Molecular Mechanisms of the Diabetogenic Effects of Arsenic: Inhibition of Insulin Signaling by Arsenite and Methylarsonous Acid

BACKGROUND: Increased prevalences of diabetes mellitus have been reported among individuals chronically exposed to inorganic arsenic (iAs). However, the mechanisms underlying the diabetogenic effects of iAs have not been characterized. We have previously shown that trivalent metabolites of iAs, arsenite (iAs(III)) and methylarsonous acid (MAs(III)) inhibit insulin-stimulated glucose uptake (ISGU) in 3T3-L1 adipocytes by suppressing the insulin-dependent phosphorylation of protein kinase B (PKB/Akt). OBJECTIVES: Our goal was to identify the molecular mechanisms responsible for the suppression of PKB/Akt phosphorylation by iAs(III) and MAs(III). METHODS: The effects of iAs(III) and MAs(III) on components of the insulin-activated signal transduction pathway that regulate PKB/Akt phosphorylation were examined in 3T3-L1 adipocytes. RESULTS: Subtoxic concentrations of iAs(III) or MAs(III) had little or no effect on the activity of phosphatidylinositol 3-kinase (PI-3K), which synthesizes phosphatidylinositol-3,4,5-triphosphate (PIP(3)), or on phosphorylation of PTEN (phosphatase and tensin homolog deleted on chromosome ten), a PIP(3) phosphatase. Neither iAs(III) nor MAs(III) interfered with the phosphorylation of 3-phosphoinositide-dependent kinase-1 (PDK-1) located downstream from PI-3K. However, PDK-1 activity was inhibited by both iAs(III) and MAs(III). Consistent with these findings, PDK-1-catalyzed phosphorylation of PKB/Akt(Thr308) and PKB/Akt activity were suppressed in exposed cells. In addition, PKB/Akt(Ser473) phosphorylation, which is catalyzed by a putative PDK-2, was also suppressed. Notably, expression of constitutively active PKB/Akt restored the normal ISGU pattern in adipocytes treated with either iAs(III) or MAs(III). CONCLUSIONS: These results suggest that inhibition of the PDK-1/PKB/Akt-mediated transduction step is the key mechanism for the inhibition of ISGU in adipocytes exposed to iAs(III) or MAs(III), and possibly for impaired glucose tolerance associated with human exposures to iAs

Services just for men? Insights from a national study of the well men services pilots.

Men continue to have a lower life expectancy in most countries compared to women. Explanations of this gendered health inequality tend to focus on male risk taking, unhealthy lifestyle choices and resistance to seeking help from health services. In the period 2005-2008 the Scottish Government funded a nationwide community health promotion programme aimed at improving men's health, called Well Men Service Pilots (henceforth WMS)

Understanding Dwarf Galaxies in order to Understand Dark Matter

Much progress has been made in recent years by the galaxy simulation community in making realistic galaxies, mostly by more accurately capturing the effects of baryons on the structural evolution of dark matter halos at high resolutions. This progress has altered theoretical expectations for galaxy evolution within a Cold Dark Matter (CDM) model, reconciling many earlier discrepancies between theory and observations. Despite this reconciliation, CDM may not be an accurate model for our Universe. Much more work must be done to understand the predictions for galaxy formation within alternative dark matter models.Comment: Refereed contribution to the Proceedings of the Simons Symposium on Illuminating Dark Matter, to be published by Springe

Effect of refrigeration at -1°C on spermatozoa quality of domestic cats

ABSTRACT: The objective of this study was to evaluate the sperm quality obtained of domestic cats by electroejaculation and recovery of the tail of the epididymis after cooling at -1°C and 4°C for 24 and 48 hours. Twenty-nine adult cats (2 to 6kg) were used. Sperm collection was performed by electroejaculation (EEJ), and after 48 hours, the cats were orchiectomized, and sperm sample was obtained from the vas deferens and epididymis tail (EPD). The samples were diluted in ACP-117® extender, and the sperm characteristics were evaluated at three different moments: when still fresh, 24 and 48 hours after cooling. In order to compare the two refrigeration temperatures, the first stage was to analyze if there was a difference between the harvesting techniques. After this, two experiments were conducted: in the first, sperm sample from 14 cats were used and the cooling was performed at -1°C; and in the second, sample from 15 cats were used and the sperm were refrigerated at 4°C. Sperm kinetics were evaluated by computerized analysis (CASA) and concentration by Neubauer chamber, spermatic morphology was evaluated by modified Karras staining, and membrane integrity was evaluated by eosin nigrosine. The results obtained were analyzed in R software, version 3.2.5 using the Mann-Whitney test for variables with abnormal distributions, considering significance at the level of 5%. In ejaculate samples, higher values of total morphological defects were observed after 24 and 48 hours of refrigeration at 4°C (P<0.022) compared to refrigeration at -1°C, using Friedman test. To quantify the decrease in sperm quality, parameter reductions were calculated among time points (F-24h/F-48h/24h-48h). In EPD samples, a greater reduction in sperm quality was detected after 24 hours of refrigeration at 4°C, both in motility and sperm kinetics and in the movement and velocity indices, compared to refrigeration at -1°C. Based on the results, it can be concluded that cooling of feline spermatozoa at -1°C for up to 48 hours was efficient in maintaining spermatic quality collected by EEJ and EPD, and it could be an alternative to spermatozoa cryopreservation in domestic felines

