Cross-validation of bioelectrical impedance analysis for the assessment of body composition in a representative sample of 6- to 13-year-old children.

BACKGROUND/OBJECTIVES: (1) To cross-validate tetra- (4-BIA) and octopolar (8-BIA) bioelectrical impedance analysis vs dual-energy X-ray absorptiometry (DXA) for the assessment of total and appendicular body composition and (2) to evaluate the accuracy of external 4-BIA algorithms for the prediction of total body composition, in a representative sample of Swiss children. SUBJECTS/METHODS: A representative sample of 333 Swiss children aged 6-13 years from the Kinder-Sportstudie (KISS) (ISRCTN15360785). Whole-body fat-free mass (FFM) and appendicular lean tissue mass were measured with DXA. Body resistance (R) was measured at 50 kHz with 4-BIA and segmental body resistance at 5, 50, 250 and 500 kHz with 8-BIA. The resistance index (RI) was calculated as height(2)/R. Selection of predictors (gender, age, weight, RI4 and RI8) for BIA algorithms was performed using bootstrapped stepwise linear regression on 1000 samples. We calculated 95% confidence intervals (CI) of regression coefficients and measures of model fit using bootstrap analysis. Limits of agreement were used as measures of interchangeability of BIA with DXA. RESULTS: 8-BIA was more accurate than 4-BIA for the assessment of FFM (root mean square error (RMSE)=0.90 (95% CI 0.82-0.98) vs 1.12 kg (1.01-1.24); limits of agreement 1.80 to -1.80 kg vs 2.24 to -2.24 kg). 8-BIA also gave accurate estimates of appendicular body composition, with RMSE < or = 0.10 kg for arms and < or = 0.24 kg for legs. All external 4-BIA algorithms performed poorly with substantial negative proportional bias (r> or = 0.48, P<0.001). CONCLUSIONS: In a representative sample of young Swiss children (1) 8-BIA was superior to 4-BIA for the prediction of FFM, (2) external 4-BIA algorithms gave biased predictions of FFM and (3) 8-BIA was an accurate predictor of segmental body composition.

Fat-free mass index and fat mass index percentiles in Caucasians aged 18-98 y.

OBJECTIVE: To determine reference values for fat-free mass index (FFMI) and fat mass index (FMI) in a large Caucasian group of apparently healthy subjects, as a function of age and gender and to develop percentile distribution for these two parameters. DESIGN: Cross-sectional study in which bioelectrical impedance analysis (50 kHz) was measured (using tetrapolar electrodes and cross-validated formulae by dual-energy X-ray absorptiometry in order to calculate FFMI (fat-free mass/height squared) and FMI (fat mass/height squared). SUBJECTS: A total of 5635 apparently healthy adults from a mixed non-randomly selected Caucasian population in Switzerland (2986 men and 2649 women), varying in age from 24 to 98 y. RESULTS: The median FFMI (18-34 y) were 18.9 kg/m(2) in young males and 15.4 kg/m(2) in young females. No difference with age in males and a modest increase in females were observed. The median FMI was 4.0 kg/m(2) in males and 5.5 kg/m(2) in females. From young to elderly age categories, FMI progressively rose by an average of 55% in males and 62% in females, compared to an increase in body mass index (BMI) of 9 and 19% respectively. CONCLUSIONS: Reference intervals for FFMI and FMI could be of practical value for the clinical evaluation of a deficit in fat-free mass with or without excess fat mass (sarcopenic obesity) for a given age category, complementing the classical concept of body mass index (BMI) in a more qualitative manner. In contrast to BMI, similar reference ranges seems to be utilizable for FFMI with advancing age, in particular in men.

How Can Nanotechnology Help to Repair the Body? Advances in Cardiac, Skin, Bone, Cartilage and Nerve Tissue Regeneration

Nanotechnologists have become involved in regenerative medicine via creation of biomaterials and nanostructures with potential clinical implications. Their aim is to develop systems that can mimic, reinforce or even create in vivo tissue repair strategies. In fact, in the last decade, important advances in the field of tissue engineering, cell therapy and cell delivery have already been achieved. In this review, we will delve into the latest research advances and discuss whether cell and/or tissue repair devices are a possibility. Focusing on the application of nanotechnology in tissue engineering research, this review highlights recent advances in the application of nano-engineered scaffolds designed to replace or restore the followed tissues: (i) skin; (ii) cartilage; (iii) bone; (iv) nerve; and (v) cardiac.

Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance.

