The CDC Foundation's COVID-19 emergency response pilot project: a case study in knowledge brokering for older adults and caregivers.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) public health emergency has disproportionately affected older adults and their caregivers, requiring evidence-based and coordinated efforts to meet their health and social needs. This paper describes the role of the CDC Foundation as a knowledge broker working with public health partners to rapidly meet the unmet health, social, and other needs of older adults and caregivers during the COVID-19 pandemic. Type of program or service: Qualitative case study using the Role Model for Knowledge Brokering framework to describe a project that translated public health research into practice during the COVID-19 pandemic response. METHODS: This case study documents the experiences of a US-based foundation serving as a knowledge broker, carrying out three roles: establishing research partnerships to study unmet health, social, and other needs of older adults and caregivers during COVID-19; coordinating with partners to identify evidence-based strategies; and rapidly implementing four emergency response pilot projects. RESULTS: The emergency response pilot projects created included: an online resource library - -SearchFindHelp.org - of public health programs and resources for organisations serving older adults and caregivers; digital literacy training for older adults and caregivers; multicultural caregiver tools to serve rural and Asian American and Pacific Islander older adults; and a grant program to expand local, direct services for older adults. SearchFindHelp.org had 46 781 new users and 101 908 total views from June 2021-March 2023. Older adults and caregivers who participated in digital literacy training from May-September 2021 were more likely to find health resources online and schedule and attend an online doctor's visit. A paid media campaign in December 2021 was launched to raise awareness of multicultural caregiver tools. Ten community organisations expanded direct, local services for older adults. LESSONS LEARNT: This project highlights the valuable role a foundation can play as a knowledge broker in rapidly translating research into practice during a public health emergency response, to address emerging community needs.

Androgen Effects on Neural Plasticity.

Androgens are synthesized in the brain, gonads, and adrenal glands, in both sexes, exerting physiologically important effects on the structure and function of the central nervous system. These effects may contribute to the incidence and progression of neurological disorders such as autism spectrum disorder, schizophrenia, and Alzheimer's disease, which occur at different rates in males and females. This review briefly summarizes the current state of knowledge with respect to the neuroplastic effects of androgens, with particular emphasis on the hippocampus, which has been the focus of much of the research in this field.

Inhibition of 5α Reductase Impairs Cognitive Performance, Alters Dendritic Morphology and Increases Tau Phosphorylation in the Hippocampus of Male 3xTg-AD Mice.

Recent work has suggested that 5α-reduced metabolites of testosterone may contribute to the neuroprotection conferred by their parent androgen, as well as to sex differences in the incidence and progression of Alzheimer's disease (AD). This study investigated the effects of inhibiting 5α-reductase on object recognition memory (ORM), hippocampal dendritic morphology and proteins involved in AD pathology, in male 3xTg-AD mice. Male 6-month old wild-type or 3xTg-AD mice received daily injections of finasteride (50 mg/kg i.p.) or vehicle (18% ß-cyclodextrin, 1% v/b.w.) for 20 days. Female wild-type and 3xTg-AD mice received only the vehicle. Finasteride treatment differentially impaired ORM in males after short-term (3xTg-AD only) or long-term (3xTg-AD and wild-type) retention delays. Dendritic spine density and dendritic branching of pyramidal neurons in the CA3 hippocampal subfield were significantly lower in 3xTg-AD females than in males. Finasteride reduced CA3 dendritic branching and spine density in 3xTg-AD males, to within the range observed in vehicle-treated females. In the CA1 hippocampal subfield, dendritic branching and spine density were reduced in both male and female 3xTg-AD mice, compared to wild type controls. Hippocampal amyloid ß levels were substantially higher in 3xTg-AD females compared to both vehicle and finasteride-treated 3xTg-AD males. Site-specific Tau phosphorylation was higher in 3xTg-AD mice compared to sex-matched wild-type controls, increasing slightly after finasteride treatment. These results suggest that 5α-reduced neurosteroids may play a role in testosterone-mediated neuroprotection and may contribute to sex differences in the development and severity of AD.

Basal p38 mitogen-activated protein kinase regulates unliganded glucocorticoid receptor function in airway smooth muscle cells.

Like many steroid receptors, the glucocorticoid (GC) receptor (GR) is a phosphoprotein. Although there are multiple phosphorylation sites critical for GR transcriptional activity (i.e., serine [S]203, S211, and S226), their respective role in driving GR functions is highly cell specific. We have recently identified protein phosphatase 5 as an essential Ser/Thr phosphatase responsible for impairing GR function via S211 dephosphorylation in airway smooth muscle (ASM) cells. Because p38 mitogen-activated protein kinase (MAPK) directly phosphorylates GR in different cell types in a stimulus- and cell-dependent manner, we investigated the role of p38 MAPK on GR phosphorylation and function in ASM cells. Cells were transfected with 100 nM p38 MAPK small interfering RNA or 2 µg MAPK kinase 3 expression vector (a specific kinase that directly activates p38 MAPK) in the presence or absence of fluticasone (100 nM) and/or p38 MAPK pharmacological inhibitor SB203580. We found that p38 MAPK blockade positively regulates GR nuclear translocation and GR-dependent induction of the steroid-target gene GC-induced leucine zipper in a hormone-independent manner. We also found that p38 MAPK-dependent regulation of GR functions was associated with a differential action on GR phosphorylation at S203 and S211 residues. This study demonstrated that the inactive state of GR in resting conditions is not only ensured by the absence of the GC ligand but also by p38 MAPK-dependent phosphorylation of unliganded GR at specific residues, which appears to be important in determining the overall GC responsiveness of ASM cells.