Emilie Counil

agr Expression Precedes Escape of Internalized Staphylococcus aureus from the Host Endosome

ABSTRACT 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 megateriumxylA 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 gfp-lux 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 thatagr induction occurs prior to endosomal lysis and thatagr-regulated exoproteins appear to be required prior to the release and replication of S. aureus within the infected MAC-T cells.

Cardiovascular burden and related risk factors among Nunavik (Quebec) Inuit: Insights from baseline findings in the circumpolar Inuit Health in Transition cohort study

BACKGROUND The Inuit are commonly portrayed to be somehow protected from cardiovascular diseases (CVDs) through their traditional lifestyle and diet. However, actual sociocultural transition and related major, modifiable risk factors have scarcely been quantified in the Inuit population. Such knowledge is extremely valuable in terms of public health intervention. METHODS A total of 887 Inuit residents from Nunavik, Quebec, participated in a cohort study. The estimates presented were derived from anthropometric and biological measurements gathered at the time of recruitment and enhanced by information collected in the medical file of each participant. All estimates were corrected for a complex sampling strategy and bootstrapped to ensure the representativeness of the general Nunavik population. RESULTS Overall, 19% of Inuit had a disease of the circulatory system according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision. Among all disorders, peripheral circulatory system disease was the most prevalent (9%). Prevalences of ischemic heart disease and cerebrovascular disease were of similar magnitude (2.5%). No significant difference in disease prevalence was noted between sexes. The major modifiable CVD risk factors were smoking (84%), obesity (49%) [corrected] (body mass index of greater than 30 kgm2) and elevated blood pressure (13085 mmHg or greater) (18%). Prevalences were globally higher among women. CONCLUSION 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.

Association between trans-fatty acids in erythrocytes and pro-atherogenic lipid profiles among Canadian Inuit of Nunavik: possible influences of sex and age.

Dietary exposure to trans-fatty acids (TFA) is likely to be high among Canadian Inuit; yet no data are available on the physiological effects of TFA in this population. The purpose of the present study was to assess the association between TFA and plasma lipid profiles in Inuit men and women living in Nunavik (Québec, Canada). In a cross-sectional, population-based survey, a total of 795 Nunavik Inuit eligible participants gave a blood sample. Exposure to TFA was assessed by their relative proportion in erythrocyte membrane. We performed multiple regression analysis using plasma lipids or their linear combinations as the dependent variables and TFA as the main predictor, adjusting for potential confounders. The associations varied markedly between the sexes and according to age. In men (n 357, aged 36.3 (sd 14.3) years, TFA 1.24 (sd 0.54) %), TFA tended to be negatively associated with HDL-cholesterol (HDL-C), apoA1 and LDL particle size, and positively associated with non-HDL-C, LDL-cholesterol (LDL-C), apoB100, the apoB100:apoA1 ratio and the ratios of total cholesterol (TC), LDL-C and TAG to HDL-C. No such trends were observed in women (n 438, aged 37.0 (sd 14.1) years, TFA 1.16 (sd 0.54) %), except for HDL-C and apoA1 in women aged 50 years and more. These results suggest that TFA could raise the risk of CHD in Inuit men at least through their physiological effects on plasma lipids. The differential associations reported in pre- and postmenopausal women need to be reproduced in other populations and in experimental studies addressing the influence of sex hormones in response to dietary fats.

Influence of mercury exposure on blood pressure, resting heart rate and heart rate variability in French Polynesians: a cross-sectional study

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

Hypertension among the Inuit from Nunavik: should we expect an increase because of obesity?

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/m2) was the highest prevalent cardiovascular risk factor (23%), and was significantly associated with HTN (OR for BMI&25 kg/m2 vs. BMI 30–34 kg/m2: 7.9 [3.5–17.9]; OR for BMI&25 kg/m2 vs. BMI ≥35 kg/m2: 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.

