Rabbi Ezra ben Solomon of Gerona, Commentary on the Song of Songs and Other Kabbalistic Commentaries

The commentary of Rabbi Ezra ben Solomon of Gerona (d. ca. 1245) on the Song of Songs is one of the most important texts of the first clearly identified circle of Kabbalists, those operating in the Catalonian town of Gerona at the middle of the thirteenth century.https://scholarworks.wmich.edu/mip_teamscs/1012/thumbnail.jp

Screening for Gestational Diabetes: A Summary of the Evidence for the U.S. Preventive Services Task Force

Gestational diabetes mellitus (GDM) is defined as glucose intolerance with the onset or first detection during pregnancy. About 135,000 cases of GDM are diagnosed annually in the United States. Important risk factors include higher maternal age, family history of diabetes, and increased pregravid body mass index (BMI). The prevalence of GDM in low-risk populations ranges from 1.4% to 2.8%; in high-risk populations, prevalence ranges from 3.3% to 6.1%. Markedly elevated maternal glucose levels most often occur in women with pregestational diabetes. Pregnant women with pregestational diabetes are at higher risk for multiple complications affecting both the mother and the fetus than those women without diabetes. Current therapy improves outcomes for both mother and neonate. The additional risk for adverse health outcomes attributable to the milder degrees of maternal hyperglycemia associated with GDM and the magnitude of the benefit from treating that risk are less certain. No well-designed and conducted randomized controlled trial (RCT) of screening for GDM has been completed, and thus the evidence for screening is indirect. National groups disagree about whether to recommend screening for GDM. Despite no strong recommendations in favor of universal screening from the American College of Obstetricians and Gynecologists (ACOG), 94% of Fellows in office-based practices reported performing universal screening for GDM in 1996. Fellows performed this screening even though ACOG acknowledged the weakness in the evidence in both 1994 and 2000. With continued controversy around the advisability of GDM screening, the RTI-University of North Carolina Evidence-based Practice Center (RTI-UNC EPC) conducted a systematic evidence review to assist the U.S. Preventive Services Task Force (USPSTF) in reconsidering its 1996 review, which found insufficient evidence to recommend screening. We restricted this review to screening for GDM after 24 weeks' gestation, thus excluding both women with known pregestational diabetes and those who are discovered by symptoms earlier in pregnancy.Master of Public Healt

Posttranscriptional Upregulation of IDH1 by HuR Establishes a Powerful Survival Phenotype in Pancreatic Cancer Cells.

Cancer aggressiveness may result from the selective pressure of a harsh nutrient-deprived microenvironment. Here we illustrate how such conditions promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Glucose or glutamine withdrawal resulted in a 5- to 10-fold protective effect with chemotherapy treatment. PDAC xenografts were less sensitive to gemcitabine in hypoglycemic mice compared with hyperglycemic mice. Consistent with this observation, patients receiving adjuvant gemcitabine (n = 107) with elevated serum glucose levels (HgbA1C \u3e 6.5%) exhibited improved survival. We identified enhanced antioxidant defense as a driver of chemoresistance in this setting. ROS levels were doubled in vitro by either nutrient withdrawal or gemcitabine treatment, but depriving PDAC cells of nutrients before gemcitabine treatment attenuated this effect. Mechanistic investigations based on RNAi or CRISPR approaches implicated the RNA binding protein HuR in preserving survival under nutrient withdrawal, with or without gemcitabine. Notably, RNA deep sequencing and functional analyses in HuR-deficient PDAC cell lines identified isocitrate dehydrogenase 1 (IDH1) as the sole antioxidant enzyme under HuR regulation. HuR-deficient PDAC cells lacked the ability to engraft successfully in immunocompromised mice, but IDH1 overexpression in these cells was sufficient to fully restore chemoresistance under low nutrient conditions. Overall, our findings highlight the HuR–IDH1 regulatory axis as a critical, actionable therapeutic target in pancreatic cancer

Rationale, design, and methodology for the optimizing outcomes in women with gestational diabetes mellitus and their infants study

