Veterans Medical Research Foundation

San Diego, CA, United States

Veterans Medical Research Foundation

San Diego, CA, United States
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Receive press releases from MedAware Systems, Inc.: By Email Broomfield, CO, May 03, 2017 --( Dr. Piland is a recognized authority in healthcare economics and research, Dr. Piland is Research Professor, Emeritus, Institute of Rural Health, Idaho State University. He also served as Director of the Institute for thirteen years. Dr. Piland brings over forty-five years of experience in health services research, health care financing, and healthcare economics. Prior to his tenure at Idaho State University, he served as Director of the Medical Group Management Center for Research; was founding director of the Lovelace Medical Foundation’s Institute for Health and Population Research. He also served as Health Economist and Assistant Manager of Health Services Research at Stanford Research Institute (now SRI International). Dr. Piland held senior administrative and faculty positions at the Colorado Health Institute; the University of Colorado School of Medicine; the University of New Mexico School of Medicine; the University of Denver; the San Diego Veterans Administration Medical Center; and the Veterans Medical Research Foundation. He served as Principal Investigator on more than 30 major health services research projects and published over 100 scientific and health policy related articles and book chapters and has coauthored four books. He holds numerous awards, including the Indian Health Service (USDHHS) Director Award; Professional Leadership Award from the American Lung Association; Scientific Research Award from the Lovelace Medical Foundation; and a United States Public Health Service Training Fellowship, among others. “We are honored to have Dr. Piland join our Scientific Advisory Board” said Founder and Chief Science Officer, Dr. Zung Vu Tran. He adds, “Dr. Piland brings a wealth of knowledge and experience in healthcare economics and research that will add critical economic data components that are highly valuable to our customers.” About MedAware Systems, Inc. MedAware Systems, Inc. disrupts the health informatics industry by forever changing the way Pharma and medical device companies, physicians, payers and consumers derive usable evidence from published clinical trials research. The Company’s Science of Health Informatics (SOHInfo™) is a Scientific-Data-as-a-Service (SDaaS™) solving the problem of making the vast and chaotic body of human clinical trials research instantly available and indispensable in understanding medical treatment safety and efficacy. SOHInfo organizes and standardizes data from all human clinical trials and provides immediate and actionable information on evidence-based medical treatments and outcomes. Broomfield, CO, May 03, 2017 --( PR.com )-- MedAware Systems, Inc. announced today that Dr. Neill Piland is joining the Company’s Scientific Advisory Board.Dr. Piland is a recognized authority in healthcare economics and research, Dr. Piland is Research Professor, Emeritus, Institute of Rural Health, Idaho State University. He also served as Director of the Institute for thirteen years.Dr. Piland brings over forty-five years of experience in health services research, health care financing, and healthcare economics. Prior to his tenure at Idaho State University, he served as Director of the Medical Group Management Center for Research; was founding director of the Lovelace Medical Foundation’s Institute for Health and Population Research. He also served as Health Economist and Assistant Manager of Health Services Research at Stanford Research Institute (now SRI International). Dr. Piland held senior administrative and faculty positions at the Colorado Health Institute; the University of Colorado School of Medicine; the University of New Mexico School of Medicine; the University of Denver; the San Diego Veterans Administration Medical Center; and the Veterans Medical Research Foundation.He served as Principal Investigator on more than 30 major health services research projects and published over 100 scientific and health policy related articles and book chapters and has coauthored four books. He holds numerous awards, including the Indian Health Service (USDHHS) Director Award; Professional Leadership Award from the American Lung Association; Scientific Research Award from the Lovelace Medical Foundation; and a United States Public Health Service Training Fellowship, among others.“We are honored to have Dr. Piland join our Scientific Advisory Board” said Founder and Chief Science Officer, Dr. Zung Vu Tran. He adds, “Dr. Piland brings a wealth of knowledge and experience in healthcare economics and research that will add critical economic data components that are highly valuable to our customers.”About MedAware Systems, Inc.MedAware Systems, Inc. disrupts the health informatics industry by forever changing the way Pharma and medical device companies, physicians, payers and consumers derive usable evidence from published clinical trials research. The Company’s Science of Health Informatics (SOHInfo™) is a Scientific-Data-as-a-Service (SDaaS™) solving the problem of making the vast and chaotic body of human clinical trials research instantly available and indispensable in understanding medical treatment safety and efficacy. SOHInfo organizes and standardizes data from all human clinical trials and provides immediate and actionable information on evidence-based medical treatments and outcomes. Click here to view the list of recent Press Releases from MedAware Systems, Inc.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 306.90K | Year: 2013

