Impact of dementia and mild cognitive impairment on bone health in older people.

Mild cognitive impairment, dementia and osteoporosis are common diseases of ageing and, with the increasingly ageing global population, are increasing in prevalence. These conditions are closely associated, with shared risk factors, common underlying biological mechanisms and potential direct causal pathways. In this review, the epidemiological and mechanistic links between mild cognitive impairment, dementia and skeletal health are explored.

Establishing methods to monitor H5N1 influenza virus in dairy cattle milk.

Highly Pathogenic Avian Influenza strain H5N1 has caused a multi-state outbreak among US dairy cattle, spreading across 15 states and infecting hundreds of herds since its onset. We rapidly developed and optimized PCR-based detection assays and sequencing protocols to support H5N1 molecular surveillance. Using 214 retail milk from 20 states for methods development, we found that H5N1 concentrations by digital PCR strongly correlated with qPCR cycle threshold (Ct) values, with dPCR exhibiting greater sensitivity.

Enhancing transcription-replication conflict targets ecDNA-positive cancers.

Extrachromosomal DNA (ecDNA) presents a major challenge for cancer patients. ecDNA renders tumours treatment resistant by facilitating massive oncogene transcription and rapid genome evolution, contributing to poor patient survival. At present, there are no ecDNA-specific treatments.

Coordinated inheritance of extrachromosomal DNAs in cancer cells.

The chromosomal theory of inheritance dictates that genes on the same chromosome segregate together while genes on different chromosomes assort independently. Extrachromosomal DNAs (ecDNAs) are common in cancer and drive oncogene amplification, dysregulated gene expression and intratumoural heterogeneity through random segregation during cell division. Distinct ecDNA sequences, termed ecDNA species, can co-exist to facilitate intermolecular cooperation in cancer cells.

Diagnosis of pulmonary embolism in patients with haemoptysis: the POPEIHE study.

Aim: To determine the prevalence and characteristics of pulmonary embolism (PE) in patients presenting with haemoptysis. Additionally, we assessed the efficiency and failure rates of different clinical diagnostic algorithms for PE in this patient population.

Methods: We enrolled consecutive adult patients who presented to nine Italian emergency departments with haemoptysis as the primary complaint.

A randomized crossover design study comparing the pharmacokinetics and pharmacodynamics of 2 single doses of oral aspirin (75 mg v 150 mg) in pregnant women at risk of preeclampsia: implications on assessing aspirin response and patient adherence to therapy.

Background: Pregnancy is associated with physiological changes that can alter the pharmacokinetic and pharmacodynamic profile of many drugs. Low-dose aspirin is used for preeclampsia prevention; however, aspirin's pharmacokinetics and pharmacodynamics are poorly studied in pregnant women.

Objective: The aim of this study was to compare the pharmacodynamics of 2 common doses of aspirin (75 and 150 mg) used for preeclampsia prevention in high-risk women by examining their effect on thromboxane B inhibition.

Pregnancy vitamin D supplementation and offspring bone mineral density in childhood follow-up of a randomized controlled trial.

Background: Findings from the Maternal Vitamin D Osteoporosis Study (MAVIDOS) trial demonstrated a positive effect of gestational cholecalciferol supplementation on offspring bone mineral density (BMD) at age 4 y. Demonstrating the persistence of this effect is important to understanding whether maternal vitamin D supplementation could be a useful public health strategy to improving bone health.

Objectives: We investigated whether gestational vitamin D supplementation increases offspring BMD at ages 6-7 y in an exploratory post-hoc analysis of an existing trial.

NMR Screen Reveals the Diverse Structural Landscape of a G-Quadruplex Library.

G-quadruplexes are noncanonical nucleic acid structures formed by stacked guanosine tetrads. Despite their functional and structural diversity, a single consensus model is typically used to describe sequences with the potential to form G-quadruplex structures. We are interested in developing more specific sequence models for G-quadruplexes.

Optimized gadolinium-DO3A loading in RAFT-polymerized copolymers for superior MR imaging of aging blood-brain barrier.

The development of gadolinium-based contrast agents (GBCAs) has been pivotal in advancing magnetic resonance imaging (MRI), offering enhanced soft tissue contrast without ionizing radiation exposure. Despite their widespread clinical use, the need for improved GBCAs has led to innovations in ligand chemistry and polymer science. We report a novel approach using methacrylate-functionalized DO3A ligands to synthesize a series of copolymers through direct reversible addition-fragmentation chain transfer (RAFT) polymerization.

