The review synthesised evidence examining the association between a. loneliness with inflammation and b. social isolation with inflammation in adults aged 16 or older from the general population. From an initial 7,400 articles we identified 14 papers that examined loneliness, and 16 that examined social isolation. Qualitative syntheses indicated mixed results, variable study quality, and methodological heterogeneity. Most studies provided associations for C-reactive protein CRP, fibrinogen and Interleukin-6 IL-6, and these results were synthesised using random-effects meta-analyses. There was no association between loneliness with CRP or fibrinogen, but there was a significant association between loneliness and IL-6 for most-adjusted but not least-adjusted analyses. There was also a significant least-adjusted association between social isolation with CRP and fibrinogen, which remained significant for fibrinogen in most-adjusted analyses. There was no association between social isolation with IL-6. Sensitivity analyses indicated that methodological heterogeneity impacted on results. Results indicate that social isolation and loneliness could be linked with systemic inflammation, but more robust methodology is needed to confirm these associations and unpack mechanisms. Crown All rights reserved.Perceptual control theory (PCT) proposes that perceptual inputs are controlled to intentional 'reference' states by hierarchical negative feedback control, evidence for which comes from manual tracking experiments in humans. We reviewed these experiments to determine whether tracking is a process of perceptual control, and to assess the state-of-the-evidence for PCT. A systematic literature search was conducted of peer-review journal and book chapters in which tracking data were simulated with a PCT model (13 studies, 53 participants). We report a narrative review of these studies and a qualitative assessment of their methodological quality. We found evidence that individuals track to individual-specific endogenously-specified reference states and act against disturbances, and evidence that hierarchical PCT can simulate complex tracking. PCT's learning algorithm, reorganization, was not modelled. Limitations exist in the range of tracking conditions under which the PCT model has been tested. Future PCT research should apply the PCT methodology to identify control variables in real-world tasks and develop hierarchical PCT architectures for goal-oriented robotics to test the plausibility of PCT model-based action control. BACKGROUND Human exposure to mercury (Hg) is widespread and both organic and inorganic Hg are routinely found in the human brain. Millions of people are exposed to methyl Hg (MeHg) due to the consumption of fish and to inorganic Hg from dental amalgams, small scale gold mining operations, use of Hg containing products, or their occupations. Neuropathology information associated with exposures to different species of Hg is primarily based on case reports of single individuals or collections of case studies involving a single species of Hg at toxic exposure levels such as occurred in Japan and Iraq. METHODS/RESULTS This study brings together information on the neuropathological findings and deposition of Hg in the central nervous system of people exposed to different species of Hg at varying concentrations. https://www.selleckchem.com/products/jsh-23.html The low dose exposures were lifetime exposures while the high dose exposures were generally acute or short term by different exposure routes with survival lasting various lengths of time. Total and inorganicre present in the brains of either Rochester or Seychelles residents despite substantial differences in dietary MeHg exposure. Increasing concentrations of inorganic Hg were present in the brain of relatively low exposure subjects with increasing age. V.BACKGROUND AIMS Refractory gastroesophageal reflux disease (GERD) reduces quality of life and creates significant financial burden on the healthcare system. Approximately 30% of patients with GERD who receive label-dose proton pump inhibitors (PPIs) still have symptoms. We performed a trial to evaluate the efficacy and safety of IW-3718, a bile acid sequestrant, as an adjunct to PPI therapy. METHODS We performed a multicenter, double-blind, placebo-controlled trial from March 2016 through April 2017, of 280 patients with confirmed GERD. The patients, stratified by esophagitis status, were randomly assigned (1111) to groups given placebo or IW-3718 (500, 1000, or 1500 mg) twice daily, with ongoing label-dose PPI. The primary end point was percent change from baseline to week 8 in weekly heartburn severity score. We also analyzed percent change from baseline to week 8 in weekly regurgitation frequency score. RESULTS Mean changes from baseline to week 8 in weekly heartburn severity scores were reductions of 46.0% in the placebo group, 49.0% in the 500 mg group, 55.1% in the 1000 mg group, and 58.0% in the 1500 mg IW-3718 groups (dose-response P=.02). The treatment difference was 11.9% between the 1500-mg IW-3718 and placebo groups (P=.04, analysis of covariance). The mean change in weekly regurgitation frequency score from baseline to week 8 in the 1500-mg IW-3718 vs placebo groups was a reduction of 17.5% (95% CI, reductions of 31.4% to 3.6%). The most common adverse event was constipation (in 8.1% of patients receiving IW-3718 and 7.1% of patients receiving placebo). There were no drug-related serious adverse events. CONCLUSIONS In a randomized trial of patients with refractory GERD, adding 1500-mg IW-3718 to label-dose PPIs significantly reduced heartburn symptoms compared with adding placebo. Regurgitation symptoms also decreased. IW-3718 was well tolerated. ClinicalTrials.gov no NCT02637557. BACKGROUND & AIMS We evaluated the efficacy and safety of upadacitinib, an oral selective inhibitor of Janus kinase 1, as induction therapy for ulcerative colitis (UC). METHODS We performed a multicenter, double-blind, phase 2b study of 250 adults with moderately to severely active UC and an inadequate response, loss of response, or intolerance to corticosteroids, immunosuppressive agents, and/or biologic therapies. Patients were randomly assigned to groups that received placebo or induction therapy with upadacitinib (7.5 mg, 15 mg, 30 mg, or 45 mg, extended release), once daily for 8 weeks. The primary endpoint was the proportion of subjects who achieve clinical remission according to the Adapted Mayo score at week 8. No multiplicity adjustments were applied. RESULTS At week 8, 8.5%, 14.3%, 13.5%, and 19.6% of patients receiving 7.5 mg, 15 mg, 30 mg, or 45 mg upadacitinib, respectively, achieved clinical remission compared with none of the patients receiving placebo (P = .052, P = .013, P = .011, and P = .002, compared with placebo, respectively).