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Transcriptome‐based drug screening is emerging as a powerful tool to identify geroprotective compounds to intervene in age‐related disease. We hypothesized that, by mimicking the transcriptional signature of the highly conserved longevity intervention of FOXO3 (daf‐16 in worms) overexpression, we could identify and repurpose compounds with similar downstream effects to increase longevity. Our in silico screen, utilizing the LINCS transcriptome database of genetic and compound interventions, identified several FDA‐approved compounds that activate FOXO downstream targets in mammalian cells. These included the neuromuscular blocker atracurium, which also robustly extends both lifespan and healthspan in Caenorhabditis elegans. This longevity is dependent on both daf‐16 signaling and inhibition of the neuromuscular acetylcholine receptor subunit unc‐38. We found unc‐38 RNAi to improve healthspan, lifespan, and stimulate DAF‐16 nuclear localization, similar to atracurium treatment. Finally, using RNA‐seq transcriptomics, we identify atracurium activation of DAF‐16 downstream effectors. Together, these data demonstrate the capacity to mimic genetic lifespan interventions with drugs, and in doing so, reveal that the neuromuscular acetylcholine receptor regulates the highly conserved FOXO/DAF‐16 longevity pathway. [ABSTRACT FROM AUTHOR]

Background: Unlike perianal fistula, long‐term outcomes of nonperianal fistulae (NPF) in Crohn's disease (CD) are not clear. We aimed to compare the outcomes of medical and surgical therapies in patients with NPF. Methods: We retrospectively analyzed the records of patients of CD with NPF who were prospectively followed from January 2005 to December 2018. Results: Of the 53 patients with NPF [mean age at presentation:29 ± 14 years; 54.7% male; median duration of follow‐up: 47 months (interquartile range [IQR]:26–76 months)], enteroenteric fistula (37.8%) was the most common presentation. Of 22 patients treated with anti‐tumor necrosis factor (TNF) therapy, complete response was achieved in 40.9% (n = 9). Overall probability of maintaining response was similar between the anti‐TNF and surgical groups (95.2% vs 82.4%; 71% vs 76%; and 63% vs 69%% [P = 0.8] at 1, 2, and 3 years, respectively), with only 13.6% of patients treated with biologicals requiring surgery over 56 months. Twenty‐one patients required upfront surgery (small bowel or ileocolonic resection with/without diversion; 28.5% emergent), with 47.6% postoperative recurrence over 36 months, of which nine patients required biologicals (77.7% response to anti‐TNF therapy). Long‐term outcome was comparable between medically and surgically treated patients; 6.4% developed tuberculosis on anti‐TNF therapy. Two patients (3.7%) developed malignancy (one ‐ enteroenteric, one ‐ colovesical). Conclusion: Anti‐TNF therapy appears to be as effective as surgery in this retrospective analysis of patients with NPFCD, and it may be indicated in the absence of abscess and other complications. These patients are at higher risk of fistula‐associated malignancy, which requires a lower threshold for suspicion, especially over the long term in the presence of nonresponse to medical therapy. [ABSTRACT FROM AUTHOR]

Background and Aim: Demonstration of villous abnormalities is an essential component of diagnosis of celiac disease (CeD) that requires duodenal biopsies. There is a need for non‐invasive biomarker(s) that can predict the presence of villous abnormalities. Methods: Levels of plasma citrulline, plasma intestinal fatty acid binding protein (I‐FABP), and serum regenerating gene 1α (Reg1α) were estimated in treatment naïve patients with CeD and controls. The levels of these biomarkers and their cyclical pattern were validated in a predicted model of enteropathy. Optimum diagnostic cut‐off values were derived, and the results were further validated in a prospective validation cohort. Results: While level of plasma citrulline was significantly lower, the levels of plasma I‐FABP and serum Reg1α were significantly higher in patients with CeD (n = 131) in comparison with healthy (n = 216) and disease controls (n = 133), and their levels reversed after a gluten‐free diet (GFD). In the model of predicted enteropathy (n = 70), a sequential decrease and then increase in the level of plasma citrulline was observed; such a sequential change was not observed with I‐FABP and Reg1α. The diagnostic accuracy for prediction of presence of villous abnormality was 89% and 78% if citrulline level was ≤ 30 μM/L and I‐FABP levels were ≥ 1100 pg/mL, respectively. The results were validated in a prospective validation cohort (n = 104) with a sensitivity and specificity of 79.5% and 83.1%, respectively, for predicting villous abnormalities of modified Marsh grade > 2 at calculated cut‐off values of citrulline and I‐FABP. Conclusions: Plasma citrulline ≤ 30 μM/L is the most consistent, highly reproducible non‐invasive biomarker that can predict the presence of villous abnormality and has the potential for avoiding duodenal biopsies in 78% patients suspected to have CeD. [ABSTRACT FROM AUTHOR]

