Krishna M

References (3)

Title : Mixed methods implementation research of cognitive stimulation therapy (CST) for dementia in low and middle-income countries: study protocol for Brazil, India and Tanzania (CST-International) - Spector_2019_BMJ.Open_9_e030933
Author(s) : Spector A , Stoner CR , Chandra M , Vaitheswaran S , Du B , Comas-Herrera A , Dotchin C , Ferri C , Knapp M , Krishna M , Laks J , Michie S , Mograbi DC , Orrell MW , Paddick SM , Ks S , Rangawsamy T , Walker R
Ref : BMJ Open , 9 :e030933 , 2019
Abstract : INTRODUCTION: In low/middle-income countries (LMICs), the prevalence of people diagnosed with dementia is expected to increase substantially and treatment options are limited, with acetylcholinesterase inhibitors not used as frequently as in high-income countries (HICs). Cognitive stimulation therapy (CST) is a group-based, brief, non-pharmacological intervention for people with dementia that significantly improves cognition and quality of life in clinical trials and is cost-effective in HIC. However, its implementation in other countries is less researched. This protocol describes CST-International; an implementation research study of CST. The aim of this research is to develop, test, refine and disseminate implementation strategies for CST for people with mild to moderate dementia in three LMICs: Brazil (upper middle-income), India (lower middle-income) and Tanzania (low-income). METHODS AND ANALYSIS: Four overlapping phases: (1) exploration of barriers to implementation in each country using meetings with stakeholders, including clinicians, policymakers, people with dementia and their families; (2) development of implementation plans for each country; (3) evaluation of implementation plans using a study of CST in each country (n=50, total n=150). Outcomes will include adherence, attendance, acceptability and attrition, agreed parameters of success, outcomes (cognition, quality of life, activities of daily living) and cost/affordability; (4) refinement and dissemination of implementation strategies, enabling ongoing pathways to practice which address barriers and facilitators to implementation. ETHICS AND DISSEMINATION: Ethical approval has been granted for each country. There are no documented adverse effects associated with CST and data held will be in accordance with relevant legislation. Train the trainer models will be developed to increase CST provision in each country and policymakers/governmental bodies will be continually engaged with to aid successful implementation. Findings will be disseminated at conferences, in peer-reviewed articles and newsletters, in collaboration with Alzheimer's Disease International, and via ongoing engagement with key policymakers.
ESTHER : Spector_2019_BMJ.Open_9_e030933
PubMedSearch : Spector_2019_BMJ.Open_9_e030933
PubMedID: 31434784

Title : Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group - Packard_2000_N.Engl.J.Med_343_1148
Author(s) : Packard CJ , O'Reilly DS , Caslake MJ , McMahon AD , Ford I , Cooney J , Macphee CH , Suckling KE , Krishna M , Wilkinson FE , Rumley A , Lowe GD
Ref : N Engl J Med , 343 :1148 , 2000
Abstract : BACKGROUND: Chronic inflammation is believed to increase the risk of coronary events by making atherosclerotic plaques in coronary vessels prone to rupture. We examined blood constituents potentially affected by inflammation as predictors of risk in men with hypercholesterolemia who were enrolled in the West of Scotland Coronary Prevention Study, a trial that evaluated the value of pravastatin in the prevention of coronary events.
METHODS: A total of 580 men who had had a coronary event (nonfatal myocardial infarction, death from coronary heart disease, or a revascularization procedure) were each matched for age and smoking status with 2 control subjects (total, 1160) from the same cohort who had not had a coronary event. Lipoprotein-associated phospholipase A2, C-reactive protein, and fibrinogen levels, and the white-cell count were measured at base line, along with other traditional risk factors. The association of these variables with the risk of coronary events was tested in regression models and by dividing the range of values according to quintiles.
RESULTS: Levels of C-reactive protein, the white-cell count, and fibrinogen levels were strong predictors of the risk of coronary events; the risk in the highest quintile of the study cohort for each variable was approximately twice that in the lowest quintile. However, the association of these variables with risk was markedly attenuated when age, systolic blood pressure, and lipoprotein levels were included in multivariate models. Levels of lipoprotein-associated phospholipase A2 (platelet-activating factor acetylhydrolase), the expression of which is regulated by mediators of inflammation, had a strong, positive association with risk that was not confounded by other factors. It was associated with almost a doubling of the risk in the highest quintile as compared with the lowest quintile.
CONCLUSIONS: Inflammatory markers are predictors of the risk of coronary events, but their predictive ability is attenuated by associations with other coronary risk factors. Elevated levels of lipoprotein-associated phospholipase A2 appear to be a strong risk factor for coronary heart disease, a finding that has implications for atherogenesis and the assessment of risk.
ESTHER : Packard_2000_N.Engl.J.Med_343_1148
PubMedSearch : Packard_2000_N.Engl.J.Med_343_1148
PubMedID: 11036120
Gene_locus related to this paper: human-PLA2G7

