Differential mosquito attraction to humans is associated with skin-derived carboxylic acid levels.

Some people are more attractive to mosquitoes than others, but the mechanistic basis of this phenomenon is poorly understood. We tested mosquito attraction to human skin odor and identified people who are exceptionally attractive or unattractive to mosquitoes. These differences were stable over several years. Chemical analysis revealed that highly attractive people produce significantly more carboxylic acids in their skin emanations. Mutant mosquitoes lacking the chemosensory co-receptors Ir8a, Ir25a, or Ir76b were severely impaired in attraction to human scent, but retained the ability to differentiate highly and weakly attractive people. The link between elevated carboxylic acids in "mosquito-magnet" human skin odor and phenotypes of genetic mutations in carboxylic acid receptors suggests that such compounds contribute to differential mosquito attraction. Understanding why some humans are more attractive than others provides insights into what skin odorants are most important to the mosquito and could inform the development of more effective repellents.

Non-canonical odor coding in the mosquito.

Aedes aegypti mosquitoes are a persistent human foe, transmitting arboviruses including dengue when they feed on human blood. Mosquitoes are intensely attracted to body odor and carbon dioxide, which they detect using ionotropic chemosensory receptors encoded by three large multi-gene families. Genetic mutations that disrupt the olfactory system have modest effects on human attraction, suggesting redundancy in odor coding. The canonical view is that olfactory sensory neurons each express a single chemosensory receptor that defines its ligand selectivity. We discovered that Ae. aegypti uses a different organizational principle, with many neurons co-expressing multiple chemosensory receptor genes. In vivo electrophysiology demonstrates that the broad ligand-sensitivity of mosquito olfactory neurons depends on this non-canonical co-expression. The redundancy afforded by an olfactory system in which neurons co-express multiple chemosensory receptors may increase the robustness of the mosquito olfactory system and explain our long-standing inability to disrupt the detection of humans by mosquitoes.

Small-Molecule Agonists of Ae. aegypti Neuropeptide Y Receptor Block Mosquito Biting.

Female Aedes aegypti mosquitoes bite humans to obtain blood to develop their eggs. Remarkably, their strong attraction to humans is suppressed for days after the blood meal by an unknown mechanism. We investigated a role for neuropeptide Y (NPY)-related signaling in long-term behavioral suppression and discovered that drugs targeting human NPY receptors modulate mosquito host-seeking. In a screen of all 49 predicted Ae. aegypti peptide receptors, we identified NPY-like receptor 7 (NPYLR7) as the sole target of these drugs. To obtain small-molecule agonists selective for NPYLR7, we performed a high-throughput cell-based assay of 265,211 compounds and isolated six highly selective NPYLR7 agonists that inhibit mosquito attraction to humans. NPYLR7 CRISPR-Cas9 null mutants are defective in behavioral suppression and resistant to these drugs. Finally, we show that these drugs can inhibit biting and blood-feeding on a live host, suggesting a novel approach to control infectious disease transmission by controlling mosquito behavior. VIDEO ABSTRACT.

A Taste Circuit that Regulates Ingestion by Integrating Food and Hunger Signals.

Ingestion is a highly regulated behavior that integrates taste and hunger cues to balance food intake with metabolic needs. To study the dynamics of ingestion in the vinegar fly Drosophila melanogaster, we developed Expresso, an automated feeding assay that measures individual meal-bouts with high temporal resolution at nanoliter scale. Flies showed discrete, temporally precise ingestion that was regulated by hunger state and sucrose concentration. We identify 12 cholinergic local interneurons (IN1, for "ingestion neurons") necessary for this behavior. Sucrose ingestion caused a rapid and persistent increase in IN1 interneuron activity in fasted flies that decreased proportionally in response to subsequent feeding bouts. Sucrose responses of IN1 interneurons in fed flies were significantly smaller and lacked persistent activity. We propose that IN1 neurons monitor ingestion by connecting sugar-sensitive taste neurons in the pharynx to neural circuits that control the drive to ingest. Similar mechanisms for monitoring and regulating ingestion may exist in vertebrates.