Background and Aim: While the prevalence of celiac disease (CD) is increasing globally, the prevalence of tropical sprue (TS) is declining. Still, there are certain regions in the world where both patients with CD and TS exist and differentiation between them is a challenging task. We conducted a systematic review of the literature to find out differentiating clinical, endoscopic, and histological characteristics between CD and TS. Methods: Medline, PubMed, and EMBASE databases were searched for keywords: celiac disease, coeliac, celiac, tropical sprue, sprue, clinical presentation, endoscopy, and histology. Studies published between August 1960 and January 2018 were reviewed. Out of 1063 articles available, 12 articles were included in the final analysis. Results: Between the patients with CD and TS, there was no difference in the prevalence and duration of chronic diarrhea, abdominal distension, weight loss, extent of abnormal fecal fat content, and density of intestinal inflammation. The following features were more common in CD: short stature, vomiting/dyspepsia, endoscopic scalloping/attenuation of duodenal folds, histological high modified Marsh changes, crescendo type of IELosis, surface epithelial denudation, surface mucosal flattening, thickening of subepithelial basement membrane and celiac seropositivity; while those in TS include anemia, abnormal urinary D‐xylose test, endoscopic either normal duodenal folds or mild attenuation, histologically decrescendo type of IELosis, low modified Marsh changes, patchy mucosal changes, and mucosal eosinophilia. Conclusions: Both patients with CD and TS have overlapping clinical, endoscopic, and histological characteristics, and there is no single diagnostic feature for differentiating CD from TS except for celiac specific serological tests. [ABSTRACT FROM AUTHOR]

Background: Risk calculators have traditionally utilized serum prostate-specific antigen (PSA) values in addition to clinical variables to predict the likelihood of prostate cancer (PCa).Purpose: To develop a prebiopsy multiparametric MRI (mpMRI)-based risk score (RS) and a statistical equation for predicting the risk of PCa in biopsy-naive men with serum PSA between 4-10 ng/mL that may help reduce unnecessary biopsies.Study Type: Prospective cross-sectional study.Subjects: In all, 137 consecutive men with PSA between 4-10 ng/mL underwent prebiopsy mpMRI (diffusion-weighted [DW]-MRI and MR spectroscopic imaging [MRSI]) during 2009-2015 were recruited for this study.Field Strength/sequence: 1.5T (Avanto, Siemens Health Care, Erlangen, Germany); T1 -weighted, T2 -weighted, DW-MRI, and MRSI sequences were used.Assessment: All eligible patients underwent mpMRI-directed, cognitive-fusion transrectal ultrasound (TRUS)-guided biopsies.Statistical Tests: An equation model and an RS were developed using receiver operating characteristic (ROC) curve analysis and a multivariable logistic regression approach. A 10-fold crossvalidation and simulation analyses were performed to assess diagnostic performance of various combinations of mpMRI parameters.Results: Of 137 patients, 32 were diagnosed with PCa on biopsy. Multivariable analysis, adjusted with positive pathology, showed apparent diffusion coefficient (ADC), metabolite ratio, and PSA as significant predictors of PCa (P < 0.05). A statistical equation was derived using these predictors. A simple 6-point mpMRI-based RS was derived for calculating the risk of PCa and it showed that it is highly predictive for PCa (odds ratio = 3.74, 95% confidence interval [CI]: 2.24-6.27, area under the curve [AUC] = 0.87). Both models (equation and RS) yielded high predictive performance (AUC ≥0.85) on validation analysis.Data Conclusion: A statistical equation and a simple 6-point mpMRI-based RS can be used as a point-of-care tool to potentially help limit the number of negative biopsies in men with PSA between 4 and 10 ng/mL.Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1227-1236. [ABSTRACT FROM AUTHOR]

Background and Aim The literature on possible factors that could trigger a relapse in patients with ulcerative colitis (UC) in clinical, endoscopic, and histological remission on long-term follow up is scarce. To determine the relapse rate in patients with UC in clinical, endoscopic, and histological remission and identify factors that may influence the risk of relapse. Methods Patients with UC in clinical, endoscopic, and histological remission were enrolled between January and July 2010 and followed up for 1 year to determine the effect of clinical, dietary, and psychological factors on relapse. Information regarding factors that may affect relapse such as infection, antibiotic, or non-steroidal anti-inflammatory drugs (NSAIDs) use and any other factor that the patient felt important and compliance with medications was obtained. Results Ninety-seven patients (59 males, mean age 39 ± 11.9 years) were followed up for a mean duration of 9 ± 2.3 months. Eighteen (18.6%) relapsed with the median time to relapse being 3.5 months. On univariate analysis, more relapsers had significantly higher NSAIDs use within 15 days of relapse, respiratory tract infection within 4 weeks, use of steroids more than once in past, higher consumption of calcium, riboflavin, and vitamin A, and lower consumption of sugars. On multivariate analysis, NSAIDs use (HR [95% CI]: 6.41 [1.88-21.9]) and intake of vitamin A (HR [95% CI]: 1.008 [1.000-1.016]) were statistically significant predictors of relapse. Conclusion With a relapse rate of 18.6% over a follow up of 9 months in patients with UC in clinical, endoscopic, and histological remission, independent predictors of relapse were history of NSAIDs use within 15 days of relapse and higher intake of vitamin A. [ABSTRACT FROM AUTHOR]

