Veterans Administration Palo Alto Health Care System

Palo Alto, CA, United States

Veterans Administration Palo Alto Health Care System

Palo Alto, CA, United States
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Zhang S.,Columbia University | Bantum E.O.,University of Hawaii at Manoa | Owen J.,Veterans Administration Palo Alto Health Care System | Bakken S.,Columbia University | Elhadad N.,Columbia University
Journal of the American Medical Informatics Association | Year: 2017

Objectives: The Internet and social media are revolutionizing how social support is exchanged and perceived, making online health communities (OHCs) one of the most exciting research areas in health informatics. This paper aims to provide a framework for organizing research of OHCs and help identify questions to explore for future informatics research. Based on the framework, we conceptualize OHCs from a social support standpoint and identify variables of interest in characterizing community members. For the sake of this tutorial, we focus our review on online cancer communities. Target audience: The primary target audience is informaticists interested in understanding ways to characterize OHCs, their members, and the impact of participation, and in creating tools to facilitate outcome research of OHCs. OHC designers and moderators are also among the target audience for this tutorial. Scope: The tutorial provides an informatics point of view of online cancer communities, with social support as their leading element. We conceptualize OHCs according to 3 major variables: type of support, source of support, and setting in which the support is exchanged. We summarize current research and synthesize the findings for 2 primary research questions on online cancer communities: (1) the impact of using online social support on an individual's health, and (2) the characteristics of the community, its members, and their interactions. We discuss ways in which future research in informatics in social support and OHCs can ultimately benefit patients. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved.

Moriyama M.,Stanford University | Fukuhara T.,Stanford University | Britschgi M.,Stanford University | Britschgi M.,Hoffmann-La Roche | And 8 more authors.
Journal of Neuroscience | Year: 2011

Injury and inflammation are potent regulators of adult neurogenesis. As the complement system forms a key immune pathway that may also exert critical functions in neural development and neurodegeneration, we asked whether complement receptors regulate neurogenesis. We discovered that complement receptor 2 (CR2), classically known as a coreceptor of the B-lymphocyte antigen receptor, is expressed in adult neural progenitor cells (NPCs) of the dentate gyrus. Two of its ligands, C3d and interferon-α (IFN-α), inhibited proliferation of wild-type NPCs but not NPCs derived from mice lacking Cr2 (Cr2-/-), indicating functional Cr2 expression. Young and old Cr2-/- mice exhibited prominent increases in basal neurogenesis compared with wild-type littermates, whereas intracerebral injection of C3d resulted in fewer proliferating neuroblasts in wild-type than in Cr2 -/- mice. We conclude that Cr2 regulates hippocampal neurogenesis and propose that increased C3d and IFN-α production associated with brain injury or viral infections may inhibit neurogenesis. Copyright © 2011 the authors.

Okerlund N.D.,Stanford University | Okerlund N.D.,Veterans Administration Palo Alto Health Care System | Schneider K.,German Center for Neurodegenerative Diseases | Leal-Ortiz S.,Stanford University | And 10 more authors.
Neuron | Year: 2017

Mechanisms regulating the surveillance and clearance of synaptic proteins are not well understood. Intriguingly, the loss of the presynaptic active zone proteins Piccolo and Bassoon triggers the loss of synaptic vesicles (SVs) and compromises synaptic integrity. Here we report that the destruction of SVs in boutons lacking Piccolo and Bassoon was associated with the induction of presynaptic autophagy, a process that depended on poly-ubiquitination, but not the E3 ubiquitin ligase Siah1. Surprisingly, gain or loss of function (LOF) of Bassoon alone suppressed or enhanced presynaptic autophagy, respectively, implying a fundamental role for Bassoon in the local regulation of presynaptic autophagy. Mechanistically, Bassoon was found to interact with Atg5, an E3-like ligase essential for autophagy, and to inhibit the induction of autophagy in heterologous cells. Importantly, Atg5 LOF as well as targeting an Atg5-binding peptide derived from Bassoon inhibited presynaptic autophagy in boutons lacking Piccolo and Bassoon, providing insights into the molecular mechanisms regulating presynaptic autophagy. © 2017 Elsevier Inc.

