FADD adaptor and PEA-15/ERK1/2 partners in major depression and schizophrenia postmortem brains: Basal contents and effects of psychotropic treatments.

Enhanced brain apoptosis (neurons and glia) may be involved in major depression (MD) and schizophrenia (SZ), mainly through the activation of the intrinsic (mitochondrial) apoptotic pathway. In the extrinsic death pathway, pro-apoptotic Fas-associated death domain (FADD) adaptor and its non-apoptotic p-Ser194 FADD form have critical roles interacting with other death regulators such as phosphoprotein enriched in astrocytes of 15kDa (PEA-15) and extracellular signal-regulated kinase (ERK). The basal status of FADD (protein and messenger RNA (mRNA)) and the effects of psychotropic drugs (detected in blood/urine samples) were first assessed in postmortem prefrontal cortex of MD and SZ subjects (including a non-MD/SZ suicide group). In MD, p-FADD, but not total FADD (and mRNA), was increased (26%, n=24; all MD subjects) as well as p-FADD/FADD ratio (a pro-survival marker) in antidepressant-free MD subjects (50%, n=10). In contrast, cortical FADD (and mRNA), p-FADD, and p-FADD/FADD were not altered in SZ brains (n=21) regardless of antipsychotic medications (except enhanced mRNA in treated subjects). Similar negative results were quantified in the non-MD/SZ suicide group. In MD, the regulation of multifunctional PEA-15 (i.e., p-Ser116 PEA-15 blocks pro-apoptotic FADD and PEA-15 prevents pro-survival ERK action) and the modulation of p-ERK1/2 were also investigated. Cortical p-PEA-15 was not changed whereas PEA-15 was increased mainly in antidepressant-treated subjects (16-20%). Interestingly, cortical p-ERK1/2/ERK1/2 ratio was reduced (33%) in antidepressant-free when compared to antidepressant-treated MD subjects. The neurochemical adaptations of brain FADD (increased p-FADD and pro-survival p-FADD/FADD ratio), as well as its interaction with PEA-15, could play a major role to counteract the known activation of the mitochondrial apoptotic pathway in MD.

Mutations in DNAH5 account for only 15% of a non-preselected cohort of patients with primary ciliary dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is characterised by recurrent infections of the upper respiratory airways (nose, bronchi, and frontal sinuses) and randomisation of left-right body asymmetry. To date, PCD is mainly described with autosomal recessive inheritance and mutations have been found in five genes: the dynein arm protein subunits DNAI1, DNAH5 and DNAH11, the kinase TXNDC3, and the X-linked retinitis pigmentosa GTPase regulator RPGR. METHODS: We screened 89 unrelated individuals with PCD for mutations in the coding and splice site regions of the gene DNAH5 by denaturing high performance liquid chromatography (DHPLC) and sequencing. Patients were mainly of European origin and were recruited without any phenotypic preselection. RESULTS: We identified 18 novel (nonsense, splicing, small deletion and missense) and six previously described mutations. Interestingly, these DNAH5 mutations were mainly associated with outer + inner dyneins arm ultrastructural defects (50%). CONCLUSION: Overall, mutations on both alleles of DNAH5 were identified in 15% of our clinically heterogeneous cohort of patients. Although genetic alterations remain to be identified in most patients, DNAH5 is to date the main PCD gene.

Seasonality of cardiovascular risk factors: an analysis including over 230 000 participants in 15 countries.

OBJECTIVE: To assess the seasonality of cardiovascular risk factors (CVRF) in a large set of population-based studies. METHODS: Cross-sectional data from 24 population-based studies from 15 countries, with a total sample size of 237 979 subjects. CVRFs included Body Mass Index (BMI) and waist circumference; systolic (SBP) and diastolic (DBP) blood pressure; total, high (HDL) and low (LDL) density lipoprotein cholesterol; triglycerides and glucose levels. Within each study, all data were adjusted for age, gender and current smoking. For blood pressure, lipids and glucose levels, further adjustments on BMI and drug treatment were performed. RESULTS: In the Northern and Southern Hemispheres, CVRFs levels tended to be higher in winter and lower in summer months. These patterns were observed for most studies. In the Northern Hemisphere, the estimated seasonal variations were 0.26 kg/m(2) for BMI, 0.6 cm for waist circumference, 2.9 mm Hg for SBP, 1.4 mm Hg for DBP, 0.02 mmol/L for triglycerides, 0.10 mmol/L for total cholesterol, 0.01 mmol/L for HDL cholesterol, 0.11 mmol/L for LDL cholesterol, and 0.07 mmol/L for glycaemia. Similar results were obtained when the analysis was restricted to studies collecting fasting blood samples. Similar seasonal variations were found for most CVRFs in the Southern Hemisphere, with the exception of waist circumference, HDL, and LDL cholesterol. CONCLUSIONS: CVRFs show a seasonal pattern characterised by higher levels in winter, and lower levels in summer. This pattern could contribute to the seasonality of CV mortality.

