Staphylococcus aureus is a versatile pathogen capable of causing life-threatening infections. Many of its cell wall and exoproduct virulence determinants are controlled via the accessory gene regulator (agr). Although considered primarily as an extracellular pathogen, it is now recognized that S. aureus can be internalized by epithelial and endothelial cells. Traditional experimental approaches to investigate bacterial internalization are extremely time-consuming and notoriously irreproducible. We present here a new reporter gene method to assess intracellular growth of S. aureus in MAC-T cells that utilizes a gfp-luxABCDE reporter operon under the control of the Bacillus megaterium xylA promoter, which in S. aureus is expressed in a growth-dependent manner. This facilitates assessment of the growth of internalized bacteria in a nondestructive assay. The dual gfplux reporter cassette was also evaluated as a reporter of agr expression and used to monitor the temporal induction of agr during the MAC-T internalization process. The data obtained suggest that agr induction occurs prior to endosomal lysis and that agr-regulated exoproteins appear to be required prior to the release and replication of S. aureus within the infected MAC-T cells.Staphylococcus aureus is the etiologic agent of numerous infections in humans and domesticated animals and has been implicated in a multitude of diseases, ranging from minor wound infections to more serious diseases, including endocarditis, osteomyelitis, and septic shock (reviewed by Projan and Novick [34]). The expression of many S. aureus virulence factors is under the control of the accessory gene regulator (agr) which, on entering post-exponential phase, downregulates the production of cell surface-associated proteins and upregulates the expression of secreted toxins and extracellular enzymes (28,33,38). The role of the agr regulon is supported by in vivo studies, which show that agr mutants are greatly attenuated in several animal models, including intramammary infections (13), arthritis in mice (1), and endocarditis in rabbits (7). The agr locus is a quorum-sensing-regulated system activated by autoinducing peptide pheromone (AIP) (21, 25). The agr locus consists of two divergent transcriptional units, RNAII and RNAIII, which are under the control of the P2 and P3 promoters, respectively (reviewed by Novick and Muir [30]). RNAII is a polycistronic mRNA that encodes the agrB and agrD genes required for the synthesis of the AIP and also the two component signal transduction proteins, AgrA and AgrC, which are responsible for sensing and responding to the AIP. RNAIII is the effector molecule in the agr regulon acting primarily at the level of gene transcription. Different S. aureus strains produce AIPs with distinct structures, and strains can be grouped on this basis since they will activate the agr response of strains within the same group and inhibit the agr response of strains from different groups by competitive inhibition (21,30). This inhibitory action of AIPs has identi...

The current belief that the Inuit are protected from CVD is seriously questioned by the results of the present study. Considering the extremely high prevalence of CVD risk factors, a population-based intervention reinforced for women is urgently needed to reduce their risk.

Background We aimed to estimate the seroprevalence of SARS-CoV-2 infection in France and to identify the populations most exposed during the first epidemic wave. Methods Random selection of individuals aged 15 years or over, from the national tax register (96% coverage). Socio-economic data, migration history, and living conditions were collected via self-computer-assisted-web or computer-assisted-telephone interviews. Home self-sampling was performed for a random subsample, to detect IgG antibodies against spike protein (Euroimmun), and neutralizing antibodies with in-house assays, in dried blood spots (DBS). Results The questionnaire was completed by 134,391 participants from May 2nd to June 2st, 2020, including 17,441 eligible for DBS 12,114 of whom were tested. ELISA-S seroprevalence was 4.5% [95% CI 3.9–5.0] overall, reaching up to 10% in the two most affected areas. High-density residences, larger household size, having reported a suspected COVID-19 case in the household, working in healthcare, being of intermediate age and non-daily tobacco smoking were independently associated with seropositivity, whereas living with children or adolescents did not remain associated after adjustment for household size. Adjustment for both residential density and household size accounted for much of the higher seroprevalence in immigrants born outside Europe, twice that in French natives in univariate analysis. Conclusion The EPICOV cohort is one of the largest national representative population-based seroprevalence surveys for COVID-19. It shows the major role of contextual living conditions in the initial spread of COVID-19 in France, during which the availability of masks and virological tests was limited.