Progeria: a paradigm for translational medicine.

Rare diseases are powerful windows into biological processes and can serve as models for the development of therapeutic strategies. The progress made on the premature aging disorder Progeria is a shining example of the impact that studies of rare diseases can have.

Multimodal integration of carbon dioxide and other sensory cues drives mosquito attraction to humans.

Multiple sensory cues emanating from humans are thought to guide blood-feeding female mosquitoes to a host. To determine the relative contribution of carbon dioxide (CO2) detection to mosquito host-seeking behavior, we mutated the AaegGr3 gene, a subunit of the heteromeric CO2 receptor in Aedes aegypti mosquitoes. Gr3 mutants lack electrophysiological and behavioral responses to CO2. These mutants also fail to show CO2-evoked responses to heat and lactic acid, a human-derived attractant, suggesting that CO2 can gate responses to other sensory stimuli. Whereas attraction of Gr3 mutants to live humans in a large semi-field environment was only slightly impaired, responses to an animal host were greatly reduced in a spatial-scale-dependent manner. Synergistic integration of heat and odor cues likely drive host-seeking behavior in the absence of CO2 detection. We reveal a networked series of interactions by which multimodal integration of CO2, human odor, and heat orchestrates mosquito attraction to humans.

Opposing dopaminergic and GABAergic neurons control the duration and persistence of copulation in Drosophila.

Behavioral persistence is a major factor in determining when and under which circumstances animals will terminate their current activity and transition into more profitable, appropriate, or urgent behavior. We show that, for the first 5 min of copulation in Drosophila, stressful stimuli do not interrupt mating, whereas 10 min later, even minor perturbations are sufficient to terminate copulation. This decline in persistence occurs as the probability of successful mating increases and is promoted by approximately eight sexually dimorphic, GABAergic interneurons of the male abdominal ganglion. When these interneurons were silenced, persistence increased and males copulated far longer than required for successful mating. When these interneurons were stimulated, persistence decreased and copulations were shortened. In contrast, dopaminergic neurons of the ventral nerve cord promote copulation persistence and extend copulation duration. Thus, copulation duration in Drosophila is a product of gradually declining persistence controlled by opposing neuronal populations using conserved neurotransmission systems.

In vivo base editing rescues Hutchinson-Gilford progeria syndrome in mice.

Hutchinson-Gilford progeria syndrome (HGPS or progeria) is typically caused by a dominant-negative C•G-to-T•A mutation (c.1824 C>T; p.G608G) in LMNA, the gene that encodes nuclear lamin A. This mutation causes RNA mis-splicing that produces progerin, a toxic protein that induces rapid ageing and shortens the lifespan of children with progeria to approximately 14 years1-4. Adenine base editors (ABEs) convert targeted A•T base pairs to G•C base pairs with minimal by-products and without requiring double-strand DNA breaks or donor DNA templates5,6. Here we describe the use of an ABE to directly correct the pathogenic HGPS mutation in cultured fibroblasts derived from children with progeria and in a mouse model of HGPS. Lentiviral delivery of the ABE to fibroblasts from children with HGPS resulted in 87-91% correction of the pathogenic allele, mitigation of RNA mis-splicing, reduced levels of progerin and correction of nuclear abnormalities. Unbiased off-target DNA and RNA editing analysis did not detect off-target editing in treated patient-derived fibroblasts. In transgenic mice that are homozygous for the human LMNA c.1824 C>T allele, a single retro-orbital injection of adeno-associated virus 9 (AAV9) encoding the ABE resulted in substantial, durable correction of the pathogenic mutation (around 20-60% across various organs six months after injection), restoration of normal RNA splicing and reduction of progerin protein levels. In vivo base editing rescued the vascular pathology of the mice, preserving vascular smooth muscle cell counts and preventing adventitial fibrosis. A single injection of ABE-expressing AAV9 at postnatal day 14 improved vitality and greatly extended the median lifespan of the mice from 215 to 510 days. These findings demonstrate the potential of in vivo base editing as a possible treatment for HGPS and other genetic diseases by directly correcting their root cause.