Background Patients with idiopathic hypoparathyroidism (IH) require variable doses of calcium and 1-α-(OH)D. The reasons for such variability are not clear. As autoimmune mechanisms may play a role in IH, there is a possibility of coexistent coeliac disease with calcium/vitamin D malabsorption. Objective We assessed the prevalence of coeliac disease and antitissue transglutaminase autoantibodies (anti-tTGAbs) in IH and analysed the effect of a gluten-free diet on calcaemic control. Method A total of 171 patients with IH and 126 healthy controls were screened for anti-tTGAb. IH patients with anti-tTGAb >20 RU/ml underwent duodenoscopy and intestinal biopsy; those with biopsy-proven coeliac disease were followed up on a gluten-free diet. Results Eleven of 171 (6·4%) patients with IH and seven of 126 (5·6%) controls had anti-tTGAb ( P = 0·81). There was no difference in the clinical and biochemical parameters at diagnosis and during long-term follow-up of 7·2 ± 4·8 year (mean serum total calcium = 1·88 ± 0·16 vs 1·82 ± 0·36 mmol/l, P = 0·52; phosphorus = 1·81 ± 0·17 vs 1·87 ± 0·36 mmol/l, P = 0·53) in IH patients with and without anti-tTGAb. Although CaSRAb positivity was comparable in the two groups, IH patients with anti-tTGAb had higher TPOAb positivity (45·5% vs 12·8%, P = 0·02). Coeliac disease was diagnosed in only 2/9 patients with IH on biopsy, both of whom showed improved calcaemic control with a gluten-free diet. Conclusion The prevalence of coeliac autoimmunity (6·4%) and coeliac disease (1·2%) in patients with IH seems to be similar to that in the general population. Notwithstanding this modest prevalence, it is important to be aware of the potential occurrence of coeliac disease with IH and the beneficial effect of a gluten-free diet on calcium control. [ABSTRACT FROM AUTHOR]

Background and Aim: Acute on chronic liver failure (ACLF) because of precipitating factors (variceal bleed/infections) identifies cirrhotics at risk for high short-term mortality. Information on ACLF because of acute hepatic insults is lacking. The aim of the study was to evaluate acute hepatic insults in ACLF and their effect on the course and outcome. Methods: In a prospective study, 213 consecutive patients of ACLF because of acute hepatic insults were included. Etiology of acute hepatic insult, frequency of silent, and overt chronic liver disease (CLD), organ failure (OF), and outcomes were assessed. Prognostic models such as model for endstage liver disease (MELD), acute physiology and chronic health evaluation (APACHE II), and chronic liver failure-sequential organ failure (CLIF-SOFA) were evaluated. Results: Etiologies of acute hepatic insult were hepatitis virus(es)- 81 (38%; HBV-42, HEV-39), continuous alcohol consumption-77 (33.3%), antituberculosis drugs-11 (5.2%), autoimmune hepatitis flare-5(2.3%), cryptogenic-44 (20.7%). The common causes of CLD were alcohol ( n = 85/40%), HBV( n = 52/24%), and cryptogenic( n = 50/20%). The MELD, APACHE II, and CLIF-SOFA scores were similar among silent and overt CLD and did not influence outcome. Predominant etiologies of ACLF were hepatitis virus(es) reactivation or superinfection in silent CLD(52/112, 46.4%) and alcohol among overt CLD(43/101, 43%). Independent predictors of mortality included hepatic-encephalopathy (early, HR: 4.01; advanced, HR: 6.10), serum creatinine ≥1.5 mg/dl (HR: 4.53), CLIF-SOFA ≥8(HR: 1.69), and etiology of acute hepatic insult (alcohol, HR: 4.08; cryptogenic, HR: 3.18). HEV-ACLF had lower mortality (12.8% vs. 33-54% in other etiologies; P < 0.001). OF was major determinant of mortality. With increasing number of OF, mortality increased linearly( P = 0.001). Conclusions: Hepatitis virus(es) and continuous alcohol consumption are important causes of ACLF caused by acute hepatic insults. HEV-ACLF has lower mortality. OF is an important prognostic predictor. [ABSTRACT FROM AUTHOR]

