Genome-Wide Association to Body Mass Index and Waist Circumference: The Framingham Heart Study 100K Project

BACKGROUND: Obesity is related to multiple cardiovascular disease (CVD) risk factors as well as CVD and has a strong familial component. We tested for association between SNPs on the Affymetrix 100K SNP GeneChip and measures of adiposity in the Framingham Heart Study. METHODS: A total of 1341 Framingham Heart Study participants in 310 families genotyped with the Affymetrix 100K SNP GeneChip had adiposity traits measured over 30 years of follow up. Body mass index (BMI), waist circumference (WC), weight change, height, and radiographic measures of adiposity (subcutaneous adipose tissue, visceral adipose tissue, waist circumference, sagittal height) were measured at multiple examination cycles. Multivariable-adjusted residuals, adjusting for age, age-squared, sex, smoking, and menopausal status, were evaluated in association with the genotype data using additive Generalized Estimating Equations (GEE) and Family Based Association Test (FBAT) models. We prioritized mean BMI over offspring examinations (1–7) and cohort examinations (10, 16, 18, 20, 22, 24, 26) and mean WC over offspring examinations (4–7) for presentation. We evaluated associations with 70,987 SNPs on autosomes with minor allele frequencies of at least 0.10, Hardy-Weinberg equilibrium p ≥ 0.001, and call rates of at least 80%. RESULTS: The top SNPs to be associated with mean BMI and mean WC by GEE were rs110683 (p-value 1.22*10-7) and rs4471028 (p-values 1.96*10-7). Please see for the complete set of results. We were able to validate SNPs in known genes that have been related to BMI or other adiposity traits, including the ESR1 Xba1 SNP, PPARG, and ADIPOQ. CONCLUSION: Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC.National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195); Atwood (R01 DK066241); National Institutes of Health National Center for Research Resources Shared Instrumentation grant (1S10RR163736-01A1

Hadronization dynamics from the spectral representation of the gauge invariant quark propagator

Using the spectral representation of the quark propagator we study the Dirac decomposition of the gauge invariant quark propagator, whose imaginary part describes the hadronization of a quark as this interacts with the vacuum. We then demonstrate the formal gauge invariance of the so-called jet mass, that is of the coefficient of the chiral-odd part of the gauge invariant propagator, that can be expressed in any gauge as the first moment of the chiral-odd quark spectral function. This is therefore revealed to be a \textit{bona fide} QCD observable encoding aspects of the dynamical mass generation in the QCD vacuum, and is furthermore experimentally measurable in specific twist-3 longitudinal-transverse asymmetries in DIS and in semi-inclusive electron-positron collisions. In light-like axial gauges, we also obtain a new sum rule for the spectral function associated with the gauge fixing vector. We finally present a gauge-dependent formula that connects the second moment of the chiral-even coefficient of the quark spectral function to invariant mass generation and final state rescattering in the hadronization of a quark. Finding twist-4 experimental observables sensitive to this quantity is left for future work.Comment: Contribution to DIS2023: XXX International Workshop on Deep-Inelastic Scattering and Related Subjects, Michigan State University, USA, 27-31 March 202

Benefits of Vine Leaf on Different Biological Systems

For centuries, the therapeutic benefits of grapes and other byproducts have been empirically used for medical purposes such as bleeding, pain, inflammation, nausea, diarrhea, gastroenteritis, or skin diseases. Moderated intake of the red wine improves parameters as blood lipids, endothelial dysfunction, platelet aggregation, and other risk factors for cardiovascular disease. However, few studies have been explored the potential benefits from vine byproducts. Vine leaves, a waste product from the vine, are also rich source of polyphenols and other therapeutic compounds. In this chapter, we explored the therapeutic properties from vine leaf in different biological systems

Sex and age specific effects of chromosomal regions linked to body mass index in the Framingham Study

BACKGROUND: Previously, we reported significant linkage of body mass index (BMI) to chromosomes 6 and 11 across six examinations, covering 28 years, of the Framingham Heart Study. These results were on all individuals available at each exam, thus the sample size varied from exam to exam. To remove any effect of sample size variation we have now constructed six subsets; for each exam individuals were only included if they were measured at every exam, i.e. for each exam, included individuals comprise the intersection of the original six exams. This strategy preferentially removed older individuals who died before reaching the sixth exam, thus the intersection datasets are smaller (n = 1114) and significantly younger than the full datasets. We performed variance components linkage analysis on these intersection datasets and on their sex-specific subsets. RESULTS: Results from the sex-specific genome scans revealed 11 regions in which a sex-specific maximum lodscore was at least 2.0 for at least one dataset. Randomization tests indicated that all 11 regions had significant (p < 0.05) differences in sex-specific maximum lodscores for at least three datasets. The strongest sex-specific linkage was for men on chromosome 16 with maximum lodscores 2.70, 3.00, 3.42, 3.61, 2.56 and 1.93 for datasets 1–6 respectively. Results from the full genome scans revealed that linked regions on chromosomes 6 and 11 remained significantly and consistently linked in the intersection datasets. Surprisingly, the maximum lodscore on chromosome 10 for dataset 1 increased from 0.97 in the older original dataset to 4.23 in the younger smaller intersection dataset. This difference in maximum lodscores was highly significant (p < 0.0001), implying that the effect of this chromosome may vary with age. Age effects may also exist for the linked regions on chromosomes 6 and 11. CONCLUSION: Sex specific effects of chromosomal regions on BMI are common in the Framingham study. Some evidence also exists for age-specific effects of chromosomal regions

