Population genetics of the Chilean frog Batrachyla Leptopus (Leptodactylidae)

Electrophoretic variation of proteins encoded by 14 loci was analyzed in eight (five continental and three insular) populations of the Chilean leptodactylid frog Batrachyla leptopus. The overall proportion of polymorphic loci was estimated to be 18.7% and the average number of alleles per locus, 1.2, while observed and expected heterozygosities were 1.7 and 5.1%, respectively. The estimated coefficient of genetic identity was 0.940; the corresponding figure for genetic distance was 0.063. F-statistics analysis showed a total inbreeding coefficient (Fit) of 0.855 and high levels of genetic subdivision (Fst = 0.596) as well as of inbreeding within populations (Fis = 0.640). However, there was only a moderate level of genetic differentiation (Fst = 0.181) between the insular group of populations and the continental group.<br>A variação eletroforética de proteínas codificadas por 14 loci foi analisada em oito populações (5 continentais e 3 insulares) da rã leptodactilídea chilena Batrachyla leptopus. A proporção geral de loci polimórficos foi estimada como sendo de 18,7% e o número médio de alelos por loco, 1,2, enquanto que as heterozigosidades observada e esperada foram 1,7 e 5,1%, respectivamente. O coeficiente esperado de identidade genética foi 0,940; o número correspondente para a distância genética foi 0,063. A análise estatística F mostrou um coeficiente de endogamia total (Fit) de 0,855 e altos níveis de subdivisão genética (Fst = 0,596), assim como de endogamia dentro das populações (Fis = 0,640). Contudo, houve apenas um nível moderado de diferenciação genética (Fst = 0,181) entre o grupo insular de populações e o grupo continental

Antiinflammatory therapy with canakinumab for atherosclerotic disease

BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. Copyright © 2017 Massachusetts Medical Society