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[ [ "we describe herein a successful case of newly diagnosed primary pcl , treated with a regimen that included bortezomib , followed by auto stem cell transplantation ( asct ) and nonmyeloablative allogeneic stem cell transplantation ( allo - sct ) .", "plasma cell leukemia ( pcl ) is a rare disease that represents approximately 4% of plasma cell malignant disorders.1 diagnosis of pcl is established based on kyle s criteria , which includes an absolute plasma cell number accounting for greater than 2000/l or 20% of white blood cell differentiation.2 pcl consists of two variants : primary pcl presents in patients with no previous history of multiple myeloma ( mm ) , while secondary pcl consists of a leukemic transformation in previously recognized mm.3 primary pcl is an extremely resistant , rapidly progressive , fatal disease , with a median overall survival of 6.8 months.4 there is no standard therapeutic strategy because none of the treatment options have been prospectively evaluated ." ], [ "he remained in a state of remission , with only the complication of mild skin gvhd .", "serum / , a surrogate marker for the treatment effect of this case , became similar to normal levels .", "graft - versus - host disease ( gvhd ) prophylaxis included tacrolimus and short - term methotrexate .", "this acute heart failure was probably caused by cardiac amyloidosis , as cardiac ultrasound showed a granular sparkling pattern .", "in addition , the granular sparkling pattern detected by cardiac ultrasound at the time of admission disappeared . the patient was then administered high - dose therapy ( hdt ) + asct . before hdt + asct , his p eripheral blood stem cells containing 10.9 10/kg cd34-positive cells were harvested with high - dose cyclophosphamide ." ], [ "we have a successful case of newly diagnosed primary pcl , treated with a regimen that included bortezomib and asct , followed by nonmyeloablative allo - sct .", "our case represented a potential curative strategy for pcl , with the safe introduction of allo - immunization with a n onmyeloablative regimen following pad and hdt + asct . for multiple mm , the most common malignant disease in plasma cells ,", "allo - sct is a promising therapy . because of the graft - versus - myeloma effect ,", "there are no established therapeutic regimens for pcl . several regimens that include an alkylating agent are sufficient to improve the overall survival ( os ) of pcl patients ." ] ]

[ [ "an abdominal computed tomography ( ct ) scan may reveal subcapsular enhancement of the liver in arterial phase ( 4 ) . we herein report a case of fitz hugh curtis syndrome in a male patient that was diagnosed via laparoscopy .", "fitz hugh curtis syndrome is an extra - pelvic manifestation of pelvic inflammatory disease ( pid ) and is characterized by perihepatic adhesions between liver capsule and diaphragm or anterior peritoneal surface(13 ) .", "most fitz hugh curtis syndrome patients are women of child bearing age and rarely has the syndrome been reported in males .", "the predominant symptom is pain in the right upper quadrant , which may be confused with biliary disease" ], [ "a 29 year - old african american male with russel - silver dwarfism presented with one day history of diarrhea , nausea , vomiting , right side abdominal pain , and abdominal distention .", "he was refusing any surgical intervention at this point . on hospital day 5 , a repeat abdominal ct scan demonstrated a normal appearing liver , small bowel , large bowel , and appendix , with a mild increase in pelvic free fluid .", "as the patient 's symptoms did not improve with conservative management , he ultimately agreed to undergo a diagnostic laparoscopy , and was taken to the operating room on hospital day 9 .", "his diet was gradually advanced , which he tolerated well , and was discharged on post operative day 2 .", "the pain was constant , gradually increasing in severity , and not related to food intake .", "appendectomy was not performed as per patient'swishes . following the procedure , the patient reported complete resolution of his symptoms ." ], [ "these symptoms can pose diagnostic challenges as they may be confused with biliary tract symptoms . in a clinical setting ,", "it occurs mostly in premenopausal women , however , cases in males have also been reported .", "most cases of fitz hugh curtis syndrome are managed with antibiotics against gonorrhea and chlamydia .", "fitz -hugh curtis syndrome was first described in 1920 by carlos stajano . in the 1930 's thomas fitz " ] ]

[ [ "although this may seem adequate for example , the talos database contains 186 proteins subdivided into over 24,000 tripeptide fragments ( http://spin.niddk.nih.gov/nmrpipe/talos/)the sequence / conformation search space is very large , and the database coverage is unevenly distributed . as a result , rare combinations of amino - acid and conformation may be under - represented in the database , leading to significant under - prediction and even to errors outside of the heavily populated regions of the ramachandran map .", "chemical shifts are now routinely used as a source of local conformational restraints in the structure determination of proteins by nmr , due mostly to the widespread use of programs such as talos ( cornilescu et al .", "we benchmark the program against talos as a standard for current methods and hhpred , a sequence search method based on hidden markov models ( sding et al .", "we have adopted an alternative approach to extracting structural data from chemical shifts based on our simshiftdb algorithm .", "2007a ) routine for standardizing chemical shift referencing to produce a pipeline for analysis of chemical shift data .", "it searches a synthetic chemical shift database of 13,000 proteins based on the astral library ( chandonia et al .", "the original simshift was designed to test for structural similarities between proteins in a pair wise manner using chemical shifts to supplement sequence data ." ], [ "given a target protein , simshiftdb analyzes each possible pairing of the target protein with one of the template protein structures in the database .", "here we use the proteins from the astral database ( version 1.71 , filtered for 95% sequence identity ) to build the simshiftdb template database . as simshiftdb", "is based on the comparison of chemical shift data , the chemical shifts for all entries in the template database are back - calculated from the three - dimensional structure using shiftx ( neal et al . 2003 ) . for each combination of the target protein with a template from the database ," ], [ "hhsearch , a sensitive search tool based on hidden markov models , calculates alignments between proteins using the primary sequence complemented by sequence - based predictions of secondary structure .", "therefore a mapping between bmrb and astral is calculated based on amino acid sequence similarity .", "additionally , it is freely available for download and gives the user the possibility to define arbitrary template databases . therefore it is perfectly suited to serve as a reference for purely sequence - based methods . to compare the performance of simshiftdb and hhsearch we used the benchmark set defined in the previous section . for both methods we ran each target protein against the simshiftdb template database and used alignments achieving an e - value better than 10 to predict torsion angles for the residues in the target protein .", "2005 ) , a protein structure prediction method based on hhsearch alignments , ranked second best in the casp7 ( battey et al .", "the lines show the overall secondary structure content in all predictions difference between secondary structure content in erroneous predictions versus the content for all predictions using the same scheme as in fig . 3 to show empirically that simshiftdb uses the information in the chemical shift data to yield more sensitive alignments , especially in the case of low sequence similarity , we compare simshiftdb to hhsearch ( sding 2005 ) .", ", we applied the program to all entries in the benchmark set , using all proteins from the simshiftdb template database as potential templates ." ], [ "at least 100 residues with associated chemical shifts ( to exclude very short protein fragments ; e.g. single helices ) . to identify protein structures corresponding to the respective bmrb entries , a blast - search ( altschul et al . 1990 ) against the sequences from the astral database is conducted for each bmrb entry . if the full bmrb sequence can be matched without gaps against an astral sequence , the corresponding astral structure is assigned to the bmrb entry .", "as some entries in bmrb match more than one sequence in astral , one representative structure has to be chosen .", "2004 ) provided for each astral entry , thereby selecting the structure with the best resolution . through this procedure", "every entry in the benchmark set has to fulfill the following constraints : a 100% sequence match to an astral entry.at least 100 residues with associated chemical shifts ( to exclude very short protein fragments ; e.g. single helices ) .", "therefore a mapping between bmrb and astral is calculated based on amino acid sequence similarity .", "to test the performance of simshiftdb , a benchmark set has to be defined for which both chemical shifts and the three - dimensional structure of the protein are available ." ], [ "when calculating the similarity score for two residues , simshiftdb is restricted to at most three chemical shifts from the following list : h , h , n , c , c , and c. thus it is important to select a combination of shifts to extract maximum information , and a priority for replacing missing shifts . to identify the most successful strategy , we tested all possible priorities for the six atom types , resulting in 6 ! = 720 evaluations .", "the lines show the overall secondary structure content in all predictions difference between secondary structure content in erroneous predictions versus the content for all predictions using the same scheme as in fig . 3", "3difference between secondary structure content in high quality predictions versus the content for all predictions .", "3 difference between secondary structure content in high quality predictions versus the content for all predictions .", "4difference between secondary structure content in erroneous predictions versus the content for all predictions using the same scheme as in fig . ", "this test shows empirically that simshiftdb has no significant bias when comparing performance in predicting helix versus sheet .", "about 70% of all torsion angles predicted using simshiftdb have a high accuracy ( 15 error ) ." ], [ "to show empirically that simshiftdb uses the information in the chemical shift data to yield more sensitive alignments , especially in the case of low sequence similarity , we compare simshiftdb to hhsearch ( sding 2005 ) .", "hhsearch , a sensitive search tool based on hidden markov models , calculates alignments between proteins using the primary sequence complemented by sequence - based predictions of secondary structure .", "the following notation is used for the presentation of the results :- a simshiftdb prediction is called better if it has an error of 30 and the corresponding hhsearch prediction has an error which is worse by more than 5.two predictions are called equal if both have an error of 30 and the difference between the errors is less than 5 , or both predictions have an error > 30.missing predictions are treated as predictions with an error > 30. a simshiftdb prediction is called better if it has an error of 30 and the corresponding hhsearch prediction has an error which is worse by more than 5. two predictions are called equal if both have an error of 30 and the difference between the errors is less than 5 , or both predictions have an error > 30. missing predictions are treated as predictions with an error > 30. figure 5 shows the results of this evaluation for alignments with maximal sequence identities ranging from 10 to 100% .", "for both methods we ran each target protein against the simshiftdb template database and used alignments achieving an e - value better than 10 to predict torsion angles for the residues in the target protein .", "5simshiftdb predictions compared to the respective hhsearch predictions , separated according to the maximum allowed sequence identity between query and target .", "therefore it is perfectly suited to serve as a reference for purely sequence - based methods . to compare the performance of simshiftdb and hhsearch we used the benchmark set defined in the previous section .", "2005 ) , a protein structure prediction method based on hhsearch alignments , ranked second best in the casp7 ( battey et al . 2007 ) experiment ." ], [ "it should be noted that there is likely to be a significant bias towards talos in these results , as many members of the benchmark set will have been calculated using talos restraints.fig . ", "it is important to compare simshiftdb to the most prominent method for predicting torsion angles from chemical shifts , namely talos ( cornilescu et al . 1999 ) .", "we then compared the quality of each torsion angle prediction to the corresponding talos prediction .", "again we used the benchmark set defined earlier , and made torsion angle predictions based on simshiftdb alignments that achieved an e - value better than 10 .", "figure 6 shows that simshiftdb outperforms talos in at least 30% of all cases ." ], [ "we have presented simshiftdb and shown that the program is able to sensitively extract structural information from chemical shift data .", ", we were able to show that one - third of the predictions by simshiftdb clearly have a higher quality than the corresponding talos predictions , and this is largely independent of sequence similarity .", "simshiftdb shows its strength especially in cases of low sequence similarity , which underlines the advantage of including chemical shift information in the alignment algorithm . on the other hand", "this information is to a certain extent complementary to that from currently available tools . on one hand", "the main advantage of simshiftdb is derived from its superior coverage of the search space , due to the large and quickly adaptable template database ." ] ]

[ [ "the data reported here summarize the astigmatic changes produced with a small ( 2.2 mm ) square posterior limbal incision .", "sutureless clear corneal incisions are now arguably the most common incisions made to perform cataract surgery with phacoemulsification , replacing scleral tunnel and limbal incisions .", "vascular arcades are present , providing a potential source of fibroblasts . the differences in the healing effects of incisions at the limbus and the cornea have been previously discussed in the literature [ 24 ] .", "there are significant differences in the effects of clear corneal and scleral or limbal incisions , related to anatomical and physiological differences in the respective structures where the incisions are made ." ], [ "a retrospective patient chart review was conducted at one site ( pe ) for a study of toric and spherical iols . those eyes with preoperative and postoperative keratometry results", "comparative surgically induced astigmatism data were obtained from one of the authors ( w. hill ) from a website specifically designed to collect preoperative and postoperative keratometry data for the purposes of calculating surgically induced astigmatism .", "the automated keratometry readings were repeated on all patients postoperatively , and the comparison to the preoperative automated keratometry was used to calculate sia .", "surgical technique was not described in the aggregate sia data collected off the web , but incision type ( e.g. , clear corneal , limbal ) was generally indicated , and the size of the incision was noted .", "the surgical technique employed in the time period in which the retrospective data were collected was constant for all patients .", "the data were corroborated with an automated keratometry reading and the automated keratometry feature of the iolmaster ( carl zeiss meditec , jena , germany ) .", "an option allows any surgeon who uses the spreadsheet to upload their data to the website for the purposes of aggregate analysis ." ], [ "surgically induced astigmatism was calculated as the vector difference between preoperative and postoperative anterior corneal astigmatism as measured with automated keratometry .", ". looking at the aggregate clear corneal incision data versus the ernest posterior limbal data , there was a statistically significant difference in the surgically induced astigmatism by incision type ( p < 0.001 ) . inside the clear corneal group", "the review of available clinical records from pe yielded a total of 38 eyes that both met the criteria for inclusion and had available postoperative keratometry data for analysis .", "as a post hoc test , the ernest data were compared to the surgeon with the lowest average sia from the clear corneal incision group ( surgeon 5 ) ; there was a statistically significantly lower mean sia in the ernest cohort ( p = 0.001 ) .", "post hoc testing showed that the ernest data yielded a statistically significantly lower sia than the other surgeons ' data ." ], [ "the results suggest that the magnitude and the variability of surgically induced astigmatism with small incision surgery ( 2.2 mm ) is significantly lower if a posterior limbal incision is used instead of a clear corneal incision .", "the minimization of the magnitude ( and variability ) of surgically induced astigmatism is important for modern day cataract surgery , particularly with the use of toric and multifocal intraocular lenses", "surgeons interested in reducing the magnitude and variability of induced astigmatism at the time of cataract surgery may want to consider the use of a 2.2 mm square posterior limbal incision ." ] ]

[ [ "the objective of this study is to compare the measurements of transverse cerebellar and anterior - posterior cisterna magna diameter obtained by 2d and 3dus using the software 3d xi in normal pregnant women between 18 and 24 weeks .", "the measurement of the transverse cerebellar diameter by two - dimensional ultrasonography ( 2dus ) is a very reliable parameter in the evaluation and early detection of intrauterine growth restriction . on the other hand , an adequate evaluation of the posterior fossa abnormalities", "allows the diagnosis of the cisterna magna as the dandy - walker complex , megacisterna magna , and blake 's cyst ." ], [ "to evaluate the difference between the two techniques the wilcoxon test was used . to evaluate the correlation of 2d and 3d , measurements of the transverse cerebellar diameter and antero - posterior cisterna magna as well as measurements of biparietal diameter ( bpd ) and head circumference ( hc ) according to the gestational age , the spearman 's correlation coefficient ( r ) was used . in cases of high correlation , polynomial regression models , with adjustments by the coefficient of determination ( r )", "a second examiner ( lsvf ) , with the same experience in obstetric ultrasound performed a third measure of these same 8 cases , and the results were armored one of the other . for this purpose , to calculate the reproducibility intraclass correlation coefficient ( icc ) and", "initially , a realtime 2d evaluation was performed in order to evaluate the biometry , morphology , and quantification of amniotic fluid volume . for the 2d measurement of transverse cerebellar and anterior - posterior cisterna magna", "a prospective cross - sectional study between march 2010 and february 2011 , involving 69 normal pregnant women between 18 and 24 weeks was performed .", "the patients were randomly selected , and all evaluation made by a single examiner ( fsbb ) , with five years experience in obstetric ultrasound .", "for the 2d and 3d measurements of the transverse cerebellar diameter and antero - posterior cisterna magna , mean , median , maximum , and minimum values were calculated . and for the 3d measurements percentiles 5 , 10 , 90 , and 95 were also calculated in each gestational age evaluated ." ], [ "the equation that best represented the correlation between the extent of the transverse cerebellar diameter and gestational age was of a second degree : dtc = 7.231 + 1.851 ga 0.027 ga2 ( r = 0879 ) . for the measurement of antero - posterior diameter of the cisterna magna ,", "tables 3 and 4 show the percentiles 5 , 10 , 90 , and 95 for measurements of the transverse and anterior - posterior cerebellum and cisterna magna diameter at each gestational age evaluated . an icc > 0.66 for all intra- and interobserver measurements of the cerebellum and cisterna magna length by 3dus was observed , with the exception of the intraobserver measurement of the length of cisterna magna ( icc = 0.792 , 0.668 , 0.691 , and 0.287 , resp . ) .", "it was observed that on average the measurements obtained by 3dus were significantly higher , 0.76 and 1.02 mm for the length of the cerebellum and cisterna magna , respectively ( p < 0.001 ) ( tables 1 and 2 ) .", "the low correlation between the antero - posterior diameter of the cisterna magna and gestational age did not allow the construction of polynomial regression models ." ], [ ", we compared the measurements of the transverse and antero - posterior cerebellum and cisterna magna diameters by 2d and 3dus between 18 and 24 weeks .", "measures the length of the cerebellum and cisterna magna by 3dus proved to be reproducible .", "we believe that the great importance of this study is the evaluation of borderline cases , such as an anterior - posterior diameter of the fetal cisterna magna of 9.0 mm and a transverse cerebellar diameter of 16 mm at 18 weeks of gestational age . in these cases the 3dus with the program multislice view can help in decision making between normal and pathological cases , modifying the prenatal , and counseling of the parents . in summary , this was the first study that compared the measurements of the transverse and antero - posterior fetal cerebellum and cisterna magna diameters by 2d- and 3dus using the 3d xi ( multislice view ) software .", "the measurements the length of the fetal cerebellum and cisterna magna by 3dus were significantly higher than those obtained by 2dus .", "the length measurement of the cisterna magna by 3dus showed low correlation with gestational age ." ] ]

[ [ "ten healthy nondiabetic volunteers were recruited to serve as control subjects . finally , five patients with type 1 diabetes awaiting pancreas or islet transplant , all of whom demonstrated no c - peptide production at the time of study inclusion , served as negative control subjects .", "fifteen islet transplant recipients were enrolled in the islet group , which was further subdivided into an insulin - independent group ( ii - isl ) and an insulin - requiring group ( ir - isl ) .", "ratios of insulin to total proinsulin and insulin [ insulin/(total proinsulin+insulin ) ] as well as proinsulin fragments to total proinsulin ( proinsulin fragments / total proinsulin ) were calculated to quantify the rate of proinsulin processing .", "an arginine stimulation test was performed on all subjects to determine basal and stimulated pancreatic hormone levels .", "serum levels of insulin , c - peptide , total proinsulin , and intact proinsulin ( ipi ) were then measured using commercially available elisas as described below .", "commercially available elisas were used to measure hormone levels for insulin , c - peptide , total proinsulin , and ipi .", "insulin/(total proinsulin+insulin ) ratio represents the quantity of fully processed insulin with respect to all circulating forms of the hormone ." ], [ "all samples were obtained from patients during either their annual posttransplantation follow - up or one of their regularly scheduled outpatient consultations .", "the serum was labeled using the same anonymous codes assigned to the tubes at the time of the test ." ], [ "ratios of insulin to total proinsulin and insulin [ insulin/(total proinsulin+insulin ) ] as well as proinsulin fragments to total proinsulin ( proinsulin fragments / total proinsulin ) were calculated to quantify the rate of proinsulin processing .", "proinsulin fragments , including split-32,33 proinsulin , des-31,32 proinsulin , split-65,66 proinsulin , and des-64,65 proinsulin , were obtained by subtracting ipi from total proinsulin .", "insulin/(total proinsulin+insulin ) ratio represents the quantity of fully processed insulin with respect to all circulating forms of the hormone .", "serum levels of insulin , c - peptide , total proinsulin , and intact proinsulin ( ipi ) were then measured using commercially available elisas as described below . acute insulin response ( air )", "ratios representing peak stimulation were calculated as the mean of ratios for the three highest time points between 2 and 5 min after arginine stimulation .", "the area under the curve ( auc ) between 0 and 10 min postinjection for insulin and c - peptide was calculated by the trapezoidal rule with the mean of the baseline values subtracted .", "was calculated as the mean of the three highest values between 2 and 5 min minus the mean of the basal values at 10 and 0 min .", "an arginine stimulation test was performed on all subjects to determine basal and stimulated pancreatic hormone levels ." ], [ "cross - reactivities of the assays were provided by the manufacturer and are as follows : the insulin assay cross - reacts 98% with des-64,65 proinsulin , < 0.01% with c - peptide and proinsulin , and < 0.05% with des-31,32 proinsulin and split-32,33 proinsulin ; the c - peptide elisa cross - reacts <", "the lower limits of detection of the assays were provided by the manufacturer and are as follows : the insulin assay has a detection limit of 6", "pmol / l , the c - peptide elisa has a limit of 15 pmol / l , the total proinsulin assay has a limit of 0.5 pmol / l , and the ipi assay has a lower limit of 0.1 pmol / l .", "0.0006% with insulin , < 1.8% with proinsulin , 10% with split-65,66 proinsulin , 74% with des-64,65 proinsulin , 3% with des-31,32 proinsulin , and 2% with split-32,33 proinsulin ; the total proinsulin elisa cross - reacts 100% with intact and des-31,32 proinsulin , and 81% with des-64,65 proinsulin ; the ipi elisa cross - reacts 36% with des-64,54 proinsulin , and it shows no cross - reactivity with des-31,32 proinsulin .", "commercially available elisas were used to measure hormone levels for insulin , c - peptide , total proinsulin , and ipi .", "concentrations were determined using a standard curve with high- and low - level control subjects ." ], [ "student t test was used to compare two groups , and one - way anova was used to compare between more than two groups . for data that had non - gaussian distributions , we used the mann - whitney test to compare between two groups and the kruskal - wallis test to compare between more than two groups .", "all statistical analyses were performed using prism 6 software ( graphpad software , la jolla , ca ) . for all analyses , values obtained from healthy subjects were used as control subjects . for data that were normally distributed ," ], [ "insulin levels were higher in pancreas recipients but lower in islet recipients compared with healthy control subjects .", "these values were higher in pancreas recipients and lower in islet recipients compared with healthy control subjects .", "creatinine levels were elevated in the pancreas and ir - isl groups with respect to the ii - isl and healthy control groups ( p < 0.005 vs. control , p < 0.05 vs. ii - isl ) .", "these figures show that total proinsulin levels are reduced in the ir - isl group with respect to all other groups and follow a distribution similar to that of c - peptide . a : box plots of basal c - peptide and total proinsulin levels in healthy control group , ir - isl group , ii - isr group , and pancreas group before arginine injection ( basal values ) .", "a : mean insulin levels during arginine stimulation of healthy control group , ir - isl group , ii - isl group , pancreas group , and diabetic control group .", "the auc of c - peptide for the ir - isl group was significantly lower than in all other groups ." ], [ "subjects in the healthy control group were slightly younger than the rest of the study population ( p < 0.01 ) .", "islet recipients exhibited higher fasting glycemia and hba1c levels than other groups ( p < 0.05 ) .", "creatinine levels were elevated in the pancreas and ir - isl groups with respect to the ii - isl and healthy control groups ( p < 0.005 vs. control , p < 0.05 vs. ii - isl ) .", "nonetheless , hba1c levels remained in the normal range for the ii - isl group ." ], [ "these values were higher in pancreas recipients and lower in islet recipients compared with healthy control subjects .", "insulin levels were higher in pancreas recipients but lower in islet recipients compared with healthy control subjects .", "the auc of c - peptide for the ir - isl group was significantly lower than in all other groups .", "the insulin and c - peptide response curves maintain the same overall shape in all groups , with the exception of the diabetic control subjects who demonstrate no response to arginine stimulation .", "auc values for c - peptide response in healthy control subjects , ir - isl , ii - isl , and pancreas groups were 4,955 3,158 , 630 428 , 1,843 875 , and 3,859 2,061 pmol ", "auc values for insulin response in healthy control subjects , ir - isl , ii - isl , and pancreas groups were 1,332 959 , 152 91 , 774 528 , and 1,540 707 pmol ", "insulin levels in the pancreas group were significantly higher than those of the healthy control group ." ], [ "these figures show that total proinsulin levels are reduced in the ir - isl group with respect to all other groups and follow a distribution similar to that of c - peptide . a : box plots of basal c - peptide and total proinsulin levels in healthy control group , ir - isl group , ii - isr group , and pancreas group before arginine injection ( basal values ) .", "mean values for c - peptide and total proinsulin before and after arginine stimulation are shown in fig .", "b : box plots of stimulated c - peptide and total proinsulin levels in healthy control group , ir - isl group , ii - isl group , and pancreas group during peak stimulation after arginine injection ( stimulated values ) .", "data are expressed as median ( solid line ) , interquartile range ( box ) , and range ( whiskers ) ." ], [ "the healthy control group demonstrated lower basal proinsulin - processing rates than the pancreas ( p < 0.01 ) and ii - isl ( p < 0.05 ) groups [ 74 14% vs. 83 7% vs. 86 12% , respectively , for insulin/(total proinsulin+insulin ) and 54 25% vs. 67 ", "a : box plots of the proinsulin - processing ratios [ ( insulin / total proinsulin+insulin ) and ( proinsulin fragments / total proinsulin ) ] in healthy control group , ir - isl group , ii - isl group , and pancreas group before arginine injection ( basal values ) .", "b : box plots of the proinsulin - processing ratios [ ( insulin / total proinsulin+insulin ) and ( proinsulin fragments / total proinsulin ) ] in healthy control group , ir - isl group , ii - isl group , and pancreas group during peak stimulation after arginine injection ( stimulated values ) .", "the ir - isl group displayed a basal insulin/(total proinsulin+insulin ) rate of 75 14% and a basal proinsulin fragments / total proinsulin rate of 54 25% .", "data are expressed as median ( solid line ) , interquartile range ( box ) , and range ( whiskers ) .", "18% vs. 76 16% , respectively , for proinsulin fragments / total proinsulin ] .", "i / tp+i , insulin / total proinsulin+insulin ; pf / tp , proinsulin fragments / total proinsulin ." ], [ "although ir - isl proinsulin - processing ratios do increase slightly after stimulation to 87 4% and 58 18% for insulin/(total proinsulin + insulin ) and proinsulin fragments / total proinsulin , respectively , these values remain significantly lower than all other groups ( p < 0.01 vs. control and pancreas groups , p < 0.05 vs. ii - isl ) .", "9% vs. 76 12% , respectively , for proinsulin fragments / total proinsulin ) , while ir - isl transplant recipients ratios do not demonstrate a comparable increase .", "3b . interestingly , healthy control subjects , pancreas recipients , and ii - isl recipients all attain similarly elevated processing ratios after stimulation ( 93 2% vs. 93 ", "3% vs. 93 5% , respectively , for insulin/(total proinsulin+insulin ) and 80 7% vs. 77 " ], [ "this study explores for the first time proinsulin processing in islet transplant recipients , not only in comparison with healthy control subjects , but also with respect to pancreas transplant recipients .", "ir - isl transplant recipients demonstrate both lower insulin response and lower basal rates of proinsulin processing , which remain suboptimal even after arginine stimulation ( i.e. , loss of graft function is associated with less effective processing and relative hyperproinsulinemia )", ". finally , the higher airs of pancreas transplant recipients are a reflection of systemic venous drainage of endocrine secretions .", "as expected , recipients of pancreas transplants with systemic venous drainage demonstrate higher insulin response to arginine than healthy control subjects .", "we have shown , first , that the exposure to arginine stimulation is in fact similar in ii - isl transplant recipients and healthy control subjects ." ], [] ]

[ [ "we have demonstrated that , melatonin is a bioprecursor of hypnotic acetyl metabolites produced by enzymatic acetylation of melatonin and 2-oxomelatonin under the control of acetyltransferases , most probably the nat enzymes . in 1994 , in our laboratory , we developed a specific and highly sensitive gas chromatography - mass spectrometry ( gc - ms ) method to assay , simultaneously and distinct ! ) , plasma concentrations of endogenous melatonin ( d0melatonin ) and exogenous melatonin ( d7-melatonin ) , in which 7 atoms of h have been substituted by 7 atoms of deuterium .", "there is a large interindividual variability in the amount , of melatonin released in plasma by the pineal gland during the night in young and old subjects alike .", "duration of melatonin pineal secretion is between 7.5 and 8 h. therefore , melatonin secretion and sleep are contemporaneous .", "pharmacokinetic analysis shows that the rate of melatonin secretion by the pineal gland is constant throughout the whole nocturnal pineal melatonin production , for the same subject .", "the beginning and end of melatonin secretion from the pineal gland are the same for each subject , whatever the season and night , length .", "using the same human volunteers ( 12 young subjects in june 1994 and 12 elderly subjects in october 1994 ) , we determined the pharmacokinetics of exogenous d7-melatonin , when given orally and intravenously , and the kinetics of the pineal secretion of endogenous d0-melatonin . , the results shown in figure 2 led to the following conclusions : secretion of melatonin by the pineal gland occurs only during the night ." ], [ "results of previous related studies show that melatonin secretion , and therefore the presence of melatonin in the central nervous system ( cns ) , is necessary for the induction and maintenance of nocturnal sleep . however , the presence of melatonin in the cns is insufficient for the induction and maintenance of sleep . indeed , figure 3 and table", "i show results of observations in chicks in an alternate light ( l)-dark ( d ) program ( l / d , 12 h:12 h ) , in which the light phase lasted from 8.00 am until 8.00 pm .", "in contrast , when chicks were observed in a 7-day permanent light , program ( l / l , 12 h:12 h ) , during which nat activity level was constantly higher , the administration of melatonin induced a significant , hypnotic effect .", "when melatonin was administered intramuscularly ( pectoralis major muscle ) during the light phase from 2.00 pm to 8.00 pm , the chicks did not .", "the absence of a hypnotic effect during the light phase correlated with the very low level of nat activity in the pineal glands of chicks measured at the same times .", "these results lead to the following conclusions : the simultaneous presence of melatonin and nat in the cns ( pineal gland ) is a necessary and sufficient condition for the induction and maintenance of sleep .", "the duration of sleep ( between 4 and 5 h ) was much greater than that , observed with diazepam ( between 1 and 2 h ) when it ." ], [ "we conclude that melatonin is a bioprecursor of hypnotic acetyl metabolites , such as carbo2 .", ", we assumed that melatonin undergoes enzymatic acetylation during the night , under the control of nat , and that this leads to an n - acetyl--carboline , which we call carbo2 .", "during the development of the gc - ms method for the assay of melatonin in plasma , our attention was focussed on the chemical reactivity of melatonin at position 3 , which allows cyciization of the side chain after acylation ." ], [ "figure 5 and figure 6 show that melatonin ( or 2-oxomelatonin ) undergoes an aeetylation that is significantly higher ( p<0.002 , in the middle of dark phase ; p<0.0005 , 1 h before end of dark phase [ or p<0.00005 for 2oxomelatonin over the whole dark phase ] ) than that observed in controls ( nonsignificant when melatonin was replaced by phosphate buffer ) .", "chick pineal glands were observed during an alternate light - dark program at 37c for 7 days . in the middle of dark phase ,", "gc - ms indicated the biosynthesis of [ h]carbo2 for five chick pineal glands collected in the middle of dark phase ( table ii ) .", "they were treated with phjacetyl coenzyme a and melatonin ( or 2-oxomelatonin ) for 30 min ." ], [ "we have synthesized several acetyl derivatives , such as carbo2 ( figure 7 ) , which is an n-acetyl-p-carboline.we have found 20 to 40 pg carbo2 per gram of lamb pineal gland collected on the middle of the dark phase of an alternate light - dark program ." ], [ "the hypnotic activity of carbo2 has been observed and measured in chicks and beagles : in chicks , the tests were performed at 2.00 pm , in the middle of light phase , a time at which nat activity in the pineal gland is very low .", "the essential role of acetyl group is demonstrated by the fact that 10-mcthoxyharmalan ( as well as harmaline ) , which is the product of jv - deacetylation of compound carbo2 , does not exhibit any hypnotic effect .", "in contrast , it induces excitatory effects in chicks by increasing locomotor activity in beagles , polysomnographic studies showed that when carbo2 was administered intravenously , it induced sleep of longer duration and shorter time latencies than the sleep induced by zolpidem and diazepam ( table iv ) . the most interesting feature , which provides more support for our assumption , is the eeg architecture of the sleep produced , which is similar to that of physiological sleep ( see results with placebo in table iv ) , characterized by the significant proportion of slow - wave deep sleep and rapid eye movement ( rem ) sleep , in sharp contrast to the eeg sleep architecture observed with gabaergic ( gaba , -aminobutyric acid ) compounds , such as zolpidem or diazepam , which induce mainly drowsiness ( light sleep ) and little rem sleep ." ], [ "since insomnia and sleep disorders may be due to a lack of nat enzymes in the pineal gland , a therapeutic approach to sleep disorders could be suggested .", "we have evidenced the role played by melatonin in both inducing and maintaining nocturnal sleep .", "melatonin is the bioprecursor of hypnotic acetyl metabolites , such as carbo2 , which result from the enzymatic acetylation of melatonin ( and 2-oxomelatonin ) by nat .", "patients with insomnia may be treated by administering hypnotic acetyl metabolites of melatonin or their synthetic analogs ." ] ]

[ [ "more specifically , the purposes of this study were to ( 1 ) describe sociodemographic variables , health indicators , healthcare - related frustrations , and perceptions of physician support among middle - aged and older adult women with one or more chronic conditions and ( 2 ) identify these factors ' association with reporting the need to help learning how to take better care of their health among this female population .", ", this secondary data analysis assesses issues surrounding self - care barriers , healthcare - related frustrations , and perceived supports among middle - aged and older adults with one or more chronic conditions . in an effort to further understand the multilevel influences on perceived barriers to self - care , this study will examine the roles of healthcare frustrations and doctor - patient interactions alongside other simultaneously occurring contextual factors ( see figure 1 ) .", "additional efforts are needed to examine the influence of sociodemographics on self - care skills and behavior among aging women , especially in the presence of perceptions about healthcare - related factors .", "healthcare professionals often encounter challenges to address their female patients ' mcc alongside existing barriers to self - care behavior in their home or community environments .", "although many individuals will age in relatively good health , a growing number will encounter challenges associated with the burdens of chronic conditions and associated disabilities [ 13 ] ." ], [ "lake research partners utilized telephone - based interviewing to collect data using random digit dialing ( rdd ) sampling techniques , which oversampled those aged 65 and older and hispanics / latinos .", "\n the national council on aging ( ncoa ) , with support from atlantic philanthropies and the california healthcare foundation ( chcf ) , commissioned the ncoa chronic care survey , which offers unique insight into the lives of americans with chronic health conditions .", "logistic regression was performed to examine how sociodemographics , health indicators , perceived support , and frustrations were associated with reporting the need to help learning how to take better care of their health ( i.e. , not needing help served as the referent group ) .", "participants were asked to report their frustrations with healthcare interactions using items intended to measure their feelings about repeatedly having to describe their conditions at each doctor visit , the self - care instructions they received from the healthcare provider , the time spent interacting with the healthcare provider , and having a friend or family member attend physician 's visits with them . for example , participants were asked to rate their level of agreement to statements like how often do you feel tired of describing your same conditions and problems every time you go to a hospital or doctor 's office ? and how often do you wish you had a friend or family member who could go to the doctor with you ?", "the ncoa chronic care survey is a nationally representative probability survey of 960 community - dwelling men and women aged 44 years and older with at least one chronic condition ." ], [ "compared to participants with the highest level ( tertile ) of healthcare - related frustrations , those with middle ( or = 0.17 , p < 0.001 ) and lowest ( or = 0.44 , p = 0.017 ) frustration levels were significantly less likely to report needing help learning how to better care for their health problems , respectively . compared to participants with the lowest level ( tertile ) of perceived physician support , those with the highest level of perceived support were significantly less likely to report needing help learning how to better care for their health problems ( or = 0.49 , p = 0.033 ) .", "approximately 33% of participants reported being limited from activities because of physical , mental , or emotional problems . on average , participants reported taking 3.67 ( 3.83 ) medications daily and visiting a physician 3.07 ( 1.94 ) times in the previous 12 months . over 45% of participants reported relying on the internet for ongoing help and support to manage their health problems , and 67% of participants reported frequently or always getting the help and support they need to improve their health and manage their health problems . compared to women aged 65 years and older , a significantly larger proportion of participants aged 4464 years had some college education or more ( = 7.14 , p = 0.008 ) and relied on the internet for ongoing support to manage their health problems ( = 21.15 , p < 0.001 ) .", "a significantly larger proportion of participants who reported needing help learning how to better care for their health problems were non - white ( = 4.78 , p = 0.029 ) and had a high school education or less ( = 4.23 , p = 0.040 ) . " ], [ "despite our concerns that the majority of older women would likely experience self - care problems [ 4850 ] , our analyses revealed that only about one - third of the women in our sample reported needing help learning how to take better care of their chronic conditions . but", "this study reveals two strong modifiable correlates of women needing help learning how to care for their chronic conditions , even after controlling for sociodemographic and health status indicators in multivariate analyses : healthcare - related frustrations and perceived physician support .", "consistent with health disparities in the epidemiology of chronic illnesses [ 22 , 24 ] , persistent health disparities related to self - care behavior were noted among minorities and those with less education .", "the lack of a significant relationship between age and healthcare - related frustrations or perceptions about physician support may be attributed to the fact that the sample was selected based on the presence of chronic conditions .", "however , the lack of a significant relationship is consistent with the fact that participation in community - based disease self - management programs is not limited to those of only older ages ; rather , program enrollment is based on the participant 's chronic disease status . ", "these findings suggest middle - aged and older women in this sample were comparable in terms of having a variety of social supports for learning how to take care of their health . additionally , despite the previous assumption that older women might be disadvantaged relative to younger baby - boomers , no significant differences in help needed based on age group were reported ." ], [ "thus , this study contributes to a fuller understanding of the complex interrelationships that exist between self - care strategies , provider - patient interactions , and policies / programs in community contexts .", "however , this national study contained many variables of interest to address the current research gaps in knowledge about associations of healthcare frustrations , physician support , and self - care needs to chronic disease management . ", "substantial numbers of participants were lost due to incomplete data on particular scale items , resulting in an analytical sample that was systematically different from the full sample ( e.g. , younger , married , and more white ) and potentially limited the generalizability of study findings .", "this secondary dataset did not contain all variables necessary to fully contextualize barriers and challenges associated with chronic disease self - care behavior among this aging population .", "however , the sample was derived from random digit dialing and included items that deeply explore the challenges and frustrations with chronic condition self - management , which are not typically seen in other studies that investigate correlations between self - care behavior and other healthcare or physical health indicators .", "another study limitation reducing the ability to widely generalize findings to the greater female community was the self - report and cross - sectional nature of these data ." ], [ "learning more about healthcare - related frustrations of and self - management supports utilized by middle - aged and older women has the potential to help program deliverers , healthcare providers , and health agencies provide the services and resources that women with chronic conditions want and think are helpful .", "the current study adds to the existing science base by examining barriers to self - care with a new lens , exploring healthcare - related frustrations and perceptions of physician support , and how these perceptions relate to various life domains , including diverse health status and sociodemographic contexts . identifying these common and unique challenges and correlates of these challenges , with a representative national population ,", "findings from this investigation has potential to inform and guide modifications in the implementation and dissemination of evidence - based programs for older women to better match individuals with programs that meet their needs .", "advance our current knowledge about self - care issues among middle - aged and older women ." ] ]

[ [ "the purpose of this study was to examine the neural correlates of source memory in schizophrenia . while most previous studies of source memory ( in both controls and schizophrenia ) have used less ecologically valid task ( e.g. identifying the color of the stimuli during encoding ) , we utilized a paradigm involving encounters ( with a person and an object in a specific place ) within a realistic 3d environment ( burgess et al . , 2001 ; king et al . , 2005 ) , which may better evaluate source memory networks used in everyday life .", "we hypothesized that patients would show deficits in source memory relative to object memory and may show compensatory activation in source memory retrieval contrasts .", "we expected to observe relationships between hallucinations and the neural activity of source memory retrieval .", ", we can identify regions in the cortex which are specific to source memory compared to object memory and determine if any deficits observed in schizophrenia are source - memory specific .", "fmri scanning a source recognition memory task was employed , which was contrasted with an object memory task . by directly comparing source memory to object memory", "patients with schizophrenia ( scz ) exhibit a wide variety of cognitive deficits , particularly with memory ( barch and ceaser , 2012 ; ranganath et al . , 2008 ) ." ], [ "as such , this can be conceptualized as a trait based approach to symptom evaluation . saps scores for global hallucinations and global thought disorder were entered into a whole - brain regression model with the person > object and place > object contrasts . the global delusion score was not included as most patients were highly delusional at baseline . in order to account for differences in time since initial diagnosis ,", "we propose that the pre - treatment ratings best represent the underlying neurobiology and clinical characteristics of individual patients , as they show their symptom characteristics in an untreated state of illness .", "as patients were stabilized and undergoing treatment at the time of scanning , few patients were actively experiencing positive symptoms as of the assessment closest to the date of scanning . as a result", "the presence of specific symptoms at initial clinical assessment was considered as a proxy of how prone to those symptoms each patient may be .", "while it is not possible to make several such assessments prior to treatment onset ( which would best capture the potential symptom profile of each patient ) , such an approach may allow for a data exploration which separates patients who are prone to certain symptoms ( such as hallucinations ) from those who have experienced less or never experienced those symptoms while in an untreated state .", "twenty - five people with schizophrenia spectrum disorders were recruited , diagnosed according to the structured clinical interview for dsm - iv ( first et al . , 1997 ) and confirmed between two senior research psychiatrists ( a.m. and r.j . ) ." ], [ "2010 ) . in order to examine the relationship between recognition memory performance and neural activity , spearman 's correlations were run on global hallucination score , memory performance in the place and object conditions , and values from the three clusters .", "we observed significant negative correlations with the global hallucination score from the saps ( at first assessment ) and place > object contrast , in the right midtemporal gyrus , left prefrontal cortex , and right cerebellum ( in a region noted in at least one lesional case study to be associated with source memory deficits ; tamagni et al . ,", "while hallucinations did not significantly correlate with performance in either condition ( place , rho = .228 , p = 0.32 ; object , rho = 0.28 , p = 0.22 ) , there was a marginally significant correlation between performance in the object condition and value in the dlpfc cluster ( rho = 0.38 , p = 0.088 ) .", "rois were selected to represent a range of representative patterns of activity across the brain ( e.g. regions in which controls showed differences from scz in both person > object and place > object , and regions in which scz showed greater activity in place > object ) .", "numerous cortical regions showed significant increases in neural activity for retrieval of source memory over retrieval of object memory , similar to the pattern observed in previous studies using a similar paradigm ( burgess et al ." ], [ "this study examined differences in the neural correlates of source memory in patients with schizophrenia and controls .", "furthermore , we examined a group of patients , who were within the first 4.5 years of treatment avoiding potential issues associated with illness chronicity such as cognitive decline , prolonged exposure to medications ( although medication exposure remains an issue ) , social isolation , and sedentary lifestyle ( pelletier et al . , 2005 ) . while patients with scz demonstrated some activation in the source memory contrasts , the extent and magnitude of activity were substantially less than those in controls . even in regions in which the difference appeared to be in the directions of scz > controls", "our results overall suggest a relationship between mal - adaptive neural activity related to source memory retrieval and how prone participants are to hallucinatory symptoms , further verifying the relationship between source memory and hallucinations ( woodward et al . , 2007 ) . however , some limitations must be considered as well .", "our finding of an overall pattern of lack of differentiation between conditions may be a fairly consistent finding in the cognitive neuroscience of memory in scz , regardless if one considers activity during encoding or retrieval / recognition .", "we examined this issue using a virtual reality paradigm , which has improved ecological validity when assessing the source of a memory , as compared to other studies which have used less ecologically valid tasks ." ], [ "we have reported the results of a study looking at source memory retrieval in scz using a virtual reality environment on a group of patients relatively early into treatment .", "this reduction was borne out in the group comparison , and appears to be related to the fact that patients with scz are failing to activate these regions or differentiate between object and source retrieval . despite the large - scale group differences , patients were still able to perform the source retrieval tasks , suggesting that at least some of the core system involved in source retrieval is intact . instead , we propose that the observed differences are related to supporting regions which are not critical to task performance but instead facilitate source retrieval .", "while controls activated a large , extensive network for source relative to object retrieval , scz showed a marked reduction in activity .", "that is , patients may generally fail to engage extended cortical networks which facilitate task performance and facilitate overall cognitive functioning ." ] ]

[ [ "moreover , we also found that the signaling pathways used by oncogenic ras to stimulate proliferation and repress differentiation in myogenic cells are distinct and mediated independently .", "we report that constitutively active ras stimulates mm14 myoblast proliferation via a novel mechanism that is dependent on export of endogenously produced fgf-2 and subsequent release or activation of the exported fgf-2 .", "ras is a multifunctional signaling molecule acting as an essential component of signal transduction pathways that regulate cellular physiology ( campbell et al ." ], [ "the reporter contained the firefly luciferase gene driven by a muscle - specific promoter ( msp ; human anti - cardiac actin promoter ) ( kudla et al .", "a differentiation - sensitive muscle - specific reporter activity assay was used to determine the extent of mm14 differentiation after transient transfection .", "the pdcr - h - ras ( g12v ) expression vector encoding a constitutively active mutant of human ha - ras , rasg12v ( white et al .", "baf3/fr1 cells , a baf3 cell clone stably expressing fgf receptor ( fgfr)-1 , was cultured as described by ornitz et al . 1992 .", "baf3/fr1 cells ( 10 cells per well in 24-well plates ) were incubated in the collected medium for 72 h. the number of living cells in each well was quantified by counting the number of cells that exclude trypan blue .", "dna was transiently transfected into mm14 cells by a calcium phosphate dna precipitation method as described previously ( kudla et al .", "the cells were maintained in the presence or absence of fgf-2 ( 0.3 nm unless otherwise indicated ) , cultured for 36 h , then processed for -galactosidase histochemistry as described elsewhere ( sanes et al .", "transfected cells were plated at 10 cells per well in 6-well plates and incubated for 36 h in growth media without fgf .", "mm14 cells were grown on 6-well plates to a density of 5 10 and transfected with the indicated expression vectors or control plasmids ." ], [ "baf3/fr1 cells , a baf3 cell clone stably expressing fgf receptor ( fgfr)-1 , was cultured as described by ornitz et al . 1992 .", "mouse mm14 cells ( lim and hauschka 1984 ) were cultured as described previously ( kudla et al .", "human recombinant fgf-2 was purified from a yeast strain expressing this growth factor ( rapraeger et al .", "wehi3 cells were purchased from the american type culture collection and baf3/fr1 cells ( ornitz et al .", "1993 ) and anticysteine - rich fgfr control antibody ( zuber et al . 1997 ) were used as described previously ( hannon et al .", "heparin , nacl , and naclo3 were purchased from sigma - aldrich . a monoclonal anti " ], [ "the pdcr - h - ras ( g12v ) expression vector encoding a constitutively active mutant of human ha - ras , rasg12v ( white et al .", "dna was transiently transfected into mm14 cells by a calcium phosphate dna precipitation method as described previously ( kudla et al .", "equivalent dna concentrations were maintained by the addition of a pbssk+ ( stratagene ) plasmid ." ], [ "mm14 cells were grown on 6-well plates to a density of 5 10 and transfected with the indicated expression vectors or control plasmids .", "the cells were maintained in the presence or absence of fgf-2 ( 0.3 nm unless otherwise indicated ) , cultured for 36 h , then processed for -galactosidase histochemistry as described elsewhere ( sanes et al .", "cells were trypsinized ( 0.05% trypsin , 0.53 mm edta ) and replated at clonal density ( 1,000 cells per 10-cm plate ) 1 h after transfection ." ], [ "a differentiation - sensitive muscle - specific reporter activity assay was used to determine the extent of mm14 differentiation after transient transfection .", "the reporter contained the firefly luciferase gene driven by a muscle - specific promoter ( msp ; human anti - cardiac actin promoter ) ( kudla et al ." ], [ "to determine their fgf-2 export capabilities , transfected cells were plated at 10 cells per well in 6-well plates and incubated for 36 h in growth media without fgf .", "baf3/fr1 cells ( 10 cells per well in 24-well plates ) were incubated in the collected medium for 72 h. the number of living cells in each well was quantified by counting the number of cells that exclude trypan blue .", "cells were then washed once with pbs ( ph 7.2 ) and incubated for 1 h at room temperature in 1 ml of baf3/fr1 growth medium supplemented with 50 g / ml of heparin . the medium was then collected and filtered through a 0.2-m filter ." ], [ "together with the prevalence of oncogenic ras mutants in rhabdomyosarcomas and the involvement of fgfs in regulation of myogenesis , our data suggest that fgf-2 may be a critical factor for supporting ras - dependent growth of rhabdomyosarcomas .", "we conclude that oncogenic ras does not affect the level of fgf-2 export from mm14 cells .", "we hypothesized that ha - ras may induce fgf export or secretion of endogenously produced fgfs and therefore treated mm14 cells expressing rasg12v with agents that block fgf signaling .", "added fgf-2 suggests a more complicated role for hspgs in addition to their known requirement for signaling . taken together , our data demonstrate that rasg12v induces proliferation of skeletal muscle cells and that induction of proliferation requires an autocrine fgf-2 response .", "unexpectedly , we found that the ability of ha - ras to stimulate proliferation appears dependent on extracellularly supplied fgf-2 ." ] ]

[ [ "lipomas represent uncommon neoplasms of the oral cavity ; only 1% to 5% of cases occur at this site . based on their histopathological features of conspicuous multiple components", "review of the literature and clinicopathological analysis from the files of the oral pathology department , nihon university school of dentistry at matsudo from 1995 to 2007 of these cases were performed and compared .", ", lipomas can be divided into some subclasses [ 2 , 3 ] , and the most common is the fibrolipoma [ 1 , 3 , 4 ] .", "cases reporting on lipoma with osteo / chondroid differentiaion were only 16 cases as a result of retrieving literature from 1960 to 2008 .", "further , other names of this subclassification exist in literature ; osteo / chondrolipoma , ossifying / osseous lipoma , lipoma with chondro / osseous metaplasia , and lipoma with cartilaginous / osseous change . the obscure etiology of osseous / chondroid differentiaion led to confusion of the name . to clarify the etiology of osseous / chondroid differentiaion in lipoma , the authors report additional 2 cases of oral lipoma / fibrolipoma with osseous and/or chondroid differentiation and describe the clinical , histopathological , and immunohistological features of these ." ], [ "two cases that had been diagnosed as lipoma with osteo / chondroid differentiation were retrieved from the files mentioned earlier . in these cases ,", "the literature from 1960 to 2008 of lipoma with osseous / chondroid differentiation was reviewed .", "positive controls consisted of specimens of schwannoma for s-100 and ; squamous cell carcinoma for ema , cd34 and ki-67 ; ossifying fibroma for fgf-1 and runx-2 , normal lung tissue for sox-9 ; and inflammatory granulation tissue for myod-1 . as a negative control , mouse igg1 ( ki-67 , vegf , cd34 , s-100 ) , igg2a ( ema , s-100 ) and igg2b ( fgf-1 ) , goat igg ( runx-2 ) and rabbit igg ( sox-9 ) were used instead of the primary antibodies .", "clinical data were retrieved from patient records , and all cases were reviewed microscopically and subclassified .", "the primary antibodies were generally used at a dilution of 1 : 50 , and the incubation time was 1 hour at room temperature .", "at least 500 nuclei were counted in 5 high - power ( x400 ) fields and ki-67 labeling index was calculated ." ], [ "the literature from 1960 to 2008 of lipoma with osseous / chondroid differentiation was reviewed .", "the files for all cases of oral lipoma at this department showed 909 cases of nonepithelial tumors in the oral soft tissue .", "fourteen reports ( including 16 cases ) were described , and our cases are number 17 and 18 . of all cases ,", "of all the lipoma cases , 27 occurred in males and 19 in females ; their mean age was 53.8 years ( range : 2872 years ) ." ], [ "the two cases this reports contributed to pile up of rare lipoma / fibrolipoma with osseous / chondroid differentiation case , and , in addition , immunohistochemical result is contributed to the clarification of the etiology .", "our case 2 is namely the first report of fibrolipoma with osseous / chondroid differentiation .", "fujimara have reported , but our case 2 is the first report of fibrolipoma with osseous / chondroid differentiation .", "\n\t\t\t\t according to our review of the english - language literature , which included our cases , 6 cases were described as lipoma with osseous component [ 57 , 9 , 14 , 15 ] , 11 cases as chondroid component [ 4 , 813 , 16 , 17 ] and 1 case as fibrolipoma with osseous / chondroid components .", "lipoma with osseous / chondroid differentiaion is extremely rare and occurs mainly in large long - standing lipomas [ 15 , 19 ] ." ] ]

