Correlation between unproven therapies and delayed return-to-work for COVID-19-infected healthcare workers.

The objective of this study is to investigate factors influencing the time to return to work (RTW) of HealthCare Workers (HCW) infected with COVID-19 during the initial wave of the pandemic in a southern French university hospital. Data collection of 170 HCW (between March 16 to June 1, 2020) included demographic and professional information, clinical profiles, comorbidities, medical management, therapies and RT-PCR results. The mean time to RTW was 15.6 days. Multivariate analyses revealed that the time to RTW was shorter among laboratory and emergency workers, while it was longer for HCW aged 40 to 49 years, at higher risk of severe illness, with a delayed negative SARS-CoV-2 PCR or those treated with azithromycin and/or hydroxychloroquine. This study highlights diverse factors affecting HCW RTW post-COVID-19 infection, underscoring the importance of exercising caution in administering unproven therapies to HCW during the early stages of a novel infectious pandemic.

Permanent unfitness for work and mental disorders: a multicentric cross-sectional study of 2,788 unfit employees.

In France, Mental Disorders (MD) are the second most common medical cause of unfitness-for-work notices. The main objective is to describe the MD causing permanent medically unfitness at the workstation. A cross-sectional multicenter survey was conducted among employees followed by 323 physicians from occupational health services of the South of France in 2017. The MD responsible for unfitness for the job were coded according to the ICD-10 nomenclature and their occupational origin was estimated by each physician. On 359,966 employees screened, 2,788 were unfitted. Among the 2,779 unfitness cases which were analysed, 985 were unfitted for MD. The incidence rate of unfitness for MD was 2.78 unfit per 1,000 employees followed. Representing 36.8% (985 cases) of all grounds for unfitness, MD were estimated to be work-related in 614 (63.6%) of cases. The main MD were 449 (45.6%) cases of major depressive episodes, 227 (23.0%) anxiety disorders and 131 (13.3%) recurrent depressive disorders. Their occupational origin was mentioned in 296 (67.3%), 168 (74.7%), 62 (49.6%) cases and the link with a Burnout (BO) in 166 (38.3%), 61 (27.9%) and 41 (34.2%) cases respectively among 364 all pathologies reported to a BO. Unfitness for MD was more common among women (ORa = 1.79 95% CI [1.50-2.13]), working in trade, transport, accommodation and catering (ORa = 1.47 95% CI [1.04-2.09]) and increase with age (ORa = 4.24 95% CI [2.73-6.60] for over 55). Major depressive episodes represent the MD most frequently responsible for unfitness and the most related to occupational origin.

Over 25 Years of Hope: Development of Lymphatic Filariasis Patient Support Groups in Haiti.

Support groups can create environments that are conducive to healing and well-being, particularly for persons with stigmatizing chronic diseases. In 1998, the support group concept was adapted in Haiti for persons with disabling lymphedema caused by lymphatic filariasis (LF). The project was developed with the expectation that the support group model conceived in the developed world be interpreted and modified by persons affected with lymphedema in the Haitian setting. Initiated with modest financial support within a research initiative to eliminate LF, a total of 50 "Hope Clubs" were formed from 1998 to 2023 across seven communes (districts) located in 3 of Haiti's 10 regional Departments. Documented benefits of the support groups included improved limb self-care, decreased incidence of inflammatory episodes (adenolymphangitis), enhanced self-efficacy, economic benefit through microenterprise, and improved quality of life. Despite challenges of funding shortfalls, natural disasters, and political insecurity, persistence of LF support groups in Haiti highlights the crucial role of group ownership by affected persons and the freedom to reinvent the support group concept in light of local social, cultural, and economic conditions.

Gabapentin-Induced Myoclonus in a Patient With Chronic Kidney Disease.

Gabapentin contains a cyclohexyl group and is a form of gamma-aminobutyric acid (GABA). Despite its name, gabapentin does not affect the inhibitory neurotransmitter GABA or its receptors. Instead, it acts as a ligand, binding strongly to the α2δ (Ca) channel subunit and interfering with its regulatory function and the release of excitatory neurotransmitters. Gabapentin is approved by the FDA for treating seizure disorders and neuropathic pain, except for trigeminal neuralgia. However, it is frequently used off-label to treat other pain conditions and psychological disorders, such as anxiety. Unlike other drugs, gabapentin is not metabolized in the liver and is solely excreted by the kidneys. Therefore, it is crucial to adjust the dosage in patients with renal insufficiency to avoid severe adverse effects. In this case report, we present a patient with chronic renal impairment who experienced devastating myoclonic jerky movements shortly after increasing his gabapentin dose.

