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Hallucinogen use for both recreational and medical purposes is rapidly increasing globally, raising concerns about potential adverse effects. This study examined the risk of incident mania or bipolar disorder (BD) diagnosis associated with having an emergency department (ED) visit or hospitalization involving hallucinogens. We used a population-based cohort study of all individuals aged 14-65 years with no baseline history of BD and registered in the Ontario Health Insurance Plan in Ontario, Canada, between 2008-2022. Incident mania (primary outcome) and incident BD (secondary outcome) were compared between individuals with acute care (an ED visit or hospitalization) involving hallucinogens and the general population using overlap propensity score weighted Cox proportional hazard models. Models were adjusted for age, sex, rural residence, income quintile, recent documentation of homelessness, and healthcare encounters for mental health or other substance use in the past five years. The study included 9,311,844 individuals of which 7,285 (0.08%) had acute care involving hallucinogens. Within 3-years of acute care involving hallucinogens, 1.43% (n = 104) of individuals had an incident episode of mania requiring acute care compared to 0.06% (n = 41) of individuals in the age-sex matched general population, a 25-fold increase in risk. After weighting, acute care for hallucinogens was associated with a 6-fold (weighted Hazard Ratio [HR] 5.97, 95% CI 3.29, 10.82) increase in risk of incident mania relative to individuals without hallucinogen acute care who had otherwise similar demographic and mental health histories. Associated increases were also observed for risk of an incident diagnosis of BD (HR 3.75 95%CI 2.49, 5.65, absolute proportion 2.50% versus 0.11%). The main limitation of the study is the risk associated with the exposure examined in this study may not generalize to the majority of people who use hallucinogens who do not require acute care. These findings suggest the need for ongoing caution regarding hallucinogen use in individuals at risk of bipolar disorder. They also have potential implications for clinical practice, research, and public health policy, including substance regulation and targeted education for high-risk groups in the context of rising hallucinogen use.

Electrolytes (sodium, potassium, calcium, magnesium, chloride, phosphate) are required in specific amounts for proper functioning of the human body. Although the body has different organ systems, such as the kidneys, that regulate electrolyte levels in the blood, electrolyte abnormalities occur frequently in people with eating disorders. The objective of this review will be to examine the association between electrolyte imbalances and adverse outcomes in people with eating disorders. A systematic review of studies on eating and electrolyte disorders shall be conducted. Electronic searches shall be done in the Ovid MEDLINE, EMBASE, and PsycINFO databases. Selected studies shall include randomized control trials (RCTs), non-randomized controlled trials, and cross-sectional studies published in English or French. Quality appraisal of studies and a narrative synthesis of extracted data shall be conducted. This review will synthesize existing evidence on electrolyte abnormalities in people with eating disorders. It will identify the type of electrolyte imbalances, their impact, and outcomes in people with eating disorders. We anticipate that information that will be useful to policy makers and clinicians in designing better policies to prevent eating disorders and or manage people with eating disorders shall be elucidated in this study. The final manuscript will be submitted for publication in a journal. This protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO); registration number CRD42023477497.

Background Physician wellness programs are being implemented to offset rises in physician burnout. Insight into the effectiveness of these programs and to whom they are being offered, remains unclear. Objectives To identify and characterize wellness program interventions to improve physician wellness. Methods A PRISMA-P 2020-compliant systematic review as conducted, searching PubMed, Scopus, and Medline from May 2006 to July 2024. Search terms included Medical Subject Headings terms and keywords related to physicians and wellness program interventions. Peer reviewed published studies that qualitatively and/or quantitively measured outcomes of wellness interventions for practicing physicians were included. Results Thirty-six studies involving 6,708 total participants were included. Interventions were heterogenous and included group therapy, stress reduction strategies, time off/workload reductions, education, and peer support. The efficacy of interventions varied, with sixteen studies (44.4%) demonstrating some measurable degree of effectiveness, with statistically significant changes ( p  < 0.05) post-intervention. Few studies reported improvements by physician sex, age groups, or comparisons across specialities. Conclusion Studies examining physician wellness program interventions are highly heterogenous in terms of intervention, study design and methods of outcome assessment, limiting definitive conclusions about their general effectiveness. Trial registration The review protocol has been registered on Open Science Framework ( https://doi.org/10.17605/OSF.IO/8SDM9 ).

Background Language and cultural discordance refer to when a physician and patient do not share the same language or culture. This can create barriers to providing high-quality care at the end-of-life (EoL). This study explores the intersections of language, culture, geography, and care model in EoL care from the perspectives of palliative care physicians. Methods In this exploratory-descriptive qualitative study, semi-structured interviews (1-h) were conducted virtually between July and November 2023. We interviewed 16 family physicians with experience providing linguistic and/or culturally discordant palliative/EoL care in various urban, suburban, and rural regions of Ontario, who practiced at community and hospital outpatient clinics, home-based care, or long-term care homes. We used reflexive thematic analysis to identify themes across the interviews guided by the intersectionality theoretical framework. Results We identified three themes 1) Visible barriers to care access due to the inability to communicate accurate information and insufficient time spent during appointments with patients; 2) Invisible barriers to care access, shaped by the Eurocentric approach to palliative care and physicians’ lack of awareness on cultural discordance; 3) Workplace supports that currently exist and interventions that physicians would like to see. Community physicians following fee-for-service models were less likely to have access to professional interpreter services. Physicians in long-term care emphasized resource limitations to providing culturally-appropriate care environments. Conclusion Cultural discordance required awareness of personal biases, while language discordance hindered basic communication. These findings will be useful in informing clinical practice guidelines and mobilizing policy-level change to improve palliative/EoL care for patients from linguistic and cultural minority groups.

