Muscle-specific, liver-detargeted adeno-associated virus gene therapy rescues Pompe phenotype in adult and neonate Gaa-/- mice.

Pompe disease (PD) is a neuromuscular disorder caused by acid α-glucosidase (GAA) deficiency. Reduced GAA activity leads to pathological glycogen accumulation in cardiac and skeletal muscles responsible for severe heart impairment, respiratory defects, and muscle weakness. Enzyme replacement therapy with recombinant human GAA (rhGAA) is the standard-of-care treatment for PD, however, its efficacy is limited due to poor uptake in muscle and the development of an immune response. Multiple clinical trials are ongoing in PD with adeno-associated virus (AAV) vectors based on liver- and muscle-targeting. Current gene therapy approaches are limited by liver proliferation, poor muscle targeting, and the potential immune response to the hGAA transgene. To generate a treatment tailored to infantile-onset PD, we took advantage of a novel AAV capsid able to increase skeletal muscle targeting compared to AAV9 while reducing liver overload. When combined with a liver-muscle tandem promoter (LiMP), and despite the extensive liver-detargeting, this vector had a limited immune response to the hGAA transgene. This combination of capsid and promoter with improved muscle expression and specificity allowed for glycogen clearance in cardiac and skeletal muscles of Gaa-/- adult mice. In neonate Gaa-/- , complete rescue of glycogen content and muscle strength was observed 6 months after AAV vector injection. Our work highlights the importance of residual liver expression to control the immune response toward a potentially immunogenic transgene expressed in muscle. In conclusion, the demonstration of the efficacy of a muscle-specific AAV capsid-promoter combination for the full rescue of PD manifestation in both neonate and adult Gaa-/- provides a potential therapeutic avenue for the infantile-onset form of this devastating disease.

Risk of contamination of semen, vaginal secretions, follicular fluid and ovarian medulla with SARS-CoV-2 in patients undergoing ART.

STUDY QUESTION: Can severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA be detected in the reproductive tract of asymptomatic patients undergoing ART? SUMMARY ANSWER: SARS-CoV-2 mRNA is not detectable in semen, follicular fluid, vaginal secretions or residual medulla from ovarian tissue cryopreservation procedures in asymptomatic patients who undergo ART, irrespective of the results of a triage questionnaire and a nasopharyngeal SARS-CoV-2 RNA detection test. WHAT IS KNOWN ALREADY: The SARS-CoV-2 pandemic had a huge impact on the activities of fertility clinics. Although some studies reported the presence of SARS-CoV-2 mRNA in the reproductive system during or after acute COVID-19 symptomatic infections, uncertainties remain regarding the presence of viral mRNA in the reproductive material and follicular fluid of asymptomatic patients undergoing ART. STUDY DESIGN, SIZE, DURATION: An observational cohort trial of residual material samples including semen, follicular fluid, vaginal secretions and ovarian medulla was conducted during the second pandemic wave in Brussels from September 2020 to April 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients who underwent ART (IUI, IVF/ICSI, oocyte and ovarian tissue cryopreservation) responded to a triage questionnaire at the beginning and end of the cycle and underwent nasopharyngeal swab collection for SARS-CoV-2 RNA detection by RT-PCR before the procedure according to standard recommendations. For semen analysis, only the questionnaire was requested the day before the sample collection. The ART cycles of patients with positive nasopharyngeal SARS-CoV-2 RNA detection tests and/or questionnaires were cancelled except for those that could not be postponed. After providing informed consent, swabs on residual materials were collected the day of the oocyte, ovarian tissue or semen collection and were processed for RT-qPCR. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 394 samples from 291 patients were analysed. Amongst them, 20 samples were obtained from patients with a positive questionnaire but negative nasopharyngeal SARS-CoV-2 test and 20 others were from patients with a positive nasopharyngeal SARS-CoV-2 test. The remaining samples were collected from patients with a negative or unknown nasopharyngeal SARS-CoV-2 test and/or a negative or unknown triage questionnaire. Viral RNA for SARS-CoV-2 was undetectable in all of the samples. LIMITATIONS, REASONS FOR CAUTION: Considering the cancellation policy, only a limited number of samples from patients with positive triage questionnaires or nasopharyngeal SARS-CoV-2 tests were included in the analysis. WIDER IMPLICATIONS OF THE FINDINGS: The study suggested that there was no risk of reproductive tract contamination by SARS-CoV-2 in asymptomatic patients, irrespective of the results from a triage questionnaire or nasopharyngeal SARS-CoV-2 test. The results suggested that no additional measures to prevent staff or cross-patient contamination need to be implemented in the IVF and andrology laboratories. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Université Libre de Bruxelles and by a grant from Ferring. A.D. and I.D. received a grant from Ferring for the study. The authors have no other conflict of interest to declare related to this study. TRIAL REGISTRATION NUMBER: N/A.

