Longitudinal multi-omics of host-microbe dynamics in prediabetes.

Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. To understand the earliest stages of T2D better, we obtained samples from 106 healthy individuals and individuals with prediabetes over approximately four years and performed deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, as well as changes in the microbiome. This rich longitudinal data set revealed many insights: first, healthy profiles are distinct among individuals while displaying diverse patterns of intra- and/or inter-personal variability.

Role of Glutamine Synthetase Isogenes and Herbicide Metabolism in the Mechanism of Resistance to Glufosinate in L. spp. Biotypes from Oregon.

Glufosinate-resistant L. spp. biotypes from Oregon exhibited resistance levels up to 2.

Progressive multifocal leukoencephalopathy in Zambia is caused by JC virus with prototype regulatory region.

There are only few documented cases of progressive multifocal leukoencephalopathy (PML) in Africa. Whether this is caused by a lack of JC virus (JCV) spread or alteration in the JCV genome is unknown. We characterized the clinical presentation, laboratory findings, and JCV regulatory region (RR) pattern of the first documented PML cases in Zambia as well as JCV seroprevalence among HIV and HIV Zambians.

Characterizing the clinical implementation of a novel activation-repolarization metric to identify targets for catheter ablation of ventricular tachycardias using computational models.

Identification of targets for catheter ablation of ventricular tachycardias (VTs) remains a significant challenge. VTs are often driven by re-entrant circuits resulting from a complex interaction between the front (activation) and tail (repolarization) of the electrical wavefront. Most mapping techniques do not take into account the tissue repolarization which may hinder the detection of ablation targets.

Mucispirillum schaedleri Antagonizes Salmonella Virulence to Protect Mice against Colitis.

The microbiota and the gastrointestinal mucus layer play a pivotal role in protection against non-typhoidal Salmonella enterica serovar Typhimurium (S. Tm) colitis. Here, we analyzed the course of Salmonella colitis in mice lacking a functional mucus layer in the gut.

The effect of the speed and range of motion of movement on the hyperemic response to passive leg movement.

Passive leg movement (PLM)-induced hyperemia is used to assess the function of the vascular endothelium. This study sought to determine the impact of movement speed and range of motion (ROM) on the hyperemic response to PLM and determine if the currently recommended protocol of moving the leg through a 90° ROM at 180°/sec provides a peak hyperemic response to PLM. 11 healthy adults underwent multiple bouts of PLM, in which either movement speed (60-240°/sec) or ROM (30-120° knee flexion) were varied.

AO Patient Outcomes Center: Design, Implementation, and Evaluation of a Software Application for the Collection of Patient-Reported Outcome Measures in Orthopedic Outpatient Clinics.

Background: Patient-reported outcomes are increasingly utilized in routine orthopedic clinical care. Computer adaptive tests (CATs) from the Patient-Reported Outcomes Measurement Information System (PROMIS) offer a brief and precise assessment that is well suited for collection within busy clinical environments. However, software apps that support the administration and scoring of CATs, provide immediate access to patient-reported outcome (PRO) scores, and minimize clinician burden are not widely available.

Modulation of Tongue Pressure According to Liquid Flow Properties in Healthy Swallowing.

Purpose During swallowing, the tongue generates the primary propulsive forces that transport material through the oral cavity toward the pharynx. Previous literature suggests that higher tongue pressure amplitudes are generated for extremely thick liquids compared with thin liquids. The purpose of this study was to collect detailed information about the modulation of tongue pressure amplitude and timing across the range from thin to moderately thick liquids.

Extracellular microRNAs exhibit sequence-dependent stability and cellular release kinetics.

Multiple studies have described extracellular microRNAs (ex-miRNAs) as being remarkably stable despite the hostile extracellular environment, when stored at 4ºC or lower. Here we show that many ex-miRNAs are rapidly degraded when incubated at 37ºC in the presence of serum (thereby simulating physiologically relevant conditions). Stability varied widely between miRNAs, with half-lives ranging from ~1.

Defining the structural basis for human alloantibody binding to human leukocyte antigen allele HLA-A*11:01.

Our understanding of the conformational and electrostatic determinants that underlie targeting of human leukocyte antigens (HLA) by anti-HLA alloantibodies is principally based upon in silico modelling. Here we provide a biochemical/biophysical and functional characterization of a human monoclonal alloantibody specific for a common HLA type, HLA-A*11:01. We present a 2.

