Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth.

The development of life-threatening cancer metastases at distant organs requires disseminated tumour cells' adaptation to, and co-evolution with, the drastically different microenvironments of metastatic sites. Cancer cells of common origin manifest distinct gene expression patterns after metastasizing to different organs. Clearly, the dynamic interaction between metastatic tumour cells and extrinsic signals at individual metastatic organ sites critically effects the subsequent metastatic outgrowth.

Biomarker-guided sequential targeted therapies to overcome therapy resistance in rapidly evolving highly aggressive mammary tumors.

Combinatorial targeted therapies are more effective in treating cancer by blocking by-pass mechanisms or inducing synthetic lethality. However, their clinical application is hampered by resistance and toxicity. To meet this important challenge, we developed and tested a novel concept of biomarker-guided sequential applications of various targeted therapies using ErbB2-overexpressing/PTEN-low, highly aggressive breast cancer as our model.

Solid anthropomorphic infant whole-body DXA phantom: design, evaluation, and multisite testing.

Background: Dual-energy X-ray absorptiometry (DXA) requires phantoms for quality control and cross-calibration. No commercially available phantoms are designed specifically for whole-body scanning of infants.

Methods: We fabricated a phantom closely matching a 7-kg human infant in body habitus using polyvinyl chloride (PVC), nylon mix, and polyethylene for bone, lean tissue, and fat, respectively, for evaluating the comparability of instruments used in studies on infant body composition.

Effect of soy isoflavone supplementation on menopausal quality of life.

Objective: The purpose of this study was to assess the effect of soy isoflavone supplementation on quality of life in postmenopausal women.

Methods: A multicenter, randomized, double-blind, placebo-controlled 24-month trial was conducted to assess the effect of 80 or 120 mg of daily aglycone hypocotyl soy isoflavone supplementation on quality of life in 403 postmenopausal women using a validated Menopause-Specific Quality of Life questionnaire.

Results: Menopause-Specific Quality of Life domain scores at 1 year and 2 years were similar to baseline.

Assessment of bone mineral status in children with Marfan syndrome.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with skeletal involvement. It is caused by mutations in fibrillin1 (FBN1) gene resulting in activation of TGF-β, which developmentally regulates bone mass and matrix properties. There is no consensus regarding bone mineralization in children with MFS.

Decreased bone mineralization in children with Noonan syndrome: another consequence of dysregulated RAS MAPKinase pathway?

Introduction: Noonan syndrome (NS) is a disorder of RAS- mitogen activated protein kinase (MAPK) pathway with clinical features of skeletal dysplasia. This pathway is essential for regulation of cell differentiation and growth including bone homeostasis. Currently, limited information exists regarding bone mineralization in NS.

Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women.

Background: Soy isoflavones are naturally occurring phytochemicals with weak estrogenic cellular effects. Despite numerous clinical trials of short-term isoflavone supplementation, there is a paucity of data regarding longer-term outcomes and safety.

Objective: Our aim was to evaluate the clinical outcomes of soy hypocotyl isoflavone supplementation in healthy menopausal women as a secondary outcome of a trial on bone health.

Chronic parenteral nutrition induces hepatic inflammation, steatosis, and insulin resistance in neonatal pigs.

Prematurity and overfeeding in infants are associated with insulin resistance in childhood and may increase the risk of adult disease. Total parenteral nutrition (TPN) is a major source of infant nutritional support and may influence neonatal metabolic function. Our aim was to test the hypothesis that TPN induces increased adiposity and insulin resistance compared with enteral nutrition (EN) in neonatal pigs.

Exposing college students to exercise: the Training Interventions and Genetics of Exercise Response (TIGER) study.

Objective: The Training Interventions and Genetics of Exercise Response (TIGER) study is an exercise program designed to introduce sedentary college students to regular physical activity and to identify genetic factors that influence response to exercise.

Participants: A multiracial/ethnic cohort (N = 1,567; 39% male), age 18 to 35 years, participated in the study.

Methods: Subjects underwent 30 weeks of exercise training, 3 days/week, for 40 minutes at 65% to 85% of age- and gender-predicted maximum heart rate reserve.

Generalized equations for estimating DXA percent fat of diverse young women and men: the TIGER study.

Purpose: Popular generalized equations for estimating percent body fat (BF%) developed with cross-sectional data are biased when applied to racially/ethnically diverse populations. We developed accurate anthropometric models to estimate dual-energy x-ray absorptiometry BF% (DXA-BF%) that can be generalized to ethnically diverse young adults in both cross-sectional and longitudinal field settings.

Methods: This longitudinal study enrolled 705 women and 428 men (aged 17-35 yr) for 30 wk of exercise training (3 d·wk(-1) for 30 min·d(-1) of 65%-85% predicted V˙O2max).

Body composition in infancy: impact on health later in life.

From retrospective studies, there is substantial evidence that birthweight and the rate of weight gain during early infancy are associated with increased risk for adverse health outcomes later in life. Birthweight is the marker of the integrative effects of the prenatal environment, while the rate of weight gain after birth reflects both genetic potential and external postnatal influences. The adulthood-to-infancy associations constitute the basis for the 'fetal origins' and 'catch-up growth' hypotheses for some diseases.

A comparison of the growth responses following intramuscular GHRH plasmid administration versus daily growth hormone injections in young pigs.

