Faculty Bibliography

Background and aim/UNASSIGNED:Resveratrol is a bioactive molecule used in dietary supplements and herbal medicines and consumed worldwide. Prior work showed that resveratrol's anti-atherogenic properties are mediated in part through the adenosine A2A receptor. The present study explores the potential contribution of adenosine A2A receptor activation to neuroprotective action of resveratrol on cognitive deficits in a model of atherosclerosis-prone systemic lupus erythematosus. Experimental procedure/UNASSIGNED:Using behavioral analysis (open field, static rod, novel object recognition) and QRT-PCR, this study measured working memory, anxiety, motor coordination, and expression of mRNA in the brain. Results and conclusion/UNASSIGNED:Data indicate that resveratrol increases working memory, on average but not statistically, and shows a trend towards improved motor coordination (p = 0.07) in atherosclerosis-prone lupus mice. Additionally, resveratrol tends to increase mRNA levels of SIRT1, decrease vascular endothelial growth factor and CX3CL1 mRNA in the hippocampus. Istradefylline, an adenosine A2A receptor antagonist, antagonizes the effects of resveratrol on working memory (p = 0.04) and the expression of SIRT1 (p = 0.03), vascular endothelial growth factor (p = 0.04), and CX3CL1 (p = 0.03) in the hippocampus.This study demonstrates that resveratrol could potentially be a therapeutic candidate in the modulation of cognitive dysfunction in neuropsychiatric lupus, especially motor incoordination. Further human studies, as well as optimization of resveratrol administration, could confirm whether resveratrol may be an additional resource available to reduce the burden of cognitive impairment associated with lupus. Additionally, further studies need to address the role of A2A blockade in cognitive function among the autoimmune population. Section/UNASSIGNED:3. Dietary therapy/nutrients supplements. Taxonomy classification by EVISE/UNASSIGNED:autoimmunity, inflammation, neurology.

Cholesterol and lipid metabolism is a broad topic that encompasses multiple aspects of cellular function in every organ [...].

The Cardiovascular Inflammation Reduction Trial (CIRT) was designed to assess whether low-dose methotrexate (LD-MTX) would reduce future cardiac events in patients with metabolic syndrome or type 2 diabetes (T2DM) who are post-myocardial infarction (MI) or have multivessel disease. Our previous work indicates that MTX confers atheroprotection via adenosine A2A receptor (A2AR) activation. In order for A2AR ligation to reduce cardiovascular events, A2AR levels would need to be preserved during MTX treatment. This study was conducted to determine whether LD-MTX alters peripheral blood mononuclear cell (PBMC) adenosine receptor expression in persons at risk for cardiovascular events. Post-MI T2DM CIRT patients were randomized to LD-MTX or placebo (n=10/group). PBMC isolated from blood drawn at enrollment and after 6 weeks were evaluated for expression of adenosine receptors and reverse cholesterol transporters by real-time PCR. Fold change between time points was calculated using factorial analyses of variance. Compared with placebo, the LD-MTX group exhibited a trend toward an increase in A2AR (p=0.06), while A3R expression was significantly decreased (p=0.01) after 6 weeks. Cholesterol efflux gene expression did not change significantly. Persistence of A2AR combined with A3R downregulation indicates that failure of MTX to be atheroprotective in CIRT was not due to loss of adenosine receptors on PBMC (ClinicalTrials.gov identifier: NCT01594333).

Traumatic Brain Injury (TBI) is a major global public health problem. Neurological damage from TBI may be mild, moderate, or severe and occurs both immediately at the time of impact (primary injury) and continues to evolve afterwards (secondary injury). In mild (m)TBI, common symptoms are headaches, dizziness and fatigue. Visual impairment is especially prevalent. Insomnia, attentional deficits and memory problems often occur. Neuroimaging methods for the management of TBI include computed tomography and magnetic resonance imaging. The location and the extent of injuries determine the motor and/or sensory deficits that result. Parietal lobe damage can lead to deficits in sensorimotor function, memory, and attention span. The processing of visual information may be disrupted, with consequences such as poor hand-eye coordination and balance. TBI may cause lesions in the occipital or parietal lobe that leave the TBI patient with incomplete homonymous hemianopia. Overall, TBI can interfere with everyday life by compromising the ability to work, sleep, drive, read, communicate and perform numerous activities previously taken for granted. Treatment and rehabilitation options available to TBI sufferers are inadequate and there is a pressing need for new ways to help these patients to optimize their functioning and maintain productivity and participation in life activities, family and community.