Dang V.,Stanford University | Dang V.,Veterans Administration Palo Alto Health Care System | Medina B.,Veterans Administration Palo Alto Health Care System | Das D.,Veterans Administration Palo Alto Health Care System | And 10 more authors.
Biological Psychiatry | Year: 2014

Background Down syndrome is associated with significant failure in cognitive function. Our previous investigation revealed age-dependent degeneration of locus coeruleus, a major player in contextual learning, in the Ts65Dn mouse model of Down syndrome. We studied whether drugs already available for use in humans can be used to improve cognitive function in these mice. Methods We studied the status of β adrenergic signaling in the dentate gyrus of the Ts65Dn mouse model of Down syndrome. Furthermore, we used fear conditioning to study learning and memory in these mice. Postmortem analyses included the analysis of synaptic density, dendritic arborization, and neurogenesis. Results We found significant atrophy of dentate gyrus and failure of β adrenergic signaling in the hippocampus of Ts65Dn mice. Our behavioral analyses revealed that formoterol, a long-acting β2 adrenergic receptor agonist, caused significant improvement in the cognitive function in Ts65Dn mice. Postmortem analyses revealed that the use of formoterol was associated with a significant improvement in the synaptic density and increased complexity of newly born dentate granule neurons in the hippocampus of Ts65Dn mice. Conclusions Our data suggest that targeting β2 adrenergic receptors is an effective strategy for restoring synaptic plasticity and cognitive function in these mice. Considering its widespread use in humans and positive effects on cognition in Ts65Dn mice, formoterol or similar β2 adrenergic receptor agonists with ability to cross the blood brain barrier might be attractive candidates for clinical trials to improve cognitive function in individuals with Down syndrome. © 2014 Society of Biological Psychiatry.

Zhou W.,Stanford University | Zhou W.,Veterans Administration Palo Alto Health Care System | Blay Jr. E.,Duke University | Varu V.,Stanford University | And 4 more authors.
Journal of Vascular Surgery | Year: 2014

Objective Endovascular aneurysm repair (EVAR) is considered the standard therapy for most patients with abdominal aortic aneurysm (AAA). Endoleak is a well-known EVAR-related complication that requires long-term follow-up. However, patient follow-up is often challenging outside clinical trials. We sought to evaluate the incidence and the effect of delayed endoleaks in a Veterans Administration (VA) health care system where long-term follow-up is ensured. Methods We retrospectively evaluated 213 consecutive patients who underwent EVAR at a referral Veterans Administration medical center. Age, aneurysm size, patency of lumbar and inferior mesenteric arteries, and follow-up evaluations were recorded. Type of endoleak, date of detection, and intervention were also documented. Patients who had <1 year of follow-up were excluded. The χ2 test, Student t-test, Mann-Whitney test, and Spearman correlation were used for data analysis. Results The analysis included 183 patients with a mean follow-up of 53 months (range, 12-141 months); of these, 48 patients (26%) had endoleaks, and 31 (17%) had aneurysm progression. The mean diagnosis time for nontype II (n = 14) endoleaks was 45 months (range, 3-127 months), and 71% were diagnosed >1 year after EVAR. All except one nontype II endoleak received prompt secondary interventions, and the one without intervention presented with aneurysm rupture. An isolated type II endoleak was detected in 34 patients at an average of 14.4 months (range, 0-76 months) after EVAR, 41% of which were detected >1 year after EVAR. Patients without a documented endoleak had a significant decrease in aneurysm size at the latest computed tomography evaluation compared to the preoperative size (4.8 vs 5.7 cm; P <.001), whereas those with isolated type II endoleak had an increase at the latest computed tomography follow-up compared to preoperative size (5.8 vs 5.7 cm). Importantly, 59% of the patients with a type II endoleak had significant AAA enlargement (0.8 cm), and delayed type II endoleak was significantly associated with sac enlargement compared to type II endoleaks detected early. No significant correlation was seen between the diameter of inferior mesenteric artery or lumbar to AAA enlargement among the patients with a type II endoleak. Secondary interventions in 12 patients with isolated type II endoleak resulted in overall aneurysm stabilization or regression. Conclusions This long-term outcome study demonstrated that delayed endoleaks appearing >1 year after EVAR contributed to most of the overall endoleaks and were significantly associated with aneurysm sac growth. This study underscores that type II endoleak is not benign and that vigilant lifelong surveillance after EVAR is critical. © 2014 by the Society for Vascular Surgery.