Nuclear-localized, iron-bound superoxide dismutase-2 antagonizes epithelial lineage programs to promote stemness of breast cancer cells via a histone demethylase activity.

The dichotomous behavior of superoxide dismutase-2 (SOD2) in cancer biology has long been acknowledged and more recently linked to different posttranslational forms of the enzyme. However, a distinctive activity underlying its tumor-promoting function is yet to be described. Here, we report that acetylation, one of such posttranslational modifications (PTMs), increases SOD2 affinity for iron, effectively changing the biochemical function of this enzyme from that of an antioxidant to a demethylase. Acetylated, iron-bound SOD2 localizes to the nucleus, promoting stem cell gene expression via removal of suppressive epigenetic marks such as H3K9me3 and H3K927me3. Particularly, H3K9me3 was specifically removed from regulatory regions upstream of Nanog and Oct-4, two pluripotency factors involved in cancer stem cell reprogramming. Phenotypically, cells expressing nucleus-targeted SOD2 (NLS-SOD2) have increased clonogenicity and metastatic potential. FeSOD2 operating as H3 demethylase requires H2O2 as substrate, which unlike cofactors of canonical demethylases (i.e., oxygen and 2-oxoglutarate), is more abundant in tumor cells than in normal tissue. Therefore, our results indicate that FeSOD2 is a demethylase with unique activities and functions in the promotion of cancer evolution toward metastatic phenotypes.

Plasma Progerin in Patients With Hutchinson-Gilford Progeria Syndrome: Immunoassay Development and Clinical Evaluation.

BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) is an ultrarare, fatal, premature aging disease caused by a toxic protein called progerin. Circulating progerin has not been previously detected, precluding research using readily available biological samples. This study aimed to develop a plasma progerin assay to evaluate progerin's quantity, response to progerin-targeted therapy, and relationship to patient survival. METHODS: Biological samples were collected by The Progeria Research Foundation Cell and Tissue Bank from a non-HGPS cohort cross-sectionally and a HGPS cohort longitudinally. HGPS donations occurred at baseline and intermittently while treated with farnesylation inhibitors lonafarnib±pravastatin and zoledronate, within 3 sequential open-label clinical trials at Boston Children's Hospital totaling >10 years of treatment. An ultrasensitive single-molecule counting progerin immunoassay was developed with prespecified performance parameters. Intra- and interpatient group statistics were descriptive. The relationship between progerin and survival was assessed by using joint modeling with time-dependent slopes parameterization. RESULTS: The assay's dynamic detection range was 59 to 30 000 pg/mL (R2=0.9987). There was no lamin A cross-reactivity. Mean plasma progerin in non-HGPS participants (n=69; 39 male, 30 female; age, 0.2-71.3 years) was 351±251 pg/mL, and in drug-naive participants with HGPS (n=74; 37 female, 37 male; age, 2.1-17.5 years) was 33 261±12 346 pg/mL, reflecting a 95-fold increase in affected children (P<0.0001). Progerin levels did not differ by sex (P=0.99). Lonafarnib treatment resulted in an average per-visit progerin decrease from baseline of between 35% to 62% (all P<0.005); effects were not augmented by adding pravastatin and zoledronate. Progerin levels fell within 4 months of therapy and remained lower for up to 10 years. The magnitude of progerin decrease positively associated with patient survival (P<0.0001; ie, 15 000 pg/mL decrease yields a 63.9% decreased risk of death). For any given decrease in progerin, life expectancy incrementally increased with longer treatment duration. CONCLUSIONS: A sensitive, quantitative immunoassay for progerin was developed and used to demonstrate high progerin levels in HGPS plasma that decreased with lonafarnib therapy. The extent of improved survival was associated with both the magnitude of progerin decrease and duration at lower levels. Thus, plasma progerin is a biomarker for HGPS whose reduction enables short- and long-term assessment of progerin-targeted treatment efficacy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifiers: NCT00879034 and NCT00916747.