Cyberlindnera jadinii and Kluyveromyces lactis, two fungi used in food processes, have potential probiotic effects on gut inflammation.

IMPORTANCE: The food industry has always used many strains of microorganisms including fungi in their production processes. These strains have been widely characterized for their biotechnological value, but we still know very little about their interaction capacities with the host at a time when the intestinal microbiota is at the center of many pathologies. In this study, we characterized five yeast strains from food production which allowed us to identify two new strains with high probiotic potential and beneficial effects in a model of intestinal inflammation.

Well-being as a performance pillar: a holistic approach for monitoring tennis players.

This perspective article aims to discuss the usefulness of tools that can assist tennis professionals effectively manage the well-being of their players. This includes identifying and monitoring meaningful metrics (i.e., training load, training intensity, heart rate variability), as well as careful planning of training and competition schedules with appropriate recovery periods. The use of innovative training methods (i.e., repeated-sprint training in hypoxia and heat training), and proper dietary practices, along with biometric assessment for young players, represents should be considered. Adopting a holistic approach to decision-making about training and competition, balancing both health and performance considerations, is crucial for tennis players and their support teams. More research is needed to refine best practices for enhancing tennis performance while prioritizing the well-being of players.

Factors associated with internal contamination of nurses by antineoplastic drugs based on biomonitoring data from a previous study.

Internal contamination of healthcare professionals by antineoplastic drugs (ADs) remains a current occupational health issue, particularly because these compounds are classified as dangerous to handle by the NIOSH. In order to improve preventive actions, a study of the factors associated with this internal contamination was conducted among nursing staff in health care institutions. This study is a statistical analysis of metadata from a cross-sectional observational study conducted among nurses in two French hospitals. The internal contamination of each nurse was assessed in a previous study and was defined by whether or not at least one studied AD was detected in at least one urine sample. Three urine samples and a self-questionnaire were collected for each participant. Analysis of five ADs (cyclophosphamide, ifosfamide, metabolite of 5-fluorouracil, methotrexate, doxorubicin) were performed by liquid chromatography coupled to tandem mass spectrometry. A multivariate stepwise descending regression model was used to determine factors associated with internal contamination by coupling data from a self-questionnaire with internal contamination data. A total of 74 nurses participated to the study and 68 were included for this work: 39 nurses with and 29 without detectable internal ADs contamination. Two protective factors of internal contamination could be identified: a high "glove wearing score" (OR: 0.957; 95%CI: 0.93-0.98; p < 0.01) and a high "total number of years handling ADs and/or caring for patients treated with ADs" (OR: 0.797; 95%CI: 0.67-0.91; p < 0.01). In addition, three factors contributing to internal contamination were identified, namely "feeling sufficiently informed about tasks exposing to ADs" (OR: 9.585; 95%CI: 2.23-57.05; p < 0.01), "disposal of a waste bin containing equipment used for administration of the ADs studied" (OR: 8.04; 95%CI: 1.87-46.08; p < 0.01) and "changing sheets and/or making bed of a patient treated by one of the ADs studied" (OR: 10.479; 95%CI: 1.43-133.30; p < 0.05). Thus, the use of gloves when handling ADs directly or indirectly and the contaminating nature of certain tasks should be taken into account when (1) implementing preventive actions in health care services and (2) training and informing exposed staff. Further studies would be desirable to confirm these results and extend them to other professional categories.

Saccharomyces boulardii CNCM I-745 supplementation during and after antibiotic treatment positively influences the bacterial gut microbiota.