Thyroid-stimulating hormone is associated with trabecular bone score and 5-year incident fracture risk in euthyroid postmenopausal women: the OsteoLaus cohort.

Thyroid-stimulating hormone (TSH) excess or deficiency influences bone density and fracture risk. Nevertheless, does TSH in the reference range influence bone health? In euthyroid postmenopausal women, TSH levels in the reference range were positively associated with trabecular bone score and negatively with incident fractures, without affecting BMD. PURPOSE: Subclinical hyperthyroidism is associated with low bone mineral density (BMD) and increased fracture risk. In healthy postmenopausal women, association between thyroid-stimulating hormone (TSH) in the normal range and BMD is contradictory. Trabecular bone score (TBS), an index of bone micro-architecture, is often decreased in secondary osteoporosis (OP). The aim was to determine the association between thyroid hormones (TSH, fT4) and BMD, TBS, and the incident 5-year OP fractures, in euthyroid post-menopausal women. METHODS: We assessed 1475 women of the CoLaus/OsteoLaus cohort. We evaluated BMD at lumbar spine, femoral neck and total hip, lumbar spine TBS, and vertebral fracture with DXA. Incident major OP fractures were evaluated 5 years later by questionnaire and DXA. Women with anti-osteoporotic, antidiabetic, thyroid-modifying, hormone replacement, or systemic corticoid treatment were excluded. RESULTS: Five hundred thirty-three women (age 68.4 ± 7.3 years, BMI 25.9 ± 4.6 kg/m2, TSH 2.03 ± 0.87 mU/l, fT4 15.51 ± 1.85 pmol/l) met the inclusion criteria. There was no significant association between TSH or fT4 and BMD measures at any site. A positive association was found between TSH and TBS (ß = 0.138, p < 0.01), even after adjusting for age, BMI, and duration of menopause (ß = 0.086, p < 0.05). After a 5-year follow-up, women with incident major OP fractures had lower TSH levels (1.77 ± 0.13 vs. 2.05 ± 0.04 mU/l, p < 0.05) than women without fractures, while no difference was found for fT4. CONCLUSION: In euthyroid postmenopausal women, TSH levels were positively associated with TBS and negatively with incident fractures, without affecting BMD. Further studies are needed to evaluate the influence of thyroid hormones on TBS.

Postmenopausal women with osteoporosis consume high amounts of vegetables but insufficient dairy products and calcium to benefit from their virtues: the CoLaus/OsteoLaus cohort.

