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Indianapolis, IN, United States

Dobscha S.K.,Portland Center for the Study of Chronic | Dobscha S.K.,Oregon Health And Science University | Corson K.,Portland Center for the Study of Chronic | Corson K.,Oregon Health And Science University | And 9 more authors.
General Hospital Psychiatry | Year: 2013

Objectives: We describe processes, rates, and patient and system correlates of brief structured assessments (BSAs) for suicidal ideation among Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans with positive depression screens. Methods: Electronic Veterans Affairs (VA) medical record and Department of Defense data were used to identify individual-level and BSA-process variables for 1662 OEF/OIF veterans at three VA Medical Centers. Results: Overall, 1349/1662 (81%) veterans received BSAs for suicidal ideation within 1 month of depression screening; 94% of BSAs were conducted within 1 day. Stratified analyses revealed significant intersite differences in veteran demographics, instruments used, clinical setting and staff performing assessments, and correlates of assessment completion. At two sites, men were more likely to be assessed than women [odds ratio (OR)=2.15 (95% confidence interval {CI}=1.06-4.38) and 3.14 (CI=1.27-7.76)]. In a combined model adjusted for intrasite correlation, assessment was less likely during months 8-12 and 13-18 of the study period [OR=0.39 (CI=0.28-0.54) and OR=0.48 (95% CI=0.35-0.68), respectively] and more likely to occur among veterans receiving depression or posttraumatic stress disorder diagnoses on the day of depression screening [OR=1.83 (CI=1.36-2.46) and OR=1.50 (CI=1.13-1.98), respectively]. Conclusions: Most veterans with positive depression screens receive timely BSAs for suicidal ideation. Processes used for brief assessment for suicidal ideation vary substantially across VA settings. © 2013. Source

Kamocki K.,Indianapolis | Van Demark M.,Indianapolis | Fisher A.,Indianapolis | Rush N.I.,Indianapolis | And 9 more authors.
American Journal of Respiratory Cell and Molecular Biology | Year: 2013

Key host responses to the stress induced by environmental exposure to cigarette smoke (CS) are responsible for initiating pathogenic effects thatmay culminate in emphysema development. CS increases lung ceramides, sphingolipids involved in oxidative stress, structural alveolar cell apoptosis, and inhibition of apoptotic cell clearance by alveolar macrophages, leading to the development of emphysemalike pathology. RTP801, a hypoxia and oxidative stress sensor, is also increased by CS, and has been recently implicated in both apoptosis and inflammation. We investigated whether inductions of ceramide and RTP801 are mechanistically linked, and evaluated their relative importance in lung cell apoptosis and airspace enlargement in vivo. As reported, direct lung instillation of either RTP801 expression plasmid or ceramides in mice triggered alveolar cell apoptosis and oxidative stress. RTP801 overexpression up-regulated lung ceramide levels 2.6-fold. In turn, instillation of lung ceramides doubled the lung content of RTP801. Cell sorting after lung tissue dissociation into single-cell suspension showed that ceramide triggers both endothelial and epithelial cell apoptosis in vivo. Interestingly, mice lacking rtp801 were protected against ceramide-induced apoptosis of epithelial type II cells, but not type I or endothelial cells. Furthermore, rtp801-null mice were protected from ceramide-induced alveolar enlargement, and exhibited improved static lung compliance compared with wild-type mice. In conclusion, ceramide and RTP801 participate in alveolar cell apoptosis through a process of mutual up-regulation, which may result in self-amplification loops, leading to alveolar damage. Copyright © 2013 by the American Thoracic Society. Source

Lockett A.D.,Indiana University | Brown M.B.,Indiana University | Santos-Falcon N.,University of Miami | Rush N.I.,Indiana University | And 11 more authors.
PLoS ONE | Year: 2014

The homeostatic lung protective effects of alpha-1 antitrypsin (A1AT) may require the transport of circulating proteinase inhibitor across an intact lung endothelial barrier. We hypothesized that uninjured pulmonary endothelial cells transport A1AT to lung epithelial cells. Purified human A1AT was rapidly taken up by confluent primary rat pulmonary endothelial cell monolayers, was secreted extracellularly, both apically and basolaterally, and was taken up by adjacent rat lung epithelial cells co-cultured on polarized transwells. Similarly, polarized primary human lung epithelial cells took up basolaterally-, but not apically-supplied A1AT, followed by apical secretion. Evidence of A1AT transcytosis across lung microcirculation was confirmed in vivo by two-photon intravital microscopy in mice. Time-lapse confocal microscopy indicated that A1AT colocalized with Golgi in the endothelium whilst inhibition of the classical secretory pathway with tunicamycin significantly increased intracellular retention of A1AT. However, inhibition of Golgi secretion promoted non-classical A1AT secretion, associated with microparticle release. Polymerized A1AT or A1AT supplied to endothelial cells exposed to soluble cigarette smoke extract had decreased transcytosis. These results suggest previously unappreciated pathways of A1AT bidirectional uptake and secretion from lung endothelial cells towards the alveolar epithelium and airspaces. A1AT trafficking may determine its functional bioavailablity in the lung, which could be impaired in individuals exposed to smoking or in those with A1AT deficiency. Source