Trends of Incident Dialysis Patients in Tunisia Between 1992 and 2001

BACKGROUND Reliable information about the burden of end-stage renal disease (ESRD) is still scarce in the developing world. STUDY DESIGN Observational study of a national dialysis registry. SETTING & PARTICIPANTS Patients incident to dialysis therapy captured in the Tunisian registry of renal replacement therapy (RRT). PREDICTOR Intervals from 1992 to 2001. OUTCOMES Incidence rates of patients beginning dialysis therapy by age, sex, primary cause of ESRD, and region. RESULTS The incidence of treated ESRD dramatically rose in Tunisia during the 10-year period to reach 158.8 cases/million people in 2000 to 2001. We hypothesize that the Tunisian population is experiencing better access to RRT, a decrease in mortality from other causes, and an increase in chronic kidney diseases from chronic disease causes. Chronic diseases that develop with aging and economic development prevailed in urban environments, with diabetic nephropathy rising at the rate of 16.1%/y, whereas renovascular diseases, which include hypertensive nephropathy, rose by 7.6% annually. Interestingly, tubulointerstitial nephropathies increased by 10.4% each year, which may be related to such environmental risk factors as dietary exposure to ochratoxin A, especially in rural settings. ESRD from unknown causes or with missing information about cause increased by 12.7% yearly. Large regional differences in total incidence persist despite constant efforts to level off inequalities in access to health care facilities and RRT treatment. LIMITATIONS Possible underreferral for RRT, underreporting of cases, and misdiagnosis. CONCLUSIONS The growing incidence of patients on dialysis therapy in Tunisia emphasizes that preventing chronic kidney disease and its progression should be a public health priority.

Trans-polar-fat: all Inuit are not equal.

As part of the rapid socio-cultural transition observed in Arctic populations, the Inuit diet is changing. We present original data derived from the baseline Inuit Health in Transition cohort study regarding biological levels of n-3 fatty acids and trans-fatty acids (TFA), lipids with opposite health effects found respectively in traditional marine diets and recently introduced low-quality imported foods. A total of 524 Inuit from the Disko Bay area (Greenland) and 888 Inuit from the fourteen communities of Northern Québec (Nunavik) participated in the study. We measured the fatty acid profile of erythrocyte (RBC) membrane phospholipids (PL) as a surrogate for individual intakes. Moreover, the contribution of store-bought foods to energy intakes was assessed through dietary questionnaires. Our results show that while n-3 fatty acid levels were slightly lower in Nunavik (9.4% of RBC membrane PL) than in Greenland (12.1%), TFA levels were on average nearly thrice as high in Nunavik Inuit (1.20%) as they were in Greenlanders (0.43%). Moreover, younger Nunavik Inuit accumulated higher intakes of TFA and lower intakes of n-3 fatty acids. Finally, the average proportion of energy derived from store-bought foods was high in both groups (77.5% and 83.5%), especially in youth. Our results call for action to rehabilitate and recover access to country foods and point to the importance for Nunavik and the entire circumpolar world to follow the example of Denmark and Greenland, which imposed a maximum content of 2 g/100 g fat on industrially produced trans-fats in 2003.

