Carneyboll5665
INTRODUCTION Limited work has directly compared the role of different neighborhood factors or examined their interactive effects on pediatric asthma outcomes. Our objective was to quantify the main and interactive effects of neighborhood deprivation and residential instability (RI) on pediatric asthma outcomes. METHODS We conducted a retrospective cross-sectional study of patients with a primary diagnosis of asthma hospitalized at a tertiary care pediatric hospital. Residential addresses at the index hospitalization were linked to the state area deprivation index (ADI). RI was coded as the number of residences in the past 4 years. Logistic and ordinal regression and Cox regression survival analyses were used to estimate the effect on the primary outcomes of chronic asthma severity (intermittent, mild persistent, moderate persistent, severe persistent/other) as defined by the National Heart, Lung, and Blood Institute, severe hospitalization (requiring continuous albuterol or intensive care unit care), and time to emergency department (ED) readmission and rehospitalization within 365 days of the index visit, respectively. RESULTS In the sample (N = 664), 21% had severe persistent/other asthma, 22% had severe hospitalization, 37% were readmitted to the ED, and 19% were rehospitalized. Increasing RI was independently associated with more severe chronic asthma (odds ratio = 1.18, 95% confidence interval [CI] = 1.05, 1.32, P = .004), greater risk of 365-day ED readmission (hazard ratio [HR] = 1.10, 95% CI = 1.05, 1.15, P less then .0001), and greater risk of 365-day rehospitalization (HR = 1.09, 95% CI = 1.03, 1.14, P = .002). selleckchem There were no significant associations between ADI and these outcomes. Further, we did not find significant evidence of interactive effects. CONCLUSIONS RI appears to be modestly associated with pediatric asthma outcomes, independent of current neighborhood deprivation. © 2020 Wiley Periodicals, Inc.Abamectin (ABA) as one of the worldwide used compounds in agriculture has raised safety concerns on nontarget organism toxicity. However, the study of male reproductive system damage caused by ABA remains unclear. Our aim is to investigate the effect of ABA-induced cytotoxicity in TM3 Leydig cells and their underlying mechanisms. ABA inhibits TM3 cell viability and proliferation via cell cycle arrested in the G0/G1 phase. In addition, ABA-induced mitochondrial depolarization leads to an imbalance in Bcl-2 family expression, causing caspase-dependent apoptosis in TM3 cells. The increased ratio of cells expression LC3 protein and LC3-II to LC3-I indicated the activation of autophagy potentially. Further experiments revealed ABA treatment reduced phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) phosphorylation, and mammalian target of rapamycin (mTOR) phosphorylation. Pretreatment with a PI3K/AKT inhibitor, LY294002, mimicked the ABA-mediated effects on cytotoxicity. Pretreatment with a PI3K/AKT agonist, insulin-like growth factor-1, reversed the effects of ABA. ABA caused the accumulation of intracellular reactive oxygen species (ROS) by increased intensity of the ROS indicator. However, N-acetylcysteine as ROS scavengers inhibited ABA-induced apoptosis and autophagy and reversed these ABA-mediated effects on PI3K/AKT/mTOR pathway. On the basis of the above results, it is suggested that ABA exposure induces apoptosis and autophagy in TM3 cells by ROS accumulation to mediate PI3K/AKT/mTOR signaling pathway suppression. © 2020 Wiley Periodicals, Inc.BACKGROUND Diffuse large B-cell lymphoma (DLBCL) patients with concurrent hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection have distinct clinical features. Nevertheless, the prognostic value of HBsAg in DLBCL in the rituximab era remains unclear. PATIENTS AND METHODS We conducted a retrospective cohort study to investigate the clinical relevance of HBsAg in immunocompetent patients with DLBCL treated with homogeneous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone between 2002 and 2016. RESULTS Among 416 analyzed patients, 98 (23.6%) were HBsAg-positive. HBsAg positivity was associated with a younger age and more advanced stage at diagnosis, more frequent hepatic impairment during perichemotherapy, and a trend of higher National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score at diagnosis. Compared with the HBsAg-negative patients, the HBsAg-positive patients had a lower overall response rate (76.5% vs. 85.5%, P = 0.043), poo In this large, retrospective cohort study from an area with high prevalence of HBV infection, the authors demonstrated that HBsAg was an independent unfavorable factor significantly associated with survival, highlighting its potential as a novel prognostic indicator to improve the risk stratification of patients with DLBCL in the rituximab era. © AlphaMed Press 2020.BACKGROUND DNA damage response (DDR) genomic alterations may play an important role in clinical outcomes of patients with urothelial cancer (UC). However, data on the prognostic role of DDR gene alterations in patients with advanced UC remains unclear. METHODS We retrospectively collected data of three independent patient cohorts with relapsed or advanced UC including 81 and 91 patients from four institutions who underwent FoundationOne genomic sequencing as well as 129 patients selected from TCGA bladder cohort. Fisher's exact test was used to determine differences of mutation frequency among the three cohorts. Logistic regression analysis was performed to calculate odds ratio (OR) and 95% confidence interval (CI). Overall survival (OS) was measured from time of initial diagnosis and Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% CI. RESULTS DDR genomic alterations were present in 76.5% (62/81), 40.7% (37/91) and 51.2% (66/129) of the three cohorts. ATM a a complex role of ATM in tumor progression and calls for further studies to to determine the underlying mechanisms and biomarker clinical utility. © AlphaMed Press 2020.