The Chatbot Assessment Reporting Tool (CHART) is a reporting guideline developed to provide reporting recommendations for studies evaluating the performance of generative artificial intelligence (AI)-driven chatbots when summarizing clinical evidence and providing health advice, referred to as Chatbot Health Advice (CHA) studies. CHART was developed in several phases after performing a comprehensive systematic review to identify variation in the conduct, reporting and methodology in CHA studies. Findings from the review were used to develop a draft checklist that was revised through an international, multidisciplinary modified asynchronous Delphi consensus process of 531 stakeholders, three synchronous panel consensus meetings of 48 stakeholders, and subsequent pilot testing of the checklist. CHART includes 12 items and 39 subitems to promote transparent and comprehensive reporting of CHA studies. These include Title (subitem 1a), Abstract/Summary (subitem 1b), Background (subitems 2ab), Model Identifiers (subitem 3ab), Model Details (subitems 4abc), Prompt Engineering (subitems 5ab), Query Strategy (subitems 6abcd), Performance Evaluation (subitems 7ab), Sample Size (subitem 8), Data Analysis (subitem 9a), Results (subitems 10abc), Discussion (subitems 11abc), Disclosures (subitem 12a), Funding (subitem 12b), Ethics (subitem 12c), Protocol (subitem 12d), and Data Availability (subitem 12e). The CHART checklist and corresponding methodological diagram were designed to support key stakeholders including clinicians, researchers, editors, peer reviewers, and readers in reporting, understanding, and interpreting the findings of CHA studies.

IMPORTANCE: The rise in chatbot health advice (CHA) studies is accompanied by heterogeneity in reporting standards, impacting their interpretability. OBJECTIVE: To provide reporting recommendations for studies evaluating the performance of generative artificial intelligence (AI)-driven chatbots when summarizing clinical evidence and providing health advice. DESIGN, SETTING, AND PARTICIPANTS: CHART was developed in several phases after performing a comprehensive systematic review to identify variation in the conduct, reporting, and methodology in CHA studies. Findings from the review were used to develop a draft checklist that was revised through an international, multidisciplinary modified asynchronous Delphi consensus process of 531 stakeholders, 3 synchronous panel consensus meetings of 48 stakeholders, and subsequent pilot testing of the checklist. RESULTS: CHART includes 12 items and 39 subitems to promote transparent and comprehensive reporting of CHA studies. These include title (subitem 1a), abstract or summary (subitem 1b), background (subitems 2ab), model identifiers (subitem 3ab), model details (subitems 4abc), prompt engineering (subitems 5ab), query strategy (subitems 6abcd), performance evaluation (subitems 7ab), sample size (subitem 8), data analysis (subitem 9a), results (subitems 10abc), discussion (subitems 11abc), disclosures (subitem 12a), funding (subitem 12b), ethics (subitem 12c), protocol (subitem 12d), and data availability (subitem 12e). CONCLUSIONS AND RELEVANCE: The CHART checklist and corresponding methodological diagram were designed to support key stakeholders including clinicians, researchers, editors, peer reviewers, and readers in reporting, understanding, and interpreting the findings of CHA studies.

BACKGROUND: The Chatbot Assessment Reporting Tool (CHART) is a reporting guideline developed to provide reporting recommendations for studies evaluating the performance of generative artificial intelligence (AI)-driven chatbots when summarizing clinical evidence and providing health advice, referred to as Chatbot Health Advice (CHA) studies. METHODS: CHART was developed in several phases after performing a comprehensive systematic review to identify variation in the conduct, reporting, and methodology in CHA studies. Findings from the review were used to develop a draft checklist that was revised through an international, multidisciplinary modified asynchronous Delphi consensus process of 531 stakeholders, three synchronous panel consensus meetings of 48 stakeholders, and subsequent pilot testing of the checklist. RESULTS: CHART includes 12 items and 39 subitems to promote transparent and comprehensive reporting of CHA studies. These include Title (subitem 1a), Abstract/Summary (subitem 1b), Background (subitems 2ab), Model Identifiers (subitems 3ab), Model Details (subitems 4abc), Prompt Engineering (subitems 5ab), Query Strategy (subitems 6abcd), Performance Evaluation (subitems 7ab), Sample Size (subitem 8), Data Analysis (subitem 9a), Results (subitems 10abc), Discussion (subitems 11abc), Disclosures (subitem 12a), Funding (subitem 12b), Ethics (subitem 12c), Protocol (subitem 12d), and Data Availability (subitem 12e). CONCLUSION: The CHART checklist and corresponding methodological diagram were designed to support key stakeholders including clinicians, researchers, editors, peer reviewers, and readers in reporting, understanding, and interpreting the findings of CHA studies.