Epidemiological characteristics of patients with Hutchinson-Gilford progeria syndrome and progeroid laminopathies in China.

BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) and progeroid laminopathies (PL) are extremely rare genetic diseases with extremely poor prognoses. This study aims to investigate the epidemiological and genotypic characteristics of patients with HGPS/PL in China. METHODS: Using a cross-sectional study design, general characteristics and genotypic data of 46 patients with HGPS/PL from 17 provinces in China were analyzed. RESULTS: Among the 46 patients with HGPS/PL, 20 patients are HGPS, and the rest are PL; the identified total prevalence of HGPS/PL is 1/23 million. Among 42 patients with gene reports, 3 carried compound heterozygous mutations in the ZMPSTE24 while the other 39 carried LMNA mutations. Among PL, LMNA c.1579 C > T homozygous mutation was the most common. The onset of classic genotype HGPS is skin sclerosis in the first month after birth. The primary clinical manifestations of PL patients include skin abnormalities, growth retardation, and joint stiffness. The median age of onset for PL was 12 (6,12) months. CONCLUSIONS: In China, the identified total prevalence of HGPS/PL is 1/23 million. 92.8% of the genetic mutations of HGPS/PL were located in LMNA, and the rest in ZMPSTE24. Most patients of HGPS/PL have skin abnormalities as the earliest manifestation. Compared to PL, the classic genotype HGPS starts earlier. IMPACT STATEMENT: Hutchinson-Gilford progeria syndrome (HGPS) and progeroid laminopathies (PL) are extremely rare genetic diseases with extremely poor prognoses. To date, there is a paucity of epidemiological data related to HGPS/PL in China. This study first examined the genotypic, phenotypic, and prevalence characteristics of 40-50% of the cases of HGPS/PL in mainland China through a collaborative international registry effort. In China, the identified total prevalence of HGPS/PL is 1/23 million. 92.8% of the genetic mutations of HGPS/PL are located in LMNA. LMNA c.1579 C > T homozygous mutations are the most common form of gene mutations among the Chinese PL population.

Safety Responsiveness and Psychological Distress Among Health Care Workers During COVID-19 (2020-2022) in the Pacific Northwest.

Objectives. The COVID-19 pandemic imposed unprecedented safety challenges on health care facilities. This study examined whether health care workers who deemed a better safety response to the pandemic by their units or employers experienced lower psychological distress. Methods. Patient care workers at a health care system in the Pacific Northwest were surveyed every 6 to 8 months from May 2020 to May 2022 (n = 3468). Psychological distress was measured with the Well-being Index (range: -2 to 7 points). Safety response was scored on the basis of participants' ratings (on a 1-5 scale) of equipment sufficiency and responsiveness to safety concerns by their health care system and unit. Results. Adjusted multilevel regressions showed an inverse association between safety responsiveness and psychological distress at the individual level (b = -0.54; 95% confidence interval [CI] = -0.67, -0.41) and the unit level (b = -0.73; 95% CI = -1.46, -0.01). The cross-level interaction was also statistically significant (b = -0.46; 95% CI = -0.87, -0.05). Conclusions. Health care workers who deemed a better response to safety challenges reported lower psychological distress. This study highlights the need for continued efforts to ensure adequate safety resources. (Am J Public Health. 2024;114(S2):S204-S212. https://doi.org/10.2105/AJPH.2024.307582).

Variant ionotropic glutamate receptors as chemosensory receptors in Drosophila.

Ionotropic glutamate receptors (iGluRs) mediate neuronal communication at synapses throughout vertebrate and invertebrate nervous systems. We have characterized a family of iGluR-related genes in Drosophila, which we name ionotropic receptors (IRs). These receptors do not belong to the well-described kainate, AMPA, or NMDA classes of iGluRs, and they have divergent ligand-binding domains that lack their characteristic glutamate-interacting residues. IRs are expressed in a combinatorial fashion in sensory neurons that respond to many distinct odors but do not express either insect odorant receptors (ORs) or gustatory receptors (GRs). IR proteins accumulate in sensory dendrites and not at synapses. Misexpression of IRs in different olfactory neurons is sufficient to confer ectopic odor responsiveness. Together, these results lead us to propose that the IRs comprise a novel family of chemosensory receptors. Conservation of IR/iGluR-related proteins in bacteria, plants, and animals suggests that this receptor family represents an evolutionarily ancient mechanism for sensing both internal and external chemical cues.

A natural variant and engineered mutation in a GPCR promote DEET resistance in C. elegans.

DEET (N,N-diethyl-meta-toluamide) is a synthetic chemical identified by the US Department of Agriculture in 1946 in a screen for repellents to protect soldiers from mosquito-borne diseases1,2. Since its discovery, DEET has become the world's most widely used arthropod repellent and is effective against invertebrates separated by millions of years of evolution-including biting flies3, honeybees4, ticks5, and land leeches3. In insects, DEET acts on the olfactory system5-12 and requires the olfactory receptor co-receptor Orco7,9-12, but exactly how it works remains controversial13. Here we show that the nematode Caenorhabditis elegans is sensitive to DEET and use this genetically tractable animal to study the mechanism of action of this chemical. We found that DEET is not a volatile repellent, but instead interferes selectively with chemotaxis to a variety of attractant and repellent molecules. In a forward genetic screen for DEET-resistant worms, we identified a gene that encodes a single G protein-coupled receptor, str-217, which is expressed in a single pair of chemosensory neurons that are responsive to DEET, called ADL neurons. Mis-expression of str-217 in another chemosensory neuron conferred responses to DEET. Engineered str-217 mutants, and a wild isolate of C. elegans that carries a str-217 deletion, are resistant to DEET. We found that DEET can interfere with behaviour by inducing an increase in average pause length during locomotion, and show that this increase in pausing requires both str-217 and ADL neurons. Finally, we demonstrated that ADL neurons are activated by DEET and that optogenetic activation of ADL neurons increased average pause length. This is consistent with the 'confusant' hypothesis, which proposes that DEET is not a simple repellent but that it instead modulates multiple olfactory pathways to scramble behavioural responses10,11. Our results suggest a consistent motif in the effectiveness of DEET across widely divergent taxa: an effect on multiple chemosensory neurons that disrupts the pairing between odorant stimulus and behavioural response.

An analysis of suspected microplastics in the muscle and gastrointestinal tissues of fish from Sarasota Bay, FL: exposure and implications for apex predators and seafood consumers.

Microplastics have been found in the gastrointestinal (GI) fluid of bottlenose dolphins (Tursiops truncatus), inhabiting Sarasota Bay, FL, suggesting exposure by ingestion, possibly via contaminated fish. To better understand the potential for trophic transfer, muscle and GI tissues from 11 species of dolphin prey fish collected from Sarasota Bay were screened for microplastics (particles <5 mm diameter). Suspected microplastics were found in 82% of muscle samples (n=89), and 97% of GI samples (n=86). Particle abundance and shapes varied by species (p<0.05) and foraging habit (omnivore vs. carnivore, p<0.05). Pinfish (Lagodon rhomboides) had the highest particle abundance for both tissue types (muscle: 0.38 particles/g; GI: 15.20 particles/g), which has implications for dolphins as they are a common prey item. Findings from this study support research demonstrating the ubiquity of estuarine plastic contamination and underscore the risks of ingestion exposure for wildlife and potentially seafood consumers.

Oncogenic KRAS G12C: Kinetic and redox characterization of covalent inhibition.

