Amy B. Goldstein

Launched in 2018, the National Institutes of Health (NIH) Helping to End Addiction Long-term Initiative®, or NIH HEAL Initiative, is an aggressive effort to speed scientific solutions to stem this national public health crisis. Investments in new strategies to prevent opioid misuse are a key component of this comprehensive response to the opioid epidemic. In 2019, funded through the NIH HEAL Initiative® and administered by the National Institute on Drug Abuse (NIDA), HEAL Preventing Opioid Use Disorder (HEAL Preventing OUD) research program began, filling the gap of needed upstream prevention interventions. The vision for HEAL Preventing OUD is that: Healthcare organizations and public systems will be able to make evidence-based preventive intervention services accessible to all persons who experience risk for opioid and other substance misuse or use disorder. Realizing this vision will require research investments in four strategic areas: (1) risk identification; (2) intervention development; (3) social determinants, health equity, and policy; and (4) dissemination, implementation, scale up, and sustainment. There exists tremendous potential for prevention to be a viable solution for the ongoing opioid crisis, particularly through investments in upstream, equitable, and sustainable prevention services.

Despite its solid theoretical foundations, sophisticated conceptual models, and ability to generate findings generalizable to community populations, epidemiology’s potential for influencing advances in our understanding and treatment of substance use and other psychiatric disorders remains underused. Research on the etiology of psychiatric disorders tends to be guided by biologically based approaches, such as neuroimaging, animal models, and human organoids, rather than by population-based science; workforce distribution and availability of services seldom match estimates of need; preventive interventions are often based on theoretical models from prevention science, rather than from epidemiologic findings; and policy development rarely includes a process of systematic incorporation of epidemiologic evidence. Identify all potential conflicts of interest that might be relevant to your comment. Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. Err on the side of full disclosure. If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response. Not all submitted comments are published. Please see our commenting policy for details.

Dysfunction of mitochondrial gene expression, caused by mutations in either the mitochondrial or nuclear genomes, is associated with a diverse group of human disorders characterized by impaired mitochondrial respiration. Within this group, an increasing number of mutations have been identified in nuclear genes involved in mitochondrial RNA metabolism. For instance, pathogenic mutations have been identified in the genes encoding enzymes involved in the precursor transcript processing, including ELAC2. The ELAC2 gene codes for the mitochondrial RNase Z, which is responsible for endonucleolytic cleavage of the 3’ ends of mitochondrial pre-tRNAs. Here, we report the identification of sixteen novel ELAC2 variants in individuals presenting with mitochondrial respiratory chain deficiency, hypertrophic cardiomyopathy and lactic acidosis. We provided further evidence for the pathogenicity of the three previously reported variants by studying the RNase Z activity in an in vitro system and applied this recombinant system to investigate all novel missense variants, confirming the pathogenic role of these new ELAC2 mutations. We also modelled the residues affected by missense mutation in solved RNase Z structures, providing insight into enzyme structure and function. Finally, we show that primary fibroblasts from the individuals with novel ELAC2 variants have elevated levels of unprocessed mitochondrial RNA precursors. Our study thus broadly confirms the correlation of ELAC2 variants with severe infantile-onset forms of hypertrophic cardiomyopathy and mitochondrial respiratory chain dysfunction. One rare missense variant associated with the occurrence of prostate cancer (p.Arg781His) impairs the mitochondrial RNase Z activity of ELAC2, possibly indicating a functional link between tumorigenesis and mitochondrial RNA metabolism.

The emergency department (ED) visit provides an opportunity to impact the health of the public throughout the entire spectrum of care, from prevention to treatment. As the federal government has a vested interest in funding research and providing programmatic opportunities that promote the health of the public, emergency medicine (EM) is prime to develop a research agenda to advance the field. EM researchers need to be aware of federal funding opportunities, which entails an understanding of the organizational structure of the federal agencies that fund medical research, and the rules and regulations governing applications for grants. Additionally, there are numerous funding streams outside of the National Institutes of Health (NIH; the primary federal health research agency). EM researchers should seek funding from agencies according to each agency's mission and aims. Finally, while funds from the Department of Health and Human Services (HHS) are an important source of support for EM research, we need to look beyond traditional sources and appeal to other agencies with a vested interest in promoting public health in EDs. EM requires a broad skill set from a multitude of medical disciplines, and conducting research in the field will require looking for funding opportunities in a variety of traditional and not so traditional places within and without the federal government. The following is the discussion of a moderated session at the 2009 Academic Emergency Medicine consensus conference that included panel discussants from the National Institutes of Mental Health, Drug Abuse, and Alcoholism and Alcohol Abuse and the Centers for Disease Control and Prevention (CDC). Further information is also provided to discuss those agencies and centers not represented.