Can fast wall shear stress computation predict adverse cardiac events in patients with intermediate non-flow limiting stenoses?

Background And Aims: Coronary angiography-derived wall shear stress (WSS) may enable identification of vulnerable plaques and patients. A new recently introduced software allows seamless three-dimensional quantitative coronary angiography (3D-QCA) reconstruction and WSS computation within a single user-friendly platform carrying promise for clinical applications. This study examines for the first time the efficacy of this software in detecting vulnerable lesions in patients with intermediate non-flow limiting stenoses.

A whole-brain functional connectivity model of Alzheimer's disease pathology.

Introduction: Alzheimer's disease (AD) is characterized by the presence of two proteinopathies, amyloid and tau, which have a cascading effect on the functional and structural organization of the brain.

Methods: In this study, we used a supervised machine learning technique to build a model of functional connections that predicts cerebrospinal fluid (CSF) p-tau/Aβ (the PATH-fc model). Resting-state functional magnetic resonance imaging (fMRI) data from 289 older adults in the Alzheimer's Disease Neuroimaging Initiative (ADNI) were utilized for this model.

Linking the neural signature of response time variability to Alzheimer's disease pathology and cognitive functioning.

Promising evidence has suggested potential links between mind-wandering and Alzheimer's disease (AD). Yet, older adults with diagnosable neurocognitive disorders show reduced meta-awareness, thus questioning the validity of probe-assessed mind-wandering in older adults. In prior work, we employed response time variability as an objective, albeit indirect, marker of mind-wandering to identify patterns of functional connectivity that predicted mind-wandering.

Digoxin and exercise effects on skeletal muscle Na,K-ATPase isoform gene expression in healthy humans.

In muscle, digoxin inhibits Na,K-ATPase (NKA) whereas acute exercise can increase NKA gene expression, consistent with training-induced increased NKA content. We investigated whether oral digoxin increased NKA isoform mRNA expression (qPCR) in muscle at rest, during and post-exercise in 10 healthy adults, who received digoxin (DIG, 0.25 mg per day) or placebo (CON) for 14 days, in a randomised, double-blind and cross-over design.

Physical activity and depression symptoms in people with osteoarthritis-related pain: A cross-sectional study.

Osteoarthritis is a leading cause of chronic pain and is associated with high rates of depression. Physical activity reduces depression symptoms and pain levels. It remains unknown if physical activity is associated with lower symptoms of depression irrespective of pain levels in individuals with osteoarthritis.

Haemoglobin mass responses and performance outcomes among high-performance swimmers following a 3-week live-high, train-high camp at 2320 m.

Aim: Greater quantification and characterisation of training load (TL) throughout Live-high, train-high (LHTH) altitude (ALT) training is required to identify periodisation strategies that may lead to physiological and performance improvements in swimmers.

Purpose: This study aimed to examine the physiological responses and performance outcomes of 14 high-performance swimmers (FINA points: 836.0 ± 35.

A century of exercise physiology: effects of muscle contraction and exercise on skeletal muscle Na,K-ATPase, Na and K ions, and on plasma K concentration-historical developments.

This historical review traces key discoveries regarding K and Na ions in skeletal muscle at rest and with exercise, including contents and concentrations, Na,K-ATPase (NKA) and exercise effects on plasma [K] in humans. Following initial measures in 1896 of muscle contents in various species, including humans, electrical stimulation of animal muscle showed K loss and gains in Na, Cl and H0, then subsequently bidirectional muscle K and Na fluxes. After NKA discovery in 1957, methods were developed to quantify muscle NKA activity via rates of ATP hydrolysis, Na/K radioisotope fluxes, [H]-ouabain binding and phosphatase activity.

Predictors of outcome in patients with moderate mixed aortic valve disease.

Objectives: Grading the severity of moderate mixed aortic stenosis and regurgitation (MAVD) is challenging and the disease poorly understood. Identifying markers of haemodynamic severity will improve risk stratification and potentially guide timely treatment. This study aims to identify prognostic haemodynamic markers in patients with moderate MAVD.

Development of a Digital Health Intervention to Support Patients on a Waitlist for Orthopedic Specialist Care: Co-Design Study.

Background: The demand for orthopedic specialist consultations for patients with osteoarthritis in public hospitals is high and continues to grow. Lengthy waiting times are increasingly affecting patients from low socioeconomic and culturally and linguistically diverse backgrounds who are more likely to rely on public health care.

Objective: This study aimed to co-design a digital health intervention for patients with OA who are waiting for an orthopedic specialist consultation at a public health service, which is located in local government areas (LGAs) of identified social and economic disadvantage.

Accelerometry measures of physical activity and sedentary behavior: Associations with cognitive functioning in MS.

Background: Cognitive dysfunction is a pervasive symptom of multiple sclerosis (MS). Correlational evidence on the relationships between physical activity, sedentary behavior, and cognition has been mixed and limited to a few activity measures. The collinearity of accelerometry-based metrics has precluded an assessment of the full activity spectrum.

Prevalence of diagnosable depression in patients awaiting orthopaedic specialist consultation: a cross-sectional analysis.

Background: Musculoskeletal conditions, including osteoarthritis (OA), are a leading cause of disability and chronic pain, and are associated with high rates of comorbid depression. However, signs of depression are often masked by pain. The aim of this study was to determine the prevalence and severity of depression and pain in individuals awaiting specialist orthopaedic consultation.

