Richard udebush Veteran Affairs Medical Center

Indianapolis, IN, United States

Richard udebush Veteran Affairs Medical Center

Indianapolis, IN, United States
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Ganzini L.,Portland Center for the Study of Chronic | Ganzini L.,Oregon Health And Science University | Denneson L.M.,Portland Center for the Study of Chronic | Denneson L.M.,Oregon Health And Science University | And 6 more authors.
Journal of General Internal Medicine | Year: 2013

BACKGROUND: To reduce suicides among Veterans, the Department of Veterans Affairs (VA) has designated suicide risk assessments for Veterans who screen positive for depression or post-traumatic stress disorder as a national performance goal. Many VA Medical Centers (VAMCs) are using brief suicidal ideation screens, administered in non-mental health ambulatory care settings, as the first step in the assessment process. OBJECTIVE: To explore Veterans' perceptions of the suicide screening and risk assessment process, the barriers and facilitators to disclosing suicidal thoughts, and perceptions of possible consequences of revealing suicidal thoughts. DESIGN: Investigators recorded one semi-structured interview with each Veteran. Transcripts were analyzed using a modified grounded theory approach. PARTICIPANTS: Thirty-four Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans who screened positive for suicidal ideation in non-mental health ambulatory care settings in 2009 and 2010. KEY RESULTS: Veterans accepted the need to assess suicide risk. They increasingly experienced attempts to suppress and avoid thoughts of suicide as burdensome and exhausting. Despite this, Veterans often failed to disclose severe and pervasive suicidal thoughts when screened because: (1) they considered suicidal thoughts as shameful and a sign of weakness; (2) they believed suicidal thoughts were private and not to be divulged to strangers; (3) they worried that disclosure would lead to unwanted hospitalization or medication recommendations; and (4) the templated computer reminder process was perceived as perfunctory and disrespectful. In contrast, admitting and discussing thoughts of suicide with a health provider who focused on building a relationship, demonstrated genuineness and empathy, offered information on the rationale for suicide risk assessment, and used straightforward and understandable language, all promoted trust that resulted in more honest disclosure of suicidal thoughts. CONCLUSION: In ambulatory care settings, both provider behaviors and system modifications may lead to more honest disclosure of suicidal thoughts. © 2013 Society of General Internal Medicine.

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.

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.

Denneson L.M.,Improve-in | Denneson L.M.,Oregon Health And Science University | Corson K.,Improve-in | Corson K.,Oregon Health And Science University | And 4 more authors.
Psychiatry Research | Year: 2014

We evaluated the impact of brief structured suicidal ideation (SI) assessments on mental health care among new-to-care Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) veterans. National datasets provided military, demographic, and clinical information. For all new-to-care OEF/OIF veterans administered depression screens (PHQ-2: Patient Health Questionnaire-2) and structured SI assessments in primary care or ambulatory mental health settings of three Veterans Affairs (VA) Medical Centers between April 2008 and September 2009 (N=465), generalized estimating equations were used to examine associations between SI and number of subsequent-year specialty mental health visits and antidepressant prescriptions. Approximately one-third of the veterans reported SI. In multivariate models, PTSD and anxiety diagnoses, severe depression symptoms, being married, and SI assessment by a mental health clinician were associated with more mental health visits in the subsequent year. Depression, PTSD, and anxiety diagnoses, and SI assessment by a mental health clinician were associated with receiving antidepressants. Presence of SI did not significantly affect subsequent year mental health utilization when adjusting for diagnostic and clinician variables, but inaugural visits involving mental health clinicians were consistently associated with subsequent mental health care. © 2014.

Petrusca D.N.,Indiana University | Van Demark M.,Indiana University | Gu Y.,Indiana University | Justice M.J.,Indiana University | And 4 more authors.
American Journal of Respiratory Cell and Molecular Biology | Year: 2014