Prevalence of overweight in the Seychelles: 15 year trends and association with socio-economic status.

We assessed the 15-year trends in the distribution of body mass index (BMI) and the prevalence of overweight in the Seychelles (Indian Ocean, African Region) and the relationship with socio-economic status (SES). Three population-based examination surveys were conducted in 1989, 1994 and 2004. Occupation was categorized as 'labourer', 'intermediate' or 'professional'. Education was also assessed in 1994 and 2004. Between 1989 and 2004, mean BMI increased markedly in all sex and age categories (overall: 0.16 kg m(-2) per calendar year, which corresponds to 0.46 kg per calendar year). The prevalence of overweight (including obesity, BMI >or= 25 kg m(-2)) increased from 29% to 52% in men and from 50% to 67% in women. The prevalence of obesity (BMI >or= 30 kg m(-2)) increased from 4% to 15% in men and from 23% to 34% in women. Overweight was associated inversely with occupation in women and directly in men in all surveys. In multivariate analysis, overweight was associated similarly (direction and magnitude) to occupation and education. In conclusion, the increasing prevalence of overweight and obesity over time in all age, sex and SES categories suggests large-scale changes in societal obesogenic factors. The sex-specific association of SES with overweight suggests that prevention measures should be tailored accordingly.

Cardiorespiratory and Cardiac Autonomic Responses to 30-15 Intermittent Fitness Test in Team Sport Players

Buchheit, M, Al Haddad, H, Millet GP, Lepretre, PM, Newton, M, and Ahmaidi, S. Cardiorespiratory and cardiac autonomic responses to 30-15 Intermittent Fitness Test in team sport players. J Strength Cond Res 23(1): xxx-xxx, 2009-The 30-15 Intermittent Fitness Test (30-15IFT) is an attractive alternative to classic continuous incremental field tests for defining a reference velocity for interval training prescription in team sport athletes. The aim of the present study was to compare cardiorespiratory and autonomic responses to 30-15IFT with those observed during a standard continuous test (CT). In 20 team sport players (20.9 +/- 2.2 years), cardiopulmonary parameters were measured during exercise and for 10 minutes after both tests. Final running velocity, peak lactate ([La]peak), and rating of perceived exertion (RPE) were also measured. Parasympathetic function was assessed during the postexercise recovery phase via heart rate (HR) recovery time constant (HRRtau) and HR variability (HRV) vagal-related indices. At exhaustion, no difference was observed in peak oxygen uptake (&OV0312;o2peak), respiratory exchange ratio, HR, or RPE between 30-15IFT and CT. In contrast, 30-15IFT led to significantly higher minute ventilation, [La]peak, and final velocity than CT (p < 0.05 for all parameters). All maximal cardiorespiratory variables observed during both tests were moderately to well correlated (e.g., r = 0.76, p = 0.001 for &OV0312;o2peak). Regarding ventilatory thresholds (VThs), all cardiorespiratory measurements were similar and well correlated between the 2 tests. Parasympathetic function was lower after 30-15IFT than after CT, as indicated by significantly longer HHRtau (81.9 +/- 18.2 vs. 60.5 +/- 19.5 for 30-15IFT and CT, respectively, p < 0.001) and lower HRV vagal-related indices (i.e., the root mean square of successive R-R intervals differences [rMSSD]: 4.1 +/- 2.4 and 7.0 +/- 4.9 milliseconds, p < 0.05). In conclusion, the 30-15IFT is accurate for assessing VThs and &OV0312;o2peak, but it alters postexercise parasympathetic function more than a continuous incremental protocol.