Short-Term Mediterranean Diet Improves Endurance Exercise Performance: A Randomized-Sequence Crossover Trial.

Objective: Healthful dietary patterns have constituents that are known to improve exercise performance, such as antioxidants, nitrates, and alkalizing effects. However, ergogenic effects of such diets have not been evaluated. We hypothesized that a short-term Mediterranean diet results in better exercise performance, as compared to a typical Western diet. Methods: Eleven recreationally active women (n = 7) and men (n = 4) (body mass index, 24.6 ± 3.2 kg/m2; age 28 ± 3 years) were studied in a randomized-sequence crossover study, in which they underwent exercise performance testing on one occasion after 4 days of a Mediterranean diet and on another occasion after 4 days of a Western diet. A 9- to 16-day washout period separated the two trials. Endurance exercise performance was evaluated with a 5-km treadmill time trial. Anaerobic exercise performance tests included a Wingate cycle test, a vertical jump test, and hand grip dynamometry. Results: Five-kilometer run time was 6% ± 3% shorter (faster) in the Mediterranean diet trial than in the Western diet trial (27.09 ± 3.55 vs 28.59 ± 3.21 minutes; p = 0.030) despite similar heart rates (160 ± 5 vs 160 ± 4 beats/min; p = 0.941) and ratings of perceived exertion (14.6 ± 0.5 vs 15.0 ± 0.5; p = 0.356). No differences between the diet conditions were observed for anaerobic exercise tests, including peak and mean power from the Wingate test (both p ≥ 0.05), the vertical jump test (p = 0.19), and the hand grip strength test (p = 0.69). Conclusions: Our findings extend existing evidence of the health benefits of the Mediterranean diet by showing that this diet is also effective for improving endurance exercise performance in as little as 4 days. Further studies are warranted to determine whether a longer-term Mediterranean diet provides greater benefits and whether it might also be beneficial for anaerobic exercise performance and muscle strength and power.

Loss of vitamin D receptor signaling from the mammary epithelium or adipose tissue alters pubertal glandular development.

Vitamin D3 receptor (VDR) signaling within the mammary gland regulates various postnatal stages of glandular development, including puberty, pregnancy, involution, and tumorigenesis. Previous studies have shown that vitamin D3 treatment induces cell-autonomous growth inhibition and differentiation of mammary epithelial cells in culture. Furthermore, mammary adipose tissue serves as a depot for vitamin D3 storage, and both epithelial cells and adipocytes are capable of bioactivating vitamin D3. Despite the pervasiveness of VDR in mammary tissue, individual contributions of epithelial cells and adipocytes, as well as the VDR-regulated cross-talk between these two cell types during pubertal mammary development, have yet to be investigated. To assess the cell-type specific effect of VDR signaling during pubertal mammary development, novel mouse models with mammary epithelial- or adipocyte-specific loss of VDR were generated. Interestingly, loss of VDR in either cellular compartment accelerated ductal morphogenesis with increased epithelial cell proliferation and decreased apoptosis within terminal end buds. Conversely, VDR signaling specifically in the mammary epithelium modulated hormone-induced alveolar growth, as ablation of VDR in this cell type resulted in precocious alveolar development. In examining cellular cross-talk ex vivo, we show that ligand-dependent VDR signaling in adipocytes significantly inhibits mammary epithelial cell growth in part through the vitamin D3-dependent production of the cytokine IL-6. Collectively, these studies delineate independent roles for vitamin D3-dependent VDR signaling in mammary adipocytes and epithelial cells in controlling pubertal mammary gland development.

Intergenerational continuity in alcohol misuse: Maternal alcohol use disorder and the sequelae of maternal and family functioning.

Early onset of alcohol use is associated with a host of detrimental outcomes. As such, understanding the complex etiology of early onset alcohol use for prevention purposes is an important goal. Specific environmental stressors within the family (i.e., financial stress, negative parental well-being and negative family climate) heighten the risk of early onset alcohol use; however, the extent to which these factors are set in motion by prior maternal history of alcohol misuse has yet to be investigated. We used prospective, longitudinal data from 385 mother-child dyads to examine the link between a maternal alcohol use disorder and her child's early onset of alcohol use through the sequelae of maternal financial strain, maternal depressive symptoms, maternal excessive alcohol use, and negative family climate. Results indicate that a maternal alcohol use disorder itself, and the confluence of a maternal alcohol use disorder, subsequent financial strain, and depressive symptoms produce a negative family climate. In turn, a negative family climate increases the likelihood of alcohol use by the age of 15 among offspring. Moreover, we demonstrate that the cascade of consequences on maternal and family functioning linking a maternal alcohol use disorder to her child's early onset of alcohol use is proximal in nature, unfolding concurrently rather than in yearly spans of time. We discuss the implications of these findings with respect to the etiology of early onset alcohol use (and extant theoretical models) and prevention programming. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Assessing Resting Metabolic Rate in Overweight and Obese Adolescents With a Portable Indirect Calorimeter: A Pilot Study for Validation and Reliability.

