[Avian cytogenetics goes functional] Third report on chicken genes and chromosomes 2015

High-density gridded libraries of large-insert clones using bacterial artificial chromosome (BAC) and other vectors are essential tools for genetic and genomic research in chicken and other avian species... Taken together, these studies demonstrate that applications of large-insert clones and BAC libraries derived from birds are, and will continue to be, effective tools to aid high-throughput and state-of-the-art genomic efforts and the important biological insight that arises from them

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer’s disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer’s disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer’s disease and other tau-mediated neurodegenerative diseases

Inflammatory biomarkers in Alzheimer's disease plasma

Introduction:Plasma biomarkers for Alzheimer’s disease (AD) diagnosis/stratification are a“Holy Grail” of AD research and intensively sought; however, there are no well-established plasmamarkers.Methods:A hypothesis-led plasma biomarker search was conducted in the context of internationalmulticenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL;259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.Results:Ten analytes showed significant intergroup differences. Logistic regression identified five(FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD andCTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI(AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Twoanalytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).Discussion:Plasma markers of inflammation and complement dysregulation support diagnosis andoutcome prediction in AD and MCI. Further replication is needed before clinical translatio

Percutaneous revascularization for ischemic left ventricular dysfunction: Cost-effectiveness analysis of the REVIVED-BCIS2 trial

BACKGROUND: Percutaneous coronary intervention (PCI) is frequently undertaken in patients with ischemic left ventricular systolic dysfunction. The REVIVED (Revascularization for Ischemic Ventricular Dysfunction)-BCIS2 (British Cardiovascular Society-2) trial concluded that PCI did not reduce the incidence of all-cause death or heart failure hospitalization; however, patients assigned to PCI reported better initial health-related quality of life than those assigned to optimal medical therapy (OMT) alone. The aim of this study was to assess the cost-effectiveness of PCI+OMT compared with OMT alone. METHODS: REVIVED-BCIS2 was a prospective, multicenter UK trial, which randomized patients with severe ischemic left ventricular systolic dysfunction to either PCI+OMT or OMT alone. Health care resource use (including planned and unplanned revascularizations, medication, device implantation, and heart failure hospitalizations) and health outcomes data (EuroQol 5-dimension 5-level questionnaire) on each patient were collected at baseline and up to 8 years post-randomization. Resource use was costed using publicly available national unit costs. Within the trial, mean total costs and quality-adjusted life-years (QALYs) were estimated from the perspective of the UK health system. Cost-effectiveness was evaluated using estimated mean costs and QALYs in both groups. Regression analysis was used to adjust for clinically relevant predictors. RESULTS: Between 2013 and 2020, 700 patients were recruited (mean age: PCI+OMT=70 years, OMT=68 years; male (%): PCI+OMT=87, OMT=88); median follow-up was 3.4 years. Over all follow-ups, patients undergoing PCI yielded similar health benefits at higher costs compared with OMT alone (PCI+OMT: 4.14 QALYs, £22 352; OMT alone: 4.16 QALYs, £15 569; difference: −0.015, £6782). For both groups, most health resource consumption occurred in the first 2 years post-randomization. Probabilistic results showed that the probability of PCI being cost-effective was 0. CONCLUSIONS: A minimal difference in total QALYs was identified between arms, and PCI+OMT was not cost-effective compared with OMT, given its additional cost. A strategy of routine PCI to treat ischemic left ventricular systolic dysfunction does not seem to be a justifiable use of health care resources in the United Kingdom

Arrhythmia and death following percutaneous revascularization in ischemic left ventricular dysfunction: Prespecified analyses from the REVIVED-BCIS2 trial

