**PALO ALTO FY2006 HIGHLIGHTS**

**I. [Collaboration with Other VA Entities]{.underline}**

-   ATHENA Decision Support System (DSS) ([A]{.underline}ssessment and
    [T]{.underline}reatment of [H]{.underline}ypertension
    [E]{.underline}vidence-based [A]{.underline}utomation), now know as
    ATHENA-Hypertension (HTN), is being used at Durham VAMC as part of a
    study of medication management and behavioral management for
    hypertension. ATHENA-HTN is being installed in five medical centers
    in VISN 1, as part of a VA HSR&D VISN Collaborative project.

-   Living with Memory Loss Program, a collaborative between the VA Palo
    Alto Health Care System (VAPAHCS) and the Northern
    California/Northern Nevada Alzheimer\'s Association, enables
    veterans with dementia and their caregivers to access community
    support systems quickly, and is a support for VA providers.

**II. [Aging Research]{.underline}**

-   Dr. Azhar's lab findings suggest that the plant-derived compound
    masoprocol, which exhibits glucose and triglyceride lowering
    properties and anti-inflammatory actions, also improves high sugar
    (such as fructose) induced and inflammation mediated lipid
    abnormalities in animal models. These studies support the concept of
    using anti-inflammatory medications as one method to correct
    metabolic lipid abnormalities.

-   Dr. Chua's lab identified a novel function for the ING2 gene, which
    is a candidate tumor suppressor gene. The work shows that when
    cellular DNA is damaged, ING2 functions to inactivate genes that
    normally promote cell division. By turning off such genes, this ING2
    function prevents the propagation of cells harboring damaged DNA and
    potentially cancer-promoting mutations. Such a mechanism may
    contribute to the tumor suppressive function of ING2.

-   Dr. Goldstein's group developed multimedia software for interviewing
    computer-inexperienced older adults about Activities of Daily Living
    (ADLs). The software program is known as FLAIR2 (Functional
    Limitation and Independence Rating, version 2), which assists older
    adults in self-reporting ADL dependency and then elicits health
    preference ratings for health states of dependency in ADLs, alone
    and in combinations.

-   Dr. Huang's genetic study identified the modifier gene(s) that
    modulates the phenotype of a mouse model for mitochondrial defects.
    Mitochondria are the energy generating organelles in cells and
    mitochondrial defects have been implicated in diabetes and a number
    of neuron-muscular problems. The same modifier gene that they
    identified in this study has also been shown to modulate the level
    of glucose sensitivity I mouse models for type II diabetes.

-   Dr. Huang's lab found that inactivation of SIRT6 in mice leads to
    dramatically shortened lifespan and acute degenerative symptoms
    reminiscent of premature aging. Molecular characterization of cells
    from SIRT6 mutant mice revealed potential defects in DNA repair
    machinery and increased genomic instability.

-   Dr. Huang's lab studied Mouse models and molecular biology methods
    to determine the effects of oxygen free radicals on DNA mutations in
    different organs. The results showed that increased oxygen free
    radicals can lead to increased DNA mutation, which can lead to a
    higher probability for cancer development.

-   Dr. Huang's lab used mouse models and biochemical and
    histopathological analyses to determine the effects of increased
    oxygen free radicals on thymic tumor development in a mouse model
    defective of a DNA repair enzyme, ataxia-telangiectasia, a
    progressive neurodegenerative disease affecting the brain and other
    tissue systems. They found that whereas antioxidant treatment can
    delay the disease onset and reduce the severity of the disease in
    the mouse model, increased oxygen free radical production does not
    accelerate the disease process. In fact, the data suggested that
    increased oxygen free radicals may help to eliminate cells that
    would otherwise turn into cancerous cells in this mouse model.

-   Dr. Rando has expanded his collaborative research program as part of
    his receipt of a NIH Director's Pioneer Award, which has benefited
    VAPAHCS in terms of increased funding for collaborative research on
    aging and has brought together researchers with diverse interests
    but with a common interest in stem cell biology and tissue
    regeneration.

