Familial Aggregation of Amount and Distribution of Subcutaneous Fat and Their Responses to Exercise Training in the HERITAGE Family Study

Objective: Investigate the familial aggregation of amount and distribution of subcutaneous fat and their changes in response to endurance training. Research Methods and Procedures: A total of 483 sedentary subjects from 99 nuclear families were recruited, trained for 20 weeks of exercising on cycle ergometers, and measured before and after training for the following indicators of subcutaneous fat and fat distribution: trunk fat (TRUNK = sum of abdominal, subscapular, suprailiac, and midaxillary skinfolds), extremity fat (EXTREM = sum of biceps, triceps, thigh, and calf skinfolds), subcutaneous fat (SF8 = sum of the eight skinfolds), the trunk to extremity skinfolds ratio adjusted for SF8 (TER) and waist girth adjusted for body mass index (WAIST). The familial aggregation of the age‐ and sex‐adjusted baseline phenotypes and their responses to training (Δ) after adjustment for the baseline values was investigated using a familial correlation model. Results: Significant familial aggregation was observed for all the phenotypes measured at baseline and for ΔTRUNK and ΔWAIST. Transmissibility estimates reached about 30% to 35% for TRUNK, EXTREM, and SF8 and 50% for TER and WAIST. The transmissibilities of the response phenotypes were lower, ranging from 0% for ΔWAIST to 21% for ΔTRUNK and the pattern of familial correlations suggested a greater within‐ than between‐generation resemblance in the response. Discussion: This study suggests that the amount and distribution of subcutaneous fat strongly aggregates in families, whereas the response to exercise training is characterized by a moderate and more complex pattern of familial resemblance. We conclude that familial/genetic factors are more important in determining the amount and distribution of subcutaneous fat than their responses to exercise training.     

Prevalence and Associated Factors for Dual Form of Malnutrition in Mother-Child Pairs at the Same Household in the Gaza Strip-Palestine

Background

In many developing countries nutritional, and epidemiological transitions are emerging into continuing undernutrition and escalating overnutrition, giving rise to the double burden of the malnutrition phenomenon.

Objectives

This study aims to determine the prevalence of the dual form of malnutrition (overweight mother/underweight child) in the same household and its associated factors in the Gaza Strip.

Methods

A total of 357 mother-child pairs from the same households were surveyed from three different geographical locations in the Gaza Strip, namely, El Remal urban area, Jabalia refugee camp, and Al Qarara rural area. The height and weight of mothers aged 18–50 years were measured, and their body mass index (BMI) was computed. The mothers were categorized according to the criterion of the World Health Organization (WHO) for BMI as overweight if they have a BMI ≥ 25 kg/m². Anthropometric indices were measured for children aged two to five years to classify the underweight children Z-score <-1.

Results

The results showed the prevalence of the dual form of malnutrition in the Gaza Strip was 15.7%, and its associated factors were child’s birth order (OR_adj, 1.50, 95% CL, 1.22, 1.82; p = <0.001), father’s educational (low or medium) levels (OR_adj, 3.19, 95% CL, 1.07, 9.5; p = 0. 036), or (OR_adj, 3.4, 95% CL, 1.12, 10.37; p = 0. 031), high scores of mothers'' nutrition knowledge (OR_adj, 1.23, 95% CL, 1.01, 1.52; p = 0. 048), and low monthly income (OR_adj, 0.28, 95% CL, 0.09, 0.88; p = 0. 030).

Conclusions

The results from this study showed the dual form of malnutrition in the same household was prevalent in the Gaza Strip. This is a public health issue that must be understood and addressed and policy makers must implement an appropriate nutrition action plan to control dual form of malnutrition based on the underlying specific risk factors in the study population. In addition, interventions are needed to help individuals to translate their nutrition knowledge into healthy dietary behaviors.     