[ [ "leydig cell tumours are rare stromal tumours of the testis accounting for 13% of testicular neoplasms .", "they exhibit a peak incidence in the preadolescent as well as in the older ( > 50 years ) age groups [ 1 , 2 , 3 , 4 ] .", "the diagnosis of a malignant leydig cell tumour is not always easy since no definite histological criteria for malignancy exist ." ], [ "a 35-year - old man presented to our hospital with a 3-month history of a painless left testicular mass .", "a left radical orchidectomy was performed and the specimen submitted for histopathological examination . on microscopic examination , a malignant leydig cell tumour was found .", "many cells with large atypical pleomorphic nuclei could also be observed ( fig . 1 , fig .", "2 ) . there was no angiolymphatic invasion , foci of necrosis or extension beyond the capsule of the testis .", "the cells displayed acidophilic cytoplasm , intranuclear inclusions and increased mitotic activity ( > 3/10 hpf ) .", "3 ) . retroperitoneal lymph node dissection was suggested , but the patient declined further surgery .", "the immunohistochemical study showed that the tumour cells were positive for vimentin , melan a and inhibin , and negative for ckae1 , ckae3 , s100p , p63 , cea , afp and actin ." ], [ "leydig cell tumours are rare and only about 3% of them are bilateral . about 1520% of the patients already present with metastatic disease , particularly in the lymph nodes , lung and liver", "leydig cell tumours in an undescended testis may exhibit only manifestation of endocrinological disorders such as gynaecomastia , impotence and loss of libido ." ] ]

[ [ "our study aimed to identify the role of strail in the pathophysiology of allergic rhinoconjunctivitis , and to explore whether allergen - specific subcutaneous immunotherapy treatment of allergic rhinoconjunctivitis patients altered any observed effect of strail .", "the prevalences of asthma , allergic rhinitis and allergic eye disease in antalya , on the south coast of turkey , have been reported as 8.2% , 10.8% and 7.5% , respectively .", "a number of epidemiologic studies have also supported a relationship between allergic rhinoconjunctivitis and diet , hygiene , and life - style , suggesting that environmental factors also impact the development of allergic rhinoconjunctivitis .", "trail is also seen as the basis for a miracle drug for cancer because of its ability to selectively kill cancer cells .", "a detailed knowledge of the sensitization pattern may have relevant implications for the prescription of specific immunotherapy .", "the micro - array techniques for the detection of specific ige have improved the diagnostic procedures for allergic diseases ." ], [ "serum ige levels , hepatitis markers ( hbs ag , anti hbs , anti hcv ) were evaluated in all patients .", "the first group included 2 measurements in the same patients ; group - ia represents data recorded before subcutaneous allergen - specific immunotherapy , and group - ib shows data recorded 12 months after the subcutaneous allergen - specific immunotherapy .", "the first group of 25 patients included 11 male and 14 female subjects with allergic rhinoconjunctivitis , having a combined mean age of 38.5612.03 years .", "all patients received immunotherapy every 4 weeks . the symptoms and severity of allergic reactions were recorded before and after treatment .", "a second group of 25 healthy individuals ( 11 male and 14 female ) ( group ii ) had a mean age of 38.2312.21 years ( table 1 ) .", "serum strail levels in all individuals ( patients and healthy controls ) were measured by a sandwich enzyme - linked immunosorbent assay ( diaclone , france ) .", "skin prick tests on the forearm were performed in all patients , using standardized latex extract containing high ammonia natural rubber latex , and a full set of 10 common allergens ." ], [ "the first group of 25 patients included 11 male and 14 female subjects with allergic rhinoconjunctivitis , having a combined mean age of 38.5612.03 years .", "the first group included 2 measurements in the same patients ; group - ia represents data recorded before subcutaneous allergen - specific immunotherapy , and group - ib shows data recorded 12 months after the subcutaneous allergen - specific immunotherapy .", "all patients received immunotherapy every 4 weeks . the symptoms and severity of allergic reactions were recorded before and after treatment .", "a second group of 25 healthy individuals ( 11 male and 14 female ) ( group ii ) had a mean age of 38.2312.21 years ( table 1 ) .", "subjects with kidney disease , heart disease , liver disease , diabetes mellitus , cancer status , obesity ( body mass index ( bmi ) 30 kgm ) , and autoimmune disease were excluded clinically and serologically .", "subjects with kidney disease , heart disease , liver disease , diabetes mellitus , cancer status , obesity , ( body mass index ( bmi ) 30 kgm ) , and autoimmune disease were excluded clinically and serologically .", "the study was conducted in antalya , turkey between 9 january 2009 and 28 january 2010 ." ], [ "serum ige levels , hepatitis markers ( hbs ag , anti hbs , anti hcv ) were evaluated in all patients .", "values above 100 ku / l and 0.35 ku / l for total and specific ige levels were considered abnormal .", "serum strail levels in all individuals ( patients and healthy controls ) were measured by a sandwich enzyme - linked immunosorbent assay ( diaclone , france ) .", "total and specific ige levels were enumerated by fluoroenzyme immunoassay ( immunocap - feia ) using an immunocap kit ( phar - macia , uppsala , sweden ) .", "blood samples were collected into 5 ml plain vacutainer tubes and centrifuged at 3000 g for 10 min ." ], [ "skin prick tests on the forearm were performed in all patients , using standardized latex extract containing high ammonia natural rubber latex , and a full set of 10 common allergens .", "in addition , venom spt was performed on 1 patient based on the subject s clinical history ." ], [ "student s t test was used for comparison of controls and patient groups ( group ia and group ib ) ." ], [ "in this clinical follow - up study , 25 patients were already receiving subcutaneous immunotherapy , and these subjects were included for further analysis at our clinic .", "as shown in figure 1 , significant difference was seen in the mean values of strail in allergic rhinitis patients before immunotherapy ( n=25 ; 939.85352.52 pg / ml ) , afterc immunotherapy ( n=25 ; 628.93170.5 pg / ml ) and healthy controls ( n=25 ; 612.64135.6 pg / ml ) .", "the mean ige levels were : group ia 699.505 iu / ml ; group ib 164.115 iu / ml ; and group ii ", "41.08 iu / ml . there was a statistically significant difference between the values of the research group before and after immunotherapy ( p=0/0005 ) .", "as shown in table 3 , there was a statistically significant difference between the values of the research group before and after immunotherapy ( grasses mixture , barley mixture , oleaauropeae , d. pteronyssinus , d. farinae )", "while there was a statistically significant difference between the pre - treated group and control group ( p<0.0001 ) , there was no difference between the post - treated group and healthy individuals ( p=0.801 ) .", "prick tests in all patients in group i were detected in mite , olive and grass allergy ." ], [ "as shown in figure 1 , significant difference was seen in the mean values of strail in allergic rhinitis patients before immunotherapy ( n=25 ; 939.85352.52 pg / ml ) , afterc immunotherapy ( n=25 ; 628.93170.5 pg / ml ) and healthy controls ( n=25 ; 612.64135.6 pg / ml ) .", "in this clinical follow - up study , 25 patients were already receiving subcutaneous immunotherapy , and these subjects were included for further analysis at our clinic .", "the mean ige levels were : group ia 699.505 iu / ml ; group ib 164.115 iu / ml ; and group ii ", "41.08 iu / ml . there was a statistically significant difference between the values of the research group before and after immunotherapy ( p=0/0005 ) .", "while there was a statistically significant difference between the pre - treated group and control group ( p<0.0001 ) , there was no difference between the post - treated group and healthy individuals ( p=0.801 ) .", "there was a statistically significant difference between the values of the research group before and after immunotherapy ( p=0.001 ) .", "these results correlated with specific ige , and hepatitis markers were negative in all patients ." ], [ "as shown in table 3 , there was a statistically significant difference between the values of the research group before and after immunotherapy ( grasses mixture , barley mixture , oleaauropeae , d. pteronyssinus , d. farinae )" ], [ "allergen - specific immunotherapy has been used in the management of allergic diseases for nearly 100 years .", "ige levels had a statistically significant difference between the values of the research group before and after allergen - specific subcutaneous immunotherapy .", "our earlier studies provided a novel perspective on severe persistent allergic asthma and the effect of anti - ige treatment , using as markers serum soluble tnf - related apoptosis - inducing ligand , total antioxidant capacity , hydrogen peroxide , malondialdehyde , ceruloplasmine oxidase activity , high sensitive c reactive protein and total nitric oxide concentrations measurements [ 1316 ] . in our previous study we found that the trail levels in variances of the patients who had the effective anti ige treatment were significantly lower than the healthy controls .", "allergen - specific immunotherapy treatment significantly reduced the nasal symptom score across all group i patients studied . in this study ,", "spt was a statistically significant difference between the values of the research group before and after allergen - specific subcutaneous immunotherapy ( grasses mixture , barley mixture , oleaauropeae , d. pteronyssinus , d. farinae ) .", "engagement of the fas / fasl system has not yet been shown to contribute to increase apoptosis ." ], [ "taken together , our results and those of others , suggest that characterization of the specific receptor systems activated , and the pro - inflammatory factors regulated , by trail in vivo may lead to the development of novel therapeutic strategies for diseases as diverse as infection , autoimmunity , and allergy ." ] ]

[ [ "calcimimetics provide an alternative approach to the traditional therapy with active vitamin d and phosphate binders for the management of secondary hyperparathyroidism ( shpt ) . type ii calcimimetics are positive allosteric modulators of the parathyroid gland calcium - sensing receptor ( car ) that increase its sensitivity to serum calcium , so that lower concentrations of calcium are sufficient to mediate signalling through the car .", "in addition to being effective in patients with mild to moderate disease , calcimimetics may be the most viable option for chronic kidney disease ( ckd ) patients with advanced hyperparathyroidism , who are often refractory to standard calcitriol therapy [ 810 ] .", "taken together , the mechanistic data presented here , and reviewed in greater detail in another article in this supplement ( riccardi and martin ) , suggest that calcimimetics have the potential to retard shpt disease progression . preclinical studies in uraemic rats indicate that calcimimetics can modify the defining parameters in shpt by significantly lowering pth and blood - ionized calcium in a dose - dependent manner without inducing significant changes in serum phosphate .", "these data indicate that , in addition to regulating pth levels and restoring car density , calcimimetics can up - regulate vdr expression in parathyroid cells ." ], [ "administration of cinacalcet or the calcimimetic r-568 to 5/6 nephrectomized rats prevented hyperplasia or increased car expression .", "interestingly , in an in vitro study , the calcimimetic cinacalcet suppressed pth secretion in human parathyroid cells with advanced hyperparathyroidism , even though car expression was significantly diminished ." ], [ "recent studies indicate that type ii calcimimetics , in the presence of low concentrations of calcium , can up - regulate vdr mrna .", "these data indicate that , in addition to regulating pth levels and restoring car density , calcimimetics can up - regulate vdr expression in parathyroid cells .", "expression of vitamin d receptor ( vdr ) mrna is reduced in the parathyroid gland of hypocalcaemic rats compared with normocalcaemic rats . because the vdr is a transcriptional repressor of pth", "this effect of calcimimetics on vdr expression is of clinical importance because it may result in an additive interaction between calcimimetic and vitamin d sterol therapy .", "rats were treated with r-568 ( 1 mg / kg intravenously 3 and 6 h before euthanasia ; n = 22 ) , calcitriol ( 10 pmol / kg intraperitoneally every 30 min for 5.5 h before euthanasia ; n = 22 ) , or a combination of r-568 and calcitriol ( n = 22 ) before euthanasia and measurement of vdr mrna by quantitative real - time polymerase chain reaction . a control group ( n = 20 ) received no treatment . mean serum concentrations of ionized calcium and pth are also included ." ], [ "although parathyroid cells are relatively quiescent under normal conditions , the mineral and hormonal imbalances characteristic of shpt , particularly low serum calcium and high serum phosphorus , drive cell proliferation leading to polyclonal and oligoclonal cell expansion .", "calcimimetics , in the presence of low serum calcium , can hold proliferation in check , as evidenced by decreased parathyroid cell proliferation in uraemic rats following treatment and their ability to cause regression of advanced hyperplasia in some experimental animal models .", "preclinical studies in uraemic rats indicate that calcimimetics can modify the defining parameters in shpt by significantly lowering pth and blood - ionized calcium in a dose - dependent manner without inducing significant changes in serum phosphate .", "taken together , the mechanistic data presented here , and reviewed in greater detail in another article in this supplement ( riccardi and martin ) , suggest that calcimimetics have the potential to retard shpt disease progression .", "this effect was parathyroid tissue - specific and was due to a direct effect on cell growth , rather than to induction of apoptosis .", "the importance of maintaining calcium homeostasis is evidenced in weanling rats fed a low - calcium diet for 10 days , in which the number of proliferating cell nuclear antigen ( pcna)-positive parathyroid cells was increased sixfold compared with controls ." ], [ "analysis of the data from these trials has been performed to investigate the efficacy of cinacalcet in the treatment of both early- and later - stage shpt and to investigate the potential of long - term cinacalcet therapy to stabilize disease progression .", "these findings underscore the need for new or adjunct treatments with improved efficacy over current modalities that can stabilize disease progression during a long - term course when initiated early , but can also maintain effectiveness in patients with more severe disease . because of the ability of calcimimetics , demonstrated in animal studies , to modulate disease - related processes through multiple mechanisms of action implicated in the development of disease , this therapeutic modality appears to be well suited for use in combination with moderate doses of vitamin d as the primary mode of treatment in shpt management .", "one of the primary treatment goals of shpt is to restore mineral and hormone balance .", "results of these analyses , presented below , suggest that calcimimetics have the ability to address these unmet therapeutic needs .", "phase 3 clinical trials in shpt patients with advanced disease have shown that cinacalcet decreased pth , as well as serum calcium , phosphorus and ca p .", "these multiple mechanisms of action may allow calcimimetics to ( 1 ) maintain effectiveness during long - term therapy ; ( 2 ) maintain enhanced efficacy in patients with severe disease despite decreased car and vdr expression and ( 3 ) halt development of severe disease if initiated early in patients with mild or moderate shpt .", "as described earlier , calcimimetics up - regulate car and vdr expression and inhibit parathyroid cell proliferation and hyperplasia ." ], [ "these data demonstrate that cinacalcet effectively reduces and maintains the four critical disease biomarkers associated with shpt in ckd patients .", "these findings again highlight the progressive nature of shpt in patients receiving standard therapy as first - line treatment , as well as the inability of traditional therapies to effectively control or stabilize disease in both the short and long term . these and other clinical observations discussed in this section are also consistent with preclinical evidence supporting the car as a therapeutic target to optimize the achievement of treatment goals and slow or prevent disease progression .", "a post - hoc analysis of the combined results of three 26-week , placebo - controlled , phase 3 studies evaluating the efficacy and safety of a once - daily dose of cinacalcet for the treatment of shpt demonstrated the impact of therapy initiated in early or advanced disease .", "these data suggest that early treatment of shpt provides the best opportunity to maintain control of serum pth , calcium , phosphorus and ca p. treatment with cinacalcet for up to 1 year resulted in increased attainment of kdoqi targets compared with standard therapy ." ], [ "these studies raise the possibility that treatment with calcimimetics might improve the sensitivity of the parathyroid glands to calcitriol and vitamin d analogues , allowing reduced doses to be used and thus minimizing the risk of hypercalcaemia and hyperphosphataemia .", "the mechanism of action involves allosteric modification of the car , rendering it more sensitive to calcium signalling , thereby helping counteract the decreased car expression and prevent and halt the progression of parathyroid hyperplasia .", "preclinical mechanistic studies with calcimimetics have suggested that this modality may arrest disease progression , even in patients with advanced disease at treatment onset , and stabilize shpt , thereby allowing improved maintenance of kdoqi targets .", "calcimimetics are highly specific therapeutic agents that effectively lower concentrations of plasma pth and partially correct disturbances in mineral metabolism that are characteristic of shpt .", "cinacalcet has been shown to allow more patients to achieve and maintain kdoqi targets compared with standard therapy , and extended use ( up to 4 years ) has been shown to be effective and well tolerated .", "in addition to effects on car signalling , new experimental studies indicate that calcimimetics may act to increase vdr expression ." ] ]

[ [ "we will mainly focus on those aggregates assembled from tau \n protein , aggregates that could be present in the neurological \n disorders known as tauopathies ( for a review see ) ( table 1 ) .", "recently , some good reviews have been published on protein \n aggregation and neurodegenerative disorders [ 6 , 7 ] . in this \n review", "many neurodegenerative disorders are characterized by \n their presence in neural tissue of aberrant protein aggregates \n ( see table 1 ) . in general , these aggregates arise after the modification of a \n native protein . that modification could result in a conformational \n change of the native protein that promotes the aberrant \n aggregation .", ", conformational changes between a native protein \n and its aberrant protein counterpart with capacity for \n self - assembly have been studied in many neurodegenerative \n diseases . among the most common techniques used for these analyses \n" ], [ "the chaperone associated ubiquitin ligase chip could \n be able to target phosphotau for proteasomal degradation \n [ 16 , 18 ] .", "it has been described that large amounts of native or unmodified \n tau protein were enough to promote tau assembly into fibrillar \n polymers resembling those found in ad [ 912 ] .", "it should be also indicated that in some cases like parkinson 's disease or lafora disease , mutations in the e3 \n ubiquitin ligases like parkin or malin will \n result in the appearance of aberrant protein aggregates . a conformational change , that could be followed by antibodies that \n react with tau molecule after that conformational change \n [ 2124 ] has been also suggested to be required for the \n transition tau monomer - tau polymer . also , it has been suggested that different posttranslational \n modifications like phosphorylation , glycation , \n or truncation , may play a role in the formation of tau \n polymers . due to the alternative splicing of its heterogenous ( or nuclear ) \n rna , different tau isoforms could be expressed and , therefore , \n different tau aggregates with different tau isoforms in different \n tauopathies could occur , but we will not discuss this point here . \n for further information see .", "some work has been done in vitro and in vivo [ 30 , 31 ] about a possible role of tau phosphorylation on tau \n assembly , suggesting that in some conditions tau phosphorylation \n may increase the capacity of tau for its self - assembly .", "thus , \n obviously , an increase in tau concentration will favour the \n formation of tau polymers ." ], [ "it has been described that tau binding to microtubules is regulated by the level of tau phosphorylation at some specific sites .", ", it has been suggested that tau phosphorylation may represent a \n protective function in ad .", "this \n phosphotau could have a decreased capacity for microtubule binding \n and it could be toxic for the cell . additionally , it has been \n indicated that hyperphosphorylated tau can cause \n neurodegeneration , in the absence of large tau aggregates \n . on the other hand , only the overexpression of wild - type human tau in a mouse is sufficient to cause tau phosphorylation , aggregation , and neural toxicity . on the other hand", "more recently , it has been indicated that expression of a tau mutant ( p301l ) \n could result in an increase of its phosphorylation , since once it is phosphorylated , that mutation can prevent the binding of those phosphatases involved in its dephosphorylation .", "also , tau phosphorylation could result , as indicated above , in a decrease of its proteolysis ." ], [ "sometime ago , the development of tau pathology , related with \n dementia in ad , was clearly described by braak and braak \n by following the development of neurofibrillary lesions at different stages of the disease . also , the formation of \n neurofibrillary ( tau aggregates ) pathology within those neurons of \n hippocampus and cerebral cortex affected at different stages was \n found .", "although , more recently , the discussion of those experiments suggested that hyperphosphorylated , aggregated tau intermediates could be the ones that cause neurodegeneration . in this way , the implication of different types of protein aggregates in neurodegeneration has been extensively \n discussed [ 19 , 54 ] . a possibility about the existence of neurotoxic tau intermediate aggregates in human tauopathies", "is \n based in the fact that patients with ftdp-17 show an extensive \n neurodegeneration with a high level of tau phosphorylation but \n with a low number of tangles . in any case , even if the formation of tau aggregates has a \n protective function for the neurons , that function is not working \n well , as described by braak and braak , and afterwards by delacourte et al , indicating a correlation between \n progression of tau pathology and progression of the disease .", "these neurons could degenerate yielding extracellular ghost \n tangles ( enft ) . in the hippocampus" ], [ "examples of neurological diseases where aberrant protein \n aggregates are found , and the suggested conformations in the \n aberrant aggregates are indicated ." ] ]

[ [ "induced abortion that can be the important complication followed by unwanted pregnancy play a significant role in the incidence of infection , fever , risk of the next premature delivery , low birth weight , and infertility [ 1 , 4 ] .", "therefore , conscious and accurate decision making for pregnancy and precise care play an important role in decreasing the maternal mortality .", "conscious and accurate decision making for pregnancy , continuation , and precise care play an important role in declining the maternal mortality . according to the studies by world health organization , close to one - third of the pregnancies in the third world countries", "the rate of pregnancy in women with a high potency for fertility who use no contraceptive method is 90% during one year .", "therefore , we decided to evaluate some factors related to unwanted pregnancy in women referred to health centers .", "the world population is doubled every 54 years ; however , in poor countries , population is doubled in less than 20 years . to complete and preserve personal health during pregnancy ,", "planning for pregnancy can help the safety of childbirth , and unplanned pregnancies increase the maternal mortality . despite the attempts by the authors in health centers , some unwanted pregnancies occur that can danger the women ." ], [ "\n\t\t\t\t it was a cross - sectional study on 400 randomly pregnant women , who were referred to several clinics and health center in ahwaz city during 2010 .", "data was collected through interview and filling up a designed questionnaire containing demographic characteristics , fertility , and so forth ." ], [ "this study has shown that 26% of women who wish to become pregnant had more knowledge and performance about pregnancy health 26% , and the low levels of knowledge and performance were more observed in unwanted pregnancy .", "the mean age of women with unwanted pregnancy was 27.5 5.7 years , and in women with intended pregnancy was 24.6 4.5 years .", "the percentage of the older women ( 35 years ) in unwanted pregnancy was 3 times of intended pregnancy which was statistically significant .", "most of pregnant women lived in urban area ( 70.1% ) , and the percentage of rural women who intended pregnancy was higher ( 35.6% ) .", "the findings have shown that most of pregnant women were housewives ( 82% ) , and their husbands had self - employment ( 40% ) , and 7.1% of subjects with unwanted pregnancy had unemployed husband .", "half of the women with unwanted pregnancy had low economic status , while , in women with intended pregnancy , this rate was only 20% . according to the interviews , good relationship with" ], [ ", more attempts must be taken to decrease complication of pregnancies such as unwanted cases . in the recent years , it has been proved that , in addition , the population control and educational program for contraceptive methods are important and necessary in preventing unwanted pregnancy . because in iran abortion is illegal consider in the muslim religious , unwanted pregnant women can not do abortion except if physician has diagnosis that mother has complication to continue of her pregnancy or there is intrauterine growth retardation in the first trimester .", "\n\t\t\t\t the incidence of unwanted pregnancy is different in the world , but it has the same undesired outcomes . our study has shown that prevalence of unwanted pregnancy was 26% , and similar conducted studies indicated that the incidence rate of unplanned pregnancy was 25% , 30% , 43% , and 52% [ 69 ] . in this study ,", ", it has been indicated that the failure of the contraceptive method has been the main cause of unwanted pregnancy .", "so , regulating reproduction and adequate planning for pregnancy is significant in these countries . in conclusion", "it seems that of the most important educational needs and the most effective attempts to prevent unwanted pregnancy are creating motivations in families , providing necessary facilities , and helping them in selection and accurate use of different methods by holding educational classes in health centers .", "therefore , introducing accurate information about the contraceptive methods acquires a profound understanding , and using this information is very important in planning for the pregnancy . considering the lack of safe methods , educational programs , introducing adequate contraceptive options , and consultation before pregnancy" ] ]

[ [ "at the end of past millennium , flexible bronchoscopy was regarded as one of the most frequently performed procedures by the physicians of multiple disciplines to inspect the airway . in our institute , the fibreoptic bronchoscopies are performed by either the pulmonologists or the anaesthetist . at many places , fibreoptic bronchoscopies are still performed after topical anaesthesia only , without any sedation .", "topical lignocaine applied by the spray as you go technique with direct instillation of 4% solutions is used by a few bronchoscopists , while the others use transcricoid route for local anaesthesia of the vocal cords and tracheobronchial mucosa .", ", intravenous sedation was reported in 50% of the procedures ; however , this technique requires the use of adequate anaesthetic resources and is associated with a low but real morbidity and mortality .", "therefore , a risk benefit approach comparing the same procedure performed under sedation and under local anaesthesia alone is indicated .", "the intravenous sedation limits dynamic analysis of the airways such as vocal cords , presence of local or diffuse malacia or effects of voluntary cough .", "we have compared a transcricoid injection of local anaesthesia with the spray as you go ", "technique without sedation in patients posted for elective fibreoptic bronchoscopies requiring only bronchoalveolar aspirate for diagnosis and not biopsies of any kind ." ], [ "group i patients were given a single transcricoid injection of lignocaine , while in group ii patients lignocaine was used as spray as the bronchoscopist entered inside , after the lignocaine sensitivity test was done in all the patients .", "the patients of the specified age group coming to the bronchoscopy suit , requiring only diagnostic bronchoalveolar lavage over a period of 6 months , were selected and alternatively divided into two groups of 30 each .", "after obtaining institutional ethical committee approval , 60 patients in the age group 2070 years of either sex , undergoing elective fibreoptic bronchoscopies for diagnostic bronchoalveolar aspirate , were included in this study .", "thirty min after the procedure , an assistant who was unaware of the patients group was asked to assess any discomfort to the patients , using a 10-cm visual analogue scale ( vas ) .", "a bout of coughing was considered as a single episode of cough . the total dose of lignocaine used in both the groups was also noted .", "if any contraindication for transcricoid injection was present , like any local pathology , then these patients were included in the other group . after taking", "further boluses of lignocaine were instilled through the bronchoscope if local anaesthesia was thought to be inadequate in both the groups .", "the assistant as well as the bronchoscopist could not be blinded to the local anaesthetic techniques ." ], [ "group i was transcricoid group and group ii patients received spray as you go technique .", "cough episodes plotted against the no . of patients as shown in table 3 , the values of vas score were comparable after 30 min of the procedure in both the groups . there were no cases of haematoma or subcutaneous emphysema when the neck was examined after the procedure in the transcricoid group .", "the age of patients in group i ( 51.6614.08 years ) was comparable with that in group ii patients ( 48.2613.32 , p = ns ) .", "the carina was significantly shorter in group i ( 57.3312.98 sec ) compared to group ii ( 79.3322.35 sec , p<0.02 ) .", "the total dose of lignocaine used in group ii ( 372.6624.90 mg ) was significantly higher than that used in group i ( 3149.32 mg , p<0.001 ) as shown in figure 1 ." ], [ "the present study was designed to compare the techniques of applying topical anaesthesia to the respiratory mucosa for elective diagnostic fibreoptic bronchoscopy .", "the present study compared two techniques of anaesthetising the respiratory mucosa for diagnostic bronchoscopy without sedation .", "no complication was associated with transcricoid injection and minor bleeding associated with the technique did not interfere with the bronchoscopy .", "the time to reach the carina was also significantly lesser in group i ( 57.3312.98 sec ) compared to group ii ( 79.3322.35 sec , p<0.02 ) as the transcricoid injection given probably brought about excellent relaxation of the vocal cords , making the introduction of the bronchoscope smooth .", "the transcricoid method was more effective than the spray as you go technique .", "lignocaine is the most commonly used local anaesthetic agent for fibreoptic bronchoscopy and has a wide margin of safety .", "performed a double - blinded , placebo - controlled trial in 100 patients in a centre that normally performs unsedated bronchoscopy , and could not demonstrate improved patient tolerance , comfort and co - operation with lorazepam ." ], [ "diagnostic fibreoptic bronchoscopy without sedation with transcricoid injection of lignocaine can be recommended as a safe method of anaesthetising the respiratory mucosa , which is well tolerated by the patients with negligible side effects and provides acceptable conditions for the bronchoscopist as compared to the spray as you go technique ." ] ]

[ [ "charcot - marie - tooth disease ( cmt ) is the most common hereditary motor and sensory neuropathy , and cmt type 1a ( cmt1a ) neuropathy , which is the most common type of cmt , is subject to a gene dosage effect.1 the primary genetic cause of cmt1a is a duplication of pmp22 resulting from the unequal crossover between two homologous repetitive elements that flank the 1.4-mb region of chromosome 17p12.2 a new mechanism responsible for the outbreak of cmt1a - which is related to a nonrecurrent rearrangement has recently been reported.3 cmt1a is also caused by a point mutation in pmp22.4 abnormal axon - schwann cell interactions cause abnormalities in axonal structure and function , but the exact pathogenic mechanism causing cmt1a is unknown.5 one obvious possibility is that the weakness and sensory loss are the result of axonal degeneration ; secondary axonal degeneration is common in cmt1a patients , and its degree determines the patient 's functional disability.6 this finding is consistent with the electrophysiological and clinical findings in patients with cmt1a and in several animal models of demyelinating neuropathy.7,8 axonal dysfunction induced by demyelinating schwann cells can also occur without axonal degeneration.9 the relationship between motor nerve conduction velocities ( mncvs ) and disease disabilities has been the subject of much debate.10 - 14 most cmt1a research groups have found a relatively weak correlation between the severity of muscle weakness and nerve conduction velocities,10 - 12 although some have noted that patients with slower velocities developed more weakness.13,14 moreover , longitudinal studies have shown that the velocities remained unchanged over decades , whereas the compound muscle action potential ( cmap ) amplitudes decreased.15,16 however , the relationship between mncvs , cmaps , and the disease severity has not been investigated in koreans .", "therefore , we determined whether there is a correlation between clinical disabilities and electrophysiological values in korean cmt1a patients with pmp22 duplication ." ], [ "the impairment and progression of cmt was evaluated in these patients using two scales : the functional disability scale ( fds)13 and the cmt neuropathy score ( cmtns).17 disease severity was quantified for each patient using a 9-point fds based on the following criteria : 0 , normal ; 1 , normal but with cramps and fatigability ; 2 , unable to run ; 3 , difficulty walking but still able to walk unaided ; 4 , walking with a cane ; 5 , walking with crutches ; 6 , walking with a walking frame ; 7 , wheelchair bound ; and 8 , bedridden . in addition , we determined the cmtns based on the motor and sensory symptoms , and according to the pain and vibration , muscle strength , and neurophysiologic test results .", "the mncvs and sensory nerve conduction velocities ( sncvs ) for the median , ulnar , peroneal , tibial , and sural nerves were determined in all 167 patients .", "we enrolled 167 cmt1a patients ( 93 males , 74 females ) with pmp22 duplication who took part in nerve conduction studies at 20 university hospitals in korea .", "the mncvs of the median and ulnar nerves were determined by stimulating at the elbow and wrist , respectfully , while cmaps were recorded over the abductor pollicis brevis and the adductor digiti quinti , respectively .", "the mncvs of the peroneal and tibial nerves were determined by stimulating at the knee and ankle while recording the cmaps over the extensor digitorum brevis and adductor hallucis , respectively .", "the patients ' clinical information was obtained and analyzed , including assessment of the gender ratio , age at onset , disease duration , motor and sensory impairment , deep tendon reflex , and muscle atrophy .", "the sncvs and sensory nerve action potentials ( snaps ) were obtained over a finger - wrist segment from the median and ulnar nerves , and they were also recorded for the sural nerves ." ], [ "we enrolled 167 cmt1a patients ( 93 males , 74 females ) with pmp22 duplication who took part in nerve conduction studies at 20 university hospitals in korea .", "this study was approved by the institutional review board of the ethics committee of the ewha womans university hospital ." ], [ "the patients ' clinical information was obtained and analyzed , including assessment of the gender ratio , age at onset , disease duration , motor and sensory impairment , deep tendon reflex , and muscle atrophy .", "the age at onset was determined by asking the patients when their symptoms - such as distal muscle weakness , foot deformity and/or sensory change - first appeared .", "the impairment and progression of cmt was evaluated in these patients using two scales : the functional disability scale ( fds)13 and the cmt neuropathy score ( cmtns).17 disease severity was quantified for each patient using a 9-point fds based on the following criteria : 0 , normal ; 1 , normal but with cramps and fatigability ; 2 , unable to run ; 3 , difficulty walking but still able to walk unaided ; 4 , walking with a cane ; 5 , walking with crutches ; 6 , walking with a walking frame ; 7 , wheelchair bound ; and 8 , bedridden . in addition , we determined the cmtns based on the motor and sensory symptoms , and according to the pain and vibration , muscle strength , and neurophysiologic test results .", "the scores of this test were used to divide the patients into two groups : mild ( 0<cmtns10 ) and moderate or severe ( cmtns11 ) ." ], [ "the mncvs of the peroneal and tibial nerves were determined by stimulating at the knee and ankle while recording the cmaps over the extensor digitorum brevis and adductor hallucis , respectively .", "the mncvs and sensory nerve conduction velocities ( sncvs ) for the median , ulnar , peroneal , tibial , and sural nerves were determined in all 167 patients .", "the sncvs and sensory nerve action potentials ( snaps ) were obtained over a finger - wrist segment from the median and ulnar nerves , and they were also recorded for the sural nerves .", "the mncvs of the median and ulnar nerves were determined by stimulating at the elbow and wrist , respectfully , while cmaps were recorded over the abductor pollicis brevis and the adductor digiti quinti , respectively .", "the terminal latency indices ( tlis ) that adjust the distal motor latency for the terminal distance and the proximal mncv were calculated .", "the calculated tli was compared to the tli of the normal population as reported previously.18 tlis were calculated for the median nerves as follows : tli = terminal distance ( mm)/[mncv ( ms)distal motor latency ( ms ) ] ." ], [ "correlations were determined using pearson 's correlation coefficient ( r ) , and probability values of p<0.05 were considered to be indicative of statistical significance .", "11.0 ( spss , chicago , il , usa ) . percentages and means were compared by the chi - square test and student 's t - test , respectively ." ], [ "in contrast , the mncv of the median nerve was only correlated with the cmtns ( p<0.05 ) . the snaps and sncvs of the median , ulnar , and sural nerves", "these results suggest that demyelination in cmt1a patients is uniformly distributed between the proximal and distal portions of the nerves .", "the cmaps of the median ( p<0.001 ) , ulnar ( p<0.001 ) , peroneal ( p<0.05 ) , and tibial ( p<0.001 ) nerves were significantly correlated with the cmtns , and the cmaps of the median ( p<0.001 ) , ulnar ( p<0.001 ) , peroneal ( p<0.05 ) , and tibial ( p<0.001 ) nerves were correlated with the fds score ( table 2 ) .", "however , no correlations were found between the age at onset and the cmaps in the median and ulnar nerves ( fig .", "the cmap of the median nerve was significantly correlated with the disease duration ( fig ." ], [ "the mean age at examination was 36.9 years ( range , 5 - 75 ye - ars ) and the mean age at onset was 15.5 years ( range , 2 - 45 years ) .", "heel gait defects occurred more commonly than toe gait defects ( p<0.001 ) , and high - arched foot deformities were common ( 89% ) .", "the mean disease duration at the time of examination was 22.3 years ( range , 0 - 57 years ) .", "atrophy started predominantly in the distal legs , with these symptoms being noted to a lesser extent in the distal upper limbs .", "the paresis in the distal regions of the lower limbs varied from asymptomatic to severe weakness .", "the disease had manifested before the second decade of life in 69% of the patients ." ], [ "these results suggest that demyelination in cmt1a patients is uniformly distributed between the proximal and distal portions of the nerves .", "the tli of the patients ' median nerve ( 0.310.10 , meansd ; range , 0.13 - 0.72 ) did not differ significantly from the normal values seen in healthy control subjects ( 0.310.04 ; range , 0.23 - 0.43 ) .", "however , no correlations were found between the age at onset and the cmaps in the median and ulnar nerves ( fig .", "both the mncv and sncv of the median nerve were uniformly reduced in the cmt1a patients .", "the cmap of the median nerve was significantly correlated with the disease duration ( fig .", "1a ; p<0.001 ) and the cmap of the ulnar nerve ( fig . 1b ; p<0.01 ) ." ], [ "the characteristics of the mild ( 0<cmtns10 ) and the moderate or severe ( cmtns11 ) cmtns groups are listed in table 1 .", "the amplitudes of the evoked median nerve motor responses were more severely affected in the moderate or severe cmtns group than in the mild cmtns group . in contrast , neither the mncvs nor the sncvs differed significantly between the two groups .", "the gender ratio was similar in the two groups , and the mean age at onset did not differ significantly between them .", "however , the disease duration at the time of examination was significantly longer in the moderate or severe cmtns group ( p<0.001 ) .", "the patients in the moderate or severe cmtns group were more severely affected than those of the mild cmtns group by muscle weakness ( p<0.001 ) , muscle atrophy ( p<0.001 ) , sensory loss ( p<0.001 ) , the frequency of areflexia ( upper , p<0.001 ; lower , p<0.01 ) , heel and toe gait defects ( p<0.001 ) , and foot deformity ( p<0.05 ) ." ], [ "the cmaps of the median ( p<0.001 ) , ulnar ( p<0.001 ) , peroneal ( p<0.05 ) , and tibial ( p<0.001 ) nerves were significantly correlated with the cmtns , and the cmaps of the median ( p<0.001 ) , ulnar ( p<0.001 ) , peroneal ( p<0.05 ) , and tibial ( p<0.001 ) nerves were correlated with the fds score ( table 2 ) .", "in contrast , the mncv of the median nerve was only correlated with the cmtns ( p<0.05 ) . the snaps and sncvs of the median , ulnar , and sural nerves" ], [ "the present study investigated the correlations between disease disabilities and the electrophysiological findings in korean cmt1a patients with pmp22 duplication , and found that the disabilities were related to the cmaps rather than to the ncvs .", ", a significant correlation was found between the clinical - electrophysiological manifestations and the physical disabilities among the korean cmt1a patients in this study .", "these results suggest that the degree of change in cmap amplitude is useful for predicting the clinical severity of the disease . as a marker of axonal loss ,", "we also found that the clinical manifestations of muscle atrophy were also strongly correlated with the cmaps and axonal loss , which became more pronounced as the disease progressed ." ] ]

[ [ "some scholars have proposed that chronic hcv infection without liver cirrhosis contributes to reduced bone mineral density , whereas other scholars have asserted the opposite . to assess the association between hcv exposure and subsequent development of osteoporosis", "although the role of osteoporosis as a sequence of cirrhosis or advanced liver disease has been thoroughly documented , the effect of hcv exposure on bone mineral density in the absence of advanced liver disease remains debated .", "it is estimated that > 50% of hip fractures worldwide will occur in asia by 2050 . the functional outcome and increased mortality of osteoporotic fracture", "osteoporosis increases the risk of fracture and thus has been considered a major public health concern . traditionally , the development of osteoporosis is related to several risk factors , such as aging , immobility , hypertension , antihypertensive agents , hyperparathyroidism , menopause , diabetes mellitus , corticosteroid usage , low calcium intake , vitamin d deficiency , and genetic vulnerability .", "a negative balance between the formation and resorption of bone mass can lead to the development of osteoporosis .", "moreover , osteoporosisis characterized by skeletal fragility resulting from reduced bone mass and disrupted bone microarchitecture .", "hepatitis c virus infection is a hepatotropic virus that mainly causes inflammation and fibrosis of the liver ." ], [ "4 insurers with no history of hcv exposure , hbv infection , and osteoporosis were assigned to a comparison cohort and frequency matched with the hcv exposure cohorts according to age ( every 5-year span ) , sex , and index year .", "the incidence densities of osteoporosis were estimated in person - years for the various risk factors . to estimate the hazard ratios ( hrs ) and 95% confidence intervals ( cis ) of osteoporosis ,", "the irb also specifically waived the consent requirement . from 2000 to 2011 , patients aged 20 years and older with diagnosed hcv infection ( icd-9-cm codes 070.41 , 070.44 , 070.51 , and 070.54 ) identified from the lhid2000 comprised the hcv infection cohort .", "multivariable models were simultaneously adjusted for age , sex , and the comorbidities of diabetes , hypertension , hyperlipidemia , heart failure , stroke , and cirrhosis .", "meier estimates were plotted to illustrate the cumulative incidence of osteoporosis , and the log - rank test was performed to examine the difference between the hcv exposure and the comparison cohorts .", "individuals were excluded from the comparison cohort using the same criteria used for the hcv exposure cohort . the primary endpoint in this study" ], [ "23.75 million people ( 99.9% of the population ) were enrolled in the program . in cooperation with the bureau of national health insurance ( bnhi ) , the national health research institutes established several data sets for public use , including the longitudinal health insurance database 2000 ( lhid2000 ) , a cohort data set comprising 1,000,000 randomly selected cases from the registry of nhi beneficiaries in 2000 . to maintain confidentiality , personal information , such as patient identification numbers and sensitive personal data ,", "the national health insurance ( nhi ) program , initiated on march 1 , 1995 , provides comprehensive coverage for the medical care of taiwan residents . at the end of 2014 ,", "are encrypted in the database , and international classification of diseases , ninth edition , clinical modification ( icd-9-cm ) codes are used for disease classification .", "this study was approved to fulfill the condition for exemption by the institutional review board ( irb ) of china medical university ( cmuh-104-rec2 - 115 ) ." ], [ "for each hcv case , 4 insurers with no history of hcv exposure , hbv infection , and osteoporosis were assigned to a comparison cohort and frequency matched with the hcv exposure cohorts according to age ( every 5-year span ) , sex , and index year .", "from 2000 to 2011 , patients aged 20 years and older with diagnosed hcv infection ( icd-9-cm codes 070.41 , 070.44 , 070.51 , and 070.54 ) identified from the lhid2000 comprised the hcv infection cohort . the date for hcv exposure coding", "patients with a history of osteoporosis ( icd-9-cm codes 733.0 and 733.1 ) and hepatitis b virus ( hbv ) infection ( icd-9-cm codes 070.20 , 070.22 , 070.30 , and 070.32 ) diagnosed before the index date , those with missing information , and those younger than 20 years were excluded . using 1:m case - control studies is to increase the power and to control possible confounding . based on the statistical efficiency", "does not gain much when m > 4 , we constructed a 1:4 matched cohort study .", "individuals were excluded from the comparison cohort using the same criteria used for the hcv exposure cohort ." ], [ "each participant was followed from the index date until the endpoint , withdrawal from the nhi program , or december 31 , 2011 .", "the baseline characteristics of participant comorbidities were also analyzed ; the comorbidities included diabetes ( icd-9-cm code 250 ) , hypertension ( icd-9-cm codes 401405 ) , hyperlipidemia ( icd-9-cm code 272 ) , heart failure ( icd-9-cm code 428 ) , stroke ( icd-9-cm codes 430438 ) , obesity ( icd-9-cm code 278 ) , and cirrhosis ( icd-9-cm codes 571.2 , 571.5 , and 571.6 ) ." ], [ "the incidence densities of osteoporosis were estimated in person - years for the various risk factors . to estimate the hazard ratios ( hrs ) and 95% confidence intervals ( cis ) of osteoporosis ,", "the chi - square test and t test for categorical and continuous variables , respectively , were first used to compare the distributions of age , sex , and baseline comorbidities between the hcv exposure and the comparison cohorts .", "meier estimates were plotted to illustrate the cumulative incidence of osteoporosis , and the log - rank test was performed to examine the difference between the hcv exposure and the comparison cohorts .", "multivariable models were simultaneously adjusted for age , sex , and the comorbidities of diabetes , hypertension , hyperlipidemia , heart failure , stroke , and cirrhosis ." ], [ "incidence of osteoporosis by age , sex , and comorbidity and cox model measured hazards ratio for patients with hcv infection compared those without hcv exposure the patients exposed to hcv exhibited a 1.38-fold ( 95% ci = 1.241.55 ) higher risk of developing osteoporosis compared with the patients who were not exposed to hcv ( table 4 ) .", "demographic characteristics and comorbidities in cohorts with and without hcv exposure cumulative incidence comparison of osteoporosis for patients with ( dashed line ) or without ( solid line ) hcv exposure.hcv = hepatitis c virus .", "comparisons of hazard ratios between patients with and without hcv exposure for different outcomes osteoporosis ( or osteoporotic fracture )", "the overall risk of osteoporosis related to several variables including age , sex , and presence of comorbidities was compared in the hcv exposure cohort and the comparison cohort .", "the risk of osteoporosis in patients exposed to hcv in all stratifications was higher than that in the comparison cohorts ." ], [ ", this nationwide population - based cohort study concludes that hcv exposure increases the risk of developing subsequent osteoporosis , but no detrimental effect on osteoporotic fracture was observed .", ", this is the first population - based study to assess the relation between hcv exposure and the incidences of osteoporosis and osteoporotic fracture .", "our results revealed that the hcv exposure cohort had more comorbidities ; however , the risk of osteoporosis remained higher in the hcv exposure cohort after adjusting for age , sex , and the comorbidities of diabetes , hypertension , hyperlipidemia , heart failure , stroke , and cirrhosis .", "consistent with the literature proposing that hcv seroprevalence peaks after age 55 and that women are predisposed to hcv infection , our results revealed that most patients ( 61.7% ) were aged 50 years and that 54.6% of the patients were women .", "furthermore , hcv may be less influential than other risk factors , such as hypertension , hyperlipidemia , and heart failure , in contributing to the development of osteoporosis .", "by contrast , our epidemiological study demonstrated that hcv exposure increases the risk of osteoporosis and the detrimental effect of hcv on osteoporotic fracture was not obvious ." ] ]

[ [ "each disaster leaves an imprint on the affected population , a singular signature . a critical unmet need in the field of disaster mental / behavioral health is the capability to tailor mental health and psychosocial support ( mhpss ) to the unique constellation of psychological risk factors operating within each disaster event .", "we have developed and introduced trauma signature ( tsig ) analysis to the fields of disaster mental / behavioral health and disaster public health in response to this identified need .", "we define tsig analysis in the following manner : trauma signature ( tsig ) analysis is an evidence - based method that examines the interrelationship between population exposure to a disaster , extreme event , or complex emergency and the interrelated physical and psychological consequences for the purpose of providing timely , actionable guidance for effective mental health and psychosocial support ( mhpss)or disaster behavioral health ( dbh ) * \n support that is organically tailored and targeted to the defining features of the event . according to shultz et al .", "2013 ( in press ) , tsig examines the extent to which disaster survivors were exposed to empirically - documented risk factors for psychological distress and mental health disorders . grounded on the disaster ecology model , tsig is premised on the assumption that each disaster exposes the affected population to a novel pattern of traumatizing hazards , loss , and change ." ], [ "optimal mental health and psychosocial support ( mhpss ) : six sequential steps while the components that are uniquely contributed by tsig analysis are primarily incorporated into steps 1 and 2 , in order to achieve optimal mhpss response , significant quality improvement is needed and desirable for steps 36 . an electronic appendix , entitled operationalizing tsig ( www.landesbioscience.com/journals/disasterhealth/commart-sup.pdf ) provides details for each of the six steps in the categories of description , rationale , operationalization , unmet needs , research questions , and opportunities .", "optimal mhpss response that incorporates tsig analysis can be summarized as a sequence of six steps ( see also figure 1 ) : 1 ) initial tsig analysis to guide response based on the defining features of the disaster or potentially - traumatizing event ( pte ) , 2 ) tsig - guided preparation of responders for what to expect and deployment of appropriate response assets , 3 ) delivery and evaluation of evidence - informed early interventions , 4 ) implementation of onsite validated disaster behavioral health needs assessment , 5 ) identification and intervention with individuals at high risk for disaster - related psychological distress , impairment , or psychopathology , and 6 ) continuous monitoring of responder and survivor mental health throughout recovery with comprehensive ( end - to - end ) evaluation of the mhpss response ." ], [ "this is summarized in a stressor matrix : risk factors are arrayed by disaster phase for categories of exposure to hazard , loss , and change . news media and social media feeds", "the next step involves matching the scientific event description to the ever - expanding literature on psychological risk factors ( for distress , disorder , and psychiatric diagnosis ) .", "this step describes the physical forces of harm that impact the human population in harm s way in order to characterize exposure to hazard .", "the final step in the initial tsig analysis involves the construction of a summary table of salient psychological risk factors , grouped into categories of exposure to hazard , loss , and change with an estimate of the exposure severity for each risk factor .", ", tsig begins with review of disaster data including sitreps from governmental and ngo agencies and available data from disaster monitoring and scientific resources ." ], [ "to demonstrate the feasibility of conducting tsig analysis , we developed a series of disaster case studies , beginning with post hoc analyses of historical disasters and progressing to real - time analyses of unfolding events .", "in addition to tsig analyses for the 2010 haiti earthquake , we performed analyses on other natural disaster events including the 2011 us , super tornado outbreak , 2009 and 2011 river floods in the upper midwest , and 2012 superstorm sandy . in the realm of hybrid ( interacting natural and human - generated components ) , we carefully analyzed the 2011 great east japan disaster .", "our first tsig case study was performed on data from the 2010 haiti earthquake which we described as a potent example of the rare catastrophic event where all major risk factors for psychological distress and impairment are prominent and compounding . ", "the 2010 deepwater horizon oil spill provided an application of tsig for an anthropogenic ( human - generated ) event . in the realm of complex emergencies / humanitarian crises , we have examined patterns of internal displacement in colombia and the russia - georgia conflict in south ossetia . with each case study , the research literature database of evidence - based research studies is expanded .", "the case studies have provided an open invitation for colleagues with interest in a particular disaster event to join with us both in authorship and in advancing the tsig methodology .", "our tsig case studies have been wide - ranging , including examples of natural , human - generated , and hybrid disasters , and complex emergencies ." ], [ "however , at present we are soliciting additional disaster case studies , consulting with subject matter experts , creating the structure for the literature database , and launching an internet - based delphi process in 2013 to develop expert consensus regarding the methodology .", "we will then seek opportunities to partner with lead response agencies in real - world , real - time applications of the tsig process .", "once refined , our intention is to develop a practical system that can help infuse evidence - based science into the decision - making process for matching mhpss response to the defining features of the disaster event .", "tsig is designed to contribute to the creation of mhpss response that increasingly approaches the attributes of optimal response outlined in table 2 ." ], [], [] ]

[ [ ", we evaluated the utility of tens for patients with spasticity due to \n cvd , who were undergoing rehabilitation , was evaluated using clinical scoring systems and \n electrophysiological assessment .", "spasticity is a major problem in rehabilitation programs , and it hampers patient \n progress and may trigger severe complications2 , 3 . quantitative assessment of spasticity is \n critical when gauging responses to medical treatment and physical therapy , and when making a \n prognosis . at present , rather limited clinical scoring systems of spasticity , and \n biomechanical and electrophysiological data , are used .", "transcutaneous electrical nerve stimulation ( tens ) is a rehabilitative form of physical \n therapy used to treat pain .", "spasticity is a speed - dependent resistance to the passive motion of muscles and tendons , \n developing secondary to enhanced stretch reflexes in patients with upper motor neuron \n lesions .", "this study also aimed to explore whether tens affects \n spasticity electrophysiologically , and the extent of the effects on clinical features .", "cerebrovascular diseases ( cvds ) are associated with balance disturbances , dependency in \n performing daily living activities , and limited ambulation . as life expectancy increases" ], [ "in addition , to evaluate alpha motor neuron excitability and the extent of \n spasticity , the slopes of the rising sides of the h and m amplitude - stimulus severity slopes \n were calculated using excel and the h slope , m slope , and h slope / m slope values were \n obtained .", "all patients were asked to relax \n their muscles as much as possible during the electrophysiological study . the h reflexes and \n m responses of the gastrocnemius - soleus muscle were electrophysiologically recorded on both \n the healthy and hemiplegic sides .", "patients with spasticity of at least ashworth grade 1 in the lower extremities were \n included . the active motor power and spasticity of all patients", "patients hospitalized in ankara physical therapy and rehabilitation training and research \n hospital , who were participating in a rehabilitation program for hemiplegia with spasticity \n in the lower extremity , were recruited .", "reflex , and superficial and deep \n sensorial examinations were performed . the time taken to walk 10 m by patients who could \n walk was measured before and after tens . after a clinical evaluation", "ten minutes later , the h reflexes and m responses were \n re - assessed and compared with the pre - tens data .", "stimuli were created randomly , \n and delivered to the popliteal fossa with the posterior tibial nerve lying proximal to the \n cathode . a rectangular flow 1 ms in duration , delivered every 2 s , served as the stimulus . \n" ], [ "after tens , 11 patients \n exhibited increased walking speeds and 3 reduced speeds . when patient hemiplegic and healthy lower extremities were electrophysiologically compared , \n the mean maxima of the h reflex , the h / m ratio , the h slope , and h slope / m slope ratio , were \n significantly greater on the affected side .", "however , only the mean h slope differed significantly among the spasticity subgroups , with \n significant differences being found between subgroups i and iii , and ii and iii , in parallel \n with worsening of spasticity .", "the patient group with hemiplegia secondary to cvd numbered 27 [ 12 females ( 44.4% ) and 15 \n males ( 55.6% ) ] . a total of 24 healthy subjects [ 10 females ( 41.7% ) and 14 males ( 58.3% ) ] \n served as controls .", "the duration of disease was positively associated with the mean h maximum amplitude , the \n h / m ratio , and the h / m slope ratio ; however , no association was statistically significant . \n", "however , the mean m amplitude was higher on the normal than on the hemiplegic side . \n the mean h reflex amplitude , the h / m amplitude ratio , the h maximum latency , the h slope , \n and the h / m slope ratio , differed significantly pre- and post - tens on the hemiplegic \n side .", "higher mean h maximum amplitudes , h / m ratios , and h slopes evident as spasticity worsened . \n" ], [ "tens significantly reduced spasticity scores and increased the walking speed . on the \n spastic side , tens significantly reduced the m amplitude and increased the h reflex \n amplitude , the h / m maximum amplitude ratio , the h slope , and the h slope / m slope ratio . \n also , the mean patient h reflex amplitude , the h / m ratio , the h slope , and the h slope / m \n slope ratio , decreased significantly , and the h reflex maximum latency increased , after \n tens . in controls , tens significantly decreased the h maximum amplitude , the h / m ratio , the \n m maximum amplitude , and the m slope ratio , and lengthened the h and m maximum latencies . \n the h maximum latency was the only variable affected by lesional duration .", "tens for hemiplegic patients with spastic lower extremities due to cvd \n markedly improved clinical parameters and significantly changed electrophysiological \n variables .", "the results of this study suggest that tens is effective when used to manage \n spasticity .", "on the spastic side , tens \n significantly decreased the mean h reflex amplitude , the h / m ratio , the h slope , and the h \n slope / m slope ratio ; and increased the h reflex maximum latency .", "the mean h \n maximum amplitude , the h / m ratio , and the mean h slope increased as spasticity worsened on \n the ashworth scale .", "in the present study , steeper h slope and \n greater h slope / m slope ratio on the spastic ( compared to healthy ) side of hemiplegic \n patients prior to tens were observed ." ] ]

