niv treatments were registered prospectively at the acute medical and respiratory ward of the odense university hospital , with patients receiving niv for the first time in the period january 1 , 2005 to december 31 , 2007 included for this analysis .", "niv was initiated for weaning in patients with prior longer intubation need due to respiratory failure ; these patients are reported on separately .", "order , based on the severity of the underlying illness(es ) . on a few occasions ,", "where possible , patients initiated on niv were referred to the respiratory ward the next day .", "since niv was initiated in the acute medical ward , standard niv protocols were followed ( initial inspiratory positive airway pressure 10 cm h20 and expiratory positive airway pressure 4 cm h20 ) , with oxygen supplement depending on response ( aim : peripheral oxygen saturation measure of 90%92% ) , and changes in pressure were performed depending on the clinical manifestation in accordance with the danish national guideline.5 the protocol on use of niv remained unchanged in the period of the study .", "patients either continued standard medical treatment or were provided additional ventilatory support with niv in the medical acute ward ." ], [ "niv was initiated for weaning in patients with prior longer intubation need due to respiratory failure ; these patients are reported on separately .", "patients were admitted to the acute medical ward from either the general practitioner or the emergency ward at the hospital . when patients were suspected of having an acute exacerbation of copd based on clinical presentation , prior records , arterial blood gas analyses , and chest x - ray , patients were assessed after initial standard treatment with oxygen , inhaled bronchodilator treatment , administration of systemic steroids , and , if needed , antibiotics .", "order , based on the severity of the underlying illness(es ) . on a few occasions ,", "patients either continued standard medical treatment or were provided additional ventilatory support with niv in the medical acute ward ." ], [ "in the study period 20052007 , niv was initiated on 390 occasions : 107 times in 2005 , 143 times in 2006 , and 140 times in 2007 . of", "the 302 patients registered , 253 patients received niv for the first time and were included in this study .", "descriptive data of copd patients versus non - copd patients receiving niv for the first time are shown in table 2 , and supplementary information in figure 1 .", "there was no statistically significant difference in survival for men and women , although we did see a trend towards better long - term 5-year survival in females compared to males ( 25.7% vs 19.2% , p = 0.25 [ logrank ] ) ." ], [ "treatment with niv was provided to 9% of all copd patients admitted with an exacerbation in 2009 and 10% in 2010 and 2011.9", "niv was given as a last treatment option in patients with a not - to - intubate order .", "data on long - term survival of patients receiving niv for the first time revealed an expected high 30-day mortality rate , considerably higher than that seen in pivotal trials of niv in copd,1,2 but in line with other observational audits and studies.3,6,7 however , the 5-year survival rate was higher than earlier anticipated , which could be due to more stringent selection criteria for initiation of niv , and the fact that the study was only conducted in one center , giving patients more homogenous treatment . one significant difference between survivors and nonsurvivors was age , survivors being , as a group , younger than the group of patients who died , but the oldest patient ( 91 years ) registered in this study was alive at the end of 5 years of observation .", "niv was also seen used as a ceiling of treatment in which efficacy was uncertain . the primary focus of this present study", "it seems apparent that patients labeled not - to - intubate have a particularly poor prognosis and , based , on our findings probably did not benefit from the treatment .", "has not been evaluation of the indication for niv treatment ; since 2008 , an annual national surveillance of patients with copd ( dansk register for kol [ drkol ] ) has been launched , registration practice ( international classification of diseases [ icd]-10 ) has been reviewed , and audits performed . in denmark ," ], [ "it casts some doubt as to what is achievable from niv in a non - icu setting and suggests that regular audits are required to ensure that the right patients are offered the right treatment when admitted with mild hypercapnic respiratory failure .", "however , the 5-year survival rate was higher than earlier anticipated , justifying the broad approach to niv treatment in this setting .", "our study confirms that patients with hypercapnic respiratory failure are a high - risk group , often with a poor prognosis .", "the high 30-day mortality rate for all niv - initiated patients was higher ( 29.3% ) than for the group of patients with copd ( 24.3% ) , and this supports the notion that niv should be dedicated primarily to patients with copd in exacerbation .", "monitoring of patient outcomes in a real - life setting is necessary to ensure optimal selection of patients for niv in a non - icu setting .", "the 30-day mortality rate for copd patients receiving niv was similar in an audit from 2010 , and patients with ph < 7.25 had a worse outcome than patients presenting with higher ph at niv initiation ( unpublished data ) ." ] ]

[ [ "takayasu arteritis ( ta ) is a chronic inflammatory arteritis affecting the aorta and its main branches .", "the occurrence of the disease in young children and infants is extremely rare with only a few cases reported all over the world .", "the disease has a world - wide distribution , but has a high prevalence in japan .", "although there are no population based studies from india , reports have shown than the prevalence may be as high as in japan .", "most of the patients diagnosed to have this condition are women in their second and third decades of life ." ], [ "the present case report is about a 2-year - old female patient who was brought to the hospital with a history of incidentally detected hypertension of 2 months duration .", "a diagnosis of ta was made according to the european league against rheumatism / pediatric rheumatology international trials organization / pediatric rheumatology european society ( eular / printo / pres ) criteria - 2008 ." ], [ "ta , also known as pulseless disease , occlusive thromboaortopathy and martorell syndrome , was first systematically described by a japanese ophthalmologist mikito takayasu .", "diagnostic criteria for takayasu arteritis in children ta is certainly underdiagnosed and underreported from india , due to the fact that the disease may not present with classical features and the imaging modalities are available only in tertiary care centers .", "however , the mean age of the subjects was 27 years and the youngest child was 5 years of age . to the best of our knowledge , there are no reports from india of a case of ta in an infant .", "the disease remains an enigma as the exact cause of the disease is still not elucidated .", "a human leucocyte antigen ( hla ) association and viral etiology have also been postulated ." ], [ "if the disease is active , steroids can be tried and the lesions amenable to angioplasty may be corrected by a percutaneous transluminal angioplasty .", "although the world - wide prevalence of ta is very low , it is more prevalent in asian countries like japan and india .", "type iv disease involving abdominal aorta and renal arteries is more common in indians and hypertension is the most common sign .", "the clinical manifestations of the disease in india are different from that seen in japan ." ] ]

[ [ "however , its widely used was limited by the expensive costs , shortage of donor organs and invasive procedure ( 1 ) .", "hepatocyte transplantation has emerged as a feasible alternative to liver transplantation in some liver diseases ( 2 ) , but it is limited by organ donors and the low cell quality of available liver tissues ( 3 , 4 ) .", "recently , the adult stem cells ( ascs ) derived from various tissues , including bone marrow derived mesenchymal stem cells ( bmscs ) , adipose tissue derived mesenchymal stem cells ( adscs ) , and peripheral blood mononuclear cells ( pbmcs ) have been developed as new cell sources contributing to liver regeneration for their high efficiency of hepatogenic differentiation using simple procedures and no ethnic issues ( 710 ) . in the present study , we investigated whether ascs are the ideal seed cells for the liver regeneration from the followings : ascs biology , including isolation , culture , differentiation to hepatocytes , and the further role of ascs in cell therapy and tissue engineering", "currently , liver transplantation is the only definitive treatment for the end stage liver diseases .", "although human embryonic stem cells ( hescs ) and umbilical cord blood stem cells ( ucbsc ) could be induced into hepatocyte - like cells in vitro ( 5 ) , their widely used were limited by the low differentiation quality , ethics , and teratoma formation ( 6 ) ." ], [ "in recent studies , samples of human bone marrow were obtained by lumbar puncture ( lp ) , human adipose tissue were obtained from abdominal subcutaneous adipose tissue of gastric cancer patients or liposuction patients , human peripheral blood were obtained from patients with hbv or healthy adult blood donors , in accordance with the local ethics committee .", "the hepatocyte - like cells from ascs were confirmed from the gene and protein expression .", "protein expressions were usually identified by immunohistochemistry or mmunofluorescence , western blot , from the expression of albumin , ck18 , cyp3a4 , cyp1a1 , cyp2c9 and nadph - p450 ( 3538 ) . to compare the potential of hepatogenic differentiation of the different adult stem cells in vitro , researches indicated adscs have a similar differentiation potential towards the hepatic lineage , similar to bmscs .", "gene expressions were identified by rt - pcr , using the common markers of hepatocytes , including alb , afp , ck18 , ck19 , and cyp3a4 ( 34 ) .", "however , the potential of the ascs transdifferentiation is generally low . therefore , researchers are keen to explore new methods to induce ascs differentiate into functional hepatocytes in vitro currently ." ], [ "in recent studies , samples of human bone marrow were obtained by lumbar puncture ( lp ) , human adipose tissue were obtained from abdominal subcutaneous adipose tissue of gastric cancer patients or liposuction patients , human peripheral blood were obtained from patients with hbv or healthy adult blood donors , in accordance with the local ethics committee ." ], [ "most laboratory data showed that bmscs could be prepared through the density degree of centrifuge , flow cytometry sorting , and sidewall sieve method ( 1114 ) .", "side - wall sieve method has become popular one for its simple operation , lower cost , less injury to cell ( 15 ) .", "adipose tissue was minced with scissors and scalpels into less than 3 mm pieces and isolation of adscs proceeded as previously described ( 16 , 17 ) . generally , human peripheral blood monocytes isolated from donors were isolated by density gradient centrifugation and further purified by adherence separation . in order to obtain more pbscs in shortly time ,", "pbmcs were mobilized with recombinant g - csf at 510 g / kg / d , administered subcutaneously daily to mobilize pbmcs from bone marrow to peripheral blood ( 18 , 19 ) ." ], [ "conget et al indicated that the bmscs express many surface agents including cd13 , cd44 , cd29 , cd105 , but did nt express cd1a , cd14 , cd31 , cd34 , cd56 , cd45 ( 20 ) .", "cd105 was expressed by a significantly lower percentage of pbscs compared with bm- or ad - scs , whereas , more pb- and bm - scs expressed cd106 than adscs .", "ascs derived from all three sources displayed no expression of hematopoietic markers ( cd14 , cd34 , cd45 ) , of the stem cell marker cd133 , or the marker for endothelial cells cd144 .", "besides the fact , that they are more heterogeneous ( 23 ) , they reveal a surface antigen marker profile ( 22 , 2426 ) , and differentiation potential similar to bmscs ( 2732 ) .", "more than 90% of the ascs derived from all three sources expressed hla i ; however , none of the mscs expressed hla ii .", "more than 90% of mscs derived from the three sources expressed the typical msc marker proteins cd44 , cd73 , cd29 , and cd90 .", "however , the intensity of expression of cd90 of pbscs was significantly below that of the other tissues ." ], [ "however , the potential of the ascs transdifferentiation is generally low . therefore , researchers are keen to explore new methods to induce ascs differentiate into functional hepatocytes in vitro currently .", "some studies indicated that functional hepatocytes could be induced from ascs by some cytokines or through coculture with other cell types ." ], [ "protein expressions were usually identified by immunohistochemistry or mmunofluorescence , western blot , from the expression of albumin , ck18 , cyp3a4 , cyp1a1 , cyp2c9 and nadph - p450 ( 3538 ) . to compare the potential of hepatogenic differentiation of the different adult stem cells in vitro , researches indicated adscs have a similar differentiation potential towards the hepatic lineage , similar to bmscs .", "however , their longer culture period and proliferation capacity differ from the bmscs ( 3941 ) .", "the hepatocyte - like cells from ascs were confirmed from the gene and protein expression .", "gene expressions were identified by rt - pcr , using the common markers of hepatocytes , including alb , afp , ck18 , ck19 , and cyp3a4 ( 34 ) ." ], [ "this paper firstly provides such a concise review focused on ascs biology and differentiates potential , indicating ascs might be an ideal seed cells in cell transplant therapy and tissue engineering .", "it is very safe and easy to acquire the enough ascs , and then induce them into functional hepatocytes in vitro .", "based on this progress , ascs transplantation might be a novel therapy for the severe liver diseases , and also will be ideal seed cells for liver tissue engineering .", "in the present study , we described different ascs could be induced into hepatocyte lineage cells in different culture systems in vitro .", "however , which ascs are better still needs us to investigate from their preparation , molecular characterization , and functional assay .", "we also believe in the future , some studies will show us the most appropriate ascs for cell transplant or tissue engineering ." ] ]

[ [ "waldenstrom 's macroglobulinemia ( wm ) is the result of a clonal proliferation of lymphocytes that produce monoclonal immunoglobulin m ( igm ) .", "the hyperviscosity syndrome is characterized by headache , tinnitus , vertigo , blurred vision , and chronic bleeding from the nose and gums ( 3 ) .", "it is now considered to correspond to lymphoplasmacytoid lymphoma as defined by the world health organization classification system ( 1 , 2 ) .", "however , cns infiltration by plasmacytoid lymphocytes ( bing - neel syndrome ) has only rarely been reported ( 4 ) .", "many central nervous system ( cns ) complications have been described in wm patients ; the majority have been associated with blood hyperviscosity caused by igm ." ], [ "a 51-yr - old woman was diagnosed with wm three years prior to this presentation .", ". however , the igm level has been increasing slowly , so further chemotherapy , including rituximab may be considered .", "high - dose cyclophosphamide and granulocyte colony - stimulating factor were administered to induce peripheral blood progenitor cell ( pbpcs ) mobilization for autologous stem - cell transplantation ; however , the number of pbpcs collected was not sufficient .", "the patient had no evidence of cns recurrence during the follow - up period of one year" ], [ "however , the effect of rituximab treatment on the cerebrospinal fluid b - cell compartment is limited in comparison with the effect on the b cells in the periphery ( 20 ) , and it has not been tried in bing - neel syndrome as yet . therefore , the effect of rituximab on cns involovement of wm need to be validated by of future studies .", "it has been reported that a patient with bing - neel syndrome ( in its diffuse form ) was successfully treated with cladribine administration ( 17 ) , or radiation therapy and combination of cladribine , cyclophosphamide , and prednisone ( 18 ) . in the present case", "intraventricular chemotherapy for bing - neel syndrome was reported to be effective in 1984 ( 15 ) .", "recently , a great deal of interest has been noted by treatments with purine nucleoside analogs ( fludarabine , cladribine , and pentostatin ) because of their remarkable activity in lymphoproliferative disorders ." ] ]

[ [ "the objective of our study was to determine how maternal physical activity , maternal insulin sensitivity ( isogtt ) , prepregnancy bmi , infant feeding practices ( breastfeeding duration , age of introduction of formula , and complementary foods ) , and screen time contribute to infant weight gain and adiposity at 1 year of age .", ". there is little known about the impact of maternal and infant lifestyle on weight gain and adiposity at 1 year of life .", " the increasing prevalence of childhood obesity , especially in preschool aged children [ 1 , 2 ] , has stimulated research targeting critical periods of growth . according to freinkel 's hypothesis of fuel - mediated teratogenesis , ", "additionally , reduced physical activity and increased screen time ( television and video ) are associated with obesity risk in older children , although limited data is available in infants [ 33 , 34 ]", "harder et al . reported a dose - dependent association between breastfeeding and risk of obesity , where each month of prolonged breastfeeding decreased obesity risk in the child ." ], [ "at the 1 year visit , infant weight and length were measured , and weight - for - length z - score was calculated according to the world health organization ( who ) 2006 child growth standards to provide a surrogate measure of adiposity . the infant lifestyle questionnaire was completed by the mothers when the infants were 3 and 12 months of age and provided information on exclusive breastfeeding duration , age of introduction to formula and cereal , and screen time based on predictors found to be important for the development of obesity ( average daily exposure to tv or video viewing , meals eaten while tv is on , tv in bedroom ) [ 34 , 42 ] .", "nonmodifiable risk factors ( infant age , sex , ethnicity , birth weight , and family history of diabetes ) were forced into the model and modifiable risk factors ( maternal prepregnancy bmi , gdm status , maternal physical activity indices prior to pregnancy , socioeconomic status , maternal log isogtt , infant exclusive breastfeeding duration , age of introduction to formula , age of introduction to cereal , and daily screen time ) were entered according to the forward stepwise method .", "participants were recruited for this prospective cohort study at the time of antepartum gestational diabetes mellitus ( gdm ) screening and were consented to be followed into the postpartum .", "data collected included maternal age , maternal prepregnancy weight , maternal and paternal ethnicity , family history of diabetes , socioeconomic status , and maternal physical activity indices .", "the baecke questionnaire measures three domains of physical activity : ( i ) occupation - associated activity ( work index ) ; ( ii ) sport - related physical activity ( vigorous / sport index ) ; ( iii ) leisure - time physical activity not including sports ( leisure index ) .", "the work index quantifies the exertion related to occupational activities , including sitting , standing , lifting , and walking , as well as effects on the individual ( e.g. , fatigue and perspiration ) ." ], [ "infant sex , infant ethnicity , and family history of diabetes were not significantly associated with infant weight - for - length z - score .", "infant birth weight , infant ethnicity , and family history of diabetes did not significantly predict infant weight gain at 1 year . additionally , socioeconomic status , maternal prepregnancy bmi , maternal isogtt , gdm status , maternal pregravid work index , maternal pregravid leisure index , infant age of introduction to formula , and infant screen time did not emerge in the model when entered . for weight - for - length z - score , an increase in one unit of maternal prepregnancy bmi ( kg / m )", "variables that did not emerge in the model included : socioeconomic status , maternal isogtt , gdm status , maternal pregravid work index , maternal pregravid leisure index , infant age of introduction to formula , and infant screen time .", "there were no significant differences in gdm status , prepregnancy bmi , maternal education , or maternal physical activity between mothers retained in the study versus those lost to followup .", "weight - for - length z - score was positively associated with maternal prepregnancy bmi ( p = 0.003 ) and birth weight ( p < 0.001 ) , and negatively associated with maternal log isogtt during pregnancy ( p = 0.031 ) and maternal pregravid vigorous / sport index ( p = 0.006 ) ." ], [ " these findings demonstrate that maternal pregravid physical activity , prepregnancy bmi , and infant feeding practices have a significant influence on infant weight gain and adiposity .", "nevertheless , we examined maternal and infant lifestyle variables that have not been previously studied together , providing further insight into the effects of the maternal and infant environment on weight gain and adiposity while controlling for important confounding variables . in summary , increased maternal pregravid physical activity and longer exclusive breastfeeding duration may have a critical influence on reducing infant weight gain and adiposity as early as 1 year of age .", "future directions include examining the additive effects of maternal diet during and after pregnancy , infant physical activity , and sedentary time on infant weight gain and adiposity .", "weight gain from birth to 1 year was negatively predicted by infant female sex , maternal pregravid vigorous / sport activity , and exclusive breastfeeding duration and positively predicted by infant age at time of 1 year visit .", "weight - for - length z - score at 1 year was negatively predicted by maternal pregravid vigorous / sport activity and exclusive breastfeeding duration and positively predicted by birth weight , infant age at time of 1 year visit , and maternal prepregnancy bmi .", "the effect of maternal prepregnancy bmi on infant adiposity is consistent with existing literature [ 1214 , 31 ] . in mothers with ngt or gdm ," ] ]

[ [ "phylogenetic networks represent the evolutionary relationships of taxa , including sequences , genes , chromosomes , genomes , or species .", "specifically , we will quantify the different classes of networks ( regular , tree sibling , tree child , and galled trees ) produced by the coalescent as a function of the population recombination rate .", "independent of particular organisms or genomic regions , we will use coalescent theory ( kingman 1982 ) to generate the type of reticulate networks that result from the evolutionary process .", "reticulate networks have been extensively used in evolutionary studies , especially at the population level , where reticulate events are , in general , quite common ( posada and crandall 2001 ) ." ], [ ", we show a typical genealogy for a sample of 10 genes . a single realization of the coalescent with recombination .", "the standard coalescent describes the possible histories of a sample of genes back in time to their mrca ( kingman 1982 ) . in the absence of evolutionary forces like selection , migration , or recombination ,", "the only types of events that can occur are coalescent events , in which two lineages ( branches ) fuse into one .", "if recombination is included , the recombination events will result actually in the opposite pattern going backward in time , as in this case one lineage ( the recombinant ) separates into two ( the parents of the recombination event ) .", "therefore , the genealogies produced by the coalescent with recombination ( also known as arg , for ancestral recombination graph ) will be explicit reticulate networks as internal nodes actually represent evolutionary events . in figure 1", "therefore , for a sample of n genes , there will be n 1 coalescent events until the mrca is reached ." ], [ ", we show a typical genealogy for a sample of 10 genes . a single realization of the coalescent with recombination .", "we varied the recombination rate that much because the recombination events actually determine the different network classes produced ( regular , tree sibling , tree child , galled trees , or binary trees ) .", "the standard coalescent describes the possible histories of a sample of genes back in time to their mrca ( kingman 1982 ) . in the absence of evolutionary forces like selection , migration , or recombination ,", "therefore , the genealogies produced by the coalescent with recombination ( also known as arg , for ancestral recombination graph ) will be explicit reticulate networks as internal nodes actually represent evolutionary events . in figure 1", "the genealogy goes from the present ( bottom ) to the past ( up ) .", "the only types of events that can occur are coalescent events , in which two lineages ( branches ) fuse into one ." ], [ "first , hybrid and tree nodes in the graphs were identified as the recombinant and coalescent nodes in the genealogies , respectively , while superfluous nodes were eliminated ( fig .", "superfluous nodes have just one parent and one child and result from concatenated recombination and coalescent events .", "the simulated genealogies were classified into five different network classes : regular , tree sibling , tree child , galled trees , and binary trees .", "although they are real nodes ( and therefore count for r(n ) ) , they can not be estimated from real data and , therefore , were removed from the networks before their classification . the corresponding graph for the arg shown in figure 1 ." ], [ "we can conclude that the reticulate networks produced by the evolutionary process , at least as modeled by the coalescent with recombination , are much more convoluted than regular , tree sibling , tree child , or galled tree networks .", "with recombination , different classes of reticulate networks were produced whose complexity was a function of the population recombination rate ( tables 1 and 2 ) . for n = 10 , at small recombination rates ( = 1 ) many networks were tree sibling , but half were already non - tree child . with twice as much recombination ,", "half the networks were more complex than tree sibling networks , and only a few were tree child networks or galled trees . with moderate recombination rates ( = 4 ) , only 15% of the networks were tree sibling , whereas with larger recombination rates .", "in the absence of recombination , all the simulated genealogies were binary trees , as expected .", "therefore , we believe that these results are likely to be very similar for models of lateral gene transfer and/or hybridization the assumptions underlying the standard classes of networks should eventually fail given sufficient reticulation ." ] ]

[ [ "we compared the effects of these diets on the development of dental caries in a diabetic rodent model focusing on the difference in hardness between the powdered and pelletized diets .", "we recently demonstrated that diabetes directly induced dental caries in rats and mice , although a direct association between the 2 was less evident and conflicting in humans [ 14 ] .", "however , no reports have investigated the effects of the physical properties of non - cariogenic standard diets on dental caries in diabetic animals . ", "currently , 2 types of non - cariogenic standard diet formulations ( i.e. , powdered and pelletized diets ) are widely used in experimental rodents . in the present study ,", "we demonstrated that dental caries were produced using noncariogenic diets with a low concentration of sugar in diabetic rodent models [ 57 ] , although many studies usually add large amounts of sugar to the diet to induce dental caries [ 8 , 9 ] .", "thus , modifying the dietary formulation may possibly enhance or reduce caries development in diabetic animals ." ], [ "the molar teeth were classified into 5 groups according to caries characteristics by observing and analyzing the radiographs : no radiolucent change ( grade 0 ) , radiolucent area only on the occlusal surface of the crown ( grade 1 ) , radiolucent areas on occlusal surface and either of the mesiodistal surfaces of the crown ( grade 2 ) , radiolucent areas over the entire surface of the crown ( grade 3 ) , and radiolucent areas over most of the surface of the dental root ( grade 4 ) .", "the severity of the caries lesion was graded as follows : slight , dentin caries localized in occlusal surface of dentin ; mild , dentin caries extended into the dental pulp with pulpitis and/or pulp necrosis ; moderate , dental crowns were partially decayed ; and severe , dental crowns were completely decayed ( only the molar roots remained ) .", "after a 24 h fixation , the occlusal , buccolingual , and proximal surfaces of all of the molar teeth were intensively observed under a binocular stereoscope .", "the blood glucose levels in the tail vein samples were also measured semi - quantitatively using the glucose oxidase method ( glutest e ; sanwakagaku , aichi , japan ) once every month from the fourth week after alloxan injection .", "the chi - square test was used to determine the caries incidence using soft x - ray examination and the incidence of histopathological lesions in each group of rats .", "the mean score of the caries was used as indicator for comparing the severity of the carious lesions between the groups .", "the wilcoxon rank - sum test was employed to compare the differences in the mean scores of the caries lesions using soft x - ray examination between the groups .", "the dose of alloxan was determined as the given dose at which a rat survives for a long period after the onset of diabetic symptoms . after the confirmation of hyperglycemia and glucosuria following the dosing of alloxan ," ], [ "histopathologically , the severity of the carious lesions in the diabetic rats fed with a powdered diet was significantly enhanced compared to the diabetic rats fed with the pelletized diet ( table 2 ) . in control non - diabetic rats , slight carious lesions , which were macroscopically and radiographically normal ,", "the incidence of dental caries in the diabetic rats fed on both the pelletized and powdered diets was apparently higher ( p < 0.01 ) compared to the non - diabetic control rats ( table 1 ) . in the diabetic rats fed with the pelletized diet , 96.7% of their molar teeth were affected with dental caries , and the mean caries score was 2.7 .", "radiographically , the dental caries progressed both horizontally and vertically . in diabetic rats fed with a pelletized diet ,", "were detected in a few animals ; however , there were no differences observed between the non - diabetic rats on the pelletized and powdered diets ( table 2 ) ." ], [ "it was clear that food hardness affected the development of dental caries in diabetic rats fed on a non - cariogenic diet .", "dental caries developed and extended to all of the molars in diabetic rats fed on both the pelletized and powdered diets .", "the development of caries is known to be profoundly affected by food hardness , and hard and coarse foods can exert a detergent activity during mastication , which is effective in the prevention of caries [ 17 , 19 ] . furthermore , a lower degree of caries was reported in animals fed with the hardest food diet . in the present study , the severity of caries in diabetic rats was enhanced in the powdered diet group compared to the pelletized diet group .", ", food hardness could have an effect on the development of dental caries in diabetic rats , and appropriate consideration of the food formulation should be made in experimental caries studies using diabetic rodent models ." ] ]

