Meeting the challenge of diabetes in ageing and diverse populations: a review of the literature from the UK

The impact of type 2 diabetes on ageing societies is great and populations across the globe are becoming more diverse. Complications of diabetes unequally affect particular groups in the UK older people, and people with a South Asian background are two population groups with increased risk whose numbers will grow in the future. We explored the evidence about diabetes care for older people with South Asian ethnicity to understand the contexts and mechanisms behind interventions to reduce inequalities. We used a realist approach to review the literature, mapped the main areas where relevant evidence exists, and explored the concepts and mechanisms which underpinned interventions. From this we constructed a theoretical framework for a programme of research and put forward suggestions for what our analysis might mean to providers, researchers, and policy makers. Broad themes of cultural competency; comorbidities and stratification; and access emerged as mid-level mechanisms which have individualised, culturally intelligent, and ethical care at their heart and through which inequalities can be addressed. These provide a theoretical framework for future research to advance knowledge about concordance; culturally meaningful measures of depression and cognitive impairment; and care planning in different contexts which support effective diabetes care for aging and diverse populations

Describing return to work after stroke : a feasibility trial of 12-month outcomes

Objective: Stroke is the greatest cause of disability in adults. A quarter of strokes in the UK affect people of working age, yet under half of them return to work after stroke. There has been little investigation into what constitutes “return to work” following stroke. The aim of this study is to describe the work metrics of stroke survivor participants in a feasibility randomized controlled trial of an early stroke specific vocational rehabilitation intervention. Methods: Retrospective analysis of trial data. Metrics on work status, working hours, workplace accommodations and costs were extracted from trial out - comes gathered by postal questionnaire at 3, 6, and 12 months’ post-randomization for 46 stroke participants in a feasibility randomized controlled trial. Participants were randomized to receive vocational rehabilitation (intervention) or usual care (control). Results: Two-thirds ( n = 29; 63%) of participants re - turned to work at some point in the 12 months following stroke. Participants took a mean of 90 days to return to work. Most returned to the same role with an existing employer. Only one-third of participants who were employed full-time at stroke onset were working full-time at 12 months post-stroke. Most participants experienced a reduction in pre-stroke earnings. Workplace accommodations were more common among intervention group participants. More intervention participants than control participants reported satisfaction with work at both 6 and 12 months post-randomization. Conclusion: This study illustrates the heterogeneous nature of return to work and the dramatic impact of stroke on work status, working hours and income. Longitudinal research should explore the socioeconomic legacy of stroke and include clear definitions of work and accurate measures of working hours and income from all sources

Descriptions of memory rehabilitation group interventions for neurological conditions: a systematic review

Objective: To establish what aspects of group-based cognitive rehabilitation for memory problems are reported, and to develop a checklist for authors, which may to improve reporting of these interventions in future studies. Data sources: A systematic search was conducted on Web of Knowledge, CINAHL, MEDLINE, AMED, EMBASE and PsycINFO electronic databases (last search: 01/05/2015). Review methods: Articles were included if the sample were adults with a neurological disorder, the intervention was group-based cognitive rehabilitation for memory problems, and if the study was a randomised controlled trial. Articles were independently screened for inclusion and data extracted by two researchers, with the third researcher arbitrating any disputes. Results: Fourteen studies were included in this review. The reporting of certain aspects of an intervention was found to be poor, particularly in relation to: duration of the programme (6 of 14 studies did not report), the development of the intervention (7 of 14 studies did not discuss), and the content and structure of intervention (7 of the 14 studies did not provide details). Conclusion: This review found that the overall reporting of memory rehabilitation content and format is poor. Refinement and adaption of pre-existing checklists to capture aspects of cognitive rehabilitation programmes may help authors when reporting complex interventions. A draft checklist is provided that could be refined and validated in further research

A BMPR2/YY1 Signaling Axis Is Required for Human Cytomegalovirus Latency in Undifferentiated Myeloid Cells.

Human cytomegalovirus (HCMV) presents a major health burden in the immunocompromised and in stem cell transplant medicine. A lack of understanding about the mechanisms of HCMV latency in undifferentiated CD34+ stem cells, and how latency is broken for the virus to enter the lytic phase of its infective cycle, has hampered the development of essential therapeutics. Using a human induced pluripotent stem cell (iPSC) model of HCMV latency and patient-derived myeloid cell progenitors, we demonstrate that bone morphogenetic protein receptor type 2 (BMPR2) is necessary for HCMV latency. In addition, we define a crucial role for the transcription factor Yin Yang 1 (YY1) in HCMV latency; high levels of YY1 are maintained in latently infected cells as a result of BMPR2 signaling through the SMAD4/SMAD6 axis. Activation of SMAD4/6, through BMPR2, inhibits TGFbeta receptor signaling, which leads to the degradation of YY1 via induction of a cellular microRNA (miRNA), hsa-miR-29a. Pharmacological targeting of BMPR2 in progenitor cells results in the degradation of YY1 and an inability to maintain latency and renders cells susceptible to T cell killing. These data argue that BMPR2 plays a role in HCMV latency and is a new potential therapeutic target for maintaining or disrupting HCMV latency in myeloid progenitors. IMPORTANCE Understanding the mechanisms which regulate HCMV latency could allow therapeutic targeting of the latent virus reservoir from where virus reactivation can cause severe disease. We show that the BMPR2/TGFbeta receptor/YY1 signaling axis is crucial to maintain HCMV latency in undifferentiated cells and that pharmacological reduction of BMPR2 in latently infected cells leads to reactivation of the viral lytic transcription program, which renders the infected cell open to immune detection and clearance in infected individuals. Therefore, this work identifies key host-virus interactions which regulate HCMV latent infection. It also demonstrates a potential new therapeutic approach to reduce HCMV reactivation-mediated disease by the treatment of donor stem cells/organs prior to transplantation, which could have a major impact in the transplant disease setting

Craft, Community and the Material Culture of Place and Politics, 19th–20th Century

Book Review: Craft, Community and the Material Culture of Place and Politics, 19th-20th century Edited by Janice Helland, Beverley Lemire and Alena Buis Ashgate, February 2014; 245pp. 46 b&w illustrations; hardback £60.00 ISBN: 978-1-4094-6207-

Vertical Structure and Color of Jovian Latitudinal Cloud Bands during the Juno Era

The identity of the coloring agent(s) in Jupiter's atmosphere and the exact structure of Jupiter's uppermost cloud deck are yet to be conclusively understood. The Cr\`{e}me Br\^ul\'ee model of Jupiter's tropospheric clouds, originally proposed by Baines et al. (2014) and expanded upon by Sromovsky et al. (2017) and Baines et al. (2019), presumes that the chromophore measured by Carlson et al. (2016) is the singular coloring agent in Jupiter's troposphere. In this work, we test the validity of the Cr\`{e}me Br\^ul\'ee model of Jupiter's uppermost cloud deck using spectra measured during the Juno spacecraft's 5$^{\mathrm{th}}$ perijove pass in March 2017. These data were obtained as part of an international ground-based observing campaign in support of the Juno mission using the NMSU Acousto-optic Imaging Camera (NAIC) at the 3.5-m telescope at Apache Point Observatory in Sunspot, NM. We find that the Cr\`{e}me Br\^ul\'ee model cloud layering scheme can reproduce Jupiter's visible spectrum both with the Carlson et al. (2016) chromophore and with modifications to its imaginary index of refraction spectrum. While the Cr\`{e}me Br\^ul\'ee model provides reasonable results for regions of Jupiter's cloud bands such as the North Equatorial Belt and Equatorial Zone, we find that it is not a safe assumption for unique weather events, such as the 2016-2017 Southern Equatorial Belt outbreak that was captured by our measurements.Comment: 38 pages, 21 figures; Accepted for publication in AAS Planetary Science Journa

Interferon-Responsive Genes Are Targeted during the Establishment of Human Cytomegalovirus Latency.