[ [ "the aim of the present study is to investigate roles of thrombin , tryptase , trypsin , elastase , and agonist peptides of pars in the secretion of tnf from purified human t cells and subtypes of t cells .", "tnf is a major proinflammatory cytokine that is thought to be important in the pathogenesis of asthma , food allergy , ocular allergy , and atopic dermatitis .", "proteinase - activated receptors ( pars ) belong to a family of g - protein - coupled receptors with seven transmembrane domains activated via proteolytic cleavage by serine proteinases .", "activation of pars affects their main functions such as proliferation , degranulation , and release of inflammatory mediators [ 10 , 11 ] . in our previous study , we have showed the expression of par-1 , par-2 , and par-3 on t cells , and thrombin- , trypsin- , and tryptase - induced interleukin ( il-6 ) release from t cells ." ], [ "cellular activation of signaling kits for extracellular signal - regulated kinase ( erk ) , 2-(2-diamino)-3-methoxyphenyl-4h-1-benzopyran-4-one ( pd98059 ) , akt , pi3k , and p38 2-(4-morpholinyl)-8-phenyl-4h-1-benzopyran-4-one ( ly294002 ) was purchased from cell signaling technology ( beverly , ma , usa ) .", "agonist peptides of pars , and their reverse forms , and par-2 antagonist peptide fsllry - nh2 were synthesized in cl bio - scientific inc .", ", the cells were resuspended in pbs and incubated with pe - conjugated monoclonal antibody against human cd3 for 1 h. the purity of t cells was consistently more than 95% and cell viability was more than 98% .", "human t cells were isolated from peripheral blood mononuclear cells ( pbmcs ) by a macs system with t cell isolation kit i according to the manufacturer 's protocol . in brief", "expression of mrna in each sample was finally determined after correction with -actin expression . the gene specific threshold cycle ( ct ) for each sample ( ct ) was corrected by subtracting the ct for the housekeeping gene -actin .", "after washing , cells were analyzed on a fluorescence - activated cell sorting ( facs ) arial flow cytometer with celldevia software ( bd biosciences , usa ) . to test the secretion of tnf from subtypes of t cells", "the purified cd3 + t cells were then used for the further cell challenge tests .", "the levels of tnf in culture supernatants were measured with opteia elisa kits according to the manufacturer 's instructions ." ], [ "the results showed that trypsin and thrombin induced upregulated expression of tnf in cd4 + t cells , but not cd8 + t cells , following 16 h incubation period . among cd4 + t cells , trypsin and thrombin enhanced tnf expression in il-4 + or cd25 + t cells , but not in ifn+ or il-17 + t cells .", "we , therefore , investigated subtypes of t cells by flow cytometer analysis in order to determine the subtypes that upregulate tnf in response to trypsin or thrombin .", ", we investigated the influence of the serine proteinases on the expression of tnf mrna in t cells .", "sch 79797 was able to inhibit enhanced tnf expression induced by trypsin and thrombin ( figures 3(a ) and 3(b ) ) . in order to examine signal transduction pathways of thrombin and trypsin" ], [ "these findings indicate that tnf is one of key mediators of inflammation ; therefore , our current study is of importance in understanding tnf - related inflammation and the mechanism of proteinase - induced cytokine production in t cells .", "we discovered in the present study that serine proteinases thrombin and trypsin , but not tryptase induced tnf release from human t cells .", "our previous report which found thrombin - induced il-6 secretion from human peripheral blood t cells may support our current findings . while little information is available on induction of tnf release from t cells by trypsin , the ability of trypsin to stimulate il-6 secretion from t cells may support the anticipation that trypsin is capable of inducing cytokine release from t cells .", "inhibition of thrombin - induced tnf release by a specific inhibitor of thrombin and hirudin indicates that action of thrombin on t cells was dependent on the enzymatic activity of this serine proteinase ." ], [ "stimulation of tnf secretion from t cells by serine proteinases further proved that these proteinases are actively involved in the pathogenesis of inflammation and regulation of immune response in man .", "in conclusion , it is discovered in the present study that serine proteinases thrombin and trypsin are potent stimuli of tnf secretion from highly purified t cells .", "their actions on t cells depend on their enzymatic activities and are likely through activation of par-1 ." ] ]

[ [ "our findings reveal that hbo2 treatment may effectively modulate the intestinal milieu in inflammatory conditions involving hif-1-mediated regulation of antioxidative gene expression .", "a recent study revealed increased activity of antioxidative enzymes and reduced oxidative stress in the inflamed gut mucosa following hbo2 exposure ; however , specific mechanisms inducing activation of antioxidative enzymes in the inflamed colonic tissue upon hbo2 remain unknown . since there is evidence that the intracellular redox status is in a close correlation with the inflammatory microenvironment , and it can also be changed by hbo2 , the aim of this study was to investigate the effects of hbo2 on the mrna expression of hif-1 , proinflammatory cytokines , and antioxidative enzymes in the gut and peripheral lymphoid organs of balb / c mice with dss - induced colitis . an additional aim was to assess the activity of antioxidative enzymes and whether hif-1 gene expression regulation during the gut inflammation and hbo2 treatment correlates with the changes in antioxidative and proinflammatory gene expression .", "relapsing chronic inflammation found in the gut of individuals affected by inflammatory bowel diseases ( ibd ) is a result of several overlapping factors , including dysregulation of the immune response to the enteric microbiota , genetic susceptibility , and environmental factors [ 1 , 2 ] .", ", hyperbaric oxygen ( hbo2 ) therapy has been introduced as a possible additional treatment for ibd patients , especially in the case of refractory disease when the standard therapy is ineffective ." ], [ "grade 1 ( chronic inflammatory infiltrate ) : \n 0 : no increase , 1 : mild but unequivocal increase , 2 : moderate increase , 3 : marked increase . \n 1 : mild but unequivocal increase , 2 : moderate increase , \n grade 2 ( lamina propria leukocytes ) : \n 0 : no increase , 1 : mild but unequivocal increase , 2 : moderate increase , 3 : marked increase . \n 1 : mild but unequivocal increase , 2 : moderate increase , \n grade 3 ( intraepithelial neutrophils ) : \n 0 : none , 1 : < 5% crypts involved , 2 : < 50% crypts involved , 3 : > 50% crypts involved . \n 1 : < 5% crypts involved , 2 : < 50% crypts involved , 3 : > 50% crypts involved . \n grade 4 ( crypt destruction ) : \n 0 : none , 1 : probable , local excess of neutrophils in part of crypt , 2 : probable , marked attenuation . \n 1 : probable , local excess of neutrophils in part of crypt , 2 : probable , marked attenuation", "the average body weight of the mice at the time of inclusion into the study was 22.8 0.4 g. colitis was induced by 5% ( w / v ) of dss ( mr 36.00050.000 , mp biomedicals , illkrich , france ) in drinking water ad libitum for 7 consecutive days [ 26 , 27 ] .", "real - time pcr was performed on cfx96 system ( bio rad , singapore ) to assess relative expression of catalase ( cat ) , glutathione peroxidase 1 ( gpx1 ) , superoxide dismutase 1 ( sod1 ) , hif-1 , il-1 , il-2 , and il-6 .", "all procedures involving live animals were conducted in accordance with the european guidelines for the care and use of laboratory animals ( directive 86/609/eec ) and were approved by the local ethical committee ( faculty of medicine , university of osijek ) and croatian ministry of agriculture . for each experiment male mice at the age of 1012 weeks were randomized into 4 groups ( n = 4 - 5 mice / group / experiment ) : control mice ( ctrl ) , control mice undergoing hbo2 ( ctrl + hbo2 ) , mice receiving dextran sodium sulphate ( dss ) , and dss treated mice undergoing hbo2 ( dss + hbo2 ) .", "mice were sacrificed by cervical dislocation on day 8 , after the morning hbo2 session .", "mice were sacrificed by cervical dislocation on day 8 following the last morning hbo2 treatment ." ], [ "to summarize , colitis resulted in gpx1 gene upregulation and cat gene downregulation , while hbo2 downregulated sod1 and further upregulated gpx1 in a tissue - specific manner . to examine the possible role of hif-1 in transcriptional control of antioxidative genes in the colon ,", "inflammatory conditions have been known to include the enhanced production of ros and other oxidative mediators that may affect transcriptional regulation via hif-1. to investigate the role of hif-1 in the regulation of the antioxidative response / capacity during dss - induced colitis and hbo2 treatment , hif-1 , cat , gpx1 , and sod1 mrna expressions were determined using quantitative pcr method .", "we found that both the inflammation and the hbo2 treatment per se were able to change the activity of antioxidative enzymes in the colonic mucosa and the peripheral lymphoid organs ( mln and spleen ) . in spleen hbo2 treatment per", "inflammation during dss - induced colitis and the hbo2 treatment also induced significant changes in mrna expression of target antioxidative genes .", "mrna expression was significantly changed by the hbo2 treatment and the inflammatory microenvironment in the gut mucosa ." ], [ "in the present study , the experimental model of dss - induced colitis in balb / c mice was employed to explore the effects of hbo2 on the antioxidative enzymes , transcription factor hif-1 , and proinflammatory cytokine genes during colonic inflammation and their role in modulating the course of the disease via hbo2 treatment .", "previous studies revealed that hif-1 mediated transcriptional regulation of different proinflammatory cytokines and growth factor genes are tissue and cell specific and include regulation trough alternative splicing , mrna stability , and interactions with other transcription factors like nf-b [ 6669 ] . in our study we found a strong correlation between hif-1 and il-6 mrna levels suggesting involvement of hif-1 in transcriptional regulation of il-6 gene during colonic inflammation and hbo2 . in conclusion , our results confirmed that hbo2 exerts an anti - inflammatory effect on dss - induced colitis in mice , and this effect at least involves hif-1 and antioxidative genes expression regulation ( as outlined in figure 7 ) .", "the most important findings are that ( a ) hbo2 significantly reduces symptoms and severity of dss - induced colitis , as evidenced by clinical appearance , contraction of the immune cell expansion and mobilization , and reversal of il-1 , il-2 , and il-6 gene expression ; ( b ) hbo2 modulates the expression of antioxidative enzyme genes and enzyme activities during colitis ; and ( c ) hbo2 enhances hif-1 mrna expression in the inflamed colonic tissue which is in a strong correlation with gpx1 , sod1 , and il-6 mrna expression .", "colitis resulted in a significant downregulation of cat mrna expression in the colonic mucosa , and the hbo2 treatment induced its upregulation in the spleen of dss + hbo2 group of mice ." ] ]

[ [ "sexuality in women is a complex issue with physiological , psychological , and cultural components .", "determination of sexual partner involvement , intimate relationships , and past abusive relationships is crucial in female sexual dysfunction ( fsd ) ( 1 , 2 ) .", "intimate sexual function is one of the best predictors of quality of life , and sexual dysfunction causes many problems for couples .", "some researchers have found that the frequency of sexual relationship and sexual satisfaction are positively associated with marital satisfaction ( 11 , 12 ) . among other factors , illicit drug dependency changes", "furthermore , morphine has been found to inhibit sexual behavior in a dose - dependent manner through a complex pharmacological domain ( 13 , 14 ) .", ". moreover , opioids act on a variety of neurotransmitters in the brain , including endorphins ." ], [ "although many studies have looked at the frequency of sexual dysfunction in women , limited research has focused on the impact of addiction on spouse sexual function . to the best of our knowledge", ", most studies on drug abuse and sexual performance have focused on addicted populations , and have usually considered men .", ", few studies have been conducted on the effect of males opium dependency on their wives sexuality .", "thus , the present cross - sectional study aimed to assess the prevalence of fsd among women with addicted partners . we hypothesized that substance dependency in males would affect their wives sexual function ." ], [ "the case group included 160 women whose husbands were opioid dependent . some of them were the wives of opioid - dependent males hospitalized in the addiction treatment units of teaching hospitals affiliated with the shiraz university of medical sciences , shiraz , iran .", "the interview focused on hsdd , sexual arousal disorder , orgasmic disorder , and sexual pain disorder .", "this cross - sectional controlled study was conducted on 340 women of reproductive age ( 25 - 50 years old ) selected through convenience sampling .", "the exclusion criteria of the study were a history of substance use disorders , gynecological disorders ( gyn ) , and chronic medical disease that has been shown to affect sexual functioning ( e.g. hypertension , diabetes mellitus , chronic kidney disease , cancer , spinal cord injury , lupus , fibromyalgia , chronic pain and chronic depression ) .", "in contrast , the control group ( n = 160 ) included women whose spouses were not opioid dependent ; they were selected from the general population referring to the clinics of the shiraz university of medical sciences . after giving informed consent ,", "in addition , the subjects demographic information , such as age , level of education , marital status , and duration of marriage , was obtained using a self - constructed questionnaire designed by the authors . to include the women in the study", "the participants were interviewed privately according to the dsm - iv - tr criteria by a senior female medical student who was one of the researchers and had been properly trained regarding the nature of the study .", "other women were encountered in centers where opioid - dependent males spouses were referred for group therapies ." ], [ "in addition , 73 women in the case group ( 46.2% ) and 20 in the control group ( 12.6% ) had sexual aversion disorder , with a significant difference between the two groups ( p < 0.05 ) . in this study ,", "furthermore , 75 out of the 155 women in the case group ( 46.9% ) and 16 out of the 145 women in the control group ( 10% ) had hsdd , and the difference between the two groups was statistically significant ( p < 0.05 ) .", "out of the 340 women who were selected , 5 in the case group and 15 in the control group were excluded due to missing data .", "the mean ages of the case and the control group were 36.35 and 33.2 years , respectively . in this study , statistical significance was defined as p < 0.05 .", "it should be noted that in terms of demographic characteristics , there was no significant difference between the case and the control group ( p > 0.05 ) , so , we could use further statistical methods on the data .", "approximately more than 50% of the participants had problems in at least one domain of sexual function . moreover ," ], [ "the frequency of hsdd and aversive sexual desire disorder was more common in the case group than the control group , and the difference was statistically significant ( p < 0.05 ) .", "this high prevalence may have resulted from various causes . although studies have shown that many factors , such as age and level of education , affect sexual function ( 15 - 17 ) , the findings of the current study revealed no relationship between the demographic characteristics , that is , age , duration of marriage , and level of education , and sexual dysfunction . as can be seen in table 2 ,", "this disorder was a significant problem affecting a considerable number of women in both the case and control groups ( table 2 ) .", "the findings of the present study showed that the addicts spouses suffered from hsdd significantly more than the control group .", "another finding was the higher frequency of orgasmic disorder in the case group ; however , this difference was not statistically significant . the higher rate of orgasmic disorder among the addicts spouses obtained in this research was in line with the study by noori et al ." ] ]

[ [ "although laparoscopic appendectomy ( la ) is more expensive than is open appendectomy ( oa ) due to the costs of the disposable equipment , and can be more technically challenging in children , the overall cost of the operation has been shown to be similar to that of open appendectomy .", "laparoscopic surgery has gained widespread acceptance in a variety of procedures , ranging from gastric fundoplication to cholecystectomy .", "the real cost savings of la are due to the shorter postoperative length of hospital stay ( los ) and the infrequent postoperative complications . the ultimate reduction in postoperative hospital costs to make la", "most cost - effective would be to perform the procedure as same - day surgery or so - called fast - track surgery . because it has been our observation that many children can be discharged within 24 hours after a laparoscopic appendectomy , we reviewed our records to determine its feasibility ." ], [ "a retrospective chart review was performed on 79 children who underwent a laparoscopic operation for the suspected diagnosis of acute appendicitis over a 3-year period between july 1997 and july 2000 .", "prior to the operation , if the diagnosis of acute appendicitis was unclear , the patients were evaluated with further laboratory and diagnostic testing , which included an abdominal computed tomography scan or ultrasound evaluation , or both of these , in select patients .", "postoperative analgesia was obtained usually with ketorolac tromethamine and acetaminophen . to be discharged home , patients had to be tolerating oral liquids , be afebrile , and free of nausea and vomiting .", "if any evidence of localized or generalized peritonitis was visualized during the operation , patients were sent home on oral antibiotics , usually a 5-day course of amoxicillin plus clavulanate .", "if any evidence of abscess formation or peritoneal soilage was noted , the abdominal cavity was vigorously lavaged with normal saline .", "if the appendix was perforated prior to removal , patients were placed on triple antibiotic coverage intravenously , which included ampicillin , gentamicin , and clindamycin for 5 days while in the hospital ." ], [ "seventy - nine children ( 44 boys and 35 girls ) between 2 to 17 years of age ( mean , 11 years ) underwent la . in 4 ( 5% ) children , all with perforated appendicitis , the la was converted to an open appendectomy , secondary to technical difficulties in completing the operation laparoscopically . at operation , 51 ( 64.5% )", "had acute appendicitis , 22 ( 27.8% ) had perforated appendicitis , 4 ( 5% ) had ruptured ovarian cysts , and 2 ( 2.5% ) had no obvious pathology .", "no significant morbidity occurred in the nonperforated group ( drug rash , 1 ; fever > 24 hrs , 3 ) ; and no readmissions or reoperations were necessary on follow - up .", "total los for all 79 patients was a median of 58 hours , and median postoperative los was 35 hours .", "thirty - two ( 56% ) of the children without perforated appendicitis went home in 24 hours following la .", "all but one complication ( drug rash , 1 ) occurred in the perforated group . in the 57 ( 72% ) children without perforated appendicitis , the total los was a median of 42 hours , while median postoperative los was only 28 hours ." ], [ "we suggest that laparoscopic appendectomy is a safe and effective treatment in the pediatric population , and that in cases of nonperforated appendicitis this may be performed as a fast - track or short - stay procedure .", "we anticipate that in the future , a greater percentage of our pediatric patients will be discharged within 24 hours , and we feel that in cases of simple appendicitis , laparoscopic appendectomy can be done as fast - track or short - stay surgery .", "laparoscopy can be used to delineate the source of abdominal pain when the diagnosis of appendicitis is suspected but not certain . in 4 of our patients with the presumed diagnosis of appendicitis ,", "an additional benefit of laparoscopic surgery is that it leads to greater accuracy of diagnosis , especially in teenage female patients with suspected appendicitis . in cases such as obesity and mental retardation , the diagnosis of appendicitis", "although most appendectomies , especially in children , are not done laparoscopically , many studies have shown that laparoscopic appendectomy ( la ) is at least as good as open appendectomy ( oa ) , with several benefits , including less postoperative pain and shorter lengths of stay ( los ) ." ], [ "it may be safely performed as fast - track or same - day surgery , in select children without perforated appendicitis , with a postoperative stay of 24 hours in the majority of such patients ." ] ]

[ [ "a major effort in the nucleocytoplasmic transport field has been directed towards the analysis of all members of the importin family , in particular with the aim of identifying specific transport cargoes .", "little is known about the gross structure of the genes encoding these nuclear transport receptors , and our knowledge of the chromosomal localization or the organization of the individual genes encoding members of this family is very poor .", "this has led to the characterization of a large number of related proteins ( both importins and exportins ) in all eukaryotic species analyzed .", "new members have primarily been identified by sequence homology or biochemically via their interaction with the small gtpase ran .", "strikingly , the roles of many of these receptors is conserved from yeast to humans .", "there are 14 putative members of the importin family in the completed saccharomyces cerevisiae genome , nine of which have been shown to function as importins and four as exportins ." ], [ "this suggests that importin undergoes twisted conformational changes in its heat - repeat helix stacking , which could be essential for the regulation of cargo binding and release and/or for protein interactions during the translocation through the npc .", "( b ) structure of importin bound to the ibb domain of importin ( adapted from ) .", "structure of importin . ( a ) importin is composed of 19 helical - repeat motifs ( heat repeats ) .", "full - length importin complexed with the importin--binding domain of importin ( ibb ) forms a snail - like superhelical structure wrapping tightly around the ibb domain ." ], [ "in addition , importin is able to interact directly with a large variety of different cargoes , including the t - cell protein tyrosine phosphatase , the human immunodeficency virus ( hiv ) tat and rev proteins , human t - cell leukemia virus rex protein , ribosomal proteins l23a , s7 , and l5 , cyclin b1 , smad and the parathyroid - hormone - related protein .", "import and export are multistep processes that are initiated by the recognition of nuclear localization signals ( nlss ) and nuclear export signals ( ness ) .", "a major function of transport factors of the importin family is to mediate the transport between the nucleus and cytoplasm of macromolecules that contain nuclear import or export signals . to this end ,", "given that several nucleoporins implicated in binding to importins and exportins have distinctive locations in the structure of the npc , the asymmetric design of the npc may also be important to efficiently drive nuclear import and export .", "as illustrated in these examples , the rangtp cycle plays a key role in conferring directionality to nucleocytoplasmic transport events and rangtp acts as a marker of the nuclear compartment for both nuclear import and export ( figure 2 ; reviewed in ) ." ], [ "given that several nucleoporins implicated in binding to importins and exportins have distinctive locations in the structure of the npc , the asymmetric design of the npc may also be important to efficiently drive nuclear import and export .", "as illustrated in these examples , the rangtp cycle plays a key role in conferring directionality to nucleocytoplasmic transport events and rangtp acts as a marker of the nuclear compartment for both nuclear import and export ( figure 2 ; reviewed in ) .", "nuclear transport mediated by importins and exportins is strongly directional in vivo : importins bind their cargo in the cytoplasm and transfer it to the nucleus , whereas exportins interact with their substrates in the nucleus and mediate their export to the cytoplasm ( figure 2 ) .", "this is mediated by importin together with its adaptor importin , which binds both the nls - containing cargo and importin in the cytoplasm . after a trimeric importin -importin -nls complex is formed , importin mediates docking at the npc . in the presence of rangdp and free gtp ,", "a paradigm for transport out of the nucleus is the export of leucine - rich nes - containing proteins ." ], [ "mex67p / tap does not belong to the family of importin--like proteins , suggesting that there are alternative translocation pathways through the npc .", "a key mechanistic topic that is poorly understood is the export of rnas and rnps .", "the further characterization of new transport receptors and adaptors , and the identification of new import and export substrates , will lead to a more complete picture of nucleocytoplasmic transport .", "a big challenge for the future will be to understand how translocation through the npc occurs , and how nucleocytoplasmic transport is regulated .", "despite the large amount of progress that has been made in the nucleocytoplasmic transport field in recent years , many important questions remain unsolved .", "many import and export receptors have now been characterized and their first cargoes have been identified ." ] ]

[ [ "the overall objective of this research was to create an adaptive home - use robotic rehabilitation system for the upper body .", "this paper presents results from comparison testing between the customized exercise tasks and the standard exercise tasks , as well as preliminary testing of a pneumatically actuated prototype for the wearable robot .", "the specific goals for the system were to collect data from the subject in real - time using simple and portable sensors , to create a customized exercise task for the subject by adapting a standard exercise task , and to build a simple and non - rigid wearable robot that will provide subject - specific resistance training .", "robotic rehabilitation systems , designed to address the limitations of traditional physiotherapy , have been developed primarily for upper extremity rehabilitation of stroke patients .", ", previous research has suggested that pneumatically actuated rehabilitation robots can be used by patients with movement disabilities or stroke to improve their motor function .", "the most common non - medication treatment for musculoskeletal conditions and stroke is rehabilitation . for patients" ], [ "4 , part b ) , was given to the neural network as input data ( combined with the healthy emg data for that particular task ) , and a customized exercise task was output from the neural network .", "a test platform was built to model the human arm and elbow joint ; in this way , the basic prototype and the control algorithms for the wearable robot could be developed and validated in a safe environment without a risk of injury . the platform was designed to replicate the mass properties \\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 total~mass}=1.6~{\\rm kg})$ \n \\end{document } , inertial properties \\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 i}=0.1~{\\rm kg}{^{\\ast}}{\\rm m}^{2})$ \n \\end{document } , and dimensions of the human arm . the test platform consisted of two \\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 } { } $ 7\\times 7\\times 30~{\\rm cm}$ \n \\end{document } aluminum cages ( simulating the upper arm and forearm segments ) connected together by two ball bearing assemblies to simulate an elbow joint ( fig .", "data was collected during these exercise tasks using both the robotic rehabilitation system and a 10 camera opto - electronic vicon mx motion capture system ( vicon , oxford , uk ) as a gold - standard for validation . for the robotic rehabilitation system ,", "the subject then completed 10 full cycles of this customized output exercise task ( custom ) , as well as 10 full cycles of the unmodified original task used as input to the neural network ( standard ) ( fig .", "a microsoft \\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 kinect}^{\\rm tm}$ \n \\end{document } sensor and an electromyograph ( emg ) system were combined with custom software written in c++ in order to collect data from the subject in real time ." ], [ "the results from the validation testing between the \\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 kinect}^{\\rm tm}$ \n \\end{document } data and the vicon data are presented for all trials of the 10 subjects for the right arm joints ( wrist , elbow , and shoulder ) by exercise task in table i. for the rom task , the largest rmse was observed for the shoulder joint . for the visual follow task , the largest rmse was observed for the elbow joint , then the wrist joint , and last the shoulder joint .", "the wearable robot prototype was able to accurately mimic the angle of the subject 's elbow in real - time .", "furthermore , the rmse for the elbow and shoulder joints was greater during the visual follow task when compared to the rom task , while the rmse for the shoulder joint was greater during the rom task . \n", "table ivicon - kinect comparisons by joint and task vicon - kinect comparisons by joint and task a comparison of the standard and custom exercise tasks by exercise set is presented in table ii ." ], [ "the overall objective of this research was to create an adaptive home - use robotic rehabilitation system for the upper body .", "this paper presented results from comparison testing between different exercise tasks and from preliminary testing of a pneumatically actuated prototype for the wearable robot , all of which demonstrate that this robotic rehabilitation system achieved the stated objective .", "experimental testing was conducted to determine the accuracy of the joint center measurements from the \\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 kinect}^{\\rm tm}$ \n \\end{document } as compared to the vicon gold - standard measurements during two upper - body exercise tasks ( table i ) .", "the \\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 kinect}^{\\rm tm}$ \n \\end{document } sensor measured the 3d position and 3d velocity of the subject 's hand at 30 hz .", "furthermore , this test demonstrates the feasibility of the entire robotic rehabilitation system because the subject was able to actuate the wearable robot using only the movement of his elbow ." ], [ "the addition of force feedback to the system should significantly enhance the results as the subject will have additional biofeedback information to help them complete the rehabilitation exercises .", "this study described a promising home - use robotic rehabilitation system comprised of low - cost components .", "the immediate next steps are to create a gui for the system to increase usability and to optimize the model generation code for speed and accuracy .", "future iterations of the robot prototype should be designed for wearability and human safety so that it can be worn by the subjects in order to provide force feedback .", "further research is necessary to create a commercial version of this system , specifically on the prototype of the wearable robot .", "however , the data collection component of the system could be used in the near future for large scale research studies .", "the wearable robot was designed to provide force feedback during the exercise tasks , but the current prototype was not tested on human subjects ." ] ]

[ [ "diabetes was related to one million deaths and mortality was higher under age of 60 years . by 2030 there will more than 79 million diabetics , making it one of the major public health challenge to the country .", "different studies conducted in countries like united states have observed the positive association of patient 's knowledge regarding the disease and self care to the treatment compliance .", "international diabetic federation estimated that in india there are 66.8 million patients in 2013 , with nearly 50% undiagnosed .", "hence , this study was planned to assess knowledge about diabetes and its correlation with pharmacological and non - pharmacological compliance , among the diabetics attending a rural health center from sangli district , maharashtra ( india ) .", "the investigators of a1 cheive study observed high prevalence of macrovascular and microvascular complications among the indian diabetic patients .", "observed retinopathy in 28.9% , nephropathy in 32.5% , neuropathy in 30.1% , cardio - atherosclerotic diseases in 19.2% and peripheral vascular diseases in 18.1% diabetic patients ." ], [ "the study population was adult type-2 diabetes patients on oral hypoglycemic drugs for at least 6 months attending the rural health centre .", "this was a cross - sectional study conducted in a rural health center attached to a medical college from sangli district of maharashtra , india .", "prevalence of knowledge regarding diabetes in the pilot study was 52.71% ; considering level of significance as 5% and error 15% ;", "due to lack of exact definition of compliance to the non - pharmacological management , a scale was developed with equal importance to diet modifications and physical exercises .", "the patients attending for routine check up or drug re - prescription and consenting to participate were included in the study .", "pharmacological compliance was self - reported , with participants reporting to have missed more than two doses in last 15 days were considered as non - compliant .", "those scoring under 50% , 5075% and more than 75% were considered to be having poor , moderate and good knowledge , respectively .", "the maximum possible score was 12 and the participants scoring above 9 ( 75% ) were considered as compliant to non - pharmacological management ." ], [ "two hundred twenty - three ( 72.6% ) participants were male while 84 ( 27.4% ) were female [ table 1 ] . the mean age of study participants was 55.6 years ( range 3585 years and standard deviation 12.22 years ) .", "pharmacological and non - pharmacological management compliance were the highly significant predictors , while education and age were also significant predictors for knowledge regarding diabetes [ table 3 ] .", "out of 329 questionnaires collected , 307 were complete and hence used in the final analysis .", "pharmacological compliance was associated with knowledge . among the participants with good compliance , 88.5% had moderate to good knowledge as compared to only 56.2% participants with poor compliance .", "association between knowledge regarding diabetes with pharmacological compliance and non - pharmacological management compliance binary logistic regression was applied with knowledge regarding diabetes as dependent variable , while age , gender , education , occupation , pharmacological compliance and non - pharmacological management compliance as independent variables ." ], [ "in the current study , we observed that the patients compliant with pharmacological and non - pharmacological management had good knowledge regarding diabetes .", ", may be present and are not considered in the current study . only self - reported compliance was considered without confirming .", "confounders like economical state , availability of medications , counseling by health professionals , exposure to information through media , additional use of ayurvedic / homeopathic / other indigenous systems of medicines etc .", "al - qazaz hkh et al . , ( 2010 ) , observed significant correlations between the knowledge about diabetes and adherence to the treatment in subjects from penang .", "when carried out a study at al - makhfia governmental diabetes primary healthcare clinic in nablus , palestine in 2012 , observed that diabetic patients with high knowledge were less likely to be non - adherent .", "abdella and mohammad studied awareness of diabetic patients about their illness and associated complications in ethiopia ( 2012 ) ; majority of patients ( 67% ) had good knowledge on actions to be taken on the occurrence of acute complications and reasons for developing acute complications . while we observed that less than 10% participants had good knowledge ." ], [ ". however , many of the patients have poor knowledge regarding the disease , the situation is worse among the females .", "seminars , counseling sessions and workshop should be arranged periodically for diabetic patients to increase their awareness regarding diabetes disease in total per say .", "lower level of literacy and old age hinder the presence of knowledge regarding the diabetes ." ] ]

[ [ "it was the german physician chemist johann joseph scherer who first demonstrated the occurrence of lactic acid in human blood under pathological conditions after death in 1843 and 1851 [ 15 , 17 ] , and carl folwarczny in 1858 who first demonstrated lactic acid in blood of a living patient . in this article", "lactic acid was first found and described in sour milk by the swedish chemist karl wilhelm scheele ( 17421786 ) in 1780 .", "we wish to honour scherer 's forgotten observations and describe the influence of his finding on further research on lactic acid at the end of the 19th century .", "this was the first demonstration of the relationship between tissue hypoxia and the formation of lactate .", "the swedish chemist jns jakob berzelius ( 17791848 ) found lactic acid in fluid extracted from meat in 1808 [ 2 , 3 ] , and the german chemist justus von liebig ( 18031873 ) , who established the world 's first school of chemistry at giessen , proved that lactic acid was always present in muscular tissue of dead organisms . in 1859 , emil heinrich du bois - reymond ( 18181896 ) published several articles on the influence of lactic acid on muscle contraction [ 59 ] .", "araki and zillessen found that if they interrupted oxygen supply to muscles in mammals and birds , lactic acid was formed and increased [ 1014 ] .", "the occurrence of increased lactic acid in blood ( hyperlactataemia ) nowadays reflects severe illness , in which the increased blood lactate levels may result from both anaerobic and aerobic production or from a decreased clearance ." ], [ "he practised medicine in wipfeld , but inspired by the chemist ernst von bibra ( 18061878 ) he completed his studies in chemistry at the university of munich between 18381840 . in 1840", "he was employed at the laboratory of justus liebig at giessen , and became professor at the medical faculty in 1842 , professor of organic chemistry in 1847 , and later professor of general , anorganic and pharmaceutical chemistry .", "he obtained his phd in medicine and surgery in 1838 with a thesis entitled versuche ber die wirkung einiger gifte auf verscheidene thierclassen ", "born on 18 march 1814 in aschaffenburg , germany , scherer studied medicine , chemistry , geology and mineralogy at the university of wrzburg between 1833 and 1836 .", "his work especially concerned quantitative research on blood and urine in pathological conditions . in 1843", "he published his book chemische und mikroskopische untersuchungen zur pathologie angestellt an den kliniken des julius - hospitales zu wrzburg ( chemical and microscopic investigations of pathology carried out at the julius clinic at wrzburg ) ( fig . 1 )", ", in which he described 72 case reports , giving details on clinical course , diagnosis , and results obtained during autopsy and analysis of body fluids ." ], [ "most likely this unfortunate woman had died from a fulminant septic shock caused by group a haemolytic streptococci ( streptococcus pyogenes ) .", "we could think of a haemorrhagic shock and cerebral haemorrhage due to clotting disorders possibly resulting from either acute fatty liver of pregnancy / hellp syndrome , idiopathic thrombocytopenic purpura , thrombotic microangiopathy ( ttp / hus ) or dic .", "louis pasteur ( 18221894 ) found in 1879 that infection with streptococci was the most important cause of puerperal fever ." ], [ "virchow and scherer had previously studied the spleens of patients who died from leukaemia , and were curious if they could find the same results in the blood .", "scherer worked closely with the famous pathologist rudolf virchow ( 18211902 ) on several projects ( fig . 2 ) . in 1851", "the results of this analysis were published the same year in the verhandlungen der physikalisch - medicinischen gesellschaft in wrzburg .", "scherer reached the conclusion that : the blood of this patient contains : ameisensure , essigsure und milchsure , die gleichfalls von mir schon frher als in der milzflssigkeit vorkommend bezeichnet wurden ", "virchow performed an autopsy on a patient who had died from leukaemia and offered scherer blood from this patient for analysis .", "( formic acid , acetic acid , and lactic acid , as also found by me previously in fluids from the spleen ) . \n" ], [ "folwarczny , in 1858 , was the first to demonstrate lactic acid in blood in a living patient .", "gaglio is often erroneously mentioned as the first author to find lactic acid in blood [ 2729 ] .", "scherer 's observations inspired others to conduct further research , primarily in patients with leukaemia [ 1922 ] , but also in patients with other conditions and diseases and in animal experiments with dogs and rabbits .", "poul astrup and john severingshaus mentioned scherer 's 1851 article as first demonstration of lactic acid in blood , but overlooked the 1843 cases and folwarczny 's work . in conclusion , scherer 's 1843 case reports should be cited as the first description of lactic acid in human blood and also as the first demonstration of lactic acid as a pathological finding in septic and haemorrhagic shock ." ] ]

[ [ ", we review recent reports investigating the skin - whitening effect of ginseng and its components and the underlying mechanisms of action , and then discuss their potential as candidates for novel skin - whitening agents .", "several studies have shown that ginsenosides play important roles in the pharmacological effects of ginseng .", "their potential therapeutic effects have been mainly attributed to its immunomodulatory , neuroprotective , antioxidative , antitumor , and hepatoprotective activities .", "thus there is a need for novel skin - whitening agents that are highly effective and tolerable . in this article", "panax ginseng ( ginseng ) has been used traditionally in eastern asia over thousands of years .", ", it has been proved that ginseng extracts actually show a wide range of effects against human diseases ." ], [ "the tyrosinase inhibitory activity of fermented red ginseng extract was more potent compared with red ginseng extract in a test using mushroom tyrosinase .", "it is already known that the pharmacological actions of these ginsenosides have been closely related to their biotransformation by human intestinal bacteria . although the contents of total ginsenosides in red ginseng and fermented red ginseng using lactobacillus brevis were not significantly different , the ginsenoside metabolite content was higher in fermented red ginseng compared to red ginseng .", "most of reports investigating the antimelanogenic effect of ginseng were conducted in vitro used purified tyrosinase or melanocyte cell lines . in melan - a cells treated with ethanol extract of ginseng seeds , melanin content and", "p. ginseng is one of the most widely used medicinal plants in traditional oriental medicine . over thousands of years", "several reports have shown that ginseng extract , powder , or some other constituents could inhibit melanogenesis in vitro and in vivo . table 1 summarizes the direct effects of ginseng and its components on skin color and key enzymes involved in melanogenesis ." ], [ "a cream containing 0.1% ginsenoside f1 ( a metabolite of ginsenoside rg1 ) showed a significant whitening effect on artificially tanned human skin .", "these results suggest that ginsenosides might be able to regulate melanogenesis via their effect on skin immune cells .", "instead , ginsenoside f1 enhanced production of il-13 from human epidermal t cells , and il-13 significantly reduced the mrna expression and protein amount of both tyrosinase and dct resulting in visible brightening of normal human epidermal melanocyte pellets .", "these findings suggest that ginseng extracts and ginsenosides might affect melanogenesis through their anti - inflammatory activities . the effect of ginseng on no production is still questionable .", "however , ginsenoside f1 did not directly inhibit mrna expression of tyrosinase or dct in normal human epidermal melanocytes ." ], [ "recently , several reports have shown that extract , powder , or some constituents of ginseng could inhibit melanogenesis in vivo or in vitro", "although issues surrounding the antimelanogenic activity of ginseng still remain controversial , especially in its effect on the production of proinflammatory cytokines and no , these recent findings suggest that ginseng and its constituents might be potential candidates for novel skin - whitening agents .", ". the underlying mechanisms of the antimelanogenic effect of ginseng or its components included the direct inhibition of key enzymes of melanogenesis ( tyrosinase and dct ) , inhibition of transcription factors ( mitf , nf-b ) or signaling pathways ( protein kinase a pathway and protein kinase c pathway ) involved in melanogenesis , decreasing the production of inducers of melanogenesis ( camp , gm - csf ) , and enhancing production of antimelanogenic factor ( il-13 ) . fig . " ], [] ]

[ [ "the aim of this retrospective investigation was to evaluate ( 1 ) possible associations between tissue kim-1 expression and tubulointerstitial ( tin ) inflammation , atrophy , and fibrosis in different chronic kidney diseases and ( 2 ) possible associations between tissue kim-1 expression and some demographic and laboratory parameters as well as kidney function and proteinuria at the time of biopsy and 6 , 12 , 24 , and 36 months later .", "therefore , that investigation was the basis of this long - term retrospective study , where only kim-1 tissue expression as a predictor of long - term kidney function was examined . ", "kidney injury molecule-1 ( kim-1 ) is a new specific biomarker of proximal tubule injury that can be measured both in urine and kidney tissue samples .", "also , much attention has been paid to its possible pathophysiological role in modulation of tubular damage and repair [ 57 ] . besides a close relationship between tissue kim-1 expression and urinary kim-1 concentration ,", "our previous six - month prospective pilot study showed that kim-1 expression in tissue correlated better with tin features and renal function in different chronic kidney diseases than with urinary kim-1 concentration .", "chronic kidney disease ( ckd ) is associated with a number of comorbidities and prognosis is poor , because many patients experience progression to end - stage renal disease ." ], [ "pathohistological analysis revealed minimal change glomerulonephritis ( mcgn ) in two patients , non - iga gn in nine , iga gn in six , membranous and membranoproliferative gn in seven patients each , focal glomerulosclerosis in eleven , lupus nephritis in ten , and crescentic gn in eight patients .", "the retrospective study included 60 patients ( 27 men ) of mean age 34.42 12.15 years ( range 1859 years ) , who were hospitalized in the clinical center of serbia for kidney biopsy from 2006 to 2009 .", "indications for kidney biopsy were nephrotic syndrome , pathologic proteinuria without nephrotic syndrome , and abnormal urinary sediment ( erythrocyturia and leukocyturia ) in several samples .", "estimated glomerular filtration rate ( egfr ) was calculated with a shortened version of the modification of diet in renal disease ( mdrd ; patients 18 years ) .", "unaffected parts of kidneys from patients with renal cell carcinoma were used as the negative control .", "independent predictors of renal function 6 , 12 , 24 , and 36 months after the kidney biopsy were identified by stepwise multivariant regression analysis ." ], [ "however tissue kim-1 expression was the best predictor of egfr 6 ( p = 0.016 ) along with tin inflammation ( p = 0.016 ) ( table 4 ) . ", "multivariant stepwise regression analysis showed that the best predictor of kidney function at the time of biopsy ( egfr 0 ) was tin inflammation ( p < 0.001 ) , as well as of egfr12 ( p = 0.015 ) , egfr 24 ( p = 0.039 ) , and egfr 36 ( p = 0.012 ) .", "tissue kim-1 expression was significantly induced in all kidney biopsies except in one patient with mcgn .", "tissue kim-1 had a typically apical localization , but it could also be found in the cytoplasm with no apparent affinity for the apical membrane of tubulocytes . kim-1", "positive tubules were located mainly in the tin regions affected by inflammation or fibrosis but were not observed in regions with end - stage fibrosis . kim-1", "figure 2 presents the linear correlation between tin inflammation ( p < 0.001 ) , tissue kim-1 expression ( p < 0.001 ) , and egfr 6 ." ], [ "therefore , we retrospectively examined sixty patients with different kidney diseases in order to evaluate the importance of tissue kim-1 expression in predicting kidney function in the ensuing 36 months after kidney biopsy . in the present study tissue", "although , urine kim-1 content reflected tissue kim-1 expression , tissue kim-1 correlated better with tin inflammation and fibrosis as well as with kidney function at the time of biopsy and 3 and 6 months later .", "in our previous 6-month prospective study , we found higher urine kim-1 concentrations in twenty chronic renal patients than in control subjects and a significant positive correlation between urine kim-1 level and kim-1 expression in tissue .", "it is well known that proteinuria is an ominous biomarker of progressive kidney disease and our study revealed that only proteinuria 6 months after kidney biopsy correlated negatively with kidney function 24 and 36 months after the biopsies and positively with kim-1 expression in tissue .", "the present study revealed a significant negative correlation between tissue kim-1 expression and all estimated gfr at the time of kidney biopsy and 6 , 24 , and 36 months later ." ], [ "although multivariate analysis pointed to tin inflammation , as the best predictor of kidney function at biopsy and 6 , 12 , 24 , and 36 months later , tissue kim-1 expression is one of the best predictor of kidney function 6 months after biopsy , the time when treatment effects are the strongest .", "the present study exposed a strong association between kim-1 tissue staining and tin inflammation and fibrosis but not with tin atrophy .", "therefore , we can speculate that kim-1 has a potential role in the development of interstitial fibrosis and poor treatment responses .", "the major limitation of this investigation is the relatively small number of patients examined but it could be the basis for a larger prospective follow - up study for evaluation of urinary kim-1 concentration and tissue kim-1 expression in patients with various chronic and acute renal diseases ." ] ]

[ [ ", nasal angiofibromas ( nas ) are the most common and nas occurring in the region other than the nose are called as extranasopharyngeal angiofibromas ( ena ) .", "angiofibromas are one such group of tumors arising in this region , which present as swellings . of these", "these range from various slow - growing benign tumors and low - grade malignancies to fast growing high - grade malignancies ." ], [ "a 54-year - old male reported to our department with history of swelling over the right side of face since 5 years .", "the patient reported insidious onset of swelling with a gradual progress to the present size .", "it was observed to be extending anteriorly over the superficial lobe of the parotid gland , with anterior displacement of parotid gland .", "fnac revealed numerous vascular channels with occasional singly scattered and single cluster of plump spindle cells ." ], [ "occurrence of enas , although rare in the maxillofacial region , should be considered in differential diagnosis of swellings in this region .", "based on the clinical findings of location , consistency and borders a differential diagnosis of pleomorphic adenoma , solitary fibrous tumor ( sft ) , low - grade fibrosarcoma , and lipoma was made . as the most common tumors found in the region are parotid tumors , a provisional diagnosis of mixed parotid tumor was made . however , fnac and contrast - enhanced ct scan were in favor of a tumor with vascular component , shifting the differential diagnosis towards tumors with a vascular component presenting as slow - growing , circumscribed firm swellings .", "cellular angiofibroma , usually occurs in the pelviperineal region , which would be an unusual location for the tumors reported herein ; however , cases have been reported to have occurred in the buccal mucosa , raising a diagnostic possibility .", "the differential diagnosis included low - grade vascular lesions , spindle cell neoplasms , comprising of a large range of benign and low - grade malignant soft tissue lesions , including cellular angiofibroma , sft , low - grade fibromyxoid sarcoma ( lgfms ) , low - grade myxofibrosarcoma , myxoid liposarcoma , giant cell angiofibroma ( gca ) , angiomyolipoma , and angiomyofibroblastoma ." ] ]

[ [ "atherosclerotic renal artery hypertension is reported in almost 7% of adults older than 65 years1 ) and is associated with cardiovascular events , and may double risk of mortality2 ) . in the 1990s , radiological angioplasty began to replace surgical revascularization .", "galaria et al . showed that percutaneous and open renal revascularization had equivalent long - term functional outcomes3 ) . over time , the less - invasive procedure became more accessible .", "stent placement might also provide additional force to increase the rates of technical success5 ) and to reduce the rate of restenosis at 6 months after the initial procedure6 ) .", "intervention with stents has become a standard procedure ; in patients with stenosis of the renal artery , placement of a stent is likely to be the initial form of treatment .", "most cases of atherosclerotic renovascular disease ( arvd ) are located in the ostium , and are extensions of calcified aortic plaques4 ) .", "however , there is limited evidence to support revascularization over medical therapy for patients with atherosclerotic renal artery stenosis7 , 8) ." ], [ "a retrospective study of the effects of statins on the progression of arvd has shown that the use of statins reduces the risk of progression and the development of arvd11 ) .", "retrospective studies previously reported that renal artery lesions might progress to severe stenosis and ultimately to renal artery occlusion9 ) .", "another prospective population - based study reported that the progression to significant arvd was observed in only 4.0% during 8 years of follow - up ( annualized rate , 0.5% per year ) , and no case of arvd progressed to occlusion12 ) .", "michael et al . performed a prospective study that reported that the progression of renal artery disease was a frequent occurrence with an annual rate of progression of renal artery lesions reported to be 7%10 ) .", "however , at the time of these studies , statins were being used in fewer patients ." ], [ "renal injury distal to an atherosclerotic renovascular obstruction is due to multiple intrinsic factors producing parenchymal tissue injury ( fig .", "essential hypertension and clinically silent renal artery stenosis often coexist , and essential hypertension also coexists with renovascular hypertension13 ) .", "; these findings suggest that renal parenchymal damage is a major determinant of renal dysfunction and outcome rather than the severity of the renal artery stenosis in arvd16 ) .", "clinical data support dissociation of improved renal artery patency from clinical outcome in patients with atherosclerotic renal artery stenosis ; this may illustrate the effects of irreversible injury on the post stenotic kidney . a prospective clinical study reported by wright et al . showed absence of a correlation between renal artery anatomy and baseline renal function or functional outcome , and a good correlation between renal functional outcome and proteinuria", ". when patients with chronic kidney disease undergo renal angioplasty with / without stent placement , the response with regard to renal function can be negative as well as positive ." ], [ "previously , statin therapy was discussed as a method of altering the natural history of arvd11 ) .", "two large randomized trials of intervention vs. medical therapy showed negative results for the intervention .", "the nature of this disorder suggests that a systemic approach is necessary to provide cardiovascular protection .", "angiotensin - converting enzyme inhibitors and angiotensin receptor blockers effectively reduce blood pressure in patients with renovascular disease . in addition , a population - based cohort study of over 3,500 patients with arvd in canada found that angiotensin inhibitors could cause acute renal toxicity in a small subset of vulnerable patients ; however , they still improved the cardiovascular and renal outcomes in patients with arvd , but at the expense of acute renal toxicity21 ) . recently" ], [ "the results of the coral and the post hoc analysis of astral might provide additional evidence for revascularization .", "intervention should be considered only in patients with arvd and rapidly progressive cardiac or renal dysfunction .", "the aim of treatment for arvd should include the prevention of cardiovascular and/or renal events .", "the results of two recent studies suggest that patients with arvd and stable renal function can be controlled medically .", "treatment of patients with arvd should include consideration of the following factors : age , co - morbidity , blood pressure , renal function , and kidney size ." ] ]

[ [ "the results showed that mice vaccinated with rbcg186 or rbcg486 generally induced higher antigen - specific effector and memory immune responses , as well as protective efficacies compared to mice vaccinated with the parent bcg strain .", "however , the two rbcg strains between themselves , which expressed the chimeric antigen ag856a2 at different levels , induced different antigen - specific ifn- production and comparable number of m. tb - specific cd4 t cells expressing il-2 . and the protective efficacies imposed by the two rbcg strains displayed no significant differences although higher protection was observed in rbcg486 vaccinated mice than that in rbcg186 vaccinated mice .", "we tested their efficacy as vaccines in c57bl/6 mice , comparing immune response and protection against m. tb challenge .", "for the current study , we selected two rbcg strains overexpressing the same chimeric antigen ag856a2 at the maximum difference : rbcg186 and rbcg486 overexpressing the fusion protein under control of the wild - type or the optimized double - mutated fura promoters , respectively .", "we have previously reported the construction of a m. tb fura gene operator / promoter ( pfura)-based differential expression system , from which it is feasible to express target antigens of interest in a modular fashion ." ], [ "briefly , the ag856a2 coding gene , which is a recombinant ag85a gene with 2 copies of esat-6 gene inserted in its acc i site , was amplified from the plasmid template of dna vaccine hg856a and then cloned into mycobacterial differential expression vectors pmfa11 and pmfa41 under control of the prototypical and double - mutated ( mutations : initial codon change from gtg to aug and 6 bp substitution at upstream at - rich region ) fura promoter , respectively .", "eight weeks after vaccination , groups of 6 mice were either sacrificed for assessment of antigen - specific t cell responses in splenocytes or exposed to an aerosol of virulent m. tb h37rv strain to deposit an inhaled dose of 100200 cfu per lung by an inhalation exposure system ( glas - col , usa ) .", "two rbcg strains overexpressing m. tb chimeric immunodominant antigen ag856a2 at different levels were constructed as previously described .", "mice were vaccinated subcutaneously ( s.c . ) with 2 10 colony - forming units ( cfu ) of bcg or rbcgs in 100 l saline .", "five weeks after infection , mice were sacrificed and the mycobacterial burden was determined by plating homogenates of lung , excluding right postcaval lobe , and entire spleen onto middlebrook 7h11 agar plates supplemented with 10% oadc enrichment and a 4-antibiotic mixture ( 40 u / ml polymycin b , 4 g / ml amphotericin , 50 g / ml carbenicillin , 2 g / ml trimethoprim ) that prevents growth of contaminating microorganisms .", "splenocytes ( 2 10 cells / well ) isolated at 8 weeks after immunization were plated in 96-well plates and stimulated with 10 g / ml ppd for 14 h in the presence of 1 g / ml anti - cd28 ( bd biosciences ) and subsequently incubated for an additional 5 h at 37c following the addition of 0.5 l / ml monensin / golgistop ( bd biosciences ) ." ], [ "we have previously developed a novel mycobacterial differential expression system ( pmfa series ) based on the m. tb fura gene operator / promoter ( pfura ) or its derivatives .", "rbcg and bcg - vaccination did not differ in their ability to induce m. tb - specific cd4 t cells producing other combinations of cytokines ( p > 0.05 ) . in accordance , we also observed higher integrated mean fluorescence intensities ( imfi = % frequency mfi ) of il-2 in il-2-producing cd4 t cells , even though it is statistically insignificant ( figure 3(c ) ) . in general , rbcg induced higher antigen - specific cytokine responses as compared to bcg ( figures 2 and 3 ) , and rbcg486 induced higher antigen - specific ifn- response ( figure 2 ) and comparable frequency of m. tb - specific cd4 t cells expressing il-2 ( figure 3 ) .", "eight weeks after vaccination , elispot assay of splenocytes showed that more cells in the rbcg486-vaccinated mice expressed ag85a - specific ifn- compared to those of rbcg186- and bcg - vaccinated mice ( figure 2 , left panel ) .", "also , significantly elevated numbers of splenocytes expressed esat-6-specific ifn- in both rbcg186- and rbcg486-vaccinated mice compared to that of bcg - vaccinated mice ( figure 2 , middle panel ) ." ], [ "another is that the expression levels of such antigens should be optimal enough to elicit effective immune responses . here , we constructed two rbcg strains overexpressing immunodominant chimeric antigen ag856a2 at varying levels depending upon the strengths of the different fura promoters and then compared the cellular immune response and protection in mice induced by these two rbcg strains . one way to improve bcg efficacy", "rbcgs , especially rbcg486 , induced enhanced protection against m. tb infection in this study ( figure 4 ) .", "mfi provides one measure of the quality of the immune response since the cells that are more actively producing cytokine stain more brightly , thus the lower imfi values of cytokines reflected poor quality although mildly higher frequency of polyfunctional cd4 t cells was seen in bcg - vaccinated mice , and this further emphasizes that not only the magnitude but also the quality of vaccine - induced t cells responses are critical to guide development of effective immunization strategies . in addition , higher il-2 secretion , both in the levels of percentage and imfi , were seen in the rbcg486-vaccinated mice than that of bcg group ; this data support our recent findings that il-2 production in the spleens of vaccinated mice after vaccination can predict vaccine efficacy ( kang h , et al .", "consistent with the protective efficacy , the inflammation responses in the infected lungs alleviated greatly in rbcgs - vaccinated mice after infection ( figure 5 ) ." ] ]