BACKGROUND: Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or percutaneous coronary intervention is often recommended for these patients before implantation of a cardiac defibrillator because it is assumed that this may reduce the incidence of fatal and potentially fatal ventricular arrhythmias, although this premise has not been evaluated in a randomized trial to date. METHODS: Patients with severe left ventricular dysfunction, extensive coronary disease, and viable myocardium were randomly assigned to receive either percutaneous coronary intervention (PCI) plus optimal medical and device therapy (OMT) or OMT alone. The composite primary outcome was all-cause death or aborted sudden death (defined as an appropriate implantable cardioverter defibrillator therapy or a resuscitated cardiac arrest) at a minimum of 24 months, analyzed as time to first event on an intention-to-treat basis. Secondary outcomes included cardiovascular death or aborted sudden death, appropriate implantable cardioverter defibrillator (ICD) therapy or sustained ventricular arrhythmia, and number of appropriate ICD therapies. RESULTS: Between August 28, 2013, and March 19, 2020, 700 patients were enrolled across 40 centers in the United Kingdom. A total of 347 patients were assigned to the PCI+OMT group and 353 to the OMT alone group. The mean age of participants was 69 years; 88% were male; 56% had hypertension; 41% had diabetes; and 53% had a clinical history of myocardial infarction. The median left ventricular ejection fraction was 28%; 53.1% had an implantable defibrillator inserted before randomization or during follow-up. All-cause death or aborted sudden death occurred in 144 patients (41.6%) in the PCI group and 142 patients (40.2%) in the OMT group (hazard ratio, 1.03 [95% CI, 0.82–1.30]; P =0.80). There was no between-group difference in the occurrence of any of the secondary outcomes. CONCLUSIONS: PCI was not associated with a reduction in all-cause mortality or aborted sudden death. In patients with ischemic cardiomyopathy, PCI is not beneficial solely for the purpose of reducing potentially fatal ventricular arrhythmias. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01920048

Applying Intersectionality & Complexity Theory to Address the Social Determinants of Women's Health

It is now well recognized that the compounding effects of lack of access to education create far reaching implications for income, access to the goods and services of society, and women’s physical and psychological health. A social determinants of health (SDH) perspective takes aim at the structural causes-of-the-causes of social and material deprivation that lead to ill health. This paper builds on previous work (McGibbon & Etowa, 2007; McGibbon, 2009; McPherson & McGibbon, 2010) to describe how feminist intersectionality theory can be applied in tandem with complexity theory to support the amelioration of inequities in the social determinants of women’s health. We explore the ways that this bridging can further our understanding of social and economic marginalization of women. A brief overview of feminist intersectionality theory is presented, with an emphasis on its utility for extending an analysis of intersections of the SDH. We hope to stimulate a debate about how feminist intersectionality theory, feminist political economy, and complexity theory are natural antecedents to inform public policy to address SDH inequities in women’s health. A case example grounds our theoretical discussion in the everyday pointy edges of how material deprivation unfolds in women’s everyday lived experience

Stress, Oppression & Women’s Mental Health: A Discussion of the Health Consequences of Injustice

Oppression results in persistent and intersecting impacts on women’s health, including their spiritual, psychological and biophysical health. Although the concepts of oppression and stress have been discussed extensively in the literature, there is relatively little discussion of the complex interplay among the body’s biophysical stress handling systems and the everyday impacts of oppression. This article focuses on the root causes of women’s mental health struggles, with emphasis on the nature and impacts of intersecting oppressions and the social determinants of health. Violence against women is highlighted as a key foundation for women’s stress across the lifecourse. Oppression has a profound and long-lasting impact on the body’s stress handling system. These pathways are detailed with a focus on mental health and biophysical health consequences of oppression. The article concludes with a discussion of the new drivers of medicalization, and psychiatrization in particular, in the context of oppression and women’s mental health

IMMIGRANT YOUTH IN CANADIAN HEALTH PROMOTING SCHOOLS: A LITERATURE REVIEW

In this essay, we review empirical, theoretical, and substantial grey literature in relation to immigrant youth and health promoting schools (HPS). We examine the health promotion concept to consider how it may inform the HPS model. Using Canada as an example, we examine current immigrant youth demographics and define several key terms including immigrant, youth, and health. Our review highlights important knowledge gaps related to the role of education and migration as antecedents to immigrant youth health and wellbeing as well as qualitative and educational research approaches. We conclude by providing recommendations for future immigrant youth research in the context of HPS.Cet article explore la documentation empirique, théorique ainsi que la littérature grise traitant des jeunes immigrants et des écoles axées sur la promotion de la santé. Nous y faisons l’examen du concept de promotion de la santé et la manière dont celui-ci peut façonner le contexte de ces écoles. En utilisant le Canada comme exemple, nous examinons les tendances démographiques actuelles chez la jeunesse immigrante. Nous définissons également plusieurs termes-clés tels qu’immigrant, jeunesse et santé. Notre étude met en lumière d’importants fossés cognitifs en lien avec le rôle de l’éducation et la migration comme préalables à la santé et au bien-être des jeunes immigrants. Celle-ci aborde aussi des approches qualitatives et éducationnelles. Nous terminons en formulant des suggestions de pistes de recherches concernant la recherche sur les jeunes immigrants dans le contexte des écoles axées sur la promotion de la santé