DESCRIPTION (provided by applicant): Activation of hepatic stellate cells (HSC) is responsible for the development of liver fibrosis in chronic liver diseases of all causes and remarkably, HSC clearance by apoptosis may allow recovery from liver injury andreversal of liver fibrosis. There is full agreement among liver fibrosis experts that inhibiting o reversing HS activation (the therapeutic target) is critical for the treatment of liver fibrosis. Both regressio of liver fibrosis as well as lack of progression of liver fibrosis, in spite of continued liver injury as we clearly documented in our pre-clinical studies, are considered important clinical targets for patients with chronic liver disease and liver fibrosis. Finally, blocking the progression of liver fibrosis would decrease development of primary liver cancer in these patients since the majority of hepatocellular carcinomas arise in cirrhotic livers. The basis for our Research and Development of the Ac-KAVD-CHO related peptoids are the following: i]that the nonphosphorylatable C/EBP -Ala217 transgene prevents phosphorylation of endogenous C/EBP , and activates caspase 8 resulting in apoptosis of HSC upon their activation, preventing progression and inducing regression liver fibrosis; ii] that neither the transactivation nor the leucine zipper domains are required for these effects; and iii] that a cell permeant tetrapeptide containing the RSK phosphoacceptor domain of C/EBP is sufficient to replicate these effects . We created a library using analogsynthesis to improve potential pitfalls for human use; ii] use in a step-wise manner assays to select the safest and most efficient peptides (including apoptosis assays in activated primary human HSC; cell-free caspase 8 activation assays; acute liver injury/fibrogenesis models; toxicology assays in highly differentiated, primary human hepatocyte cultures and mice). We have developed effective antifibrotic compounds with expected decreased immunogenicity and improved stability and bioavailability during clinical trials. The proposed compounds markedly inhibit activation of human and mouse hepatic stellate cells in culture and in vivo in preclinical models of liver fibrosis and decreased liver injury. These compounds were not toxic in the preliminary toxicology studies, including toxicogenomics, to highly differentiated hepatocytes and mice at least at 100-fold the therapeutic dose. The aims that are proposed for completion by this STTR are: Chronic liver fibrogenesis assays in mouse models; Pharmacokinetics; In Vitro ADMET Studies :Metabolic stability; CYP-450 Inhibition; and Exploratory Toxicology; Dose Escalation Study and Repeat-Dose Range-finding Toxicity Study. There is no medication for the treatment or prevention of liver fibrosis. Completion of thesetasks for the proposed compounds will allow us proceeding with a Phase-2 STTR and clinical development in patients with liver fibrosis. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Chronic liver diseases, through inflammation and injury induce the development of scar tissue in the liver; this is called liver fibrosis. Excessive liver fibrosis can result in liver cirrhosis, which accounts for the significant complications and mortalty among the population with chronic liver diseases. The medical and financial burden of cirrhosis to the USA is substantial, as it is associated with Hepatitis B and C, fatty liver of obesity and diabetes and alcoholism. Additional knowledge gained by Xfibra with this work will facilitate the development of medication for the treatment of liver fibrosis. Development of effective treatments for liver fibrosis may also facilitate future treatments for lung and kidney fibrosis.


Mckenna B.S.,Mental Illness Research | Mckenna B.S.,University of California at San Diego | Sutherland A.N.,Veterans Medical Research Foundation | Legenkaya A.P.,University of California at San Diego | And 2 more authors.
Bipolar Disorders | Year: 2014

Objectives: Individuals with bipolar disorder (BD) have trait-like deficits in attention and working memory (WM). A fundamental dissociation for most verbal WM theories involves the separation of sensory-perceptual encoding, reliant upon attention, from the maintenance of this information in WM proper. The present study examined if patients with BD demonstrate differential neural changes in encoding and maintenance WM processes that underlie cognitive impairment. Methods: Event-related functional magnetic resonance imaging during a delayed match-to-sample WM paradigm was employed in 23 inter-episode medicated patients with BD and 23 demographically similar healthy comparison participants. We examined brain regions during encoding and maintenance task intervals to identify regions that demonstrated differential effects between groups. Medication effects and functional connectivity between prefrontal cortex and basal ganglia/thalamus were examined during the encoding interval due to the importance of these regions and the connection among them for encoding into WM. Results: Patients with BD exhibited deficits in task accuracy and attenuated brain response during the encoding interval in areas of the prefrontal cortex, caudate, thalamus, and posterior visual regions. In contrast, patients with BD exhibited hyperactivation in posterior sensory regions during the maintenance interval. Among the BD group, those with greater medication load exhibited the greatest brain response within the prefrontal cortex. Conclusions: Reduction in activation during the encoding interval suggests that attentional deficits underlie WM deficits in patients with BD. These deficits appear to be trait-like in so far as they were observed during periods of euthymia in patients with BD. Medication effects remain to be further explored as there was evidence of prefrontal changes dependent on medication load. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Park H.W.,University of California at San Diego | Kim Y.C.,University of California at San Diego | Kim Y.C.,Veterans Medical Research Foundation | Yu B.,University of California at Los Angeles | And 9 more authors.
Cell | Year: 2015