3D printing holds great promise to revolutionize pharmaceutical manufacturing, so for widespread clinical application, it is imperative to evaluate its safety and maximize its benefits. Herein, for the first time, particle emissions of the printing process of a model drug (fluorescein) were monitored in a test chamber to evaluate release. A filament extrusion-type 3D printer was used to make tablets from filaments loaded with fluorescein prepared by hot melt extrusion (HME) or diffusion (passive loading) techniques. Surface contamination of the printer was qualitatively documented. Average concentrations of fluorescein released into air during printing were below the analytical limit of detection for HME and 0.92 ± 0.20 ng/m(3) for diffusion. Particle yield from the aerodynamic particle sizer data (#/g extruded) during printing with HME filament (5.01 x 10(4)) was significantly lower (p < 0.05) compared with diffusion filament (1.07 x 10(6)). Mathematical modeling was used to predict where particles might deposit in the respiratory system if inhaled by a worker. Predictions showed larger fractions of particles deposited in the head and pulmonary (alveolar) regions from diffusion-loaded filament compared with HME, albeit non-significant. Fluorescein was transferred onto personal protective equipment (gloves) and printer surfaces, which indicated potential for dermal exposure and cross-contamination. Assuming our results are representative of active pharmaceutical ingredients, they support the importance of controls such as containment to minimize inhalation exposure and housekeeping to minimize dermal exposure and cross-contamination of tablets.

INTRODUCTION: Associations between screen time and health outcomes among teenagers are well established. However, most studies use parent-reported information, which may misrepresent the magnitude or nature of these associations. In addition, timely nationally representative estimates are needed to correspond with evolving screen use. This study aimed to address these gaps by using data from a nationally representative survey of teenagers. METHODS: Data came from the 2021-2023 National Health Interview Survey-Teen (NHIS-Teen), a follow-back web-based survey designed to collect health information directly from teenagers aged 12 to 17 years. NHIS-Teen provides a unique opportunity to assess teenagers' self-reported health in conjunction with a rich set of parent-reported covariates, including family income, from the National Health Interview Survey. This study examines associations between high daily non-schoolwork screen time, defined as 4 or more hours of daily screen time, and adverse health outcomes across the domains of physical activity, sleep, weight, mental health, and perceived support. RESULTS: Teenagers with higher non-schoolwork screen use were more likely to experience a series of adverse health outcomes, including infrequent physical activity, infrequent strength training, being infrequently well-rested, having an irregular sleep routine, weight concerns, depression symptoms, anxiety symptoms, infrequent social and emotional support, and insufficient peer support. CONCLUSION: Results of this study include associations between high screen time and poor health among teenagers using self-reported data. Future work may further investigate these associations and their underlying mechanisms, including the content viewed on screens and the interactions taking place across screens.

Tobacco cigarette smoking is the leading cause of preventable diseases and death in the US. Exposure to secondhand smoke (SHS) can also cause heart disease, lung cancer, and respiratory illness. Cotinine (COT) and trans-3'-hydroxycotinine (HCT) are the primary metabolites of nicotine, the main addictive alkaloid in tobacco products. For many years, we have measured serum levels of COT and HCT in National Health and Nutritional Examination Survey (NHANES) participants to monitor exposure of the U.S. population to active smoking and SHS. As exposure to SHS is decreasing, a more sensitive analytical method is needed to detect the lower levels of these biomarkers for SHS assessment. We developed and validated a new automated method for the detection of COT and HCT in human serum. We implemented a new liquid handling automation system to aliquot and prepare samples using supported liquid extraction. Samples were analyzed by liquid chromatography-tandem mass spectrometry. The new automated sample preparation method increases sample throughput by reducing sample cleanup time to 2 hours for preparing a 96-well plate. The method has excellent sensitivity, specificity, precision (<10%), and accuracy (±15%). We were able to lower the estimated limit of detection (LOD) for COT by 33% and HCT by 73% from our previous LOD. The new LODs for COT and HCT are 0.010 ng/mL and 0.004 ng/mL, respectively. These lower LODs would enable better detection of SHS in future NHANES surveys.

