Association Between Alcohol Consumption and Blood Pressure Levels Among HIV Sero-Positive and Sero-Negative Cohorts: A Secondary Analysis of the Vukuzazzi Study.

BACKGROUND: The effect of hypertension is aggravated by lifestyle factors such as alcohol consumption. This study sought to determine the association between alcohol consumption and the level of blood pressures among HIV seronegative and seropositive cohorts. METHODS: This secondary analysis was performed on a cross-sectional survey data of 17 922 participants during the period between 2018 and 2020. A questionnaire was used to obtain participants' alcohol consumption history, which was categorized into non-alcohol consumers, non-heavy alcohol consumers, and heavy alcohol consumers. A linear regression model was used to establish relationships among participants with raised blood pressure (BP ≥ 140/90 mmHg). RESULTS: Out of the total participants, 3553 (19.82%) were hypertensives. Almost 13% of the hypertensives (n = 458; 12.89%) were undiagnosed, and 12.44 % (442) had uncontrolled hypertension. About 14.52% of the hypertensives (3553) were not on any antihypertensive medication. Male non-consumers of alcohol had the highest systolic and diastolic BP; uncontrolled systolic BP (165.53 ± 20.87 mmHg), uncontrolled diastolic BP (102.28 ± 19.21mmHg). Adjusted for covariates, moderate alcohol consumption was associated with HTN among participants who were HIV seropositive [unadjusted (RR = 1.772, P = .006, 95% CI (1.178-2.665)], [RR = 1.772, P = .005, 95% CI (1.187-2.64)]. [unadjusted RR = 1.876, P = .036, 95% CI (1.043-3.378)], adjusted RR = 1.876, P = .041, 95% CI (1.024-3.437). Both moderate and heavy alcohol consumption were significantly related to hypertension among HIV sero-negative [unadjusted model, moderate consumption RR = 1.534 P = .003, 95% CI (1.152-2.044)], [adjusted model, moderate alcohol consumption RR = 1.535, P = .006, 95% CI (1.132-2.080)], [unadjusted model, heavy alcohol consumption, RR = 2.480, P = .030, 95% CI (1.091-5.638)], [adjusted model RR = 2.480, P = .034, 95% CI (1.072-5.738)]. CONCLUSION: Alcohol consumption is significantly related to increase BP regardless of HIV infection.

Silhouette showcards confirm altered obesity-associated body image perception in international cohort study of African-origin populations.

OBJECTIVES: Given the increasing prevalence of obesity and need for effective interventions, there is a growing interest in understanding how an individual's body image can inform obesity prevention and management. This study's objective was to examine the use of silhouette showcards to measure body size perception compared with measured body mass index, and assess body size dissatisfaction, in three different African-origin populations spanning the epidemiological transition. An ancillary objective was to investigate associations between body size perception and dissatisfaction with diabetes and hypertension. SETTING: Research visits were completed in local research clinics in respective countries. PARTICIPANTS: Seven hundred and fifty-one African-origin participants from the USA and the Republic of Seychelles (both high-income countries), and Ghana (low/middle-income country). PRIMARY AND SECONDARY OUTCOME MEASURES: Silhouette showcards were used to measure perceived body size and body size dissatisfaction. Objectively measured body size was measured using a scale and stadiometer. Diabetes was defined as fasting blood glucose ≥126 mg/dL and hypertension was defined as ≥130 mm Hg/80 mm Hg. RESULTS: Most women and men from the USA and Seychelles had 'Perceived minus Actual weight status Discrepancy' scores less than 0, meaning they underestimated their actual body size. Similarly, most overweight or obese men and women also underestimated their body size, while normal weight men and women were accurately able to estimate their body size. Finally, participants with diabetes were able to accurately estimate their body size and similarly desired a smaller body size. CONCLUSIONS: This study highlights that overweight and obese women and men from countries spanning the epidemiological transition were unable to accurately perceive their actual body size. Understanding people's perception of their body size is critical to implementing successful obesity prevention programmes across the epidemiological transition.

