Impact of high-fat feeding on basic helix-loop-helix transcription factors controlling enteroendocrine cell differentiation.

BACKGROUND AND OBJECTIVES: Gut hormones secreted by enteroendocrine cells (EECs) play a major role in energy regulation. Differentiation of EEC is controlled by the expression of basic helix-loop-helix (bHLH) transcription factors. High-fat (HF) feeding alters gut hormone levels; however, the impact of HF feeding on bHLH transcription factors in mediating EEC differentiation and subsequent gut hormone secretion and expression is not known. METHODS: Outbred Sprague-Dawley rats were maintained on chow or HF diet for 12 weeks. Gene and protein expression of intestinal bHLH transcription factors, combined with immunofluorescence studies, were analyzed for both groups in the small intestine and colon. Gut permeability, intestinal lipid and carbohydrate transporters as well as circulating levels and intestinal protein expression of gut peptides were determined. RESULTS: We showed that HF feeding resulted in hyperphagia and increased adiposity. HF-fed animals exhibited decreased expression of bHLH transcription factors controlling EEC differentiation (MATH1, NGN3, NEUROD1) and increased expression of bHLH factors modulating enterocyte expression. Furthermore, HF-fed animals had decreased number of total EECs and L-cells. This was accompanied by increased gut permeability and expression of lipid and carbohydrate transporters, and a decrease in circulating and intestinal gut hormone levels. CONCLUSIONS: Taken together, our results demonstrate that HF feeding caused decreased secretory lineage (that is, EECs) differentiation through downregulation of bHLH transcription factors, resulting in reduced EEC number and gut hormone levels. Thus, impaired EEC differentiation pathways by HF feeding may promote hyperphagia and subsequent obesity.

Prefrontal synaptic markers of cocaine addiction-like behavior in rats.

Defining the drug-induced neuroadaptations specifically associated with the behavioral manifestation of addiction is a daunting task. To address this issue, we used a behavioral model that differentiates rats controlling their drug use (Non-Addict-like) from rats undergoing transition to addiction (Addict-like). Dysfunctions in prefrontal cortex (PFC) synaptic circuits are thought to be responsible for the loss of control over drug taking that characterizes addicted individuals. Here, we studied the synaptic alterations in prelimbic PFC (pPFC) circuits associated with transition to addiction. We discovered that some of the changes induced by cocaine self-administration (SA), such as the impairment of the endocannabinoid-mediated long-term synaptic depression (eCB-LTD) was similarly abolished in Non-Addict- and Addict-like rats and thus unrelated to transition to addiction. In contrast, metabotropic glutamate receptor 2/3-mediated LTD (mGluR2/3-LTD) was specifically suppressed in Addict-like rats, which also show a concomitant postsynaptic plasticity expressed as a change in the relative contribution of AMPAR and NMDAR to basal glutamate-mediated synaptic transmission. Addiction-associated synaptic alterations in the pPFC were not fully developed at early stages of cocaine SA, when addiction-like behaviors are still absent, suggesting that pathological behaviors appear once the pPFC is compromised. These data identify specific synaptic impairments in the pPFC associated with addiction and support the idea that alterations of synaptic plasticity are core markers of drug dependence.

Charge density waves tuned by biaxial tensile stress.

The precise arrangement and nature of atoms drive electronic phase transitions in condensed matter. To explore this tenuous link, we developed a true biaxial mechanical deformation device working at cryogenic temperatures, compatible with x-ray diffraction and transport measurements, well adapted to layered samples. Here we show that a slight deformation of TbTe3 can have a dramatic influence on its Charge Density Wave (CDW), with an orientational transition from c to a driven by the a/c parameter, a tiny coexistence region near a = c, and without space group change. The CDW transition temperature Tc displays a linear dependence with a / c - 1 while the gap saturates out of the coexistence region. This behaviour is well accounted for within a tight-binding model. Our results question the relationship between gap and Tc in RTe3 systems. This method opens a new route towards the study of coexisting or competing electronic orders in condensed matter.