BACKGROUND: Patients reporting sexual contact with a person(s) with chlamydia (CT) and/or gonorrhea (NG) are at increased risk of acquiring these sexually transmitted infections (STIs). Presumptive antimicrobial therapy is recommended for sexual contacts, but concerns have been raised about unnecessary antibiotic use. METHODS: We reviewed visits of patients who reported sexual contact to a partner with CT or NG ("contacts") from 1/2021-10/2023 in 10 STI clinics. We calculated CT and NG positivity, stratified by 3 patient groups (women, men who have sex with men [MSM], and men who have sex with women only [MSW]) and symptomatic status. RESULTS: Overall, 11,072 (6.8%) CT and/or NG contacts were identified (7,660 [4.7%] CT contacts and 4,988 [3.1%] NG contacts). CT positivity among CT contacts was 35%; NG positivity among NG contacts was 31%. CT positivity did not differ by symptomatic status across patient groups. NG positivity was higher for symptomatic vs. asymptomatic MSM (34%, 95% confidence interval [CI] 31-37% vs 28% [CI 26-30%]) and MSW (37%, CI 33-41% vs 23%, CI 20-27%), but not in women (38%, CI 33-43% vs 37%, CI 32-42%). CONCLUSIONS: Substantial CT/NG positivity among sexual contacts to CT or NG was observed. Among CT contacts, CT infection was most often detected in MSW; among NG contacts, NG infection was most often detected in women. However, ~60% did not have either CT or NG. The use of point-of-care tests in this population may optimize antimicrobial use while prioritizing individual clinical care.

OBJECTIVES: Cruise ship settings can facilitate transmission of respiratory infections. In March 2020, a COVID-19 outbreak occurred on the Grand Princess cruise ship. We describe the public health response, including a large-scale US federal quarantine intended to limit spread to communities not yet affected by COVID-19. METHODS: All US residents and symptomatic people requiring hospitalization disembarked beginning on March 9 and were transported to designated US military bases for federal quarantine or to hospitals or alternate care sites for medical care. Foreign nationals remained on board (crew) or were repatriated (passengers). People under federal quarantine were monitored daily for symptoms and tested voluntarily for SARS-CoV-2 upon arrival, as tests became available, and if symptoms developed. RESULTS: Of 3582 travelers (passengers and crew) on board, 2013 (56%) went to military bases, 59 (2%) went to hospitals or alternate care sites, 419 (12%) were repatriated, and the remainder (crew) quarantined on board. Overall, 1144 travelers (32%) were tested for SARS-CoV-2; of those, 155 (14%) had a positive test result. Among 2013 US residents quarantined, 1054 (52%) were tested. Of those, 115 (11%) had a positive test result, 37 (32%) of whom were symptomatic at testing. Proportions tested across bases ranged from 28% to 89%; test positivity ranged from 10% to 16%. Of 31 travelers hospitalized, the median (IQR) stay was 4 (4-9) nights, and 9 (29%) travelers died of SARS-CoV-2 complications. CONCLUSIONS: The Grand Princess outbreak was the first confirmed COVID-19 outbreak on a cruise ship in US waters. Multiagency public health responses allowed for isolation and quarantine, potentially helping to slow transmission into US communities. Ensuring that cruise ships have plans for communicable disease control and mitigation helps protect passenger and crew well-being.

