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Autism is a complex neurodevelopmental disorder with many associated genetic factors, including the forkhead transcription factor FOXP1. Although FOXP1's neuronal role is well-studied, the specific molecular consequences of different FOXP1 pathogenic variants in physiologically-relevant contexts are unknown. Here we ascribe the first function to Caenorhabditis elegans FKH-7/FOXP, which acts in two chemosensory neuron classes to promote the larval decision to enter the alternative, developmentally-arrested dauer life stage. We demonstrate that human FOXP1 can functionally substitute for C. elegans FKH-7 in these neurons and that engineering analogous FOXP1 hypomorphic missense mutations in the endogenous fkh-7 locus also impairs developmental decision-making. In a fkh-7/FOXP1 missense variant, single-cell transcriptomics identifies downregulated expression of autism-associated kcnl-2/KCNN2 calcium-activated potassium channel in a serotonergic sensory neuron. Our findings establish a novel framework linking two evolutionarily-conserved autism-associated genes for deeper characterization of variant-specific molecular pathology at single neuron resolution in the context of a developmental decision-making paradigm.

Background: Acute intoxication is common in patients evaluated for traumatic brain injury (TBI). However, the effect of elevated blood alcohol levels (BALs) on the diagnostic accuracy of FDA-cleared biomarkers for evaluating traumatic intracranial injury on computed tomography (CT) scan, namely, glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), has not been well studied., Methods: We investigated the effect of significantly elevated (>300 mg/dL) and modestly elevated BAL (81-300 mg/dL) at emergency department presentation on the diagnostic accuracy of GFAP and UCH-L1 for predicting a positive CT in patients presenting to 18 U.S. Level I trauma centers within 24 h of TBI as part of the prospective, Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Plasma GFAP and UCH-L1 were measured using Abbott i-STAT Alinity and ARCHITECT assays. Discrimination was evaluated using the area under the receiver operating characteristic curve (AUC)., Results: Of 2320 TRACK-TBI participants studied, 54 (2.3%), 332 (14.3%), 1209 (52.1%), and 725 (31.3%) had significantly elevated BAL, modestly elevated BAL, nonelevated BAL (0-80 mg/dL), and no BAL available, respectively; 48.3% of the cohort had a positive brain CT. Those with significantly elevated and modestly elevated BAL were more likely to have positive CT (61.1% and 60.5% vs. 46.9% and 44.0%) and had higher plasma GFAP and UCH-L1 levels than those with nonelevated BAL and no BAL available. The AUC of GFAP and UCH-L1 combined for predicting CT positivity was higher in those with significantly elevated BAL (0.949) than those with modestly elevated BAL (0.858), nonelevated BAL (0.849), and no BAL available (0.883)., Conclusions: Modestly and significantly elevated BAL does not lower the diagnostic accuracy of GFAP and UCH-L1 for predicting traumatic intracranial injury on CT. These biomarkers may be useful in decreasing avoidable brain CT imaging in persons with acute alcohol intoxication., (© 2025 Society for Academic Emergency Medicine.)

Background: Thyroid hormone is one of the most commonly prescribed medications in the United States. Misuse of and overtreatment with thyroid hormone is common in older adults and can lead to cardiovascular and skeletal adverse events. Even though deprescribing can reduce inappropriate care, no studies have yet explored specific barriers and facilitators to guide thyroid hormone deprescribing in older adults (defined as discontinuation of thyroid hormone when initiated without an appropriate indication or dose reduction in those overtreated)., Methods: We conducted semi-structured interviews with 19 endocrinologists, geriatricians, and primary care physicians who prescribe thyroid hormone. Interviews were completed between July 2020 and December 2021 via two-way video conferencing. We used both an inductive and deductive content analysis guided by the Theoretical Domains Framework to evaluate transcribed and coded participant responses. Thematic analysis characterized themes related to barriers and facilitators to thyroid hormone deprescribing practices in older adults., Results: The most commonly reported barriers to thyroid hormone deprescribing were related to patient-level factors, followed by physician- and system-level factors. Patient factors included patients' perceived need for thyroid hormone use and patient anxiety/concerns about potential side effects related to thyroid hormone dose reduction, patient lack of knowledge, and misinformation regarding deprescribing. Physician- and system-level barriers included clinic visit time constraints, physician inertia, physician lack of knowledge about deprescribing, perceived lack of sufficient patient follow-up, and electronic health record limitations. The most prominent physician-reported facilitators to thyroid hormone deprescribing were effective physician-to-patient communication, and positive physician-patient relationship, including patients' trust in their treating physician., Conclusion: Barriers and facilitators to thyroid hormone deprescribing in older adults were reported at multiple levels including patient-, physician-, and system-level factors. Interventions to improve thyroid hormone deprescribing in older adults should aim to improve patient education and expectations, increase multidisciplinary physician awareness, and overcome physician inertia., (© 2024 The American Geriatrics Society.)

Reliable methods for detecting and analyzing gene expression are necessary tools for understanding development and investigating biological responses to genetic and environmental perturbation. With its fully sequenced genome, invariant cell lineage, transparent body, wiring diagram, detailed anatomy, and wide array of genetic tools, Caenorhabditis elegans is an exceptionally useful model organism for linking gene expression to cellular phenotypes. The development of new techniques in recent years has greatly expanded our ability to detect gene expression at high resolution. Here, we provide an overview of gene expression methods for C. elegans, including techniques for detecting transcripts and proteins in situ, bulk RNA sequencing of whole worms and specific tissues and cells, single-cell RNA sequencing, and high-throughput proteomics. We discuss important considerations for choosing among these techniques and provide an overview of publicly available online resources for gene expression data., Competing Interests: Conflicts of interest: The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)