Cardiovascular risk factors and subclinical atherosclerosis among Nunavik Inuit

OBJECTIVE To evaluate subclinical atherosclerosis in Nunavik Inuit and its correlation to traditional cardiovascular disease risk factor. METHOD The intima-media thickness (IMT) of 12 segments of the carotid arteries (IMT(12_seg)) free of plaque were assessed in randomly selected 40 years old and older Inuit from. Clinical assessment was performed which included fasting plasma glucose, fasting insulin, systemic blood pressure, body mass index, smoking, circulating blood lipids and oral glucose tolerance test. In addition, documented presence of ischemic heart disease (IHD), stroke, diabetes mellitus, hypertension and dyslipidemia were determined from medical files. RESULTS The average age of the 287 participants was 51.2 ± 0.6 years (56.8% women). Mean IMT(12_seg) was 0.80 ± 0.17 mm (range: 0.55-1.47 mm). Compared with disease free Inuit, individuals with history of stroke showed greater carotid internal IMT (0.68 ± 0.01 mm vs. 0.96 ± 0.15 mm respectively; p<0.005) but no difference was observed for IHD. Hypertensive and dyslipidemic Inuit had higher IMT(12_seg) compared to risk factor free individuals but no difference was observed in diabetics. None of the clinical assessments were associated with IMT(12_seg). In a multivariate backward elimination model, only age, gender, and medically documented history of hypertension were found to be predictors of IMT(12_seg) (adjusted r-square of 0.54; p<0.0001). CONCLUSION Compared with disease free Nunavik Inuit, subclinical signs of atherosclerosis determined by IMT was higher in individual diagnosed with stroke. Independent predictors of IMT(12_seg) in our group were age, gender and history of hypertension. No other traditional risk factors imparted IMT.

Influence of polyunsaturated fatty acids on blood pressure, resting heart rate and heart rate variability among French Polynesians.

Objective: To analyze the associations between marine n-3 polyunsaturated fatty acids (PUFAs) and blood pressure (BP), resting heart rate (HR), and heart rate variability (HRV) in a population highly exposed to methylmercury through the diet. Methods: Concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in erythrocytes membranes were measured in 180 French Polynesian adults (≥18 years) residing in Tubuai, which is a community with a traditional lifestyle, or Papeete, which has a modern lifestyle. HRV was measured using a 2-hour ambulatory electrocardiogram (Holter). Resting HR and BP were measured using standardized protocols and pulse pressure (PP) was calculated as systolic BP − diastolic BP. The associations between n-3 PUFAs and the dependent variables were studied using simple and multiple linear regressions. Results: Increasing DHA concentration was associated with lower resting HR (β = −2.57, p = 0.005) and diastolic BP (β = −1.96, p = 0.05) and higher HRV in multivariable models. Specifically, DHA was associated with high frequency (HF; β = 0.19, p = 0.02) and the square root of the mean squared differences of successive R-R intervals (difference between two consecutive R waves; rMSSD; β = 0.08, p = 0.03), which are specific indices of the parasympathetic activity of the autonomic nervous system. Conclusion: DHA was associated with lower BP and resting HR and higher HRV among French Polynesians who are also exposed to high methylmercury levels.

Dairy Product Intake and Its Association with Body Weight and Cardiovascular Disease Risk Factors in a Population in Dietary Transition

Objective: Higher dairy product intake has shown beneficial effects on body weight, blood pressure, type 2 diabetes, and cardiovascular disease (CVD) risk factors in Caucasian populations. This study evaluated dairy product intake and its association with body weight and CVD risk profile among a population undergoing a dietary transition in Canada, the Nunavik Inuit. Methods: Data were collected from August 27 to October 1, 2004, in the 14 villages of Nunavik on a Canadian research icebreaker (Canadian Coast Guard ship Amundsen). Dairy product intake and calcium intake were evaluated in 543 Inuit using a food frequency questionnaire. Physiological (lipid profile, fasting glucose, and insulin) and anthropometrical measurements were also obtained. Results: The range of median dairy product intake extended from 120 g/d in the lowest tertile to 290 g/d in the highest tertile. The median of calcium intake was 524 mg/d. Participants in the highest tertile of dairy product consumption had higher body weight, fat-free mass, waist circumference, waist-to-hip ratio, and fasting glucose concentrations than participants in the lowest tertile (all p < 0.01). After adjustments for potential cofactors, no significant association was observed. A higher prevalence of Inuit participants with metabolic syndrome was observed in the higher tertile compared with the first tertile (10.3% vs 1.6%; p < 0.001). Conclusions: Higher dairy product intake in Nunavik Inuit is not related to protective effects on body weight and CVD. The consumption of dairy products in Nunavik Inuit is probably not sufficient to withdraw beneficial effects on body weight or CVD risk factors, as observed in North American populations.