Hôpital de Cery

Yeast vitality during storage is essential for maintaining consistent fermentation performance. This study compares the physiological responses of top- and bottom-cropped Saccharomyces cerevisiae stored at 4 °C for 20 days and evaluates Optical Nanomotion Detection (ONMD) as a rapid, label-free vitality assessment tool. Classical assays (FUN-1, methylene blue, propidium iodide, glucose acidification power, glycogen content, and ethanol tolerance) were used to monitor metabolic activity, membrane integrity, and stress resilience. Bottom-cropped yeast retained metabolic activity, membrane stability, and energy reserves longer than top-cropped cells. ONMD revealed distinct single-cell nanomotion signatures and detected mechanically active subpopulations even when traditional vitality indicators declined. Analysis of nanomotion slopes showed an increasingly negative trend in the decline over storage time in top-cropped cells, indicating reduced temporal stability of nanomechanical activity during the 180 min recordings. Ethanol-challenge experiments confirmed the vitality dependence and stress-sensitivity of the ONMD signal. Together, these findings demonstrate that ONMD resolves cold-storage-induced changes in yeast nanomechanical vitality and provides complementary information beyond conventional vitality and viability assays. ONMD offers a fast, reagent-free method for monitoring brewing yeast physiology and represents a promising basis for future development toward brewery quality-control applications.

Substance use disorder (SUD) is common in first-episode psychosis (FEP) and linked to poorer clinical and functional outcomes. Previous studies were mostly cross-sectional or short-term, leaving the longitudinal impact of SUD course unclear. This study aimed to (A) group patients based on different trajectories of cannabis use disorder (CUD) and alcohol use disorder (AUD) over 3-year follow-up and to (B) examine associations with baseline characteristics and clinical outcomes. We included 467 FEP patients enrolled in a 3-year early intervention program. Latent class analysis found subgroups based on cannabis and alcohol use trajectories. Groups were then compared using logistic regressions and mixed-model repeated measures (MMRM), adjusting for relevant confounders. We found different evolution of AUD and CUD: alcohol users tended to maintain consumption over time, while a subset of cannabis users reduced their consumption. Persistent alcohol users showed worst baseline characteristics and outcomes if compared to abstinent or light consumers. Concerning cannabis, MMRM analyses showed that abstinent or light users consistently had better symptom evolution compared to persistent or decreased users. However, the decreased group showed higher hospitalization rates than the other groups. They also showed gradual improvement in negative symptoms, reaching similar levels to abstinent users by the end of the program. This study outlines the distinct evolution of alcohol and cannabis consumption in FEP patients, suggesting the importance of tailored therapeutic approaches. Consistently with existing literature, abstinence or light use seems to be beneficial, while reducing cannabis use appears to offer a limited clinical improvement.

BACKGROUNDThe apolipoprotein E (APOE) gene includes the strongest protective (ε2) and risk (ε4) variants for sporadic Alzheimer's disease (AD), but underlying mechanisms remain unclear. We studied APOE genotype effects on the cerebrospinal fluid (CSF) proteome.METHODSUsing untargeted tandem mass tag mass spectrometry, we analyzed CSF from 227 cognitively normal (CN) controls (A–T–), 165 CN A+, and 177 individuals with mild cognitive impairment (MCI A+) from two large cohorts. We compared protein levels across APOE genotypes using linear regression and characterized biological pathways.RESULTSFive hundred forty‐nine of 978 proteins (56%) differed between ε2/ε3 (n = 32 individuals) or ε4 carriers (n = 181 individuals) and ε3/ε3 controls. ε2/ε3 controls showed the most differences, with higher levels of 280 proteins enriched for neuronal plasticity. ε4 carrier controls showed increased proteins linked to blood–brain barrier dysfunction, and A+ ε4 carriers were related to glucose metabolism.DISCUSSIONCombining two cohorts enabled analysis of the rare APOE ε2 genotype, suggesting protective effects may occur through improved neuronal plasticity.HighlightsApolipoprotein E (APOE) genotypes show distinct cerebrospinal fluid proteomic mechanisms in early Alzheimer's disease (AD).Combining cohorts enabled analysis of rare APOE ε2–associated protection in AD.The rare ε2 genotype may confer protection through improved neuronal plasticity.APOE ε4 carriers show increased blood–brain barrier dysfunction and glucose metabolism.These findings offer new insights into genotype‐specific mechanisms in early AD.

