Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
French Guiana is a South American French territory, where HIV prevalence consistently exceeds 1% in the adult population. In the only correctional facility, HIV prevalence fluctuates at around 4%.
After describing the population of HIV-positive inmates, we aimed to evaluate mortality after release from the correctional facility, and to identify its predictive factors.
Outside North American settings, data on treatment outcome and vital status of HIV-positive former inmates are scarce. There were no data in French Guiana. Filling this gap represents a basis for potential improvements.
All HIV-infected adults released from an incarceration of 30 days or more, between 2007 and 2013, were enrolled in a retrospective cohort study. Mortality was described over time, one to seven years following release, using Kaplan-Meier estimates. Factors associated with mortality were identified through a non-parametric survival regression model.
147 former inmates were included. The male to female ratio was 4.4. The median age was 37.3 years. The majority were migrants, 25.8% were homeless, 70.1% suffered from substance abuse, with 34.0% of crack-cocaine users. On admission, 78.1% had an early HIV-stage infection (CDC-stage A), with a median CD4 count of 397.5/mm3, 34.0% had one comorbidity, mainly hypertension. Upon release, 50.3% were on ART. Reasons for not being treated were not fulfilling the criteria for 74.6%, and refusing for 15.1%. Before release, 84.5% of the patients on ART had a viral load≤200cp/ml. After release, 8.2% of the cohort had died, with a crude incidence of 33.8/1000 person-years. All recorded deaths were males, with an incidence of 42.2/1000 person-years. Comparing with the age-specific mortality rates for males in French Guiana, the standardized mortality ratio was 14.8. In multivariate analysis, factors associated with death were age and CD4 count before release.
Despite access to ART while incarcerated, with good virological outcome, the post-release mortality was very high for males, almost 15 times what is observed in the general male population living in French Guiana, after age standardization. Access to ART in correctional facilities may be a necessary, but not sufficient condition to protect male inmates from death after release.
ISSN: 1932-6203

inserm-01519987
http://www.hal.inserm.fr/inserm-01519987
http://www.hal.inserm.fr/inserm-01519987/document
http://www.hal.inserm.fr/inserm-01519987/file/2017%2C%20Huber%20-%20Mortality%20HIV%20prisoners%20after%20release.pdf
DOI : 10.1371/journal.pone.0175740.t002

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Benzo[a]pyrene (B[a]P), the prototype molecule of polycyclic aromatic hydrocarbons, exhibits genotoxic and carcinogenic effects, which has led the International Agency for Research on Cancer to recognize it as a human carcinogen. Besides the well-known apoptotic signals triggered by B[a]P, survival signals have also been suggested to occur, both signals likely involved in cancer promotion. Our previous work showed that B[a]P induced an hyperpolarization of mitochondrial membrane potential (ΔΨm) in rat hepatic epithelial F258 cells. Elevated ΔΨm plays a role in tumor development and progression, and nitric oxide (NO) has been suggested to be responsible for increases in ΔΨm. The present study therefore aimed at evaluating the impact of B[a]P on NO level in F258 cells, and at testing the putative role for NO as a survival signal, notably in link with ΔΨm. Our data demonstrated that B[a]P exposure resulted in an NO production which was dependent upon the activation of the inducible NO synthase. This enzyme activation involved AhR and possibly p53 activation. Preventing NO production not only increased B[a]P-induced cell death but also blocked mitochondrial hyperpolarization. This therefore points to a role for NO as a survival signal upon B[a]P exposure, possibly targeting ΔΨm
ISSN: 0887-2333

hal-01163757
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01163757
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01163757/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01163757/file/Benzo%5Ba%5Dpyrene-induced%20nitric.pdf
DOI : 10.1016/j.tiv.2015.06.010