Human cytomegalovirus (HCMV) latency is an active process which remodels the latently infected cell to optimize latent carriage and reactivation. This is achieved, in part, through the expression of viral genes, including the G-protein-coupled receptor US28. Here, we use an unbiased proteomic screen to assess changes in host proteins induced by US28, revealing that interferon-inducible genes are downregulated by US28. We validate that major histocompatibility complex (MHC) class II and two pyrin and HIN domain (PYHIN) proteins, myeloid cell nuclear differentiation antigen (MNDA) and IFI16, are downregulated during experimental latency in primary human CD14+ monocytes. We find that IFI16 is targeted rapidly during the establishment of latency in a US28-dependent manner but only in undifferentiated myeloid cells, a natural site of latent carriage. Finally, by overexpressing IFI16, we show that IFI16 can activate the viral major immediate early promoter and immediate early gene expression during latency via NF-κB, a function which explains why downregulation of IFI16 during latency is advantageous for the virus.IMPORTANCE Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus which infects 50 to 100% of humans worldwide. HCMV causes a lifelong subclinical infection in immunocompetent individuals but is a serious cause of mortality and morbidity in the immunocompromised and neonates. In particular, reactivation of HCMV in the transplant setting is a major cause of transplant failure and related disease. Therefore, a molecular understanding of HCMV latency and reactivation could provide insights into potential ways to target the latent viral reservoir in at-risk patient populations

A meta-synthesis of qualitative research on perceptions of people with long-term neurological conditions about group-based memory rehabilitation

The effectiveness of memory rehabilitation based on randomised controlled trials and meta-analyses has been inconclusive, but patient reports based on qualitative studies have been largely positive. We conducted a meta-synthesis of qualitative studies of group-based memory rehabilitation programmes for people with neurological conditions. Based on systematic searches of electronic databases and reference lists, five papers (87 participants) were selected. Quality appraisal of papers was conducted by two independent reviewers using the Critical Appraisal Skills Programme tool. Data synthesis was guided by the meta-ethnography approach. Fiver higher order themes were elicited. These suggested that memory rehabilitation was associated with insight and acceptance of participants’ neurological condition and resultant cognitive deficits. The therapeutic effects of the groups, with social support and leisure activities, helped with participants’ confidence. There were improvements in memory related to better self-awareness and learning to use new skills and strategies to compensate for memory deficits. These improvements also related to other psychological effects, in terms of positively affected mood, confidence and fatigue. Ultimately, these changes had a positive impact on daily life, with changes seen in the personal, inter-personal and professional spheres. Therefore, this synthesis of qualitative studies suggests that memory rehabilitation offers positive outcomes for people with long-term neurological conditions

Canagliflozin impairs T cell effector function via metabolic suppression in autoimmunity

Augmented T cell function leading to host damage in autoimmunity is supported by metabolic dysregulation, making targeting immunometabolism an attractive therapeutic avenue. Canagliflozin, a type 2 diabetes drug, is a sodium glucose co-transporter 2 (SGLT2) inhibitor with known off-target effects on glutamate dehydrogenase and complex I. However, the effects of SGLT2 inhibitors on human T cell function have not been extensively explored. Here, we show that canagliflozin-treated T cells are compromised in their ability to activate, proliferate, and initiate effector functions. Canagliflozin inhibits T cell receptor signaling, impacting on ERK and mTORC1 activity, concomitantly associated with reduced c-Myc. Compromised c-Myc levels were encapsulated by a failure to engage translational machinery resulting in impaired metabolic protein and solute carrier production among others. Importantly, canagliflozin-treated T cells derived from patients with autoimmune disorders impaired their effector function. Taken together, our work highlights a potential therapeutic avenue for repurposing canagliflozin as an intervention for T cell-mediated autoimmunity