Background: Longitudinal studies on cognitive disengagement syndrome (CDS) are scarce, and only one study has investigated the trajectory of CDS from childhood to early adulthood. Given this, the aims of the present study were to explore, with a quasi-longitudinal design, (1) whether scores for childhood CDS were associated with scores for CDS during early adulthood; (2) whether childhood CDS scores were associated with childhood and adult scores for depression, anxiety, stress, and insomnia; (3) whether childhood CDS, depression, anxiety, stress, and insomnia and adult depression, anxiety, stress, and insomnia were independently associated with adult scores for CDS, and (4) whether childhood CDS scores were directly and indirectly associated with adult CDS scores via adult depression and stress in two conditional effect models. Methods: A total of 246 young adult students (mean age = 22.62; 56.3% females) participated in a cross-sectional and quasi-longitudinal study. The participants completed questionnaires assessing CDS (Adult Concentration Inventory; ACI), depression, anxiety, stress, and insomnia for the following two developmental periods: for the present time point as young adults and for a past time point, when they were about eight years old. To enable retrospective past recall, the participants undertook a standardized imagination exercise. Results: Childhood scores for CDS, depression, anxiety, stress, and insomnia were highly associated with adult scores for CDS, depression, anxiety, stress, and insomnia. In the regression model, higher childhood scores for CDS, depression, and anxiety and higher adult scores for depression, stress, and insomnia, but not adult anxiety, were strongly and independently associated with adult scores for CDS. In the two conditional effects models, childhood CDS was associated with adult CDS directly and indirectly via adult depression and adult stress. Conclusions: In this quasi-longitudinal study, childhood scores for CDS were associated with adult scores for CDS, suggesting a potentially stable trajectory of CDS from childhood to early adulthood. Further, the two conditional effects models suggested that childhood and adult CDS were both directly and indirectly associated via adult depression and stress. As such, symptoms of depression, anxiety, stress, and insomnia should be considered in conceptualizations of adult CDS. Next, given that standardized psychotherapeutic interventions for depression, stress, and insomnia are available, such interventions might also favorably impact CDS symptoms. These findings further underscore the importance of prospective longitudinal and intervention studies on adult CDS.

To analyse the prevalence of depressive symptoms in centenarians, identify their predictors, and explore the role of functional dependence as a contributing factor. Cross-sectional baseline data from the Swiss Centenarian Study (n=102), including community-dwelling and institutionalised participants with complete data on depressive symptoms and functional capacity. Functional capacity was assessed using the Older Americans Resources and Services Multidimensional Functional Assessment Questionnaire. Depressive symptoms were measured with the Geriatric Depression Scale - Short Form. Group differences were analysed using Chi-squared tests; relationships were examined with correlations. Multiple linear regressions identified predictors. Mediation analysis explored the interplay between functional capacity, living situation, and depressive symptoms. Functional capacity varied, with basic activities of daily living generally better preserved than instrumental activities. Almost one-fourth of participants screened positive for possible clinical depression, which was significantly more common among institutionalised centenarians (p<.05). Health conditions, anxiety, and lower functional capacity were significant predictors of depressive symptoms and together explained 24.7% of the variance, with anxiety being the strongest predictor followed by health conditions and functional capacity. Mediation analysis showed that functional capacity mediated the relationship between living situation and depressive symptoms, highlighting its critical role in mental health. A significant proportion of centenarians screened positive for depression, underscoring the need for greater attention to depressive symptoms and systematic screening. Targeted interventions promoting functional independence may play an important role to prevent depression, and strategies are needed to encourage institutionalised very old individuals to re-develop and maintain a certain level of independence.

<b><i>Conclusions:</i></b> This study provides evidence that valproate dose, mainly for doses at or above 1,300 mg/d, is associated with weight gain in psychiatric patients, suggesting that the lowest effective doses should be prescribed to minimize weight gain.

