Expansion of a novel population of NK cells with low ribosome expression in juvenile dermatomyositis

Juvenile dermatomyositis (JDM) is a pediatric autoimmune disease associated with characteristic rash and proximal muscle weakness. To gain insight into differential lymphocyte gene expression in JDM, peripheral blood mononuclear cells from 4 new-onset JDM patients and 4 healthy controls were sorted into highly enriched lymphocyte populations for RNAseq analysis. NK cells from JDM patients had substantially greater differentially expressed genes (273) than T (57) and B (33) cells. Upregulated genes were associated with the innate immune response and cell cycle, while downregulated genes were associated with decreased ribosomal RNA. Suppressed ribosomal RNA in JDM NK cells was validated by measuring transcription and phosphorylation levels. We confirmed a population of low ribosome expressing NK cells in healthy adults and children. This population of low ribosome NK cells was substantially expanded in 6 treatment-naïve JDM patients and was associated with decreased NK cell degranulation. The enrichment of this NK low ribosome population was completely abrogated in JDM patients with quiescent disease. Together, these data suggest NK cells are highly activated in new-onset JDM patients with an increased population of low ribosome expressing NK cells, which correlates with decreased NK cell function and resolved with control of active disease

Ischemic Time and Risk Factors Associated With The Incidence Of Cardiogenic Shock In Patients Presenting With ST Elevation Myocardial Infarction

Cardiogenic shock (CS) is the number one predictor of mortality in patients with ST-elevation myocardial infarction (STEMI). Emergent evaluation and treatment including revascularization when indicated is recommended upon arrival to hospital. There is variation in time to presentation and total ischemic time in this patient population. We sought to evaluate the impact of ischemic time on incidence of CS and variables which may influence its presentation

How Knowledge Transfer Impact Happens at the Farm Level: Insights from Advisers and Farmers in the Irish Agricultural Sector

Many studies show that interaction with agricultural advisory services impacts productivity and profitability on farms. However, less attention is paid to explaining how this impact is achieved. This paper explores the factors that determine the implementation of newly learned knowledge from advisory engagement to achieve an impact on farm level performance. Focusing on the Irish case, a series of semi-structured interviews from a purposive sample of advisers and farmers from the more profitable dairy sector were undertaken to analyse the key drivers of impact. Results show that a combination of group-based and individual activities based on relevant content focused on key management practices for grassland, breeding, and financial management were key to achieving impact. Furthermore, positive outcomes were dependent on a high degree of trust between the farmer and the organisation, between the farmer and the adviser, and between the farmer and their peers. The findings indicate that while some barriers remain for farmers to apply newly learned knowledge, those that do implement the practices report a positive impact. This has implications for knowledge transfer design which is timely given the focus on these activities in the upcoming Common Agricultural Policy 2023–2027

How Knowledge Transfer Impact Happens at the Farm Level: Insights from Advisers and Farmers in the Irish Agricultural Sector

Many studies show that interaction with agricultural advisory services impacts productivity and profitability on farms. However, less attention is paid to explaining how this impact is achieved. This paper explores the factors that determine the implementation of newly learned knowledge from advisory engagement to achieve an impact on farm level performance. Focusing on the Irish case, a series of semi-structured interviews from a purposive sample of advisers and farmers from the more profitable dairy sector were undertaken to analyse the key drivers of impact. Results show that a combination of group-based and individual activities based on relevant content focused on key management practices for grassland, breeding, and financial management were key to achieving impact. Furthermore, positive outcomes were dependent on a high degree of trust between the farmer and the organisation, between the farmer and the adviser, and between the farmer and their peers. The findings indicate that while some barriers remain for farmers to apply newly learned knowledge, those that do implement the practices report a positive impact. This has implications for knowledge transfer design which is timely given the focus on these activities in the upcoming Common Agricultural Policy 2023–2027

Glycemic control in insulin and non-insulin dependent diabetic patients with ST elevation predicts time to presentation