Changes in serum adipokines during natural extended fasts in female northern elephant seals

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Rzucidlo, C. L., Sperou, E. S., Holser, R. R., Khudyakov, J., Costa, D. P., & Crocker, D. E. Changes in serum adipokines during natural extended fasts in female northern elephant seals. General and Comparative Endocrinology, 308, (2021): 113760, https://doi.org/10.1016/j.ygcen.2021.113760.Adipose tissue is essential to endotherms for thermoregulation and energy storage as well as functioning as an endocrine organ. Adipose derived hormones, or adipokines, regulate metabolism, energy expenditure, reproduction, and immune function in model systems but are less well studied in wildlife. Female northern elephant seals (NES) achieve high adiposity during foraging and then undergo natural fasts up to five weeks long during haul-outs associated with reproduction and molting, resulting in large changes in adipose reserves. We measured circulating levels of four adipokines: leptin, resistin, adiponectin, and kisspeptin-54, in 196 serum samples from female NES at the beginning and end of their breeding and molting fasts. We examined the relationships between these adipokines and life-history stage, adiposity, mass, cortisol, and an immune cytokine involved in the innate immune response interleukin 6 (IL-6). All four adipokines varied with life-history stage. Leptin concentrations were highest at the beginning of the breeding haul-out. Resistin concentrations were higher throughout the breeding haul-out compared to the molt haul-out. Adiponectin concentrations were highest at the beginning of both haul-outs. Kisspeptin-54 concentrations were highest at the end of the breeding haul-out. Leptin, resistin, and adiponectin were associated with measures of body condition, either adiposity, mass, or both. Resistin, adiponectin, and kisspeptin-54 were associated with circulating cortisol concentrations. Resistin was strongly associated with circulating IL-6, a multifunctional cytokine. Adiponectin was associated with glucose concentrations, suggesting a potential role in tissue-specific insulin sensitivity during life-history stages categorized by high adiposity. Increased cortisol concentrations late in lactation were associated with increased kisspeptin-54, suggesting a link to ovulation initiation in NES. This study suggests dramatic changes in circulating adipokines with life-history and body condition that may exert important regulatory roles in NES. The positive relationship between adiponectin and adiposity as well as the lack of a relationship between leptin and kisspeptin-54 differed from model systems. These differences from biomedical model systems suggest the potential for modifications of expression and function of adipose-derived hormones in species that undergo natural changes in adiposity as part of their life-history.This project was supported by a grant from the Office of Naval Research (#N00014-18-1-2822) to DPC and DEC and the Marine Life Joint Industry Program of the IAGOP. We thank the Año Nuevo State Reserve rangers for logistical support

Reinterpretando a Lei de lavagem de dinheiro: sob a ótica da jurisprudência do Supremo Tribunal Federal

- Divulgação dos SUMÁRIOS das obras recentemente incorporadas ao acervo da Biblioteca Ministro Oscar Saraiva do STJ. Em respeito à Lei de Direitos Autorais, não disponibilizamos a obra na íntegra.- Localização na estante: 343.72(81) C837

Acute and chronic bovine pulmonary edema and emphysema in Uruguay

An outbreak of pulmonary edema and emphysema with acute and chronic cases is reported in a farm in Uruguay. In a herd of 40 Hereford steers, 20 died. The deaths began four days after a change of paddock, from an old pasture of Avena sativa to a lush growing pasture of the same grass. Acutely affected animals showed severe dyspnea, sialorrhea, cough, and subcutaneous edema, and died within 72 hours. Chronically affected steers showed dyspnea, respiratory noises, weight loss, and intolerance to exercise. The deaths began four days after the change of paddock. Ten days after the first death, the steers were withdrawn from the pasture, but continued dying throughout the following 40 days. Twenty animals died and six were necropsied. Grossly, the lungs were diffusely armed and glistening, with reddish and crepitant cut surface, and presented alveolar septae sharply distended by edema and emphysema. There was subpleural emphysema with air blebs distributed across the pleural surface. Presence of Dictyocaulus viviparus was observed in three steers. In some animals, the trachea was diffusely reddish with presence of pink foam; in some others, there was bloody liquid in the tracheal lumen. Histologic examination showed severe diffuse alveolar and interstitial emphysema, hyaline membranes adhered to the alveolar wall, thickening of the interlobular septae with proliferation of type II pneumocytes, and moderate-to-severe multifocal histiocytic, neutrophilic and eosinophilic infiltrate. In the trachea, there was submucosal hemorrhage and moderate multifocal eosinophilic and lymphocytic infiltrate. The steers with chronic signs presented similar lung lesions, but multifocal pulmonary fibrosis and cardiac dilatation were also observed. The diagnosis of acute bovine pulmonary emphysema and edema (ABPE) was based on the occurrence of the disease after introduction of the herd in a lush green pasture, on the characteristic gross and histologic lesions, and on the absence of other toxic or infectious agents causing similar lesions. Cattle raisers should be alert to the risks of occurrence of this disease after the introduction of the herds into paddocks with green and lush pasture

