Levels of procoagulant factors and peak thrombin generation in relation to dementia risk in older adults: The Cardiovascular Health Study.

Introduction: Markers of hemostasis such as procoagulant factors and peak thrombin generation are associated with cardiovascular outcomes, but their associations with dementia risk are unclear. We aimed to evaluate prospective associations of selected procoagulant factors and peak thrombin generation with dementia risk.

Methods: We measured levels of 7 hemostatic factors (fibrinogen, factor VII coagulant activity [FVIIc], activated factor VII [FVIIa], factor VIIa-antithrombin [FVIIa-AT], factor XI antigen [FXI], peak thrombin generation, and platelet count) among participants in the Cardiovascular Health Study, a cohort of older adults free of dementia in 1992/1993 (n = 3185).

Differential Activities of the Botanical Extract PBI-05204 and Oleandrin on Innate Immune Functions under Viral Challenge Versus Inflammatory Culture Conditions.

The extract PBI 05204 (PBI) and its cardiac glycoside constituent oleandrin have direct anti-viral properties. Their effect on the immune system, however, is largely unknown. We used an in vitro model of human peripheral blood mononuclear cells to document effects under three different culture conditions: normal, challenged with the viral mimetic polyinosinic:polycytidylic acid Poly I:C, and inflamed by lipopolysaccharide (LPS).

Giving Gold Wings: Ultrabright and Fragmentation Free Mass Spectrometry Reporters for Barcoding, Bioconjugation Monitoring, and Data Storage.

The widespread application of laser desorption/ionization mass spectrometry (LDI-MS) highlights the need for a bright and multiplexable labeling platform. While ligand-capped Au nanoparticles (AuNPs) have emerged as a promising LDI-MS contrast agent, the predominant thiol ligands suffer from low ion yields and extensive fragmentation. In this work, we develop a N-heterocyclic carbene (NHC) ligand platform that enhances AuNP LDI-MS performance.

Clinical Characteristics, Incidences, and Mortality Rates for Type A and B Aortic Dissections: A Nationwide Danish Population-Based Cohort Study From 1996 to 2016.

Background: Population-based epidemiologic studies of aortic dissections (ADs) are needed. This study aimed to report clinical characteristics, incidences, and mortality rates for adult patients admitted to Danish hospitals with type A AD (TAAD) or type B AD (TBAD) from 1996 through 2016.

Methods: We conducted a nationwide, population-based register study.

Anatomy of the heart with the highest heart rate.

Shrews occupy the lower extreme of the seven orders of magnitude mammals range in size. Their hearts are large relative to body weight and heart rate can exceed a thousand beats a minute. It is not known whether traits typical of mammal hearts scale to these extremes.

Structural basis of cyclic oligoadenylate degradation by ancillary Type III CRISPR-Cas ring nucleases.

Type III CRISPR-Cas effector systems detect foreign RNA triggering DNA and RNA cleavage and synthesizing cyclic oligoadenylate molecules (cA) in their Cas10 subunit. cAs act as a second messenger activating auxiliary nucleases, leading to an indiscriminate RNA degradation that can end in cell dormancy or death. Standalone ring nucleases are CRISPR ancillary proteins which downregulate the strong immune response of Type III systems by degrading cA.

Toward best practice in cancer mutation detection with whole-genome and whole-exome sequencing.

Clinical applications of precision oncology require accurate tests that can distinguish true cancer-specific mutations from errors introduced at each step of next-generation sequencing (NGS). To date, no bulk sequencing study has addressed the effects of cross-site reproducibility, nor the biological, technical and computational factors that influence variant identification. Here we report a systematic interrogation of somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy at six different centers.

The exogenous progesterone-free luteal phase: two pilot randomized controlled trials in IVF patients.

Research Question: Is the reproductive outcome similar after gonadotrophin-releasing hormone agonist (GnRHa) trigger followed by luteal human chorionic gonadotrophin (HCG) boluses compared with HCG trigger and a standard luteal phase support (LPS)?

Design: Two open-label pilot randomized controlled trials (RCT) with 250 patients from 2014 to 2019, with a primary outcome of ongoing pregnancy per embryo transfer. Patients with ≤13 follicles on the trigger day were randomized (RCT 1) to: Group A (n = 65): GnRHa trigger followed by a bolus of 1500 IU HCG s.c.

Hemostatic factor levels and cognitive decline in older adults: The Cardiovascular Health Study.

Background: Hemostasis is a key factor in cerebrovascular disease, but the association of hemostatic factors with cognitive decline is unclear.

Objective: To prospectively evaluate associations of 20 hemostatic factor levels with changes in cognition during ≥8 years of follow-up in the Cardiovascular Health Study (CHS) of older adults.

Methods: We included participants of an existing CHS cross-sectional substudy (n = 400) with hemostatic factors measured in 1989-1990.

A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19.

Background: LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019 (Covid-19). Data are needed on the effect of this antibody in patients who are hospitalized with Covid-19.

Methods: In this platform trial of therapeutic agents, we randomly assigned hospitalized patients who had Covid-19 without end-organ failure in a 1:1 ratio to receive either LY-CoV555 or matching placebo.

Randomized Phase II Trial of Anthracycline-free and Anthracycline-containing Neoadjuvant Carboplatin Chemotherapy Regimens in Stage I-III Triple-negative Breast Cancer (NeoSTOP).