[ [ "ct now shows a hypodense body surrounded by secondary granulomatous inflammation pre - operative ( a ) and post - operative ( b ) photographs of 12-year - old boy with a history of penetrating injury by a 2 inch wooden foreign body ( c ) sustained while pond - diving", "a 6-year - old boy presented with a history of penetrating injury to the upper left eyelid sustained while diving head - first into a pond . on presentation , he could only perceive hand movements very close to his face . since a computed tomography ( ct )", "axial ( a ) and coronal ( b ) ct of a 6-year - old boy with a history of penetrating injury shows an empty abscess tract without obvious foreign body .", "the patient subsequently developed septic arthritis of the left hip joint , which was treated separately ." ], [ "axial ( a ) and coronal ( b ) ct of a 6-year - old boy with a history of penetrating injury shows an empty abscess tract without obvious foreign body .", "a 6-year - old boy presented with a history of penetrating injury to the upper left eyelid sustained while diving head - first into a pond . on presentation , he could only perceive hand movements very close to his face . since a computed tomography ( ct )", "the patient subsequently developed septic arthritis of the left hip joint , which was treated separately .", "re - evaluation of the ct scan showed a single hypodense superomedial lesion corresponding to the previously noted sinus tract ." ], [ "a 12-year - old boy presented to an outside hospital with fever , vomiting , and a prominent right eye with a painful , swollen lower lid .", "he had a history of a penetrating injury sustained while diving head - first into a river 12 days previously .", "post - operatively , the patient showed symptomatic improvement with a reduction in proptosis and a visual acuity of 20/30 in the affected eye [ fig . 3 ] .", "repeat ct scan showed a hypodense body surrounded by secondary granulomatous inflammation [ fig . 2 ] ." ], [ "the injuries sustained in the cases we present are troubling since swimming and diving in rivers , ponds , and other natural bodies of water is a common pastime of children in rural areas worldwide .", "penetration injuries by wooden foreign bodies embedded in shallow riverbeds have not been previously recognized as a risk of outdoor swimming and diving . however , in our experience these types of injuries represent a true threat to vision .", ", ophthalmologists attending to cases of penetrating orbital injuries sustained during river and pond diving should maintain a high index of suspicion for a retained wooden orbital foreign body and realize that neither orbital exploration nor imaging may be sufficient for diagnosis ." ] ]

[ [ "the purpose of this review is to provide an evidence - based review and synthesis of the literature regarding the risks of icc when administered for the prevention of postcataract surgery endophthalmitis , thereby informing decisions regarding best practices for cataract surgery .", "the categories of risk to be reviewed are : \n risk of anaphylaxis , especially in penicillin or cephalosporin allergic patientsrisk of toxicity at routine clinical dosesrisk of toxicity at increased doses due to compounding errorsidiosyncratic reactions , including toxic anterior segment syndrome ( tass ) . \n ", "risk of anaphylaxis , especially in penicillin or cephalosporin allergic patients risk of toxicity at routine clinical doses risk of toxicity at increased doses due to compounding errors idiosyncratic reactions , including toxic anterior segment syndrome ( tass ) .", "postcataract surgery endophthalmitis is a relatively uncommon but devastating complication of modern cataract surgery , and there is not complete consensus regarding the ideal practice patterns for prophylaxis ." ], [ "all articles were read in full by both authors with the exception of two that were available only as abstracts .", "the highest level of evidence for each aspect of the intervention was assigned utilizing the oxford center for evidence - based medicine guidelines .", "we performed a systematic review of the existing scientific literature using pubmed and google scholar .", "the key words used were cefuroxime , endophthalmitis and cataract surgeries ." ], [ "there are two case reports of an anaphylactic reaction in penicillin or cephalosporin allergic patients who received icc .", "icc injection during cataract surgery was well tolerated in a prospective study of forty penicillin - allergic patients with a negative preoperative cefuroxime skin test .", "adverse events attributed to cefuroxime compounding errors tass after cataract surgery has been reported in association with the intracameral use of cefuroxime .", "no other studies were found that studied the relationship of cefuroxime to tass , or the effects of specific interventions to reduce the incidence of tass related to cefuroxime .", "the use of icc in patients with penicillin allergy was explored between 2004 and 2012 in a case control registry study ; the control group was the cohort of patients undergoing cataract surgery under a hospital policy of excluding patients with self - reported penicillin allergy ." ], [ "there are two case reports of an anaphylactic reaction in penicillin or cephalosporin allergic patients who received icc .", "icc injection during cataract surgery was well tolerated in a prospective study of forty penicillin - allergic patients with a negative preoperative cefuroxime skin test .", "the number of patients from these centers that had received icc were not reported , preventing an estimation of the incidence of this complication .", "the use of icc in patients with penicillin allergy was explored between 2004 and 2012 in a case control registry study ; the control group was the cohort of patients undergoing cataract surgery under a hospital policy of excluding patients with self - reported penicillin allergy .", "control study comparing the endophthalmitis rates before and after instituting a standard icc regimen ; patients with cefuroxime allergy were excluded , but penicillin - allergic patients received icc ." ], [ "adverse effects that have rarely been reported with routine clinical doses include serous macular detachment , cystoid macular edema ( cme ) , increased central foveal thickness , decreased best - corrected distance visual acuity , anterior chamber inflammation , and vitritis .", "however , a prospective study found that icc at the standard dose of 1 mg/0.1 ml did not have a statistically significant effect on postoperative macular thickness compared with nonadministration of intracameral antibiotic ; although , this study was under - powered to detect rare events .", "the escrs study and other longitudinal cohort studies were not designed to assess safety or adverse events as primary endpoints , but a large number of patients enrolled without a reported increase in these adverse events suggests that they are not associated , are masked by confounding factors , or are exceedingly rare ." ], [ "a lingering concern for some ophthalmologists is the risk of ocular toxicity attributable to inadvertent exposure to elevated concentrations ( typically due to compounding errors ) .", "table 1 summarizes the reported complications related to inadvertent administration of increased concentrations or volumes of cefuroxime . a limitation in assigning risk based on studies such as this is the lack of incidence data ; it is unknown how many patients have received increased doses of icc , and therefore , the rate of these adverse events is unknown .", "the incidence rate of compounding errors for icc is also unknown and is presumably highly dependent on local factors such as the mechanisms of medication preparation and quality control measures .", "high doses of cefuroxime are associated with anterior and posterior segment inflammation with fibrin formation , corneal edema , elevated intraocular pressure , serous macular detachment , cme , hemorrhagic retinal infarction , and reduced rod photoreceptor cell function by electroretinography ." ], [ "tass after cataract surgery has been reported in association with the intracameral use of cefuroxime .", "reported an ongoing cluster of tass cases at a single center , with a resolution of the outbreak after discontinuing icc in favor of intracameral moxifloxacin .", "there was also no reported analysis of cefuroxime concentration to ascertain the potential role of dilution errors or other factors related to preparation .", "as expected , there was no rechallenge in affected patients to determine conclusively if cefuroxime or other factor contributed to tass .", "no other studies were found that studied the relationship of cefuroxime to tass , or the effects of specific interventions to reduce the incidence of tass related to cefuroxime ." ], [ "the authors suggest that a commercial preparation would likely reduce the risk of dilution errors , but commercial preparations of intracameral antibiotic agents may not be financially viable in all health care environments .", "the consensus of the literature from systemic administration of antibiotics is that the risk of cross - reactivity between second - generation cephalosporins ( such as cefuroxime ) and penicillin is very low .", "the efficacy of icc as a prophylaxis for postcataract surgery endophthalmitis has been well established , but concerns regarding the risks of this intervention remain .", "however , many us cataract surgeons believe that intra - cameral antibiotics are unnecessary , based on concerns about the methodology of the escrs and other studies , or that the absolute benefits do not outweigh the risks of dilution errors and toxicity . not surprisingly , a clinical study demonstrated that the mathematical accuracy of a dilution protocol does not ensure dosage accuracy in a real - world clinical scenario .", "implementation of icc should include measures to audit and provide quality assurance of the cefuroxime dilution protocol .", "our review of the literature supports a low rate of anaphylactic reactions , even among penicillin - allergic patients . a postal survey conducted among consultant ophthalmic surgeons working in the national health service ophthalmic departments in england revealed that of 262 consultants , 103 ( 37% ) used cefuroxime in patients allergic to penicillin ." ], [ "our review and synthesis of the literature regarding the risks of cefuroxime therapy support the following recommendations : \n cefuroxime may be used safely in patients with penicillin allergy ( level 2a evidence)efforts to reduce the risk of dilution errors may include the use of a commercially prepared product , or strict quality assurance measures ( level 4 evidence)routine measures to reduce tass should also apply to the use of cefuroxime ( level 5 evidence ) ; even though , there is no proven association . \n ", "cefuroxime may be used safely in patients with penicillin allergy ( level 2a evidence ) efforts to reduce the risk of dilution errors may include the use of a commercially prepared product , or strict quality assurance measures ( level 4 evidence ) routine measures to reduce tass should also apply to the use of cefuroxime ( level 5 evidence ) ; even though , there is no proven association .", "future studies may further define the cost - effectiveness of icc , and continued efforts to reduce the risk attributable to dilution errors are indicated .", "finally , comparative studies of the efficacy and safety of cefuroxime compared to other intracameral antibiotics are needed to help define the optimal endophthalmitis prophylaxis regimen for our patients undergoing cataract surgery .", "since endophthalmitis is a rare event , even a slight increase in the risk of prophylactic therapy may negate the potential benefits .", "the remaining barriers to more widespread adoption include concerns about risks such as anaphylaxis , dilution errors , and toxicity ( especially with noncommercial preparation ) and finally , the additional costs of this therapy .", "half of the risk - benefit equation of icc has been solved to the satisfaction of most clinicians ; the efficacy is clear ." ], [], [] ]

[ [ "medullary thyroid carcinoma ( mtc ) is a rare neoplasm of the calcitonin - secreting thyroid cells and accounts for 510% of all thyroid cancers .", "it seems , two of these ret snps ( g691s and s904s ) may modify the age at onset of mtc tumor in family members ( 5 , 15 ) but fabienne lesueur et al . have rejected this hypothesis ( 7 ) . in the present study , we report the frequency of g691s / s904s haplotype in iranian mtc patients and their relatives .", "recent studies have found g691s in exon11 , s904s single neucleotide polymorphisms in exon15 of the ret pathway to be associated with the risk of developing sporadic mtc ( smtc ) ( 7 ) .", "thyroid cancer is the most common endocrine neoplasia and accounts for 1% of all human cancers ( 1 ) ." ], [ "over the last ten years , one hundred ninety mtc patients , were referred to cellular and molecular research center of shahid beheshti university of medical sciences in order to ret genetic screening .", "a questionnaire was used to collect information about age , sex , and history of neoplasia . if any mutation was found in patients , their first - degree relatives were invited for screening .", "for identification of ret variant 691 ( rs1799939 , codon 691 of exon 11 , ggt > agt , gly > ser ) and 904 ( rs1800863 , codon 904 of exon 15 , tcc > tcg , ser > ser , ) , dna samples were amplified using the polymerase chain reaction ( pcr ) and the specific oligonucleotides primers ( table1 ) .", "121 first - degree relatives from 31 index cases comprised 57 males and 64 females , with meansd age 29.0916.34 years .", "genomic dna was extracted from peripheral blood leucocytes using standard salting out / proteinase k method and stored at -20c .", "the amplimers were confirmed for the presence or absence of mutations by direct dna sequencing method ( abi 3100 genetic analyzer and big dye terminator v3.1 cycle sequencing kit , applied biosystems , california , usa ) . to detect the ret mutations and snps , sequences were analyzed by chromas 2.33 software and were also compared with the reference ret gene sequence using web based tool ncbi blast .", "sequences of oligonucleotide primers used for pcr amplification of exons 11 , 15 of the ret pcr reaction for exon 15 was constituted initial denaturation at 94c for 3min and , followed by 35 cycles of 94c for 30s , annealing starting at 56c for 1min , 72c for 1min , and a final extension at 72c for 10min ." ], [ "over the last ten years , one hundred ninety mtc patients , were referred to cellular and molecular research center of shahid beheshti university of medical sciences in order to ret genetic screening .", "a questionnaire was used to collect information about age , sex , and history of neoplasia . if any mutation was found in patients , their first - degree relatives were invited for screening .", "121 first - degree relatives from 31 index cases comprised 57 males and 64 females , with meansd age 29.0916.34 years .", "this study has been approved by the ethics committee of cellular and molecular research center , research institute for endocrine sciences , shahid beheshti university of medical sciences ." ], [ "genomic dna was extracted from peripheral blood leucocytes using standard salting out / proteinase k method and stored at -20c ." ], [ "for identification of ret variant 691 ( rs1799939 , codon 691 of exon 11 , ggt > agt , gly > ser ) and 904 ( rs1800863 , codon 904 of exon 15 , tcc > tcg , ser > ser , ) , dna samples were amplified using the polymerase chain reaction ( pcr ) and the specific oligonucleotides primers ( table1 ) .", "sequences of oligonucleotide primers used for pcr amplification of exons 11 , 15 of the ret pcr reaction for exon 15 was constituted initial denaturation at 94c for 3min and , followed by 35 cycles of 94c for 30s , annealing starting at 56c for 1min , 72c for 1min , and a final extension at 72c for 10min .", "the amplimers were confirmed for the presence or absence of mutations by direct dna sequencing method ( abi 3100 genetic analyzer and big dye terminator v3.1 cycle sequencing kit , applied biosystems , california , usa ) .", "the exon11 running profile was constituted initial denaturation at 96 c for 1min and , followed by 30 cycles with 96 c for 45s , annealing at 60 c for 1min dependent on the primer sequences , and extension at 72c for 45s , with a final extension at 72 c for 10 min ." ], [ "to detect the ret mutations and snps , sequences were analyzed by chromas 2.33 software and were also compared with the reference ret gene sequence using web based tool ncbi blast ." ], [ "the frequency of g691s and s904s variants in the population the frequency distribution of g691s and s904s variants among mtc patients and their relatives", "we analyzed germline dna mutations of ret gene in 181 iranian mtc patients and 112 relatives , with a total of 293 members .", "the analysis of g691s / s904s ret gene haplotype showed that 104 of 181 ( 57.45% ) mtc patients and 55 of 112 ( 49.1% ) relatives had this haplotype .", "there was not significant correlation between age of diagnosis and the presence of g691s / s904s haplotype ." ], [ "in this study , we found two variants of ret gene , g691s ( ggt > agt , exon 11 , rs1799939 ) and s904s ( tcc > tcg , exon 15 , rs1800863 ) that are cosegregated together as a haplotype , suggesting that these polymorphisms are in linkage disequilibrium with each other .", "overall , these data strengthen the potential role of the ret - g691s polymorphism in mtc .", "two studies have shown that this haplotype may modify the age at onset of mtc tumor in family members ( 5 , 15 ) , however , this hypothesis is controversial ( 7 ) . the ret - g691s polymorphism has been suggested as a genetic modifier in men2a ( 15 ) .", "some studies support our data that both g691s and s904s snps are associated with sporadic mtc and men2a ( 5 , 7 , 18 ) ." ], [ "this data showed the frequency of g691s / s904s haplotype among iranian mtc patients and their family , for the first time .", "even though g691s / s904s haplotype are not considered as oncogenic mutations at this time , its functional role should be investigated .", "further researches on this issue can contribute toward clarifying the prevalence of this haplotype and its probable modifying effect on the phenotypic characteristic of mtc ." ], [ "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 ." ] ]

[ [ "after initial establishment and derivation of human embryonic stem cells ( hesc ; thomson et al . , 1998 ; reubinoff et al . , 2000 )", "steps have been taken ; initially , hesc were grown on irradiated mouse feeders , later human fore - skin fibroblast were used ( hovatta et al . , 2003 ) , now we can use gmp compliant coating substrates specially designed for hesc growth ( rodin et al . ,", "steps were also taken for the generation defined xeno - free gmp compliant medium for derivation and for expansion ( ludwig et al . , 2006 ;", "the culture systems currently encounter the problem of suboptimal quality of xeno - free culture constituents . thus strategies are needed to overcome this difficulty ( sidhu et al . , 2008 ) .", "first the infection free status of the donors has to be addressed , in europe couples are tested before any fertility treatment is offered , but the cells themselves have to be tested , too ( hovatta , 2011 ) .", "second , optimized good manufacturing practice ( gmp ) compliant systems must be implemented for derivation , scaling - up , banking of cells , and their corresponding quality assurance controls ( unger et al . , 2008 ; ausubel et al . , 2011 ) ." ], [ "it is also important to address the safety of long - term culture , as shown recently ; the occurrence of chromosomal rearrangements in long - term culture of 125 hesc and 11 hipsc ( amps et al . , 2011 ) .", "the potential of somatic cell reprogramming via expression of specific transcription factors and thus the generation of hesc induced pluripotent stem cells ( hipsc ; takahashi and yamanaka , 2006 ; takahashi et al . , 2007 ) has the advantage that they could be generated from the recipient patients own cells .", "for successful reprogramming of somatic cells , many epigenetic changes must occur in an adequate manner .", "hence fast reactivity is already present in healthy individuals for controlling any rapidly amplifying cells ( dhodapkar et al . , 2010 ) .", "dna methylation changes during reprogramming must occur in important developmental and oncogenic regions , which increases the oncogenic risk of the reprogrammed cells ( doi et al .", "un - silenced expression of the reprogramming factor oct-4 might then cause undesired immunoreactivity on the transplanted cells ." ], [ "in addition to this initial report regarding the neural lineage , differentiation protocols for other cell types are needed . even if transplantation in animal models is successful , it is important to generate safety strategies before clinical trials to appropriately remove undifferentiated psc from their psc derived therapeutic cells .", "there is a consensus that undifferentiated pluripotent stem cells ( psc ) will not be used directly in any clinical transplantations procedure , but instead their psc derived differentiated cells recently , results using hesc derived dopaminergic neurons have shown correct phenotype differentiation and grafting potential given by no tumor formation , maintenance of the grafted cells , and functional recovery in parkinsonian animal models in mice , rats , and monkeys ( kriks et al . , 2011 ) .", "the protocols designed for this cell replacement assay were optimal regarding the phenotype , quantity of the cells , functionality , and immunological properties .", "integration of transplanted cells was achieved when single cells were transplanted , the use of proper biodegradable scaffolds must also be considered .", "alternatively , strategies such as removal of undifferentiated cells using antibodies might be safer ( tang et al . , 2011 ) .", ") might have controversial outcomes under clinical trials given their safety ( yi et al ." ], [ "as discussed earlier , an optimal engraftment and cell replacement strategy should account for a minimal immune reaction in the recipient .", "immunoreactivity toward the graft is mainly caused by t cell response toward unmatched major histocompatibility complex ( mhc ) ; in humans called human leukocyte antigen ( hla ) .", "this immune reaction occurs because the immune system of the recipient recognizes the grafted cells as foreign material or mismatched cellular components and thus generates a cascade of events that ultimately results in destruction and rejection of the grafted cells .", "careful selection of culture conditions , both for the undifferentiated hesc and for their differentiated derivatives is needed .", "these culture conditions must be carefully analyzed and scientific consensus must be achieved in order to raise current methodologies ." ], [ "challenges with the immunoreactivity of the transplantable cells could be addressed by rigorous immunosuppressive treatments . unfortunately , this is not desired , since there is a clear correlation between the length and intensity of exposure to immunosuppressive therapy and post - transplant risk of malignancy and tumor aggressiveness ( gutierrez - dalmau and campistol , 2007 ) .", ". this immunosuppression strategy will generate tolerance to the grafted cells and thus increase graft survival ; initial pharmaceutical agents have been developed and pending clinical applications to the fda are to give in the near future more information .", "an interesting solution is costimulatory blockage of t cell response ( grinnemo et al . , 2006 , 2008 ; swijnenburg et al . , 2008 ; pearl et al . , 2011" ], [ "these profiles can then be used in combination with methodologies focused at monitoring the status of the transplanted cells . in a given scenario that undesired cells persist in the transplant , adequate counteracting actions have immediately to be taken .", "next , the management of immunosuppression schemes must aim to a minimal time influencing the immunological status of the recipient . from all the information obtained ,", "such information has to be well protected so that it will not be lost in any given situation .", "the possibility of using hipsc derived therapeutic cells in cell replacement therapies requires still long - term studies in non - human animal models addressing the questions of immunogenicity , epigenetic and genetic stability of these cells , and the optimized differentiation of the cells .", "the importance of profiling immunogenic markers as part of the stem - ness characterization and profiling of cells allocated in stem cell banks must be consider .", "adequate culture conditions , supporting correct immunogenicity of the cells under a transplantation assay is also required .", "in this mini - review we highlighted the most important areas to be considered under a cell replacement therapy ." ], [ "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 ." ] ]

[ [ "to report two cases of femtosecond laser - assisted small incision deep lamellar endothelial keratoplasty ( dlek ) for patients with corneal endothelial decompensation by fuchs dystrophy and glaucoma" ], [ "irvine , ca ) with 15 khz of repetition rate , was used for a 9.5 mm diameter by 400 m thickness donor corneal lamellar dissection ." ], [ "in case 1 , the graft was clear and compact without interface haze , orbscan showed smooth and regular corneal surface , specular microscopy was unremarkable without sign of corneal endothelial damage , and optical coherence tomography showed uniform graft well attached to recipient stroma with minimal interface reflection at 2 months postoperation . in case 2 , the graft was clear and compact with minimal interface haze at 1 month postoperation .", "femtosecond laser - assisted small incision dlek was safe and technically feasible in our cases ; however , further evaluation is required to determine long - term effects ." ], [ "3 ) . femtosecond laser - assisted small incision dlek was performed in the left eye of a 94-year - old female with corneal edema , glaucoma , and dry type age - related macular degeneration ( armd ) .", "femtosecond laser - assisted small incision dlek was performed in the right eye of a 73-year - old male with fuchs dystrophy ( fig .", "this was to assure a donor corneal thickness between 500 and 565 m , in order to approximate a graft thickness of 100 to 165 m . the femtosecond laser ( intralase ; intralase corp . , irvine , ca ) was then used to create a corneal flap of 9.5 mm diameter and 400 m thickness .", "after laser application , stromal and side cut adhesions were fully released and the anterior corneal flap was fully lifted .", "optical coherence tomography ( oct ) findings showed compact and uniform graft , well attached to the recipient stromal bed with minimal interface reflection ( fig .", "corneal topography showed smooth and regular corneal surface and specular microscopy was unremarkable without sign of corneal endothelial damage ( fig ." ], [ "this was to assure a donor corneal thickness between 500 and 565 m , in order to approximate a graft thickness of 100 to 165 m . the femtosecond laser ( intralase ; intralase corp . , irvine , ca ) was then used to create a corneal flap of 9.5 mm diameter and 400 m thickness .", "the folded donor disc was opened and attached to the recipient stromal bed by injecting air underneath the graft .", "the donor corneoscleral button was then placed in medium and transported to the operating room , where the anterior flap was excised with scissors and an 8.0 mm trephine ( katena products , inc . , denville , nj ) was used to punch out the posterior donor corneoscleral button . the recipient corneal lamellar dissection and graft transplantation", "the donor corneoscleral button was mounted in a dedicated artificial anterior chamber ( bausch & lomb , st .", "the excised posterior recipient disc was removed from the lamellar pocket and spread over recipient corneal epithelium to verify size .", "was performed as previously described.5,6 briefly , following an 8.0 mm epithelial marking and 5.0 mm scleral incision , a deep lamellar pocket was created to approximately 75 - 85% of corneal thickness ." ], [ "femtosecond laser - assisted small incision dlek was performed in the right eye of a 73-year - old male with fuchs dystrophy ( fig .", "corneal topography showed smooth and regular corneal surface and specular microscopy was unremarkable without sign of corneal endothelial damage ( fig .", "2b and c ) . optical coherence tomography ( oct ) findings showed compact and uniform graft , well attached to the recipient stromal bed with minimal interface reflection ( fig .", "ucva and bscva was 20/150 and 20/100 respectively and manifest refraction was + 2.75 -1.0050 .", "preoperative uncorrected visual acuity ( ucva ) and best spectacle corrected visual acuity ( bscva ) was 20/100 and 20/80 respectively and manifest refraction was + 0.75 -1.7530 .", "donor corneoscleral button lamellar dissection was performed using intralase femtosecond laser ( intralase corp . ) , set at a depth of 400 m and flap diameter of 9.5 mm ." ], [ "femtosecond laser - assisted small incision dlek was performed in the left eye of a 94-year - old female with corneal edema , glaucoma , and dry type age - related macular degeneration ( armd ) .", "her preoperative ucva and bscva was 20/400 and 20/200 respectively and her manifest refraction was -1.00 -1.7595 .", "postoperation , the graft was clear and compact , iop was 19 mmhg , and ucva was 20/400 .", "at one month , the graft was clear and compact with minimal interface haze ; iop measured 31 mmhg .", "we were not able to perform further examinations due to follow - up loss at two months postoperation .", "iop was well controlled with topical medication ( cosopt ; merck & co. , whitehouse station , nj ) .", "anti - glaucoma medication ( alphagan ; allergan , irvine , ca ) was added and topical steroid tapered ." ], [ "recently , the femtosecond laser was introduced in refractive surgery fields for lasik flap creation . according to recent papers", "however , these cases demonstrate graft uniformity , technical feasibility , and potential application of femtosecond laser in lamellar keratoplasty .", "following we describe small incision dlek by femtosecond laser for donor corneal lamellar dissection . before performing femtosecond laser - assisted donor lamellar dissection , we measured donor corneal thickness by ultrasound pachymetry .", "it is not only time consuming , but also has the potential risk of corneal perforation.8 moreover , even with uncomplicated dissection , the plane may not be smooth and uniform , which results in interface scarring and reduction in potential best vision.6,7 in a recent paper , azar and coauthors described microkeratome - assisted posterior keratoplasty.16 given that laser - assisted in situ keratomileusis ( lasik ) shows almost no interface haze on the cornea,17,18 this technique 's potential advantage is less interface scarring than manual dissection .", ", it demonstrated improved flap uniformity and better flap thickness predictability than mechanical microkeratomes.9 - 12,19 similar to the microkeratome , femtosecond laser technology has evolved .", "however , microkeratome - assisted lamellar dissection does have the risk of corneal perforation in deeper dissection ." ] ]

[ [ "dipeptidyl peptidase-4 inhibitors ( dpp4i ) have been recently introduced in clinic as a new oral hypoglycemic agent .", "therefore , in this study , we investigated the effects of pacap on kidney cells and the mechanisms of how pacap decreases the expression of inflammatory cytokines .", "these results indicated that pacap has protective roles in the kidney ; however , it is unknown which cell types pacap affects and how it decreases cytokine expression .", "dn is not only the leading cause of end - stage kidney disease but also a significant risk factor for cardiovascular disease .", "although the treatment for dn is important to improve patients ' prognosis , the current treatment remains suboptimal and therefore novel approaches for dn are urgently needed .", "in addition to the reduction in the blood glucose level , it has been reported that dpp4i possesses properties and can protect the cardiovascular system , kidney , liver , and bone from injuries ." ], [ "the protein was transferred to pvdf membranes ( immobilon - p transfer membrane ) ; the membranes were blocked for 1 h at room temperature to block the nonspecific binding of the protein and incubated for 18 h at 4c with primary antibodies .", "the glomeruli were isolated by dynabeads ( invitrogen , norway ) perfusion technique as previously described .", "to correct for potential variation in transfection efficiency , prl - tk vector ( promega ) was cotransfected in all experiments .", "after washing for several times , the antibody binding sites were visualized using an ecl western blotting detection system ( ge healthcare : rpn2106 ) .", "the primary antibodies that were used were as follows : anti - vpac1 antibody ( 1 : 200 dilution , santa cruz : sc-30019 ) , anti - phospho - p44/42 mapk ( extracellular signal - regulated kinase ( erk1/2 ) ) antibody ( 1 : 1000 dilution , cell - signaling : number 9106 ) , and anti - p44/42 mapk ( erk1/2 ) antibody ( 1 : 1000 dilution , cell - signaling : number 9102 ) .", "the cells that had accumulated nf-b in their nuclei were counted at 10 randomly selected areas ." ], [ "therefore , we examined the effects of pacap on the nf-b transnuclear localization and phosphorylation of erk .", "then , we examined the effect of h89 , an inhibitor of the pka signaling pathway , and of u-73122 , a known plc inhibitor , on the increased levels of mcp-1 .", "figures 6 and 7 showed that , in the presence of lps , nf-b transnuclear localization and phosphorylation of erk were significantly increased and pacap significantly ameliorated both .", "these results indicated that pacap suppressed the expression of mcp-1 through the camp / pka - dependent signaling pathway .", "these results indicated that pacap primarily sent signals to glomerular podocytes , especially activating the camp / pka pathway in the podocytes ." ], [ "pacap , a substrate for dpp4 , activated the camp / pka signaling pathway in cultured podocytes and inhibited the expression of inflammatory cytokines , which were induced by lps / tlr4 signaling .", "in the present study , we reported that vpac1 , a pacap receptor , was exclusively expressed in glomerular podocytes .", ", we demonstrated that pacap had anti - inflammatory effects on podocytes , leading to an assumption that dpp4i protects kidney from injuries through the stabilization of pacap .", "tlr , a sensor in the innate immune system , has been highlighted in the development of dn .", "thus , it is intriguing that pacap may give signals to podocytes . because it has been reported that pacap has anti - inflammatory effects in a wide variety of disease models , we focused on the anti - inflammatory effects of pacap on cultured podocytes . among the inflammatory signals ,", "the kidney is injured by a wide variety of insults leading to chronic kidney diseases ( ckd ) . among ckd" ], [ "in conclusion , we have shown that pacap has anti - inflammatory effects on glomerular podocytes . because treatment options for dn are still limited , pacap may be a good candidate for prevention / attenuation of dn . however , more study is definitely needed to prove this possibility ." ] ]

[ [ "dancing eye syndrome , is a serious , rare , and often chronic neurological disorder .", "international consensus has described three of the following four diagnostic criteria should be present to describe the typical syndrome : ( 1 ) opsoclonus , ( 2 ) myoclonus / ataxia , ( 3 ) behavioral change and/or sleep disturbance , and ( 4 ) nb . we present a retrospective study of five children presented to the pediatric oncology clinic ( poc ) of all india institute of medical sciences ( aiims ) with a diagnosis of opsoclonus - myoclonus syndrome ( oms ) .", "the diagnosis of omas may be difficult in some patients and should be considered even when only some of the features are present .", "opsoclonus - myoclonus - ataxia syndrome ( omas ) , also called kinsbourne syndrome or ", "although most patients with nb and omas have good survival rates , 70%80% of these children will have long - term neurologic sequelae . in pediatric age , omas may be associated with neuroblastic tumors ( nb , ganglioneuroblastoma , or ganglioneuroma ) .", "the objective of this study was to describe the clinical profile and outcome of this disorder ." ], [ "the diagnosis of opsoclonus - myoclonus was based on a constellation of any three of the four clinical features : opsoclonus , myoclonus , ataxia , and encephalopathy / irritability / behavioral change / sleep disturbance .", "the medical records of all children presented to poc , department of pediatrics , aiims , with a diagnosis of opsoclonus - myoclonus were retrieved and reviewed .", "outcome was assessed on follow - up by direct assessment and by telephonic communication ( in one patient ) ." ], [ "of the six cases with paraneoplastic oms , four cases were treated with surgical resection of tumor and chemotherapy . in one child (", "a total of six patients with a diagnosis of opsoclonus - myoclonus were admitted over 4-year period [ table 1 ] .", "clinical profile and outcome in six children with opsoclonus - myoclonus syndrome the reasons for the delay in diagnosis included misdiagnosis by peripheral physicians and delayed referral to our center .", "one child ( case 3 ) died of febrile encephalopathy ( not related to disease ) ." ], [ "other names for oms include omas , paraneoplastic opsoclonus - myoclonus ataxia , kinsbourne syndrome , myoclonic encephalopathy of infants , dancing eyes - dancing feet syndrome , and dancing eyes syndrome . in our study , all six children were between 2 and 3 years of age , similar to the trend seen in other reports , in which oma was uncommonly diagnosed before 1 year of age . one possible explanation for the low incidence in infancy may be due to ability to develop specific antibodies is less in younger infants .", "oms , the most frequent paraneoplastic syndrome in pediatric age group , remains a challenge for treatment .", "we observed , alike to previously published studies , a similar median age at clinical presentation , acute / subacute onset of presentation , association of nb , and response to immunomodulator therapy .", "we have seen a good therapeutic response with immunomodulators , including acth , ivig , and corticosteroids .", "patients with nb and oma have been reported to have excellent survival . according to children 's cancer group data ," ], [ "oms is a rare disorder , but it affects children more frequently than adults and exhibits an excellent rate of survival . screening for an occult nb is necessary in all children with this syndrome .", "oms ( paraneoplastic ) had a good outcome without significant neurological deficits in our experience ." ], [], [] ]

[ [ ". if antagonism between the two classes of drugs is really the biological basis for the aforementioned negative experience , then an optimal combination of tkis and chemotherapy should be in an intermittent , rather than a continuous schedule .", "this brief report presents a single - institution experience on intermittent chemotherapy and tki in a small series of patients with advanced adenocarcinoma of the lung .", "to the surprise and deep disappointment of all involved in the treatment of lung cancer , several large trials did not demonstrate any benefit of tyrosine kinase inhibitors ( tkis ) as an addition to chemotherapy [ 13 ] .", ", we believe that the cells of tumors sensitive to tkis are pushed into the g-0 phase of the cell cycle and therefore become resistant to cytotoxic drugs", "our hypothesis was that intermittent treatment would lead to superior time to progression , when compared to experience with chemotherapy alone .", "gefitinib and erlotinib met all three standard criteria for inclusion in a combination with chemotherapy : activity as monotherapy , different mechanism of action , and different toxicity .", "basic and clinical research then focused on mutations of the gene for epidermal growth factor receptor ( egfr ) as a predictive factor for response to monotherapy with tkis and to development of new compounds with broader and/or irreversible inhibition . the biological basis for the negative experience with combined treatment" ], [ "after standard chemotherapy for metastatic nonsmall cell carcinoma , the expected ttp is 5 months .", "the first evaluation of response was done during the third cycle of intermittent therapy , with confirmation of response during the fifth cycle .", "the number of cycles depended on tolerance to cisplatin - based chemotherapy and was determined individually . immediately after the last cycle", "the size of this single - arm nonrandomised trial of intermittent therapy was based on the assumption of 9 months as the median time to progression ( ttp ) .", "pet - ct scanning has been available and included in the initial diagnostics and in followup .", "patients eligible for the trial were chemonave with microscopically confirmed adenocarcinoma of the lung , had stage iii b ( wet ) or iv according to uicc - tnm classification ( 6th edition ) , had smoking history of less than 10 packs in years , had an ecog performance status 0 or 1 , and had adequate parameters of hematological , liver , and renal function to receive cisplatin - based chemotherapy . in the absence of neurological symptoms , patients with brain metastases were eligible and were treated with brain irradiation only in case of intracranial progression .", "the treatment started with four cycles of intermittent chemotherapy and erlotinib according to the following schedule : day 1 : gemcitabine 1250 mg / m in 30-minute infusion , day 2 : cisplatin 75 mg / m , with appropriate hydration and antiemetics , day 4 : gemcitabine 1250 mg / m in 30-minute infusion , days 515 : erlotinib 150 mg daily p.o ." ], [ "for patients without egfr mutations , ttp was 5 months , and os was 7 months ( table 2 and figures 3 and 4 ) .", "for the whole group , median time to progression ( ttp ) was 13.4 months , and median overall survival ( os ) was 23 months .", "all patients are evaluable for response , and no patient has been lost to followup . for the whole group of 24 patients , complete remission ( cr ) was seen in 5 pts ; partial remission ( pr ) in 9 pts ( response rate 58% ) , minimal response or stable disease ( sd ) in 8 pts , and progression in 2 pts . a clear and statistically significant ( p <", "one patient was later found to have metastatic carcinoma of the pancreas rather than primary lung cancer and was excluded from all further analyses . with 12 patients each ,", ".05 ) correlation was seen between the presence of activating egfr mutations and response . among the 8 patients who were positive for egfr gene - activating mutations , 4 complete and" ], [ "this clinical trial was launched at a time when routine testing for egfr gene - activating mutations was not yet available .", "while the number of patients in our trial is small and any definitive conclusion would be premature , we nevertheless believe that further research of intermittent therapy for patients positive for egfr gene - activating mutations is warranted . a randomised trial comparing first - line tki as monotherapy to the intermittent schedule should clarify the real value of this new approach .", "selection of patients for a combination of chemotherapy and erlotinib was made on the basis of classical histopathology ( adenocarcinoma ) and smoking status . ", "looking at the whole series of patients , we can conclude that intermittent chemotherapy and erlotinib is a treatment of very low toxicity .", "since continuing a trial with the same selection criteria and without considering the status of egfr gene activating mutations was not justified , the research group made a decision to close the trial and analyse the experience . in order to get a longer interval for intermittent erlotinib , gemcitabine was given on days 1 and 4 of the cycle . when compared to the standard day 1 and day 8 schedule", "two other groups recently reported promising experience with intermittent chemotherapy and tkis . in a trial from the usa ," ], [] ]

[ [ "fpv , feline parvovirus ; mev , mink enteritis virus ; cpv , canine parvovirus ; rapv , raccoon parvovirus ; rpv1 , rat parvovirus 1 ; mvmp , minute virus of mice , prototype ; hapv , hamster parvovirus ; ppv - kr , porcine parvovirus kresse ; simian bupv , simian bufavirus ; bupv1 , bufavirus 1 ; bupv2 , bufavirus 2 ; amdv , aleutian mink disease virus ; gfav , gray fox amdovirus ; b19v - lali , human parvovirus b19-lali .", "we used a nested pcr targeting ns1 to determine the prevalence of this virus in the 180 tunisia diarrhea samples .", "we named this virus tusavirus 1 for tunisian stool - associated parvovirus . \n a nearly complete 4,424-bp genome ( tusavirus 1 , genbank accession no .", "vp1 and vp2 shared identities of 39% and 37% , respectively , to those of kilham rat parvovirus ." ], [ "we detected fecal shedding of a previously uncharacterized parvovirus in a child with unexplained diarrhea .", "the 18-month - old girl showed twice daily liquid and greenish feces over 3 days but no fever ( 37.4c ) , vomiting , or dehydration . to identify other viral infections in this patient ,", "no other mammalian virus was detected , suggesting a possible role for tusavirus 1 in this patient s gastrointestinal illness , although the lack of testing for pathogenic bacteria and parasites does not enable us to exclude these alternative explanations .", "control pcr studies of unexplained diarrhea and serologic tests , are needed to define the prevalence and disease association of this new parvovirus species in different age groups and populations ." ] ]

[ [ "mpi was originally derived from data collected from 1253 patients with peritonitis treated between 1963 and 1979 and was developed by discriminant analysis of 17 possible risk factors , by wacha , 8 of these were of prognostic relevance and was currently employed widely for predicting mortality from peritonitis .", "it may be regarded as the localized equivalent of the systemic inflammatory response seen after any trigger of inflammation , which recently has been described as systemic inflammatory response syndrome .", "the complex nature of surgical infections , the multifaceted aspects of treatment , and the complexity of intensive care unit ( icu ) support makes evaluation of new diagnostic and therapeutic advances in this field very difficult .", "the information is collected at the time of admission and first laparotomy [ tables 1 and 2 ] .", "mannheim peritonitis index ( mpi ) is a scoring system used in peritonitis which is simple and cost - effective ." ], [ "the study was done in fifty patients with peritonitis who presented at government medical college , amritsar , and were operated after taking informed consent .", "patients were followed up for the final outcome , and results were analyzed with the score of mpi ." ], [ "mortality and mannheim peritonitis index score morbidity and mannheim peritonitis index score for a score of 27 , the sensitivity was 66.67% , specificity was 100% , and positive predictive value for mortality is 100% at an accuracy of 94% [ p < 0.001 , table 4 ] . sensitivity and specificity of mannheim peritonitis index score 27", "in this study , majority of patients belonged to age group of 21 - 50 years .", "summary of risk factors of mannheim peritonitis index and mortality the study showed that mortality steadily increases with increase in mpi score showing statistically significant results [ p < 0.001 , figure 2 ] ." ], [ "this study proves that mpi scoring system is a simple and effective tool for assessing the morbidity and mortality in patients with peritonitis with statistically significant results .", "duration of pain > 24 h , organ failure on admission , female sex , and feculent exudate were found to be independently significant factors in predicting the mortality .", "peritonitis remains a hot spot for the surgeons despite advancements in surgical technique and intensive care treatment .", "it may also depend on exact recognition of the seriousness of the disease , an accurate assessment , and classification of the patient 's risks . despite the surgical treatment and sophisticated icus , last generation antibiotics and a better understanding of pathophysiology of peritonitis mortality rate are still very high , i.e. , 1020% even in good institutions .", "mpi can be used to define risk groups as well as predict outcome in patients with peritonitis , as indicated by various studies .", "various factors such as age , sex , duration , site of perforation , extent of peritonitis , and delay in surgical intervention are associated with morbidity and mortality ." ], [ "such patients should be monitored closely with close attention to be given to support the vital systems . to conclude , mpi is a simple and reliable tool in predicting the outcome in cases of peritonitis ." ], [], [] ]

[ [ "maximum - likelihood phylogenetic tree of dengue virus type 1 , including isolates from key west , florida , usa , and representative isolates from 5 genotypes with global geographic distribution .", "during 20092010 , serum samples from patients with suspected dengue were received by the fdoh for dengue diagnostic testing ; the samples came from 16 of florida s 67counties .", "this phylogenetic analysis showed that all the florida denv-1 isolates belong to the american african genotype ( genotype v ) ( 12,13 ) together with other viruses isolated throughout the americas ( figure 1 ) . " ], [ "collectively , these findings indicate that endemic denv-1 was transmitted in key west over a period of > 2 years .", "the epidemiologic and phylogenetic evidence suggests that the 2010 cases appeared to be a continuation of the 2009 outbreak . unlike cases along the texas mexico border ( 14 ) ,", "in addition , denv-1 was detected in a blood donation from the monroe county in 2010 , further supporting local transmission of denv ( 7 ) .", "conversely , the scattered and separate phylogenetic positioning of virus strains from patients with travel - associated cases from other florida counties indicates a different origin from the majority of key west isolates ." ], [ "table showing the dengue virus type 1 ( denv-1 ) envelope gene reverse transcription pcr and another showing denv-1 strains used in a study of the genetic relatedness of dengue viruses in key west , florida , usa , 20092010 ." ] ]

[ [ "previous studies used confocal microscopy to measure epithelial thickness , but the number of points measured was limited and the measurement was time consuming . very high - frequency digital ultrasound was also used to map corneal epithelium and stromal thickness [ 4 , 5 ] . however , because ultrasound can not pass through air , this technique required immersing the cornea in a fluid bath .", "direct measurement of epithelial thickness change may help to better understand corneal epithelial remodeling after lasik and improve lasik ablation patterns with less regression and surgery - induced aberrations .", "though both confocal microscopy and very high - frequency digital ultrasound are feasible in measuring corneal epithelial thickness , they are not often used in routine lasik because they required touching the cornea .", ", we demonstrated that a commercial fourier - domain oct could automatically map the corneal epithelial thickness with good repeatability . in this study , we use this algorithm to map corneal epithelial thickness for eyes before and after myopic lasik surgeries .", "we estimated the extent of the epithelial remodeling after lasik with a mathematical model in a previous study .", "instead , we constructed the model constants based on regression in manifest refraction after lasik .", "corneal epithelium is able to alter its thickness to mask subepithelial stromal irregularities and maintain a smooth anterior surface of the eye ." ], [ "correlation of lasik - induced change in epithelial thickness with the amount of spherical equivalent of lasik correction was investigated . a smoothing constant ", "the cutoff frequency of the butterworth filter was the reciprocal of the smoothing constant . if we simulated the ablation profile for 1 d special myopic lasik using munnerlyn algorithm and assumed the optical zone diameter to be 6.5 mm , the smoothing contact could be estimated .", "soft contact lenses wearers were asked to stop wearing contact lenses at least two weeks prior to lasik .", "the lasik subjects enrolled in this study had no history of eye surgery and were comprehensively examined to exclude any eye diseases including dry eye .", "the laser settings were based on manifest and cycloplegic refractions calculated at the corneal plane .", "based on our epithelial smoothing model , the change in epithelial thickness could be calculated by applying a first - order , 2-dimensional butterworth low - pass filter to the ablation profile .", "the lasik flap was created with a 60 khz femtosecond laser ( intralase , abbott medical optics , santa ana , ca ) ." ], [ "nineteen eyes ( 10 right eyes , 9 left eyes ) from 11 myopic lasik patients ( 6 women , 5 men ) were analyzed in the study .", "the slope of 1.15 indicated that , for every diopter of myopic lasik correction , the central epithelial thickness increased by 1.15 m , which corresponded to a smoothing constant of about 0.46 mm . based on this smoothing constant", "pattern ; that is , the maximum epithelial thickening occurred at an annular area around the center ( figure 5 ) .", "the change in average central epithelial thickness was significantly correlated with lasik spherical equivalent setting ( figure 4 ) .", "corneal epithelium was thicker on the inferior side compared to that on the superior side both before ( figure 1(a ) ) and after lasik ( figure 1(b ) ) ." ], [ "fourier - domain oct was demonstrated to be a valuable tool for noncontact measurements of corneal epithelial thicknesses change caused by lasik .", "the maximum epithelial thickening occurred at an annular area about 3~4 mm in diameter .", "however , wider scans are needed to measure epithelial thickness change toward the edge of the ablation zone .", "previous studies have demonstrated that it is feasible to use oct to measure the thickness of different layers of the cornea , such as the epithelium , stroma , and lasik flap using time - domain oct . however , the axial resolution of the earlier oct systems was low and the manual computer - caliper measurement was time consuming . in this study , we used newer fourier - domain oct which has faster scan rate and higher axial resolution with automated measurement of epithelial thickness .", "similar inferior / superior asymmetry in the thickness of corneal epithelium was also found after lasik ( figure 1(b ) ) ." ] ]

[ [ "this is particularly the case of the health of people living in contaminated site(s ) ( cs ) which is affected by the legacy of past industrialization and current industrial activities , often in absence of environmental remediation .", "european community legislation addresses the concept of cs only in the context of the thematic strategy for soil protection and the soil framework directive proposed by the european commission ( ec ) in 2006 ; for details on the legal framework and definitions at eu level refer to who 2013 . according to 2007 estimates ,", "sentieri project is a national project developed to evaluate the health profile of populations residing in the italian sites of national interest for environmental remediation - national priority contaminated sites ( npcs ) .", "this paper 's objective is to present the rationale and methods underlying sentieri project and to describe data and resources required to apply a similar approach in other countries .", "the methods proposed under the approach exemplified by sentieri can be generalized and applied to other npcss . ", "these sites were labelled as sites of national interest because of their substantial contamination , documented in qualitative and/or quantitative terms , and the consequent potential impact on the health of residents ." ], [ "it describes the health profile of residents in contaminated sites through small area analysis by applying the multistep procedure described in the following sections .", "in addition , these relationships are influenced by individual factors ( e.g. , genetic , diet , life - style , occupation , and socioeconomic status ) that can also have a role on both exposure level and disease development .", "when studying how the environment can adversely affect human health , it is usually very difficult to identify clear cause - effect relationships because they are characterized by multicausality with different strengths of association .", "a selection of epidemiologic terms are defined in glossary to facilitate the reading of the paper ." ], [ "expertise in environmental and occupational epidemiology , statistics , and public health clinical medicine , toxicology , and analytical chemistry are needed to tackle this complex environmental issue .", "a detailed discussion on the use and critical aspects of the application of di in small area studies of environment and health can be found in an open access systematic review . when performing epidemiologic studies , there is a risk for researchers to become data - driven .", "once the environmental exposures of interest identified , researchers should examine the updated scientific literature to evaluate the associated health effects .", "the aims of the study will imply a sound outcomes selection to include the ones for which environmental exposure / s ( see environmental data ) is suspected or ascertained to play an etiologic role . the possible health impact from environmental exposures", "therefore , the first decision to be taken is about the relevance to give to the collected material and how to use it to define the strength of the association between the specific health outcome and the environmental exposure / s that characterize / s the npcss . ", "as a first step , npcss to be studied should be chosen , and the criteria adopted to define npcs / npcss are clearly indicated . the npcs selection will depend on the aims of the study to be undertaken , on the availability of the npccs - related information , and on any other consideration researchers would make and consider appropriate ." ], [ "the epidemiologists developed a procedure to examine the epidemiological literature published from 1998 to 2009 on the health risk of populations living in npcss .", "sentieri project studied populations residing in the sites of national interest for environmental remediation ( national priority contaminated sites npcss ) . in sentieri", "all data about contamination sources and characterization of contamination should be collected and examined to identify the contamination diffusion and finally define the areas and populations possibly affected by contaminants .", "the criteria adopted for the classification are reported in table 1 . at the end of the second phase , a matrix of epidemiological a priori evidence about the strength of each outcome - cause / environmental exposure or outcome - cause/other exposure causal association was prepared ( example in table 2 ) .", "the epidemiologists examined each cause of death / exposure combination ( mortality was the first outcome to be analyzed ) in terms of strength of causal inference . environmental exposures " ], [ "it included a summary description of population and contamination data : specific sections dedicated to ( a ) results by gender ( general health profile and specific , a priori selected causes ) ; ( b ) previous studies carried out in the investigated area ; and ( c ) a conclusive paragraph with suggestions for further scientific and/or remediation priorities as well as recommendations for public health interventions", ". in single sites examples of recommendations aimed at a better description and clarification of the observed health effects include the investigation of the respiratory diseases prevalence in children , the conduction of occupational and residential cohort studies , and health surveillance activities as well as exposure assessment and biological monitoring investigations . ", "data acquisition for the appraisal of the present lead environmental pollution and occupational exposure is suggested .", "specific causes with a certain level of strength of causal association with the environmental exposures present in each npcs were reported and discussed in detail in sentieri . in order to have a general description of the residents ' health profile , main broad groups of causes of death" ], [ "the present paper referred as a common thread to sentieri project , in its main components of mortality study and a priori evaluation of the epidemiological evidence .", "its major strengths are the standardization of the mortality analysis and npcss classification in terms of environmental exposure which allow the study of all npcss in one country ; the a priori evidence evaluation to comment and interpret study results is a key characterizing element of the project .", "additional assets are that the mortality analysis can be updated and other vital statistics data can be analysed ; also the a priori evidence evaluation can be brought up to date following the established criteria and procedures .", "the ecological approach used in sentieri does not allow to draw firm conclusions on the causal relationships between residential exposure and health status in residents in a contaminated site ; furthermore , the causal inference might be complicated for causes with multifactorial etiology in areas with multiple sources of different pollutants and concurrent presence of air pollution from urban areas .", "occupational exposures are potential confounders in ecological studies of environment and health ; individual based studies may be needed to disentangle environmental and occupational risk . " ], [ "other strengths of the sentieri approach are that the a priori evidence evaluation and mortality analysis can be updated ; other health outcomes in addition to mortality can be analyzed , for example , cancer incidence , morbidity , and adverse reproductive effects ; also the a priori evaluation can be carried out for environmental exposures different from the ones in sentieri project . notwithstanding the remarkably laborious activities required to set up a national project such as sentieri", "the links between environmental exposures and health effects depend on the environmental pollutants and diseases being considered but are also influenced by factors such as genetic constitution , age , nutrition and lifestyles , occupation , and socioeconomic factors such as poverty and level of education .", "identifying these relationships is therefore challenging ; however , the effort is often worthwhile as it may help to redefine priorities and unlock resources .", ", major benefits in terms of quality and quantity of findings , and a favourable cost / gain balance can be expected inasmuch as this becomes a permanent system of epidemiological observation on health of residents in npcss .", "the approach can also be of value for health surveillance activities in npcss ( possibly analysing different outcomes ) ; in addition it can contribute to etiological evaluation of cause - effect associations if additional data from biomonitoring investigations , risk assessment studies , and individual - based epidemiological studies are available .", "the sentieri approach is , in its essence , a tool to describe the health profile of residents in npcss to document ascertained or suspected associations with local environmental risks ; it does not require an ad hoc data collection .", "furthermore , it is suitable for an overall analysis of data from different npcss and comparative analysis of data from npcss with the same contamination sources ." ] ]