IMPORTANCE: Enterovirus D68 (EV-D68) typically causes mild to severe acute respiratory illness (ARI). Testing and surveillance for EV-D68 in the US are limited, and important epidemiologic gaps remain. OBJECTIVE: To characterize the epidemiology and clinical severity of EV-D68 among US children seeking care for ARI from 2017 to 2022, using a multisite, active, systematic surveillance network. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study collected data from the New Vaccine Surveillance Network, an active, prospective, population-based surveillance system of emergency departments (EDs) and hospitals at 7 US academic medical centers. Children with ARI and EV-D68-positive results were enrolled during platform-wide EV-D68 testing periods (July to October 2017, July to November 2018, July to November 2020, and July 2021 to December 2022). Included children were aged younger than 18 years, reported 1 or more qualifying ARI symptoms, with a symptom duration less than 14 days at enrollment. Data were analyzed from in October 2024. EXPOSURES: Laboratory-confirmed EV-D68 infection, including overall infections or those without viral codetection. MAIN OUTCOMES AND MEASURES: Trends and characteristics of EV-D68, including demographics, underlying conditions, and clinical severity by health care setting, were explored. Among hospitalized children with EV-D68-positive results without viral codetection, multivariable logistic regression was used to examine factors associated with receipt of (1) supplemental oxygen or (2) intensive care. RESULTS: From 2017 to 2022, 976 children with EV-D68-positive results were identified (median [IQR] age, 47 [18-63] months; 391 [40.1%] female); most were enrolled in 2018 (382 children) and 2022 (533 children). Among these, 856 had no viral codetection, of which 320 were discharged home from the ED (median [IQR] age, 33 [16-59] months; 180 male [56.3%]; 237 [74.1%] with no reported underlying conditions) and 536 were hospitalized (median [IQR] age, 40 [19-69] months; 330 male [61.6%]; 268 [50.0%] with no reported underlying conditions). Among those hospitalized, 199 (37.1%) reported a history of asthma or reactive airway disease (RAD) and 77 (14.4%) reported a condition other than asthma or RAD. Having an underlying condition other than asthma or RAD was associated with increased odds of receiving supplemental oxygen (adjusted odds ratio, 2.72; 95% CI, 1.43-5.18) or intensive care admission (adjusted odds ratio, 3.09; 95% CI, 1.72-5.56); neither age group nor history of asthma or RAD were associated with oxygen receipt or intensive care admission. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of children with medically attended EV-D68 infections, EV-D68 was associated with severe disease in otherwise healthy children of all ages, and children with nonasthma or RAD comorbidities were at higher risk for severe outcomes when hospitalized.

We report the complete genome sequences of four parechovirus-A3 (PeV-A3) isolates from Children's Mercy Kansas City (CMKC), United States of America (USA): PeV-A3-MO-12-CMKC/CSF/MO/USA/2012 (isolated in 2012 from cerebrospinal fluid), PeV-A3-8C-CMKC/CSF/MO/USA/2022/ (isolated in 2022 from cerebrospinal fluid), PeV-A3-9C-CMKC/CSF/MO/USA/2022 (isolated in 2022 from cerebrospinal fluid), and PeV-A3-11B-CMKC/Blood/MO/USA/2022 (isolated in 2022 from blood). Sequence analysis revealed multiple mutations throughout the genome of the PeV-A3 isolates in comparison to the prototypic PeV-A3 A308/99 reference sequence (AB084913). Several unique amino acid changes were observed in the PeV-A3 isolates from 2022 that were absent in the PeV-A3 isolate from 2012. Phylogenetic analysis comparison determined that the sequenced PeV-A3 isolates from 2022 cluster together as a separate clade.