We evaluated the associations between nutrients, dietary patterns or compliance to dietary guidelines and bone health among postmenopausal women from the CoLaus/OsteoLaus cohort. Postmenopausal women with osteoporosis consume a high amount of vegetables but insufficient amount of dairy products and calcium to benefit from their adherence to dietary guidelines. INTRODUCTION: Diet plays a significant role in the prevention of osteoporosis (OP). We evaluated the associations between nutrients, dietary patterns or compliance (expressed in odds of meeting) to dietary Swiss guidelines and bone health (T score < - 2.5 SD, TBS < 1230) among postmenopausal women. METHODS: One thousand two hundred fifteen women (64.3 ± 7.5 years) from the CoLaus/OsteoLaus cohort (Lausanne, Switzerland) had their dietary intake assessed using a validated food frequency questionnaire. Bone mineral density (BMD), trabecular bone score (TBS) and vertebral fractures were evaluated with DXA. OP risk factors, calcium supplements (> 500 mg) and prevalent major OP fractures were assessed by questionnaire. RESULTS: One hundred eighty of 1195 women had OP according to BMD, 87/1185 a low TBS and 141/1215 prevalent major OP fractures. In multivariate analysis (adjusted for total energy intake, age, antiosteoporotic treatment, educational level, BMI, sedentary status and diabetes), OP women consumed more vegetable proteins (21.3 ± 0.4 vs 19.6 ± 0.2 g/day), more fibres (18.2 ± 0.5 vs 16.5 ± 0.2 g/day), less animal proteins (40.0 ± 1.1 vs 42.8 ± 0.4 g/day), less calcium (928 ± 30 vs 1010 ± 12 mg/day) and less dairy products (175 ± 12 vs 215 ± 5 g/day), all p ≤ 0.02. According to guidelines, OP women had a tendency to higher compliance for vegetables (OR (95% CI) 1.50 (0.99-2.26)) and a lower compliance for dairy (OR (95% CI) 0.44 (0.22-0.86)) than those without OP. Women taking calcium supplements consumed significantly higher amounts of dairy products. No association was found between TBS values or prevalent OP fractures and any dietary components. CONCLUSION: Postmenopausal women with OP consume a high amount of vegetables but insufficient amount of dairy products and calcium. TBS does not seem to be influenced by diet.

Mood disorders and circulating levels of inflammatory markers in a longitudinal population-based study.

BACKGROUND: There has been increasing evidence that chronic low-grade inflammation is associated with mood disorders. However, the findings have been inconsistent because of heterogeneity across studies and methodological limitations. Our aim is to prospectively evaluate the bi-directional associations between inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α and high sensitivity C-reactive protein (hsCRP) with mood disorders. METHODS: The sample consisted of 3118 participants (53.7% women; mean age: 51.0, s.d. 8.8 years), randomly selected from the general population, who underwent comprehensive somatic and psychiatric evaluations at baseline and follow-up (mean follow-up duration = 5.5 years, s.d. 0.6). Current and remitted mood disorders including bipolar and major depressive disorders (MDD) and its subtypes (atypical, melancholic, combined atypical and melancholic, and unspecified) were based on semi-structured diagnostic interviews. Inflammatory biomarkers were analyzed in fasting blood samples. Associations were tested by multiple linear and logistic regression models. RESULTS: Current combined MDD [ß = 0.29, 95% confidence interval (CI) 0.03-0.55] and current atypical MDD (ß = 0.32, 95% CI 0.10-0.55) at baseline were associated with increased levels of hsCRP at follow-up. There was little evidence for inflammation markers at baseline predicting mood disorders at follow-up. CONCLUSIONS: The prospective unidirectional association between current MDD subtype with atypical features and hsCRP levels at follow-up suggests that inflammation may be a consequence of this condition. The role of inflammation, particularly hsCRP that is critically involved in cardiovascular diseases, warrants further study. Future research that examines potential influences of medications on inflammatory processes is indicated.

Prospective associations of depression subtypes with cardio-metabolic risk factors in the general population.

The mechanisms and temporal sequence underlying the association between major depressive disorder (MDD) and cardio-metabolic diseases are still poorly understood. Recent research suggests subtyping depression to study the mechanisms underlying its association with biological correlates. Accordingly, our aims were to (1) assess the prospective associations of the atypical, melancholic and unspecified subtypes of MDD with changes of fasting glucose, high-density lipoprotein-cholesterol, triglycerides, systolic blood pressure and the incidence of the metabolic syndrome, (2) determine the potential mediating role of inflammatory marker or adipokine concentrations, eating behaviors and changes in waist circumference during follow-up. Data stemmed from CoLaus|PsyCoLaus, a prospective cohort study including 35-66-year-old randomly selected residents of an urban area. Among the Caucasian participants who underwent the physical and psychiatric baseline evaluations, 2813 (87% participation rate) also accepted the physical follow-up exam (mean follow-up duration=5.5 years). Symptoms of mental disorders were elicited using a semi-structured interview. The atypical MDD subtype, and only this subtype, was prospectively associated with a higher incidence of the metabolic syndrome (OR=2.49; 95% CI 1.30-4.77), a steeper increase of waist circumference (ß=2.41; 95% CI 1.19-3.63) and independently of this, with a steeper increase of the fasting glucose level (ß=131; 95% CI 38-225) during follow-up. These associations were not attributable to or mediated by inflammatory marker or adipokine concentrations, eating behaviors, comorbid psychiatric disorders or lifestyle factors. Accordingly, our results further support the subtyping of MDD and highlight the particular need for prevention and treatment of metabolic consequences in patients with atypical MDD.

