Body composition and the brain: investigating life history trade-offs in living humans

The ‘expensive-tissue’ hypothesis of Aiello and Wheeler is well-known in anthropology for positing that an increasingly small gut was a key factor in the evolution of the large hominin brain. The insight that organs and tissues in the body compete for energy resources was also central to the ‘thrifty phenotype’ hypothesis of Hales and Barker, which proposed that nutritional stress in fetal life resulted in differential growth of the brain and pancreas. Both hypotheses are consistent with life history theory, which assumes that energy allocation trade-offs occur in energylimited environments. The prediction that somatic traits trade off against one another in the context of the body’s fixed energy budget has, however, yet to be rigorously tested in humans. The current thesis project aimed to fill this gap by recruiting 70 healthy young women and obtaining comprehensive, high-quality data on their brain and body composition. This included, specifically, measures of brain gray and white matter volume, fat mass, skeletal muscle mass, and volumes of the heart, liver, kidneys and spleen. Additional outcomes included resting energy expenditure and two proxies of early-life growth: birth weight, a marker of fetal weight gain, and tibia length, a marker of linear growth indexing postnatal experience. With these data, three principal hypotheses were tested: 1) there is variation in the energy expenditure of tissues and organs; 2) trade-offs are observed between brain and body organs/tissues; and 3) trade-off relationships are mediated by early-life growth. Results suggest the metabolic cost of organs and tissues is variable, and that the brain – in particular its gray matter component – trades off against lean tissues in the body (i.e. skeletal muscle, the liver and kidneys), but not fat mass. However, less support was found for the prediction that trade-offs are mediated by fetal and infant growth

Implications of leg length for metabolic health and fitness

BACKGROUND AND OBJECTIVES: Several studies have linked longer legs with favorable adult metabolic health outcomes and greater offspring birth weight. A recent Mendelian randomization study suggested a causal link between height and cardiometabolic risk; however, the underlying reasons remain poorly understood. METHODOLOGY: Using a cross-sectional design, we tested in a convenience sample of 70 healthy young women whether birth weight and tibia length as markers of early-life conditions associated more strongly with metabolically beneficial traits like organ size and skeletal muscle mass (SMM) than a statistically derived height-residual variable indexing later, more canalized growth. RESULTS: Consistent with the ‘developmental origins of health and disease’ hypothesis, we found relatively strong associations of tibia length—but not birth weight—with adult organ size, brain size, SMM and resting energy expenditure measured by magnetic resonance imaging (MRI), dual-energy X-ray absorptiometry and indirect calorimetry, respectively. CONCLUSIONS AND IMPLICATIONS: Building on prior work, these results suggest that leg length is a sensitive marker of traits directly impacting metabolic and reproductive health. Alongside findings in the same sample relating tibia length and height-residual to MRI-measured pelvic dimensions, we suggest there may exist a degree of coordination in the development of long bone, lean mass and pelvic traits, possibly centered on early, pre-pubertal growth periods. Such phenotypic coordination has important implications for fitness, serving to benefit both adult health and the health of offspring in subsequent generations

The Relationship Between Intermittent Limit Cycles and Postural Instability Associated with Parkinson’s Disease

Background: Many disease-specifc factors such as muscular weakness, increased muscle stiffness, varying postural strategies, and changes in postural refexes have been shown to lead to postural instability and fall risk in people with Parkinson’s disease (PD). Recently, analytical techniques, inspired by the dynamical systems perspective on movement control and coordination, have been used to examine the mechanisms underlying the dynamics of postural declines and the emergence of postural instabilities in people with PD. Methods: A wavelet-based technique was used to identify limit cycle oscillations (LCOs) in the anterior–posterior (AP) postural sway of people with mild PD (n = 10) compared to age-matched controls (n = 10). Participants stood on a foam and on a rigid surface while completing a dual task (speaking). Results: There was no signifcant difference in the root mean square of center of pressure between groups. Three out of 10 participants with PD demonstrated LCOs on the foam surface, while none in the control group demonstrated LCOs. An inverted pendulum model of bipedal stance was used to demonstrate that LCOs occur due to disease-specifc changes associated with PD: time-delay and neuromuscular feedback gain. Conclusion: Overall, the LCO analysis and mathematical model appear to capture the subtle postural instabilities associated with mild PD. In addition, these fndings provide insights into the mechanisms that lead to the emergence of unstable posture in patients with PD

Growth, body composition, and cardiovascular and nutritional risk of 5- to 10-y-old children consuming vegetarian, vegan, or omnivore diets.

