Long title: Protocol for evaluating a consultation for suffering at work in French-speaking Switzerland

Introduction: Psychosocial suffering entails human, social and economic costs. In Switzerland, 34.4% of workers report chronic work-related stress. Our medical Consultation for Suffering at Work aims to preserve—or restore—the patient's capacity to act and make decisions after a diagnosis of work-related psychological suffering; it also aims to help employees get back to or remain at work. Our hypothesis is that the dynamic of the consultation itself and adherence to its medical advice are active factors of these results. Objectives: Understand changes in patients' work and health status 12 months after a Consultation for Suffering at Work. Determine the effects of the consultation on health and working status via identified active factors: the consultation dynamic and the ability to adhere to the consultation's advice. Evaluate the consultation's effects qualitatively. Materials and Methods: This longitudinal, monocentric study with a quasi-experimental design will include patients consulting between 1 January and 31 December 2018. Changes in patients' work and health status will be analysed using data collected via questionnaires at 0, 3 and 12 months. Qualitative data will be collected via a semi-structured telephone interview 3 months after the consultation. The quantitative part will include 150–170 patients; the qualitative part will include 30. Conclusion: This exploratory research project will provide a better understanding of issues of work-related psychological suffering and effective strategies to support patients. The absence of a control group and the impossibility of applying a randomised controlled design are constraints on this study

STUDI PENAMBATAN MOLEKUL SENYAWA-SENYAWA BIOAKTIF DARI KULIT AKAR MURBEI (Morus sp.) TERHADAP RESEPTOR TNF-α

Tumor necrosis factor alfa (TNF)-α memiliki peranan penting dalam patogenesis beberapa penyakit inflamasi. Murbei dilaporkan memiliki efek penghambatan pada proses inflamasi. Penelitian ini ditujukan untuk mengetahui interaksi antara senyawa-senyawa bioaktif yang terdapat pada murbei terhadap reseptor TNF-α dengan metode simulasi docking molekuler. Docking dilakukan dengan menggunakan program AutoDock 4.2, dengan menambatkan senyawa pada sisi aktif reseptor TNF-α (PDB ID : 3EWJ) secara in silico. Hasil docking menunjukkan bahwa senyawa-senyawa bioaktif dari kulit akar murbei dapat berinteraksi dengan sisi aktif. Interaksi terbaik ditunjukkan oleh senyawa 86 dengan energi bebas ikatan -13,03 12kkal/mol, yang berinteraksi dengan residu asam amino yang penting pada reseptor TNF-α dan memiliki ikatan hidrogen yang sama pada Leu348, Glu406 dan Gly349 dengan menggunakan pembanding (1S, 3R, 6S)-4-oxo-6{4-[2-phenylquinolon-4-yl)methoxy]phenyl}-5-azaspiro [2.4]heptane-1-carboxylic acid sebagai ligan alami

GWAS in the SIGNAL/PHARE clinical cohort restricts the association between the FGFR2 locus and estrogen receptor status to HER2-negative breast cancer patients

International audienceGenetic polymorphisms are associated with breast cancer risk. Clinical and epidemiological observations suggest that clinical characteristics of breast cancer, such as estrogen receptor or HER2 status, are also influenced by hereditary factors. To identify genetic variants associated with pathological characteristics of breast cancer patients, a Genome Wide Association Study was performed in a cohort of 9365 women from the French nationwide SIGNAL/PHARE studies (NCT00381901/RECF1098). Strong association between the FGFR2 locus and ER status of breast cancer patients was observed (ER-positive n=6211, ER-negative n=2516; rs3135718 OR=1.34 p=5.46x10-12). This association was limited to patients with HER2-negative tumors (ER-positive n=4267, ER-negative n=1185; rs3135724 OR=1.85 p=1.16x10-11). The FGFR2 locus is known to be associated with breast cancer risk. This study provides sound evidence for an association between variants in the FGFR2 locus and ER status among breast cancer patients, particularly among patients with HER2-negative disease. This refinement of the association between FGFR2 variants and ER-status to HER2-negative disease provides novel insight to potential biological and clinical influence of genetic polymorphisms on breast tumors

Harmonized definition of occupational burnout : A systematic review, semantic analysis, and Delphi consensus in 29 countries

Funding Information: This study was supported by the University of Lausanne and European Cooperation in Science and Technology, Action CA 16216 "Network on the Coordination and Harmonisation of European Occupational Cohorts” (OMEGA-NET). Publisher Copyright: © 2021, Nordic Association of Occupational Safety and Health. All rights reserved.Objective A consensual definition of occupational burnout is currently lacking. We aimed to harmonize the definition of occupational burnout as a health outcome in medical research and reach a consensus on this definition within the Network on the Coordination and Harmonisation of European Occupational Cohorts (OMEGA-NET). Methods First, we performed a systematic review in MEDLINE, PsycINFO and Embase (January 1990 to August 2018) and a semantic analysis of the available definitions. We used the definitions of burnout and burnout-related concepts from the Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) to formulate a consistent harmonized definition of the concept. Second, we sought to obtain the Delphi consensus on the proposed definition. Results We identified 88 unique definitions of burnout and assigned each of them to 1 of the 11 original definitions. The semantic analysis yielded a first proposal, further reformulated according to SNOMED-CT and the panelists` comments as follows: "In a worker, occupational burnout or occupational physical AND emotional exhaustion state is an exhaustion due to prolonged exposure to work-related problems". A panel of 50 experts (researchers and healthcare professionals with an interest for occupational burnout) reached consensus on this proposal at the second round of the Delphi, with 82% of experts agreeing on it. Conclusion This study resulted in a harmonized definition of occupational burnout approved by experts from 29 countries within OMEGA-NET. Future research should address the reproducibility of the Delphi consensus in a larger panel of experts, representing more countries, and examine the practicability of the definition.Peer reviewe

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele