Th17, Th22, and Th1 cells are detected in psoriatic skin lesions and implicated in psoriasis pathogenesis, but inflammatory T cell numbers in blood, as well as the relative importance of each cell type, is unclear. Using 7-color flow cytometry, circulating Th17, Th22, and Th1 cells were quantified in 21 untreated psoriatics and 17 healthy individuals. CCR6 was the best cell surface marker for IL-17A+ cells when compared with IL-23R or CD161. CCR6+, IL-17A+, IL-22+, CCR6+ IL-17A+, CCR6+ IL-22+, CCR6+ tumor necrosis factor-α+, IL-17A + IFN-γ−, IL-17A + IL-22 + IFN-γ−, and IL-17A + IL-22−IFN-γ− cells were increased in psoriatics (all values P < 0.001), indicating elevations in circulating Th17 cells, using multiple criteria to define these cells. Th22 (IL-17A−IL-22 + IFN-γ−, P < 0.05) and Th1 (IL-17A−IFN-γ+, P < 0.05) cells were also increased in psoriatics, but to a lesser extent. Inhibition of either NF-κB or STAT3 in vitro blocked cytokine production by both Th17 and Th1 cells. Circulating levels of Th17 and Th1 cells decreased in a subset of five psoriasis patients serially evaluated following induction therapy with infliximab. In summary, elevated numbers of circulating inflammatory T cells may contribute to cutaneous inflammation and systemic inflammatory disease that occurs in individuals with psoriasis.

What individual differences in neural activity predict the future escalation of alcohol drinking from casual to compulsive? The neurobiological mechanisms that gate the transition from moderate to compulsive drinking remain poorly understood. We longitudinally tracked the development of compulsive drinking across a binge-drinking experience in male mice. Binge drinking unmasked individual differences, revealing latent traits in alcohol consumption and compulsive drinking despite equal prior exposure to alcohol. Distinct neural activity signatures of cortical neurons projecting to the brainstem before binge drinking predicted the ultimate emergence of compulsivity. Mimicry of activity patterns that predicted drinking phenotypes was sufficient to bidirectionally modulate drinking. Our results provide a mechanistic explanation for individual variance in vulnerability to compulsive alcohol drinking.

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IMPORTANCE There are concerns that low-and no-calorie sweetened beverages (LNCSBs) do not have established benefits, with major dietary guidelines recommending the use of water and not LNCSBs to replace sugar-sweetened beverages (SSBs). Whether LNCSB as a substitute can yield similar improvements in cardiometabolic risk factors vs water in their intended substitution for SSBs is unclear. OBJECTIVETo assess the association of LNCSBs (using 3 prespecified substitutions of LNCSBs for SSBs, water for SSBs, and LNCSBs for water) with body weight and cardiometabolic risk factors in adults with and without diabetes. DATA SOURCES Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception through December 26, 2021. STUDY SELECTION Randomized clinical trials (RCTs) with at least 2 weeks of interventions comparing LNCSBs, SSBs, and/or water were included.DATA EXTRACTION AND SYNTHESIS Data were extracted and risk of bias was assessed by 2 independent reviewers. A network meta-analysis was performed with data expressed as mean difference (MD) or standardized mean difference (SMD) with 95% CIs. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to assess the certainty of the evidence. MAIN OUTCOMES AND MEASURESThe primary outcome was body weight. Secondary outcomes were other measures of adiposity, glycemic control, blood lipids, blood pressure, measures of nonalcoholic fatty liver disease, and uric acid. RESULTSA total of 17 RCTs with 24 trial comparisons were included, involving 1733 adults (mean [SD] age, 33.1 [6.6] years; 1341 women [77.4%]) with overweight or obesity who were at risk for or had diabetes. Overall, LNCSBs were a substitute for SSBs in 12 RCTs (n = 601 participants), water was a substitute for SSBs in 3 RCTs (n = 429), and LNCSBs were a substitute for water in 9 RCTs (n = 974). Substitution of LNCSBs for SSBs was associated with reduced body weight (MD, −1.06 kg; 95% CI, −1.71 to -0.41 kg), body mass index (MD, −0.32; 95% CI, −0.58 to -0.07), percentage of body fat (MD, −0.60%; 95% CI, −1.03% to -0.18%), and intrahepatocellular lipid (SMD, −0.42; 95% CI, −0.70 to -0.14). Substituting water for SSBs was not associated with any outcome. There was also no association found between substituting LNCSBs for water with any outcome except glycated (continued) Key Points Question Are low-and no-calorie sweetened beverages (LNCSBs) as the intended substitute for sugarsweetened beverages (SSBs) associated with improved body weight and cardiometabolic risk factors similar to water replacement? Findings In this systematic review and meta-analysis of 17 randomized clinical trials, LNCSBs as a substitute for SSBs were associated with reduced body weight, body mass index, percentage of body fat, and intrahepatocellular lipid, providing benefits that were similar to those of water, the standard-of-care substitution.Meaning The findings of this study suggest that over the moderate term, LNCSBs are a viable alternative to water as a replacemen...

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