An Exploratory Analysis of Sociodemographic Factors Associated With Physical Functional Impairment in ICU Survivors.

Importance: Physical functional impairment is one of three components of postintensive care syndrome (PICS) that affects up to 60% of ICU survivors.

Objectives: To explore the prevalence of objective physical functional impairment among a diverse cohort of ICU survivors, both at discharge and longitudinally, and to highlight sociodemographic factors that might be associated with the presence of objective physical functional impairment.

Design, Setting, And Participants: This was a secondary analysis of 37 patients admitted to the ICU in New Orleans, Louisiana, and Denver, Colorado between 2016 and 2019 who survived with longitudinal follow-up data.

Sildenafil Versus Placebo for Early Pulmonary Vascular Disease in Scleroderma (SEPVADIS): protocol for a randomized controlled trial.

Background: Pulmonary hypertension (PH) is a leading cause of death in patients with systemic sclerosis (SSc). An important component of SSc patient management is early detection and treatment of PH. Recently the threshold for the diagnosis of PH has been lowered to a mean pulmonary artery pressure (mPAP) threshold of > 20 mmHg on right heart catheterization (RHC).

Arhgef2 regulates mitotic spindle orientation in hematopoietic stem cells and is essential for productive hematopoiesis.

How hematopoietic stem cells (HSCs) coordinate their divisional axis and whether this orientation is important for stem cell-driven hematopoiesis is poorly understood. Single-cell RNA sequencing data from patients with Shwachman-Diamond syndrome (SDS), an inherited bone marrow failure syndrome, show that ARHGEF2, a RhoA-specific guanine nucleotide exchange factor and determinant of mitotic spindle orientation, is specifically downregulated in SDS hematopoietic stem and progenitor cells (HSPCs). We demonstrate that transplanted Arhgef2-/- fetal liver and bone marrow cells yield impaired hematopoietic recovery and a production deficit from long-term HSCs, phenotypes that are not the result of differences in numbers of transplanted HSCs, their cell cycle status, level of apoptosis, progenitor output, or homing ability.

Spatiotemporal dynamics of GEF-H1 activation controlled by microtubule- and Src-mediated pathways.

Rho family GTPases are activated with precise spatiotemporal control by guanine nucleotide exchange factors (GEFs). Guanine exchange factor H1 (GEF-H1), a RhoA activator, is thought to act as an integrator of microtubule (MT) and actin dynamics in diverse cell functions. Here we identify a GEF-H1 autoinhibitory sequence and exploit it to produce an activation biosensor to quantitatively probe the relationship between GEF-H1 conformational change, RhoA activity, and edge motion in migrating cells with micrometer- and second-scale resolution.

FAST-1 antisense RNA epigenetically alters FXN expression.

Friedreich ataxia (FRDA) is a multisystem genetic disorder caused by GAA repeat expansion mutations within the FXN gene, resulting in heterochromatin formation and deficiency of frataxin protein. Elevated levels of the FXN antisense transcript (FAST-1) have previously been detected in FRDA. To investigate the effects of FAST-1 on the FXN gene expression, we first stably overexpressed FAST-1 in non-FRDA cell lines and then we knocked down FAST-1 in FRDA fibroblast cells.