Stakeholder Perspectives on Advancing Understanding of Prenatal Opioid Exposure and Brain Development From the iOPEN Consortium of the Healthy Brain and Child Development Study.

Introduction: There is a dire need for research regarding the implications of opioid use during pregnancy on fetal and childhood development to better inform both medical practice and policy. The Healthy Brain and Child Development Study will examine brain and behavioral development from birth through the first decade of life. Due to large scope and anticipated complexity of this initiative, an 18-month planning phase was implemented across 28 sites across the nation. A core element of the Phase I initiative involved the development of Stakeholder Advisory Committees to inform the next phase of the initiative. Methods: Phase I stakeholder meetings were conducted at Oregon Health and Science University, New York University Langone Medical Center, the University of Pittsburgh, and the University of Vermont to better understand perspectives and inform upcoming research. Despite differences in the structure of the stakeholder meetings by site, the overarching goals for the meetings included establishing relationships, gathering input, and learning about research engagement. Documents from each meeting were reviewed for location, duration, attendees, common research themes, and pertinent suggestions for improving research approaches. Results: All stakeholders had high levels of interest in research for pregnant people with substance use disorders and agreed on research priorities including collaboration, connection, communication, and support. Different stakeholders offered unique perspectives on various aspects of study design and themes that emerged through meetings. Discussion: Overall, there was excitement about the research, especially the opportunity to include the voices of people with lived experience; collaboration between providers, peer support specialists, patients, and others; and excitement around contributing to research that could elucidate new and pertinent findings in the realm of addiction medicine and child development. Sites also found that there is mistrust between people with substance use disorder and the medical system, and this could be addressed by including people with lived experience on the research team, forming connections, communicating clearly, training the research team in implicit bias, and practicing trauma-informed care. In conclusion, these stakeholder meetings provided valuable information for structuring upcoming studies; however, researchers would have benefitted from more time and more opportunities for in-person connection

Stromal immune infiltration in HIV-related diffuse large B-cell lymphoma is associated with HIV disease history and patient survival

OBJECTIVE: Understanding tumor microenvironment and its impact on prognosis of HIV-related lymphomas may provide insight into novel therapeutic strategies. DESIGN: We characterized the relationship between infiltrating immune cells with tumor characteristics, HIV disease history and survival in 80 HIV-related diffuse large B-cell lymphoma (DLBCL) patients diagnosed in the era of combined antiretroviral therapy (1996–2007) at Kaiser Permanente (KP) California. Eighty HIV-unrelated DLBCL patients were included for comparison. METHODS: Data on patients’ clinical history were obtained from KP’s electronic health records. The density of stromal CD4+, CD8+ and FOXP3+ T cells and CD68+ macrophages, as well as tumor molecular characteristics were examined using immunohistochemistry. The associations between stromal immune infiltration and patient’s clinical history or tumor characteristics were examined using Kruskal Wallis tests or Peasrons’ correlation coefficient. The effect of stromal immune infiltration on two-year mortality was evaluated in multivariable logistic regression. RESULTS: Compared to HIV-unrelated DLBCL, patients with HIV-related DLBCL had significantly reduced stromal CD4+ and FOXP3+ T cells, but increased density of macrophages. Increased density of stromal macrophages was correlated with lower circulating CD4 cell count at DLBCL diagnosis. Tumor molecular characteristics, including BCL6, p53 and cMYC expression, but not EBV infection status, were significantly correlated with stromal immune infiltration, particularly FOXP3+ T cells. A higher density of infiltrating CD8+ T cell was significantly associated with reduced mortality in HIV-related DLBCL patients [odds ratio=0.30 (0.09–0.97) for ≥25% vs. <10%]. CONCLUSION: These data provide evidence for the prognostic significance of cytotoxic T cells in determining outcomes of HIV-related lymphoma

Advances in adipose tissue metabolism.

International audienceThis review will focus on the recent findings in adipose tissue metabolism with special attention to human adipocyte biology and physiology. There are major advances stemming from the concomitant results obtained from studies on mature human adipocytes, human preadipocytes differentiated in vitro and murine adipose cell lines. Physiological developments have been based on the expanded utilization of various kinds of murine transgenic models and physiological techniques such as microdialysis, open-flow microperfusion, arteriovenous techniques and the utilization of deuterium- or tritium-labelled metabolites that have provided a number of physiological advances in the understanding of human adipose tissue physiology. Gene expression profiling studies and nutrigenomics are emerging methods that herald interesting approaches for the future. An overview of recent discoveries in the mechanisms involved in the control of free fatty acid uptake, triacylglycerol synthesis and fat deposition will be discussed, as well as recent advances in the mechanisms involved in the lipolytic pathways, the role of lipases and perilipins. In addition, the in vivo validation of catecholamine action and the discovery of the lipolytic effects of natriuretic peptides will also be covered