Durability of annuloplasty in patients with atrial functional mitral regurgitation associated with atrial fibrillation.

Objective: To determine the durability of mitral valve repair (MVr) with complete ring or flexible band annuloplasty in patients with atrial functional mitral regurgitation (AFMR) due to atrial fibrillation (AF) and identify risk factors associated with postoperative recurrence of mitral regurgitation.

Methods: Between January 1, 2000, and January 1, 2023, 194 adults with a history of AF underwent MVr with annuloplasty alone for moderate/severe AFMR. Exclusion criteria were prior cardiac surgery, additional repair techniques, ejection fraction <45%, ischemic heart disease, aortic valve disease, mitral annular calcification, and concomitant procedures other than surgical ablation or tricuspid repair/replacement.

The nuclear export protein XPO1 provides a peptide ligand for natural killer cells.

XPO1 (Exportin-1/CRM1) is a nuclear export protein that is frequently overexpressed in cancer and functions as a driver of oncogenesis. Currently small molecules that target XPO1 are being used in the clinic as anticancer agents. We identify XPO1 as a target for natural killer (NK) cells.

Factors contributing to pesticide contamination in riverine systems: The role of wastewater and landscape sources.

Wastewater treatment plant (WWTP) discharges can be a source of organic contaminants, including pesticides, to rivers. An integrated model was developed for the Potomac River watershed (PRW) to determine the amount of accumulated wastewater percentage of streamflow (ACCWW) and calculate predicted environmental concentrations (PECs) for 14 pesticides in non-tidal National Hydrography Dataset Plus Version 2.1 stream segments.

Illuminating Protein Allostery by Chemically Accurate Contact Response Analysis (ChACRA).

Decoding allostery at the atomic level is essential for understanding the relationship between a protein's sequence, structure, and dynamics. Recently, we have shown that decomposing temperature responses of inter-residue contacts can reveal allosteric couplings and provide useful insight into the functional dynamics of proteins. The details of this Chemically Accurate Contact Response Analysis (ChACRA) are presented here along with its application to two well-known allosteric proteins.

An α-ketoglutarate conformational switch controls iron accessibility, activation, and substrate selection of the human FTO protein.

The fat mass and obesity-associated fatso (FTO) protein is a member of the Alkb family of dioxygenases and catalyzes oxidative demethylation of N-methyladenosine (mA), N-methyladenosine (mA), 3-methylthymine (mT), and 3-methyluracil (mU) in single-stranded nucleic acids. It is well established that the catalytic activity of FTO proceeds via two coupled reactions. The first reaction involves decarboxylation of alpha-ketoglutarate (αKG) and formation of an oxyferryl species.

Protein thermal sensing regulates physiological amyloid aggregation.

To survive, cells must respond to changing environmental conditions. One way that eukaryotic cells react to harsh stimuli is by forming physiological, RNA-seeded subnuclear condensates, termed amyloid bodies (A-bodies). The molecular constituents of A-bodies induced by different stressors vary significantly, suggesting this pathway can tailor the cellular response by selectively aggregating a subset of proteins under a given condition.

Outbreak of Diarrhea Caused by a Novel Subtype During British Military Training in Kenya.

Background: We report clinical, epidemiological, and laboratory features of a large diarrhea outbreak caused by a novel subtype during British military training in Kenya between February and April 2022.

Methods: Data were collated from diarrhea cases, and fecal samples were analyzed on site using the multiplex polymerase chain reaction (PCR) BioFire FilmArray. Water was tested using Colilert kits (IDEXX, UK).

Validation of oxygen saturations measured in the community by emergency medical services as a marker of clinical deterioration in patients with confirmed COVID-19: a retrospective cohort study.

Objectives: To evaluate oxygen saturation and vital signs measured in the community by emergency medical services (EMS) as clinical markers of COVID-19-positive patient deterioration.

Design: A retrospective data analysis.

Setting: Patients were conveyed by EMS to two hospitals in Hampshire, UK, between 1 March 2020 and 31 July 2020.

