Bakpalm8088

This cross-sectional cohort study uses census data to approximate population estimates of obstructive eustachian tube dysfunction among US adolescents.This cohort study assesses the incidence of coronavirus disease 2019 (COVID-19) in pediatric patients presenting for surgery at 3 tertiary care children’s hospitals across the US.Importance The contribution of long-term intraocular pressure (IOP) variability to the development of primary open-angle glaucoma is still controversial. Objective To assess whether long-term IOP variability data improve a prediction model for the development of primary open-angle glaucoma (POAG) in individuals with untreated ocular hypertension. Design, setting, and participants This post hoc secondary analysis of 2 randomized clinical trials included data from 709 of 819 participants in the observation group of the Ocular Hypertension Treatment Study (OHTS) followed up from February 28, 1994, to June 1, 2002, and 397 of 500 participants in the placebo group of the European Glaucoma Prevention Study (EGPS) followed up from January 1, 1997, to September 30, 2003. Data analyses were completed between January 1, 2019, and March 15, 2020. Exposures The original prediction model for the development of POAG included the following baseline factors age, IOP, central corneal thickness, vertical cup-disc ratio, and paas follows mean follow-up IOP, 0.784; maximum IOP, 0.781; SD of IOP, 0.745; range of IOP, 0.741; and coefficient of variation IOP, 0.729. The C statistics in the EGPS were similarly ordered. No measure of IOP variability, when added to the prediction model that included mean follow-up IOP, age, central corneal thickness, vertical cup-disc ratio, and pattern SD, increased the C statistic by more than 0.007 in either cohort. Conclusions and relevance Evidence from the OHTS and the EGPS suggests that long-term variability does not add substantial explanatory power to the prediction model as to which individuals with untreated ocular hypertension will develop POAG.Importance Reduced-intensity conditioning and nonmyeloablative conditioning (RIC-NMAC) regimens are frequently used in allogeneic hematopoietic cell transplant (HCT) for non-Hodgkin lymphoma. However, the optimal RIC-NMAC regimen in allogeneic HCT for non-Hodgkin lymphoma is not known. Objective To investigate whether RIC-NMAC regimens at a higher end of the intensity spectrum are associated with increased nonrelapse mortality and lower overall survival compared with RIC-NMAC regimens at the lower end of the intensity spectrum in patients with non-Hodgkin lymphoma undergoing allogeneic HCT. Design, setting, and participants This cohort study used data from 1823 adult patients with non-Hodgkin lymphoma in the Center for International Blood and Marrow Transplant Research registry. Included patients underwent allogeneic HCT using matched related or unrelated donors between January 2008 and December 2016. Statistical analysis was performed from June 1, 2019, to February 10, 2020. Interventions Patients received 1u-Mel140 compared with Flu-Bu (hazard ratio [HR], 1.34; 95% CI, 1.13-1.59; P less then .001). Compared with the Flu-Cy cohort, the Flu-Mel140 cohort had a higher risk of chronic GVHD (HR, 1.38; 95% CI, 1.15-1.65; P less then .001). The Flu-Mel140 regimen was associated with a higher nonrelapse mortality risk (HR, 1.78; 95% CI, 1.37-2.31; P less then .001) compared with the Flu-Bu regimen. Conclusions and relevance The findings suggest that use of the more intense RIC-NMAC regimen, Flu-Mel140, may have a negative association with overall survival and may be associated with higher nonrelapse mortality. The Flu-Bu and Flu-Cy regimens with or without 2GyTBI regimens appeared to provide comparable overall survival.A very large number of computational methods to predict the change in thermodynamic stability of proteins due to mutations have been developed during the last 30 years, and many different web servers are currently available. Nevertheless, most of them suffer from severe drawbacks that decrease their general reliability and, consequently, their applicability to different goals such as protein engineering or the predictions of the effects of mutations in genetic diseases. In this review, we have summarized all the main approaches used to develop these tools, with a survey of the web servers currently available. Moreover, we have also reviewed the different assessments made during the years, in order to allow the reader to check directly the different performances of these tools, to select the one that best fits his/her needs, and to help naïve users in finding the best option for their needs.Importance Treatment with noninvasive oxygenation strategies such as noninvasive ventilation and high-flow nasal oxygen may be more effective than standard oxygen therapy alone in patients with acute hypoxemic respiratory failure. Objective To compare the association of noninvasive oxygenation strategies with mortality and endotracheal intubation in adults with acute hypoxemic respiratory failure. Data sources The following bibliographic databases were searched from inception until April 2020 MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and LILACS. No limits were applied to language, publication year, sex, or race. Study selection Randomized clinical trials enrolling adult participants with acute hypoxemic respiratory failure comparing high-flow nasal oxygen, face mask noninvasive ventilation, helmet noninvasive ventilation, or standard oxygen therapy. Data extraction and synthesis Two reviewers independently extracted individual study data and evaluated stu.60 to -0.16]; low