Desire to lose weight, dietary intake and psychological correlates among middle-aged and older women. The CoLaus study.

Body dissatisfaction has been regularly associated with negative consequences on health of young women, but less is known regarding middle-aged or older women. However, body dissatisfaction in women has been seen for long as a "normative discontent" (i.e. widespread and chronic dissatisfaction) because of its high prevalence among all age categories. The goal of this study was to explore the relationships between the desire to lose weight, energy intake and psychological health in community-dwelling women issued from the second wave (cross-sectional data) of the cohort study CoLaus (2009-2012, Switzerland), taking age categories (40-59 and 60-80) and body mass index (BMI, normal and overweight/obese) into account. Results showed that the desire to lose weight was common even in women with normal BMI and whatever the age category. Women with normal BMI who wished to lose weight reported lower energy and protein intake per kg of body weight, more signs of depression and less satisfaction with their quality of life than those who did not wish to lose weight in both age groups. The desire to lose weight was similarly associated with psychological health in women with overweight/obesity, in both age categories as well. These results indicate that the desire to lose weight may be associated with an impaired psychological health also in middle-aged and older women, even in those with normal BMI. This should not be considered as normal by health care professionals but as a possible indicator of psychological health and of the capacity to comply with dietary recommendations.

Incidence of type 2 diabetes, hypertension, and dyslipidemia in metabolically healthy obese and non-obese.

BACKGROUND AND AIMS: Metabolically healthy obese (MHO) individuals are devoid of many metabolic abnormalities, but how this condition is maintained over time remains debated. We assessed the prevalence of MHO over time and the incidence of hypertension (HTN), dyslipidemia, and type 2 diabetes mellitus (T2DM) in MHO as compared with metabolically healthy non obese (MHNO). METHODS AND RESULTS: Prospective, population-based study including 3038 participants (49.9 ± 9.9 years; 1753 women) free from metabolic syndrome and cardiovascular disease at baseline and examined after a follow-up of 5.6 years and 10.9 years on average. At each follow-up, prevalence of MHO, MHNO, metabolically unhealthy not obese (MUNO), and metabolically unhealthy obese (MUO), as well as of HTN, dyslipidemia, and T2DM, was calculated and stratified by sex, age group, and education. At baseline, 179 (5.7%) MHO participants were identified, of which 62 (34.6%) and 79 (44.1%) remained MHO at 5.6 and 10.9 years follow-up, respectively. At 5.6 years follow-up, MHO participants were more likely to develop low HDL or be on hypolipidemic medication [multivariable-adjusted OR (95% CI): 1.56 (1.02-2.38)], to have dyslipidemia [1.94 (1.33-2.82)], and high triglycerides [2.07 (1.36-3.14)] than MHNO. At 10.9 years follow-up, MHO participants were significantly more likely to develop T2DM [3.44 (1.84-6.43)], dyslipidemia [1.64 (1.14-2.38)], and low HDL or be prescribed hypolipidemic medication [1.57 (1.08-2.27)] than MHNO. Conversely, no differences were found regarding hypertension. CONCLUSION: A considerable fraction of MHO individuals lose their status over time, and in metabolically healthy adults, obesity confers a higher risk of developing cardiovascular risk factors.

Seasonality of sodium and potassium consumption in Switzerland. Data from three cross-sectional, population-based studies.