Survival and repair durability in patients undergoing concomitant aortic valve reimplantation and mitral valve repair.

Objective: The study objective was to determine repair durability and survival in patients with and without connective tissue disorders undergoing concomitant aortic valve reimplantation and mitral valve repair.

Methods: From 2002 to 2019, 68 patients underwent concomitant aortic valve reimplantation and mitral valve repair, including 27 patients with Marfan syndrome (39.7%).

Gut microbiome and antibiotic resistance effects during travelers' diarrhea treatment and prevention.

The travelers' gut microbiome is potentially assaulted by acute and chronic perturbations (e.g., diarrhea, antibiotic use, and different environments).

Temperature sensitive contact modes allosterically gate TRPV3.

TRPV Ion channels are sophisticated molecular sensors designed to respond to distinct temperature thresholds. The recent surge in cryo-EM structures has provided numerous insights into the structural rearrangements accompanying their opening and closing; however, the molecular mechanisms by which TRPV channels establish precise and robust temperature sensing remain elusive. In this work we employ molecular simulations, multi-ensemble contact analysis, graph theory, and machine learning techniques to reveal the temperature-sensitive residue-residue interactions driving allostery in TRPV3.

Branched stented anastomosis frozen elephant trunk repair: Early results from a physician-sponsored investigational device exemption study.

Background: Multisegment thoracic aortic disease typically requires total aortic arch replacement, affects a heterogenous population, and carries a high risk even at centers of excellence. Risk has been associated with the duration of operation and complexity of repair. A novel branched stented anastomosis frozen elephant trunk repair (B-SAFER) technique has been developed at our center and is currently being studied as a physician-sponsored investigation device exemption (PS-IDE).

TOMM40 '523 Genotype Distinguishes Patterns of Cognitive Improvement for Executive Function in APOEɛ3 Homozygotes.

Background: TOMM40 '523 has been associated with cognitive performance and risk for developing Alzheimer's disease independent of the effect of APOE genotype. Few studies have considered the longitudinal effect of this genotype on change in cognition over time.

Objective: Our objective was to evaluate the relationship between TOMM40 genotype status and change in cognitive performance in the TOMMORROW study, which was designed to prospectively evaluate an algorithm that includes TOMM40 '523 for genetic risk for conversion to mild cognitive impairment.

Cattle killer immunoglobulin-like receptor expression on leukocyte subsets suggests functional divergence compared to humans.

Cattle, sheep, and goats are the only species outside primates known to have an expanded and diversified family of killer immunoglobulin-like receptors (KIR). Primate KIR are expressed on the surface of NK and T cells and bind MHC-I to control activation. However, the surface expression, ligands and function of bovid KIR remain unknown.

Assessment of atmospheric solids analysis probe as a tool for the rapid determination of drug purity.

The ability to determine the purity (% controlled compound) of drug-of-abuse samples is necessary for public health and law enforcement. Here, we describe the assessment of atmospheric solids analysis probe (ASAP) for the rapid determination of drug purity for a set of formulated pharmaceuticals, chosen due to their availability, uncontrolled status and consistency. Paracetamol and loratadine were used as models of high and low purity compounds being ~90% and ~10% active ingredient, respectively.

Solution Structure Ensembles of the Open and Closed Forms of the ∼130 kDa Enzyme I via AlphaFold Modeling, Coarse Grained Simulations, and NMR.

Large-scale interdomain rearrangements are essential to protein function, governing the activity of large enzymes and molecular machineries. Yet, obtaining an atomic-resolution understanding of how the relative domain positioning is affected by external stimuli is a hard task in modern structural biology. Here, we show that combining structural modeling by AlphaFold2 with coarse-grained molecular dynamics simulations and NMR residual dipolar coupling data is sufficient to characterize the spatial domain organization of bacterial enzyme I (EI), a ∼130 kDa multidomain oligomeric protein that undergoes large-scale conformational changes during its catalytic cycle.