Otolith morphogenesis during the early life stages of fish is temperature-dependent: Validation by experimental approach applied to European seabass (Dicentrarchus labrax).

Otolith shape is often used as a tool in fish stock identification. The goal of this study was to experimentally assess the influence of changing temperature and ontogenic evolution on the shape component of the European seabass (Dicentrarchus labrax) otolith during early-life stages. A total of 1079 individuals were reared in a water temperature of 16°C up to 232 days post hatch (dph). During this experiment, several specimens were transferred into tanks with a water temperature of 21°C to obtain at the end of this study four different temperature treatments, each with varying ratios between the number of days at 16 and 21°C. To evaluate the otolith morphogenesis, samples were examined at 43, 72, 86 and 100 dph. The evolution of normalized otolith shape from hatching up to 100 dph showed that there were two main successive changes. First, faster growth in the antero-posterior axis than in the dorso-ventral axis changed the circular-shaped otolith from that observed at hatching and, second, increasing the complexity relating to the area between the rostrum and the anti-rostrum. To test the effect of changing temperature, growing degree-day was used in three linear mixed-effect models. Otolith morphogenesis was positively correlated to growing degree-day, but was also dependent on temperature level. Otolith shape is influenced by environmental factors, particularly temperature, making it an efficient tool for fish stock identification.

Unraveling the genotype by environment interaction in a thermosensitive fish with a polygenic sex determination system.

In most animals, sex determination occurs at conception, when sex chromosomes are segregated following Mendelian laws. However, in multiple reptiles and fishes, this genetic sex can be overridden by external factors after fertilization or birth. In some species, the genetic sex may also be governed by multiple genes, further limiting our understanding of sex determination in such species. We used the European sea bass (Dicentrarchus labrax) as a model and combined genomic (using a single nucleotide polymorphism chip) and transcriptomic (RNA-Sequencing) approaches to thoroughly depict this polygenic sex determination system and its interaction with temperature. We estimated genetic sex tendency (eGST), defined as the estimated genetic liability to become a given sex under a liability threshold model for sex determination, which accurately predicts the future phenotypic sex. We found evidence that energetic pathways, concerning the regulation of lipids and glucose, are involved in sex determination and could explain why females tend to exhibit higher energy levels and improved growth compared to males. Besides, early exposure to high-temperature up-regulated sox3, followed by sox9a in individuals with intermediate eGST, but not in individuals showing highly female-biased eGST, providing the most parsimonious explanation for temperature-induced masculinization. This gonadal state was maintained likely by DNA methylation and the up-regulation of several genes involved in histone modifications, including jmjd1c Overall, we describe a sex determination system resulting from continuous genetic and environmental influences in an animal. Our results provide significant progress in our understanding of the mechanisms underlying temperature-induced masculinization in fish.

Genomic and functional characterization of a mucosal symbiont involved in early-stage colorectal cancer.

Colorectal cancer is a major health concern worldwide. Growing evidence for the role of the gut microbiota in the initiation of CRC has sparked interest in approaches that target these microorganisms. However, little is known about the composition and role of the microbiota associated with precancerous polyps. Here, we found distinct microbial signatures between patients with and without polyps and between polyp subtypes using sequencing and culturing techniques. We found a correlation between Bacteroides fragilis recovered and the level of inflammatory cytokines in the mucosa adjacent to the polyp. Additional analysis revealed that B. fragilis from patients with polyps are bft-negative, activate NF-κB through Toll-like receptor 4, induce a pro-inflammatory response, and are enriched in genes associated with LPS biosynthesis. This study provides fundamental insight into the microbial microenvironment of the pre-neoplastic polyp by highlighting strain-specific genomic and proteomic differences, as well as more broad compositional differences in the microbiome.

Parental selection for growth and early-life low stocking density increase the female-to-male ratio in European sea bass.

