Serum Markers of Hepatocyte Death and Apoptosis Are Non Invasive Biomarkers of Severe Fibrosis in Patients with Alcoholic Liver Disease

BACKGROUND: Quantification of hepatocyte death is useful to evaluate the progression of alcoholic liver diseases. Our aims were to quantify and correlate the circulating levels of Cytokeratin 18 (CK18) and its caspases-generated fragment to disease severity in heavy alcoholics. METHODOLOGY/PRINCIPAL FINDINGS: CK18 and CK18-fragment were evaluated in the serum of 143 heavy alcoholics. Serum levels of markers of hepatocyte death (CK18), apoptosis (CK18 fragment) and necrosis (CK18 -CK18 fragment) increased in patients with severe fibrosis compared to patients with mild fibrosis. These markers strongly correlated with Mallory-Denk bodies, hepatocyte ballooning, fibrosis and with hepatic TNFα and TGFβ assessed in the liver of 24 patients. Elevated levels of serum hepatocyte death and apoptotic markers were independent risk factors in predicting severe fibrosis in a model combining alkaline phosphatase, bilirubin, prothrombin index, hyaluronate, hepatocyte death and apoptotic markers. The level of markers of hepatocyte death and apoptosis had an area under the receiving operator curve that predicted severe fibrosis of 0.84 and 0.76, respectively. CONCLUSION/SIGNIFICANCE: Death of hepatocytes can be easily evaluated with serum markers and correlated with severe fibrosis in heavy alcohol drinkers. These biomarkers could be useful to rapidly evaluate liver injuries and the efficacy of therapies

Dietary and Plasma Magnesium and Risk of Coronary Heart Disease Among Women

Background: Magnesium is associated with lower risk of sudden cardiac death, possibly through antiarrhythmic mechanisms. Magnesium influences endothelial function, inflammation, blood pressure, and diabetes, but a direct relation with coronary heart disease (CHD) risk has not been established. Methods and Results: We prospectively examined the association between dietary and plasma magnesium and risk of CHD among women in the Nurses' Health Study. The association for magnesium intake was examined among 86 323 women free of disease in 1980. Information on magnesium intake and lifestyle factors was ascertained every 2 to 4 years through questionnaires. Through 2008, 3614 cases of CHD (2511 nonfatal/1103 fatal) were documented. For plasma magnesium, we conducted a nested case–control analysis, with 458 cases of incident CHD (400 nonfatal/58 fatal) matched to controls (1:1) on age, smoking, fasting status, and date of blood sampling. Higher magnesium intake was not associated with lower risk of total CHD (P‐linear trend=0.12) or nonfatal CHD (P‐linear trend=0.88) in multivariable models. However, magnesium intake was inversely associated with risk of fatal CHD. The RR comparing quintile 5 to quintile 1 of magnesium intake was 0.61 (95% CI, 0.45 to 0.84; P‐linear trend=0.003). The association between magnesium intake and risk of fatal CHD appeared to be mediated partially by hypertension. Plasma magnesium levels above 2.0 mg/dL were associated with lower risk of CHD, although not independent of other cardiovascular biomarkers (RR, 0.67; 95% CI, 0.44 to 1.04). Conclusions: Dietary and plasma magnesium were not associated with total CHD incidence in this population of women. Dietary magnesium intake was inversely associated with fatal CHD, which may be mediated in part by hypertension

Centre d’anthropologie sociale – CAS

Jean-Pierre Albert, directeur d’étudesAnne Bouchy, directrice d’études à l’EFEO La part du rite dans les attitudes religieuses contemporaines. Orthopraxie, réinterprétations, adaptations, sécularisation Avec Marlène Albert-Llorca, Alain Ballabriga, Anny Bloch-Raymond, Marine Carrin, Patrizia Ciambelli, Jean-Louis Ormières, Valérie Robin, Guillaume Rozenberg, Harald Tambs-Lyche, Sébastien Tank-Storper, Claudine Vassas. Pour sa première année, le séminaire a été consacré à une réflexion de fond..

Centre d’anthropologie sociale – CAS

Jean-Pierre Albert, directeur d’étudesAnne Bouchy, directrice d’études à l’EFEO La part du rite dans les attitudes religieuses contemporaines. Orthopraxie, réinterprétations, adaptations, sécularisation Avec Marlène Albert-Llorca, Alain Ballabriga, Anny Bloch-Raymond, Marine Carrin, Patrizia Ciambelli, Jean-Louis Ormières, Valérie Robin, Guillaume Rozenberg, Harald Tambs-Lyche, Sébastien Tank-Storper, Claudine Vassas. Pour sa seconde année, le séminaire a continué d’explorer quelques-uns des ..