Giles J.T.,Columbia University | Danoff S.K.,Johns Hopkins University | Sokolove J.,Veterans Administration Palo Alto Health Care System | Sokolove J.,Stanford University | And 9 more authors.
Annals of the Rheumatic Diseases | Year: 2014

Background: Interstitial lung disease (ILD) is associated with high morbidity and mortality in rheumatoid arthritis (RA). Citrullinated proteins are observed in RA lung tissues; however, the association of specific anticitrullinated peptide antibodies (ACPA) with ILD in RA is unknown. Methods: RA patients underwent multidetector CT (MDCT) of the chest, from which ILD features and a semiquantitative ILD Score (ILDS; range 0-32) were assessed. Anti-CCP (CCP2) and levels of a panel of antibodies against 17 citrullinated and four noncitrullinated peptides were assessed from concurrent serum samples using a custom Bio-Plex bead array. High level ACPA was defined as ≥the group 75th percentile. Results: Among the 177 RA patients studied, median levels of CCP2 and all specific ACPAs were 46-273% higher among RA patients with versus those without ILD (all p values <0.05), and higher levels correlated with higher ILDS. In contrast, levels of non-citrullinated protein antibodies were not higher in those with ILD. RA patients had a median of 2 high level ACPA reactivities (range 0-16), with each high level ACPA associated, on average, with a 0.10 unit higher ILDS (p=0.001). This association remained significant after adjusting for characteristics associated with ILD (age, gender, current and former smoking, Disease Activity Score for 28 joints, current prednisone and leflunomide use). More high level ACPA were observed in those with versus without pulmonary function restriction or impaired diffusion. Conclusions: Our findings of a broader ACPA repertoire in RA ILD suggest a possible role for ACPA in the pathogenesis of ILD.

Flores-Figueroa E.,Instituto Mexicano Del Seguro Social | Varma S.,Stanford University | Montgomery K.,Stanford University | Greenberg P.L.,Stanford University | And 2 more authors.
Laboratory Investigation | Year: 2012

Mesenchymal stromal cells (MSCs) support hematopoiesis and are cytogenetically and functionally abnormal in myelodysplastic syndrome (MDS), implying a possible pathophysiologic role in MDS and potential utility as a diagnostic or riskstratifying tool. We have analyzed putative MSC markers and their relationship to CD34+ hematopoietic stem/progenitor cells (HSPCs) within intact human bone marrow in paraffin-embedded bone marrow core biopsies of benign, MDS and leukemic (AML) marrows using tissue microarrays to facilitate scanning, image analysis and quantitation. We found that CD271+, ALP+ MSCs formed an extensive branching perivascular, periosteal and parenchymal network. Nestin was brightly positive in capillary/arteriolar endothelium and occasional subendothelial cells, whereas CD146 was most brightly expressed in SMA+ vascular smooth muscle/pericytes. CD271+ MSCs were distinct by double immunofluorescence from CD163+ macrophages and were in close contact with but distinct from brightly nestin+ and from brightly CD146+ vascular elements. Double immunofluorescence revealed an intimate spatial relationship between CD34+ HSPCs and CD271+ MSCs; remarkably, 86% of CD34+ HSPCs were in direct contact with CD271+ MSCs across benign, MDS and AML marrows, predominantly in a perivascular distribution. Expression of the intercrine chemokine CXCL12 was strong in the vasculature in both benign and neoplastic marrow, but was also present in extravascular parenchymal cells, particularly in MDS specimens. We identified these parenchymal cells as MSCs by ALP/CXCL12 and CD271/CXCL12 double immunofluorescence. The area covered by CXCL12+ ALP+ MSCs was significantly greater in MDS compared with benign and AML marrow (P=0.021, Kruskal-Wallis test). The preservation of direct CD271+ MSC/CD34+ HSPC contact across benign and neoplastic marrow suggests a physiologically important role for the CD271+ MSC/CD34+ HSPC relationship and possible abnormal exposure of CD34+ HSPCs to increased MSC CXCL12 expression in MDS. © 2012 USCAP, Inc. All rights reserved.