Asymptomatic peripheral arterial disease in HIV patients in Ghana: A case-control study.

BACKGROUND: Peripheral arterial disease (PAD) is common in HIV patients and can be diagnosed noninvasively using the ankle-brachial index (ABI). The burden of PAD has not been investigated in Ghanaian HIV patients. We investigated the prevalence and risk factors associated with PAD in HIV patients at a periurban hospital in Ghana. METHODS: In a case-control design, ABI was measured in 158 cART-treated HIV patients, 150 cART-naïve HIV patients and 156 non-HIV controls with no clinical symptoms of CVDs. PAD was defined as ABI ≤ 0.9. A structured questionnaire was used to collect socio-demographic and clinical data. Fasting venous blood samples were collected to measure plasma levels of glucose, lipid profile, and CD4+ lymphocytes. RESULTS: The prevalence of PAD was 13.9% among cART-treated HIV patients, 21.3% among cART-naïve HIV patients, and 15.4% among non-HIV controls. Patients with PAD had increased odds of having low CD4+ cell counts [OR (95% CI) = 3.68 (1.41-12.85)]. In cART-treated HIV patients, those on TDF-based [5.76 (1.1-30.01), p = 0.038] and EFV-based [9.28 (1.51-57.12), p = 0.016] regimens had increased odds of having PAD. CONCLUSION: In our study population, there was no difference in the prevalence of PAD between cART-treated HIV patients compared to cART-naïve HIV patients or non-HIV controls. Having a low CD4 cell count and being on TDF- or EFV-based regimens were associated with an increased likelihood of having PAD.

Greater male variability in daily energy expenditure develops through puberty.

There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decreasing GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages.

Gut microbiota and fecal short chain fatty acids differ with adiposity and country of origin: the METS-microbiome study.

The relationship between microbiota, short chain fatty acids (SCFAs), and obesity remains enigmatic. We employ amplicon sequencing and targeted metabolomics in a large (n = 1904) African origin cohort from Ghana, South Africa, Jamaica, Seychelles, and the US. Microbiota diversity and fecal SCFAs are greatest in Ghanaians, and lowest in Americans, representing each end of the urbanization spectrum. Obesity is significantly associated with a reduction in SCFA concentration, microbial diversity, and SCFA synthesizing bacteria, with country of origin being the strongest explanatory factor. Diabetes, glucose state, hypertension, obesity, and sex can be accurately predicted from the global microbiota, but when analyzed at the level of country, predictive accuracy is only universally maintained for sex. Diabetes, glucose, and hypertension are only predictive in certain low-income countries. Our findings suggest that adiposity-related microbiota differences differ between low-to-middle-income compared to high-income countries. Further investigation is needed to determine the factors driving this association.

Gut microbiota and fecal short chain fatty acids differ with adiposity and country of origin: The METS-Microbiome Study.

The relationship between gut microbiota, short chain fatty acid (SCFA) metabolism, and obesity is still not well understood. Here we investigated these associations in a large (n=1904) African origin cohort from Ghana, South Africa, Jamaica, Seychelles, and the US. Fecal microbiota diversity and SCFA concentration were greatest in Ghanaians, and lowest in the US population, representing the lowest and highest end of the epidemiologic transition spectrum, respectively. Obesity was significantly associated with a reduction in SCFA concentration, microbial diversity and SCFA synthesizing bacteria. Country of origin could be accurately predicted from the fecal microbiota (AUC=0.97), while the predictive accuracy for obesity was inversely correlated to the epidemiological transition, being greatest in Ghana (AUC = 0.57). The findings suggest that the microbiota differences between obesity and non-obesity may be larger in low-to-middle-income countries compared to high-income countries. Further investigation is needed to determine the factors driving this association..

Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure.

Obesity is caused by a prolonged positive energy balance1,2. Whether reduced energy expenditure stemming from reduced activity levels contributes is debated3,4. Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor.

