The adaptability of the ion-binding site by the Ag(I)/Cu(I) periplasmic chaperone SilF.

The periplasmic chaperone SilF has been identified as part of an Ag(I) detoxification system in Gram-negative bacteria. Sil proteins also bind Cu(I) but with reported weaker affinity, therefore leading to the designation of a specific detoxification system for Ag(I). Using isothermal titration calorimetry, we show that binding of both ions is not only tighter than previously thought but of very similar affinities.

Opioid-related ambulance attendances during the first 2 years of the COVID-19 pandemic in Victoria, Australia.

Background And Aims: Public health measures introduced to contain the spread of the SARS-CoV-2 virus likely affected opioid supply and demand, as well as the patterns and contexts of opioid use. We measured opioid-related harms during the first 2 years of COVID-19 restrictions in Victoria, Australia.

Design: We adopted an interrupted time series analysis design using interventional autoregressive integrated moving average (ARIMA) models.

Glutamine mimicry suppresses tumor progression through asparagine metabolism in pancreatic ductal adenocarcinoma.

In pancreatic ductal adenocarcinoma (PDAC), glutamine is a critical nutrient that drives a wide array of metabolic and biosynthetic processes that support tumor growth. Here, we elucidate how 6-diazo-5-oxo-L-norleucine (DON), a glutamine antagonist that broadly inhibits glutamine metabolism, blocks PDAC tumor growth and metastasis. We find that DON significantly reduces asparagine production by inhibiting asparagine synthetase (ASNS), and that the effects of DON are rescued by asparagine.

The Alzheimer's Disease Neuroimaging Initiative and the role and contributions of the Private Partners Scientific Board (PPSB).

The Alzheimer's Disease Neuroimaging Initiative (ADNI) Private Partners Scientific Board (PPSB) encompasses members from industry, biotechnology, diagnostic, and non-profit organizations that have until recently been managed by the Foundation for the National Institutes of Health (FNIH) and provided financial and scientific support to ADNI programs. In this article, we review some of the major activities undertaken by the PPSB, focusing on those supporting the most recently completed National Institute on Aging grant, ADNI3, and the impact it has had on streamlining biomarker discovery and validation in Alzheimer's disease. We also provide a perspective on the gaps that may be filled with future PPSB activities as part of ADNI4 and beyond.

Pulmonary tumour thrombotic microangiopathy mimicking immunotherapy-associated pneumonitis.

We present a case of pulmonary tumour thrombotic microangiopathy (PTTM) in a patient on adjuvant immunotherapy for resected triple negative breast cancer. The patient presented with deranged liver function tests and subsequently developed severe hypoxia and thrombocytopaenia, with right heart failure. The primary differential diagnosis considered was immunotherapy-associated hepatitis and pneumonitis.

PLS3 missense variants affecting the actin-binding domains cause X-linked congenital diaphragmatic hernia and body-wall defects.

Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families.

Heterogeneity of treatment responses in rheumatoid arthritis using group based trajectory models: secondary analysis of clinical trial data.

Background: Traditionally rheumatoid arthritis (RA) trials classify patients as responders and non-responders; they ignore the potential range of treatment responses. Group Based Trajectory Models (GBTMs) provide a more refined approach. They identify patient subgroups with similar outcome trajectories.

The Impact of Cat Fostering on Older Adult Well-Being and Loneliness: A Feasibility Study.

Objectives: This feasibility study explored the impact of fostering a shelter cat on loneliness and well-being in older adults living alone without a pet. The study also examined the effect of cat fostering on older adults' interest in cat adoption when perceived barriers to adoption were removed.

Methods: A total of 29 adults (age ≥60) were paired with a cat and asked to foster for a minimum of 4 months (with an option to adopt).

Racial and Ethnic Disparities in the Management of Diabetic Feet.

Purpose Of Review: Diabetes mellitus is a chronic medical condition affecting many individuals worldwide and leads to billions of dollars spent within the healthcare system for its treatment and complications. Complications from diabetes include diabetic foot conditions that can have a devasting impact on quality of life. Diabetic foot ulcers and amputations occur in minority individuals at an increased rate compared to Caucasian individuals.

Cluster Sets to Prescribe Interval Resistance Training: A Potential Method to Optimise Resistance Training Safety, Feasibility and Efficacy in Cardiac Patients.

The integration of resistance training for cardiac patients leads to important health outcomes that are not optimally obtained with aerobic exercise; these include an increase in muscle mass, maintenance of bone mineral density, and improvements in muscular fitness parameters. Despite the proliferation of evidence supporting resistance exercise in recent decades, the implementation of resistance training is underutilised, and prescription is often sub-optimal in cardiac patients. This is frequently associated with safety concerns and inadequate methods of practical exercise prescription.

The role of estrogen in female skeletal muscle aging: A systematic review.

