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Objectives(1) To identify operational issues encountered by study participants in using the ‘Care for Stroke’ intervention; (2) to evaluate the feasibility and acceptability of the intervention.DesignMixed-methods research design.SettingParticipant's home. Participants were selected from a tertiary hospital in Chennai, South India.ParticipantsSixty stroke survivors treated and discharged from the hospital, and their caregivers.Intervention‘Care for Stroke’ is a smartphone-enabled, educational intervention for management of physical disabilities following stroke. It is delivered through a web-based, smartphone-enabled application. It includes inputs from stroke rehabilitation experts in a digitised format.MethodsEvaluation of the intervention was completed in two phases. In the first phase, the preliminary intervention was field-tested with 30 stroke survivors for 2 weeks. In the second phase, the finalised intervention was provided to a further 30 stroke survivors to be used in their homes with support from their carers for 4 weeks.Primary and secondary outcome measuresPrimary outcomes: (1) operational difficulties in using the intervention; (2) feasibility and acceptability of the intervention in an Indian setting. Disability and dependency were assessed as secondary outcomes.ResultsField-testing identified operational difficulties related to connectivity, video-streaming, picture clarity, quality of videos, and functionality of the application. The intervention was reviewed, revised and finalised before pilot-testing. Findings from the pilot-testing showed that the ‘Care for Stroke’ intervention was feasible and acceptable. Over 90% (n=27) of the study participants felt that the intervention was relevant, comprehensible and useful. Over 96% (n=29) of the stroke survivors and all the caregivers (100%, n=30) rated the intervention as excellent and very useful. These findings were supported by qualitative interviews.ConclusionsEvaluation indicated that the ‘Care for Stroke’ intervention was feasible and acceptable in an Indian context. An assessment of effectiveness is now warranted.

Internal tandem duplications (ITDs) in the fms -like tyrosine kinase receptor (FLT3-ITDs) confer a poor prognosis in acute myeloid leukemia (AML). We hypothesized that increased recruitment of the protein tyrosine phosphatase, Shp2, to FLT3-ITDs contributes to FLT3 ligand (FL)-independent hyperproliferation and STAT5 activation. Co-immunoprecipitation demonstrated constitutive association of Shp2 with the FLT3-ITD, N51-FLT3, as well as with STAT5. Knockdown of Shp2 in Baf3/N51-FLT3 cells significantly reduced proliferation while having little effect on WT-FLT3-expressing cells. Consistently, mutation of N51-FLT3 tyrosine 599 to phenylalanine or genetic disruption of Shp2 in N51-FLT3-expressing bone marrow low-density mononuclear cells reduced proliferation and STAT5 activation. In transplants, genetic disruption of Shp2 in vivo yielded increased latency to and reduced severity of FLT3-ITD-induced malignancy. Mechanistically, Shp2 co-localizes with nuclear phospho-STAT5, is present at functional interferon-γ activation sites (GAS) within the BCL2L1 promoter, and positively activates the human BCL2L1 promoter, suggesting that Shp2 works with STAT5 to promote pro-leukemogenic gene expression. Further, using a small molecule Shp2 inhibitor, the proliferation of N51-FLT3-expressing bone marrow progenitors and primary AML samples was reduced in a dose-dependent manner. These findings demonstrate that Shp2 positively contributes to FLT3-ITD-induced leukemia and suggest that Shp2 inhibition may provide a novel therapeutic approach to AML.

The global pandemic of physical inactivity requires a multisectoral, multidisciplinary public-health response. Scaling up interventions that are capable of increasing levels of physical activity in populations across the varying cultural, geographic, social, and economic contexts worldwide is challenging, but feasible. In this paper, we review the factors that could help to achieve this. We use a mixed-methods approach to comprehensively examine these factors, drawing on the best available evidence from both evidence-to-practice and practice-to-evidence methods. Policies to support active living across society are needed, particularly outside the health-care sector, as demonstrated by some of the successful examples of scale up identified in this paper. Researchers, research funders, and practitioners and policymakers in culture, education, health, leisure, planning, and transport, and civil society as a whole, all have a role. We should embrace the challenge of taking action to a higher level, aligning physical activity and health objectives with broader social, environmental, and sustainable development goals.