Summary The transcriptional co-activators YAP and TAZ are key regulators of organ size and tissue homeostasis, and their dysregulation contributes to human cancer. Here, we discover YAP/TAZ as bona fide downstream effectors of the alternative Wnt signaling pathway. Wnt5a/b and Wnt3a induce YAP/TAZ activation independent of canonical Wnt/β-catenin signaling. Mechanistically, we delineate the "alternative Wnt-YAP/TAZ signaling axis" that consists of Wnt-FZD/ROR-Gα12/13-Rho GTPases-Lats1/2 to promote YAP/TAZ activation and TEAD-mediated transcription. YAP/TAZ mediate the biological functions of alternative Wnt signaling, including gene expression, osteogenic differentiation, cell migration, and antagonism of Wnt/β-catenin signaling. Together, our work establishes YAP/TAZ as critical mediators of alternative Wnt signaling. © 2015 Elsevier Inc.


Walter K.H.,Veterans Medical Research Foundation | Varkovitzky R.L.,Veterans Affairs Puget Sound Health Care System | Owens G.P.,University of Tennesse | Lewis J.,Trauma Recovery Center | Chard K.M.,Trauma Recovery Center
Journal of Consulting and Clinical Psychology | Year: 2014

Objective: Across the Veterans Affairs (VA) Healthcare System, outpatient and residential posttraumatic stress disorder (PTSD) treatment programs are available to veterans of all ages and both genders; however, no research to date has compared these treatment options. This study compared veterans who received outpatient (n = 514) to those who received residential treatment (n = 478) within a VA specialty clinic on demographic and pretreatment symptom variables. Further, the study examined pre- to posttreatment symptom trajectories across the treatment programs. Method: All 992 veterans met diagnostic criteria for PTSD and attended at least 1 session of cognitive processing therapy (CPT) in either the outpatient or residential program. Bivariate analyses were utilized to investigate differences between samples on demographic variables and severity of pretreatment symptoms. Multilevel modeling (MLM) was used to investigate the change in symptomatology between the 2 samples from pre- to posttreatment. Results: Analyses indicated that the samples differed on all demographic and pretreatment symptom variables, with residential patients reporting higher scores on all assessment measures. MLM results demonstrated that symptom scores improved for all veterans across time, with outpatients consistently reporting fewer symptoms at both time points. The time by program interaction was significant for PTSD-related symptom trajectories, but not for the depression-related symptom trajectory. Conclusion: This is the 1st study to compare pretreatment characteristics and treatment outcome between veterans receiving outpatient and residential PTSD treatment. Findings may help clinicians select appropriate care for their patients by identifying relevant pretreatment characteristics and generally informing expectations of treatment outcome. © 2014 APA.


Hostetler K.Y.,University of California at San Diego | Hostetler K.Y.,Veterans Medical Research Foundation
Viruses | Year: 2010

Hexadecyloxypropyl-cidofovir (HDP-CDV) is a novel ether lipid conjugate of (S)-1-(3-hydroxy-2-phosphonoylmethoxypropyl)-cytosine (CDV) which exhibits a remarkable increase in antiviral activity against orthopoxviruses compared with CDV. In contrast to CDV, HDP-CDV is orally active and lacks the nephrotoxicity of CDV itself. Increased oral bioavailability and increased cellular uptake is facilitated by the lipid portion of the molecule which is responsible for the improved activity profile. The lipid portion of HDP-CDV is cleaved in the cell, releasing CDV which is converted to CDV diphosphate, the active metabolite. HDP-CDV is a highly effective agent against a variety of orthopoxvirus infections in animal models of disease including vaccinia, cowpox, rabbitpox and ectromelia. Its activity was recently demonstrated in a case of human disseminated vaccinia infection after it was added to a multiple drug regimen. In addition to the activity against orthopoxviruses, HDP-CDV (CMX001) is active against all double stranded DNA viruses including CMV, HSV-1, HSV-2, EBV, adenovirus, BK virus, orf, JC, and papilloma viruses, and is under clinical evaluation as a treatment for human infections with these agents. © 2010 by the authors.


