Islet vascularization in Type 2 Diabetes Mellitus

Diabetes is a complex metabolic disorder characterized by the failure to maintain normoglycemia stemming from dysfunctional islet of Langerhans. It is caused by an autoimmune destruction of insulin secreting beta-cells in case of type 1 diabetes (T1D), or non-insulin dependent diabetes, caused by lack on insulin action and production in type 2 diabetes (T2D) and by insulin insufficiency during pregnancy as in gestational diabetes mellitus (GDM). T2D accounts for at least 90% of the cases of diabetes, although it may remain undetected or at a pre-diabetic stage for several years. Thus, therapeutic intervention to prevent the progression to T2D is a major goal to subside the incidence of the disease and thus prevent further metabolic complications. T2D is most commonly associated with obesity and thus peripheral insulin resistance. In the face of insulin resistance there occurs an array of molecular mechanisms, one of the major activator being inflammation. In serum, adipose tissue, liver and pancreatic islets from T2D patients, pro-inflammatory cytokines like IL-1beta, CXCL10, TNFalpha, IL-6 have been detected and clinical trials are initiated to prevent inflammatory action. In our study, we showed anti-mouse CXCL10 antibody prevented diabetes progression; it improved glucose tolerance, insulin sensitivity and restored glucose stimulated insulin secretion in the HFD fed mice. CXCL10 antagonism also prevented upregulation of pro-inflammatory cytokines, IL-1beta, IL-6 and CXCL10 mRNA in isolated islets, CXCL10 in adipose tissue and liver of high fat/high sucrose diet (HFD) fed mice. Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral antidiabetics widely in use for T2D treatment. The first agent of its class sitagliptin was approved by the FDA in 2006 and since has been investigated for its direct effects on islet function. The gluco-incretin hormones GIP and GLP-1 secreted by the intestinal endocrine cells potentiate glucose stimulated insulin secretion but are rapidly inactivated by DPP-4. We treated cultured human islets with a diabetic milieu of high glucose, palmitate, cytokines and H2O2 in presence of the DPP-4 inhibitor linagliptin. Linagliptin restored beta-cell function and turnover, via mechanism involving stabilization of secreted GLP-1 in islet supernatants. Obesity induced insulin resistance requires expansion of beta-cell mass to maintain normoglycemia. There occurs a compensatory islet hyperplasia, progressing with altered islet vascularization and possibly angiogenesis, inflammation and eventually leading to reduced beta-cell mass, beta-cell failure and hyperglycemia. The molecular mechanisms involved in the concomitant pathophysiology of islet endothelial cells in T2D has focused on effects mediated by VEGF-A. In this study, we aimed to identify the regulation of and the changes driven by the Angiopoietin/Tie angiogenic factors in islet vascularization and function during the progression of T2D. Ang-1 expressed by perivascular cells and beta-cells and Ang-2 expressed by endothelial cells exert their autocrine and paracrine effects via the cognate receptor Tie-2, on the endothelial cells. Tie-2 signaling maintains quiescent vasculature via constitutive Ang-1 expression whereas Ang-2 is known to be in play in demand for angiogenesis or pathological stimuli involving inflammation. Ang/Tie regulation and thus its role in diabetes and islet vascularization is so far poorly understood. Islet vessel area was increased in autopsy pancreases from T2D subjects, compared to controls. Vessel markers Tie-1, Tie-2 and CD31 were upregulated in mouse islets upon HFD feeding from 8 to 24 weeks. Ang-2 was transiently upregulated in mouse islets at 8 weeks of HFD as well under gluco-lipotoxicity in vitro in human and mouse islets, in contrast to its downregulation with cytokine treatment. Ang-1 on the other hand was oppositely regulated, with reduction under glucolipotoxic conditions and upregulation by cytokine milieu. Modulation of such changes in Ang-2 expression by its overexpression or the inhibition of its receptor Tie-2 impaired beta-cell function at basal conditions but protected islets from cytokine induced apoptosis in vitro. In vivo, beta-cell-specific Ang-2 overexpression in mice induced vascularization under normal diet but contrastingly hypovascularized islets under HFD together with increased apoptosis and reduction of beta-cell mass. Our data show that increased islet hypervascularization is paralleled with T2D. Maintaining physiological Ang-2 levels is important for islet vascularization and beta-cell survival