Increased temperatures and elevated CO levels reduce the sensitivity of Conyza canadensis and Chenopodium album to glyphosate.

Herbicides are the most commonly used means of controlling weeds. Recently, there has been growing concern over the potential impacts of global climate change, specifically, increasing temperatures and elevated carbon dioxide (CO) concentrations, on the sensitivity of weeds to herbicides. Here, glyphosate response of both Conyza canadensis and Chenopodium album was evaluated under different environmental conditions.

Pulse Arrival Time and Pulse Interval as Accurate Markers to Detect Mechanical Alternans.

Mechanical alternans (MA) is a powerful predictor of adverse prognosis in patients with heart failure and cardiomyopathy, but its use remains limited due to the need of invasive continuous arterial pressure recordings. This study aims to assess novel cardiovascular correlates of MA in the intact human heart to facilitate affordable and non-invasive detection of MA and advance our understanding of the underlying pathophysiology. Arterial pressure, respiration, and ECG were recorded in 12 subjects with healthy ventricles during voluntarily controlled breathing at different respiratory rate, before and after administration of beta-blockers.

Mechanistic insights from targeted molecular profiling of repolarization alternans in the intact human heart.

Aims: Action potential duration (APD) alternans is an established precursor or arrhythmia and sudden cardiac death. Important differences in fundamental electrophysiological properties relevant to arrhythmia exist between experimental models and the diseased in vivo human heart. To investigate mechanisms of APD alternans using a novel approach combining intact heart and cellular cardiac electrophysiology in human in vivo.

In Vitro Oral Cavity Model for Screening the Disintegration Behavior of Orodispersible Films: A Bespoke Design.

The availability of biorelevant methods for the disintegration study of pharmaceutical orodispersible dosage forms is required. The disintegration of orodispersibles should be assessed using in vitro methods that can combine biorelevant volumes of disintegration medium and mechanical stresses mimicking in vivo conditions. This study proposes an adaptation of a mechanical oral cavity model for the disintegration study of orodispersible films.

A microbial-based cancer vaccine for induction of EGFRvIII-specific CD8+ T cells and anti-tumor immunity.

Dysregulated signaling via the epidermal growth factor receptor (EGFR)-family is believed to contribute to the progression of a diverse array of cancers. The most common variant of EGFR is EGFRvIII, which results from a consistent and tumor-specific in-frame deletion of exons 2-7 of the EGFR gene. This deletion generates a novel glycine at the junction and leads to constitutive ligand-independent activity.

Induction of Human T-cell and Cytokine Responses Following Vaccination with a Novel Influenza Vaccine.

Cell mediated immunity plays a vital role in defense against influenza infection in humans. Less is known about the role of vaccine-induced cell mediated immunity and the cytokine responses elicited. We measured CD4 and CD8 T-cell reactivity in human subjects following vaccination with licensed trivalent influenza vaccine and a novel virus-like particle based vaccine.

EPSPS duplication and mutation involved in glyphosate resistance in the allotetraploid weed species Poa annua L.

Background: Poa annua is a widespread winter annual weed species in California. Recently, poor control of this species with glyphosate was reported by growers in an almond orchard in California with a history of repetitive glyphosate use. The objectives of this research were to evaluate the level of glyphosate resistance in a developed S P.

Simulating contact using the elastic foundation algorithm in OpenSim.

Modeling joint contact in OpenSim is not well understood. This study systematically investigated the variables associated with the elastic foundation contact model within OpenSim by performing a series of controlled benchtop experiment and concomitant simulations. Four metal-on-plastic interactions were modeled, including a model of a total knee replacement (TKR).

Phylogenomic Classification and the Evolution of Clonal Complex 5 Methicillin-Resistant in the Western Hemisphere.

Clonal complex 5 methicillin-resistant (CC5-MRSA) includes multiple prevalent clones that cause hospital-associated infections in the Western Hemisphere. Here, we present a phylogenomic study of these MRSA to reveal their phylogeny, spatial and temporal population structure, and the evolution of selected traits. We studied 598 genome sequences, including 409 newly generated sequences, from 11 countries in Central, North, and South America, and references from Asia and Europe.