BACKGROUND: Plant-based diets (PBDs) are increasingly recommended for human and planetary health. However, comprehensive evidence on the health effects of PBDs in children remains incomplete, particularly in vegans. OBJECTIVES: To quantify differences in body composition, cardiovascular risk, and micronutrient status of vegetarian and vegan children relative to omnivores and to estimate prevalence of abnormal micronutrient and cholesterol status in each group. METHODS: In a cross-sectional study, Polish children aged 5-10 y (63 vegetarian, 52 vegan, 72 matched omnivores) were assessed using anthropometry, deuterium dilution, DXA, and carotid ultrasound. Fasting blood samples, dietary intake, and accelerometry data were collected. RESULTS: All results are reported relative to omnivores. Vegetarians had lower gluteofemoral adiposity but similar total fat and lean mass. Vegans had lower fat indices in all regions but similar lean mass. Both groups had lower bone mineral content (BMC). The difference for vegetarians attenuated after accounting for body size but remained in vegans (total body minus the head: -3.7%; 95% CI: -7.0, -0.4; lumbar spine: -5.6%; 95% CI: -10.6, -0.5). Vegetarians had lower total cholesterol, HDL, and serum B-12 and 25-hydroxyvitamin D [25(OH)D] without supplementation but higher glucose, VLDL, and triglycerides. Vegans were shorter and had lower total LDL (-24 mg/dL; 95% CI: -35.2, -12.9) and HDL (-12.2 mg/dL; 95% CI: -17.3, -7.1), high-sensitivity C-reactive protein, iron status, and serum B-12 (-217.6 pmol/L; 95% CI: -305.7, -129.5) and 25(OH)D without supplementation but higher homocysteine and mean corpuscular volume. Vitamin B-12 deficiency, iron-deficiency anemia, low ferritin, and low HDL were more prevalent in vegans, who also had the lowest prevalence of high LDL. Supplementation resolved low B-12 and 25(OH)D concentrations. CONCLUSIONS: Vegan diets were associated with a healthier cardiovascular risk profile but also with increased risk of nutritional deficiencies and lower BMC and height. Vegetarians showed less pronounced nutritional deficiencies but, unexpectedly, a less favorable cardiometabolic risk profile. Further research may help maximize the benefits of PBDs in children

Estimating body mass and composition from proximal femur dimensions using dual energy x-ray absorptiometry.

Body mass prediction from the skeleton most commonly employs femoral head diameter (FHD). However, theoretical predictions and empirical data suggest the relationship between mass and FHD is strongest in young adults, that bone dimensions reflect lean mass better than body or fat mass and that other femoral measurements may be superior. Here, we generate prediction equations for body mass and its components using femoral head, neck and proximal shaft diameters and body composition data derived from dual-energy x-ray absorptiometry (DXA) scans of young adults (n = 155, 77 females and 78 males, mean age 22.7 ± 1.3 years) from the Andhra Pradesh Children and Parents Study, Hyderabad, India. Sex-specific regression of log-transformed data on femoral measurements predicted lean mass with smaller standard errors of estimate (SEEs) than body mass (12-14% and 16-17% respectively), while none of the femoral measurements were significant predictors of fat mass. Subtrochanteric mediolateral shaft diameter gave lower SEEs for lean mass in both sexes and for body mass in males than FHD, while FHD was a better predictor of body mass in women. Our results provide further evidence that lean mass is more closely related to proximal femur dimensions than body or fat mass and that proximal shaft diameter is a better predictor than FHD of lean but not always body mass. The mechanisms underlying these relationships have implications for selecting the most appropriate measurement and reference sample for estimating body or lean mass, which also depend on the question under investigation.This work was funded by a British Academy International Partnership and Mobility Scheme Grant to EP and VM, and a Leverhulme Trust/Isaac Newton Trust Early Career Fellowship to EP. The third survey wave of APCAPS data collection was supported by a Wellcome Trust Strategic Award (grant no. 084774) and subsidised access to DXA scan facilities given by the National Institute of Nutrition (Directors), Indian Council for Medical Research. TJC was funded by MRC grant MR/M012069/1