Prolonged exposure to cigarette smoking is the main risk factor for emphysema, a component of chronic obstructive pulmonary diseases (COPDs) characterized by destruction of alveolar walls. Moreover, smoking is associated with pulmonary artery remodeling and pulmonary hypertension, even in the absence of COPD, through as yet unexplained mechanisms. In murine models, elevations of intraand paracellular ceramides in response to smoking have been implicated in the induction of lung endothelial cell apoptosis, but the role of ceramides in human cell counterparts is yet unknown. We modeled paracrine increases (outside-in) of palmitoyl ceramide (Cer16) in primary human lung microvascular cells. In naive cells, isolated from nonsmokers, Cer16 significantly reduced cellular proliferation and induced caspase-independent apoptosis via mitochondrial membrane depolarization, apoptosis-inducing factor translocation, and poly(ADP-ribose) polymerase cleavage. In these cells, caspase-3 was inhibited by ceramide-induced Akt phosphorylation, and by the induction of autophagic microtubule-associated protein-1 light-chain × lipidation. In contrast, cells isolated from smokers exhibited increased baseline proliferative features associated with lack of p16INK4a expression and Akt hyperphosphorylation. These cells were resistant to Cer16-induced apoptosis, despite presence of both endoplasmic reticulum stress response and mitochondrial membrane depolarization. In cells from smokers, the prominent up-regulation ofAkt pathways inhibited ceramide-triggered apoptosis, and was associated with elevated sphingosine and high-mobility group box 1, skewing the cell's response toward autophagy and survival. In conclusion, the cell responses to ceramide are modulated by an intricate cross-talk between Akt signaling and sphingolipid metabolites, and profoundly modified by previous cigarette smoke exposure, which selects for an apoptosis-resistant phenotype. Copyright © 2014 by the American Thoracic Society.

Petrache I.,Indianapolis | Petrache I.,Richard udebush Veteran Affairs Medical Center | Kamocki K.,Indianapolis | Poirier C.,Indianapolis | And 7 more authors.
PLoS ONE | Year: 2013

Increases in ceramide levels have been implicated in the pathogenesis of both acute or chronic lung injury models. However, the role of individual ceramide species, or of the enzymes that are responsible for their synthesis, in lung health and disease has not been clarified. We now show that C24- and C16-ceramides are the most abundant lung ceramide species, paralleled by high expression of their synthetic enzymes, ceramide synthase 2 (CerS2) and CerS5, respectively. Furthermore, the ceramide species synthesis in the lung is homeostatically regulated, since mice lacking very long acyl chain C24-ceramides due to genetic deficiency of CerS2 displayed a ten-fold increase in C16-ceramides and C16-dihydroceramides along with elevation of acid sphingomyelinase and CerS5 activities. Despite relatively preserved total lung ceramide levels, inhibition of de novo sphingolipid synthesis at the level of CerS2 was associated with significant airflow obstruction, airway inflammation, and increased lung volumes. Our results suggest that ceramide species homeostasis is crucial for lung health and that CerS2 dysfunction may predispose to inflammatory airway and airspace diseases. © 2013 Petrache et al.

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.

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.

Dobscha S.K.,Improve-in | Dobscha S.K.,Oregon Health And Science University | Denneson L.M.,Improve-in | Denneson L.M.,Oregon Health And Science University | And 7 more authors.
General Hospital Psychiatry | Year: 2014

Objective: To examine primary care clinician actions following positive suicide risk assessments administered to Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans. Methods: We identified OEF/OIF veterans with positive templated suicide risk assessments administered in primary care settings of three Veterans Affairs (VA) Medical Centers. National VA datasets and manual record review were used to identify and code clinician discussions and actions following positive assessments. Bivariate analyses were used to examine relationships between patient characteristics and discussions of firearms access and alcohol/drug use. Results: Primary care clinicians documented awareness of suicide risk assessment results for 157 of 199 (79%) patients with positive assessments. Most patients were assessed for mental health conditions and referred for mental health follow-up. Clinicians documented discussions about firearms access for only 15% of patients. Among patients whose clinicians assessed for substance abuse, 34% received recommendations to reduce alcohol or drug use. Depression diagnoses and suicidal ideation/behavior severity were significantly associated with firearms access discussions, while patient sex, military service branch, and substance abuse diagnoses were significantly associated with recommendations to reduce substance use. Conclusion: Greater efforts are needed to understand barriers to clinicians' assessing, documenting and counseling once suicidal ideation is detected, and to develop training programs and systems changes to address these barriers. © 2014.

PubMed | Richard udebush Veteran Affairs Medical Center, War Related Illness and Injury Study Center and Improve-in
Type: Journal Article | Journal: Suicide & life-threatening behavior | Year: 2015

We sought to understand Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) veterans experiences with suicidal ideation. Semi-structured interviews with 34 OEF/OIF veterans addressed circumstances leading up to disclosure of suicidal ideation during brief clinical assessments. We used an iterative, inductive and deductive thematic analysis approach. Results revealed three pervasive, persistent domains that reinforce the uniqueness of veteran suicidal thoughts: military culture, difficult deployment experiences, and postdeployment adjustment challenges. Within postdeployment, we identified four themes that serve as intervention targets: adjusting to civilian culture, changes to sense of self, feeling overwhelmed by stressors, and lacking life purpose or meaning.

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