An analysis of DNA methylation in human adipose tissue reveals differential modification of obesity genes before and after gastric bypass and weight loss

Background Environmental factors can influence obesity by epigenetic mechanisms. Adipose tissue plays a key role in obesity-related metabolic dysfunction, and gastric bypass provides a model to investigate obesity and weight loss in humans. Results Here, we investigate DNA methylation in adipose tissue from obese women before and after gastric bypass and significant weight loss. In total, 485,577 CpG sites were profiled in matched, before and after weight loss, subcutaneous and omental adipose tissue. A paired analysis revealed significant differential methylation in omental and subcutaneous adipose tissue. A greater proportion of CpGs are hypermethylated before weight loss and increased methylation is observed in the 3′ untranslated region and gene bodies relative to promoter regions. Differential methylation is found within genes associated with obesity, epigenetic regulation and development, such as CETP, FOXP2, HDAC4, DNMT3B, KCNQ1 and HOX clusters. We identify robust correlations between changes in methylation and clinical trait, including associations between fasting glucose and HDAC4, SLC37A3 and DENND1C in subcutaneous adipose. Genes investigated with differential promoter methylation all show significantly different levels of mRNA before and after gastric bypass. Conclusions This is the first study reporting global DNA methylation profiling of adipose tissue before and after gastric bypass and associated weight loss. It provides a strong basis for future work and offers additional evidence for the role of DNA methylation of adipose tissue in obesity.

Weight and weight change following breast cancer : evidence from a prospective, population-based, breast cancer cohort study

Background: While weight gain following breast cancer is considered common, results supporting these findings are dated. This work describes changes in body weight following breast cancer over 72 months, compares weight with normative data and explores whether weight changes over time are associated with personal, diagnostic, treatment or behavioral characteristics. Methods: A population-based sample of 287 Australian women diagnosed with early-stage invasive breast cancer was assessed prospectively at six, 12, 18 and 72 months post-surgery. Weight was clinically measured and linear mixed models were used to explore associations between weight and participant characteristics (collected via self-administered questionnaire). Those with BMI changes of one or more units were considered to have experienced clinically significant changes in weight. Results: More than half (57%) of participants were overweight or obese at 6 months post-surgery, and by 72 months post-surgery 68% of women were overweight or obese. Among those who gained more weight than age-matched norms, clinically significant weight gain between 6 and 18 months and 6 and 72 months post-surgery was observed in 24% and 39% of participants, respectively (median [range] weight gain: 3.9kg [2.0-11.3kg] and 5.2kg [0.6-28.7], respectively). Clinically-significant weight losses were observed in up to 24% of the sample (median [range] weight loss between 6 and 72 months post-surgery: -6.4kg [-1.9--24.6kg]). More extensive lymph node removal, being treated on the non-dominant side, receiving radiation therapy and lower physical activity levels at 6 months was associated with higher body weights post-breast cancer (group differences >3kg; all p<0.05). Conclusions: While average weight gain among breast cancer survivors in the long-term is small, subgroups of women experience greater gains linked with adverse health and above that experienced by age-matched counterparts. Weight change post-breast cancer is a contemporary public health issue and the integration of healthy weight education and support into standard breast cancer care has potential to significantly improve the length and quality of cancer survivorship.

Relationships between maternal overweight prior to pregnancy, feeding mode and infant feeding beliefs and practices

Aim To examine whether pre-pregnancy weight status was associated with maternal feeding beliefs and practices in the early post-partum period. Methods Secondary analysis of longitudinal data from Australian mothers. Participants (N=486) were divided into two weight status groups based on self-reported pre-pregnancy weight and measured height: healthy weight (BMI <25kg/m2; n=321) and overweight (BMI>25kg/m2; n=165). Feeding beliefs and practices were self-reported via an established questionnaire that assessed concerns about infant overeating and undereating, awareness of infant cues, feeding to a schedule, and using food to calm. Results Infants of overweight mothers were more likely to have been given solid foods in the previous 24hrs (29% vs 20%) and fewer were fully breastfed (50% vs 64%). Multivariable regression analyses (adjusted for maternal education, parity, average infant weekly weight gain, feeding mode and introduction of solids) revealed pre-pregnancy weight status was not associated with using food to calm, concern about undereating, awareness of infant cues or feeding to a schedule. However feeding mode was associated with feeding beliefs and practices. Conclusions Although no evidence for a relationship between maternal weight status and early maternal feeding beliefs and practices was observed, differences in feeding mode and early introduction of solids was observed. The emergence of a relationship between feeding practices and maternal weight status may occur when the children are older, solid feeding is established and they become more independent in feeding.