[ [ "we conclude that volume exclusion in the presence of a crowding agent such as peg or dextran can be used as a general route to increase encapsulation efficiency of biomacromolecules in both giant and submicrometer lipid vesicles , up to levels expected for passive encapsulation of lower mw solutes ( i.e. , cin = cout ) .", "we find in general that the addition of peg increases the encapsulation efficiency of high molecular weight ( mw ) biomolecules compared to those encapsulated in di water alone .", "while these factors are often considered acceptable in drug delivery applications , it is preferable to have free encapsulated solute of known concentration for biophysical studies , e.g. , to evaluate the effects of confinement.(30 ) encapsulation of rh > 10 nm fluorescently labeled dextran polymers in gv has been reported to improve markedly in the presence of several weight percent additional polymeric solutes.(15 ) the additional polymers acted as volume excluders , resulting in condensation of the labeled solutes and allowing them to be more easily encapsulated during vesicle formation.(15 ) macromolecular crowding is an attractive means for improving macromolecule encapsulation because of its generality.(31 ) this approach for improving encapsulation has not previously been tested for biomacromolecules such as proteins , which in many cases already exist in globular conformations and hence may not undergo as large a rh change in response to volume excluders , nor has it been tested for encapsulation in submicrometer vesicles . herein , we report the use of peg as a macromolecular crowding agent to increase the encapsulation efficiency of fluorescently labeled biomacromolecules within gvs and 200 nm diameter luvs ." ], [ "we first describe the effect of polymeric volume excluders on encapsulation in gvs formed by gentle hydration and then discuss encapsulation in luvs prepared by a freezethaw / extrusion protocol .", "we interpret this as the result of some cf loss from the vesicle interior during centrifugation and/or other handling , which is commonly reported in submicrometer vesicles.(69 ) these data are exciting , because while the majority of reports published on bee utilize specific interactions between liposome / solute , this method is quite general and should apply to a variety of solutes that can be condensed under conditions of macromolecular crowding . although the absolute bee in these experiments was low , we have demonstrated that addition of 3 wt % peg provides a means of improving encapsulation for large solutes such that cin = cout for luvs prepared by freezethaw / extrusion . increasing", "therefore , we estimated cin and the effectiveness of solute encapsulation by comparing the percentage of total solute that has been encapsulated within a batch of vesicles ( bulk encapsulation efficiency , bee ) to the capture volume .", "this underscores the difference in the two measurements : the error in gv cin measurements indicates vesicle - to - vesicle variability within a batch , while variability in luv bee experiments reports on differences between entire batches prepared separately and as such may reflect variability in capture volume .", "these results are consistent with the role of peg 8 kda as a volume excluder , driving the condensation of macromolecular structures . proteins , nucleic acids , and enzymes are all known to adopt condensed structures in macromolecularly crowded solutions ." ], [ "our results indicate that the addition of the polymeric coencapsulants peg 8 kda and dextran 500 kda as macromolecular crowding agents during passive encapsulation of biomacromolecular solutes can substantially increase mean encapsulated concentration and in some cases homogeneity for otherwise poorly encapsulated high mw proteins in giant vesicles .", "the addition of a crowding agent also reduced vesicle - to - vesicle encapsulation variability for the lower mw aat , which was already encapsulated efficiently ( i.e. , with cin = cout ) in dilute solution .", "the mechanism for increased encapsulation is general , such that crowding agents need not be varied with the identity of the solute .", "the approach used here should be effective for a wide range of membrane / macromolecular solute combinations ." ], [ "we chose 3 wt % peg 8 kda based on prior work with dextran 500 kda condensation , in which we observed increased encapsulation efficiency in gvs up to 10 wt % peg , with the bulk of the increase achieved by 3% and decreased average gv diameter for 10 wt % peg.(15 ) following incubation , the solutions were allowed to cool to room temperature .", "the concentration of biomolecule inside ( ci ) and outside ( co ) the gv was determined directly from the intensities ( ii , io ) by a calibration curve of the labeled biomolecule free in solution . from the calibration curves", "dppc / cholesterol vesicles ( 80:20 mol ratio ) were prepared using a modified technique provided by the distributor to yield large unilamellar vesicles by extrusion ( luvet ) as previously reported .", "coverslips were also coated with n-(triethoxysilylpropyl)-o - polyethylene oxide urethane to prevent the adhesion of fluorescently labeled biomolecules to the glass surface .", "the concentrations of crowding agents are referred to in wt % , since this is the common notation used for crowding agents in the macromolecular crowding literature ; the 3% peg 8 kda used here corresponds to 3.75 mm .", "a fluorescence line scan was taken across each vesicle to determine the fluorescence intensity of the alexa fluor 488 , fitc , or fluorescein inside the vesicle ( ii ) and in the undiluted bulk solution ( io , outside the vesicle ) , as reported previously ." ] ]

[ [ "we collected all possible literature from the year 1972 ( when kfd was first described ) to the present day conducting a medical search on kikuchi fujimoto disease ( kfd ) in english language .", "we included publications in authorized medical journals including original and review articles / theses , editorials , case reports and brief communications ." ], [ "kfd is an extremely uncommon disease but cosmopolitan with higher japanese and asiatic prevalence.1,2 however , sporadic cases have also been reported from europe . in asian woman", "kikuchi s disease is rare and benign cause of cervical lymphadenopathy.3 the disease , most often , happens to occur in young adults below 40 and seldom in children.4 at first , little female predominance was considered , but the recent literature regards it as male to female ratio 1:1.1,5 a current study on the patients with kfd conducted in taiwan reports the average age of 21.5 cardiac , hepatic and pulmonary involvement raises the morbidity ." ], [ "however , role of viruses ( epstein - barr virus and others ) in the pathogenesis of kikuchi s disease is controversial and unremarked.1 on the other hand , unger and coworkers are in favor of viral etiology as kfd manifests certain viral features ie , atypical lymphocytosis , certain histologic features , flulike respiratory prodrome and no response to antibiotic therapy.7 also , kikuchi s disease has been reported in patients with aids.8 like systemic lupus erythematosus ( sle ) , lymphocytes and histiocytes in the patients with kikuchi s disease show tubular reticular structures in their cytoplasm on electron microscopy.9 it has been opinioned that in genetically susceptible individuals , kfd may belong to exuberant t - cell mediated immune response provoked by variety of stimuli.1 even though course of cell death in kfd needs to be studied and emphasized , ohshima and his associates remarked apoptotic cell death might be involved in the pathogenesis of kfd.10 regarding to this study , proliferating cd8 t - cells may kill or be killed in the apoptotic process of this disease using fas and perforine pathways ." ], [ "tender cervical lymphadenopathy is the characteristic feature ( 56%98% ) of kfd , predominantly involving the posterior cervical triangle .", "anecdotal reports bring to light the unusual features of kfd like haemophagocytic syndrome and carcinoma15 along with fatal multicentric disease .", "kikuchi s disease begins as an acute or sub - acute condition , developing over two to three week period ." ], [ "in patients with kikuchi fujimoto disease , an excisional biopsy of the involved lymph nodes is the investigation of choice .", "coagulative necrosis with ample karyorrhetic debris in paracortical areas of the involved lymph nodes is the characteristic histologic feature of kfd .", "it must be born in mind that in the individuals with kfd , atypical reactive immunoblastic component is common and can be mistaken for lymphoma.4 histiocyte - associated antigens ( lysozyme , myeloperoxidase and cd68 ) are also expressed by histiocytes in kfd ." ], [ "kfd is an extremely rare disease and the differential diagnosis can be established on the basis of enlarged lymph nodes which are associated with many other disorders .", "lymphoma ( non - hodgkin s lymphoma ) , tuberculosis , sle , plasmacytoid t - cell leukemia , kawasaki s disease , and myeloid tumor are included in the differential diagnosis of kfd.1 sometimes , because of similar clinical and histological features , it becomes problematic to differentiate kikuchi fujimoto disease from lymphadenitis associated with systemic lupus erythematosus ( sle ) .", "it is necessary to born in mind the differential diagnosis of kfd as its treatment dramatically differs from other disorders ." ], [ "kikuchi fujimoto disease ( histiocytic necrotizing lymhadenitis ) is a self - limiting condition that resolves spontaneously within 1 to 4 months of period .", "no hereditary risk has been documented in kfd.8 most of the time symptomatic relief is offered for the local and systemic complains of the disease .", "however , studies reveal recurrence of the disease in 3%4% of the patients.9 additionally , sle may happen to occur some years later .", "lymph node tenderness and fever is treated with analgesics , antipyretics , and nsaids . sometimes , but rarely , steroids can be used temporarily , especially in severe extranodal involvement or generalized clinical course.19 in order to run an excisional biopsy of the enlarged lymph nodes , surgical consultation may be prerequisite .", "very few cases have been reported as fatal . however , no standard or specific treatment of kfd has been recommended .", "individuals with kikuchi fujimoto disease should be examined systemically and they must be under regular follow - up in order to monitor the manifestations of sle . the course of cervical lymphadenopathy is benign and resolves spontaneously ." ], [ "early recognition of kikuchi s disease is of prime importance to avoid extensive and expensive investigations related to malignant lymphoma other related disorders . in order to avoid misdiagnosis , awareness of this disease", "kikuchi fujimoto disease is an idiopathic , extremely rare , more or less worldwide , and often under - diagnosed condition ; predominantly involving the posterior cervical lymph nodes ." ] ]

[ [ "whose attending physician is unsure regarding which modality will be optimal , the results demonstrate a very low feeding success rate with enteral nutrition and that complications are related to the duration of nutritional treatment , regardless of the mode of administration . in general terms it has repeatedly been shown that when patients are given only enteral nutrition , the success of feeding is below 70% .", "systematic under - feeding of icu patients may be used as a marker of suboptimal care . wherever it is considered a human right not be hungry", "in addition , evaluation of nutritional protocols in terms of success rate , nutrition related complications and outcome must be encouraged .", "intensive care medicine is a comparatively young speciality , and within our arsenal of treatments the amount of evidence - based knowledge is often embarrassingly low .", "although not evidence based in any prospective , controlled , randomized clinical trials , it is unlikely that anyone would dispute that under - feeding eventually leads to death .", "nevertheless , a short period of starvation appears to be a part of clinical treatment in many icus .", "does it have any bearing on outcome in the icu or during the post - icu period ?" ], [], [] ]

[ [ "this conclusion is strongly supported by the lack of autoimmune manifestations and changes in thymocyte maturation upon foxn1-cre mediated ablation of a conditional foxp3 allele in the thymic epithelium . in contrast , in control experiments , foxp3 ablation in the t cell lineage resulted in lethal autoimmune pathology typical of germline foxp3 mutation , as previously reported . in full agreement with these data", "these results demonstrate that deletion of the foxp3 gene in thymic epithelial cells does not result in detectable changes in thymic t cell maturation , and that an apparent decrease in dp thymocyte subset size and in total thymocyte numbers is due to loss of foxp3 in thymocytes rather than in the thymic epithelium and is most likely secondary to the severe autoimmunity and cytokine storm common to the foxp3 , foxp3 , and foxp3 cd4-cre mice .", "are the results of the bm transfer experiments , which showed that foxp3 deficiency in hematopoietic cells is solely responsible for autoimmunity , and that perturbed thymocyte subsets in foxp3-deficient mice are an indirect consequence of pathology .", "collectively , our data demonstrates that the thymic epithelium does not express detectable amounts of foxp3 protein , and that there are no measurable adverse effects on immunological tolerance attributable to foxp3 deficiency in thymic stromal cells or in other radiation - resistant nonhematopoietic cells .", "we addressed this possibility by ablation of a conditional foxp3 allele using cre recombinase expressed exclusively in thymic epithelial cells ." ], [ "recently , apparent expression of foxp3 in the majority of thymic epithelial cells was observed in experiments using flow cytometry while a subset of thymic cortical epithelial cells was found positive for foxp3 by immunofluorescence ( 16 ) .", "because epithelial cells are notorious for a high degree of nonspecific antibody binding in flow cytometric assays and are tightly associated with thymocytes in situ , potentially leading to false positive results in immunofluorescence assays , we sought to reexamine foxp3 expression in thymic epithelial cells and thymocytes by flow cytometric analysis of genetically marked foxp3-expressing cells using knock - in mice harboring a foxp3 reporter allele .", "these data demonstrate that the thymic epithelium did not express detectable levels of foxp3 protein within the sensitivity limit of these assays .", "( b ) immunohistochemical analysis of foxp3 expression in the thymus of foxp3 , foxp3rag2 , and foxp3rag mice ." ], [ "we addressed this possibility by ablation of a conditional foxp3 allele using cre recombinase expressed exclusively in thymic epithelial cells .", "thus , the possibility remained that low level of foxp3 expression in thymic epithelial cells at a certain stage of t cell differentiation is required for prevention of autoimmunity .", "although the aforementioned studies failed to detect foxp3 protein in thymic epithelial cells , it can be argued that our detection of foxp3 protein is not sufficiently sensitive .", "the findings above demonstrate that genetic ablation of foxp3 in the thymic epithelium is neither necessary nor sufficient for the development of autoimmune disease .", "disruption of foxp3 in the t cell lineage is necessary and sufficient to cause autoimmune syndrome ." ], [ "these results demonstrate that deletion of the foxp3 gene in thymic epithelial cells does not result in detectable changes in thymic t cell maturation , and that an apparent decrease in dp thymocyte subset size and in total thymocyte numbers is due to loss of foxp3 in thymocytes rather than in the thymic epithelium and is most likely secondary to the severe autoimmunity and cytokine storm common to the foxp3 , foxp3 , and foxp3 cd4-cre mice .", "collectively , our data demonstrates that the thymic epithelium does not express detectable amounts of foxp3 protein , and that there are no measurable adverse effects on immunological tolerance attributable to foxp3 deficiency in thymic stromal cells or in other radiation - resistant nonhematopoietic cells .", "are the results of the bm transfer experiments , which showed that foxp3 deficiency in hematopoietic cells is solely responsible for autoimmunity , and that perturbed thymocyte subsets in foxp3-deficient mice are an indirect consequence of pathology .", "thus , in mice the only known role for foxp3 remains promotion of t reg cell differentiation within the t cell lineage .", "together with the absence of expression of foxp3 in dn thymocytes , these experiments show that the changes in dn thymocyte maturation observed in foxp3 mutant mice are secondary effects of massive peripheral t cell activation ." ], [ "bm chimeras were constructed using 7 10 bm cells / recipient harvested from athymic nude male mice with or without the foxp3 mutation and injected i.p . into neonatal ( 23 d ) rag1 with or without the foxp3 .", "foxp3 ( 14 ) , foxp3 ( 14 ) , foxp3 ( 15 ) , cd4-cre ( 18 ) , foxn1 ( unpublished data ; cre was inserted along with an internal ribosome entry site into the 3 untranslated region of the foxn1 gene ) , rosa - stop - yfp ( 19 ) , foxp3 , nude , rag1 , and rag2 mice have all been backcrossed to the b6 background .", "s1 shows early thymopoiesis for wild - type bm - derived thymocytes developing in foxp3-sufficient and foxp3-deficient hosts assessed by cd44/cd25 flow cytometric profiles of cd4cd8 thymocytes 4 wk after bm transfer .", "b6 foxp3 mice were backcrossed either to the b6 nude or b6 rag1 backgrounds two generations to produce foxp3 nude and foxp3 rag1 strains .", "after enzymatic enrichment , cd45 thymic stromal cells were purified using cd45 microbeads ( miltenyi biotec ) and the automacs system ( miltenyi biotec ) as per the manufacturer 's recommendations before flow cytometric analysis ( 21 ) .", "thymic stroma preparations were enriched from three to six pooled thymi from 510-wk - old mice as described previously ( 20 ) .", "510-wk - old mice were analyzed using the following antibodies : cd45-apc , i - a pe , cd4-pe - cy7 , cd44-pe , cd8-percp , cd25-apc , cd8-fitc , cd4-percp , and uea-1 biotin , followed by sav - percp ( all from bd biosciences ) and g8.8 supernatant conjugated to alexa 647 .", "disease incidence was monitored by frequent visual observation , and postmortem histological analysis of the tissues was performed using hematoxylin and eosin staining ( histology consultation services ) .", "experimental mice were age and sex matched and housed in specific pathogen - free conditions ." ], [ "bm chimeras were constructed using 7 10 bm cells / recipient harvested from athymic nude male mice with or without the foxp3 mutation and injected i.p . into neonatal ( 23 d ) rag1 with or without the foxp3 .", "foxp3 ( 14 ) , foxp3 ( 14 ) , foxp3 ( 15 ) , cd4-cre ( 18 ) , foxn1 ( unpublished data ; cre was inserted along with an internal ribosome entry site into the 3 untranslated region of the foxn1 gene ) , rosa - stop - yfp ( 19 ) , foxp3 , nude , rag1 , and rag2 mice have all been backcrossed to the b6 background .", "b6 foxp3 mice were backcrossed either to the b6 nude or b6 rag1 backgrounds two generations to produce foxp3 nude and foxp3 rag1 strains .", "experimental mice were age and sex matched and housed in specific pathogen - free conditions .", "disease incidence was monitored by frequent visual observation , and postmortem histological analysis of the tissues was performed using hematoxylin and eosin staining ( histology consultation services ) .", "all mice were used in accordance with guidelines from the institutional animal care committee of the university of washington ." ], [ "thymic stroma preparations were enriched from three to six pooled thymi from 510-wk - old mice as described previously ( 20 ) .", "after enzymatic enrichment , cd45 thymic stromal cells were purified using cd45 microbeads ( miltenyi biotec ) and the automacs system ( miltenyi biotec ) as per the manufacturer 's recommendations before flow cytometric analysis ( 21 ) .", "510-wk - old mice were analyzed using the following antibodies : cd45-apc , i - a pe , cd4-pe - cy7 , cd44-pe , cd8-percp , cd25-apc , cd8-fitc , cd4-percp , and uea-1 biotin , followed by sav - percp ( all from bd biosciences ) and g8.8 supernatant conjugated to alexa 647 .", "thymic sections were prepared and stained as described previously ( 22 ) using rabbit polyclonal igg anti - foxp3 antibodies ( 14 ) , followed by alexa 546conjugated goat anti " ], [ "s1 shows early thymopoiesis for wild - type bm - derived thymocytes developing in foxp3-sufficient and foxp3-deficient hosts assessed by cd44/cd25 flow cytometric profiles of cd4cd8 thymocytes 4 wk after bm transfer ." ] ]

[ [ "we herein , report hpv b19 induced aplastic crisis in an asymptomatic and undiagnosed family of three with hs demonstrating pancytopenia on peripheral blood .", "several similar sporadic cases have been reported by now , but familial hpv b19 induced aplastic crisis leading to the diagnosis of hs in all family members is a very rare condition being only reported three times in the literature .", "the hpv b19 induced aplastic crisis can unmask several hereditary hematological disorders that have been normally compensated . among these conditions ,", "human parvovirus ( hpv ) b19 , being first discovered and introduced in 1975 , is a non - enveloped single - stranded dna virus from the parvoviridae family ." ], [ "the results were consistent with the diagnosis of hs . knowing hpv b19 as the most common causative agent in the development of aplastic crisis in hemolytic anemias ;", "pcr for parvovirus b19 . from left to right ; the siblings , their positive and negative control , and the ladder .", "specifically hereditary spherocytosis polymerase chain reaction ( pcr ) for hpv b19 , dna was performed which was positive in all three patients ( figures 1 and 2 ) ." ], [ "as hpv b19 was first discovered in 1975 and this family was reported in 1962 , thus the etiology was misdiagnosed . in the present study , we described a family with hs that all three members developed aplastic crisis secondary to hpv b19 infection leading to the detection of asymptomatic hs .", "however , the authors reached the conclusion that hpv b19 was responsible for the aplastic crisis in this family with hs .", "they also found that the children of one of the patients also developed hpv b19 induced aplastic crisis , which was resolved with supportive care .", "only three previous reports have shown that hpv b19 can induce aplastic crisis and unmask the hs in a family . previously , green et al . in 1984 reported an adult sibling pair with hs who developed aplastic crisis after a febrile illness , which was further diagnosed to be hpv b19 infection ." ], [ "hpv b19 induced aplastic crisis in a family leading to the diagnosis of hereditary hs is a very rare reported event in the literature .", "the distinguished feature of this report is that all affected members of a family developed some degrees of transient pancytopenia , not only anemia , all simultaneously in the course of their disease .", "however , it was transient and the recovery happened very soon in all of them within 10 days , which was attributed to the usage of ivig ." ] ]

[ [ "here , we have tested the therapeutic efficacy of these strategies on a genetic mitochondrial disease model , the sco2 knockout / knockin ( sco2 ) mouse ( yang et al . , 2010 ) .", "primary mitochondrial disorders due to impaired oxidative phosphorylation ( oxphos ) are a well - established cause of severe disability and precocious death in both children and adults ( koopman et al . , 2012 ) .", "recent studies have shown that sirt1 activation can prevent diet - induced obesity in mice .", "no effective therapies are currently available for these conditions , but encouraging results have recently been obtained by stimulating mitochondrial biogenesis acting on either the ppar system ( wenz et al . , 2008 ) or the amp - kinase ( ampk)/pgc1 axis ( viscomi et al . , 2011 ) ." ], [ "no effect of the nr treatment was observed on the mitochondrial respiratory chain activities in the brain of our animals ( table s4 ) .", "we found that the mtupr - specific transcripts clpp , hsp60 , and sod2 were significantly increased in muscle samples of nr - treated sco2 mice , whereas sod3 , which is unrelated to mtupr , was unchanged ( figure 2h ) .", "these results suggest that nr treatment increases mitochondrial function in the sco2 mice through nad activation of sirt1 ( cant et al . , 2012 ) .", ", nr - dependent sirt1 activation can induce the mitochondrial unfolded protein response ( mtupr ) , a stress - response protective mechanism which can improve mitochondrial function ( durieux et al .", "again , we found that expression of the mtupr genes hsp60 , clpp , and sod2 was significantly increased , unlike the mtupr - unrelated gene sod3 ( figures 3h and 3i ) ." ], [ "we have shown here that these treatments can correct the biochemical and clinical phenotype of the sco2 mouse , a model of genetically determined mitochondrial disease . increased transcription of genes related to both oxphos and mtupr", "nad biosynthesis and cellular levels are also controlled by a circadian clock related to the feeding / fasting cycle .", "was associated with activation of oxidative metabolism , increase of mitochondrial respiratory chain activities , and normalization of the endurance motor deficit , displayed by naive sco2 animals .", "ablation of the parp1 gene , supplementation of nr or administration of parp inhibitors ( parpi ) can expand the nad pool and activate sirtuins , particularly sirt1 , a master regulator of mitochondrial homeostasis .", "nr is a natural vitamin with no known adverse effects , which could be administered as a dietary supplement , particularly in case of isolated mitochondrial myopathy .", "the nad pool is set by the balance between de novo and salvage biosynthetic pathways and utilization by nad - consuming enzymes ." ], [ "note that in all panels the activity of cii has been multiplied by 10 for visualization clarity .", "muscle quadriceps samples stored in liquid nitrogen were homogenized in 10 mm phosphate buffer ( ph 7.4 ) , and the spectrophotometric activity of ci , cii , ciii , and civ , as well as cs , was measured as described ( bugiani et al . , 2004 ) .", "mitochondrial - enriched fractions were collected after centrifugation at 800 g for 10 min in the presence of protease inhibitors , and frozen and thawed three times in liquid nitrogen .", "tissue nad was analyzed with mass spectrometry as previously described ( yang and sauve , 2006 ) .", "a standard treadmill apparatus ( columbus instruments , columbus , oh ) was used to measure motor exercise endurance , as described in viscomi et al .", "mtdna content and transcripts analysis was carried out by sybr green real - time pcr , as described ( viscomi et al . , 2011 ) .", "mouse tissues were homogenized in 15 volumes of 10 mm potassium phosphate buffer ( ph 7.5 ) ." ] ]