Awareness of Diabetes Risk and Adoption of Diabetes Risk Reduction Behaviors in the Presence of Other Risk Factors in U.S Adults: An Examination of NHANES Data 2007-2008

ABSTRACT Background: Prediabetes is a precursor condition to type 2 diabetes mellitus. Previous research and clinical trials have shown that the onset of type 2 diabetes could be delayed or prevented through structured life style modifications such as dietary changes, modest weight loss and moderate-intensity exercise. This study examines U.S adults of different ethnicities that include non-Hispanic white, non-Hispanic black and Mexican Americans and whether their awareness of diabetes risk is associated with their participation in diabetes risk reduction behavior, a combination of physical activity, weight control and fat/calories intake. Methods: The 2007-2008 National Health and Nutrition Examination Survey, NHANES, was used to conduct a cross-sectional study of 4083 U.S. adults who were 20 years old and above and were aware of their diabetes risk. The association between the awareness of one’s diabetes risk and the adoption of diabetes risk reduction behavior were examined in present of other risk factors such as age, gender, ethnicity, education, annual family income, BMI, hypertension, mean systolic blood pressure, mean diastolic blood pressure, total cholesterol, LDL, HDL and triglyceride levels. Males and females were examined separately for all analyses performed. Cross tabulation was conducted and p-values were calculated by the Pearson’s chi-square test for the categorical variables which include gender, ethnicity, education, annual family income, adiposity and hypertension. One Way ANOVA and Tukey post hoc tests were conducted for the continuous variables which include age, mean systolic blood pressure, mean diastolic blood pressure, total cholesterol, LDL, HDL and triglyceride levels. Univariate and multivariate analyses were performed to determine the association between the main independent variable, awareness of one’s diabetes risk, and the dependent variable, adoption of diabetes risk reduction behavior, controlling for other risk factors. A p-value of \u3c0.05 and 95% confidence intervals were used to determine statistical significance throughout all analyses performed. Results: After controlling for age, gender, race, education, annual family income, BMI, hypertension, mean systolic blood pressure, mean diastolic blood pressure, total cholesterol, LDL, HDL, and triglycerides, results from the multivariate analysis showed that subjects who were aware of their diabetes risk were more likely to adopt diabetes risk reduction behavior (OR= 1,734, 95 % CI=1.217-2.470). Females and non-Hispanic blacks, who were aware of their diabetes risk, were also more likely to adopt diabetes risk reduction behavior compared to males, non-Hispanic whites and Mexican Americans. An increase in the levels of education, annual family income and BMI was also associated with the adoption of diabetes risk reduction behavior. Stratification according to gender and ethnicity, showed that Mexican American males and females were more likely to engage in diabetes risk reduction behavior compared to non-Hispanic whites and non-Hispanic blacks (Mexican American males: OR: 2.496, CI: 0.792-7.868; Mexican American females: OR: 2.830, CI: 0.917-8.736). Conclusion: This study provides useful insights for health care providers and public health professionals who are developing health promotion and prevention interventions to address pre diabetes before it develops into type 2 diabetes. This study also allows the development of tailored interventions for specific genders and ethnic groups that are at risk. Results of this study indicate that Mexican Americans and females (in general) are more likely to adopt diabetes risk reduction behavior. Therefore, physicians and health care providers should develop culturally, linguistically and gender- specific education materials and programs for this particular gender and ethnic group. This in turn, may reduce the overall increasing prevalence of diabetes, reduce racial and gender disparities and may have a positive impact on the overall health of the U.S. population

C.A.R.E (Cohort Assessment & Retrieval Environment)