CONTEXT Recently irisin (encoded by Fndc5 gene) has been reported to stimulate browning and uncoupling protein 1 expression in sc adipose tissue of mice. OBJECTIVE The objective of the study was to investigate FNDC5 gene expression in human muscle and adipose tissue and circulating irisin according to obesity, insulin sensitivity, and type 2 diabetes. DESIGN, PATIENTS, AND MAIN OUTCOME MEASURE Adipose tissue FNDC5 gene expression and circulating irisin (ELISA) were analyzed in 2 different cohorts (n = 125 and n = 76); muscle FNDC5 expression was also evaluated in a subcohort of 34 subjects. In vitro studies in human preadipocytes and adipocytes and in induced browning of 3T3-L1 cells (by means of retinoblastoma 1 silencing) were also performed. RESULTS In both sc and visceral adipose tissue, FNDC5 gene expression decreased significantly in association with obesity and was positively associated with brown adipose tissue markers, lipogenic, insulin pathway-related, mitochondrial, and alternative macrophage gene markers and negatively associated with LEP, TNFα, and FSP27 (a known repressor of brown genes). Circulating irisin and irisin levels in adipose tissue were significantly associated with FNDC5 gene expression in adipose tissue. In muscle, the FNDC5 gene was 200-fold more expressed than in adipose tissue, and its expression was associated with body mass index, PGC1α, and other mitochondrial genes. In obese participants, FNDC5 gene expression in muscle was significantly decreased in association with type 2 diabetes. Interestingly, muscle FNDC5 gene expression was significantly associated with FNDC5 and UCP1 gene expression in visceral adipose tissue. In men, circulating irisin levels were negatively associated with obesity and insulin resistance. Irisin was secreted from human adipocytes into the media, and the induction of browning in 3T3-L1 cells led to increased secreted irisin levels. CONCLUSIONS Decreased circulating irisin concentration and FNDC5 gene expression in adipose tissue and muscle from obese and type 2 diabetic subjects suggests a loss of brown-like characteristics and a potential target for therapy.

Reproducibility and within-day variability of body fat masurements using segmental bipolar bioelectrical impedance in women

Objective: to assess the between and within-device reproducibility, as well as within-day variability of body fat measurements. Methods: body fat percentage (%BF) was measured twice on seventeen female students aged between 18 and 20 with a body mass index of 21.9 22.6 kg/m2 (mean SD) using seven bipolar bioelectrical impedance devices (BF-306) according to the manufacturer's recommendations. Each student was also measured each hour between 7:00 and 22:00. Statistical analysis was conducted using a general linear model for repeated measurements. Results: the correlation between first and second measurements was very high (Pearson r between 0.985 and 1.000, p<0.001), as well as the correlation between devices (Pearson r between 0.986 and 0.999, all p<0.001). Repeated measurements analysis showed no differences were between devices (F test=0.83, p=0.59) or readings (first vs. second: F test=0.12, p=0.74). Conversely, significant differences were found between assessment periods throughout the day, measurements made in the morning being lower than those made in the afternoon. Assuming an overall daily average of 100 (based on all measurements), the values were 95.8 3.2 (mean SD) at 8:00 versus 101.3 3.0 at 20:00, corresponding to a mean change of 2.2 1.1 in %BF (F test for repeated values=6.58, p<0.001). Conclusions: the between and within-device reproducibility for measuring body fat is high, enabling the use of multiple devices in a single study. Conversely, small but significant changes in body fat measurements occur during the day, urging body fat measurements to be performed at fixed times.

Imaging of human leukemic T-cell xenografts in nude mice by radiolabeled monoclonal antibodies and F(ab')2 fragments.

Monoclonal antibodies (MoAb) that react with the T-lymphocyte markers called cluster of differentiation CD5 and CD2 were labeled with iodine 131 (131I) and were injected intravenously in nude mice bearing solid subcutaneous xenografts derived from the human T-cell leukemia line Ichikawa. Both MoAb anti-CD5 and anti-CD2 yielded favorable mean tumor to whole-body ratios of 3.8 and 5.1, respectively. These ratios were further increased up to 10.0 for MoAb anti-CD5 and 15.5 for MoAb anti-CD2 by using their F(ab')2 fragments. The tumors could be imaged clearly by external scanning after injection of F(ab')2 fragments from both MoAb. F(ab')2 fragments from MoAb anti-CD2 and of a third MoAb recognizing the clonotypic determinant (Ti) of the antigen receptor expressed by the human T-cell line Jurkat were injected in mice bearing intrasplenic Jurkat xenografts. A selective localization of both fragments in tumor tissue was demonstrated with mean tumor to whole-body ratios of 7.5 and 4.1 for MoAb anti-CD2 and anti-Ti, respectively. These in vivo experimental results may provide useful information for the potential use of radiolabeled MoAb and fragments in the diagnosis and treatment of patients with T-cell lymphoma and different other forms of T-cell malignancies.