BACKGROUND AND AIM: Blood pressure displays a seasonal pattern. Whether this pattern is related to high sodium and/or low potassium intakes has not been investigated. We assessed if sodium and potassium consumption present a seasonal pattern. We also simulated the impact of seasonality of sodium consumption on systolic blood pressure levels. METHODS AND RESULTS: Data from three Swiss population-based studies (n = 2845). Sodium and potassium consumption were assessed by urinary excretion using 24 h urine collection. Seasonality was assessed using the cosinor model and was adjusted for study, gender, age, body mass index, antihypertensive drug treatment, urinary creatinine and atmospheric relative humidity. The effect of sodium variation on blood pressure levels was estimated using data from a recent meta-analysis. Both sodium and potassium excretions showed a seasonal pattern. For sodium, the nadir occurred between August and October, and the peak between February and April, with a multivariate-adjusted seasonal variation (difference between peak and nadir) of 9.2 mmol. For potassium, the nadir occurred in October and the peak in April, with a multivariate-adjusted seasonal variation of 4.0 mmol. Excluding participants on antihypertensive drug treatment or stratifying the analysis by gender cancelled the seasonality of sodium consumption. The maximum impact of the seasonal variation in sodium consumption on systolic blood pressure ranged from 0.4 to 1.1 mm Hg, depending on the model considered. CONCLUSION: Sodium and potassium consumptions present specific seasonal variations. These variations do not explain the seasonal variations in blood pressure levels.

Airborne pollen levels and drug consumption for seasonal allergic rhinoconjunctivitis: a 10-year study in France.

BACKGROUND: Few time-series studies, and none lasting longer than 4 years, have investigated the etiology of treated seasonal allergic rhinoconjunctivitis (SAR) on the basis of anti-allergic medication prescriptions. The aim of this article was to study the short-term relationship between pollen exposure and drug-treated SAR over 10 years in an urban area in central France. METHODS: A SAR case was defined as the association between an oral antihistamine and a local anti-allergic drug on the same prescription. The relationship between daily changes in pollen concentrations and daily changes in the number of treated SAR cases was analysed using generalized additive models, taking into account confounding factors such as air pollution, weather and days of the week. RESULTS: Between 2003 and 2012, the total yearly number of treated SAR cases rose from 7265 to 11 315. The relative risk of treated SAR associated with an interquartile increase in pollen concentration increased significantly for Fraxinus, Betula, Carpinus, Platanus, Poaceae and Urticaceae for the whole pollen season, and for Urticaceae in the first semester. CONCLUSIONS: The prevalence of treated SAR cases rose by about 55% in 10 years. The study not only confirmed the highly allergenic role of Fraxinus, Betula and Poaceae pollens but also showed a relatively unknown association between treated SAR and Carpinus and Platanus pollens, despite their pollen counts being <1% of overall pollen concentration. It also showed robust correlations with Urticaceae pollens, especially during the first semester, suggesting a potential allergenic role of Parietaria pollination in this non-Mediterranean area.

Five year trends in dyslipidaemia prevalence and management in Switzerland: the CoLaus study.

BACKGROUND AND AIMS: Data from prospective cohorts describing dyslipidaemia prevalence and treatment trends are lacking. Using data from the prospective CoLaus study, we aimed to examine changes in serum lipid levels, dyslipidaemia prevalence and management in a population-based sample of Swiss adults. METHODS AND RESULTS: Cardiovascular risk was assessed using PROCAM. Dyslipidaemia and low-density lipoprotein cholesterol (LDL-C) target levels were defined according to the Swiss Group for Lipids and Atherosclerosis. Complete baseline and follow up (FU) data were available for n = 4863 subjects during mean FU time of 5.6 years. Overall, 32.1% of participants were dyslipidaemic at baseline vs 46.3% at FU (p < 0.001). During this time, lipid lowering medication (LLM) rates among dyslipidaemic subjects increased from 34.0% to 39.2% (p < 0.001). In secondary prevention, LLM rates were 42.7% at baseline and 53.2% at FU (p = 0.004). In multivariate analysis, LLM use among dyslipidaemic subjects, between baseline and FU, was positively associated with personal history of CVD, older age, hypertension, higher BMI and diabetes, while negatively associated with higher educational level. Among treated subjects, LDL-C target achievement was positively associated with diabetes and negatively associated with personal history of CVD and higher BMI. Among subjects treated at baseline, LLM discontinuation was negatively associated with older age, male sex, smoking, hypertension and parental history of CVD. CONCLUSIONS: In Switzerland, the increase over time in dyslipidaemia prevalence was not paralleled by a similar increase in LLM. In a real-life setting, dyslipidaemia management remains far from optimal, both in primary and secondary prevention.