In European sea bass (Dicentrarchus labrax), as in many other fish species, temperature is known to influence the sex of individuals, with more males produced at relatively high temperatures. It is however unclear to what extent growth or stress are involved in such a process, since temperature is known to influence both growth rate and cortisol production. Here, we designed an experiment aiming at reducing stress and affecting early growth rate. We exposed larvae and juveniles originating from both captive and wild parents to three different treatments: low stocking density, food supplemented with tryptophan and a control. Low stocking density and tryptophan treatment respectively increased and decreased early growth rate. Each treatment influenced the stress response depending on the developmental stage, although no clear pattern regarding the whole-body cortisol concentration was found. During sex differentiation, fish in the low-density treatment exhibited lower expression of gr1, gr2, mr, and crf in the hypothalamus when compared to the control group. Fish fed tryptophan displayed lower crf in the hypothalamus and higher level of serotonin in the telencephalon compared to controls. Overall, fish kept at low density produced significantly more females than both control and fish fed tryptophan. Parents that have been selected for growth for three generations also produced significantly more females than parents of wild origin. Our findings did not allow to detect a clear effect of stress at the group level and rather point out a key role of early sexually dimorphic growth rate in sex determination.

Sex dimorphism in European sea bass (Dicentrarchus labrax L.): New insights into sex-related growth patterns during very early life stages.

The European sea bass (Dicentrarchus labrax) exhibits female-biased sexual size dimorphism (SSD) early in development. New tagging techniques provide the opportunity to monitor individual sex-related growth during the post-larval and juvenile stages. We produced an experimental population through artificial fertilization and followed a rearing-temperature protocol (~16°C from hatching to 112 days post-hatching, dph; ~20°C from 117 to 358 dph) targeting a roughly balanced sex ratio. The fish were tagged with microchips between 61 and 96 dph in five tagging trials of 50 fish each; individual standard length (SL) was recorded through repeated biometric measurements performed between 83 to 110 dph via image analyses. Body weight (BW) was modelled using the traits measured on the digital pictures (i.e. area, perimeter and volume). At 117 dph, the fish were tagged with microtags and regularly measured for SL and BW until 335 dph. The experiment ended at 358 dph with the sexing of the fish. The sex-ratio at the end of the experiment was significantly in favor of the females (65.6% vs. 34.4%). The females were significantly longer and heavier than the males from 103 dph (~30 mm SL, ~0.44 g BW) to 165 dph, but the modeling of the growth curves suggests that differences in size already existed at 83 dph. A significant difference in the daily growth coefficient (DGC) was observed only between 96 and 103 dph, suggesting a physiological or biological change occurring during this period. The female-biased SSD pattern in European sea bass is thus strongly influenced by very early growth differences between sexes, as already shown in previous studies, and in any case long before gonadal sex differentiation has been started, and thus probably before sex has been determined. This leads to the hypothesis that early growth might be a cause rather than a consequence of sex differentiation in sea bass.

Best practices in bowel preparation for colorectal surgery: a 2020 overview.

INTRODUCTION: Cohort studies have recently initiated a paradigm shift in the field of preoperative bowel preparation. Indeed, the adjunction of oral antibiotics (OAB) to mechanical bowel preparation (MBP) is now the gold standard for the American guidelines. However, this strategy is highly controverted. AREAS COVERED: This review was an up-to-date analysis of literature on bowel preparation. We conducted a systematic review for randomized controlled trials (RCTs) and meta-analyses published since 2009. A non-exhaustive overview of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) cohort studies and the international guidelines was also given, and future leads were discussed. EXPERT OPINION: The methodology of the ACS NSQIP studies did not allow a strong conclusion in favor of the association MBP+OAB. Besides, guidelines were not univocal, with non-American guidelines promoting no preparation at all. RCTs favored OAB alone: indeed, MBP+OAB showed no benefits in terms of surgical site infection (SSI) except when compared to MBP alone, while OAB alone seemed superior to no preparation. Likewise, the meta-analyses also favored OAB alone in terms of overall SSI and organ space infection. Large RCTs are currently running and may change these conclusions. Finally, microbiota is a future lead for personalized OAB.

Chronic diseases, age and gender: examining the contribution to burnout symptoms in a sample of 2075 Canadian workers.