BACKGROUND:Alzheimer's disease (AD) is the most prevalent form of dementia worldwide and is characterized by progressive memory loss and cognitive impairment. Our understanding of AD pathogenesis is limited and no effective disease-modifying treatment is available. Mitochondria are cytoplasmic organelles critical to the homeostatic regulation of glucose and energy in the cell. METHODS:Mitochondrial abnormalities are found early in the course of AD and dysfunctional mitochondria are involved in AD progression. The resulting respiratory chain impairment, neuronal apoptosis, and generation of reactive oxygen species are highly damaging to neurons. Restoration of mitochondrial function may provide a novel therapeutic strategy for AD. RESULTS:This review discusses the specifics of mitochondrial fragmentation, imbalances in fission and fusion, and DNA damage seen in AD and the contribution of compromised mitochondrial activity to AD etiopathogenesis. It explores how an understanding of the processes underlying mitochondrial failure may lead to urgently needed treatment innovations. It considers individual mitochondrial proteins that have emerged as promising drug targets and evaluates neuroprotective agents that could improve the functional state of mitochondria in the setting of AD. CONCLUSIONS:There is great promise in exploring original approaches to preserving mitochondrial viability as a means to achieve breakthroughs in treating AD.

Prostate cancer is the second most common form of cancer in men. For advanced, high risk prostate cancer, androgen deprivation therapy (ADT) is the preferred treatment and can induce remission, but resistance to ADT brings biochemical recurrence and progression of cancer. ADT brings adverse effects such as erectile dysfunction, decreased libido, and diminished physical strength. It is estimated that between 25 and 50% of men on ADT manifest some form of cognitive dysfunction that may be self-reported or reported by a family member. There is concern that impaired cognitive function with ADT is due to loss of testosterone support. Testosterone and its metabolites are known to possess neuroprotective properties. While a direct causal relationship between ADT and cognitive decline in prostate cancer patients has not been established, this review describes the controversy surrounding the possible connection between ADT and neurocognitive deterioration. The cellular and molecular mechanisms believed to underlie the protection of neuronal integrity by androgens are discussed. Results from animal models and human clinical studies are presented. Finally, we call attention to lifestyle modifications that may minimize cognitive issues in prostate cancer patients.

OBJECTIVES/OBJECTIVE:Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease characterized by dry cough, fatigue, and progressive exertional dyspnea. Lung parenchyma and architecture is destroyed, compliance is lost, and gas exchange is compromised in this debilitating condition that leads inexorably to respiratory failure and death within 3-5 years of diagnosis. This review discusses treatment approaches to IPF in current use and those that appear promising for future development. DATA SOURCE/METHODS:The data were obtained from the Randomized Controlled Trials and scientific studies published in English literature. We used search terms related to IPF, antifibrotic treatment, lung transplant, and management. RESULTS:Etiopathogenesis of IPF is not fully understood, and treatment options are limited. Pathological features of IPF include extracellular matrix remodeling, fibroblast activation and proliferation, immune dysregulation, cell senescence, and presence of aberrant basaloid cells. The mainstay therapies are the oral antifibrotic drugs pirfenidone and nintedanib, which can improve quality of life, attenuate symptoms, and slow disease progression. Unilateral or bilateral lung transplantation is the only treatment for IPF shown to increase life expectancy. CONCLUSION/CONCLUSIONS:Clearly, there is an unmet need for accelerated research into IPF mechanisms so that progress can be made in therapeutics toward the goals of increasing life expectancy, alleviating symptoms, and improving well-being.

Primary care professionals play a critical role in the care of their patients. In clinical practice, early detection and diagnosis of Mild Cognitive Impairment, Alzheimer's disease and related dementia are often missed or delayed. Disclosure of diagnosis is not timely or not revealed. Though the methods that could improve early detection and diagnosis have remained the same over the decades with little change, they provide opportunities for early intervention, treatment and improvement in patient care. Emerging research suggests that though the disease process begins years prior to the clinical diagnosis, the healthcare system and health care professionals remain distant and reluctant to provide the service of annual cognitive assessment, which has been recommended by the Medicare program for older adults aged 65 years and older. Findings support that Alzheimer's disease and related cognitive impairments have gone under detected, underdiagnosed and undertreated. This article seeks to provide valuable and equitable information in the form of a clinician's guide for removing the barriers to early detection and diagnosis of cognitive impairments and offers an unprecedented opportunity to improve the clinical outcomes and care of older adults with various levels of cognitive decline, including mild cognitive impairment, Alzheimer's disease, and related dementias. This article provides information on understanding and addressing the challenges faced by health care professionals, including primary care clinicians; removing the barriers to cognitive assessments; educating this professional group on the importance of brain health, early detection, and diagnosis for their older adult patients; and providing these professionals with the ability to transfer their knowledge into more defined care planning. Until cognitive screening has been fully accepted and implemented for the optimal the care of older adults, health-related efforts should include the promotion and education of brain health, early detection, and diagnosis in the education of health care providers.