CB1 blockade potentiates down-regulation of lipogenic gene expression in perirenal adipose tissue in high carbohydrate diet-induced obesity.

De novo lipogenesis and hypercaloric diets are thought to contribute to increased fat mass, particularly in abdominal fat depots. CB1 is highly expressed in adipose tissue, and CB1-mediated signalling is associated with stimulation of lipogenesis and diet-induced obesity, though its contribution to increasing fat deposition in adipose tissue is controversial. Lipogenesis is regulated by transcription factors such as liver X receptor (LXR), sterol-response element binding protein (SREBP) and carbohydrate-responsive-element-binding protein (ChREBP). We evaluated the role of CB1 in the gene expression of these factors and their target genes in relation to lipogenesis in the perirenal adipose tissue (PrAT) of rats fed a high-carbohydrate diet (HCHD) or a high-fat diet (HFD). Both obesity models showed an up-regulated gene expression of CB1 and Lxrα in this adipose pad. The Srebf-1 and ChREBP gene expressions were down-regulated in HFD but not in HCHD. The expression of their target genes encoding for lipogenic enzymes showed a decrease in diet-induced obesity and was particularly dramatic in HFD. In HCHD, CB1 blockade by AM251 reduced the Srebf-1 and ChREBP expression and totally abrogated the remnant gene expression of their target lipogenic enzymes. The phosphorylated form of the extracellular signal-regulated kinase (ERK-p), which participates in the CB1-mediated signalling pathway, was markedly present in the PrAT of obese rats. ERK-p was drastically repressed by AM251 indicating that CB1 is actually functional in PrAT of obese animals, though its activation loses the ability to stimulate lipogenesis in PrAT of obese rats. Even so, the remnant expression levels of lipogenic transcription factors found in HCHD-fed rats are still dependent on CB1 activity. Hence, in HCHD-induced obesity, CB1 blockade may help to further potentiate the reduction of lipogenesis in PrAT by means of inducing down-regulation of the ChREBP and Srebf-1 gene expression, and consequently in the expression of lipogenic enzymes.

The required beta cell research for improving treatment of type 2 diabetes.

In healthy individuals, insulin resistance is associated with physiological conditions such as pregnancy or body weight gain and triggers an increase in beta cell number and insulin secretion capacity to preserve normoglycaemia. Failure of this beta cell compensation capacity is a fundamental cause of diabetic hyperglycaemia. Incomplete understanding of the molecular mechanisms controlling the plasticity of adult beta cells mechanisms and how these cells fail during the pathogenesis of diabetes strongly limits the ability to develop new beta cell-specific therapies. Here, current knowledge of the signalling pathways controlling beta cell plasticity is reviewed, and possible directions for future research are discussed.

Disruption of GIP/GIPR axis in human adipose tissue is linked to obesity and insulin resistance.

CONTEXT Glucose-dependent insulinotropic peptide (GIP) has a central role in glucose homeostasis through its amplification of insulin secretion; however, its physiological role in adipose tissue is unclear. OBJECTIVE Our objective was to define the function of GIP in human adipose tissue in relation to obesity and insulin resistance. DESIGN GIP receptor (GIPR) expression was analyzed in human sc adipose tissue (SAT) and visceral adipose (VAT) from lean and obese subjects in 3 independent cohorts. GIPR expression was associated with anthropometric and biochemical variables. GIP responsiveness on insulin sensitivity was analyzed in human adipocyte cell lines in normoxic and hypoxic environments as well as in adipose-derived stem cells obtained from lean and obese patients. RESULTS GIPR expression was downregulated in SAT from obese patients and correlated negatively with body mass index, waist circumference, systolic blood pressure, and glucose and triglyceride levels. Furthermore, homeostasis model assessment of insulin resistance, glucose, and G protein-coupled receptor kinase 2 (GRK2) emerged as variables strongly associated with GIPR expression in SAT. Glucose uptake studies and insulin signaling in human adipocytes revealed GIP as an insulin-sensitizer incretin. Immunoprecipitation experiments suggested that GIP promotes the interaction of GRK2 with GIPR and decreases the association of GRK2 to insulin receptor substrate 1. These effects of GIP observed under normoxia were lost in human fat cells cultured in hypoxia. In support of this, GIP increased insulin sensitivity in human adipose-derived stem cells from lean patients. GIP also induced GIPR expression, which was concomitant with a downregulation of the incretin-degrading enzyme dipeptidyl peptidase 4. None of the physiological effects of GIP were detected in human fat cells obtained from an obese environment with reduced levels of GIPR. CONCLUSIONS GIP/GIPR signaling is disrupted in insulin-resistant states, such as obesity, and normalizing this function might represent a potential therapy in the treatment of obesity-associated metabolic disorders.