Introduction: Antibiotic effects on gut bacteria have been widely studied, but very little is known about the consequences of such treatments on the mycobiota, the fungal part of the microbiota and how the length of administration influences both microbiota. Here, we examined the effect of antibiotics (ATB) on the composition of bacterial and fungal microbiota and how the administration of Saccharomyces boulardii CNCM I-745 influences both microbiota. Methods: In order to get closer to the human microbiota, the mice used in this study were subjected to fecal microbiota transfer (FMT) using human feces and subsequently called human microbiotaassociated (HMA) mice. These mice were then treated with amoxicillinclavulanate antibiotics and supplemented with S. boulardii during and after ATB treatment to understand the effect of the yeast probiotic on both bacterial and fungal microbiota. Bacterial and fungal microbiota analyses were done using 16S and ITS2 rRNA amplicon-based sequencing. Results: We showed that the administration of S. boulardii during ATB treatment had very limited effect on the fungal populations on the long term, once the yeast probiotic has been cleared from the gut. Concerning bacterial microbiota, S. boulardii administration allowed a better recovery of bacterial populations after the end of the ATB treatment period. Additionally, 16S and ITS2 rRNA sequence analysis revealed that 7 additional days of S. boulardii administration (17 days in total) enhanced the return of the initial bacterial equilibrium. Discussion: In this study, we provide a comprehensive analysis of how probiotic yeast administration can influence the fungal and bacterial microbiota in a model of broad-spectrum antibiotherapy.

Staphylococcus epidermidis isolates from atopic or healthy skin have opposite effect on skin cells: potential implication of the AHR pathway modulation.

Introduction: Staphylococcus epidermidis is a commensal bacterium ubiquitously present on human skin. This species is considered as a key member of the healthy skin microbiota, involved in the defense against pathogens, modulating the immune system, and involved in wound repair. Simultaneously, S. epidermidis is the second cause of nosocomial infections and an overgrowth of S. epidermidis has been described in skin disorders such as atopic dermatitis. Diverse isolates of S. epidermidis co-exist on the skin. Elucidating the genetic and phenotypic specificities of these species in skin health and disease is key to better understand their role in various skin conditions. Additionally, the exact mechanisms by which commensals interact with host cells is partially understood. We hypothesized that S. epidermidis isolates identified from different skin origins could play distinct roles on skin differentiation and that these effects could be mediated by the aryl hydrocarbon receptor (AhR) pathway. Methods: For this purpose, a library of 12 strains originated from healthy skin (non-hyperseborrheic (NH) and hyperseborrheic (H) skin types) and disease skin (atopic (AD) skin type) was characterized at the genomic and phenotypic levels. Results and discussion: Here we showed that strains from atopic lesional skin alter the epidermis structure of a 3D reconstructed skin model whereas strains from NH healthy skin do not. All strains from NH healthy skin induced AhR/OVOL1 path and produced high quantities of indole metabolites in co-culture with NHEK; especially indole-3-aldehyde (IAld) and indole-3-lactic acid (ILA); while AD strains did not induce AhR/OVOL1 path but its inhibitor STAT6 and produced the lowest levels of indoles as compared to the other strains. As a consequence, strains from AD skin altered the differentiation markers FLG and DSG1. The results presented here, on a library of 12 strains, showed that S. epidermidis originated from NH healthy skin and atopic skin have opposite effects on the epidermal cohesion and structure and that these differences could be linked to their capacity to produce metabolites, which in turn could activate AHR pathway. Our results on a specific library of strains provide new insights into how S. epidermidis may interact with the skin to promote health or disease.

Rediscovery of Remarkably Rare Anaerobic Tentaculiferous Ciliate Genera Legendrea and Dactylochlamys (Ciliophora: Litostomatea).

Free-living anaerobic ciliates are of considerable interest from an ecological and an evolutionary standpoint. Extraordinary tentacle-bearing predatory lineages have evolved independently several times within the phylum Ciliophora, including two rarely encountered anaerobic litostomatean genera, Legendrea and Dactylochlamys. In this study, we significantly extend the morphological and phylogenetic characterization of these two poorly known groups of predatory ciliates. We provide the first phylogenetic analysis of the monotypic genus Dactylochlamys and the three valid species of Legendrea based on the 18S rRNA gene and ITS-28S rRNA gene sequences. Prior to this study, neither group had been studied using silver impregnation methods. We provide the first protargol-stained material and also a unique video material including documentation, for the first time, of the hunting and feeding behavior of a Legendrea species. We briefly discuss the identity of methanogenic archaeal and bacterial endosymbionts of both genera based on 16S rRNA gene sequences, and the importance of citizen science for ciliatology from a historical and contemporary perspective.

Antibiotic treatment using amoxicillin-clavulanic acid impairs gut mycobiota development through modification of the bacterial ecosystem.