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Epigenetic Regulation of Tumor Suppressors by Helicobacter pylori Enhances EBV-Induced Proliferation of Gastric Epithelial Cells

Helicobacter pylori and Epstein-Barr virus (EBV) are two well-known contributors to cancer and can establish lifelong persistent infection in the host. This leads to chronic inflammation, which also contributes to development of cancer. Association with H. pylori increases the risk of gastric carcinoma, and coexistence with EBV enhances proliferation of infected cells. Further, H. pylori-EBV coinfection causes chronic inflammation in pediatric patients. We have established an H. pylori-EBV coinfection model system using human gastric epithelial cells. We showed that H. pylori infection can increase the oncogenic phenotype of EBV-infected cells and that the cytotoxin-associated gene (CagA) protein encoded by H. pylori stimulated EBV-mediated cell proliferation in this coinfection model system. This led to increased expression of DNA methyl transferases (DNMTs), which reprogrammed cellular transcriptional profiles, including those of tumor suppressor genes (TSGs), through hypermethylation. These findings provide new insights into a molecular mechanism whereby cooperativity between two oncogenic agents leads to enhanced oncogenic activity of gastric cancer cells

Estimating body mass and composition from proximal femur dimensions using dual energy x-ray absorptiometry.

Body mass prediction from the skeleton most commonly employs femoral head diameter (FHD). However, theoretical predictions and empirical data suggest the relationship between mass and FHD is strongest in young adults, that bone dimensions reflect lean mass better than body or fat mass and that other femoral measurements may be superior. Here, we generate prediction equations for body mass and its components using femoral head, neck and proximal shaft diameters and body composition data derived from dual-energy x-ray absorptiometry (DXA) scans of young adults (n = 155, 77 females and 78 males, mean age 22.7 ± 1.3 years) from the Andhra Pradesh Children and Parents Study, Hyderabad, India. Sex-specific regression of log-transformed data on femoral measurements predicted lean mass with smaller standard errors of estimate (SEEs) than body mass (12-14% and 16-17% respectively), while none of the femoral measurements were significant predictors of fat mass. Subtrochanteric mediolateral shaft diameter gave lower SEEs for lean mass in both sexes and for body mass in males than FHD, while FHD was a better predictor of body mass in women. Our results provide further evidence that lean mass is more closely related to proximal femur dimensions than body or fat mass and that proximal shaft diameter is a better predictor than FHD of lean but not always body mass. The mechanisms underlying these relationships have implications for selecting the most appropriate measurement and reference sample for estimating body or lean mass, which also depend on the question under investigation.This work was funded by a British Academy International Partnership and Mobility Scheme Grant to EP and VM, and a Leverhulme Trust/Isaac Newton Trust Early Career Fellowship to EP. The third survey wave of APCAPS data collection was supported by a Wellcome Trust Strategic Award (grant no. 084774) and subsidised access to DXA scan facilities given by the National Institute of Nutrition (Directors), Indian Council for Medical Research. TJC was funded by MRC grant MR/M012069/1

Prospective investigation of a PTSD personality typology among individuals with personality disorders

This study investigated the replicability of a previously proposed personality typology of posttraumatic stress disorder (PTSD, and explored stability of cluster membership over a 6-month period. Participants with current PTSD (n = 156) were drawn from the Collaborative Longitudinal Personality Disorders Study (CLPS). The CLPS project tracked a large sample of individuals who met criteria for 1 of 4 target diagnoses (borderline, schizotypal, avoidant, and obsessive-compulsive) and a contrast group of individuals who met criteria for depression but no personality disorder. A cluster analysis using scales from the Schedule of Nonadaptive and Adaptive Personality yielded 3 clusters: internalizing, externalizing, and low pathology. Using K-means cluster analysis, the results did not replicate previous work. Using Ward\u27s method, the hypothesized 3-cluster structure was confirmed at baseline but did not demonstrate temporal stability at 6 months. © 2012 Elsevier Inc