Risk stratification, based on the Gleason score (GS) of a prostate biopsy, is an important decision-making tool in prostate cancer management. As low-grade disease may not need active intervention, the ability to identify aggressive cancers on imaging could limit the need for prostate biopsies. We assessed the ability of multiparametric MRI (mpMRI) in pre-biopsy risk stratification of men with prostate cancer. One hundred and twenty men suspected to have prostate cancer underwent mpMRI (diffusion MRI and MR spectroscopic imaging) prior to biopsy. Twenty-six had cancer and were stratified into three groups based on GS: low grade (GS ≤ 6), intermediate grade (GS = 7) and high grade (GS ≥ 8). A total of 910 regions of interest (ROIs) from the peripheral zone (PZ, range 25-45) were analyzed from these 26 patients. The metabolite ratio [citrate/(choline + creatine)] and apparent diffusion coefficient (ADC) of voxels were calculated for the PZ regions corresponding to the biopsy cores and compared with histology. The median metabolite ratios for low-grade, intermediate-grade and high-grade cancer were 0.29 (range: 0.16, 0.61), 0.17 (range: 0.13, 0.32) and 0.13 (range: 0.05, 0.23), respectively ( p = 0.004). The corresponding mean ADCs (×10-3 mm2/s) for low-grade, intermediate-grade and high-grade cancer were 0.99 ± 0.08, 0.86 ± 0.11 and 0.69 ± 0.12, respectively ( p < 0.0001). The combined ADC and metabolite ratio model showed strong discriminatory ability to differentiate subjects with GS ≤ 6 from subjects with GS ≥ 7 with an area under the curve of 94%. These data indicate that pre-biopsy mpMRI may stratify PCa aggressiveness noninvasively. As the recent literature data suggest that men with GS ≤ 6 cancer may not need radical therapy, our data may help limit the need for biopsy and allow informed decision making for clinical intervention. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background and Aim Celiac disease ( CeD) is a common autoimmune disorder in which ingestion of gluten and related proteins leads to inflammation in the small intestine. Although the histological findings in CeD are characteristic, they are not specific. In this study, proton nuclear magnetic resonance ( NMR) spectroscopy was used to investigate the differences in metabolic profile of duodenal mucosal biopsies of patients with CeD and controls to find out the biomarker/s of villous atrophy. Methods Duodenal mucosal biopsies were collected from 29 CeD patients (mean age 26.2 ± 10.8 years) and 17 controls (mean age 34.1 ± 11.1 years) and were subjected to proton NMR spectroscopy following perchloric acid extraction. Assignment of metabolite resonances was carried out and their concentrations were determined. For comparison between the groups unpaired t-test/Wilcoxon rank sum test was used. Partial least squares-discriminant analysis was performed to study the clustering behavior of the samples from CeD patients and controls using the Unscrambler 10.2 software. Results Partial least squares-discriminant analysis clearly differentiated CeD patients from controls. Significantly higher concentrations of isoleucine, leucine, aspartate, succinate, and pyruvate, and lower concentration of glycerophosphocholine, were observed in the duodenal mucosa of CeD patients compared with controls. The results suggest abnormalities in glycolysis, Krebs cycle (energy deficiency), and amino acid metabolism, which may affect the biosynthetic pathways and consequently contribute to villous atrophy. Conclusions NMR spectroscopy with multivariate analysis of duodenal mucosal biopsies revealed a characteristic metabolic profile in CeD patients. The work provided an insight in determining biomarker/s for villous atrophy and diagnosis of CeD patients. [ABSTRACT FROM AUTHOR]

Background and Aim Once thought to be uncommon in Asia, coeliac disease ( CD) is now being increasingly recognized in Asia- Pacific region. In many Asian nations, CD is still considered to be either nonexistent or very rare. In recognition of such heterogeneity of knowledge and awareness, the World Gastroenterology Organization and the Asian Pacific Association of Gastroenterology commissioned a working party to address the key issues in emergence of CD in Asia. Methods A working group consisting of members from Asia- Pacific region, Europe, North America, and South America reviewed relevant existing literature with focus on those issues specific to Asia- Pacific region both in terms of what exists and what needs to be done. Results The working group identified the gaps in epidemiology, diagnosis, and management of CD in Asian- Pacific region and recommended the following: to establish prevalence of CD across region, increase in awareness about CD among physicians and patients, and recognition of atypical manifestations of CD. The challenges such as variability in performance of serological tests, lack of population-specific cut-offs values for a positive test, need for expert dietitians for proper counseling and supervision of patients, need for gluten-free infrastructure in food supply and creation of patient advocacy organizations were also emphasized. Conclusions Although absolute number of patients with CD at present is not very large, this number is expected to increase over the next few years or decades. It is thus appropriate that medical community across the Asia- Pacific region define extent of problem and get prepared to handle impending epidemic of CD. [ABSTRACT FROM AUTHOR]

