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OBJECTIVES This study aimed to evaluate whether patients stratified by age have the same level of benefits after a sacral neuromodulation (SNM) procedure for refractory lower urinary tract dysfunction. MATERIALS AND METHODS This retrospective study comprised 211 patients with refractory lower urinary tract dysfunction who had been treated with SNM and recruited from multiple medical centers across China. Patients were grouped according to age 64-year-old age groups. Quality of life scores improved in the less then 40-year-old age group. Voiding diary data among age groups varied at baseline; however, average urinary frequency did not differ at the last follow-up. Urgency and sexual life scores differed at baseline and these differences had resolved at the last follow-up. O'Leary-Sant and Pelvic Pain and Urgency/Frequency Symptoms Scale scores did not differ at baseline; however, significant differences were observed at the last follow-up. CONCLUSIONS SNM success is unrelated to age, and age alone should not be considered a limiting factor in SNM. For older patients, an overactive bladder appears a better indication for SNM treatment; however, further studies are required to confirm this finding. © 2020 International Neuromodulation Society.ABCA3 transports phospholipids across lamellar body membranes in pulmonary alveolar type II cells and is required for surfactant assembly. Rare, biallelic, pathogenic ABCA3 variants result in lethal neonatal respiratory distress syndrome and childhood interstitial lung disease. Qualitative functional characterization of ABCA3 missense variants suggests two pathogenic classes disrupted intracellular trafficking (type I mutant) or impaired ATPase-mediated phospholipid transport into the lamellar bodies (type II mutant). We qualitatively compared wild-type (WT-ABCA3) with four uncharacterized ABCA3 variants (c.418A>C;p.Asn140His, c.3609_3611delCTT;p.Phe1203del, c.3784A>G;p.Ser1262Gly, and c.4195G>A;p.Val1399Met) in A549 cells using protein processing, colocalization with intracellular organelles, lamellar body ultrastructure, and ATPase activity. We quantitatively measured lamellar body-like vesicle diameter and intracellular ABCA3 trafficking using fluorescence-based colocalization. buy Dooku1 Three ABCA3 variants (p.Asn140His, p.Ser1262Gly, and p.Val1399Met) were processed and trafficked normally and demonstrated well-organized lamellar body-like vesicles, but had reduced ATPase activity consistent with type II mutants. P.Phe1203del was processed normally, had reduced ATPase activity, and well-organized lamellar body-like vesicles, but quantitatively colocalized with both endoplasmic reticulum and lysosomal markers, an intermediate phenotype suggesting disruption of both intracellular trafficking and phospholipid transport. All ABCA3 mutants demonstrated mean vesicle diameters smaller than WT-ABCA3. Qualitative and quantitative functional characterization of ABCA3 variants informs mechanisms of pathogenicity. © 2020 Wiley Periodicals, Inc.The aberrant expression of matrix metalloproteinases (MMPs) is known to contribute to the pathogenesis of airway remodeling and alveolar disruption in chronic obstructive pulmonary disease (COPD). In the discovery stage, 11 COPD from five families were subjected to whole-genome sequencing (WGS), and 21 common polymorphisms in MMPs and TIMPs were identified. These polymorphisms were genotyped in two subsequent verification studies. Of these polymorphisms, c.2392G>A (rs2664370T>C)and c.4158C>A (rs2664369T>G) in MMP16 remained significantly different. Functionally, we found that MMP16 expression was significantly increased in peripheral blood monocytes (PBMCs) from COPD and in cigarette smoke extract (CSE)-treated 16HBE cells compared to controls. This was also shown by bioinformatic analysis. COPD carrying rs2664370CC showed decreased levels of MMP16 in the plasma and in PBMCs compared to those carrying CT and TT. Treatment with hsa-miR-576-5p mimics led to a greater reduction in luciferase reporter activity in cells transfected with rs2664370CC. Moreover, blood levels of base excess, PCO2 , and PO2 in COPD with rs2664370CC were significantly lower than those with rs2664370CT+TT. Taken together, these results demonstrate that the rs2664370T>C polymorphism in MMP16 protects against the risk of COPD, likely by favoring an interaction with hsa-miR-576-5p, leading to reduced MMP16 expression and improved blood gas levels. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND AND AIMS Cigarette smoking often results in nicotine dependence. With use of electronic cigarettes as an alternative source of nicotine, it is important to assess dependence associated with e-cigarette use. This study assesses dependence among current and former adult e-cigarette users on cigarettes and e-cigarettes, compared with dependence on cigarettes. DESIGN Cross-sectional data from the Population Assessment of Tobacco and Health (PATH) study from 2013-2016. Psychometrically-assessed dependence was compared for cigarettes and e-cigarettes among current and former exclusive and dual users of the products, and among e-cigarette users who had and had not recently stopped smoking. SETTING A population-based representative sample of US adults. PARTICIPANTS Participants were 13,311 US adults (18+) in Waves 1-3 of PATH reporting current established smoking, current use of e-cigarettes, or stopping use of either product in the past year who were administered dependence assessments for cigarettes and/rette dependence was among e-cigarette users who had stopped smoking (2.17 [0.08]). CONCLUSIONS Use of e-cigarettes appears to be consistently associated with lower nicotine dependence than cigarette smoking. This article is protected by copyright. All rights reserved.PROBLEM The dysregulation of trophoblast functions is one of the leading causes of recurrent miscarriage (RM), which frustrates 1%-5% of couples of childbearing ages. Sprouty 4 (SPRY4) is considered as a tumour suppressor and exerts a negative role in cell viability. However, its role in regulating trophoblast behaviors at the maternal-fetal interface remains largely unknown. METHOD OF STUDY First-trimester villous samples were collected from RM patients and healthy controls (HCs) to determine the SPRY4 expression in human placenta during early pregnancy. The HTR8/SVneo cell line was introduced to clarify trophoblast cell functions via transfecting with specific short interfering RNA against SPRY4 or SPRY4-overexpressing lentivirus in vitro. In addition, gene expression microarray analysis was performed to explore the downstream molecules and pathways. RESULTS Our results revealed that SPRY4 expression was significantly increased in the first-trimester cytotrophoblasts of RM patients compared with HCs. Furthermore, SPRY4 overexpression inhibited trophoblast proliferation and accelerated apoptosis in vitro, while SPRY4 knockdown reversed these effects.
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