Alcohol consumption and incidence of type 2 diabetes. Results from the CoLaus study.

BACKGROUND AND AIMS: Moderate alcohol consumption has been shown to decrease the risk of type 2 diabetes (T2DM), but whether this association is also valid for impaired fasting glucose (IFG) is less well known. We aimed at assessing the impact of alcohol consumption and of type of alcoholic beverage on the incidence of T2DM and T2DM + IFG. METHODS AND RESULTS: As many as 4765 participants (2613 women, mean age 51.7 ± 10.5 years) without T2DM at baseline and followed for an average of 5.5 years. The association between alcohol consumption, type of alcoholic beverage and outcomes was assessed after adjustment for a validated T2DM risk score. During follow-up 284 participants developed T2DM and 643 developed IFG. On bivariate analysis, alcohol consumption was positively associated with the risk of developing T2DM or T2DM + IFG. Moderate (14-27 units/week) alcohol consumption tended to be associated with a lower risk of T2DM, but no protective effect was found for T2DM + IFG. Multivariable-adjusted odds ratio (OR) and (95% confidence interval) for T2DM: 0.89 (0.65-1.22), 0.66 (0.42-1.03) and 1.63 (0.93-2.84) for 1-13, 14-27 and 28 + units/week, respectively (p for quadratic trend < 0.005). For T2DM + IFG, the corresponding ORs were 1.09 (0.90-1.32), 1.33 (1.02-1.74) and 1.54 (0.99-2.39), respectively, p for trend = 0.03. No specific effect of alcoholic beverage (wine, beer or spirits) was found for T2DM or for T2DM + IFG. CONCLUSION: Moderate alcohol consumption is associated with a reduced risk of developing T2DM, but not of developing T2DM + IFG. No specific effect of type of alcoholic beverage was found.

Iron metabolism and incidence of metabolic syndrome.

BACKGROUND AND AIMS: Whether iron metabolism affects metabolic syndrome (METS) is debated. We assessed the association between several markers of iron metabolism and incidence of METS. METHODS AND RESULTS: Data from 3271 participants (1870 women, 51.3 ± 10.4 years), free of METS at baseline and followed for 5.5 years. The association of serum iron, ferritin and transferrin with incident METS was assessed separately by gender. Incidence of METS was 22.6% in men and 16.5% in women (p < 0.001). After multivariate adjustment, a positive association was found between transferrin and incident METS in men: odds ratio (OR) and 95% confidence interval for the fourth relative to the first quartile 1.55 (1.04-2.31), p for trend = 0.03, while no association was found for iron OR = 0.81 (0.53-1.24), p for trend = 0.33 and ferritin OR = 1.30 (0.88-1.92), p for trend = 0.018. In women, a negative association was found between iron and incident METS: OR for the fourth relative to the first quartile 0.51 (0.33-0.80), p for trend<0.03; the association between transferrin and incident METS was borderline significant: OR = 1.45 (0.97-2.17), p for trend = 0.07 and no association was found for ferritin: OR = 1.11 (0.76-1.63), p for trend = 0.58. CONCLUSION: Transferrin, not ferritin, is independently associated with an increased risk of incident METS; the protective effect of iron in women should be further explored.

[Social networks and medicine]. / Réseaux sociaux: de nouveaux outils de communication et de formation pour les médecins?

Social networks (social media or #SoMe) have entered medical practice within the last few years. These new media--like Twitter or Skype--enrich interactions among physicians (telemedicine), among physicians and patients (virtual consultations) and change the way of teaching medicine. They also entail new ethical, deontological and legal issues: the extension of the consultation area beyond the medical office and the access of information by third parties were recently debated. We develop here a review of some social networks with their characteristics, applications for medicine and limitations, and we offer some recommendations of good practice.

