Identification of Cinnamein, a Component of Balsam of Tolu/Peru, as a New Ligand of PPARα for Plaque Reduction and Memory Protection in a Mouse Model of Alzheimer's Disease.

Background: Despite intense investigations, no effective treatment is yet available to reduce plaques and protect memory and learning in patients with Alzheimer's disease (AD), the most common neurodegenerative disorder. Therefore, it is important to identify a non-toxic, but effective, treatment option for AD. Objective: Cinnamein, a nontoxic compound, is naturally available in Balsam of Peru and Tolu Balsam. We examined whether cinnamein treatment could decrease plaques and improve cognitive functions in 5XFAD mouse model of AD. Methods: We employed in silico analysis, time-resolved fluorescence energy transfer assay, thermal shift assay, primary neuron isolation, western blot, immunostaining, immunohistochemistry, Barnes maze, T maze, and open field behavior. Results: Oral administration of cinnamein led to significant reduction in amyloid-ß plaque deposits in the brain and protection of spatial learning and memory in 5XFAD mice. Peroxisome proliferator-activated receptor alpha (PPARα), a nuclear hormone receptor, is involved in plaque lowering and increase in hippocampal plasticity. While investigating underlying mechanisms, we found that cinnamein served as a ligand of PPARα. Accordingly, oral cinnamein upregulated the level of PPARα, but not PPARß, in the hippocampus, and remained unable to decrease plaques from the hippocampus and improve memory and learning in 5XFAD mice lacking PPARα. While A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is one of the drivers of nonamyloidogenic pathway, transcription factor EB (TFEB) is considered as the master regulator of autophagy. Cinnamein treatment was found to upregulate both ADAM10 and TFEB in the brain of 5XFAD mice via PPARα. Conclusions: Our results suggest that this balsam component may have therapeutic importance in AD.

Preliminary Impact of Group-Based Interventions on Stigma, Mental Health, and Treatment Adherence Among Adolescents Living with Human Immunodeficiency Virus in Uganda.

OBJECTIVE: To examine the preliminary impact of group cognitive behavioral therapy and multiple family group-based family strengthening to address HIV stigma and improve the mental health functioning of adolescents living with HIV in Uganda. STUDY DESIGN: We analyzed data from the Suubi4Stigma study, a 2-year pilot randomized clinical trial that recruited adolescents living with HIV (10-14 years) and their caregivers (n = 89 dyads), from 9 health clinics. We fitted separate three-level mixed-effects linear regression models to test the effect of the interventions on adolescent outcomes at 3 and 6 months post intervention initiation. RESULTS: The average age was 12.2 years and 56% of participants were females. Participants in the multiple family group-based family strengthening intervention reported lower levels of internalized stigma (mean difference = -0.008, 95% CI = -0.015, -0.001, P = .025) and depressive symptoms at 3 months (mean difference = -0.34, 95% CI = -0.53, -0.14, P < .001), compared with usual care. On the other hand, participants in the group cognitive behavioral therapy intervention reported lower levels of anticipated stigma at 3 months (mean difference = -0.039, 95% CI = -0.072, -0.006), P = .013) and improved self-concept at 6 months follow-up (mean difference = 0.04, 95% CI = 0.01, 0.01, P = .025). CONCLUSION: Outcome trends from this pilot study provide compelling evidence to support testing the efficacy of these group-based interventions on a larger scale. TRIAL REGISTRATION: The study is registered in the Clinical trials.gov database (Identifier #: NCT04528732).

Adapting and disseminating a community-collaborative, evidence-based HIV/AIDS prevention programme: lessons from the history of CHAMP

In recent years, calls for the scaling-up, or more broad dissemination of evidence-based HIV prevention programmes, have increased. This paper responds to the call for increasing applicable knowledge about programme dissemination by reviewing the history of a major evidence-based human immunodeficiency virus (HIV) prevention and mental health promotion programme that has been adapted successfully and pilot-tested across four settings - including two major cities, as well as in the United States, Trinidad and Tobago and South Africa - to date. This programme, entitled CHAMP (the Collaborative HIV Prevention & Adolescent Mental Health Project), is distinctive primarily for its emphasis on community collaboration and power-sharing, and also its incorporation of individual, family and community-level interventions. The history of programme development, including theoretical foundations and results across sites, is discussed with a particular emphasis on the implications of CHAMP'S dissemination thus far.

Community collaborative youth-focused HIV/AIDS prevention in South Africa and Trinidad: preliminary findings.

BACKGROUND: South Africa and Trinidad and Tobago are disproportionately impacted by high rates of HIV/AIDS among adolescents. OBJECTIVE: The article describes the HIV crises in these countries; outlines a community participatory research framework to adapt and deliver family-based prevention; and presents preliminary data from intervention pilots in each setting. METHODS: Adapted interventions were piloted with N = 140 families in South Africa and N=16 families in Trinidad and Tobago to refine recruitment and retention efforts and to assess the adapted interventions' impact on family and risk-related constructs. RESULTS: Both settings reported promising results including high recruitment and retention and favourable pre to post changes in parent/youth frequency and comfort in talking about sensitive subjects, HIV transmission knowledge and attitudes about persons with HIV/AIDS. CONCLUSION: International HIV-prevention alliances are increasing. Such alliances are challenged by trust issues, power-differentials and ideological differences. Recommendations are provided on how some challenges can be overcome.