Food neophobia and its association with diet quality and weight in children aged 24 months : a cross sectional study

Background Food neophobia, the rejection of unknown or novel foods, may result in poor dietary patterns. This study investigates the cross-sectional relationship between neophobia in children aged 24 months and variety of fruit and vegetable consumption, intake of discretionary foods and weight. Methods Secondary analysis of data from 330 parents of children enrolled in the NOURISH RCT (control group only) and SAIDI studies was performed using data collected at child age 24 months. Neophobia was measured at 24 months using the Child Food Neophobia Scale (CFNS). The cross-sectional associations between total CFNS score and fruit and vegetable variety, discretionary food intake and BMI (Body Mass Index) Z-score were examined via multiple regression models; adjusting for significant covariates. Results At 24 months, more neophobic children were found to have lower variety of fruits (β=-0.16, p=0.003) and vegetables (β=-0.29, p<0.001) but have a greater proportion of daily energy from discretionary foods (β=0.11, p=0.04). There was no significant association between BMI Z-score and CFNS score. Conclusions Neophobia is associated with poorer dietary quality. Results highlight the need for interventions to (1) begin early to expose children to a wide variety of nutritious foods before neophobia peaks and (2) enable health professionals to educate parents on strategies to overcome neophobia.

What determines weight loss behaviour and body weight satisfaction in Australia? Evidence from the HILDA survey

This thesis undertakes an empirical investigation to identify factors that influence the decision to undertake weight loss behaviour using the nationally representative HILDA dataset. Although many factors influenced the decision, the findings suggested that body weight satisfaction was the greatest determinant of weight loss dieting. This thesis therefore conducted a further empirical study to analyse the determinants of body weight satisfaction. A rank-hypothesis was found to better predict variation in body weight satisfaction levels than the absolute value of the individual's Body Mass Index (BMI) or the relative-norm hypothesis, which are commonly reported in the literature.

Estimation of inhaled ultrafine particle surface area dose for urban environments

There is considerable scientific interest in personal exposure to ultrafine particles. Owing to their small size, these particles are able to penetrate deep into the lungs, where they may cause adverse respiratory, pulmonary and cardiovascular health effects. This article presents Bayesian hierarchical models for estimating and comparing inhaled particle surface area in the lung.

Household food insecurity, diet, and weight status in a disadvantaged district of Ho Chi Minh City, Vietnam: A cross-sectional study

Background Food security exists when all people, at all times, have physical, economic and socially acceptable access to safe, sufficient, and adequately nutritious food in order to meet their dietary needs for an active and healthy life. For high income countries and those experiencing the nutrition transition, food security is not only about the quantity of available food but also the nutritional quality as related to over- and under-nutrition. Vietnam is currently undergoing this nutrition transition, and as a result the relationship between food insecurity, socio-demographic factors and weight status is complex. The primary objective of this study was to therefore measure the prevalence of household food insecurity in a disadvantaged urban district in Ho Chi Minh City (HCMC) in Vietnam using a more comprehensive tool. This study also aims to examine the relationships between food insecurity and socio-demographic factors, weight status, and food intakes. Methods A cross-sectional study was conducted using multi-stage sampling. Adults who were mainly responsible for cooking were interviewed in 250 households. Data was collected on socioeconomic and demographic factors using previously validated tools. Food security was assessed using the Latin American and Caribbean Household Food Security Scale (ELCSA) tool and households were categorized as food secure or mildly, moderately or severely food insecure. Questions regarding food intake were based on routinely used and validated questions in HCMC, weight status was self-reported. Results Cronbach’s alpha coefficient was 0.87, showing the ELCSA had a good internal reliability. Approximately 34.4% of households were food insecure. Food insecurity was inversely related to total household income (OR = 0.09, 95% CI = 0.04 - 0.22) and fruit intakes (OR = 2.2, 95% CI 1.31 - 4.22). There was no association between weight and food security status. Conclusions Despite rapid industrialization and modernization, food insecurity remains an important public health issue in large urban areas of HCMC, suggesting that strategies to address food insecurity should be implemented in urban settings, and not just rural locations. Fruit consumption among food insecure households may be compromised because of financial difficulties, which may lead to poorer health outcomes particularly related to non-communicable disease prevention and management.