Gut microbiota and fecal short chain fatty acids differ with adiposity and country of origin: The METS-Microbiome Study.

The relationship between the gut microbiota, short chain fatty acid (SCFA) metabolism, and obesity remains unclear due to conflicting reports from studies with limited statistical power. Additionally, this association has rarely been explored in large scale diverse populations. Here, we investigated associations between fecal microbial composition, predicted metabolic potential, SCFA concentrations, and obesity in a large ( N = 1,934) adult cohort of African-origin spanning the epidemiologic transition, from Ghana, South Africa, Jamaica, Seychelles, and the United States (US). The greatest gut microbiota diversity and total fecal SCFA concentration was found in the Ghanaian population, while the lowest levels were found in the US population, respectively representing the lowest and the highest end of the epidemiologic transition spectrum. Country-specific bacterial taxa and predicted-functional pathways were observed, including an increased prevalence of Prevotella , Butyrivibrio , Weisella and Romboutsia in Ghana and South Africa, while Bacteroides and Parabacteroides were enriched in Jamaican and the US populations. Importantly, 'VANISH' taxa, including Butyricicoccus and Succinivibrio , were significantly enriched in the Ghanaian cohort, reflecting the participants' traditional lifestyles. Obesity was significantly associated with lower SCFA concentrations, a decrease in microbial richness, and dissimilarities in community composition, and reduction in the proportion of SCFA synthesizing bacteria including Oscillospira , Christensenella , Eubacterium , Alistipes , Clostridium and Odoribacter . Further, the predicted proportions of genes in the lipopolysaccharide (LPS) synthesis pathway were enriched in obese individuals, while genes associated with butyrate synthesis via the dominant pyruvate pathway were significantly reduced in obese individuals. Using machine learning, we identified features predictive of metabolic state and country of origin. Country of origin could accurately be predicted by the fecal microbiota (AUC = 0.97), whereas obesity could not be predicted as accurately (AUC = 0.65). Participant sex (AUC = 0.75), diabetes status (AUC = 0.63), hypertensive status (AUC = 0.65), and glucose status (AUC = 0.66) could all be predicted with different success. Interestingly, within country, the predictive accuracy of the microbiota for obesity was inversely correlated to the epidemiological transition, being greatest in Ghana (AUC = 0.57). Collectively, our findings reveal profound variation in the gut microbiota, inferred functional pathways, and SCFA synthesis as a function of country of origin. While obesity could be predicted accurately from the microbiota, the variation in accuracy in parallel with the epidemiological transition suggests that differences in the microbiota between obesity and non-obesity may be larger in low-to-middle countries compared to high-income countries. Further examination of independent study populations using multi-omic approaches will be necessary to determine the factors that drive this association.

Variation in human water turnover associated with environmental and lifestyle factors.

Water is essential for survival, but one in three individuals worldwide (2.2 billion people) lacks access to safe drinking water. Water intake requirements largely reflect water turnover (WT), the water used by the body each day. We investigated the determinants of human WT in 5604 people from the ages of 8 days to 96 years from 23 countries using isotope-tracking (2H) methods. Age, body size, and composition were significantly associated with WT, as were physical activity, athletic status, pregnancy, socioeconomic status, and environmental characteristics (latitude, altitude, air temperature, and humidity). People who lived in countries with a low human development index (HDI) had higher WT than people in high-HDI countries. On the basis of this extensive dataset, we provide equations to predict human WT in relation to anthropometric, economic, and environmental factors.

Variability in energy expenditure is much greater in males than females.

In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a cumulative effect if those traits mostly exhibit greater male variation, or a lack of greater male variation if many of them do not. Sex differences in energy expenditure variation have been little explored. We analyzed a large database on energy expenditure in adult humans (1494 males and 3108 females) to investigate whether humans have evolved sex differences in the degree of interindividual variation in energy expenditure. We found that, even when statistically comparing males and females of the same age, height, and body composition, there is much more variation in total, activity, and basal energy expenditure among males. However, with aging, variation in total energy expenditure decreases, and because this happens more rapidly in males, the magnitude of greater male variation, though still large, is attenuated in older age groups. Considerably greater male variation in both total and activity energy expenditure could be explained by greater male variation in levels of daily activity. The considerably greater male variation in basal energy expenditure is remarkable and may be explained, at least in part, by greater male variation in the size of energy-demanding organs. If energy expenditure is a trait that is of indirect interest to females when choosing a sexual partner, this would suggest that energy expenditure is under sexual selection. However, we present a novel energetics model demonstrating that it is also possible that females have been under stabilizing selection pressure for an intermediate basal energy expenditure to maximize energy available for reproduction.

Total energy expenditure is repeatable in adults but not associated with short-term changes in body composition.

Low total energy expenditure (TEE, MJ/d) has been a hypothesized risk factor for weight gain, but repeatability of TEE, a critical variable in longitudinal studies of energy balance, is understudied. We examine repeated doubly labeled water (DLW) measurements of TEE in 348 adults and 47 children from the IAEA DLW Database (mean ± SD time interval: 1.9 ± 2.9 y) to assess repeatability of TEE, and to examine if TEE adjusted for age, sex, fat-free mass, and fat mass is associated with changes in weight or body composition. Here, we report that repeatability of TEE is high for adults, but not children. Bivariate Bayesian mixed models show no among or within-individual correlation between body composition (fat mass or percentage) and unadjusted TEE in adults. For adults aged 20-60 y (N = 267; time interval: 7.4 ± 12.2 weeks), increases in adjusted TEE are associated with weight gain but not with changes in body composition; results are similar for subjects with intervals >4 weeks (N = 53; 29.1 ± 12.8 weeks). This suggests low TEE is not a risk factor for, and high TEE is not protective against, weight or body fat gain over the time intervals tested.

Utility of silhouette showcards to assess adiposity in three countries across the epidemiological transition.

The Pulvers' silhouette showcards provide a non-invasive and easy-to-use way of assessing an individual's body size perception using nine silhouette shapes. However, their utility across different populations has not been examined. This study aimed to assess: 1) the relationship between silhouette perception and measured anthropometrics, i.e., body mass index (BMI), waist circumference (WC), waist-height-ratio (WHtR), and 2) the ability to predict with silhouette showcards anthropometric adiposity measures, i.e., overweight and obesity (BMI ≥ 25 kg/m2), obesity alone (BMI ≥ 30 kg/m2), elevated WC (men ≥ 94 cm; women ≥ 80 cm), and WHtR (> 0.5) across the epidemiological transition. 751 African-origin participants, aged 20-68 years old, from the United States (US), Seychelles, and Ghana, completed anthropometrics and selected silhouettes corresponding to their perceived body size. Silhouette performance to anthropometrics was examined using a least-squares linear regression model. A receiver operator curve (ROC) was used to investigate the showcards ability to predict anthropometric adiposity measures. The relationship between silhouette ranking and BMI were similar between sexes of the same country but differed between countries: 3.65 [95% CI: 3.34-3.97] BMI units/silhouette unit in the US, 3.23 [2.93-3.74] in Seychelles, and 1.99 [1.72-2.26] in Ghana. Different silhouette cutoffs predicted obesity differently in the three countries. For example, a silhouette ≥ five had a sensitivity/specificity of 77.3%/90.6% to predict BMI ≥ 25 kg/m2 in the US, but 77.8%/85.9% in Seychelles and 84.9%/71.4% in Ghana. Ultimately, silhouettes predicted BMI, WC, and WHtR similarly within each country and sex but not across countries. Our data suggest that Pulvers' silhouette showcards may be a helpful tool to predict anthropometric and adiposity measures in different populations when direct measurement cannot be performed. However, no universal silhouette cutoff can be used for detecting overweight or obesity status, and population-specific differences may stress the need to calibrate silhouette showcards when using them as a survey tool in different countries.