[ [ "the study population included 1177 patients who underwent different types of cardiac surgeries with cardiopulmonary bypass method at sina private hospital ( isfahan , iran ) , between april 2008 and september 2009 .", "postoperative renal risk was assessed using 2 different risk scores of a simplified predictive index for renal replacement therapy after cardiac surgery and a risk score for prediction of contrast - induced nephropathy.9 the main outcome of interest was the incidence of postoperative arf , defined as postoperative serum creatinine > 2 times baseline and/or the need for renal replacement therapy .", "data for the studied patients including demographics , clinical characteristics , laboratory data , medical treatments , angiographic data , ( including amount and type of the contrast agent used ) , comorbid conditions and cardiac procedural data ( including its timing in relation to the preceding angiography ) , were collected by reviewing hospital record files in a computerized database .", "all patients underwent a cardiovascular diagnostic procedure requiring the use of a contrast agent for left ventriculography , coronary or carotid angiography , and thoracic and/or abdominal aorta angiography before their surgeries .", "thus , the patients requiring emergency dialysis therapy or those that underwent the off - pump method surgery were excluded .", "use of nonsteroidal anti - inflammatory agents and other nephrotoxic drugs were avoided or withheld for 48 hours before angiography .", "the contrast agent used were meglumine compound 76% ( urografin , bayer , usa ) as hyperosmolar , iopromide 370 ( ultravisit , berlex montville , usa , mfd . in : germany ) and iohexol 300 ( iopaque , iran or omnipaque 300 , usa ) as low - osmolar contrast agents ." ], [ "the amount of contrast media was entered into the model as both a linear ( continuous variable ) and a dichotomous term ( median or less and greater than median value ) .", "comparisons were made using chi - square test or fisher 's exact test for categorical variables and nonparametric test for continuous variables .", "odds ratio ( or ) and 95% confidence interval ( ci ) were constructed to provide an estimate of adjusted risk posed by post - procedural arf .", "multivariable logistic regression analysis was used to identify independent predictors of arf using variables found to have marginal association ( p > 0.10 ) on univariate analysis ." ], [ "the amount of contrast media was entered into the model as both a linear ( continuous variable ) and a dichotomous term ( median or less and greater than median value ) .", "comparisons were made using chi - square test or fisher 's exact test for categorical variables and nonparametric test for continuous variables .", "odds ratio ( or ) and 95% confidence interval ( ci ) were constructed to provide an estimate of adjusted risk posed by post - procedural arf .", "multivariable logistic regression analysis was used to identify independent predictors of arf using variables found to have marginal association ( p > 0.10 ) on univariate analysis ." ], [ "of 1177 patients who underwent different types of cardiac surgeries after angiography , arf occurred in 465 subjects , 2 of these patients needed dialysis .", "combined coronary artery bypass grafting ( cabg ) and valve surgery was the strongest predictor of postoperative arf ( or : 4.976 , p = 0.002 ) , followed by intra - aortic balloon pump insertion ( or : 6.890 , p = 0.009 ) and higher dose of contrast agent ( or : 1.446 , p = 0.031 ) .", "relationship between the time interval flanked by angiography and surgery and postoperative serum creatinine relationship between the time interval flanked by angiography and surgery and postoperative acute renal failure independent correlates of postoperative arf in a multivariate model are listed in table 3 .", "mean dose of hyperosmolar and low - osmolar contrast agents used overall were 1.23 and 1.21 ml / kg , respectively .", "however , the time interval between cardiac surgery and last catheterization was not different between the patients with and without arf ( p > 0.05 ) ( table 2 ) . clinical and demographic characteristics of the studied population contrast agent and cardiac surgery data overall postoperative peak creatinine was highest on day 0 ( figure 2 ) , then decreased and remained significantly unchanged after this period ( p < 0.05 ) .", "postoperative arf was more prevalent in older and male patients ( p = 0.003 and 0.002 , respectively ) , and those with a higher history of hypertension(p = 0.012 ) , but prevalence of other risk factors as well as left ventricular ejection fraction were similar in both group of patients ." ], [ "the major findings of the present study were that the higher dose of the used contrast agents besides some other determinants such as combined coronary bypass and valvular surgery as well as iabp insertion could effectively predict post - procedure acute arf .", "on the other hand , the use of high dose of contrast agent was strongly related to the incidence of arf after combined cardiac surgery .", "in fact , our data confirmed findings of other investigations that arf after cardiac surgery was associated with the amount of prescribed contrast agents . in a similar study by ranucci and his colleagues,6 cardiac surgery performed on the day of cardiac catheterization and higher dose of contrast agent", "although these investigators demonstrated a correlation between the time interval of cardiac catheterization and surgical procedure with the incidence of acute arf , we could not demonstrate this relationship in our multivariable regression model . in another study by del duca" ], [ "mms designed the study and drafted this manuscript ; mg carried out the study and drafted the tables ; pn carried out the study and drafted the tables ; hsh helped in designing the study ; hms helped in final drafting ; ak helped in designing and carried out the study ; pms data analysis ; and nf data collection ." ] ]

[ [ "we investigated , through a case - control study , the relation between polymorphisms within a series of candidate genes involved in colorectal tumorigenesis and putatively in the formation and the development of colorectal adenomas such carcinogen metabolism enzymes , methylation enzymes , dna repair genes , oncogenes and tumor suppressor genes .", "a case - control study had suggested that family history of colorectal cancer influenced only the growth of adenomas or their malignant transformation . however , relatively few epidemiologic studies explored genetic risk factors in colorectal adenomas .", "colorectal cancer ( crc ) is one of the most common human malignancies in western countries .", "therefore , the identification of factors associated with the development of colorectal adenoma represents a major goal in colorectal cancer prevention .", "the adenoma - carcinoma sequence suggests that colorectal adenomas and adenocarcinomas share common environmental and genetic risk factors .", "they could indeed allow the selection of individuals at risk of crc who may benefit from a screening by colonoscopy .", "an increased risk of colorectal tumors has been found in relatives of patients with large adenomas [ 5 , 6 ] ." ], [ "the genetics of adenomas ( geade ) study is a case - control and family study of patients with high - risk adenomas ( 10 mm ) .", "the data were obtained from 18 participating gastroenterology units of general hospitals in france . from september 1995 to march 2000 , 306 consecutive patients with newly diagnosed colorectal large adenoma ( la ) were enrolled in the study .", "genes have been selected for their role in colorectal tumorigenesis and for the presence of frequent neutral polymorphisms .", "the association was further examined using the combination test , that allows the analysis of all possible combinations of snps within a given gene or tightly linked genes to test their association with the disease .", "when several combinations of polymorphisms were significant within a given test , it was possible to test nested combinations using chi - square calculation to determine whether a given polymorphism adds a significant contribution to the association found .", "the final groups contained 295 patients with la , 302 with sa , and 568 pf as controls ." ], [ "as apc.1 alone and the combination apc.1-apc.2 appeared both significant , we tested whether apc.2 provided a significant contribution to the association , which was not the case ( = 2.12 , 1df ) showing that the association was solely due to the apc.1 ( p.glu1317gln ) polymorphism .", "however , the only significant combination was apc.1-apc.2 already found , showing that myh does not provide any additional contribution to the association between apc and adenomas .", "table 1 describes the characteristics of the polymorphisms studied and the allele frequencies in controls .", "when considering each gene separately , only apc displayed a significant difference between small and large adenomas ( p = .014 in haplotypic analysis and p = .07 in genotypic analysis ) ." ], [ "we investigated the role of candidate gene polymorphisms in a case - control study of patients with large adenomatous polyps ( n = 295 ) , compared to patients with small adenomatous polyps ( n = 302 ) and polyp - free controls ( n = 568 ) .", ", we had shown that mmp polymorphism was most probably involved in the occurrence , but not in the growth of polyps . using the combination test", ", we had shown that the effect was due to a specific combination of mmp1-mmp3 polymorphisms which was not found using logistic regression .", "our results favour the hypothesis that the p.glu1317gly variant would influence the growth and not the occurrence of adenomas , and would have thus indirectly an influence on colorectal cancer risk ." ] ]

[ [ "our patient experienced hypovolemic shock following massive gastrointestinal hemorrhage caused by a burst - through of a pancreatic pseudocyst to the stomach .", "the site of origin of hemorrhage was suspected at the gastroesophageal junction , although no peptic ulcer could be discovered .", "gastroscopy was performed 1 day later , demonstrating a large , ulcerating tumor at the cardia , of which biopsies were taken . because the patient was now diagnosed with a bleeding tumor at the gastroesophageal junction , he was transferred to the icu of the canisius - wilhelmina hospital in nijmegen ( in formation with the radboud university hospital comprising the esophagus centre eastern netherlands , scon ) ." ], [ "a pseudocyst of the pancreas consists of one or several collections of pancreatic fluid , surrounded by inflamed pancreatic tissues .", "operative intervention is advocated , precipitated by endovascular embolization in case of serious hemodynamic instability .", "case series and case reports in the available literature on hemorrhaging pseudocysts all advocate endovascular embolization , followed by resection of the pancreatic tail [ 5 , 8 , 9 , 10 , 11 , 12 , 13 ] . our patient was diagnosed with hemorrhaging pseudocyst 16 days after admission and initial laparotomy .", "the initial plan was to perform pancreatic tail resection after clinical recovery ; however , ultrasonography and ct scan revealed a rapid decline and full disappearance of the pseudocyst .", "pseudoaneurysms or hemorrhages are eligible for endovascular embolization , and transgastric drainage of cysts is contraindicated during hemorrhages , unless embolization is performed first .", "there is evidence to support the role of angiography in case of acute upper gastrointestinal hemorrhage , simultaneously offering the possibility for endovascular treatment [ 2 , 5 , 8 , 9 , 10 , 11 , 12 , 13 ] .", "the possibilities for drainage are to marsupialize the pseudocyst through laparotomy or laparoscopy to the stomach or jejunum , or to perform resection of the pancreatic tail" ], [ "however , surgery is nowadays not the only option for treatment , as possibilities in radiological endovascular diagnostics and techniques are increasing and will eventually be the first step in treating acute upper gastrointestinal hemorrhage ." ] ]

[ [ "today , implant therapy is regarded as an extremely reliable approach to replace missing teeth .", "in the united states , emineralised bone matrix ( dbm ) is considered a transplantable tissue and therefore , is regulated primarily by the american association of tissue banks.10 treatment of dehiscence and fenestration lesions with gbr technique and placing of implants simultaneously have predictable results.11 recent clinical studies have proven that the use of bone substitute materials together with placing implants led to successful coverage of pre - exposed implant surfaces.12", "the introduction of osseointegrated implants in dentistry represented a turning point in dental clinical practice.1 as a general principle in implant surgery implant surfaces should be surrounded by alveolar bone.2 following loss of teeth , natural process of bone resorption occurs.3 sometimes due to prosthetic or anatomical limitations of alveolar ridge , it is not possible to insert implants in bone appropriately.2 and also , while preparing implant sites in narrow ridges , dehiscence or fenestration defects may occur frequently that threaten the survival of implants.4 successful implant treatment depends on sufficient bone volume at the implant surface.5 insufficient amount of supporting bone , will limit the effectiveness of osseointegrated dental implants3 and will have an adverse effect on dental implant prognosis.6 several clinical studies have shown that to ensure long term success of implants , at least one millimetre thickness of bone in buccal surface and lingual surface of implant is essential ." ], [ "all the mandibular premolars teeth were extracted and then , the area was left to heal for three months . after healing period , the area assessed by periapical radiography in order to ensure full recovery , after preparing two sits on one side of each mandible and three sites on the other side which were more appropriate in terms of size and bone quality to place the implants , dehiscence bone defects , were prepared with dimensions of 5 mm apicocronaly , 4 mm mesiodistaly and 3 mm buccolingual in buccal plate using high - speed handpiece and diamond fissure bur and abundant irrigation .", "10 mm periodontal probes were used to measure dimensions of the artificial dehiscence defects ; all measurements were performed by a specialist investigator .", "sectioned samples prepared with trichro massons staining studied by optical microscope ( olympus , japon ) . using histomorphometric method , the percentage of bone implant contact ( bic ) was cal - culated and type of bone ( lamellar , woven ) was determined at 40 times magnification and recorded by an experienced pathologist using optical microscope . in this method , the area of 2 mm around the implants is evaluated .", "samples dissection was carried out in the department of materials science and engineering , sharif university of technology , tehran , iran . studied population included three healthy adult iranian dogs that were chosen by convenient method .", "this prospective clinical trial animal study was conducted in professor torabinejad dental research centre isfahan university of medical sciences , isfahan , iran .", "the animals mouth was washed twice a day using 0.2 chlorhexidine mouthwashes during the first week and thereafter , once a week . after four months of osseointegration period , dogs were anesthetized and periapical radiographs were taken to observe implants situation within the bone . then , crestal incision was done and the implants were exposed and the value of isq was recorded .", "implant stability quotient ( isq ) of each implant was recorded using ostell device ( ostell integration diagnostics , svedalen , sweden ) which was higher than 56 % in all cases , indicating good initial stability of all implants placed ." ], [ "comparison of average bic of lamellar bone , woven bone , cenobone and dembone groups defects and control group ( lamellar bone p = 0.298 and woven bone p = 0.380 ) . furthermore , there was not meaningful difference in rate of lamellar bone ( p=0.298 ) and woven bone ( p = 0.380 ) formation in defects among the three groups .", "comparison of average bic of lamellar bone , woven bone , cenobone and dembone groups defects and control group is presented in figure 1 .", "histologic view under light microscope showes contact of lamellar new bone with implant in dembone group ( magnification x40 massons 's trichromstaning ) .", "histological view under light microscope showes contact of lamellar new bone with implant in cenobone group magnification x40 massons 's trichrom staning .", "there was a positive relationship between total sample bic and isq ( p = 0.004 , r = 0.692 ) .", "average bic in cenobone group ( iranian dfdba ) , dembone group ( american dfdba ) and control group were 77.36% 9.96 ( max 89.1% and min 63.4% ) , 78.91% 11.99 ( max 91% and min 56.3% ) and 71.56% 5.61 ( max 75.8% and min 65.2% ) , respectively ." ], [ "results of this study are coincident with the findings of other researchers in efficiency of using the resonance frequency analysis method to determine the implants stability3133 and showed the resonance frequency analysis is a suitable and reliable method to determine implant stability .", "results of the current study indicated that adding dfdba ( dembone and cenobone ) to membrane , on its own did not significantly increase the obtained bic and isq amounts .", "dfdba was enriched with rhbmp-2 and growth factors and produced better results.2230 the current study results indicated that the relationship between indices of bic and isq was positive and significant . these findings are compatible with huang and colleagues study31 as well as nkenke and colleagues study32 which also found the significant and positive relationship between bic and isq amounts in implants placed in human cadaver bone .", "caplanis and colleagues placed , implants in the alveolar defects which treated with membrane on its own and membrane plus dfdba in dogs , the average bic was about 70%13 which is consistent to our study . and also , the bic obtained in this study is consistent with the findings of von arx and colleagues study14 that placed implants in areas grafted with dfdba and other hybrid materials in dogs and gained a high percentage of bic ( 59% to 75% ) . in this study , adding dfdba to the collagen membrane did not lead to strengthen induction of bone formation , and these findings were consistent with the results of other studies that showed adding dfdba to the membrane on its own did not significantly increase the clinical results obtained with the gbr procedure.151920 there were significant differences between the products of bone banks in terms of induction of bone formation ." ], [ "adding dfdba ( dembone and cenobone ) , either the american or iranian type , to membrane on its own did not significantly increase the obtained bic and isq with the gbr procedure .", "the resonance frequency analysis is still a suitable and reliable method to determine implant stability ." ] ]

[ [ "children are treated with medicines not tested for safety and efficacy and are frequently supported by the low quality of evidence . in the absence of standard prescribing information , clinicians prescribe drugs in an off - label manner .", "most of these studies have been conducted outside india and may not be applicable as hospitalization and prescribing patterns differ based on culture , healthcare infrastructure , and health policies .", "off - label use means use of medicine which is outside the terms of product license with respect to dose , route of administration , indication , or age .", "various national and international studies have been published about the amount of and problems associated with off - label medicines in children .", "hence , the objective of the research study was to quantify off - label use based on nfi , various predictors and discusses some strategies to monitor it .", "only one previous study has been conducted in india which reported 50.62% of off - label prescribing based on british national formulary .", "off - label medicine use among children represents an important health issue as the effects and health risks may be unexpected ." ], [ "the prospective observational study was carried out at a tertiary care hospital in ahmedabad ( india ) for the period of six months .", "all the pediatric patients in ages between 0 and 12 years receiving at least one medication and admitted in pediatric ward were included in the study .", "categories for off - label use were allocated for each medicine according to the reason(s ) why their use was deemed off - label when compared to the terms of the product labeling for that medicine in nfi .", "the pediatric ward was of 60 bed size and attended by 10 academic pediatricians and 28 postgraduate students .", "patients were not considered if they were in age of more than 12 years , not taking any prescription medication and undergoing surgery .", "this study was reported according to the strengthening the reporting of observational studies in epidemiology ( strobe ) guidelines .", "we utilized national formulary of india ( nfi , 4th edition , 2011 ) which is an official publication of indian pharmacopoeia commission , ministry of health and family welfare , government of india .", "the data collection was carried out by one of the researchers ( mms ) who discussed each of the medicines with attending pediatrician and clinical pharmacologist ( dr ) ." ], [ "the study included a total of 320 patients admitted in pediatric general ward of the public teaching hospital over a period of six months .", "hospital stay of six to 10 days ( or 1.91 , 95% ci , 1.332.75 ) also carried higher risk of off - label prescription .", "female patients ( or 1.41 , 95% ci , 1.131.77 ) received substantially high amount of off - label medicines compared to male .", "medicines which had no pediatric information were predominantly in antihypertensive drug class . on multivariate regression analysis as shown in table 5 , we found that pediatric patients in age of 0 to 2 years ( or 1.68 , 95% ci , 1.262.24 , ) were more likely to receive off - label medicines than any other age group ." ], [ "using the data of the pediatric ward of a tertiary care hospital , we found that 70% of medicines were prescribed in off - label manner .", "this might ensure pediatric labeling for new medicines yet to be introduced in the market ; but it is unlikely that drug companies will carry out trials to confirm pediatric use for drugs already marketed and used in children , although in an off - label manner .", "the strict drug approval procedure is the way to ensure quality data on quality , safety , and efficacy for different pediatric age groups . despite many regulatory amendments and policies , we still have apathetic outlook to pediatric clinical trials .", "indian drug regulatory authorities should also develop pediatric specific drug development regulation so that the tendency to market medicines without pediatric specific data is discouraged .", "better medicines for children to improve monitoring medicine safety in the pediatrics and highlighted its concern on off - label medicines .", "the doctor needs to be updated with latest evidence which could be accomplished by using several useful drug compendia like drugdex , clinical pharmacology , and so forth .", "the pharmaceutical companies should be convinced to have appropriate pediatric information in the label and they are not being permitted to market drugs likely to be used in children without suitable pediatric labeling .", "alternatively , the situation can be improved when prescribers report their pediatric experiences with different off - label medicines in form research articles or discussion at scientific platforms . when medicines are used as off - label ," ], [ "further studies are needed to examine why there are inadequate dosing guidelines and generation of more clinical data especially in respiratory medicines .", "based on national formulary of india , our data suggest that magnitude of off - label prescribing in pediatric inpatients is considerable higher than reported in some of the countries .", "there is need for strict drug regulation for pediatric population to ensure safety and effectiveness of pharmacotherapy .", "dose discrepancy and use in restricted age limits were identified as main contributor to off - label prescribing .", "understanding various risk factors and spectrum of off - label medicine use can assist developing prevention strategies ." ] ]

[ [ "the role of the thyroid gland in pregnancy and the impact of thyroid disorders on the course of pregnancy and development of the offspring have drawn a considerable interest in the recent years , both in the medical and in the general society . about 2 and 4%", "american thyroid association in its recently published guidelines have stated against universal screening of pregnant women for hypothyroidism .", "it seems that prevalence of hypothyroidism is more in asian countries compared to the west . in a recent study by dhanwal et al .", "looking at these data the purpose of the study was to know whether routine screening would prove to be beneficial in our country .", "a growing body of evidence suggests that subclinical hypothyroidism may be associated with in vitro fertilization failure , subfertility , infertility , spontaneous abortion , placental abruption , gestational hypertension , preeclampsia , preterm delivery , postpartum thyroid dysfunction , depression ( including postpartum depression ) , conversion to overt hypothyroidism , and impaired cognitive and psychomotor child development ." ], [ "the study was an out - patient department ( opd ) based prospective cohort , observational study in which 305 women were randomly selected and screened on opd basis by thyroid - stimulating hormone ( tsh ) levels ( cutoff level 0.10 - 2.50 miu / ml ) as per recent guidelines .", "these women were followed till term and subsequent delivery to study the effect on maternal and perinatal outcome .", "0.10mu / l , the reference values for tsh were 0.1 - 2.5miu / l , 0.2 - 3.0 miu / l and 0.3 - 3.0 miu / l in the first , second , and third trimesters of pregnancy respectively , considering the recent literature . the statistical difference between variables", "known cases of other medical disorders and women who did not give consent for tsh estimation were excluded from the study ." ], [ "in the study following are the observations made : the mean age of women was 24.46 years ( sd = 2.00 ) . the mean gestational age at time of screening 9.09 weeks .", "this study shows significant association between abnormal tsh values and adverse perinatal outcomes ( p < 0.001 ) .", ". however , the incidence of hypothyroidism in high risk population was 20.58% and in normal population was 6.7% which shows a significant association of thyroid disorders with high risk factors ( p < 0.001 ) . in the euthyroid women 7.2% had an adverse perinatal outcome , 92.7% had normal outcomes .", "( sd = 4.09 ) 38.68% of women were of gestational age less than 9 weeks and 61.31% were with gestational age 913 weeks .", "this shows statistically significant association abnormal tsh values with adverse pregnancy outcomes ( p < 0.001 ) . considering the route of delivery , 88.85% women had normal delivery , out of them 0.36% were hyperthyroid , 5.5% were hypothyroid rest were euthyroid ." ], [ "this prospective screening of thyroid function in a cohort of unselected pregnant women shows that high - risk women ( with a personal or family history of thyroid disorders or a personal history of other autoimmune diseases ) have more significant ( p < 0.001 ) increased risk of hypothyroidism ( subclinical or overt ) during early pregnancy .", "therefore with the growing evidence for an association between maternal subclinical hypothyroidism and adverse pregnancy outcomes but lack of intervention trials showing beneficial effect of thyroxine ( t4 ) in preventing these adverse outcomes , the controversy between targeted high - risk case finding and universal screening continues .", "the consensus guidelines recommend the use of t4 in pregnant women with subclinical hypothyroidism , justified on the basis of potential benefit to risk ratio .", "these data provide the basis for recommending adjustments to thyroid hormone in affected women once pregnant and for the timing of follow - up intervals for tsh in treated patients ." ], [ "so screening of thyroid disorders should be done in early pregnancy . it will help to diagnose the cases at the earliest and to carry out timely intervention to prevent adverse perinatal outcomes .", "but if we screen only high risk population we would miss 4.6% cases which could have been diagnosed and treated earlier .", "but still there is a controversy regarding universal thyroid function screening or high - risk screening in early pregnancy .", "so this study emphasizes high risk screening in early pregnancy but also supports that universal screening should be a part of our screening protocols so that all thyroid disorders are screened and treated at the earliest .", "so in our country we must follow indian thyroid society guidelines which clearly recommend that all pregnant women should be screened at 1 antenatal visit by measuring tsh levels , and highlight that ideally screening should be carried out during prepregnancy evaluation or as soon as pregnancy is confirmed . " ] ]

[ [ "this paper demonstrates the use of surgical treatment using the laparoscopic approach in the palliative care of a patient with advanced esophageal cancer .", "this factor prevents curative treatment in the majority of them , thus making palliative care a more realistic option [ 1 , 3 ] .", "however , surgical procedures in order to bypass the dietary route with relief of dysphagia have been reported in the literature but have fallen into disuse because of the morbidity and mortality of the procedure itself and advances in endoscopic treatment .", "although surgical resection remains the treatment of choice for early cancers , palliative esophagectomy is not recommended due to high mortality rates .", "esophageal cancer is a devastating disease with rapidly increasing incidence in western . despite important advances in therapy ,", "dysphagia is the most common symptom that afflicts these patients , causing 70% of complaints , and leading to severe malnutrition and reduced quality of life [ 1 , 2 ] .", "> 50% of patients have incurable disease at diagnosis and only 510% of these patients have life expectancy > 5 years ." ], [ "the finding was a circumferential lesion from 19 to 25 cm of the incisors , with biopsy diagnosing squamous cell carcinoma .", "radiological examinations showed lymphadenopathy in the celiac trunk and in the mediastinal area . a bronchoscopy diagnosed tracheal infiltration by neoplasia .", "the technique , as described by lacerda et al . in a previous report , involves the creation of a gastric tube close to 3 cm in width and with an average length of 30 cm ( fig . ", "1 ) and preservation of the right gastroepiploic vessels by laparoscopy . \n figure 1:gastric tube ." ], [ "this report demonstrates that an update in the technique proposed by postlethwait for palliation of esophageal cancer with the use of minimal access surgery is feasible .", "dysphagia from inoperable esophageal cancer is a common and complex management problem , and there is no consensus on the ideal treatment approach .", "according to the current literature , the bypass procedure in order to palliate dysphagia could be reserved for patients in which the stent has failed or contraindicated .", "surgical resection is still cited in the literature as a way to palliate esophageal cancer but is restricted to patients with severe risk of complications ( e.g. perforation or incontrollable tumor bleeding ) due to high morbidity and mortality in relation to non - surgical palliative options .", "that there are no randomized controlled studies to compare the addition of surgery to palliative chemotherapy with chemotherapy alone .", "currently , there are several methods for this purpose , including the esophageal stent , endoscopic dilation , radiotherapy ( both external and endoluminal brachytherapy ) , chemotherapy and laser recanalization ( yag ) ." ] ]

[ [ "a provisional diagnosis of orbital dermoid was made and \n the patient was taken up for an excision biopsy .", "a 35-year - old female presented with a painless , slowly growing \n mass in the right inferior orbit for the past four years .", "the right side demonstrated a solid , non - tender , \n freely mobile mass in the inferior orbit , which became more \n prominent on applying pressure on the upper part of the globe . \n", "peroperative findings were of a smooth , well - encapsulated \n mass with no attachments to the surrounding muscles .", "these tumors cells \n were arranged in palisades and this arrangement of cells \n is referred to as verocay bodies ." ], [ "orbital schwannoma arising from the infraorbital nerve \n is rare and clinical diagnosis is often difficult .", "a solitary schwannoma , though rare , should be considered \n as a preoperative differential diagnosis of a unilateral slow- \n growing orbital mass in an adult and prompt management \n is warranted to prevent development of vision - threatening \n complications .", "extensive \n literature search revealed only a few case reports of an orbital \n schwannoma arising from the infraorbital nerve.4 - 10 our \n patient presented with the tumor in this uncommon location . \n", "schwannomas are usually \n asymptomatic when small and may produce progressive , \n painless proptosis on enlargement" ] ]

[ [ "risperidone has been reported to be effective in management of disruptive behaviors , including hyperactivity , irritability , aggression , and temper tantrums . increased appetite , weight gain , headache , and sedation", "literature search revealed only four published reports of risperidone - related bleeding , including hemorrhagic cystitis,1 ) nasal bleeding,2,3 ) and gastrointestinal bleeding.4 ) we hereby describe the first pediatric case of gingival bleeding during risperidone treatment ." ], [ "an 11-year - old - girl was referred to our out - patient clinic for her hyperactivity , temper tantrums , sleep problems , and self - injurious behaviors . according to her psychiatric assessment and psychometric evaluation ,", "gingival bleeding ceased within a week . because worsening of her behavioral problems , her mother increased the dose to 0.33 mg / day .", "one - week after the dose increase , she experienced gingival bleeding when she brushed her teeth .", "she experienced gingival bleeding rarely ( twice a month ) and mildly during this dose regime , therefore we stopped the medication .", "we decided to change risperidone to methylphenidate ; however , her parents refused to continue to the treatment because of their worries about the potential side effects ." ], [ "there are several case reports about risperidone - related bleeding ; however , to our knowledge , there is no report of gingival bleeding associated with risperidone in the literature .", "this case suggests that bleeding associated with risperidone may be a dose - dependent side effect .", "there are several reports on gingival bleeding during anti - depressants;7 ) however , this is the first case on gingival bleeding associated with risperidone . although bleeding is a rare side effect , clinicians should be aware that risperidone may cause bleeding ." ] ]

[ [ "intestinal obstruction can be a result of mechanical or functional obstruction of the intestines , thereby preventing the normal transit of the products of digestion .", "intestinal pseudo - obstruction ( adynamic ) , characterized by abdominal pain , nausea , vomiting , constipation , and severe abdominal distension , is a clinical syndrome caused by severe impairment in the ability of the intestines to push the food through , in the absence of any lesion in the intestinal lumen .", "intrathecal baclofen has been reported to cause intestinal pseudo - obstruction and life - threatening constipation .", "though baclofen might sometimes cause constipation , there are only very few reports on intestinal pseudo - obstruction complicating oral baclofen therapy .", "secondary pseudo - obstruction is more common than the primary and is commonly associated with neuroleptics , opiates , diabetes mellitus , and severe metabolic illnesses ." ], [ "a 50-year - old male , post cervical discectomy ( c3 - 4 ) for prolapsed intervertebral disc with quadriparesis , neurogenic bladder , and spasticity , was on baclofen at a dose of 50 mg / day for 6 months .", "he presented to the emergency department with acute onset of bilious projectile vomiting , abdominal distension , and constipation since 3 days .", "a diagnosis of pseudo - obstruction was considered secondary to long - term baclofen intake , as he had gradually improved over 1 week without any active intervention except for the discontinuation of baclofen since admission .", "the patient was able to tolerate oral diet after 7 days of admission with no recurrence of symptoms ." ], [ ", we considered the possibilities of baclofen - induced pseudo - obstruction of the intestine and adhesive intestinal obstruction .", "baclofen , a derivative of gamma - aminobutyric acid ( gaba ) , is an agonist for the gaba b receptors , and is used to treat spasticity following spinal cord injury , multiple sclerosis , and cerebral palsy .", "colonic pseudo - obstruction is characterized by distension of the colon with features of colonic obstruction , in the absence of mechanical obstruction .", "primary pseudo - obstruction is rare and is a motility disorder involving the autonomic innervation of the intestinal wall ." ], [ "oral baclofen used for spasticity can cause constipation , but intestinal pseudo - obstruction is a rare possibility and in such cases , prompt discontinuation of the drug can be therapeutic . this rare cause of intestinal pseudo - obstruction needs to be borne in mind to avoid potentially morbid investigations like gastrograffin enema or colonoscopy , which are associated with complications like perforation ." ] ]

[ [ "this sparked the interest in how excessive lipid affects -oxidation and mitochondrial biogenesis , which may have a great impact on glucose utilization and insulin resistance [ 710 ] .", "therefore , in this study , by establishing a mouse model , we directly explored this issue . with specific knockout of carnitine palmitoyl transferase-1b ( cpt1b ) in skeletal muscles of mice ,", "however , there is no study investigating if specific cpt1b deficiency in skeletal muscles had significant impact on lipids and insulin sensitivity .", "it was suggested that inhibiting cpt1 activity by specific cpt1 inhibitors alleviates insulin resistance in diet - induced obese mice .", "lipotoxicity was regarded as the link of high levels of lipids with impaired insulin signaling [ 6 , 7 ] .", "this attracted great interest in the effect of accumulated lipid intermediates on insulin resistance [ 4 , 5 ] ." ], [ "general and metabolic profiles were measured at 12 , 18 , 24 , and 30 weeks of age , including the following : body weight , lipids in serum , food intake , body mass , and fat mass , as per related protocols [ 19 , 20 ] .", "an intraperitoneal glucose tolerance test ( igtt ) and insulin tolerance test ( itt ) were performed on nonanaesthetized mice after 8 hours ' fasting .", "skeletal muscle mrna and protein were extracted and purified with standard protocols as per our previous protocols [ 7 , 21 ] .", ", glucose blood levels were sampled at 5 , 10 , 15 , 20 , 25 , and 30 min following intraperitoneal injection of human insulin ( 0.75 u 4.5 nmol / kg ; novolin r , novo nordisk ) . as described previously [ 32 , 33 ]", "cpt1b m/ mouse model was established as per previously described [ 12 , 16 , 17 ] by using male c57/bl6 mice ( 12 weeks old ; 2025 g ) with cre - lox technology [ 17 , 18 ] .", "twenty mice from each group ( cpt1band cpt1b m/ ) were kept on a 12 h/12 h light / dark cycle , in temperature - steady rooms , and had ad libitum access to water and chow diet .", "as previously described [ 24 , 25 ] , fao was examined with radiolabeled palmitate fao assay .", "co2-trapping medium ( naoh , 0.1 m ) for c radioactivity was measured by liquid scintillation to calculate glucose oxidation and quantified by weight of the skeletal muscle tissue homogenate ." ], [ "as shown in figure 1(a ) , the mrna expression of cpt1b decreased specifically in skeletal muscles ( rt - pcr ) but not in the heart muscle in cpt1b m/ mice .", "both dags and tags are dramatically elevated in cpt1b m/ mice . as shown in figure 3(a ) , cpt1b m/ mice maintain insulin sensitivity ( insulin tolerance test ) . compared with wild type , glucose tolerance test of cpt1b m/ mice had improved significantly ( as shown in figure 3(b ) ) .", "as shown in figure 2(a ) , fao was decreased in isolated mitochondria ( radiolabeled palmitate ) in skeletal muscles of cpt1b m/ mice .", "pyruvate oxidation went up ( figure 3(c ) ) and so did insulin - stimulated pakt and glut4 ( figure 4 ) .", "compared to the mice in cpt1b group , those mice in cpt1b m/ group had similar daily food intake . however , as shown in table 1 , their body weights were lower , starting about 12 weeks of age , along with lower fat mass ( p < 0.05 , resp . ) .", "interestingly , for the ceramides , c16 , c18 , and c18:1 had significant increases for cpt1b m/ , but not for c24 or c24:1 ." ], [ "the relationship of fatty acid oxidation , lipids accumulation , and insulin sensitivity in skeletal muscles has been quite interesting .", "our study demonstrated that in mice with conditional knockout cpt1b in skeletal muscles , mitochondrial fatty acid oxidation was depressed dramatically .", "it suggested that with specific knockout of cpt1b in skeletal muscles , although there were lipids accumulations in skeletal muscles , the insulin sensitivity still remains .", "this was accompanied by increased accumulation of lipids in skeletal muscles , such as dags , tags , and ceramides .", "imbalanced fatty acid uptake and fatty acid oxidation ( fao ) have been linked to insulin resistance in muscles , which in turn worsens and complicates obesity and diabetes , as well as their complications [ 7 , 34 , 35 ] .", "we explored from these aspects the enzymes involved in mitochondrial activity such as -had and citrate synthase , genes related to transcriptions such as nrf ( nuclear respiratory factor ) , and the major nuclear receptor activator pgc1 ." ] ]

[ [ "pelvic organ prolapse ( pop ) is a major healthcare problem in middle - aged and elderly women and is usually accompanied by pelvic floor dysfunction ( pfd ) .", "the introduction of mesh repair in vaginal prolapse surgery showed possible advantageous results in early reports .", "we analyzed clinical data to identify possible risk factors for mesh exposure to reduce the tvm complication rate and to improve patients quality of life .", "however , pelvic floor structures progressively weaken in the elderly women , contributing to the high rate of recurrence .", "recent announcements from the us food and drug administration ( fda ) describe increasing concern for complications after transvaginal mesh ( tvm ) surgery .", "the risk factors for mesh exposure have been explored for decades , but it remains unclear what leads to the mesh exposure and operation failure ." ], [ "clinical data were collected including age , menopause status , body mass index ( bmi ) , gravidity and parity , stage of the pop , tvm types , concomitant procedures , operation time , blood loss , postoperative morbidity , and postoperative mesh exposure . only patients with at least 3 months of follow - up time", "the operative methods included prosima anterior leaf fixation , prolift anterior leaf fixation , small mesh fixation , prosima posterior leaf fixation , prolift total pelvic fixation , tension - free vaginal tape ( tvt ) , and tvt - obturator .", "a retrospective study of patients undergoing tvm surgery between january 2004 and december 2012 was conducted in the department of obstetrics and gynecology at the first affiliated hospital of chinese pla general hospital .", "independent sample 's t - test was used for comparisons between the two groups while binary logistic regression was adopted to explore the risk factors for mesh exposure .", "quantitative data were expressed as mean standard deviation ( minimum , maximum ) while categorical data were expressed as absolute number and rate .", "statistical analysis was performed to analyze the risk factors for mesh exposure using the spss 10.0 software ( spss inc .", "the study was approved by the institutional review board of first affiliated hospital of chinese pla general hospital ." ], [ "clinical data were collected including age , menopause status , body mass index ( bmi ) , gravidity and parity , stage of the pop , tvm types , concomitant procedures , operation time , blood loss , postoperative morbidity , and postoperative mesh exposure . only patients with at least 3 months of follow - up time", "the operative methods included prosima anterior leaf fixation , prolift anterior leaf fixation , small mesh fixation , prosima posterior leaf fixation , prolift total pelvic fixation , tension - free vaginal tape ( tvt ) , and tvt - obturator .", "a retrospective study of patients undergoing tvm surgery between january 2004 and december 2012 was conducted in the department of obstetrics and gynecology at the first affiliated hospital of chinese pla general hospital .", "the study was approved by the institutional review board of first affiliated hospital of chinese pla general hospital ." ], [ "independent sample 's t - test was used for comparisons between the two groups while binary logistic regression was adopted to explore the risk factors for mesh exposure . a value of p < 0.05 was considered statistically significant .", "quantitative data were expressed as mean standard deviation ( minimum , maximum ) while categorical data were expressed as absolute number and rate . statistical analysis was performed to analyze the risk factors for mesh exposure using the spss 10.0 software ( spss inc ." ], [ "sslf : sacrospinous ligament fixation ; hus : high uterosacral ligament suspension ; tvt : tension - free vaginal tape ; tvt - o : tension - free vaginal tape obturator technique ; pop - q : pelvic organ prolapse quantification .", "data from 218 patients who had received reconstruction pelvic surgery ( rps ) due to pfd from january 2004 to december 2012 data were collected .", "thirty - two patients with mesh exposure were recruited into the exposed group and the other 163 patients were recruited into the nonexposed group . as shown in table 2 , the median age , the operative time , and the blood loss were comparable in the nonexposed and exposed groups .", "statistical analysis revealed no significant difference for menopausal status , gravidity and parity , bmi , blood loss , age , or postoperative morbidity .", "risk factors for mesh exposure bmi : body mass index ; ci : confidence interval ; or : odds ratio .", "risk factors for mesh exposure in our analysis included operative duration and the concomitant procedures ( p = 0.043 , p = 0.001 ) ." ], [ "data from 218 patients who had received reconstruction pelvic surgery ( rps ) due to pfd from january 2004 to december 2012 data were collected .", "the average gravidity was 3.6 1.6 times ( range : 111 times ) and the average parity was 2.6 1.5 times ( range : 19 times ) .", "a total of 195 ( 89.4% ) subjects were enrolled and 150 ( 68.8% ) subjects were followed up for more than 2 years .", "the average age was 63.9 11.2 years ( 43.089.0 years , mean age 65.0 years ) .", "the median follow - up time was 35.1 23.6 months ( range : 2.0104.0 months ) .", "the median duration of menopause was 14.8 10.7 years ( range : 035.0 years ) .", "seven patients had a history of pelvic surgery , including 3 with hysterectomy plus anterior wall colporrhaphy , 1 with posterior wall colporrhaphy , and 1 with hysterectomy ." ], [ "a total of 195 patients underwent transvaginal rps with polypropylene ( pp ) mesh ; 180 ( 92.3% ) received anterior prolapse surgery , 1 ( 0.5% ) received posterior prolapse surgery , and 14 ( 7.2% ) received combined anterior and posterior prolapse surgery .", "concomitantly , transvaginal hysterectomy was performed in 189 ( 96.9% ) cases , high uterosacral ligament suspension in 176 ( 90.2% ) , sacrospinous ligament fixation in 5 ( 2.5% ) , posterior wall colporrhaphy in 130 ( 66.7% ) , perineal repair in 160 ( 82.1% ) , and tvt in 61 ( 31.3% ) .", "a total of 209 transvaginal pp meshes were placed ; 194 in the anterior wall and 15 in the posterior wall .", "the mean body temperature in the first 3 days after the operation was 37.1 0.3c ( range : 36.838.2c ) .", "the mean operative time was 2.4 1.1 h ( range : 1.04.0 h ) ." ], [ "( a and b ) mesh exposure was found in the follow - up checkup , as the black arrows show .", "most cases gradually healed in half a year . no mesh exposure progression was detected .", "there were eight patients who were admitted for removal of exposed mesh and after mesh resection the vaginal mucosa healed completely .", "the management of vaginal mesh exposure included regular observation , local application of estrogen ointment and metronidazole suppositories , and removal of exposed mesh .", "the average follow - up time was 35.1 23.6 months ( range : 2104 months ) .", "mesh exposure was found in 32 patients , whose age ranged from 43 to 81 years ." ], [ "thirty - two patients with mesh exposure were recruited into the exposed group and the other 163 patients were recruited into the nonexposed group . as shown in table 2 , the median age , the operative time , and the blood loss were comparable in the nonexposed and exposed groups .", "statistical analysis revealed no significant difference for menopausal status , gravidity and parity , bmi , blood loss , age , or postoperative morbidity .", "however , the number of concomitant procedures in the nonexposed group was significantly lower than those in the exposed group .", "sslf : sacrospinous ligament fixation ; hus : high uterosacral ligament suspension ; tvt : tension - free vaginal tape ; tvt - o : tension - free vaginal tape obturator technique ; pop - q : pelvic organ prolapse quantification ." ], [ "the relative risk was 1.899 and 0.376 , respectively , for operative time and number of operations .", "risk factors for mesh exposure in our analysis included operative duration and the concomitant procedures ( p = 0.043 , p = 0.001 ) .", "other factors such as age , menopausal status , gravidity , parity , bmi , and blood loss were not related to mesh exposure .", "logistic regression analysis of the risk factors for mesh exposure was performed in 195 patients [ table 3 ] .", "risk factors for mesh exposure bmi : body mass index ; ci : confidence interval ; or : odds ratio ." ], [ "the synthetic pp mesh has been used more widely in pelvic reconstructive surgery for the past 1020 years .", ", we have found a higher mesh exposure rate in tvm of 15.8% . in this study , we identified risk factors for pp mesh exposure .", "candidates should be carefully chosen , usually patients with advanced pop . furthermore , alternative nonsurgical treatment or autologous tissue reconstructive surgery should be explored .", "access system should be implemented to select eligible surgeons , and a standardized management system should be established for pelvic surgery . in general", "the warning from us fda regarding tvm indicates improper use of mesh may cause serious safety problems .", "however , the related complications of pp mesh have been reported occasionally and some of them are serious and life - threatening ." ], [ ", we have found a higher mesh exposure rate in tvm of 15.8% . in this study , we identified risk factors for pp mesh exposure .", "we analyzed the onset of the exposure and found that 59% occurred within 1 year after the operation and 41% beyond 1 year .", "one year after the operation the onset of exposure was rather low ( 1/31 ) .", "it was also found that 72.7% ( 24/33 ) of mesh exposure occurred within half a year . among them , 39.4% ( 13/33 ) happened within 2 months .", "the synthetic pp mesh has been used more widely in pelvic reconstructive surgery for the past 1020 years .", "however , the related complications of pp mesh have been reported occasionally and some of them are serious and life - threatening ." ], [ "according to the literature , mesh exposure is more likely to occur in patients older than 70 years due to thinner vaginal mucosa caused by the low estrogen level . in 2005 ,", "achtari et al . reported that patient age was a risk factor for mesh exposure .", "kim et al . reported that the rate of mesh erosion was not related to patient age when comparing a group > 70 years of age to a group < 70 .", "in two recent retrospective cohort studies , which included patients over 80 with pop , no mesh exposure was found after the operation . in our study , mesh exposure was found to occur mainly in patients between 50 and 75 years old .", "the subsequent regression analysis has also not revealed any effect of age for mesh exposure .", "first , we tried to reserve the vaginal mucosa as much as possible during our operation ." ], [ "access system should be implemented to select eligible surgeons , and a standardized management system should be established for pelvic surgery . in general , our results showed that tvm surgery is beneficial for patients with advanced pop . although exposure may occur after surgery , exposure rate was low and easy to manage .", "controversially , stepanian et al . found that concomitant hysterectomy would not increase the risk of mesh exposure . in our experience ,", "the number of concomitant operation procedures is another contributing factor for mesh exposure . in 2004 , thompson et al .", "believed that risk factors for mesh exposure were concomitant hysterectomy and inverted t colpotomy while ganj et al . thought the most important factor was the length of the incisions in vagina mucosa and the tension on the incision line", "exposure was significantly higher in patients who received posterior vaginal wall colporrhaphy , perineorrhaphy , and vaginal tape .", "as the number of concomitant procedures increased , the rate of mesh exposure increased , possibly due to a longer operative time . in this study , we used 3 different types of meshes .", "the warning from us fda regarding tvm indicates improper use of mesh may cause serious safety problems ." ], [], [] ]

[ [ "5-fluorouracil ( 5-fu ) is a widely used chemotherapeutic drug and cardiac complications are not rare .", "however myocardial infarction , tako - tsubo - like syndrome and cardiogenic shock are also described ." ], [ ", we decided to treat this condition by the use of an extracorporeal membrane oxygenation ( ecmo ) support by percutaneous implantation .", "transthoracic echocardiography on day 1 ( a ) apical four - chamber view during diastole , ( b ) apical four - chamber view during systole ( there is global hypokinesia with severely impaired thickening of the left ventricular wall in systole ) one day after admission , patient had persistent hypotension with increasing lactate levels as a sign of peripheral malperfusion . on repeat echocardiographic examination , left - ventricular systolic function was found to have further decreased with a left - ventricular ejection fraction of < 10% . due to the progressive cardiogenic shock", "on ecmo support , hemodynamic stabilization was evident and medical heart failure treatment including angiotensin - converting enzyme - inhibitor , diuretics and spironolactone was commenced ." ], [ "this report describes a patient with no history of cardiovascular disease who experienced acute left - ventricular failure after administration of 5-fu .", "treatment of cardiogenic shock is still a therapeutic challenge , especially if coronary artery disease was excluded .", "cardiac complications ranging from angina pectoris to cardiogenic shock after chemotherapy with 5-fu are not rare ." ], [ "cardiogenic shock should be taken into consideration as a possible complication secondary to chemotherapy with 5-fu , even in patients without a history of cardiovascular disease . to the best of our knowledge ,", "this is the first report of an ecmo support in this kind of chemotherapeutic induced cardiogenic shock .", "ecmo support enabled complete relief of cardiac workload and together with medical therapy for heart failure , complete recovery of cardiac function was possible ." ] ]

[ [ "the in vivo detoxification efficacy was tested through intravenous injection of nanosponges before or after administration of a lethal dose of -toxin to icr mice , followed by monitoring the survival rate of the mice .", "the in vivo toxin neutralization ability of the nanosponges was tested through subcutaneous injection of the nanosponge / toxin mixture to the flank region of nude mice , followed by histological analyses .", "the in vitro toxin absorption capacity of the nanosponges was determined through titrating -toxin to a fixed amount of nanosponges .", "the in vitro cellular cytotoxicity of nanosponge - sequestered toxins was examined by incubating nanosponges of different concentrations with varied amounts of -toxin , streptolysin - o , and melittin for 30 min , followed by adding to huvecs for 24 hr .", "the morphology of the nanosponges after absorbing toxins was measured by transmission electron microscopy ( tem ) . for preparation of human rbc nanosponges ," ], [] ]

[ [ ", we report a fatal case of enterovirus 71-induced hfmd that progressed rapidly with massive pulmonary hemorrhage and convulsion .", "however , to our knowledge , no cases of hfmd with sudden - onset massive pulmonary hemorrhage have been reported in korea . here", "pulmonary hemorrhage in enterovirus 71-infected hfmd patients has been reported in taiwan , china , and malaysia2,7,8,9 ) ." ], [ "the kcdc isolated enterovirus 71 with subgenotype c4a from the patient 's serum and nasopharyngeal swab .", "we reported it to the korea centers for disease control and prevention ( kcdc ) , sending his urine , serum , nasopharyngeal swab , and endotracheal aspirate .", "bocavirus was also isolated from his nasopharyngeal swab by real - time rt - pcr at our hospital .", "a 12-month - old , previously healthy boy with hfmd was referred to inje university ilsan paik hospital because of 3 episodes febrile convulsions .", "his body temperature ranged from 38.8 to 40.2. the patient was diagnosed as fatal hfmd with massive pulmonary hemorrhage ." ], [ "to our knowledge , this is the first reported case of hfmd with sudden - onset massive pulmonary hemorrhage in korea .", "pulmonary hemorrhage in enterovirus 71-infected hfmd is very rare ; the present case is likely the first to have occurred in korea .", "pulmonary edema / hemorrhage is the mysterious hallmark symptom of enteroviral hfmd and can kill a child within 1 day2 ) ." ] ]

[ [ "therefore , the present study was designed to investigate the effects of four different types of meals ( normal , high - fat , hgi , and lgi ) on fat and cho metabolism during exercise in elderly male subjects .", "generally , a high - fat , low - cho meal increases fat oxidation during subsequent exercise [ 46 ] , whereas the ingestion of cho before exercise depresses the rate of fat oxidation due to hyperinsulinemia in the postprandial period . altering the type of cho consumed has been shown to have an effect on the magnitude of hyperinsulinemia and depression of fat oxidation [ 8 , 9 ] postprandial increases in glucose and insulin concentration promote cho oxidation , resulting in decreased fatty acid oxidation .", "they also demonstrated that the hgi meal resulted in a greater glycemic and insulinemic response during the postprandial period compared with lgi meal .", "thus , at least for several hours postprandial , both at rest and during exercise , fat utilisation is depressed after hgi compared with lgi meals ." ], [ "after initial physiological measurements , participants reported to the physiology laboratory on four separate occasions , each of which was allocated for the performance of a 30-minutes exercise on a cycle ergometer at 60% vo2 max after having a high fat ( hf ) , high carbohydrate hgi ( hgi ) , high carbohydrate low lgi ( lgi ) , and normal ( n ) meal .", "participants were provided with one of the four following isoenergetic test meals : ( 1 ) and ( 2 ) hgi and lgi : 65% carbohydrate , 20% fat , and 15% protein , ( 3 ) hf : 65% fat , 20% carbohydrate and 15% protein , or ( 4 ) n : 50% carbohydrate , 35% fat , and 15% protein .", "( homa2 % b ) in fasting state were determined using a homeostasis model assessment ( homa - ir ) and were calculated from fasting insulin and fasting glucose .", "the rationale for 30-minutes exercise reflects a typical aerobic bout of exercise undertaken by such persons in a gym session and is recommended for health purposes .", "they then consumed one of the meals which were provided in a random , counterbalanced order within 2030 minutes . at 3 h 20 min after the meal , subjects started the exercise protocol that included a 30-minutes cycling at 60% vo2 max .", "in addition , subjects were requested to refrain from drinking alcohol , nor to engage in any kind of strenuous exercise 24 hours before trials ." ], [ "in addition , insulin concentration decreased significantly during exercise after n , hf and hgi ( figure 5 ) . the mean ( se ) resting value of homa2-ir ( insulin resistance ) for all subjects was 0.76 0.06 and that for homa2- ( -cell function ) was 78.5 69 .", "these resting values are indicators of normal insulin resistance and -cell function in our elderly subjects .", "although anova did not show a main significant effect of either meal or time on insulin concentration , the pre - exercise insulin concentration ( 18.9 1.7 u / ml ) in hgi trial was significantly ( p < .05 ) higher than resting values ( 15.2 1.1 u / ml ) .", "moreover , glycerol concentration increased significantly during exercise after all types of meals ( figure 2 ) .", "however , nefa concentration increased significantly in response to exercise only after hgi ( from 0.12 0.02 to 0.36 0.09 ", "no significant main effect of the meals was observed for rates of fat oxidation ( f3,21 = 1.8 ; p = .177 ) , although fat oxidation was demonstrably , but nonsignificantly , higher after hf ( 0.26 0.04 g / min ) than n ( 0.21 0.04 g / min ) , hgi ( 0.22 0.03 g / min ) , and lgi ( 0.19 0.03 g / min ) . the rates of carbohydrate oxidation during exercise were 1.79 0.28 , 1.58 0.22 , and 1.68 0.22 , 1.77 0.21 g / min for n , hf , hgi , and lgi , respectively .", "pre - exercise nefa concentration increased significantly following hf ( from 0.39 0.08 to 0.61 0.08 " ], [ "the present study is the first study designed to investigate the effects of pre - exercise mixed meals on fat and carbohydrate metabolism during exercise in elderly individuals , and its principle finding was that in spite of some changes in fat metabolites , the composition of the meal did not result in differences in cho and fat oxidation . ", "energy regulation during 30 min of cycling in elderly individuals following isoenergetic meals is associated with a relative increase in fat oxidation and a decrease in carbohydrate oxidation following hf and a corresponding increase in cho oxidation and a decrease following high carbohydrate ( low fat ) meals .", "the present study demonstrated that in elderly individuals feeding isoenergetic meals containing different proportions of carbohydrate and fat alters the metabolic variables at rest and during subsequent exercise .", "our results show that the cho oxidation was resistant to alteration during exercise in elderly males ." ] ]

