No abstract

Myalgic encephalomyelitis, also known as chronic fatigue syndrome or ME/CFS, is a multifactorial and debilitating disease that has an impact on over 4 million people in the United States alone. The pathogenesis of ME/CFS remains largely unknown; however, a genetic predisposition has been suggested. In the present study, we used a DNA single-nucleotide polymorphism (SNP) chip representing over 906,600 known SNPs to analyze DNA from ME/CFS subjects and healthy controls. To the best of our knowledge, this study represents the most comprehensive genome-wide association study (GWAS) of an ME/CFS cohort conducted to date. Here 442 SNPs were identified as candidates for association with ME/CFS (adjusted P-value<0.05). Whereas the majority of these SNPs are represented in non-coding regions of the genome, 12 SNPs were identified in the coding region of their respective gene. Among these, two candidate SNPs resulted in missense substitutions, one in a pattern recognition receptor and the other in an uncharacterized coiled-coil domain-containing protein. We also identified five SNPs that cluster in the non-coding regions of T-cell receptor loci. Further examination of these polymorphisms may help identify contributing factors to the pathophysiology of ME/CFS, as well as categorize potential targets for medical intervention strategies.

BackgroundDiet is the first line of treatment for elevated cholesterol. High-intensity dietary counseling (≥360 minutes/year of contact with providers) improves blood lipids, but is expensive and unsustainable in the current healthcare settings. Low-intensity counseling trials (≤ 30 minutes/year) have demonstrated modest diet changes, but no improvement in lipids. This pilot study evaluated the feasibility and the effects on lipids and diet of a low-intensity dietary counseling intervention provided by the primary care physician (PCP), in patients at risk for cardiovascular diseases.MethodsSix month study with a three month randomized-controlled phase (group A received the intervention, group B served as controls) followed by three months of intervention in both groups.Sixty-one adults age 21 to 75 years, with LDL-cholesterol ≥ 3.37 mmol/L, possessing Internet access and active email accounts were enrolled. Diet was evaluated using the Rate-Your-Plate questionnaire. Dietary counseling was provided by the PCP during routine office visits, three months apart, using printed educational materials and a minimally interactive counseling website. Weekly emails were sent reminding participants to use the dietary counseling resources. The outcomes were changes in LDL-cholesterol, other lipid subclasses, and diet quality.ResultsAt month 3, group A (counseling started at month 1) decreased their LDL-cholesterol by −0.23 mmol/L, (−0.04 to −0.42 mmol/L, P = 0.007) and total cholesterol by −0.26 mmol/L, (−0.05 to −0.47 mmol/L, P = 0.001). At month 6, total and LDL-cholesterol in group A remained better than in group B (counseling started at month 3). Diet score in group A improved by 50.3 points (38.4 to 62.2, P < 0.001) at month 3; and increased further by 11.8 (3.5 to 20.0, P = 0.007) at month 6. Group B made the largest improvement in diet at month 6, 55 points (40.0 to 70.1, P < 0.001), after having a small but significant improvement at month 3, 22.3 points (12.9 to 31.7, P < 0.001). No significant changes occurred in HDL-cholesterol in either group.ConclusionsA low-intensity dietary counseling provided by the PCP in patients at risk for cardiovascular diseases produced clinically meaningful improvements in both diet and lipids of magnitude similar to changes reported with high intensity interventions.Trial registrationClinicalTrials.gov: NCT01695837

Background We hypothesized that higher concentrations of LDL particles (LDL-P) and leptin, and lower concentrations of HDL particles (HDL-P), and total and high molecular weight (HMW) adiponectin, would predict incident coronary heart disease (CHD) among severely obese postmenopausal women. Methods In a case-cohort study nested in the Women’s Health Initiative Observational Study, we sampled 677 of the 1852 white or black women with body mass index (BMI) ≥40 kg/m2 and no prevalent cardiovascular disease (CVD), including all 124 cases of incident CHD over mean 5.0 year follow-up. Biomarkers were assayed on stored blood samples. Results In multivariable-adjusted weighted Cox models, higher baseline levels of total and small LDL-P, and lower levels of total and medium HDL-P, and smaller mean HDL-P size were significantly associated with incident CHD. In contrast, large HDL-P levels were inversely associated with CHD only for women without diabetes, and higher total and HMW adiponectin levels and lower leptin levels were associated with CHD only for women with diabetes. Higher total LDL-P and lower HDL-P were associated with CHD risk independently of confounders including CV risk factors and other lipoprotein measures, with adjusted HR (95%CIs) of 1.55(1.28, 1.88) and (0.70 (0.57, 0.85), respectively, and similar results for medium HDL-P. Conclusions Higher CHD risk among severely obese postmenopausal women is strongly associated with modifiable concentrations of LDL-P and HDL-P, independent of diabetes, smoking, hypertension, physical activity, BMI and waist circumference. General Significance Severely obese postmenopausal women should be considered high risk candidates for lipid lowering therapy.

