148 research outputs found

    Bariatric Surgery–Induced Cardiac and Lipidomic Changes in Obesity‐Related Heart Failure with Preserved Ejection Fraction

    Get PDF
    Objective To determine the effects of gastric bypass on myocardial lipid deposition and function and the plasma lipidome in women with obesity and heart failure with preserved ejection fraction (HFpEF). Methods A primary cohort (N = 12) with HFpEF and obesity underwent echocardiography and magnetic resonance spectroscopy both before and 3 months and 6 months after bariatric surgery. Plasma lipidomic analysis was performed before surgery and 3 months after surgery in the primary cohort and were confirmed in a validation cohort (N = 22). Results After surgery‐induced weight loss, Minnesota Living with Heart Failure questionnaire scores, cardiac mass, and liver fat decreased (P < 0.02, P < 0.001, and P = 0.007, respectively); echo‐derived e′ increased (P = 0.03), but cardiac fat was unchanged. Although weight loss was associated with decreases in many plasma ceramide and sphingolipid species, plasma lipid and cardiac function changes did not correlate. Conclusions Surgery‐induced weight loss in women with HFpEF and obesity was associated with improved symptoms, reverse cardiac remodeling, and improved relaxation. Although weight loss was associated with plasma sphingolipidome changes, cardiac function improvement was not associated with lipidomic or myocardial triglyceride changes. The results of this study suggest that gastric bypass ameliorates obesity‐related HFpEF and that cardiac fat deposition and lipidomic changes may not be critical to its pathogenesis

    Using Australia’s National Data Linkage Demonstration Project (NDLDP) to improve cardiac care: Towards a national, whole-of-population linked data resource for evidence-informed health policy

    Get PDF
    Introduction In Australia, the Commonwealth, State and Territory governments are each responsible for specific aspects of health care. Historically, cross-jurisdictional health data have not been linked routinely, resulting in significant blind spots in our understanding of the interplay between hospital and primary care, a major impediment to evidence-informed health policy. Objectives and Approach In December 2016, the Australian Health Ministers’ Advisory Council approved the NDLDP, to establish the value of national linked data to inform health planning and policy. The Australian Institute of Health and Welfare (AIHW) linked five years of hospital, emergency department, pharmaceutical dispensing, medical services claims and mortality data for Australia’s two most populous states (New South Wales and Victoria). The Victorian Agency for Health Innovation (VAHI) is leading the ‘Delivering better cardiac outcomes: Primary, specialist and hospital care’ project to demonstrate the value of the collection in identifying evidence-practice gaps and driving change in cardiac care. Results The NDLDP combined data for over 10 million individuals with over 7 billion records of health transactions, utilising a new strategy for confidentialising dates to protect patient privacy. The NDLDP is governed by a Steering Committee; the AIHW is the data custodian approving outputs from analyses within a secure host environment. VAHI established a Project Steering Committee to oversee roll-out, governance and capacity building of the approved cardiac project. The VAHI project was instigated by evidence that best-practice pharmacological treatments for cardiac care are underutilised in Australia, but with no quantification of the population-level extent of this gap. The project quantified significant variations and underuse of post-discharge pharmacological care for patients admitted to hospital with key cardiac conditions, including atrial fibrillation and acute myocardial infarction. Conclusion/Implications This collaboration between government, clinical networks and academic researchers demonstrated this novel data linkage can enable evaluation of patient care pathways across both hospital and community-based services. These linked data resources provide essential information to investigate variation in care in Australia and improve care integration in cardiac care and beyond

    Stromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis

    Get PDF
    Age is a significant risk factor for the development of cancer. However, the mechanisms that drive age-related increases in cancer remain poorly understood. To determine if senescent stromal cells influence tumorigenesis, we develop a mouse model that mimics the aged skin microenvironment. Using this model, here we find that senescent stromal cells are sufficient to drive localized increases in suppressive myeloid cells that contributed to tumour promotion. Further, we find that the stromal-derived senescence-associated secretory phenotype factor interleukin-6 orchestrates both increases in suppressive myeloid cells and their ability to inhibit anti-tumour T-cell responses. Significantly, in aged, cancer-free individuals, we find similar increases in immune cells that also localize near senescent stromal cells. This work provides evidence that the accumulation of senescent stromal cells is sufficient to establish a tumour-permissive, chronic inflammatory microenvironment that can shelter incipient tumour cells, thus allowing them to proliferate and progress unabated by the immune system

    Investigating the role of microbes in mineral weathering: Nanometre-scale characterisation of the cell-mineral interface using FIB and TEM