[ [ "therefore , the purpose of this study was to examine the effect of trampoline training intervention on anthropometric variables and physical fitness components of 1114-year - old male students , iran .", ". showed improvement in motor performance of participants with intellectual disabilities after applying trampoline training intervention .", "however , rebounding exercise for 11 weeks revealed minimal cardiorespiratory fitness improvement and no significant body composition changes in 17 sedentary women .", "very few studies were conducted to detect specific contributions derived from trampoline exercise as a different training model approach .", "additional strength training and plyometric training in 912-year - old soccer players for 2 years showed a significant improvement of motor performance factors .", ". indicated not only balance and strength improvement but also muscular imbalances equalization of the two limbs due to mini - trampoline training .", "physical training program can be effective for athletes and nonathletes in different ages to improve aerobic power , muscle strength , anaerobic power , jumping ability , and local muscle endurance ." ], [ "anthropometry and motor ability of the participants were measured before and after the 20 weeks trampoline training intervention .", "all participants were instructed to perform variety of movements with eyes opened including one foot and two - foot jump , hop with rotation in different directions , hand and toe contacts in the air , and alternate sit and stand movement . the instructor started to teach forward and backward somersault when participants were familiar with spatial awareness , spatial orientation , and body control after performing all of the mentioned movements . finally , students were asked to combine individual movements and execute them as a routine throughout the training sessions .", "motor ability of all participants was assessed after a short period of warm up using standing long jump and vertical jump based on eurofit test battery .", "they were divided into two groups of 19 students based on gender , residential school , and no trampoline training experience .", "thirty - eight healthy school - aged male students ( mean age : 12.6 years , standard deviation : 2.1 ) were selected randomly from the junior high schools of ardabil , iran .", "flow chart of the progress through the phases of the study according to the consort statements evaluation process of participants was conducted within a 2-day period by the same researcher .", "although none of the students had balance problems , some important safety guidelines were considered to prevent the possibility of injury ." ], [ "they were divided into two groups of 19 students based on gender , residential school , and no trampoline training experience .", "the first five students were omitted as they had prior experience , and the second five students were excluded because they had failed to attend the exercise sessions consistently [ figure 1 ] .", "flow chart of the progress through the phases of the study according to the consort statements", "thirty - eight healthy school - aged male students ( mean age : 12.6 years , standard deviation : 2.1 ) were selected randomly from the junior high schools of ardabil , iran .", "the study protocol received approval from the ethics committee of the university of urmia , and it was in accordance with the declaration of helsinki ( last modified in 2000 ) ." ], [ "anthropometry and motor ability of the participants were measured before and after the 20 weeks trampoline training intervention .", "the 1 day was assigned to anthropometric measurement and the 2 day for motor ability tests .", ", crymych , dyfed , uk ) and weight ( model ds-410 , seiko , tokyo , japan ) were assessed to the nearest 10 mm and 0.1 kg respectively , and body mass index was calculated using following formula : weight ( kg)/(height [ m ] ) . moreover , lower extremity girths including thigh and calf were measured on the right side of each participant .", "skinfolds thickness was measured at three body sites ( triceps , subscapula , and suprailiac ) with a harpenden skinfold caliper ." ], [ "participants in experimental group trained 20-week , 1.5 h / session with 10 min rest , in 4 times trampoline training programs per week .", "all participants were instructed to perform variety of movements with eyes opened including one foot and two - foot jump , hop with rotation in different directions , hand and toe contacts in the air , and alternate sit and stand movement . the instructor started to teach forward and backward somersault when participants were familiar with spatial awareness , spatial orientation , and body control after performing all of the mentioned movements .", "although none of the students had balance problems , some important safety guidelines were considered to prevent the possibility of injury .", "finally , students were asked to combine individual movements and execute them as a routine throughout the training sessions .", "however , participants in the control group only participated in school physical education classes 2 times / week for 45 min ." ], [ "motor ability of all participants was assessed after a short period of warm up using standing long jump and vertical jump based on eurofit test battery ." ], [ "then , participant used both arms and legs contributions to project the body as high as possible while standing away from the wall . the standing reach height and the jump height difference were the score .", "each participant standing reach height , tip of middle finger in the hand closest to the wall while participant stood side on to the wall , was marked ." ], [ "the take - off was done when the arms reached forward to lead participant as far as possible .", "each participant stood behind the marked line on the ground with swinging arms and bending knees ." ], [ ". a two - way repeated measures analysis of variance ( anova ) ( condition trial ) with repeated measures on both factors was used . to further analyze the responses of the groups" ], [ "anthropometric and physical fitness variables of the two groups are reported in tables 1 and 2 .", "characteristics of the study participants differences between pre- and post - training of anthropometric and physical fitness indicators in the trampoline and control groups post hoc paired t - tests indicated statistical significant differences in trampoline group between the two measurements about calf girth ( t = 4.35 , p = 0.001 ) , fat% ( t = 5.87 , p = 0.001 ) , vertical jump ( t = 5.53 , p = 0.001 ) , and long jump ( t = 10.00 , p = 0.001 ) .", "the anova repeated measurement test showed a statistically significant main effect of time in calf girth p = 0.001 , fat% p = 0.01 , vertical jump p = 0.001 , and long jump p = 0.001 .", "the analysis of independent t - test ( pre- to post - subtraction between two groups ) indicated significant differences in fat% p = 0.001 , high jump p = 0.02 , and long jump p = 0.02 .", "the anova repeated measurement test revealed a statistically significant main effect of group in fat% p = 0.001 ." ], [ "trampoline training stimulates proprioceptive sense that can facilitate motor performance and prevent musculoskeletal injuries as a result of sudden fall in life .", "this improvement can be attributed to the higher amount of biomechanical stimuli with jumping on a trampoline compared to other forms of activity like running .", "this study investigated whether anthropometric measures and motor performance components are changed via trampoline training considering that this is the first study in a relatively longer period . since athletes increase metabolism through practice , our finding indicated significant changes of body fat% as a result of trampoline training that is not consistent with the findings of edin et al .", "furthermore , body segments coordination due to training programs can help participants to use the ideal motor patterns for performing jumping tests .", "since the nature of this training intervention is recreational , people in different ages can be involved to promote the quality of their life .", "our findings are in agreement with those studies in this regard and showed significant improvement of jumping ability in healthy trampoline participants compared to control group ." ], [ "based on these finding , we can conclude that a 20-week trampoline training with four physical activity sessions / week in 1114-year - old students seem to have a significant effect on body fat% reduction and effective results in terms of anaerobic physical fitness .", "therefore , it is suggested that different training model approach such as trampoline exercises can help students to promote the level of health and motor performance ." ], [], [] ]

[ [ "the dynamic behaviors of solitons and gaussian pulses are well described by tasakorn et al.12 by using the proposed system , the transceiver can be integrated and performed by using a single device . here , the use of the transceiver to form the transportation of microscopic volumes of matter , especially13 for molecule transportation in liquid core waveguide,14,15 drug delivery , and dna transportation , in which the buffer is needed before reaching the required destination .", "are generated using a dark soliton , bright soliton , and gaussian pulse propagating within an add / drop optical multiplexer incorporating two nanoring resonators ( panda ring resonator ) .", "recently , the promising techniques of microscopic volume trapping and transportation within the add / drop multiplexer have been reported in both theory6 and experiment,7 respectively , in which the transporter is known as an optical tweezer . here , the optical tweezer generation technique has become a powerful tool for the manipulation of micrometer - sized particles . to date" ], [ "the trapping force is formed by using a dark soliton , in which the valley of the dark soliton is generated and controlled within the panda ring resonator by the control port signals . in this paper", "it depends upon the numerical aperture ( na ) , laser wavelength , light polarization state , laser mode structure , relative index of refraction , and the geometry of the particle .", "in operation , the trapping forces are exerted by the intensity gradients in the strongly focused beams of light to trap and move the microscopic volumes of matters , in which the optical forces are customarily defined by the relationship:16 \n ( 1)f = qnmpc here q is a dimensionless efficiency , nm is the refractive index of the suspending medium , c is the speed of light , and p is the incident laser power , measured at the specimen ." ], [ ", the dynamic tweezers ( gradient fields ) can be in the form of bright solitons , gaussian pulses , and dark solitons , which can be used to trap the required microscopic volume .", "the advantage of the proposed system is that the transmitter and receiver can be fabricated on - chip and alternatively operated by a single device .", "the important aspect of the result is that the tunable tweezers can be obtained by tuning ( controlling ) the add ( control ) port input signal , in which the required amount of microscopic volume ( atom / photon / molecule ) can be obtained and seen at the drop / through ports , otherwise they propagate within a panda ring before collapsing / decaying into the waveguide ." ], [ "we have proposed a new system that can be used to trap ( delay ) and transport molecules into an optical waveguide by using optical tweezers , which can be used for drug storage and as a delivery system . by utilizing the reasonable dark soliton input power ,", "the dynamic tweezers can be controlled and stored ( delayed ) within the system before reaching the final destination .", ", we have shown that the use of a transceiver for long distance microscopic volume by using the proposed system , in which the drug delivery or molecular communication can be performed via the wavelength router to the required ( connecting ) targets . however , the problems of large microscopic volume and neutral matter may cause a problem , in which the pursuit of new guide pipes and media,27 for instance , nano tubes and specific gases , will be the issue of investigation .", "tweezer amplification is also available by using the nanoring resonators , in which the signals can be modulated via the control port as shown in figures 4b and 5a . in conclusion" ] ]

[ [ "assessment of effects of different assisted reproductive techniques ( art ) like in vitro fertilization ( ivf ) and intra cytoplasmic sperm injection ( icsi ) on speech and language development needs comprehensive studies .", "the aim of this study is to evaluate prelinguistic behavior of 9 month old art infants of royan institute .", "regarding the importance of this subject and the lack of a comprehensive study on the prelinguistic behavior of infants of art in iran , this study was designed .", "some studies showed that they are more susceptible to cerebral palsy which causes speech and language defects .", "the majority of studies followed the children during infancy , thereby precluding pertinent conclusion on the risk of neurodevelopmental disorders which express at older ages such as fine manipulation disability or dyslexia .", "one study shows that a large proportions of preterm deliveries in ivf children have increased risk of cerebral palsy ." ], [ "the method of art , sex of infants , age of mother at pregnancy , time and speech and language defect of parents at present and past time also were mentioned in questionnaire .", "in this descriptive , cross sectional study , 151 term infants of art from royan institute have been evaluated in children 's health and development research center of tehran from august 2007 until august 2009 .", "the prelinguistic behavior of infants include : crying at birth , different cries , smiling , cooing , babbling , reduplicated babbling and echolalia , which are assessed in this study .", "the sampling method was non random sequential with the inclusion criteria of infants conceived through one of the art methods ( ivf / icsi ) , born in term and being resident in tehran .", "this scale is used for assessment of development of speech and language in children from birth to 3 years old .", "preterm born infants were excluded . after signing of research consents by parents , prelinguistic behavior of 151 infants who were born full term ( > 37 weeks ) are assessed .", "it has sensitivity of 90 - 95% for primary detection of speech , language and cognition defects ." ], [ "prevalence of prelinguistic behavior delay in assisted reproductive techniques methods ivf : invitro fertilization ; icsi : intra cytoplasmic sperm injection the prelinguistic behavior delays in different sex and mothers age is shown in table 2 . there was a significant difference only in echolalia delay in the two sexes .", "there was 129 ( 85.4% ) of infants conceived by icsi and 22 ( 14.5% ) by ivf .", "number of infants with delay in reduplicated babbling in icsi method was more than un ivf . \n ", "one - hundred one term infants of art were evaluated . in this study , 76 ( 50.5% ) were male and 75 ( 49.5% ) female .", "prevalence of prelinguistic behavior delay in different sexes and mothers age mothers of 118 infants were younger than 35 years and 33 ones were older .", "prelinguistic behavior delay which had been assessed according to elm-2 is shown in table 1 ." ], [ "zhu jl in showed that infertility treatment , especially icsi , may be associated with a slightly delayed cognitive language development .", "another study showed that there was no difference between cognitive development of infants of art and normal infants . in this study infants showed delay in reduplicated babbling and echolalia . in a study by sutcliffe children were assessed with the griffiths mental development scales .", "two studies showed that art infants had normal cognition development [ 11 , 12 ] .", "there is no study about effect of mother 's age on speech and language development in infants .", "limited sample size , difficult access to this group of infants and unwillingness of parents to complete the questionnaires render less reliable results .", "bonduelle and his collegues in their study , by selection of infants of mothers with the same age exclude affect of this variable . in our study delay of reduplicated" ], [ "detection and correction of any defect or delay in this period prevent major speech and language problems .", "this study was a new study in our country which shows differences between art infants in some prelinguistic behavior such as reduplicated babbling and echolalia .", "more studies with larger sample size to compare art infants with infants of normal conception would be desirable .", "this study showed that prelinguistic behavior of art infants are affected by art method , infants sex and mother 's age at the time of pregnancy ." ], [] ]

[ [ "therefore , given the importance of the cysteine proteases , this paper will focus on structural - functional relationship of falcipains , major cysteine proteases of p. falciparum . in cases of malaria ,", "specifically , this paper will survey available information on structure and function of different domains of falcipain-2 and falcipain-3 and their interaction with inhibitors .", "falcipain-2 and falcipain-3 share 67% sequence identity and contribute more or less equally to the digestion of hemoglobin in the food vacuole . comparing with other papain family proteases ,", "recent advances , including the sequencing of plasmodium genomes ( http://www.plasmodb.org/ ) and development of new tools for manipulating plasmodium genes , have improved our understanding of the cysteine proteases of parasites .", ", using cysteine protease inhibitors , demonstrate that clan ca cysteine proteases of p. falciparum are also involved in chloroquine - mediated programmed cell death ." ], [ "falcipains are major cysteine protease , named due to the function of a catalytic cysteine , which mediates protein hydrolysis via nucleophilic attack on the carbonyl carbon of a susceptible peptide bond .", "like many other proteases , falcipains are synthesized as a zymogen , and the prodomain inhibits the activity of the mature enzyme . to investigate how the prodomain regulates the activity of falcipain-2 , pandey et al", "falcipains may also have other functions in erythrocytic malaria parasites , and it would be interesting to explore the role of the motif in hydrolysis of other proteins of potential biological relevance . in the case of other members of the falcipain", "thus , this study suggests that the motif mediates the most biologically relevant activity of falcipain , the hydrolysis of hemoglobin during trophozoite stage .", "the sequence conservation among the motifs of falcipain subfamily proteases is not high , but , as in the case of the n - terminal extension that mediates protein folding , the presence of these unusual motifs in all related proteases probably indicates a conserved function . for genes encoding more distantly related enzymes , including falcipain-1 , dipeptidyl peptidases , and serine repeat antigens , c - terminal motifs vary greatly in sequence and size , and specific functions of predicted motifs are undefined .", "cysteine proteases of the parasite hydrolyze hemoglobin in the acidic food vacuole [ 20 , 21 ] .", "appear to be endocytosed in a process requiring the presence of both cytoplasmic and luminal prodomain trafficking motifs , followed by vesicular transport to the food vacuole . " ], [ ", we will discuss three major cysteine protease inhibitors , cystatin , chagasin , and falstatin .", "these endogenous cysteine protease inhibitors have been described in a number of eukaryotic systems . here", "there are two major classes of cysteine protease inhibitor , small inhibitors like leupeptin , vinyl sulfones , e64 , and another class known as macromolecular inhibitor .", "cysteine proteases of the malaria parasite may be targeted for inhibition by vinyl sulphones . indeed , vinyl sulphones - based cysteine protease inhibitors are already being used in preclinical trials for the chagas disease .", "the falcipain cystatin complex can be exploited to design potent inhibitors of the malaria parasite ." ], [ "the understanding of the cysteine proteases of malaria parasites has increased markedly in recent years . since cysteine proteases that play an important role in the parasite life cycle by degrading erythrocyte proteins , most notably hemoglobin , are attractive targets for antimalarial chemotherapy . falcipain-2 and falcipain-3 are the best characterized cysteine proteases of malaria parasite , the structure and function of different domains and their interaction with small and macromolecular inhibitors are studied", ". the structure - function study of falcipains and interaction with inhibitors will provide detail insights to develop rational design of inhibitor against falcipains .", "efforts to optimize current inhibitors based on the structure - function of falcipains are currently underway .", "structure - guided approaches should have great role in the design of potent and highly selective inhibitor ." ] ]

[ [ ", this information could be applied to the design of therapeutic options and prevention strategies for this devastating disease . in this review , we first summarized data on the properties of calpains and the mechanisms underlying their activation . then , we reviewed findings on the dysregulation of calpain in the context of ad and its deleterious consequences for the morphology and function of affected brain areas .", "alzheimer 's disease ( ad ) is the most common cause of dementia in the aging population .", "the diagnosis of this neurodegenerative disease relies on the presence of senile plaques and neurofibrillary tangles in affected brain areas at autopsy .", "furthermore , these findings underscore the importance of calpains as potential targets to block the activation of the signaling cascades leading to degeneration in ad . in turn", "a growing body of evidence suggests that the abnormal activation of calpains might modulate not only the formation of senile plaques and neurofibrillary tangles but also the development of synaptic pathology in ad ." ], [ " calpains constitute a family of ca - dependent cysteine proteases involved in multiple and very diverse cell functions including cell development , proliferation , and differentiation , cell motility , growth cone motility and guidance , apoptosis , learning , and memory , among others [ 51 , 52 ] .", "none of these new members of the calpain family are highly expressed in the central nervous system ( cns ) .", "in addition to ca , calpastatin has a key role in the regulation of calpain .", "therefore , the ratio calpain / calpastatin plays a key role in the regulation of calpain activity [ 7880 ] ." ], [ "as briefly reviewed above , calpain activation is a tightly regulated process to prevent deleterious consequences of massive proteolytic activity .", "the data obtained showed that a induces calpain activation by enhancing extracellular ca influx [ 9597 ] .", "these data suggest that nmda receptors play an important role in mediating the sustained ca influx and enhanced calpain activity induced by aggregated a. furthermore , these studies suggested that factors that affect nmda receptor - mediated ca influx could modulate calpain activation and its deleterious effects in central neurons .", "the mechanisms underlying the regulation of the enhanced ca influx and calpain activation in ad have also been studied .", "calpastatin also seems to play an important role in the regulation of calpain activation in ad ." ], [ "it was hypothesized that the enhanced calpain activity observed in ad brains plays an important role in the formation of senile plaques , neurofibrillary tangles , and synaptic dysfunction in the context of ad ( figure 1 ) .", "these studies have shown intense calpain immunoreactivity in dystrophic neurites associated with neurofibrillary tangles , neuritic plaques , and neuropil threads in the hippocampal region and entorhinal cortex of subjects suffering from ad and other tauopathies [ 116118 ] . based on this information ,", "recently , it has been shown that the calpain / calpastatin system can modulate the pathological deposition of a. calpain activation increases the levels of bace1 in a transgenic mouse model of ad .", "these data provided strong evidence for an important role of calpain 1 and the generation of the 17 kda tau fragment in the progression of a-mediated neurodegeneration .", "calpain - mediated tau cleavage seems to play an important role under neurodegenerative conditions [ 157164 ] .", ", calpain activation might play a role in tau - mediated neurodegeneration by inducing tau cleavage . in vitro studies" ], [ "moreover , initial studies using calpain inhibitors in mouse and rat models of ad showed an encouraging recovery of cognitive function in these animals when they were treated with calpain inhibitors at an early age [ 186 , 190 ] . together , these data underscore the potential importance of calpain inhibitors as promising therapeutic tools in ad and related neurodegenerative diseases . ", "in summary , the data briefly reviewed above provide strong support for the role of calpains in ad .", "taken together , the data reviewed above strongly suggest that calpains play an important role in the neurodegeneration mechanisms underlying ad in the aging population . based on these data", "they also highlight the tantalizing possibility that these proteases could serve as targets for the development of therapeutic interventions for this disease , one of the main challenges for decades to come in ad research .", ", it has been tempting to speculate that calpain inhibition could be a useful tool to prevent neurodegeneration in this disease . to obtain further insights into the beneficial effects of blocking calpain activation , several studies" ] ]

[ [ "the research presented here provides a better understanding of how well pepfar advanced that fight and whether the allocation of a large amount of dollars for pepfar was crucial in saving lives and decreasing hiv infection rates in sub - saharan africa .", "the rampant level of government corruption may prevent government officials from being effective leaders in addressing the hiv / aids pandemic .", "for many years , the global community has observed the calamitous effects of the human immunodeficiency virus ( hiv ) on the human population .", "the united states has contributed more funding to the fight against hiv / aids than any other country .", "the methods that were used to treat and prevent further growth in cases of hiv / aids were education , counseling , hiv testing , antiretroviral medication , and building health care infrastructure . the treatment category of funding from pepfar focused on the amount of monetary support given to an african country for hiv treatment , the purchase of antiretroviral ( arv ) drugs , and the building of health infrastructure .", "the care category of pepfar focused on counseling , testing people for hiv / aids , taking care of orphan children , and palliative care for individuals with hiv / aids .", ", africa prevails as the most hiv / aids affected continent in the world , in particular the sub - saharan areas ." ], [ "the methods that were used to treat and prevent further growth in cases of hiv / aids were education , counseling , hiv testing , antiretroviral medication , and building health care infrastructure . the treatment category of funding from pepfar focused on the amount of monetary support given to an african country for hiv treatment , the purchase of antiretroviral ( arv ) drugs , and the building of health infrastructure .", "the rampant level of government corruption may prevent government officials from being effective leaders in addressing the hiv / aids pandemic .", "health management and effective management systems are important because one of the common theories is that the spread of hiv / aids in africa is worsened by high corruption rates and lack of accountability among government officials .", "to this day , africa prevails as the most hiv / aids affected continent in the world , in particular the sub - saharan areas .", "the care category of pepfar focused on counseling , testing people for hiv / aids , taking care of orphan children , and palliative care for individuals with hiv / aids .", "safe - sex education was also a pertinent program in the fight against hiv / aids .", "the prevention category of pepfar focused on the foundational strategy of preventing the proliferation of hiv ." ], [ "this study used panel data from 2002 through 2010 covering the 12 countries that received pepfar funding in the continent of africa . even though pepfar was active from 2004 through 2008 , this research includes two years before ( 2002 and 2003 ) and two years after ( 2009 and 2010 ) in order to increase the ability to estimate the actual effect of receiving pepfar funding . in order to analyze the correlation between pepfar funding and hiv infection rates in africa ,", "the software used for the collection of hiv infection rates reduced the infectivity rates among people receiving arv treatments .", "based on theoretical evidence , this study expected that the 12 focus countries in africa that received pepfar funding would see a decrease in the hiv infection rates .", "even though arv medications are able to prolong the lives of hiv infected individuals , the hiv infection rates that are calculated by the world bank take into consideration individuals who are taking the arv medication ." ], [], [ "hivrateit= 1 + 2%pepfar per gdpit + 3%health per gdpit + 4corruptionit + 5gdppcit+ it the dependent variable was hiv infection rates in africa .", "this study used panel data from 2002 through 2010 covering the 12 countries that received pepfar funding in the continent of africa . even though pepfar was active from 2004 through 2008 , this research includes two years before ( 2002 and 2003 ) and two years after ( 2009 and 2010 ) in order to increase the ability to estimate the actual effect of receiving pepfar funding . in order to analyze the correlation between pepfar funding and hiv infection rates in africa ,", "the control independent variables were healthcare expenditure per gdp , corruption rate of a country , and gdp per capita ." ], [ "although several components have likely contributed to the declining hiv rates in the pepfar focus countries , the main objective of this research was to determine whether pepfar was an effective factor in lowering the hiv / aids infection rates , and , if so , by how much .", "based on this research , the overall hiv rate decreased , but the large amount of money invested to combat hiv infections did not drastically lower the hiv infection rates .", "comparison of hiv infection rates and pepfar funding the united states provided large monetary support toward the pepfar program ." ], [ "despite a few limitations , this study was able to analyze and illustrate the relative effectiveness of pepfar funding in lowering the hiv infection rates on the continent of africa , and has hopefully provided valuable insight for future policy considerations . \n", "a clear understanding of the global impact with the struggle against hiv / aids and the role that pepfar has played in that struggle is appropriate for future public policies , legislation , and programs . to the degree that it succeeded ,", "the objectives and intentions of pepfar were met through an embrace of global connections and cooperation in order to reduce the increasing spread of hiv / aids in sub - saharan africa ." ] ]

[ [ "descriptive investigation of a cluster of 5 sfts cases following exposure to an index patient who died from the disease was performed . a 77-year - old male farmer who died from sfts", "as for risk assessment of transmission factors , all contactors of the index patient during the period from the beginning ( 25 september 2010 ) to the end ( 8 october 2010 ) were classified through 3 types of contacts , including blood , droplet , and possible airborne contacts . the investigation was reviewed and approved by the ethics committee of china center for disease control and prevention ( cdc ) , which uses international guidelines to ensure confidentiality , anonymity , and informed consent .", "five other cases in the cluster included a 32-year - old male intensive care unit ( icu ) physician ( case 1 ) , a 48-year - old male icu consultation physician ( case 2 ) , a 42-year - old younger son of the index patient ( case 3 ) , and a 45-year - old older son of the index patient ( case 4 ) , as well as a 43-year - old male mortuary beautician ( case 5 ) .", "the investigation included a review of circumstances and medical records , specimen collection , virus isolation , real - time polymerase chain reaction for viral rna detection , and sequencing and serological tests ( capture enzyme - linked immunosorbent assay [ elisa ] for immunoglobin [ ig ] m antibody , antigen sandwich elisa for igg antibody , and microneutralization tests [ mnt ] ) ." ], [ "cases 2 and 3 were nearly 100% identical , and provided genetic evidence for the epidemic findings on the possible transmission of sftsv from the index patient to secondary patients .", "all 5 patients had virus - specific igm antibodies in the acute phase , and elevated virus - specific immunoglobin g ( igg ) antibodies in the convalescent phase . the index patient , however , had minimal or undetectable levels of virus specific igm antibodies on day 11 after onset of fever ( table 1 ) . compared with the entire genomic sequence of the virus strain isolated from the index patient ,", "we found that all 5 secondary cases had possible blood contact through skin or mucosa .", "epidemiologic investigations began with interviews with 5 secondary sfts patients and 58 other individuals who had exposure to the index patient from onset of the illness until cremation ." ], [ "here , we reported the person - to - person transmission of sftsv with a cluster of 6 sfts patients that occurred in shandong province of eastern china .", "investigation studies revealed that all 5 secondary infected patients had possible contact with the index patient s blood .", "the risk assessment revealed that blood contact was the major risk factor for the human - to - human transmission of sftsv ." ], [ "this work was supported by the china mega - project for infectious diseases ( 2008zx10004 - 001 , 2009zx10004 ) from the ministry of science and technology and ministry of health of the people s republic of china ." ], [ "conflicts that the editors consider relevant to the content of the manuscript have been disclosed ." ] ]

[ [ "several studies have revealed that the mothers level of education has a positive impact on her knowledge and how she deals with child health care issues.[213 ] our experience in pediatric practice has revealed significant gaps pertaining to child health issues in the mothers knowledge .", "therefore , the mother 's knowledge about child care influences the nature and quality of care that is given to the child .", "there seems to have been very little improvement in the knowledge of mothers on common child health matters over the years inspite of the many years of girls education in the country .", "this descriptive cross - sectional survey aimed to answer the following questions : ( 1 ) what is the level of mothers knowledge of certain aspects of child health matters ? ( 2 ) what are the main sources of health information and which ones are the most useful ? ( 3 ) is there a correlation between mothers level of knowledge and the number of years spent in formal education ? ( 4 ) in the mother 's view , does the current formal education of girls in schools / colleges have a significant impact on mothers knowledge of child health matters ." ], [ "it was indicated clearly to the mothers that participation was voluntary and their non- contribution would have no adverse effect on the quality of care given to their child in the hospital .", "mothers who attended with their children at the pediatric outpatient clinic of king khalid university hospital in riyadh during the months of july and august , in 2007 , were invited to participate in the study .", "the second part contained 40 statements about different aspects of child health issues including nutrition , immunization , development , accident prevention , certain neonatal and infants problems or behaviors and some common childhood illnesses .", "it was reviewed and refined by two other colleagues who have a lot of experience in pediatrics .", "the first part comprised information about mothers nationality , age , work , level of education and the number of children she has in addition to sources of health information and the role of formal school education in child health matters .", "those who agreed were interviewed by a trained non - medical research assistant using the items and statements of the questionnaire as a basis for the structured interview .", "the first 20 questionnaires completed were used as a pilot test to evaluate the clarity of language and level of information in the questionnaire ." ], [ "demographic data of the mothers two hundred twenty - five ( 60.6% ) of the mothers believe that formal girls education in schools and colleges does not provide sufficient child health education . on the question of where to obtain useful information of child health , 287 ( 77.6% ) of the mothers supported the increase in instruction on child health in the curriculum in schools , 284 ( 77% ) supported specific courses on child health targeting girls and women , 321 ( 86.8% ) supported the use of the mass media , and 311 ( 84.1% ) supported programs run by health care professionals .", "two - hundred and five ( 55% ) believed that the best place for a baby / an infant to sit or be carried in a car was the mother 's lap .", "two hundred two ( 59.5% ) believed that putting a baby who crawls in a walker protected him from household accidents .", "one - hundred and ninety ( 50.9% ) thought that it was not harmful to let babies sleep on their tummy in bed ( prone sleep position ) ." ], [ "every visit to a health care professional or every health care facility or institution by patients / parents should be an opportunity for the delivery of a short course in health education", "comprehensive health education programs in schools represent one effective way of providing students with the knowledge and skills to prevent health - impairing behavior .", "several previous studies stressed that health education in school curricula was not adequate , and that the knowledge of high school girls and university students on health matters was deficient.[2730 ] furthermore , studies have shown that school teachers were not trained to give health education in schools .", "in addition to all other sectors of the community , health care personnel and other health care institutions should play a major role in health education ." ], [ "these should be delivered by trained personnel in classes , courses , and special sessions . in addition , health care facilities should be reformed to make health education an essential and compulsory part of health care delivery .", "it also revealed that health education in schools was deficient and it also exposed the limited involvement of health care personnel and institutions in health care education .", "there is a need for health education programs that target high school girls , university students , mothers and other caregivers ( e.g. fathers ) .", "involvement in these educational activities should be a mandatory requirement for the issue of a license to practice ." ] ]

[ [ "indications for covered self - expandable metallic airway stent removal include recurrent mucous plugging of the stent , excessive or recurrent granuloma formation , migration of the stent , stent infection , recurrence of stenosis , stent failure , stent fractures and accomplishment of treatment . usually , it is tedious to remove a stent because of their embedding in the bronchial mucosa and epithelization of the inner surface .", "we report a case of covered self expandable metallic stent removal with a rigid bronchoscope under general anesthesia .", "granuloma formation at the extremities is a relative common occurrence in covered metallic stents possibly resulting from the radial force applied against the airway wall and the friction exerted .", "the case is unique because it had almost all the common complications associated with the stent placement but it was successfully removed without much ado . to the best of our knowledge", "this is the first case of successful removal of a complete stent reported from india ." ], [ "this is one of the rare cases of successful removal of self expandable metallic airway covered stent in benign tracheal stenosis .", "stenosis above the level of the stent granulation tissue inside the stent and at the margins fracture of stent at its lower end ( stent is seen at upper part of right main bronchus , carina is not visualized ) the stent after removal" ], [ "to conclude , this case is unique for many reasons , firstly , it had almost all of the complications that can be associated with stent placement ( stenosis of trachea at the upper end of the stent , extensive granuloma formation , migration of the stent downwards and fracture of the stent at its lower end ) , secondly , we were able to remove the stent in toto [ figure 5 ] and lastly , there were no complications after removal of the stent .", "the management of patients with tracheal / bronchial strictures of benign etiology can be quite challenging .", "various authors have come up with different methods of removal of the stent , like the technique of nashef et al . , which was similar to that of rolling spaghetti on a fork , but much more difficult and at least equally messy .", "the complications of stent removal include significant oozing , tracheal mucosal dehiscence , tracheal puncture requiring thoracotomy , retained stent pieces , need for restenting , respiratory failure , tracheotomy , and even death . in our case ," ] ]

[ [ "the role of meticulous monitoring and importance of anticipation of such disease for prompt diagnosis and management is emphasized .", "takayasu 's arteritis ( ta ) is a chronic idiopathic occlusive inflammation of aorta and its major branches predominantly affecting females in over 85% of cases .", "this case report describes the management of a trauma patient in whom the diagnosis of ta was established by specific investigations done for the same .", "the unsuspected ischemia of vital regional vascular beds may render these patients at risk for inappropriate management .", "the major clinical finding is loss of palpable pulses in the upper limbs and neck ." ], [ "a 26-year - old female was brought to the emergency room ( er ) with history of motor vehicle accident . on initial evaluation", "epidural catheter was removed on 5 day of hospitalization and patient was moved to the ward in a stable condition with advice for regular follow - up and advised to check bp measurements in the lower limb if ever required .", "dopamine infusion was then discontinued and thereafter the patient was subjected to arterial doppler and computed tomography ( ct ) angiography studies to rule out traumatic aortic rupture as a differential diagnosis .", "the radiological investigations revealed multiple left - sided rib fractures with bilateral pleural collections and small lung contusions ." ], [ "the occlusive thromboaortopathy ( ta ) is a group of diseases in which there is no or feeble pulses in upper half of body .", "stroke , congestive heart failure , and rarely ruptured aneurysm may be the heralding events . hemorrhagic shock is the commonest type of shock in trauma patients .", "but ta as a differential diagnosis of exclusion may be considered for a pulseless trauma patient .", "the natural course of disease often gives rise to four main complications : takayasu 's hypertensive ischemic retinopathy , secondary hypertension , aortic regurgitation and aortic or arterial aneurysm ." ], [ "tas may be considered as a differential diagnosis in trauma patients , if examination reveals hypotension or unequal peripheral pulses in upper and lower limb in a young adult , provided hypovolemic shock is excluded .", "a thorough detailed physical examination with palpation of all the peripheral pulses as stressed in atls guidelines is reemphasized . following the basic atls guidelines", "then , the clinician may suspect an atypical cause for hypotension if a blood pressure cuff on an upper extremity is reading a hypotensive measurement but the patient has strong , 2 + pulses in the lower extremities .", "would assist clinicians in picking up this discrepancy as part of their routine evaluation for all trauma patients .", "these patients may be issued a special identification card containing the details of the disease and treatment course for future reference ." ] ]

[ [ "ep , glu , and gaba in the brain samples , the present study was performed using a high efficiency hilic column for bh4 and da , a luna 3 c18 ( 3.0 mm 150 mm , i.d . , 3 m ) column for 5-ht , ne , ep , glu , and gaba with reversed - phase hplc separation and an esi - ms / ms , which could minimize the sample interferences . at the same time , the multiple reactions monitoring ( mrm ) scan mode was sensitive enough to identify and quantify the bh4 and nts in this new method .", ", we developed a sensitive , simple , and simultaneous method to quantify the six major nts such as da , 5-ht , ne , ep , glu , and gaba in mouse brains [ 14 , 15 ] .", "in addition , a tetrahydrobiopterin ( bh4 ) , a vital cofactor for the biosynthesis of the da , 5-ht , and ne , was also measured in the same sample . to establish a novel method for the direct measurement of biologically active levels of bh4 , da , 5-ht , ne ," ], [ "the solution of bh4 , da , 5-ht , ne , ep , glu , and gaba was prepared as a stock ( 1 mg / ml of each ) with pure acetonitrile and then diluted with acetonitrile ( 50% ) for each experiment .", "the tolerance for reliable detection was 10 ng / g for bh4 and dopamine , 20 ng / g for 5-ht , ne and ep , and 0.2 g / g for glu and gaba .", ", we analyzed successfully for 5-ht , ne , ep , glu , and gaba by using luna 3u c18 ( 3.0 mm 150 mm , i.d . , 3 m particle size ) .", "it was successful to qualify bh4 using hydrophilic interaction chromatography ( hilic ) sepax polar - imidazole ( 2.1 mm 100 mm , i.d .", "the most abundant ion in the product ion spectra was 114 for is ( figure 1(a ) ) and 166 for bh4 ( figure 1(b ) ) .", "the most abundant ion in the product ion spectra was at 166.0 for ep ( figure 3(a ) ) and at 169.0 for is ( figure 3(b ) ) ." ], [ "the endogenous levels of bh4 , da , 5-ht , ne , ep , glu , and gaba were successfully detected and measured in mice brain regions .", "the lc - ms / ms methodology was used to measure the levels of bh4 and nts in nine brain regions including ob , fc , hp , st , ht , pt , mb , cb , and bs from mice .", "the newly - developed lc - ms / ms method was used to analyze the quantity of bh4 and nts in mice brain regions ( table 4 ) .", "previously , our lab reported bh4 and dopamine levels in rat brain region . to extend this method to mouse brain regions , we applied it the bh4 and nts in the mouse brain .", "we tested the newly developed method using olfactory bulb ( ob ) , frontal cortex ( fc ) , hippocampus ( hp ) , striatum ( st ) , hypothalamus ( ht ) , pituitary gland ( pt ) , midbrain ( mb ) , cerebellum ( cb ) , and brainstem ( bs ) from the mice and subsequently confirmed that the quantity of bh4 and nts ( table 4 ) . eight different concentrations from 10 to 2000 ng / g of bh4 , from 10 to 5000 ng / g of da , from 20 to 10000 ng / g of 5-ht , ne , and ep , and from 0.2 to 200 g / g of glu , gaba is plotted against is for the standard curves ." ], [ "the present study was undertaken in order to describe a sensitive and specific lc - ms / ms method for simultaneous detection of bh4 , da , 5-ht , ne , ep , glu , and gaba from mouse brain tissue .", "the principal advantages of using lc - ms / ms method include a simple purification procedure and a simple chromatographic condition using the mrm scan mode .", "however , a simple and rapid liquid chromatography tandem mass spectrometry ( lc - ms / ms ) method has been developed for the determination of bh4 , da , 5-ht , ne , ep , glu , and gaba in mouse brain ; the quantitative determination of endogenous neurotransmitters in brain regions by chromatographic coupled mass spectrometry presented here still has a limitation because of the typical lack of analyte - free matrix .", "so , the current developed method should be very useful for brain tissue works of research , regarding the analysis of the alternation of the levels of bh4 , da , 5-ht , ne , ep , glu , and gaba ." ], [ "a simple and rapid liquid chromatography tandem mass spectrometry ( lc - ms / ms ) method has been developed for the determination of bh4 , da , 5-ht , ne , ep , glu , and gaba in mouse brain using epsilon - acetamidocaproic acid ( aaca ) and isotopically labeled neurotransmitters as an internal standard . although it is clear that further studies are necessary to understand the physiological meaning of the different levels of bh4 and nts , this new method could be applied for tracking the changes of the endogenous bh4 and nts which are affected significantly by various stimuli or in neurodegenerative diseases [ 10 , 23 ] ." ] ]

[ [ "although increasing studied are focused on the roles of gper-1 in different types of cancers , the functions of gper-1 in cancers remain unclear yet .", "increasing attention has been paid to revealing of the functions of estrogen in physiological and pathological conditions .", "characteristics and functions of reproductive system cancer will be summarized and discussed in the present review .", "it plays several important physiological and pathological roles in not only reproductive system but also other systems .", "estrogen disorder results in various diseases , such as endometrial diseases , skeletal diseases , and reproductive system tumors .", "estrogen receptors ( er ) and , the two well established nuclear estrogen receptors , have different physiological functions depending upon their various distributions .", "er are involved in the initiation , migration , and progression of estrogen - related multiorgan cancers , such as breast cancer , ovarian cancer , prostate cancer , testicular cancer , liver cancer , and lung cancer as well .", "notably , a novel transmembrane estrogen receptor , known as g - couple estrogen receptor ( gper ) , was found ." ], [ "g - protein - coupled estrogen receptor-1 ( gper-1 ) , a seven - transmembrane - domain receptor localized in cell surface , was first identified in 1996 .", "the downstream signal of pi3k and akt results in several nuclear receptors activation which is closely related the proliferation and migration of cancer cell .", "g-1 has been widely used as a target tool to evaluate the function of gper-1 in different cells and disease models .", "furthermore , numbers of environmental estrogen bind to gper-1 and activate the downstream signaling pathways , such as bisphenol a , genistein , and nonylphenol .", "hb - egf binds to the egfr leading to activation of multiple molecules such as ras , pi3k , akt , and erk1/2 ." ], [ "gper-1 is widely expressed in both of these breast cancer types and the primary breast cancers .", "recent clinical study results showed that the expression of gper-1 might correlate with clinical and pathological poor outcome biomarkers .", "estrogen has an efficacy for advanced prostate cancer ( pc ) via the mediation of the classical estrogen receptors .", "thus , gper-1 inhibits er positive breast cancers proliferation which is a potential target for er positive breast cancers and drug - resistant breast cancer .", "deficiency of er in breast cancer is correlated with poor response to endocrine therapy . in er negative breast cancers , gper-1 stimulates the erk1/2 through the egfr / mapk signal cascade , inducing target gene like c - fos expression , which is involved in the progressing of breast malignancies [ 2729 ] .", "breast cancer is generally classified into estrogen receptor positive ( er+ ) and er negative ( er ) . in clinical practices ," ], [ "there are other studies which proved that gper-1 induced proliferation , differentiation , and drug resistance of lung cancers [ 63 , 64 ] , thyroid cancers , bladder cancers , and oral squamous carcinomas .", "more studies to reveal the functions and mechanisms of gper-1 in the other system cancers are warranted ." ], [ ". controversies still exist on the gper-1 localization and related signaling pathways , in particular the potential action as proapoptotic mediator . since the function and mechanisms of gper-1 are still unclear , more researches and clinical studies are strongly warranted to clarify the different function and mechanisms in different cancer types and conditions .", "majority of the study results addressed that activation of gper-1 by estrogen and g-1 results in the downstream signals and target genes activation , which promotes the proliferation , migration , and invasion of cancer cells . and", "it is interesting that several other studies showed that g-1 , the special agonist of gper-1 , promoted the expression of gper-1 and inhibited the proliferation of er negative breast cancer cells , ovarian cancer cells , and prostate cancer cells .", "the opposite effects of gper-1 in cancer cells may be associated with the epigenetic of gper-1 , such as the snps and histone acetylation .", "the different cell types , tumor microenvironment , and hormonal level may also affect the functions of gper-1", "this effect is in nonclassical er expression dependent manner in most cancers except for ovarian cancers ." ] ]

[ [ "we used male , mouse , spleenic cd4 t cells , differentiated in vitro to t helper ( th1 ) cells to produce a population of cells ( > 95% cd4 ) , of which 69% have 2n genome content , reflecting mature cell withdrawal from the cell cycle .", "visualization of the single cell maps suggested that despite their inherent sparseness , they clearly reflect hallmarks of chromosomal organization , including frequent cis - contacts along the matrix diagonal and notably , highly clustered trans - chromosomal contacts between specific chromosomes ( fig .", "ensemble hi - c protocol to create a method to determine the contacts in an individual nucleus ( fig . 1a , supplementary information ) .", "deep sequencing of the single cell hi - c libraries demonstrated that following stringent filtering our current scheme allows recovery of up to 2.5% of this theoretical potential , and has identified at least 1000 distinct hi - c pairings in half ( 37/74 ) of the cells ." ], [ "despite different experimental procedures and sparse nature of the single cell matrices , the pooled matrix retains the most prominent properties of the ensemble map , confirming the validity of the approach and prompting us to further explore the similarities and differences among the individual cell chromosomal conformations .", "we used the same population of cd4 th1 cells to generate an ensemble hi - c library .", "sequencing and analysis of 190 million read pairs produced a contact map representing the mean contact enrichments within approximately 10 million nuclei .", "the probability of observing a contact between two chromosomal elements decays with linear distance following a power law regime for distances larger than 100 kb .", "1c ) . moreover , after normalizing the matrices given this canonical trend , comparison of intra - chromosomal interaction intensities for the pool and ensemble , by global correlation analysis of contact enrichment values at 1 mb resolution generates a highly significant correspondence ( fig .", "this is emphasized by the high similarity observed in comparisons of individual chromosomes from ensemble and pooled hi - c maps ( fig ." ], [ "a key architectural feature of ensemble hi - c datasets is their topological domain structure .", "the correlation in contact intensities between domains on the same chromosome in pairs of single cell maps is lower compared to reshuffled controls ( fig 2f ) . taken together , these data show that domains form a robust and recurrent conformational basis that is evident in each of the single cells", "2a ) , both supported the idea that domains are observed consistently in the single cell maps . to test whether domain structures are variable between individual cells , we estimated the distributions of intra - domain contact enrichments across cells and compared it to the distributions derived from reshuffled maps .", "visual inspection of the domain structure overlaid on individual intra - chromosomal contact maps ( fig .", "as expected 1403 domains were identified in the th1 cell ensemble hi - c map ( supplementary information table 1 , and supplementary information ) .", "we used the ensemble domains to ask whether the same domain structure can be observed at the single cell level .", ". however , inter - domain contacts are highly variable between individual cells , suggesting large - scale differences in higher - order chromosome folding that are obscured in ensemble maps , averaged over millions of such structures .", "while this analysis can not quantify variability in the high - resolution internal structure of domains , the data suggests that domain intactness is generally conserved at the single cell level . visual comparison of whole chromosome contact maps ( fig ." ], [ "to determine whether the single cell hi - c data is consistent with unique chromosome conformations we developed a modeling approach to reconstruct the conformations of the single - copy , male x chromosome .", "these data show that despite highly variable inter - domain structure of the x chromosomal territory , some of its key organisational properties are robustly observed across the cell population .", "we next asked whether despite their cell - to - cell variability , x chromosome structures share common folding properties that could be tested in real cells .", "these results reaffirm that the variation in single cell contacts is not the result of partial sampling of a single underlying structure ." ], [ "the approach allows for characterization of thousands of simultaneous contacts occurring in individual cells , and provides unique insights into hi - c technology and 3d chromosomal architecture ( supplementary videos 3 and 4 ) .", "we have presented a new experimental strategy to create hi - c contact maps from single cells .", "single cell contact maps reflect conservation of domain structure that was recently characterized , but show that inter - domain and trans - chromosomal contact structure is highly variable between individual cells .", "overlaying data from trans - chromosomal contacts on the x chromosome models demonstrates that trans - chromosomal contacting regions are strongly enriched toward the inferred surface of the models ( fig .", "superposition of h3k4me3 , lamin - b1 enriched domains and trans - chromosomal contacts on the x chromosome models illustrates spatial partitioning of the active , trans - contacting regions from those that are lamin - associated , although both types of domains tend toward the surface of the chromosome territory , supporting the above descriptions of differential positioning of domains ( extended data fig .", "5e ) . together , these data show that preferential localisation of active domains to territory interfaces is a hallmark of chromosome organisation in all cells ." ], [ "a combination of unambiguous distance restraints from the x intra - chromosomal contacts in the single cell hi - c dataset and anti - distance restraints between regions that were found not to contact each other in the ensemble hi - c dataset was used . to assess the precision and accuracy of the structure generation process we used the protocol to generate synthetic hilbert curve structures , and explored the impact of varying the number of restraints . for pair - wise comparison of the structures ,", "we calculated the root - mean - square deviation ( rmsd ) . to compare the x chromosome models to x chromosome structure in vivo , we selected five loci with consistently high or low structural density in the models , and compared distances between the loci and the x chromosome territory surface in cells ( dna fish ) .", "we chose 10 single cell datasets for further in - depth analyses based on several quality criteria ( see supplementary information ) . to validate the single cell hi - c procedure , we pooled the single cell hi - c datasets and compared them to ensemble hi - c dataset prepared from approximately 10 million cells essentially as described .", "we created reshuffled datasets by randomly redistributing contacts of the analyzed single cells to create the same number of cells with the same number of contacts in each cell as a control to statistically analyse the variation among single cell datasets .", "we reconstructed three - dimensional x chromosome structure models using restrained molecular dynamics calculations employing a simulated annealing protocol .", "sequences were mapped to the mouse genome , and abnormal read pairs were discarded . read pairs that occurred only once ( without duplication ) in the library sequencing were removed ." ], [ "the number of actual fends in a male mouse genome , which have two copies of each autosome and a single x chromosome are shown as well as the median fragment length ( chromosomes y and mitochondrial genome were ignored throughout the analysis ) .", "c library , which was created by amplifying the distinctly tagged human ( c1-c6 ) and mouse ( c7-c12 ) single cell samples in the same tube ( e.g. , c1 and c7 , c2 and c8 , etc . ) , the fractions of foreign pairs ( human reads with a mouse tag and vice versa ) and of spurious pairs ( human - mouse ) were consistently extremely low . to estimate the fraction of foreign and spurious pairs that could have originated simply from mapping a truly pure mouse library to a concatenated human - mouse genome , libraries from pure mouse cells ( group d ) were mapped to such a genome .", "topology of lamin b1 , h3k4me3 and trans - contacts on five - model bundles of low - resolution x chromosome models .", "a , the number of interacting chromosomes per chromosome is depicted in circles sized according to the number of single cells the value was observed in , while ordering chromosomes by the number of transcription start sites ( tsss ) in each chromosome which is shown by blue bars .", "however , the change is small , and the number of interacting autosomal chromosomes per chromosome ( the plotted value divided by two ) remains between 4 and 6 .", "however , the change is small , and the number of interacting autosomal chromosomes per chromosome ( the plotted value divided by two ) remains between 4 and 6 .", "the mean number of contacts of each chromosome with others it interacts with is shown for the ten single cells , ordering chromosomes by their size ." ] ]

[ [ "the external guide sequence rna for cleavage of etheo and efmn had the sequence 5-cguaaguugcggucucacca-3 , and for etheo and efmn had the sequence 5-auauucaugcggucucacca-3 ( nucleotides complementary to the target rna underlined ) .", "for the second pair of etheo and etheo molecules used in the multiplex experiments , the external guide sequence rnas had the sequence 5-cguaguaugcggucuacca-3 and 5-gaauaucauugcggucucacca-3 , respectively .", "the pyrophosphate standards were prepared in a solution identical to that employed in cross - replication , but lacking the rna enzymes and substrates .", ", these substrates were prepared from the corresponding e or e molecules by cleaving off the b or b portion using e. coli m1 rna , as described previously1 .", "the a and a substrates could not be obtained reliably by in vitro transcription due to heterogeneity at the 3 end of the transcripts . instead", "the reaction was initiated by mixing equal volumes of two solutions , one containing the enzymes and substrates , and the other containing the mgcl2 and epps buffer .", "aliquots were taken at various times , quenched , and the amounts of newly - synthesized e and e were quantitated as described above ." ], [ "m1 rna , the catalytic subunit of rnase p , was obtained from e. coli genomic dna ( sigma - aldrich , st .", "thermus aquaticus dna polymerase was cloned from total genomic dna and purified as described previously30 .", "histidine - tagged t7 rna polymerase was purified from e. coli strain bl21 containing plasmid pbh161 ( kindly provided by william mcallister , state university of new york , brooklyn ) .", "bovine calf serum was from omega scientific ( tarzana , ca ) and superasin ( rnase inhibitor ) was from ambion ( austin , tx ) .", "calf intestine phosphatase and t4 polynucleotide kinase were purchased from new england biolabs ( ipswich , ma ) , yeast inorganic pyrophosphatase was from sigma - aldrich , and bovine pancreatic dnase i was from roche applied science ( indianapolis , in ) ." ], [ "for the second pair of etheo and etheo molecules used in the multiplex experiments , the external guide sequence rnas had the sequence 5-cguaguaugcggucuacca-3 and 5-gaauaucauugcggucucacca-3 , respectively .", "the a and a substrates could not be obtained reliably by in vitro transcription due to heterogeneity at the 3 end of the transcripts . instead", "the external guide sequence rna for cleavage of etheo and efmn had the sequence 5-cguaaguugcggucucacca-3 , and for etheo and efmn had the sequence 5-auauucaugcggucucacca-3 ( nucleotides complementary to the target rna underlined ) .", ", these substrates were prepared from the corresponding e or e molecules by cleaving off the b or b portion using e. coli m1 rna , as described previously1 .", "transcription of m1 rna was performed similarly , except employing a double - stranded dna template that was generated by pcr ." ], [ "the data were fit to the equation : ft = fmax(a1ek1t)(a2ek2t ) , where ft is the fraction reacted at time t , fmax is the overall maximum extent of the reaction , a1 and k1 are the amplitude and rate of the initial fast phase , and a2 and k2 are the amplitude and rate of the subsequent slow phase , respectively . in the presence of 5 mm theophylline ,", "the reaction catalyzed by etheo exhibited a fast phase with an amplitude of 0.57 and rate constant of 1.4 min , followed by a slow phase with an amplitude of 0.24 and rate constant of 0.044 min ; the reaction catalyzed by etheo had an amplitude of 0.52 and rate constant of 0.59 min in the fast phase , and an amplitude of 0.26 and rate constant of 0.045 min in the slow phase .", "rna - catalyzed rna ligation was performed in a reaction mixture containing 5 m e or e , 0.1 m [ 5-p]-labeled a or a , 6 m b or b , 25 mm mgcl2 , and 50 mm epps ( ph 8.5 ) , which was incubated at 42 c .", "aliquots were taken at various times and quenched by adding an equal volume of gel - loading buffer containing 50 mm na2edta and 18 m urea .", "the products were separated by page and quantitated using a pharosfx molecular imager ( bio - rad , hercules , ca ) ." ], [ "the reaction was initiated by mixing equal volumes of two solutions , one containing the enzymes and substrates , and the other containing the mgcl2 and epps buffer .", "cross - catalytic exponential amplification was performed in a reaction mixture containing 0.02 m each of e and e , 5 m each of [ 5-p]-labeled a and a , 5 m each of b and b , 25 mm mgcl2 , and 50 mm epps ( ph 8.5 ) , which was incubated at 42 c .", "aliquots were taken at various times , quenched , and the amounts of newly - synthesized e and e were quantitated as described above .", "the data were fit to the logistic growth equation , as described in the main text ." ], [ "following addition of the sample to the luciferase mixture , luminescence was monitored for 5 min with a 0.1 s integration time .", "the pyrophosphate standards were prepared in a solution identical to that employed in cross - replication , but lacking the rna enzymes and substrates .", "the amount of light generated was linear over a pyrophosphate concentration range of 0.110 m .", "luminescence was detected using a perkin elmer ls55 luminescence spectrometer operating in bioluminescence mode , with a pmt voltage of 900 v , cycle time of 200 ms , gate time of 180 ms , and delay time of 0 .", "the flash count was set to 1 , the emission filter was fully open , and the emission slit width was 12 nm ." ], [] ]

