Integrating Commercial Healthcare Datasets for Aeromedical Risk Analyses

693KA8-22-C-00001The Federal Aviation Administration (FAA) Office of Aerospace Medicine requires comprehensive longitudinal healthcare datasets to augment internal data for the purpose of conducting safety risk assessments to update medical standards (i.e. data dirven, risk based decision making). The Federal Aviation Administration (FAA) tasked The MITRE Corporation\u2019s Center for Advanced Aviation System Development (MITRE CAASD), in its Innovation Partner role, to identify commercial healthcare datasets that hold potential value in forecasting medical risk and are suitable for integration into the Aeromedical Data Environment. MITRE CAASD performed a market survey of existing healthcare datasets available commercially or for public use. This market survey led to the identification of over 40 healthcare data sources, many of which contain numerous subordinate sets. An initial set of screening criteria ensured that candidate data sources were sufficiently suitable for modeling objectives; this screening reduced the set to three final candidate data sources. These three data sources were compared using a set of features relevant to risk modeling of aeromedically relevant outcomes by condition. This set of comparison features included their coverage of medical conditions of interest to the FAA, as well as factors impacting integration into the aeromedical data environment

Impact of bicarbonate, ammonium chloride, and acetazolamide on hepatic and renal SLC26A4 expression

SLC26A4 encodes pendrin, a transporter exchanging anions such as chloride, bicarbonate, and iodide. Loss of function mutations of SLC26A4 cause Pendred syndrome characterized by hearing loss and enlarged vestibular aqueducts as well as variable hypothyroidism and goiter. In the kidney, pendrin is expressed in the distal nephron and accomplishes HCO(3)(-) secretion and Cl(-) reabsorption. Renal pendrin expression is regulated by acid-base balance. The liver contributes to acid-base regulation by producing or consuming glutamine, which is utilized by the kidney for generation and excretion of NH(4)(+), paralleled by HCO(3)(-) formation. Little is known about the regulation of pendrin in liver. The present study thus examined the expression of Slc26a4 in liver and kidney of mice drinking tap water without or with NaHCO(3) (150 mM), NH(4)Cl (280 mM) or acetazolamide (3.6 mM) for seven days. As compared to Gapdh transcript levels, Slc26a4 transcript levels were moderately lower in liver than in renal tissue. Slc26a4 transcript levels were not significantly affected by NaHCO(3) in liver, but significantly increased by NaHCO(3) in kidney. Pendrin protein expression was significantly enhanced in kidney and reduced in liver by NaHCO(3). Slc26a4 transcript levels were significantly increased by NH(4)Cl and acetazolamide in liver, and significantly decreased by NH(4)Cl and by acetazolamide in kidney. NH(4)Cl and acetazolamide reduced pendrin protein expression significantly in kidney, but did not significantly modify pendrin protein expression in liver. The observations point to expression of pendrin in the liver and to opposite effects of acidosis on pendrin transcription in liver and kidney

DOCA sensitive pendrin expression in kidney, heart, lung and thyroid tissues

BACKGROUND/AIMS: Pendrin (SLC26A4), a transporter accomplishing anion exchange, is expressed in inner ear, thyroid gland, kidneys, lung, liver and heart. Loss or reduction of function mutations of SLC26A4 underlie Pendred syndrome, a disorder invariably leading to hearing loss with enlarged vestibular aqueducts and in some patients to hypothyroidism and goiter. Renal pendrin expression is up-regulated by mineralocorticoids such as aldosterone or deoxycorticosterone (DOCA). Little is known about the impact of mineralocorticoids on pendrin expression in extrarenal tissues. METHODS: The present study utilized RT-qPCR and Western blotting to quantify the transcript levels and protein abundance of Slc26a4 in murine kidney, thyroid, heart and lung prior to and following subcutaneous administration of 100 mg/kg DOCA. RESULTS: Slc26a4 transcript levels as compared to Gapdh transcript levels were significantly increased by DOCA treatment in kidney, heart, lung and thyroid. Accordingly pendrin protein expression was again significantly increased by DOCA treatment in kidney, heart, lung and thyroid. CONCLUSION: The observations reveal mineralocorticoid sensitivity of pendrin expression in kidney, heart, thyroid and lun