Therapeutic exploration potential of adenosine receptor antagonists through pharmacophore ligand-based modelling and pharmacokinetics studies against Parkinson disease.

Unlabelled: Parkinson's Disease (PD) is a neurodegenerative disorder that primarily affects persons aged 65 and older. It leads to a decline in motor function as a result of the buildup of abnormal protein deposits called Lewy bodies in the brain. Existing therapies exhibit restricted effectiveness and undesirable side effects.

Supporting contraceptive self-care and reproductive empowerment with a digital health game in Barbados: Development and Pre-implementation study for What's My Method?

Effective contraceptive education is essential to reducing unwanted pregnancy, increasing uptake of modern contraceptive methods, and thoughtfully planning desired births. New World Health Organization (WHO) and family planning organization guidelines recommend situating contraceptive education and counseling within a broader context of self-care that emphasizes individual agency and reproductive empowerment. Digital health interventions, and games for health specifically, have been validated as effective and scalable tools for self-guided and interactive health education, especially among younger tech-savvy individuals.

Engaging older adults in diagnostic safety: implementing a diagnostic communication note sheet in a primary care setting.

Introduction: Adults over the age of 65 are at a higher risk for diagnostic errors due to a myriad of reasons. In primary care settings, a large contributor of diagnostic errors are breakdowns in information gathering and synthesis throughout the patient-provider encounter. Diagnostic communication interventions, such as the Agency for Healthcare Research and Quality's "Be the Expert on You" note sheet, may require adaptations to address older adults' unique needs.

One-pot reaction of 3-vinylchromones, aromatic aldehydes, and ammonium acetate: an efficient approach to highly functionalized 1,6-dihydropyridine derivatives.

In this work, we present an efficient strategy for the straightforward synthesis of functionalized 1,6-dihydropyridine derivatives a three-component reaction of 3-vinylchromones, aromatic aldehydes, and ammonium acetate. A tandem procedure including NH aldimine formation/Michael-type addition/opening of the pyrone ring/isomerization/6π-electrocyclization/[1,5]-H shift allows rapid access to a series of dihydropyridines bearing an -hydroxybenzoyl and a benzoyl scaffold in good yields. Readily available precursors, simple heating conditions, and operational simplicity are some highlighted advantages of this transformation.

Association between prescribed stimulant medications and overdose among individuals receiving opioid agonist therapy: A retrospective cohort study from British Columbia, Canada.

Aims: We measured the association between prescribed stimulant medications and overdose among individuals receiving opioid agonist therapy (OAT) for opioid use disorder.

Design: Retrospective cohort study using the British Columbia Provincial Overdose Cohort, a linked administrative database.

Setting: We used data from British Columbia, Canada, from January 2015 through February 2020.

Determining a point of departure for skin sensitization potency and quantitative risk assessment of fragrance ingredients using the GARDskin dose-response assay.

Potency and quantitative risk assessment are essential for determining safe concentrations for the formulation of potential skin sensitizers into consumer products. Several new approach methodologies (NAMs) for skin sensitization hazard assessment have been developed, validated, and adopted in OECD test guidelines. However, work is ongoing to develop NAMs for predicting skin sensitization potency on a quantitative scale for use as a point of departure (POD) in next-generation risk assessment (NGRA).

Peritoneal dialysis and kidney transplantation: Your questions answered.

Peritoneal dialysis (PD) and kidney transplantation are important therapeutic options in patients with advanced kidney disease. This article delineates the relationship between PD and kidney transplantation in several key domains, including: (1) Comparative merits and limitations of PD versus center-based hemodialysis prior to kidney transplantation, (2) Patient outcomes after kidney transplantation in individuals receiving PD prior to kidney transplantation, (3) Perioperative management strategies of patients receiving PD at the time of kidney transplantation, and (4) The relative advantages and clinical outcomes of PD use following kidney allograft failure compared to other modalities. This article aims to provide comprehensive guidance for optimizing care across the PD-kidney transplant transitions continuum.

Interactions of Oligodendrocyte Precursor Cells and Dopaminergic Neurons in the Mouse Substantia Nigra.

Parkinson's disease (PD) is a prevalent neurodegenerative disease caused by the death of dopaminergic neurons within the substantia nigra pars compacta (SNpc) region of the midbrain. Recent genomic and single cell sequencing data identified oligodendrocytes and oligodendrocyte precursor cells (OPCs) to confer genetic risk in PD, but their biological role is unknown. Although SNpc dopaminergic neurons are scarcely or thinly myelinated, there is a gap in the knowledge concerning the physiological interactions between dopaminergic neurons and oligodendroglia.

Perioperative and periprocedural management of GLP-1 receptor-based agonists and SGLT2 inhibitors: narrative review and the STOP-GAP and STOP DKA-2 algorithms.

The GLP-1 receptor-based agonists (GLP-1RAs) and SGLT2 inhibitors (SGLT2i) are major 21 century breakthroughs in diabetes and obesity medicine but there are important safety considerations regarding the perioperative and periprocedural management of individuals who are treated with these agents. GLP-1RAs have been linked to an increased risk of retained gastric contents and pulmonary aspiration while SGLT2i can be associated with diabetic ketoacidosis. This manuscript provides a narrative review of the available evidence for perioperative and periprocedural risks in people prescribed GLP-1RAs and SGLT2i.

