Genetic background and thermal regime influence adaptation to novel environment in the seed beetle, Callosobruchus maculatus.

Climate change is associated with the increase in both the mean and variability of thermal conditions. Therefore, the use of more realistic fluctuating thermal regimes is the most appropriate laboratory method for predicting population responses to thermal heterogeneity. However, the long- and short-term implications of evolving under such conditions are not well understood. Here, we examined differences in key life-history traits among populations of seed beetles (Callosobruchus maculatus) that evolved under either constant control conditions or in an environment with fluctuating daily temperatures. Specifically, individuals from two distinct genetic backgrounds were kept for 19 generations at one of two temperatures, a constant temperature (T = 29 °C) or a fluctuating daily cycle (Tmean = 33 °C, Tmax = 40 °C, and Tmin = 26 °C), and were assayed either in their evolved environment or in the other environment. We found that beetles that evolved in fluctuating environments but were then switched to constant 29 °C conditions had far greater lifetime reproductive success compared with beetles that were kept in their evolved environments. This increase in reproductive success suggests that beetles raised in fluctuating environments may have evolved greater thermal breadth than control condition beetles. In addition, the degree of sexual dimorphism in body size and development varied as a function of genetic background, evolved thermal environment, and current temperature conditions. These results not only highlight the value of incorporating diel fluctuations into climate research but also suggest that populations that experience variability in temperature may be better able to respond to both short- and long-term changes in environmental conditions.

Direct oral anticoagulants compared with other strategies in patients with atrial fibrillation and stroke or transient ischemic attack: Systematic review.

BACKGROUND: For patients with atrial fibrillation and a prior stroke or transient ischemic attack (TIA), the risk-benefit of direct oral anticoagulants (DOACs) compared to alternative treatment approaches has not been firmly established. We conducted a systematic review of randomized controlled trials (RCTs) to investigate efficacy and safety of DOACs vs warfarin and DOACs vs aspirin or placebo in patients with AF and a prior stroke or TIA. METHODS: We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials from January 1, 2000, to January 31, 2023, to find RCTs. Risk ratio (RR) with 95 % CI measured the association of DOACs vs warfarin, and DOACs vs aspirin or placebo, with clinical outcomes. Primary efficacy outcome was stroke or systemic embolism and primary safety outcome was ICH. RESULTS: We identified 7 RCTs with 19,111 patients with AF and a prior stroke or TIA, of which 5 trials compared DOACs with warfarin and 2 trials compared DOACs vs aspirin or placebo. Compared with warfarin, DOACs were associated with a lower risk of stroke or systemic embolism (RR, 0.85; 95 % CI, 0.75-0.97) and ICH (RR, 0.53; 95 % CI, 0.41-0.68). Compared with aspirin or placebo, DOACs were associated with a reduced risk of stroke or systemic embolism (RR, 0.33; 95 % CI, 0.19-0.58) and risk of ICH did not differ between apixaban and aspirin. CONCLUSIONS: This contemporary evaluation of the literature indicates that DOACs, rather than other antithrombotic agents or no treatment, should be used in patients with AF and a prior stroke or TIA.

Metformin plus a low hypoglycemic risk antidiabetic drug vs. metformin monotherapy for untreated type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

AIMS: The aim of the meta-analysis of randomized controlled trials (RCTs) was to compare the effectiveness of glycemic control and hypoglycemia risk of combination therapy (metformin plus a low hypoglycemic risk antidiabetic drug) vs. standard metformin monotherapy, in patients with untreated type 2 diabetes mellitus (T2DM). METHODS: We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through October 31, 2021 to find relevant RCTs. Efficacy outcomes were changes in hemoglobulin A1c (HbA1c) and fast plasma glucose (FPG) from baseline as well as proportion of patients achieving HbA1c < 7%; the safety outcome was hypoglycemia risk. RESULTS: We identified 14 RCTs comprising 5326 patients with untreated T2DM. Mean treatment duration was 28.1 weeks. Pooled results showed that compared to metformin monotherapy, combination therapy was associated with a reduction in HbA1c (mean difference: -0.48 %, -0.58 to - 0.38) and FPG (mean difference: -0.92 mmol/L, -1.14 to - 0.69), and more patients achieving HbA1c < 7% (odds ratio: 2.21, 1.87 to 2.60). Hypoglycemic events and people experiencing hypoglycemia were not different between 2 groups. CONCLUSIONS: Initial combination of metformin plus a low hypoglycemic risk antidiabetic drug may achieve better glycemic control, without a rise in hypoglycemia, in patients with untreated T2DM.