Expression profile of tumour suppressor protein p53 and its regulator MDM2 in a cohort of breast cancer patients in a Tertiary Hospital in Ghana.

BACKGROUND: Inactivation or mutation of the tumour suppressor gene p53 or its regulator mouse double minute 2 (MDM2) is the commonest event in breast cancer. These altered genes usually express abnormally high levels of their proteins in many carcinomas. The phenotypic expression of p53 and MDM2 in breast cancer cases in our setting is not known. This study investigated the expression of the tumour suppressor protein p53 and its regulator MDM2, using immunohistochemistry in a Ghana breast cancer cohort. METHOD: A 9-year retrospective cross-sectional study on archived tissue blocks-formalin fixed paraffin embedded tissue (FFPE) was carried out. Demographic data were abstracted. Based on complete clinical data and availability of FFPE archived blocks 203 cases were selected for tissue micro array (TMA) construction. The TMA sections were subjected to immunohistochemistry (IHC) (ER, PR, HER2, p53, and MDM2). Expression of p53 and MDM2 were related to grade and molecular subtypes. RESULTS: The age ranged from 17 to 92 years (mean = 49.34 ± 13.74). Most of the cases were high grade; grade II (34.9%) and grade III (55.7%). Fifty-four percent of the cases were triple negative. Invasive ductal carcinoma no special type was the commonest histotype (87.1%). Thirty-six percent (36%) of the cases expressed p53. Significant associations were found between p53 overexpression and histological grade (p = 0.034), triple negative (p = 0.0333) and luminal B (p<0.01) tumors. Most cases (93.1%) were negative for MDM2 expression. Significant association was found between MDM2 and HER2 over-expression as well as Ki-67. There was no significant positive correlation between MDM2 and p53 co-expression (p>0.05). CONCLUSION: The elevated level of p53 expression in the aggressive breast cancer phenotypes (high histological grade and triple negative) in our cohort suggest that P53 elevation may be a poor prognostic marker in our setting. High expression of MDM2 in our cohort with high Ki67; also in cases with Her2/neu overexpression known with predictable poor prognosis in the absence of target therapy suggest MDM2 may be associated with aggressive biological behaviour in our breast cancer cases. The non-significant association of p53 and MDM2 expression in the same cases as also documented by previous studies suggest independent genetic pathway in tumourigenesis.

Gut microbiota alterations in response to sleep length among African-origin adults.

Sleep disorders are increasingly being characterized in modern society as contributing to a host of serious medical problems, including obesity and metabolic syndrome. Changes to the microbial community in the human gut have been reportedly associated with many of these cardiometabolic outcomes. In this study, we investigated the impact of sleep length on the gut microbiota in a large cohort of 655 participants of African descent, aged 25-45, from Ghana, South Africa (SA), Jamaica, and the United States (US). The sleep duration was self-reported via a questionnaire. Participants were classified into 3 sleep groups: short (<7hrs), normal (7-<9hrs), and long (≥9hrs). Forty-seven percent of US participants were classified as short sleepers and 88% of SA participants as long sleepers. Gut microbial composition analysis (16S rRNA gene sequencing) revealed that bacterial alpha diversity negatively correlated with sleep length (p<0.05). Furthermore, sleep length significantly contributed to the inter-individual beta diversity dissimilarity in gut microbial composition (p<0.01). Participants with both short and long-sleep durations exhibited significantly higher abundances of several taxonomic features, compared to normal sleep duration participants. The predicted relative proportion of two genes involved in the butyrate synthesis via lysine pathway were enriched in short sleep duration participants. Finally, co-occurrence relationships revealed by network analysis showed unique interactions among the short, normal and long duration sleepers. These results suggest that sleep length in humans may alter gut microbiota by driving population shifts of the whole microbiota and also specific changes in Exact Sequence Variants abundance, which may have implications for chronic inflammation associated diseases. The current findings suggest a possible relationship between disrupted sleep patterns and the composition of the gut microbiota. Prospective investigations in larger and more prolonged sleep researches and causally experimental studies are needed to confirm these findings, investigate the underlying mechanism and determine whether improving microbial homeostasis may buffer against sleep-related health decline in humans.