The purpose of clinical trials is to explore whether a medical treatment is safe and effective for humans or to enhance preexisting methods. The identification of patients who satisfy a set of predefined criteria for the trial is instrumental. However, the process of distinguishing these patients on the basis of their clinical records is a challenging task since it can have structured (ex: precise measurements) and unstructured data (ex: physician notes). One difficulty with this is data normalization; there are many ways to describe a single concept. For example, “heart attack” and “myocardial infarction” both refer to the death of the heart muscle. The goal of this project is to develop a system that will process clinical records for the purpose of cohort discovery and make a visual framework to allow researchers to view and explore the associations between biomedical terms and their characteristics. Steps: 1) The user inputs criteria on what they want/do not want in their patients’ medical records. 2) The criteria and patient records run through a system using MetaMap and MetaMap- DataStructures that measures the association between biomedical terms and links other terms to that word or phrase. 3) The patient records are ranked based on the user input criteria. Therefore, the records that have more prevalent information regarding the input criteria receive a higher score. 4) The user is able to see the records in the order they were ranked. This makes the process of finding patients for a clinical trial more manageable.https://scholarscompass.vcu.edu/capstone/1170/thumbnail.jp

Grafting: Making Space for International and Comparative Education in a Pre-service Teacher Social Foundations Class

This article contributes to a growing appreciation and understanding of both the ways to include exposure to Comparative and International Education (CIE) in undergraduate teacher education as well as to how students take up and respond creatively to opportunities for comparative exploration. In order to make space for comparative education in the already oversubscribed pre-service teacher’s program of study, we (1) explore a strategy to use a required undergraduate social foundations’ class for pre-service teachers at a large public university as a platform for comparative education, and (2) share the lessons learned from creating space for students to express their international and comparative curiosities. We open the article by introducing the “grafting” strategy to make space for the comparative; we then turn to the ways we employed a pedagogical tool we call “drawing out” to allow students to make comparative connections by responding to our deliberate, comparative prompts. We found that by embracing the grafting approach we created opportunities for students to make their own conclusions about the value of comparative considerations and to express their organic interest in the international to better understand domestic developments and options

Reimagining Reproductive Rights Jurisprudence in India: Reflections on the Recent Decisions on Privacy and Gender Equality from the Supreme Court of India

Despite the significant impact of decisions around pregnancy, including abortion, on a woman’s future life and enjoyment of her other human rights, the Indian judiciary has yet to clearly articulate the link between reproductive autonomy and gender equality. Puttaswamy’s recognition of the right to reproductive choice is rooted within the constitutionally protected right to privacy. While the right to privacy has been the basis for ground-breaking judgments on reproductive rights globally, feminist legal theorists have voiced significant critiques as to the limits of privacy, specifically its potential to achieve reproductive autonomy and equality. We explore the applicability of these critiques in India, including concerns voiced by legal scholars regarding the limitations of the right to privacy as a tool for meaningful enjoyment of reproductive autonomy or gender equality as a whole. The post-Puttaswamy decisions of Navtej Johar and Joseph Shine mark a shift in jurisprudence, with the Supreme Court relying on equality-based arguments to reject societal stigmatization and discrimination against the marginalized group in question. In both cases, the court set forth a framework to understand how the rights to privacy, equality, and non-discrimination on the basis of sex and gender intersect. This intersection of rights gives rise to an obligation of states to eliminate laws that reflect discriminatory gender stereotypes, including those pertaining to sexuality. Limits on the right to abortion indirectly or directly marginalize women by controlling their right to bodily autonomy and denying them privacy and equality. Hence, we argue that these cases demonstrate the potential success of arguments for reproductive rights based on equal citizenship. We first lay out the legal framework and jurisprudence of reproductive rights in India before the Puttaswamy decision. We then explore the benefits of having a constitutionally recognized right to privacy and how it can advance reproductive rights. We also examine the drawbacks of using a privacy-based analysis as a foundation for reproductive rights due to its vulnerability to restriction on grounds of compelling state interest. Further, this we engage with feminist critiques of privacy rights as well as equality-based approaches and argue for a framework that takes into consideration meaningful choice and structural barriers to the exercise of reproductive autonomy. We critically examine judgments from comparative and international law that have a strong basis in the right to equality to reflect on how recognition of reproductive rights as an issue of gender justice—beyond just individual choice—could strengthen Indian reproductive rights jurisprudence. In other words, we argue for a reimagination of reproductive rights within an equality framework. Finally, we conclude that the use of an equality-based framework could significantly benefit pregnant persons’ right to reproductive autonomy