Aging is associated with a loss of skeletal muscle mass and function that negatively impacts the independence and quality of life of older individuals. Females demonstrate a distinct pattern of muscle aging compared to males, potentially due to menopause, when the production of endogenous sex hormones declines. This systematic review aims to investigate the current knowledge about the role of estrogen in female skeletal muscle aging.

Adapting to a Robotic Era: The Transferability of Open and Laparoscopic Skills to Robotic Surgery.

Background: The learning curve of robotic surgical skills is poorly understood. There is a lack of data on the transferability of skills from open and laparoscopic training to robotic surgery. In this retrospective cohort study, we investigated the impact of training acquired during intern year on the development of robotic skills in general surgery residents, prior to formal robotic training.

Type 2 Diabetes Mellitus and Sarcopenia as Comorbid Chronic Diseases in Older Adults: Established and Emerging Treatments and Therapies.

Type 2 diabetes mellitus (T2DM) and sarcopenia (low skeletal muscle mass and function) share a bidirectional relationship. The prevalence of these diseases increases with age and they share common risk factors. Skeletal muscle fat infiltration, commonly referred to as myosteatosis, may be a major contributor to both T2DM and sarcopenia in older adults via independent effects on insulin resistance and muscle health.

NRF2 Dysregulation in Mice Leads to Inadequate Beta-Cell Mass Expansion during Pregnancy and Gestational Diabetes.

The late stages of the mammalian pregnancy are accompanied with increased insulin resistance due to the increased glucose demand of the growing fetus. Therefore, as a compensatory response to maintain the maternal normal blood glucose levels, maternal beta-cell mass expands leading to increased insulin release. Defects in beta-cell adaptive expansion during pregnancy can lead to gestational diabetes mellitus (GDM).

Clinical exome sequencing efficacy and phenotypic expansions involving anomalous pulmonary venous return.

Anomalous pulmonary venous return (APVR) frequently occurs with other congenital heart defects (CHDs) or extra-cardiac anomalies. While some genetic causes have been identified, the optimal approach to genetic testing in individuals with APVR remains uncertain, and the etiology of most cases of APVR is unclear. Here, we analyzed molecular data from 49 individuals to determine the diagnostic yield of clinical exome sequencing (ES) for non-isolated APVR.

Correlation between progression-free survival and overall survival in patients with ovarian cancer after cytoreductive surgery: a systematic literature review.

Objectives: This analysis aimed to better define the relationship between progression-free survival and overall survival in adult patients with ovarian cancer (including fallopian tube or primary peritoneal cancer) following primary cytoreductive surgery or interval cytoreductive surgery.

Methods: A systematic literature review was carried out across the Medline, Embase, and Cochrane Central databases on 7 July 2020 (date limits 1 January 2011 to 7 July 2020) to identify studies with the following eligibility criteria: clinical trials/observational studies including >200 patients with ovarian cancer aged ≥18 years, evaluating overall survival/progression-free survival following cytoreductive surgery by residual disease status in the United States, Europe, Japan, or China. Weighted linear regression models were used to assess any correlation between median progression-free survival and overall survival, and between logHR for progression-free survival and logHR for overall survival.

Interchangeability of the Assays Used to Assess the Activity of Anti-SARS-CoV-2 Monoclonal Antibodies.

The recent global COVID-19 pandemic caused by SARS-CoV-2 lasted for over three years. A key measure in combatting this pandemic involved the measurement of the monoclonal antibody (mAb)-mediated inhibition of binding between the spike receptor-binding domain (RBD) and hACE2 receptor. Potency assessments of therapeutic anti-SARS-CoV-2 mAbs typically include binding or cell-based neutralization assays.

Encounter Complexes Between the N-terminal of Neurotensin with the Extracellular Loop 2 of the Neurotensin Receptor 1 Steer Neurotensin to the Orthosteric Binding Pocket.

Neurotensin (NT) is a linear disordered peptide that activates two different class A GPCRs, neurotensin receptor 1 (NTS) and NTS. Resolved structures of the complex of the C-terminal fragment of NT, NT8-13, with NTS shows the peptide takes a well-defined structure in the bound state. However, the mechanisms underlying NT recognition of NTS, and the conformational transition of NT upon binding NTS is an open question that if answered may aid discovery of highly selective drugs and reveal potential secondary binding sites on the surface of the receptor.

Baseline performance in a robotic virtual reality platform predicts rate of skill acquisition in a proficiency-based curriculum: a cohort study of surgical trainees.

Background: Residency programs must prepare to train the next generation of surgeons on the robotic platform. The purpose of this study was to determine if baseline skills of residents on a virtual reality (VR) robotic simulator before intern year predicted future performance in a proficiency-based curriculum.

Methods: Across two academic years, 21 general surgery PGY-1s underwent the robotic surgery boot camp at the University of Texas Southwestern.