Trends in the Association of Parental History of Obesity over 60 Years

Objective: The association of familial as compared to genetic factors in the current obesogenic environment, compared to earlier, leaner time periods, is uncertain. Design and Methods Participants from the Framingham Heart Study were classified according to parental obesity status in the Original, Offspring, and Third Generation cohorts; mean BMI levels were estimated and we compared the association of parental history across generations. Finally, a genetic risk score comprised of 32 well-replicated single nucleotide polymorphisms for BMI was examined in association with BMI levels in 1948, 1971, and 2002. Results: BMI was 1.49 kg/m2 higher per each affected parent among the Offspring, and increased to 2.09 kg/m2 higher among the Third Generation participants (p-value for the cohort comparison=0.007). Parental history of obesity was associated with increased weight gain (p<0.0001) and incident obesity (p=0.009). Despite a stronger association of parental obesity with offspring BMI in more contemporary time periods, we observed no change in the effect size of a BMI genetic risk score from 1948 to 2002 (p=0.11 for test of trend across the time periods). Conclusions: The association of parental obesity has become stronger in more contemporary time period, whereas the association of a BMI genetic risk score has not changed

Infant growth and body composition from birth to 24 months: Are infants developing the same?

Background: Given the importance of infancy for establishing growth trajectories, with later-life health consequences, we investigated longitudinal body composition among infants from six economically and ethnically diverse countries.Methods: We recruited mother-infant dyads using the WHO Multicenter Growth Reference Study criteria. We measured fat-free mass (FFM) in 1393 (49% female) infants from birth to 6 months of age (Australia, India, and South Africa; n = 468), 3-24 months of age (Brazil, Pakistan, South Africa, and Sri Lanka; n = 925), and derived fat mass (FM), fat mass index (FMI), and fat-free mass index (FFMI). Height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length (WHZ) Z-scores were computed. Sex differences were assessed using a t-test, and country differences using a one-way analysis of covariance. We further compared subsamples of children with average (-0.25 \u3e HAZ \u3c +0.25), below-average (≤-0.25) and above-average (≥+0.25) HAZ.Results: HAZ performed well between 0 and 6 months, but less so between 3 and 24 months. The stunting prevalence peaked at 10.3% for boys and 7.8% for girls, at 24 months. By 24 months, girls had greater FMI (10%) than boys. There were significant differences in FFM (both sexes in all countries) and FM (Brazilian boys, Pakistani and South African girls) by 24 months of age between infants with average, above-average, and below-average HAZ.Conclusion: In a multi-country sample representing more ideal maternal conditions, body composition was heterogeneous even among infants who exhibited ideal length. Having a mean HAZ close to the median of the WHO standard for length reduced FFM between-country heterogeneity but not FM, suggesting that other factors may influence adiposity

The specialty choices of graduates from Brighton and Sussex Medical School: a longitudinal cohort study

BACKGROUND Since 2007 junior doctors in the UK have had to make major career decisions at a point when previously many had not yet chosen a specialty. This study examined when doctors in this new system make specialty choices, which factors influence choices, and whether doctors who choose a specialty they were interested in at medical school are more confident in their choice than those doctors whose interests change post-graduation. METHODS Two cohorts of students in their penultimate year at one medical school (n = 227/239) were asked which specialty interested them as a career. Two years later, 210/227 were sent a questionnaire measuring actual specialty chosen, confidence, influence of perceptions of the specialty and experiences on choice, satisfaction with medicine, personality, self-efficacy, and demographics. Medical school and post-graduation choices in the same category were deemed 'stable'. Predictors of stability, and of not having chosen a specialty, were calculated using bootstrapped logistic regression. Differences between specialties on questionnaire factors were analysed. RESULTS 50% responded (n = 105/277; 44% of the 239 Year 4 students). 65% specialty choices were 'stable'. Factors univariately associated with stability were specialty chosen, having enjoyed the specialty at medical school or since starting work, having first considered the specialty earlier. A regression found doctors who chose psychiatry were more likely to have changed choice than those who chose general practice. Confidence in the choice was not associated with stability. Those who chose general practice valued lifestyle factors. A psychiatry choice was associated with needing a job and using one's intellect to help others. The decision to choose surgical training tended to be made early. Not having applied for specialty training was associated with being lower on agreeableness and conscientiousness. CONCLUSION Medical school experiences are important in specialty choice but experiences post-graduation remain significant, particularly in some specialties (psychiatry in our sample). Career guidance is important at medical school and should be continued post-graduation, with senior clinicians supported in advising juniors. Careers advice in the first year post-graduation may be particularly important, especially for specialties which have difficulty recruiting or are poorly represented at medical school