[ [ "the purpose of this case report is to describe a patient who developed acute paralysis and aphasia while receiving her initial infusion of irinotecan .", "irinotecan is commonly used in combination with oxaliplatin as a component of folfirinox chemotherapy for several gastrointestinal malignancies ." ], [ "a 67-year - old woman with newly diagnosed metastatic pancreatic adenocarcinoma presented for her first cycle of folfirinox chemotherapy . during her infusion of irinotecan", ", she developed acute onset of generalized weakness , paralysis of all extremities , and nonfluent aphasia with complete inability to communicate .", "this episode was self - limited and resolved within 2 h. prior to subsequent infusions she received intravenous repletion of potassium and had no recurrence of symptoms ." ], [ "in selected cases , coadministration of irinotecan and oxaliplatin may result in severe generalized weakness and aphasia , which may be triggered by underlying electrolyte disturbances ." ], [ "here we report the case of a patient with a rare complication of combination therapy with irinotecan and oxaliplatin , i.e. severe generalized weakness , paralysis , and aphasia , and provide a synopsis of the current literature as well as a proposed therapeutic approach .", "irinotecan is a topoisomerase i inhibitor derived from camptothecin , an alkaloid compound extracted from deciduous trees indigenous to eastern asia .", "its antineoplastic activity is mediated by its inhibition of double - stranded dna replication through stabilizing the cleavage complexes of topoisomerase i. its most common use is in the treatment of colorectal cancer . however , since 2010 , it has been combined with 5-fluorouracil , leucovorin , and oxaliplatin in the regimen known as folfirinox , which has been utilized as an effective therapy in patients with metastatic pancreatic cancer as well as other cancers .", "atropine is commonly administered with the chemotherapy infusion both for the prevention and treatment of this syndrome ." ], [ "a 67-year old asian woman with a history of poorly controlled diabetes presented with newly diagnosed metastatic pancreatic adenocarcinoma . in november 2013", "halfway through the irinotecan infusion , she developed acute onset of generalized weakness , paralysis of all extremities , and nonfluent aphasia with complete inability to communicate . throughout this , she was awake , alert , and aware of her surroundings , with stable vital signs . at this time", "she was then given her second cycle of folfirinox with identical doses of the drugs as in the first cycle and was able to complete all of the therapy without recurrence of the symptoms previously experienced at her initial infusion ." ], [ "to date , there have been 9 reported cases of significant central nervous system toxicity during or following the administration of irinotecan , both with and without concurrent oxaliplatin administration .", "all of these cases involved the development of dysarthria , with 2 of them leading to a complete motor aphasia and 1 case with associated ataxia [ 1 , 2 , 3 , 4 , 5 ] . in each case , these symptoms developed with the initial infusion of irinotecan and completely resolved with time .", "the degree of severe generalized weakness seen in our patient following administration of irinotecan has not previously been reported in the literature .", ". if this is the case , those patients receiving combination folfirinox therapy may be at significantly higher risk of developing neurologic side effects than those receiving folfox therapy alone . from our experience in this patient , and from our review of the literature , we conclude that in selected cases , the coadministration of irinotecan and oxaliplatin ( as is used in folfirinox ) may result in severe generalized weakness and aphasia ." ] ]

[ [ "given the studies that suggest the preferential involvement of prefrontal cortex among brain structural and functional alterations in alcohol dependence , we hypothesized that patients with alcohol dependence would have thinner prefrontal cortex in comparison with healthy comparison subjects , after correcting for the global cortical thinning associated with alcohol dependence .", "we therefore undertook the cortical thickness analysis adjusting for the hemispheric average cortical thickness , in 21 detoxified alcohol - dependent patients and matched 22 healthy comparison subjects .", "the objective of this study was to identify brain regions with cortical thickness alterations that exceed the level of global alterations in alcohol dependence .", "alcohol - related atrophy , we wanted to localize the cortical regions that may be particularly vulnerable to alcohol consumption .", "we used the whole brain - wise cortical thickness analysis , which is validated histologically and with manual outlining method .", "we also investigated whether the magnitude of deficits are correlated with the alcohol use - related variable ." ], [ "hemispheric average cortical thickness was included in the model as a covariate since there was a significant difference in hemispheric average cortical thickness between groups and our aim was to identify the particularly vulnerable cortical regions beyond the global brain atrophy associated with alcohol dependence .", "pair - wise correlations were used to test whether there were associations between the magnitude of cortical thickness deficits in patients with alcohol dependence and the duration of alcohol use . considering the relatively modest sample size , sensitivity analyses to rule out the possibility that the current results may be modulated by other confounding factors such as comorbid depression , anxiety symptoms and scan parameter difference were performed .", "local maxima thickness values within the cluster extracted as described above were subjected to linear regression models that included the scan parameter difference , the presence of comorbid depression as defined by 19 or more scores on the 17-item hamilton depression rating scale ( hdrs ) , or the presence of anxiety as defined by 40 or more scores on the state - trait anxiety inventory ( stai - t ) as additional covariates .", "smoothing processes were conducted using an iterative nearest - neighbor averaging procedure with the full - width half maximum ( fwhm ) 15 mm 2-d gaussian kernel . for calculating statistical difference maps of cortical thickness between alcohol dependence and healthy comparison groups , general linear model ( glm ) with cortical thickness at each vertex as the dependent variable has been used .", "thickness values of the surface point with highest z values ( local maxima ) within the cluster , where significant group differences of cortical thickness were found , were extracted for post hoc analyses .", "t1 and t2 weighted mr images were obtained using 1.5 tesla siemens whole body scanner ." ], [ "age - matched healthy comparison subjects were recruited from the community via the local advertisement during the same study period .", "patients with alcohol dependence were enrolled from the inpatient unit of the department of neuropsychiatry in a university - affiliated hospital , seoul , south korea .", "additional exclusion criteria for control group were ( 1 ) presence or history of mental disorders including alcohol abuse and ( 2 ) current alcohol consumption greater than 14 equivalent standard drinks for men , 7 for women , per time . after being detoxified for 2 weeks , all patients underwent physical examination by a physician and the routine laboratory tests to screen out any major medical disorders .", "inclusion criteria for alcohol dependence group were ( 1 ) age between 20 and 70 , and ( 2 ) diagnosis of alcohol dependence according to the diagnostic and statistical manual of mental disorders - iv by 2 board - certified psychiatrists .", "exclusion criteria for both alcohol dependence and control groups were ( 1 ) any symptoms or signs of confusion , major medical disorders including kidney disease and chronic liver disease , and/or malnutrition , ( 2 ) presence or history of neurological disorders , ( 3 ) presence or history of any mental disorders other than alcohol dependence or comorbid depressive disorders , including alcohol - induced persistent dementia , alcohol - induced amnestic disorder , or alcohol withdrawal delirium ( 3 ) history of head injury , and ( 4 ) any contraindications to magnetic resonance imaging ( mri ) such as pace makers , claustrophobia , or metal implants ." ], [ "t1 and t2 weighted mr images were obtained using 1.5 tesla siemens whole body scanner .", "t2 weighted images were acquired in order to screen for gross brain abnormality ( tr=9,710 ms , te=120 ms , nex=2 , flip angle [ fa]=170 , slice thickness=3 mm ) .", "repetition time [ tr]=2,050 ms , echo time [ te]=4.39 ms , inversion time [ ti]=1,100 ms , number of excitation [ nex]=2 , flip angle [ fa]=15 , slice thickness=1.3 mm , field of view [ fov]=180180 mm , acquisition matrix=256180 . t1 weighted images of 7 subjects were obtained with slightly different image acquisition protocol ( tr=1,960 ms , te=4.38 ms , ti=1,100 ms , nex=2 , flip angle [ fa]=15 , slice thickness=1.5 mm , fov=250 x 250 , acquisition matrix=256 x 180 ) .", "smoothing processes were conducted using an iterative nearest - neighbor averaging procedure with the full - width half maximum ( fwhm ) 15 mm 2-d gaussian kernel ." ], [ "hemispheric average cortical thickness was included in the model as a covariate since there was a significant difference in hemispheric average cortical thickness between groups and our aim was to identify the particularly vulnerable cortical regions beyond the global brain atrophy associated with alcohol dependence .", "for calculating statistical difference maps of cortical thickness between alcohol dependence and healthy comparison groups , general linear model ( glm ) with cortical thickness at each vertex as the dependent variable has been used .", "pair - wise correlations were used to test whether there were associations between the magnitude of cortical thickness deficits in patients with alcohol dependence and the duration of alcohol use . considering the relatively modest sample size , sensitivity analyses to rule out the possibility that the current results may be modulated by other confounding factors such as comorbid depression , anxiety symptoms and scan parameter difference were performed .", "local maxima thickness values within the cluster extracted as described above were subjected to linear regression models that included the scan parameter difference , the presence of comorbid depression as defined by 19 or more scores on the 17-item hamilton depression rating scale ( hdrs ) , or the presence of anxiety as defined by 40 or more scores on the state - trait anxiety inventory ( stai - t ) as additional covariates .", "non - cortical areas of medial wall and corpus callosum were excluded from the model building .", "5,000 permutation simulations have been performed with random group - label shuffling , with a threshold for a significant vertex of p<0.05 .", "thickness values of the surface point with highest z values ( local maxima ) within the cluster , where significant group differences of cortical thickness were found , were extracted for post hoc analyses ." ], [ "patients with alcohol dependence had general cortical thinning ( left hemispheric average cortical thickness ( mm ) : 2.440.07 [ healthy comparison subjects ] vs 2.240.27 [ patients with alcohol dependence ] , t=3.35 , p=0.002 ) ( right hemispheric average cortical thickness ( mm ) : 2.450.07 [ healthy comparison subjects ] vs 2.250.23 [ patients with alcohol dependence ] , t=3.77 , p<0.001 ) . in order to identify regionally specific cortical deficits in patients with alcohol dependence compared to healthy comparison subjects , hemispheric average cortical thickness was added as a covariate in the whole brain vertex - wise analysis . in the glm model that includes age and average cortical thickness as covariates , significant cortical thickness deficits in patients with alcohol dependence , compared to healthy comparison subjects , were noted in the left superior frontal cortex , after correcting for multiple comparisons with the permutation method ( fig .", "when analysis was repeated covarying for comorbid depression that may be associated with thinner prefronto - temporal cortex , the diagnostic group effect remained significant ( p=0.001 ) . when analysis was repeated covarying for comorbid anxiety that may also be associated with thinner prefronto - temporal cortex , the diagnostic group effect remained significant in the left superior frontal cluster ( p=0.017 ) .", "cortical thicknesses in the left superior frontal cluster was also correlated with the clinical institute withdrawal assessment for alcohol scores ( r=-0.548 , p=0.028 ) .", "post hoc correlation analysis between cortical thicknesses in the left superior frontal cluster of significant group difference and duration of alcohol use in alcohol dependence group demonstrated the significant association ( r=-0.55 ; p=0.02 ) ( fig ." ], [ "the region of cortical thickness deficits in patients with alcohol dependence encompassed primarily the superior frontal cortex , after adjusting for the effects on the global cortical atrophy induced by alcohol dependence ( fig .", "in the current study , we have identified the brain region with altered cortical thickness in patients with alcohol dependence .", "the level of n - acetyl aspartate , the viability marker of neurons , was decreased in prefrontal brain regions in chronic alcohol abusers .", "this is the first study that used cortical thickness analysis in patients with alcohol dependence excluding comorbid substance use , which showed regionally specific cortical thickness deficits in alcohol dependence ." ] ]

[ [ "the purpose of this study was to examine and compare nutrient intake , dds , mar and health behaviors of asan residents by the three distinctive regions .", "evaluating the dietary diversity score ( dds ) and mar are , therefore , a good way to predict quality of diet and the entirety of dietary habits . in this study , we examined the dietary intakes and health behaviors of asan residents in order to improve health status and consequently the quality of life of asan residents , especially those who live in a rural area .", "nutrient intakes , health behaviors and quality of life are interrelated and are of particular importance among rural residents . rural areas exhibit a variety of dietary habits and food - intake patterns ( lee et al . , 2002 ;", "the dietary diversity of rural koreans is a potential way to improve their nutritional , and consequently , their health status and quality of life .", "( 1987 ) reported that variety among and within major food groups was associated with diet quality assessed by the mean adequacy ratio ( mar ) of 11 nutrients .", "a low dietary diversity is a particularly severe problem among vulnerable populations of the poor ( ruel , 2003 ) and elderly ( bernstein et al . , 2002 ;" ], [ "the mean adequate ratio ( mar ) is a mean nutrient adequate ratio ( nar ) of 12 nutrients ( protein , vitamins a , c , e and b6 , thiamin , riboflavin , niacin , folic acid , calcium , iron and zinc ) and nar of each nutrient was calculated by dividing actual nutrient intakes by recommended intakes ( ri ) of kdri ( dietary reference intakes for koreans , korean nutrition society , 2005 ) .", "the energy - adjusted nutrient intake for each individual was computed by taking the residual from the regression model in which total caloric intake was the independent variable and the observed nutrient intake was the dependent variable , plus a constant equal to the expected intake of the nutrient for the mean caloric intake of the study population ( willett , 1990 ) .", "was conducted to detect true differences among regions after controlling age and income levels as covariates .", "all nutrient intakes were adjusted for total energy intake in order to minimize extraneous errors in estimating dietary intake due to individual differences in total food intake .", "nutrients without ri values defined in kdri , such as energy , fat , carbohydrate , sodium , fiber and cholesterol , were excluded in the nar calculation .", "dietary - intake data using a one - day 24-hour recall method were obtained by one - to - one interviews from the 5 to the 26 of january 2003 .", "food records were converted to nutrient intakes using a computerized nutrient analysis program ( can - pro , v2.0 , the korean society of nutrition , seoul , korea ) .", "detailed descriptions of all foods and beverages consumed and estimated food portion sizes were recorded by trained interviewers using food models , standard household measures , and full - sized colored photographs as memory aids .", "a total of 930 subjects ( 351 men and 579 women ) , aged 61.4 13.8 ( mean sd ; range 20 - 96 ) years correctly completed a 24-hour recall interview and were finally selected as participants ." ], [ "a total of 930 subjects ( 351 men and 579 women ) , aged 61.4 13.8 ( mean sd ; range 20 - 96 ) years correctly completed a 24-hour recall interview and were finally selected as participants .", "volunteers were recruited from residents of asan during january 2003 and the purposes and content of the study were explained to all participants , who provided their written , informed consent ." ], [ "dietary - intake data using a one - day 24-hour recall method were obtained by one - to - one interviews from the 5 to the 26 of january 2003 .", "detailed descriptions of all foods and beverages consumed and estimated food portion sizes were recorded by trained interviewers using food models , standard household measures , and full - sized colored photographs as memory aids .", "information on individual characteristics such as demography and socioeconomic status and health related behaviors was obtained using pre - coded questionnaires ." ], [ "the energy - adjusted nutrient intake for each individual was computed by taking the residual from the regression model in which total caloric intake was the independent variable and the observed nutrient intake was the dependent variable , plus a constant equal to the expected intake of the nutrient for the mean caloric intake of the study population ( willett , 1990 ) . dietary diversity score ( dds ) of each individual was calculated from quantidd , which is the proportion of 17 food groups ( cereals or grains , potato and its products , simple carbohydrates or sugars , beans and its products , nuts or seeds , vegetables and their products , mushrooms , fruits and their products , meat or pork or poultry , eggs and the products , fish or shellfish and their products , seaweed and its products , milk and dairy products , fats or oils , beverages , seasonings and others ) contributing to the total amount of food intake after all the food ingredients from mixed dishes were decomposed .", "the mean adequate ratio ( mar ) is a mean nutrient adequate ratio ( nar ) of 12 nutrients ( protein , vitamins a , c , e and b6 , thiamin , riboflavin , niacin , folic acid , calcium , iron and zinc ) and nar of each nutrient was calculated by dividing actual nutrient intakes by recommended intakes ( ri ) of kdri ( dietary reference intakes for koreans , korean nutrition society , 2005 ) .", "all nutrient intakes were adjusted for total energy intake in order to minimize extraneous errors in estimating dietary intake due to individual differences in total food intake .", "food records were converted to nutrient intakes using a computerized nutrient analysis program ( can - pro , v2.0 , the korean society of nutrition , seoul , korea ) .", "information on the 17 food groups to calculate dds from quantidd is available elsewhere ( katanoda et al . , 2006 ) .", "nutrients without ri values defined in kdri , such as energy , fat , carbohydrate , sodium , fiber and cholesterol , were excluded in the nar calculation ." ], [ "was conducted to detect true differences among regions after controlling age and income levels as covariates .", "differences among regions were assessed by anova and tukey 's post - hoc analysis for continuous variables and by the test for categorical variables . since regions showed different social economic status ( ses ) such as income and education levels and age distributions were also different by regions , analysis of covariance ( ancova )" ], [ "just for the male participants , differences of fat , vitamin c , vitamin e , thiamin , riboflavin , iron and cholesterol intakes were not significant among regions while protein , vitamin a and calcium intakes were higher in the urban area and lower in the rural area .", "energy - adjusted intakes of fat , vitamin c , and thiamin were significantly higher in the urban area than in the other two areas ( p<0.05 ) by anova , but ancova models did not show any significant differences . however , for vitamin e and cholesterol , both anova and ancova models showed same results of significantly higher intake in the urban area than in the other two areas ( p<0.05 ) .", "after ses variables were controlled in ancova model for male participants , protein , vitamin a and calcium intakes remained lowest in the rural area .", "the energy - adjusted intakes of protein , riboflavin and calcium were lower in the rural area than in factory or urban areas for the total participants and after adjustment of ses variables , the results showed same significant differences ( p<0.05 ) .", "energy - adjusted protein and niacin intakes of the women were higher in the factory area ( p<0.05 ) .", "however , mars of rural participants were lowest for total , men and women after adjustment with age , income and energy intakes ( p<0.05 ) .", "the fundamental characteristics of the participants and comparisons by regions are presented in table 1 . for the total participants , mean age was 61.4 13.8 years , with the men being older ( 64.8 11.7 years ;" ], [ "therefore , in order to achieve better quality of life and health status of the rural residents of asan , improving diet quality is essential . for the urban resident , however , despite of higher ses and diet quality , their perceived stress was higher .", "the korean rural population exhibits a distinct pattern of food choices ( ministry of health and welfare , 2002 ) and korea shows a unique pattern in dietary intake in terms of a lower proportion of energy from fat compared to both developed and developing countries ( lee et al . , 2002 ) . in this study , we described the nutrient intakes , dietary diversity ( dds ) , dietary quality ( mar ) and health related behaviors of asan residents .", "ses and quality of life measured by diet intakes and perceived health were lower in the rural area residents of asan .", "therefore , the true regional differences in quality of diet exist in the population of asan , and public health strategies to improve diet quality of rural residents should be considered .", "therefore , health promotion education to reduce the stress levels for urban residents of asan should be recommended ." ] ]

[ [ "skin side effects of such drugs have few data available in the literature , although the number of reports has been increasing in the last years , including cosmetic filler site injections .", "it is well known that cutaneous side effects of treatment with ifnalpha alone or ifnalpha plus ribavirin in patients with chc have been widely reported , beyond the fact that the virus itself can cause skin lesions . however , the cutaneous side effects during therapy of chc are of inflammatory type with local erythema , edema and , much less frequently , necrosis at the injection skin sites . by contrast ,", "recent studies suggest that liver inflammation in chc is controlled by several mechanisms , including host regulatory immune responses and viral polypeptides interacting with cells involved in innate and adaptive immunity .", "more recently there have been reported dermatological diseases in patients receiving the combination of ifn / ribavirin or ifn / ribavirin / amantadine for the treatment of chc .", "the treatment of chronic hepatitis c ( chc ) has evolved in the last 15 years from monotherapy with interferon alpha ( ifnalpha ) to the combination treatment with pegylated ifn ( peg - ifn ) plus ribavirin for 24 - 48 weeks . up to now , several viral , host and drug - related reactions in response to ifnalpha - based therapy have been identified ." ], [ "we intend to call attention especially to dermatologists to the possibility of a granulomatous tattoo reaction as a side effect during chc treatment with peg - ifnalpha-2b plus ribavirin . until now", ", eight cases of sarcoidosis as a complication of ifn therapy in chc have been reported in the english language literature .", "the most relevant topic in this case is the occurrence of disease on a tattoo area ." ], [ "it seems very likely that a potent immunoregulatory protein for th-1 response such as ifn may induce the disease . in january 2003 the eighth case of ifn - related sarcoidosis was reported with a review of the literature .", "ifn has been linked to pulmonary macrophage activation , a characteristic feature of sarcoidosis which has been assumed an exaggerated t helper 1 ( th-1 ) immune response to a variety of exogenous antigens .", "the case we report presented with cutaneous sarcoidosis during chc therapy and spontaneous regression of the lesions was noted with treatment discontinuation .", "sarcoidosis is a granulomatous disorder of unknown etiology and whose epidemiology suggest a genetic tendency face to infectious agents being supposed to result of immune system deregulation leading to non - caseating granulomas as an immune reaction to an unknown persistent antigenic stimulus .", "chest x - ray revealed hilar lymphadenopathy in three patients , with reticulonodular shadows in another three , while the patient with only cutaneous involvement had a normal chest x - ray .", "we intend to emphasize , especially to dermatologists , the risks of a granulomatous tattoo and other cutaneous sites during chc treatment with peg - ifnalpha-2b plus ribavirin .", "thalidomide has been also shown to have specific activity to the inflammatory mediators of sarcoidosis and to be an alternative beneficial therapy ." ] ]

[ [ "primary sites of occurrence of extrapulmonary pleomorphic carcinomas have been described in other organs such as the stomach , thyroid , gallbladder , pancreas , kidney , liver , bladder , and colon . to the best of our knowledge , only one report described a case of giant cell carcinoma of the colon resembling that observed in the lung .", "pleomorphic carcinoma is an aggressive tumour initially described in the lung by nash and stout . in the 4th edition of the world health organization", "the possibility of the pleomorphic component as morphological expression of mitotic catastrophe is finally discussed .", "( who ) classification of tumours of the lung , pleomorphic carcinoma is defined as a poorly differentiated ( squamous cell carcinoma or adenocarcinoma ) or undifferentiated carcinoma in which at least 10% spindle and/or giant cells are identified , or as a carcinoma constituted purely of spindle and giant cells ." ], [ "a 65-year - old caucasian woman with a medical history of hypercholesterolaemia , chronic obstructive pulmonary disease , and paroxysmal tachycardia was admitted to the surgery unit of the university hospital g. martino ( messina , italy ) in 2013 for abdominal obstructive symptoms ( colicky pain to the right iliac fossa as well as borborygmi ) , change in bowel habits ( diarrhoea ) , asthenia , and severe weight loss since 6 months .", "afterwards , colonoscopy also revealed an exophytic / stenosing malignant neoplastic mass in the caecum , subsequently confirmed through histological evaluation of biopsy .", "abdominal ultrasonography highlighted an exophytic / stenosing mass at the level of the ascending colon .", "there was no family history of gastrointestinal malignancy , although familiality for bladder carcinoma was reported ." ], [ "the commercial source , clone , and dilution of the primary antibodies are detailed in table 1 .", "additional sections collected on silanized , coated slides were used for the immunohistochemical stains , using the dako envisiontm flex , high ph detection system together with autostainer instruments .", "sections were also stained with periodic acid - schiff and alcian blue at ph 2.5 .", "routine haematoxylin - eosin sections were made from formalin - fixed , paraffin - embedded tissue ." ], [ "only 1 out of the 44 harvested perivisceral lymph nodes presented carcinomatous metastasis ( pt3 , pn1 , clinical stage in accordance to the 2009 ptnm system ) .", "microscopically , the tumour was a poorly differentiated adenocarcinoma with a grade 4 pleomorphic component that occupied up to 10% of the whole tumour section .", "the pleomorphic component showed trabeculae and nests of neoplastic cells possessing eosinophilic cytoplasm , as well as irregularly shaped vesicular nuclei with a single large eosinophilic nucleolus .", "giant cells containing multiple nuclei , micronuclei , and prominent eosinophil nucleoli were also found ( fig . ", "the micronuclei appeared as round chromatin fragments with a diameter less than one third of the diameter of the nucleus .", "2b ) , whereas p53 labelling was shown in more than 90% of the tumoural nuclei ( fig . ", "the histochemical stains were negative for periodic acid - schiff and alcian blue in all of the pleomorphic neoplastic cells ." ], [ "we described a rare case of pleomorphic carcinoma of the right colon showing opposing clinicopathological features . although it was classified as a grade 4 tumour , it was characterized by a pushing growth pattern and presented only one lymph node with metastasis .", "therefore , mitotic catastrophe has recently gained attention as a potential therapeutic target in neoplasms [ 23 , 24 , 25 ] . in summary , we reported a case of colorectal carcinoma with clinicopathological features partially similar to pleomorphic cell carcinoma of the lung , a neoplasm associated with a bad prognosis . in particular , this tumour presented only one lymph node with metastasis , and the patient is still well 2 years after the operation .", "this case presented morphological and immunohistochemical features compatible with mitotic catastrophe , a form of non - apoptotic cell death due to aberrant mitosis .", "the inclusion of mitotic catastrophe as part of a microscopic evaluation may be useful for understanding the pathogenesis of this rare entity and for new cancer treatment modalities ." ], [ "no further ethical approval was necessary to perform histology and immunohistochemistry in the case included in this report ." ], [] ]