BACKGROUND: Effects of antibiotics on gut bacteria have been widely studied, but very little is known about the consequences of such treatments on the fungal microbiota (mycobiota). It is commonly believed that fungal load increases in the gastrointestinal tract following antibiotic treatment, but better characterization is clearly needed of how antibiotics directly or indirectly affect the mycobiota and thus the entire microbiota. DESIGN: We used samples from humans (infant cohort) and mice (conventional and human microbiota-associated mice) to study the consequences of antibiotic treatment (amoxicillin-clavulanic acid) on the intestinal microbiota. Bacterial and fungal communities were subjected to qPCR or 16S and ITS2 amplicon-based sequencing for microbiota analysis. In vitro assays further characterized bacterial-fungal interactions, with mixed cultures between specific bacteria and fungi. RESULTS: Amoxicillin-clavulanic acid treatment triggered a decrease in the total fungal population in mouse feces, while other antibiotics had opposite effects on the fungal load. This decrease is accompanied by a total remodelling of the fungal population with the enrichment in Aspergillus, Cladosporium, and Valsa genera. In the presence of amoxicillin-clavulanic acid, microbiota analysis showed a remodeling of bacterial microbiota with an increase in specific bacteria belonging to the Enterobacteriaceae. Using in vitro assays, we isolated different Enterobacteriaceae species and explored their effect on different fungal strains. We showed that Enterobacter hormaechei was able to reduce the fungal population in vitro and in vivo through yet unknown mechanisms. CONCLUSIONS: Bacteria and fungi have strong interactions within the microbiota; hence, the perturbation initiated by an antibiotic treatment targeting the bacterial community can have complex consequences and can induce opposite alterations of the mycobiota. Interestingly, amoxicillin-clavulanic acid treatment has a deleterious effect on the fungal community, which may have been partially due to the overgrowth of specific bacterial strains with inhibiting or competing effects on fungi. This study provides new insights into the interactions between fungi and bacteria of the intestinal microbiota and might offer new strategies to modulate gut microbiota equilibrium. Video Abstract.

Permanent Unfitness for Work and Musculoskeletal Diseases: A Multicentric Cross-sectional Study of 2788 Unfit Employees.

OBJECTIVE: To describe the various musculoskeletal diseases resulting in work-related permanent unfitness for work. Methods: In 2017, a multicenter cross-sectional employee survey in the South of France was conducted by 323 occupational physicians. Results: Of the 359,966 employees monitored, 2788 had permanent unfitness for work. This number included 1078 for musculoskeletal diseases, which was more frequent in women (odds ratio, 1.42; confidence interval, 1.20 to 1.68) and showed an increase in women older than 55 years (odds ratio, 6.42; confidence interval, 4.4 to 6.60). Back disorder was the most common work-related disorder reported (n = 488 [45.4%]), with soft tissue conditions being (n = 237 [22.0%]). Arthropathy (n = 157 [14.6%]) had occupational origins in 282 (44.3%), 169 (26.6%), and 55 (8.6%) cases, respectively. Conclusions: Musculoskeletal disability prevention should be encouraged to avoid resultant employment attrition.

Rewiring the altered tryptophan metabolism as a novel therapeutic strategy in inflammatory bowel diseases.

OBJECTIVE: The extent to which tryptophan (Trp) metabolism alterations explain or influence the outcome of inflammatory bowel diseases (IBDs) is still unclear. However, several Trp metabolism end-products are essential to intestinal homeostasis. Here, we investigated the role of metabolites from the kynurenine pathway. DESIGN: Targeted quantitative metabolomics was performed in two large human IBD cohorts (1069 patients with IBD). Dextran sodium sulphate-induced colitis experiments in mice were used to evaluate effects of identified metabolites. In vitro, ex vivo and in vivo experiments were used to decipher mechanisms involved. Effects on energy metabolism were evaluated by different methods including Single Cell mEtabolism by profiling Translation inHibition. RESULTS: In mice and humans, intestinal inflammation severity negatively correlates with the amount of xanthurenic (XANA) and kynurenic (KYNA) acids. Supplementation with XANA or KYNA decreases colitis severity through effects on intestinal epithelial cells and T cells, involving Aryl hydrocarbon Receptor (AhR) activation and the rewiring of cellular energy metabolism. Furthermore, direct modulation of the endogenous tryptophan metabolism, using the recombinant enzyme aminoadipate aminotransferase (AADAT), responsible for the generation of XANA and KYNA, was protective in rodent colitis models. CONCLUSION: Our study identified a new mechanism linking Trp metabolism to intestinal inflammation and IBD. Bringing back XANA and KYNA has protective effects involving AhR and the rewiring of the energy metabolism in intestinal epithelial cells and CD4+ T cells. This study paves the way for new therapeutic strategies aiming at pharmacologically correcting its alterations in IBD by manipulating the endogenous metabolic pathway with AADAT.