Changes in Body Composition in Anorexia Nervosa: Predictors of Recovery and Treatment Outcome.

The restoration of body composition (BC) parameters is considered to be one of the most important goals in the treatment of patients with anorexia nervosa (AN). However, little is known about differences between AN diagnostic subtypes [restricting (AN-R) and binge/purging (AN-BP)] and weekly changes in BC during refeeding treatment. Therefore, the main objectives of our study were twofold: 1) to assess the changes in BC throughout nutritional treatment in an AN sample and 2) to analyze predictors of BC changes during treatment, as well as predictors of treatment outcome. The whole sample comprised 261 participants [118 adult females with AN (70 AN-R vs. 48 AN-BP), and 143 healthy controls]. BC was measured weekly during 15 weeks of day-hospital treatment using bioelectrical impedance analysis (BIA). Assessment measures also included the Eating Disorders Inventory-2, as well as a number of other clinical indices. Overall, the results showed that AN-R and AN-BP patients statistically differed in all BC measures at admission. However, no significant time×group interaction was found for almost all BC parameters. Significant time×group interactions were only found for basal metabolic rate (p = .041) and body mass index (BMI) (p = .035). Multiple regression models showed that the best predictors of pre-post changes in BC parameters (namely fat-free mass, muscular mass, total body water and BMI) were the baseline values of BC parameters. Stepwise predictive logistic regressions showed that only BMI and age were significantly associated with outcome, but not with the percentage of body fat. In conclusion, these data suggest that although AN patients tended to restore all BC parameters during nutritional treatment, only AN-BP patients obtained the same fat mass values as healthy controls. Put succinctly, the best predictors of changes in BC were baseline BC values, which did not, however, seem to influence treatment outcome.

A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown. METHODS AND FINDINGS The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was considered statistically significant. In multivariable-adjusted conditional logistic regression models with BMI used to define adiposity, compared with metabolically healthy/normal weight individuals, we observed a higher colorectal cancer risk among metabolically unhealthy/normal weight (odds ratio [OR] = 1.59, 95% CI 1.10-2.28) and metabolically unhealthy/overweight (OR = 1.40, 95% CI 1.01-1.94) participants, but not among metabolically healthy/overweight individuals (OR = 0.96, 95% CI 0.65-1.42). Among the overweight individuals, lower colorectal cancer risk was observed for metabolically healthy/overweight individuals compared with metabolically unhealthy/overweight individuals (OR = 0.69, 95% CI 0.49-0.96). These associations were generally consistent when waist circumference was used as the measure of adiposity. To our knowledge, there is no universally accepted clinical definition for using C-peptide level as an indication of hyperinsulinaemia. Therefore, a possible limitation of our analysis was that the classification of individuals as being hyperinsulinaemic-based on their C-peptide level-was arbitrary. However, when we used quartiles or the median of C-peptide, instead of tertiles, as the cut-point of hyperinsulinaemia, a similar pattern of associations was observed. CONCLUSIONS These results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.

An unusual uterine tumor with signet ring cell features.

In 2004, a 56-year-old woman was diagnosed with Stage IA follicular lymphoma in a cervical lymph node biopsy. The patient experienced total remission after local radiation therapy. In 2009, a control computed tomography scan evidenced a pelvic mass, prompting total hysterectomy. The latter harbored a 4.8-cm intramural uterine tumor corresponding to a mostly diffuse and focally nodular proliferation of medium to large cells, with extensive, periodic acid-Schiff negative, signet ring cell changes, and a pan-keratin negative, CD20+, CD10+, Bcl2+, Bcl6+ immunophenotype. Molecular genetic studies showed the same clonal IGH gene rearrangement in the lymph node and the uterus, establishing the uterine tumor as a relapse of the preceding follicular lymphoma, although no signet ring cells were evidenced at presentation. Uterine localization of lymphomas is rare, and lymphomas with signet ring cell features are uncommon. This exceptional case exemplifies a diagnostically challenging situation and expands the differential diagnosis of uterine neoplasms displaying signet ring cell morphology.

