Oxazolone Colitis, a Th2 Colitis Model Resembling Ulcerative Colitis, Is Mediated by IL-13-Producing NK-T Cells

AbstractOxazolone colitis (OC) is an experimental colitis that has a histologic resemblance to human ulcerative colitis. Here we show that IL-13 production is a significant pathologic factor in OC since its neutralization by IL-13Rα2-Fc administration prevents colitis. We further show that OC is mediated by NK-T cells since it can be induced neither in mice depleted of NK-T cells nor in mice that cannot present antigen to NK-T cells and mice lacking an NK-T cell-associated TCR. Finally, we show that NK-T cells are the source of the IL-13, since they produce IL-13 upon stimulation by α-galactosylceramide, an NK-T cell-specific antigen. These data thus describe a cellular mechanism underlying an experimental colitis that may explain the pathogenesis of ulcerative colitis

Examining a staging model for anorexia nervosa: empirical exploration of a four stage model of severity.

Background: An illness staging model for anorexia nervosa (AN) has received increasing attention, but assessing the merits of this concept is dependent on empirically examining a model in clinical samples. Building on preliminary findings regarding the reliability and validity of the Clinician Administered Staging Instrument for Anorexia Nervosa (CASIAN), the current study explores operationalising CASIAN severity scores into stages and assesses their relationship with other clinical features. Method: In women with DSM-IV-R AN and sub-threshold AN (all met AN criteria using DSM 5), receiver operating curve (ROC) analysis (n = 67) assessed the relationship between the sensitivity and specificity of each stage of the CASIAN. Thereafter chi-square and post-hoc adjusted residual analysis provided a preliminary assessment of the validity of the stages comparing the relationship between stage and treatment intensity and AN sub-types, and explored movement between stages after six months (Time 3) in a larger cohort (n = 171). Results: The CASIAN significantly distinguished between milder stages of illness (Stage 1 and 2) versus more severe stages of illness (Stages 3 and 4), and approached statistical significance in distinguishing each of the four stages from one other. CASIAN Stages were significantly associated with treatment modality and primary diagnosis, and CASIAN Stage at Time 1 was significantly associated with Stage at 6 month follow-up. Conclusions: Provisional support is provided for a staging model in AN. Larger studies with longer follow-up of cases are now needed to replicate and extend these findings and evaluate the overall utility of staging as well as optimal staging models

Parsing cyclothymic disorder and other specified bipolar spectrum disorders in youth

© 2018 Elsevier B.V. Objective: Most studies of pediatric bipolar disorder (BP) combine youth who have manic symptoms, but do not meet criteria for BP I/II, into one “not otherwise specified” (NOS) group. Consequently, little is known about how youth with cyclothymic disorder (CycD) differ from youth with BP NOS. The objective of this study was to determine whether youth with a research diagnosis of CycD (RDCyc) differ from youth with operationalized BP NOS. Method: Participants from the Course and Outcome of Bipolar Youth study were evaluated to determine whether they met RDCyc criteria. Characteristics of RDCyc youth and BP NOS youth were compared at baseline, and over eight-years follow-up. Results: Of 154 youth (average age 11.96 (3.3), 42% female), 29 met RDCyc criteria. RDCyc youth were younger (p =.04) at baseline. Over follow-up, RDCyc youth were more likely to have a disruptive behavior disorder (p =.01), and were more likely to experience irritability (p =.03), mood reactivity (p =.02), and rejection sensitivity (p =.03). BP NOS youth were more likely to develop hypomania (p =.02), or depression (p =.02), and tended to have mood episodes earlier in the eight-year follow-up period. Limitations: RDCyc diagnoses were made retrospectively and followed stringent criteria, which may highlight differences that, under typical clinical conditions and more vague criteria, would not be evident. Conclusion: There were few differences between RDCyc and BP NOS youth. However, the ways in which the groups diverged could have implications; chronic subsyndromal mood symptoms may portend a severe, but ultimately non-bipolar, course. Longer follow-up is necessary to determine the trajectory and outcomes of CycD symptoms