Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data.

Background: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD.

Methods: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline.

Gallic acid reduces the viscosity and water binding capacity of soluble dietary fibers.

Water binding capacity and viscosity of soluble dietary fibers are known to be essential drivers of their nutritional benefits. Phenolic compounds, often found in the presence of dietary fibers, are also known to bind non-covalently with soluble dietary fibers. In this study, we characterized the impact of gallic acid (1-30 mM) on the physical properties of four soluble dietary fibers in solution (0.

Safety of Single-Stage Bilateral Versus Unilateral Anterior Total Hip Arthroplasty: A Propensity-Matched Cohort Study.

Background: Limited data exist on patient safety after single-stage bilateral and unilateral total hip arthroplasty (THA) through the anterior approach (AA). Therefore, the aim of this study was to compare length of stay (LOS), operative time, 90-day adverse events, 90-day readmission rate, and 1-year revision rate after single-stage bilateral and unilateral THA in matched patients.

Methods: This was a retrospective matched cohort study of prospectively collected data from 2008 to 2018 of a single-surgeon practice.

PTH suppression by calcitriol does not predict off-target actions in experimental CKD.

Vitamin D receptor agonist (VDRA) therapy for PTH suppression is a mainstay for patients with severe CKD. Calcitriol (1,25-(OH) D ) is a former first-line VDRA in CKD treatment. However, a consequence of its use in CKD is accelerated vascular calcification (VC).

A fully joint Bayesian quantitative trait locus mapping of human protein abundance in plasma.

Molecular quantitative trait locus (QTL) analyses are increasingly popular to explore the genetic architecture of complex traits, but existing studies do not leverage shared regulatory patterns and suffer from a large multiplicity burden, which hampers the detection of weak signals such as trans associations. Here, we present a fully multivariate proteomic QTL (pQTL) analysis performed with our recently proposed Bayesian method LOCUS on data from two clinical cohorts, with plasma protein levels quantified by mass-spectrometry and aptamer-based assays. Our two-stage study identifies 136 pQTL associations in the first cohort, of which >80% replicate in the second independent cohort and have significant enrichment with functional genomic elements and disease risk loci.

Targeted mutation of secretogranin-2 disrupts sexual behavior and reproduction in zebrafish.

The luteinizing hormone surge is essential for fertility as it triggers ovulation in females and sperm release in males. We previously reported that secretoneurin-a, a neuropeptide derived from the processing of secretogranin-2a (Scg2a), stimulates luteinizing hormone release, suggesting a role in reproduction. Here we provide evidence that mutation of the and genes using TALENs in zebrafish reduces sexual behavior, ovulation, oviposition, and fertility.

Just the facts: What drugs are safe and effective for COVID-19?

A 53-year-old male presents with cough, fever, and myalgias for 7 days. Vitals include temperature, 38.0°C; heart rate, 110; blood pressure, 118/70 mm Hg; respiration rate, 28; and oxygen saturation 83% on room air.

Changing the Landscape: An Introduction to the Agricultural and Food Chemistry Technical Program at the 258th American Chemical Society National Meeting in San Diego.

This special issue of the (JAFC) is a highlight of the Agricultural and Food Chemistry Division (AGFD) technical program at the 258th National Meeting of the American Chemical Society (ACS) in San Diego, CA, U.S.A.

Epigenome-wide association study and multi-tissue replication of individuals with alcohol use disorder: evidence for abnormal glucocorticoid signaling pathway gene regulation.

Alcohol use disorder (AUD) is a chronic debilitating disorder with limited treatment options and poorly defined pathophysiology. There are substantial genetic and epigenetic components; however, the underlying mechanisms contributing to AUD remain largely unknown. We conducted the largest DNA methylation epigenome-wide association study (EWAS) analyses currently available for AUD (total N = 625) and employed a top hit replication (N = 4798) using a cross-tissue/cross-phenotypic approach with the goal of identifying novel epigenetic targets relevant to AUD.

The implementation of rifapentine and isoniazid (3HP) in two remote Arctic communities with a predominantly Inuit population, the Taima TB 3HP study.

: The incidence of TB among Inuit is the highest in Canada. A significantly shorter latent TB infection (LTBI) treatment with rifapentine and isoniazid once weekly for 12 weeks (3HP) is now available in limited settings in Canada.: A prospective open-label 2-year observational postmarketing study was conducted introducing 3HP for the first time in Canada in Iqaluit followed by a program rollout in Qikiqtarjuaq, Nunavut.

Berberine and its structural analogs have differing effects on functional profiles of individual gut microbiomes.