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
This study aimed to compare the relative survival of patients with invasive breast cancer between women from French Guiana (a French territory in South America) and metropolitan France. No study hadever compared survival of breast cancer on the basis of immigrant status in France. Our study underlined that access to care for migrants is challenging whichwgenerates health inequalities. Background The prognosis of breast cancer in French Guiana is worse than in France with 23 deaths per 100 incident cases against 17 per 100 in metropolitan France. This study aimed to compare relative survival of patients with invasive breast cancer (IBC) between women from French Guiana and metropolitan France and to determine risk factors influencing breast cancer survival in French Guiana.Materials and methods Data were collected from the Cancer registry of French Guiana. We comparedthe relative survival of women with IBC between French Guiana and metropolitan France. We used Cox's proportional hazard regression to evaluate the effect of prognostic factors on cancer-specific mortality in French Guiana. Results We included all 269 cases of IBC in women diagnosed in French Guiana between 2003 and 2009. The overall 5-year relative survival rate of patients with IBC was 79% in French Guiana and 86% in metropolitan France. The place of birth (foreign country versus French territory), the tumor stage at the time of diagnosis, the mode of diagnosis (symptoms versus screening), the presence of hormone receptors in the tumor and the histologic type were the variables associated with survival differences. None of the other study variables were significantly associated with prognosis. Conclusion Access to care for migrants is challenging,which leads to health inequalities. Early detection through prevention programs is crucial to increaseIBC survival notably for foreign-born patients.
ISSN: 1526-8209

hal-01288657
https://hal.archives-ouvertes.fr/hal-01288657
https://hal.archives-ouvertes.fr/hal-01288657/document
https://hal.archives-ouvertes.fr/hal-01288657/file/2016%2C%20Roue%20-%20Predictive%20factors%20of%20the%20survival%20of%20women%20with%20invasive%20breast%20cancer%20in%20French%20Guiana.pdf

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Background: Health care workers (HCWs) are occupationally exposed to various hazards, some associated with adverse pregnancy outcomes in previous reviews. This systematic review aims at synthesizing the recent literature on occupational exposures among HCWs related to fetal death, congenital anomalies, and fertility disorders. Methods: We searched the Medline database from 2000 to 2015 for articles about all potential occupational exposures of women and men working in this sector. Results: We retained 32 studies, most of them (n = 30) among women HCWs. Studies based on job title reported excess risks of some congenital anomalies (especially nervous and musculoskeletal systems) among HCWs compared to non-HCWs but no evidence about fetal death. Excess risks associated with specific exposures includes reports of some congenital anomalies forwomenexposed to anesthetic gases. Exposure to some sterilizing agents and, with less evidence, to antineoplastic drugs and to ionizing radiation, is associated with increased risks of miscarriage but not stillbirth. Strenuous work schedules appear to be associated with fertility disorders, but the evidence is limited. Only a few studies have been published since 2000 about non-ionizing radiation, or about fertility disorders related to chemical or physical agents, or about male HCWs. Conclusions: Despite the establishment of recommendations to limit exposures of HCWs, some excess risks of adverse pregnancy outcomes are still reported and need to be explained.
ISSN: 0271-3586

hal-01560148
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560148
DOI : 10.1002/ajim.22711
PUBMED : 28514021

Éditeur(s) : HAL CCSD
Résumé : International audience
This paper examines the historical signatures of 18th century composer, J. S. Bach, to evaluate the effects of vision impairment on handwritten signatures. It is questioned whether Bach penned certain signatures as it is historically documented that he was virtually blind in the years just prior to his death in 1750. Applying information collected from published forensic studies about the effects of vision impairment on handwriting, handwriting indices of vision impairment are compared to Bach's signatures in the late 1740s.
17th Biennial Conference of the International Graphonomics Society
Pointe-à-Pitre, Guadeloupe

hal-01165902
https://hal.univ-antilles.fr/hal-01165902
https://hal.univ-antilles.fr/hal-01165902/document
https://hal.univ-antilles.fr/hal-01165902/file/IGS_2015_submission_25.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Sphingolipids, in particular ceramide, have been described as important components of cellular signalling pathways. Ceramide can be produced via multiple mechanisms including through the hydrolysis of sphingomyelin by acid and neutral sphingomyelinase or by a de novo synthesis pathway. Recent studies have identified sphingomyelinases and ceramide synthases as important targets for γ-irradiation and chemotherapeutic drugs. Likewise, common cancer treatment modalities, such as γ-irradiation and many chemotherapeutic agents, induce cell death via the generation of ceramide. This suggests that the manipulation of ceramide production and metabolism could offer promising a means for the enhancement of anti-tumor therapies. The focus of this mini-review will be to discuss contemporary evidence suggesting that ceramide forming pathways and ceramide itself are important targets for the treatment of tumors and the development of novel tumor treatment strategies.
ISSN: 0304-3835

hal-00682458
https://hal.archives-ouvertes.fr/hal-00682458
DOI : 10.1016/j.canlet.2011.07.010
PUBMED : 21862212

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Binding of ligand FasL to its receptor Fas triggers apoptosis via the caspase cascade. FasL itself is homotrimeric, and a productive apoptotic signal requires that FasL be oligomerized beyond the homotrimeric state. We generated a series of FasL chimeras by fusing FasL to domains of the Leukemia Inhibitory Factor receptor gp190 which confer homotypic oligomerization, and analyzed the capacity of these soluble chimeras to trigger cell death. We observed that the most efficient FasL chimera, called pFasL, was also the most polymeric, as it reached the size of a dodecamer. Using a cellular model, we investigated the structure-function relationships of the FasL/Fas interactions for our chimeras, and we demonstrated that the Fas-mediated apoptotic signal did not solely rely on ligand-mediated receptor aggregation, but also required a conformational adaptation of the Fas receptor. When injected into mice, pFasL did not trigger liver injury at a dose which displayed anti-tumor activity in a model of human tumor transplanted to immunodeficient animals, suggesting a potential therapeutic use. Therefore, the optimization of the FasL conformation has to be considered for the development of efficient FasL-derived anti-cancer drugs targeting Fas.
ISSN: 1932-6203

hal-00873684
https://hal.archives-ouvertes.fr/hal-00873684
https://hal.archives-ouvertes.fr/hal-00873684/document
https://hal.archives-ouvertes.fr/hal-00873684/file/Functional_Characterization-accepted.pdf
DOI : 10.1371/journal.pone.0054000

Éditeur(s) : HAL CCSD American Physiological Society
Résumé : International audience
Excessive or persistent inflammation and hepatocyte death are the key triggers of liver diseases. The poly(ADP-ribose) polymerase (PARP) proteins induce cell death and inflammation. Chemical inhibition of PARP activity protects against liver injury during concanavalin A (ConA)-induced hepatitis. In this mice model, ConA activates immune cells, which promote inflammation and induce hepatocyte death, mediated by the activated invariant natural killer T (iNKT) lymphocyte population. We analyzed immune cell populations in the liver and several lymphoid organs, such as the spleen, thymus, and bone marrow in Parp2-deficient mice to better define the role of PARP proteins in liver immunity and inflammation at steady state and during ConA-induced hepatitis. We show that 1) the genetic inactivation of Parp2, but not Parp1, protected mice from ConA hepatitis without deregulating cytokine expression and leucocyte recruitment; 2) cellularity was lower in the thymus, but not in spleen, liver, or bone marrow of Parp2-/- mice; 3) spleen and liver iNKT lymphocytes, as well as thymic T and NKT lymphocytes were reduced in Parp2 knockout mice. In conclusion, our results suggest that the defect of T-lymphocyte maturation in Parp2 knockout mice leads to a systemic reduction of iNKT cells, reducing hepatocyte death during ConA-mediated liver damage, thus protecting the mice from hepatitis.NEW & NOTEWORTHY The genetic inactivation of Parp2, but not Parp1, protects mice from concanavalin A hepatitis. Immune cell populations are lower in the thymus, but not in the spleen, liver, or bone marrow of Parp2-deficient mice compared with wild-type mice. Spleen and liver invariant natural killer T (NKT) lymphocytes, as well as thymic T and NKT lymphocytes, are reduced in Parp2-deficient mice
ISSN: 0193-1857

hal-01630440
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01630440
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01630440/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01630440/file/102513_1_merged_1499199857-1.pdf
DOI : 10.1152/ajpgi.00436.2016

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Neonatal infection constitutes one of Senegal’s most important public health problems, with amortality rate of 41 deaths per 1,000 live births.Methods: Between January 2007 and March 2008, 242 neonates with suspected infection were recruited at threeneonatal intensive care units in three major tertiary care centers in Dakar, the capital of Senegal. Neonatal infections wereconfirmed by positive bacterial blood or cerebrospinal fluid culture. The microbiological pattern of neonatal infectionsand the antibiotic susceptibility of the isolates were characterized. In addition, the genetic basis for antibiotic resistanceand the genetic background of third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae were studied.Results: A bacteriological infection was confirmed in 36.4 % (88/242) of neonates: 22.7 % (30/132) during the early-onsetand 52.7 % (58/110) during the late-onset periods (p > 0.20). Group B streptococci accounted for 6.8 % of the 88 collectedbacterial isolates, while most of them were Enterobacteriaceae (n = 69, 78.4 %). Of these, 55/69 (79.7 %) were 3GC-R. TheblaCTX-M-15 allele, the blaSHV and the blaTEM were highly prevalent (63.5, 65.4 and 53.8 %, respectively), usually associatedwith qnr genes (65.4 %). Clonally related strains of 3GC-R Klebsiella pneumoniae and 3GC-R Enterobacter cloacae, the twomost commonly recovered 3GC-R Enterobacteriaceae (48/55), were detected at the three hospitals, underlining the roleof cross-transmission in their spread. The overall case fatality rate was 18.6 %.Conclusions:Measures should be taken to prevent nosocomial infections and the selection of resistant bacteria
ISSN: 1471-2334

Droits : http://creativecommons.org/licenses/by/
hal-01473613
https://hal.archives-ouvertes.fr/hal-01473613
https://hal.archives-ouvertes.fr/hal-01473613/document
https://hal.archives-ouvertes.fr/hal-01473613/file/High%20third-generation%20cephalosporin%20resistant%20Enterobacteriaceae%20prevalence%20rate%20among%20neonatal%20infections%20in%20Dakar%2C%20Senegal.pdf
DOI : 10.1186/s12879-016-1935-y

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
The hematocrit-to-viscosity ratio (HVR) has been widely used has an estimate of red blood cell (RBC) oxygen transport effectiveness into the microvasculature or as an oxygen delivery index. However, no study investigated the possibility of HVR to truly reflect RBC oxygen transport effectiveness or to be an oxygen delivery index. We measured blood viscosity at high shear rate (225 s −1), hematocrit, HVR, as well as the microvascular oxyhemoglobin saturation (TOI; tissue oxygen index) by spatial resolved near-infrared spectroscopy (NIRS) at cerebral and muscle levels in three population known to have various degrees of hemorheological abnormalities: healthy subjects (AA), patients with sickle cell SC disease (SC) characterized by moderate anemia and patients with sickle cell anemia (SS) marked by severe anemia. At both the cerebral and muscle level, HVR was positively correlated with TOI (r = 0.28; p = 0.03 and r = 0.38; p = 0.003, at the cerebral and muscle level, respectively). These findings suggest that HVR probably play a key role in blood flow and hemodynamic regulation in the microvasculature, hence modulating the amount of oxygen available for tissues. Nevertheless, the strengths of the associations are weak (R 2 < 0.50), suggesting that other determinants modulate microvascular blood flow and oxygenation, such as vascular geometry and vasomotor reserve.
ISSN: 1386-0291

hal-01163460
https://hal.univ-antilles.fr/hal-01163460
DOI : 10.3233/CH-131742

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Hepatocyte death is a central event during liver disease progression, in which immune cells play key roles by activating members of the Tumor Necrosis Factor Receptor Superfamily (TNFRSF), including TNFR1 (TNFRSF1A), Fas (TNFRSF6) and TRAIL-R2 (TNFRSF10B). Receptor Interacting Protein Kinase 1 (RIPK1) emerged as a signaling node downstream of these receptors. In the case of TNFR1, RIPK1 has been demonstrated to paradoxically serve as a scaffold to promote the survival of hepatocytes and as a kinase to kill them. To evaluate whether RIPK1 also protects hepatocytes from death in response to FasL or TRAIL, we took advantage of liver parenchymal cell-specific Ripk1 knockout mice (Ripk1 (LPC-KO)). We found that Ripk1 (LPC-KO) mice, as well as primary hepatocytes derived from them, were more susceptible to Fas-mediated apoptosis than their respective WT counterparts. Fas-induced hepatocyte death was independent of TNF-α signaling. Interestingly, while TRAIL administration did not induce hepatitis in Ripk1 (LPC-KO) mice or in their WT counterparts, its combination with IFN-γ only induced TNF-α dependent apoptosis in the Ripk1 (LPC-KO) mice. Together, our data demonstrate the protective role of RIPK1 downstream of Fas and highlight the general protective function of RIPK1 in hepatocytes exposed to inflammatory conditions, where TNF-α, FasL and/or TRAIL are present.
ISSN: 2045-2322

hal-01579612
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579612
DOI : 10.1038/s41598-017-09789-8
PUBMED : 28835677

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
: Previously, we demonstrated that eicosapentaenoic acid enhanced ethanol-induced oxidative stress and cell death in primary rat hepatocytes via an increase in membrane fluidity and lipid raft clustering. In this context, another n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), was tested with a special emphasis on physical and chemical alteration of lipid rafts. Pretreatment of hepatocytes with DHA reduced significantly ethanol-induced oxidative stress and cell death. DHA protection could be related to an alteration of lipid rafts. Indeed, rafts exhibited a marked increase in membrane fluidity and packing defects leading to the exclusion of a raft protein marker, flotillin. Furthermore, DHA strongly inhibited disulfide bridge formation, even in control cells, thus suggesting a disruption of protein-protein interactions inside lipid rafts. This particular spatial organization of lipid rafts due to DHA subsequently prevented the ethanol-induced lipid raft clustering. Such a prevention was then responsible for the inhibition of phospholipase C-γ translocation into rafts, and consequently of both lysosome accumulation and elevation in cellular low-molecular-weight iron content, a prooxidant factor. In total, the present study suggests that DHA supplementation could represent a new preventive approach for patients with alcoholic liver disease based upon modulation of the membrane structures.
ISSN: 0278-6915

hal-00860153
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00860153
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00860153/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00860153/file/Sergent-et-al-incl-figures-accepted.pdf
DOI : 10.1016/j.fct.2013.07.061

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Mapping spatial distributions of disease occurrence can serve as a useful tool for identifying exposures of public health concern. Infant mortality is an important indicator of the health status of a population. Recent literature suggests that neighborhood deprivation status can modify the effect of air pollution on preterm delivery, a known risk factor for infant mortality. We investigated the effect of neighborhood social deprivation on the association between exposure to ambient air NO2 and infant mortality in the Lille and Lyon metropolitan areas, north and center of France, respectively, between 2002 and 2009. We conducted an ecological study using a neighborhood deprivation index estimated at the French census block from the 2006 census data. Infant mortality data were collected from local councils and geocoded using the address of residence. We generated maps using generalized additive models, smoothing on longitude and latitude while adjusting for covariates. We used permutation tests to examine the overall importance of location in the model and identify areas of increased and decreased risk. The average death rate was 4.2‰ and 4.6‰ live births for the Lille and Lyon metropolitan areas during the period. We found evidence of statistically significant precise clusters of elevated infant mortality for Lille and an east-west gradient of infant mortality risk for Lyon. Exposure to NO2 did not explain the spatial relationship. The Lille MA, socioeconomic deprivation index explained the spatial variation observed. These techniques provide evidence of clusters of significantly elevated infant mortality risk in relation with the neighborhood socioeconomic status. This method could be used for public policy management to determine priority areas for interventions. Moreover, taking into account the relationship between social and environmental exposure may help identify areas with cumulative inequalities.
ISSN: 0048-9697

inserm-00838330
http://www.hal.inserm.fr/inserm-00838330
DOI : 10.1016/j.scitotenv.2013.03.027
PUBMED : 23563257

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Necroptosis is a programmed cell death pathway that has been shown to be of central pathophysiological relevance in multiple disorders (hepatitis, brain and cardiac ischemia, pancreatitis, viral infection and inflammatory diseases). Necroptosis is driven by two serine threonine kinases, RIPK1 (Receptor Interacting Protein Kinase 1) and RIPK3, and a pseudo-kinase MLKL (Mixed Lineage Kinase domain-Like) associated in a multi-protein complex called necrosome. In order to find new inhibitors for use in human therapy, a chemical library containing highly diverse chemical structures was screened using a cell-based assay. The compound 6E11, a natural product derivative, was characterized as a positive hit. Interestingly, this flavanone compound: inhibits necroptosis induced by death receptors ligands TNF-α (Tumor Necrosis Factor) or TRAIL (TNF-Related Apoptosis-Inducing Ligand); is an extremely selective inhibitor, among kinases, of human RIPK1 enzymatic activity with a nM Kd; has a non-ATP competitive mode of action and a novel putative binding site; is weakly cytotoxic towards human primary blood leukocytes or retinal pigment epithelial cells at effective concentrations; protects human aortic endothelial cells (HAEC) from cold hypoxia/reoxygenation injury more effectively than necrostatin-1 (Nec-1) and Nec-1s. Altogether, these data demonstrate that 6E11 is a novel potent small molecular inhibitor of RIPK1-driven necroptosis.
ISSN: 2045-2322

hal-01616456
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456/file/s41598-017-12788-4.pdf
DOI : 10.1038/s41598-017-12788-4