Physical activity and fat-free mass during growth and in later life.

BACKGROUND: Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass. OBJECTIVES: A study is presented of the association between FFM and physical activity in relation to age. METHODS: In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3-96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical activity level (PAL = TEE/REE), and calculation of FFM from isotope dilution. RESULTS: PAL was a main determinant of body composition at all ages. Models with age, fat mass (FM), and PAL explained 76% and 85% of the variation in FFM in females and males < 18 y old, and 32% and 47% of the variation in FFM in females and males ≥ 18 y old, respectively. In participants < 18 y old, mean FM-adjusted FFM was 1.7 kg (95% CI: 0.1, 3.2 kg) and 3.4 kg (95% CI: 1.0, 5.6 kg) higher in a very active participant with PAL = 2.0 than in a sedentary participant with PAL = 1.5, for females and males, respectively. At age 18 y, height and FM-adjusted FFM was 3.6 kg (95% CI: 2.8, 4.4 kg) and 4.4 kg (95% CI: 3.2, 5.7 kg) higher, and at age 80 y 0.7 kg (95% CI: -0.2, 1.7 kg) and 1.0 kg (95% CI: -0.1, 2.1 kg) higher, in a participant with PAL = 2.0 than in a participant with PAL = 1.5, for females and males, respectively. CONCLUSIONS: If these associations are causal, they suggest physical activity is a major determinant of body composition as reflected in peak FFM, and that a physically active lifestyle can only partly protect against loss of FFM in aging adults.

Consumption of Monounsaturated Fatty Acids Is Associated with Improved Cardiometabolic Outcomes in Four African-Origin Populations Spanning the Epidemiologic Transition.

Long-chain omega-3 PUFAs, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are of increasing interest because of their favorable effect on cardiometabolic risk. This study explores the association between omega 6 and 3 fatty acids intake and cardiometabolic risk in four African-origin populations spanning the epidemiological transition. Data are obtained from a cohort of 2500 adults aged 25-45 enrolled in the Modeling the Epidemiologic Transition Study (METS), from the US, Ghana, Jamaica, and the Seychelles. Dietary intake was measured using two 24 h recalls from the Nutrient Data System for Research (NDSR). The prevalence of cardiometabolic risk was analyzed by comparing the lowest and highest quartile of omega-3 (EPA+ DHA) consumption and by comparing participants who consumed a ratio of arachidonic acid (AA)/EPA + DHA ≤4:1 and >4:1. Data were analyzed using multiple variable logistic regression adjusted for age, gender, activity, calorie intake, alcohol intake, and smoking status. The lowest quartile of EPA + DHA intake is associated with cardiometabolic risk 2.16 (1.45, 3.2), inflammation 1.59 (1.17, 2.16), and obesity 2.06 (1.50, 2.82). Additionally, consuming an AA/EPA + DHA ratio of >4:1 is also associated with cardiometabolic risk 1.80 (1.24, 2.60), inflammation 1.47 (1.06, 2.03), and obesity 1.72 (1.25, 2.39). Our findings corroborate previous research supporting a beneficial role for monounsaturated fatty acids in reducing cardiometabolic risk.

Energy compensation and adiposity in humans.

Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures.1-3 This suggestion has profound implications for both the evolution of metabolism and human health. It implies that a long-term increase in activity does not directly translate into an increase in total energy expenditure (TEE) because other components of TEE may decrease in response-energy compensation. We used the largest dataset compiled on adult TEE and basal energy expenditure (BEE) (n = 1,754) of people living normal lives to find that energy compensation by a typical human averages 28% due to reduced BEE; this suggests that only 72% of the extra calories we burn from additional activity translates into extra calories burned that day. Moreover, the degree of energy compensation varied considerably between people of different body compositions. This association between compensation and adiposity could be due to among-individual differences in compensation: people who compensate more may be more likely to accumulate body fat. Alternatively, the process might occur within individuals: as we get fatter, our body might compensate more strongly for the calories burned during activity, making losing fat progressively more difficult. Determining the causality of the relationship between energy compensation and adiposity will be key to improving public health strategies regarding obesity.