Sharma K.,University of California at San Diego | Sharma K.,Veterans Medical Research Foundation
Diabetes | Year: 2015

The concept that excess superoxide production from mitochondria is the driving, initial cellular response underlying diabetes complications has been held for the past decade. However, results of antioxidant-based trials have been largely negative. In the present review, the data supporting mitochondrial superoxide as a driving force for diabetic kidney, nerve, heart, and retinal complications are reexamined, and a new concept for diabetes complications - mitochondrial hormesis - is presented. In this view, production of mitochondrial superoxide can be an indicator of healthy mitochondria and physiologic oxidative phosphorylation. Recent data suggest that in response to excess glucose exposure or nutrient stress, there is a reduction of mitochondrial superoxide, oxidative phosphorylation, and mitochondrial ATP generation in several target tissues of diabetes complications. Persistent reduction of mitochondrial oxidative phosphorylation complex activity is associated with the release of oxidants from nonmitochondrial sources and release of proinflammatory and profibrotic cytokines, and a manifestation of organ dysfunction. Restoration of mitochondrial function and superoxide production via activation of AMPK has now been associated with improvement in markers of renal, cardiovascular, and neuronal dysfunction with diabetes. With this Perspective, approaches that stimulate AMPK and PGC1a via exercise, caloric restriction, and medications result in stimulation of mitochondrial oxidative phosphorylation activity, restore physiologic mitochondrial superoxide production, and promote organ healing. © 2015 by the American Diabetes Association.


Downs T.M.,University of California at San Diego | Burton D.W.,University of California at San Diego | Araiza F.L.,Veterans Medical Research Foundation | Hastings R.H.,University of California at San Diego | Deftos L.J.,University of California at San Diego
Cancer Letters | Year: 2011

The aim of the study was to demonstrate the role of parathyroid hormone related protein (PTHrP) in stimulating aldo-keto reductase (AKR) 1C3 expression in prostate cancer (CaP) cells. CaP cell proliferation and resistance to apoptosis was increased by PTHrP transfection. Conversely, reducing AKR1C3 expression by siRNA decreased cell proliferation. Since these effects could be mediated through AKR1C3-catalyzed reductions of the PPARγ ligand, 15-DeoxyΔ 12,14-PGJ 2, we treated the cells with prostaglandins (PG). (PG) D 2 inhibited cell proliferation, but its metabolite, 9α,11β-PGF 2, did not effect CaP cell growth. The AKR1C family members serve as potential therapeutic targets for CaP therapy. © 2011.


Depp C.A.,University of California at San Diego | Savla G.N.,University of California at San Diego | Vergel De Dios L.A.,University of California at San Diego | Mausbach B.T.,University of California at San Diego | And 2 more authors.
Psychological Medicine | Year: 2012

Background Few studies have examined the short-term course of cognitive impairments in bipolar disorder (BD). Key questions are whether trajectories in symptoms covary with cognitive function and whether BD is associated with increased intra-individual variability in cognitive abilities.Method Forty-two out-patients with BD and 49 normal comparison (NC) subjects were administered a battery of neuropsychological tests at baseline, 6, 12 and 26 weeks, along with concurrent ratings of depressive and manic symptom severity. Mixed-effects regressions were used to model relationships between time, diagnosis and symptom severity on composite cognitive performance. Within-person variance in cognitive functioning across time was calculated for each subject.Results BD patients had significantly worse performance in cognitive ability across time points, but both groups showed significant improvement in cognitive performance over repeated assessments (consistent with expected practice effects). BD was associated with significantly greater intra-individual variability in cognitive ability than NCs; within-person variation was negatively related to baseline cognitive ability in BD but not NC subjects. Changes in affective symptoms over time did not predict changes in cognitive ability.Conclusions Moderate changes in affective symptoms did not covary with cognitive ability in BD. The finding of elevated intra-individual variability in BD may reduce capacity to estimate trajectories of cognitive ability in observational and treatment studies. © 2011 Cambridge University Press.


Mo J.-S.,University of California at San Diego | Meng Z.,University of California at San Diego | Kim Y.C.,Veterans Medical Research Foundation | Park H.W.,University of California at San Diego | And 4 more authors.
Nature Cell Biology | Year: 2015

YAP (Yes-associated protein) is a transcription co-activator in the Hippo tumour suppressor pathway and controls cell growth, tissue homeostasis and organ size. YAP is inhibited by the kinase Lats, which phosphorylates YAP to induce its cytoplasmic localization and proteasomal degradation. YAP induces gene expression by binding to the TEAD family transcription factors. Dysregulation of the Hippo-YAP pathway is frequently observed in human cancers. Here we show that cellular energy stress induces YAP phosphorylation, in part due to AMPK-dependent Lats activation, thereby inhibiting YAP activity. Moreover, AMPK directly phosphorylates YAP Ser 94, a residue essential for the interaction with TEAD, thus disrupting the YAP-TEAD interaction. AMPK-induced YAP inhibition can suppress oncogenic transformation of Lats-null cells with high YAP activity. Our study establishes a molecular mechanism and functional significance of AMPK in linking cellular energy status to the Hippo-YAP pathway. © 2015 Macmillan Publishers Limited.

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