Management of Latent Autoimmune Diabetes in Adults: A Consensus Statement From an International Expert Panel

A substantial proportion of patients with adult-onset diabetes share features of both type 1 diabetes (T1D) and type 2 diabetes (T2D). These individuals, at diagnosis, clinically resemble T2D patients by not requiring insulin treatment, yet they have immunogenetic markers associated with T1D. Such a slowly evolving form of autoimmune diabetes, described as latent autoimmune diabetes of adults (LADA), accounts for 2–12% of all patients with adult-onset diabetes, though they show considerable variability according to their demographics and mode of ascertainment. While therapeutic strategies aim for metabolic control and preservation of residual insulin secretory capacity, endotype heterogeneity within LADA implies a personalized approach to treatment. Faced with a paucity of large-scale clinical trials in LADA, an expert panel reviewed data and delineated one therapeutic approach. Building on the 2020 American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) consensus for T2D and heterogeneity within autoimmune diabetes, we propose “deviations” for LADA from those guidelines. Within LADA, C-peptide values, proxy for β-cell function, drive therapeutic decisions. Three broad categories of random C-peptide levels were introduced by the panel: 1) C-peptide levels <0.3 nmol/L: a multiple-insulin regimen recommended as for T1D; 2) C-peptide values ≥0.3 and ≤0.7 nmol/L: defined by the panel as a “gray area” in which a modified ADA/EASD algorithm for T2D is recommended; consider insulin in combination with other therapies to modulate β-cell failure and limit diabetic complications; 3) C-peptide values >0.7 nmol/L: suggests a modified ADA/EASD algorithm as for T2D but allowing for the potentially progressive nature of LADA by monitoring C-peptide to adjust treatment. The panel concluded by advising general screening for LADA in newly diagnosed non–insulin-requiring diabetes and, importantly, that large randomized clinical trials are warranted.     

Viruses in Extreme Environments,Current Overview,and Biotechnological Potential

Virus research has advanced significantly since the discovery of the tobacco mosaic virus (TMV), the characterization of its infection mechanisms and the factors that determine their pathogenicity. However, most viral research has focused on pathogenic viruses to humans, animals and plants, which represent only a small fraction in the virosphere. As a result, the role of most viral genes, and the mechanisms of coevolution between mutualistic viruses, their host and their environment, beyond pathogenicity, remain poorly understood. This review focuses on general aspects of viruses that interact with extremophile organisms, characteristics and examples of mechanisms of adaptation. Finally, this review provides an overview on how knowledge of extremophile viruses sheds light on the application of new tools of relevant use in modern molecular biology, discussing their value in a biotechnological context.     

Diabetes association with self-reported health,resource utilization,and prognosis post-myocardial infarction

BackgroundDiabetes mellitus (DM) is associated with increased cardiovascular (CV) risk. We compared health‐related quality of life (HRQoL), healthcare resource utilization (HRU), and clinical outcomes of stable post‐myocardial infarction (MI) patients with and without DM.HypothesisIn post‐MI patients, DM is associated with worse HRQoL, increased HRU, and worse clinical outcomes.MethodsThe prospective, observational long‐term risk, clinical management, and healthcare Resource utilization of stable coronary artery disease study obtained data from 8968 patients aged ≥50 years 1 to 3 years post‐MI (369 centers; 25 countries). Patients with ≥1 of the following risk factors were included: age ≥65 years, history of a second MI >1 year before enrollment, multivessel coronary artery disease, creatinine clearance ≥15 and <60 mL/min, and DM treated with medication. Self‐reported health status was assessed at baseline, 1 and 2 years and converted to EQ‐5D scores. The main outcome measures were baseline HRQoL and HRU during follow‐up.ResultsDM at enrollment was 33% (2959 patients, 869 insulin treated). Mean baseline EQ‐5D score (0.86 vs 0.82; P < .0001) was higher; mean number of hospitalizations (0.38 vs 0.50, P < .0001) and mean length of stay (LoS; 9.3 vs 11.5; P = .001) were lower in patients without vs with DM. All‐cause death and the composite of CV death, MI, and stroke were significantly higher in DM patients, with adjusted 2‐year rate ratios of 1.43 (P < .01) and 1.55 (P < .001), respectively.ConclusionsStable post‐MI patients with DM (especially insulin treated) had poorer EQ‐5D scores, higher hospitalization rates and LoS, and worse clinical outcomes vs those without DM. Strategies focusing specifically on this high‐risk population should be developed to improve outcomes.Trial registration ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01866904","term_id":"NCT01866904"}}NCT01866904 (https://clinicaltrials.gov).     