An innovative tool reveals interaction mechanisms among yeast populations under oenological conditions.

Alcoholic fermentation of grape must is a complex process, involving several yeast genera and species. The early stages in fermentation are dominated by non-Saccharomyces yeasts that are gradually replaced by the Saccharomyces cerevisiae species, which takes over the fermentation. Quantitative studies have reported the influence of non-Saccharomyces yeast species on wine quality and evaluated their biotechnological interest. The industrial yeast market, which, until recently, exclusively focused on S. cerevisiae, now offers S. cerevisiae/non-Saccharomyces (including Torulaspora delbrueckii) multi-starters. The development of these new mixed industrial starters requires a better understanding of the interaction mechanisms between yeast populations in order to optimize the aromatic impact of the non-Saccharomyces yeast while ensuring complete alcoholic fermentation thanks to S. cerevisiae. For this purpose, a new double-compartment fermentor was designed with the following characteristics: (1) physical separation of two yeast populations, (2) homogeneity of the culture medium in both compartments, (3) fermentation kinetics monitored by weight loss due to CO2 release, and (4) independent monitoring of growth kinetics in the two compartments. This tool was used to compare mixed inoculations of S. cerevisiae/T. delbrueckii with and without physical separation. Our results revealed that physical contact/proximity between S. cerevisiae and T. delbrueckii induced rapid death of T. delbrueckii, a phenomenon previously described and attributed to a cell-cell contact mechanism. In contrast, when physically separated from S. cerevisiae, T. delbrueckii maintained its viability and its metabolic activity had a marked impact on S. cerevisiae growth and viability. The double fermentor is thus a powerful tool for studying yeast interactions. Our findings shed new light on interaction mechanisms described in microorganism populations.

[Discovery and follow-up of a lead-poisoning outbreak in a shantytown of Le Port, Reunion Island]. / Investigation et gestion d'un foyer de saturnisme infantile dans un quartier de la commune du Port, Île de la Réunion.

BACKGROUND: A national survey conducted in 2008-2009 by the French Institute for Public Health Surveillance for detection of lead impact in childhood identified a high blood lead level in a young boy living in the town of "Le Port", Reunion Island. Previously, cases of lead-poisoning on the island had been exceptional; only a dozen cases were reported in the 1980s in adults, related to the use of lead-containing instruments for food preparations. METHODS: The family of the index case was invited to participate in screening tests and an environmental investigation was conducted using a standardized questionnaire. Screening was then broadened to the neighborhood of the index case and samples of soil outside the home and in the immediate vicinity were taken. The environmental survey was then extended with soil samples taken from the entire geographical area. Information was then provided to local inhabitants (87 families and 287 people) in order to encourage lead blood testing for all children under six years and all pregnant women living in the area. RESULTS: The index case lived in the neighborhood of "The Oasis", a shantytown of Le Port. The results of soil analysis revealed heterogeneous pollution of superficial soils by lead throughout the area of the shantytown, the highest level recorded (5200mg/kg) reached more than 300 times the background level of the natural soils of the island. The screening identified 76 cases of childhood lead-poisoning (blood lead level greater or equal to 100µg/L) among 148 samples (51%). All cases of blood poisoning involved children under the age of 15 years. The median age of children with a positive test was 5.6 years; the median blood lead level was 196µg/L [102-392µg/L]. CONCLUSION: The main hypothesis to explain the contamination of the soil in the area of the shantytown is the presence of waste deposits (car batteries) and diffuse activities of metal recovery. The authorities managed to remove all the families from the environmental exposure to lead by rapidly ensuring rehousing outside the contaminated area.

Lebanese fermented goat milk products: From tradition to meta-omics.