The recent development of mutant-selective inhibitors for the oncogenic KRASG12C allele has generated considerable excitement. These inhibitors covalently engage the mutant C12 thiol located within the phosphoryl binding loop of RAS, locking the KRASG12C protein in an inactive state. While clinical trials of these inhibitors have been promising, mechanistic questions regarding the reactivity of this thiol remain. Here, we show by NMR and an independent biochemical assay that the pKa of the C12 thiol is depressed (pKa ∼7.6), consistent with susceptibility to chemical ligation. Using a validated fluorescent KRASY137W variant amenable to stopped-flow spectroscopy, we characterized the kinetics of KRASG12C fluorescence changes upon addition of ARS-853 or AMG 510, noting that at low temperatures, ARS-853 addition elicited both a rapid first phase of fluorescence change (attributed to binding, Kd = 36.0 ± 0.7 µM) and a second, slower pH-dependent phase, taken to represent covalent ligation. Consistent with the lower pKa of the C12 thiol, we found that reversible and irreversible oxidation of KRASG12C occurred readily both in vitro and in the cellular environment, preventing the covalent binding of ARS-853. Moreover, we found that oxidation of the KRASG12C Cys12 to a sulfinate altered RAS conformation and dynamics to be more similar to KRASG12D in comparison to the unmodified protein, as assessed by molecular dynamics simulations. Taken together, these findings provide insight for future KRASG12C drug discovery efforts, and identify the occurrence of G12C oxidation with currently unknown biological ramifications.

Employee Cardiometabolic Risk Following a Cluster-Randomized Workplace Intervention From the Work, Family and Health Network, 2009-2013.

Objectives. To examine whether workplace interventions to increase workplace flexibility and supervisor support and decrease work-family conflict can reduce cardiometabolic risk. Methods. We randomly assigned employees from information technology (n = 555) and long-term care (n = 973) industries in the United States to the Work, Family and Health Network intervention or usual practice (we collected the data 2009-2013). We calculated a validated cardiometabolic risk score (CRS) based on resting blood pressure, HbA1c (glycated hemoglobin), HDL (high-density lipoprotein) and total cholesterol, height and weight (body mass index), and tobacco consumption. We compared changes in baseline CRS to 12-month follow-up. Results. There was no significant main effect on CRS associated with the intervention in either industry. However, significant interaction effects revealed that the intervention improved CRS at the 12-month follow-up among intervention participants in both industries with a higher baseline CRS. Age also moderated intervention effects: older employees had significantly larger reductions in CRS at 12 months than did younger employees. Conclusions. The intervention benefited employee health by reducing CRS equivalent to 5 to 10 years of age-related changes for those with a higher baseline CRS and for older employees. Trial Registration. ClinicalTrials.gov Identifier: NCT02050204. (Am J Public Health. 2023;113(12):1322-1331. https://doi.org/10.2105/AJPH.2023.307413).

Timing From Symptom Onset to Hip Arthroscopy Does Not Affect Patient-Reported Outcome Measures for the Treatment of Femoroacetabular Impingement in Adolescent Patients.

PURPOSE: To evaluate symptom duration and its relationship to patient-reported outcomes (PROs) and survivorship after hip arthroscopy in adolescents. METHODS: Patients ≤18 at time of primary hip arthroscopy for femoroacetabular impingement (FAI) between January 2011 and September 2018 were included. Exclusion criteria consisted of history of previous ipsilateral hip surgery, presence of osteoarthritis or dysplasia on preoperative radiographs, previous hip fracture, or history of slipped capital femoral epiphysis or Legg-Calve-Perthes disease. Minimum 2-year PROs (modified Harris Hip Score, Hip Outcome Score [HOS]-Activities of Daily Living, HOS-Sport Scale, Short Forms 12 [SF-12]), minimum clinically significant difference (MCID) and patient-acceptable symptom state (PASS) rates, and revision surgery rates were compared based on symptom duration. RESULTS: Two-year minimal follow-up was obtained for 111 patients (134 hips) (80%), including 74 females and 37 males with a mean age of 16.4 ± 1.1 (range 13.0-18.0). The mean symptom duration was 17.2 ± 15.2 months (range 43 days to 6.0 years). Ten patients (11 hips), 6 females (7 hips) and 4 males, required revision surgery at an average of 2.3 ± 1.0 years (range 0.9-4.3 years). At a mean follow-up of 4.8 ± 2.2 years (range 2-10 years), there were statistically significant improvements in all PROs (P < .05 for all). Symptom duration showed no significant correlation to post-operative scores (correlation coefficient range -0.162 to -0.078, P > .05 for all). Symptom duration ≤12 months versus >12 months or as a continuous variable was not a predictor for requiring revision surgery or achieving MCID/PASS (95% confidence interval crosses 1 for all). CONCLUSIONS: In an adolescent cohort of symptomatic FAI patients who underwent hip arthroscopy, there is no difference in PRO measures when analyzing symptom duration by arbitrary time intervals or as a continuous variable. LEVEL OF EVIDENCE: Level IV, case series.