Factors associated with PrEP awareness according to age and willingness to use HIV prevention technologies: the 2017 online survey among MSM in Brazil*

ABSTRACT

Brazil has the largest population of individuals living with HIV/AIDS in Latin America with a disproportional prevalence of infection among men who have sex with men (MSM). This study evaluated PrEP awareness by age (18–24, 25–35, ≥36 years), its associated factors and the willingness to use HIV prevention technologies among MSM using a GSN app in Brazil. Inclusion criteria were ≥18 years-old, cisgender men and HIV-negative serostatus. Of 7242 individuals, 4136 (57%) completed the questionnaire. PrEP awareness was reported by 51% (though lower among MSM aged 18–24 and ≥36 years) and its associated factors were higher family income, most friends with the same sexual orientation, high number of male sexual partners and marijuana use. HIV testing (never vs. at least once) lead to an almost 3-fold increase in the odds of PrEP awareness. High HIV risk perception led to increased PrEP awareness only among MSM aged 18–24 years. A total of 2335 (56%) was willing to use daily oral PrEP. PrEP awareness remains low in Brazil and mobile tools are key strategies to reach MSM and increase awareness of prevention technologies. Community-based interventions could add to online campaigns to reach the most vulnerable, which include young, non-white and lower-income MSM.     

Fitness costs and benefits of novel herbicide tolerance in a noxious weed

Glyphosate, the active ingredient in the herbicide RoundUp, has increased dramatically in use over the past decade and constitutes a potent anthropogenic source of selection. In the southeastern United States, weedy morning glories have begun to develop tolerance to glyphosate, representing a unique opportunity to examine the evolutionary genetics of a novel trait. We found genetic variation for tolerance, indicating the potential for the population to respond to selection by glyphosate. However, the following significant evolutionary constraint exists: in the absence of glyphosate, tolerant genotypes produced fewer seeds than susceptible genotypes. The combination of strong positive directional selection in the presence of glyphosate and strong negative directional selection in its absence may indicate that the selective landscape of land use could drive the evolutionary trajectory of glyphosate tolerance. Understanding these evolutionary forces is imperative for devising comprehensive management strategies to help slow the rate of the evolution of tolerance.     

Hypothalamic expression of anorexigenic and orexigenic hormone receptors in obese females Neotomodon alstoni: Effect of fasting

Obesity is a world problem that requires a better understanding of its physiological and genetic basis, as well as the mechanisms by which the hypothalamus controls feeding behavior. The volcano mouse Neotomodon alstoni develops obesity in captivity when fed with regular chow diet, providing a novel model for the study of obesity. Females develop obesity more often than males; therefore, in this study, we analysed in females, in proestrous lean and obese, the differences in hypothalamus expression of receptors for leptin, ghrelin (growth hormone secretagogue receptor GHS-R), and VPAC, and correlates for plasma levels of total ghrelin. The main comparisons are between mice fed ad libitum and mice after 24 hours of fasting. Mice above 65 g body weight were considered obese, based on behavioral and physiological parameters such as food intake, plasma free fatty acids, and glucose tolerance. Hypothalamic tissue from obese and lean mice was analysed by western blot. Our results indicate that after ad libitum food access, obese mice show no significant differences in hypothalamic leptin receptors, but a significant increase of 60% in the GHS-R, and a nearly 62% decrease in VPAC2 was noted. After a 24-hour fast, plasma ghrelin increased nearly two fold in both lean and obese mice; increases of hypothalamic leptin receptors and GHS-R were also noted, while VPAC2 did not change significantly; levels of plasma free fatty acids were 50% less after fasting in obese than in lean animals. Our results indicate that in obese N. alstoni mice, the levels of orexigenic receptors in the hypothalamus correlate with overfeeding, and the fact that lean and obese females respond in different ways to a metabolic demand such as a 24-hour fast.     

Development of twenty-one polymorphic microsatellite markers for the fungus-growing ant,Mycocepurus goeldii (Formicidae: Attini), using Illumina paired-end genomic sequencing

Obligate social parasites, or inquilines, exploit the colonies of free-living social species and evolved at least 80 times in ants alone. Most species of the highly specialized inquiline social parasites are rare, only known from one or very few, geographically isolated populations, and the sexual offspring of most inquiline species mates inside the maternal colony. Therefore, inquiline populations are believed to be small and genetically homogeneous due to inbreeding. To comparatively study the genetic diversity of the socially parasitic fungus-growing ant, Mycocepurus castrator, and its only known host species, Mycocepurus goeldii, and to infer the parasite’s conservation status, we developed 21 microsatellite markers for the host species, M. goeldii, and evaluated whether these markers cross-amplify in the social parasite, M. castrator. We isolated and characterized a total of 21 microsatellite loci for M. goeldii. The loci were screened for 24 individuals from geographically distant and genetically divergent populations in Brazil. The number of alleles per locus ranged from 18 to 4, the observed heterozygosity ranged from 0.25 to 0.636, and the probability of identity values ranged from 0.011 to 0.146. Preliminary analyses show that these markers cross amplify in the closely related social parasite species M. castrator. These newly developed loci provide tools for studying the genetic diversity and the evolution of social parasitism in the Mycocepurus host–parasite system.