The understanding of the effects of compounds on the gut microbiome is limited. In particular, it is unclear whether structurally similar compounds would have similar or distinct effects on the gut microbiome. Here, we selected berberine (BBR), an isoquinoline quaternary alkaloid, and 16 structural analogs and evaluated their effects on seven individual gut microbiomes cultured .

A multicentre, randomised trial comparing schedules of G-CSF (filgrastim) administration for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer.

Background: The optimal duration of filgrastim as primary febrile neutropenia (FN) prophylaxis in early breast cancer patients is unknown, with 5, 7 or 10 days being commonly prescribed. This trial evaluates whether 5 days of filgrastim was non-inferior to 7/10 days.

Patients And Methods: In this randomised, open-label trial, early breast cancer patients who were to receive filgrastim as primary FN prophylaxis were randomly allocated to 5 versus 7 versus 10 days of filgrastim for all chemotherapy cycles.

Does α-adrenergic receptor blockade modulate sweating during incremental exercise in young endurance-trained men?

Purpose: Human eccrine sweat glands respond to α-adrenergic receptor agonists. We recently reported that adrenergic mechanisms contribute to sweating in endurance-trained men during an incremental exercise to volitional fatigue. However, it remains unclear if this response is mediated by α-adrenergic receptor activation.

Phosphatidylinositol-(4,5)-Bisphosphate Regulates Plasma Cholesterol Through LDL (Low-Density Lipoprotein) Receptor Lysosomal Degradation.

TMEM55B (transmembrane protein 55B) is a phosphatidylinositol-(4,5)-bisphosphate (PI[4,5]P) phosphatase that regulates cellular cholesterol, modulates LDLR (low-density lipoprotein receptor) decay, and lysosome function. We tested the effects of knockdown on plasma lipids in mice and assessed the roles of LDLR lysosomal degradation and change in (PI[4,5]P) in mediating these effects. Approach and Results: Western diet-fed C57BL/6J mice were treated with antisense oligonucleotides against or a nontargeting control for 3 to 4 weeks.

Real-time fMRI feedback impacts brain activation, results in auditory hallucinations reduction: Part 1: Superior temporal gyrus -Preliminary evidence.

Auditory hallucinations (AH) are one of the core symptoms of schizophrenia (SZ) and constitute a significant source of suffering and disability. One third of SZ patients experience pharmacology-resistant AH, so an alternative/complementary treatment strategy is needed to alleviate this debilitating condition. In this study, real-time functional Magnetic Resonance Imaging neurofeedback (rt-fMRI NFB), a non-invasive technique, was used to teach 10 SZ patients with pharmacology-resistant AH to modulate their brain activity in the superior temporal gyrus (STG), a key area in the neurophysiology of AH.

Fear of Failure Mediates the Relation Between Parental Psychological Control and Academic Outcomes: A Latent Mediated-Moderation Model of Parents' and Children's Genders.

Given the negative relations between parental psychological control and various aspects of emerging adults' social and emotional adaptation, there is a need to determine whether similar relations exist for emerging adults' academic adjustment. The current study tested an integrative model using an interactionist approach of dyadic gender composition to test whether maternal and paternal psychological control are unique and interactive predictors of four different indicators of academic adjustment (i.e.

Major Revisions in Arthropod Phylogeny Through Improved Supermatrix, With Support for Two Possible Waves of Land Invasion by Chelicerates.

Deep phylogeny involving arthropod lineages is difficult to recover because the erosion of phylogenetic signals over time leads to unreliable multiple sequence alignment (MSA) and subsequent phylogenetic reconstruction. One way to alleviate the problem is to assemble a large number of gene sequences to compensate for the weakness in each individual gene. Such an approach has led to many robustly supported but contradictory phylogenies.

Impact of the KidneyWise toolkit on chronic kidney disease referral practices in Ontario primary care: a prospective evaluation.

Objectives: Chronic kidney disease (CKD) is common; therefore, coordination of care between primary care and nephrology is important. Ontario Renal Network's KidneyWise toolkit was developed to provide guidance on the detection and management of people with CKD in primary care (www.kidneywise.

Identification of a C3'-nitrile nucleoside analogue inhibitor of pancreatic cancer cell line growth.

A synthetic strategy to access a novel family of nucleoside analogues bearing a C3'-nitrile substituted all-carbon quaternary center is presented herein. These purine bearing scaffolds were tested in two pancreatic cancer cell lines harboring either wild-type (BxPC3) or G12V KRAS (Capan2) mutations. A promising compound was shown to have significantly greater efficacy in the Capan2 cell line as compared to Gemcitabine, the clinical gold standard used to treat pancreatic cancer.

An International Multicenter Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition.

Background: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare variants implicated in LQT5 was sought through an international multicenter collaboration.

Methods: Patients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries.