The health of women and girls determines the health and well-being of our modern world: A White Paper From the International Council on Women's Health Issues

The International Council on Women's Health Issues (ICOWHI) is an international nonprofit association dedicated to the goal of promoting health, health care, and well-being of women and girls throughout the world through participation, empowerment, advocacy, education, and research. We are a multidisciplinary network of women's health providers, planners, and advocates from all over the globe. We constitute an international professional and lay network of those committed to improving women and girl's health and quality of life. This document provides a description of our organization mission, vision, and commitment to improving the health and well-being of women and girls globally

Tyrosine hydroxylase activity in the endocrine pancreas: changes induced by short-term dietary manipulation

BACKGROUND: Tyrosine hydroxylase (TH) activity and its possible participation in the control of insulin secretion were studied in pancreatic islets of adult Wistar rats fed a standard commercial diet (SD) or carbohydrates alone (CHD) for one week. TH activity, norepinephrine (NE) content, and glucose-induced insulin secretion were assessed. Blood glucose and insulin levels were measured at the time of sacrifice. RESULTS: CHD rats had significantly higher blood glucose and lower insulin levels than SD rats (114.5 ± 6.7 vs 80.7 ± 7.25 mg/dl, p < 0.001; 20.25 ± 2.45 vs 42.5 ± 4.99 μU/ml, p < 0.01, respectively). Whereas TH activity was significantly higher in CHD isolated islets (600 ± 60 vs 330 ± 40 pmol/mg protein/h; p < 0.001), NE content was significantly lower (18 ± 1 vs 31 ± 5 pmol/mg protein), suggesting that TH activity would be inhibited by the end-products of catecholamines (CAs) biosynthetic pathway. A similar TH activity was found in control and solarectomized rats (330 ± 40 vs 300 ± 80 pmol/mg protein/h), suggesting an endogenous rather than a neural origin of TH activity. CHD islets released significantly less insulin in response to glucose than SD islets (7.4 ± 0.9 vs 11.4 ± 1.1 ng/islet/h; p < 0.02). CONCLUSIONS: TH activity is present in islet cells; dietary manipulation simultaneously induces an increase in this activity together with a decrease in glucose-induced insulin secretion in rat islets. TH activity – and the consequent endogenous CAs turnover – would participate in the paracrine control of insulin secretion

Extreme Makeover: Bending the Rules to Reduce Risk Rewriting Complex Systems

Abstract. We describe our experience using XP to reimplement sophisticated, high-performance imaging software in a research environment. We focus espe-cially on practices we used to derive value from the existing software, notably reimplementation by ransacking and conversion as learning. Our experience suggests that some of the classic 12 practices which define XP should be ad-justed when there is a existing, well-structured system to serve as a guide.

Musashi expression in β-cells coordinates insulin expression, apoptosis and proliferation in response to endoplasmic reticulum stress in diabetes

Diabetes is associated with the death and dysfunction of insulin-producing pancreatic β-cells. In other systems, Musashi genes regulate cell fate via Notch signaling, which we recently showed regulates β-cell survival. Here we show for the first time that human and mouse adult islet cells express mRNA and protein of both Musashi isoforms, as well Numb/Notch/Hes/neurogenin-3 pathway components. Musashi expression was observed in insulin/glucagon double-positive cells during human fetal development and increased during directed differentiation of human embryonic stem cells (hESCs) to the pancreatic lineage. De-differentiation of β-cells with activin A increased Msi1 expression. Endoplasmic reticulum (ER) stress increased Msi2 and Hes1, while it decreased Ins1 and Ins2 expression, revealing a molecular link between ER stress and β-cell dedifferentiation in type 2 diabetes. These effects were independent of changes in Numb protein levels and Notch activation. Overexpression of MSI1 was sufficient to increase Hes1, stimulate proliferation, inhibit apoptosis and reduce insulin expression, whereas Msi1 knockdown had the converse effects on proliferation and insulin expression. Overexpression of MSI2 resulted in a decrease in MSI1 expression. Taken together, these results demonstrate overlapping, but distinct roles for Musashi-1 and Musashi-2 in the control of insulin expression and β-cell proliferation. Our data also suggest that Musashi is a novel link between ER stress and the compensatory β-cell proliferation and the loss of β-cell gene expression seen in specific phases of the progression to type 2 diabetes