Éditeur(s) : HAL CCSD
Résumé : International audience
We have previously shown that primary rat hepatocyte treatment by n-3 polyunsaturated fatty acids (omega 3) gave opposite results concerning early ethanol cytotoxicity (only a 5-hours-intoxication period) depending on the tested omega 3 type. The aim of this study was to follow on experiments in other in vitro and in vivo models that allowed longer intoxication times with ethanol. When highly differentiated hepatocytes from WIF-B9 line were treated with ethanol for 4 days, docosahexaenoic acid (DHA) protected from ethanol-induced cell death and oxidative stress, whereas eicosapentaenoic acid (EPA) increased ethanol toxic effects. In vivo, Zebrafish larvae exhibited a similar behavior after 7 days of ethanol intoxication depending on the omega 3 introduced in the bath. Altogether, these data confirm differential effects for omega 3s even for longer exposure times with ethanol.
Cahiers de l'Ireb

hal-01117633
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01117633

Éditeur(s) : HAL CCSD
Résumé : 28 pages, 6 figures
We study a universal object for the genealogy of a sample in populations with mutations: the critical birth-death process with Poissonian mutations, conditioned on its population size at a fixed time horizon. We show how this process arises as the law of the genealogy of a sample in a large class of critical branching populations with mutations at birth, namely populations converging, in a large population asymptotic, towards the continuum random tree. We extend this model to populations with random foundation times, with (potentially improper) prior distributions g_i: xmapsto x^{-i}, iinZ_+, including the so-called uniform (i=0) and log-uniform (i=1) priors. We first investigate the mutational patterns arising from these models, by studying the site frequency spectrum of a sample with fixed size, i.e. the number of mutations carried by k individuals in the sample. Explicit formulae for the expected frequency spectrum of a sample are provided, in the cases of a fixed foundation time, and of a uniform and log-uniform prior on the foundation time. Second, we establish the convergence in distribution, for large sample sizes, of the (suitably renormalized) tree spanned by the sample genealogy with prior g_i on the time of origin. We finally prove that the limiting genealogies with different priors can all be embedded in the same realization of a given Poisson point measure.
https://hal.archives-ouvertes.fr/hal-01053343

hal-01053343
https://hal.archives-ouvertes.fr/hal-01053343
ARXIV : 1407.7720

Éditeur(s) : HAL CCSD
Résumé : Background and objectives.[br/] Dairy propionibacteria are isolated from various ecological niches, including soil, grass, silage, rumen, raw milk and dairy plants, showing great adaptability and robustness. Used as ripening starters in Swiss type cheeses, these food grade bacteria are described as nutraceutical producers and they release into the external medium short chain fatty acids (SCFA), folic acid, cobalamin and the bifidogenic 1,4- dihydroxy-2-naphthoic acid (DHNA). These compounds are known to play a pivotal role in the modulation of intestinal physiology through diet. Considering the pro-apoptotic potential of some of these metabolites, we investigated the potential of dairy products fermented by the main species, Propionibacterium freudenreichii, to prevent colon carcinogenesis. Methods.[br/] We developed a new fermented milk. Taking advantage of milk fractions, high and stable populations of P. freudenreichii were obtained in this product. It was tested in vitro on gastric HGT-1 and colic HT-29 cells with respect to the typical hallmarks of apoptosis. In vivo, the fermented milk was evaluated in piglets with respect to general health parameters and in human microbiota-associated rats, treated or not with dimethylhydrazine (DMH), with respect to intestinal proliferation and apoptosis. Results. Fermented milk induced cell death in both gastric and colon cancer cells. Cellular and molecular characterization of cells dying in response to SCFA treatment revealed cell cycle arrest, drop in intracellular ATP, depolarization of mitochondria, translocation of key apoptosis proteins, processing of caspases and fragmentation of the nucleus. Interestingly, the new fermented milk was shown to potentiate the cytotoxic effect of molecules used in cancer chemotherapy. In accordance, it modulated expression of key apoptotic proteins. In vivo, the fermented milk was evaluated in piglets. Daily oral gavage led to high colic P. freudenreichii populations, to modulation of the intestinal microbiota and modulation of intestinal cytokines. Promotion of piglets’ growth also revealed general probiotic effects of fermented milk. Considering that propionibacteria were metabolically active in the intestine, we further investigated their impact on colon carcinogenesis (induced by dimethylhydrazine, DMH) in human microbiota-associated rats. Consumption of selected strains of propionibacteria resulted in enhanced apoptotic depletion of DMH damaged epithelial cells, yet had no effect on neither proliferation nor apoptosis in healthy rats. Conclusions and perspectives.[br/] These results open new perspectives in the field of colon cancer cells prevention and/or treatment. The synergy with pro-apoptotic chemotherapy molecules suggests that such a fermented product may be proposed as a food supplement to enhance the effects of anticancer treatments.
colloque international « Nutrition and Cancer : Hot topics from biology to public health issues »
Paris, France