Daily energy expenditure through the human life course.

Total daily energy expenditure ("total expenditure") reflects daily energy needs and is a critical variable in human health and physiology, but its trajectory over the life course is poorly studied. We analyzed a large, diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 years. Total expenditure increased with fat-free mass in a power-law manner, with four distinct life stages. Fat-free mass-adjusted expenditure accelerates rapidly in neonates to ~50% above adult values at ~1 year; declines slowly to adult levels by ~20 years; remains stable in adulthood (20 to 60 years), even during pregnancy; then declines in older adults. These changes shed light on human development and aging and should help shape nutrition and health strategies across the life span.

The Analysis of bcl-2 in Association with p53 and Ki-67 in Triple Negative Breast Cancer and Other Molecular Subtypes in Ghana.

BACKGROUND: Little is known about the role of apoptosis in the tumorigenesis and prognosis of breast cancer in Ghana. Chemotherapeutic drug efficacy partially relates to apoptosis induction, rendering it a vital target in cancer therapy with unique biomarker opportunities that have not been exploited. Aberrations in this pathway are central to tumorigenesis, tumor progression, overall tumor growth, and regression during treatment therapies. Antiapoptotic bcl-2 (gene) and p53 are known to play roles in apoptosis while Ki-67 is a proliferative marker. The aim of our study is to determine the association of bcl-2 (protein) with p53 and Ki-67 in 203 consecutive breast cancer cases over a 10-year period. METHOD: A retrospective cross-sectional study on archival FFPE tissue blocks over a 9-year period with abstraction of clinicopathologic data. Two hundred and three consecutive and suitable FFPE blocks were selected for tissue microarray (TMA) construction, and IHC (bcl-2 (protein), Ki-67, p53, cyclin D, pan cytokeratins A and E, ER, PR, and HER2/neu) was done. Expressions of bcl-2 (protein), p53, and Ki-67 were related to histological grade, lymphovascular invasion, and molecular subtypes. SPSS version 23 was used to analyze results. RESULTS: Most of our cases were in the fifth decade of life (31%); invasive carcinoma of no special type (NST) was predominant (87%); histological grade III (38%) was the highest; and Luminal A (19.8%), Luminal B (9.9%), HER2 (16%), and TNBC (54.3%) constituted the molecular classes. bcl-2 expression was found in 38% of the cases. Our cases also showed mutation in p53 (36.7%) and ki-67 expression (62.5%). bcl-2 (protein) and p53 significantly correlated with Luminal B and TNBC (p < 0.01). Ki-67 also correlated significantly with Luminal A and B and HER2 overexpression (p < 0.01). Premenopausal age (40-49) and histological grade inversely correlated with bcl-2 (protein) expression. p53 statistically correlated with Ki-67 (p < 0.05). CONCLUSION: Our results show high expression of bcl-2 (protein) suggesting an important role of apoptosis in Ghanaian breast cancer cases. bcl-2 (protein), p53, and Ki-67 expressions emerged interdependently from this research and can thus be manipulated in prediction and prognosis of breast cancers in our setting.

A standard calculation methodology for human doubly labeled water studies.

The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The estimated rCO2 is sensitive to the dilution space ratio (DSR) of the two isotopes. Based on performance in validation studies, we propose a new equation based on a new estimate of the mean DSR. The DSR is lower at low body masses (<10 kg). Using data for 1,021 babies and infants, we show that the DSR varies non-linearly with body mass between 0 and 10 kg. Using this relationship to predict DSR from weight provides an equation for rCO2 over this size range that agrees well with indirect calorimetry (average difference 0.64%; SD = 12.2%). We propose adoption of these equations in future studies.