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Aim Materials and Methods Results Conclusions To synthesize the evidence on the effects of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) in adolescents with overweight or obesity.For this systematic review and network meta‐analysis, we searched five databases and registries until 2 March 2024 for eligible randomized controlled trials (RCTs). The primary outcome was weight change. We did a pairwise meta‐analysis to compare GLP‐1RAs and placebo, followed by a drug‐wise network meta‐analysis (NMA) to compare GLP‐1RAs against each other.We screened 770 records to include 12 RCTs with 883 participants. The evidence suggests that GLP‐1RAs reduced weight (mean difference −4.21 kg, 95% confidence interval [CI] −7.08 to −1.35) and body mass index (BMI; mean difference −2.11 kg/m2, 95% CI −3.60 to −0.62). The evidence on waist circumference, body fat percentage and adverse events (AEs) was very uncertain. The results remained consistent with subgroup analyses for coexisting type 2 diabetes. Longer therapy duration led to a greater reduction in weight and BMI. In the NMA, semaglutide led to the greatest weight reduction, followed by exenatide, liraglutide and lixisenatide.The evidence suggests that GLP‐1RAs reduce most weight‐related outcomes in adolescents, with semaglutide being the most efficacious. There is uncertain evidence on body fat and serious AEs, probably due to fewer studies and low incidence, respectively. Larger RCTs with head‐to‐head comparisons, pragmatic design, adiposity‐related outcomes, and economic evaluation can further guide the use and choice of GLP‐1RAs. [ABSTRACT FROM AUTHOR]

Introduction: There is a close association between the use of broad‐spectrum antibiotics, gut microbiome alteration, multidrug resistant (MDR) gram‐negative bacilli (GNB) bacteremia, graft versus host disease (GVHD), and mortality post‐allogeneic hematopoietic cell transplantation (allo‐HCT). This study reports the impact of the high use of carbapenems and colistin and MDR bacteremia pre‐ and post‐HCT on HCT outcomes. Methods: This was a single‐center, partial retrospective, and prospective study from 2016 to 2020. Both pre‐ and post‐HCT antibiotic exposures and blood culture/sensitivity were recorded. MDR GNB was defined as either non‐susceptibility to third‐generation cephalosporin or carbapenems. In the absence of positive cultures, the treating physician escalated antibiotics from third‐generation cephalosporins to carbapenem and/or colistin as per clinical discretion. De‐escalation policy was not strictly enforced. Results: MDR GNB bacteremia was seen in 29 of 76 (38%) of patients peri‐HCT. The utilization rates for carbapenems and colistin was significantly higher in the cohort with MDR GNB bacteremia pre‐HCT (70% vs. 32%, p = 0.002 and 31% vs. 6.4%, p = 0.007, respectively) and post‐HCT (100% vs. 74.5%, p = 0.002, and 55.2% vs. 8.5%, p < 0.0001, respectively). The cohort with MDR GNB bacteremia had significantly more severe acute GVHD at day+100 (45% vs. 17.5%, p = 0.009). The median survival was 204 days compared to not reached in the cohort without any MDR GNB bacteremia (p = 0.005). Conclusion: This study shows pre‐ and post‐HCT MDR GNB bacteremia is associated with an increased risk of severe acute GVHD and mortality. Patients with MDR GNB bacteremia had higher exposure to pre‐ and post‐HCT carbapenems and colistin. [ABSTRACT FROM AUTHOR]

Black pepper, though commonly employed as a spice, has many medicinal properties. It consists of volatile oils, alkaloids, pungent resins, etc., of which piperine is a major constituent. Though safe at low doses, piperine causes alteration in the activity of drug metabolising enzymes and transporters at high dose and is known to precipitate liver toxicity. It has a potential to form reactive metabolite(s) (RM) owing to the presence of structural alerts, such as methylenedioxyphenyl (MDP), α, β‐unsaturated carbonyl group (Michael acceptor), and piperidine. The present study was designed to detect and characterize stable and RM(s) of piperine formed on in vitro incubation with human liver microsomes. The investigation of RMs was done with the aid of trapping agents, viz, glutathione (GSH) and N‐acetylcysteine (NAC). The samples were analysed by ultra‐high performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC‐HRMS) using Thermo Scientific Q Exactive Plus Orbitrap. Full scan MS followed by data‐dependent MS2 (Full MS‐ddMS2) mode was used to establish mass spectrometric fragmentation pathways of protonated piperine and its metabolites. In total, four stable metabolites and their isomers (M1a‐c, M2a‐b, M3a‐c, and M4a‐b) were detected. Their formation involved removal of carbon (3, M1a‐c), hydroxylation (2, M2a‐b), hydroxylation with hydrogenation (3, M3a‐c), and dehydrogenation (2, M4a‐b). Out of these metabolites, M1, M2, and M3 are reported earlier in the literature, but their isomers and two M4 variants are novel. In addition, six novel conjugates of RMs, including three GSH conjugates of m/z 579 and three NAC conjugates of m/z 435, were also observed. [ABSTRACT FROM AUTHOR]

Polypyrrole (PPy) is one of the preferred alternatives among the intrinsically conductive polymers (ICPs). In this study, PPy-coated cotton (PPy-CT) fabrics were synthesized by two step in situ chemical polymerization. The reaction parameters, such as monomer concentration and temperature, were studied in detail. The surface resistivity of PPy-CT fabrics ranged ∼ 15-5000 Ω−2. To assess long-term usage potential, the atmospheric aging of conductivity characteristics of treated fabrics was monitored over a period of 6 months. It was found that the synthesis temperature had a significant impact on conductivity and atmospheric aging of PPy-CT fabrics. Furthermore, various sulfonic acid sodium salts added as external doping agents during polymerization also had a positive effect. The scanning electron microscopy revealed smoother morphology of sulfonic acid salt doped PPy coatings. The overall study addresses the durability aspect of PPy-CT fabrics in potential applications areas. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012 [ABSTRACT FROM AUTHOR]

Growth of the mandibular condylar cartilage (MCC) is reviewed as a function of genetic and epigenetic factors. The growth centers around the differential spatial concentration of the chondrocytes, influence of growth factors like TGF-β and heterogeneity in the number of IGF receptors, control the action of IGF. Besides these factors, growth of the mandibular condyle is influenced by differential response of chondrocytes as a function of their source/ageing, which in turn is regulated by TGF-β, BMPs and IGFs. While IGF-1 promotes proteoglycan synthesis and survival of the chondrocytes to maintain cartilage homeostasis, TGF-β synergistically catalysed the effect of IGF-1, while BMPs catalysed proteolysis as and when physiologically needed. To understand these processes, role of IGF-1 and its six receptors is at the center to a number of physiological processes being regulated by its mode of application for the growth and differentiation. Probing deeper, biological functions of IGFs seemed to depend on their level of free status rather than bound status to respective IGF-binding proteins (IGF-BPs), considered prerequisite to modulate their biological functions. Genetic regulation of their secretion has thrown light on their insulin-like structural homology, level and response in osteo-arthritis (OA), rheumatic arthritis (RA) and diabetes type-II. Biochemistry and spatial distribution of IGF receptors in different domains exerts control on IGF-1 activities. In ultimate analysis, IGF-axis conserved during the evolution to regulate cell growth and proliferation affect nearly every organ in the body as judged from the techniques determining skeletal maturity and decision making dependent on it for orthodontic, orthognathic/orthopedic and dental implant applications. J. Cell. Physiol. 227: 1796-1804, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]