Drug Development.

Background: VY-TAU01 is a recombinant humanized IgG4 monoclonal antibody (mAb) directed against pathological tau for the treatment of patients with mild dementia or mild cognitive impairment due to Alzheimer's disease (AD). Both VY-TAU01 and its parental mouse IgG1 mAb Ab-01 target an epitope in the C-terminus of tau, bind pathological tau with high affinity and selectivity over wild-type tau, block paired helical filament seed-induced tau aggregates in vitro, and selectively stain tau tangles in AD and P301S mouse (C57/B6J-Tg[Thy1-MAPT*P301S]2541Godt) brain. Ab-01 robustly inhibits seeding and propagation of pathological tau in a P301S mouse seeding model.

Molecular survey for Chlamydia among southern greater gliders (Petauroides volans) from southeastern New South Wales, Australia.

Southern greater gliders (Petauroides volans) are endangered Australian marsupials for which there is little health data currently available. Chlamydia pecorum is the only reported pathogen of greater gliders and infects a broad range of hosts, including other marsupials, ruminants, swine and birds. Conjunctival and cloacal swabs collected from thirty-two southern greater gliders across southeastern New South Wales, Australia were screened for Chlamydia spp.

Structural and Evolutionary Relationships of Melanin Cascade Proteins in Cnidarian Innate Immunity.

Melanin is an essential product that plays an important role in innate immunity in a variety of organisms across the animal kingdom. Melanin synthesis is performed by many organisms using the tyrosine metabolism pathway, a general pathway that utilizes a type-three copper oxidase protein, called PO-candidates (phenoloxidase candidates). While melanin synthesis is well-characterized in organisms like arthropods and humans, it is not as well-understood in non-model organisms such as cnidarians.

Ethnic Differences in Survival among Brazilian Modern-era Olympic Medalists from 1920 to 1992: A Cohort Study.

Background: Disparities in health outcomes among racial groups warrant investigation, even among elite athletes. Therefore, understanding the impact of race upon post-medal survival in Brazilian Olympians becomes essential.

Objective: To compare post-medal survival between white and non-white Brazilian Olympic medalists from 1920 to 1992.

Targeted enrichment of whole-genome SNPs from highly burned skeletal remains.

Genetic assessment of highly incinerated and/or degraded human skeletal material is a persistent challenge in forensic DNA analysis, including identifying victims of mass disasters. Few studies have investigated the impact of thermal degradation on whole-genome single-nucleotide polymorphism (SNP) quality and quantity using next-generation sequencing (NGS). We present whole-genome SNP data obtained from the bones and teeth of 27 fire victims using two DNA extraction techniques.

Cardiopulmonary Exercise Testing Interpretation in Athletes: What the Cardiologist Should Know.

The noninvasive assessment of oxygen consumption, carbon dioxide production, and ventilation during a cardiopulmonary exercise test (CPET) provides insight into the cardiovascular, pulmonary, and metabolic system's ability to respond to exercise. Exercise physiology has been shown to be distinct for competitive athletes and highly active persons (CAHAPs), thus creating more nuanced interpretations of CPET parameters. CPET in CAHAP is an important test that can be used for both diagnosis (provoking symptoms during a truly maximal test) and performance.

Amplifying PCR productivity and environmental sustainability through shortened cycling protocols.

Since its inception in the 1980s, advancements in PCR technology using improved thermal cyclers, engineered DNA polymerases and commercial master mixes, have led to increased PCR productivity. Despite these advancements, PCR cycling protocols have largely remained unchanged over the same period. This study aimed to systemically evaluate the effect of reduced PCR cycling parameters on amplicon production.

Personalized Cancer Monitoring Assay for the Detection of ctDNA in Patients with Solid Tumors.

Background: Highly sensitive molecular assays have been developed to detect plasma-based circulating tumor DNA (ctDNA), and emerging evidence suggests their clinical utility for monitoring minimal residual disease and recurrent disease, providing prognostic information, and monitoring therapy responses in patients with solid tumors. The Invitae Personalized Cancer Monitoring assay uses a patient-specific, tumor-informed variant signature identified through whole exome sequencing to detect ctDNA in peripheral blood of patients with solid tumors.