PURPOSE: This cross-sectional study aims to evaluate the role of chronic diseases, and their interactions with age and gender, on the emotional exhaustion component of the burnout syndrome. METHODS: Data came from the Salveo Study conducted in 2009-2012. It contained a random sample of 2075 Canadian workers employed in 63 workplaces. Multilevel regression models were estimated. Main effects of chronic diseases were first evaluated, and then age-chronic diseases interactions were tested. Analyses were performed on the total sample and stratified by gender. All analyses were adjusted for work conditions decision latitude, physical and psychological demands, work hours, social support and rewards. RESULTS: Mental and behavioural disorders, diseases of the nervous system, the musculoskeletal system and connective tissue, and genitourinary system are associated with a higher level of burnout symptoms. Associations with mental and behavioural disorders, and diseases of the nervous system are stronger for men than women. Age increases the association of behavioural disorders, diseases of the nervous system, and genitourinary system and burnout. Age may moderate the association of nervous and genitourinary systems diseases with burnout in women. CONCLUSION: Workplaces must be more proactive to better recognise the role of chronic diseases on burnout and to implement preventive measures. The development of interventions towards specific risk groups is needed.

Low temperature has opposite effects on sex determination in a marine fish at the larval/postlarval and juvenile stages.

Temperature-dependent sex determination (TSD) can be observed in multiple reptile and fish species. It is adaptive when varying environmental conditions advantage either males or females. A good knowledge of the thermosensitive period is key to understand how environmental changes may lead to changes in population sex ratio. Here, by manipulating temperature during development, we confirm that cold temperature (16°C) increases the proportion of fish that develop as females in European sea bass (Dicentrarchus labrax) until 56 days posthatching, but show that it has an opposite effect at later stages, with the proportion of males reaching ~90% after 230 days at 16°C. This is the first observation of opposite effects of temperature at different time periods on the sex ratio of a vertebrate. Our results highlight the potential complexity of environmental effects on sex determination.

ß-Barrel outer membrane proteins suppress mTORC2 activation and induce autophagic responses.

The outer membranes of Gram-negative bacteria and mitochondria contain proteins with a distinct ß-barrel tertiary structure that could function as a molecular pattern recognized by the innate immune system. Here, we report that purified outer membrane proteins (OMPs) from different bacterial and mitochondrial sources triggered the induction of autophagy-related endosomal acidification, LC3B lipidation, and p62 degradation. Furthermore, OMPs reduced the phosphorylation and therefore activation of the multiprotein complex mTORC2 and its substrate Akt in macrophages and epithelial cells. The cell surface receptor SlamF8 and the DNA-protein kinase subunit XRCC6 were required for these OMP-specific responses in macrophages and epithelial cells, respectively. The addition of OMPs to mouse bone marrow-derived macrophages infected with Salmonella Typhimurium facilitated bacterial clearance. These data identify a specific cellular response mediated by bacterial and mitochondrial OMPs that can alter inflammatory responses and influence the killing of pathogens.

Exposure to Work and Nonwork Stressors and the Development of Heart Disease Among Canadian Workers Aged 40 Years and Older: A 16-year Follow-up Study (1994 to 2010).

OBJECTIVE: The aim of this study was to evaluate the contribution of work, nonwork, and individual factors to self-reported heart disease, and to evaluate gender-related differences over a period of 16 years among Canadian workers aged 40 years and more. METHODS: Using the National Population Health Survey (NPHS, 1994 to 2010), we estimated multilevel logistic regression models (N = 2996). RESULTS: Couple-related strains, being a man, age, hypertension, and body mass index, are associated with an increased risk of heart disease. In analysis stratified by gender, physical demands at work and having high child-related strains were associated with heart disease specifically among women. Psychotropic drug use increased the risk of heart disease only in men. CONCLUSION: Our study suggests that work stressors measured by Statistics Canada NPHS are largely not associated with the risk of heart disease, except in women exposed to physical demands at work.

Human Diversity in a Cell Surface Receptor that Inhibits Autophagy.