Sahbaie P.,Veterans Administration Palo Alto Health Care System | Sahbaie P.,Stanford University | Li X.,Veterans Administration Palo Alto Health Care System | Li X.,Stanford University | And 4 more authors.
Anesthesiology | Year: 2012

BACKGROUND:: Neutrophils are one of the predominant immune cells initially migrating to surgical wound edges. They produce mediators both associated with supporting (interleukin [IL]-1β, C5a) and reducing (opioid peptides) pain. Studies demonstrate neutrophil depletion/blockade reduces nociceptive sensitization after nerve injury and carrageenan administration, but enhance sensitization in complete Freund's adjuvant inflammation. This research identifies the contribution of infiltrating neutrophils to incisional pain and inflammation. METHODS:: Antibody-mediated Gr1 neutrophil depletion preceded hind paw incisions. Sensitization to mechanical and thermal stimuli, effects on edema and local levels of IL-1β and C5a were measured. Local effects of C5a or IL-1 receptor antagonists PMX-53 and anakinra on sensitization after neutrophil depletion were examined. Groups of 4-8 mice were used. RESULTS:: Anti-Gr1 antibody depleted more than 90% of circulating and infiltrating skin neutrophils after incision. Neutrophil depletion did not change magnitude or duration of mechanical hypersensitivity in incised mice. However, paw edema was significantly reduced and heat hypersensitivity was slightly increased in depleted animals. In depleted animals IL-1β levels were half of controls 24 h after incision, whereas C5a levels were increased in both. Prominent IL-1β immunohistochemical staining of epidermis was seen in both groups. PMX-53 and anakinra reduced incisional mechanical and heat nociceptive sensitization to the same extent, regardless of neutrophil depletion. CONCLUSIONS:: Neutrophil-derived IL-1β and C5a do not appear to contribute critically to peri-incisional nociceptive signaling. Other sources of mediators, such as epidermal cells, may need to be considered. Controlling inflammatory activation of resident cells in epidermis/deeper structures may show therapeutic efficacy in reducing pain from surgical incisions. Copyright © 2012, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.

Friedland S.,Veterans Administration Palo Alto Health Care System | Friedland S.,Stanford University | Kothari S.,Stanford University | Chen A.,Stanford University | And 2 more authors.
Gastrointestinal Endoscopy | Year: 2012

Background: Hyaluronic acid (HA) provides a long-lasting and distinct mucosal elevation for EMR, but expense and inconvenience have limited its adoption. Objective: To evaluate the safety and efficacy of an over-the-counter 0.15% HA preparation for EMR. Design: Retrospective study. Setting: Veterans Administration Hospital and university hospital. Patients: 30 patients with a total of 32 colonic lesions and 1 duodenal lesion. Intervention: EMR by using HA. Main Outcome Measurements: En bloc resection rate and complications. Results: EMR was successful in all cases. En bloc resection was achieved in 26 of the 28 lesions up to 25 mm in diameter. Two lesions, both with fibrosis from prior attempted resection, had trace residual tissue necessitating cauterization with argon plasma. Five lesions measuring 30 mm to 60 mm all required piecemeal resection. There was one complication, a postpolypectomy bleed. Limitations: Small number of patients and retrospective design. Conclusions: EMR may be performed safely and effectively by using an inexpensive, over-the-counter 0.15% HA preparation. Further studies are needed to verify the results of this study and to compare the safety and efficacy of this HA preparation with saline solution. © 2012 American Society for Gastrointestinal Endoscopy.

Nair V.S.,Stanford University | Gevaert O.,Stanford University | Davidzon G.,Stanford University | Napel S.,Stanford University | And 7 more authors.
Cancer Research | Year: 2012

Although 2[18F]fluoro-2-deoxy-D-glucose (FDG) uptake during positron emission tomography (PET) predicts post-surgical outcome in patients with non-small cell lung cancer (NSCLC), the biologic basis for this observation is not fully understood. Here, we analyzed 25 tumors from patients with NSCLCs to identify tumor PET-FDG uptake features associated with gene expression signatures and survival. Fourteen quantitative PET imaging features describing FDG uptake were correlated with gene expression for single genes and coexpressed gene clusters (metagenes). For each FDG uptake feature, an associated metagene signature was derived, and a prognostic model was identified in an external cohort and then tested in a validation cohort of patients with NSCLC. Four of eight single genes associated with FDG uptake (LY6E, RNF149, MCM6, and FAP) were also associated with survival. The most prognostic metagene signature was associated with a multivariate FDG uptake feature [maximum standard uptake value (SUV max), SUV variance, and SUV PCA2], each highly associated with survival in the external [HR, 5.87; confidence interval (CI), 2.49-13.8] and validation (HR, 6.12; CI, 1.08-34.8) cohorts, respectively. Cell-cycle, proliferation, death, and self-recognition pathways were altered in this radiogenomic profile. Together, our findings suggest that leveraging tumor genomics with an expanded collection of PET-FDG imaging features may enhance our understanding of FDG uptake as an imaging biomarker beyond its association with glycolysis. ©2012 AACR.

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