Pressler S.J.,University of Michigan | Subramanian U.,Indiana University | Subramanian U.,Richard udebush Veteran Affairs Medical Center | Kareken D.,Indiana University | And 8 more authors.
Journal of Cardiovascular Nursing | Year: 2010

BACKGROUND: Patients with chronic heart failure (HF) have cognitive deficits in memory, psychomotor speed, and executive function and poor health-related quality of life (HRQL), but the association between cognitive deficits and HRQL is unknown. OBJECTIVES: The objectives of this study were to (1) evaluate the relationship between HF severity, age, comorbidities, and cognitive deficits and HRQL among patients with chronic HF and (2) examine whether cognitive deficits mediated the relationship between HF severity and HRQL. DESIGN AND SAMPLE: This study was part of a larger explanatory study; 249 patients with HF completed face-to-face interviews. METHODS: Measures of HF severity, comorbidity (multiple comorbid conditions, hypertension, and depressive symptoms), cognitive function (domains of language, working memory, memory, psychomotor speed, and executive function), and HRQL were obtained. Clinical variables were abstracted from patients' records. Statistical analyses were conducted using descriptive statistics, Pearson correlation coefficients, and multiple linear regression analyses. RESULTS: Overall, the HRQL of patients was moderately poor. Heart failure severity, age, depressive symptoms, and total recall memory explained 55% of the variance in HRQL, but the contribution of memory was minimal (1%). Patients with more severe HF, younger age, and more depressive symptoms had poorer HRQL. Other cognitive function variables, multiple comorbidity, and hypertension were not significant explanatory variables for HRQL. Cognitive deficits did not mediate the relationship between HF severity and HRQL. CONCLUSIONS: Novel interventions targeted at improving HRQL continue to be urgently needed, particularly among younger patients and patients with depressive symptoms. Measures of HRQL are not sufficient as outcomes when investigating cognitive deficits in HF. Investigators need to include outcome measures of patients' actual abilities to perform daily activities and HF self-care. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

McCaslin C.A.,Indiana University - Purdue University Indianapolis | Petrusca D.N.,Indiana University - Purdue University Indianapolis | Poirier C.,Indiana University - Purdue University Indianapolis | Serban K.A.,Indiana University - Purdue University Indianapolis | And 3 more authors.
Journal of Cystic Fibrosis | Year: 2015

Pseudomonas aeruginosa infection is a hallmark of lung disease in cystic fibrosis. Acute infection with P. aeruginosa profoundly inhibits alveolar macrophage clearance of apoptotic cells (efferocytosis) via direct effect of virulence factors. During chronic infection, P. aeruginosa evades host defense by decreased virulence, which includes the production or, in the case of mucoidy, overproduction of alginate. The impact of alginate on innate immunity, in particular on macrophage clearance of apoptotic cells is not known.We hypothesized that P. aeruginosa strains that exhibit reduced virulence impair macrophage clearance of apoptotic cells and we investigated if the polysaccharide alginate produced by mucoid P. aeruginosa is sufficient to inhibit alveolar macrophage efferocytosis.Rat alveolar or human peripheral blood monocyte (THP-1)-derived macrophage cell lines were exposed in vitro to exogenous alginate or to wild type or alginate-overproducing mucoid P. aeruginosa prior to challenge with apoptotic human Jurkat T-lymphocytes. The importance of LPS contamination and that of structural integrity of alginate polymers was tested using alginate of different purities and alginate lyase, respectively.Alginate inhibited alveolar macrophage efferocytosis in a dose- and time-dependent manner. This effect was augmented but not exclusively attributed to lipopolysaccharide (LPS) present in alginates. Alginate-producing P. aeruginosa inhibited macrophage efferocytosis by more than 50%. A mannuronic-specific alginate lyase did not restore efferocytosis inhibited by exogenous guluronic-rich marine alginate, but had a marked beneficial effect on efferocytosis of alveolar macrophages exposed to mucoid P. aeruginosa.Despite decreased virulence, mucoid P. aeruginosa may contribute to chronic airway inflammation through significant inhibition of alveolar clearance of apoptotic cells and debris. The mechanism by which mucoid bacteria inhibit efferocytosis may involve alginate production and synergy with LPS, suggesting that alginate lyase may be an attractive therapeutic approach to airway inflammation in cystic fibrosis and other chronic obstructive pulmonary diseases characterized by P. aeruginosa colonization. © 2014 European Cystic Fibrosis Society. Source

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