Mutations in genes encoding autophagy proteins have been associated with human autoimmune diseases, suggesting that diversity in autophagy responses could be associated with disease susceptibility or severity. A cellular genome-wide association study (GWAS) screen was performed to explore normal human diversity in responses to rapamycin, a microbial product that induces autophagy. Cells from several human populations demonstrated variability in expression of a cell surface receptor, CD244 (SlamF4, 2B4), that correlated with changes in rapamycin-induced autophagy. High expression of CD244 and receptor activation with its endogenous ligand CD48 inhibited starvation- and rapamycin-induced autophagy by promoting association of CD244 with the autophagy complex proteins Vps34 and Beclin-1. The association of CD244 with this complex reduced Vps34 lipid kinase activity. Lack of CD244 is associated with auto-antibody production in mice, and lower expression of human CD244 has previously been implicated in severity of human rheumatoid arthritis and systemic lupus erythematosus, indicating that increased autophagy as a result of low levels of CD244 may alter disease outcomes.

[Gender, age, occupation, economic sector and mental health in the workplace: the results of the study SALVEO]. / Genre, âge, catégorie professionnelle, secteur économique et santé mentale en milieu de travail : les résultats de l'étude SALVEO.

OBJECTIVES: This article examined the contribution of gender, age, occupation and economic sector on psychological distress, depression and burnout. METHODS: The data came from the SALVEO study carried out in 2009- 2012 among 2,162 workers employed in 63 Canadian workplaces. Multilevel logistic regression models were estimated on the total sample and separately for men and women. RESULTS: The prevalences of psychological distress, depression and burnout were 23.8%, 5.8% and 3.9% respectively. Mental health problems varied between workplaces, but variations between workplaces were stronger for burnout. Differences between men and women were significant only for psychological distress, depression, and emotional exhaustion. Unskilled workers were found more at risk for depression and burnout. Associations among age, occupation and economic sector were not the same between genders. CONCLUSION: Results from the SALVEO study highlight important mental health problems in workers that vary between workplaces, and that differences in symptomatology are associated with gender, age, occupation and economic sector. Gender reveals differentiated profiles of relationships. These results point towards the development of targeted approaches to the prevention of and intervention on mental health problems in workplaces.

Acidic pH and divalent cation sensing by PhoQ are dispensable for systemic salmonellae virulence.

Salmonella PhoQ is a histidine kinase with a periplasmic sensor domain (PD) that promotes virulence by detecting the macrophage phagosome. PhoQ activity is repressed by divalent cations and induced in environments of acidic pH, limited divalent cations, and cationic antimicrobial peptides (CAMP). Previously, it was unclear which signals are sensed by salmonellae to promote PhoQ-mediated virulence. We defined conformational changes produced in the PhoQ PD on exposure to acidic pH that indicate structural flexibility is induced in α-helices 4 and 5, suggesting this region contributes to pH sensing. Therefore, we engineered a disulfide bond between W104C and A128C in the PhoQ PD that restrains conformational flexibility in α-helices 4 and 5. PhoQ(W104C-A128C) is responsive to CAMP, but is inhibited for activation by acidic pH and divalent cation limitation. phoQ(W104C-A128C) Salmonella enterica Typhimurium is virulent in mice, indicating that acidic pH and divalent cation sensing by PhoQ are dispensable for virulence.

Delivery of cardiolipins to the Salmonella outer membrane is necessary for survival within host tissues and virulence.

The outer membrane (OM) of Gram-negative bacteria is an asymmetric lipid bilayer that serves as a barrier to the environment. During infection, Gram-negative bacteria remodel their OM to promote survival and replication within host tissues. Salmonella rely on the PhoPQ two-component regulators to coordinate OM remodeling in response to environmental cues. In a screen for mediators of PhoPQ-regulated OM remodeling in Salmonella Typhimurium, we identified PbgA, a periplasmic domain-containing transmembrane protein, which binds cardiolipin glycerophospholipids near the inner membrane and promotes their PhoPQ-regulated trafficking to the OM. Purified-PbgA oligomers are tetrameric, and the periplasmic domain contains a globular region that binds to the OM in a PhoPQ-dependent manner. Thus, PbgA forms a complex that may bridge the envelope for regulated cardiolipin delivery. PbgA globular region-deleted mutant bacteria are severely attenuated for pathogenesis, suggesting that increased cardiolipin trafficking to the OM is necessary for Salmonella to survive within host tissues that activate PhoPQ.