Background Women who are diagnosed with gestational diabetes mellitus (GDM) are at increased risk for developing prediabetes and type 2 diabetes mellitus (T2DM). To date, there have been few interdisciplinary interventions that target predominantly ethnic minority low-income women diagnosed with GDM. This paper describes the rationale, design and methodology of a 2-year, randomized, controlled study being conducted in North Carolina. Methods/Design Using a two-group, repeated measures, experimental design, we will test a 14- week intensive intervention on the benefits of breastfeeding, understanding gestational diabetes and risk of progression to prediabetes and T2DM, nutrition and exercise education, coping skills training, physical activity (Phase I), educational and motivational text messaging and 3 months of continued monthly contact (Phase II). A total of 100 African American, non-Hispanic white, and bilingual Hispanic women between 22–36 weeks of pregnancy who are diagnosed with GDM and their infants will be randomized to either the experimental group or the wait-listed control group. The first aim of the study is to determine the feasibility of the intervention. The second aim of study is to test the effects of the intervention on maternal outcomes from baseline (22–36 weeks pregnant) to 10 months postpartum. Primary maternal outcomes will include fasting blood glucose and weight (BMI) from baseline to 10 months postpartum. Secondary maternal outcomes will include clinical, adiposity, health behaviors and self-efficacy outcomes from baseline to 10 months postpartum. The third aim of the study is to quantify the effects of the intervention on infant feeding and growth. Infant outcomes will include weight status and breastfeeding from birth through 10 months of age. Data analysis will include general linear mixed-effects models. Safety endpoints include adverse event reporting. Discussion Findings from this trial may lead to an effective intervention to assist women diagnosed with GDM to improve maternal glucose homeostasis and weight as well as stabilize infant growth trajectory, reducing the burden of metabolic disease across two generations. Trial registration NCT0180943

Enhanced Fusion Pore Expansion Mediated by the Trans-Acting Endodomain of the Reovirus FAST Proteins

The reovirus fusion-associated small transmembrane (FAST) proteins are virus-encoded membrane fusion proteins that function as dedicated cell–cell fusogens. The topology of these small, single-pass membrane proteins orients the majority of the protein on the distal side of the membrane (i.e., inside the cell). We now show that ectopic expression of the endodomains of the p10, p14, and p15 FAST proteins enhances syncytiogenesis induced by the full-length FAST proteins, both homotypically and heterotypically. Results further indicate that the 68-residue cytoplasmic endodomain of the p14 FAST protein (1) is endogenously generated from full-length p14 protein expressed in virus-infected or transfected cells; (2) enhances syncytiogenesis subsequent to stable pore formation; (3) increases the syncytiogenic activity of heterologous fusion proteins, including the differentiation-dependent fusion of murine myoblasts; (4) exerts its enhancing activity from the cytosol, independent of direct interactions with either the fusogen or the membranes being fused; and (5) contains several regions with protein–protein interaction motifs that influence enhancing activity. We propose that the unique evolution of the FAST proteins as virus-encoded cellular fusogens has allowed them to generate a trans-acting, soluble endodomain peptide to harness a cellular pathway or process involved in the poorly understood process that facilitates the transition from microfusion pores to macrofusion and syncytiogenesis

Nutritive value of unconventional fibrous ingredients fed to Guinea pigs in the Democratic Republic of Congo

peer reviewedThe energy and protein value for Guinea pigs (GP) of 9 forages (7 dicots and 2 grasses) and 5 hay-based diets was determined. The apparent faecal digestibility of dry matter, organic matter, crude protein and energy was measured on GP housed in metabolic cages. The forages and the diets were digested in vitro using pepsin and pancreatin hydrolysis and gas fermentation test to simulate stomach, small intestine and large intestine, respectively. Most of the dicots had high digestible crude protein content (152–201 g/kg DM) and the 2 grasses showed lower values (80–85 g/kg DM). Digestible energy content of the forages ranged between 5.79 to 13.08 MJ/kg DM. None of the forage species or hay-based diets provided sufficient energy to supply the 11.7 MJ/kg metabolic energy requirements. The influence of intestinal fermentation on energy and protein values was highlighted by correlations (P<0.05) between in vivo and in vitro data, including gas fermentation. It is the first time that such relationships are reported in single-stomach animals

Can the performance effect be ignored in the attendance policy discussion?

Should universities require students to attend? Academics disagree. One side in the discussion of university attendance policies has tried to dismiss any association between attendance and student performance, insisting that students have a fundamental right to choose what and when to attend. By merging student record data and course attendance data for three cohorts of final-year undergraduate students at a London-based university, we are able to isolate attendance effects for 674 students, giving us a large sample, without the inherent weaknesses of more traditional survey methods. We provide fresh empirical evidence for the positive association between attendance and exam performance, and argue for a more balanced view in the attendance policy discussion. Politicians and higher education policies are increasingly focused on employability, student retention, and completion indicators. Carefully crafted attendance policies can have positive effects on pass and completion rates, primary policy targets of higher education funders and policymakers. Attendance effects therefore cannot be ignored