Background: Performance of thyroid function assays can vary significantly. To address this issue, the Centers for Disease Control and Prevention (CDC) Clinical Standardization Programs conducted an interlaboratory comparison of free thyroxine (fT4) immunoassays (IAs) and laboratory-developed tests (LDTs). This assessment aimed to determine the current performance characteristics of these assays as a first step toward measurement standardization. Thyrotropin (TSH) IAs were also evaluated. Methods: Assays measured 41 blinded individual-donor sera, including a sample from a pregnant woman (for fT4 analysis only) and three serum pools, with 11.3-32.1 pmol/L (0.881-2.49 ng/dL) fT4 and 0.337-21.6 mIU/L TSH in duplicate over 2 days. Passing-Bablok regression analysis performed pre-recalibration compared assays performance to the CDC fT4 reference measurement procedure (RMP) or TSH all-lab mean (ALM). Additionally, the impact of linear regression-based recalibration of assays to the CDC fT4 RMP or TSH ALM was estimated. Inter-assay agreement of sample classification according to the assay-specific reference interval (RI) was assessed pre- and post-recalibration. Results: A total of 21 fT4 and 17 TSH assays participated. Pre-recalibration, median biases of TSH measurements to the ALM were -1.2% [confidence interval or CI -1.8% to -0.4%], and good classification agreement among TSH assays was observed. fT4 assays all showed a negative median bias to the RMP, with higher bias among IAs (median: -20.3%, CI [-21.5% to -19.4%]) than LDTs (median: -4.5%, [CI -6.1% to -3.2%]). Of the individual-donor sera, only 21 out of 40 samples were classified uniformly by all fT4 assays, indicating poor inter-assay agreement. Post-recalibration, agreement improved to 33 out of 40 individual-donor sera correctly classified by all tested IAs and LDTs. Similar improvement in post-recalibration median percent bias was observed for fT4 IAs (median: -0.2, [CI -1.2% to 0.6%]) and LDTs (median: -0.3%, [CI -2.5% to 1.4%]). Conclusions: The comparison among fT4 assays emphasizes the need for measurement standardization to improve accuracy and comparability. This and previous studies demonstrate the possibility to develop common fT4 RIs via standardization, enabling the use of evidence-based clinical guidelines universally in patient care. Recalibration can effectively address high variability in fT4 assays, ensuring consistent diagnostic classification.

PURPOSE: Per- and polyfluoroalkyl substances (PFAS) are associated with multiple health effects including pregnancy-induced hypertension and pre-eclampsia, increased serum hepatic enzymes, increased in serum lipids, decreased antibody response to vaccines, and decreased birth weight. Millions of US workers are exposed to PFAS at their workplaces. Our objective was to estimate the serum levels of the five PFAS that are most frequently detected in the US general population(perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDA), and perfluorononanoic acid (PFNA)) among US adult workers. METHODS: Participants were 4476 workers aged ≥ 20 years with PFAS analyte results available who participated in the National Health and Nutrition Examination Survey (NHANES), 2005-2014. Geometric mean serum levels of PFAS (ng/mL) were obtained across industry and occupation groups using the PFAS subsample weight in SAS-callable SUDAAN V11. RESULTS: Among 21 industry groups, the highest geometric mean PFAS levels (ng/mL) were observed in Construction (PFOS = 12.61 ng/mL, PFOA = 3.76, PFHxS = 2.10, PFNA = 1.23, and PFDA = 0.33), followed by Utilities (PFOS = 12.46), and Real Estate/Rental/Leasing (PFOS = 12.15). The lowest geometric mean PFAS levels were seen in Private Households (PFOS = 6.34, PFOA = 2.12, PFHxS=0.75, PFNA = 0.86, and PFDA = 0.25). Among 22 occupation groups, the highest geometric mean PFAS levels were observed in Life/Physical/Social Science occupations (PFOS = 13.19, PFOA = 3.54, PFHxS= 1.69, PFNA = 1.23, and PFDA = 0.33), followed by Installation/Maintenance/Repair occupations (PFOS = 12.75), and Construction/Extraction occupations (PFOS = 12.15). The lowest geometric mean PFAS levels were found in Personal Care/Service occupations (PFOS = 7.25, PFOA = 2.43, PFHxS = 1.07, PFNA = 0.94, and PFDA = 0.25). CONCLUSIONS: Some industry and occupation groups had higher geometric mean levels of PFAS in serum compared to others. Further investigation of these industries and occupations may result in a better understanding of the sources and degree of occupational exposure to PFAS.

OBJECTIVES: To identify associations between perceived neighborhood walkability and sleep across racial and ethnic groups of US adults. METHODS: Data from the 2020 National Health Interview Survey (N=27,521) were used to assess self-reported measures of walkability (pedestrian access, accessible amenities, unsafe walking conditions) and sleep (short and long duration; frequency of waking up unrested, trouble falling and staying asleep, sleep medication use). Stratified by racial and ethnic group, we calculated the age-adjusted prevalence of neighborhood walkability features and sleep measures and estimated prevalence ratios assessing associations between neighborhood walkability and sleep while adjusting for sociodemographic and health covariates. RESULTS: The prevalence of unsafe walking conditions due to crime was lowest among non-Hispanic White adults (6.9%), and access to places to relax was lowest among non-Hispanic Black adults (72.5%). The prevalence of short sleep duration was highest among non-Hispanic Black adults (37.9%). Neighborhood environment features had differential associations with sleep when stratified by race and ethnicity. For example, walking path access was related to lower sleep medication use among non-Hispanic Asian adults (adjusted prevalence ratio (aPR): 0.42, 95% CI: 0.19-0.91) but greater use among non-Hispanic White adults (aPR: 1.24, 95% CI: 1.05-1.46). More associations were observed among non-Hispanic White adults than other groups; and the strongest magnitude of association was observed among non-Hispanic Asian adults (traffic and sleep medication aPR: 0.31, 95% CI: 0.12-0.84). CONCLUSIONS: Associations between the neighborhood environment and sleep vary and may be inconsistent by race and ethnicity. Future research may help identify determinants.

