Publications by authors named "Gamble-George J"

Article Synopsis
  • The All of Us Research Program wants to create a huge and diverse database for medical research that scientists can easily use through a special platform called the Researcher Workbench (RW).
  • Researchers with different levels of experience helped design a new tool called SAS by sharing their ideas and testing it out.
  • The feedback from these researchers was super helpful in making the SAS tool better, which means more people can use the All of Us data easily and effectively in their studies.
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HIV testing rates vary by race and ethnicity. Whether social capital indicators are related to HIV testing and whether these associations differ by race or ethnicity is unknown. Multivariable analysis was used to examine whether social capital (collective engagement and civic and social participation), including social cohesion (trust in neighbors, neighbors willing to help, feelings of belongingness) were associated with testing for HIV in the past 12 months.

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Biotechnology offers vast benefits to the environment, animals, and human health, and contributes to improving socioeconomic conditions for the public. However, biotechnology innovations continue to trigger public concern and opposition over their potential social, health, and ecological risks. There is an opportunity to increase knowledge and acceptance of biotechnology through engagement, education, and community participation.

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The sudden increase in alcohol use in the young adult population during the COVID-19 pandemic may be partially explained by social isolation and stress due to restricted stay-at-home orders. The goal of this study was to assess specific psychological factors (e.g.

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Pathophysiological changes in dopamine neurons precede their demise and contribute to the early phases of Parkinson's disease (PD). Intracellular pathological inclusions of the protein α-synuclein within dopaminergic neurons are a cardinal feature of PD, but the mechanisms by which α-synuclein contributes to dopaminergic neuron vulnerability remain unknown. The inaccessibility to diseased tissue has been a limitation in studying progression of pathophysiology prior to degeneration of dopamine neurons.

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The National Institutes of Health (NIH) recognizes that, despite HIV scientific advances, stigma and discrimination continue to be critical barriers to the uptake of evidence-based HIV interventions. Achieving the Ending the HIV Epidemic: A Plan for America (EHE) goals will require eliminating HIV-related stigma. NIH has a significant history of supporting HIV stigma research across its Institutes, Centers, and Offices (ICOs) as a research priority.

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Cardiovascular disease (CVD), including hypertensive disorders of pregnancy (HDP) and peripartum cardiomyopathy, is a leading cause of pregnancy-related death in the United States. Women who are African American or American Indian/Alaskan Native, have HDP, are medically underserved, are older, or are obese have a major risk for the onset and/or progression of CVD during and after pregnancy. Paradoxically, women with no preexisting chronic conditions or risk factors also experience significant pregnancy-related cardiovascular (CV) complications.

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Antiretroviral therapy (ART) prevented premature mortality and improved the quality of life among people living with the human immunodeficiency virus (PLWH), such that now more than half of PLWH in the United States are 50 years of age and older. Increased longevity among PLWH has resulted in a significant rise in chronic, comorbid diseases. However, the implementation of guideline-based interventions for preventing, treating, and managing such age-related, chronic conditions among the HIV population is lacking.

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The transactivator of transcription protein, HIV-1 Tat, is linked to neuroAIDS, where degeneration of dopamine neurons occurs. Using a mouse model expressing GFAP-driven Tat protein under doxycycline (Dox) regulation, we investigated microglial-neuronal interactions in the rostral substantia nigra pars compacta (SNc). Immunohistochemistry for microglia and tyrosine hydroxylase (TH) showed that the ratio of microglia to dopamine neurons is smaller in the SNc than in the ventral tegmental area (VTA) and that this difference is maintained following 7-day Dox exposure in wild type animals.

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Human Immunodeficiency Virus (HIV) is a progressive infection that targets the immune system, affecting more than 37 million people around the world. While combinatorial antiretroviral therapy (cART) has lowered mortality rates and improved quality of life in infected individuals, the prevalence of HIV associated neurocognitive disorders is increasing and HIV associated cognitive decline remains prevalent. Recent research has suggested that HIV accessory proteins may be involved in this decline, and several studies have indicated that the HIV protein transactivator of transcription (Tat) can disrupt normal neuronal and glial function.

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Mood and anxiety disorders are the most prevalent psychiatric conditions and are exacerbated by stress. Recent studies have suggested cyclooxygenase-2 (COX-2) inhibition could represent a novel treatment approach or augmentation strategy for affective disorders including anxiety disorders and major depression. We show that traditional COX-2 inhibitors and a newly developed substrate-selective COX-2 inhibitor (SSCI) reduce a variety of stress-induced behavioral pathologies in mice.