    No full text
    Focused ion beam (FIB) sample preparation in combination with subsequent transmission electron microscopy (TEM) analysis are powerful tools for nanometre-scale examination of the cell-mineral interface in bio-geological samples. In this study, we used FIB-TEM to investigate the interaction between a cyanobacterium (Hassallia byssoidea) and a common sheet silicate mineral (biotite) following a laboratory-based bioweathering, incubation experiment. We discuss the FIB preparation of cross-sections of the cell mineral interface for TEM investigation. We also establish an electron fluence threshold (at 200. keV) in biotite for the transition from scanning (S)TEM electron beam induced contamination build up on the surface of biotite thin sections to mass loss, or hole-drilling within the sections. Working below this threshold fluence nanometre-scale structural and elemental information has been obtained from biotite directly underneath cyanobacterial cells incubated on the biotite for 3 months. No physical alteration of the biotite was detected by TEM imaging and diffraction with little or no elemental alteration detected by STEM-energy dispersive X-ray (EDX) elemental line-scanning or by energy filtered TEM (EF-TEM) jump ratio elemental mapping. As such we present evidence that the cyanobacterial strain of H. byssoidea did not cause any measurable alteration of biotite, within the resolution limits of the analysis techniques used, after 3 months of incubation on its surface

    Hippocampal pyramidal cells: the reemergence of cortical lamination

    Get PDF
    The increasing resolution of tract-tracing studies has led to the definition of segments along the transverse axis of the hippocampal pyramidal cell layer, which may represent functionally defined elements. This review will summarize evidence for a morphological and functional differentiation of pyramidal cells along the radial (deep to superficial) axis of the cell layer. In many species, deep and superficial sublayers can be identified histologically throughout large parts of the septotemporal extent of the hippocampus. Neurons in these sublayers are generated during different periods of development. During development, deep and superficial cells express genes (Sox5, SatB2) that also specify the phenotypes of superficial and deep cells in the neocortex. Deep and superficial cells differ neurochemically (e.g. calbindin and zinc) and in their adult gene expression patterns. These markers also distinguish sublayers in the septal hippocampus, where they are not readily apparent histologically in rat or mouse. Deep and superficial pyramidal cells differ in septal, striatal, and neocortical efferent connections. Distributions of deep and superficial pyramidal cell dendrites and studies in reeler or sparsely GFP-expressing mice indicate that this also applies to afferent pathways. Histological, neurochemical, and connective differences between deep and superficial neurons may correlate with (patho-) physiological phenomena specific to pyramidal cells at different radial locations. We feel that an appreciation of radial subdivisions in the pyramidal cell layer reminiscent of lamination in other cortical areas may be critical in the interpretation of studies of hippocampal anatomy and function

    Family Communication in Inherited Cardiovascular Conditions in Ireland

    Get PDF
    Over 100,000 individuals living in Ireland carry a mutated gene for an inherited cardiac condition (ICC), most of which demonstrate an autosomal dominant pattern of inheritance. First-degree relatives of individuals with these mutations are at a 50 % risk of being a carrier: disclosing genetic information to family members can be complex. This study explored how families living in Ireland communicate genetic information about ICCs and looked at the challenges of communicating information, factors that may affect communication and what influence this had on family relationships. Face to face interviews were conducted with nine participants using an approved topic guide and results analysed using thematic analysis. The participants disclosed that responsibility to future generations, gender, proximity and lack of contact all played a role in family communication. The media was cited as a source of information about genetic information and knowledge of genetic information tended to have a positive effect on families. Results from this study indicate that individuals are willing to inform family members, particularly when there are children and grandchildren at risk, and different strategies are utilised. Furthermore, understanding of genetics is partially regulated not only by their families, but by the way society handles information. Therefore, genetic health professionals should take into account the familial influence on individuals and their decision to attend genetic services, and also that of the media.postprin

    STYLE AS EXEMPLIFICATIONAL ASPECT OF DISCOURSE

    Get PDF
    Goodmanova semiotika i teorija stila znatno utječu na suvremena promišljanja pojma stil i određivanja nadležnosti literarne stilistike, naročito u Francuskoj. Ključnim se u tome kontekstu pokazuje Goodmanov koncept egzemplifikacije kao specifične referencijalne funkcije. U ovome radu donosi se kritički pregled Goodmanovih teza i njegovih nastavljača, posebice G. Genettea.Goodman\u27s semiotics and the theory of style are highly influental in contemporary conteptualizations of style and in defining the scope of literary stylistics, particulary in France. The key concept in that context is exemplification – a specific referential function. This paper presents a critical summary of Nelson Goodman\u27s hypotheses as well as his successors\u27, namely Gérard Genette
    corecore