[Cardiac rehabilitation, a proven intervention underutilized in the French-speaking part of Switzerland]. / Réadaptation cardiovasculaire, un- bien sous-utilisé.

Cardiac rehabilitation is associated with a reduced risk of recurrence and mortality after an acute coronary syndrome. Cardiac rehabilitation is a multidisciplinary approach which starts during the acute hospital phase, then followed by a four to six weeks home-based or stationary program, in order to maintain long-term lifestyle changes. Despite the important health benefits of cardiac rehabilitation and its cost-effectiveness, only half of the patients in Europe will achieve a cardiovascular prevention program after an acute coronary syndrome. In the French part of Switzerland, one explanation for this low adherence might be the lack of both stationary and home-based program facilities.

Relationship between dietary characteristics and heel quantitative ultrasound parameters in postmenopausal women from the OsteoLaus cohort.

The role of dietary patterns in the development of osteoporosis is unclear. The heel quantitative ultrasound (QUS) is a potential alternative to Dual X-Ray Absorptiometry. Nutrients, foods, dietary patterns and compliance to dietary guidelines were compared between the lowest and the highest tertiles of QUS parameters [Broadband Ultrasound Attenuation (BUA), Speed of Sound (SOS), Stiffness Index (SI)], using data from the OsteoLaus cohort. Participants in the highest tertiles of QUS parameters (385 for BUA, 397 for SOS, 386 for SI) were younger, of higher body weight, and had less major osteoporotic fractures. Women in the highest tertiles of SI and BUA consumed more fat (35.1 ± 0.4 vs 33.9 ± 0.4 and 34.9 ± 0.4 vs 33.8 ± 0.4 gr/day for SI and BUA, respectively, p < 0.05), and complied less frequently with dairy intake guidelines [odds ratio (95% confidence interval): 0.70 (0.53-0.92) and 0.72 (0.55-0.95) for SI and BUA, respectively, p < 0.05] than women in the lowest tertile. No differences were found regarding dietary patterns, healthy dietary scores, or compliance to dietary guidelines. Postmenopausal women in the highest QUS tertiles were younger, of higher weight and BMI, consumed more monounsaturated fatty acids and less dairy and calcium than women in the lowest tertiles. No differences were found between QUS tertiles regarding dietary patterns.

Levels of persistent organic pollutants (POPs) and the role of anthropic subsidies in the diet of avian scavengers tracked by stable isotopes.

Persistent Organic Pollutants (POPs) have been identified as a significant factor driving declines in wildlife populations. These contaminants exhibit a dual tendency to biomagnify up the food chains and persist within tissues, rendering long-lived vertebrates, such as raptors, highly vulnerable to their adverse effects. We assessed the concentrations of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in fledglings of two vulture species, the Egyptian vulture (Neophron percnopterus) and the griffon vulture (Gyps fulvus), coexisting in northern Spain. Vultures, currently facing a severe threat with a population decline exceeding 90%, represent one of the most critically endangered avian groups in the Old World. Despite this critical situation, there remains a scarcity of research examining the intricate relationship between contaminant levels and individual foraging behaviors. In parallel, we analyzed stable isotope levels (δ15N and δ13C) in fledgling's feathers and prey hair to determine the association between individual dietary and contaminant burdens. Our findings revealed higher levels of PCBs in Egyptian vultures, while pesticide concentrations remained very similar between focal species. Furthermore, higher individual values of δ13C, indicating a diet based on intensive farming carcasses and landfills, were associated with higher levels of PCBs. While the levels of POPs found do not raise immediate alarm, the presence of individuals with unusually high values reveals the existence of accessible contamination sources in the environment for avian scavengers. The increasing reliance of these birds on intensive livestock farming and landfills, due to the decline of extensive livestock farming, necessitates long-term monitoring of potential contaminant effects on their populations.

Atypical depression and alcohol misuse are related to the cardiovascular risk in the general population.

