Award Data

Project Summary: Alzheimer’s Disease is associated with metabolic dysfunction, glucose and insulin resistance, oxidative stress, mitochondrial dysfunction, and reduced exercise capacity. Oxidative stress and mitochondrial dysfunction correlate with the development of beta-amyloid (Aβ) deposits, one of the hallmarks of AD that begin years before the onset of memory and cognitive decline. Moreove ...

PROJECT SUMMARY/ABSTRACT The cysteine protease caspase-6 (Casp6) has been associated with neurodegenerative diseases for over fifteen years. In Alzheimer’s disease (AD), Casp6 is colocalized with amyloid plaques and tau tangles in human brain, and both human and animal model data indicate that activated Casp6 contributes to neuronal inflammation, neurodegeneration, and cleavage of proteins to to ...

PROJECT SUMMARY/ABSTRACT In response to National Institute on Aging's (NIA) strategic plan and PAS-19-317, we propose novel therapeuticsto treat Alzheimer disease and related dementias (ADRDs). We have developed novel combinations of three natural product compounds, which modulate complementary pathways in multiple types of CNS cells (i.e., neurons, microglia) associated with AD pathology. These c ...

PROJECT SUMMARY Actively involving informal caregivers in direct patient care at the bedside in the intensive care unit (ICU) has the potential to improve patient, informal caregiver, and health care system outcomes. Practice guidelines call for the liberal inclusion of informal caregivers as active partners in ICU care, but there is a critical, unmet need to develop tools that effectively operati ...

ABSTRACT / PROJECT SUMMARYAcute ischemic stroke is poised for a revolution. With the advent of mechanical thrombectomy in the last decade, the worst clots can be removed. While thrombectomy has improved outcomes, most treated patients still have severe deficits, in large part due to secondary injury caused by ischemia-reperfusion injury. To solve this problem, many neuroprotective drugs were trial ...

SUMMARY Patients with pulmonary hypertension (PH) experience low oxygen saturation, shortness of breath, low quality of life, and a short life span (lt10 years) following diagnosis. These patients frequently present to emergency rooms, and many are admitted to intensive care units (ICUs), straining the health care system. Despite therapy with phosphodiesterase-5 inhibitors, prostacyclin analogs, a ...

Abstract This fast-track STTR application proposes to enhance, validate, and scale Sepsis Watch, a deep learning sepsis detection and management system built using data from the Emergency Department (ED) Duke University Hospital (DUH). The proposal will extend and enhance Sepsis Watch to EDs, general inpatient wards, and intensive care unit (ICU) settings across multiple health systems in the Unit ...

PROJECT SUMMARY Congenital Myasthenic Syndromes (CMS) are a group of clinically similar neuromuscular transmission disorders that differ in their underlying genetic mutation. While some phenotypical variation exists, CMS are commonly characterized by muscle weakness (myasthenia) that worsens with physical exertion. Defects in Collagen Q (ColQ), a multidomain functional protein of the Neuro Muscula ...

Abstract Currently, clinically used drug abuse medications exist for treatment of addiction to opiates, alcohol, and nicotine, but not psychostimulants, such as methamphetamine (METH). Compounds that co-activate both nociceptin opioid peptide (NOP) and mu receptors have potential for treatment of drug abuse. In particular, buprenorphine, a partial mu agonist/kappa antagonist, which also acts as a ...

For more than a decade, our work has focused on development of therapeutic interventions for viral- and bacterial-induced acute lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS). Significantly, we identified the Toll-like receptor 4 (TLR4) signaling pathway as key to the host response to influenza and secondary bacterial infection following influenza. We also identif ...