Adverse cardiac remodeling due to maternal low protein diet is associated with alterations in expression of genes regulating glucose metabolism

Background and aimsWe have previously shown that a maternal low protein (LP) diet during pregnancy in the rat results in adverse ventricular remodeling and contractile deficiencies of the neonatal rat heart. Since pathological cardiac hypertrophy is associated with increased expression of genes involved in glucose handling, this study was undertaken to examine if maternal LP diet alters the expression of genes encoding for some key components of glucose metabolism and uptake, and of the insulin receptor (IR) signal transduction in the heart of male offspring.Methods and resultsWe determined the effect of maternal LP and normal diet (90 and 180 g/casein/kg respectively) on IR β-subunit, insulin receptor substrate (IRS)-1, phosphotyrosyl protein phosphatase (PTP) 1B, GLUT4 and phosphatidylinositol (PI) 3-kinase in male rat offspring at 24 h and at 1, 4 and 8 wks post-partum. Quantitative real-time RT-PCR revealed significant age-dependent increases in the expression of IR β-subunit, IRS-1, PTP1B, GLUT4 and PI3-kinase in the LP group with concomitant increases in corresponding protein abundance at 4 wks of age. These changes were associated with increases in left ventricular (LV) internal diameters as well as increases in LV wall thickness.ConclusionA maternal LP diet can induce increases in the gene expression and protein levels of key components of glucose metabolism and the IR signal transduction pathway in the neonatal rat heart, which may be related to accelerated energy supply, demand and utilization for ventricular remodeling due to compromised contractile performance during early life.     

Is Biblioleaks Inevitable?

In 2014, the vast majority of published biomedical research is still hidden behind paywalls rather than open access. For more than a decade, similar restrictions over other digitally available content have engendered illegal activity. Music file sharing became rampant in the late 1990s as communities formed around new ways to share. The frequency and scale of cyber-attacks against commercial and government interests has increased dramatically. Massive troves of classified government documents have become public through the actions of a few. Yet we have not seen significant growth in the illegal sharing of peer-reviewed academic articles. Should we truly expect that biomedical publishing is somehow at less risk than other content-generating industries? What of the larger threat—a “Biblioleaks” event—a database breach and public leak of the substantial archives of biomedical literature? As the expectation that all research should be available to everyone becomes the norm for a younger generation of researchers and the broader community, the motivations for such a leak are likely to grow. We explore the feasibility and consequences of a Biblioleaks event for researchers, journals, publishers, and the broader communities of doctors and the patients they serve.     

Feeding of a well‐cooked beef diet containing a high heterocyclic amine content enhances colon and stomach carcinogenesis in 1,2‐dimethylhydrazine‐treated rats

Epidemiologic studies have linked the consumption of red meat and the consumption of highly browned meats containing high levels of heterocyclic aromatic amines (HCAs) to increased risk of colorectal cancer or polyps. The present study determined the effects of long‐term feeding of beef‐containing diets with low and high levels of HCAs (in the context of a low or high beef tallow diet) on a standard 1,2‐dimethylhydrazine (DMH)‐induced colon tumorigenesis protocol. Very lean beef was cooked by a variety of methods at different temperatures, and the levels of the major HCAs (2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline, 2‐amino‐3,4,8‐trimethylimidazo[4,5‐f]quinoxaline, and 2‐amino‐l‐methyl‐6‐phenylimidazo[4,5‐f]pyridine) were measured by high‐performance liquid chromatogra‐phy. Diets incorporating beef containing low or high levels of HCAs were fed for 12 weeks, during which DMH was administered to induce colon tumors, followed by various dietary regimens as promotional stimuli. Feeding of a beef diet high in HCAs resulted in more DMH‐induced colon adenocarcinomas, but only in the context of a low‐fat diet. The high‐HCA diets increased stomach tumors in all DMH‐treated rats. An apparent interaction of high HCA with a high fat level reduced the colon tumor incidence and tumor numbers in those diets containing both factors. These results support the epidemiologic data linking well‐cooked meat to increased risk for colon and stomach cancer, but the role of dietary fat level remains puzzling.     

SELF-EFFICACY AND LOCUS OF CONTROL AFFECT MANAGEMENT OF AGGRESSION BY MENTAL HEALTH NURSES

The safe and effective management of aggression has become an increasingly critical skill for mental health nurses, particularly those working in acute inpatient settings. There is considerable evidence to suggest that the psychological constructs of self-efficacy and locus of control are closely related to work performance in a variety of occupations. By drawing upon literature published in the past 15 years, this paper highlights this evidence and draws attention to the relationship between self-efficacy and locus of control. The central argument of the paper is that there may be direct relationships among mental health nurses” self-efficacy, their degree of internality or externality in relation to locus of control, and their ability to safely and effectively manage aggressive incidents. We argue the need to further investigate these relationships and discover whether these variables can be modified through professional development activities.     

Twin Studies and Sports: Estimating the Future?

Twins are a scientist's dream, because studying them reveals the relative Influences of heredity and environment on many facets of human nature—including human performance.     

The differential diagnosis of pilocytic astrocytoma with atypical features and malignant glioma: an analysis of 16 cases with emphasis on distinguishing molecular features

Rare pilocytic astrocytomas (PA) have atypical histologic and clinicoradiologic features that raise the differential diagnosis of glioblastoma. Whether ancillary studies can supplement histopathologic examination in placing these cases accurately on the spectrum of WHO Grade I PA to higher-grade glioma is not always clear, partly because these cases are not common. Here, ten PAs with atypical clinicoradiologic and histologic features and six pediatric glioblastoma multiforme (pGBMs) were analyzed for BRAF V600E, IDH1, IDH2, and TP53 mutations. Ki-67, p53, and p16 protein expression were also examined by immunohistochemistry. BRAF–KIAA1549 fusion status was assessed in the PA subgroup. The rate of BRAF–KIAA1549 fusion was high in these PAs (5/7 tumors) including four extracerebellar examples. A single BRAF V600E mutation was identified in the fusion-negative extracerebellar PA of a very young child who succumbed to the disease. TP53 mutations were present only in malignant gliomas, including three pGBMs and one case designated as PA with anaplastic features (with consultation opinion of pGBM). IDH1 and IDH2 were wild type in all cases, consistent with earlier findings that IDH mutations are not typical in high-grade gliomas of patients ≤14 years of age. Immunohistochemical studies showed substantial overlap in Ki-67 labeling indices, an imperfect correlation between p53 labeling and TP53 mutation status, and complete p16 loss in only two pGBMs but in no PAs. These results suggest that (a) BRAF–KIAA1549 fusion may be common in PAs with atypical clinicoradiologic and histologic features, including those at extracerebellar sites, (b) BRAF V600E mutation is uncommon in extracerebellar PAs, and (c) TP53 mutation analysis remains a valuable tool in identifying childhood gliomas that will likely behave in a malignant fashion.