Estimating the burden of disease attributable to childhood and maternal undernutrition in South Africa in 2000

OBJECTIVES To estimate the disease burden attributable to being underweight as an indicator of undernutrition in children under 5 years of age and in pregnant women for the year 2000. DESIGN World Health Organization comparative risk assessment (CRA) methodology was followed. The 1999 National Food Consumption Survey prevalence of underweight classified in three low weight-for-age categories was compared with standard growth charts to estimate population-attributable fractions for mortality and morbidity outcomes, based on increased risk for each category and applied to revised burden of disease estimates for South Africa in 2000. Maternal underweight, leading to an increased risk of intra-uterine growth retardation and further risk of low birth weight (LBW), was also assessed using the approach adopted by the global assessment. Monte Carlo simulation-modeling techniques were used for the uncertainty analysis. SETTING South Africa. SUBJECTS Children under 5 years of age and pregnant women. OUTCOME MEASURES Mortality and disability-adjusted life years (DALYs) from protein- energy malnutrition and a fraction of those from diarrhoeal disease, pneumonia, malaria, other non- HIV/AIDS infectious and parasitic conditions in children aged 0 - 4 years, and LBW. RESULTS Among children under 5 years, 11.8% were underweight. In the same age group, 11,808 deaths (95% uncertainty interval 11,100 - 12,642) or 12.3% (95% uncertainty interval 11.5 - 13.1%) were attributable to being underweight. Protein-energy malnutrition contributed 44.7% and diarrhoeal disease 29.6% of the total attributable burden. Childhood and maternal underweight accounted for 2.7% (95% uncertainty interval 2.6 - 2.9%) of all DALYs in South Africa in 2000 and 10.8% (95% uncertainty interval 10.2 - 11.5%) of DALYs in children under 5. CONCLUSIONS The study shows that reduction of the occurrence of underweight would have a substantial impact on child mortality, and also highlights the need to monitor this important indicator of child health.

Enhanced cortisol suppression following administration of low-dose dexamethasone in first-episode psychosis patients

OBJECTIVE Impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis and hyper-activity of this system have been described in patients with psychosis. Conversely, some psychiatric disorders such as post-traumatic stress disorder (PTSD) are characterised by HPA hypo-activity, which could be related to prior exposure to trauma. This study examined the cortisol response to the administration of low-dose dexamethasone in first-episode psychosis (FEP) patients and its relationship to childhood trauma. METHOD The low-dose (0.25 mg) Dexamethasone Suppression Test (DST) was performed in 21 neuroleptic-naive or minimally treated FEP patients and 20 healthy control participants. Childhood traumatic events were assessed in all participants using the Childhood Trauma Questionnaire (CTQ) and psychiatric symptoms were assessed in patients using standard rating scales. RESULTS FEP patients reported significantly higher rates of childhood trauma compared to controls (p = 0.001) and exhibited lower basal (a.m.) cortisol (p = 0.04) and an increased rate of cortisol hyper-suppression following dexamethasone administration compared to controls (33% (7/21) vs 5% (1/20), respectively; p = 0.04). There were no significant group differences in mean cortisol decline or percent cortisol suppression following the 0.25 mg DST. This study shows for the first time that a subset of patients experiencing their first episode of psychosis display enhanced cortisol suppression. CONCLUSIONS These findings suggest there may be distinct profiles of HPA axis dysfunction in psychosis which should be further explored.

Inhaled particle surface area dose: Stationary vs personal monitoring

The aim of this paper is to determine the suitability of solely stationary measurements for exposure assessment and management applications. For this purpose, quantified inhaled particle surface area (IPSA) doses using both stationary and personal particle exposure monitors were evaluated and compared.

Weight-related risk perception among healthy and overweight pregnant women: A cross-sectional study

Objective The objective of this study was to evaluate weight-related risk perception in early pregnancy and to compare this perception between women commencing pregnancy healthy weight and overweight. Study design Pregnant women (n=664) aged 29±5 (mean±s.d.) years were recruited from a metropolitan teaching hospital in Australia. A self-administered questionnaire was completed at around 16 weeks of gestation. Height measured at baseline and self-reported pre-pregnancy weight were used to calculate body mass index. Cross-sectional analysis was conducted. Differences between groups were assessed using chi-squared tests for categorical variables and t-tests or Mann–Whitney U tests for continuous variables depending on distribution. Result Excess gestational weight gain (GWG) during pregnancy was more important in leading to health problems for women or their child compared with pre-pregnancy weight. Personal risk perception for complications was low for all women, although overweight women had slightly higher scores than healthy-weight women (2.4±1.0 vs 2.9±1.0; P<0.001). All women perceived their risk for complications to be below that of an average pregnant woman. Conclusion Women should be informed of the risk associated with their pre-pregnancy weight (in the case of maternal overweight) and excess GWG. If efforts to raise risk awareness are to result in preventative action, this information needs to be accompanied by advice and appropriate support on how to reduce risk.