Prediction of fat-free mass using bioelectrical impedance analysis in young adults from five populations of African origin.

Background/objectives:Bioelectrical impedance analysis (BIA) is used in population and clinical studies as a technique for estimating body composition. Because of significant under-representation in existing literature, we sought to develop and validate predictive equation(s) for BIA for studies in populations of African origin.Subjects/methods:Among five cohorts of the Modeling the Epidemiologic Transition Study, height, weight, waist circumference and body composition, using isotope dilution, were measured in 362 adults, ages 25-45 with mean body mass indexes ranging from 24 to 32. BIA measures of resistance and reactance were measured using tetrapolar placement of electrodes and the same model of analyzer across sites (BIA 101Q, RJL Systems). Multiple linear regression analysis was used to develop equations for predicting fat-free mass (FFM), as measured by isotope dilution; covariates included sex, age, waist, reactance and height(2)/resistance, along with dummy variables for each site. Developed equations were then tested in a validation sample; FFM predicted by previously published equations were tested in the total sample.Results:A site-combined equation and site-specific equations were developed. The mean differences between FFM (reference) and FFM predicted by the study-derived equations were between 0.4 and 0.6âeuro0/00kg (that is, 1% difference between the actual and predicted FFM), and the measured and predicted values were highly correlated. The site-combined equation performed slightly better than the site-specific equations and the previously published equations.Conclusions:Relatively small differences exist between BIA equations to estimate FFM, whether study-derived or published equations, although the site-combined equation performed slightly better than others. The study-derived equations provide an important tool for research in these understudied populations.

Cell disposition of raltegravir and newer antiretrovirals in HIV-infected patients: high inter-individual variability in raltegravir cellular penetration.

Objectives The site of pharmacological activity of raltegravir is intracellular. Our aim was to determine the extent of raltegravir cellular penetration and whether raltegravir total plasma concentration (C(tot)) predicts cellular concentration (C(cell)). Methods Open-label, prospective, pharmacokinetic study on HIV-infected patients on a stable raltegravir-containing regimen. Plasma and peripheral blood mononuclear cells were simultaneously collected during a 12 h dosing interval after drug intake. C(tot) and C(cell) of raltegravir, darunavir, etravirine, maraviroc and ritonavir were measured by liquid chromatography coupled to tandem mass spectrometry after protein precipitation. Longitudinal mixed effects analysis was applied to the C(cell)/C(tot) ratio. Results Ten HIV-infected patients were included. The geometric mean (GM) raltegravir total plasma maximum concentration (C(max)), minimum concentration (C(min)) and area under the time-concentration curve from 0-12 h (AUC(0-12)) were 1068 ng/mL, 51.1 ng/mL and 4171 ng·h/mL, respectively. GM raltegravir cellular C(max), C(min) and AUC(0-12) were 27.5 ng/mL, 2.9 ng/mL and 165 ng·h/mL, respectively. Raltegravir C(cell) corresponded to 5.3% of C(tot) measured simultaneously. Both concentrations fluctuate in parallel, with C(cell)/C(tot) ratios remaining fairly constant for each patient without a significant time-related trend over the dosing interval. The AUC(cell)/AUC(tot) GM ratios for raltegravir, darunavir and etravirine were 0.039, 0.14 and 1.55, respectively. Conclusions Raltegravir C(cell) correlated with C(tot) (r = 0.86). Raltegravir penetration into cells is low overall (∼5% of plasma levels), with distinct raltegravir cellular penetration varying by as much as 15-fold between patients. The importance of this finding in the context of development of resistance to integrase inhibitors needs to be further investigated.

Répartition du tissu adipeux: implications cliniques [Localization of adipose tissue: clinical implications]

The excessive accumulation of the adipose tissue is at the origin of the obesity. However its severity has no direct correlation with the comorbidities. These last ones are rather linked to the type of distribution of the fat than to its total quantity. The morphological and functional analysis of the adipose tissue reveals specific differences in its localization. The adipose tissue is thus a complex organ constituted by several cell types having various capacities of hypertrophy, hyperplasia and differentiation. While the first one is more predominant in the subcutaneous compartment, where the cell size is big, the others are more specific of the visceral adipocytes. Finally the severity of the obesity is linked to hypertrophy, while the comorbidities are associated with the capacity of proliferation and differentiation.