Background and Aim Liver fibrosis is an established determinant of prognosis and therapy in chronic hepatitis B ( CHB). The role of fibroscan in assessing fibrosis in CHB remains unclear. Present study was designed to correlate fibroscan with liver biopsy and determine whether fibroscan can avoid liver biopsy in patients with CHB. Methods Fibroscan and liver biopsy were performed in 382 consecutive patients with CHB. Biopsies were reviewed by pathologist blinded to the fibroscan value. Discriminant values of liver stiffness measurement ( LSM) to reasonably exclude and predict significant fibrosis were calculated from receiver operating characteristic ( ROC) curves. The factors affecting LSM independent of fibrosis were assessed. Results Three hundred fifty-seven patients were included (mean age 30.1 ± 9.7 years, male : female 17 : 3). There was significant correlation between LSM and histological fibrosis ( r = 0.58, P < 0.001). The area under ROC curve of LSM for significant fibrosis ( F0-1 vs F2-4), bridging fibrosis ( F0-2 vs F3-4), and cirrhosis ( F0-3 vs F4) was 0.84 (95% CI:0.78-0.89), 0.94 (95% CI:0.89-0.99), and 0.93 (95% CI:0.85-1.00), respectively. LSM < 6.0 KPa could exclude significant (F ≥ 2) and bridging fibrosis (F ≥ 3) with a negative predictive value ( NPV) of 92.4% and 99.5%, respectively. Cut-off of 9 KPa could detect significant (F ≥ 2) and bridging fibrosis (F ≥ 3) with specificity of 95% and 97%, respectively, and had a positive predictive value ( PPV) of 84.3% in predicting significant fibrosis. LSM < 6 KPa and > 9 KPa matched with histological fibrosis in 227/250 (91%) patients. Therefore, fibroscan could avoid liver biopsy in 70% (250/357) patients with an accuracy > 90%. Histological fibrosis, ALT > 5 times, and age > 40 years were independent determinants of increased liver stiffness. Conclusions Fibroscan accurately assessed fibrosis and could avoid liver biopsy in more than two-thirds of patients with CHB. [ABSTRACT FROM AUTHOR]

Objective We aimed to determine the characteristics of patients with celiac disease and differences between those who presented during adolescence or adulthood. Methods We retrospectively reviewed the case records of 233 consecutive patients with celiac disease who were diagnosed at 12-18 years or >18 years of age. The diagnosis of celiac disease was made on the basis of the modified European Society of Pediatric Gastroenterology, Hepatology and Nutrition criteria. Results The diagnosis of celiac disease was made after 18 years of age in 153 (65.7%) patients. Median duration of symptoms at the diagnosis was 54 months (range 1 month to 29 years). In all, 103 (44.2%) patients with atypical manifestations were referred by other departments for evaluation. Chronic diarrhea (48.5%), short stature (27.0%) and chronic anemia (9.0%) were the common modes of presentation. Elevated level of aminotransaminase were present in 50 (24.3%) patients. Chronic diarrhea, hypocalcemia and hypoalbuminemia were present in significantly higher number of adult than adolescent patients. In all, 227 (97.4%) patients responded to a 6-month gluten-free diet and six non-responders were non-compliant. Conclusions More than 40% of the patients with celiac disease present to clinicians other than gastroenterologists or internists with atypical manifestations. A high index of suspicion is required for diagnosing its variant forms. [ABSTRACT FROM AUTHOR]

Objective. To study the histological and proliferation characteristics of the pars tensa retraction pocket. To investigate the hypothesis that such retraction pockets may demonstrate breaks in the epithelial basement membrane.Study Design. Prospective evaluation. Fifty stage II-IV surgically resected retraction pockets.Setting. Tertiary care academic hospital.Methods. Paraffin sections stained with hematoxylin and eosin. Basement membrane evaluation by Periodic acid-Schiff (PAS) and silver-methenamine (SM). Evaluation of cellular proliferation by immunohistochemistry (MIB-1 score).Results. Following are findings noted as frequent but not invariable in pars tensa retraction pockets: (1) subepithelial chronic inflammation (86%), (2) proliferation and hyperkeratinization of the outer epithelial layer, (3) epithelial cones with proliferating cells (increased MIB-1 score) in the basal epithelial layer (39%), (4) loss of the middle double collagen layer (71%), and (5) loss of the inner mucosal layer (33%). Inflammation and cellular proliferation were noted as ubiquitous among all grades. A trend was noted along progressive grades of retraction (II-IV) for an increasing incidence of basal epithelial cones, middle collagen layer loss, and inner mucosal layer loss. Focal loss of basement membrane was noted in several cases with PAS staining, but further staining with the SM in all such cases indicated the basement membrane to be intact.Conclusion. A continuum of progressive histological features akin to cholesteatoma is noted with increasing grades of retraction (II-IV). Breach of the basement membrane was recently reported as a feature of cholesteatoma but is not a feature of retraction. The near universal presence of inflammation as noted suggests an etiological role. [ABSTRACT FROM AUTHOR]

