MCC950 mitigates SIRT3-NLRP3-driven inflammation and rescues post-stroke neurogenesis.

Sustained activation of the SIRT3-NLRP3 inflammasome has been associated with worse outcomes after ischemic stroke. The objective of this study was to examine the potential mechanism by which the SIRT3-NLRP3 inflammasome affects neural stem and progenitor cells (NSPCs) after transient middle cerebral artery occlusion (tMCAO) in rats. Following tMCAO, significantly elevated levels of NLRP3, ASC, cleaved caspase 1, IL-1β, and IL-18 were observed in the ischemic subventricular zone.

Rational choices elicit stronger sense of agency in brain and behavior.

The sense of agency is the subjective feeling of control over one's own actions and the associated outcomes. Here, we asked whether and to what extent the reasons behind our choices (operationalized by value differences, expected utility, and counterfactual option sets) drive our sense of agency. We simultaneously tested these three dimensions during a novel value-based decision-making task while recording explicit (self-reported) and implicit (brain signals) measures of agency.

Review: A systematic review of dairy cow health, welfare, and behaviour in year-round loose range housing.

This systematic review compares the health, welfare, and behaviour of dairy cows in year-round loose housing systems against those kept in other housing systems in temperate regions. Year-round loose housing systems comprised housing where dairy cows had no access to the outdoors or only had access to a yard, pen or run. The comparator housing systems also comprised housing with and without outdoor access (including grazing).

Brown adipose tissue is associated with reduced weight loss and risk of cancer cachexia: A retrospective cohort study.

Background & Aims: Brown adipose tissue (BAT) has been mainly investigated as a potential target against cardiometabolic disease, but it has also been linked to cancer-related outcomes. Although preclinical data support that BAT and the thermogenic adipocytes in white adipose tissue may play an adverse role in the pathogenesis of cancer cachexia, results from studies in patients have reported inconsistent results. The purpose of this study was to examine the interrelationship between presence of detectable BAT, changes in body weight, and cachexia in patients with cancer.

Unveiling the trends: Growing cancer and venous thromboembolism mortality in older adults in the United States, 1999-2020.

Background: While cancer mortality rates in the United States (U.S.) have decreased due to advances in chemotherapy, older adults with cancer face an elevated risk of venous thromboembolism (VTE).

Changes to social and healthcare providers support in the perinatal period: Impact on coping strategies, depression and anxiety.

Background: During the perinatal period, risk of depression and anxiety (D&A) increases. As in other crisis events, the COVID-19 pandemic, imposed social distancing measures, diminished social support and changes in perinatal healthcare provision which heightened this risk. This study aimed to examine how changes in social and healthcare provider support during the pandemic affected coping strategies and depression and anxiety symptoms (D&As) among perinatal women.

Pregnancy and postnatal outcomes for women with intellectual disability and their infants: A systematic review.

Background: While the perinatal period is a vulnerable time for women and their infants, it is also a window to promote adjustment and support. Women with intellectual disability might be a uniquely vulnerable group owing to pre-existing health and care inequalities. The aim of this paper is to explore the pregnancy and postnatal outcomes of women with intellectual disability and the health and development of their infants.

Long-Term Impact of Using Mobile Phones and Playing Computer Games on the Brain Structure and the Risk of Neurodegenerative Diseases: Large Population-Based Study.

Background: Despite the increasing popularity of electronic devices, the longitudinal effects of daily prolonged electronic device usage on brain health and the aging process remain unclear.

Objective: The aim of this study was to investigate the impact of the daily use of mobile phones/computers on the brain structure and the risk of neurodegenerative diseases.

Methods: We used data from the UK Biobank, a longitudinal population-based cohort study, to analyze the impact of mobile phone use duration, weekly usage time, and playing computer games on the future brain structure and the future risk of various neurodegenerative diseases, including all-cause dementia (ACD), Alzheimer disease (AD), vascular dementia (VD), all-cause parkinsonism (ACP), and Parkinson disease (PD).