Worldwide, the annual number of people diagnosed with diabetes continues to increase. Classically, Diabetes Mellitus (DM) has been associated with silent or atypical initial symptoms and increased time to presentation in patients presenting with ST elevation myocardial infarction (STEMI) compared to non-DM patients. It is less clear whether the type of treatment or the adequacy of glycemic control impacts the time to presentation and type of symptoms. Therefore, we sought to evaluate the impact of poor glycemic control on these outcomes as measured by hemoglobin A1c

Challenges facing early career academic cardiologists

Early career academic cardiologists currently face unprecedented challenges that threaten a highly valued career path. A team consisting of early career professionals and senior leadership members of American College of Cardiology completed this white paper to inform the cardiovascular medicine profession regarding the plight of early career cardiologists and to suggest possible solutions. This paper includes: 1) definition of categories of early career academic cardiologists; 2) general challenges to all categories and specific challenges to each category; 3) obstacles as identified by a survey of current early career members of the American College of Cardiology; 4) major reasons for the failure of physician-scientists to receive funding from National Institute of Health/National Heart Lung and Blood Institute career development grants; 5) potential solutions; and 6) a call to action with specific recommendations

Inflammasome-Mediated IL-1β Production in Humans with Cystic Fibrosis

Inflammation and infection are major determinants of disease severity and consequently, the quality of life and outcome for patients with cystic fibrosis (CF). Interleukin-1 beta (IL-1β) is a key inflammatory mediator. Secretion of biologically active IL-1β involves inflammasome-mediated processing. Little is known about the contribution of IL-1β and the inflammasomes in CF inflammatory disease. This study examines inflammasome-mediated IL-1β production in CF bronchial epithelial cell lines and human patients with CF.Bronchial epithelial cell lines were found to produce negligible amounts of basal or stimulated IL-1β compared to hematopoeitic cells and they did not significantly upregulate caspase-1 activity upon inflammasome stimulation. In contrast, peripheral blood mononuclear cells (PBMCs) from both CF and healthy control subjects produced large amounts of IL-1β and strongly upregulated caspase-1 activity upon inflammasome stimulation. PBMCs from CF patients and controls displayed similar levels of caspase-1 activation and IL-1β production when stimulated with inflammasome activators. This IL-1β production was dependent on NF-κB activity and could be enhanced by priming with LPS. Finally, chemical inhibition of CFTR activity in control PBMCs and THP-1 cells did not significantly alter IL-1β or IL-8 production in response to P. aeruginosa.Hematopoeitic cells appear to be the predominant source of inflammasome-induced pro-inflammatory IL-1β in CF. PBMCs derived from CF subjects display preserved inflammasome activation and IL-1β secretion in response to the major CF pathogen Pseudomonas aeruginosa. However, our data do not support the hypothesis that increased IL-1β production in CF subjects is due to an intrinsic increase in NF-κB activity through loss of CFTR function

The prevention of psychopathology in African Americans: An epidemiologic perspective

Although improving the mental health status of African Americans is an important goal, it is not clear that this can be accomplished by increasing access to professional services. Many have argued that stressful social conditions are the major cause of mental disorder in blacks and thus, psychopathology can be prevented by eliminating racism, oppression and poor economic conditions. This review argues that while the notion of primary prevention with African Americans should be taken seriously, there is still a need for more and better epidemiologic research. Three bodies of knowledge relevant to black mental health are addressed: 1) the need for an epidemiologic knowledge base for prevention; 2) coping capacity and vulnerability to stress; 3) risk factor identification. Findings from a national survey of adult African Americans are presented as an example of risk factor identification for the purpose of specifying targets for preventive interventions. The paper concludes that before the prevention of psychopathology in black populations can be achieved, a number of measurement, theoretical and policy issues must be addressed. Specific directions for future research are outlined.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44304/1/10597_2004_Article_BF00752393.pd