“Buddy System” of Peer Mentors may Help Control Diabetes

Type 2 diabetes is more prevalent and severe among African Americans. Even within the Veterans Health Administration, which is thought to have minimized barriers in access to care, racial disparities in glucose control and outcomes persist. This Issue Brief summarizes work testing two novel interventions—one-on-one peer mentoring (a “buddy system”) and financial incentives—designed to help patients with consistently poor diabetes control achieve better results. In this case, a telephone buddy makes a big difference

Community Health Worker Support For Disadvantaged Patients With Multiple Chronic Diseases: A Randomized Clinical Trial

In a randomized trial, a community health worker intervention reduced hospitalization and improved outcomes in uninsured or publicly insured patients with multiple chronic conditions such as diabetes, obesity, and smoking. Community health workers can improve health and lower costs, and provide a scalable strategy to improve population health

Incorporating African American Veterans\u27 Success Stories for Hypertension Management: Developing a Behavioral Support Texting Protocol

BACKGROUND: Peer narratives engage listeners through personally relevant content and have been shown to promote lifestyle change and effective self-management among patients with hypertension. Incorporating key quotations from these stories into follow-up text messages is a novel way to continue the conversation, providing reinforcement of health behaviors in the patients\u27 daily lives. OBJECTIVE: In our previous work, we developed and tested videos in which African American Veterans shared stories of challenges and success strategies related to hypertension self-management. This study aims to describe our process for developing a text-messaging protocol intended for use after viewing videos that incorporate the voices of these Veterans. METHODS: We used a multistep process, transforming video-recorded story excerpts from 5 Veterans into 160-character texts. We then integrated these into comprehensive 6-month texting protocols. We began with an iterative review of story transcripts to identify vernacular features and key self-management concepts emphasized by each storyteller. We worked with 2 Veteran consultants who guided our narrative text message development in substantive ways, as we sought to craft culturally sensitive content for texts. Informed by Veteran input on timing and integration, supplementary educational and 2-way interactive assessment text messages were also developed. RESULTS: Within the Veterans Affairs texting system Annie, we programmed five 6-month text-messaging protocols that included cycles of 3 text message types: narrative messages, nonnarrative educational messages, and 2-way interactive messages assessing self-efficacy and behavior related to hypertension self-management. Each protocol corresponds to a single Veteran storyteller, allowing Veterans to choose the story that most resonates with their own life experiences. CONCLUSIONS: We crafted a culturally sensitive text-messaging protocol using narrative content referenced in Veteran stories to support effective hypertension self-management. Integrating narrative content into a mobile health texting intervention provides a low-cost way to support longitudinal behavior change. A randomized trial is underway to test its impact on the lifestyle changes and blood pressure of African American Veterans. TRIAL REGISTRATION: ClinicalTrials.gov NCT03970590; https://clinicaltrials.gov/ct2/show/NCT03970590. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29423

Systemic LRG1 Expression in Melanoma is Associated with Disease Progression and Recurrence

The response rates upon neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma are higher as compared with stage IV disease. Given that successful ICB depends on systemic immune response, we hypothesized that systemic immune suppression might be a mechanism responsible for lower response rates in late-stage disease, and also potentially with disease recurrence in early-stage disease. Plasma and serum samples of cohorts of patients with melanoma were analyzed for circulating proteins using mass spectrometry proteomic profiling and Olink proteomic assay. A cohort of paired samples of patients with stage III that progressed to stage IV disease (n = 64) was used to identify markers associated with higher tumor burden. Baseline patient samples from the OpACIN-neo study (n = 83) and PRADO study (n = 49; NCT02977052) were used as two independent cohorts to analyze whether the potential identified markers are also associated with disease recurrence after neoadjuvant ICB therapy. When comparing baseline proteins overlapping between patients with progressive disease and patients with recurrent disease, we found leucine-rich alpha-2-glycoprotein 1 (LRG1) to be associated with worse prognosis. Especially nonresponder patients to neoadjuvant ICB (OpACIN-neo) with high LRG1 expression had a poor outcome with an estimated 36-month event-free survival of 14% as compared with 83% for nonresponders with a low LRG1 expression (P = 0.014). This finding was validated in an independent cohort (P = 0.0021). LRG1 can be used as a biomarker to identify patients with high risk for disease progression and recurrence, and might be a target to be combined with neoadjuvant ICB. Significance: LRG1 could serve as a potential target and as a biomarker to identify patients with high risk for disease recurrence, and consequently benefit from additional therapies and intensive follow-up