Assessing patient autonomy in the context of TeamBirth, a quality improvement intervention to improve shared decision-making during labor and birth.

Background: Respectful maternity care includes shared decision-making (SDM). However, research on SDM is lacking from the intrapartum period and instruments to measure it have only recently been developed. TeamBirth is a quality improvement initiative that uses team huddles to improve SDM during labor and birth.

Disparate pathways for extrachromosomal DNA biogenesis and genomic DNA repair.

Oncogene amplification on extrachromosomal DNA (ecDNA) is a pervasive driver event in cancer, yet our understanding of how ecDNA forms is limited. Here, we couple a CRISPR-based method for ecDNA induction with extensive characterization of newly formed ecDNA to examine their biogenesis. We find that DNA circularization is efficient, irrespective of 3D genome context, with formation of 800kb, 1 Mb, and 1.

Right atrial and right ventricular strain: prognostic value depends on the severity of tricuspid regurgitation.

Aims: Assessing right heart function is challenging, particularly when significant tricuspid regurgitation (TR) is present. Amongst available echocardiographic techniques for assessment, literatures suggest that strain imaging may be more reliable and less susceptible to loading conditions. Thus, we aimed to assess the validity of right atrial (RA) and right ventricular (RV) strain relative to conventional metrics as well as their utility in predicting patient outcomes in TR.

Racism and Health Among Aotearoa New Zealand Young People Aged 15-24 years: Analysis of Multiple National Surveys.

Purpose: This Aotearoa New Zealand-based study addresses a gap in literature focusing on individual experiences of racism among adolescents and young adults and its links to health.

Methods: This cross-sectional study uses data from multiple instances of the New Zealand Health Survey (2002/03, 2006/07, 2011/12, 2016/17) and General Social Survey (2008-2016) restricted to participants aged 15-24 years. Prevalence of reported experiences of racism are estimated.

Clinical Practice Patterns for Transradial Coronary Artery Catheterisation in Australian and New Zealand: Mixed-Methods Survey and Interview Study.

Background: While there has been an increase in the use of the transradial approach when performing percutaneous coronary angiography and intervention, there is evidence of variations in international practice. Ensuring that operators' practices are supported by evidence is important to ensure optimal outcomes.

Method: Interventional cardiologists and advanced trainees completed a cross-sectional survey followed by semi-structured interviews to map current practices for transradial coronary artery procedures in Australia and New Zealand and explore factors that influence clinical decision-making around procedural practice.

Apollon: a deoxyribozyme that generates a yellow product.

Colorimetric assays in which the color of a solution changes in the presence of an input provide a simple and inexpensive way to monitor experimental readouts. In this study we used in vitro selection to identify a self-phosphorylating kinase deoxyribozyme that produces a colorimetric signal by converting the colorless substrate pNPP into the yellow product pNP. The minimized catalytic core, sequence requirements, secondary structure, and buffer requirements of this deoxyribozyme, which we named Apollon, were characterized using a variety of techniques including reselection experiments, high-throughput sequencing, comparative analysis, biochemical activity assays, and NMR.

Aurora: a fluorescent deoxyribozyme for high-throughput screening.

Fluorescence facilitates the detection, visualization, and tracking of molecules with high sensitivity and specificity. A functional DNA molecule that generates a robust fluorescent signal would offer significant advantages for many applications compared to intrinsically fluorescent proteins, which are expensive and labor intensive to synthesize, and fluorescent RNA aptamers, which are unstable under most conditions. Here, we describe a novel deoxyriboyzme that rapidly and efficiently generates a stable fluorescent product using a readily available coumarin substrate.

Predictive value of sarcopenia components for all-cause mortality: findings from population-based cohorts.

Background: Low grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited.

Aim: We examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors.

Bone health, cardiovascular disease, and imaging outcomes in UK Biobank: a causal analysis.

This study examined the association of estimated heel bone mineral density (eBMD, derived from quantitative ultrasound) with: (1) prevalent and incident cardiovascular diseases (CVDs: ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), non-ischemic cardiomyopathy (NICM), arrhythmia), (2) mortality (all-cause, CVD, IHD), and (3) cardiovascular magnetic resonance (CMR) measures of left ventricular and atrial structure and function and aortic distensibility, in the UK Biobank. Clinical outcomes were ascertained using health record linkage over 12.3 yr of prospective follow-up.