Promotion of physical activity is a priority for health agencies. We searched for reviews of physical activity interventions, published between 2000 and 2011, and identified effective, promising, or emerging interventions from around the world. The informational approaches of community-wide and mass media campaigns, and short physical activity messages targeting key community sites are recommended. Behavioural and social approaches are effective, introducing social support for physical activity within communities and worksites, and school-based strategies that encompass physical education, classroom activities, after-school sports, and active transport. Recommended environmental and policy approaches include creation and improvement of access to places for physical activity with informational outreach activities, community-scale and street-scale urban design and land use, active transport policy and practices, and community-wide policies and planning. Thus, many approaches lead to acceptable increases in physical activity among people of various ages, and from different social groups, countries, and communities.

The way we design our cities can improve the health of populations. The Lancet Series on urban design, transport, and health 1-3 highlights how science-based contextualised city planning and transport can address key health, environmental, and economic burdens. Road traffic and transport injuries are a leading cause of preventable death among young people, 4 and 90% of these deaths occur in low-income and middle-income countries (LMICs). 5

Study designRandomized controlled trial.ObjectivesTo determine the effect of zoledronic acid on bone loss in people with acute spinal cord injury (SCI)SettingsSawai Man Singh Medical College, India.MethodsSixty patients with acute SCI were randomized to receive either standard treatment alone or standard treatment with zoledronic acid within 3 months after injury. Areal bone mineral density (aBMD) was measured at the hip using dual-energy X-ray absorptiometry (DXA) at baseline 3, 6, and 12 months.ResultsSignificant differences in aBMD were found between the standard treatment alone and standard treatment plus zoledronic acid group at the femoral neck (−0.13; 95% CI, −0.18 to −0.09, p < 0.0001), and total hip (−0.16; 95% CI, −0.19 to −0.12, p < 0.0001), respectively, at 1 year and bone loss was reduced in the zoledronic acid treated group as compared to the standard treatment group. Significant differences in aBMD between the groups at 6 months post infusion was also observed at these sites. [Femoral neck −0.08; 95% CI, −0.12 to −0.03; p = 0.002 and total hip −0.12; 95% CI, −0.15 to −0.08; p < 0.0001]ConclusionA zoledronic acid 5 mg infusion given within 3 month significantly reduces bone loss at the hip after 6 months post infusion in patients with acute SCI.

Inducible protection from apoptosis in vivo controls the size of cell populations. An important question in this respect is how differentiation affects mechanisms of apoptosis regulation. Among mature T lymphocytes, the NF- κ B/Rel transcription factors are coupled to receptors that control cell population sizes by concurrently regulating survival and multiplication. In the present study, we used a transgenic inhibitor of NF- κ B/Rel signaling to investigate the role of this pathway in proliferation and death of mature T cells in vivo . The results indicate that NF- κ B integrates two critical yet distinct molecular pathways preventing apoptosis affected by the death receptor Fas, coordinately regulating levels of FLIP and Bcl-x L in primary T cells. Surprisingly, NF- κ B blockade preferentially impacted naive as compared to memory T cells. The Fas/FasL pathway was linked to these findings by evidence that the abnormalities imposed by NF- κ B inhibition were ameliorated by Fas deficiency, particularly for the CD4 + lineage. Moreover, levels of an inhibitor of Fas-mediated apoptosis, c-FLIP, were diminished in cells expressing the transgenic inhibitor. NF- κ B was also linked to T cell survival in vivo by mediating induction of Bcl-x L : restoration of Bcl-x L levels reversed the preferential deficit of naive T cells, differentially impacting the CD4 and CD8 subsets. These results show that promoting survival and effective multiplication are central roles for NF- κ B in T lymphoid homeostasis in vivo , but this effect and its underlying mechanisms are influenced by the developmental state of the lymphocyte.

The molecular mechanisms by which transcription is selectively activated and precisely controlled by signal transducer and activator of transcription (Stat) factors represent a central issue in cytokine-mediated cellular responses. Stat6 mediates responses to IL-4 and antagonizes Statl activated by IFN-γ. We have discovered that Stat6 binds to collaborator of Stat6 (CoaSt6), a protein that lacks conventional coactivator motifs but contains three iterations of a domain found in the variant histone macroH2A. Although macroH2A participates in transcriptional silencing, the macro domains of CoaSt6 increased IL-4-induced gene expression. Moreover, CoaSt6 amplified Stat6-mediated but not IFN-γ-induced gene expression, providing evidence of a selective coregulator of Statmediated gene transcription.