While celiac disease is estimated to affect about 1% of the world's population, it is thought to be uncommon not only in India but in Asia also. There is a lack of studies on the prevalence of celiac disease from Asian nations. The aim of the present study was to estimate the prevalence of celiac disease in the community. In a cross sectional study, we estimated the prevalence of celiac disease in urban and rural populations in the National Capital Region, Delhi, India. A structured questionnaire was administered, by door-to-door visits, to all participants to collect socio-demographic data and to screen for features of celiac disease, namely chronic or recurrent diarrhea and, anemia. In children, additional features, namely short stature (linear height below 5th percentile for age) and failure to thrive/gain weight were also used. All respondents who were screen positive (any one of above) and 10% of screen negative individuals were called for serological testing, which is anti-tissue transglutaminase antibody. All serologically positive respondents were invited to undergo further evaluation including endoscopic biopsy. Celiac disease was diagnosed on the basis of a positive serology, the presence of villous atrophy and/or response to gluten free diet. Among 12 573 contacted, 10 488 (83.4%) (50.6% male) agreed to participate. Based on screening, 5622 (53.6%) participants were screen positive. Of all those screen positive, 2167 (38.5%) agreed for serological testing; additionally 712 (14%) negatives were also tested. The overall sero-prevalence of celiac disease was 1.44% (95% confidence interval [CI] 1.22 1.69) and the overall prevalence of celiac disease was 1.04% (95% CI 0.85 1.25). The prevalence of celiac disease in this north Indian community is 1 in 96. Celiac disease is more common than is recognized in India. [ABSTRACT FROM AUTHOR]

Background. Aberrant nuclear accumulation of proteins influences tumor development and may predict biologic aggressiveness and disease prognosis. This study determined the prognostic significance of pSTAT3 (phosphorylayed signal transducer and activator of transcription 3) in oral squamous cell carcinomas (OSCCs). Methods and Results. Using immunohistochemistry, a significant increase in nuclear accumulation of pSTAT3 was observed in 49 of 90 leukoplakias (54.4%) and 63/94 OSCCs (67%) (ptrend < .001). Increased pSTAT3 was associated with tumor stage (p ¼ .01), nodal metastasis (p ¼ .0018), and tobacco consumption (p ¼ .004). Kaplan–Meier analysis demonstrated that OSCC with increased nuclear pSTAT3 showed significantly reduced disease-free survival (13 months), compared with the patients with no nuclear pSTAT3 expression (64 months, p ¼ .019). Cox regression analysis revealed nuclear pSTAT3 as the most significant predictor of poor prognosis (p ¼ .024, hazard ratio [HR] ¼ 2.7). Conclusions. Increased nuclear accumulation of pSTAT3 occurs in early premalignant stages and is a marker for poor prognosis of OSCC. [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2010) 39: 477–485 Background: In search of novel molecular markers for oral cancer, we reported increased levels of TC21/R-Ras2 transcripts in oral squamous cell carcinoma by differential display. The aim of this study was to determine the clinical significance of TC21 in oral cancer. Methods: Immunohistochemical analysis of TC21 protein expression was carried out in 120 leukoplakias, 83 OSCCs and 30 non-malignant tissues, confirmed by immunoblotting, and correlated with clinicopathological parameters as well as disease prognosis. Co-immunoprecipitation assays were carried out to identify the interaction partners of TC21 protein in oral cancer cells and tissues. Results: TC21 nuclear expression increased from normal oral tissues to leukoplakia and frank malignancy ( P < 0.001). TC21 overexpression was observed in 74.2% leukoplakia with no dysplasia, 75.9% dysplasias and 79.5% OSCCs in comparison with normal oral tissues. Receiver operating characteristic analysis showed that the area-under-the curve values were 0.895, 0.885, and 0.919, while the positive predictive values were 95.8%, 95.6%, and 97.1%, for nuclear immunostaining for normal versus leukoplakia with no dysplasia, leukoplakic lesions with dysplasia, and OSCCs, respectively. Immunoblotting confirmed overexpression of TC21 in oral lesions. Using co-immunoprecipitation assays, we showed interactions of TC21 with Erk2, PI3-K, 14-3-3ζ and 14-3-3σ proteins in oral cancer cells. Conclusion: Our findings suggested that alteration in TC21 expression is an early event in oral cancer and correlates with poor prognosis of OSCCs. TC21 interactions with Erk2, PI3-K, 14-3-3ζ and 14-3-3σ proteins in oral cancer cells and tissues suggests the involvement of TC21 in signaling pathways in oral cancer. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the potential of MR spectroscopic imaging (MRSI) to segregate patients who, upon prostate biopsy, are more likely to show a malignancy in the peripheral zone (PZ) of the prostate gland. Materials and Methods: Before biopsy, MRSI was carried in 123 men with elevated prostate specific antigen level or an abnormal digital rectal examination. After the MRSI investigation, all patients underwent systematic transrectal ultrasound guided biopsy and were categorized using standard random number tables into the following two groups: (i) Group I, a 62 member training set; and (ii) Group II, a 61-member test set. The cutoff value for the [citrate/(choline+creatine)] ratio for patients in the training set was obtained using the receiver operating characteristic (ROC) curve method. This value was then applied to the test set of patients as well. Results: The ROC method gave a cutoff value of 1.2 for the [Citrate/(Choline+Creatine)] ratio. When applied as a malignancy-predictor to the test group of patients (Group II), the ROC method generated the following results: sensitivity, 77%; specificity, 83%; negative predictive value, 93%; positive predictive value, 55% and accuracy, 82%. Conclusion: The results indicate that patients who are deemed as malignancy-positive in the PZ by MRSI using the ROC cutoff may be subjected to prostate biopsy to confirm the diagnosis of cancer. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the potential of MR spectroscopic imaging (MRSI) to segregate patients who, upon prostate biopsy, are more likely to show a malignancy in the peripheral zone (PZ) of the prostate gland. Materials and Methods Before biopsy, MRSI was carried in 123 men with elevated prostate specific antigen level or an abnormal digital rectal examination. After the MRSI investigation, all patients underwent systematic transrectal ultrasound guided biopsy and were categorized using standard random number tables into the following two groups: (i) Group I, a 62 member training set; and (ii) Group II, a 61-member test set. The cutoff value for the [citrate/(choline+creatine)] ratio for patients in the training set was obtained using the receiver operating characteristic (ROC) curve method. This value was then applied to the test set of patients as well. Results The ROC method gave a cutoff value of 1.2 for the [Citrate/(Choline+Creatine)] ratio. When applied as a malignancy-predictor to the test group of patients (Group II), the ROC method generated the following results: sensitivity, 77%; specificity, 83%; negative predictive value, 93%; positive predictive value, 55% and accuracy, 82%. Conclusion The results indicate that patients who are deemed as malignancy-positive in the PZ by MRSI using the ROC cutoff may be subjected to prostate biopsy to confirm the diagnosis of cancer. J. Magn. Reson. Imaging 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Nuclear Factor-κB (NF-κB) activation and COX-2 overexpression have been reported in head and neck cancer, but the relationship between these proteins remains to be investigated. To determine the relationship between NF-κB and COX-2 in Smokeless Tobacco (ST) associated oral tumorigenesis, we performed immunohistochemistry in serial sections from 107 OSCCs, 78 oral precancerous lesions (OPLs) (58 hyperplasias, 20 dysplasias) and 15 histologically normal oral tissues and correlated with clinicopathological data. Significant increase in NF-κB and COX-2 immunopositivity was observed from normal oral mucosa to OPLs to OSCCs ( p = 0.009 and p = 0.002 respectively). Upregulation of NF-κB and COX-2 was observed as early as in hyperplasia [ p = 0.006; OR = 6.1 and p = 0.003; OR = 7.6, respectively]. Expression of both proteins was found to be significantly associated in OPLs ( p = 0.000; OR = 12.6) and OSCCs ( p = 0.001; OR = 4.0). Intriguingly, khaini consumption correlated with NF-κB immunopositivity in OPLs ( p = 0.05, OR = 3.8) and OSCCs ( p = 0.01, OR = 3.4) and with COX-2 expression in OPLs ( p = 0.03; OR = 4.3). In vitro experimental system of ST associated oral carcinogenesis was used to demonstrate ST (khaini) and NNK mediated activation of NF-κB and COX-2, supporting the clinical data. In conclusion, this study demonstrates correlation between over expression of NF-κB and COX-2 in early precancerous stages of development of oral cancer and sustained elevation down the tumorigenic pathway, underscoring their potential as targets for early intervention. In vitro studies demonstrated that NNK may be one of the carcinogenic components of ST (khaini) inducing activation of NF-κB and COX-2 in oral precancer and cancer cells, suggesting plausible role in ST-induced oral carcinogenesis. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Abstract Bladder leiomyomas are rare tumors. They very rarely present as a pelvic mass. We present an interesting case where a giant bladder leiomyoma was mistaken to be an ovarian mass. A bladder preserving surgery was performed. The literature is reviewed and the management is discussed. [ABSTRACT FROM AUTHOR]

