A pilot study to evaluate the effect of Taeumjowi-tang on obesity in Korean adults: study protocol for a randomised, double-blind, placebo-controlled, multicentre trial

<p>Abstract</p> <p>Background</p> <p>Obesity, which is described as excessive or abnormal body fat, increases the risk of diet-related diseases. In Korea and around the world, the prevalence of obesity has grown annually from 1998 to 2008. This growth has continued despite various therapeutic efforts. The discovery of new and alternative treatments for obesity should be considered an important priority. Taeumjowi-tang (TJ001), a traditional Korean medicinal extract consisting of eight herbs, is a widely used herbal remedy for obesity in Korea. However, the efficacy and safety of TJ001 have not been fully investigated in a clinical trial. The purpose of this pilot study is to estimate obesity-related parameters and to assess the efficacy and safety of TJ001.</p> <p>Methods</p> <p>Our study is a randomised, double-blind, placebo-controlled, multicentre clinical trial of Taeumjowi-tang (TJ001). For this study, we will recruit obese Korean patients of both sexes, ages 18 to 65 years, from four university hospitals. A total of 104 subjects will be recruited. The participants will receive either 7 g of TJ001 or a placebo three times daily for 12 weeks. The primary end point will be the rate of subjects who lose at least 5% of their baseline body weight. The secondary end points will be changes in body weight, body mass index, waist circumference, hip circumference, waist/hip circumference ratio, lipid profiles, body fat composition, blood pressure, fasting glucose concentration, C-reactive protein and questionnaires related to the quality of life. The outcomes will be measured every 4 weeks. The study period will be 12 weeks and will include a total of five visits with each subject (at screening and at 0, 4, 8 and 12 weeks).</p> <p>Conclusions</p> <p>The results of our study will inform various estimates of TJ001 and will serve as the basis for a larger-scale trial. This study will assess the efficacy and safety of TJ001 as an alternative herbal remedy for obesity.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN87153759">ISRCTN87153759</a></p

Orientia tsutsugamushi Stimulates an Original Gene Expression Program in Monocytes: Relationship with Gene Expression in Patients with Scrub Typhus

Orientia tsutsugamushi is the causal agent of scrub typhus, a public health problem in the Asia-Pacific region and a life-threatening disease. O. tsutsugamushi is an obligate intracellular bacterium that mainly infects endothelial cells. We demonstrated here that O. tsutsugamushi also replicated in monocytes isolated from healthy donors. In addition, O. tsutsugamushi altered the expression of more than 4,500 genes, as demonstrated by microarray analysis. The expression of type I interferon, interferon-stimulated genes and genes associated with the M1 polarization of macrophages was significantly upregulated. O. tsutsugamushi also induced the expression of apoptosis-related genes and promoted cell death in a small percentage of monocytes. Live organisms were indispensable to the type I interferon response and apoptosis and enhanced the expression of M1-associated cytokines. These data were related to the transcriptional changes detected in mononuclear cells isolated from patients with scrub typhus. Here, the microarray analyses revealed the upregulation of 613 genes, which included interferon-related genes, and some features of M1 polarization were observed in these patients, similar to what was observed in O. tsutsugamushi-stimulated monocytes in vitro. This is the first report demonstrating that monocytes are clearly polarized in vitro and ex vivo following exposure to O. tsutsugamushi. These results would improve our understanding of the pathogenesis of scrub typhus, during which interferon-mediated activation of monocytes and their subsequent polarization into an M1 phenotype appear critical. This study may give us a clue of new tools for the diagnosis of patients with scrub typhus

Targeting Huntington’s disease through histone deacetylases

Huntington’s disease (HD) is a debilitating neurodegenerative condition with significant burdens on both patient and healthcare costs. Despite extensive research, treatment options for patients with this condition remain limited. Aberrant post-translational modification (PTM) of proteins is emerging as an important element in the pathogenesis of HD. These PTMs include acetylation, phosphorylation, methylation, sumoylation and ubiquitination. Several families of proteins are involved with the regulation of these PTMs. In this review, I discuss the current evidence linking aberrant PTMs and/or aberrant regulation of the cellular machinery regulating these PTMs to HD pathogenesis. Finally, I discuss the evidence suggesting that pharmacologically targeting one of these protein families the histone deacetylases may be of potential therapeutic benefit in the treatment of HD

ICAR: endoscopic skull‐base surgery

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Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe