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

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

Percutaneous Coronary Intervention of Unprotected Left Main Coronary Artery in Cardiac Allograft Vasculopathy: A Case Series of Pediatric Patients

Cardiac allograft vasculopathy is a major cause of morbidity and mortality in orthotopic heart transplantation. The optimal management remains uncertain, especially in left main coronary artery lesions. With the limited data available in the literature, we present a review of three pediatric cases of cardiac allograft vasculopathy, involving the left main coronary artery, treated with percutaneous coronary intervention

Impact of hospital and sociodemographic factors on utilization of drug-eluting stents in 2011-2012 Medicare cohort

Objective: Insurance status is a predictor of drug-eluting stent (DES) usage. Our study sought to determine the effect of hospital and sociodemographic characteristics on utilization of DES in nationwide inpatient discharges with uniform insurance (Medicare). Methods: We linked data from the 2011 to 2012 Medicare discharges, 2011 Medicare hospital referral region (HRR) report (racial composition of each HRR), American Hospital Association (number of beds, rural/urban location, public/private status, and academic affiliation of hospitals), and American Community Survey 2011 (median income using zip code). We analyzed diagnosis-related group (DRG) codes 249 (bare metal stent without complications), 246, and 247 (DES with and without complications, respectively). Univariate and multivariable logistic regression was conducted to determine odds ratios (OR) for utilization of DES. Results: There were 322,002 discharges with DRG codes 246 (54,279), 247 (209,365), and 249 (58,358) in our database. Higher odds of DES usage was observed in Hispanic dominant HRR(s) (OR: 1.37, 95% confidence interval [CI]: 1.33-1.42, P < 0.001) compared to Caucasian dominant HRR(s). DES utilization was similar in African-American and Caucasian dominant HRR (s). Higher odds of DES use was observed in median household income groups ≥$20,001 (OR: 1.07, 95% CI: 1.01-1.13, P - 0.03). Lower DES usage was observed in hospitals with higher total stent volume (quartile 4 vs. quartile 1: OR: 0.66, 95% CI: 0.63-0.69, P < 0.001) and for-profit hospitals (OR: 0.88, 95% CI: 0.85-0.92, P < 0.001). Conclusions: Our study findings suggest that there are significant differences in DES utilization in a national cohort of individuals with uniform insurance

Post-mortem Findings in Huntington's Deep Brain Stimulation: A Moving Target Due to Atrophy

Background: Deep brain stimulation (DBS) has been shown to be effective for Parkinson&rsquo;s disease, essential tremor, and primary dystonia. However, mixed results have been reported in Huntington&rsquo;s disease (HD). Case Report: A single case of HD DBS was identified from the University of Florida DBS Brain Tissue Network. The clinical presentation, evolution, surgical planning, DBS parameters, clinical outcomes, and brain pathological changes are summarized. Discussion: This case of HD DBS revealed that chorea may improve and be sustained. Minimal histopathological changes were noted around the DBS leads. Severe atrophy due to HD likely changed the DBS lead position relative to the internal capsule.</p