[ [ "management of suspected scaphoid fractures with normal x - rays at emergency department ( ed ) presentation is a common clinical challenge .", "there has long been concern that failure to identify and immobilise a scaphoid fracture might result in avascular necrosis or non - union with significant functional impact for the patient and potential medico - legal risk for the practitioner .", "traditional management would see the patient immobilised in a plaster cast for 714 days followed by clinical examination and re - x - ray to identify fractures not visible on the initial films . that approach can been challenged on two fronts : whether cast immobilisation while awaiting clinical review is justified and the role of alternative imaging modalities at or near the time of initial presentation .", "the aim of this project was to characterise current management of adult patients with possible occult scaphoid fracture in australasia ." ], [ "demts are the designated supervisors of specialist training at hospitals accredited for training , both metropolitan and rural ( one / hospital ) . as such , they are easily identifiable , experienced specialists with a good understanding of clinical practice within the ed in which they work . participants", "data were collected using internet - based survey software ( www.surveymonkey.com ) and included the most common management strategy used for patients with possible occult scaphoid fracture ( from a range of options , see table 1 ) and whether there was a written ed guideline regarding management of such cases .", "were sent an invitation to participate in the confidential on - line survey by e - mail ( where one could be found ) or by post .", "this was an internet - based survey of directors of emergency medicine training ( demt ) throughout australasia as identified from the australasian college for emergency medicine web - site ( www.acem.org.au ) .", "table 1management options and reported frequencymanagement strategyfrequency ( n , % ) backslab ( half - cast ) with assessment and re - x - ray at 714 days23 , 38%plaster cast ( full ) with assessment and re - x - ray at 714 days19 , 32%backslab with early ct ( within 7 days)6 , 10%backslab with early bone scan ( within 7 days)5 , 8%backslab with early mri ( within 7 days)2 , 3%support bandage with early mri ( within 7 days)1 , 1.7%support bandage with early ct ( within 7 days)1 , 1.7%plaster cast ( full ) with early ct ( within 7 days)1 , 1.7%plaster cast ( full ) with early bone scan ( within 7 days)1 , 1.7%support bandage with re - assessment at 1 week , with further tests only if symptoms or signs persist1 , 1.7%support bandage with assessment and re - x - ray at 714 days0plaster cast ( full ) with early mri ( within 7 days)0support bandage with early bone scan ( within 7 days)0othersame / next day ct1 , 1.7% management options and reported frequency this project was approved by western health under the nhrmc quality assurance guidelines .", "the outcome of interest was the most common management strategy for possible occult scaphoid fractures ." ], [ "the most common management reported was immobilisation in a backslab ( 23 , 38% ) or full cast ( 19 , 32% ) with clinical assessment and re - x - ray in 710 days .", "ct scan within 7 days was used by 9 ( 15% ) , bone scan within 7 days by 6 ( 10% ) and mri within 7 days by 3 ( 5% ) .", "eighty - three percent of sites reported not having a written guideline / protocol for this condition ." ], [ "we found that most australasian eds continue to use plaster immobilisation for this patient group ( backslab or full cast , 70% ) and that uptake of alternative imaging modalities is only moderate ( 30% ) .", "traditional treatment for suspected occult scaphoid fracture is cast immobilisation with clinical re - assessment and re - x - ray at 710 days .", "there is a clear need for further research comparing combinations of the various immobilisation and imaging strategies and reporting clinical outcomes ( including time off work and time immobilised ) and cost - effectiveness outcomes .", "there is no evidence that lack of access to advanced imaging impacts adversely on clinical outcome .", "ct , mri and bone scan have all been shown to be effective in the diagnosis of occult scaphoid fractures , but to date no studies have shown additional benefit from early advanced imaging for hard clinical outcomes . at present , the logical role for advanced imaging is for patients with persistent symptoms and normal follow - up x - rays .", "the weight of evidence would suggest that this is over - treatment and that a simple bandage is sufficient ." ], [ "the traditional approach to management of possible occult scaphoid fracture of immobilisation with re - x - ray at 710 days remains the most commonly used in australasia , despite evidence that this is probably over - treatment with significant consequences for patients ." ] ]

[ [ "thus , this study was conducted with following objectives among interstate female migrants . \n to study socioeconomic and demographic profile of migrant womento estimate proportion of women utilizing full anc package and reasons for nonutilization of full anc servicesto estimate the proportion of institutional deliveries and reasons for home deliveries among the migrant women . \n to study socioeconomic and demographic profile of migrant women to estimate proportion of women utilizing full anc package and reasons for nonutilization of full anc services to estimate the proportion of institutional deliveries and reasons for home deliveries among the migrant women .", "maternal complications and poor perinatal outcome are highly associated with nonutilization of antenatal and delivery care services and poor socioeconomic conditions of the patient .", "women 's reproductive health is a major area of concern , especially in developing countries .", "hence , assessment of present situation of migrant women with reference to anc services utilization and institutional deliveries becomes essential .", "migration of women has been acknowledged as a demographic factor which affects the reproductive health of women .", "women of socially disadvantaged groups , migrant , and/or from ethnic minority groups have been recognized to be less likely to receive early prenatal care and the necessary care during pregnancy , childbirth , and postnatal period .", "empirical evidence has pointed out that migrant groups face several barriers in accessing national maternal health services ." ], [ "\n to study socioeconomic and demographic profile of migrant womento estimate proportion of women utilizing full anc package and reasons for nonutilization of full anc servicesto estimate the proportion of institutional deliveries and reasons for home deliveries among the migrant women . \n to study socioeconomic and demographic profile of migrant women to estimate proportion of women utilizing full anc package and reasons for nonutilization of full anc services to estimate the proportion of institutional deliveries and reasons for home deliveries among the migrant women ." ], [ "a cross - sectional community - based survey was conducted among migrant women in reproductive age group in an urban slum of population ( 30,000 ) , which is the field practice area of a medical college .", "the national sample survey organization 2008 defined migrant as a household member whose last usual place of residence ( upr ) any time in the past was different from the present place of enumeration was considered as a migrant member in a household . in this survey , upr of a person was defined as a place ( village / town ) where the person had stayed continuously for a period of 6 months or more .", "migrants ( as per the above definition ) from outside maharashtra ( interstate migrants ) married women in the age group of 1545 years who had delivered within last 2 years those who consent was included in the study .", "initial visits to the above - said areas were done to build rapport with the population as they are hesitant to get interviewed .", "full anc received by women : it is defined as having 3 components ( a ) at least 3 antenatal visits to health center , ( b ) at least 1 tetanus toxoid ( tt ) vaccine taken before delivery , and ( c ) consumption of 100 or more iron and folic acid ( ifa ) tablets . \n migrants ( as per the above definition ) from outside maharashtra ( interstate migrants)married women in the age group of 1545 years who had delivered within last 2 yearsthose who consent was included in the study . \n ", "while interacting with the participants , one representative from the social workers was always present .", "their household was visited with the female social workers , and meetings conducted by social workers were attended .", "if there is more than one woman in a household fulfilling inclusion criteria , then only one woman was selected by lottery method from that household ." ], [ "the national sample survey organization 2008 defined migrant as a household member whose last usual place of residence ( upr ) any time in the past was different from the present place of enumeration was considered as a migrant member in a household . in this survey , upr of a person was defined as a place ( village / town ) where the person had stayed continuously for a period of 6 months or more .", "full anc received by women : it is defined as having 3 components ( a ) at least 3 antenatal visits to health center , ( b ) at least 1 tetanus toxoid ( tt ) vaccine taken before delivery , and ( c ) consumption of 100 or more iron and folic acid ( ifa ) tablets ." ], [ "\n migrants ( as per the above definition ) from outside maharashtra ( interstate migrants)married women in the age group of 1545 years who had delivered within last 2 yearsthose who consent was included in the study . \n migrants ( as per the above definition ) from outside maharashtra ( interstate migrants ) married women in the age group of 1545 years who had delivered within last 2 years those who consent", "initial visits to the above - said areas were done to build rapport with the population as they are hesitant to get interviewed .", "interviews were conducted at the randomly selected households after getting informed written consent of participants . pretested semi - structured questionnaire for face - to - face interview was prepared .", "while interacting with the participants , one representative from the social workers was always present .", "their household was visited with the female social workers , and meetings conducted by social workers were attended .", "chi - square test was used for evaluating association between anc utilization and categorical variables ." ], [ "table 1 shows that 77% ( 93/120 ) of migrants were under the age of 29 years .", "antenatal care services utilization by migrant women table 4 shows that 12% ( 15/120 ) of deliveries occurred in home . even after implementation of rch program with janani suraksha yojana which emphasizes on institutional delivery", "delivery practices of migrant women table 5 shows that most of the participants , i.e. , 30% ( 36/120 ) mentioned that too far location of government health facility was the most common reason for full nonutilization of anc services .", "sixty - two percent ( 74/120 ) of migrants were married before the age of 18 years though marriage before the age of 18 years is punishable by law ." ], [ "it mentioned that the major barrier toward utilization of these services was ignorance followed by distance to the health - care center .", "a cross - sectional study was carried out among recently delivered women residing in tea gardens of darjeeling district of west bengal .", "according to the district level household and facility survey 2007/2008 , the percentage of institutional delivery and home delivery in urban area is 87.5% and 12.5% , respectively .", "maternity care is an essential care which has to be made acceptable , accessible , and available at a cost affordable to women , but in case of migrant women , it is available but not acceptable and accessible due to above - mentioned reasons .", "a community - based cross - sectional study conducted in urban area in nainital district mentioned that high proportion of home deliveries even in urban area despite proximity to hospitals is a result of many factors including weak demand , minimal outreach services , weak community - provider linkages , and timings that often do not suit the daily - wage - earning urban poor . in the present study , out of 15 home deliveries , 11 deliveries reason mentioned was lack of transport facility to hospital .", "a study conducted in urban slums of delhi showed that majority of migrants were hindus ( 61% ) , aged 2429 years ( 44% ) , with a literacy rate of 38% ." ], [ "health - care workers and influential people from muslim community should be made aware and trained in explaining necessity of maternal and child health ( mch ) care .", "the present study revealed low utilization of pregnancy - related health - care utilization among the study population .", "for this purpose , during health awareness session , elder members of the family specially mother - in - laws have to be involved on a priority basis and educated about importance of full anc care utilization and institutional delivery .", "this study can provide new insight for policy makers to devote resources for achieving the best possible quality of mch services .", "if necessary , one - to - one counseling should be provided to convince them about correct practices . in the present study ," ], [], [] ]

[ [ "hence , to explore the mechanism of actions of daidzein , its effect on cell proliferation , mammary gland differentiation , and the expression of ers in a prepubertal mammary tumour model was carried out .", "although daidzein also has the ability to bind to the ers , the precise mechanism of action by which it shows a chemoprevention against breast cancer has not been clearly elucidated .", "some studies suggest that the dietary intake of phytoestrogens decreases the risk of breast cancer in humans [ 6 , 7 ] .", "phytoestrogens have been also associated with reduced incidence of various cancers , cardiovascular disease , and osteoporosis and lower cholesterol level [ 25 ] .", "a study on sprague dawley rats ( mammary tumor model ) shows that daidzein has been an effective inhibitor of dmba - induced mammary tumor .", "considering the above literature , it could be hypothesized that daidzein could also affect the differentiation and signaling pathways as a mechanism of chemoprevention ." ], [ "experiment 1a total of thirty - six animals ( female sprague dawley offsprings ) of the same age were divided into 3 groups of 12 each . on postnatal days 16 , 18 , and 20 , while group ii and iii were injected subcutaneously with 500 g / g body weight daidzein and 500 ng / g body weight of estradiol benzoate ( eb ) , respectively [ 19 , 23 ] , an equal volume of vehicle ( dmso ) was injected to the animals of group i ( control , dmso ) . on the 21st day , 18 hours after the last injection ,", "a total of thirty - six animals ( female sprague dawley offsprings ) of the same age were divided into 3 groups of 12 each . on postnatal days 16 , 18 , and 20 , while group ii and iii were injected subcutaneously with 500 g / g body weight daidzein and 500 ng / g body weight of estradiol benzoate ( eb ) , respectively [ 19 , 23 ] , an equal volume of vehicle ( dmso ) was injected to the animals of group i ( control , dmso ) . on the 21st day , 18 hours after the last injection , 6 animals from each group were sacrificed and the rest of the 6 were maintained till the 50th day and sacrificed thereafter .", "all mounts were evaluated for the number of terminal end buds , terminal ducts , and lobules type i by the help of the software imagepro . ", "however , this time the mammary glands obtained at pnd21 and pnd50 were stored for immuno - histochemical experiments . all mounts of fourth pair of the mammary gland of the animals were prepared .", "the mammary glands obtained at both times ( pnd21 and pnd50 ) were preserved for differentiation study . \n ", "the mammary glands obtained at both times ( pnd21 and pnd50 ) were preserved for differentiation study . \n", "the total cells ( unstained ) and immunostained cells were counted with the help of the software imagetool ( uthscsa ) .", "however , this time the mammary glands obtained at pnd21 and pnd50 were stored for immuno - histochemical experiments . \n " ], [ "differentiation of mammary gland was studied by observing the branching of mammary gland and the terminal end buds and ducts and lobular count at two different stages ( i.e. , pnd21 and pnd50 ) after a prepubertal exposure of daidzein to the animals .", "an increase in the count of tebs , tds , and lobules has been seen in the daidzein - treated rat mammary glands at pnd21 , whereas there is a decrease in the teb and td count and further increase of lobule i count at pnd50 as compared to the control , as shown in figure 1 . a similar significant increase of tebs , tds , and lobules has also been seen in the eb - treated animals at pnd21 , and a decrease is seen in tebs and tds and an increase in mammary gland lobules at pnd50 . ", "bcl2/bax ratio was found to be enhanced in mammary gland at pnd21 but not at pnd50 ." ], [ "our data clearly demonstrates , the prepubertal exposure to daidzein by the female sprague dawley rats produces an enhancement in the differentiation of the mammary gland as well as influences apoptosis and the er expression .", "since the development of mammary gland is controlled by female reproductive hormones like estrogen , it is likely that exogenously the administration of the estrogen agonist estradiol benzoate ( eb ) will show an enhancement in the mammary gland development , which has also been reported earlier .", "hence this chemopreventive effect of daidzein can be correlated to the increased differentiation rate of mammary gland caused by the prepubertal exposure of compound . ", "this was further confirmed when the apoptotic marker protein , caspase-3 , which is also known to be one of the principal intracellular effectors of the apoptotic cascade , simultaneously increased in the daidzein - and eb - treated cells along with the increase in apoptotic nuclei , at pnd50 . since daidzein and eb decrease the expression of er- in prepubertal epithelial cells along with the increase in the proliferation and differentiation of cells at the same time , it can be said that the estrogen receptor expression and the mechanism for the proliferation of cells may not be directly correlated , and both proteins might have been influenced by the test compound by separate pathways ." ], [ "thus , it can be concluded that daidzein , in a similar mechanism of action as that of eb , influences the differentiation of mammary gland by affecting cell proliferation proteins and the er- expression .", "since the more differentiated the mammary gland is , the less susceptible it is to cancer incidence , dietary intake of daidzein from an early developmental stages may be beneficial to women folk in particular , which can be further confirmed through clinical trials .", "although the influence of daidzein on some key proliferative and apoptotic proteins has been discussed here , investigations on other cellular pathways integral to the differentiation process can be explored to have a better understanding of the mechanism of actions of daidzein .", "the phytoestrogen daidzein has a potential to regulate the differentiation of mammary gland by maintaining a balance between proliferation and apoptotic death of the cells which is critical for its normal development .", "perturbations in this balance can contribute to the development of various disorders in mammary gland including cancer .", "conditions that upregulate cell proliferation or downregulate apoptosis can allow the accumulation of mutations that contribute to the subsequent development of breast cancer ." ] ]

[ [ "the prevalence of faecoliths in the general population is 3% , and appendicoliths are seen in 10% cases of acute appendicitis .", "faecoliths formed by mineral deposits layered with faecal debris and lodged in the appendix are called appendicoliths .", "acute appendicitis , one of the commonest surgical emergencies , affects nearly 7% of the world 's population and accounts for about 1% of all surgical operations ." ], [ "a 25-year - old male presented to us with pain in the right flank for 1 day .", "a pre - ileal appendix was found hidden in flimsy adhesions posterior to the terminal ileum .", "he underwent laparoscopic appendectomy using a 10-mm supra - umbilical camera port and two 5 mm ports at the supra - pubic region and the left iliac fossa , respectively .", "ncct abdomen ( a and b ) the ct spectral analysis of the appendicolith shows the highest peak of the histogram corresponding to struvite - calcium ( c ) multiplanar reconstruction ( mpr ) coronal image showing appendicolith 2.50 cm size ( longitudinal ) ( d ) axial image showing appendicolith 2.10 cm size ( transverse ) ( e - h ) laparoscopic appendectomy , procedure , specimen and appendicolith ( e ) multiple ligations of base of appendix ( f ) meckel 's diverticulum ( g ) size of appendicolith 3 cm on longest axis ( h ) size of appendicolith 2.5 cm on the perpendicular axis", "urinalysis was normal , and abdominal ultrasound raised a suspicion of small calculi in the right kidney ." ], [ "a giant appendicolith ( > 2 cm ) is extremely rare and only sporadically reported .", "our case is probably the largest documented stone ( 3 2.5 cm ) and the first whose chemical composition has been determined preoperatively by spectral analysis .", "acute appendicitis was first reported by fitz in 1886 , and wangensteen and bowers proposed the theory of an obstructive component as a causative factor in 1937 .", "appendicolith on plain abdominal x - ray is a reliable sign of appendicitis ( 70% ) .", "however , computed tomography ( ct ) is more sensitive , detecting even non - calcified faecoliths ." ], [], [ "the authors have not received any resources from a third party , directly or indirectly , to complete this work ." ] ]

[ [ "it is commonly treated with conservative surgery ; prognosis is rapidly improved by performing concomitant chemotherapy after the initial surgery.1,2 gliomatosis peritonei is the metastatic implantation of mature glial tissue within the peritoneal cavity of patients with ovarian teratomas.3 as second - look or secondary debulking surgery is not generally performed for immature teratoma , as gliomatosis peritonei is not usually discovered in a patient who has completed chemotherapy and shows no evidence of disease.4 this is a rare case of a patient with ovarian teratoma recurrence in the contralateral ovary .", "the first and later occurrences were treated with conservative surgery , using local resections or cystectomies ." ], [ "the tumor is a mass with cystic regions of many sizes , with solid parts and adipocyte - laden parts ( fig .", "although this patient has never conceived a child , she has maintained a regular menstrual cycle , despite multiple surgeries for ovarian teratoma and chemotherapy .", "gravia 0 , para 0was referred to us because of a lower abdominal mass ; magnetic resonance ( mr ) imaging revealed a tumor 20 cm in size .", "sixteen months after the first operation , the patient underwent cystectomy of a left ovarian tumor and a douglas pouch biopsy . pathological diagnosis was mature cystic teratoma of left ovary and gliomatosis peritonei ( fig .", "the diagnosis was stage ii c(a ) immature teratoma grade2 of the right ovary with gliomatosis peritonei .", "the pathological diagnosis was endometrial cyst of left ovary , gliomatosis peritonei and glial implant in lymph node ( fig ." ], [ "we re - performed conservative surgery for contralateral recurrence of an ovarian immature teratoma . as such cases", "presence of glial tissue in lymph nodes is rare , with very few reported cases .", "immature teratoma of grades 1 and 2 are considered ovarian germ cell borderline tumors , according to the world health organization s classification .", "twenty patients ( 42.6% ) attempted conception after chemotherapy , 19 of whom ( 95% ) were successful ; 14 healthy live births were recorded , with no documented birth defects.5 in patients with ovarian germ - cell tumors , a recurrence in the contralateral ovary still could be treated by a local resection or cystectomy followed by chemotherapy if fertility was desired , thereby preserving some normal ovarian tissue , if present.5 however , there is little information about recurrence in the contralateral ovary in patients with immature teratomas . in the present case ,", "patients with intraperitoneal and lymph node metastases of mature glial tissue do not need therapy for such metastases .", "although the gliomatosis peritonei shrank , a lymph node glioma was detected in the fourth surgery ." ] ]

[ [ "the purpose of this study was to determine cesarean birth rates and to find out social factors affecting the cesarean birth in primiparous women .", "cesarean delivery rates have been increasing in a fast manner throughout the world within past few decades ( 1 ) .", "although reasonable cesarean rates have been proposed as 510% by who , cesarean delivery rates across the world varies between 0.4% and 41% ( 2 ) .", "the birth and postpartum processes can imply significant risks for both mother and infant health .", "one of the most important conditions , which have effect on these risks during the birth process is the way of delivery .", "cesarean birth rates are also increasing in turkey in parallel to the developments in the world .", "cesarean delivery rates are influenced by many non - medical factors such as cultural factors , personal characteristics of the woman and socioeconomic features ( 9 ) ." ], [ "the dependent variable of the study is cesarean delivery , and independent variables are the factors related to women s sociodemographic , socioeconomic , health features , health behavior and violence .", "ninety - six percent of the universe was reached ( 214/223 ) . the most prominent reasons for inability to reach the women were absence at the address given ( 2 women ) , permanent migration out of the province ( 1 woman ) and temporary visit to their parents residing in neighboring provinces ( 6 women ) .", "this study was conducted in burdur province , turkey between the dates of 1 jan 201231 dec 2012 .", "a total of 737 childbirths were realized between the dates of 1 jan31 mar 2012 .", "pregnancies and pregnancy outcomes ( abortion , stillbirth and live birth ) are reported to provincial public health directorate by the hospitals and family physicians .", "there are 78 family health units and four general hospitals including three public , and one private sector in the province of the study ." ], [ "the most prominent reasons for inability to reach the women were absence at the address given ( 2 women ) , permanent migration out of the province ( 1 woman ) and temporary visit to their parents residing in neighboring provinces ( 6 women ) .", "the universe of this cross - sectional type study was formed by 223 primiparous women ." ], [ "data collection form was made up of the questionnaire containing women s sociodemographic , biodemographic , birth characteristics and babies gender and weight .", "the dependent variable of the study is cesarean delivery , and independent variables are the factors related to women s sociodemographic , socioeconomic , health features , health behavior and violence ." ], [ "the data was collected using face - to - face interview technique after getting verbal consent from the woman , by midwives working in community health center between the dates of 15 apr31 may 2012 after necessary permissions were obtained from public health directorate .", "the midwives who would collect data were provided 3-h training , which includes the aim of the study , what each of questions targeted and the circumstances required to be considered at the stage of data collection in order to ensure standardization before data collection ." ], [ "the independent variables ( p<0.05 ) which resulted as statistically significant in chi - square analyses , have been taken into backward logistic regression analyses .", "chi - square and backward lr logistic regression analyses were used , odds ratio and confidence interval was calculated .", "the data was analyzed in spss 20 ( chicago , il , usa ) packaged software . in these analyses ," ], [ "when the table is monitored , it is seen that there is statistically significant relationship between the delivery mode and the place of residence , women s age , women s family type and her husband s employment status and presence of health insurance . when it is examined in terms of birth and infants characteristics", ", a significant relationship was shown between the delivery mode with doctor s influence in taking decision and the place of birth ( table 2 ) .", "sociodemographic features of women birth and infant features 3 data is missing in cesarean group the factors affecting caesarean deliveries are seen in table 3 . accordingly , when public hospitals are taken as reference , caesarean deliveries were increased by 11.2 fold in the event of the delivery in private hospital ; 6.1 fold in the event of the delivery in university hospital . again with reference to the conditions of woman s husband work on her own account , working in private sector or public sector increases 2.2 fold the caesarean birth .", "doctor s guidance increases the caesarean 4.0 times with reference to those who say doctor had no impact on the delivery mode . when the deliveries made between 17:0007:59 are taken as reference , caesarean deliveries are increased by 7.1 times between 08:0016:59 ." ], [ "women s place of residence , age , presence of health insurance , family type , husband s job , the place of birth , the birth hour and doctor s intervention to delivery mode have been identified as factors affecting the caesarean section delivery in univariate analyses performed .", "one of the surprising aspects of the study was the 11.2 fold increase in caesarean delivery rates at private hospitals in spite of its equivalent adequacy with 2nd step health institutions in terms of the equipment with reference to public hospitals .", "caesarean deliveries are preferred because of physicians habits , caesarean deliveries bring more income and vaginal births take more time and defensive medicine application due to the fear of malpractice and complication during birth or pregnancy ( 18 ) .", "caesarean deliveries are preferred especially for pregnant women at risk due to possible complications in terms of mother and infant during delivery , cephalopelvic disproportion or high birth weight infants . in such cases ,", "we believe that the increase with doctor s effect in caesarean deliveries occurs in two ways ." ], [ "although the results do not show all of the factors affecting the caesarean delivery in primiparous , they also reveal that medical reasons are not the only reason in this increase trend .", "the strong side of the study is taking only the women who gave first birth in the study and reaching the complete universe of the study . on the other hand , indetermination and non - exclusion of caesarean sections with medical causes in study questions", "health policy makers and health professionals are required to identify the causes of this increase and to take measures ." ], [ "ethical issues ( including plagiarism , informed consent , misconduct , data fabrication and/or falsification , double publication and/or submission , redundancy , etc . ) have been completely observed by the authors ." ] ]

