Leucine-resveratrol reduced insulin resistance (homeostatic model assessment for insulin resistance) 33% with corresponding reductions in glucose and insulin area under the curve in oral glucose tolerance tests. We extended these concepts in preclinical studies using both direct Sirt1 activators and Sirt1 pathway activators. Low-dose (10 nM) NAD+ precursors (nicotinic acid, nicotinamide mononucleotide, and nicotinamide riboside) synergized with leucine to increase Sirt1 activity in adipocytes, hepatocytes, and muscle cells (30-100%, P  less then  .01) and lifespan in Caenorhabditis elegans (25%, P = .025) and to significantly regress atherosclerotic lesion size and macrophage infiltration in a mouse model of atherosclerosis. Thus, synergistic activation of Sirt1 using leucine and a co-activator exerts pleiotropic effects impacting cardiometabolic endpoints.Growth rate, development time, and response to environmental stressors vary tremendously across organisms, suggesting trade-offs that are affected by evolutionary or ecological factors, but such trade-offs are poorly understood. Prior studies using artificially selected lines of Manduca sexta suggest that insects with high growth rates, long development time, and large body size are more sensitive to hypoxic or hyperoxic stresses, such as reactive oxygen species (ROS) production, but the mechanisms and specific life-history associations remain unclear. Here, we manipulated the social environment to differentiate the effects of size, growth rate, and development time on oxygen sensitivity of the giant mealworm, Zophobas morio. Crowding reduced growth rates but yielded larger adults as a result of supernumerary molts and longer development times. The juvenile performance (growth rate, development time, adult mass) of crowd-reared mealworms was less sensitive to variation in atmospheric oxygen than it was for individually reared animals, consistent with the hypothesis that high growth rates are associated with increased sensitivity to ROS. Life span in normoxia was extended by crowd rearing, perhaps due to the larger size and/or increased resources of the larger adults. Life spans of crowd-reared animals were more negatively affected by hypoxia or hyperoxia than life spans of individually reared animals, possibly due to the longer total stress exposure of crowd-reared animals. These data suggest that animals with high growth rates experience a negative trade-off of performance with greater sensitivity to stress during the juvenile phase, while animals with long development times or life spans experience a negative trade-off of greater susceptibility of life span to environmental stress.In 2019, ∼ 463 million people globally had diabetes mellitus (DM), with China (25.1%), India (16.6%), and the United States (6.69%) representing nearly 50% of that total. The primary objectives of this exploratory study were to assess the safety and potential efficacy of Nigella sativa and fenugreek seed supplemented chapatis in overweight (OW) and type 2 DM subjects.  https://www.selleckchem.com/CDK.html  Forty subjects (15/OW; 9/DM; 16/DM/OW) consumed two chapatis twice a day 6 days/week for a daily dose of 5.45 g of an N. sativa/fenugreek combination over 12 weeks with no changes in lifestyle or medications. Anthropometric, glycemic, and vascular variables were recorded at baseline and after 6 and 12 weeks. Glycated hemoglobin (HbA1c), plasma lipids, and complete metabolic profile were measured at baseline and termination. Compliance, estimated during twice-daily individual delivery of precooked chapatis, was 100%, with no significant adverse effects. At termination, body weights, body mass index, waist and hip circumferences, index of central subjects, improvement (P  less then  .05) was seen in CRS (-10.7%), fatty liver index (-19.8%), lipid accumulation product (-13.8%), and HSI (-7.53%). N. sativa/fenugreek supplemented chapatis present a safe and seamless dietary modification to address cardiometabolic risk.Purpose Rhabdomyosarcoma (RMS) has a worse prognosis in adults than in children, but there is evidence of a better outcome in the former if treated using a pediatric-like approach. This study describes treatment for RMS in patients more than 10 years old and examines to what extent treatment contributes to explain the different age-related survival observed and to what extent treatment centers impact treatment appropriateness. Methods A retrospective population-based study was developed considering 104 RMS cases (excluding the pleomorphic subtype) diagnosed in Italy between 2000 and 2015. Patients were grouped by age (10-19 vs. 20-60 years old) and scored according to whether or not their chemotherapy was consistent with the schemes used in pediatric protocols (score 1 = chemotherapy in line with pediatric protocols). Treatment centers were grouped according to whether or not they have a pediatric-dedicated unit affiliated to the national pediatric oncology network (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP]). Results Older patients were more likely to have tumors at unfavorable sites (p = 0.045). A treatment score of 1 was assigned to 85% of younger patients, but only to 32% of older patients (p  less then  0.001). Furthermore, the proportion of score 1 was higher in younger patients treated in centers with an AIEOP Unit. A multivariate model confirmed age as a significant prognostic factor (Hazard rate ratio [HR] = 2.06; p = 0.04) and showed a significant impact of treatment on survival (HR = 2.13; p = 0.03). Conclusions Adult RMS patients are still relatively unlikely to be treated with pediatric protocols and in centers with a pediatric oncology expertise. This may explain the survival gap between older and younger patients.Objective The aim of this study was to quantitatively and qualitatively evaluate the effects of the indocyanine green (ICG)-near-infrared (NIR) photoreaction on Streptococcus mutans biofilms. Background ICG recently emerged as a photosensitive agent for photodynamic therapy. Although the effects of ICG-NIR on S. mutans inhibition are documented, little is known about its influence on biofilms, which are resistant to antimicrobial treatment and a major cause of plaque that leads to dental caries. Methods ICG was used as a photosensitizer with a diode laser irradiated in a rectangular shape (810 nm, 300 mW) as a light source on S. mutans ATCC 25175 biofilms. Viability was determined by the colony forming unit (CFU) count and confocal laser-scanning microscopy. The biofilm surface temperature was measured with a one-channel thermocouple thermometer. Results ICG and NIR diode laser significantly decreased the CFU count of S. mutans compared with the control group in a time-dependent manner. When irradiated with light after ICG application, temperature changes of 8.