Ambriss, Serdaleh and Labneh El Darff are traditional Lebanese products made from fermented goat's milk. A questionnaire completed by 50 producers of these products showed that they are prepared by periodic percolation either by milk or by Laban in amphora or goat skins during the lactation season. Production is carried out on a small scale and in a limited number of production units, often by elderly people, resulting in a real risk of disappearance of these products and loss of the corresponding microbial resources. In this study, 34 samples from 18 producers were characterized by culture-dependent and -independent analyses. The results obtained from these two methods were radically different, the latter revealing in Ambriss and Serdaleh the co-dominance of Lactobacillus kefiranofaciens, a fastidious-growing species, and Lactococcus lactis in a viable but not culturable state. Overall, their composition is reminiscent of kefir grains. Phylogenomic and functional analyses of the genomes of the key species Lb. kefiranofaciens have revealed differences from those found in kefir, particularly in their polysaccharide genes, which may explain the absence of grains. However, Labneh El Darff displayed a dominance of Lactobacillus delbrueckii, probably due to the addition of Laban. In addition, the study identified several zoonotic pathogens, including Streptococcus parasuis, which dominated in one sample. Metagenome-Assembled Genome (MAG) analysis indicated that this pathogen acquired lactose utilization genes through horizontal gene transfer. The contamination of the herd with Mycoplasmopsis agalactiae in the Chouf region was also revealed by MAG analysis of the Serdaleh samples. Antibiotic resistance genes were detected in most of the samples, particularly in the Serdaleh ones, where the dominant L. lactis strains possessed a plasmid with a multi-resistance island. Finally, this study paves the way for further analyses to shed light on the resilience of these ecosystems established in amphora or in goatskins and to improve hygiene practices for milk production.

Genotyping of Streptococcus thermophilus strains isolated from traditional Egyptian dairy products by sequence analysis of the phosphoserine phosphatase (serB) gene with phenotypic characterizations of the strains.

AIMS: To develop a new, simplified genotyping method for examining the genetic diversity of Streptococcus thermophilus strains isolated from traditional Egyptian fermented dairy products and to characterize phenotypic traits of those strains related to their potential use in bioprocessing applications. METHODS AND RESULTS: A novel, simplified approach was developed for genotyping Strep. thermophilus involving the analysis of nucleotide sequence variations within a housekeeping gene encoding the phosphoserine phosphatase (SerB). Using this method, it was possible to identify ten genotypes involving diverse serB alleles among 54 Strep. thermophilus isolates cultured from Egyptian dairy products. These isolates harboured five de novo serB alleles that have not been detected in other Strep. thermophilus strains, deposited in a multilocus sequence typing (MLST) database. To assess distinct genotypes of the organism with phenotypic traits relevant to their potential use in industry, Strep. thermophilus strains were all subjected to a series of phenotypic characterizations. The strains were found to exhibit phenotypic diversity in terms of their ability to ferment lactose and galactose, express urease activity, produce exopolysaccharides and develop acidity. CONCLUSIONS: The analysis of nucleotide sequence variations within the serB gene could serve as a suitable tool for probing diverse genotypes of Strep. thermophilus. Streptococcus thermophilus isolates associated with traditional Egyptian dairy products show high degree of genetic and phenotypic diversity. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents a novel, simplified procedure based on serB nucleotide sequencing for genotyping Strep. thermophilus. It also provides a pool of phenotypically diverse Strep. thermophilus cultures, from which certain strains could be selected for use in bioprocessing applications including the preparation of fermented dairy products.

Salivaricin 9, a new lantibiotic produced by Streptococcus salivarius.

