Mediterranean mussels (Mytilus galloprovincialis) exposure to fluoxetine: Bioaccumulation and biotransformation products.

The significant rise in antidepressant consumption in recent years was accentuated by COVID-19 pandemic. Among these antidepressant, fluoxetine, a selective serotonin re-uptake inhibitor (SSRI), is the most prescribed worldwide. The present study investigated its bioaccumulation and metabolization in the mussel Mytilus galloprovincialis, generally recognized as a reliable bioindicator for assessing environmental quality and the accumulation of various contaminants. Mussels were exposed to a nominal concentration of fluoxetine (3.1 µg/L) for 28 days. Mussels were sacrificed at day 2, 7, 14 and 28 of exposure. The order of accumulation level was gills > digestive glands > soft tissues, and a regular increase in fluoxetine and norfluoxetine was observed across the various sampling days for both digestive glands and soft tissues. The calculated bioconcentration factor (BCF) ranged from 253 at D2 to 1734 at D28 for fluoxetine, and pseudo-BCF from 7 at D2 to 64 at D28 for norfluoxetine. Non-targeted approaches highlighted ten metabolites, which are reported for the first time in Mytilus, in addition to norfluoxetine. Notably, this study highlighted two phase I metabolites and one phase II metabolite previously unreported. These findings contribute to the understanding of fluoxetine accumulation and metabolism in Mytilus and enhance the knowledge of pharmaceuticals detoxification processes in non-target organisms.

COVID-19 Prevalence in UNIVI Group Nursing Homes and Multilevel Geriatric Hospitals: Epidemiological Study of Immunological Status with Rapid Serological Tests for Diagnostic Guidance and Follow Up.

BACKGROUND/OBJECTIVES: To date, data are lacking on the proportion of residents, and employees who have actually been exposed to SARS-Cov-2 in nursing homes and geriatric healthcare institutions, as well as the evolution of their serological status and the recurrence of Covid-19. The primary objective was to determine the prevalence of COVID-19 using NG Biotech rapid serological tests among caregivers and residents. The secondary objectives were to determine: prevalence according to RT PCR tests or clinical diagnosis; the risk factors (autonomy, arterial hypertension, diabetes mellitus) and clinical presentation (e.g. respiratory, abdominal or cutaneous symptoms, asthenia, fever) among residents; the risk factors (age, sex, profession, family situation) among caregivers; the evolution of the serological status at 1, 3 and 6 months using NG Biotech rapid serological tests; the symptomatic recurrence of Covid 19 at 1, 3 and 6 months. DESIGN: Multicentric prospective observational. SETTING: Study location: 27 nursing homes and 3 multilevel geriatric hospitals belonging to the UNIVI Group in France. PARTICIPANTS: 1334 professionals: 692 among multilevel geriatric hospitals (mean age: 43.6+/-11.8; 441 (82.4%) female) and 642 among nursing homes (mean age: 43.5+/-12.4; 685 (85.9%) female), and 1145 residents (mean age: 89+/-7.5; 898 (78.7%) female). MEASUREMENTS: Prevalence using NG Biotech rapid serological tests, medical diagnosis, RT-PCR tests.Risk factors among residents using the medical file and among caregivers using questionnaires.Clinical presentation in residents using the medical file. RESULTS: The prevalence using NG Biotech rapid serological test in residents was 14.4 % (168 of 1142 available diagnostics), the global prevalence (positive RT-PCR or positive serological test) was 22.7% (203 of 895 available diagnostics). The prevalence using NG Biotech rapid serological test in professionals was 12.8% (164 of 1315 available diagnostics), the global prevalence (positive RT-PCR test or positive serological test) was 23.8% (222 of 933 available diagnostics). The risk factors among residents were: living in an Alzheimer unit, and being a contact case. Being independent for activities of daily living was protective. The risk factor among caregivers was being a contact case. Another risk factor was the job; nurse assistants, nurses, and physicians were the most exposed. Residents had atypical clinical presentations including frequent geriatric syndromes (falls, delirium). 68.3% (71 of 104) of the initially positive residents still had a positive rapid serological test at 1 month follow up and 74 % (54 of 73) at 3 months follow up. 77.9% (88 of 113) of the initially positive employees still had a positive rapid serological test at 1 month follow up. Symptomatic reinfection was exceptional in caregivers or in residents during follow up. CONCLUSION: COVID 19 prevalence among caregivers and residents in nursing homes and geriatric health Institutions is underestimated when using only one method for diagnosis. Geriatric syndromes such as falls and delirium in residents should trigger further investigations on a COVID-19 cause. Immunity was persistent in ¾ of caregivers and residents during the 3 months follow up. The high prevalence of COVID 19 in geriatric institutions pleads in favor of the French vaccination policy, initially targeting as a priority the most vulnerable and dependent people, followed by staff members in healthcare institutions and nursing homes. More studies on the persistence of immunity and the perspective of Covid 19 mutations will help determine the long-term vaccine booster policy.

[Seroprevalence, risk factors and clinical presentation after the first wave of COVID-19 in nursing homes of the UNIVI group: The SEROCOVID study]. / Séroprévalence, facteurs de risque et présentation clinique après la première vague COVID-19 dans les EHPAD du groupe UNIVI : étude SEROCOVID.