-   Dr. Rando's lab reported on a methodology to enhance gene therapy
    approaches to the protection of muscle degeneration. They
    collaborated with Dr. Michele Calos at Stanford University, a
    pioneer in this area of gene therapy research, and combined their
    expertise to apply the technology to a clinically relevant issue of
    the prevention of tissue damage.

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-   Dr. Robinson's lab demonstrated that lipids are prominent targets of
    the autoimmune response in multiple sclerosis and that fibrinogen
    (the clotting protein) is targeted in human rheumatoid arthritis.
    These findings could lead to the development of more effective
    diagnostic tests and therapeutics benefiting veterans.

-   Dr. Robinson received the American College of Rheumatology Research
    and Education Foundation-ASP Junior Career Development Award in
    Geriatric Medicine for his work, "Proteomic Analysis of Rheumatoid
    Arthritis in the Geriatric Population."

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-   Dr. Robinson's lab created lipid microarrays, and applied lipid
    arrays to discover that myelin lipids are prominent targets of the
    autoimmune response in human multiple sclerosis. Detection of
    anti-lipid antibodies could provide a novel diagnostic test for the
    diagnosis of MS.

-   Dr. Robinson's lab discovered that the cancer drug imatinib
    (Gleevec) provides potent efficacy in rodent models of rheumatoid
    arthritis. Discoveries such as this provide the rationale for
    clinical trials to investigate the efficacy of imatinib and other
    kinase inhibitors in RA and other autoimmune diseases, which could
    result in a new therapy for these diseases.

-   Dr. Wyss-Coray's lab developed a model to image and monitor
    neurodegeneration in living mice using bioluminescence imaging. A
    reporter mouse was developed for the TGF-β signaling pathway in 2002
    and characterized the model over the past 4 years at the VA.
    Excitotoxic injury results in activation of the reporter and
    corresponds to brain injury. Drugs that inhibit neurodegeneration
    can be tested quickly in living animals. The results will be
    published later in 2007 in the journal PNAS.

-   Dr. Wyss-Coray's article in Cell Biology describes a bioassay for
    TGF-b1 as an important regulator of immune functions and cell
    growth, and has been linked to cancer. The cell line has been sent
    to 16 different labs around the world.

-   Dr. Wyss-Coray's lab found that TGF-b1 can reduce the formation of
    new neurons in the adult mouse brain. Because TGF-b1 is increased
    with age and more prominently after injury, brain injury could
    reduce the formation of new neurons and affect memory and learning.

**III. [Education and Training]{.underline}**

-   Approved as a site for the VA Special Fellowship Program in Advanced
    Geriatrics (SFPAG), with Dr. Goldstein as the Fellowship Program
    Director.

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-   Caregiver and Veteran support groups are held monthly, enabling both
    caregivers and veterans to get their needs met at the same time. The
    group permits very demented patients to attend and normalize their
    disabilities.

-   Web portal for evidence-based medicine for VA staff, developed in
    conjunction with other VAMCs, is targeted for release to VA
    clinicians in FY07.

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-   VISN 21 and 22 collaborated on a Web-based educational initiative
    designed to provide the required five hours of continuing education
    in geriatrics, now mandated for all California physicians renewing
    their licenses.

-   The Curriculum for geriatric medicine fellows was re-designed
    creating innovations in both didactics and clinical teaching: (1)
    Didactics on geriatric assessment tools using a workshop format,
    where fellows are taught how to apply these assessment tools at the
    bedside and are supervised by faculty on a one-to-one basis, which
    ensures timely and accurate feedback on their performance. (2)
    Didactics on geriatric interdisciplinary team care using role play.

**IV. [Clinical Demonstrations Models/Best Practices]{.underline}**

-   Group Medical Visits, a VA HSR&D Quality Enhancement Research
    Initiative (QUERI)-funded project, developed for patients with
    hypertension suitable for primary care clinics, was implemented and
    studied in a randomized controlled trial. The intervention and data
    collection phases were completed in FY2006, and the data analysis
    phase is underway.

**V. [Dissemination of GRECC Products]{.underline}**

-   Development of CPRS templates from paper tools to facilitate
    electronic documentation: 8 Domains of Assessment, Falls Assessment,
    and CNS. These templates were exported to the geriatric clinic at
    VAMC, Battle Creek, Michigan.