Salivaricin 9 (Sal9) is a 2560 Da lantibiotic having just 46 % amino acid identity with its closest known homologue, the Streptococcus pyogenes lantibiotic SA-FF22. The Sal9 locus (designated siv) in Streptococcus salivarius strain 9 was partially sequenced and localized to an approximately 170 kb megaplasmid, which also harbours the locus for the lantibiotic salivaricin A4. The entire locus was fully characterized in the draft genome sequence of S. salivarius strain JIM8780 and shown to consist of eight genes, having the following putative functions: sivK, sensor kinase; sivR, response regulator; sivA, Sal9 precursor peptide; sivM, lantibiotic modification enzyme; sivT, ABC transporter involved in the export of Sal9 and concomitant cleavage of its leader peptide; and sivFEG, encoding lantibiotic self-immunity. Intriguingly, in contrast to strain 9, the siv locus was chromosomally located in strain JIM8780--the first lantibiotic locus shown not to be exclusively plasmid-associated in S. salivarius. Sal9-containing extracts specifically induced lantibiotic production in both strain 9 and strain JIM8780, indicating that Sal9 functions as a signal peptide for upregulation of its own biosynthesis. Screening representative strains of three streptococcal species (S. salivarius, S. pyogenes and S. mitis) for sivA indicated that it was present only in S. salivarius, with 12 of 28 tested S. salivarius positive. Since Sal9 was inhibitory to all tested S. pyogenes strains it appears to have potential as an important component of the bacteriocin armoury of S. salivarius probiotics intended to control S. pyogenes infections of the human oral cavity.

[Using French national health insurance data for non-specific monitoring on Reunion Island]. / Utilisation des données de la Caisse générale de Sécurité sociale de la Réunion dans le cadre de la surveillance non spécifique.

BACKGROUND: In Reunion Island, non-specific surveillance developed mainly in 2009 and was based on the activity of hospital emergency department, emergency calls and mortality. From March 2010, a new surveillance was implemented in collaboration between the Indian Ocean regional epidemiology unit and the regional office of the National Health Insurance. The system is based on the weekly number of general practitioner consultations and home visits by municipality. This article presents methods of using these data for non-specific monitoring in Reunion Island. MATERIALS AND METHODS: Data analyzed cover consultations and visits to general practitioners and pediatricians for each of the 24 municipalities. Data were received in week S+1 and were updated week by week following the flow of repayments. To perform weekly monitoring, determine monitoring impact and detect any unusual health event, a correction factor was thus calculated and applied for the overall data set and for each municipality. Received data covered 72% of the population of the island. RESULTS: Over the study period from 2005 to 2009, the monthly average of consultations was 80,000 (min: 58,000 - max 12,0000). Two main peaks of activity were noticed throughout the island during the study period, the first one from weeks 4 to 9 of 2006 with a peak of 105,000 consultations in week 8 and the second one from weeks 34 to 41 of 2009 with a peak of 120,000 consultations in week 35. CONCLUSION: The two peaks described in 2006 and 2009 respectively correspond to outbreaks of chikungunya and influenza A(H1N1) 2009. This monitoring study has two main advantages: an almost exhaustive data set corresponding to three-quarters of the Reunion Island population and the geographic analysis by municipality. Positioned alongside other monitoring networks, this system expands the indicators monitored reflecting varying uses of care.

[Epidemiological surveillance of leptospirosis on Reunion Island in 2004-2008: possible impact of Chikungunya infection on the case fatality rate of leptospirosis]. / Surveillance épidémiologique de la leptospirose à la Réunion, 2004-2008: possible impact de l'épidémie de chikungunya sur la létalité de la leptospirose.

In 2006, increased mortality due to leptospirosis in Reunion Island had alerted the authorities and justified the conduct of this study in order to update knowledge on the epidemiology of leptospirosis, whereas the latest epidemiological data published on the disease dated back to 2003. This study followed the scheme of a descriptive retrospective survey based on data from reporting and investigation of hospitalized cases of leptospirosis that occurred in Reunion between the 1st January 2004 and 31st December 2008. Data from the National Reference Center (NRC) have also been used. The annual number of reported cases (40 to 50) was stable over the period, which contrasted with the historical decreasing trend of incidence reported by the NRC. The circumstances of exposure were those usually associated with the disease on the island: about 80% of cases were infected between January and June, during the wet season; the main exposure factor identified was the practice of agriculture, declared or not; Leptospira icterohaemorrhagiae remained the most frequently isolated serovar, although regressing. Finally, our study has shown that excess mortality observed in 2006 did not result from an increased incidence but from a rise in the case fatality rate. This could be linked to the outbreak of chikungunya, which peaked in February 2006. In endemic areas of leptospirosis, health professionals should remain aware of the risk of occurrence of fatal cases during arbovirosis outbreaks.