Purpose: Addition of carboplatin (Cb) to anthracycline chemotherapy improves pathologic complete response (pCR), and carboplatin plus taxane regimens also yield encouraging pCR rates in triple-negative breast cancer (TNBC). Aim of the NeoSTOP multisite randomized phase II trial was to assess efficacy of anthracycline-free and anthracycline-containing neoadjuvant carboplatin regimens.

Patients And Methods: Patients aged ≥18 years with stage I-III TNBC were randomized (1:1) to receive either paclitaxel (P) weekly × 12 plus carboplatin AUC6 every 21 days × 4 followed by doxorubicin/cyclophosphamide (AC) every 14 days × 4 (CbP → AC, arm A), or carboplatin AUC6 + docetaxel (D) every 21 days × 6 (CbD, arm B).

Evaluation of therapeutic efficacy of At-labeled farletuzumab in an intraperitoneal mouse model of disseminated ovarian cancer.

Introduction: Antibodies labeled with alpha-emitter astatine-211 have previously shown effective in intraperitoneal (i.p.) treatments of ovarian cancer.

Pathological and microbiological impact of a gentamicin-loaded biocomposite following limited or extensive debridement in a porcine model of osteomyelitis.

Aims: CERAMENT|G is an absorbable gentamicin-loaded biocomposite used as an on-site vehicle of antimicrobials for the treatment of chronic osteomyelitis. The purpose of the present study was to investigate the sole effect of CERAMENT|G, i.e.

Comparison of 10- versus 14-gauge angiocatheter for treatment of tension pneumothorax and tension-induced pulseless electrical activity with hemorrhagic shock: Bigger is still better.

Background: Little is known regarding the effect of hemorrhagic shock on the diagnosis and treatment of tension pneumothorax (tPTX). Recently, the Tactical Combat Casualty Care guidelines included the 10-gauge angiocatheter (10-g AC) as an acceptable alternative to the 14-g AC. This study sought to compare these two devices for decompression of tPTX and rescue from tension-induced pulseless electric activity (tPEA) in the setting of a concomitant 30% estimated blood volume hemorrhage.

Characterization of Signaling Pathways Associated with Pancreatic β-cell Adaptive Flexibility in Compensation of Obesity-linked Diabetes in Mice.

The onset of obesity-linked type 2 diabetes (T2D) is marked by an eventual failure in pancreatic β-cell function and mass that is no longer able to compensate for the inherent insulin resistance and increased metabolic load intrinsic to obesity. However, in a commonly used model of T2D, the mouse, β-cells have an inbuilt adaptive flexibility enabling them to effectively adjust insulin production rates relative to the metabolic demand. Pancreatic β-cells from these animals have markedly reduced intracellular insulin stores, yet high rates of (pro)insulin secretion, together with a substantial increase in proinsulin biosynthesis highlighted by expanded rough endoplasmic reticulum and Golgi apparatus.

Management of Nonvariceal Upper Gastrointestinal Bleeding: Guideline Recommendations From the International Consensus Group.

Description: This update of the 2010 International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding (UGIB) refines previous important statements and presents new clinically relevant recommendations.

Methods: An international multidisciplinary group of experts developed the recommendations. Data sources included evidence summarized in previous recommendations, as well as systematic reviews and trials identified from a series of literature searches of several electronic bibliographic databases from inception to April 2018.

A Longitudinal Study of Ebola Sequelae in Liberia.

Background: Multiple health problems have been reported in survivors of Ebola virus disease (EVD). Attribution of these problems to the disease without a control group for analysis is difficult.

Methods: We enrolled a cohort of EVD survivors and their close contacts and prospectively collected data on symptoms, physical examination findings, and laboratory results.

Left Ventricular Strain Is Abnormal in Preclinical and Overt Hypertrophic Cardiomyopathy: Cardiac MR Feature Tracking.

Purpose To evaluate myocardial strain and circumferential transmural strain difference (cTSD; the difference between epicardial and endocardial circumferential strain) in a genotyped cohort with hypertrophic cardiomyopathy (HCM) and to explore correlations between cTSD and other anatomic and functional markers of disease status. Left ventricular (LV) dysfunction may indicate early disease in preclinical HCM (sarcomere mutation carriers without LV hypertrophy). Cardiac MRI feature tracking may be used to evaluate myocardial strain in carriers of HCM sarcomere mutation.

Gentamicin Susceptibility Test for Prevention of Bacterial Biofilms in Bone Tissue and on Implants.

The objective of this study was to set up an gentamicin susceptibility test for biofilm prevention in bone tissue and on implants. Twenty-five pigs were allocated to six groups. Pigs in group A ( = 6) were inoculated with saline.

Survival and phosphate solubilisation activity of desiccated formulations of Penicillium bilaiae and Aspergillus niger influenced by water activity.

The impact of formulation and desiccation on the shelf life of phosphate (P)-solubilising microorganisms is often under-studied, particularly relating to their ability to recover P-solubilisation activity. Here, Penicilllium bilaiae and Aspergillus niger were formulated on vermiculite (V) alone, or with the addition of protectants (skimmed milk (V + SM) and trehalose (V + T)), and on sewage sludge ash with (A + N) and without nutrients (A), and dried in a convective air dryer. After drying, the spore viability of P.