[ [ "las fracturas por fragilidad asociadas a la osteoporosis suponen un gran coste econmico y personal para la sociedad .", "aunque los productos lcteos son una buena fuente de calcio , los pacientes que no pueden digerir la lactosa tienden a evitarlos y tienen un mayor riesgo de fractura que la poblacin general ." ], [ "153 de 1527 miembros de una comunidad que compra leche cruda complet una encuesta online en relacin a la leche cruda ." ], [ "el motivo principal que los encuestados citaron para beber leche cruda fue que crean que era ms sano ; el 30 % notific ciertas molestias gastrointestinales al beber leche pasteurizada , aunque casi todos ( 99 % ) notificaron consumir leche cruda sin molestias ." ], [ "el motivo principal para beber leche cruda es su valor saludable percibido , no su digestibilidad .", "aunque la leche cruda parece ser digerida ms fcilmente que la pasteurizada en la muestra de nuestra encuesta , se desconoce el mecanismo de digestibilidad ." ], [ "we intend to clinically evaluate the digestibility of raw milk vs pasteurized milk , but to guide the design of our study ,", "we need more background information . therefore , we surveyed consumers of raw milk to determine the health - related motivations for consuming raw milk , especially as they relate to lactose maldigestion .", "so what are perceived by some to be the benefits of raw milk may have as much to do with the type of cow ( a1 vs a2 ) and husbandry ( pastured and grass - fed vs confined and ration - fed ) as with the manner in which the milk is pasteurized ( or not ) .", "yet we found no reports in the literature supporting the anecdotal reports that lactose maldigesters are able to consume raw milk without discomfort . also unreported or under debate in the literature", "is the mechanism that allows maldigesters of pasteurized milk to consume raw milk without discomfort .", "the popular media occasionally present anecdotal stories regarding the benefits of consuming raw dairy products ." ], [ "we analyzed differences in reported discomfort from drinking raw vs pasteurized milk and in drinking pasteurized milk before and after drinking raw milk for significance ( p<.05 ) using mcnemar 's test .", "we queried on the digestibility of drinking milk under three conditions : ( 1 ) the reaction to drinking pasteurized milk before switching to raw milk ; ( 2 ) the reaction experienced currently when drinking raw milk ; and ( 3 ) the reaction of drinking pasteurized milk after having switched to raw milk .", "we asked about the digestibility of other dairy products , namely yogurt , cheese , and ice cream .", "we developed an online survey of 16 questions , which was available from december 7 , 2012 , until january 31 , 2013 ." ], [ "of the 16 questions on the survey , only four were answered by all respondents , but all were answered by at least 148 ( 96.7% ) ( table ) . of the 153 respondents , most ( 86 ) cited that they consumed raw milk because they believed it to be more healthful and easier to digest .", "there was no significant reduction in discomfort of the respondents between the before and after drinking raw milk periods .", ": 12 said raw milk tasted better than pasteurized milk ; 8 cited social / environmental concerns such as supporting local farmers , it is better for the cows , etc ; 6 cited that they had allergies to pasteurized milk ; two claimed it cured unspecified ills ; and six cited individual reasons such as i grew up on it or [ i ] do n't eat processed food .", "two respondents reported not drinking pasteurized milk but symptoms when they did drink pasteurized milk ." ], [ "these findings suggest that the symptoms of lactose intolerance were mild enough to not warrant the respondents ' seeking a medical diagnosis or that the respondents self - diagnosed and sought alternatives to pasteurized milk .", "we hypothesized that one motivation for raw milk consumption was to avoid symptoms associated with lactose maldigestion .", "yet almost half of the respondents indicated that they had no ill effects after drinking pasteurized milk . despite the number of respondents indicating some gastrointestinal ( gi ) discomfort when", "having previously consumed pasteurized milk , only 5 ( 3% ) respondents were diagnosed as lactose intolerant , and only 1 ( 0.7% ) was confirmed lactose intolerant by means of an hbt .", "in the current study , survey results suggest that the motivation for raw milk consumption is complex ." ] ]

[ [ "the present manuscript sought to exploit dab photo - oxidation of mag - fura 2 for visualizing er ca distribution in hela cells , which are among the most widespread model cell lines used for studying intracellular ca signaling .", "this method combines the specificity of available fluorophores to the high spatial resolution offered by transmission em to detect fluorescing molecules even when present in low amounts in membrane - bounded organelles .", "the technique utilizes the photo - oxidation of diaminobenzidine ( dab ) in presence of the emission of an excited fluorochrome , and it has been shown to be efficient on different dyes and conditions ." ], [ "the solutions , different in ca concentration , are the following : physiological salt solution ( pss ) , with the following composition : 150 mm nacl , 6 mm kcl , 1.5 mm cacl2 , 1 mm mgcl2 , 10 mm glucose , and 10 mm hepes ; ca - free solution ( 0 ca ) , where ca has been substituted by 2 mm nacl , and 0.5 mm egta was added , whereas the solution with ca more concentrated is similar to pss in composition except for 120 mm nacl and 20 mm cacl2 .", "intracellular ca deposits have been marked by fluorescent dye - based calcium indicator mag - fura-2 , acetoxymethyl ( am ) ester uv light - excitable ( life tchnologies , carslbad , ca , usa ) , added to the three calcium solutions to obtain a final concentration of 5 m .", "ninety nm ultrathin sections have been cut by a reichert ultramicrotome , transferred to grids without membrane and visualized by a zeiss em900 transmission electron microscope operating at 80kv .", "cells have thus been incubated at 37c in the dark , for 1 h. cells cultured on chamber slides , and treated as hereto described , have been analyzed at fluorescence microscopy .", "cells have been plated in 6 wells cell culture plate ( 1x10 cells per well ) , or in chamber slides for staining and microscopic examination ( 8x10 cells per well ) .", ", some cells were incubated in the absence of mag - fura 2 , treated with dab and processed as above ." ], [ "the solutions , different in ca concentration , are the following : physiological salt solution ( pss ) , with the following composition : 150 mm nacl , 6 mm kcl , 1.5 mm cacl2 , 1 mm mgcl2 , 10 mm glucose , and 10 mm hepes ; ca - free solution ( 0 ca ) , where ca has been substituted by 2 mm nacl , and 0.5 mm egta was added , whereas the solution with ca more concentrated is similar to pss in composition except for 120 mm nacl and 20 mm cacl2 .", "the day after seeding , when cells reached about 90% confluence , the medium has been removed from the wells and replaced with three solutions , one for each experimental condition .", "cells have been plated in 6 wells cell culture plate ( 1x10 cells per well ) , or in chamber slides for staining and microscopic examination ( 8x10 cells per well ) .", "all the solutions have been brought to ph 7.4 with an osmolality of 338 mmol / kg , measured with an osmometer ( wescor 5500 ; wescor , inc . , logan , ut , usa ) .", "hela cells have been cultured in iscove s modified dulbecco s medium ( imdm , lonza , basel , switzerland ) supplemented with 10% fetal bovine serum , 2% l - glutamine , 1% penicillin and streptomycin , at 37c air atmosphere with 5% co2 . after reaching 90% confluence ," ], [ "intracellular ca deposits have been marked by fluorescent dye - based calcium indicator mag - fura-2 , acetoxymethyl ( am ) ester uv light - excitable ( life tchnologies , carslbad , ca , usa ) , added to the three calcium solutions to obtain a final concentration of 5 m .", "cells have thus been incubated at 37c in the dark , for 1 h. cells cultured on chamber slides , and treated as hereto described , have been analyzed at fluorescence microscopy .", ", some cells were incubated in the absence of mag - fura 2 , treated with dab and processed as above .", "an olympus bx51 microscope ( olympus italia srl , segrate , italy ) was used under the following conditions : 100-w hg lamp as the excitation source , 330- to 385-nm excitation filter ( excf ) , 400-nm dichroic mirror ( dm ) , and 420-nm barrier filter ( bf ) ; 100 olympus uplanfl oil - immersion objective lens ( na 1.25 ) . images were recorded with an olympus magnifier digital camera system , and stored by the olympus cellf software ." ], [ "ninety nm ultrathin sections have been cut by a reichert ultramicrotome , transferred to grids without membrane and visualized by a zeiss em900 transmission electron microscope operating at 80kv .", "fixed and photoconverted cells have been washed twice with distilled water and postfixed with 2% osmium tetroxide in water for 1 h , at room temperature .", "once the osmium was removed and the cells rinsed several times with distilled water , cells have been scraped , centrifuged discarding supernatant , dehydrated in a graded series of ethanol and embedded in lrwhite resin ( sigma aldrich ) ." ], [ "the end product of the dab photoconversion is a speckled , dense precipitate of varying size .", "calcium labeling with mag - fura 2 results in highly fluorescent staining mainly localized in the cytoplasm .", "the dab photoconversion is an efficient way to stabilize the ions and to visualize them .", "however , another abundant end product is present as small sized dots , showing a markedly lower electrondensity ( figure 3f , inset ) and a widespread distribution .", "when the cells are incubated in pss , the signal is lower ( figure 1b ) and mostly present in the perinuclear vesicles , while the cytoplasmic signal far from the nucleus somehow disappears . in the last condition , without calcium and in the presence of egta , some labeling is still visible , although to a much reduced level ( figure 1c ) ." ], [ "we show in this paper that mag - fura 2 photoconversion via dab oxidation is an efficient way for localizing ca ions at em level . moreover ,", "an important amount of precipitates were found in the cell and especially in the nucleus ; our method gives a much finer end product , and this allows a superior resolution and localization . in conclusion , this method is a reliable and efficient technique for stabilizing and visualizing ca ions at em .", "this could be considered also as a means of stabilizing their presence , thus limiting the loss of ions . as for the method ," ] ]

[ [ "nearly , 90% of metastatic tumors occur in jaw bones , especially premolar - molar region of the mandible , whereas metastases to soft tissues are extraordinarily rare and account for 0.1% of all oral malignancies .", "hence , this article emphasizes on detailed dentoalveolar examination and early diagnosis for finding the primary focus of metastatic tumor .", "although infrequent , oral metastases are rarely encountered as the first sign of occult cancer .", "oral metastatic tumors are found to be the first sign of metastatic spread and in some instances ; they are an indication for unidentified primary tumor of the distant site .", "the primary site differs according to oral site colonization . in men , primary tumor of the lung followed by the prostate gland and kidney" ], [ "the lesion was diagnosed as a metastatic malignant tumor , probably metastasizing from the lung .", "based on the clinical presentation , a differential diagnosis of inflammatory swelling , odontogenic cyst , odontogenic tumor , soft tissue tumor or metastatic tumor to the jawbones was given .", "a 60-year - old male patient presented with a swelling in the right lower back teeth region of the jaw since 3 months [ figure 1 ] .", "the patient was a known hypertensive since 4 years . a well - defined solitary swelling present on the right side of mandible on extraoral examination , a well - defined , solitary swelling measuring 4 cm" ], [ "the common primary sources of tumors metastatic to the oral region are the breast , lung and kidney .", "the most common primary sites for oral metastases were the lung , kidney , liver and prostate for men ; breast , female genital organs , kidney , and colorectum for women . in our case too , lung was found to be the primary site .", "most of the patients are aware of primary tumors before the metastatic spread to the oral cavity . in our case ,", "most of the patients complain of rapidly progressing swelling , pain , paresthesia , difficulty in chewing , dysphagia , disfigurement and bleeding .", "the actual incidence of these cancers is unknown since oral metastatic disease is usually a manifestation of advanced disease ." ], [], [] ]

[ [ "wisconsin card sorting test ( wcst-64 ) is a neuropsychological test for assessing problem solving , sorting , abstract thinking , ability to maintain concepts and cognitive flexibility skills which are related to performances of the frontal lobe . in this test", "all cases in the study and the control group were matched based on age , sex and iq level . in the current study four tools of structured interview , wechsler intelligence scale for children - revised ( wisc - r ) and child symptom inventory-4 ( csi-4 ) were used .", "child symptom inventory-4 ( csi-4 ) is a screening tool for the symptoms of behavioral and emotional disorders in children based on the diagnostic criteria of dsm - iv .", "the study population was all the 6 to 9 year- old students from the districts of one and two in yazd , an old and big city located in the center of iran .", "the test - retest reliability of the parent checklist in an iranian sample was reported as 0.90 .", "moderate internal consistency for total iq , verbal iq and performance iq were reported as 0.96 , 0.95 and 0.91 by wechsler , respectively(34 ) . in the present study we used total iq score to match the participants ." ], [ "the study population was all the 6 to 9 year- old students from the districts of one and two in yazd , an old and big city located in the center of iran .", "all cases in the study and the control group were matched based on age , sex and iq level .", "finally , 45 students ( 15 students in each adhd subtype groups ) were remained as the study group .", "all the students ( from both sexes ) with all adhd subtypes were participated as the study group .", "students who were diagnosed with adhd in the past and were under treatment with medicine were excluded from the study due to the medicines effect on attention . in the current study ,", "for the study group , 56 students were selected from imam hussein counseling center ( counseling center of educational organization of yazd province ) who were referred by their school staff and had received adhd diagnosis by a child psychiatrist based on dsm - iv - tr criteria and had no comorbid disorders .", "none had a history of psychiatric disorders or developmental delay based on their parents report .", "the child symptom inventory-4 ( csi-4 ) was filed out by parents to be used for the diagnosis and differentiation between the adhd subtypes . of the participants ," ], [ "in the current study four tools of structured interview , wechsler intelligence scale for children - revised ( wisc - r ) and child symptom inventory-4 ( csi-4 ) were used .", "wisconsin card sorting test ( wcst-64 ) is a neuropsychological test for assessing problem solving , sorting , abstract thinking , ability to maintain concepts and cognitive flexibility skills which are related to performances of the frontal lobe . in this test", "child symptom inventory-4 ( csi-4 ) is a screening tool for the symptoms of behavioral and emotional disorders in children based on the diagnostic criteria of dsm - iv .", "the test - retest reliability of the parent checklist in an iranian sample was reported as 0.90 ." ], [ "data were entered in spss-17 and analyzed by t - test and anova static tests to clarify the differences between adhd and normal group and between adhd subtypes .", "scheffe s test was also used to identify which groups were different . the mean and standard divisions ( sd ) were used for descriptive analysis ." ], [ "the study group consisted of 45 school aged children ; of whom , 27 were male and 18 were female . in the control group", "data analysis showed that adhd and normal group were significantly different in terms of perseverative responses , perseverative errors and total errors on wsct ( tables 2 and 3 ) as shown in table 4 , adhd subtypes were significantly different in terms of perseverative responses ( p 0/01 ) and perseverative errors ( p0/001 ) . based on scheffe s test ,", "adhd - h was not different from adhd - i and adhd - c but there were significant differences between adhd - i and adhd - c in terms of perseverative responses and perseverative errors .", ", there were 30 school aged children , of whom 18were male and 12 were female .", "other characteristics of the two groups ( age , iq , adhd subtype frequency ) are presented in table 1 ." ], [ "the aim of the present study was to investigate the differences between adhd subtypes in terms of executive function profile .", "investigated the executive function in 94 children with adhd ( without any co - morbid disorder ) in terms of subtype and gender using five tests of the wisconsin card sorting test , the stroop color - word test , the matching familiar figures test , the trail making test , and the tower of london .", "also , we found that adhd subtypes operated differently in the executive function domain ( p 0.01 ) ; children with adhd predominantly combined type showed more perseverative responses and perseverative errors than children with adhd predominantly inattentive type .", ", we found that children with adhd significantly differed from normal children in terms of total errors , perseverative errors and perseverative responses ( p 0.01 ) ." ], [ "the first and most notable limitation of our study was that we only used one test to assess the executive function ; and the second limitation was that we did not directly evaluate the control group for psychiatric disorder and only relied on the parental report .", "our findings revealed that executive function patterns are different in children with adhd compared to normal children .", "our study also confirmed that adhd subtypes are different in terms of perseveration and response inhibition domains ; adhd - c type showed more deficits in perseveration and response inhibition ." ], [ "our findings revealed that executive function patterns are different in children with adhd compared to normal children .", "our study also confirmed that adhd subtypes are different in terms of perseveration and response inhibition domains ; adhd - c type showed more deficits in perseveration and response inhibition ." ] ]

[ [ "the visual environment provides a vast assortment of information to the sighted individual during the acts of daily living . for the visually - impaired individual ,", "our proposed device uses a vibrotactile stimulator to provide visual information gathered from a color camera system .", "we believe that this placement promotes an intuitive coupling between the scene pointed to by the camera mounted on the fingertip and the feedback felt by that finger . in general , it is imperative for designers of any sensory substitution system to consider not only what is technologically feasible , but also what is functional in the context of the sensory and cognitive limitations of the user . in a review of sensory substitution for the blind , loomis and klatzky pointed to the need to couple device design to the capabilities of the user for a given task .", "devices using a concept we call fingersight are intended to allow visually impaired users to remotely identify objects of interest in , and navigate through , natural environments , by acting as a sensory substitution system for the user 's sense of sight .", "we specifically consider substitution for the visual system by the haptic system ( i.e. , one 's sense of touch ) ." ], [ "thus the system created a haptic stimulus ( vibration ) whenever a properly oriented visual edge was encountered by the laser . \n", "regenerative feedback between the amplitude of the detected signal from the reflected laser and the solenoid caused the laser to vibrate vertically when the laser spot was located on any edge between light and dark objects .", "the laser was modulated at 10 khz , allowing its reflection by objects in the environment to be detected by a non - directional phototransistor in the midst of other sources of light .", ", we review them briefly here . our initial system permitted active interrogation of the visual surroundings with a miniature red laser attached to the fingertip ( see fig . 1 ) .", "a full video image captured at each pose of the finger offers many advantages , including immediate extraction of more complex features , identification of entire objects , and even determination of camera motion directly from the changing image .", "real - time analysis of the video signal from a miniature camera was used to control the cell - phone vibrator ." ], [ "each entry is the number of occurrences of the associated stimulus / response pair . \n ", "each entry is the number of occurrences of the associated stimulus / response pair . \n", "the data were also analyzed by measuring information transfer \\documentclass[12pt]{minimal } \n \\usepackage{amsmath } \n \\usepackage{wasysym } \n \\usepackage{amsfonts } \n \\usepackage{amssymb } \n \\usepackage{amsbsy } \n \\usepackage{upgreek } \n \\usepackage{mathrsfs } \n \\setlength{\\oddsidemargin}{-69pt } \n \\begin{document } \n } { } $ i$\\end{document } , in order to determine the number of bits that can be transmitted by the device under the experimental conditions .\\documentclass[12pt]{minimal } \n \\usepackage{amsmath } \n \\usepackage{wasysym } \n \\usepackage{amsfonts } \n \\usepackage{amssymb } \n \\usepackage{amsbsy } \n \\usepackage{upgreek } \n \\usepackage{mathrsfs } \n \\setlength{\\oddsidemargin}{-69pt } \n \\begin{document } \n } { } $ $ i=\\sum_{j=1}^{k}\\sum_{i=1}^{k}{p\\left(s_{i},r_{j}\\right)\\log_{2}\\left({{p\\left(s_{i}\\vert r_{j}\\right)}\\over{p\\left(s_{i}\\right)}}\\right)}.\\eqno{\\hbox{(4)}}$$\\end{document } here , \\documentclass[12pt]{minimal } \n \\usepackage{amsmath } \n \\usepackage{wasysym } \n \\usepackage{amsfonts } \n \\usepackage{amssymb } \n \\usepackage{amsbsy } \n \\usepackage{upgreek } \n \\usepackage{mathrsfs } \n \\setlength{\\oddsidemargin}{-69pt } \n \\begin{document } \n } { } $ k$\\end{document } is the number of possible stimuli , and \\documentclass[12pt]{minimal } \n \\usepackage{amsmath } \n \\usepackage{wasysym } \n \\usepackage{amsfonts } \n \\usepackage{amssymb } \n \\usepackage{amsbsy } \n \\usepackage{upgreek } \n \\usepackage{mathrsfs } \n \\setlength{\\oddsidemargin}{-69pt } \n \\begin{document } \n } { } $ s_{i}$\\end{document } and \\documentclass[12pt]{minimal } \n \\usepackage{amsmath } \n \\usepackage{wasysym } \n \\usepackage{amsfonts } \n \\usepackage{amssymb } \n \\usepackage{amsbsy } \n \\usepackage{upgreek } \n \\usepackage{mathrsfs } \n \\setlength{\\oddsidemargin}{-69pt } \n \\begin{document } \n } { } $ r_{j}$\\end{document } represent a specific stimulus - response pair .", "these levels are well above chance in this six - alternative choice task \\documentclass[12pt]{minimal } \n \\usepackage{amsmath } \n \\usepackage{wasysym } \n \\usepackage{amsfonts } \n \\usepackage{amssymb } \n \\usepackage{amsbsy } \n \\usepackage{upgreek } \n \\usepackage{mathrsfs } \n \\setlength{\\oddsidemargin}{-69pt } \n \\begin{document } \n } { } $ ( { \\rm chance}=0.16)$\\end{document}. \n table iconfusion matrix for set 1reported angle ( deg)90603003060stimulus angle ( deg)9071131011060168252003008843100101081313000068196040003260confusion matrix for angle set 1 .", "relative to the 2.58 bits of information in the six - alternative choice task , angle set 1 ( angles with 30 increments ) had an information transfer of 1.62 bits , while angle set 2 ( angles with 15 increments ) had an information transfer of 1.12 bits ." ], [ "we have developed a new method of providing the finger with haptic feedback about visual targets in the general environment , by permitting the finger to scan the environment directly to locate those targets .", "we have developed this idea , which we call fingersight , through a series of prototypes , exploring the particular application of detecting edges . in the process , we have developed a new spatiotemporal \\documentclass[12pt]{minimal } \n \\usepackage{amsmath } \n \\usepackage{wasysym } \n \\usepackage{amsfonts } \n \\usepackage{amssymb } \n \\usepackage{amsbsy } \n \\usepackage{upgreek } \n \\usepackage{mathrsfs } \n \\setlength{\\oddsidemargin}{-69pt } \n \\begin{document } \n } { } $ n$\\end{document}-dimensional edge detection algorithm of potentially general interest , which is simultaneously capable of detecting the presence of a stationary edge as well as having passed over an edge between successive timeframes .", "the information transmission of the fingersight device is intrinsically constrained by basic sensorimotor abilities of motor control , kinesthetic sensing , and spatial cognitive processing .", "we have conducted proof - of - concept experiments showing that under active exploration the fingersight device is capable of transmitting visual spatial information through haptic channels . sighted , blindfolded subjects were able to use the device to differentiate between angles separated by as little as 15. performance with the coarser angle set , where responses were separated by 30 showed that fingersight transmitted close to 2/3 of the available information in the stimulus , with most errors being near misses ." ] ]

