Lessons Learned: The Varied Responses of Massachusetts' Local Health Departments During the COVID-19 Pandemic.

CONTEXT: Massachusetts' decentralized public health model holds tightly to its founding principle of home rule and a board of health system established in 1799. Consequently, Massachusetts has more local health departments (n = 351) than any other state. During COVID-19, each health department, steeped in centuries of independence, launched its own response to the pandemic. OBJECTIVES: To analyze local public health resources and responses to COVID-19. DESIGN: Semistructured interviews and a survey gathered quantitative and qualitative information about communities' responses and resources before and during the pandemic. Municipality demographics (American Community Survey) served as a proxy for community health literacy. We tracked the frequency and content of local board of health meetings using minutes and agendas; we rated the quality of COVID-19 communications on town Web sites. SETTING: The first 6 months of the COVID-19 pandemic in Massachusetts: March-August 2020. PARTICIPANTS: Health directors and agents in 10 south-central Massachusetts municipalities, identified as the point of contact by the Academic Public Health Corps. MAIN OUTCOME MEASURES: We measured municipality resources using self-reported budgets, staffing levels, and demographic-based estimates of community health literacy. We identified COVID-19 responses through communities' self-reported efforts, information on town Web sites, and meeting minutes and agendas. RESULTS: Municipalities excelled in communicating with residents, local businesses, and neighboring towns but lacked the staffing and funding for an efficient and coordinated response. On average, municipal budgets ranged from $5 to $16 per capita, and COVID-19 consumed 75% of health department staff time. All respondents noted extreme workload increases. While municipal Web sites received high scores for Accurate Information, other categories (Navigability; Timeliness; Information Present) were less than 50%. CONCLUSIONS: Increased support for regionalization and sustained public health funding would improve local health responses during complex emergencies in states with local public health administration.

Harmine, a natural beta-carboline alkaloid, upregulates astroglial glutamate transporter expression.

Glutamate is the predominant excitatory amino acid neurotransmitter in the mammalian central nervous system (CNS). Glutamate transporter EAAT2/GLT-1 is the physiologically dominant astroglial protein that inactivates synaptic glutamate. Previous studies have shown that EAAT2 dysfunction leads to excessive extracellular glutamate and may contribute to various neurological disorders including amyotrophic lateral sclerosis (ALS). The recent discovery of the neuroprotective properties of ceftriaxone, a beta lactam antibiotic, suggested that increasing EAAT2/GLT-1 gene expression might be beneficial in ALS and other neurological/psychiatric disorders by augmenting astrocytic glutamate uptake. Here we report our efforts to develop a new screening assay for identifying compounds that activate EAAT2 gene expression. We generated fetal derived-human immortalized astroglial cells that are stably expressing a firefly luciferase reporter under the control of the human EAAT2 promoter. When screening a library of 1040 FDA approved compounds and natural products, we identified harmine, a naturally occurring beta-carboline alkaloid, as one of the top hits for activating the EAAT2 promoter. We further tested harmine in our in vitro cell culture systems and confirmed its ability to increase EAAT2/GLT1 gene expression and functional glutamate uptake activity. We next tested its efficacy in both wild type animals and in an ALS animal model of disease and demonstrated that harmine effectively increased GLT-1 protein and glutamate transporter activity in vivo. Our studies provide potential novel neurotherapeutics by modulating the activity of glutamate transporters via gene activation. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.