Endothelial cell-derived oxysterol ablation attenuates experimental autoimmune encephalomyelitis.

The vasculature is a key regulator of leukocyte trafficking into the central nervous system (CNS) during inflammatory diseases including multiple sclerosis (MS). However, the impact of endothelial-derived factors on CNS immune responses remains unknown. Bioactive lipids, in particular oxysterols downstream of Cholesterol-25-hydroxylase (Ch25h), promote neuroinflammation but their functions in the CNS are not well-understood. Using floxed-reporter Ch25h knock-in mice, we trace Ch25h expression to CNS endothelial cells (ECs) and myeloid cells and demonstrate that Ch25h ablation specifically from ECs attenuates experimental autoimmune encephalomyelitis (EAE). Mechanistically, inflamed Ch25h-deficient CNS ECs display altered lipid metabolism favoring polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) expansion, which suppresses encephalitogenic T lymphocyte proliferation. Additionally, endothelial Ch25h-deficiency combined with immature neutrophil mobilization into the blood circulation nearly completely protects mice from EAE. Our findings reveal a central role for CNS endothelial Ch25h in promoting neuroinflammation by inhibiting the expansion of immunosuppressive myeloid cell populations.

Factors associated with intent to stay in the profession: an exploratory cluster analysis across healthcare professions in Switzerland.

Retention issues are widespread within the health workforce. This cross-sectional study used data collected from 1707 healthcare professionals in 2022-23 to identify with k-means clustering groups of individuals sharing similar working experiences. These profiles were linked with varying levels of turnover intentions and a range of healthcare professions. While occupational therapists and paramedics reported in average better working conditions, registered nurses and intermediate caregivers reported the poorest experiences. In other clusters, salaries were high where work-life balance was low, and inversely. By learning from similarities and differences in the working conditions of diverse healthcare professionals, shared initiatives aimed at improving retention across professions can be facilitated.

Hydroxy Acid Activation in Fungal Non-Ribosomal Peptide Synthesis Assessed by Site-Directed Mutagenesis.

The fungal cyclodepsipeptides (CDPs) enniatin, beauvericin, bassianolide, and PF1022 consist of alternating N-methylated l-amino and d-hydroxy acids. They are synthesized by non-ribosomal peptide synthetases (NRPS). The amino acid and hydroxy acid substrates are activated by adenylation (A) domains. Although various A domains have been characterized thus giving insights into the mechanism of substrate conversion, little is known about the utilization of hydroxy acids in NRPSs. Therefore, we used homology modelling and molecular docking of the A1 domain of enniatin synthetase (EnSyn) to gain insights into the mechanism of hydroxy acid activation. We introduced point mutations into the active site and used a photometric assay to study the substrate activation. The results suggest that the hydroxy acid is selected by interaction with backbone carbonyls rather than by a specific side chain. These insights enhance the understanding of non-amino acid substrate activation and could contribute to the engineering of depsipeptide synthetases.

Identifying common patterns of health services use: a longitudinal study of older Swiss adults' care trajectories.

BACKGROUND: Population ageing puts pressure on health systems initially designed to handle acute and episodic illnesses. Segmenting an ageing population based on its healthcare utilization may enable policymakers to undertake evidence-based resource planning. We aimed to derive a typology of healthcare utilization trajectories in Swiss older adults. METHODS: Our work used data from the Lc65 + study, a population-based cohort of individuals aged 65 to 70 years at enrolment. The dimensions of healthcare utilization considered were ambulatory care, emergency care, hospitalizations, professional home care and nursing home stay. We applied the Sequence Analysis framework, within which we quantified the variation between each multidimensional pair of sequences, implemented a clustering procedure that grouped together older persons with similar profiles of health services use, and characterized clusters of individuals using selected baseline covariates. RESULTS: Healthcare utilization trajectories were analysed for 2271 community-dwelling older adults over a period of 11 years. Six homogeneous subgroups were identified: constant low utilization (83.3% of participants), increased utilization (4.9%), late health deterioration (4.4%), ambulatory care to nursing home (1.5%), early fatal event (3.8%) and high ambulatory care (2.1%). Associations were found between cluster membership and age, sex, household composition, self-perceived health, grip strength measurement, comorbidities, and functional dependency. CONCLUSIONS: The heterogeneous healthcare utilization profiles can be clustered into six common patterns. Different manifestations of functional decline were apparent in two distinct trajectory groups featuring regular home care use. Furthermore, a small proportion of individuals with a unique set of characteristics was related to the highest levels of ambulatory and emergency care use. New research avenues are outlined to investigate time-varying effects of health factors inside the clusters containing most unfavourable outcomes.