Suitability of diodes for point dose measurements in IMRT/VMAT beams

This study investigated a potential source of inaccuracy for diode measurements in modulated beams; the effect of diode housing asymmetry on measurement results. The possible effects of diode housing asymmetry on the measurement of steep dose gradients were evaluated by measuring 5x5 cm2 beam profiles, with three cylindrical diodes and two commonly used ionization chambers, with each dosimeter positioned in a 3D scanning water tank with its stem perpendicular to the beam axis (horizontal) and parallel to the direction of scanning. The resulting profiles were used to compare the penumbrae measured with the diode stem pointing into (equivalent to a “stem-first” setup) and out of the field (equivalent to a “stem-last” setup) in order to evaluate the effects of dosimeter alignment and thereby identify the effects of dosimeter asymmetry. The stem-first and stem-last orientations resulted in differences of up to 0.2 mm in the measured 20-80% penumbra widths and differences of up to 0.4 mm in the off axis position of the 90% isodose. These differences, which are smaller than previously reported for older model dosimeters, were apparent in the profile results for both diodes and small volume ionization chambers. As an extension to this study, the practical use of all five dosimeters was exemplified by measuring point doses in IMRT test beams. These measurements showed good agreement (within 2%) between the diodes and the small volume ionization chamber, with all of these dosimeters being able to identify a region 3% under-dosage which was not identified by a larger volume (6 mm diameter) ionization chamber. The results of this work should help to remove some of the barriers to the use of diodes for modulated radiotherapy dosimetry in the future.

Development of height-weight based equation for assessment of body composition in Sri Lankan children

Objective To develop a height and weight based equation to estimate total body water (TBW) in Sri Lankan children. Methods Cross sectional descriptive study done involving 5–15 year old healthy children. Height and weight were measured. TBW was assessed using isotope dilution method (D2O) and fat free mass (FFM) calculated. Multiple regression analysis was used to develop prediction equation and validated using PRESS statistical technique. Height, weight and sex code (male=1; female=0) were used as prediction variables. Results This study provides height and weight equation for the prediction of TBW in Sri Lankan children. To the best of our knowledge there are no published height weight prediction equations validated on South Asian populations. Conclusion Results of this study need to be affirmed by more studies on other closely related populations by using multicomponent body composition.

Exercise, Appetite Control, and Body Weight Regulation

Exercise has many health benefits and should be an effective weight loss strategy because it increases energy expenditure. However, the success of exercise in producing and sustaining weight loss is influenced by compensatory changes in energy intake and non-exercise activity, among other factors (see King et al. Obesity 15(6):1373–1383, 2007 for a detailed review). The aim of this chapter is to discuss the evidence describing the relationship between exercise and body weight regulation, with a particular focus on appetite control. Evidence is discussed which demonstrates that weight loss responses to exercise are highly variable between individuals. The mechanisms underlying the relationship between exercise, appetite and energy intake, and hence body weight are also discussed. Some people experience an increase in fasting hunger in response to 12 weeks of supervised exercise. However, this is offset by an increase in meal-related satiety in overweight and obese individuals. It is worth noting that weight loss should not be considered as the only successful outcome of an exercise program. Indeed, exercise, even in the absence of weight loss, is associated with numerous health benefits. Nevertheless, an improved understanding of compensatory responses to exercise is vital so that exercise can be more effectively used in weight management; such an understanding may assist us to devise strategies to sustain greater long-term participation in physical activity.

Molecular and functional characterizations of a Kunitz-type serine protease inhibitor FcKuSPI of the shrimp Fenneropenaeus chinensis

Serine proteinase inhibitors play important and diverse roles in biological processes such as coagulation, defense mechanisms, and immune responses. Here, we identified and characterized a Kunitz-type proteinase inhibitor, designated FcKuSPI, of the BPTI/Kunitz family of serine proteinase inhibitors from the hemocyte cDNA library of the shrimp Fenneropenaeus chinensis. The deduced amino acid sequence of FcKuSPI comprises 80 residues with a putative signal peptide of 15 amino acids. The predicted molecular weight of the mature peptide is 7.66 kDa and its predicted isoelectric point is 8.84. FcKuSPI includes a Kunitz domain containing six conserved cysteine residues that are predicted to form three disulfide bonds. FcKuSPI shares 44e53% homology with BPTI/Kunitz family members from other species. FcKuSPI mRNAwas expressed highly in the hemocytes and moderately in muscle in healthy shrimp. Recombinant FcKuSPI protein demonstrated anti-protease activity against trypsin and anticoagulant activity against citrated human plasma in a dose-dependent manner in in vitro assays.