[Epidemic of influenza A(H1N1) 2009 in Reunion Island: epidemiological data]. / L'épidémie de grippe à virus A(H1N1) 2009 à la Réunion: données épidémiologiques.

In Reunion Island, a French subtropical island located in the southern hemisphere, the monitoring of the epidemiological dynamics of the epidemic linked to the emergence of pandemic virus A(H1N1) 2009 was achieved through the regular influenza surveillance system which has been reinforced on that occasion. It was mainly based on a network of sentinel physicians, combined with virologic monitoring, and on surveillance of severe cases and deaths. The data were analyzed and retroinformation was distributed according to a weekly frequency. The first imported case was confirmed on July 5, 2009 in a traveler arriving from Australia, whereas the first autochthonous cases were reported on July 23. The epidemic peak was reached in five weeks and the duration of the whole epidemic episode was 9 weeks. Pandemic virus has quickly supplanted seasonal viruses that had begun to circulate. The estimated attack rate for symptomatic cases of infection with virus influenza A(H1N1) 2009 was 12.85%. The hospitalization rate was 32 per 10,000 estimated cases, and 24 people had a serious form requiring care in ICU. Among death certificates received at the regional office for health and social affairs, 14 mentioned the influenza, including 7 in whom the pandemic virus has been laboratory confirmed. These deaths occurred in patients significantly younger than usually observed in Reunion Island during the seasonal influenza epidemics. Overall, the epidemic intensity and severity have been similar to those of seasonal influenza in Reunion Island.

[Third degree atrio-ventricular blockade during a myocarditis occurring under anti-PD1 : Case report and literature review]. / Bloc atrio-ventriculaire de grade III compliquant une myocardite au décours d'un traitement par anti-PD1 : observation d'un cas et revue de la littérature.

INTRODUCTION: Immune Checkpoint Inhibitor (ICI) therapy is now a standard of care in numerous cancers with very promising results. Nevertheless, adverse events, and especially immune-related adverse events (irAEs) not reported during clinical trials, are emerging and can be life-threatening. OBSERVATION: We report here a teachable case of a 80 year-old man, of third-degree atrioventricular block consecutive to myocarditis associated with the administration of nivolumab (anti-PD1) monotherapy. CONCLUSION: Myocarditis occurring during ICI treatment is a rare but potentially lethal event. Daily serum troponin level seems to predict ICI-related myocarditis but interpretation could be difficult in the context of associated myositis. Echocardiography and cardiac MRI are also useful but can remain negative. Electrocardiogram is a cornerstone of myocarditis diagnosis. In case of cardiac involvement, continuous heart rhythm monitoring should be performed in addition to the administration of high-dose corticosteroids therapy and the cessation of ICI therapy. Add-on treatments should be discussed with a well-trained multidisciplinary team.

Marihuana: standardized smoke administration and dose effect curves on heart rate in humans.

A spirometer was used to deliver marihuana and placebo smoke to human subjects. This procedure produced linear dose-effect curves on heart rate and replicable dose effects in individual subjects. No differences were observed between experienced and inexperienced smokers in responsiveness to heart rate increases produced by marihuana.

Characterisation of thermotolerant cocci from indigenous flora of 'leben' in algerian arid area and DNA identification of atypical Lactococcus lactis strains.