Our analysis identified 89 SNPs that reach statistical significance (p < 1 × 10), some of which are associated with genes of biological pathways that influences dietary behavior; others are associated with genes previously linked to obesity and cardiometabolic disease as well as neuroimmune disease. This study, to the best of our knowledge, represents the first genetic screening of a cardiometabolically healthy, but significantly obese population.

The present work introduces the use of environmental sensors to assess indoor air quality (IAQ) in combination with human biometrics. The sensor array included temperature, relative humidity, carbon dioxide, and noise monitors. The array was used in a classroom as well as in a vehicle cabin to assess the carbon dioxide production rate of individuals in a closed ventilation environment. Analysis of carbon dioxide production allowed for the quantification of the average metabolic rate of the group of individuals in the classroom, and for one individual in the vehicle cabin. These results yielded a mere 5% difference from the values assessed using commercial metabolic rate instruments, and averaged values from epidemiological studies. The results presented in this work verify the feasibility of determining an individual's metabolic rate using passive environmental sensors; these same sensors are able to provide a metric of IAQ that helps characterize the safety of the environment in which the individual is present.

BackgroundWell-known risk factors for cognitive impairment are also associated with obesity. Research has highlighted genetic risk factors for obesity, yet the relationship of those risk factors with cognitive impairment is unknown. The objective of this study was to determine the associations between cognition, hypertension, diabetes, sleep-disordered breathing, and obesity. Genetic risk factors of obesity were also examined.MethodsThe sample consisted of 369 nondemented individuals aged 50 years or older from four community cohorts. Primary outcome measures included auditory verbal memory, as measured by the Rey Auditory Verbal Learning Test, and executive functioning, as measured by the Color–Word Interference Test of the Delis–Kaplan Executive Function System battery. Apnea–hypopnea index indicators were determined during standard overnight polysomnography. Statistical analyses included Pearson correlations and linear regressions.ResultsPoor executive function and auditory verbal memory were linked to cardiovascular risk factors, but not directly to obesity. Genetic factors appeared to have a small but measureable association to obesity.ConclusionA direct linkage between obesity and poor executive function and auditory verbal memory is difficult to discern, possibly because nonobese individuals may show cognitive impairment due to insulin resistance and the “metabolic syndrome”.

Weight disorders are strikingly prevalent globally and can contribute to a wide array of potentially fatal diseases spanning from type II diabetes to coronary heart disease. These disorders have a common cause: poor calorie balance. Since energy expenditure (EE) (kcal d−1) constitutes one half of the calorie balance equation (the other half being food intake), its measurement could be of great value to those suffering from weight disorders. A technique for contact free assessment of EE is presented, which only relies on CO2 concentration monitoring within a sealed office space, and assessment of carbon dioxide production rate (VCO2). Twenty healthy subjects were tested in a cross-sectional study to evaluate the performance of the aforementioned technique in measuring both resting EE (REE) and exercise EE using the proposed system (the ‘SmartPad’) and a U.S. Food and Drug Administration (FDA) cleared gold standard reference instrument for EE measurement. For VCO2 and EE measurements, the method showed a correlation slope of 1.00 and 1.03 with regression coefficients of 0.99 and 0.99, respectively, and Bland–Altman plots with a mean bias = −0.232% with respect to the reference instrument. Furthermore, two subjects were also tested as part of a proof-of-concept longitudinal study where EE patterns were simultaneously tracked with body weight, sleep, stress, and step counts using a smartwatch over the course of a month, to determine correlation between the aforementioned parameters and EE. Analysis revealed moderately high correlation coefficients (Pearson’s r) for stress (r average = 0.609) and body weight (r average = 0.597) for the two subjects. The new SmartPad method was demonstrated to be a promising technique for EE measurement under free-living conditions.