[ [ "neoadjuvant chemotherapy actually takes an important place in treatment of operable breast cancer in the hope of improving conservative surgery rate of female patients .", "this last decade , fnac technique is improved by the development of new cytological methods allowing standardization of fixation and assuring constant results with ancillary tests such as immunocytochemistry and in situ molecular biology .", "neoadjuvant chemotherapy includes today on target therapies involving the research on expression of specific molecules by tumoral cells . in routine practice , estrogen receptors ( er )", "also , one of the advantages of fnac is the management of small tissue fragments permitting a repetitive evaluation of the chronological evolution in expression of tumoral biomarkers .", "new pharmaceutical molecules , other than er / pr or her2 , are now already evaluated in clinical research as new biomarkers and new target for neoadjuvant therapy .", "fine - needle aspiration cytology ( fnac ) of the breast is wellknown as a safe , effective , economical , and accurate technique for diagnosing palpable breast lesion [ 24 ] .", ", progesterone receptors ( pr ) , and human epidermal growth factor receptor 2 ( her2 ) are the common used biomarkers ." ], [ "apparition of new lesion in patient treated for breast cancer.evaluation of biomarkers.evaluation of biomarker changes following time or metastasis . when cnb technique is not available . \n ", "evaluation of biomarker changes following time or metastasis . when cnb technique is not available .", ", the result of rapid fnac prior to cnb improves the quality of cnb and gives an immediate diagnosis decreasing anxiety of patient . ", "palpable breast lesion.rapid diagnosis to decrease anxiety of patient.patient with morbidity ( senile , cardiac , diabetic etc.).clinical staging : multiple lesions , suspicious lymph node , and so on .", "finally , fnac could be an excellent alternative when radiographic screening of breast is not available . ", "other indications of fnac are staging of multiple tumors or suspicious zones and apparition of a new suspicious lesion during neoadjuvant chemotherapy ." ], [ "it is well known that the combination of clinical evaluation , mammography , and fnac , called triple diagnosis , gives a precise diagnosis [ 10 , 11 ] .", "moreover , fnac interpretation requires serious experience of the cytopathologist and they think that this is one of the main reasons that overall cnb is to be preferred . a recent japanese study of 5693 fnac and 7 different laboratories illustrated a great variability between the institutions suggesting likely difference between education of cytologists and the lack of clinical or radiological information ( triple diagnosis ) .", "these authors concluded that fnac was an accurate material for evaluation on breast malignancy if rigorous criteria are used .", "therefore , when fnac is unsatisfactory , cnb is required to minimize the probability of a missed malignant diagnosis . in a study of fnac and immediate diagnosis performed in 408 palpable breast lesions , liew et al . in 2010 " ], [ "these last years a new cytological technique , called liquid - based cytology ( lbc ) , has been developed and approved by the food and drug administration .", "the efficiency of lbc in the breast cytology has been demonstrated by numerous publications . ", "the main advantage of lbc is surely to adjunct ancillary tests such as immunocytochemistry , flow cytometry , or molecular biology [ 1820 ] .", "briefly , lbc standardises the cell fixation , concentrates epithelial cells , and discards blood cells and/or cell debris that obscure the smear ." ], [ "thus , axillary fnac plays a role in staging of advanced cases for systemic and neoadjuvant therapy and in evaluating candidates for sentinel lymph node surgical procedure or axillary lymph node dissection .", "fnac in lymph node is a cost effective and safe method , false positive is virtually non - existent , and false negative can occur when lymph node is partially involved such as by micrometastase , or isolated tumor cells . in our experience", ", we improve axillary lymph node fnac / lbc by immunocytochemistry using cytokeratin antibody . ", "the clinical staging and preoperative lymph node status are important for the evaluation of eligible patient to neoadjuvant therapy . in the axillary lymph node fnac , chang et al . " ], [ "despite the fact that cnb has been progressively replaced by fnac in the investigation of nonpalpable lesions or microcalcifications without a clinical or radiological mass lesion , fnac has yet a role in palpable lesions in the triple diagnosis association and performed by experienced cytologists . in these conditions , fnac is a safe , effective , economical , and accurate technique for breast cancer evaluation . ", "if the limits of its indications are well known , fnac still plays a role in the modern oncological practice .", "recently , cytological methods using lbc technology , associated or not with the cellblock cytological technique , improve immunocytological and molecular tests with the same efficiency as classical histology . " ] ]

[ [ "documented information about individual and household risk factors associated with malaria transmission is lacking in botswana . in order to address this paucity of information we assessed household and individual risk factors that may be contributing to malaria transmission in tubu village community in the okavango subdistrict in northern botswana .", "the results of this study are relevant to an initiative by the ministry of health in botswana to eliminate malaria by year 2016 .", "the study was conducted in the context of a larger project , botswana ecohealth project ( bep ) , which is investigating the impacts of hydroclimate change on population health . apart from contributing towards the objectives of bep ,", "understanding how and why vector - borne diseases like malaria remain a persistent problem despite being tools for diagnosis and treatment is essential for developing effective control measures for sub - saharan africa ." ], [ "the study was conducted in tubu village on the banks of the thaoge river , one of the distributaries of the okavango delta .", "mosquito sampling was conducted in houses , in pit traps , and in larval breeding sites located within the study area .", "data from clinic records for the period of 2005 to 2010 indicated that 2009 had the highest with 131 unconfirmed cases and 2005 the lowest with 50 cases .", "malaria cases in the okavango subdistrict have been fluctuating since 2005 with unconfirmed cases ranging between 4,686 in 2005 and 10,993 in 2006 and confirmed cases ranging between five ( in 2012 ) and 791 ( in 2006 ) ( ministry of health annual report , 2012 ) .", "the questionnaire had four thematic sections ; first part focused on sociodemographic characteristics such as gender , age , marital status , education level , farming practice , household income , ethnicity , respondent 's relationship to household head , employment status , and occupation and the second part included aspects on how the community or individuals got exposed to mosquito bites due to late night activities , location of homesteads in relation to animal shelters and mosquito breeding sites , visits made to other areas outside tubu village in the last 8 months , and history of malaria episodes in the last 8 months .", "was used to determine straight line distances of study homesteads from the nearest mosquito breeding habitats ." ], [ "mosquitoes were also observed resting outdoors in animal burrow pits located within the village and close to breeding sites . \n ", "forty - eight point four percent ( 31/64 ) of the anopheles arabiensis mosquitoes caught resting indoors in selected huts were blood - fed and at different stages of their gonotrophic cycle .", "there was a significant association between travel outside tubu village and history of malaria disease ( table 3 ) .", "a borderline association between the period spent outdoors and history of malaria episodes was established ( table 2 ) ." ], [ "close proximity of homesteads to vector mosquito breeding sites increased the risk of malaria in many countries including uganda and ethiopia .", "the presence of culicine mosquitoes breeding in the same habitats exacerbated the problem of mosquito biting , though the species were of no medical importance in botswana .", "the location of homesteads relative to mosquito breeding habitats was one of the major risk factors for malaria transmission .", "although active screening for malaria parasites was not done among the respondents , the responses to questions crafted to determine malaria risk implications of travel outside the study area indicated that travel to more intense malaria transmission areas exposed individuals to malaria . reported visitors from malaria endemic areas", "irs , in addition to itns , is a mainstay of all national malaria control programmes in southern africa .", "it is clear that the association between the presence of livestock as a risk factor and malaria transmission is a complex issue that needs further investigations in botswana , where the ratio of cattle to humans is very high .", "abundance of larvae and larval habitats and proximity of humans to larval habitats have been found to correlate very well with vector mosquito biting rates ." ], [ "however a previous study among the same community / individuals showed that the community was well aware of the disease ( 95.6% ) in terms of signs and symptoms ( 88.7% ) and prevention measures ( 98.6% ) and 100% of the respondents who had suspected a malaria attack sought medical treatment at the clinic .", "the ministry of health changed its policy on malaria case management and recording in botswana .", "similar case studies in different malaria prone settings in botswana should be undertaken for comparative purposes .", "as from october 2010 to date all suspected malaria cases are not handled at any clinic , tubu included , but promptly referred to gumare district hospital .", "because of the small sample and population sizes of the study area , the results can only be extrapolated to other villages with similar demographic , ecological , and environmental characteristics and can not be generalized to all malaria prone villages in botswana .", "furthermore the outcome on malaria patients referred to gumare district hospital is never conveyed back to the clinic of origin . as a result of these anomalies ,", "there is a possibility of both over- or underreporting of malaria episodes by the respondents ." ], [ "in conclusion , socioeconomic status , exposure to mosquito bites through individual nocturnal outdoor activities , and mobility of the community were identified as high risk factors for malaria transmission in tubu village .", "the overwhelming use of mosquito nets treated , untreated , or home - made proved to be a viable tool for malaria control in the village .", "limited use of malaria protective measures such as insecticide treated nets , house structure ( traditional or modern ) , and close location of homesteads in relation to breeding sites exposed individuals to mosquito bites .", "however the number of mosquito nets possessed in each household and the farming status were not considered as risk factors for malaria ." ] ]

[ [ "endoscopic ultrasound ( eus ) plays a pivotal role in the evaluation of patients with pancreatic cysts but eus and cross - sectional imaging alone have proven to be inaccurate in identifying the exact nature of the cysts .", "the prevalence of pancreatic cystic neoplasms ( pcns ) is around 2.5%.1,2 pancreatic cysts are increasingly discovered probably because of the ubiquitous presence of multi - detector computed tomography ( ct ) scans and their increased use to evaluate patients with abdominal complaints .", "this paper will review the role of eus - fna in the evaluation of pcns .", "there is inadequate information on the natural history of pancreatic cysts but our knowledge base can not be expanded without being able to determine the exact nature of the cyst noninvasively . toward this end ,", "eus with fine needle aspiration ( fna ) along with cyst fluid analysis has been advocated to improve the utility of eus in the diagnosis of pancreatic cysts .", "size > 3 cm and/or the presence of mural nodules appear to be the best indicators of malignant change in patients with the side branch form of intraductal papillary mucinous neoplasm ( sb - ipmn ) and mucinous cystic neoplasms ( mcn).3 eus with cyst fluid aspiration and/or fna can play a role in differentiating pcns ." ], [ "magnetic resonance imaging ( mri ) is superior in imaging sb - ipmn by virtue of its ability to visualize the pancreatic ductal system .", "studies have shown that imaging alone is inaccurate in differentiating each of the types of cystic neoplasms.9 in a recent study from the group at the academic medical center in amsterdam , the accuracy in identifying the nature of a pancreatic cyst using eus imaging alone was only 23% to 46% amongst a group of expert endosonographers.10 this study used 4 criteria to differentiate cysts : 1 ) septations , 2 ) mural nodules , 3 ) a solid component , and 4 ) communication with the pancreatic duct . as a result of these discouraging reports , eus - guided cyst aspiration and analysis along with cytology have been used to improve diagnostic accuracy ; especially the differentiation between macrocystic serous cyst adenoma , sb - ipmn and mcn .", "secretin stimulated mri / magnetic resonance cholangiopancreatography can be used to highlight the ductal anatomy8 and is commonly used in pancreatic centers but its superiority to non - secretin studies in the evaluation of ipmn has not been proven .", "serous cyst adenomas consist of multiple \" micro cysts \" with thin septae coursing through the lesion ." ], [ "the idea of using analysis of cyst aspirates to diagnose pcn dates back to 1991.11 the massachusetts general hospital surgical group is credited with advancing the clinical application of this concept12 and brugge13 then applied eus - fna techniques to obtain cyst fluid noninvasively .", "difficulties in establishing an accurate diagnosis with imaging alone have prompted investigators to pursue adjunctive measures .", "there have also been reports using the optical catheter used in the spyglass system ( boston scientific , natick , ma , usa ) to directly visualize the cyst lining .", "there have been recent reports of using a small confocal microscopy probe ( mauna kea technologies , paris , france ) ." ], [ "identification of masses or nodules emanating from the cyst wall can indicate the presence of cancer or high grade dysplasia.3 however , it is important to make a differentiation between a mural nodule and an aggregate of mucin .", "our japanese colleagues have been most vocal in expressing concerns about the potential of needle tract seeding of cancer cells.24,25 a resectable cystic mass in the body of the pancreas should be considered for surgical resection without fna in most circumstances .", "aspiration of cyst contents is indicated if identification of the cyst can not be made with imaging alone . however ," ], [ "pancreatic cysts are being increasingly recognized and when detected incidentally , they are likely neoplastic and should undergo further evaluation which should include eus .", ", safe techniques should be developed to improve the cytologic yield because it appears that the exact nature of the lining in mucinous cysts is predictive of their malignant potential.26,27", "the cyst fluid should be sent for cea , amylase and cytology . in the future" ] ]

[ [ "brucellosis is a zoonotic disease mostly transmitted to humans through consumption of unpasteurized dairy products and can lead to a systemic disease with any organ involvement . in this report , we describe a case of brucellosis - induced avascular necrosis of the hip .", "the patient was treated with a combination of antimicrobial treatments and referred to the orthopedic service for total hip arthroplasty .", "brucellosis was diagnosed through serological tests , and avascular necrosis of the femoral head was confirmed by pelvic mri .", "brucellosis may present with unusual manifestations and should be always taken into consideration , particularly in endemic areas ." ], [ ", we describe a case of brucellosis that complicated by avascular necrosis of the femoral head .", "it is a serious public health problem particularly in endemic areas , and is accompanied by .", "the disease is endemic in iran and has a high prevalence in lorestan province , central iran ( 3 ) .", "brucellosis is a zoonotic disease mostly transmitted to humans through consumption of unpasteurized dairy products of infected animals ( 1 ) ." ], [ "the patient was a 50-year - old rural farmer and rancher who presented with groin pain for six months before admission .", ".despite the improvement in the patient s general condition and laboratory evidence showing infection control , the patient was suffered from right groin pain and limitation of motion in the hip joint .", "the patient was visited by a local therapist ; in addition there was a delay in timely referral due to his addiction to opium .", "pelvic radiography and magnetic resonance imaging ( mri ) were administered showing avascular necrosis of right femoral head ( fig . 1 , 2 ) ." ], [ "although osteoarticular involvements , especially arthritis in the large peripheral joints , are among the most common manifestations of brucellosis , no joint destruction has been reported in many studies ( 5 ) . despite few reports on the permanent joint complications of brucellosis - induced peripheral joint arthritis , hip joints pyogenic infection has a poor prognosis , particularly if treatment is delayed ( 6 ) .", "delays in diagnosis and treatment of brucellosis - induced hip arthritis could lead to complications including dislocation and avascular necrosis of the femoral head ( 4 ) .", "finally , the following questions arise : was avascular necrosis caused by increased intra - articular pressure related to the infection or due to direct involvement of the femoral head by the organism ?", "although aspiration and examination of the joint fluid were not performed due to lack of synovial effusion on admission , considering the positive serological tests for brucellosis and concurrent avascular necrosis of the femoral head on mri , it seems that the delay in diagnosis and treatment of brucellosis in this patient had led to avascular necrosis of the femoral head ." ], [ "since brucellosis is a systemic infection with a broad clinical spectrum ranging from asymptomatic forms to deaths in severe cases , this disease should be taken into considerations when dealing with any patient with various and nonspecific symptoms in endemic areas with extension of the clinical signs of brucellosis .", "moreover , early diagnosis and long - term treatment and follow - up are of great importance in brucellosis ." ], [] ]

[ [ "therefore , the present study was conducted on a large registry of 6,084 patients from 18 different clinics to better characterize dtm index of vascular reactivity ( vri ) in relation to patients ' phenotypes .", "we and other researchers have previously reported the relationships between dtm and cvd risk factors , coronary calcium score , myocardial perfusion defects , and coronary angiographic findings [ 1320 ] .", ", it must be ( 1 ) incrementally predictive over risk factors , ( 2 ) responsive to therapy , ( 3 ) operator - independent and reproducible , ( 4 ) low - cost and widely accessible in primary care settings , and ( 5 ) posing no significant side effects . in recent years , endothelial function measurement has emerged as a reasonable candidate that could fit the above criteria .", "a comprehensive cardiovascular risk assessment requires measurement of risk factors as well as structural and functional markers of the arterial system . for the widespread acceptance and clinical adoption of a new test", "since the framingham heart study first reported risk factors for atherosclerotic cardiovascular disease , numerous efforts have aimed at improving risk assessment in the asymptomatic population . over time , these efforts have resulted in the introduction of framingham risk score ( frs ) and other biomarkers including the use of noninvasive imaging modalities such as coronary calcium scoring with ct scan and carotid imt and plaque measurement .", "a new technique named digital thermal monitoring ( dtm ) has been developed to evaluate endothelial function by measuring vascular reactivity during a 5-minute arm - cuff reactive hyperemia test .", ", a number of noninvasive methods of assessing peripheral endothelial function have been introduced , including ultrasound imaging of brachial flow - mediated dilatation ( fmd ) , fingertip arterial tonometry , fingertip photoplethysmography , and laser doppler flowmetry [ 512 ] ." ], [ "the methodology for measuring endothelial function and vascular reactivity using dtm has been previously described [ 2125 ] .", "was restored , and this resulted in a temperature rebound in the fingertip that is directly related to the subject 's hyperemic blood flow response , endothelial function , and vascular reactivity [ 21 , 22 ] . using the recorded fingertip temperatures , the ambient temperature of the testing room , the observed slope of temperature decline , and a multivariate bioheat formula , the vendys software calculated and plotted a zero reactivity curve ( zrc ) .", "in addition to monitoring temperature at the index finger of the right arm , we studied temperature changes at the index finger of the left ( nonoccluded ) arm and observed interesting signals that are currently under further investigations and not included in the results below .", "the vendys dtm test registry includes age , sex , blood pressure , heart rate , vri , and fingertip temperature measurements recorded during dtm tests .", "temperatures < 27c often resulted in technically poor results . sympathetic response flag was defined as the condition in which left finger temperature continuously declines ( > 0.5c temperature drop over a 5-minute time period ) after right arm - cuff occlusion . when evaluating vri , tests that exhibited cold finger flag ", "vascular reactivity index ( vri ) was determined by taking the maximum difference between the observed temperature rebound curve and the zrc during the reactive hyperemia period .", "cold finger flag was defined as the condition in which the right finger temperature at start of cuff occlusion ( time 300 s ) is 27c ." ], [ "overall , the study population had the typical age and sex distribution seen in internal medicine and cardiology clinics .", ", 54% men , 46% women , systolic blood pressure ( sbp ) 138 20 mmhg , diastolic blood pressure ( dbp ) 77 12 mmhg , and heart rate ( hr ) 70 13 bpm . the vri distribution with cumulative percentages", "the percentage of good vri was higher in women than in men ( 21% versus 13% ; p < 0.0001 ) . in contrast , men were slightly less likely to have poor vri than women ( 12% versus 14% ; p = 0.03 ) .", "a trend was seen of higher vri scores in subjects with higher diastolic blood pressure ( r = 0.10 ; p = ns ) . however , none of the blood pressure variables were significantly correlated with vri .", "as shown in table 2 , age , sex , and diastolic blood pressure were significant but weak predictors of vri .", "vri was slightly higher in women than in men ( 1.56 0.58 versus 1.50 0.49 ; p = 0.0001 ) ." ], [ "together , these data clearly point to the clinical utility of endothelial function in primary and secondary prevention", ". a detailed comparison of fmd , pat , dtm , and other noninvasive cvd risk assessment methods is shown in table 3 .", "this is the largest report to date on any fingertip - based measurement of vascular reactivity and endothelial function [ 7 , 26 ] .", "these findings support the clinical utility of dtm as a test that can differentiate good vascular function from poor vascular function , regardless of patient 's age .", "this clearly indicates that endothelial function provides a new angle into the status of vascular risk ." ], [ "we also did not know when the dtm tests were performed in relation to each individual 's medical history and use of medications that might have affected vascular reactivity .", "strengths of our study include a large sample size and a mixed population of males and females , geographically dispersed and from various outpatient clinics .", "the primary limitation was that the vendys registry data do not include information about patients ' clinical conditions or medication use ." ], [ "the present study using the largest database of finger - based assessment of endothelial function shows that digital thermal monitoring of vascular reactivity provides meaningful and reproducible physiological variables .", "it is essentially a combination of a blood pressure and a thermometer empowered by intelligent software that can be used both at clinics and at home .", "it also suggests independent roles for vri as new indices of vascular reactivity and endothelial function .", "however , further studies are needed to incorporate these functional measurements into clinical practice guidelines for primary and secondary prevention ." ] ]

[ [ "however , no studies to date have evaluated the bond strength between glass - ionomers and giomers ; therefore , the aim of the present study was to evaluate the effect of three surface preparation methods on the shear bond strength of giomer to different surface treated conventional glass - ionomer .", "the success of the laminate technique depends on the strength of the bond between the glass - ionomer and the resin composite materials in addition to the strength of the bond between the glass - ionomer cement and dentin . however , there is a relatively weak bond strength between conventional glass - ionomers and composite resin materials , mainly because of the lack of a chemical bond between these two materials and the low cohesive strength of glass - ionomer.[35 ] several studies have evaluated different surface preparation techniques for glass - ionomers , such as the use of different bonding systems and surface etching procedures in order to increase the bond strength between these two materials in the laminate technique ." ], [ "three groups were compared ; a total - etch adhesive resin or a self - etch giomer - based adhesive resin on set glass - ionomer ; or the self - etch giomer - based adhesive resin on the unset glass - ionomer ( before completion of the initial setting ) . in group 1 the surfaces of the specimens were etched with 37% phosphoric acid ( 3 m espe dental products , st .", "chemical composition and application mode of adhesives used in group 2 , the procedures were similar to those in group 1 except that fl - bond ii ( shofu dental corporation , osaka , japan ) self - etch adhesive resin was used on set glass - ionomer surface according to the manufacturer 's instructions and light cured [ table 1 ] , without acid etching . in group 3 ,", "scanning electron micrographs of conventional glass - ionomer and giomer interface in the study groups ( mag 500 ) .", ", the initial setting of gc fuji ii conventional glass - ionomer lasts in 5 minutes and a half , and the net setting time is 2 minutes and a half .", "all the procedures were similar to those in group 2 except that fl - bond ii adhesive was applied according to the manufacturer 's instructions right after the initial setting and before hardening of glass - ionomer ( 2 minutes and a half after the initiation of mixing , which is equal to the cement 's net setting time ) .", "arrows indicate margins of adhesive resin between glass - ionomer and giomer . in the three scanning electron micrographs ,", "in addition , to evaluate the interface between the conventional glass - ionomer and giomer in the groups under study , two additional specimens were prepared in each group and subsequent to longitudinal sectioning , they were evaluated under an scanning electron microscope [ sem ] ( tescan , vega ii xmu , brno , czech republic ) [ figure 1 ] ." ], [ "moreover , the use of self - etch adhesive resin ( fl - bond ii ) in groups 2 and 3 resulted in the thicker hybrid zone than total - etch adhesive resin ( single bond ) in group 1 .", "failure modes of the study groups sem photomicrographs of the glass - ionomer and giomer interface in the study groups are represented in figure 1 . in the sem photomicrograph in group 1", "[ figure 1a ] the hybrid zone ( the area of adhesive resin penetration into glass - ionomer ) is almost homogeneous but has irregular borders on the glass - ionomer cement side . in the sem photomicrograph in group 2", "shear bond strengths in mpa ( means and standard deviations ) for the study groups are represented in table 2 .", "there were statistically significant differences in shear bond strength values between the study groups ( p < 0.0005 ) ." ], [ "an appropriate bond between glass - ionomer and the superficial resin materials is very important for the success of the sandwich technique . in the present study shear bond strength of conventional glass - ionomer to giomer", "was evaluated using three different surface preparations for glass - ionomer ( use of self - etch adhesive on glass - ionomer with or without complete initial setting reaction and use of total - etch adhesive on glass - ionomer after completion of the initial setting reaction ) . in designing the present study ,", "a disadvantage of sandwich technique is the absence of a chemical bond between conventional glass - ionomer and superficial resin materials ; therefore , researchers have focused on the establishment of a chemical bond between them .", "considering the results of the present study , use of giomer - based self - etch systems not only decreases the time needed for the clinical application but also can result in the establishment of a chemical bond between giomer and conventional glass - ionomer ." ], [ "taking into account the limitation of this in vitro study , etching the surface of set glass - ionomer with a total - etch system or placement of self - etch adhesive on the surface of glass - ionomer with incomplete initial setting compromised bonding of giomer to glass - ionomer ." ] ]

[ [ "the present study was designed to examine the social network size of the tehran province residents and the demographic factors affecting it in order to prepare the grounds for estimating the size of hidden populations .", "however , tehran , as a megacity and the capital of iran , has unique demographic , cultural , and social features , special inter - individual relationship patterns , and different subpopulation proportions .", "in addition , due to the migration of different ethnic groups to this city , various ethnic networks have been formed ( 22 ) . therefore to observe these different characteristics and the technical considerations which are recommended in the nsu method ,", "this difference points to the need for local studies to determine this value and its determinants ( 1421 ) . in iran , the estimated social network size on a national scale is between 308 and 380 .", "planning , evaluating , and budget allocation for prevention programs are contingent upon estimating the size of their target groups .", ", several studies in different countries including the united states , ukraine , brazil , moldova , rwanda , japan , china , and thailand have used this method to determine social network sizes as a pre - requisite for estimating high risk population sizes ." ], [ "the effect of various demographic and background factors on the social network size of the residents of tehran province was analyzed using a linear regression model .", "participants were briefed on the study objectives , and their informed consent was obtained . in order to determine the social network size , participants were asked questions regarding the number of people in their personal networks using the indirect method , that is , they were asked how many people they each knew in specific subpopulations . after coordination with the ministry of health and the statistical center of iran , twenty - three known populations with clear and available provincial level statistics were selected to be used in this study . in order to improve estimation accuracy , and in view of the findings of similar studies ( 20 , 28 ) , several considerations were taken into account in preparing the final list of the known populations to be used in the present study ; for instance , the size of all selected populations was between 0.1% and 4% of the total population of tehran province .", "a has contacted b by phone , email or in person at least once within the past 2 years , and b is a resident of tehran province ( 2527 ) . for the total sample size 1029 , we selected 829 persons from tehran and 200 from robat karim , the capital of robat karim county in tehran provincein 2012 .", "the social network size was estimated using an indirect approach , that is , respondents were asked how many persons they knew in a certain sub - population within the society , and estimations were made based on the respondents answers . the term knowing a person has a specific definition in this study , and involves a certain time span and space ( 23 , 24 ) ; therefore by saying a knows b , it is understood that a knows b by name and face ; a can visit , call or email b whenever he / she wants , and vice versa . moreover ," ], [ "a total of 1029 people were interviewed in this study ; 46.7% participants were male .", "age was also proved to have a significant impact on the respondents knowing the studied subpopulations ( p < 0.001 ) . comparison of social network size in different sub groups based on different background variables the possibility of knowing a person who had graduated from high school , participated in the university entrance exam , or been admitted into university in the past year was higher in the younger age group ( 56.6% , 63.4% and 39.3% respectively ) ( table 6 ) .", "demographics of study participants using the thirteen known populations , the social network size was estimated at 200.4 ( ci95% : 188.3 , 212.5 ) , which was used for the back estimation of the known populations in this study .", "multivariate analysis showed that variables of gender and age impacted social network size ( table 5 ) ." ], [ "although in the kerman study , there was no significant relationship between the social network size and any of the demographic factors ( age , education , marital status , and occupation ) ( 27 ) ; the results of the present study showed that men comparing to women and younger people comparing older ones had a significantly larger social network , which seems understandable on account of cultural and social considerations .", "based on the findings of this study and by using the mle method , the social network size of the residents of tehran province was estimated at 259.1 which were calculated using 10 known populations with an e / r ratio between 0.5 and 2 . age and gender were determinants of peoples network sizes .", "the difference seems to be understandable considering the nature of these subpopulations and the iranian culture : an iranian male respondent would be less likely to be aware of childbirth conditions or first graders in his social network compared to a female respondent in a similar situation . in the ukrainian study , similar circumstances were encountered when estimating the number of militiamen , since there was a higher likelihood for male respondents to know someone in this subpopulation on account of their cultural status and social relations compared to women ( 77% vs. 68% ) . therefore , using the militiamen subpopulation to estimate the social network size leads to different results in male and female respondents ( 14 ) .", "although it was not a fully random sample of whole community and there are some methodological considerations , based on the existing experiences in iran and the result of a methodological study that was performed for comparing three popular sampling method in this type of studies ( street - based , telephone - based and home - based interviews ) in this regard , it seems street - based sampling from deferent geographical zones would be a feasible sampling scheme which was used in the national study as well .", "conducted a research in ukraine to estimate the number of idu s fsw s and msm ." ], [ "based on the above explanation , it seems that the social network size of tehran s residents is different not only with similar studies in other countries but also with the results of national survey in iran , which might be mainly because of the special social and cultural pattern of communications among different communities .", "we also showed that the c varies considerably in males and females , in young and old people .", "therefore , local estimations for c in different sub - populations are needed to improve the accuracy of nsu estimations ." ], [ "ethical issues ( including plagiarism , informed consent , misconduct , data fabrication and/or fal sification , double publication and/or submission , redundancy , etc . ) have been completely observed by the authors ." ] ]

[ [], [ "therefore , in the present study , the authors aimed to estimate the amount of health care utilization due to bph by surveying the records of patients who visited the designated medical institutions by the health insurance review and assessment service ( hira ) of korea . the hira monitors and analyzes reimbursement records from the korean national health insurance ( nhi ) and medical aid . because almost the entire nation is required to join the nhi ( approximately 96.6% of the population ) and medical aid ( approximately 3.4% ) , hira records cover all citizens ( approximately 49 million people ) in korea .", "benign prostatic hyperplasia ( bph ) is a highly prevalent disease affecting middle aged and elderly men ( 1 ) . in the united states ,", "lastly , this nationwide , large - scale survey was conducted to offer the most reliable and objective epidemiological data in order to provide fundamental information for authorities formulating health care policy to improve the national health - related qol .", "it seems certain that , before long , bph will emerge as one of the main priorities of concern for health care service authorities , as well as the government .", "bph is the most common benign tumor in men and is the most typically the disorder that reduces the quality of life ( qol ) in men , causing lower urinary tract symptoms ( luts ) ( 2 ) .", "we also aimed to find any seasonal or regional variation in the cost of health care utilization due to bph , as well as to examine economic burdens on the health insurance system and the pattern of practice in the management of bph ." ], [ "we evaluated data from the hira from a span of 5 yr ( 2004 to 2008 ) .", "we used all claims records of outpatient visits or hospital admissions of patients aged 20 yr or older , diagnosed with bph ( international classification of diseases [ icd]-10 diagnostic code : n40 ) as the primary diagnosis .", "we then assessed the seasonal and annualpatterns of hospital visits and duration of treatment due to bph , as well as the changes in the amount of insurance payment for the diagnosis and treatment of bph , during the research period .", "a time series analysis was performed to explore the seasonal and annual variation of the amount of hv , dt , taip , and pcip .", "data consisted of the patient 's age , residence at diagnosis , treatment cost for bph ( medical and surgical ) , time to surgery from medication , emergency visits , etc .", "hospital visit ( hv ) meant the number of days that the patients visited the hospital due to bph and duration of treatment ( dt ) indicated the period of prescription if the patients received medications due to bph .", "total amount of insurance payment ( taip ) gave the information of the total cost of national insurance payment for bph within one year , and per capitainsurance payment ( pcip ) signified calculated values using this total amount of insurance payment and national population data ( 9 , 10 ) ." ], [ "this study was exempted from review and evaluation by the institutional review board of the boramae medical center , seoul ." ], [ "there was no regional difference between urban and rural areas in terms of hv count , dt , and taip due to bph .", "the total number of hv from 2004 to 2008 was 12,088,995 . the number of visits increased with time and reached the almost 1.7 fold in 2008 compared to 2004 ( table 1 ) .", "patients in the 20s showed a decrease in hv from year to year , those in the 30s showed an increase until 2006 and then a decrease , those in the 40s showed an increase throughout the study period .", "the total dt almost doubled from 3,463,520 days in 2004 to 6,598,787 days in 2008 ( table 1 ) .", "the variation of dt by years was significantly different according to the age groups . per capita insurance payment ( pcip ) increased with increasing age and with times ( table 3 and fig .", ", in patients in the 30s or older , pcip significantly increased 1.05 , 1.20 , 1.21 , 1.21 , and 1.20 times compared with the previous year ." ], [ "this is the first nation - wide , population - based study demonstrating not only seasonal and age - specific variation in the incidence of bph , but also the amount of the economic costs for bph patients in korea .", "health care utilization due to bph is rapidly increasing in korea and is more remarkable in the elderly population .", "the main contributors of the rising prevalence of bph in korea are suspected to be the elevated standard of living , westernized diet with increased consumption of animal fat , and aging population ( 11 ) . although the fact that the prevalence of bph increases with age is widely accepted and presumed to apply to the korean society , the rate of increase in this study is noteworthy and greater than expected . in the us ,", ", we demonstrated that the demand for bph treatment nearly doubled throughout the 5 yr of study period .", "our study is the largest scale population study , as well as the most objective clinical data in korea , so it could provide fundamental epidemiological information on bph ." ] ]

[ [ "the present case is a patient with giant retroperitoneal cavernous hemangioma originating from the ilium with atypical clinical course who was referred for surgical treatment .", "primary retroperitoneal tumors ( prts ) of vascular origin are a diverse group of rare abdominal neoplasms , both benign and malignant", "an interventional staged therapy is becoming more popular with the aim of reducing the diameter of the main hemangioma , especially that surrounded with diffuse hemangiomatosis .", "successful combination of transcatheter arterial embolization ( tae ) prior to the surgery of cavernous hemangioma of the liver was reported recently . nevertheless , the treatment of choice for primary retroperitoneal tumors is still radical surgical resection that leads to recovery ." ], [ "a 71-year - old female patient was referred to the department of surgical oncology with a giant retroperitoneal tumor located in the left iliac fossa .", "2 a , b ) . \n a giant tumor with sigmoid colon tight on it .", "c the tumor after resection ( arrow peduncle connecting the tumor to the ala ) during the surgery a large mass on the ala was found . there were no signs of infiltration of neighboring organs , and the sigmoid colon was tight on the tumor . after separating the sigmoid and identification of the left ureter and iliac vessels", "physical examination revealed a large , skin modeling , nonpulsatile mass in the left iliac fossa ( fig ." ], [ "we considered an interventional staged therapy with tae for its possible advantage of reduction of the diameter of the main tumor mass , and surrounding diffuse hemangiomatosis , which was reported in the case of cavernous hemangioma of the liver .", "the literature review shows that in differential diagnosis of giant abdominal tumors , rare benign neoplasms should be considered in every case .", "in the present case the size and localization of the tumor and urgent necessity made the operation a high - risk procedure with possibility of resecting vital structures , such as the sigmoid colon or ureter . in the present case the long - term history of abdominal tumor indicated a benign tumor , while radiological and clinical findings suggested malignant disease .", "however , one can find publications on treatment of hepatic cavernous hemangioma with percutaneous radiofrequency ablation ." ], [ "radical surgical resection remains the treatment of choice for primary retroperitoneal cavernous hemangiomas , although the decision of performing such operations should be taken after thorough analysis of indications ( escalation of symptoms ) and contraindications ( risk of damaging vital retroperitoneal organs with massive bleeding ) .", "because of their initially symptomless course , primary retroperitoneal tumors are usually diagnosed in an advanced stage of the disease , which is the reason for many uncertainties regarding safe surgical resection ." ] ]

[ [ "in the current study , we aimed to evaluate the applicability of the 50-g gct for the detection of gmd in non - diabetic continuous ambulatory pd patients with normal fasting glucose levels .", "the pathogenesis of gmd in pd patients is related to factors such as weight gain and insulin resistance evoked by peritoneal glucose load [ 13 ] .", "the recent data suggest that high glucose exposure from dialysis solution may be a risk factor for vascular calcification in non - diabetic pd patients .", "considering the mentioned similarities , we aimed to examine the utility of the oral glucose tolerance screening test ( 50-g gct ) for pd patients , which is used in a two - step approach to evaluate gestational diabetes . the first step ", "the periodical evaluation of pd patients for gmd is of clinical relevance and should be an element of the surveillance protocol ." ], [ "the study was performed in 20 prevalent patients without history of diabetes before pd treatment onset who had been on a pd program at our institution as their first dialysis modality .", "patients were assessed at the study onset ( on the day of the 50-g gct ) and at the end of pd treatment ( 13 patients ) or at end of the observation period ( december 2012 ) for continuing the pd program ( seven patients ) . at the study onset", "based on fasting insulin and glucose values , insulin resistance ( ir ) was determined according to the homeostasis model assessment insulin resistance ( homa - ir ) .", ", all patients underwent 50-g gct with a glucose dose of 50 g. the test is performed at any time of the day ( the fasting state is not required ) , using 50 g of glucose , and the glucose is measured at 1 h after the administration .", "in addition , the following parameters of glucose metabolism were measured : c - peptide , fasting insulin serum concentration , and the glycated hemoglobin level ( hba1c ) .", "interpretation of our 50-g gct results was as follows : glucose < 140 mg / dl normal value ; 140199 mg / dl impaired glucose tolerance ( igt ) , 200 mg / dl diabetes . \n in case of a fasting glucose value 100125 " ], [ "homa - ir and c - peptide determinations did not correlate with other investigated parameters , i.e. , serum albumin , crp , lipid profile , glucose load in the dialysis fluid , dialysis dose , ultrafiltration , and residual diuresis .", "patients with gmd were recommended a low - carbohydrate diet , lifestyle modification to promote weight loss , and increased physical activity .", "four patients , in whom diabetes was recognized after the first 50-g gct , additionally received short - acting sulphonylurea compounds ( glipizide ) for a few months ( 35 ) , and then , a diet satisfactorily corrected the glucose value .", "all patients who exhibited the highest abnormalities suggesting diabetes in the first gct when retested at the end of the observation achieved a normal range . \n", "igt persisted in eight patients ( 40 % ) , and of particular note , ifg ( 100125 mg / dl ) occurred in four patients ( 20 % ) despite 50-g gct being in the normal range .", "the patients were prospectively observed , and after a median time of 25.8 months , the glucose metabolism evaluation was repeated . during the second 50-g gct ," ], [ "the occurrence of gmd in 75 % of the study subjects representing a small single - center cohort of prevalent pd patients gives a good illustration of the epidemiological dimension of the problem .", "however , the strong correlation with homa - ir can be treated as a sign of preserved excretory pancreatic cells capacity .", "however , we believe that abnormalities revealed by 50-g gct are already of clinical value alerting the patient and physician . it provides a stimulus for preventive measures , which as shown by our experience can be effective , i.e. , the normalization of the test in four patients with the worst results at the onset . the other positive aspect of the current study is supplying evidence that gmd are not inexorably progressive under pd treatment .", "the maintenance of normal glucose metabolism in pd patients is in the context of obtained results a feasible goal .", "discovery of gmd in 75 % of patients with such clinical characteristics highlights the clinical significance of this issue .", "after the first oral glucose load of 50 g , igt was revealed in 11 subjects ( 55 % ) , and a glucose rise suggesting diabetes appeared in four patients ( 20 % ) ." ], [ "the oral glucose challenge screening gct test appears to be a sensitive instrument for the detection of glucose metabolism disorders in pd patients with normal fasting glucose ." ], [] ]

[ [ "using proteins in aqueous solution , we demonstrated that \n the majority of protein formaldehyde adducts and cross - links were \n consistently reversed with mild heating following the removal of excess \n formaldehyde by dialysis .", "consequently , \n we hypothesized that the combined effects of heat and elevated pressure \n would facilitate the rehydration of the highly cross - linked protein \n aggregates in ffpe tissues .", "encouraged by these results , we extracted ffpe mouse liver tissues \n with heat augmented by elevated hydrostatic pressure , with the goal \n of reducing extraction bias , improving the recovery of intact proteins , \n and obtaining tryptic digests that more closely resemble those from \n matched fresh - frozen tissue .", "we then developed \n a tissue surrogate , which consists of one or more proteins that form \n a gel - like plug when treated with formaldehyde at protein concentrations \n exceeding 75 mg / ml . these tissue surrogates have sufficient physical \n integrity to be processed using normal histological methods .", "the increased exposure to water should \n greatly improve protein solubilization while simultaneously promoting \n the reversal of protein formaldehyde adducts and cross - links . \n", "further , some studies report high rates of \n false - positive protein identification and are limited to the analysis \n of tryptic digests of ffpe tissues by liquid chromatography ms \n ( lc ms ) .", "initial physical studies on tissue surrogates supported this hypothesis and suggested that the effect of pressure was \n to reduce the size of protein aggregates through increased water penetration , \n rather than to increase the rate of reversal of protein formaldehyde \n adducts and cross - links directly ." ], [ "the ability \n of elevated hydrostatic pressure combined with heat to improve the \n recovery of proteins from ffpe mouse liver tissue was evaluated using \n two heat - based ffpe proteomic protocols recently reported in the literature .", "matched fresh - frozen and ffpe liver tissue sections \n were analyzed after 30 days , and again after 1 year , of storage .", "recovery experiments , 10 m sections of ffpe mouse liver were \n cleared of paraffin by incubating the sections through two changes \n of xylene for 10 min each .", "separation of the \n digested peptides was performed using nanocolumns prepared in - house \n ( 75 m i.d . packed with jupiter c18 particles , 5 m , 300 \n ) connected to an agilent 1100 nanoflow lc system , which \n was used to deliver binary gradient solvents a ( 0.1% formic acid ( fa ) \n in water ) and b ( 0.1% fa in acetonitrile ) . reversed - phase chromatography \n was performed by solubilizing the lyophilized tryptic peptides in \n 10 l of 0.1% trifluoroacetic acid and injecting 7 l \n of sample per analysis .", "the sections were rehydrated through a \n series of graded alcohols for 10 min each2 changes each of \n 100% ethanol , 85% ethanol , and 70% ethanol and then incubated \n in distilled water for a minimum of 30 min , as described previously .", "the nanoflow reversed - phase lc column was coupled \n online to a linear ion trap mass spectrometer ( ltq , thermoelectron ) \n using the manufacturer s nanoelectrospray source with an applied \n electrospray potential of 1.75 kv and a capillary transfer tube temperature \n of 185 c ." ], [ "few of these measurements are directly obtainable using bottom - up \n proteomic approaches in which proteins are digested into peptides . \n the ability to extract intact proteins from the seemingly inexhaustible \n source of ffpe tissues will increase the diagnostic and prognostic \n efficacy of proteomic - based biomarker discovery by allowing biomarker \n validation using orthogonal methods such as western blotting , immunohistochemistry , \n immunoassays , and structural and interaction proteomics . in this context , \n the > 3-fold increase in the recovery of intact proteins from ffpe \n tissue achieved by using elevated pressure represents a significant \n breakthrough .", "unbiased protein \n extraction and standardized protocols are particularly important with \n techniques such as reverse phase protein arrays ( rppas ) , where the \n protein components of cell signaling pathways are quantified to direct \n clinical treatment of cancer .", "while most \n published proteomic studies of ffpe tissue analyze only a few thousand \n cells from microdissected tissue , the use of elevated pressure has the advantage of improving protein \n extraction from whole tissue sections .", "ffpe tissue extracted with heat alone resulted in the identification \n of 5565 unique peptides and 3449 unique proteins .", "these results are similar to \n those for the matched fresh - frozen mouse liver tissue ( not shown ) . \n" ], [ "the ability of elevated pressure to significantly \n improve the recovery of intact proteins from ffpe tissues over the \n use of heat alone has great potential for broad application to top - down \n proteomic studies for the identification of disease biomarkers .", "virtually all protocols reported in the \n literature for the extraction \n of proteins from ffpe tissue use a variation of the heat - induced antigen \n retrieval technique developed by shi and taylor for the recovery of antigenicity in immunohistochemical \n studies .", "this should allow its integration into a wide \n range of protein extraction protocols for ms - based proteomics with \n little to no alteration to downstream sample preparation and analysis . \n", "this was demonstrated in this report by the successful application \n of elevated pressure to two very different published ffpe protein \n extraction protocols ." ] ]

[ [ "the present study was thus designed to investigate the association between polymorphisms of the vegf gene ( rs2010963 ) and the kdr gene ( rs2071559 ) and markers of carotid atherosclerosis ( such as carotid intima - media thickness ( cimt ) , the number of affected segments of carotid arteries , and the sum of plaques thickness ) in patients with t2 dm .", "however , data about vegf polymorphisms and their possible association with carotid atherosclerosis in patients with diabetes mellitus are limited [ 1820 ] .", "chronic , low - grade inflammation has been demonstrated to be involved in the pathogenesis of atherosclerosis in subjects at high risk to develop cardiovascular disease [ 37 ] . among immune cells infiltrating atherosclerotic lesions , polymorphonuclear neutrophil leukocytes with their products", "moreover , rs2010963 was demonstrated to be associated with several disorders , such as diabetic retinopathy , diabetic nephropathy , myocardial infarction , and impaired prognosis in patients with chronic heart failure [ 1315 , 17 ] . despite these findings ,", "additionally , cimt is highly heritable and associated with stroke and myocardial infarction , making it a promising quantitative intermediate phenotype for genetic studies of vascular disease .", "t2 dm is associated with accelerated progression of atherosclerosis , the major cause of vascular complications leading to increased morbidity and mortality .", "type 2 diabetes mellitus ( t2 dm ) is considered a major epidemic of this century ." ], [ "in addition , the fasting serum vegf levels were analyzed in 70 subjects with t2 dm and in 33 subjects with t2 dm .", "this cross - sectional study included 595 subjects with t2 dm and 200 subjects without t2 dm ( control group ) .", "for the determination of the fasting serum vegf concentration ( isoform vegf 165 ) , a solid phase sandwich elisa using two kinds of high specific antibodies ( hvegf assay kit , ibl co. , ltd .", "thermal cycling employed the following conditions : hot - start enzyme activation ( 15 min at 94c ) , denaturation ( 20 sec at 94c ) followed by 10 cycles of touchdown over 6557c for 60 sec ( dropping 0.8c per cycle ) , and final 26 cycles ( 20 sec at 94c and 60 sec at annealing temperature 57c ) . for rs2071559 ( kdr ) everything was the same with the exception of thermal conditions . hot - start enzyme activation ( 15 min at 94c ) and denaturation ( 20 sec at 94c ) were followed by 15 cycles of touchdown over 5565c for 60 sec ( dropping 0.8c per cycle ) and final 26 cycles ( 20 sec at 93c and 60 sec at annealing temperature 58c ) .", "plaques were defined as a focal intima - media thickening and divided into 5 types according to their echogenic / echolucent characteristics , as previously described . the interobserver reliability for carotid plaque characterization", "the cimt , defined as the distance from the leading edge of the lumen - intima interface to the leading edge of the media - adventitia interface , was measured , as described previously .", "they were selected among patients admitted to the diabetes outpatient clinics of the general hospitals murska sobota and slovenj gradec , slovenia ." ], [ "we did , however , demonstrate an association between the rs2071559 and either cimt or the sum of plaque thickness in subjects with t2 dm ( table 3 ) .", "higher vegf serum levels were demonstrated in subjects with t2 dm with the cc genotype ( rs2010963 ) compared to those with other ( cg + gg ) genotypes ( table 2 ) . moreover , higher vegf serum levels were found in subjects with the cc genotype ( rs2071559 ) compared to those with other ( ct + tt ) genotypes ( table 2 ) .", ", we did not demonstrate any association between the rs2010963 and either cimt , the sum of plaque thickness , the number of involved segments , hscrp or the presence of carotid plaques , or the presence of unstable carotid plaques ( tables 3 and 4 ) .", "the comparison of atherosclerosis parameters was performed with regard to different genotypes of the vegf polymorphism ( rs2010963 ) upon enrolment . in our study", "plasma levels of inflammatory markers ( i.e. , hs - crp and fibrinogen ) were higher in patients with t2 dm compared to controls ( table 1 ) . additionally , there was higher percentage of men , statin therapy , and antihypertensive therapy and lower percentage of smokers in t2 dm group compared to control group ( table 1 ) ." ], [ "in our study , we demonstrated an association between the rs2071559 of kdr and cimt in subjects with t2 dm , whereas we did not demonstrate an association between tested polymorphism of vegf ( rs2010963 ) and cimt .", "variations in the vegf gene were reported to be weakly associated with cimt . none of the single genotyped polymorphisms ( 2578a > c rs699947 ,", "additionally , we also demonstrated an association between the rs2071559 of kdr and the sum of plaque thickness in subjects with t2 dm , whereas no association between tested polymorphism of vegf ( rs2010963 ) and markers of carotid atherosclerosis was demonstrated .", "in contrast to the minor effect of the rs2071559 of kdr and the absence of the rs2010963 of the vegf , an association of either rs2071559 or rs2010963 with mi has recently been reported in caucasians with t2 dm [ 13 , 16 , 24 ] . our present findings and previous reports are additional evidence that markers of carotid atherosclerosis and atherothrombotic events ( i.e. , mi ) are most probably not regulated via similar genetical / biological mechanisms . to conclude , in our study we demonstrated a minor effect of the rs2071559 of kdr on markers of carotid atherosclerosis ( cimt , sum of plaque thickness ) in subjects with t2 dm , whereas we failed to demonstrate an effect of tested polymorphism of the vegf gene ( rs2010963 ) on markers of carotid atherosclerosis" ] ]

[ [ "we describe a young girl , in whom nodular hidradenoma developed at the age of 6 years .", "hidradenomas are benign cutaneous tumors of sweat gland origin , with the clear cell type constituting the most frequent histologic variety . usually , they are diagnosed in the elderly population , the peak incidence being the fifth to sixth decade .", "hence , our case demonstrates that nodular hidradenoma is a rare differential diagnosis of skin tumors , even in the pediatric age group ." ], [ "a 10-year - old girl presented to us with a swelling on the left thigh , which had been progressively enlarging over the preceding 4 years .", "solitary dome - shaped , well - circumscribed tumor over the left thigh photomicrograph showing a well - encapsulated mass composed of solid and cystic portions ( h and e , 40 ) photomicrograph showing a well - encapsulated mass with large cystic spaces within it .", "the solid portion was largely composed of a cell type having finely granular , faintly eosinophilic cytoplasm with a dark - colored round to oval nucleus .", "the cyst was lined by a single layer of cuboidal epithelium without evidence of decapitation secretion [ figure 5 ] ." ], [ "nodular hidradenoma in the pediatric age group is extremely rare it is usually located over the head , neck , and trunk . in our case ,", "however , a case of nodular hidradenoma masquerading as umbilical polyp has been reported in a 1-year - old male child", "our patient was a young girl who presented with a gradually increasing swelling on the lower limb , a site that is unusual for the development of nodular hidradenoma .", "nodular hidradenoma in the pediatric age group is extremely rareit is usually located over the head , neck , and trunk . in our case ,", "clear cell hidradenoma or eccrine acrospiroma of the skin was first described by liu , in 1949 , as clear cell papillary carcinoma of the skin ." ], [ "nodular hidradenoma in the pediatric age group is extremely rareit is usually located over the head , neck , and trunk . in our case ,", "the lesion was present in the lower limbthe presence of an unusually large cystic cavity within the tumoral mass , leading to serous discharge , makes our case even more interesting . \n ", "nodular hidradenoma in the pediatric age group is extremely rare it is usually located over the head , neck , and trunk . in our case ," ], [], [ "nodular hidradenoma in the pediatric age group is extremely rareit is usually located over the head , neck , and trunk . in our case ,", "the lesion was present in the lower limbthe presence of an unusually large cystic cavity within the tumoral mass , leading to serous discharge , makes our case even more interesting . \n ", "nodular hidradenoma in the pediatric age group is extremely rare it is usually located over the head , neck , and trunk . in our case ," ] ]