Nanoemulsion with wine lees: a green approach

Abstract Bioactive substances can be found in wine lees, a waste from the winemaking industry. This work developed two formulations, a nanoemulsion with coconut oil (NE-OC) and a nanoemulsion with coconut oil and 0.5% of wine lees extract (NE-OC-Ext), to investigate their effect on untreated, bleached, and bleached-colored hair. The oil-in-water (O/W) nanoemulsions were prepared with coconut oil, TweenTM 80, SpanTM 80, AristoflexTM AVC, Conserve NovaMit MFTM, wine lees extract, and deionized water. The hydration measurements were carried out using a Corneometer® CM 825 with the capacitance method. Scanning electron microscopy (SEM) was used to characterize the effect of formulations on hair fibers. Differential Thermal Analysis (DTA) was to assess the thermal stability and compatibility of wine lees and coconut oil in formulations. Compared to NE-OC, NE-OC-Ext showed a greater hydration effect on bleached-colored hair. DTA showed that NE-OC-Ext presented a smaller number of exothermic degradation events than those of NE-OC, suggesting good interaction and compatibility of the wine lees extract in this formulation. This study highlights the value of wine lees, a residue from the winemaking process, and its possibility of use as raw material for the cosmetic hair industry since it shows a greater moisturizing potential in colored hair

Maternal risk factors for abnormal placental growth: The national collaborative perinatal project

<p>Abstract</p> <p>Background</p> <p>Previous studies of maternal risk factors for abnormal placental growth have focused on placental weight and placental ratio as measures of placental growth. We sought to identify maternal risk factors for placental weight and two neglected dimensions of placental growth: placental thickness and chorionic plate area.</p> <p>Methods</p> <p>We conducted an analysis of 24,135 mother-placenta pairs enrolled in the National Collaborative Perinatal Project, a prospective cohort study of pregnancy and child health. We defined growth restriction as < 10^thpercentile and hypertrophy as > 90^thpercentile for three placental growth dimensions: placental weight, placental thickness and chorionic plate area. We constructed parallel multinomial logistic regression analyses to identify (a) predictors of restricted growth (vs. normal) and (b) predictors of hypertrophic growth (vs. normal).</p> <p>Results</p> <p>Black race was associated with an increased likelihood of growth restriction for placental weight, thickness and chorionic plate area, but was associated with a reduced likelihood of hypertrophy for these three placental growth dimensions. We observed an increased likelihood of growth restriction for placental weight and chorionic plate area among mothers with hypertensive disease at 24 weeks or beyond. Anemia was associated with a reduced likelihood of growth restriction for placental weight and chorionic plate area. Pre-pregnancy BMI and pregnancy weight gain were associated with a reduced likelihood of growth restriction and an increased likelihood of hypertrophy for all three dimensions of placental growth.</p> <p>Conclusion</p> <p>Maternal risk factors are either associated with placental growth restriction or placental hypertrophy not both. Our findings suggest that the placenta may have compensatory responses to certain maternal risk factors suggesting different underlying biological mechanisms.</p

From theoretical concepts to policies and applied programmes: the landscape of integration of oral health in primary care

Background: Despite its importance, the integration of oral health into primary care is still an emerging practice in the field of health care services. This scoping review aims to map the literature and provide a summary on the conceptual frameworks, policies and programs related to this concept. Methods: Using the Levac et al. six-stage framework, we performed a systematic search of electronic databases, organizational websites and grey literature from 1978 to April 2016. All relevant original publications with a focus on the integration of oral health into primary care were retrieved. Content analyses were performed to synthesize the results. Results: From a total of 1619 citations, 67 publications were included in the review. Two conceptual frameworks were identified. Policies regarding oral heath integration into primary care were mostly oriented toward common risk factors approach and care coordination processes. In general, oral health integrated care programs were designed in the public health sector and based on partnerships with various private and public health organizations, governmental bodies and academic institutions. These programmes used various strategies to empower oral health integrated care, including building interdisciplinary networks, training nondental care providers, oral health champion modelling, enabling care linkages and care coordinated process, as well as the use of e-health technologies. The majority of studies on the programs outcomes were descriptive in nature without reporting long-term outcomes. Conclusions: This scoping review provided a comprehensive overview on the concept of integration of oral health in primary care. The findings identified major gaps in reported programs outcomes mainly because of the lack of related research. However, the results could be considered as a first step in the development of health care policies that support collaborative practices and patient-centred care in the field of primary care sector