Little cigars are similar to cigarettes, with respect to dimensions, filters, and overall appearance. Some smokers also use little cigars as substitutes for cigarettes. Comparison of little cigars with cigarettes is relevant to understanding their respective public health impact. To understand their relative toxicities, mainstream smoke yields of benzo[a]pyrene (B[a]P), a human carcinogen, were measured for 60 commercial little cigars. The little cigars were smoked on a linear smoking machine using the International Organization of Standardization (ISO) nonintense and Canadian Intense (CI) smoking regimens followed by analysis with a validated gas chromatography/mass spectrometry (GC/MS) method. The average analytical quantitative variability of the measured little cigar constituents was lower compared to previously tested commercial cigarettes (%RSD 9.6 vs 14.5, respectively). B[a]P yields ranged from 14.5-44.0 ng/cigar (ISO) and 24.0-65.7 ng/cigar (CI). The mean ISO yield is 25.5 ng/cigar versus the CI yield of 42.2 ng/cigar, which are 2.5- and 2-fold greater, respectively, than the corresponding mean cigarette yields. When normalized to tobacco weight, B[a]P yields of the little cigars are 1.5- (ISO) and 1.3- (CI) fold greater than cigarette yields. B[a]P smoke yields are known to correlate with tobacco weight. The little cigar B[a]P yield correlations to tobacco weight (CI R(2) = 0.35; ISO R(2) = 0.24) are similar to cigarette yield correlations (CI R(2) = 0.31; ISO R(2) = 0.21). Other physical properties (i.e., filter length, filter ventilation, and packing density) that may impact B[a]P smoke yields for the little cigars had very weak correlations. Except for cigarette packing density, cigars and cigarettes have similar correlations between B[a]P yields and physical design parameters. In summary, the little cigars, although physically similar to cigarettes, differ in smoke chemistry by generating higher B[a]P yields, even when normalized to tobacco weight.

BACKGROUND: Parent-reported surveys are commonly used in child health research. However, few national surveys have examined concordance between parent- and teen-reported Adverse Childhood Experiences (ACEs). OBJECTIVE: To examine concordance between parent- and teen-reported ACEs among a nationally representative sample of teens and understand sociodemographic correlates of concordance. PARTICIPANTS AND SETTING: Data were collected as part of the National Health Interview Survey (NHIS), an annual nationally representative survey of the United States, with parent-reported interviews and its follow-back survey, the National Health Interview Survey-Teen (NHIS-Teen), a self-administered web survey of youth aged 12-17 years. METHODS: Parent- and teen-reported ACEs, and several measures of concordance (e.g. weighted Cohen's kappa, prevalence adjusted bias adjusted kappa (PABAK)) are presented. Unadjusted logistic regressions tested associations between sociodemographic characteristics and likelihood of concordance for each ACE. RESULTS: ACEs prevalence based on parent report were lower compared to teen report (e.g. victim of or witnessed violence in the neighborhood, 6.5 % parent-reported vs. 15.5 %, teen-reported). Weighted Cohen's kappa statistics showed fair to moderate agreement (ks ranging from 0.27 to 0.53), with PABAK statistics showing slightly higher levels (ks ranging from 0.41 to 0.88). CONCLUSIONS: There is discordance in ACEs reporting between teens and their parents, with parents less likely to report that their teen experience an ACE than teens are. This emphasizes the importance of collecting information directly from teenagers, which may help inform intervention work.

