2 research outputs found
Impact of extreme weather on healthcare utilization by people with hiv in metropolitan miami
Extreme weather events (EWE) are expected to increase as climate change intensifies, leaving coastal regions exposed to higher risks. South Florida has the highest HIV infection rate in the United States, and disruptions in clinic utilization due to extreme weather conditions could affect adherence to treatment and increase community transmission. The objective of this study was to identify the association between EWE and HIV-clinic attendance rates at a large academic medical system serving the Miami-Dade communities. The following methods were utilized: (1) Extreme heat index (EHI) and extreme precipitation (EP) were identified using daily observations from 1990â2019 that were collected at the Miami International Airport weather station located 3.6 miles from the studied HIV clinics. Data on hurricanes, coastal storms and flooding were collected from the National Oceanic and Atmospheric Administration Storms Database (NOAA) for Miami-Dade County. (2) An all-HIV clinic registry identified scheduled daily visits during the study period (hurricane seasons from 2017â2019). (3) Daily weather data were linked to the all-HIV clinic registry, where patientsâ âno-showâ status was the variable of interest. (4) A time-stratified, case crossover model was used to estimate the relative risk of no-show on days with a high heat index, precipitation, and/or an extreme natural event. A total of 26,444 scheduled visits were analyzed during the 383-day study period. A steady increase in the relative risk of âno-showâ was observed in successive categories, with a 14% increase observed on days when the heat index was extreme compared to days with a relatively low EHI, 13% on days with EP compared to days with no EP, and 10% higher on days with a reported extreme weather event compared to days without such incident. This study represents a novel approach to improving local understanding of the impacts of EWE on the HIV-populationâs utilization of healthcare, particularly when the frequency and intensity of EWE is expected to increase and disproportionately affect vulnerable populations. More studies are needed to understand the impact of EWE on routine outpatient settings
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Acetylcholinesterase inhibitors enhance its folding and assembly in the endoplasmic reticulum
Acetylcholinesterase (AChE) is responsible for terminating synaptic transmission by the hydrolysis of acetylcholine (ACh) in the synaptic cleft. AChE is synthesized at a constant rate in the rough endoplasmic reticulum with only an estimated 20% of all synthesized enzyme assembling into catalytically active oligomeric forms. The overwhelming majority of the enzyme undergoes degradation through the ERAD. It is this large inactive pool we seek to understand through inâvitro analysis using human embryonic kidney cells expressing mouse acetylcholinesterase (HEKmAChE). In particular we wished to determine whether the inhibitors could rescue inactive AChE protein into catalytically active enzyme. Galantamine and Donepezil, two commonly used therapeutics for Alzheimer's disease (AD), act as active site AChE inhibitors with the purpose of allowing ACh to persist for prolonged synaptic transmission. To understand the effects of Galantamine on inactive AChE, HEKmAChE cultures were first treated with diisopropylfluorophosphate (DFP), an irreversible and membrane permeable AChE inhibitor, and then allowed to synthesize new AChE in the presence of Galantamine during a 60 minute recovery period. Preliminary results indicated a significant increase in active AChE when exposed to Galantamine in comparison to control (defined medium alone). To focus on the mechanism by which Galantamine enhances AChE folding and assembly, HEKmAChE cultures were incubated with DFP and subsequently treated with Puromycin alone or in combination with either Galantamine or Donepezil. Using Ellman's assay for AChE we observed a significant increase in catalytically active AChE in the presence of Donepezil or Galantamine. These results suggest current therapeutic treatments may be acting as molecular chaperones during the protein folding process, enabling otherwise inactive AChE bound for degradation to become catalytically active. This research was supported by the Florida Department of Health, Biomedical research program, grant 7AZ04.
This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal