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BackgroundOne in 5 young people grow up in a family where one parent has experienced a mental health problem or substance use concern. Compared with their same-aged peers, these youth are at a higher risk of academic failure and acquiring a substance abuse and/or mental health issue. There is a paucity of accessible, age-appropriate interventions that address their needs. ObjectiveA 6-week, web-based intervention, “mental illness: supported, preventative, online, targeted” (mi.spot), was developed based on previous research and the competence enhancement model. This paper describes the protocol for a randomized controlled trial and details how the usage, safety, acceptability, and feasibility of the intervention will be determined. MethodsParticipants will be recruited through social media and clinician referral. A total of 70 Australians, aged 18 to 25 years, who grew up with parents with a mental illness or substance use concern will participate in a 2-arm parallel randomized controlled trial. The assessment will consist of a baseline measurement and 2 follow-up periods, posttest and 6-week follow-up, using the Mental Health Continuum short form; the Depression, Anxiety, and Stress Scale; the Coping Orientation to Problems Experienced inventory; the General Help Seeking Questionnaire; the Social Connectedness Scale; the Mental Health Literacy Scale; the General Self-Efficacy Scale; and the Attribution of Responsibility for Parental Mental Illness Measure. Impact will be examined at pre, post, and follow-up time periods using analyses of variance that will include a within-subjects factor (time) and a between-subjects factor (intervention/control). Facilitator interviews will ascertain intervention feasibility. Participant interviews will ascertain intervention acceptability. Interview data will be analyzed within a qualitative framework. Usage (data analytics) across site features and several indicators of clinical safety will also be reported. ResultsThe impact of mi.spot will be examined at pre, post, and follow-up time periods using analyses of variance on each of the measures outlined above. There will be a within-subjects factor (time) and a between-subjects factor (intervention/control). Data analysis will employ the intention-to-treat principle by including all participants in the analyses. Qualitative interview data will be analyzed using interpretative phenomenological analysis along with respondent validation. The Monash University Human Research Ethics Committee (reference number: 2019-18660-30434) approved the trial on April 17, 2019. As of October 2, 2019, 30 participants were enrolled in the control group and 34 participants were enrolled in the intervention group. Result are expected to be submitted for publication in December 2020. ConclusionsStudy results will provide reliable evidence on a web-based intervention that has the potential to make a difference to the lives of many vulnerable young adults. Implementation guidelines are needed to embed the intervention in different service sectors. Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12619000335190; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12619000335190 International Registered Report Identifier (IRRID)DERR1-10.2196/15626

Background & Aims The immunosuppressant rapamycin frequently causes noninfectious diarrhea in organ transplant recipients. We investigated the mechanisms of this process. Methods We performed a retrospective analysis of renal transplant recipients treated with rapamycin from 2003 through 2010 at Albany Medical College, collecting data on serum levels of rapamycin. Levels of the Na+/H+ exchanger 3 (NHE3) were measured in human ileal biopsy specimens from patients who did and did not receive rapamycin (controls), in ileum tissues from rats or mice given rapamycin, and in mice with intestine-specific disruption of mammalian target of rapamycin ( Mtor ) ( mTOR f/f :Villin-cre mice) or Atg7 ( Atg7 flox/flox ; Villin-Cre ). Exchange activity and intestinal water absorption were measured using a pH-sensitive dye and small intestine perfusion, respectively. Results Episodes of noninfectious diarrhea occurred in organ recipients after increases in serum levels of rapamycin. The expression of NHE3 was reduced in the ileal brush border of patients with diarrhea. In rats and mice, continuous administration of low doses of rapamycin reduced levels of NHE3 in intestinal tissues; this effect was not observed in mice with intestinal deletion of ATG7, indicating that autophagy is required for the reduction. Administration of single high doses of rapamycin to mice, to model the spikes in rapamycin levels that occur in patients with severe diarrheal episodes, resulted in reduced phosphorylation of S6 and AKT in ileal tissues, indicating inhibition of the mTOR complex (mTORC1 and mTORC2). The intestines of mice with intestine-specific deletion of mTOR were dilated and contained large amounts of liquid stools; they also had reduced levels of total NHE3 and NHERF1 compared with control mice. We observed a significant reduction in Na + /H + exchange activity in ileum tissues from these mice. Conclusions Rapamycin inhibition of mTOR reduces levels of NHE3 and Na + /H + exchange activity in intestinal tissues of patients and rodents. This process appears to require the autophagic activity mediated by ATG7. Loss of mTOR regulation of NHE3 could mediate the development of diarrhea in patients undergoing rapamycin therapy. [ABSTRACT FROM AUTHOR]

In this paper, the morphology, chemical composition and reactivity of MCM-48 powders impregnated with , or both toward hydrodesulphurization (HDS) of thiophene were characterized. The reactivity of the catalyst was quantitatively compared with a standard industrial catalyst (from HaldorTopsoe, Denmark) and a novel 2 nanotube-based catalysts (from R. Tenne, Israel). Morphology and chemical composition were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), and EDX elemental maps. Reactivity was determined in a gas-chromatograph based mini flow reactor using thiophene as a probe molecule. The sulfided MCM-48 supported catalyst showed the largest HDS activity with turnover frequencies (TOF) about half as large as for the commercial system under the test conditions used here. Presulfiding did increase activity of all MCM-48 catalysts. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Immune alterations involving heightened T-helper-1 responses have been proposed to play a major role in the pathogenesis of sarcoidosis. Interferon-alpha therapy and hepatitis C infection have been implicated in the development of a variety of autoimmune diseases. However, despite the wide use of IFN-alpha therapy for hepatitis C, only a few cases of sarcoidosis have been reported in this context. We report the case of a 42-year-old white female with hepatitis C, who developed systemic sarcoidosis shortly after therapy with IFN-alpha2b. The disease was heralded by the appearance of a cutaneous sarcoid/ foreign body granulomatous reaction at the site of an old tattoo. The sarcoidosis responded to a short course of oral prednisone therapy. We also reviewed the other reported cases and discussed the possible immunological mechanisms involved. [ABSTRACT FROM AUTHOR]