• Childers James posted an update 4 hours, 39 minutes ago

    Nalmefene had a greater effect on ACTH and cortisol, compared with naltrexone. Both compounds also caused elevations in prolactin in males (females were not examined, due to the influence of menstrual cycle on prolactin). CONCLUSIONS This study suggests that both nalmefene and naltrexone have effects potentially due to κ-partial agonism in humans, as well as antagonist effects at μ-receptors. © 2020 John Wiley & Sons Ltd.BACKGROUND Although pelvic floor dysfunction (PFD) has a multifactorial etiology, pregnancy and childbirth are considered crucial events predisposing to urinary incontinence as well as pelvic organ prolapse, which are highly prevalent. Rats are the most frequently used animal model and pudendal nerve crush (PNC) and vaginal distension (VD) are often used to mimic vaginal delivery. OBJECTIVE To document the time course of events after simulated vaginal delivery (SVD) on the urethral sphincter and the vaginal smooth muscle layer. MATERIALS AND METHODS Virgin female Sprague-Dawley rats were subjected to SVD (PNC + VD) or sham surgery and evaluated at 7, 14, 21, and 42 days after the injury. Urethral function was determined in vivo by microultrasound during cystometry and vaginal smooth muscle layer was harvested for in vitro pharmacologic investigation by isometric tension recording. Furthermore, vaginal and urethral samples were investigated by immunohistochemistry and real-time quantitative polymerase chain reaction. RESULTS Microultrasound showed no bursting of the urethral sphincter in the SVD group at 7 days with a functional recovery starting at 14 days, and normal bursting at 21 and 42 days. Vaginal smooth muscle showed higher sensitivity to carbachol at 14 and 21 days after injury; however, at 42 days, its sensitivity decreased when compared with sham. CONCLUSION SVD induces urethral dysfunction and a shift in vaginal smooth muscle contractile responses to carbachol. © 2020 Wiley Periodicals, Inc.BACKGROUND The use of remote support technologies is a newer form of service that can contribute to increased independence while giving adults with intellectual and developmental disabilities a sense of home safety. This research reviewed the use of remote support services, which is a waiver service that includes smart home technologies and remote support staff that can be called upon, when needed. METHOD Using focus groups and telephone interviews, the present authors asked users of remote support services about their experience, including what they liked most and least about their experience with these technologies. RESULTS Overall, increased independence and a sense of security and home safety were identified as the two principal benefits. Remote support technologies may be a part of the solution to addressing the lack of direct support professionals available to provide in-home care. CONCLUSIONS The present authors discuss the benefits of remote support technologies and offer recommendations for future research regarding remote support technologies and the potential benefits of this newer form of support service. © 2020 John Wiley & Sons Ltd.OBJECTIVE Our objective was to perform a systematic review and meta-analysis on randomized controlled trials (RCTs) assessing the effect of flaxseed supplementation on serum adiponectin and leptin concentration. METHODS Electronic searches were performed in PubMed, Scopus, Web of Science, and Google Scholar up to May 2019 without any restriction. All RCTs that reported the effect of flaxseed supplementation on circulating adiponectin and leptin concentration were included. A random-effects model was used to pool calculated effect sizes. RESULTS Nine RCTs (11 arms) were eligible to be included. Our analysis showed that flaxseed supplementation did not significantly affect adiponectin (weighted mean difference [WMD] 0.15 μg/ml; 95% CI [-0.16, 0.47], p = .34) and leptin (WMD 0.47 ng/ml; 95% CI [-3.10, 4.06], p = .79) concentration in comparison with control. Furthermore, subgroup analysis revealed that effects remained nonsignificant in all subgroups of trial duration, flaxseed type, and health status of participants. The pooled effect size was also robust and remained nonsignificant in the sensitivity analysis. CONCLUSION Flaxseed supplementation had no significant effect on adiponectin and leptin levels in adults. However, future well-designed trials are still needed to confirm these results. © 2020 John Wiley & Sons, Ltd.A highly efficient and targeted clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system was constructed for Pichia pastoris (syn Komagataella phaffii). Plasmids containing single guide RNA and the methanol expression regulator 1 (MXR1) homology arms were used to precisely edit the transcriptional activator Mxr1 on the P. pastoris genome. At the S215 amino acid position of Mxr1, one, two, and three nucleotides were precisely deleted or inserted, and S215 was also mutated to S215A via a single-base substitution. Sequencing of polymerase chain reaction (PCR) amplicons in the region spanning MXR1 showed that CRISPR/Cas9 technology enabled efficient and precise gene editing of P. pastoris. The expression levels of several of the Mxr1-targeted genes, AOX1, AOX2, DAS1, and DAS2, in strains containing the various mutated variants of MXR1, were then detected through reverse transcription PCR following induction in methanol-containing culture medium. The frameshift mutations of Mxr1 led to almost zero transcription of AOX1, DAS1, and DAS2, while that of AOX2 was reduced to 60%. For the Mxr1 S215A mutant, the transcription of AOX1, AOX2, DAS1, and DAS2 was also reduced by nearly 60%. find more Based on these results, it is apparent that the transcription of AOX1, DAS1, and DAS2 is exclusively regulated by Mxr1 and serine phosphorylation at Mxr1 residue 215 is not critical for this function. In contrast, the transcription of AOX2 is mainly dependent on the phosphorylation of this residue. CRISPR/Cas9 technology was, therefore, successfully applied to the targeted editing of MXR1 on the P. pastoris genome, and it provided an effective method for the study of this transcription factor and its targets. © 2020 John Wiley & Sons, Ltd.