Health and Experiences During the COVID-19 Pandemic Among Children and Young People: Analysis of Free-Text Responses From the Children and Young People With Long COVID Study.

Background: The literature is equivocal as to whether the predicted negative mental health impact of the COVID-19 pandemic came to fruition. Some quantitative studies report increased emotional problems and depression; others report improved mental health and well-being. Qualitative explorations reveal heterogeneity, with themes ranging from feelings of loss to growth and development.

The Effects of Hospital Delivery Volume and Travel Time on Perinatal Mortality and Delivery in Transit: Causal Inference with Triangulation.

Background: Hospital regionalization involves balancing hospital volume and travel time. We investigated how hospital volume and travel time affect perinatal mortality and the risk of delivery in transit using three different study designs.

Methods: This nationwide cohort study used data from the Medical Birth Registry of Norway (1999-2016) and Statistics Norway.

Directed Evolution's Selective Use of Quantum Tunneling in Designed Enzymes─A Combined Theoretical and Experimental Study.

Natural enzymes are powerful catalysts, reducing the apparent activation energy for reactions and enabling chemistry to proceed as much as 10 times faster than the corresponding solution reaction. It has been suggested for some time that, in some cases, quantum tunneling can contribute to this rate enhancement by offering pathways through a barrier inaccessible to activated events. A central question of interest to both physical chemists and biochemists is the extent to which evolution introduces mechanisms below the barrier, or tunneling mechanisms.

The Derivation of Acute and Chronic Environmental Quality Standards for Nickel in European Surface Waters: A Demonstrable need to follow scientific evidence.

Environmental Quality Standards (EQS) derived under the European Water Framework Directive are legally binding and enshrined in individual European Member State Country national legislation. These EQS are derived following well-established guidance documents. In 2013, EQS for nickel were derived for freshwaters to be protective against long and short-term exposures, at 4 and 34 µg L-1, respectively.

Prion Protein Endoproteolysis: Cleavage Sites, Mechanisms and Connections to Prion Disease.

Highly abundant in neurons, the cellular prion protein (PrP) is an obligatory precursor to the disease-associated misfolded isoform denoted PrP that accumulates in the rare neurodegenerative disorders referred to either as transmissible spongiform encephalopathies (TSEs) or as prion diseases. The ability of PrP to serve as a substrate for this template-mediated conversion process depends on several criteria but importantly includes the presence or absence of certain endoproteolytic events performed at the cell surface or in acidic endolysosomal compartments. The major endoproteolytic events affecting PrP are referred to as α- and β-cleavages, and in this review we outline the sites within PrP at which the cleavages occur, the mechanisms potentially responsible and their relevance to pathology.

Potential links between human bloodstream infection by Salmonella enterica serovar Typhimurium and international transmission to Colombia.

Salmonella enterica serovar Typhimurium is a prevalent food-borne pathogen that is usually associated with gastroenteritis infection. S. Typhimurium is also a major cause of bloodstream infections in sub-Saharan Africa, and is responsible for invasive non-typhoidal Salmonella (iNTS) disease.

European Society of Cardiology quality indicators for the management of acute coronary syndrome.

Background: Closing the evidence-practice gap for the treatment of acute coronary syndrome (ACS) is central to improving quality of care. Under the European Society of Cardiology (ESC) framework, we aimed to develop updated quality indicators (QIs) for the evaluation of quality of care and outcomes for patients with ACS.

Methods: A Working Group of experts including members of the ESC Clinical Practice Guidelines Task Force for ACS, Acute CardioVascular Care Association and European Association of Percutaneous Cardiovascular Interventions followed the ESC methodology for QI development.

A TTPA deletion is associated with Retinopathy with Vitamin E Deficiency (RVED) in the English Cocker Spaniel Dog.

Retinopathy with Vitamin E Deficiency (RVED) is a familial disease in the English Cocker Spaniel (ECS) dog breed. Ophthalmic abnormalities observed in RVED-affected ECS include lipofuscin granule deposition within the tapetal fundus and subsequent retinal degeneration resulting in visual deficits. Affected dogs may also exhibit neurological signs that include ataxia and hindlimb proprioceptive deficit.