[ [ "it negatively influences the child 's quality of life and is an important cause of absence from school and also a significant factor in health - related costs among children and adolescents .", "frequency of headache increases with age in this population . in the present study we aimed to determine epidemiologic characteristics and compare socioeconomic and some clinical factors related to primary headaches in children / adolescents ( 4 - 15 year olds ) presented to neurology clinics of tabriz university of medical sciences .", "its prevalence varies greatly from 5.9 to 82% , depending on the definition criteria and the age of the patients .", "primary headache is not attributed to any other disorder . in the majority of patients with primary headache , general and neurological examinations are normal and", "the international headache society classifies headaches into primary and secondary type in classification of headache disorders 2 edition ( ichd - ii ) ." ], [ "the institutional review board at tabriz university of medical sciences approved the study protocol . after obtaining a written informed consent from parents , children with 4 - 15 years of age and with the diagnosis of primary headache ( migraine or tension - type headaches ) who presented to the neurology clinics affiliated to tabriz university of medical sciences , tabriz , iran from march 2009 to october 2011 were included in this cross - sectional study .", "we noted the type of headache , history of atopy , asphyxia during labor ( according to the history of admission in the neonatal intensive care unit after birth due to respiratory problems based on the parents report and review of the previous medical records ) and breast feeding , family history of headache , presence of headache triggers and the socioeconomic status of the family .", "a total of 190 patients fulfilled the criteria for enrollment in the study and their demographics were collected .", "diagnosis of migraine and tension - type headache was based on the international headache society diagnostic criteria for the primary headache disorders .", "socioeconomic status was determined according to the total monthly family income ( < 7,000,000 rl vs = 7,000,000 rl ) based on the index of statistical center of iran for grand cities in the years of study in addition to the highest level of education of the father ( < or = high school vs. > or = college ) ." ], [ "eighty eight patients ( 46.3% ) had migraine and 102 patients ( 53.7% ) had tension - type headache .", "in female patients the frequencies of both migraine and tension - type headache were significantly higher in the age group of 10 - 15 years as compared to the age group of 4 - 9 years ( p=0.03 and 0.04 , respectively ) .", "the clinical presentations of aura in patients with migraine the characteristics compared between patients with migraine and tension - type headache as triggering factors for headache ; or : odds ratio ; ci : confidence interval history of asphyxia during labor was more prevalent among patients with migraine as compared to the tension - type headache ( p=0.007 , or = 3.24 ) . history of headache in parents was also significantly higher in patients with migraine as compared to tension - type headache ( p=0.001 , or = 3.19 ) .", "migraine and tension - type headache had comparable frequency in different age groups of male patients ( p=0.1 and 0.07 , respectively ) .", "the low socioeconomic status was more prevalent in patients with migraine headache ( p=0.003 , or = 2.38 ) .", "the distributions of gender and age groups in patients with migraine or tension - type headache data are presented as numbers no significant differences were seen in the distribution of gender between the patients with migraine and tension - type headache .", "the distributions of gender and age groups in patients with migraine or tension - type headache are shown in table 1 . \n " ], [ "the main finding in the present study was that gender can not predict the type of primary headache in younger children , as no gender differences were seen between the patients with migraine or tension - type headache in the age group 4 - 9 years .", "this finding reveals that female adolescents had higher risk for developing primary headache specially migraine as compared to female children .", "our results showed that socioeconomic status of the patients could significantly influence the frequency of migraine in comparison to tension - type headache .", "we also showed that atopy is more prevalent in patients with migraine as compared to tension - type headache .", "our results also demonstrated that the frequencies of migraine and tension - type headache were comparable in different age groups of male patients , whereas female patients in the age group 10 - 15 years had higher frequency of both types of headache especially migraine as compared to the age group 4 - 9 years ." ], [ "while some variables have been checked by the present report , further prospective studies with larger sample sizes are needed to provide more comprehensive data regarding associated factors in childhood primary headache ." ], [] ]

[ [ ". the study will evaluate overall survival of metastatic colorectal cancer patients with cachexia who are administered the mab as a monotherapy .", "the efficacy and safety of induction and four maintenance regimens of brodalumab compared with placebo and ustekinumab in patients with moderate - to - severe plaque psoriasis is being evaluated .", "the recombinant immunotoxin moxetumomab pasudotox ( cat-8015 , astrazeneca ) is undergoing evaluation in a phase 3 study ( nct01829711 ) of patients with relapsed / refractory hairy cell leukemia .", "abbreviations : cd , cluster of differentiation ; il , interleukin ; pcsk9 , proprotein convertase subtilisin / kexin type ; sle , systemic lupus erythematosus . note : table compiled from information available as of april 25 , 2013 . * in - licensed" ], [ "recently announced results for three late - stage studies of two mabs for cancer ( farletuzumab , naptumomab estafenatox ) and tabalumab , a mab treatment for autoimmune disorders , indicate that clinical endpoints were not met .", "farletuzumab ( morab-003 , morphotek / eisai ) is a humanized igg1 mab that targets human folate receptor , which is overexpressed in most epithelial ovarian cancers , as well as some forms of endometrial , breast , renal , lung and colorectal cancers .", "tabalumab in combination with bortezomib and dexamethasone is also being evaluated in a phase 2/3 study ( nct01602224 ) of patients with previously treated multiple myeloma .", "the primary endpoint of progression - free survival ( pfs ) was not met in the phase 3 far-131 study ( nct00849667 ) of farletuzumab in combination with carboplatin and a taxane in patients with platinum - sensitive epithelial ovarian cancer in first relapse .", "tabalumab , a human igg4 targeting b - lymphocyte stimulator , was being evaluated in five phase 3 studies of ra patients ." ], [ "historically , ~50% of mabs in the commercial clinical pipeline have been studied as cancer agents ; however , ~67% of the current cohort of mabs at phase 3 is in studies for non - cancer indications ( table 1 ) .", "the mabs are being developed as treatments for immunological disorders such as ra , sle , ms and psoriasis , but also for hypercholesterolemia , cachexia and alzheimer disease . reflecting the overall greater challenge of demonstrating safety and efficacy in cancers ,", "of particular note is the inclusion of a toxin in three molecules ( naptumomab estafenatox , moxetumomab pasudotox , inotuzumab ozogamicin ) and use of less than a full - length sequence for three molecules ( naptumomab estafenatox , moxetumomab pasudotox , onartuzumab ) . the majority ( 70% ) of the 10 product candidates", "mabs will continue to track the progress of antibody therapeutics in clinical study throughout 2013 , and we look forward to reporting on results that may be released during the year in which are the antibodies to watch in 2014 ?", "the molecular types of the 10 mabs in late - stage studies of cancer ( table 2 ) are more diverse than those for non - cancer indications .", "the number of anti - cancer mabs at phase 3 is likely to increase in the next 35 y as more adcs move into and through the clinical pipeline . \n", "these 20 mabs are human or humanized , with more than half ( 55% ) targeting an interleukin or an interleukin receptor ." ] ]

[ [ "they may be seen in midline or para - axial location , from the brain to the sacral area .", "the oropharyngeal cavity is exceedingly rare for teratomas , 2% of all teratomas , present as large masses protruding from the oropharyngeal area .", "they display a particular tendency to locate in the sacrococcygeal and pre - sacral regions . reported incidence of tumors at these sites", "so , principles of management in such patients comprise of the immediate postpartum establishment of a secure airway , if needed via tracheostomy and complete surgical resection of the mass .", "though oropharyngeal teratomas have a benign histopathology , they are potentially lethal as they may cause airway obstruction and respiratory compromise ." ], [ "a 1980 g female infant born to 22-year - old mother after 38 weeks gestation presented with a growth in oral cavity associated with respiratory distress .", "now , the patient is under routine follow - up , and palatoplasty has been done .", "no intracranial extension [ figure 2 ] . computed tomography scan image after due preparation , the patient was operated , and the mass was excised in toto [ figure 3 ] .", "it was hampering feeding . computed tomography scan showed mass lesion in the palatal region ( attached to the palate , more on the right side ) .", "microscopic picture 1 microscopic picture 2 following excision , patient recovered faster and gained weight ." ], [ "early diagnosis , the establishment of the good airway , complete excision of tumor and timely follow - up should increase the survival of newborns with oral teratomas .", "most of the teratomas in the pediatric age group are benign , but reports of malignant teratoma do exist .", "teratomas are the tumors which contain tissues derived from all three germ layers . these contain tissues foreign to the anatomical site of origin .", "the basic principle of management of oropharyngeal teratomas is the establishment and maintenance of a secure airway ." ], [], [] ]

[ [ "the rationale underlying treatment recommendations based on esthetic impairment come from the social science researches , which indicate that unacceptable dental appearance may stigmatize , impede career advancement and peer group acceptance , encourage negative stereotyping , and have a negative effect on self - concept .", "the study was undertaken to assess the orthodontic treatment need in 2025-year - old patients reporting to the department of orthodontics and dentofacial orthopaedics , as assessed by orthodontists to plan future orthodontic services in the region as per priority in orthodontic triage , for worldwide comparisons , and as a powerful tool for patient counseling .", ", epidemiologic studies of malocclusion suffered from considerable disagreement among investigators , especially regarding how much deviation from the ideal should be accepted within the bounds of normal .", "orthodontic problems are usually not associated with grave mortality or morbidity ; hence , they tend to be overlooked by most health professionals as less important .", "it is being widely used in dental epidemiology to prioritize orthodontic treatment and seeks to quantify the likely sociopsychological effects of each patient 's malocclusion .", "the orthodontic treatment need in the study group was assessed by esthetic component ( ac ) of the index of orthodontic treatment need ( iotn ) .", "however , studies reveal that malocclusions have a significant impact on the psychosocial health of the affected individual . for many years" ], [ "the study was undertaken to assess the orthodontic treatment need in 2025-year - old patients reporting to the department of orthodontics and dentofacial orthopaedics , as assessed by orthodontists to plan future orthodontic services in the region as per priority in orthodontic triage , for worldwide comparisons , and as a powerful tool for patient counseling ." ], [ "this states that the examiner , in general , expressed satisfaction with the esthetics of most of the screened patients , like the one shown in figure 2 unlike the one in figure 3 that without doubt required treatment . a patient categorized with slight need for orthodontic treatment a patient in severe / definite need for orthodontic treatment", "esthetic component of the index of orthodontic treatment need scale ( photographs 110 ) the ac of iotn has commonly been used to evaluate the treatment need on esthetic grounds by dentists ( operator - rated ) or patients ( self - rated ) .", "the division of sample according to gender division of the subpopulation according to the age patients were examined clinically using mouth mirror and explorer .", "the anterior teeth were graded in their dental attractiveness as seen and no endeavor was made to predict the future appearance of the dentition .", "ac was assessed by comparing and matching digitally clicked intraoral frontal view photograph in occlusion to the nearest resemblance on standardized photographs of iotn ." ], [ "all the data were analyzed using the statistical package for the social sciences 13.0 software program , ibm corporation , new york , usa . results of the ac revealed that 78.1% exhibited no or slight need for treatment , whereas 13.2% demonstrated moderate to borderline need , and only 8.7% proved to have a definite need for orthodontic treatment .", "this states that the examiner , in general , expressed satisfaction with the esthetics of most of the screened patients , like the one shown in figure 2 unlike the one in figure 3 that without doubt required treatment . a patient categorized with slight need for orthodontic treatment a patient in severe / definite need for orthodontic treatment" ], [ "management of malocclusion is contained by a number of disciplines in dentistry , primarily orthodontics and attempts to prioritize treatment have used the measure of iotn , which relates to treatment need rather than its complexity .", "it is essential , therefore , that health authorities should carefully prioritize and plan the provision of orthodontic treatment . the introductions of easily comprehensible , reproducible , valid , and reliable indices of therapeutic need such as the ac of iotn have allowed improved focusing of services", "malocclusions may range from the severe , rather uncommon conditions such as cleft lip and palate to the more common irregularities of teeth resulting from biological variations .", ". in some european countries , general dentists and orthodontists have been using indices of treatment need to prioritize state - funded orthodontic treatment for children with major irregularities ." ], [ "the data collected can help for worldwide comparisons with other populations the ac - iotn is , hence , being used as a powerful tool for patient counseling and planning desired orthodontic mechanotherapy in the department .", "\n a baseline data were obtained for planning future orthodontic services in the region as per priority in orthodontic triage .", "the data collected can help for worldwide comparisons with other populationsthe ac - iotn is , hence , being used as a powerful tool for patient counseling and planning desired orthodontic mechanotherapy in the department . \n ", "a baseline data were obtained for planning future orthodontic services in the region as per priority in orthodontic triage ." ], [], [] ]

[ [ "thus , understanding how nuclear shape is regulated and identifying genes that contribute to nuclear morphology are of interest from both a medical and a basic biology standpoint .", "in order to proliferate , cells must accurately transmit their chromosomes from one generation to the next . in eukaryotes ,", "the nuclear envelope not only serves as a diffusion barrier but also as a physical barrier separating the chromosomes from cytoplasmic structures . in most animal cells", "however , during anaphase , the nuclear envelope ruptures as the nucleus elongates without nuclear envelope expansion . the historic definition of open vs. closed mitosis was based on cytology : during open mitosis the nuclear envelope disappears , opening the nucleus and exposing its content to the cytoplasm , while in closed mitosis the nuclear envelope remains intact . from a functional standpoint , the presence or absence of a nuclear envelope affects at least two processes : the free diffusion of molecules between the cytoplasm and the nucleus ( which occurs during open , but not closed , mitosis ) and the presence of a physical barrier between the chromosomes and cytoplasmic structures ( which exists in closed , but not open , mitosis ) . over the years , mitotic divisions that fall somewhere in between open and closed have been described , warranting a brief discussion on how these forms of mitosis should be defined . in aspergillus nidulans , which was originally defined as undergoing closed mitosis , npcs", "it is conceivable that , during syncytial divisions , partially open mitosis evolved to overcome the diffusion barrier and microtubule accessibility problems , while protecting chromosomes from aberrant attachments to microtubules from neighboring nuclei ." ], [ "however , phospholipid synthesis alone was not sufficient to induce flares , as g2 arrested cells accumulated just as much phospholipid as mitotic arrested cells . taken together , these results suggest that nuclear expansion during closed mitosis of budding yeast is independent of spindle elongation , but rather occurs in response to a cell cycle cue that signals mitotic entry .", "closed mitosis appears at first glance to be an economical solution to the issue of microtubule - chromosome accessibility : nuclear envelope breakdown is circumvented , the chromosomes do not get entangled with cytoplasmic structures , and cells do not have to reassemble the nuclear envelope at the end of mitosis , risking leaving one or more chromosomes outside the nuclear perimeter .", ". further examination of these mutants revealed that this altered nuclear phenotype was not due to a direct involvement of the deleted genes in nuclear morphology , but rather due to the activation of a checkpoint pathway ( e.g. , the dna damage checkpoint or the spindle assembly checkpoint ) that induced a mitotic delay .", "finally , what happens to nuclear envelope expansion if cells are delayed in mitosis , for example due to checkpoint activation ?", "is it a consequence of spindle elongation or is it an independent process regulated by the cell cycle machinery ? and how are nuclear envelope components added ?" ], [ "spindle elongation may also play a role in nuclear envelope expansion : although the surface area of the nucleus increases during a mitotic arrest in the absence of a spindle ( i.e. , during an arrest induced by nocodazole ) , it is possible that spindle elongation contributes to the rate , and perhaps magnitude , of nuclear envelope expansion .", "first , what regulates nuclear envelope expansion ? as noted above , the process is independent of spindle elongation , much like nuclear envelope rupture in s. japonicus .", "the observation that a nuclear flare forms when checkpoint pathways are activated suggests that phospholipid synthesis is not subjected to checkpoint regulation . however , phospholipid synthesis is unlikely to be the only cell cycle target required for nuclear expansion , because g2-arrested cells accumulate just as much phospholipid as mitotic - arrested cells , yet they do n't form a flare ( ref .", "the synthesis of phospholipids , the main components of the nuclear membrane , is required for nuclear envelope expansion , as shown previously for both budding and fission yeast .", "it is tempting to speculate that the cell cycle target may be a protein or a process that is responsible for allocating membrane addition specifically to the nuclear envelope , either by localized phospholipid synthesis or by drawing membrane from the er preferentially during mitosis .", "thus , in these yeasts there are likely targets of the cell cycle machinery that affect nuclear envelope dynamics during mitosis", "moreover , at least one enzyme that negatively regulates membrane expansion , pah1 , is regulated by cdk1 phosphorylation ( ref ." ], [ "observed that nuclear envelope expansion during a mitotic arrest occurs in a curious fashion : rather than expanding isometrically , thereby generating a larger sphere , the flare occurs at the nuclear envelope that is adjacent to the nucleolus ( fig . ", "why , then , in both pah1 pathway mutants and in a mitotic arrest is the expansion of the nuclear envelope specific to the region adjacent to the nucleolus ?", "nonetheless , the flare induced by a mitotic arrest is similar to the nuclear expansion observed when the pah1 pathway is misregulated .", "whether the nucleolus , or its remnant , affects the adjacent nuclear envelope remains unknown .", "alternatively , the membrane could come from the er , and if this were the case then the cell would have a mechanism for allocating membrane from the er to the nuclear envelope specifically during mitosis ." ], [ "thus , studies on nuclear envelope dynamics in budding yeast will likely shed light on processes related to nuclear envelope formation , tumorigenesis and aging in higher eukaryotes .", "if so , do changes in the nuclear envelope have consequences for cell function ? despite the different modes of mitosis in budding yeast and mammalian cells , cell cycle processes have often proved to be based on conserved proteins .", "much like in yeast , the source of membrane , and both the temporal and spatial regulation of this process , are unknown ." ] ]

[ [ "fibro - osseous lesions ( fol ) are a poorly defined group of lesions affecting the jaws and craniofacial bones .", "recent world health organization classification ( 2005 ) for fibro - osseous lesions was considered while sub - dividing these into various groups [ table 1 ] .", "the aim of this study was to analyze various clinico - pathological and radiological features in the benign fol reported and to compare the features between fibrous dysplasia ( fd ) and cemento - ossifying fibroma ( cof ) .", "all are characterized by the replacement of bone by cellular fibrous tissue containing foci of mineralization that vary in amount and appearance .", "these patients were treated for fol , reported to the hospital between 1989 and 2009 .", "so proper categorization requires good correlation of the history , clinical findings , radiographic characteristics , operative findings , and histologic appearance ." ], [ "the mandible was divided into four anatomic regions such as anterior ( midline to distal surface of canine ) , posterior ( mesial surface of first premolar distally ) , angle ( from distal of third molar to the inferior portion of ramus ) , and ramus ( upper portion of the ramus beyond the occlusal plane ) .", "regarding site distribution , the maxilla was divided into two anatomic regions as anterior ( midline to distal surface of canine ) and posterior ( mesial surface of first premolar distally ) .", "radiological features were assessed for radiolucency , radiopacity , margin of the lesion , cortical - plate expansion , involvement of antrum , displacement , and resorption of teeth .", "histopathologically , parameters such as type of bone ( mature / immature ) , cellularity , presence of cementum - like material , and nature of stroma were assessed .", "basic clinical parameters such as age , sex , duration of lesion , family history , history of trauma , associated symptoms , palpatory findings , status of associated / involved teeth , associated pigmentation , site of the lesion , treatment , and recurrence details were retrospectively analyzed .", "the clinical parameters included were age , sex , location , duration , family history , associated symptoms , and behavior of the lesion .", "the radiographic appearance , histologic features , treatment , and follow - up data were also recorded ." ], [ "a total of 80 cases of benign fols were recorded over the 20 years . among these , cof ( all variants ) was the most frequent tumor found in 60 patients with 63 lesions ( 73.2% ) and fd was found in 20 patients ( 24.4% ) . in general for fol ,", "the site distribution of 80 patients with fibro - osseous lesions mobility of teeth was seen in 13 patients which included 11 cases of cof and two cases of fds . in one case of cof ,", "eight patients of cof showed recurrences within a period ranging from 2 months to 4 years .", "comparison of histopathological features between cemento - ossifying fibroma and fibrous dysplasia the treatment procedures rendered in these cases has been summarized in the table 3 ." ], [ "the site distribution of 80 patients with fibro - osseous lesions mobility of teeth was seen in 13 patients which included 11 cases of cof and two cases of fds . in one case of cof ,", "the lesion was associated with displacement of teeth , whereas one cof showed impacted tooth .", "a total of 80 cases of benign fols were recorded over the 20 years . among these , cof ( all variants ) was the most frequent tumor found in 60 patients with 63 lesions ( 73.2% ) and fd was found in 20 patients ( 24.4% ) . in general for fol ,", ". extensive involvement of facial bones like ethmoidal and frontal bone was seen in fd ( 2 patients ) , in four cases of cof { juvenile ossifying fibroma ( jof ) variant } , and in two patients with aggressive form of ossifying fibroma ( of ) ( which can not be classified as jof ) ." ], [ "radiographically , 23 ( 38.3% ) cofs showed mixed opaque and lucent areas , 19 ( 31.6% ) cases showed only radiolucent areas and 18 ( 30% ) cases showed only radiopacity . among these ,", "a total of eight cofs , showed involvement of antrum , displacement and resorption of the teeth . among fds", ", most of them showed mixed opaque and lucent areas ( 75% ) , diffuse borders ( 60% ) with only four cases ( 20% ) showing expansion of cortical plates , and five cases showing expansion of antrum .", "55 ( 91.6% ) had a well - defined border whereas 5 ( 8.3% ) cases were having diffuse outline ." ], [ "other provisional diagnosis considered were adenomatoid odontogenic tumor , ameloblastoma , aneurysmal bone cyst , odontoma , calcifying epithelial odontogenic tumor , odontogenic myxoma , central giant cell granuloma , and odontogenic keratocyst for cof and osteoma for fd .", "in case of cof , on 34 ( 56% ) occasions it was provisionally diagnosed as cof and fd was considered in four cases . among 20 fds , 15 ( 75% ) times fd was considered as a provisional diagnosis and only in two occasions , it was thought in terms of cof ." ], [ "the stroma was fibro - cellular ( 42 cases ) and fibrous ( 18 cases ) with irregular thin trabeculae of woven bone ( 43 patients ) or lamellar bone ( 11 patients ) rimmed by osteoblasts .", "the cof on the post - operative histologic findings was seen as a well - demarcated lesion that was separated from the overlying cortical bone by a thin zone of fibrous tissue .", "fd showed merging of lesional bone with the normal along with highly fibrous stroma ( 8 cases ) consisting of immature trabeculae of woven bone ( 18 lesions ) giving a chinese letter ", "basophilic , ovoid , cementum - like material was evident in 21 cofs : among these four were considered as jof psammamatoid type .", "other features evident with regular histopathology were the presence of giant cells ( 5 cof ) , myxoid areas ( 1 jof ) , and endothelial proliferation ( 1 cof ) ." ], [ "eight patients of cof showed recurrences within a period ranging from 2 months to 4 years .", "one case of jof showed three recurrences every year . among three patients with fds , two patients had recurrences after 2 and 4 years respectively , with last one showing multiple ( 3 times ) recurrences almost after 3 years each time ." ], [ "the involvement of other facial bones ( frontal , ethmoidal , antrum ) was a frequent finding in cof when compared with fd .", "however , in our data , there was a definite male predilection ( 1.8:1 ) for fd which was contrasting to the previous studies.[468 ] when compared with fd , many of cof presented with associated symptoms like pus discharge , egg shell crackling , tenderness , ulceration of the overlying mucosa , numbness of lip , and proptosis which is unusual for these groups of lesions ( this involvement was seen in four patients diagnosed as jof ) .", "mature bone was seen in one of our case and osteoblastic rimming was evident in few areas of five cases and stroma was mostly fibrocellular , although few showed a completely fibrous or vascular background . compared with previous studies,[468 ] both cof and fd were predominantly seen in younger population ( 25.5 years and 21 years respectively ) .", "24 cases were diagnosed as of , 21 as cof , 11 as cf , and 4 as jof .", "early lesions may be radiolucent , but they become increasingly radiopaque and typically show a diffuse radiopacity or ground glass appearance . in the present study , 75% of the lesions showed mixed opacity and lucency , whereas two cases were completely radiolucent and three cases with complete radiopaque picture .", "it is monostotic , whereas all 20 cases in our data showed a solitary lesion in the jaws , although few of maxillary lesions extending up to infra - orbital margin affect vision ." ], [ "both cof and fd showed multiple recurrences . since few of our cof cases showed history of trauma and association with osteosarcoma , a careful detailing of these in the history", "is emphasized although its correlation with the occurrence of the lesion can not be established through this study . as aggressive behavior and recurrence", "was a frequent finding in few patients with cof , a long follow - up was advised .", "juvenile ossifying fibroma was of predominantly psammamatoid type and finally , not a single cementoid lesion was reported for last 20 years ." ] ]

