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Recent studies highlight the importance of disinhibited eating and underlying inhibitory control deficits in the maintenance of obesity. So far, inhibition facets have been examined in isolation and findings are inconsistent due to different measures. This study illustrates the multifaceted nature of inhibitory control by comparing different inhibition stages in outpatients with chronic overweight (with binge eating disorder, BED, n = 24; Non-BED, n = 47) and healthy controls (HC, n = 30). Besides reporting impulsive patterns (UPPS), participants performed the Food Stroop (FST), Door Opening (DOT) and Stop Signal (SST) task with food and generic stimuli. The results showed a significant influence of self-reported inhibition deficits on body weight in outpatients irrespective of binge eating. On a behavioral level, BED exhibited deficits in focusing on a task (FST) but not to Non-BED but performed better in inhibiting an already initiated response (SST) compared to Non-BED and HC regardless of stimulus category. In sum, first-stage deficits in interference inhibition might be attributable to the initiation of eating episodes, while deficits in the late-stage interruptive inhibition might result in loss of control over an eating episode especially in BED if executive resources are depleted. Under executive control, BED might perform better, given their daily practice. The inclusion of a holistic inhibitory control pathway offers a further step in obesity research., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Stimulator of interferon genes (STING) is a receptor in the endoplasmic reticulum that propagates innate immune sensing of cytosolic pathogen-derived and self DNA 1 . The development of compounds that modulate STING has recently been the focus of intense research for the treatment of cancer and infectious diseases and as vaccine adjuvants 2 . To our knowledge, current efforts are focused on the development of modified cyclic dinucleotides that mimic the endogenous STING ligand cGAMP; these have progressed into clinical trials in patients with solid accessible tumours amenable to intratumoral delivery 3 . Here we report the discovery of a small molecule STING agonist that is not a cyclic dinucleotide and is systemically efficacious for treating tumours in mice. We developed a linking strategy to synergize the effect of two symmetry-related amidobenzimidazole (ABZI)-based compounds to create linked ABZIs (diABZIs) with enhanced binding to STING and cellular function. Intravenous administration of a diABZI STING agonist to immunocompetent mice with established syngeneic colon tumours elicited strong anti-tumour activity, with complete and lasting regression of tumours. Our findings represent a milestone in the rapidly growing field of immune-modifying cancer therapies.

Background: Fumaric acid esters (FAEs) are a broadly used therapy option for patients suffering from moderate-to-severe plaque psoriasis. Various studies in psoriasis have already shown peripheral blood lymphopenia during oral FAE therapy. Smaller studies also documented a reduction of CD4+ and CD8+ cell counts. Up to now, there are few case reports on opportunistic infections under FAE therapy - all of them associated with lymphopenia., Objective: To examine the influence of FAEs on white blood cells with special regard to leukocytes, lymphocytes, and CD4+ and CD8+ cells during psoriasis therapy., Patients and Methods: A cohort of 105 patients with diagnosed moderate-to-severe chronic plaque psoriasis was enrolled in this single-centre observational trial. For a cohort of 36 patients, T-cell subset analyses were performed., Results: Of the total, 65 patients were male (61.9%) and 40 (38.1%) female; the mean age was 43.3 years (range 16-73 years). The median lymphocyte count was significantly reduced by about 35.8% after the first 6 months of therapy. When assessing the lymphocyte count nadir over the whole period observed, 46.7% of the patients developed lymphopenia. Severe lymphopenia (<500/µL) was documented in 11.4% of the patients. The CD4+ and CD8+ cell counts were significantly reduced by about 30.2 and 45.3%, respectively., Conclusion: To the best of our knowledge this is the largest clinical investigation analysing prospectively CD4+ and CD8+ cell counts in psoriasis patients receiving FAEs. We suggest periodic monitoring of absolute lymphocyte counts as well as the establishment of the determination of T-cell subsets prior to and during therapy., (© 2017 S. Karger AG, Basel.)