Common mouse models of tauopathy reflect early but not late human disease

BACKGROUND: Mouse models that overexpress human mutant Tau (P301S and P301L) are commonly used in preclinical studies of Alzheimer’s Disease (AD) and while several drugs showed therapeutic effects in these mice, they were ineffective in humans. This leads to the question to which extent the murine models reflect human Tau pathology on the molecular level. METHODS: We isolated insoluble, aggregated Tau species from two common AD mouse models during different stages of disease and characterized the modification landscape of the aggregated Tau using targeted and untargeted mass spectrometry-based proteomics. The results were compared to human AD and to human patients that suffered from early onset dementia and that carry the P301L Tau mutation. RESULTS: Both mouse models accumulate insoluble Tau species during disease. The Tau aggregation is driven by progressive phosphorylation within the proline rich domain and the C-terminus of the protein. This is reflective of early disease stages of human AD and of the pathology of dementia patients carrying the P301L Tau mutation. However, Tau ubiquitination and acetylation, which are important to late-stage human AD are not represented in the mouse models. CONCLUSION: AD mouse models that overexpress human Tau using risk mutations are a suitable tool for testing drug candidates that aim to intervene in the early formation of insoluble Tau species promoted by increased phosphorylation of Tau. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13024-023-00601-y

EZH2 Codon 641 Mutations are Common in BCL2-Rearranged Germinal Center B Cell Lymphomas

Mutations at codon 641 of EZH2 are recurrent in germinal center B cell lymphomas, and the most common variants lead to altered EZH2 enzymatic activity and enhanced tri-methylation of histone H3 at lysine 27, a repressive chromatin modification. As an initial step toward screening patients for cancer genotype-directed therapy, we developed a screening assay for EZH2 codon 641 mutations amenable for testing formalin-fixed clinical specimens, based on the sensitive SNaPshot single nucleotide extension technology. We detected EZH2 mutations in 12/55 (22%) follicular lymphomas (FL), 5/35 (14%) diffuse large B cell lymphomas with a germinal center immunophenotype (GCB-DLBCL), and 2/11 (18%) high grade B cell lymphomas with concurrent rearrangements of BCL2 and MYC. No EZH2 mutations were detected in cases of Burkitt lymphoma (0/23). EZH2 mutations were frequently associated with the presence of BCL2 rearrangement (BCL2-R) in both the FL (28% of BCL-R cases versus 0% of BCL2-WT cases, p<0.05) and GCB-DLBCL groups (33% of BCL2-R cases versus 4% of BCL2-WT cases, p<0.04), and across all lymphoma types excluding BL (27% of BCL2-R cases versus 3% of BCL2-WT cases, p<0.003). We confirmed gain-of-function activity for all previously reported EZH2 codon 641 mutation variants. Our findings suggest that EZH2 mutations constitute an additional genetic “hit” in many BCL2-rearranged germinal center B cell lymphomas. Our work may be helpful in the selection of lymphoma patients for future trials of pharmacologic agents targeting EZH2 and EZH2-regulated pathways

Transportations of space, time and self: the role of reading groups in managing mental distress in the community

Background: The practice of reading and discussing literature in groups is long established, stretching back into classical antiquity. Although benefits of therapeutic reading groups have been highlighted, research into participants’ perceptions of these groups has been limited. Aims: To explore the experiences of those attending therapeutic reading groups, considering the role of both the group, and the literature itself, in participants’ ongoing experiences of distress. Method: Eleven participants were recruited from two reading groups in the South-East of England. One focus group was run, and eight individuals self-selected for individual interviews. The data were analysed together using a thematic analysis drawing on dialogical theories. Results: Participants described the group as an anchor, which enabled them to use fiction to facilitate the discussion of difficult emotional topics, without referring directly to personal experience. Two aspects of this process are explored in detail: the use of narratives as transportation, helping to mitigate the intensity of distress; and using fiction to explore possibilities, alternative selves and lives. Conclusions: For those who are interested and able, reading groups offer a relatively de-stigmatised route to exploring and mediating experiences of distress. Implications in the present UK funding environment are discussed