Work and non-work stressors, psychological distress and obesity: evidence from a 14-year study on Canadian workers.

OBJECTIVE: This study aimed to evaluate the contribution of work, non-work and individual factors to obesity with regard to gender-related differences, and to clarify the mediating role that psychological distress plays in these dynamics in Canada from 1994 to 2008 using the Canadian National Population Health Survey (NPHS). DESIGN: Longitudinal. SETTINGS: The NPHS is a randomised longitudinal cohort study with biennial interviews of the Canadian adult population from 18 to 64. PARTICIPANTS: 5925 non-obese workers in cycle 1 (49% were women). MEASUREMENTS: Obesity was measured using the body mass index (BMI), with a threshold of BMI >30 kg/m(2). BMI was corrected in accordance with the recommendations of Connor Gorber et al to adjust for gender bias in responses. RESULTS: Of the work characteristics evaluated, only decision authority was associated with obesity for women but not for men. Living as a couple, child-related strains, psychotropic drug use, hypertension, being physically inactive and low psychological distress were obesity risk factors but were not moderated by gender. Overall, psychological distress did not mediate the associations that work factors have on obesity. CONCLUSIONS: Our study suggests that men and women differ little in the extent to which work, non-work and individual factors predict obesity. However, for women, the level of decision authority is associated with a lower obesity risk. In addition, psychological distress did not mediate the contribution of work factors and actually seems, contrary to expectations, to decrease the obesity risk when work, non-work and individual factors are taken into account.

[Method and participation in a preschool immunization survey in Isère (France) during the 2010-11 school year]. / Méthode et participation à une enquête en milieu scolaire sur la vaccination des enfants isérois (2010/2011).

INTRODUCTION: The Isère department has carried out a study on vaccination programmes and sites of vaccination among schoolchildren in Isère. The objective of this article is to present the original and robust method used in the study. We also describe the participation rate in the study. METHODS: A cross-sectional study was conducted among 4-year-old children in 2010/2011 during nursery school checkups. One hundred schools were randomly selected according to a complex sampling plan. The vaccination records of all children examined at checkups were photographed and data were cleared and adjusted. The participation of children in the study was investigated by distinguishing the reasons for exclusion from the study due to the mode of data collection and due to factors specific to the checkups. The factors studied concerned the intrinsic characteristics of the schools as well as data on organisation of the checkups. A total of 2,588 children from the 100 schools surveyed were included in the study, corresponding to a participation rate of 85.1%. RESULTS: 9.6% of the children selected were excluded for reasons specific to the checkups and 5.3% for reasons related to the study. Participation was higher for children examined by a team from the Maternal and Child Protection Unit (PMI: Protection maternelle et infantile), specialised in checkups. This was the only factor that appeared to impact the typical attendance of children at in nursery school health checkups. DISCUSSION: This result can probably be generalised to the other tasks of the PMI and provides important information for the future organisation of the PMI's activities.

Temporal and anatomical host resistance to chronic Salmonella infection is quantitatively dictated by Nramp1 and influenced by host genetic background.

The lysosomal membrane transporter, Nramp1, plays a key role in innate immunity and resistance to infection with intracellular pathogens such as non-typhoidal Salmonella (NTS). NTS-susceptible C57BL/6 (B6) mice, which express the mutant Nramp1D169 allele, are unable to control acute infection with Salmonella enterica serovar Typhimurium following intraperitoneal or oral inoculation. Introducing functional Nramp1G169 into the B6 host background, either by constructing a congenic strain carrying Nramp1G169 from resistant A/J mice (Nramp-Cg) or overexpressing Nramp1G169 from a transgene (Nramp-Tg), conferred equivalent protection against acute Salmonella infection. In contrast, the contributions of Nramp1 for controlling chronic infection are more complex, involving temporal and anatomical differences in Nramp1-dependent host responses. Nramp-Cg, Nramp-Tg and NTS-resistant 129×1/SvJ mice survived oral Salmonella infection equally well for the first 2-3 weeks, providing evidence that Nramp1 contributes to the initial control of NTS bacteremia preceding establishment of chronic Salmonella infection. By day 30, increased host Nramp1 expression (Tg>Cg) provided greater protection as indicated by decreased splenic bacterial colonization (Tg

