Sex-Based Mechanisms of Cardiac Development and Function: Applications for Induced-Pluripotent Stem Cell Derived-Cardiomyocytes.

Males and females exhibit intrinsic differences in the structure and function of the heart, while the prevalence and severity of cardiovascular disease vary in the two sexes. However, the mechanisms of this sex-based dimorphism are yet to be elucidated. Sex chromosomes and sex hormones are the main contributors to sex-based differences in cardiac physiology and pathophysiology.

Malnutrition and protein energy wasting are associated with severity and progression of pediatric chronic kidney disease.

Background: Protein energy wasting (PEW), a state of deficient protein storage, is not well understood in children and adolescents with chronic kidney disease (CKD). We aimed to re-define PEW using pediatric malnutrition guidelines from the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition (AND/ASPEN), and to describe the relationship between PEW, malnutrition, and kidney function.

Methods: This was a retrospective review of outpatients ≤ 20 years old with a diagnosis of CKD from January 1, 2013, to August 31, 2018.

Bioprosthetic Valve Remodeling in Nonfracturable Surgical Valves: Impact on THV Expansion and Hydrodynamic Performance.

Background: There are limited data on the effect of bioprosthetic valve remodeling (BVR) on transcatheter heart valve (THV) expansion and function following valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) in a nonfracturable surgical heart valve (SHV).

Objectives: This study sought to assess the impact of BVR of nonfracturable SHVs on THVs after VIV implantation.

Methods: VIV TAVR was performed using 23-mm SAPIEN3 (S3, Edwards Lifesciences) or 23/26-mm Evolut Pro (Medtronic) THVs implanted in 21/23-mm Trifecta (Abbott Structural Heart) and 21/23-mm Hancock (Medtronic) SHVs with BVR performed with a noncompliant TRUE balloon (Bard Peripheral Vascular Inc).

Collection of patient race, ethnicity, and language data in emergency departments: a national survey.

Purpose: There is mounting evidence of racial and ethnic discrimination in the Canadian health care system. Patient level race and ethnicity data are required to identify potential disparities in clinical outcomes and access to health care. However, it is not known what patient race, ethnicity, and language data are collected by Canadian hospitals.

AKI in COVID-19-Associated Multisystem Inflammatory Syndrome in Children (MIS-C).

Background: Multisystem inflammatory syndrome in children (MIS-C) is a recently identified entity in association with COVID-19. AKI has been widely reported in patients with primary COVID-19 infection. However, there is a paucity of literature regarding renal injury in MIS-C.

COVID-19-Related Internet Search Patterns Among People in the United States: Exploratory Analysis.

Background: The internet is a well-known source of information that patients use to better inform their opinions and to guide their conversations with physicians during clinic visits. The novelty of the recent COVID-19 outbreak has led patients to turn more frequently to the internet to gather more information and to alleviate their concerns about the virus.

Objective: The aims of the study were to (1) determine the most commonly searched phrases related to COVID-19 in the United States and (2) identify the sources of information for these web searches.

Genetic Factors Contribute to Risk for Neonatal Respiratory Distress Syndrome among Moderately Preterm, Late Preterm, and Term Infants.

Objective: To determine the genetic contribution to risk for respiratory distress syndrome (RDS) among moderately preterm, late preterm, and term infants (estimated gestational age ≥32 weeks) of African- and European-descent.

Study Design: We reviewed clinical records for 524 consecutive twin pairs ≥32 weeks gestation. We identified pairs in which at least 1 twin had RDS (n = 225) and compared the concordance of RDS between monozygotic and dizygotic twins.

Structural basis of DNA gyrase inhibition by antibacterial QPT-1, anticancer drug etoposide and moxifloxacin.

New antibacterials are needed to tackle antibiotic-resistant bacteria. Type IIA topoisomerases (topo2As), the targets of fluoroquinolones, regulate DNA topology by creating transient double-strand DNA breaks. Here we report the first co-crystal structures of the antibacterial QPT-1 and the anticancer drug etoposide with Staphylococcus aureus DNA gyrase, showing binding at the same sites in the cleaved DNA as the fluoroquinolone moxifloxacin.

The long tail and rare disease research: the impact of next-generation sequencing for rare Mendelian disorders.

There are an estimated 6000-8000 rare Mendelian diseases that collectively affect 30 million individuals in the United States. The low incidence and prevalence of these diseases present significant challenges to improving diagnostics and treatments. Next-generation sequencing (NGS) technologies have revolutionized research of rare diseases.

Type IIA topoisomerase inhibition by a new class of antibacterial agents.

Despite the success of genomics in identifying new essential bacterial genes, there is a lack of sustainable leads in antibacterial drug discovery to address increasing multidrug resistance. Type IIA topoisomerases cleave and religate DNA to regulate DNA topology and are a major class of antibacterial and anticancer drug targets, yet there is no well developed structural basis for understanding drug action. Here we report the 2.

ERK activation drives intestinal tumorigenesis in Apc(min/+) mice.

Toll-like receptor (TLR) signaling is essential for intestinal tumorigenesis in Apc(min/+) mice, but the mechanisms by which Apc enhances tumor growth are unknown. Here we show that microflora-MyD88-ERK signaling in intestinal epithelial cells (IECs) promotes tumorigenesis by increasing the stability of the c-Myc oncoprotein. Activation of ERK (extracellular signal-related kinase) phosphorylates c-Myc, preventing its ubiquitination and subsequent proteasomal degradation.

Conventional dendritic cells regulate the outcome of colonic inflammation independently of T cells.

We explored the physiological role of conventional dendritic cells (cDCs) in acute colitis induced by a single cycle of dextran sodium sulfate administration. Depending on their mode of activation and independently of T cells, cDCs can enhance or attenuate the severity of dextran sodium sulfate-induced colitis. The latter beneficial effect was achieved, in part, by IFN-1 induced by Toll-like receptor 9-activated cDCs.

Toll-like receptor signaling in intestinal epithelial cells contributes to colonic homoeostasis.

Purpose Of Review: Since intestinal epithelium expresses Toll-like receptors, it was suggested that the intestinal epithelium is actively involved in the maintenance of colonic homeostasis. Here we describe our recent findings, which support an active contribution of colonic epithelium to intestinal homeostasis via a unique activation of epithelial TLR9.

Recent Findings: Recent data indicate that stimulation of Toll-like receptors by intestinal microbiota supports colonic homeostasis.

Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells.

The mechanisms by which commensal bacteria suppress inflammatory signalling in the gut are still unclear. Here, we present a cellular mechanism whereby the polarity of intestinal epithelial cells (IECs) has a major role in colonic homeostasis. TLR9 activation through apical and basolateral surface domains have distinct transcriptional responses, evident by NF-kappaB activation and cDNA microarray analysis.

Activation of anti-hepatitis C virus responses via Toll-like receptor 7.

IFN-alpha is used to suppress the replication of hepatitis C virus (HCV) in chronically infected patients with partial success. Here we present evidence showing that a ligand of Toll-like receptor 7 (TLR7) can induce anti-HCV immunity not only by IFN induction, but also through an IFN-independent mechanism. Human hepatocyte line Huh-7 carrying an HCV replicon expressed TLR7, and activation of the receptor induced several antiviral genes including IFN regulatory factor-7.

Induction and inhibition of the Th2 phenotype spread: implications for childhood asthma.

The interactions between genetic and environmental factors play a major role in the development of childhood asthma. We hypothesized that a pre-existing Th2/asthmatic response can promote Th2 responses to newly encountered Ags (i.e.