Assessing Body Composition among 3‐ to 8‐Year‐Old Children: Anthropometry,BIA, and DXA

Objective: To examine the inter‐relationships of body composition variables derived from simple anthropometry [BMI and skinfolds (SFs)], bioelectrical impedance analysis (BIA), and dual energy x‐ray (DXA) in young children. Research Methods and Procedures: Seventy‐five children (41 girls, 34 boys) 3 to 8 years of age were assessed for body composition by the following methods: BMI, SF thickness, BIA, and DXA. DXA served as the criterion measure. Predicted percentage body fat (%BF), fat‐free mass (FFM; kilograms), and fat mass (FM; kilograms) were derived from SF equations [Slaughter (SL)1 and SL2, Deurenberg (D) and Dezenberg] and BIA. Indices of truncal fatness were also determined from anthropometry. Results: Repeated measures ANOVA showed significant differences among the methods for %BF, FFM, and FM. All methods, except the D equation (p = 0.08), significantly underestimated measured %BF (p < 0.05). In general, correlations between the BMI and estimated %BF were moderate (r = 0.61 to 0.75). Estimated %BF from the SL2 also showed a high correlation with DXA %BF (r = 0.82). In contrast, estimated %BF derived from SFs showed a low correlation with estimated %BF derived from BIA (r = 0.38); likewise, the correlation between DXA %BF and BIA %BF was low (r = 0.30). Correlations among indicators of truncal fatness ranged from 0.43 to 0.98. Discussion: The results suggest that BIA has limited utility in estimating body composition, whereas BMI and SFs seem to be more useful in estimating body composition during the adiposity rebound. However, all methods significantly underestimated body fatness as determined by DXA, and, overall, the various methods and prediction equations are not interchangeable.     

Bioelectrical impedance underestimates total and truncal fatness in abdominally obese women

Objective: To compare estimates of total and truncal fatness from eight‐electrode bioelectrical impedance analysis equipment (BIA₈) with those from DXA in centrally obese women. The secondary aim was to examine BMI and waist circumference (WC) as proxy measures for percentage total body fat (%TBF) and truncal body fat percentage (tr%BF). Research Methods and Procedures: This was a cross‐sectional study of 136 women (age, 48.1 ± 7.7 years; BMI, 30.4 ± 2.9 kg/m²; %TBF_DXA, 46.0 ± 3.7%; WC, 104 ± 8 cm). Fatness was measured by DXA and Tanita BC‐418 equipment (Tanita Corp., Tokyo, Japan). Agreement among methods was assessed by Bland‐Altman plots, and regression analysis was used to evaluate anthropometric measures as proxies for total and abdominal fatness. Results: The percentage of overweight subjects was 41.9%, whereas 55.9% of the subjects were obese, as defined by BMI, and all subjects had a WC exceeding the World Health Organization cut‐off point for abdominal obesity. Compared with DXA, the BIA₈ equipment significantly underestimated total %BF (?5.0; ?3.6 to ?8.5 [mean; 95% confidence interval]), fat mass (?3.6; ?3.9 to ?3.2), and tr%BF (?8.5; ?9.1 to ?7.9). The discrepancies between the methods increased with increasing adiposity for both %TBF and tr%BF (both p < 0.001). Variation in BMI explained 28% of the variation in %TBF_DXA and 51% of %TBF_BIA8. Using WC as a proxy for truncal adiposity, it explained only 18% of tr%BF_DXA variance and 27% of tr%BF_BIA8 variance. The corresponding figures for truncal fat mass were 49% and 35%, respectively. No significant age effects were observed in any of the regressions. Discussion: BIA₈ underestimated both total and truncal fatness, compared with DXA, with higher dispersion for tr%BF than %TBF. The discrepancies increased with degree of adiposity, suggesting that the accuracy of BIA is negatively affected by obesity.     

