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Nanomedicines along with microneedles: helpful information for their particular analysis and program.
BACKGROUND Both tioguanine and low-dose thiopurines combined with allopurinol (LDTA) can be considered for the treatment of inflammatory bowel disease (IBD) when conventional thiopurines fail due to adverse events. AIM To compare the safety of tioguanine and LDTA in IBD patients. METHODS Inflammatory bowel disease patients who failed conventional thiopurines due to adverse events and initiated LDTA in standard care were identified in the prospective ICC Registry. IBD patients who failed conventional thiopurines due to adverse events and initiated tioguanine were enrolled in three university hospitals. Patients on concomitant biologicals were excluded. The primary outcome was discontinuation of therapy due to adverse events. Secondary outcomes included safety outcomes and surgery-, biological- and corticosteroid-free clinical remission (physician global assessment = 0) after 104 weeks. Both multiple logistic regression and propensity score matching were used to correct for confounders. RESULTS In total, 182 IBD patients treated with tioguanine (n = 94) or LDTA (n = 88) were included with a median follow-up of 104 weeks (IQR 91-104). Of these, 19% (tioguanine 20%, LDTA 18%) of patients discontinued therapy due to adverse events. After adjusting for confounders, there were no differences in terms of discontinuation rate due to adverse events (OR 0.50, 95% CI 0.15-1.68, P = 0.26), adverse events (OR 0.89, 95% CI 0.44-1.81, P = 0.75), infections (OR 1.05, 95% CI 0.40-2.73, P = 0.93), hospitalisations (OR 2.00, 95% CI 0.64-6.23, P = 0.23) or clinical remission (OR 0.74, 95%CI 0.33-1.68, P = 0.48). All results are comparable with the propensity score matched cohort. CONCLUSION Nineteen percent of IBD patients with prior failure to conventional thiopurines due to adverse events discontinued therapy with tioguanine or LDTA due to adverse events. Either therapy may be considered before escalating to biological therapy. © 2020 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.Gastrointestinal stromal tumor (GIST) is a common mesenchymal tumor in the gastrointestinal tract. see more Prostate cancer associated transcript 6 (PCAT6) is a long noncoding RNA (lncRNA) and plays a pivotal role in tumor formation. Present study was designed to explore the function of PCAT6 in GIST. Ki67 staining, colony formation and trypan blue staining assays revealed that PCAT6 boosted GIST cell proliferation but inhibited cell apoptosis. Also, sphere formation assay and Western blot uncovered the promoting role of PCAT6 in GIST stemness. Then, we identified that PCAT6 could activate Wnt/β-catenin pathway. And the tumor facilitator role of Wnt/β-catenin pathway was validated in the rescue assays. Next, miR-143-3p was identified as the downstream microRNA of PCAT6. Moreover, miR-143-3p itself served as a tumor suppressor in GIST. Subsequently, peroxiredoxin 5 (PRDX5) was verified as the target of miR-143-3p. PCAT6 promoted GIST cell proliferation and stemness via sponging miR-143-3p to upregulate PRDX5. In a word, PCAT6 promoted GIST cell proliferation and stemness but inhibited cell apoptosis via competing endogenous RNA pattern and activation of Wnt pathway, which might contribute to GIST treatment. © 2020 Wiley Periodicals, Inc.OBJECTIVES The malignant ultrasound (US) features of breast cancer are known to include an irregular shape, a noncircumscribed margin, an echogenic halo, a nonparallel orientation, posterior acoustic attenuation, microcalcification, and others. However, these US features are uncertain and controversial for the diagnosis of triple-negative breast cancer (TNBC). This study aimed to analyze the diagnostic value of malignant US features for TNBC by a systematic review and meta-analysis, analyze the US characteristics of TNBC, and provide US evidence for clinical diagnosis. METHODS A comprehensive search was performed to identify relevant English articles concerning the US diagnosis of TNBC (from the date of database establishment to November 2019). The pooled sensitivity, pooled specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio with 95% confidence interval, summary receiver operating characteristic curve, and area under the curve for the different malignant US features were calculated. RESULTS Ten studies (620 patients) met the eligibility criteria. The sensitivity (range, 0.14-0.68) and specificity (range, 0.19-0.66) of the malignant US features were not high. Summary receiver operating characteristic curves showed that the area under the curve (range, 0.25-0.47) of the malignant US features was low, demonstrating that these features have poor diagnostic value for TNBC. The positive likelihood ratio (range, 0.4-to 0.9) of the malignant US features was low, and the negative likelihood ratio (range, 1.09-2.02) was not low, revealing that these features had a poor ability to confirm or exclude TNBC. CONCLUSIONS Triple-negative breast cancer lacks the typical malignant US features of breast cancer and has its own US features. © 2020 by the American Institute of Ultrasound in Medicine.The Global Polio Eradication Initiative (GPEI) partners engaged modelers during the past nearly 20 years to support strategy and policy discussions and decisions, and to provide estimates of the risks, costs, and benefits of different options for managing the polio endgame. Limited efforts to date provided insights related to the validation of the models used for GPEI strategy and policy decisions. However, modeling results only influenced decisions in some cases, with other factors carrying more weight in many key decisions. In addition, the results from multiple modeling groups do not always agree, which supports selection of some strategies and/or policies counter to the recommendations from some modelers but not others. This analysis reflects on our modeling, and summarizes our premises and recommendations, the outcomes of these recommendations, and the implications of key limitations of models with respect to polio endgame strategy. We briefly review the current state of the GPEI given epidemiological experience as of early 2020, which includes failure of the GPEI to deliver on the objectives of its 2013-2018 strategic plan despite full financial support. Looking ahead, we provide context for why the GPEI strategy of global oral poliovirus vaccine (OPV) cessation to end all cases of poliomyelitis looks infeasible given the current state of the GPEI and the failure to successfully stop all transmission of serotype 2 live polioviruses within four years of the April-May 2016 coordinated cessation of serotype 2 OPV use in routine immunization. © 2020 The Authors. Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.BACKGROUND Taurine is an antioxidant that is abundant in some common energy drinks. Here we hypothesized that the antioxidant activity of taurine in red blood cells (RBCs) could be leveraged to counteract storage-induced oxidant stress. STUDY DESIGN AND METHODS Metabolomics analyses were performed on plasma and RBCs from healthy volunteers (n = 4) at baseline and after consumption of a whole can of a common, taurine-rich (1000 mg/serving) energy drink. Reductionistic studies were also performed by incubating human RBCs with taurine ex vivo (unlabeled or 13 C15 N-labeled) at increasing doses (0, 100, 500, and 1000 μmol/L) at 37°C for up to 16 hours, with and without oxidant stress challenge with hydrogen peroxide (0.1% or 0.5%). Finally, we stored human and murine RBCs under blood bank conditions in additives supplemented with 500 μmol/L taurine, before metabolomics and posttransfusion recovery studies. RESULTS Consumption of energy drinks increased plasma and RBC levels of taurine, which was paralleled by increases in glycolysis and glutathione (GSH) metabolism in the RBC. These observations were recapitulated ex vivo after incubation with taurine and hydrogen peroxide. Taurine levels in the RBCs from the REDS-III RBC-Omics donor biobank were directly proportional to the total levels of GSH and glutathionylated metabolites and inversely correlated to oxidative hemolysis measurements. Storage of human RBCs in the presence of taurine improved energy and redox markers of storage quality and increased posttransfusion recoveries in FVB mice. CONCLUSION Taurine modulates RBC antioxidant metabolism in vivo and ex vivo, an observation of potential relevance to transfusion medicine. © 2020 AABB.OBJECTIVES To the best of our knowledge, no study has examined the reliability of assessment methods for male pelvic floor muscle (PFM) function. Therefore, this study aimed to clarify the reliability of manometry with an anal sensor (Peritron cat 9300A) to assess PFM function in healthy men. METHODS Healthy male subjects (n = 21) without urinary leakage underwent testing to assess PFM function, and intra- and interrater reliability tests among examiners were performed. The PFM function included maximal anorectal squeeze pressure, endurance, mean anorectal squeeze pressure, gradient, and area under the curve during PFM voluntary contraction. RESULTS Participants had a median age of 38 years (range 26-51), and a mean BMI of 23.2 ± 2.0 kg/m2 . Satisfactory intra- and interrater reliability scores were found for resting pressure, anorectal squeeze pressure, and endurance. The intra-rater reliability of resting pressure, anorectal squeeze pressure, and endurance were 0.71, 0.89, and 0.75 for examiner 1 and 0.72, 0.89, and 0.87 for examiner 2. The interrater reliability for resting pressure, anorectal squeeze pressure, and endurance were 0.58, 0.93, and 0.61, respectively. CONCLUSIONS This is the first prospective study showing the favorable intra- and interrater reliability of manometry for PFM function in healthy men. Our findings demonstrated that manometry can provide both reliable and reproducible data regarding PFM function in continent men, suggesting Peritron cat 9300A can be used to evaluate the PFM function in men. © 2020 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.Returning veterans often face multiple concurrent psychiatric and behavioral conditions that negatively impact reintegration into civilian life and are associated with functional disability. Understanding how conditions interact to negatively impact functioning is an important step toward developing holistic treatment approaches optimized for this population. This study utilized a cross-sectional and prospective longitudinal cohort design, applying regression algorithms to understand the relative contribution of common clinical issues to functional disability in U.S. veterans who served after the September 11, 2001 (9/11), terror attacks. Community-dwelling post-9/11 veterans (N = 397) completed detailed assessments, including common clinical condition diagnoses, combat experience, and demographics, which were used to predict functional disability (World Health Organization Disability Assessment Schedule); 205 participants were reassessed approximately 1-2 years after enrollment. Regression analyses showed a strong association between the predictor variables and functional disability, f 2 = 1.488. Validation analyses showed a high prediction ability of functional disability to independent samples, r = .719, and across time in the same individuals, r = .780. The strongest predictors included current posttraumatic stress disorder, depressive disorder, sleep disturbance, and pain diagnoses. These results demonstrate the importance of considering multiple common co-occurring conditions when assessing functional disability in post-9/11 veterans and suggest that certain syndromes contribute the most unique information to predicting functional disability with high confidence. As most U.S. veterans utilize private healthcare systems, these results have clinical utility for both Veterans Affairs and civilian healthcare practitioners in assessing and monitoring functional disability in post-9/11 veterans over time. © 2020 International Society for Traumatic Stress Studies.
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