Tourette syndrome (TS) is a disabling neurodevelopmental disorder characterized by multiple, recurrent tics. The pharmacological treatment of TS is currently based on dopaminergic antagonists; however, these drugs are associated with extrapyramidal symptoms and other serious adverse events. Recent evidence suggests that positive allosteric modulators (PAMs) of GABAA receptors containing α6 subunits (α6 GABAARs) oppose the behavioral effects of dopamine. Building on this evidence, in the present study, we tested the efficacy of DK-I-56-1, a highly selective PAM for α6 GABAARs, in mouse models of TS exhibiting tic-related responses. DK-I-56-1 significantly reduced tic-like jerks and prepulse inhibition (PPI) deficits in D1CT-7 transgenic mice, a well-documented mouse model of TS. DK-I-56-1 also prevented the exacerbation of spontaneous eyeblink reflex induced by the potent dopamine D1 receptor agonist SKF 82958, a proxy for tic-like responses. We also showed that both systemic and prefrontal cortical administration of DK-I-56-1 countered the PPI disruption caused by SKF 82958. Although the effects of DK-I-56-1 were akin to those elicited by dopaminergic antagonists, this drug did not elicit extrapyramidal effects, as measured by catalepsy. These results point to α6 GABAAR PAMs as promising TS therapies with a better safety profile than dopaminergic antagonists.(1) Background. Visceral adiposity index (VAI) has been recently identified as a new cardiometabolic risk marker reflecting abdominal fat distribution and dyslipidaemia. The aim of the present paper was to evaluate the relationship between VAI, daily energy intake and metabolic syndrome (MetS) in a cohort of obese Caucasian children and adolescents, aged 8 to 15 years. (2) Methods. Consecutive Italian children and adolescents with obesity, according to World Health Organization were enrolled. Anthropometric parameters and blood pressure were measured. Fasting blood samples have been analyzed for lipids, insulin and glucose levels. MetS was diagnosed using identification and prevention of dietary- and lifestyle-induced health effects in children and infants (IDEFICS) or International Diabetes Federation (IDF) criteria according to age. Homeostatic model assessment index (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), A body shape index (ABSI) and VAI were calculated. Multivariable logistic rescore but no association was found with VAI. (4) Conclusion. VAI is a promising tool to identify MetS in children and adolescents with obesity and should be used in the management of abdominal obesity together with dietary assessment.Epilepsy is one of the most common neurological disorders, and it is characterized by spontaneous seizures. In a previous study, we identified 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) as a novel anti-epileptic agent in chemically- or genetically-induced epileptic zebrafish and mouse models. In this study, we investigated the anti-epileptic effects of GM-90432 through neurochemical profiling-based approach to understand the neuroprotective mechanism in a pentylenetetrazole (PTZ)-induced epileptic seizure zebrafish model. GM-90432 effectively improved PTZ-induced epileptic behaviors via upregulation of 5-hydroxytryptamine, 17-β-estradiol, dihydrotestosterone, progesterone, 5α -dihydroprogesterone, and allopregnanolone levels, and downregulation of normetanephrine, gamma-aminobutyric acid, and cortisol levels in brain tissue. GM-90432 also had a protective effect against PTZ-induced oxidative stress and zebrafish death, suggesting that it exhibits biphasic neuroprotective effects via scavenging of reactive oxygen species and anti-epileptic activities in a zebrafish model. In conclusion, our results suggest that neurochemical profiling study could be used to better understand of anti-epileptic mechanism of GM-90432, potentially leading to new drug discovery and development of anti-seizure agents.Container-based virtualization is becoming a de facto way to build and deploy applications because of its simplicity and convenience. Kubernetes is a well-known open-source project that provides an orchestration platform for containerized applications. An application in Kubernetes can contain multiple replicas to achieve high scalability and availability. Stateless applications have no requirement for persistent storage; however, stateful applications require persistent storage for each replica. Therefore, stateful applications usually require a strong consistency of data among replicas. To achieve this, the application often relies on a leader, which is responsible for maintaining consistency and coordinating tasks among replicas. This leads to a problem that the leader often has heavy loads due to its inherent design. In a Kubernetes cluster, having the leaders of multiple applications concentrated in a specific node may become a bottleneck within the system. In this paper, we propose a leader election algorithm that overcomes the bottleneck problem by evenly distributing the leaders throughout nodes in the cluster. We also conduct experiments to prove the correctness and effectiveness of our leader election algorithm compared with a default algorithm in Kubernetes.Tissue chips (TCs) and microphysiological systems (MPSs) that incorporate human cells are novel platforms to model disease and screen drugs and provide an alternative to traditional animal studies. This review highlights the basic definitions of TCs and MPSs, examines four major organs/tissues, identifies critical parameters for organization and function (tissue organization, blood flow, and physical stresses), reviews current microfluidic approaches to recreate tissues, and discusses current shortcomings and future directions for the development and application of these technologies. The organs emphasized are those involved in the metabolism or excretion of drugs (hepatic and renal systems) and organs sensitive to drug toxicity (cardiovascular system). https://www.selleckchem.com/products/pim447-lgh447.html This article examines the microfluidic/microfabrication approaches for each organ individually and identifies specific examples of TCs. This review will provide an excellent starting point for understanding, designing, and constructing novel TCs for possible integration within MPS.