OBJECTIVE: The aims of the present study were to assess the associations between mood, anxiety and substance use disorders, including their subtypes, and the prevalence of cardiovascular risk factors (CVRFs). METHOD: Thorough physical investigations, biological measures and standardized interview techniques were used to assess 3716 subjects of an urban area, aged 35-66 years. RESULTS: Atypical depression was associated with increased prevalence of overweight, diabetes and the metabolic syndrome (OR = 1.5, 95% C.I. 1.1-2.0; OR = 2.0, 95% C.I. 1.1-3.5, OR = 1.6, 95% C.I. 1.0-2.4 respectively), whereas decreased prevalence of overweight was found in melancholic (OR = 0.7, 95% C.I. 0.6-0.9) and unspecified depression (OR = 0.8, 95% C.I. 0.7-1.0). Alcohol abuse was associated with diabetes (OR = 1.8, 95% C.I. 1.1-2.9) and dyslipidemia (OR = 1.3, 95% C.I. 1.0-1.8), alcohol dependence with dyslipidemia only (OR = 1.4, 95% C.I. 1.0-2.0). Almost all mental disorders were associated with a lifetime history of regular cigarette smoking, and atypical depression, alcohol misuse and drug dependence were associated with inactivity. CONCLUSION: To conclude results emphasize the need to subtype depression and to pay particular attention to the atypical subtype. Comorbid alcohol misuse may further increase the cardiovascular risk. Efforts to diminish smoking in subjects with mental disorders could be crucial measures to reduce their high incidence of cardiovascular disease.

The relation of body mass index and abdominal adiposity with dyslipidemia in 27 general populations of the WHO MONICA Project.

BACKGROUND AND AIMS: The association between adiposity measures and dyslipidemia has seldom been assessed in a multipopulational setting. METHODS AND RESULTS: 27 populations from Europe, Australia, New Zealand and Canada (WHO MONICA project) using health surveys conducted between 1990 and 1997 in adults aged 35-64 years (n = 40,480). Dyslipidemia was defined as the total/HDL cholesterol ratio >6 (men) and >5 (women). Overall prevalence of dyslipidemia was 25% in men and 23% in women. Logistic regression showed that dyslipidemia was strongly associated with body mass index (BMI) in men and with waist circumference (WC) in women, after adjusting for region, age and smoking. Among normal-weight men and women (BMI<25 kg/m(2)), an increase in the odds for being dyslipidemic was observed between lowest and highest WC quartiles (OR = 3.6, p < 0.001). Among obese men (BMI ≥ 30), the corresponding increase was smaller (OR = 1.2, p = 0.036). A similar weakening was observed among women. Classification tree analysis was performed to assign subjects into classes of risk for dyslipidemia. BMI thresholds (25.4 and 29.2 kg/m(2)) in men and WC thresholds (81.7 and 92.6 cm) in women came out at first stages. High WC (>84.8 cm) in normal-weight men, menopause in women and regular smoking further defined subgroups at increased risk. CONCLUSION: standard categories of BMI and WC, or their combinations, do not lead to optimal risk stratification for dyslipidemia in middle-age adults. Sex-specific adaptations are necessary, in particular by taking into account abdominal obesity in normal-weight men, post-menopausal age in women and regular smoking in both sexes.

[Dysmetabolic hyperferritinemia: a new target for treatment?]. / Hyperferritinémie associée au syndrome métabolique: une nouvelle cible thérapeutique?

Dysmetabolic hyperferritinemia is currently the most frequent cause of elevated ferritin levels in the general population. Whether dysmetabolic hyperferritinemia is a cause or an effect of insulin resistance is still a matter of debate. Still, several findings have been well established: increased iron intake or elevated ferritin levels are individual risk factors for diabetes, metabolic syndrome or gestational diabetes. When in presence of dysmetabolic hyperferritinemia, a small number of randomized controlled trials have suggested that therapeutic measures aimed at reducing ferritin levels such as low red meat consumption, deferoxamin or therapeutic phlebotomies have shown a beneficial effect on glucose homeostasis, lipid profile and impaired hepatic markers observed in non-alcoholic steatohepatitis.