Racial Differences in Metabolic Predictors of Obesity among Postmenopausal Women

NICKLAS, BARBARA S., DORA M. BERMAN, DAWN C. DAVIS, C. LYNNE DOBROVOLNY, AND KAREN E. DENNIS. Racial differences in metabolic predictors of obesity among postmenopausal women. Ober Res. Objective: This study determined whether there are racial differences in resting metabolic rate (RMR), fat oxidation, and maximal oxygen consumption (VO,max) in obese [body mass index (BMI = 34±2 kg/m²)], postmenopausal (58±2 years) women. Research Methods and Procedures: Twenty black and 20 white women were matched for fat mass and lean mass (LM), as determined by dual energy X-ray absorptiometry. RMR and fat oxidation were measured by indirect calorimetry in the early morning after a 12-hour fast using the ventilated hood technique. VO₂max was measured on a treadmill during a progressive exercise test to voluntary exhaustion. Results: RMR, adjusted for differences in LM, was 5% higher in white than black women (1566±27 and 1490±26 kcal/day, respectively; p<0. 05); and fat oxidation rate was 17% higher in white than black women (87±4 and 72±3 g/day, respectively; p<0. 01). VO₂max (L/minute) was 150 mL per minute (8%) higher (p<0. 05) in white than black women. VO₂max correlated with LM in black (r = 0. 44, p = 0. 05) and white (r=0. 53, p<0. 05) women, but the intercept of the regression line was higher in white than black women (p<0. 05), with no significant difference in slopes. In a multiple regression model including race, body weight, LM, and age, LM was the only independent predictor of RMR (r² = 0. 46, p<0. 0001), whereas race was the only independent predictor of fat oxidation (r² = 0. 18,p<0. 05). The best predictors of VO,max were LM (r² = 0. 22, p<0. 05) and race (cumulative r² = 0. 30, p<0. 05). Discussion: These results show there are racial differences in metabolic predictors of obesity. Determination of whether these ethnic differences lead to, or are an effect of, obesity status or other lifestyle factors requires further study.     

U‐shaped response Unifies views on temperature dependency of stoichiometric requirements

Temperature and nutrient availability, which are major drivers of consumer performance, are dramatically affected by global change. To date, there is no consensus on whether warming increases or decreases consumer needs for dietary carbon (C) relatively to phosphorus (P), thus hindering predictions of secondary production responses to global change. Here, we investigate how the dietary C:P ratio optimising consumer growth (TER_C:P: Threshold Elemental Ratio) changes along temperature gradients by combining a temperature‐dependent TER_C:P model with growth experiments on Daphnia magna. Both lines of evidence show that the TER_C:P response to temperature is U‐shaped. This shape indicates that consumer nutrient requirements can both increase or decrease with increasing temperature, thus reconciling previous contradictive observations into a common framework. This unified framework improves our capacity to forecast the combined effects of nutrient cycle and climatic alterations on invertebrate production.     

The IL-33-ST2L Pathway Is Associated with Coronary Artery Disease in a Chinese Han Population

The effects of interleukin-33 (IL-33) on the immune system have been clearly demonstrated; however, in cardiovascular diseases, especially in coronary artery disease (CAD), these effects have not yet been clarified. In this study, we investigate the genetic role of the IL-33-ST2L pathway in CAD. We performed three-stage case-control association analyses on a total of 4,521 individuals with CAD and 4,809 controls via tag SNPs in the genes encoding IL-33 and ST2L-IL-1RL1. One tag SNP in each gene was significantly associated with CAD (rs7025417^T in IL33, p_adj = 1.19 × 10⁻²⁸, OR = 1.39, 95% CI: 1.31–1.47; rs11685424^G in IL1RL1, p_adj = 6.93 × 10⁻³⁰, OR = 1.40, 95% CI: 1.32–1.48). Combining significant variants in two genes, the risk for CAD increased nearly 5-fold (p_adj = 8.90 × 10⁻²¹, OR = 4.98, 95% CI: 3.56–6.97). Traditional risk factors for CAD were adjusted for the association studies by SPSS with logistic regression analysis. With the two variants above, both located within the gene promoter regions, reporter gene analysis indicated that the rs7025417 C>T and rs11685424 A>G changes resulted in altered regulation of IL33 and IL1RL1 gene expression, respectively (p < 0.005). Further studies revealed that the rs7025417 genotype was significantly associated with plasma IL-33 levels in the detectable subjects (n = 227, R² = 0.276, p = 1.77 × 10⁻¹⁷): the level of IL-33 protein increased with the number of rs7025417 risk (T) alleles. Based on genetic evidence in humans, the IL-33-ST2L pathway appears to have a causal role in the development of CAD, highlighting this pathway as a valuable target for the prevention and treatment of CAD.     

Household Ventilation May Reduce Effects of Indoor Air Pollutants for Prevention of Lung Cancer: A Case-Control Study in a Chinese Population

Background

Although the International Agency for Research on Cancer (IARC) has classified various indoor air pollutants as carcinogenic to humans, few studies evaluated the role of household ventilation in reducing the impact of indoor air pollutants on lung cancer risk.

Objectives

To explore the association between household ventilation and lung cancer.

Methods

A population-based case-control study was conducted in a Chinese population from 2003 to 2010. Epidemiologic and household ventilation data were collected using a standardized questionnaire. Unconditional logistic regression was employed to estimate adjusted odds ratios (OR_adj) and their 95% confidence intervals (CI).

Results

Among 1,424 lung cancer cases and 4,543 healthy controls, inverse associations were observed for good ventilation in the kitchen (OR_adj = 0.86, 95% CI: 0.75, 0.98), bedroom (OR_adj = 0.90, 95% CI: 0.79, 1.03), and both kitchen and bedroom (OR_adj = 0.87, 95% CI: 0.75, 1.00). Stratified analyses showed lung cancer inversely associated with good ventilation among active smokers (OR_adj = 0.85, 95% CI: 0.72, 1.00), secondhand smokers at home (OR_adj = 0.77, 95% CI: 0.63, 0.94), and those exposed to high-temperature cooking oil fumes (OR_adj = 0.82, 95% CI: 0.68, 0.99). Additive interactions were found between household ventilation and secondhand smoke at home as well as number of household pollutant sources.

Conclusions

A protective association was observed between good ventilation of households and lung cancer, most likely through the reduction of exposure to indoor air pollutants, indicating ventilation may serve as one of the preventive measures for lung cancer, in addition to tobacco cessation.     

Familial Resemblance of 7‐Year Changes in Body Mass and Adiposity

Objective: To investigate the familial resemblance of 7‐year changes in body mass and adiposity among Canadian families. Research Methods and Procedures: The sample consisted of 655 women and 660 men from 521 families who participated in the Canada Fitness Survey in 1981 and the follow‐up Campbell's Survey in 1988. Indicators of baseline and 7‐year changes in body mass and adiposity included body mass (kilograms), body mass index (BMI; kilograms per square meter), sum of five skinfolds (SF5; millimeters), and waist circumference (WC; millimeters). The data were adjusted for the effects of age and sex, and the change scores were adjusted for baseline levels. A familial correlation model was used to determine the heritability of each phenotype using maximum likelihood techniques. Results: Significant familial resemblance was observed at baseline and for 7‐year changes in all phenotypes. At baseline, moderate heritabilities were observed [body mass: heritability coefficient (h²) = 56%; BMI, h² = 39%; SF5, h² = 41%; and WC, h² = 39%], whereas values were attenuated for each change score except for WC (Δbody mass, h² = 23%; ΔBMI, h² = 14%; ΔSF5, h² = 12%; and ΔWC, h² = 45%). Discussion: Changes in body mass and adiposity significantly aggregate within families over 7 years. However, baseline values are characterized by higher heritability levels except WC. The significant heritabilities observed for change scores suggest that lifestyle, transient environmental factors, and possibly age‐related gene effects are important determinants of changes in body mass and adiposity.     