[ [ "the gothenburg osteoporosis and obesity determinants ( good ) study was initiated with the aim to determine both environmental and genetic factors involved in the regulation of fat mass as previously described ( 23 ) . to be included in the good study , subjects had to be male , 18 to 20 years of age , and willing to participate in the study", "dual - energy x - ray absorptiometry analyses were performed on 610 subjects of the growth chart subsample , whereas abdominal ct scans were performed on 201 ( the ct subsample ) of the 612 study subjects in the growth chart subsample .", "total body fat mass , percentage body fat , total body lean mass , and fat mass of the trunk were assessed using the lunar prodigy dxa ( ge lunar , madison , wi ) .", "complete growth charts with enough data to determine pubertal timing , requiring several height and weight measurements around the pubertal growth spurt , were not available for the complete growth chart subsample used in the present study .", "we have therefore chosen to use measurements of bmi before and after , but not during , puberty .", "growth and weight charts were collected for the subjects of the good study and longitudinal growth was curve fitted according to the infancy - childhood puberty ( icp ) model ( 26 ) as previously described ( 16,27 ) .", "however , the subjects of the ct subsample were slightly younger ( ct subsample 18.7 0.5 years ) than both the subjects of the entire good cohort and the subjects of the growth chart subsample ( p < 0.05 ) ." ], [ "height was measured using a wall - mounted stadiometer and weight was measured to the nearest 0.1 kg as previously described ( 16,23 ) ." ], [ "total body fat mass , percentage body fat , total body lean mass , and fat mass of the trunk were assessed using the lunar prodigy dxa ( ge lunar , madison , wi ) ." ], [ "a previously described ct technique was used to measure the cross - sectional adipose area of the abdomen ( 16,24,25 ) .", "subcutaneous and visceral adipose tissue areas were measured , and then the visceral adipose tissue area was divided into an intraperitoneal and a retroperitoneal adipose tissue area .", "a single slice at the level of the fourth lumbar vertebra was acquired with a general electric high speed advantage ct system ( version rp2 ; ge medical systems , milwaukee , wi ) ." ], [ "complete growth charts with enough data to determine pubertal timing , requiring several height and weight measurements around the pubertal growth spurt , were not available for the complete growth chart subsample used in the present study .", "we have therefore chosen to use measurements of bmi before and after , but not during , puberty .", "growth and weight charts were collected for the subjects of the good study and longitudinal growth was curve fitted according to the infancy - childhood puberty ( icp ) model ( 26 ) as previously described ( 16,27 ) .", "the icp model represents a widely used model for fitting of human growth data to mathematical functions ( 26 ) .", "the variance of young adult body composition parameters ( r ) explained by bmi or bmi z score changes and the corresponding coefficients during childhood and adolescence was calculated using linear regression analyses with age - adjusted adult body composition variables as the dependent variable .", "body composition , including bmi , is greatly influenced by pubertal stage and thereby pubertal timing ( 28 ) ." ], [ "bmi and bmi changes during early and late childhood contributed only marginally to the explanation of the variance in intraperitoneal adipose tissue area , and the corresponding coefficient for the correlation between change in bmi and amount of young - adult intraperitoneal adipose tissue was low ( figs . 1d and f and 2 ) . instead , adolescence was the developmental period when bmi changes started to contribute substantially to the explanation of the variance in amount of adult intraperitoneal adipose tissue , and the corresponding coefficients for the correlations between change in bmi and amount of young - adult intraperitoneal adipose tissue were then higher than seen during early and late childhood ( fig .", "bmi alterations during development reflect changes in fat mass , lean mass , or both . to study the role of childhood bmi and bmi changes for the prediction of different adult body compartments , the associations between bmi during development and age - adjusted adult body composition variables were analyzed . the variance ( r ) in adult total body lean mass explained by bmi as well as the corresponding coefficients for the correlations increased during early childhood , leveled off during late childhood , and increased again during adolescence ( figs .", "bmi increases during adolescence are associated with high adult visceral fat mass in subjects with low , average , and high prepubertal bmi .", "childhood bmi and variance in body composition and fat variables ( bmi [ a ] and bmi change [ b ] ) during early and late childhood .", "bmi increases during adolescence predicted the amount of adult visceral adipose tissue independently of prepubertal bmi ." ], [ "at , adipose tissue ; ip , intraperitoneal ; ns , not significant ; sc , subcutaneous .", "95% cis are given for the coefficients , making it possible to evaluate the differences in relative contribution of the three time periods for each dependent parameter .", "association between childhood bmi between 1 and 10 years of age and young - adult body composition parameters is expressed as accumulated r ( % , c and d ) or coefficients ( sd in adult body composition parameter per sd in bmi at that age , e and f ) .", "correlation between change in standardized bmi during different developmental time periods and adult body composition and fat distribution parameters ( early childhood defined as 14 years , late childhood defined as 410 years , and adolescence defined as 10 years to young adult ) .", "childhood bmi and variance in body composition and fat variables ( bmi [ a ] and bmi change [ b ] ) during early and late childhood .", "variables of adult body composition and fat distribution have been age adjusted . * * * p < 0.01 , * p < 0.05 significant association between the developmental time period and the investigated body composition parameter .", "because interindividual variations in pubertal onset will confound the calculations during adolescence , the predictive role of bmi for each individual year during adolescence for adult bmi and body composition is not shown . instead", "bars indicate coefficient ( 95% cis ) expressed as sd in investigated adult body composition parameter per sd change in bmi during that growth period ." ], [ "bmi alterations during development reflect changes in fat mass , lean mass , or both . to study the role of childhood bmi and bmi changes for the prediction of different adult body compartments , the associations between bmi during development and age - adjusted adult body composition variables were analyzed . the variance ( r ) in adult total body lean mass explained by bmi as well as the corresponding coefficients for the correlations increased during early childhood , leveled off during late childhood , and increased again during adolescence ( figs .", "the variance in adult bmi and the variance in adult lean mass explained by childhood bmi and the corresponding coefficients for the correlations were similar until 4 years of age , when they separated distinctly ( fig .", ", bmi changes during early childhood and adolescence but not during late childhood were major determinants of young adult lean mass .", "the coefficient for the correlation between change in bmi and adult lean mass was higher during adolescence than during late childhood ( fig ." ], [ "bmi changes during late childhood and adolescence , but not during early childhood , clearly predicted young - adult total fat mass and the amount of subcutaneous adipose tissue .", "the abdominal ct measurements revealed that the contribution of bmi during development for the explanation of the variance in young - adult subcutaneous adipose tissue area and the corresponding coefficients for the correlations followed a pattern similar to that of total body fat mass and percentage total body fat , with a distinct increase after 4 years of age ( fig .", "the predictive value of childhood bmi for young - adult percentage total body fat increased substantially during late childhood years , as demonstrated by the fact that the variance in percentage total body fat explained by bmi at 4 years of age was only 1.7% , whereas it was 20.8% at 10 years of age ( fig .", "the prediction of young - adult total body fat mass from bmi and bmi changes during different developmental periods followed a different pattern from that of lean mass .", "to analyze fat distribution in detail , we performed abdominal ct scans ( on a subset of the present good sample [ ct subsample ] , n = 201 ) for measurements of abdominal subcutaneous and visceral adipose tissue areas .", "the coefficients for the correlations were of similar magnitude during late childhood and adolescence but clearly higher than seen during early childhood ( fig .", "the variances in total body fat mass and percentage total body fat explained by childhood bmi and the corresponding coefficients for the correlation were low before 4 years of age , but after 4 years of age , the plotted cumulated variance ( r ) and the corresponding coefficients for the correlation for young- adult total body fat mass and percentage body fat tightly followed the curve displaying the variance of adult bmi explained ( fig ." ], [ "the contribution of bmi during the different developmental periods for the explanation of the variance in amount of young - adult visceral adipose tissue ( intraperitoneal + retroperitoneal adipose tissue areas ) and the corresponding coefficients for the correlations followed a pattern different and clearly distinct from that of total body fat mass and subcutaneous adipose tissue area .", "analyses using weight for age during childhood and adolescence showed , in a manner similar to that seen for bmi for age , clear age - dependent associations with adult fat parameters ( data not shown ) .", "bmi and bmi changes during early and late childhood contributed only marginally to the explanation of the variance in intraperitoneal adipose tissue area , and the corresponding coefficient for the correlation between change in bmi and amount of young - adult intraperitoneal adipose tissue was low ( figs .", ", adolescence was the developmental period when bmi changes started to contribute substantially to the explanation of the variance in amount of adult intraperitoneal adipose tissue , and the corresponding coefficients for the correlations between change in bmi and amount of young - adult intraperitoneal adipose tissue were then higher than seen during early and late childhood ( fig .", "in contrast , analyses of height for age did not show any obvious age - dependent association with fat parameters ( data not shown ) .", "changes in bmi during adolescence , but not during early or late childhood , predicted the amount of adult visceral adipose tissue .", "the results for retroperitoneal adipose tissue were similar as seen for intraperitoneal adipose tissue ( data not shown ) ." ], [ "to further describe the association between developmental changes in bmi and adult fat mass / adipose tissue areas , subjects were divided into groups based on change in bmi z score ( > 1 sd , less than 1 sd , and average bmi z score change ) during the three different developmental time periods ( fig .", "a specific association between high young - adult subcutaneous , but not visceral ( intraperitoneal + retroperitoneal ) , adipose tissue area and increased bmi z score during late childhood is supported by the finding that young - adult visceral adipose tissue area adjusted for total adipose tissue area was clearly reduced in subjects with more than 1 sd increase in bmi z score during late childhood ( fig .", "subjects with more than 1 sd increase were compared with subjects with average change or less than 1 sd decrease in standardized bmi during early childhood ( 14 years of age ) , late childhood ( 410 years of age ) , and adolescence ( 1019 years of age ) .", "thus , the amount of visceral adipose tissue was predicted by large increases in standardized bmi specifically during adolescence , whereas a high amount of subcutaneous adipose tissue area was predicted by increases in bmi during both late childhood and adolescence . the impact of developmental bmi changes for percentage total body fat ( a ) , subcutaneous adipose tissue area ( b ) , intraperitoneal adipose tissue area ( c ) , and visceral ( intraperitoneal + retroperitoneal ) adipose tissue adjusted for total abdominal ( visceral + subcutaneous ) adipose tissue area ( d ) ." ], [ "4 ) . for all three prepubertal bmi groups , subjects with greater increase in adolescence bmi had significantly larger visceral adipose tissue areas ( low prepubertal bmi + 56% , average prepubertal bmi + 53% , and high prepubertal bmi + 57% ;", "we next investigated if bmi increases in subjects with low prepubertal bmi had a similar impact on the amount of adult visceral adipose tissue as seen in subjects with a high prepubertal bmi .", "n for lowest bmi during adolescence ( ) from low prepubertal bmi to high ( left to right ) 9 , 19 , and 39 ; for average bmi during adolescence ( ) low prepubertal bmi to high ( left to right ) 26 , 25 , and 16 ; and for high bmi during adolescence ( ) from low prepubertal bmi to high ( left to right ) 32 , 23 , and 12 .", "bmi increases during adolescence are associated with high adult visceral fat mass in subjects with low , average , and high prepubertal bmi .", "subjects were divided into tertiles according to prepubertal ( 10 years of age ) bmi ( low 15.2 0.8", "bmi increases during adolescence predicted the amount of adult visceral adipose tissue independently of prepubertal bmi .", "data are expressed as means and were analyzed using anova followed by tukey 's post hoc analysis . * p < 0.05 , * * p < 0.01 versus average bmi z score change during adolescence ( ) ; # # p < 0.01 versus low ( ) ." ], [ "the main objective of the present study was to investigate the association between bmi changes during different developmental periods and young - adult fat distribution in a well - characterized cohort of young - adult men .", "both bmi and obesity track strongly from childhood to adulthood ( 79,30,31 ) , but the role for bmi changes during development as predictors of adult body composition and fat distribution is unclear .", "the present study demonstrates that the amount of young - adult subcutaneous adipose tissue was associated with bmi changes both during late childhood and adolescence , although young - adult visceral adipose tissue areas were associated with bmi changes specifically during adolescence .", "our main finding was that the amount of adult visceral adipose tissue was associated with bmi changes specifically during adolescence , whereas the amount of subcutaneous adipose tissue was associated with bmi changes during both late childhood and adolescence .", "we demonstrate that the amount of adult subcutaneous adipose tissue and visceral adipose tissue was associated with bmi changes during distinct developmental periods ." ] ]

[ [ "this study is aimed at testing the efficacy of hyaluronan gel as an adjunct to caf in root coverage .", "however , evidence regarding the beneficial impact of these procedures on the stability of root coverage is inconclusive .", "hence despite sctg being the gold standard for root coverage research is always aimed at finding a suitable alternative to this procedure to reduce patient morbidity .", "key factors in the treatment of gingival recession are to prevent the progressive marginal tissue recession and to facilitate plaque control in the affected area .", "this procedure has been modified by many others with an intention to improve the stability and predictability of this technique . in a recent 14 year follow - up study pini prato et al ." ], [ "a total of 20 buccal gingival recession sites in 10 patients were considered for the study .", "( d ) postoperative 1-week in the control site ; ( e ) postoperative 24 weeks in the experimental site ; ( f ) postoperative 24 weeks in the control site in the experimental group , hyaluronan gel ( gengigel 0.2% ) applied on the root surface using a sterile instrument prior to flap advancement and suturing [ figure 1b ] whereas in the control group the flap was advanced coronally without application of ha gel .", "the study sample included 10 subjects of which seven are male , and three female ( at least 20 sites ) having miller 's class i gingival recession on the canine and premolar region were recruited from department of periodontics , coorg institute of dental sciences .", "this was a randomized clinical trial with split mouth study design , carried out in the postgraduate clinic of department of periodontics , coorg institute of dental sciences , virajpet .", "both experimental group and control group sites were evaluated postoperatively at 1 , 3 , 6 , 12 , and 24 weeks after surgery [ figure 1e and f ] .", "the rd was assessed at baseline , 1 , 3 , 6 , 12 and 24 weeks , and the pd and cal were recorded at 12 and 24 weeks with the patients consent .", "the sites were randomly assigned to the control group or the test group using a flip coin technique immediately before surgery ." ], [ "the patients who were selected and gave their approval for the surgical intervention were educated and motivated with more emphasis on proper oral hygiene maintenance . all the patients underwent the initial phase of treatment of thorough scaling and root planning ." ], [ "( d ) postoperative 1-week in the control site ; ( e ) postoperative 24 weeks in the experimental site ; ( f ) postoperative 24 weeks in the control site in the experimental group , hyaluronan gel ( gengigel 0.2% ) applied on the root surface using a sterile instrument prior to flap advancement and suturing [ figure 1b ] whereas in the control group the flap was advanced coronally without application of ha gel .", "in addition a mesiodistal and apical dissection parallel to the vestibular lining mucosa was performed with a blade to release residual muscle tension and to facilitate the passive coronal displacement of the flap .", "suturing of oblique releasing incisions was performed , with 5 - 0 ethicon nonresorbable sutures , while the coronal mesial and distal extremities of the flap were secured by two single sutures placed in the interdental areas [ figure 1c ] .", "( a ) horizontal and vertical incisions given in relation to 23 ; ( b ) hyaluronan gel applied on the root surface of experimental site ; ( c ) suturing done .", "additional interrupted sutures were applied , when necessary , to close the oblique releasing incisions in the alveolar mucosa .", "this incision was horizontally extended to the adjacent papillae avoiding the gingival margin of the adjacent teeth ." ], [ "immediately following surgery , use of ice packs was recommended for 3 h. all patients were instructed to discontinue tooth brushing , avoid trauma around the surgical site . in the event of pain ,", "three weeks after surgery , the patients were instructed to resume mechanical tooth cleaning of the treated areas using a soft toothbrush with a careful roll technique .", "adverse effects such as inflammation , bleeding on probing , pain and abscess formation were assessed postsurgically by first examiner ( ms ) .", "the patients were instructed to clean the surgical sites with a cotton pellet soaked in a 0.2% chlorhexidine digluconate solution twice daily for 10 days .", "a 0.2% chlorhexidine digluconate solution rinse was prescribed 2 times ( 60 s ) daily for the first 10 days ." ], [ "both experimental group and control group sites were evaluated postoperatively at 1 , 3 , 6 , 12 , and 24 weeks after surgery [ figure 1e and f ] .", "the patients were recalled for collection of data at 1 , 3 , 6 , 12 and 24 weeks using prefabricated acrylic stent .", "stent made of acrylic was used to standardize the direction and position of the probe . on each visit ,", "the area was checked for meticulous plaque control , but no subgingival instrumentation was performed until the 6 week ." ], [ "a total of 20 buccal gingival recession sites in 10 patients were considered for the study .", "in addition , the effects of constant covariates and covariate interactions between - subjects factors can be included .", "the descriptive procedure displays univariate summary statistics for several variables in a single table and calculates standardized values ( z scores ) . using the general linear model procedure , null hypotheses about the effects of both within and between the subject factors", "the values obtained were tabulated and statistically analyzed using student 's t - test and repeated measure anova tests .", "all the statistical methods were carried out through the statistical package for the social sciences ( spss ) for windows ( version 16.0 ) ." ], [ "mean probing pocket depth ( ppd ) in experimental sites at baseline was 1.8 0.42 mm , and in control sites it was 2.0 0.47 mm . at the end of 24 weeks", "the percentage of root coverage for experimental and control group was 68.33% 28% and 61.67% 30.22% , respectively [ table 5 and figure 5 ] .", "descriptive analysis of two groups mean recession depth values plotted against time for experimental and control groups percentage of root coverage comparison of mean percentage of root coverage between control ( c ) and experimental ( e ) group at 24 weeks , the change in rd was statistically significant ( p = 0.00 ) in both groups [ tables 6 and 7 ] .", "descriptive analysis of two groups mean probing pocket depth values plotted against time for experimental and control groups results of repeated measure anova for ppd for between experimental and control groups clinical attachment level had a significant gain and stability , at 24 weeks follow - up both groups .", "cal gain was significant for both groups , but no intergroup difference was reported at 12 months [ table 3 and figure 3 ] .", "results of repeated measure anova for rd for experimental group results of repeated measure anova for rd for control group" ], [ "the present study was conceived in an effort to merge two simple and cost effective techniques to achieve better root coverage .", "hyaluronan as previously mentioned has been extensively studied in the field of dentistry , but to the best of our knowledge , there is no published data on the usage of ha in the treatment of root coverage procedures .", "it has been used extensively in the field of dentistry for its various beneficial applications . in periodontics", "the clinical stability of the root coverage achieved after 24 weeks in this study supports this aspect of previous studies .", "it has been used to treat gingivitis and periodontitis and more recently in the treatment of periodontal intra bony defects ." ], [ "this study shows that hyaluronan affects treatment outcome when used as an adjunct to caf procedure .", "although results are not statistically significant , clinically experimental group shows better results as compared to the control group .", "though caf gives 100% coverage immediately following the surgery only 61 - 64% can be expected 24 weeks after surgery .", "hyaluronan can be easily combined with caf procedure in compromised cases and situations where more stable results are desired ." ] ]

[ [ "the aim of this study is to explore the pharmacokinetic differences of the four flavonoids after oral administration of pure baicalin , radix scutellariae extract and scutellariae - paeoniae couple extract to rats and to compare the pharmacokinetic parameters of uc rats with those of normal rats .", "however , to the best of our knowledge , there are no published studies reporting the pharmacokinetics of bg , wg , b , and w after oral administration of pure baicalin , radix scutellariae and scutellariae - paeoniae couple extracts to normal rats , let alone to uc rats .", "radix scutellariae has been widely used in traditional chinese medicine ( tcm ) for the treatment of inflammation , fever , hepatitis , allergic diseases and hypertension , and is comprised of the flavonoids , baicalin ( bg ) , wogonoside ( wg ) , baicalein ( b ) and wogonin ( w ) as the active ingredients ( figure 1 ) ( 24 ) . to date , the pharmacokinetic ( pk ) profiles of bg and wg in plasma , brain and eyes of rats and rabbits have been reported ( 511 ) .", "the syndrome of the trinitro - benzene - sulfonic acid)tnbs(-induced colonitis model is similar to the spontaneous uc ." ], [ "successful replication of the model of uc was characterized by reduction in activities , apathy and occult blood in stool .", "preparation of radix scutellariae and scutellariae - paeoniae couple extracts \n \n radix scutellariae and radix paeoniae alba were mixed in the ratio of 1.5 : 1 g / g and the total weight was 200 g. the mixture was decocted twice by refluxing with 70% ethanol ( 1 : 10 and then 1 : 8 w / v ) for 1 h , and the solution obtained was concentrated to give an extract of 60.5 g. radix scutellariae ( 200 g ) was treated as above to provide an extract of 43.3 g. the dried powder was stored at 4 c before use . for estimation of the administered dose , the concentrations of baicalin , wogonoside , baicalein and wogonin in the extracts and pure baicalin", "apparatus and chromatographic conditions \n the concentrations of the four flavonoids in plasma were assayed using reverse - phase high performance liquid chromatography ( agilent 1100 series ) equipped with a variable wave length uv detector and pump ( agilent model g1314a vwd ) .", "the stabilities of baicalin , wogonoside , baicalein and wogonin were determined by analyzing qc samples at three concentrations exposed to encounter during sample storage .", "biosample collection \n the uc rats were divided into three subgroups randomly , the pure baicalin , radix scutellariae extract and scutellariae - paeoniae couple extract subgroup .", "each group was respectively administrated an oral dose of 200 mg / kg baicalin ( in the form of pure compound or co - administrated mixture , 0.21 g / kg pure baicalin , 0.46 g / kg radix scutellariae extract and 1.16 g / kg scutellariae - paeoniae couple extract ) , all of the compounds were suspended in water and homogenized using ultrasonic technology just prior to dosing ." ], [ "the findings of this study demonstrated that the pharmacokinetic behaviors of baicalin and wogonoside were remarkably altered in uc rats .", "scutellariae - paeoniae couple extract may exert more effectiveness than pure baicalin or radix scutellariae extract .", "the present study demonstrated that herb extract could enhance the bioavailability of baicalin and wogonoside in rat plasma , a significant drug - drug interaction may occur and improve the absorption of baicalin and wogonoside when radix paeoniae alba is administered in combination with radix scutellariae ( 35 ) . either in uc or in normal rats , baicalin and wogonoside demonstrated bimodal phenomenon in rat plasma after oral administration of pure baicalin , radix scutellariae or scutellariae - paeoniae couple extracts ( figure 3 ) .", "pharmacokinetics of baicalin and wogonoside after oral administration of pure baicalin , radix scutellariae and scutellariae - paeoniae couple extracts to rats . \n ", "it proves the rationality of using scutellariae - paeoniae couple for the treatment of ulcerative colonitis disease .", "comparative pharmacokinetics of baicalin and wogonoside after oral administration of pure baicalin , radix scutellariae and scutellariae - paeoniae couple extracts between uc and normal rats \n from figure 4 and table 1 - 2 , it was noteworthy that uc rats showed better absorption than normal rats , regardless of oral administration of pure baicalin , radix scutellariae or scutellariae - paeoniae couple extracts ." ], [ "in summary , the results of the present study highlighted that drug drug interactions , herb drug interactions and herb herb interactions always existed and affected the pharmacokinetic behavior of herbal ingredients . statistically significant differences ( p < 0.05 ) in pharmacokinetic parameters of baicalin and wogonoside including cmax and auc(0t ) were obtained among the rats orally administered pure baicalin , radix scutellariae or scutellariae - paeoniae couple extracts .", "baicalin and wogonoside had a better absorption effect , which would improve the therapeutic efficacy .", "we need to take caution when extrapolating pk and exposure data from healthy animals to diseased animals in designing pharmacological studies .", "the huge number of active ingredients in tcm made them suitable for multi - target actions ." ] ]

[ [ "similar \n correlation of egfr with ccr was reported by khosla , et al . , although the analyzed patients were \n restricted to the population with a difference between two measurements of ccr of less than \n 25% . to clarify the actual utility of egfr in peritoneal dialysis practice", "weekly creatinine clearance ( wccr ) and kt / v are well - known parameters reflecting dialysis \n dose and adequacy , and are applied to adjustment of the dialysis menu in each patient who \n undergoes peritoneal dialysis ( pd ) . however , the limitations of these parameters in \n predicting survival and morbidity have been reported .", "we reported that egfr was well correlated with tccr in pd patients by cross - sectional \n analysis .", ", we retrospectively \n collected the data from 21 pd patients at ja toride medical center for the period of one \n year .", "but it was also reported that eccr calculated by the \n cockcroft - gault formula substantially overestimated the effect of age on creatinine \n excretion in pd patients .", "estimated glomerular filtration rate ( egfr ) is an alternative marker for measured gfr \n ( mgfr ) , and it might be a possible indicator for prognosis in the general population without \n known cardiovascular disease , diabetes or kidney disease and in ckd patients included in the modification of diet in \n renal disease ( mdrd ) study", "moreover , the collection of urine and peritoneal effluent \n is cumbersome work not only for patients , but also for medical staff ." ], [ "pd patients with a treatment period \n of less than a year , and patients who underwent combined pd and hemodialysis ( hd ) therapy \n were excluded . to measure renal ccr ,", "the serum , urine , and effluent cr were measured by the established enzyme method . the formula proposed by the japanese society of nephrology", "the sum of the peritoneal and renal ccr was defined as the measured tccr . \n", "urine was collected for 24 hours ( from the second voiding of the day \n before visiting the hospital to the first voiding on the day of visiting the hospital ) .", "pd \n effluent was also collected for 24 hours on the day before visiting the hospital to measure \n peritoneal ccr .", "patients who underwent pd at ja toride medical center for one year or longer were enrolled \n in the study after their informed consent was obtained .", "was applied for calculation of egfr as follows : egfr ( ml / min/1.73 m ) = 194 serum cr age \n ( 0.739 in females ) protein catabolic rate ( pcr ) was calculated by the formula proposed by teehan as follows : pcr ( g / day ) = 6.25 ( urinary urea excretion + peritoneal urea excretion + 1.39 + 0.15 + \n 0.031 body weight in kg ) ." ], [ "continuous ambulatory pd ( capd ) was undertaken in 13 patients , and the other eight patients \n received automated pd ( apd ) . during the period of one year from november 2010 to october \n 2011 , 114 data sets of egfr and tccr from the 21 patients were suitable for data analysis . \n according to the analysis , egfr and tccr were correlated ( r. = 0.435 in figure 1figure 1egfr and tccr .", "total cr excretion and npcr were also correlated with \n each other in total samples .", "differences between egfr and tccr were \n well correlated with total cr excretion in total samples .", "variations in the difference between egfr and tccr were correlated with both \n total cr excretion and npcr . tccr - egfr difference and total cr excretion .", "variations in the difference between egfr and tccr were correlated with both \n total cr excretion and npcr .", "- egfr difference and npcr ( a ) and total cr excretion and npcr ( b ) in one \n patient who showed fluctuating diet intake .", "the open circles in the plotted data were obtained from one patient \n who denied the habitual intake of creatine supplements , such as creatine \n monophosphate , but poorly complied with the diet therapy . tccr - egfr difference and npcr ( a ) and total cr excretion and npcr ( b ) in one \n patient who showed fluctuating diet intake . more detailed data from the patient , \n exhibited as open circles in figure 1 are \n shown .", "differences between egfr and tccr were \n well correlated with total cr excretion in total samples . ) and npcr ( r. = 0.636 in figure 4figure 4tccr - egfr and npcr ." ], [ "this feature may be valuable in routine \n clinical practice , and it is worth investigating the significance of egfr as a possible \n prognostic factor in pd patients , as reported in pre - dialysis patients , \n .", "this retrospective study with the data collected for a year from 21 pd patients showed that \n the correlation of egfr with tccr was less than that of a previous cross - sectional \n study .", "the difference \n between tccr and egfr was mostly dependent on total cr excretion , as reported in \n pre - dialysis patients , but \n this has never been reported in pd patients . moreover , total cr excretion fluctuated \n according to the npcr .", "although the peritoneal clearance of small solutes represented by \n creatinine should be taken into consideration in pd patients , egfr derived from serum creatinine , age and \n gender may diminish the compensatory fluctuation of small solute clearance in the kidney , \n and provide a more stable level in each pd patient .", "consequently , protein intake estimated by npcr may affect the \n difference between tccr and egfr . because creatinine is homogeneously distributed in the body water , serum creatinine level \n is determined by the balance of several factors , such as oral intake , generation in the \n muscle , intrinsic degradation ( metabolic clearance ) and clearance by peritoneal dialysis and \n the kidney ( figure 6figure 6considerable factors determining serum cr levels .", "it is possible \n that egfr has a similar independency and distinct feature as a predictive indicator even in \n pd patients ." ], [ "this study revealed the practical profile of egfr , distinct from tccr , as a more stable \n marker for small solutes clearance by dialysis and the kidney .", "a more extended and \n longitudinal study will be needed to verify the actual value of egfr in pd practice ." ] ]

[ [ "mesenchymal stem cells ( mscs ) , also referred to as multipotent mesenchymal stromal cells , have been a focus of recent research , partially because they are an extraordinary model for investigating the biological mechanisms that allow a cellular population to generate diverse cell types and because they are a potential tool in cellular therapies for several clinical applications .", "this review addresses current knowledge of the biological aspects involved in msc immunoregulatory capacity and the clinical focus of these characteristics that allows these cells to be used in the treatment of several diseases with an immune component involved .", "several studies have demonstrated that mscs possess an immunoregulatory function in vitro and in vivo and that this property suggests clinical applications in the regulation of immunocompetent cell responses [ 2 , 3 ] .", "mscs can differentiate into mesenchymal lineages and secrete cytokines and growth factors with paracrine effects that favor the regeneration of damaged tissues [ 1 , 2 ] .", "this review culminates with a clinical description of the diseases treated with mscs as a component of cell therapy procedures ." ], [ "the current understanding is that , in addition to diverse mesodermal differentiation capacity , msc benefits arise primarily from the secretion of trophic factors and immunoregulatory capacity [ 13 ] .", "mscs cultivated in vitro possess three biological properties that qualify them for use in cellular therapy : ( a ) broad potential of differentiation , ( b ) secretion of trophic factors that favor tissue remodeling , and ( c ) immunoregulatory properties .", "mscs are adult stem cells that are initially isolated from bone marrow ( bm ) and can generate stromal bm components , such as adipocytes , reticular cells , and osteoblasts , whereas in conjunction with additional cellular components , mscs maintain hematopoiesis .", "because of this potential for differentiation , mscs were initially used in the treatment of imperfect osteogenesis and myocardial damage .", "the benefits observed in these initial cell therapy protocols were thought to be the result of osteogenic and myogenic differentiation ." ], [ "below , we describe the immunoregulatory effects of mscs on specific immune cells with special emphasis on the effect of mscs on t lymphocytes because of their role as effector cells in many diseases with an immune component .", "mscs profoundly affect immune response through their interactions with the cellular components of the innate ( natural killer cells ( nk ) ) and adaptive ( dendritic cells ( dcs ) , b lymphocytes , and t lymphocytes ) immune system .", "because of these properties , mscs can prevent the inappropriate activation of t lymphocytes and generate a tolerogenic environment during wound repair or stop an immune response during healing , thus contributing to the maintenance of immune homeostasis [ 2 , 3 ] .", "msc immunoregulation can occur through cellular contact and/or the secretion of diverse factors [ 1317 ] .", "nk cells are important in innate immunity and participate in the body 's defenses against infections and cancer ." ], [ "the importance of an inflammatory environment for msc immunosuppressive capacity has been shown both in vitro and in vivo .", "many studies suggest that mscs and immune cells have established two - way regulatory mechanisms ; thus , the activation of msc immunoregulatory properties requires the presence of derived proinflammatory cytokines from immune cells .", "this evidence suggests that bidirectional regulatory mechanisms drive the interaction between mscs and nk cells .", "in vivo studies in mouse models suggest that mscs are effective in the treatment , but not prevention of gvhd .", "broad evidence demonstrates that this activation requires the presence of proinflammatory cytokines derived from t lymphocytes , macrophages , and nk cells , thus indicating that there are bidirectional regulatory mechanisms between mscs and immune cells .", "the activation of tlrs is essential to initiate an innate immune response and supports the adaptive immune response ." ], [ "a different study comparing uc- , ucb- , pl- , and wj - derived mscs observed differences in the capacity to express hla - g or tgf1 after activation with ifn. there were no differences observed in ido secretion .", "it is important to pursue comparative studies to determine whether mscs from alternative sources operate with the identical immunoregulatory mechanisms as bm - mscs , which are used in cellular therapy .", "some reports have compared the immunoregulatory properties of mscs from different sources to determine which is the most viable for bm replacement . in this", "the inconsistency of the results observed in clinical application of pl - mscs could be related to the inconsistent results obtained in vitro by various groups .", "regard , our research group has demonstrated that mscs from bm and ucb , have identical immunoregulatory capacity .", "however we have shown , in the same way as other groups , that in contrast to bm - mscs , pl - derived mscs have a lower capacity [ 24 , 107 ] ." ], [ "the beneficial effects of mscs administration regarding several of the aforementioned diseases have been analyzed in animal models and phases i , ii , and iii clinical studies have been initiated [ 115 , 116 ] . in the following sections , we focus on the use of mscs in the treatment of immune - associated diseases with special emphasis on the treatment of gvhd . because of their immunoregulatory properties , bm - mscs have been applied principally in hsc transplants because mscs are capable of treating and preventing gvhd [ 89 , 117119 ] .", "mscs are potentially applicable to many diseases , such as gvhd , autoimmune diseases and bone , cartilage , and cardiovascular diseases .", "the use of stem cells to replace cells and tissues damaged by congenital or degenerative disease or trauma is called stem cell therapy . in such procedures ,", "we previously outlined that mscs have three biological properties that make them potential candidates for this use : high differentiation potential , trophic factor secretion , and immunoregulatory capacity .", "after hsc transplant , gvhd presents when donor t lymphocytes recognize patient hla molecules ( alloantigen ) as nonself and mount an immune response ( allogeneic immune response ) .", "several of such studies , analyzing the efficacy and safety of autologous or allogeneic mscs for the treatment of ms and als , are in progress [ http://www.clinicaltrials.gov/ ] ." ], [ "bm - derived mscs have an immunoregulatory capacity because they can regulate the function of multiple immune system components . to fulfill this role , mscs must be activated by proinflammatory cytokines such as ifn. mscs can inhibit dcs maturation and thus prevent the activation of t lymphocytes and even more and decrease the proliferation and cytotoxic activity of nk cells . as a result of these characteristics , mscs are a promising alternative treatment for immune - related diseases .", "it is necessary to perform more clinical trials that extend the current knowledge of the biology of msc immunoregulatory activity to optimize and control the patient 's immune response for maximum benefits .", "currently , mscs have been used in the treatment of autoimmune diseases , including gvhd , and have rendered positive results . despite this encouraging debut in clinical application ,", "these studies will be relevant to clinical decisions in the treatment of gvhd , autoimmune diseases , and other illnesses with an immune component , such as cancer , in which mscs play an important role in the tumor microenvironment that favors growth as our group has previously demonstrated ." ] ]

[ [ "carpal instability is broad category consisting of various patterns of injury , with dissociative type more common ." ], [ "patient had sustained a closed distal one -third both bones fracture forearm fixed with k -wire , and volar lunate instability was found during sequential follow -up .", "a 13 -year -old boy presented at 6 months following a fall with restriction of wrist movements ." ], [ "posttraumatic carpal instability should be identified at the earliest to avoid poor hand function and morbidity associated with it ." ], [ "volar intercalated segment instability ( visi ) is a less common manifestation of dissociative carpal instability .", "lunate plays a pivotal role and acts like an intercalated segment in carpal stability , loss of anchorage of this key structure cause intercalated segment instability .", "carpal instability and its biomechanics have always been evolving due to the advancement in the field of radiology and arthroscopy ." ], [ "serial radiographs during follow - up showed a volar facing lunate with alteration of scapholunate and lunatocapitate angle and was diagnosed with a volar intercalated lunate instability ( fig .", "( b ) volar facing lunate with loss of alignment between radius , lunate and capitate .", "( a ) radiograh of right wrist at 1 year follow - up , post - anterior view and ( b and c ) lateral views , ( a ) showing healed distal one - third radius and ulna fracture , signet ring sign of scaphoid and moon like appearance of lunate .", "( a ) radiograph of both wrists lateral view left and ( b ) right at 6 month follow - up showing volar facing lunate with loss of carpal alignment .", "loss of gilula arc with flexed scaphoid suggesting carpal instability at 6-month follow - up .", "( a ) post - operative radiograph of right wrist posterior - anterior and ( b ) lateral view showing reduced distal one - third radius and ulna fracture with implants in situ .", "open reduction and k - wire fixation was performed for both bone fracture forearm ( fig ." ], [ "carpal instability should be considered as a differential in patients presenting with chronic wrist pain and restricted movements following trauma .", "classified carpal instability into four categories and lunato - triquetral ligament is involved in stage three which leads to volar lunate instability .", "visi is a condition in which there is pathologic volar flexion of the lunate , with or without a similar posture of the other proximal row carpal bones ." ], [ "wrist function is a complex interaction of various biomechanics involving the carpal bones , ligaments , and the distal radio - ulnar complex .", "awareness of carpal instability associated with fractures or injuries around the wrist is needed by the treating surgeon to avoid delay in diagnosis and treatment . to suspect visi following a wrist injury and also following reduction with k - wire fixation .", "follow - up of patient at regular intervals to prevent morbidity due to this deformity ." ] ]

[ [ "we sought to study the use of podocyturia to diagnose preeclampsia and differentiate it from other conditions that may have a similar presentation in a high risk pregnancy population .", "\n preeclampsia is a disorder affecting 5 to 10% of pregnancies and is clinically characterized by new - onset hypertension and proteinuria . despite significant progress in our understanding of preeclampsia , there is a need for a reliable diagnostic biomarker for use in clinical practice . in the search for a biologically plausible biomarker , there have been attempts to reconcile clinical findings with pathologic changes in renal biopsies of preeclampsia . for example , renal pathology of preeclampsia in the kidney is classically described as endotheliosis , or swelling of endothelial cells in the glomerulus .", "studied the use of podocytes in the urine ( podocyturia ) as diagnostic markers and found podocyturia to be highly sensitive and specific for preeclampsia .", "furthermore , podocyturia was found frequently in other high risk pregnancy states such as chronic hypertension and gestational diabetes .", "furthermore , there is evidence that selected podocyte - specific proteins such as nephrin , synaptopodin , and glepp-1 are downregulated in preeclampsia , while vegf and flt-1 are increased [ 2 , 3 ] ." ], [ "\n we recruited two groups of patients all 18 years of age : uncomplicated pregnant subjects ( control group ) and women at risk for pregnancy complications ( high - risk group ) as described below from the obstetric inpatient service at jacobi medical center , bronx , ny , usa . random urine samples", "inclusion criteria for high - risk group were diagnosis of preeclampsia , chronic hypertension ( htn ) , gestational htn , type i and type ii diabetes mellitus ( dm ) , gestational dm , mixed connective tissue disease , and pregnancies with fetal chromosomal abnormalities .", "urinary protein was quantified either from a 24-hour urine sample collection or extrapolated from a random urine dipstick .", "for example , when only a dipstick urine protein was available , the value was extrapolated to a 24-hour value based on the following : negative protein corresponds to less than 150 mg/24 hours , trace protein corresponds to 150 mg/24 hours , 1 + corresponds to about 200500 mg/24 hours , 2 + to 0.51.5 g/24 hours , and 3 + to 25 g/24 hours .", "gestational dm was defined as any degree of glucose intolerance with onset of first recognition during pregnancy .", "diagnosis of preeclampsia fulfilled the criteria of new onset of htn with blood pressure of 140/90 mmhg after 20 weeks of gestation and proteinuria of > 300 mg of protein in a 24-hour urine specimen or 1 + protein on a urinalysis sample without evidence of another cause , such as urinary tract infection or inflammation ." ], [ "podocyturia ( figures 1(a ) and 1(b ) ) was present in 11 out of 29 ( 38% ) patients with preeclampsia / eclampsia , 3 out of 9 ( 33% ) with chronic and gestational htn , and 3 out of 6 ( 50% ) with gestational dm and type i / ii dm ( table 2 ) . among patients categorized as ", "the negative predictive value , however , was poor for preeclampsia at 51% , as compared with 83% and 91% for htn of any type and dm of any type , respectively .", "the positive predictive value was 57% for preeclampsia , as compared with 15% for both htn of any type and dm of any type .", ", 2 ( marginal previa and chromosomal anomaly ) out of 3 patients exhibited podocyturia ( 66% ) . in contrast , 0 out of 9 patients ( 0% ) with uncomplicated pregnancies demonstrated podocyturia . based on these findings", ", we calculated the sensitivity and specificity of podocyturia for preeclampsia to be 38% and 70% , as compared to women of htn of any type , in whom it was 33% and 66% , respectively ( table 3 ) .", "the sensitivity and specificity for dm of any type were 50% and 68% , respectively .", "the diagnoses at time of urine collection were as follows : preeclampsia ( n = 28 ) , eclampsia ( n = 1 ) , chronic hypertension ( n = 3 ) , gestational hypertension ( n = 6 ) , type i dm ( n = 1 ) , type ii dm ( n = 1 ) , gestational dm ( n = 4 ) , connective tissue disorder ( n = 1 ) , marginal previa ( n = 1 ) , chromosomal anomaly ( n = 1 ) , and uncomplicated pregnancy ( n = 9 ) . the clinical characteristics of all subjects are described in table 1 ." ], [ ", we sought to describe the presence of podocyturia in preeclampsia and other high risk pregnancy states using the podocyte marker synaptopodin for identification .", "podocyturia is well described in many glomerular diseases such as type i dm , iga nephropathy , lupus nephritis , and membranous nephropathy [ 5 , 6 ] .", "though endothelial injury is thought to be the main lesion in preeclampsia , more recently , derangements of the podocyte with downregulation of selected podocyte - specific proteins in renal biopsies and presence of nephrin and podocalyxin ( podocyte specific proteins ) in the urine have been described [ 2 , 7 ] . in this study", "thus , the utility of urinary podocytes to detect ongoing glomerular damage in women with preeclampsia as previously suggested is unclear .", "thus , a specific marker that is discovered through our understanding of the pathophysiology of preeclampsia remains crucial ." ], [ "our goal was to confirm the previously shown high sensitivity and specificity of podocyturia in preeclampsia .", "though a larger sample size would be ideal , we feel that of our total sample size of 56 with 29 patients diagnosed with preeclampsia / eclampsia , and 18 patients with other high - risk diagnoses , is an adequate sample size to demonstrate that podocyturia lacks sensitivity and specificity to be a diagnostic marker of preeclampsia ." ], [ "however , our findings raise an important note of caution of relying on the limited findings in the literature regarding the predictive value of podocyturia in preeclampsia and encourage larger studies .", "we discovered that podocyte loss is present not only in preeclampsia but in other high risk pregnancy states .", "in addition , podocyturia was not found in a majority of patients diagnosed with preeclampsia .", "given our current knowledge of the complex pathophysiology of the disease such as the significant role of vascular endothelial growth factor ( vegf ) signaling in maintaining a healthy endothelium and cross talk between the podocyte and vascular endothelial cell , it is unlikely that any single test or cell type will be able to predict preeclampsia ." ] ]

[ [ "the increasing prevalence of chronic diseases , the very different but constant environmental challenges faced by people in the developing and developed world alike , provide us with constant salutogenetic opportunities .", "illness is a challenge to our physical , psychological and spiritual wellbeing that has repercussions on our identity and our social context . in a pathogenetic approach ,", "each medical intervention should aim to strengthen soc and a person s physiological , psychological and spiritual resilience .", "health is therefore a concept that goes beyond the absence of disease to include physical , mental and social wellbeing .", "a salutogenetic healthcare system needs to be oriented in such a way that illness is considered an adverse event that can become the foundation for better future health ." ], [ "salutogenetic parameters such as the quality of life of patients and caregivers , sustainable change , treatment satisfaction , job satisfaction and prevention of burn - out need to be assessed as well as cost - effectiveness and technological excellence .", "it broadens the technological advances of biomedicine with the epistemological approach , the relationship - based care and the salutogenetic treatments of non - conventional medicine .", "complementary and alternative medicine ( cam ) and traditional medicine ( tm ) are grouped together as cam / tm or non - conventional medicine ( ncm ) .", "salutogenetic healthcare practices are personalised using the principles and methods of person - centred medicine . in salutogenetic healthcare the caregiver - person relationship", "person - centred medicine ( pcm ) takes into account the physical , psychological and spiritual aspects of a person in health and illness in order to individualise health promotion practices , diagnosis and treatment .", "each professional role needs to be developed to provide salutogenetic care from as early as undergraduate training . in order to have a person - centred approach , technological proficiency , solid grounding in evidence - based medicine ( ebm ) and knowledge of international protocols need to be complemented by knowledge of the epistemological systems and practical tools of ncm ." ], [ "encouraging locally sourced , high quality foods , encouraging biodiversity and fair - trade , has positive effects on the sustainability of primary resources and the stability of the eco - system as well as people s health . in order to be adopted by individuals in their lifestyles ,", "health education is both a therapeutic intervention and the key form of disease prevention in salutogenetic healthcare .", "this can be applied to overcome future challenges or unknown life - situations with strengthened soc .", "people learn new skills and their achievements have a positive effect on their self - esteem .", "it should take place at population levels , in primary care , in hospitals , as part of any rehabilitation process , in schools and families .", "these are peace , shelter , education , food , income , a stable eco - system , sustainable resources , social justice , and equity . at the same time , individuals need to be encouraged to actively increase control over their health in order to improve it . to reach a state of complete physical , mental and social well - being , an individual or group must be able to identify and to realize aspirations , to satisfy needs , and to change or cope with the environment ." ], [ "the initial steps towards a salutogenetic healthcare reform , are to broaden undergraduate training and to develop pilot projects in the fields of health promotion and salutogenetic rehabilitation . the person and the caregiver - person relationship needs to be placed at the centre of the therapeutic process through the principles of person - centred medicine both in education and in practice .", "medical interventions should not only be aimed at removing the disease but also at improving health by strengthening a person s soc and their resilience at physical , psychological and spiritual levels . reasons for illness can be explored during rehabilitation . through health promotion programmes , during rehabilitation , in education , people are taught how to take better care of themselves by adopting individually tailored , healthier lifestyles better suited to their own physiological , emotional and personal needs .", "methods for the scientific investigation of effects on small numbers or single cases need to be included in the evaluation of a person - centred , salutogenetic healthcare system alongside ebm .", "active involvement needs to be encouraged both on the part of the to patient and healthcare giver , the use of clinical judgment needs to be taught .", "caregivers need to be given the tools to consider the person in all their aspects and characteristics through the adoption of the epistemological basis of ncm that broadens the technological advances of biomedicine ." ] ]

[ [ "recent studies have also examined potential cross - talk between the signaling pathways that regulate autophagy and those that regulate distinct forms of regulated cell death such as apoptosis .", "macroautophagy ( abbreviated as autophagy ) is a genetically regulated and evolutionarily conserved pathway for the degradation of subcellular components [ 15 ] .", "the role of autophagy in diseases is an emerging area of investigation , with recent studies indicating that autophagy may exert multifunctional roles in specific diseases , with the potential for both adaptive and maladaptive outcomes .", "the major types of cell death which have been studied most extensively in the context of autophagy research include apoptosis , necrosis , necroptosis , and pyroptosis , as briefly summarized here .", "apoptosis has a crucial function in the maintenance of tissue homeostasis under physiological conditions and also serves as a component of developmental programs and furthermore may also contribute to disease pathogenesis ." ], [ "furthermore , autophagy can degrade exogenously derived substrates , most notably bacteria , virus particles , and other parasites , in a selective process termed xenophagy [ 10 , 15 , 16 ] . although recent studies begin to unravel the role of mitochondrial selective autophagy in cell death pathways , the role of diverse selective autophagy pathways in the modulation of cell death programs remains largely uncharted territory .", "in addition to protein , autophagic processes have been implicated in the degradation of diverse cellular biomolecules , including lipids and rna .", "these studies have suggested a role for autophagy as a means for prolonging cell survival during starvation .", "recent studies suggest that autophagy may provide an alternative pathway to proteolysis in addition to the ubiquitin proteasome system [ 7678 ] .", "such selective autophagy pathways have been identified for the turnover of mitochondria ( mitophagy ) and other organelles and the turnover of denatured protein ( aggrephagy ) . during starvation ( e.g. ," ], [ "recent studies suggest that factors well known to regulate apoptosis pathways also have the potential to exert regulatory activity on factors that regulate autophagy and vice - versa ( figure 2 ) .", "despite a widely accepted role for autophagy in cellular survival , autophagy has also been associated with the regulation of various cell death pathways , most notably apoptosis .", "further studies suggest that certain atg proteins may play dual roles in autophagy / apoptosis regulation ; for example , the autophagic protein atg5 may affect extrinsic apoptosis pathways through interactions with the fas - associated death domain ( fadd ) protein .", "these interactions suggest that autophagy and apoptosis may be coordinately regulated by bcl-2 family proteins .", "cse exposure caused the rapid dissociation of lc3b from fas , in association with the activation of apoptosis signaling . in conclusion , these results using genetic knockdown experiments have implicated a proapoptotic role for lc3b , in a specialized model of cse - induced toxicity , though the relative role of autophagic activity in promoting cell death in this model remains unclear [ 100 , 101 ] . it should be noted that cse - induced autophagy may differ from starvation - induced autophagy in that it occurs in the presence of a complex mixture of foreign matter , which may potentially alter the functionality of the autophagy response .", "the p53 tumor suppressor protein is a well studied regulator of cell cycle progression and apoptosis ." ], [ "these observations suggest that autophagy may be induced by necroptosis , raising the possibility that cellular stress during cell death may lead to the induction of autophagy .", "it is tempting to speculate that so - called autophagic cell death may involve elements of necroptosis , though further research will be needed to clarify this relationship , as well as the signaling pathways linking autophagy to necroptosis .", "the terms autophagic cell death or type ii programmed cell death have been previously used to refer to cell death distinct from apoptosis that occurs in association with increases in autophagosome formation and independently of caspases .", "autophagy provides a protective function to limit tumor necrosis and inflammation in response to metabolic stress ." ], [ "recent observations have revealed a relationship between autophagic proteins and inflammasome - associated proinflammatory cytokine maturation in macrophages [ 122124 ] .", "chemical inhibition of autophagy using 3-methyladenine or inhibition of the atg4 protease resulted in increased incidence of pyroptotic cell death in activated macrophages . the impact of autophagy modulation on the regulation of pyroptosis , and the relevance of these interactions in in vivo models of inflammatory disease and sepsis , warrants further exploration .", "recent studies suggest that macrophages activate autophagy in parallel with inflammasome activation , as a means to delay the onset of pyroptosis .", "it is possible that a distinct type of autophagy induction might differentially regulate the inflammasome pathway . taken together these studies suggest an important role for autophagic proteins in the dampening of proinflammatory responses , which warrants further investigation in models of inflammatory disease ." ], [ ". an increased understanding of these relationships would be essential in the development of therapeutics targeting the autophagy pathway for the treatment of disease .", "the role of autophagy in diseases is an emerging area of investigation , with recent studies indicating that autophagy may exert multifunctional roles in specific diseases , with the potential for both adaptive and harmful outcomes .", "furthermore , additional studies are needed to determine the relevance of autophagic regulation of pyroptosis in inflammatory diseases", "autophagy is generally defined as a cellular program that ensures survival under conditions of stress . the ability of autophagy to clear damaged or denatured subcellular constituents such as aggregated protein ( i.e. , aggrephagy ) as well as to maintain mitochondrial homeostasis ( i.e. , mitophagy ) appears to play important roles in the cytoprotective and homeostatic functions of autophagy . despite the homeostatic roles , autophagy is now recognized to play complex and incompletely understood roles in cell death programs ( figure 3 ) .", "additional studies are needed to define the dynamic equilibrium between autophagy , apoptosis , regulated necrosis , and other modes of cell death in the context of human disease pathogenesis .", "furthermore , there is considerable cross - talk between the molecular regulation of autophagy and other regulated forms of cell death [ 2326 ] ." ] ]

[ [ "systemic symptoms are present in a third of patients at presentation and among them fever is the most common followed by night sweats and weight loss . on review of literature , we found 18 case reports with similar finding of hypotension and hypothermia associated with hl .", "we report the case of a patient who presented with hypotension and hypothermia and was diagnosed initially with septic shock .", "he was found to have ill - defined liver lesions on the computed tomography ( ct ) scan which were new on comparison with a recent ct abdomen done for evaluation of nephrolithiasis .", "koreich in 1981 first reported the case of a 22 year old man diagnosed as hodgkin lymphoma ( hl ) who developed hypothermia and hypotension during the course of his admission , which resolved only after initiation of chemotherapy .", "the pathophysiology of development of hypotension and hypothermia in patients during chemotherapy or prior to diagnosis remains unexplained .", "a complex interaction between cytokines , tumor and blood vessels has been proposed as the genesis of such a presentation ." ], [ "a 61 year old man presented to emergency room with history of flank pain on right side , dysuria , urgency and frequency with occasional hematuria for 3 days associated with fever , chills and rigors .", "3 weeks before this presentation he was admitted for renal colic and was found to have a new staghorn calculus in the kidney which was managed conservatively with 7 days of oral antibiotics .", "the hypotension did not correct with bolus of 3 liters of 0.9% normal saline ( ns ) and in view of his history of dysuria and intermittent hematuria and recent diagnosis of staghorn calculus he was diagnosed with urinary tract infection ( uti ) leading to urosepsis and septic shock .", "soon after the diagnosis patient was started on chemotherapy with doxorubicin , dacarbazine , vinblastine .", "colonoscopy and esophago - gastro - duo - denoscopy ( egd ) done as part of malignancy workup , showed 2 polyps which were diagnosed as tubular adenoma and thick gastric folds with chronic gastritis on histopathology respectively ." ], [ "reported the first patient with hl who developed hypothermia and hypotension during the course of admission , prior to initiation of chemotherapy . since then 18 more cases have been reported with hypothermia as presenting feature and in 8 out of 18 patients , hypotension has also been recorded ( table 2 ) .", "moreover treatment with vancomycin and piperacillintazobactam did not lead to improvement in the condition of the patient , essentially ruling out infectious cause and sepsis as the primary cause of hypotension .", "interestingly , most of the patients described with hypothermia and hypotension have been reported to have liver metastases . to date", "in addition to this , cytokines also cause endothelial damage , a mechanism which is very well defined in patients with sepsis and septic shock . in patients with sepsis infection", "we postulate from the above , that the probable cause of hypotension in this patient could be release of cytokines from the tumor especially from liver metastasis , which is an extremely vascular organ .", ", the mechanism behind hypotension and hypothermia as isolated manifestations of hl remains unexplained . in our patient" ] ]