Rapamycin restores peripheral blood flow in aged mice and in mouse models of atherosclerosis and Alzheimer's disease.

Peripheral artery disease (PAD), defined as reduced blood flow to the lower limbs, is a serious disorder that can lead to loss of function in the lower extremities and even loss of limbs. One of the main risk factors for PAD is age, with up to 25% of adults over the age of 55 and up to 40% over the age of 80 presenting with some form of the disease. While age is the largest risk factor for PAD, other risk factors include atherosclerosis, smoking, hypertension, and diabetes.

Genetic and pharmacologic proteasome augmentation ameliorates Alzheimer's-like pathology in mouse and fly APP overexpression models.

The proteasome has key roles in neuronal proteostasis, including the removal of misfolded and oxidized proteins, presynaptic protein turnover, and synaptic efficacy and plasticity. Proteasome dysfunction is a prominent feature of Alzheimer's disease (AD). We show that prevention of proteasome dysfunction by genetic manipulation delays mortality, cell death, and cognitive deficits in fly and cell culture AD models.

Pharmacist Allowances for the Dispensing of Emergency or Continuation of Therapy Prescription Refills and the COVID-19 Impact: A Multistate Legal Review.

The COVID-19 pandemic has taught Americans many lessons, including what can happen when our healthcare system is strained. During the pandemic, certain healthcare related activities such as seeing or contacting a practitioner to receive a prescription refill may have been a challenge for some patients that could have interfered in the patient's medication adherence and continuity of care. Given these circumstances, the pandemic also shed light on the necessity for pharmacists to dispense emergency refills, which often is based on variable state pharmacy laws and regulations.

Adenosine A1R/A3R agonist AST-004 reduces brain infarction in mouse and rat models of acute ischemic stroke.

Acute ischemic stroke (AIS) is the second leading cause of death globally. No Food and Drug Administration (FDA) approved therapies exist that target cerebroprotection following stroke. Our group recently reported significant cerebroprotection with the adenosine A1/A3 receptor agonist, AST-004, in a transient stroke model in non-human primates (NHP) and in a preclinical mouse model of traumatic brain injury (TBI).

mTOR Attenuation with Rapamycin Reverses Neurovascular Uncoupling and Memory Deficits in Mice Modeling Alzheimer's Disease.

Vascular dysfunction is a universal feature of aging and decreased cerebral blood flow has been identified as an early event in the pathogenesis of Alzheimer's disease (AD). Cerebrovascular dysfunction in AD includes deficits in neurovascular coupling (NVC), a mechanism that ensures rapid delivery of energy substrates to active neurons through the blood supply. The mechanisms underlying NVC impairment in AD, however, are not well understood.

Inborn Errors of RNA Lariat Metabolism in Humans with Brainstem Viral Infection.

Viruses that are typically benign sometimes invade the brainstem in otherwise healthy children. We report bi-allelic DBR1 mutations in unrelated patients from different ethnicities, each of whom had brainstem infection due to herpes simplex virus 1 (HSV1), influenza virus, or norovirus. DBR1 encodes the only known RNA lariat debranching enzyme.

mTOR drives cerebral blood flow and memory deficits in LDLR mice modeling atherosclerosis and vascular cognitive impairment.

We recently showed that mTOR attenuation blocks progression and abrogates established cognitive deficits in Alzheimer's disease (AD) mouse models. These outcomes were associated with the restoration of cerebral blood flow (CBF) and brain vascular density (BVD) resulting from relief of mTOR inhibition of NO release. Recent reports suggested a role of mTOR in atherosclerosis.

Rapamycin rescues vascular, metabolic and learning deficits in apolipoprotein E4 transgenic mice with pre-symptomatic Alzheimer's disease.

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice.

Risk behaviors in a rural community with a known point-source exposure to chronic wasting disease.

Background: The emergence and continuing spread of Chronic Wasting Disease (CWD) in cervids has now reached 14 U.S. states, two Canadian provinces, and South Korea, producing a potential for transmission of CWD prions to humans and other animals globally.