Aeromedical Risk of Migraine.

INTRODUCTION: Migraine is a common condition that can carry considerable risk to aeromedical duties. Because randomized controlled trials are not an appropriate method to evaluate flight safety risk for medical conditions that may cause subtle or sudden incapacitation, the determination of fitness-to-fly must be based on risk assessments informed by extrapolated evidence. Therefore, we conducted a review of current literature to provide background information to inform the aeromedical risk assessment of migraine using a risk matrix approach.METHODS: We identified studies on topics pertinent to conducting an aeromedical risk assessment of migraine. We generated an overview of the literature synthesizing the findings of articles retrieved from searches of Scopus, Ovid, PubMed, and the Cochrane Library published in English from all years, in both general and aircrew populations. International headache and neurology guidelines, as well as headache policies from the U.S. Air Force, were also reviewed.RESULTS: This review includes information on the following topics relevant to conducting an evidence-based risk assessment of migraine: diagnosis, prevalence, incidence, natural course, clinical presentation, triggers, comorbidities, neuroimaging, implications of family history, and efficacy of pharmacological and nonpharmacological therapies.DISCUSSION: This review summarizes current literature on migraine for use in a risk matrix approach to the aeromedical assessment of migraine in prospective and current aircrew. Awareness of the most current epidemiological data related to a variety of migraine parameters facilitates an evidence-based risk assessment of migraine in aircrew and requires iterative updates as new information becomes available.Mainland RL, Skinner CR, Saary J. Aeromedical risk of migraine. Aerosp Med Hum Perform. 2024; 95(2):101-112.

Individual components of the SWI/SNF chromatin remodelling complex have distinct roles in memory neurons of the Drosophila mushroom body.

Technology has led to rapid progress in the identification of genes involved in neurodevelopmental disorders such as intellectual disability (ID), but our functional understanding of the causative genes is lagging. Here, we show that the SWI/SNF chromatin remodelling complex is one of the most over-represented cellular components disrupted in ID. We investigated the role of individual subunits of this large protein complex using targeted RNA interference in post-mitotic memory-forming neurons of the Drosophila mushroom body (MB). Knockdown flies were tested for defects in MB morphology, short-term memory and long-term memory. Using this approach, we identified distinct roles for individual subunits of the Drosophila SWI/SNF complex. Bap60, Snr1 and E(y)3 are required for pruning of the MBγ neurons during pupal morphogenesis, while Brm and Osa are required for survival of MBγ axons during ageing. We used the courtship conditioning assay to test the effect of MB-specific SWI/SNF knockdown on short- and long-term memory. Several subunits, including Brm, Bap60, Snr1 and E(y)3, were required in the MB for both short- and long-term memory. In contrast, Osa knockdown only reduced long-term memory. Our results suggest that individual components of the SWI/SNF complex have different roles in the regulation of structural plasticity, survival and functionality of post-mitotic MB neurons. This study highlights the many possible processes that might be disrupted in SWI/SNF-related ID disorders. Our broad phenotypic characterization provides a starting point for understanding SWI/SNF-mediated gene regulatory mechanisms that are important for development and function of post-mitotic neurons.

Optimal RNA isolation method and primer design to detect gene knockdown by qPCR when validating Drosophila transgenic RNAi lines.

OBJECTIVE: RNA interference is employed extensively in Drosophila research to study gene function within a specific cell-type or tissue. Thousands of transgenic Drosophila lines have been generated to express double stranded RNA for gene knockdown; however, no standardized method exists for quantifying their knockdown efficiency. Since antibodies are not available for many proteins, quantitative real-time PCR is often used. Here, we explore how primer design and RNA isolation method can influence detection of gene knockdown using qPCR. RESULTS: We tested differences in detected gene knockdown efficiency when using purified polyadenylated mRNA or total RNA as templates for cDNA synthesis. We also tested two different primer locations for each gene: one to amplify a region 5' of the RNAi cut site, and one to amplify a region 3' of the cut site. Consistently, the strongest gene knockdown was detected when qPCR was performed using 5' primer sets in combination with mRNA-derived cDNA. Our results indicate that detection of undegraded mRNA cleavage fragments can result in underestimation of true knockdown efficiency for a RNAi construct. Purification of polyadenylated mRNA, combined with primers designed to amplify the non-polyadenylated 5' mRNA cleavage fragment can avoid this problem.