Overeating in America: Association between Restaurant Food Consumption and Body Fatness in Healthy Adult Men and Women Ages 19 to 80

McCRORY, MEGAN A., PAUL J. FUSS, NICHOLAS P. HAYS, ANGELA G. VINKEN, ANDREW S. GREENBERG, AND SUSAN B. ROBERTS. Overeating in America: association between restaurant food consumption and body fatness in healthy adult men and women ages 19 to 80. Obes Res. Purpose: To examine the association between the frequency of consuming restaurant food and body fatness in adults. Research Methods and Procedures: Usual free-living dietary intake and the frequency of consuming food from seven different restaurant types (fried chicken, burger, pizza, Chinese, Mexican, fried fish, and “other”) were assessed by food frequency questionnaire in 73 healthy men and women [ages 19 to 80, body mass index (BMI) 18 to 331. In addition, body fatness (percent weight) was determined by hydrostatic weighing, and physical activity and other lifestyle parameters were assessed by questionnaire. The relationship between the frequency of consuming restaurant food and body fatness was determined after controlling for age, sex, and other confounders by using multiple regression techniques. Results: Restaurant food consumption averaged 7.5±8.5 (Standard Deviation) timedmonth. After controlling for age and sex, the frequency of consuming restaurant food was positively associated with body fatness (partial r = 0. 36, p = 0. 003). The strength of this association did not change after controlling for education level, smoking status, and alcohol intake, but after additionally controlling for physical activity, the partial r increased to 0. 42 (p = 0. 004). Total daily intakes of energy, fat, and fiber were significantly associated with restaurant food consumption frequency (r = 0. 59, 0. 28, and ?0.45, respectively, p = 0.02 to 0.0001). Discussion: The frequency of consuming restaurant food was positively associated with increased body fatness in adults. The increasing proportion of household food income spent on food prepared away from home in the United States may therefore help explain the rising national prevalence of obesity.     

Importance of Both Fatness and Aerobic Fitness on Metabolic Syndrome Risk in Japanese Children

Associations between body mass index (BMI), peak oxygen consumption (VO_2peak), and metabolic syndrome (MetS) risk factors have not been adequately studied in Japanese children. Here the relationships between these parameters and the threshold aerobic fitness level necessary for low MetS risk were determined. The participants (299 children; 140 boys and 159 girls, aged 9.1 ± 0.3 years) were divided into four groups using the medians of predicted VO_2peak (_pVO_2peak) and BMI. MetS risk scores were calculated using z-scores. Receiver Operating Characteristic analysis was used to determine the threshold aerobic fitness level necessary for low MetS risk. The MetS risk score of the High BMI group was significantly higher than that of the Low BMI group for both sexes (p < 0.0001). However, the High BMI/High Fitness group had a significantly lower MetS risk score than the High BMI/Low Fitness group for both sexes. The _pVO_2peak cut-off values for low MetS risk were 47.9 and 44.9 ml/kg/min for boys and girls, respectively. Our results suggest that improvements in both fatness and aerobic fitness are important for decreasing MetS risk. We also confirmed the _pVO_2peak of cut-off values necessary for low MetS risk in Japanese children.     

Lowered risk of nasopharyngeal carcinoma and intake of plant vitamin, fresh fish, green tea and coffee: a case-control study in taiwan

Background

A case-control study was conducted to evaluate the role of adult diet on nasopharyngeal carcinoma (NPC) in Taiwan.

Methods

A total of 375 incident NPC cases and 327 controls matched to the cases on sex, age, and residence were recruited between July 1991 and December 1994. A structured questionnaire inquiring complete dietary history, socio-demographic characteristics, and other potential confounding factors was used in the personal interview. Unconditional logistic regression analysis was used to estimate multivariate-adjusted odds ratio (OR_adj) with 95% confidence interval (CI) after accounting for known risk factors.

Results

Fresh fish (OR_adj, 0.56; 95% CI, 0.38–0.83 for the highest vs. lowest tertile of intake), green tea (OR_adj, 0.61; 95% CI, 0.40–0.91 for drinking ≥1 times/week vs. never) and coffee (OR_adj, 0.56; 95% CI, 0.37–0.85 for drinking ≥0.5 times/week vs. never) were inversely associated with the NPC risk. No association with NPC risk was observed for the intake of meats, salted fish, fresh vegetables, fruits and milk. Intake of vitamin A from plant sources was associated with a decreased NPC risk (OR_adj, 0.62; 95% CI, 0.41–0.94 for the highest vs. lowest tertile).