Abstract Background Facial massage is an extremely popular form of beauty treatment and is thought to rejuvenate the skin. We decided to study the benefits and untoward effects of this form of facial beauty treatment. Methods One hundred and forty-two women (aged 17–63 years), who had received facial beauty treatment in three well-established beauty parlours in New Delhi, were entered into the study and observed for a period of 12 weeks after the facial beauty treatment. Twenty-seven of the subjects had a repeat facial beauty treatment 4–6 weeks after entry into the study, giving a total of 169 massage episodes observed. Immediate and delayed effects of the beauty treatment were examined. Results Facial beauty treatment generally consists of three steps: vigorous massaging of the face with creams, steaming (using a hot towel or a steaming gadget), and application of a face mask containing adsorbents and astringents. In our study, the creams used for massage included “off the shelf” creams manufactured by standard cosmetic companies in 95 (56.3%) subjects, herbal creams in 61 (36.1%), and creams containing exotic ingredients, such as gold salts, in 13 (7.7%). Sixty-one (36.1%) patients developed erythema and puffiness within 15 min to 2 h after the beauty treatment. This lasted for 2–6 h. Forty-one (24.3%) women underwent the procedure of comedone extraction after steaming. In 12 (7.1%) of these women, persistent erythema was noticed at the site of comedone extraction. Eight (4.7%) women developed mild dermatitis on the face, 2–7 days after the facial beauty treatment. Patch testing with constituents used in the facial beauty treatment was positive in four patients (herbal cream, 1; witch hazel, 1; orange face pack, 1; and gold cream, 1). In 47 (33.1%) subjects, an acneiform eruption was observed 3–10 weeks after the facial beauty treatment (mean, 6.1 ± 3 weeks). Thirteen (27.7%) of these subjects had taken... [ABSTRACT FROM AUTHOR]