BACKGROUND: Indirect calorimetry measured via the traditional indirect calorimeter is considered the "gold standard" for determining resting metabolic rate (RMR). Portable devices for assessing RMR are a less expensive option for measuring RMR in the clinical setting. This pilot study tested the reliability and validity of a portable device for measuring RMR, specifically in overweight and obese adolescents. MATERIALS AND METHODS: Participants aged 17-19 years (n = 19) and ≥85th percentile on the Centers for Disease Control and Prevention body mass index growth curves for age and sex were recruited from a university campus. Participants completed testing on a traditional indirect calorimeter and a portable indirect calorimeter in a randomized order on 2 separate testing days. RESULTS: A paired samples t test comparing the means of the portable device and the traditional indirect calorimeter found no significant difference (P = .22). The test-retest intraclass correlation coefficient for assessing RMR was 0.91, indicating reliability of the portable indirect calorimeter. Compared with measured RMR, the Mifflin-St Jeor equation demonstrated 37% accuracy, and the Molnar equation demonstrated 57% accuracy. CONCLUSION: This pilot study found portable indirect calorimetry to be reliable and valid for assessing RMR in an overweight and obese adolescent population. In addition, this study indicates that portable indirect calorimetry may be an acceptable option for assessing RMR in this population compared with the traditional indirect calorimeter or predictive equations.

Deregulation of NR2E3, an orphan nuclear receptor, by benzo(a)pyrene-induced oxidative stress is associated with histone modification status change of the estrogen receptor gene promoter.

We previously reported that NR2E3, an orphan nuclear receptor, plays an important role in maintaining the basal expression of estrogen receptor α (ER) and that the NR2E3 level is highly correlated with the relapse-free survival of breast cancer patients. Here, we investigated the role of NR2E3 in benzo(a)pyrene (BaP)-mediated cell injury. BaP treatment reduced NR2E3 homo-dimer formation and expression and subsequently decreased ER expression. The chromatin immunoprecipitation assay results showed that the treatment of MCF-7 breast cancer cells and the mouse liver with BaP released NR2E3 from the ER promoter to transform the transcriptionally active histone modification status into a repressive state. NR2E3 depletion in MCF-7 cells also induced a similar inactive epigenetic status in the ER promoter region, indicating that NR2E3 is an essential epigenetic player that maintains basal ER expression. Interestingly, these negative effects of BaP on the expression levels of NR2E3 and ER were rescued by antioxidant treatment. Collectively, our study provides novel evidence to show that BaP-induced oxidative stress decreases ER expression, in part by regulating NR2E3 function, which modulates the epigenetic status of the ER promoter. NR2E3 is likely an essential epigenetic player that maintains basal ER expression to protect cells from BaP-induced oxidative injury.

Vitamin D3-dependent VDR signaling delays ron-mediated breast tumorigenesis through suppression of ß-catenin activity.

The Ron receptor is upregulated in human breast cancers and correlates with enhanced metastasis and reduced patient survival. Ron overexpression drives mammary tumorigenesis through direct ß-catenin activation and augmented tumor cell proliferation, migration and invasion. Ron and ß-catenin are also coordinately elevated in breast cancers. The vitamin D receptor (VDR) antagonizes ß-catenin signaling. Herein, we examined mammary tumor onset and progression using a Ron-driven murine model of breast tumorigenesis crossed with VDR deficient mice. VDR ablation accelerated mammary tumor onset and led to tumors that exhibited a desmoplastic phenotype and enhanced metastases. Tumor levels of active ß-catenin were markedly increased in the absence of VDR. In vitro, VDR activation in breast cancer cells reduced ß-catenin activation and transcriptional activity leading to elevated expression of the extracellular Wnt inhibitor dickkopf-related protein 1, and a reduction in the interaction of ß-catenin with the cyclin D1 promoter. Expression of a stabilized form or ß-catenin ablated the protective effects of VDR activation.Collectively, these studies delineate a protective role for VDR signaling in Ron-induced mammary tumorigenesis through disruption of ß-catenin activation.

Hepatocyte growth factor-like protein is a positive regulator of early mammary gland ductal morphogenesis.