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Methamphetamine is the second most widely used illicit drug worldwide. More than 290 tons of methamphetamine was synthesized in the year 2005 alone, corresponding to approximately ~3 billion 100 mg doses of methamphetamine. Drug addicts abuse high concentrations of methamphetamine for months and even years.

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Stress is a major risk factor for the development of mood and anxiety disorders; elucidation of novel approaches to mitigate the deleterious effects of stress could have broad clinical applications. Pharmacological augmentation of central endogenous cannabinoid (eCB) signaling may be an effective therapeutic strategy to mitigate the adverse behavioral and physiological consequences of stress. Here we show that acute foot-shock stress induces a transient anxiety state measured 24 h later using the light-dark box assay and novelty-induced hypophagia test.

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Pharmacologic augmentation of endogenous cannabinoid (eCB) signaling is an emerging therapeutic approach for the treatment of a broad range of pathophysiological conditions. Thus far, pharmacological approaches have focused on inhibition of the canonical eCB inactivation pathways - fatty acid amide hydrolase (FAAH) for anandamide and monoacylglycerol lipase (MAGL) for 2-arachidonoylglycerol. We review here the experimental evidence that cyclooxygenase-2 (COX-2)-mediated eCB oxygenation represents a third mechanism for terminating eCB action at cannabinoid receptors.

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The central amygdala (CeA) is a key structure at the limbic-motor interface regulating stress responses and emotional learning. Endocannabinoid (eCB) signaling is heavily implicated in the regulation of stress-response physiology and emotional learning processes; however, the role of eCBs in the modulation of synaptic efficacy in the CeA is not well understood. Here we describe the subcellular localization of CB1 cannabinoid receptors and eCB synthetic machinery at glutamatergic synapses in the CeA and find that CeA neurons exhibit multiple mechanistically and temporally distinct modes of postsynaptic eCB mobilization.

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Augmentation of endogenous cannabinoid (eCB) signaling represents an emerging approach to the treatment of affective disorders. Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid to form prostaglandins, but also inactivates eCBs in vitro. However, the viability of COX-2 as a therapeutic target for in vivo eCB augmentation has not been explored.

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Rationale: Central CB1 cannabinoid receptors regulate anxiety-like and appetitive consummatory behaviors. Pharmacological antagonism/inverse-agonism of CB1 receptors increases anxiety and decreases appetitive behaviors; however, neither well-defined dose nor context dependence of these effects has been simultaneously assessed in one behavioral assay.

Objectives: We sought to determine the context and dose dependence of the effects of CB1 receptor blockade on anxiety-like and consummatory behaviors in a model that allowed for simultaneous detection of anxiety-like and consummatory-related behaviors.

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Methamphetamine (METH) is a highly addictive and neurotoxic psychostimulant. Its use in humans is often associated with neurocognitive impairment. Whether this is due to long-term deficits in short-term memory and/or hippocampal plasticity remains unclear.

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Endocannabinoids are released 'on-demand' on the basis of physiological need, and can be pharmacologically augmented by inhibiting their catabolic degradation. The endocannabinoid anandamide is degraded by the catabolic enzyme fatty acid amide hydrolase (FAAH). Anandamide is implicated in the mediation of fear behaviors, including fear extinction, suggesting that selectively elevating brain anandamide could modulate plastic changes in fear.

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Dysregulation of dopamine (DA) homeostasis is implicated in neurodegenerative diseases, drug addiction, and neuropsychiatric disorders. The neuronal plasma membrane dopamine transporter (DAT) is essential for the maintenance of DA homeostasis in the brain. α-Synuclein is a 140-amino acid protein that forms a stable complex with DAT and is linked to the pathogenesis of neurodegenerative disease.

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Alzheimer's disease (AD) is characterized by memory loss and the upregulation of pro-neuroinflammatory factors such as cRaf-1, cyclooxygenase-2 (Cox-2), and the nuclear factor kappa B (NF-kappaB), as well as a downregulation of protein kinase A (PKA) activity and the activation by phosphorylation of its downstream factor CREB. We investigated the effect of the anti-cancer cRaf-1 inhibitor, sorafenib tosylate (Nexavar), on the expression of these factors and on the cognitive performance of aged APPswe mice. We found that chronic treatment with sorafenib stimulated PKA and CREB phosphorylation and inhibited cRaf-1 and NF-kappaB in the brains of APPswe mice.

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Alzheimer's disease (AD) is the main cause of dementia in the elderly. The discovery of new targets of therapeutic intervention is fundamental to the development of new drugs against AD pathology. Upregulation of cRaf-1 has been found post-mortem in the brains of AD patients.

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