Rural physicians and social capital: the potential and promises of a rural health research capacity building program.

Background: Accessible and contextually relevant healthcare research programs and networks for rural physicians are exceedingly rare, which hinders the development of social capital in an already isolating profession. This study aims to examine the impact of the Rural Health Research Capacity Building (RRCB) Program on enhancing cognitive, structural, and relational social capital through comprehensive research skills training, supported by professional teams and resources.

Methods: This study uses a mixed-methods approach with utilization of qualitative and quantitative data and pre-post quasi-experimental design.

Using the adaptive action method to tackle wicked problems in rural faculty development.

Medical educators face wicked (complex) problems. Few faculty development (FD) programs exist specifically designed for rural physicians. Memorial University created the 6for6 program, a longitudinal FD program in foundational research skills for rural physicians.

Targeting CLK3 with Covalent Inhibitors: A Novel Strategy for Malaria Treatment.

Malaria still causes over 600,000 deaths annually, with rising resistance to frontline drugs by increasing this number each year. New medicines with novel mechanisms of action are, therefore, urgently needed. In this work, we solved the cocrystal structure of the essential malarial kinase CLK3 with the reversible inhibitor TCMDC-135051 (), enabling the design of covalent inhibitors targeting a unique cysteine residue (Cys368) poorly conserved in the human kinome.

A golden age of muscarinic acetylcholine receptor modulation in neurological diseases.

Over the past 40 years, the muscarinic acetylcholine receptor family, particularly the M-receptor and M-receptor subtypes, have emerged as validated targets for the symptomatic treatment of neurological diseases such as schizophrenia and Alzheimer disease. However, despite considerable effort and investment, no drugs have yet gained clinical approval. This is largely attributable to cholinergic adverse effects that have halted the majority of programmes and resulted in a waning of interest in these G-protein-coupled receptor targets.

Evolving through multiple, co-existing pressures to change: a case study of self-organization in primary care during the COVID-19 pandemic in Canada.

Background: Primary care is often described as slow to change. But conceptualized through complexity theory, primary care is continually changing in unpredictable, non-linear ways through self-organization processes. Self-organization has proven hard to study directly.

The C-terminus of the prototypical M2 muscarinic receptor localizes to the mitochondria and regulates cell respiration under stress conditions.

Muscarinic acetylcholine receptors are prototypical G protein-coupled receptors (GPCRs), members of a large family of 7 transmembrane receptors mediating a wide variety of extracellular signals. We show here, in cultured cells and in a murine model, that the carboxyl terminal fragment of the muscarinic M2 receptor, comprising the transmembrane regions 6 and 7 (M2tail), is expressed by virtue of an internal ribosome entry site localized in the third intracellular loop. Single-cell imaging and import in isolated yeast mitochondria reveals that M2tail, whose expression is up-regulated in cells undergoing integrated stress response, does not follow the normal route to the plasma membrane, but is almost exclusively sorted to the mitochondria inner membrane: here, it controls oxygen consumption, cell proliferation, and the formation of reactive oxygen species (ROS) by reducing oxidative phosphorylation.

Severe DRESS with myocarditis secondary to naproxen/esomeprazole.

A man in his 60s presented with a widespread erythematous rash and associated chills, paraesthesia and haematuria. He had recently commenced naproxen/esomeprazole. Blood tests showed hypereosinophilia (0.

Large Language and Vision Assistant in dermatology: a game changer or just hype?

The integration of artificial intelligence (AI) in healthcare, particularly in the field of dermatology, has experienced significant progress through the creation of advanced tools such as the Large Language and Vision Assistant (LLaVA). This comprehensive review examines whether LLaVA represents a significant breakthrough or merely a passing trend in dermatological practice. By incorporating both language and visual analysis capabilities, LLaVA aims to support enhanced diagnostic accuracy, patient engagement and customized treatment planning, as evidenced by current research and case studies.

An analysis of direct and indirect costs in Hidradenitis Suppurativa.

Background: Hidradenitis Suppurativa (HS) is a chronic inflammatory skin condition with recurrent nodules and abscesses that culminate in purulent discharge and scarring. It has significant physical, psychological and financial impact.

Objectives: This study plans to analyse patient costs associated with HS.

Phosphorylation bar-coding of free fatty acid receptor 2 is generated in a tissue-specific manner.

Free fatty acid receptor 2 (FFAR2) is activated by short-chain fatty acids and expressed widely, including in white adipocytes and various immune and enteroendocrine cells. Using both wild-type human FFAR2 and a designer receptor exclusively activated by designer drug (DREADD) variant we explored the activation and phosphorylation profile of the receptor, both in heterologous cell lines and in tissues from transgenic knock-in mouse lines expressing either human FFAR2 or the FFAR2-DREADD. FFAR2 phospho-site-specific antisera targeting either pSer/pSer or pThr/pThr provided sensitive biomarkers of both constitutive and agonist-mediated phosphorylation as well as an effective means to visualise agonist-activated receptors in situ.

A minimally invasive, field-applicable CRISPR/Cas biosensor to aid in the detection of Pseudogymnoascus destructans, the causative fungal agent of white-nose syndrome in bats.

The accessibility to CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein) genetic tools has given rise to applications beyond site-directed genome editing for the detection of DNA and RNA. These tools include precise diagnostic detection of human disease pathogens, such as SARS-CoV-2 and Zika virus. Despite the technology being rapid and cost-effective, the use of CRISPR/Cas tools in the surveillance of the causative agents of wildlife diseases has not been prominent.

Comparative diet-gut microbiome analysis in Crohn's disease and Hidradenitis suppurativa.

Introduction: The chronic inflammatory skin disease Hidradenitis suppurativa (HS) is strongly associated with Crohn's Disease (CD). HS and CD share clinical similarities and similar inflammatory pathways are upregulated in both conditions. Increased prevalence of inflammatory disease in industrialised nations has been linked to the Western diet.