Secondary Immunodeficiency.

The field of medicine is constantly changing and, as healthcare providers, we are fortunate to be practicing in a time when patients are living longer and novel therapeutic options continue to evolve. However, these new advances may be associated with adverse effects that practitioners need to be aware of. Some of these impair the immune system leading to secondary immunodeficiencies (SID) that increase host susceptibility to infections and other complications.

Falls and balance impairment; what and how has this been measured in adults with joint hypermobility? A scoping review.

Background: People with joint hypermobility have excessive joint flexibility, which is more common in young women. The people with symptomatic hypermobility report poor balance and even falls. This scoping review aims to identify and map the available evidence related to balance and falling in adults with joint hypermobility to support research planning and ideas for treatment direction.

Patients with neurological or psychiatric complications of COVID-19 have worse long-term functional outcomes: COVID-CNS-A multicentre case-control study.

It is established that patients hospitalised with COVID-19 often have ongoing morbidity affecting activity of daily living (ADL), employment, and mental health. However, little is known about the relative outcomes in patients with COVID-19 neurological or psychiatric complications. We conducted a UK multicentre case-control study of patients hospitalised with COVID-19 (controls) and those who developed COVID-19 associated acute neurological or psychiatric complications (cases).

Splicing accuracy varies across human introns, tissues, age and disease.

Alternative splicing impacts most multi-exonic human genes. Inaccuracies during this process may have an important role in ageing and disease. Here, we investigate splicing accuracy using RNA-sequencing data from >14k control samples and 40 human body sites, focusing on split reads partially mapping to known transcripts in annotation.

Editing specificity of ADAR isoforms.

Adenosine to inosine deaminases acting on RNA (ADARs) enzymes are found in all metazoa. Their sequence and protein organization is conserved but also shows distinct differences. Moreover, the number of ADAR genes differs between organisms, ranging from one in flies to three in mammals.

Utilization of smartphone technology and wearable technology following TKA.

Introduction: The widespread adoption of smartphones and wearable technology has introduced innovative approaches in healthcare, particularly in postoperative rehabilitation. These technologies hold significant promise for improving recovery following lower extremity arthroplasty, especially total knee arthroplasty (TKA). Despite growing interest, the evidence on their effectiveness and long-term impact remains variable.

Crop rotation effects on the population density of soybean soilborne pathogens under no-till cropping system.

Soilborne diseases are persistent problems in soybean production. Long-term crop rotation can contribute to soilborne disease management. However, the response of soilborne pathogens to crop rotation is inconsistent, and rotation efficacy is highly variable.

Guidelines International Network: Principles for Use of Artificial Intelligence in the Health Guideline Enterprise.

Description: Artificial intelligence (AI) has been defined by the High-Level Expert Group on AI of the European Commission as "systems that display intelligent behaviour by analysing their environment and taking actions-with some degree of autonomy-to achieve specific goals." Artificial intelligence has the potential to support guideline planning, development and adaptation, reporting, implementation, impact evaluation, certification, and appraisal of recommendations, which we will refer to as "guideline enterprise." Considering this potential, as well as the lack of guidance for the use of AI in guidelines, the Guidelines International Network (GIN) proposes a set of principles for the development and use of AI tools or processes to support the health guideline enterprise.

Endovascular Thrombectomy for Extracranial Internal Carotid Artery Occlusions With Large Ischemic Strokes: Insights From the SELECT2 Trial.

Background And Objectives: Although previous trials have established the efficacy and safety of endovascular thrombectomy (EVT) in large ischemic core strokes, most of them excluded patients with extracranial internal carotid artery (e-ICA) occlusion. We aimed to compare outcomes in patients with e-ICA occlusion and large ischemic core infarcts treated with EVT vs medical management (MM).

Methods: This was a secondary analysis of the SELECT2 trial, a randomized controlled trial conducted at 31 international sites.

Poor Olfaction and Risk of Stroke in Older Adults: The Atherosclerosis Risk in Communities Study.

Background: Poor olfaction may be associated with adverse cerebrovascular events, but empirical evidence is limited. We aimed to investigate the association of olfaction with the risk of stroke in the Atherosclerosis Risk in Communities Study.

Methods: We included 5799 older adults with no history of stroke at baseline from 2011 to 2013 (75.

Site-selective photo-crosslinking for the characterisation of transient ubiquitin-like protein-protein interactions.

Non-covalent protein-protein interactions are one of the most fundamental building blocks in cellular signalling pathways. Despite this, they have been historically hard to identify using conventional methods due to their often weak and transient nature. Using genetic code expansion and incorporation of commercially available unnatural amino acids, we have developed a highly accessible method whereby interactions between biotinylated ubiquitin-like protein (UBL) probes and their binding partners can be stabilised using ultraviolet (UV) light-induced crosslinks.