Methods: The assay's tumor whole exome sequencing and ctDNA detection components were analytically validated using 250 unique human specimens and nine commercial reference samples that generated 1349 whole exome sequencing and cell-free DNA (cfDNA)-derived libraries.

Phase 1, Single- and Multiple-Ascending-Dose, Food-Effect, and East Asian Subject Studies to Assess the Pharmacokinetics, Safety, and Tolerability of Bempedoic Acid, a Selective Inhibitor of Adenosine Triphosphate Citrate Lyase.

Bempedoic acid is an adenosine triphosphate citrate lyase inhibitor that lowers low-density lipoprotein cholesterol by inhibiting cholesterol synthesis and upregulating hepatic low-density lipoprotein receptor expression. After oral dosing, bempedoic acid was readily absorbed, attaining maximum concentrations with a median time of 3.5 hours, and may be taken without regard to food.

Ancient mitochondrial genome diversity in South America: Contributions from Quebrada del Toro, Northwestern Argentina.

Objectives: The objective of this study was to enhance our understanding of the population history in South America, specifically Northwestern Argentina, by analyzing complete ancient mitogenomes of individuals from the Ojo de Agua archeological site (970 BP) in Quebrada del Toro (Salta, Argentina).

Materials And Methods: We analyzed teeth from four individuals from the site Ojo de Agua (970 ± 60 BP), located in Quebrada del Toro (Andean region of Northwestern Argentina). DNA extracts were converted to double-stranded DNA libraries and indexed using unique dual-indexing primer combinations.

Population pharmacokinetic and pharmacokinetic-pharmacodynamic modeling of bempedoic acid and low-density lipoprotein cholesterol in healthy subjects and patients with dyslipidemia.

Population pharmacokinetics (popPK) of bempedoic acid and the popPK/pharmacodynamic (popPK/PD) relationship between bempedoic acid concentrations and serum low-density lipoprotein cholesterol (LDL-C) from baseline were characterized. A two-compartment disposition model with a transit absorption compartment and linear elimination best described bempedoic acid oral pharmacokinetics (PK). Multiple covariates, including renal function, sex, and weight, had statistically significant effects on the predicted steady-state area under the curve.

Physiologically Based Pharmacokinetic Model Development and Verification for Bioequivalence Testing of Bempedoic Acid Oral Suspension and Reference Tablet Formulation.

The bioequivalence of bempedoic acid oral suspension and commercial immediate release (IR) tablet formulations were assessed using a physiologically based pharmacokinetic (PBPK) model. The mechanistic model, developed from clinical mass balance results and in vitro intrinsic solubility, permeability, and dissolution data, was verified against observed clinical pharmacokinetics (PK) results. Model inputs included a fraction of a dose in solution (0.

Exercise recommendations for patients with hypertrophic cardiomyopathy.

Individuals with hypertrophic cardiomyopathy (HCM) have historically been advised to limit exercise and sports participation to mild-intensity activities due to concerns for sudden cardiac arrest (SCA). However, more contemporary data have shown SCA is rare in patients with HCM and emerging data is shifting towards support for the safety of exercise in this patient population. Recent guidelines endorse exercise in patients with HCM after a comprehensive evaluation and shared-decision making with an expert provider.

Impacts of dual active-ingredient bed nets on the behavioural responses of pyrethroid resistant Anopheles gambiae determined by room-scale infrared video tracking.

Background: The success of insecticide treated bed nets (ITNs) for malaria vector control in Africa relies on the behaviour of various species of Anopheles. Previous research has described mosquito behavioural alterations resulting from widespread ITN coverage, which could result in a decrease in net efficacy. Here, behaviours were compared including timings of net contact, willingness to refeed and longevity post-exposure to two next-generation nets, PermaNet 3.

Novel use of riboflavin as a fluorescent tracer in the dissemination of aerosol and splatter in an open operatory dental clinic.

Objectives: The rapid spread of severe acute respiratory syndrome coronavirus 2 and the ensuing rise of the COVID-19 pandemic have impacted healthcare unprecedentedly. With the scarcity of available resources, including healthcare providers themselves, novel methods for tracking aerosol and splatter in real time are required to alleviate demand and increase safety. This study evaluates the utility of riboflavin (vitamin B ) as a tracer for splatter/aerosol distribution from ultrasonic scaling in an open operatory clinic.