INTRODUCTION: The pandemic caused by SARS-COV-2 infection spread rapidly during the "first wave" through France between March and May 2020. It was responsible for high mortality in subjects with comorbidities and the elderly who lived in nursing homes. In May 2020, 75% of the deaths occurred in people over 75 years old in nursing homes. It is difficult to estimate accurately the prevalence of COVID-19 infection during this period because only 50% of the diagnoses in nursing homes were made by RT-PCR. During this period, the diagnosis was mainly based on the clinical symptoms. POPULATION AND METHODS: We carried out a prospective study among residents of the 27 EHPADs in the UNIVI group (SEROCOVID study) between August 31 and October 16, 2020 using rapid ELISA serotests carried out by pricking the fingertip. We looked for the seroprevalence by the use of rapid serotests as well as the overall prevalence by cumulating the positive results of the RT-PCR when done and of the rapid serotest. The secondary objectives were the study of risk factors for infection by multivariate analysis as well as the description of the symptoms that led to the diagnosis. RESULTS: In total, 1145 residents were included aged on average 89±7.5 years old (female 78.7%). The time between the COVID-19 disease and the rapid inclusion serotest was on average 5±1.7 months. The prevalence estimated by the three diagnostic evaluation methods (medical diagnosis, RT-PCR or by rapid serotest ELISA) is about 14%, underestimated compared to the overall prevalence at 22.7%. The study of risk factors in multivariate analysis shows that the most dependent residents, living in a protected unit due to behavioral disorders or whose close contact with a person with COVID-19 had significantly higher rates of infection. Finally, the symptoms most frequently observed in residents differed from those in younger subjects with geriatric characteristics, such as the higher frequency of digestive symptoms and geriatric syndromes. Fever has only been observed in one third of cases in the elderly. Smell and taste disorders were seldom described. CONCLUSION: Our study provides an estimate of the overall prevalence as well as the mean seroprevalence of COVID-19 in EHPAD residents five months after the diagnosis of COVID-19 disease. The difference between the two estimates is probably explained by the frailty and decreased immunity of the nursing home residents. Therefore, it would need to be reactivated by vaccination of all residents, even those already infected with SARS-COV-2. These elements corroborate the governmental strategy of vaccination deployed in all residents of EHPAD regardless of their previous contact with the virus.

Expression and evaluation of enzymes required for the hydrolysis of galactomannan.

The cost-effective production of bioethanol from lignocellulose requires the complete conversion of plant biomass, which contains up to 30 % mannan. To ensure utilisation of galactomannan during consolidated bioprocessing, heterologous production of mannan-degrading enzymes in fungal hosts was explored. The Aspergillus aculeatus endo-ß-mannanase (Man1) and Talaromyces emersonii α-galactosidase (Agal) genes were expressed in Saccharomyces cerevisiae Y294, and the Aspergillus niger ß-mannosidase (cMndA) and synthetic Cellvibrio mixtus ß-mannosidase (Man5A) genes in A. niger. Maximum enzyme activity for Man1 (374 nkat ml(-1), pH 5.47), Agal (135 nkat ml(-1), pH 2.37), cMndA (12 nkat ml(-1), pH 3.40) and Man5A (8 nkat ml(-1), pH 3.40) was observed between 60 and 70 °C. Co-expression of the Man1 and Agal genes in S. cerevisiae Y294[Agal-Man1] reduced the extracellular activity relative to individual expression of the respective genes. However, the combined action of crude Man1, Agal and Man5A enzyme preparations significantly decreased the viscosity of galactomannan in locust bean gum, confirming hydrolysis thereof. Furthermore, when complemented with exogenous Man5A, S. cerevisiae Y294[Agal-Man1] produced 56 % of the theoretical ethanol yield, corresponding to a 66 % carbohydrate conversion, on 5 g l(-1) mannose and 10 g l(-1) locust bean gum.

Feedback inhibition of phosphatidate phosphatase from spinach chloroplast envelope membranes by diacylglycerol.

Because the envelope phosphatidate phosphatase plays a pivotal role in chloroplast glycerolipid metabolism, we have analyzed whether diacylglycerol could be a regulatory factor of the enzyme. Using isolated envelope membranes in which the level of diacylglycerol was modified by thermolysin treatment of intact chloroplasts to destroy the galactolipid:galactolipid galactosyltransferase, we have demonstrated that phosphatidate phosphatase activity was reduced when the membrane was enriched in diacylglycerol. All 1,2-diacylglycerol molecular species assayed were demonstrated to inhibit the enzyme to about the same extent. Kinetic studies with envelope from thermolysin-treated chloroplasts were performed in the absence and presence of diacylglycerol, and diacylglycerol was shown to be a powerful competitive inhibitor of the reaction. Finally, using isolated intact spinach chloroplasts, we have demonstrated that in situ phosphatidate phosphatase activity can be modulated by the level of diacylglycerol present in the membrane. The relevance of phosphatidate phosphatase inhibition by diacylglycerol in the regulation of chloroplast glycerolipid biosynthesis is discussed.