certainty), face mask noninvasive ventilation (RR, 0.76 [95% CrI, 0.62-0.90]; absolute risk difference, -0.12 [95% CrI, -0.25 to -0.05]; moderate certainty) and high-flow nasal oxygen (RR, 0.76 [95% CrI, 0.55-0.99]; absolute risk difference, -0.11 [95% CrI, -0.27 to -0.01]; moderate certainty) were associated with lower risk of endotracheal intubation (25 studies [3804 patients]). The risk of bias due to lack of blinding for intubation was deemed high. Conclusions and relevance In this network meta-analysis of trials of adult patients with acute hypoxemic respiratory failure, treatment with noninvasive oxygenation strategies compared with standard oxygen therapy was associated with lower risk of death. Further research is needed to better understand the relative benefits of each strategy.The dynamic topological structure of telomeric DNA is closely related to its biological function; however, no such structural information on full-length telomeric DNA has been reported due to difficulties synthesizing long double-stranded telomeric DNA. Herein, we developed an EM-PCR and TA cloning-based approach to synthesize long-chain double-stranded tandem repeats of telomeric DNA. Using mechanical manipulation assays based on single-molecule atomic force microscopy, we found that mechanical force can trigger the melting of double-stranded telomeric DNA and the formation of higher-order structures (G-quadruplexes or i-motifs). Our results show that only when both the G-strand and C-strand of double-stranded telomeric DNA form higher-order structures (G-quadruplexes or i-motifs) at the same time (e.g. in the presence of 100 mM KCl under pH 4.7), that the higher-order structure(s) can remain after the external force is removed. The presence of monovalent K+, single-wall carbon nanotubes (SWCNTs), acidic conditions, or short G-rich fragments (∼30 nt) can shift the transition from dsDNA to higher-order structures. Our results provide a new way to regulate the topology of telomeric DNA.Study objectives The objective of this study was to evaluate the association between gestational sleep deprivation and childhood adiposity and cardio metabolic profile. Methods Data were used from two population-based birth cohorts (Rhea study and Amsterdam Born Children and their Development study). A total of 3,608 pregnant women and their children were followed up until the age of 11 years. Gestational sleep deprivation was defined as six or fewer hours of sleep per day, reported by questionnaire. The primary outcomes included repeated measures of body mass index (BMI), waist circumference, body fat, serum lipids, systolic and diastolic blood pressure levels in childhood. We performed a pooled analysis with adjusted linear mixed effect and Cox proportional hazards models. We tested for mediation by birthweight, gestational age and gestational diabetes. Results Gestational sleep deprivation was associated with higher BMI (beta; 95%CI 0.7; 0.4, 1.0 kg/m2) and waist circumference (beta; 95%CI 0.9; 0.1, 1.6 cm) in childhood, and increased risk for overweight or obesity (HR; 95%CI 1.4; 1.1, 2.0). Gestational sleep deprivation was also associated with higher offspring diastolic blood pressure (beta; 95%CI 1.6; 0.5, 2.7 mmHg). The observed associations were modified by sex (all p-values for interaction less then 0.05); and were more pronounced in girls. Gestational diabetes and shorter gestational age partly mediated the seen associations. Conclusions This is the first study showing that gestational sleep deprivation may increase offspring's adiposity and blood pressure, while exploring possible mechanisms. Attention to glucose metabolism and preterm birth might be extra warranted in mothers with gestational sleep deprivation.The long non-coding RNA NEAT1 serves as a scaffold for the assembly of paraspeckles, membraneless nuclear organelles involved in gene regulation. Paraspeckle assembly requires NEAT1 recruitment of the RNA-binding protein NONO, however the NEAT1 elements responsible for recruitment are unknown. Herein we present evidence that previously unrecognized structural features of NEAT1 serve an important role in these interactions. Led by the initial observation that NONO preferentially binds the G-quadruplex conformation of G-rich C9orf72 repeat RNA, we find that G-quadruplex motifs are abundant and conserved features of NEAT1. Furthermore, we determine that NONO binds NEAT1 G-quadruplexes with structural specificity and provide evidence that G-quadruplex motifs mediate NONO-NEAT1 association, with NONO binding sites on NEAT1 corresponding largely to G-quadruplex motifs, and treatment with a G-quadruplex-disrupting small molecule causing dissociation of native NONO-NEAT1 complexes. Together, these findings position G-quadruplexes as a primary candidate for the NONO-recruiting elements of NEAT1 and provide a framework for further investigation into the role of G-quadruplexes in paraspeckle formation and function.AIDS Clinical Trials Group study A5308 found reduced T-cell activation and exhaustion in HIV controllers initiating antiretroviral therapy (ART). We further assessed HIV-specific T-cell responses and post-ART viral loads. Pre-ART, the 31% of participants with persistently undetectable viremia had more robust HIV-specific T-cell responses. On ART, significant decreases were observed in a broad range of T-cell responses. Eight controllers in A5308 and the SCOPE cohort showed no viremia above the level of quantification in the first 12 weeks after ART discontinuation. ART significantly reduced HIV-specific T-cell responses in HIV controllers but did not adversely affect controller status after ART discontinuation.