Factors Associated With Intent to Leave the Profession for the Allied Health Workforce: A Rapid Review.

Shortages of satisfied and well-trained health care professionals are an urgent threat for health systems worldwide. Although numerous studies have focused on retention issues for nurses and physicians, the situation for the allied health workforce remains understudied. We conducted a rapid review of the literature on allied health workers to investigate the main reasons for leaving their profession. 1,305 original research articles were retrieved from databases MEDLINE, CINAHL, PsycInfo, and Epistemonikos, of which 29 were eligible for data extraction. Reviewed studies featured mainly pharmacists, psychologists, dietitians, physical therapists, emergency medical professionals, and occupational therapists. We categorized 17 typical factors of the intent to leave as organizational, psychological, team and management, and job characteristics. The relative importance of each factor was assessed by measuring its prevalence in the selected literature. By revealing common themes across allied health professions, our work suggests actionable insights to improve retention in these vital services.

Health Workforce Challenges: Key Findings From the Swiss Cohort of Healthcare Professionals and Informal Caregivers (SCOHPICA).

Objectives: The Swiss Cohort of Healthcare Professionals and Informal Caregivers (SCOHPICA) was created to study the career trajectories, retention intentions, and wellbeing of healthcare professionals (HCPs), addressing challenges such as staff turnover, low job satisfaction and burnout. Methods: SCOHPICA is a prospective open cohort. An electronic questionnaire was used to collect data from HCPs across multiple healthcare settings in Switzerland, encompassing the intention to stay in the profession, wellbeing, and various organizational, psychosocial, occupational and sociodemographic determinants. Results: The first (2022) baseline sample included 1707 HCPs from over 20 professions. Notably, 13% did not intend to stay in their profession, with intermediate caregivers (24%), registered nurses (17%) and pharmacists (17%) reporting the highest rates. Pharmacists scored lowest in wellbeing. Across determinants, pharmacists, physicians, and registered nurses reported worse scores for workload and work-life balance. Nursing professions had lower scores in various determinants, including influence at work, staffing and resource adequacy, and possibilities for development. Conclusion: SCOHPICA will provide critical insights on HCPs' work conditions and experiences, supporting health workforce monitoring and management, and informing policy-making to ensure high-quality healthcare delivery.

Protocol for the Swiss COhort of Healthcare Professionals and Informal CAregivers (SCOHPICA): Professional trajectories, intention to stay in or leave the job and well-being of healthcare professionals.

INTRODUCTION: Healthcare professionals' shortage, low job satisfaction, high levels of burnout, and excessive staff turnover are some of the challenges health systems face worldwide. In Switzerland, healthcare stakeholders have called to address the health workforce crisis and have pointed out the scarcity of data on the conditions of healthcare professionals (HCPs). Hence, the Swiss Cohort of Healthcare Professionals and Informal Caregivers (SCOHPICA) was developed to study the career trajectories, well-being, intention to stay in or leave the position/profession/health sector, and their determinants, of HCPs and informal caregivers, respectively. This paper describes the protocol for the HCPs cohort of SCOHPICA and discusses its implications. METHODS: SCOHPICA is a prospective open cohort using an explanatory sequential mixed methods design. All types of HCPs working directly with patients and practicing in Switzerland are eligible, irrespective of their healthcare setting and employment status. Baseline and annual follow-up electronic surveys will take place once a year, featuring both core questions and modules developed according to information needs. While outcome variables are HCPs' trajectories, well-being, intention to stay in or leave the position/profession/health sector, independent variables include organizational, psychosocial, and psychological determinants, as well as occupational (professional) and sociodemographic factors. The qualitative phase will be organized every two years, inviting participants who agreed to take part in this phase. The findings from quantitative analyses, along with the issues raised by healthcare stakeholders in the field, will guide the topics investigated in the qualitative phase. DISCUSSION: Using innovative methodologies, SCOHPICA will gather nationwide and longitudinal data on HCPs practicing in Switzerland. These data could have numerous implications: promoting the development of research related to HCPs' well-being and retention intentions; supporting the development of policies to improve working conditions and career prospects; contributing to the evolution of training curricula for future or current healthcare professionals; aiding in the development of health systems capable of delivering quality care; and finally, providing the general public and stakeholders with free and open access to the study results through an online dashboard.