The efficacy of daily porcine growth hormone (GH) injections versus plasmid-driven porcine GH-releasing hormone (pGHRH) production to promote growth was assessed. Ten-day-old piglets were injected intramuscularly with 0.1, 1, or 3 mg pGHRH, or a control plasmid followed by electroporation.

Soy isoflavone supplementation and bone mineral density in menopausal women: a 2-y multicenter clinical trial.

Background: Isoflavones are naturally occurring plant estrogens that are abundant in soy. Although purported to protect against bone loss, the efficacy of soy isoflavone supplementation in the prevention of osteoporosis in postmenopausal women remains controversial.

Objective: Our aim was to test the effect of soy isoflavone supplementation on bone health.

Body mass index bias in defining obesity of diverse young adults: the Training Intervention and Genetics of Exercise Response (TIGER) study.

The BMI cut-score used to define overweight and obesity was derived primarily using data from Caucasian men and women. The present study evaluated the racial/ethnic bias of BMI to estimate the adiposity of young men and women (aged 17-35 years) using dual-energy X-ray absorptiometry (DXA) determination of percentage body fat (DXA-BF%) as the referent standard. The samples were 806 women and 509 men who were tested from one to three times over 9 months providing 1300 observations for women and 820 observations for men.

Impact of body composition on pharmacokinetics of doxorubicin in children: a Glaser Pediatric Research Network study.

Purpose: We studied the relationship between doxorubicin pharmacokinetics and body composition in children with cancer.

Patients And Methods: Children between 1 and 21 years of age, receiving doxorubicin as an infusion of any duration <24 h on either a 1-day or 2-day schedule were eligible if they had no significant abnormality of liver function tests, their dose of doxorubicin was not based on ideal body weight or otherwise "capped," and they weighed > or =12 kg. Body composition was measured by dual-energy X-ray absorptiometry.

Bone mineral content and bone mineral density are lower in older than in younger females with Rett syndrome.

Although bone mineral deficits have been identified in Rett syndrome (RTT), the prevalence of low bone mineral density (BMD) and its association with skeletal fractures and scoliosis has not been characterized fully in girls and women with RTT. Accordingly, we measured total body bone mineral content (BMC) and BMD using dual energy x-ray absorptiometry in a cross-sectional group of 50 females, aged 2-38 y, with RTT. Methyl-CpG-binding 2 (MECP2) mutations, skeletal fractures, and scoliosis were documented.

Generalized metabolic bone disease in Neurofibromatosis type I.

Skeletal abnormalities are a recognized component of Neurofibromatosis type I (NF1) but a generalized metabolic bone defect in NF1 has not been fully characterized thus far. The purpose of this study was to characterize at the densitometric, biochemical and pathological level the bone involvement in NF1 patients. Using dual energy X-ray absorptiometry (DXA) we analyzed bone status in 73 unselected NF1 subjects, 26 males and 47 females, mainly children and adolescents (mean age: 16.

DXA: can it be used as a criterion reference for body fat measurements in children?

Objective: Dual-energy X-ray absorptiometry (DXA) is often cited as a criterion method for body composition measurements. We have previously shown that a new DXA software version (Hologic Discovery V12.1) will affect whole-body bone mineral results for subjects weighing <40 kg.

Effect of prebiotic supplementation and calcium intake on body mass index.

Objective: To assess the effects of a prebiotic supplement and usual calcium intake on body composition changes during pubertal growth.

Study Design: We measured anthropometry and body fat with dual-energy X-ray absorptiometry in 97 young adolescents who were randomized to receive either a daily prebiotic supplement or maltodextrin (control) for 1 year.

Results: Subjects who received the prebiotic supplement had a smaller increase in body mass index (BMI) compared with the control group (BMI difference 0.

Visceral and subcutaneous adiposity measurements in adults: influence of measurement site.

Objective: Excess abdominal adiposity is a known risk factor for cardiovascular diseases. Computed tomography can be used to examine the visceral (VAT) and subcutaneous (SAT) components of abdominal adiposity, but it is unresolved whether single-slice or multi-slice protocols are needed.

Research Method And Procedures: Nine computed tomography scans were obtained in the lumbar spine region of 24 adults.

Metabolic and behavioral predictors of weight gain in Hispanic children: the Viva la Familia Study.

Background: Despite the high prevalence of overweight among Hispanic children in the United States, definitive predictors of weight gain have not been identified in this population.

Objective: The study objective was to test sociodemographic, metabolic, and behavioral predictors of 1-y weight gains in a large cohort of Hispanic children studied longitudinally.

Design: Subjects (n = 879) were siblings from 319 Hispanic families enrolled in the Viva la Familia Study.

Body-composition assessment in infancy: air-displacement plethysmography compared with a reference 4-compartment model.

Background: A better understanding of the associations of early infant nutrition and growth with adult health requires accurate assessment of body composition in infancy.

Objective: This study evaluated the performance of an infant-sized air-displacement plethysmograph (PEA POD Infant Body Composition System) for the measurement of body composition in infants.

Design: Healthy infants (n = 49; age: 1.

Evaluation of body composition in neonates and infants.

A better understanding of the nutritional needs of both healthy and sick infants is important. Not only does too much or too little nutrition during early life have long-term effects on health, but periods of rapid growth during the first year of life also have long-term consequences. Knowledge of the changes in body composition in early life can help to better define nutritional needs at these ages.