Gene Expression Profiling of a Mouse Model of Pancreatic Islet Dysmorphogenesis

In the past decade, several transcription factors critical for pancreas organogenesis have been identified. Despite this success, many of the factors necessary for proper islet morphogenesis and function remain uncharacterized. Previous studies have shown that transgenic over-expression of the transcription factor Hnf6 specifically in the pancreatic endocrine cell lineage resulted in disruptions in islet morphogenesis, including dysfunctional endocrine cell sorting, increased individual islet size, increased number of peripheral endocrine cell types, and failure of islets to migrate away from the ductal epithelium. The mechanisms whereby maintained Hnf6 causes defects in islet morphogenesis have yet to be elucidated.We exploited the dysmorphic islets in Hnf6 transgenic animals as a tool to identify factors important for islet morphogenesis. Genome-wide microarray analysis was used to identify differences in the gene expression profiles of late gestation and early postnatal total pancreas tissue from wild type and Hnf6 transgenic animals. Here we report the identification of genes with an altered expression in Hnf6 transgenic animals and highlight factors with potential importance in islet morphogenesis. Importantly, gene products involved in cell adhesion, cell migration, ECM remodeling and proliferation were found to be altered in Hnf6 transgenic pancreata, revealing specific candidates that can now be analyzed directly for their role in these processes during islet development.This study provides a unique dataset that can act as a starting point for other investigators to explore the role of the identified genes in pancreatogenesis, islet morphogenesis and mature beta cell function

Sweet Taste Receptor Expressed in Pancreatic β-Cells Activates the Calcium and Cyclic AMP Signaling Systems and Stimulates Insulin Secretion

BACKGROUND:Sweet taste receptor is expressed in the taste buds and enteroendocrine cells acting as a sugar sensor. We investigated the expression and function of the sweet taste receptor in MIN6 cells and mouse islets. METHODOLOGY/PRINCIPAL FINDINGS:The expression of the sweet taste receptor was determined by RT-PCR and immunohistochemistry. Changes in cytoplasmic Ca(2+) ([Ca(2+)](c)) and cAMP ([cAMP](c)) were monitored in MIN6 cells using fura-2 and Epac1-camps. Activation of protein kinase C was monitored by measuring translocation of MARCKS-GFP. Insulin was measured by radioimmunoassay. mRNA for T1R2, T1R3, and gustducin was expressed in MIN6 cells. In these cells, artificial sweeteners such as sucralose, succharin, and acesulfame-K increased insulin secretion and augmented secretion induced by glucose. Sucralose increased biphasic increase in [Ca(2+)](c). The second sustained phase was blocked by removal of extracellular calcium and addition of nifedipine. An inhibitor of inositol(1, 4, 5)-trisphophate receptor, 2-aminoethoxydiphenyl borate, blocked both phases of [Ca(2+)](c) response. The effect of sucralose on [Ca(2+)](c) was inhibited by gurmarin, an inhibitor of the sweet taste receptor, but not affected by a G(q) inhibitor. Sucralose also induced sustained elevation of [cAMP](c), which was only partially inhibited by removal of extracellular calcium and nifedipine. Finally, mouse islets expressed T1R2 and T1R3, and artificial sweeteners stimulated insulin secretion. CONCLUSIONS:Sweet taste receptor is expressed in beta-cells, and activation of this receptor induces insulin secretion by Ca(2+) and cAMP-dependent mechanisms

Intimate partner violence among pregnant women in Rwanda

<p>Abstract</p> <p>Background</p> <p>Intimate partner violence (IPV), defined as actual or threatened physical, sexual, psychological, and emotional abuse by current or former partners is a global public health concern. The prevalence and determinants of intimate partner violence (IPV) against pregnant women has not been described in Rwanda. A study was conducted to identify variables associated with IPV among Rwandan pregnant women.</p> <p>Methods</p> <p>A convenient sample of 600 pregnant women attending antenatal clinics were administered a questionnaire which included items on demographics, HIV status, IPV, and alcohol use by the male partner. Mean age and proportions of IPV in different groups were assessed. Odds of IPV were estimated using logistic regression analysis.</p> <p>Results</p> <p>Of the 600 respondents, 35.1% reported IPV in the last 12 months. HIV+ pregnant women had higher rates of all forms of IVP violence than HIV- pregnant women: pulling hair (44.3% vs. 20.3%), slapping (32.0% vs. 15.3%), kicking with fists (36.3% vs. 19.7%), throwing to the ground and kicking with feet (23.3% vs. 12.7%), and burning with hot liquid (4.1% vs. 3.5%). HIV positive participants were more than twice likely to report physical IPV than those who were HIV negative (OR = 2.38; 95% CI [1.59, 3.57]). Other factors positively associated with physical IPV included sexual abuse before the age of 14 years (OR = 2.69; 95% CI [1.69, 4.29]), having an alcohol drinking male partner (OR = 4.10; 95% CI [2.48, 6.77] for occasional drinkers and OR = 3.37; 95% CI [2.05, 5.54] for heavy drinkers), and having a male partner with other sexual partners (OR = 1.53; 95% CI [1.15, 2.20]. Education was negatively associated with lifetime IPV.</p> <p>Conclusion</p> <p>We have reported on prevalence of IPV violence among pregnant women attending antenatal care in Rwanda, Central Africa. We advocate that screening for IPV be an integral part of HIV and AIDS care, as well as routine antenatal care. Services for battered women should also be made available.</p