Social Network Analysis of Diffusion Among American Indian Youth in a Culturally Adapted, Family-focused Prevention Program.

Diffusion can contribute to the spread of preventive intervention effects from participants to non-participants, but best practices for randomized trials prevent contamination of conditions. These practices conflict with cultural values of community benefit, which are salient among American Indians. This study embedded social network measures within a randomized trial of the Bii-Zin-Da-De-Dah (BZDDD) family-focused prevention program to characterize youth's social networks, describe the nature and content of sharing, and test for diffusion effects on cultural engagement (ethnic identification, cultural socialization, cultural practices) and substance use. Participants were 256 American Indian youths enrolled in the trial who provided self-reports of their social networks and indicated whether specific program content was shared with or received from others, while completing cultural engagement and substance use questionnaires across three waves. Results indicated that social networks were comprised mainly of peers and same-age family members (e.g., cousins). Program sharing was not uncommon. For example, 51% of responding intervention youth reported talking with non-participants about BZDDD at wave 2, typically (53%) with similar-age friends and family who were, most often (71%), out of the home. Evidence for diffusion effects was limited, but did indicate that control youth who had some exposure to BZDDD had a significantly higher average cultural/ethnic identity scale score at wave 2 and were more likely to ask an elder for advice than control youth who had no BZDDD exposure in adjusted analyses. Findings illustrate the value of measuring and testing for potential effects of diffusion in prevention trials with American Indians.

Accuracy of Emergency Medicine Residents Using Point-of-Care Ultrasound (POCUS) to Detect Retained Stingray Barbs.

BACKGROUND: Stingray envenomation is a common presenting complaint for coastal emergency departments in the United States. Currently, radiograph is the gold standard to evaluate for a retained stingray barb, but ultrasound may be a useful tool to detect retained barbs. OBJECTIVE: To determine if emergency medicine residents could use ultrasound to identify stingray barbs embedded in animal tissue models. A secondary objective was to determine if resident experience affected their ability to detect stingray barbs. METHODS: Thirty-two emergency medicine residents participated in the study. After a short didactic session on foreign body identification with ultrasound, they rotated through six simulation stations and were asked to identify whether a stingray barb was present in pig and chicken tissue models. They were given 2 min per model to identify the presence, size, and depth of a stingray barb. Pre- and postexperiment surveys were collected to assess the residents' level of experience and confidence regarding foreign body identification using ultrasound. RESULTS: Residents accurately identified barbs in chicken drumsticks with a sensitivity of 72.92% (95% confidence interval [CI] 63.89-81.48) and a specificity of 64.58% (95% CI 54.16-74.08), and in pig's feet with a sensitivity of 50.00% (95% CI 39.62-60.38) and specificity of 68.75% (95% CI 58.48-77.82). There was no statistically significant difference regarding accuracy for any outcome measured based on experience or level of training. CONCLUSIONS: The use of point-of-care ultrasound by novice sonographers lacks sensitivity to identify retained stingray barbs in animal models and is not significantly impacted by resident experience with point-of-care ultrasound.