A typology of modifications to peer support work for adults with mental health problems:systematic review

© The Authors 2020. Background Peer support work roles are being implemented internationally, and increasingly in lower-resource settings. However, there is no framework to inform what types of modifications are needed to address local contextual and cultural aspects. Aims To conduct a systematic review identifying a typology of modifications to peer support work for adults with mental health problems. Method We systematically reviewed the peer support literature following PRISMA guidelines for systematic reviews (registered on PROSPERO (International Prospective Register of Systematic Reviews) on 24 July 2018: CRD42018094832). All study designs were eligible and studies were selected according to the stated eligibility criteria and analysed with standardised critical appraisal tools. A narrative synthesis was conducted to identify types of, and rationales for modifications. Results A total of 15 300 unique studies were identified, from which 39 studies were included with only one from a low-resource setting. Six types of modifications were identified: role expectations; initial training; type of contact; role extension; workplace support for peer support workers; and recruitment. Five rationales for modifications were identified: to provide best possible peer support; to best meet service user needs; to meet organisational needs, to maximise role clarity; and to address socioeconomic issues. Conclusions Peer support work is modified in both pre-planned and unplanned ways when implemented. Considering each identified modification as a candidate change will lead to a more systematic consideration of whether and how to modify peer support in different settings. Future evaluative research of modifiable versus non-modifiable components of peer support work is needed to understand the modifications needed for implementation among different mental health systems and cultural settings. Declaration of interest None

Skin and gut imprinted helper T cell subsets exhibit distinct functional phenotypes in central nervous system autoimmunity

Korn and colleagues demonstrate that the site of T cell priming (gut versus skin draining lymph nodes) dictates their effector phenotypes and homing to distal sites of immunopathology. Multidimensional single-cell analyses of T cells have fueled the debate about whether there is extensive plasticity or 'mixed' priming of helper T cell subsets in vivo. Here, we developed an experimental framework to probe the idea that the site of priming in the systemic immune compartment is a determinant of helper T cell-induced immunopathology in remote organs. By site-specific in vivo labeling of antigen-specific T cells in inguinal (i) or gut draining mesenteric (m) lymph nodes, we show that i-T cells and m-T cells isolated from the inflamed central nervous system (CNS) in a model of multiple sclerosis (MS) are distinct. i-T cells were Cxcr6(+), and m-T cells expressed P2rx7. Notably, m-T cells infiltrated white matter, while i-T cells were also recruited to gray matter. Therefore, we propose that the definition of helper T cell subsets by their site of priming may guide an advanced understanding of helper T cell biology in health and disease

Synthesis and structure-activity relationships of new quinolone-type molecules against Trypanosoma brucei

Human African trypanosomiasis (HAT) or sleeping sickness is caused by two subspecies of Trypanosoma brucei , Trypanosoma brucei gambiense , and Trypanosoma brucei rhodesiense and is one of Africa's old plagues. It causes a huge number of infections and cases of death per year because, apart from limited access to health services, only inefficient chemotherapy is available. Since it was reported that quinolones such as ciprofloxacin show antitrypanosomal activity, a novel quinolone-type library was synthesized and tested. The biological evaluation illustrated that 4-quinolones with a benzylamide function in position 3 and cyclic or acyclic amines in position 7 exhibit high antitrypanosomal activity. Structure-activity relationships (SAR) are established to identify essential structural elements. This analysis led to lead structure 29, which exhibits promising in vitro activity against T. b. brucei (IC(50) = 47 nM) and T. b. rhodesiense (IC(50) = 9 nM) combined with low cytotoxicity against macrophages J774.1. Screening for morphological changes of trypanosomes treated with compounds 19 and 29 suggested differences in the morphology of mitochondria of treated cells compared to those of untreated cells. Segregation of the kinetoplast is hampered in trypanosomes treated with these compounds; however, topoisomerase II is probably not the main drug targe

Myeloid-derived suppressor cells control B cell accumulation in the central nervous system during autoimmunity

Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) have been characterized in the context of malignancies. Here we show that PMN-MDSCs can restrain B cell accumulation during central nervous system (CNS) autoimmunity. Ly6G+ cells were recruited to the CNS during experimental autoimmune encephalomyelitis (EAE), interacted with B cells that produced the cytokines GM-CSF and interleukin-6 (IL-6), and acquired properties of PMN-MDSCs in the CNS in a manner dependent on the signal transducer STAT3. Depletion of Ly6G+ cells or dysfunction of Ly6G+ cells through conditional ablation of STAT3 led to the selective accumulation of GM-CSF-producing B cells in the CNS compartment, which in turn promoted an activated microglial phenotype and lack of recovery from EAE. The frequency of CD138+ B cells in the cerebrospinal fluid (CSF) of human subjects with multiple sclerosis was negatively correlated with the frequency of PMN-MDSCs in the CSF. Thus PMN-MDSCs might selectively control the accumulation and cytokine secretion of B cells in the inflamed CNS