Abstract Background and Aims: Subacute hepatic failure (SHF) is a fatal complicaton of acute viral hepatitis. Renal failure has been implicated as the main cause of death in this disease. However, renal functional and structural evaluation in such patients have not been performed. The present prospective study evaluated the renal functional and structural abnormalities in patients with subacute hepatic failure. Methods: Fourteen consecutive patients with SHF, 11 with acute liver failure (ALF) and 15 with cirrhosis of the liver (Child's B or C) were included in the present study. All 40 patients had liver disease caused by hepatitis viruses. The glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) estimations were measured in all patients by the use of technetium-99m diethylenetriaminepentaacetic acid and [131I]-labeled ortho-iodohippuric acid, respectively. Ante-mortem or post-mortem liver biopsies were performed in all patients. In three patients with SHF, post-mortem kidney biopsies were also performed. Results: Thirty six percent (5/14) of patients with SHF, 18% (2/11) of patients with ALF and 20% (3/15) of patients with cirrhosis had renal failure. Seven patients with SHF, seven with ALF and nine with cirrhosis died. All the patients with renal failure in each of the three groups were among the deceased patients. Glomerular function was markedly affected among patients with SHF, which was shown by significantly higher (P < 0.05) proteinuria levels (0.367 ± 0.38 g/24 h) compared to levels in patients with ALF (0.178 ± 0.11 g/24 h) and cirrhosis (0.212 ± 0.133 g/24 h). The GFR in SHF (56 ± 27 mL/min per 1.73 m2) and cirrhotic patients (58 ± 36 mL/min per 1.73 m2) was significantly lower compared to those in ALF patients (102 ± 51 mL/min per 1.73 m2; P < 0.05). A significantly higher proportion (P < 0.05) of patients with SHF and cirrhosis (64 and 73%, respectively) had a GFR below 80 mL/min per 1.73 m2 compared to patients with ALF (18%). The GFR value among the deceased SHF patients (46 ± 26 mL/min per 1.73 m2) was significantly lower (P < 0.05) than those SHF patients who survived (65 ± 25 mL/min per 1.73 m2). However, similar features could not be documented among patients with ALF or cirrhosis. Subtle structural changes in the glomerulus were also noted in patients with SHF. These included mesangial proliferation and thickening, basal membrane thickening and increased cellularity with interstitial edema. The ERPF was markedly reduced (P = 0.058) among patients with SHF (347 ± 131 mL/min per 1.73 m2) and cirrhosis (395 ± 137 mL/min per 1.73 m2) in comparison to ERPF documented among patients with ALF (436 ± 217 mL/min per 1.73 m2). Such a reduction in renal tubular blood flow, along with histologic documentation of hyaline presence, bile and grannular cast in the tubule, indicated a possible tubular dysfunction in patients with SHF. Conclusion: It is concluded that glomerular and tubular dysfunction with subtle structural abnormalities does occur in patients with SHF. These are similar to renal changes in cirrhosis and may have similar pathogenetic mechanisms that require further evaluation. [ABSTRACT FROM AUTHOR]

AbstractBackground Female patients in the post-adolescent age group presented with predominantly deep-seated nodules and a few comedones situated mainly on the cheeks. As most of these subjects related the onset of their symptoms to antecedent facial beauty treatment, we decided to study the clinical and histologic profile of these patients. Methods Thirty seven subjects (36 women and one man) were questioned in detail about their acneiform eruptions. The patients were examined and a biopsy of typical lesions was taken in eight patients. Results On direct questioning, all patients related the onset of their lesions to facial beauty treatment taken 3–8 weeks previously. The predominant types of lesion were deep-seated nodules, although a few closed comedones were present in some cases. Most lesions took a long time to heal and, on healing, left behind hyperpigmentation. The cheeks were universally involved in all patients, and the chin and forehead were involved in 14. The histopathologic study revealed a predominantly peri-appendageal dermal infiltrate consisting of lymphocytes and histiocytes admixed with polymorphs. A granulomatous infiltrate was seen in one-third of the biopsies. Conclusions This eruption is unlike the earlier eruption described as acne cosmetica in being inflammatory, indolent, and often occurring after the first cream massage itself. [ABSTRACT FROM AUTHOR]

Discusses the occurrence of dermatitis caused by friction of garment on sweaty skin. Prick test results; Clinical characteristics; Duration of lesions.