472 Background: Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) prognosis. However, AFP is not useful in establishing a prognosis for patients with a tumor in the early stages. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers including HCC, even at early stages. In this study, we evaluated the prognostic value of plasma hPG80 in patients with HCC at early and intermediate stages. Methods: A total of 79 HCC patients including 44 BCLC from 0 to A and 35 BCLC B managed with local or systemic treatments, (“Liverpool” biobank) were enrolled prospectively and analyzed retrospectively. hPG80 was quantified using DxPG80 Lab kit (ECS-Progastrin) with a limit of detection at 1 pM and AFP was quantified using Cobas E411 in the blood of HCC patients. An optimal cutoff value of hPG80 was identified at 4.5 pM by calculating the minimal p-value based on the log-rank method. For AFP, a cutoff of 100 ng/mL was used as for liver transplantation (Notarpaolo, 2016). The prognostic impact of hPG80 and AFP levels on patient overall survival (OS) was assessed using Kaplan-Meier curves and log-rank tests. Results: hPG80 was detected in 36 of 44 (81.8%) HCC patients at stages BCLC 0 to A and 29 of 35 (82.9%) at stage BCLC B by contrast to AFP present in only 5 (11.4%) and 9 (25.7%) patients respectively. The median of hPG80 was 5.7 pM (IQR: 1.7-22.4 pM) at stages BCLC 0 to A, 6.0 pM (IQR: 1.5-22.2 pM) at stage BCLC B and significantly different from a non-HCC age-range matched control group cohort (median value: 1.5 pM, IQR 0.6-3.2 pM, p &lt; 0.0001). When combining BCLC 0 to B, the median OS for hPG80+ patients (n = 46) was significantly shorter than that of hPG80- patients (n = 33) (25 months versus undefined, HR: 3.07, 95% CI: 1.46-6.43; p = 0.0064). AFP+ patients were also significantly correlated with poorer OS (17.5 months versus undefined, HR: 3.16, 95% CI: 1.06-9.47; p = 0.0030). Then, we evaluated the prognostic significance of hPG80 in combination with AFP levels. hPG80+ patients with AFP &gt; 100 ng/mL (n = 46) had a worse OS than that of patients with AFP &lt; 100 ng/mL patients (n = 33) (15.8 months versus undefined, HR: 6.38, 95% CI: 1.74-23.41; p = 0.0052). Conclusions: Our findings show that hPG80 could serve as a new prognostic biomarker for HCC patients at early to intermediate stages. These results will need to be confirmed in a prospective study, but it opens the possibility to use hPG80 as a biomarker for HCC patients at early stage at a time they can be treated to be cured.

La relation entre science empirique et pratique clinique est complexe et difficile. Bien que les organismes qui contrôlent la pratique psychothérapeutique demandent que les connaissances et les savoir-être des thérapeutes soient scientifiquement et empiriquement fondés, force est de constater que ce n’est pas – ou peu – le cas actuellement. Deux éléments dans l’histoire de la relation entre cliniciens et chercheurs expliquent certains des malentendus actuels : le modèle du « scientifique-praticien » développé à partir de la conférence de Boulder à la fin des années 1940, et l’importance exagérée donnée au modèle de la « pratique basée sur les données probantes » et à la méthodologie de l’essai randomisé contrôlé. L’article cherche à montrer en quoi la recherche empirique est bien plus vaste que cela, et que des aires de rapprochement avec la pratique clinique sont possibles. Le renouveau de l’intérêt scientifique pour l’étude de cas et la constitution de réseaux de praticiens-chercheurs sont deux exemples qui montrent comment une collaboration – une alliance en d’autres termes – est possible et nécessaire.

The management of patients who have become dependent on benzodiazepines and analogues is a problem frequently encountered in both somatic and psychiatric medicine. No pharmacological treatment is currently recognized as effective in the management of these addictions, apart from a gradual reduction of doses. We propose practical strategies for the implementation of gradual dose reduction and choice of molecules while promoting individual adaptation to the withdrawal symptoms presented by the patient.