Rational design of elastin-like polypeptide fusion proteins to tune self-assembly and properties of protein vesicles.

Protein vesicles made from bioactive proteins have potential value in drug delivery, biocatalysis, and as artificial cells. As the proteins are produced recombinantly, the ability to precisely tune the protein sequence provides control not possible with polymeric vesicles. The tunability and biocompatibility motivated this work to develop protein vesicles using rationally designed protein building blocks to investigate how protein sequence influences vesicle self-assembly and properties.

Effect of Food on the Pediatric Dispersible Tablet Formulations of TRIUMEQ and DOVATO in Healthy Adult Participants.

This randomized food effect study in healthy adult participants examined dispersible tablet formulations of fixed-dose combinations of dolutegravir/abacavir/lamivudine (TRIUMEQ) and dolutegravir/lamivudine (DOVATO). While adult tablet formulations of these combinations are currently approved for the treatment of human immunodeficiency virus, alternate formulations for children are urgently needed to facilitate appropriate pediatric dosing for patients who may have difficulty swallowing a conventional tablet. This study compared the effect of a high-fat, high-calorie meal on the pharmacokinetics, safety, and tolerability of dispersible tablet (DT) formulations of the two-drug and three-drug regimens, with administration under fasting conditions.

ATP13A1 prevents ERAD of folding-competent mislocalized and misoriented proteins.

The biosynthesis of thousands of proteins requires targeting a signal sequence or transmembrane segment (TM) to the endoplasmic reticulum (ER). These hydrophobic ɑ helices must localize to the appropriate cellular membrane and integrate in the correct topology to maintain a high-fidelity proteome. Here, we show that the P5A-ATPase ATP13A1 prevents the accumulation of mislocalized and misoriented proteins, which are eliminated by different ER-associated degradation (ERAD) pathways in mammalian cells.

Otopathologic and Computed Tomography Correlation of Internal Auditory Canal Diverticula in Otosclerosis.

Introduction: Internal auditory canal (IAC) diverticula, also known as IAC cavitary lesions or anterior cupping of the IAC, observed in otopathologic specimens and high-resolution computed tomography (CT) scans of the temporal bone are thought to be related to otosclerosis. Herein, we examined the usefulness of CT scans in identifying diverticula and determined whether IAC diverticula are associated with otosclerosis on otopathology.

Methods: One hundred five consecutive specimens were identified from the National Temporal Bone Hearing and Balance Pathology Resource Registry.

The Endoplasmic Reticulum and the Fidelity of Nascent Protein Localization.

High-fidelity protein localization is essential to define the identities and functions of different organelles and to maintain cellular homeostasis. Accurate localization of nascent proteins requires specific protein targeting pathways as well as quality control (QC) mechanisms to remove mislocalized proteins. The endoplasmic reticulum (ER) is the first destination for approximately one-third of the eukaryotic proteome and a major site of protein biosynthesis and QC.

Protocol for a randomized controlled trial of mindfulness-based stress reduction to improve attentional control in older adults (HealthyAgers trial).

Background: Mindfulness meditation is a form of mind-body intervention that has increasing scientific support for its ability to reduce age-related declines in cognitive functioning, improve affective health, and strengthen the neural circuitry supporting improved cognitive and affective health. However, the majority of existent studies have been pilot investigations with small sample sizes, limited follow-up data, and a lack of attention to expectancy effects. Here, we present the study design of a Phase I/II, efficacy trial-HealthyAgers trial-that examines the benefits of a manualized mindfulness-based stress reduction program in improving attentional control and reducing mind-wandering in older adults.

Oral digoxin effects on exercise performance, K regulation and skeletal muscle Na ,K -ATPase in healthy humans.

We investigated whether digoxin lowered muscle Na ,K -ATPase (NKA), impaired muscle performance and exacerbated exercise K disturbances. Ten healthy adults ingested digoxin (0.25 mg; DIG) or placebo (CON) for 14 days and performed quadriceps strength and fatiguability, finger flexion (FF, 105% , 3 × 1 min, fourth bout to fatigue) and leg cycling (LC, 10 min at 33% and 67% , 90% to fatigue) trials using a double-blind, crossover, randomised, counter-balanced design.

Computed Tomography Density as a Bio-marker for Histologic Grade of Otosclerosis: A Human Temporal Bone Pathology Study.

Hypothesis: Computed tomography (CT) density measurement can be used to objectively distinguish otosclerosis from normal bone and to determine histologic grades of otosclerosis.

Background: Otosclerosis can be seen on CT as subtle radiolucent areas. An objective radiologic measurement that corresponds to known otosclerosis pathology may improve diagnostic accuracy, and could be used as a radiologic biomarker for otosclerosis grade.

Organotypic whole hemisphere brain slice models to study the effects of donor age and oxygen-glucose-deprivation on the extracellular properties of cortical and striatal tissue.

Background: The brain extracellular environment is involved in many critical processes associated with neurodevelopment, neural function, and repair following injury. Organization of the extracellular matrix and properties of the extracellular space vary throughout development and across different brain regions, motivating the need for platforms that provide access to multiple brain regions at different stages of development. We demonstrate the utility of organotypic whole hemisphere brain slices as a platform to probe regional and developmental changes in the brain extracellular environment.