Spleen tyrosine kinase mediates innate and adaptive immune crosstalk in SARS-CoV-2 mRNA vaccination

Durable cell-mediated immune responses require efficient innate immune signaling and the release of pro-inflammatory cytokines. How precisely mRNA vaccines trigger innate immune cells for shaping antigen specific adaptive immunity remains unknown. Here, we show that SARS-CoV-2 mRNA vaccination primes human monocyte-derived macrophages for activation of the NLRP3 inflammasome. Spike protein exposed macrophages undergo NLRP3-driven pyroptotic cell death and subsequently secrete mature interleukin-1β. These effects depend on activation of spleen tyrosine kinase (SYK) coupled to C-type lectin receptors. Using autologous cocultures, we show that SYK and NLRP3 orchestrate macrophage-driven activation of effector memory T cells. Furthermore, vaccination-induced macrophage priming can be enhanced with repetitive antigen exposure providing a rationale for prime-boost concepts to augment innate immune signaling in SARS-CoV-2 vaccination. Collectively, these findings identify SYK as a regulatory node capable of differentiating between primed and unprimed macrophages, which modulate spike protein-specific T cell responses

Centre d’anthropologie sociale – CAS

Jean-Pierre Albert, directeur d’étudesAnne Bouchy, directrice d’études à l’EFEO La mort et les religions. Études comparatives Avec Marlène Albert-Llorca, Alain Ballabriga, Anny Bloch-Raymond, Marine Carrin, Patrizia Ciambelli, Jean-Louis Ormières, Valérle Robin, Guillaume Rozenberg, Harald Tambs-Lyche, Sébastien Tank-Storper, Claudine Vassas. Les séances ont été centrées sur le thème « Mort, religion et politique », avec deux orientations principales : Les enjeux des rites funéraires et de la..

Centre d’anthropologie sociale – CAS

Jean-Pierre Albert, directeur d’étudesAnne Bouchy, directrice d’études à l’EFEO La mort et les religions. Études comparatives Avec Marlène Albert-Llorca, Alain Ballabriga, Anny Bloch-Raymond, Marine Carrin, Patrizia Ciambelli, Jean-Louis Ormières, Valérle Robin, Guillaume Rozenberg, Harald Tambs-Lyche, Sébastien Tank-Storper, Claudine Vassas. Les séances ont été centrées sur le thème « Mort, religion et politique », avec deux orientations principales : Les enjeux des rites funéraires et de la..

Female Genital Schistosomiasis (FGS) in Cameroon: A formative epidemiological and socioeconomic investigation in eleven rural fishing communities

Background Female Genital Schistosomiasis (FGS) is most often caused by presence of Schistosoma haematobium eggs lodged in the female reproductive tract which results in chronic fibrosis and scarring. In Cameroon, despite high community prevalences of urine-patent S. haematobium infections, FGS has yet to be studied in depth. To shed light on the clinical prevalence and socioeconomic effects of FGS, we undertook a formative community-based epidemiological and qualitative survey. Method A cross sectional multidisciplinary study of 304 girls and women from 11 remote rural fishing communities in Cameroon was undertaken using parasitological sampling, clinical colposcopy, and interviews. The lived experiences of those with FGS were documented using a process of ethnography with participant observation and in-depth interviews. Result Amongst 304 women and girls aged >5 years (Median age: 18; Interquartile range: 9.6–28), 198 females were eligible for FGS testing and 58 adult women were examined by clinical colposcopy. Of these, 34 were positive for FGS (proportion: 58.6%; 95% CI: 45.8–70.4), younger girls showing a higher FGS prevalence, and older women not shedding eggs showing a pattern for cervical lesions from earlier infection. In a subset of women with FGS selected purposively (12/58), in-depth interviews with participant observation revealed out-of-pocket expenditures of up to 500USD related health spending for repeated diagnosis and treatment of gynecological illnesses, and 9 hours daily lost reproductive labour. Psychosocial unrest, loss in social capital, and despair were linked with sub-fertility and persistent vaginal itch. Conclusion With our first formative evidence on prevalence, socioeconomic effects and experiences of FGS amongst women and girls in Cameroon, we have clarified to a new level of detail the deficit in provision of and access to peripheral health services in remote areas of Cameroon. Using this information, there is now strong evidence for national programs and services on women’s health and schistosomiasis to update and revise policies targeted on prevention and management of FGS. We therefore stress the need for regular provision of Praziquantel treatment to adolescent girls and women in S. haematobium endemic areas, alongside better access to tailored diagnostic services that can detect FGS and appropriately triage care at primary health level

Centre de recherche sur la pré- et protohistoire de la Méditerranée - CRPPM

François Briois, maître de conférencesBéatrix Midant-Reynes, directrice de recherche au CNRS Archéologie des déserts Ce séminaire a été introduit par une présentation synthétique sur l’Holocène du Sahara égyptien. Depuis les premières recherches de Bagnols et de Almasy au début du XXe siècle jusqu’aux travaux plus récents de F. Wendorf et de R. Kuper la connaissance sur les conditions de mise en place des premiers peuplements néolithiques d’Afrique du nord-est s’est considérablement précisée...