[ [ "this paper was focused on developing a rapid analysis method for discriminating specific subproducing areas of longjing tea by electronic tongue and chemometrics .", "longjing tea is a green tea produced in xihu and its surrounding areas ( hangzhou , china ) . as a famous green tea with protected designation of origin ( pdo ) ,", "however , little information has been available on the feasibility of discriminating longjing from its three specific subproducing areas , namely , xihu , qiantang , and yuezhou . as the quality and prices of longjing tea from the above three producing areas are different", "robust principal component analysis ( robpca ) [ 11 , 12 ] was used to detect outliers in each class .", "partial least squares discriminant analysis ( plsda ) was used to develop the classification model .", "recent years have witnessed increased applications of electronic tongue technology to analysis of wines , milk , tea , beer , juice , and so on [ 710 ] . in these applications , a very good time stability and sensitivity", ", it is necessary to develop effective analysis methods for discrimination of longjing from different subproducing areas . because of the similarity ( processing , appearance , and taste ) among different subproducing areas , the specific geographical origins of longjing are usually distinguished by sensory analysis ." ], [ "155 longjing samples were collected from the local tea plantations in xihu ( 32 samples , class a ) , qiantang ( 59 samples , class b ) , and yuezhou ( 64 samples , class c ) .", "model sensitivity and specificity of prediction for each class were used to evaluate the performance of classification models : \n ( 2)sensitivity = tptp+fn , specificity = tntn+fp , \n where tp , fn , tn , and fp represent the numbers of true positives , false negatives , true negatives , and false positives , respectively . for classification ,", "duplex algorithm can obtain a test set of samples distributed uniformly in the range of training samples . for multiclass classification", "the sensors array analyzed the solutions of tea samples with sampling interval of 1 s. each sample was measured for 150 s , which can ensure a stable response .", "outliers in the data would degrade the classification models and prediction performance , so robust principal component analysis ( robpca ) was used to detect outliers in each class of samples .", "monte carlo cross validation ( mccv ) was used to estimate the number of components in plsda by minimizing the mean percentage error of mccv ( mpemccv ) : \n ( 1)mpemccv=i=1bnii=1bmi , \n where b is the numbers of mccv data splitting , mi is the number of prediction objects , and ni is the number of wrongly predicted for the ith mccv data splitting .", "deleted , the duplex algorithm was used to divide the measured data into a training set and test set ." ], [ "the features of class b and c are very similar and different from those of class a , especially in the responses of ga and ha .", "the average electronic tongue features for each class of longjing tea are shown in figure 1 . seen from figure 1 , the features of the three classes have very similar response patterns .", "the training accuracy was 1 and for prediction only one object from class c was wrongly assigned to class b , indicating the effectiveness of electronic tongue for classification of longjing tea samples .", "figure 2 demonstrates the robpca plots for the three classes . for each class , a robpca model with three principal components ( pcs )" ], [ "the sensitivity / specificity of plsda for classes a , b , and c was 1.000/1.000 , 1.000/0.967 , and 0.950/1.000 , respectively . electronic tongue and chemometrics can provide a rapid and reliable tool for discriminating the specific producing areas of longjing . compared with human sensory analysis , this method is easier to perform and the more attractive economically . in the future studies", "rapid and effective discrimination of longjing green tea from different subproducing areas was performed using electronic tongue and chemometrics .", ", the comparison of chemical methods , for example , lc / uv / ms , to the electronic tongue analysis will be performed to investigate the statistical correlation between the chemistry and the tastes of longjing tea ." ] ]

[ [ "in accordance with the aforementioned dose response relationship , it was hypothesized that muscle protein accretion would be greater with the higher frequency program .", "therefore , the main purpose of this investigation was to analyze the effect of rt performed at different weekly frequencies on flexibility in untrained older women .", "response relationship between training volume and muscle strength and hypertrophy,21,22 whereby greater training volumes are associated with enhanced muscular adaptations .", "a secondary aim of the study was to assess rt frequency - related changes in skeletal muscle mass .", "previous studies are limited to analyzing the impact of rt on flexibility without regard for manipulation of the variables that make up the training program . considering the importance of flexibility in the health and wellness of the elderly", "we hypothesized that higher rt frequencies would result in greater flexibility increases than lower frequencies . the rational for our hypothesis" ], [ "the remaining 64 older women ( 60 years old ) were randomly assigned to one of two groups : a group that performed rt two times per week ( n=32 ; group ", "the study was carried out over a period of 16 weeks , with 12 weeks dedicated to the rt program and 4 weeks used for testing .", "participants passed a diagnostic , graded exercise stress test with twelve - lead electrocardiography reviewed by a cardiologist and were released with no restrictions for participation in this study .", "anthropometric , body - composition , and flexibility measurements were performed at weeks 12 and 1516 for baseline and post - training analysis , respectively , while the supervised rt program was performed during weeks 314 .", "retest , the standard error of measurement and the intra - class correlation coefficient among the movements were 2.26 degrees and 0.950 , respectively , and the maximal technical error among the movements analyzed was 1.19 degrees . during the intervention period , in each session , the instructors registered the load ( kg ) for each of the eight exercises for all the subjects .", "g2x ) or a group that performed rt three times per week ( n=32 ; group g3x ) . a total of 53 women ( g2x=28 ; g3x=25 ) completed the study and therefore were included in the analysis ." ], [ "the remaining 64 older women ( 60 years old ) were randomly assigned to one of two groups : a group that performed rt two times per week ( n=32 ; group ", "the women were subsequently admitted to the study if they met the following inclusion criteria : non - hypertensive ( systolic blood pressure < 140 mmhg and diastolic blood pressure < 90 mmhg ) , nondiabetic , free from cardiac or renal dysfunction , nonsmoking , not receiving hormonal replacement therapy , not performing any regular physical exercise more than once per week over the preceding 6 months , and participated in > 85% of the study training sessions .", "participants passed a diagnostic , graded exercise stress test with twelve - lead electrocardiography reviewed by a cardiologist and were released with no restrictions for participation in this study .", "g2x ) or a group that performed rt three times per week ( n=32 ; group g3x ) . a total of 53 women ( g2x=28 ; g3x=25 ) completed the study and therefore were included in the analysis .", "a total of 350 older women responded to the advertisements , and then completed detailed health history and physical activity questionnaires .", "recruitment of the participants was carried out through newspaper and radio advertisements and home delivery of flyers in londrina , paran , brazil ." ], [ "the study was carried out over a period of 16 weeks , with 12 weeks dedicated to the rt program and 4 weeks used for testing .", "anthropometric , body - composition , and flexibility measurements were performed at weeks 12 and 1516 for baseline and post - training analysis , respectively , while the supervised rt program was performed during weeks 314 .", "subjects were instructed not to perform any other type of physical exercise during the entire study period ." ], [ "body mass was measured to the nearest 0.1 kg using a calibrated electronic scale ( balmak scale , model iii , so paulo , brazil ) , with the participants wearing light workout clothing and no shoes .", "height was measured with a stadiometer attached on the scale to the nearest 0.1 cm with subjects standing without shoes .", "body mass index was calculated as body mass in kilograms divided by the square root of height in meters ." ], [ "the skeletal muscle mass was estimated by the predictive equation proposed by kim et al.23 the appendicular fat - free mass used in the equation was determined by a dual energy x - ray absorptiometry scan ( lunar prodigy nrl 41990 , ge lunar , madison , wi , usa ) . before scanning , participants were instructed to remove from their person all objects containing metal .", "retest scans resulted in a standard error of measurement of 0.29 kg and intra - class correlation coefficient of 0.997 for skeletal muscle mass .", "analyses during the intervention were performed by the same technician who was blinded to intervention time point .", "the software generated standard lines that set apart the limbs from the trunk and head .", "these lines were adjusted by the same technician using specific anatomical points determined by the manufacturer .", "feet were taped together at the toes to immobilize the legs , while the hands were maintained in a pronated position within the scanning region ." ], [ "to evaluate a subject s flexibility , five joint movements were adopted : cervical flexion ( cf ) , cervical extension ( ce ) , frontal hip flexion ( fhf ) , left hip flexion , and right hip flexion .", "these movements were chosen because the flexibility of the hip and cervical spine are highly important for the elderly , especially for locomotion , eye orientation , and good timeline perception.24 all measurements were obtained by a fleximeter ( code , american do brazil ltda , so paulo , brazil ) with a degree scale .", "it is worth emphasizing that the evaluator had over 2 years experience , and based on the test ", "the information obtained at baseline was not made available to the evaluator at the time of revaluation in an attempt to avoid their unduly influencing the results .", "retest , the standard error of measurement and the intra - class correlation coefficient among the movements were 2.26 degrees and 0.950 , respectively , and the maximal technical error among the movements analyzed was 1.19 degrees ." ], [ "during the intervention period , in each session , the instructors registered the load ( kg ) for each of the eight exercises for all the subjects . afterwards , training load for each subject was weekly calculated , using the sum of the load employed in the exercises as a reference for each week ." ], [ "the protocol was based on recommendations for rt in an older population to improve muscular endurance and strength.12,13 all participants were personally supervised by physical - education professionals with substantial rt experience to help ensure consistent and safe performance .", "instructors adjusted the loads of each exercise according to the subject s ability and improvements in exercise capacity throughout the study in order to ensure that the subjects were exercising with as much resistance as possible while maintaining proper exercise technique .", "progression was planned so that when 15 repetitions were completed for two consecutive training sessions , weight was increased 2%5% for the upper limb exercises and 5%10% for the lower limb exercises in the next session.12 it is important to note that the participants did not perform any type of warm - up or cool - down exercises at the beginning or end of the session , respectively .", "participants were instructed to inhale during the eccentric phase and exhale during the concentric phase while maintaining a constant velocity of movement at a ratio of approximately 1:2 seconds ( concentric and eccentric phases , respectively ) .", "supervised rt was carried out for 12 weeks during the morning hours , in the londrina state university facilities .", "the rt program was a whole - body program with eight exercises comprising one exercise with free weights and seven with machines , performed exactly in the following order : chest press , horizontal leg press , seated row , knee extension , preacher curl ( free weights ) , leg curl , triceps push - down , and seated calf raise .", "g2x performed two rt sessions per week on tuesdays and thursdays , while g3x performed the same exercises in three sessions per week on mondays , wednesdays , and fridays ." ], [ "two - way analysis of variance for repeated measures was used for within - group comparisons . in variables where sphericity was violated , as indicated by mauchly s test", "was calculated to verify the magnitude of the differences by cohen s d , where an es of 0.200.40 was considered small , 0.500.79 as moderate , and 0.80 as large.26 for all statistical analyses , significance was accepted at p<0.05 .", ", the analyses were adjusted using a greenhouse geisser correction . when the f - ratio was significant , bonferroni s post - hoc test was employed to identify the mean differences .", "baseline differences between groups were explored with an independent t - test . the effect size ( es )", "the data were stored and analyzed using statistica software ( v 10.0 ; statsoft inc , tulsa , ok , usa ) ." ], [ "a significant main effect for group - by - time interaction ( f=2.53 , p<0.05 ) was observed , in which g3x showed a higher increase than g2x ( g2x=+87.8% , es=7.31 ; g3x=+92.2% , es=10.39 ) .", "only the main effect of time reached statistical significance ( f=22.05 , p<0.001 ) , with both groups having a similar increase after the 12 weeks of the rt program .", "significant group - by - time interaction ( p<0.01 ) was observed only for fhf , in which g3x showed a higher increase than g2x ( + 12.8% , and + 3.0% , respectively ) .", "the ess for skeletal muscle mass changes were 0.21 and 0.43 for twice and thrice per week sessions , respectively .", "the information regarding flexibility indicators pre - and post - training according to group are presented in table 2 . a main effect of time ( p<0.01 )" ], [ "our findings indicate that rt performed at a minimum of twice per week can result in positive effects on flexibility in the elderly , reversing or slowing the aging - induced losses .", "the main finding of the present study is that 12 weeks of rt was sufficient to increase or at least maintain flexibility in elderly women .", ", the present study is the first to have investigated the effect of different rt frequencies on flexibility in older women .", "the novel and important feature of our study was the comparison of two versus three rt sessions per week with respect to flexibility outcomes .", "results show that only fhf benefited from an increased rt frequency , while all other flexibility outcomes were similar regardless of the number of weekly sessions ." ], [ "the results of our study suggest that 12 weeks of rt improves or at least preserves the flexibility of different joint movements in older women . in addition" ] ]

[ [ "a fasta database file of all human ecm proteins was constructed . for both human and bovine samples ,", "comprehensive lists of ecm proteins for human and mouse have been compiled ( http://matrisomeproject.mit.edu , in the public domain ) , and the lists of core and ecm - associated proteins for human were used to extract the corresponding protein sequence from uniprot .", "the ensembl bovine database ( release 79 , march 2015 ) had 22,118 protein sequences .", "this was because the bovine ensemble protein database ( unlike the human swiss prot database ) contained multiple entries for protein isoforms of nearly identical sequence . to facilitate comparison to the human samples", "a single bovine eye yielded sufficient tissue for a proteomic analysis of the equatorial zonule , hyaloid zonule , and vitreous humor .", "the lists of identified proteins were used to extract separate fasta database files for identified proteins .", "the human database consisted of 20,207 uniprot reviewed canonical sequences ( swiss - prot ) downloaded july 2015 ." ], [ "human eyes ( from 10 donors 2366 years of age ; table ) were obtained from a local eye bank and dissected using a similar approach to that described for the bovine eye . because the vitreous of the aged human eye was often partially liquefied , it was not possible to collect a human hyaloid zonule sample .", "a single bovine eye yielded sufficient tissue for a proteomic analysis of the equatorial zonule , hyaloid zonule , and vitreous humor .", "thus , the human zonular sample was equivalent to the bovine equatorial zonule sample . description of human zonular samples to have sufficient material for analysis , human zonular samples were pooled ( table ) .", "other investigators have subdivided these fibers into anterior , equatorial , and posterior groupings , but here they were all included in a single sample , the equatorial zonule . using iridectomy scissors , fibers from the equatorial zonule", "the hyaloid zonule was defined as the set of fibers that were closely associated with the anterior face of the vitreous .", "we divided the zonular fibers into two groups : the equatorial zonule ( blue fibers in fig ." ], [ "human eyes were fixed for 1 week in 4% paraformaldehyde / pbs , dehydrated through graded ethanols and xylene , and embedded in paraffin wax . sections ( 4 m thick ) were cut in the midsagittal plane and processed for immunofluorescence .", ", sections were incubated for 2 hours in 1:300 dilution of appropriate secondary antibody ( alexa 488conjugated goat anti - mouse or anti - rabbit ; invitrogen , carlsbad , ca , usa ) containing methyl green ( a nuclear counterstain ) .", "the following antibodies were used : adamtsl-6/thsd4 ( atlas antibodies , stockholm , sweden ) , emilin-1 ( santa cruz biotechnology , santa cruz , ca , usa ) , fbn1 ( millipore , temecula , ca , usa ) , fibulin-6/hemicentin-1 ( millipore ) , ltbp2 ( gift of tomoyuki nakamura , kansai medical university , osaka , japan ) , and mfap2 ( santa cruz biotechnology ) . after washing in pbs ( 3 10 minutes )", "sections were blocked with 3% bsa for 2 hours and incubated overnight at 4c in a 1:501:100 dilution of primary antibody .", "sections were then washed , coverslipped ( prolong gold ; invitrogen ) , and viewed using an olympus fv1000 confocal microscope ( center valley , pa , usa ) ." ], [ "the dca in the combined filtrates was then extracted using ethyl acetate as previously described , and peptides in the aqueous phase were dried by vacuum centrifugation .", "peptides were recovered by centrifugation and passage through the ultrafiltration membrane , and membranes were further washed with two 50-l portions of 50 mm ammonium bicarbonate .", "the remaining sample preparation and digestion used the enhanced filter - aided sample preparation ( efasp ) method of erde et al .", "bovine and human zonules were suspended in 50 l buffer containing 4% sds , 0.2% deoxycholic acid ( dca ) , and 100 mm ammonium bicarbonate ( ph 8) and sonicated using a fisher scientific model 60 sonic dismembranator ( thermo fischer scientific , waltham , ma , usa ) , using three treatments of 10 seconds each .", "briefly , the sds containing lysis buffer was replaced with exchange buffer , proteins were alkylated with iodoacetamide , and exchange buffer was replaced with digestion buffer containing 0.2% dca and 50 mm ammonium bicarbonate . a ratio of 1:50 of sequencing grade modified trypsin ( promega , madison , wi , usa ) to substrate", "five microliters was removed for a pierce bicinchoninic acid ( bca ) assay ( thermo fisher scientific ) using bsa as a standard ." ], [ "samples were reduced by addition of 4 l 0.2 m dithiothreitol and incubation at 50c for 15 minutes , followed by alkylation through addition of 4 l 0.5 m iodoacetamide and incubation at room temperature ( rt ) for 30 minutes in the dark .", "bovine vitreous humor samples ( 200 l ) containing approximately 100 g protein were dried by vacuum centrifugation and dissolved in 50 l 8 m urea , 1.0 m tris ( ph 8.5 ) , 8 mm cacl2 , and 0.2 m methylamine .", "digestion proceeded overnight at 37c and then 10 l formic acid was added to stop the reaction .", "an additional 8 l 0.2 m dithiothreitol was then added , samples were incubated for an additional 15 minutes at rt , and 94 l water was added , followed by 40 l 0.1 g/l trypsin .", "peptides were solid phase extracted using sep - pak light c18 cartridges ( waters , milford , ma , usa ) , and the final eluate was dried by vacuum concentration ." ], [ "the quadrupole was used to isolate ions for mass spectroscopy ( ms)/ms scans with a 1.6-m / z isolation window , and fragmentation was performed by higher - energy collisional dissociation ( hcd ) with normalized collision energy of 35% .", "survey scans were performed in the orbitrap mass analyzer at a resolution of 120,000 with a scan range of 4001500 , maximum inject time of 50 ms , and automatic gain control ( acg ) target of 2 10 .", "top speed data - dependent ms / ms spectra were collected in parallel using the ion trap , with a maximum 35-ms inject time , single scan , signal - to - noise ration ( s / n ) threshold = 2 , minimum ion intensity threshold of 5000 , and a maximum interval of 3 seconds between survey scans .", "dynamic exclusion was performed with the monoisotopic precursor selection ( mips ) filter on , exclusion of + 1 ions , 60-second exclusion time , exclusion mass tolerance of 10 ppm , and count = 1 .", "samples were dissolved in water containing 5% formic acid and transferred to autosampler vials , and 4 g of each zonule peptide digest ( or 2 g of each vitreous humor digest ) was analyzed .", "peptides were eluted with a 90-minute gradient of 7.5%30% mobile phase b containing acetonitrile and 0.1% formic acid at a flow rate of 0.3 l / min .", "the samples were injected at a flow rate of 5 l / min onto an acclaim pepmap 100-m 2-cm nanoviper 5-m c18 trap ( thermo fisher scientific ) using mobile phase a containing water and 0.1% formic acid .", "after 5 minutes , the trap was switched in - line with a pepmap rslc c18 , 2 m , 75-m 25-cm easyspray column fitted in an easyspray nano electrospray source ( thermo fisher scientific ) at 40c ." ], [ "the ensembl bovine database ( release 79 , march 2015 ) had 22,118 protein sequences .", "the human database consisted of 20,207 uniprot reviewed canonical sequences ( swiss - prot ) downloaded july 2015 .", "databases were downloaded from ensembl ( www.ensembl.org , in the public domain ) for bovine samples or from uniprot ( www.uniprot.org , in the public domain ) for human samples and processed with utilities available from www.proteomicanalysisworkbench.com , in the public domain .", "the paw analysis pipeline was used to control peptide sequencing errors , infer protein identities from observed peptides , and provide quantitative protein abundance estimates .", "protein inference used basic parsimony logic where proteins having indistinguishable peptide sets were combined into protein groups and proteins having peptide sets that were subset of other protein 's peptide sets were removed .", "target and decoy discriminant scores were displayed as histograms and overlaid for interactive setting of score thresholds to filter peptide - spectral matches at an overall false discovery rate ( fdr ) of 3% .", "protein inference was performed experiment - wide with additional requirements of a minimum of two distinct peptides per protein per biological sample applied after protein inference . in a final round of processing , straightforward extensions of parsimony principles", "other parameters were as follows : tryptic enzyme specificity , static modifications of + 57 da on cysteine residues , variable modifications of + 16 da on methionine residues ( maximum of 2 modifications ) , and use of y- and b - ions in scoring ." ], [ "the open source proteowizard toolkit was used to convert thermo raw files into compressed text files using msconvert via command line .", "an in - house python program was used to convert information in the compressed text file into appropriately formatted ms2 files .", "ms2 scans were extracted with a minimum ion count of 15 and minimum total absolute intensity of 100 ." ], [ "the ensembl bovine database ( release 79 , march 2015 ) had 22,118 protein sequences .", "other parameters were as follows : tryptic enzyme specificity , static modifications of + 57 da on cysteine residues , variable modifications of + 16 da on methionine residues ( maximum of 2 modifications ) , and use of y- and b - ions in scoring .", "the human database consisted of 20,207 uniprot reviewed canonical sequences ( swiss - prot ) downloaded july 2015 .", "databases were downloaded from ensembl ( www.ensembl.org , in the public domain ) for bovine samples or from uniprot ( www.uniprot.org , in the public domain ) for human samples and processed with utilities available from www.proteomicanalysisworkbench.com , in the public domain .", "2 ( bovine samples ) . monoisotopic mass parent ion and fragment ion tolerances of 1.25 and 1.0005 da were used , respectively .", "searches were performed using comet version 2015.02 rev . 1 ( human samples ) or 2016.01 rev .", "common contaminant sequences ( 179 ) were added before all sequences were reversed for peptide and protein error estimation using the target / decoy method ." ], [ "protein inference was performed experiment - wide with additional requirements of a minimum of two distinct peptides per protein per biological sample applied after protein inference . in a final round of processing , straightforward extensions of parsimony principles", "the paw analysis pipeline was used to control peptide sequencing errors , infer protein identities from observed peptides , and provide quantitative protein abundance estimates .", "target and decoy discriminant scores were displayed as histograms and overlaid for interactive setting of score thresholds to filter peptide - spectral matches at an overall false discovery rate ( fdr ) of 3% .", "protein inference used basic parsimony logic where proteins having indistinguishable peptide sets were combined into protein groups and proteins having peptide sets that were subset of other protein 's peptide sets were removed .", "comet search scores were transformed into discriminant scores using functions similar to those used in peptideprophet .", "these results were used for quantitative analyses using ms2 fragment ion intensity weighted spectral counting ." ], [ "comprehensive lists of ecm proteins for human and mouse have been compiled ( http://matrisomeproject.mit.edu , in the public domain ) , and the lists of core and ecm - associated proteins for human were used to extract the corresponding protein sequence from uniprot .", "a fasta database file of all human ecm proteins was constructed . for both human and bovine samples ,", "it was assumed that the zonule would be composed predominantly of extracellular matrix ( ecm ) proteins .", "to more confidently determine the composition of the zonule , contaminating proteins from surrounding tissues have to be identified and excluded .", "this was because the bovine ensemble protein database ( unlike the human swiss prot database ) contained multiple entries for protein isoforms of nearly identical sequence . to facilitate comparison to the human samples", "the lists of identified proteins were used to extract separate fasta database files for identified proteins .", "analysis of alignment scores was used to categorize likely matches to matrisome proteins from poor alignments between matrisome proteins and contaminating proteins . once matrisome proteins were identified" ], [ "we examined human and bovine zonules for the presence of known crosslinking enzymes that might play a role in bundling of microfibrils .", "in vitro studies suggest that adamtsl-6 can bind directly to fbn1 , promoting the assembly of fibrillin - rich ecm .", "unlike the bovine zonule ( where members of a single glycoprotein family , the fbn / ltbp family , accounted for > 80% of the protein ) , the composition of the vitreous was not dominated by a restricted set of super abundant proteins ( supplementary material s3 ) . among the more abundant vitreous proteins were broad spectrum protease inhibitors ( a2ml1 , a2 m , cpmd8 , cst3 , and serping1 ) , collagens ( col9a2 , col18a1 , and col2a1 ) , fibulins ( fbln1 , fbln2 , and fbnl3 ) , the proteoglycans opt and hspg2 , and wnt signaling components sfrp2 and sfrp3 .", "expression of crosslinking enzymes ( transglutaminases and lysyloxidase - like 1 ) in the ciliary zonule .", "transglutaminase - derived crosslinks have been identified previously in fibrillin microfibrils and may be important in the zonule .", "the presence of loxl1 is intriguing because variants in the loxl1 gene have been shown to predispose to exfoliation syndrome .", "the high representation of fbn / ltbp superfamily members in the zonule is consistent with the ocular phenotypes of syndromes resulting from mutations in those proteins .", "mutations in fbn1 underlie marfan syndrome , a condition in which progressive lysis of the zonular fibers leads to ectopia lentis in most ( 71% ) patients ." ], [ "we examined human and bovine zonules for the presence of known crosslinking enzymes that might play a role in bundling of microfibrils .", "in vitro studies suggest that adamtsl-6 can bind directly to fbn1 , promoting the assembly of fibrillin - rich ecm .", "cxcl14 is a chemokine implicated in the recruitment of immune cells in all types of inflammatory conditions .", "the presence of loxl1 is intriguing because variants in the loxl1 gene have been shown to predispose to exfoliation syndrome .", "the high representation of fbn / ltbp superfamily members in the zonule is consistent with the ocular phenotypes of syndromes resulting from mutations in those proteins .", "transglutaminase - derived crosslinks have been identified previously in fibrillin microfibrils and may be important in the zonule ." ], [ "recent proteomic analyses of human vitreous humor have identified many hundreds of protein components , of which a core set of 231 proteins were detected in all studies . in the present study , after filtering against the matrisome database , we identified 200 components of the bovine vitreous . comparing the bovine vitreous proteome with that of the equatorial and hyaloid zonular samples , it was evident that the zonular samples were quite distinct from the vitreous sample ( figs .", "proteins such as mfap2 and fbn2 , for example , were almost undetectable in the vitreous but relatively abundant in the zonular samples . overlapping distribution of matrisome proteins in samples from the bovine equatorial zonule , hyaloid zonule , and vitreous humor .", "fbn1 , the most abundant single component in the equatorial zonule , accounted for only 2.5% of the protein in the vitreous sample .", "the set of hyaloid - enriched proteins included opt , a3i3bp , cochlin , and the collagens col2a1 , col11a1 , col5a3 , and col5a2 ( fig ." ], [ "the zonule is adversely affected in several pathologic conditions , including exfoliation syndrome , homocystinuria , and marfan syndrome . to understand how and why the zonule is compromised in these diseases , a detailed analysis of its composition", "the pleitropic ocular effects of mutations in zonular genes ( which include congenital glaucoma , cataract , ectopia lentis , and microspherophakia ) are consistent with the notion that the role of the ciliary zonule is not solely to secure the lens in place .", "the ciliary zonule plays a key role in ocular function , centering the lens on the optical axis and transmitting the forces that mold its shape during accommodation .", "immunoelectron microscopy studies have previously suggested that adamts10 is abundant in the human ciliary zonule so its absence from the proteome is perplexing . a striking feature of the zonulome in human and cows was the presence of a diverse set of protease inhibitors , the most abundant in humans being timp3 .", "adamts proteins and adamtsl proteins have well - documented roles in ocular biology and pathology ." ], [] ]