Milestone events in recessive dystrophic epidermolysis bullosa (RDEB): findings of the PEBLES Study.

Background: In recessive dystrophic epidermolysis bullosa (RDEB), complications like oesophageal strictures, hand contractures, cardiomyopathy and cutaneous squamous cell carcinoma (SCC) may develop, necessitating procedures such as oesophageal dilatation (OD), gastrostomy tube placement and hand surgery.

Objectives: To determine prevalence and age of onset of milestone events by RDEB subtype, specifically dysphagia, first OD, first gastrostomy tube, first hand surgery, cardiomyopathy, first SCC and death.

Methods: The Prospective Epidermolysis Bullosa Longitudinal Evaluation Study (PEBLES) is a register study of individuals with RDEB which records comprehensive EB- and non-EB-related health information.

Results from the international collaborative systematic literature review informing the 2023 EULAR recommendations for the treatment of systemic sclerosis.

Background: The EULAR recommendations for the treatment of systemic sclerosis (SSc) were updated in 2017, informed by a systematic literature review (SLR) completed in 2014.

Objectives: The aim of this new SLR was to provide the most up-to-date literature to underpin contemporary EULAR recommendations for the management of SSc.

Methods: 30 searches for 30 interventions (including several outcomes/clinical questions), and 1 dedicated search (with several interventions) for calcinosis were prioritised by the task force.

Performance analysis of a deep-learning algorithm to detect the presence of inflammation in MRI of sacroiliac joints in patients with axial spondyloarthritis.

Objectives: To assess the ability of a previously trained deep-learning algorithm to identify the presence of inflammation on MRI of sacroiliac joints (SIJ) in a large external validation set of patients with axial spondyloarthritis (axSpA).

Methods: Baseline SIJ MRI scans were collected from two prospective randomised controlled trials in patients with non-radiographic (nr-) and radiographic (r-) axSpA (RAPID-axSpA: NCT01087762 and C-OPTIMISE: NCT02505542) and were centrally evaluated by two expert readers (and adjudicator in case of disagreement) for the presence of inflammation by the 2009 Assessment of SpondyloArthritis International Society (ASAS) definition. Scans were processed by the deep-learning algorithm, blinded to clinical information and central expert readings.

EULAR recommendations for the treatment of systemic sclerosis: 2023 update.

Objectives: To update the 2017 European Alliance of Associations for Rheumatology (EULAR) recommendations for treatment of systemic sclerosis (SSc), incorporating new evidence and therapies.

Methods: An international task force was convened in line with EULAR standard operating procedures. A nominal group technique exercise was performed in two rounds to define questions underpinning a subsequent systematic literature review.

Therapeutic interception in individuals at risk of rheumatoid arthritis to prevent clinically impactful disease.

Multiple clinical trials for rheumatoid arthritis (RA) prevention have been completed. Here, we set out to report on the lessons learnt from these studies. Researchers who conducted RA prevention trials shared the background, rationale, approach and outcomes and evaluated the lessons learnt to inform the next generation of RA prevention trials.

Predicting rapid progression in knee osteoarthritis: a novel and interpretable automated machine learning approach, with specific focus on young patients and early disease.

Objectives: To facilitate the stratification of patients with osteoarthritis (OA) for new treatment development and clinical trial recruitment, we created an automated machine learning (autoML) tool predicting the rapid progression of knee OA over a 2-year period.

Methods: We developed autoML models integrating clinical, biochemical, X-ray and MRI data. Using two data sets within the OA Initiative-the Foundation for the National Institutes of Health OA Biomarker Consortium for training and hold-out validation, and the Pivotal Osteoarthritis Initiative MRI Analyses study for external validation-we employed two distinct definitions of clinical outcomes: Multiclass (categorising OA progression into pain and/or radiographic) and binary.