Upper reference limits of high-sensitivity cardiac troponin T in a general population: comparison with those of sensitive cardiac troponin I.

BACKGROUND: Upper reference limits (97.5th, 99th percentiles) of high-sensitivity and sensitive cardiac troponins (hs-cTn and s-cTn) can be influenced by several factors. Our aim was to study: (1) the ability of hs-cTnT and s-cTnI to detect circulating cTn in a general community population, and (2) the effects of age, renal function, and gender on their 97.5th - 99th percentile values. METHODS: Hs-cTnT and s-cTnI values were measured in 177 subjects. RESULTS: Thirty-six subjects (20%) presented hs-cTnT values above the limit of detection (LoD), whereas no subjects presented detectable s-cTnI values. Men presented more frequently than women with detectable hs-cTnT levels (37% vs. 11%; p = 0.0001). Hs-cTnT was more frequently found in older (> or = 70 years) than in younger subjects (57 vs. 14%; p < 0.0001). Subjects with low estimated glomerular filtration rates (eGFR < 60 mL/min1/ 1.73m2) presented more frequently with detectable hs-cTnT levels than subjects with higher eGFR (71% vs. 17%; p < 0.0001). Hs-cTnT 97.5th - 99th percentiles varied according to selection by age, renal function, and gender; percentile values of s-cTnI were below the LoD of the assay. CONCLUSIONS: Hs-cTnT is more often quantified than s-cTnI in healthy subjects. Age, gender, and eGFR values influence 97.5th - 99th hs-cTnT percentile values.

Arginine-supplemented enteral nutrition in critically ill diabetic and obese rats: a dose-ranging study evaluating nutritional status and macrophage function.

OBJECTIVE: Critically ill diabetic and obese patients are at high risk of complications. Arginine availability is lowered in diabetes and in stress situations, yet arginine is necessary for immune response, mainly by its action through nitric oxide (NO). These facts argue for arginine-supplemented diets in critically ill patients. However, studies have raised concerns about possible adverse effects of such diets in intensive-care patients. We therefore analyzed the metabolic and immunologic effects of an arginine-enriched diet in stressed diabetic-obese rats. METHODS: Zucker Diabetic Fatty rats (fa/fa) were made endotoxemic by an intraperitoneal injection of lipopolysaccharide and then fed 4-d enteral nutrition enriched with arginine (ARG group) or a non-essential amino acid mix (NEAA group). The two groups each were subdivided into three subgroups: the ARG subgroups received 0.5 g (ARG0.5), 2 g (ARG2), and 5 g (ARG5) of arginine per kilogram daily, and the NEAA groups were made isonitrogenous with the corresponding ARG subgroups (NEAA0.5, NEAA2, and NEAA5). Plasma and urinary biomarkers were measured. Cytokine and NO production levels and inducible NO synthase and arginase protein levels were determined from peritoneal macrophages. RESULTS: The survival rate was lower in the ARG5 and NEAA5 subgroups than in all the other subgroups. The nitrogen balance was higher in the ARG5 group than in the NEAA5 group. Plasma triacylglycerol levels were lower in the ARG2 group than in the NEAA2 group. Interleukin-6, tumor necrosis factor-α, and NO production in the macrophages decreased and arginase-1 was upregulated in the ARG-treated rats. CONCLUSIONS: In this model, mortality was increased by the nitrogen burden rather than by arginine per se. Arginine improved nitrogen balance and had an anti-inflammatory action on macrophages by regulating NO production, probably through arginase-1 expression.