hal-01190452
https://hal.archives-ouvertes.fr/hal-01190452
PRODINRA : 201853

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
BACKGROUND: The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. METHODS: Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. RESULTS: Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). CONCLUSIONS: There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes.
ISSN: 1058-4838

hal-00875143
https://hal.archives-ouvertes.fr/hal-00875143
DOI : 10.1093/cid/cis878
PUBMED : 23074311

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
BACKGROUND: A prospective study of infectious encephalitis was conducted in France in 2007. In total, 253 patients were enrolled with a proven etiological diagnosis for 52%. The cohort of surviving patients with encephalitis was assessed for sequelae and impairment 3 years after enrollment. METHODS: Patients, their family, and general practitioners (GPs) were interviewed by phone to document persisting symptoms, return to work, and past and current leisure activities, with standardized questionnaires. The IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly) was completed with relatives. The global outcome was determined in all patients with the Glasgow outcome scale. RESULTS: In 2010, 20 patients (10%) were unavailable for follow-up, 2 (1%) were excluded, and 18 (9%) had died since hospital discharge. Data were available for 167 survivors and 9 patients whose death was related to the encephalitis. The outcome was favorable in 108 of 176 patients (61%) (71 with complete resolution), 31 (18%) were mildly impaired, 25 (14%) were severely impaired, and 3 (1%) were in a vegetative state. The most frequent symptoms were difficulty concentrating (42%), behavioral disorders (27%), speech disorders (20%), and memory loss (19%). Fifteen of 63 patients (24%) previously employed were still unable to resume work. Long-term outcome was significantly associated with comorbid conditions, age, level of education, and the causative agent of encephalitis. CONCLUSIONS: Most patients with encephalitis experienced a favorable outcome 3 years after hospital discharge. However, minor to severe disability persists in a high number of cases with consequences for everyday life. Physical and mental impairment should be evaluated in all patients with encephalitis, and neuropsychological rehabilitation implemented whenever needed.
ISSN: 1058-4838

hal-00875190
https://hal.archives-ouvertes.fr/hal-00875190
DOI : 10.1093/cid/cis226
PUBMED : 22460967

Éditeur(s) : HAL CCSD
Résumé : International audience
Objective: In order to determine how risk factors of death among HIV-infected patients in French Guiana interact with one another and to define high risk population segments, an alternative statistical method to Cox proportional hazards models was used. Patients and methods: Data from HIV+ patients followed in the three main hospitals of French Guiana were used. Data were extracted from the prospective French Hospital Database for HIV (FHDH). To examine the nature of the relationships between time of death since the first consultation and a set of predictor variables (age at enrolment, gender, nationality, CD4 count at enrolment, presence or absence of HAART at enrolment, a declared addiction, and mode of acquisition of the virus) a survival tree analysis was used. Survival rates at 5 years and 10 years and their 95% confidence interval were also calculated. Results: This analysis permitted to reveal a new specific subgroup of HIV+ patients particularly at risk in French Guiana not already mentioned in the literature: the HIV+ female patients with a declared addiction. Conclusions: Prevention and care in this vulnerable segment of the HIV+ population identified by this methodology should be reinforced.
J AIDS Clinic Res

Droits : info:eu-repo/semantics/OpenAccess
inserm-00914956
http://www.hal.inserm.fr/inserm-00914956
http://www.hal.inserm.fr/inserm-00914956/document
http://www.hal.inserm.fr/inserm-00914956/file/2012_Hanf_-_Hierarchysur Determinants_Underlying_Death_among_HIV-Infected_patients_in_French_Guiana.pdf
DOI : 10.4172/2155-6113.1000172