Conclusion

The study findings suggest that certain adult dietary patterns might protect against the development of NPC.     

Influence of Serotonin Transporter Gene Polymorphisms and Adverse Life Events on Depressive Symptoms in the Elderly: A Population-Based Study

BackgroundDepression is common in the elderly. The role of genetic and environmental factors in modulating depressive symptoms is not clear.MethodsWe evaluated the influence of serotonin transporter gene polymorphisms and recent adverse life events on depressive symptoms in an elderly Italian population. We used data from “InveCe.Ab”, a population-based study of 1321 subjects aged 70–74 years. We used the 15-item Geriatric Depression Scale (GDS) to assess depressive symptoms–a GDS score ≥5 points (GDS≥5) indicated the presence of clinically relevant symptoms–and performed 5-HTTLPR and rs25531 genotyping to obtain the triallelic polymorphism of the serotonin transporter. We used the Geriatric Adverse Life Events Scale to measure adverse life events, and logistic regression models to evaluate the role of genotype and recent adverse life events in depressive symptoms, controlling for potential confounders and independent predictors.ResultsTwo hundred subjects (15.76%) had a GDS≥5. The 5-HTTLPR triallelic polymorphism was significantly associated with GDS≥5. Only S′S′ carriers showed an increased risk of depressive symptoms (OR_adj = 1.81, p = .022); one extra adverse life event increased this risk by 14% (p = .061) independently of genotype. Other factors significantly related to GDS≥5 were: female gender (OR_adj = 2.49, p < .001), age (OR_adj = 1.19, p = .007), a history of depression (OR_adj = 4.73, p < .001), and comorbidity (OR_adj = 1.23, p = .001). One extra adverse life event increased the risk of depressive symptoms by 57% (p = .005) only in the L′L′ carriers, while antidepressant intake was directly related to GDS≥5 in the L′S′ carriers (OR_adj = 2.46, p = .036) and borderline significant in the S′S′ carriers (OR_adj = 2.41, p = .081).DiscussionThe S′S′ genotype and recent exposure to adverse life events were independently associated with depressive symptoms. The S′S′ genotype, compared with the environment, exerted a predominant effect on depressive symptoms, suggesting that it reduces the efficacy of antidepressant therapy. We conclude that genetics may be an important risk factor for depressive symptoms in late adulthood.     

Which Metric of Relative Weight Best Captures Body Fatness in Children?

Objective: To evaluate the relative merits of BMI (kilograms per meter squared) and age‐ and gender‐adjusted BMI, age‐ and gender‐specific z score of BMI, and age‐ and gender‐specific percentiles of BMI as surrogate measures of body fatness among a sample of youth. Research Methods and Procedures: The sample comprised 596 children and adolescents 5 to 18.7 years old and was 40% male and 55% white. Height and weight were measured by trained research staff. DXA was used to determine body fat mass. BMI, age‐ and gender‐specific percentile of BMI, and age‐ and gender‐specific z scores of BMI were computed, and these metrics were compared with measured body fatness. Results: The BMI values in the sample ranged from 12.9 to 55.0 kg/m², with a mean of 24.9 kg/m². The Spearman correlations with percentage body fat were similar for all of the BMI metrics (r = 0.82 to 0.88). Linear regression models with age‐ and gender‐specific percentiles of BMI explained significantly less of the variance (65%) than models with log‐transformed BMI (81%) or age‐ and gender‐specific z scores of BMI (75% to 79%). z scores were the most accurate at classifying children who were overfat (sensitivity = 0.84, specificity = 0.96 for z score ≥1). However, using a BMI ≥85th percentile or a BMI ≥20 kg/m² was also accurate at classifying youth. Discussion: The BMI metrics had similar correlations with body fatness, but age‐ and gender‐specific percentiles of BMI were the least accurate proxy measure of body fatness. However, a BMI z score ≥1, BMI percentile ≥85, and BMI ≥20 kg/m² are all useful for identifying children who may be overfat.     