Title : 9-O-Acetylation of sialomucins: a novel marker of murine CD4 T cells that is regulated during maturation and activation - Krishna_1997_J.Exp.Med_185_1997
Author(s) : Krishna M , Varki A
Ref : J Exp Med , 185 :1997 , 1997
Abstract : Terminal sialic acids on cell surface glycoconjugates can carry 9-O-acetyl esters. For technical reasons, it has previously been difficult to determine their precise distribution on different cell types. Using a recombinant soluble form of the Influenza C virus hemagglutinin-esterase as a probe for 9-O-acetylated sialic acids, we demonstrate here their preferential expression on the CD4 T cell lineage in normal B10.A mouse lymphoid organs. Of total thymocytes, 8-10% carry 9-O-acetylation; the great majority of these are the more mature PNA-, HSA-, and TCRhi medullary cells. While low levels of 9-O-acetylation are seen on some CD4/CD8 double positive (DP) and CD8 single positive (SP) cells, high levels are present primarily on 80- 85% of CD4 SP cells. Correlation with CD4 and CD8 levels suggests that 9-O-acetylation appears as an early differentiation marker as cells mature from the DP to the CD4 SP phenotype. This high degree of 9-O-acetylation is also present on 90-95% of peripheral spleen and lymph node CD4 T cells. In contrast, only a small minority of CD8 T cells and B cells show such levels of 9-O-acetylation. Among mature peripheral CD4 T lymphocytes, the highly O-acetylated cells are Mel 14(hi), CD44(lo), and CD45R(exon B)hi, features typical of naive cells. Digestions with trypsin and O-sialoglycoprotease (OSGPase) and ELISA studies of lipid extracts indicate that the 9-O-acetylated sialic acids on peripheral CD4 T cells are predominantly on O-linked mucintype glycoproteins and to a lesser degree, on sialylated glycolipids (gangliosides). In contrast, sialic acids on mucin type molecules of CD8 T cells are not O-acetylated; instead these molecules mask the recognition of O-acetylated gangliosides that seem to be present at similar levels as on CD4 cells. The 9-O-acetylated gangliosides on mouse T cells are not bound by CD60 antibodies, which recognize O-acetylated gangliosides in human T cells. Tethering 9-O-acetylated mucins with the Influenza C probe with or without secondary cross-linking did not cause activation of CD4 T cells. However, activation by other stimuli including TCR ligation is associated with a substantial decrease in surface 9-O-acetylation, primarily in the mucin glycoprotein component. Thus, 9-O-acetylation of sialic acids on cell surface mucins is a novel marker on CD4 T cells that appears on maturation and is modulated downwards upon activation.
ESTHER : Krishna_1997_J.Exp.Med_185_1997
PubMedSearch : Krishna_1997_J.Exp.Med_185_1997
PubMedID: 9166429