A mechanism of lysosomal calcium entry.

Lysosomal calcium (Ca2+) release is critical to cell signaling and is mediated by well-known lysosomal Ca2+ channels. Yet, how lysosomes refill their Ca2+ remains hitherto undescribed. Here, from an RNA interference screen in Caenorhabditis elegans, we identify an evolutionarily conserved gene, lci-1, that facilitates lysosomal Ca2+ entry in C. elegans and mammalian cells. We found that its human homolog TMEM165, previously designated as a Ca2+/H+ exchanger, imports Ca2+ pH dependently into lysosomes. Using two-ion mapping and electrophysiology, we show that TMEM165, hereafter referred to as human LCI, acts as a proton-activated, lysosomal Ca2+ importer. Defects in lysosomal Ca2+ channels cause several neurodegenerative diseases, and knowledge of lysosomal Ca2+ importers may provide previously unidentified avenues to explore the physiology of Ca2+ channels.

Implementation of a Naloxone Best Practice Advisory Into an Electronic Health Record.

OBJECTIVES: Naloxone is a harm reduction tool for mitigating the rising rate of opioid overdose deaths. We sought to develop and implement an alert in the electronic health record outlining which patients are at higher risk of opioid overdose and should be coprescribed naloxone. Our aim was to increase coprescribing of naloxone to qualified patients. We also endeavored to evaluate naloxone prescription volume, fill rates, and statewide dispenses before and after alert implementation. METHODS: We developed the electronic alert according to a state opioid safety initiative specifying under which conditions it should activate. We collected data on naloxone prescriptions ordered in the 5 months before and after alert implementation and unique patients with a naloxone dispense statewide. We used internal pharmacy data to evaluate the percentage of fills and used a χ 2 test to assess changes in percentage of fills. We used descriptive statistics and t tests to analyze changes in the number of prescriptions and changes in unique patients dispensed naloxone. RESULTS: We found a 2144% increase in the number of monthly naloxone prescriptions written after the alert became active. There was no statistically significant change in the percentage of fills. There was a 402.8% increase in unique patients statewide with a naloxone dispense after alert implementation. CONCLUSIONS: Designing and implementing an electronic alert prompting naloxone coprescription are feasible and were associated with substantial increases in numbers of naloxone prescriptions and patients with naloxone dispenses statewide. Our findings expand on prior literature about electronic decision support for naloxone coprescription.