Interventions in ambulatory healthcare settings to reduce social isolation among adults aged 18-64: a systematic review.

BACKGROUND: Social isolation is associated with increased all-cause and premature mortality, poor chronic disease management, and mental health concerns. Limited research exists on interventions addressing social isolation among individuals under 65 despite its increasing prevalence among young and middle-aged adults. AIM: To identify interventions from the extant literature that address social isolation and loneliness in ambulatory healthcare settings in adults aged 18-64, and to identify elements of successful studies for future intervention design. DESIGN & SETTING: Systematic review of interventions targeting social isolation in community-dwelling adults aged 18-64 within ambulatory healthcare settings. METHOD: A search strategy was developed to identify relevant articles in the following databases: Ovid MEDLINE, Embase, EBM Reviews, Scopus, CINAHL and PsychInfo. Data were extracted on study design and setting, intervention type, outcome related to social isolation/loneliness and scale of measure used. RESULTS: 25,078 citations were identified and underwent title and abstract screening. 75 articles met our inclusion criteria and were synthesised, including an assessment of bias. Effective interventions were delivered in community health settings, incorporated a group component, and used digital technologies. They also addressed the association between mental health and social isolation using CBT approaches and enhanced self-management and coping strategies for chronic conditions through psycho-educational interventions. CONCLUSION: Future research should prioritise adults living in low- and middle-income countries, racialized individuals, as well as those with fewer educational opportunities. There is also a need to advance research in primary care settings, where longitudinal patient-provider relationships would facilitate the success of interventions.

Stereotypic Expansion of T Regulatory and Th17 Cells during Infancy Is Disrupted by HIV Exposure and Gut Epithelial Damage.

Few studies have investigated immune cell ontogeny throughout the neonatal and early pediatric period, when there is often increased vulnerability to infections. In this study, we evaluated the dynamics of two critical T cell populations, T regulatory (Treg) cells and Th17 cells, over the first 36 wk of human life. First, we observed distinct CD4+ T cells phenotypes between cord blood and peripheral blood, collected within 12 h of birth, showing that cord blood is not a surrogate for newborn blood. Second, both Treg and Th17 cells expanded in a synchronous fashion over 36 wk of life. However, comparing infants exposed to HIV in utero, but remaining uninfected, with HIV-unexposed uninfected control infants, there was a lower frequency of peripheral blood Treg cells at birth, resulting in a delayed expansion, and then declining again at 36 wk. Focusing on birth events, we found that Treg cells coexpressing CCR4 and α4ß7 inversely correlated with plasma concentrations of CCL17 (the ligand for CCR4) and intestinal fatty acid binding protein, IL-7, and CCL20. This was in contrast with Th17 cells, which showed a positive association with these plasma analytes. Thus, despite the stereotypic expansion of both cell subsets over the first few months of life, there was a disruption in the balance of Th17 to Treg cells at birth likely being a result of gut damage and homing of newborn Treg cells from the blood circulation to the gut.

Interleukin-15 in cancer immunotherapy: IL-15 receptor complex versus soluble IL-15 in a cancer cell-delivered murine leukemia model.

Cytokines of the common γ-chain receptor family such as IL-15 are vital with respect to activating immune cells, sustaining healthy immune functions, and augmenting the anti-tumor activity of effector cells, making them ideal candidates for cancer immunotherapy. IL-15, either in its soluble form (IL-15sol) or complexed with IL-15Rα (IL-15Rc), has been shown to exhibit potent anti-tumor activities in various experimental cancer studies. Here we describe the impact of intraperitoneal IL-15 in a cancer cell-delivered IL-15 immunotherapy approach using the 70Z/3-L leukemia mouse model. Whereas both forms of IL-15 led to significantly improved survival rates compared to the parent cell line, there were striking differences in the extent of the improved survival: mice receiving cancer cells secreting IL-15sol showed significantly longer survival and protective long-term immunity compared to those producing IL-15Rc. Interestingly, injection of leukemia cells secreting IL-15sol lead to heightened expansion of CD4+ and CD8+ T-cell populations in the peritoneum compared to IL-15Rc. Cell-secreted IL-15Rc resulted in an influx and/or expansion of NK1.1+ cells in the peritoneum which was much less pronounced in the IL-15sol model. Furthermore, IL-15Rc but not IL-15sol lead to T-cell exhaustion and disease progression. To our knowledge, this is the first study detailing a significantly different biological effect of cell-delivered IL-15sol versus IL-15Rc in a mouse cancer immunotherapy study.