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Previous studies have found no female predominance in irritable bowel syndrome (IBS) in non-Western countries. The aim of the study was to assess the prevalence and correlates of Rome II (IBS) in both sexes in Pakistan. A Population-based survey in a low-income inner city area using questionnaires to diagnose Rome II IBS and assess distress, disability and stressful life events. Data were collected from 880/938 (93%) randomly selected residents. 13.4% of women and 13.1% men met criteria for Rome II IBS; 34 (3.9%) had diarrhoea-predominant, 59 (6.7%) had constipation-predominant IBS and 24 (2.7%) had 'mixed IBS'. In logistic regression analysis, IBS was associated in men with high income (OR = 1.56; 95% CI: 1.05-2.3) and few years of education (OR = 2.17; 95% CI: 1.2-3.9) and in women with being married (OR = 3.6; 95% CI: 1.1-11.9) and stressful life events score (OR = 1.14; 95% CI: 1.01-1.3). Disability was associated with constipation-predominant IBS (OR = 1.99; 95% CI: 1.1-3.6), distress (OR = 1.19; 95% CI: 1.14-1.23) and stressful life events (OR = 1.19; 95% CI: 1.1-1.3). Investigations were more likely in men (54%) than in women (27%) (P = 0.003). These findings suggest that the equal sex ratio of IBS in urban Pakistan could result from a close association between marked distress and IBS in men similar to that found in women in western studies.

Background Peroral cholangioscopy (POCS) of indeterminate biliary strictures aims to achieve a diagnosis through visual examination and/or by obtaining targeted biopsies under direct visualization. In this large, prospective, multinational, real-life experience of POCS-guided evaluation of indeterminate biliary strictures, we evaluated the performance of POCS in this difficult-to-manage patient population. Methods This prospective registry enrolled patients, with indeterminate biliary strictures across 20 centers in Asia, the Middle East, and Africa. The primary end points were the ability to visualize the lesion, obtain histological sampling when intended, and an assessment of the diagnostic accuracy of POCS for malignant strictures. Patients were followed for 6 months after POCS or until a definitive malignant diagnosis was made, whichever occurred first. Results 289 patients underwent 290 POCS procedures with intent to biopsy in 182 cases. The stricture/filling defect was successfully visualized in 286/290 (98.6 %), providing a visual diagnostic impression in 253/290 (87.2 %) and obtaining adequate biopsies in 169/182 (92.9 %). Procedure-related adverse events occurred in 5/289 patients (1.7 %). POCS influenced patient management principally by elucidating filling defects or the causes of bile duct stricture or dilation. The visual impression of malignancy showed 86.7 % sensitivity, 71.2 % specificity, 65.8 % positive and 89.4 % negative predictive value, and 77.2 % overall accuracy compared with final diagnosis. Histological POCS-guided samples showed 75.3 % sensitivity, 100 % specificity, 100 % positive and 77.1 % negative predictive value, and 86.5 % overall accuracy. Conclusion In this large, real-life, prospective series, POCS was demonstrated to be an effective and safe intervention guiding the management of patients with indeterminate biliary strictures.

Background Peroral cholangioscopy (POCS) can be useful for difficult bile duct stone clearance. Large prospective multinational data on POCS-guided lithotripsy for clearing difficult bile duct stones in a single session of endoscopic retrograde cholangiopancreatography (ERCP) are missing. Methods Patients with difficult bile duct stones (defined as one or more of: largest stone diameter ≥ 15 mm, failed prior attempt at stone clearance, impacted, multiple, hepatic duct location, or located above a stricture) were enrolled at 17 centers in 10 countries. The principal endpoint was stone clearance in a single ERCP procedure using POCS. Results 156 patients underwent 174 sessions of POCS-guided electrohydraulic or laser lithotripsy. Stone clearance had failed in a previous ERCP using traditional techniques in 124/156 patients (80 %), while 32 /156 patients (21 %) were referred directly to POCS-guided therapy based on preprocedural assessment of the difficulty of stone clearance. In 101/156 patients (65 %), there were impacted stones. POCS-guided stone clearance was achieved in a single POCS procedure in 125 /156 patients (80 %, 95 % confidence interval [CI] 73 % – 86 %), and was significantly more likely for stones ≤ 30 mm compared with > 30 mm (odds ratio 7.9, 95 %CI 2.4 – 26.2; P = 0.002). Serious adverse events occurred in 3/156 patients (1.9 %, 95 %CI 0.4 % – 5.5 %), and included pancreatitis, perforation due to laser lithotripsy, and cholangitis (n = 1 each), all resolved within 1 week. Conclusion POCS-guided lithotripsy is highly effective for clearance of difficult bile duct stones in a single procedure and successfully salvages most prior treatment failures. It may also be considered first-line therapy for patients with difficult choledocholithiasis to avoid serial procedures.

Several challenges exist for successful nanoparticle cellular uptake—they must be able to cross many physical barriers to reach their target and overcome the cell membrane. A strategy to overcome this challenge is to exploit natural uptake mechanisms namely passive and endocytic (i.e., clathrin- and caveolin-dependent/-independent endocytosis, macropinocytosis and phagocytosis). The influence of nanoparticle material and size is well documented and understood compared to the influence of nanomaterial shape. Generally, nanoparticle shape is referred to as being either spherical or non-spherical and is known to be an important factor in many processes. Nanoparticle shape-dependent effects in areas such as immune response, cancer drug delivery, theranostics and overall implications for nanomedicines are of great interest. Studies have looked at the cellular uptake of spherical NPs, however, fewer in comparison have investigated the cellular uptake of non-spherical NPs. This review explores the exploitation of endocytic pathways for mainly inorganic non-spherical (shapes of focus include rod, triangular, star-shaped and nanospiked) nanoparticles cellular uptake. The role of mathematical modelling as predictive tools for non-spherical nanoparticle cellular uptake is also reviewed. Both quantitative structure-activity relationship (QSAR) and continuum membrane modelling have been used to gain greater insight into the cellular uptake of complex non-spherical NPs at a greater depth difficult to achieve using experimental methods.