Relative contributions of adiposity and muscularity to physical function in community-dwelling older adults

Objective: To determine the relative contributions of adiposity and muscularity to multi‐dimensional performance‐based and perceived physical function in older adults living independently. Methods and Procedures: Data from 109 women and men, aged 60 or older, with low serum dehydroepiandrosterone (DHEA) sulfate levels were included in this cross‐sectional analysis of baseline measures from a single‐site, randomized, controlled trial of DHEA replacement therapy. Physical function was determined by means of performance on the 100‐point Continuous Scale‐Physical Functional Performance (CS‐PFP) test and by self‐reporting using the physical function subscale of the Medical Outcomes Short Form‐36 (SF36_PF). Body composition was measured by dual‐energy X‐ray absorptiometry (DXA). Linear regression analyses were used to determine the contributions of body mass index (BMI; kg body mass/m²), fat index (FI; kg fat/m²), and appendicular skeletal muscle index (ASMI; kg muscle/m²) to the CS‐PFP and SF36_PF scores, adjusted for age and sex. Results: Age‐adjusted regression analyses indicated that FI, but not ASMI, was a significant (P < 0.001) determinant of CS‐PFP (R ² = 0.54) and SF36_PF (R ² = 0.37). When adjusted for age and sex, BMI was nearly as good a predictor of CS‐PFP (R ² = 0.50) and SF36_PF (R ² = 0.34) as FI. Discussion: Adiposity was a stronger predictor of measured and self‐reported physical function than was muscularity in older adults living independently. BMI, adjusted for sex, is a reasonable substitute for adiposity in the prediction of physical function.     

Interplay between Caveolin-1 and body and tumor size affects clinical outcomes in breast cancer

BackgroundCaveolin-1 (CAV1) is associated with cholesterol-rich membrane raft domains and is a master regulator of cell signaling and membrane transport. Here, we investigated CAV1’s role in cellular compartments of breast cancer in relation to signaling pathways, clinicopathological features, and clinical outcomes.MethodsCAV1 levels were evaluated with immunohistochemistry in cytoplasm of invasive tumor cells and stromal cells in tumor tissue microarrays from a cohort of 1018 breast cancer patients (inclusion 2002–2012, Sweden). Cytoplasmic and stromal CAV1 were categorized as positive/negative and strong/not strong, respectively. CAV1 expression in relation to clinical outcomes was assessed with Cox regression. Investigations into CAV1 functional pathways was conducted in the STRING, GOBO, and TCGA databases.ResultsCAV1 expression was associated with non-luminal subtypes, cell cycle control, inflammation, epithelial-mesenchymal transition, and the IGF/Insulin system. Generally, CAV1 was not associated with recurrence risk. Stromal CAV1’s impact on recurrence risk was modified by BMI ≥25 kg/m² (P_interaction = 0.002), waist ≥80 cm (P_interaction = 0.005), and invasive tumor size (pT2/3/4) (P_interaction = 0.028). In low-risk patients only, strong stromal CAV1 significantly increased recurrence risk (HRs_adj ≥1.61). In all patients, positive cytoplasmic CAV1 conferred >2-fold risk for contralateral disease HR_adj 2.63 (95% CI 1.36–5.10). Strong stromal CAV1 conferred nearly 2-fold risk for locoregional recurrence HR_adj 1.88 (95% CI 1.09–3.24).ConclusionsCAV1’s prognostic impact depended on its localization, anthropometric, and tumor factors. Stromal CAV1 predicted high recurrence risk in a group of supposedly ‘low-risk’ patients. Cytoplasmic CAV1 predicted metachronous contralateral disease. If confirmed, CAV1 could be used as treatment target and for risk-stratification.     