Job retention for people with bipolar disorder: A qualitative analysis.

At least half of people with bipolar disorder, whose global prevalence is greater than 1% of the general population, do not have a stable occupation. The objective of this study is to identify the factors perceived by bipolar people as having an impact on retention in employment. Semi-directed individual interviews were offered to subjects with bipolar disorder, of working age, who had been seen by three different hospital departments in the south of France. These people had to be medically stable and have at least one occupational experience. Each interview was recorded and transcribed manually and then analyzed according to a thematic classification of verbatims. Nineteen people participated in the interviews. Three major themes identified were classified into intrinsic (working routine and working environment) and extrinsic (external aids) factors for the bipolar person. The majority believe that working regular hours is a balancing factor. For everyone, night work and stress factors can lead to relapses. All stressed the need to destigmatize the disease. Most believe that it is necessary to develop employment support organizations specific to mental illnesses. This research helps to inform people with bipolar disorder about the occupational factors that help balance their condition. Personalized multidisciplinary care pathways involving occupational medicine must be developed in order to promote the balance of the disease and job retention.

CARD9 in neutrophils protects from colitis and controls mitochondrial metabolism and cell survival.

OBJECTIVES: Inflammatory bowel disease (IBD) results from a combination of genetic predisposition, dysbiosis of the gut microbiota and environmental factors, leading to alterations in the gastrointestinal immune response and chronic inflammation. Caspase recruitment domain 9 (Card9), one of the IBD susceptibility genes, has been shown to protect against intestinal inflammation and fungal infection. However, the cell types and mechanisms involved in the CARD9 protective role against inflammation remain unknown. DESIGN: We used dextran sulfate sodium (DSS)-induced and adoptive transfer colitis models in total and conditional CARD9 knock-out mice to uncover which cell types play a role in the CARD9 protective phenotype. The impact of Card9 deletion on neutrophil function was assessed by an in vivo model of fungal infection and various functional assays, including endpoint dilution assay, apoptosis assay by flow cytometry, proteomics and real-time bioenergetic profile analysis (Seahorse). RESULTS: Lymphocytes are not intrinsically involved in the CARD9 protective role against colitis. CARD9 expression in neutrophils, but not in epithelial or CD11c+cells, protects against DSS-induced colitis. In the absence of CARD9, mitochondrial dysfunction increases mitochondrial reactive oxygen species production leading to the premature death of neutrophilsthrough apoptosis, especially in oxidative environment. The decreased functional neutrophils in tissues might explain the impaired containment of fungi and increased susceptibility to intestinal inflammation. CONCLUSION: These results provide new insight into the role of CARD9 in neutrophil mitochondrial function and its involvement in intestinal inflammation, paving the way for new therapeutic strategies targeting neutrophils.

Help from commensals: ß-hex to regulate gut immunity.

In a recent Science issue, Bousbaine et al. (2022) identified ß-N-acetylhexosaminidase, a conserved antigen expressed by commensals that drives expansion and differentiation of intestinal intra-epithelial cells and protects against gut inflammation.

Effects of Five Filamentous Fungi Used in Food Processes on In Vitro and In Vivo Gut Inflammation.

Food processes use different microorganisms, from bacteria to fungi. Yeast strains have been extensively studied, especially Saccharomyces cerevisiae. However, to date, very little is known about the potential beneficial effects of molds on gut health as part of gut microbiota. We undertook a comprehensive characterization of five mold strains, Penicillium camemberti, P. nalgiovense, P. roqueforti, Fusarium domesticum, and Geotrichum candidum used in food processes, on their ability to trigger or protect intestinal inflammation using in vitro human cell models and in vivo susceptibility to sodium dextran sulfate-induced colitis. Comparison of spore adhesion to epithelial cells showed a very wide disparity in results, with F. domesticum and P. roqueforti being the two extremes, with almost no adhesion and 20% adhesion, respectively. Interaction with human immune cells showed mild pro-inflammatory properties of all Penicillium strains and no effect of the others. However, the potential anti-inflammatory abilities detected for G. candidum in vitro were not confirmed in vivo after oral gavage to mice before and during induced colitis. According to the different series of experiments carried out in this study, the impact of the spores of these molds used in food production is limited, with no specific beneficial or harmful effect on the gut.