Cytokinins (CKs) are a group of adenine-derived, small signaling molecules of crucial importance for growth and multiple developmental processes in plants. Biological roles of classical CKs: isopentenyladenine (iP), trans and cis isomers of zeatin ( t Z, c Z), and dihydrozeatin, have been studied extensively and their functions are well defined in many aspects of plant physiology. In parallel, extensive knowledge exists for genes involved in tRNA modifications that lead to the production of tRNA-bound methylthiolated CKs, especially in bacterial and mammalian systems. However, not much is known about the origins, fates, and possible functions of the unbound methylthiolated CKs (2MeS-CKs) in biological systems. 2MeS-CKs are the free base or riboside derivatives of iP or Z-type CKs, modified by the addition of a thiol group (–SH) at position 2 of the adenine ring that is subsequently methylated. Based on the evidence to date, these distinctive CK conjugates are derived exclusively via the tRNA degradation pathway. This review summarizes the knowledge on the probable steps involved in the biosynthesis of unbound 2MeS-CKs across diverse kingdoms of life. Furthermore, it provides examples of CK profiles of organisms from which the presence of 2MeS-CKs have been detected and confirms a close association and balance between the production of classical CKs and 2MeS-CKs. Finally, it discusses available reports regarding the possible physiological functions of 2MeS-CKs in different biological systems.

BackgroundEquity, diversity and inclusion (EDI) in the healthcare field are crucial in meeting the healthcare needs of a progressively diverse society. In fact, a diverse healthcare workforce enables culturally sensitive care, promotes health equity and enhances the understanding of various needs and patients’ viewpoints, potentially resulting in more effective patient treatment and improved patient outcomes. Despite this, information on the effectiveness of policies or programmes promoting EDI in health institutions is scarce. The objective of this systematic review is to assess the effects and outcomes of EDI programmes in healthcare institutions.MethodsWe will conduct Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of studies on EDI programmes and describe their effects and outcomes in healthcare institutions. We will search PubMed, Scopus, Web of Science, CINAHL and PsycINFO databases. Selected studies will include randomised control trials (RCTs), non-RCTs and cross-sectional studies published either in English or French. Quality appraisal of studies and a narrative synthesis of extracted data will be conducted as well as a meta-analysis if possible. The quality of evidence in this review will be assessed by the Grades of Recommendation, Assessment, Development and Evaluation.Anticipated resultsWe anticipate that this systematic review will reveal information on the effect of EDI programmes and their outcomes in healthcare institutions. We expect this information will provide insights that will lead to improvements in designing EDI policies and programmes in healthcare institutions.Ethics and disseminationNo ethical clearance is required for this study as no primary data will be collected. The final manuscript will be submitted to a journal for publication. In addition to this, the results of the study will also be disseminated through conference presentations to inform the research and clinical practice.Review registrationThis protocol has been registered with the International Prospective Register of Systematic Reviews; registration number CRD42024502781.

Health disparities exist across different linguistic groups. Language barriers in primary care can negatively affect access to healthcare services and the quality and safety of care at the end-of-life. This study will take a novel, in-depth look at the experience of language- and/or cultural-discordant care for adults from linguistic minority groups through the eyes of primary care physicians providing palliative and/or end-of-life care. Language and cultural discordance means that the physician and patient do not speak the same language or are not from the same cultural background. Qualitative data from primary care physicians (n = 12–24) providing language-discordant end-of-life care to Francophone and/or Allophone older adults across different care models and diverse geographies in Ontario will be collected through semi-structured interviews. Reflexive thematic analysis will be used to report themes within the data and consider the influence of the social locations of the researcher and research participants, geographic considerations impacting service provision, and barriers imposed by differing primary care funding structures on the provision of palliative and end-of-life care for linguistic and cultural minority groups in Ontario. Findings from this study will identify the interconnections among language and cultural discordance, care model, geographic region, and physician perceptions of their combined effects on access to, and quality of, palliative and end-of-life care. This evidence will be key to informing clinical practice guidelines and mobilizing change to improve primary care access and quality for adults at the end-of-life from linguistic and cultural minority populations across Ontario.

Genetic and bioinformatic analyses have identified missense mutations in GRIN2B encoding the NMDA receptor GluN2B subunit in autism, intellectual disability, Lennox Gastaut and West Syndromes. Here, we investigated several such mutations using a near-complete, hybrid 3D model of the human NMDAR and studied their consequences with kinetic modelling and electrophysiology. The mutants revealed reductions in glutamate potency; increased receptor desensitisation; and ablation of voltage-dependent Mg 2+ block. In addition, we provide new views on Mg 2+ and NMDA channel blocker binding sites. We demonstrate that these mutants have significant impact on excitatory transmission in developing neurons, revealing profound changes that could underlie their associated neurological disorders. Of note, the NMDAR channel mutant GluN2B V618G unusually allowed Mg 2+ permeation, whereas nearby N615I reduced Ca 2+ permeability. By identifying the binding site for an NMDAR antagonist that is used in the clinic to rescue gain-of-function phenotypes, we show that drug binding may be modified by some GluN2B disease-causing mutations. N-methyl- d -aspartate-receptors (NMDARs) are glutamate receptors critical for synaptic transmission, plasticity, and cognition. Here, the authors look at four neurodevelopmental disease-related mutations of NMDAR, gaining insight into binding of Mg 2+ and mechanism of memantine, an NMDAR antagonist.