Lactic acid bacteria (LAB) are widely used in food industry and their growth performance is important for the quality of the fermented product. By combining results from conventional isolation methods and molecular investigation of 16S rRNA gene and lactococcal/enterococcal specific genes, we identify at species level catalase negative gram positive thermoresistant cocci isolated from traditional 'leben', a 24-h fermented milk in arid area of west Algeria. Forty strains phenotypically related to cocci LAB were identified as belonging to the species Lactococcus lactis ssp. lactis, Enterococcus faecalis, Enterococcus faecium, and other Enterococcus species. No Streptococcus thermophilus strain was isolated. Ten different phenotype groups were recognized, and the species content of these groups were in some cases different from the expected features usually given in genus and species descriptions. In particular, atypical lactococci, able to grow in 6.5% NaCl, at pH 9.5 and showing high resistance to thermal stresses were isolated. Lactococci, but also enterococci isolated from traditional 'leben' produced in the desert area, may be therefore of interest in milk fermentation. Further studies to assess this source of diversity within the wild microbial population should provide starter new strains for product innovation.

Enhanced influenza surveillance on Réunion Island (southern hemisphere) in the context of the emergence of influenza A(H1N1)v.

With the winter season on the southern hemisphere that starts in Reunion Island in June seasonal influenza activity usually increases shortly afterwards. The new influenza A(H1N1)v virus is rapidly spreading worldwide and may reach the island during the coming winter season. We have therefore enhanced influenza surveillance to detect the introduction of influenza A(H1N1)v, monitor its spread and impact on public health and characterise potential viral changes, particularly if seasonal influenza A(H1N1), resistant to oseltamivir, co-circulates with A(H1N1)v.

Investigating transmission in a two-wave epidemic of Chikungunya fever, Réunion Island.

An epidemic of Chikungunya fever, a mosquito-borne viral disease, spectacularly swept through Réunion Island (population 780,000) in 2005-2006. There were 3,000 cases in a first wave (March-June 2005) and more than 250,000 cases in a second (December 2005-April 2006). Adapting newly developed epidemiological tools to vector-borne diseases, we show that despite this massive difference in magnitude, the transmission potential as measured by the number of secondary cases per index case (or reproduction number), remained similar during the two consecutive waves. The best estimate for the initial reproduction number R(0) was 3.7, with a possible range from 2 to 11 depending on incubation duration and lifespan of the mosquito. We conclude that an increase in virulence between the two seasons was not necessary to explain the change in magnitude of the epidemics, and that the attack rate may be well over 50% in Chikungunya fever epidemics in the absence of intervention.

First report of a Salmonella enterica serovar Weltevreden outbreak on Reunion Island, France, August 2007.

An outbreak of gastroenteritis involving 26 guests of a wedding dinner occurred in August 2007 in Réunion Island, a French Overseas Department. Salmonella was isolated in 61.5% of cases and the two isolates serotyped were of serovar Weltevreden. We believe this to be the first food-borne outbreak due to S. enterica serovar Weltevreden described in Réunion Island. The epidemiological and environmental investigations of this outbreak did not provide enough evidence to identify a single vehicle of infection. It is necessary to improve surveillance of salmonellosis by multidisciplinary cooperation between clinicians, epidemiologists, microbiologists and veterinarians on Réunion Island.

Aqueous, solid and gaseous partitioning of selenium in an oxic sandy soil under different microbiological states.

The aim of this study was to investigate the role of microorganisms on the behaviour of selenium in natural soil maintained under strictly aerobic conditions. Six-day batch experiments were performed with soils constrained to different microbiological states, either by sterilisation or by adding organic substrates. Selenium was added to the soil as selenite. The distribution of selenium in the gaseous, liquid and solid phases of the batch was measured. Selenium partitioning between the various solid phases was investigated by chemical sequential extractions. Active microorganisms played major effects on the distribution of selenium within the soil. On the one hand, microorganisms could promote selenium volatilisation (in relatively small amounts), leading to the spreading of selenium compounds outside the soil. On the other hand, microbial activities increased both amount of selenium retained by the soil and the strength of its retention (less exchangeable selenium), making selenium less susceptible to remobilisation.