Relationships between Insulin Sensitivity and Measures of Body Fat in Asymptomatic Men and Women

Objective: To assess whether measures of body fat by DXA scanning can improve prediction of insulin sensitivity (S_I) beyond what is possible with traditional measures, such as BMI, waist circumference, and waist‐to‐hip ratio (WHR). Research Methods and Procedures: Frequently sampled intravenous glucose tolerance tests were performed in 256 asymptomatic non‐Hispanic white subjects from Rochester, MN (age 19‐60 years; 123 men and 133 women) to determine the S_I index by Bergman's minimal model technique. Height, weight, and waist and hip circumferences were measured for calculation of BMI and WHR; DXA was used to determine fat in the head, upper body, abdomen, and lower body. Linear regression was used to assess their relationships with S_I after sex stratification and adjustment for age. Results: After controlling for age, increases in traditional and DXA measures of fat were consistently associated with smaller declines in S_I among women than among men. In men, after controlling for age, all of the predictive information of S_I was provided by waist circumference (additional R² = 0.39, p < 0.001); none of the DXA measures improved the ability to predict S_I. In women, after adjustment for age, BMI, and WHR, the only DXA measure that improved the prediction of S_I was percentage head fat (additional R² = 0.03, p < 0.001). Discussion: Equivalent increases in most measures of body fat had lesser impact on S_I in women than in men. In both sexes, the predictive information provided by DXA measures is approximately equal to, but not additive to, that provided by simpler, traditional measures.     

Independent Effects of Sleep Duration and Body Mass Index on the Risk of a Work-Related Injury: Evidence From the US National Health Interview Survey (2004–2010)

Fatigue has been linked to adverse safety outcomes, and poor quality or decreased sleep has been associated with obesity (higher body mass index, BMI). Additionally, higher BMI is related to an increased risk for injury; however, it is unclear whether BMI modifies the effect of short sleep or has an independent effect on work-related injury risk. To answer this question, the authors examined the risk of a work-related injury as a function of total daily sleep time and BMI using the US National Health Interview Survey (NHIS). The NHIS is an in-person household survey using a multistage, stratified, clustered sample design representing the US civilian population. Data were pooled for the 7-yr survey period from 2004 to 2010 for 101 891 “employed” adult subjects (51.7%; 41.1?±?yrs of age [mean?±?SEM]) with data on both sleep and BMI. Weighted annualized work-related injury rates were estimated across a priori defined categories of BMI: healthy weight (BMI: <25), overweight (BMI: 25–29.99), and obese (BMI: ≥30) and also categories of usual daily sleep duration: <6, 6–6.99, 7–7.99, 8–8.99, and ≥9?h. To account for the complex sampling design, including stratification, clustering, and unequal weighting, weighted multiple logistic regression was used to estimate the risk of a work-related injury. The initial model examined the interaction among daily sleep duration and BMI, controlling for weekly working hours, age, sex, race/ethnicity, education, type of pay, industry, and occupation. No significant interaction was found between usual daily sleep duration and BMI (p?=?.72); thus, the interaction term of the final logistic model included these two variables as independent predictors of injury, along with the aforementioned covariates. Statistically significant covariates (p?≤?.05) included age, sex, weekly work hours, occupation, and if the worker was paid hourly. The lowest categories of usual sleep duration (<6 and 6–6.9?h) showed significantly (p?≤?.05) elevated injury risks than the referent category (7–8?h sleep), whereas sleeping >7–8?h did not significantly elevate risk. The adjusted injury risk odds ratio (OR) for a worker with a usual daily sleep of <6?h was 1.86 (95% confidence interval [CI]: 1.37–2.52), and for 6–6.9?h it was 1.46 (95% CI: 1.18–1.80). With regards to BMI, the adjusted injury risk OR comparing workers who were obese (BMI: ≥30) to healthy weight workers (BMI: <25) was 1.34 (95% CI: 1.09–1.66), whereas the risk in comparing overweight workers (BMI: 25–29.99) to healthy weight risk was elevated, but not statistically significant (OR?=?1.08; 95% CI: .88–1.33). These results from a large representative sample of US workers suggest increase in work-related injury risk for reduced sleep regardless of worker's body mass. However, being an overweight worker also increases work-injury risk regardless of usual daily sleep duration. The independent additive risk of these factors on work-related injury suggests a substantial, but at least partially preventable, risk. (Author correspondence: david.lombardi@libertymutual.com)