BackgroundPopulations which diet is rich in seafood are highly exposed to contaminants such as mercury, which could affect cardiovascular risk factorsObjectiveTo assess the associations between mercury and blood pressure (BP), resting heart rate (HR) and HR variability (HRV) among French PolynesiansMethodsData were collected among 180 adults (≥ 18 years) and 101 teenagers (12-17 years). HRV was measured using a two-hour ambulatory electrocardiogram (Holter) and BP was measured using a standardized protocol. The association between mercury and HRV and BP parameters was studied using analysis of variance (ANOVA) and analysis of covariance (ANCOVA)ResultsAmong teenagers, the high frequency (HF) decreased between the 2nd and 3rd tertile (380 vs. 204 ms2, p = 0.03) and a similar pattern was observed for the square root of the mean squared differences of successive R-R intervals (rMSSD) (43 vs. 30 ms, p = 0.005) after adjusting for confounders. In addition, the ratio low/high frequency (LF/HF) increased between the 2nd and 3rd tertile (2.3 vs. 3.0, p = 0.04). Among adults, the standard deviation of R-R intervals (SDNN) tended to decrease between the 1st and 2nd tertile (84 vs. 75 ms, p = 0.069) after adjusting for confounders. Furthermore, diastolic BP tended to increase between the 2nd and 3rd tertile (86 vs. 91 mm Hg, p = 0.09). No significant difference was observed in resting HR or pulse pressure (PP)ConclusionsMercury was associated with decreased HRV among French Polynesian teenagers while no significant association was observed with resting HR, BP, or PP among teenagers or adults

Following our results, based on population studies conducted in Greenland and Northern Canada, that Nunavik Inuit were thrice as highly exposed to dietary trans -fat as were Greenlandic Inuit, and that the biological levels found in Nunavik were already associated with deleterious blood lipid profiles, we decided to engage in translational activities. Our goal was to support Inuit communities in the practical implementation of a reduction of the trans -fat content of food sold in Nunavik. We carried out a preliminary feasibility study in Kuujjuaq and participated in several meetings. This translational phase involved an Inuk leader, an Inuk student, a southern student, a southern nutritionist and a southern researcher in the framework of a public health project. In the present article, we recount the different phases of the process, from research implementation to results dissemination and institutional commitment to implement a primary prevention program of reduction in trans -fat exposure in Nunavik. This is the occasion to draw broader conclusions on the factors that could either act in favour of or, on the contrary, would likely compromise the implementation of primary prevention interventions dealing with food and nutrition in the Arctic. Finally, we share some reflections on future translational activities dealing with trans -fat as well as other junk food issues. The analytical framework we propose integrates a range of factors, from geo-climatic to socio-economic, ethno-cultural, and even political, that we think should be examined while identifying and building preventive recommendations and strategies related to the Northern diet.

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ObjectiveAlthough social inequalities in COVID-19 mortality by race, gender and socioeconomic status are well documented, less is known about social disparities in infection rates and their shift over time. We aim to study the evolution of social disparities in infection at the early stage of the epidemic in France with regard to the policies implemented.DesignRandom population-based prospective cohort.SettingFrom May to June 2020 in France.ParticipantsAdults included in the Epidémiologie et Conditions de Vie cohort (n=77 588).Main outcome measuresSelf-reported anosmia and/or ageusia in three categories: no symptom, during the first epidemic peak (in March 2020) or thereafter (during lockdown).ResultsIn all, 2052 participants (1.53%) reported anosmia/ageusia. The social distribution of exposure factors (density of place of residence, overcrowded housing and working outside the home) was described. Multinomial regressions were used to identify changes in social variables (gender, class and race) associated with symptoms of anosmia/ageusia. Women were more likely to report symptoms during the peak and after. Racialised minorities accumulated more exposure risk factors than the mainstream population and were at higher risk of anosmia/ageusia during the peak and after. By contrast, senior executive professionals were the least exposed to the virus with the lower rate of working outside the home during lockdown. They were more affected than lower social classes at the peak of the epidemic, but this effect disappeared after the peak.ConclusionThe shift in the social profile of the epidemic was related to a shift in exposure factors under the implementation of a stringent stay-at-home order. Our study shows the importance to consider in a dynamic way the gender, socioeconomic and race direct and indirect effects of the COVID-19 pandemic, notably to implement policies that do not widen health inequalities.

Objectives. Because of their recent adoption of a Westernized lifestyle, an increased risk of developing hypertension (HTN) is suspected among Inuit populations. This study aimed to assess the exact prevalence of HTN in Nunavik Inuit and to examine its association with other major risk factors of cardiovascular disease. Study design. A cross-sectional population-based study. Methods. We analysed biological and anthropometric data and the medical history of 832 Inuit. Results. The overall prevalence of HTN (≥140/90 mmHg or the use of medication) was 19% with no gender difference. Obesity (body mass index [BMI] ≥30 kg/m 2 ) was the highest prevalent cardiovascular risk factor (23%), and was significantly associated with HTN (OR for BMI<25 kg/m 2 vs. BMI 30-34 kg/m 2 : 7.9 [3.5-17.9]; OR for BMI<25 kg/m 2 vs. BMI ≥35 kg/m 2 : 14. 4 [5.6-36.7]). An increase in odds of prehypertension (preHTN) (130-139/80-89 mmHg) was also observed as the BMI increased (p for trend, p<0.0001). Conclusion. The prevalence of HTN in the Inuit populations has reached values similar to those of their Westernized counterparts. Furthermore, not only HTN but also preHTN states are significantly associated with obesity even after adjusting for confounding variables. These results clearly indicate that HTN is becoming a growing health challenge in Nunavik because of pandemic obesity.