The Ron receptor tyrosine kinase regulates multiple cellular processes and is important during mammary gland development and tumor progression. Hepatocyte growth factor-like protein [HGFL] is the only known ligand for the Ron receptor and recent studies have identified major roles for HGFL during breast cancer metastasis. Understanding the functional importance HGFL during mammary gland development will provide significant insights onto its contribution during tumor development and metastasis. In this study, we assessed the role of HGFL during postnatal mammary gland development using mice that were either proficient [HGFL +/+] or deficient [HGFL-/-] for HGFL. Postnatal ductal morphology and stromal cell associations were analyzed at multiple time points through puberty until adulthood. HGFL deficiency resulted in several mammary gland developmental defects including smaller terminal end buds [TEBs], significantly fewer TEBs, and delayed ductal outgrowth during early puberty. Additionally, HGFL deficient animals exhibited significantly altered TEB epithelial cell turnover with decreased proliferation and increased apoptosis coupled with decreased TEB diameter. Macrophage recruitment to the TEBs was also significantly decreased in the HGFL-/- mice compared to controls. Moreover, the levels of STAT3 mRNA as well as the phosphorylation status of this protein were lower in the HGFL-/- mammary glands compared to controls. Taken together, our data provide the first evidence for HGFL as a positive regulator of mammary gland ductal morphogenesis by controlling overall epithelial cell turnover, macrophage recruitment, and STAT3 activation in the developing mammary gland. With a function in early mammary gland development, HGFL represents a potential target for the development of novel breast cancer therapies.

Environmental epigenetics and its implication on disease risk and health outcomes.

This review focuses on how environmental factors through epigenetics modify disease risk and health outcomes. Major epigenetic events, such as histone modifications, DNA methylation, and microRNA expression, are described. The function of dose, duration, composition, and window of exposure in remodeling the individual's epigenetic terrain and disease susceptibility are addressed. The ideas of lifelong editing of early-life epigenetic memories, transgenerational effects through germline transmission, and the potential role of hydroxylmethylation of cytosine in developmental reprogramming are discussed. Finally, the epigenetic effects of several major classes of environmental factors are reviewed in the context of pathogenesis of disease. These include endocrine disruptors, tobacco smoke, polycyclic aromatic hydrocarbons, infectious pathogens, particulate matter, diesel exhaust particles, dust mites, fungi, heavy metals, and other indoor and outdoor pollutants. We conclude that the summation of epigenetic modifications induced by multiple environmental exposures, accumulated over time, represented as broad or narrow, acute or chronic, developmental or lifelong, may provide a more precise assessment of risk and consequences. Future investigations may focus on their use as readouts or biomarkers of the totality of past exposure for the prediction of future disease risk and the prescription of effective countermeasures.

Iron sufficient to cause hepatic fibrosis and ascites does not cause cardiac arrhythmias in the gerbil.

Chronic iron overload associated with hereditary hemochromatosis or repeated red cell transfusions is known to cause cardiac failure. Cardiac arrhythmias have been incidentally noted in patients with iron overload, but they are often dismissed as being related to comorbid conditions. Studies with anesthetized iron-loaded gerbils using short recordings suggest a role for iron in the development of arrhythmias. Our goal was to characterize iron-induced arrhythmias in the chronically instrumented, untethered, telemetered gerbil. Electrocardiograms were recorded for 10 s every 30 min for approximately 6 months in iron-loaded (n=23) and control (n=8) gerbils. All gerbils in both groups showed evidence of frequent sinus arrhythmia. There was no difference in heart rate, electrocardiographic parameters, or number of arrhythmias per minute between groups. Gerbils rarely showed significant arrhythmias. Body weight and heart weight were not significantly different between groups, whereas liver weight increased with increasing iron dose in the treated group. Cardiac and hepatic iron concentrations were significantly increased in iron-loaded gerbils. Eight of 14 gerbils loaded to 6.2 g/kg body weight developed ascites. We conclude that an iron load sufficient to cause clinical liver disease does not cause cardiac arrhythmias in the gerbil model of iron overload.

Effect of pH on the viscosity of titanium dioxide aqueous dispersions with carboxylic acids.

Dispersions of titanium dioxide nanoparticles with terephthalic acid, isophthalic acid, salicylic acid, benzoic acid, and pyridine-2,5-dicarboxylic acid were prepared by aqueous grinding. The pH of the dispersions was adjusted by adding either HCl or NaOH, and the viscosity of the dispersions was measured. It was found that the viscosity of the system depends strongly on pH. The qualitative interpretation of the results based on the DLVO theory is presented. The evidence of the effect of bridging interactions on the viscosity of titanium dioxide-dicarboxylic acid dispersions is discussed.