Managing risk and uncertainty in systematic conservation planning with insufficient information

This research was supported by Japan Society for the Promotion of Science and by the Okinawa Institute of Science and Technology Graduate University. RKR was supported by an Australian Research Council Discovery Early Career Research Award (DE210100492). JRR was supported by an Australian Research Council Future Fellowship (FT200100096) .1. Recent advances in systematic conservation planning make use of modern portfolio theory - a framework to construct and select optimal allocation of assets - to address the challenges posed by climate change uncertainty. However, these methods are difficult to implement for fine scale conservation planning when the information on future climate scenarios is insufficient. Insufficient information makes the estimators of the key inputs in the optimisation procedure unreliable leading to technical problems for the construction of optimal asset allocation. 2. We identify three statistical methods - Constant Correlation Model, the Ledoit-Wolf approach and the weighted non-negative least-squares approach - that can overcome the lack of sufficient information and enable the use of modern portfolio theory for fine scale conservation planning. 3. We illustrate the use of the three methods for identifying efficient portfolio allocation strategies, i.e. strategies that give minimum amount of risk for a chosen level of return or maximum return for a chosen level of risk, using case studies of wetland conservation planning in North America and coastal conservation planning in Australia. We compare conservation planning strategies with complete information using standard portfolio theory and with insufficient information using the three methods to highlight their advantages and disadvantages. We find the Ledoit-Wolf and weighted non-negative least-squares approaches perform well and can identify risk-return out-comes that are close to those identified with complete information. 4. The methods presented in this study broaden the range of cases where the application of modern portfolio theory is possible in conservation planning to enhance its uptake and lead to more efficient allocation of conservation resources.Publisher PDFPeer reviewe

Algorithmically Generated Visual Knowledge Panels

Information about a particular topic, e.g., in response to a search query, is sometimes presented in a concise user interface (UI) such as a knowledge card or panel. Such panels are typically text intensive and can be unsuitable for certain users, e.g., users that have limited reading capability, or those who prefer visual content. This disclosure describes techniques to render a visual knowledge panel, e.g., one that primarily includes images, videos, and other visual content. Per the techniques, the visual knowledge panel is algorithmically created by mapping a text knowledge panel to existing video or image content such as video Q&A, a short video, a story illustrated by slideshow, etc

Neonatal outcome in deliveries complicated by meconium-stained amniotic fluid

Background: Meconium staining amniotic fluid is associated with lots of adverse outcome and has long been considered to be a bad predictor of fetal outcome. This prospective observational study was undertaken to find out immediate fetal outcome in meconium-stained liquor.Methods: The design of the study was prospective. This study was conducted from July 2021 to December 2021.The study included women with meconium-stained amniotic fluid in labor with gestational age >37 completed weeks.Results: Total 100 cases were enrolled. Majority of the patients (74%) were in the age group of 21-30 years with the mean age being 24.6±2.4 years. Fetal distress occurred in 30% of babies, more in association with thick meconium (15%). Caesarean deliveries were 70%. Apgar scores between 0-3 was seen in 17% babies and 1% at fifth minute, between 4-6 in 21% babies and between 7-10 in 62% babies at first minute of birth. Admission in neonatal ward was 32% with perinatal mortality of 6%.Conclusions: Meconium-stained amniotic fluid was associated with higher rate of caesarean delivery, increased need for neonatal resuscitation, increased rate of birth asphyxia with hypoxic ischemic encephalopathy, meconium aspiration syndrome, hospital admission and mortality. It is more commonly associated with pregnancy induced hypertension (PIH), post-datism, oligohydramnios and gestational diabetes mellitus.