[ [ "the subtype of 19 well - characterized breast cancer cell lines was obtained by use of gene expression profiling , including normal - like , basal - like , her2-positive , and luminal a and b. cells from each line were mixed with blood from a healthy donor and subjected to the cellsearch circulating tumor cell assay .", "normal - like breast cancer cells have especially aggressive features , and so assays that recognize this subtype would provide valuable prognostic information .", "the cellsearch assay , which uses epithelial cell adhesion molecules on the cell surface , did not recognize normal - like breast cancer cells , although other subtypes were recognized .", "new assays are needed that include antibodies that specifically recognize this breast cancer subtype but not other cell types , including those of hematopoietic origin .", "identification of specific subtypes of circulating tumor cells in the peripheral blood of cancer patients can provide important prognostic information , but to be effective , the method used must recognize all tumor cell types ." ], [ "identification of specific subtypes of circulating tumor cells in the peripheral blood of cancer patients can provide important prognostic information , but to be effective , the method used must recognize all tumor cell types ." ], [ "the subtype of 19 well - characterized breast cancer cell lines was obtained by use of gene expression profiling , including normal - like , basal - like , her2-positive , and luminal a and b. cells from each line were mixed with blood from a healthy donor and subjected to the cellsearch circulating tumor cell assay ." ], [ "the cellsearch assay , which uses epithelial cell adhesion molecules on the cell surface , did not recognize normal - like breast cancer cells , although other subtypes were recognized ." ], [ "normal - like breast cancer cells have especially aggressive features , and so assays that recognize this subtype would provide valuable prognostic information .", "new assays are needed that include antibodies that specifically recognize this breast cancer subtype but not other cell types , including those of hematopoietic origin ." ], [], [ "this study was in part financially supported by the netherlands genomic initiative / netherlands organisation for scientific research ." ], [] ]

[ [ "pcr is a new alternative to existing diagnostic procedures , such as direct smear of parasites from clinical specimens or by cultivation , with microscopic examination .", "zoonotic cutaneous leishmaniasis ( zcl ) is polymorphic disease with various clinical manifestations ( 1 , 2 ) .", "leishmaniasis , a group of parasitic infections , has a worldwide distribution ( 3 ) ; the world health organization estimates a prevalence of approximately 12 million cases , with an annual mortality rate of 60,000 and an at - risk population of approximately 350 million ( 4 ) .", "approximately 90% of cl cases occur in just seven countries , including iran ( 5 ) ." ], [ "in the present study , as described previously ( 1 , 11 , 12 ) , we used the rflp analysis of amplified its1 in ribosomal operons to investigate the parasite that causes zcl , and the genetic variations among l. major isolates from chabahar , a port city in southeast iran ( situated at the iran - pakistan border ) . in this region ,", "the manifestation of zcl as a new focus of disease was in doubt , but our findings showed that the species is l. major with variable genes . the disease was correlated with the clinical manifestations of zcl in chabahar , so this is a new major public health problem ." ], [ "each diagnosis was confirmed by the demonstration of amastigotes on the slit smear and/or the presence of flagellated promastigotes in novy - macneal - nicolle ( nnn ) medium from skin samples of 24 patients with typical and atypical lesions . for the parasitological investigation ,", "we evaluated the pcr - rflp assay of the its1 genes for direct identification of leishmania species in 24 out of 33 suspected patients .", "the its1-rflp pcr assay is a multipurpose tool for the diagnosis of leishmania from clinical samples , and it enables determination of the infecting species ( 3 ) .", "the diagnosis of leishmaniasis was confirmed by the presence of amastigotes in slit smears and/or the presence of flagellated promastigotes in nnn medium from typical and atypical lesions . for parasitological investigations ,", "the clinical samples were taken from patients suspected to have cl in different endemic areas of chabahar , including negor and other districts and villages ." ], [ "each diagnosis was confirmed by the demonstration of amastigotes on the slit smear and/or the presence of flagellated promastigotes in novy - macneal - nicolle ( nnn ) medium from skin samples of 24 patients with typical and atypical lesions . for the parasitological investigation ,", "the clinical samples were taken from patients suspected to have cl in different endemic areas of chabahar , including negor and other districts and villages .", "two were used for direct smears and were stained with giemsa , and the third was inoculated into sterile screw - tap tubes that contained blood agar slanted in nnn medium , then incubated at 25 1c .", "we evaluated the pcr - rflp assay of the its1 genes for direct identification of leishmania species in 24 out of 33 suspected patients .", "these patients were referred for diagnosis to the central laboratory of chabahar ( 25 17 n.70 38e ; 13,162 km ) for evaluation of skin diseases .", "the its1-rflp pcr assay is a multipurpose tool for the diagnosis of leishmania from clinical samples , and it enables determination of the infecting species ( 3 ) .", "the isolated promastigotes were subcultured in rpmi-1640 medium supplemented with 15% fetal bovine serum ( fbs ) , 100 g / ml streptomycin , and 100 u / ml penicillin ." ], [ "the diagnosis of leishmaniasis was confirmed by the presence of amastigotes in slit smears and/or the presence of flagellated promastigotes in nnn medium from typical and atypical lesions . for parasitological investigations ,", "parasites from a 15 ml mid - logarithmic phase of the bulk culture were harvested by centrifugation ( 700 g for 20 min at 4c ) and washed three times in ice - cold sterile pbs ( ph 7.2 ) .", "two of the samples were used for direct smears and were stained with giemsa , and the third was inoculated into sterile screw - top tubes containing blood agar slanted in nnn medium , then incubated at 25 1c .", "three skin samples were collected from the edges of the lesions using sterile surgical blades ." ], [ "for species identification , the dna isolated from amastigotes in ulcers and promastigotes in cultures was extracted using a commercial extraction kit ( high pure template dna preparation kit , roche , germany ) , according to the manufacturer s instructions .", "the designed program for leishmania dna amplification was an initial denaturation cycle at 95c for 5 minutes ; 30 cycles with cycle 1 at 95c for 20 seconds ( denaturation ) , cycle 2 at 53c for 30 seconds ( annealing ) , cycle 3 at 72c for 1 minute ( extension ) , and a final extension at 72c for 7 minutes .", "the reaction was carried out with the pcr - ready supreme mix in 47 l of total reaction , 15 l of deionized water , 5 l of target dna , and 25 l of master mix .", "the target its1-dna was amplified in a reaction mixture that consisted of 1 l of litsr : 5-cttg gatcattttccgatg-3 and 1 l of l5.8s 5-tga tac cac tta tcg cat t-3 ( 12 ) .", "major ( mhom / ir/15/er ) and l. tropica ( mhm / su/79/k27 ) ( 13 ) were used as positive controls .", "amplification products were separated in 1% agar gel and visualized under ultraviolet light after staining with ethidium bromide ." ], [ "the its1 sequence was amplified from all isolates , and reference stains were digested separately with restriction enzymes , according to the manufacturer s instructions .", "the pcr products from its1-dna pcr were digested using the haeiii restriction endonuclease enzyme and the taq1 restriction enzyme , as recommended by the manufacture ( new england biolabs , inc . ) ." ], [ "we used the pcr - rflp assay of its1 genes for the direct identification of leishmania species in 24 out of 33 patients suspected to have cl .", "rflp was performed on the its1 region in the ribosomal operons of 24 isolates of l. major . after using the restriction enzyme haeiii , banding patterns , including fragments of 140 bp and 210 bp bands ,", "single products of the expected size of 350 bp of l. major were detected in 21 patients ( figure 1 ) . in three isolates , a nonspecific 450 bp band was seen .", "were observed in 19 cases ( lma ) . in three cases with this enzyme , 300 bp and 150 bp bands ( figure 2 )", "were observed in 19 cases , same as the standard of l. major ( genotype pattern lma ) . in three isolates ," ], [ "thus , the results of the present study confirm that in the border area of sistan va baluchestan , on the peninsula of chabahar , l. major is the causative agent of cl , with genotypic variation in this area .", "the present study shows that cl is caused by l. major in chabahar , iran .", "it should be emphasized that leishmaniasis in chabahar is new , and genetic variation is limited .", "( 20 ) , two profile bandings ( 220 bp and 140 bp ) in haeiii digestion were detected , similar to the standard ." ] ]

[ [ "recently , improvement and progress in outcomes have been observed through better understanding of the disease , finding the effective factors in the start and progression of the disease , and ultimately in better management of the disease ( 16 ) .", "in addition , the research results could have an effective role in changing of the culture and laws of a society .", "retrospective research , in spite of some disadvantages , plays an important role in depicting the disease ( 16 , 19 ) .", "therefore , the link among researchers and clinicians will be stronger due to extensive research on the disease and improved introduction of the disease ( 17 , 18 ) .", "these factors have led to earlier diagnosis and more timely treatment , which could affect the clinical course and change the outcome for a patient .", "this research has been conducted after searching the electronic databases and performing a literature review , to ensure that no similar study had been undertaken in the region .", "it is a multisystem disorder affecting the gastrointestinal , respiratory , hepatobiliary , and reproductive systems , as well as the sweat glands ( 1 - 6 ) .", "cystic fibrosis ( cf ; omim 219700 ) is the most common lethal autosomal recessive disorder ( 1 , 2 ) , with an incidence rate of 1 in 2000 - 3000 live births in europe and 1 in 10,000 births for asians living in the united kingdom ( 1 ) .", "although numerous mutations in the cftr gene have been reported as a primary cause in the clinical manifestations and outcome of cf ( 9 ) , recent research has focused on the role of other factors such as gender ( 11 , 12 ) , race ( 1 ) , age ( 11 ) , geographic area ( 2 ) , infection with pseudomonas aeruginosa ( 11 , 13 ) , religion ( 8) , culture ( 1 , 14 ) , and nutritional status ( 13 - 15 ) ." ], [ "this study aimed to assess the association between outcomes and demographic status in azeri turkish patients with cystic fibrosis ." ], [ "this was a cross sectional study conducted at the educational and treatment children s hospital of the university of medical sciences and the medical genetic laboratory , tabriz , iran , from march 2001 to september 2014 .", "meq / l , according to the method of gibson and cooke , or detection of mutations in the cftr gene known to cause cf ( 21 ) .", "ranking in birth order of the family s children was divided into two groups , including one child as the first group , and two children or more as the second group .", "the kappa agreement rate was higher than 85% , as inclusion criteria to the next phase . in the end ,", "the diagnosis of cf was based on typical clinical features and confirmed by sweat chloride level > 60", "331 cases were included in this study , which was conducted over a 13-year period from 2001 to 2014 .", "this study was performed on azeri turks , who are members of one of the largest ethnic groups in iran ( 20 ) ." ], [ "the diagnosis of cf was based on typical clinical features and confirmed by sweat chloride level > 60 meq / l , according to the method of gibson and cooke , or detection of mutations in the cftr gene known to cause cf ( 21 ) .", "the kappa agreement rate was higher than 85% , as inclusion criteria to the next phase . in the end ,", "patients with incomplete records and who were not diagnosed as having cf were excluded with the reviewer s agreement .", "the medical records of 442 patients who met the inclusion criteria were separately reviewed by two authors .", "331 cases were included in this study , which was conducted over a 13-year period from 2001 to 2014 ." ], [ "ranking in birth order of the family s children was divided into two groups , including one child as the first group , and two children or more as the second group .", "data included patient outcome , gender , age , residence , ranking in birth order of the family s children , family history , consanguineous marriage , degree of consanguineous marriage , and weight at birth .", "a positive family history for cf was considered as having had a first , second , or third - degree relative affected with cf ( 22 ) .", "a consanguineous marriage was defined as a union between two persons who are related as first cousins ( 3rd degree ) , first cousins once removed or double second cousins ( 4 degree ) , and second cousins ( 5 degree ) . the first degree and the second degree", ", first cousins were classified as the first group and the others as the second group .", "logistic regression analyses were carried out to identify variables independently associated with gender . in all analyses ,", "the comparison between variables was analyzed with a chi - square or fisher s exact test , and independent samples t test .", "odds ratio ( or ) with a 95% confidence interval , and p < 0.05 indicated statistical significance ." ], [ "participants were assured of confidentiality , and consent was obtained from the patients or their parents .", "ethical aspects were considered and approval for the study was gained by the ethics committee of the university ( no = 5/4/1775 ) ." ], [ "there was no significant difference between outcome and ranking among the family s children , while 38 ( 23.9% ) were first - born children , and 47 ( 27.3% ) were second or later born children ( or = 0.83 [ 95% ci , 0.50 - 1.37 ] , p = 0.4 ) . in this study , we analyzed family history status among these patients , and the risk of mortality was approximately two times higher in patients with a positive family history than in those with a negative family history ( or = 1.91 [ 95% ci , 1.09 - 3.36 ] , p = 0.02 ) .", "associations between gender , ranking in birth order of the family s children , degree of consanguineous marriage , and weight at birth were not significant in terms of outcome , and therefore , omitted from the final model . when residential area , family history , and consanguineous marriage were entered into the model , the difference associated with outcome and or was somewhat reduced .", "the risk of mortality was 1.94 times higher for patients in consanguineous marriages than for those in non - consanguineous marriages .", ", age was assumed as non - normal distribution that uses the sample median and the iqr ( minimum - maximum ) , consequently , median age for living patients was 0.4 years ( 7 days30 years ) and median age at death was 4.8 years ( 3 months 43 years ) .", "demographic data of this study is shown in table 1.there was a significant difference between frequencies of deceased and living patients ( p < 0.001 ) . in the application of the kolmogorov - smirnov test" ], [ "there was no significant difference between outcome and ranking among the family s children , while 38 ( 23.9% ) were first - born children , and 47 ( 27.3% ) were second or later born children ( or = 0.83 [ 95% ci , 0.50 - 1.37 ] , p = 0.4 ) . in this study , we analyzed family history status among these patients , and the risk of mortality was approximately two times higher in patients with a positive family history than in those with a negative family history ( or = 1.91 [ 95% ci , 1.09 - 3.36 ] , p = 0.02 ) .", "at first , we calculated the association between outcome and gender . at the time of the study , 51 ( 26.7% ) of the deceased patients were males and 34(24.3% ) were females .", "the risk of mortality was 1.94 times higher for patients in consanguineous marriages than for those in non - consanguineous marriages .", "the test did not show any significant difference between outcome and gender ( or = 1.13 [ 95% ci , 0.68 - 1.87 ] , p = 0.6 ) . in the next step ,", "there was a significant difference between the outcome and the geographic location ( or = 0.55 [ 95% ci , 0.32 - 0.95 ] , p = 0.03 ) .", "there was a statistically significant difference between the outcome and consanguineous marriage ( or = 1.94 [ 95% ci , 1.14 - 3.29 ] , p = 0.01 ) , but no significant difference in degree of positive consanguineous marriage ( or = 0.68 [ 95% ci , 0.34 - 1.37 ] , p = 0.2 ) ." ], [ "associations between gender , ranking in birth order of the family s children , degree of consanguineous marriage , and weight at birth were not significant in terms of outcome , and therefore , omitted from the final model . when residential area , family history , and consanguineous marriage were entered into the model , the difference associated with outcome and or was somewhat reduced .", "there was no statistically significant difference when logistic regression analysis was considered with the or for all of the variables ( p > 0.05 ) .", "results of logistic regression analysis illustrated the adjusted or for the final model and are shown in table 3 ." ], [ "the association between non - genetic variables and mortality in individuals with cf has been established ( 2 , 6 ) . despite improved management and increased awareness , outcome remains an important issue for cf patients , because non - genetic parameters , especially demographic factors , have been ignored by researchers and clinicians .", "this study indicates an association between outcome and the number of demographic factors in cf patients and emphasized the role of these factors in outcomes .", "the current study was performed to highlight the associations between demographic parameters and outcomes in cf patients . in this study ,", "clinicians need to be aware and educate patients and their families about treatments such as the correct use of medicines ( oral nutritional supplements , antibiotics , and nebulizers ) , physiotherapy , and proper nutrition , which are essential for a positive prognosis , especially in patients living in rural areas .", "couples with consanguineous marriages , especially with a positive family history of the disease , require more frequent and thorough evaluations before pregnancy ." ], [ "in this study , the ratio of deceased patients to living patients was 1:3 , with a significant difference .", "eighty - five patients expired during the period of 13 years , with a mean of six deaths per year . in a study performed by dodge et al . in the uk from 1996 to 2003 , there were 1,066 deaths , with a mean of 133 deaths per year ( 15 ) .", "we hypothesize that this difference may be due to the lack of proper equipment , inadequate diagnostic processes , and absence of treatment by specialists and expert staff , as well as poor nutritional status in our region compared to developed countries ( 13 , 24 ) .", "therefore , based on these findings the mortality rate is lower in our study than in the uk , perhaps because this study has been performed on an ethnic group in iran with a low incidence of cf .", "european countries ( 24 ) . in our study , living cf patients had lower mean , median , and were of an older age than that reported in developed countries . also , in deceased cf patients the mean and median age at death were lower than in developed countries ." ], [ "the presence of ranking among the family s children , degree of consanguineous marriage , and weight at birth do not rule in the mortality of cf , although location of residence , family history , and consanguineous marriage are predictors of increased mortality in cf patients .", "in our study , there was no significant difference between outcome and gender ; however , the mortality rate was somewhat higher in males than females .", "growth and lung health of children is influenced by proper treatment , and decreased pulmonary function is associated with morbidity and shortened survival for cf patients ( 28 ) .", "high socioeconomic status with adequate income , suitable occupation , and employment status were identified as factors related to a good prognosis in affected individuals ( 30 ) . in crowded families ,", "management of patients with cf is one of the greatest challenges for families , and the family plays an important role in the treatment of cf ( 30 ) . cf patients need constant care such as physiotherapy , various medications , proper dietary intake , exercise , and adequate support ( 21 , 31 ) . on the other hand ,", "preventive treatments , such as adequate exercise , have been introduced at early ages for cf patients , and it appears to be an important factor in health maintenance in patients with cf ( 27 ) ." ], [ "data were limited to the children s hospital of the university of medical sciences and medical genetic laboratory in tabriz , and it was possible that some cf patients were not referred to these centers .", "the strength of this study was the adequate sample size in this population , and that it was conducted over a long period of time .", "data that was approved by two reviewers were collected from educational , referral , and therapeutic centers , and were designed to evaluate the effects of non - genetic factors on outcomes .", "the primary weakness of this study was that it was a retrospective study and may have limited accuracy , but it does lead the way to prospective research .", "another weak point was the investigation was limited to a specialist group , which decreases the ability to generalize the study results .", "this study was conducted in a population with a unique religion , ethnic origin , and culture , which could be a basis for the performance of comparative studies ." ], [ "clinicians need to be aware and educate patients and their families about treatments such as the correct use of medicines ( oral nutritional supplements , antibiotics , and nebulizers ) , physiotherapy , and proper nutrition , which are essential for a positive prognosis , especially in patients living in rural areas .", "it should be required that the government and relevant organizations focus on informing the public of the dangers of consanguinity .", "this study indicates an association between outcome and the number of demographic factors in cf patients and emphasized the role of these factors in outcomes .", "couples with consanguineous marriages , especially with a positive family history of the disease , require more frequent and thorough evaluations before pregnancy .", "other studies were performed for evaluating the association , if any , between outcome and other demographic factors ." ] ]

[ [ "the original technique of staining the anterior capsule with trypan blue ( tb ) in eyes with no red reflex involves the injection of the dye with a cannula after filling the anterior chamber with an air bubble.1 the stability of the anterior chamber can be compromised by air escaping when the cannula is introduced and the dye is injected .", "we present an under - air staining technique of the anterior capsule using one drop of tb injected with a 30 g needle through the peripheral cornea .", "our procedure prevents the exit of air during the injection of the dye , resulting in increased stability of the anterior chamber .", "several techniques using viscoelastic substances as an alternative to air have been presented to increase the stability of the anterior chamber.25 however , staining under viscoelastic material can be time - consuming and expensive , as it requires the mechanical spreading of tb onto the anterior capsule and the replacement of the viscous solution when an excessive diffusion of dye affects its transparency .", "moreover , the superficial tension of air bubble and capillary action between tb and the metal cannula can force the dye to build up within the aqueous meniscus surrounding the air bubble , making selective staining of the capsule difficult .", "moreover , it allows selective staining of the capsule using the needle and avoids an excessive buildup of tb in the anterior chamber ." ], [ "inject viscoelastic substance in the anterior chamber through the side - port incision , allowing the air and the leftover dye to exit the eye .", "the needle tip allows precise control on the injected dye , similarly to a dropper . if the staining is not sufficient , it is possible to inject one more drop of tb on the unstained area .", "once the needle is removed , the perforation will close spontaneously in a few seconds , and if necessary an absorbent stick can be used to stop tiny leakages of air and/ or dye .", "unlike what occurs using a cannula , the air can not escape from the anterior chamber .", "introduce the 30 g needle bevel - up in the anterior chamber through the peripheral cornea between the side - port incision and the site chosen for the corneal tunnel ." ], [ ", the use of the 30 g needle technique could be dangerous and should be avoided . in conclusion , in a small series of seven patients , the staining of the anterior capsule using tb under air with a 30 g needle allowed for enhanced stability of the anterior chamber and the use of the smallest quantity of dye .", "tb is the most used dye to perform capsulorhexis in eyes with no red reflex.6 the main staining techniques involve tb injection under air,1 under viscoelastic material,25 or directly under aqueous humor .", "an air bubble within the anterior chamber reduces the contact between the dye and the corneal endothelium and allows the delivery of undiluted tb onto the anterior capsule ." ] ]