Emerging role of GLP-1 receptor agonists in the treatment of obesity

The prevalence of obesity has increased dramatically in recent decades, both in the US and worldwide. Pharmacotherapy can augment the weight-reducing effects of lifestyle modification and can facilitate long-term weight maintenance. However, there is a paucity of pharmacologic agents approved for the treatment of obesity, and the use of existing weight loss medications is frequently limited by contraindications, drug interactions, adverse effects, limited coverage by third-party payers, and cost. In recent years, there has been an increased understanding and appreciation of the role of gastrointestinal hormones in the control of body weight. One such hormone, GLP-1, also plays an important role in glucose homeostasis. GLP-1 receptor agonists, such as exenatide and liraglutide, have been developed and are already approved for the treatment of type 2 diabetes. There has also been interest in the use of GLP-1 receptor agonists for the treatment of obesity in nondiabetic patients. This review explores the potential utility and limitations of exenatide and liraglutide as therapeutic agents for obesity

Nitrogen Production in Starburst Galaxies Detected by GALEX

We investigate the production of nitrogen in star-forming galaxies with ultraviolet (UV) radiation detected by the Galaxy Evolution Explorer Satellite (GALEX). We use a sample of 8745 GALEX emission-line galaxies matched to the Sloan Digital Sky Survey (SDSS) spectroscopic sample. We derive both gas-phase oxygen and nitrogen abundances for the sample and apply stellar population synthesis models to derive stellar masses and star formation histories of the galaxies. We compare oxygen abundances derived using three different diagnostics. We derive the specific star formation rates of the galaxies by modeling the seven-band GALEX+SDSS photometry. We find that galaxies that have log (SFR/M_*) ≳ − 10.0 typically have values of log (N/O) ~ 0.05 dex less than galaxies with log (SFR/M_*) ≾ − 10.0 and similar oxygen abundances

Vitamin D Supplementation and Prevention of Type 2 Diabetes

BACKGROUND Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the risk of diabetes is unknown. METHODS We randomly assigned adults who met at least two of three glycemic criteria for prediabetes (fasting plasma glucose level, 100 to 125 mg per deciliter; plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter; and glycated hemoglobin level, 5.7 to 6.4%) and no diagnostic criteria for diabetes to receive 4000 IU per day of vitamin D3 or placebo, regardless of the baseline serum 25-hydroxyvitamin D level. The primary outcome in this time-to-event analysis was new-onset diabetes, and the trial design was event-driven, with a target number of diabetes events of 508. RESULTS A total of 2423 participants underwent randomization (1211 to the vitamin D group and 1212 to the placebo group). By month 24, the mean serum 25-hydroxyvitamin D level in the vitamin D group was 54.3 ng per milliliter (from 27.7 ng per milliliter at baseline), as compared with 28.8 ng per milliliter in the placebo group (from 28.2 ng per milliliter at baseline). After a median follow-up of 2.5 years, the primary outcome of diabetes occurred in 293 participants in the vitamin D group and 323 in the placebo group (9.39 and 10.66 events per 100 person-years, respectively). The hazard ratio for vitamin D as compared with placebo was 0.88 (95% confidence interval, 0.75 to 1.04; P = 0.12). The incidence of adverse events did not differ significantly between the two groups. CONCLUSIONS Among persons at high risk for type 2 diabetes not selected for vitamin D insufficiency, vitamin D3 supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; D2d ClinicalTrials.gov number, NCT01942694.

A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A

Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979-1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 Δ32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Δ32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this populatio

Measurement of Λ4H\rm ^4_{\Lambda}H and Λ4He\rm ^4_{\Lambda}He binding energy in Au+Au collisions at sNN\sqrt{s_\mathrm{NN}} = 3 GeV

Measurements of mass and $\Lambda$ binding energy of $\rm ^4_{\Lambda}H$ and $\rm ^4_{\Lambda}He$ in Au+Au collisions at $\sqrt{s_{_{\rm NN}}}=3$ GeV are presented, with an aim to address the charge symmetry breaking (CSB) problem in hypernuclei systems with atomic number A = 4. The $\Lambda$ binding energies are measured to be $\rm 2.22\pm0.06(stat.) \pm0.14(syst.)$ MeV and $\rm 2.38\pm0.13(stat.) \pm0.12(syst.)$ MeV for $\rm ^4_{\Lambda}H$ and $\rm ^4_{\Lambda}He$, respectively. The measured $\Lambda$ binding-energy difference is $\rm 0.16\pm0.14(stat.)\pm0.10(syst.)$ MeV for ground states. Combined with the $\gamma$-ray transition energies, the binding-energy difference for excited states is $\rm -0.16\pm0.14(stat.)\pm0.10(syst.)$ MeV, which is negative and comparable to the value of the ground states within uncertainties. These new measurements on the $\Lambda$ binding-energy difference in A = 4 hypernuclei systems are consistent with the theoretical calculations that result in $\rm \Delta B_{\Lambda}^4(1_{exc}^{+})\approx -\Delta B_{\Lambda}^4(0_{g.s.}^{+})<0$ and present a new method for the study of CSB effect using relativistic heavy-ion collisions.Comment: 8 pages, 5 figure