The 2015-16 Zika virus epidemic emerged in the Americas and rapidly spread throughout the region and beyond, showing the epidemic potential of this mosquito-borne Orthoflavivirus and its capacity to cause severe congenital malformations and neurological sequelae. WHO declared the Zika virus epidemic a public health emergency of international concern in 2016. Despite this declaration, there are no licensed Zika virus vaccines, therapeutics, or diagnostic tests appropriate for routine antenatal screening. To address this absence of essential tools to detect and mitigate the threat of future Zika virus outbreaks, a group of global experts developed a priority agenda for Zika virus research and development. This Series paper summarises crucial challenges and knowledge gaps and outlines a comprehensive strategy to advance research, surveillance, global capacity, policy, and investment for Zika virus preparedness and response.

BACKGROUND: Synergists reduce insecticide metabolism in mosquitoes by competing with insecticides for the active sites of metabolic enzymes, such as cytochrome P450s (CYPs). This increases the availability of the insecticide at its specific target site. The combination of both insecticides and synergists increases the toxicity of the mixture. Given the demonstrated resistance to the classical insecticides in numerous Anopheles spp., the use of synergists is becoming increasingly pertinent. Tropical plants synthesize diverse phytochemicals, presenting a repository of potential synergists. METHODS: Extracts prepared from medicinal plants found in Jamaica were screened against recombinant Anopheles gambiae CYP6M2 and CYP6P3, and Anopheles funestus CYP6P9a, CYPs associated with anopheline resistance to pyrethroids and several other insecticide classes. The toxicity of these extracts alone or as synergists, was evaluated using bottle bioassays with the insecticide permethrin. RNA sequencing and in silico modelling were used to determine the mode of action of the extracts. RESULTS: Aqueous extracts of Piper amalago var. amalago inhibited CYP6P9a, CYP6M2, and CYP6P3 with IC(50)s of 2.61 ± 0.17, 4.3 ± 0.42, and 5.84 ± 0.42 μg/ml, respectively, while extracts of Kalanchoe pinnata, inhibited CYP6M2 with an IC(50) of 3.52 ± 0.68 μg/ml. Ethanol extracts of P. amalago var. amalago and K. pinnata displayed dose-dependent insecticidal activity against An. gambiae, with LD(50)s of 368.42 and 282.37 ng/mosquito, respectively. Additionally, An. gambiae pretreated with K. pinnata (dose: 1.43 μg/mosquito) demonstrated increased susceptibility (83.19 ± 6.14%) to permethrin in a bottle bioassay at 30 min compared to the permethrin only treatment (0% mortality). RNA sequencing demonstrated gene modulation for CYP genes in anopheline mosquitoes exposed to 715 ng of ethanolic plant extract at 24 h. In silico modelling showed good binding affinity between CYPs and the plants' secondary metabolites. CONCLUSION: This study demonstrates that extracts from P. amalago var. amalago and K. pinnata, with inhibitory properties, IC(50) < 6.95 μg/ml, against recombinant anopheline CYPs may be developed as natural synergists against anopheline mosquitoes. Novel synergists can help to overcome metabolic resistance to insecticides, which is increasingly reported in malaria vectors.

The organophosphate pesticide coumaphos is used to control Cattle Tick Fever carried by multiple species of ticks and is a known hazard for workers treating livestock. The USDA Cattle Fever Tick Eradication Program requires regular blood draws to measure depressed cholinesterase levels as biomarkers of effect of long-term coumaphos exposure, however, the gap between blood draws may miss intermittent high exposures. Urine biomonitoring can supplement blood draws, offering personnel a sensitive and cost-effective method to monitor short-term exposures. Our objective was to improve and validate a previously published method to analyze the coumaphos metabolite 3‑chloro-7‑hydroxy-4-methylcoumarin (CHMC). Urine samples were hydrolyzed with glucuronidase and then extracted prior to analysis with high-performance liquid chromatography-fluorescence detection. Calibration curves were linear over a wide CHMC range (0.49 – 250.07 ng/mL) with a method detection limit of 0.06 ng/mL. This research will help establish an accessible urine biomonitoring method for assessing coumaphos exposures. • The modified bioanalytical method maintained high sensitivity and specificity while reducing duration of the sample treatment steps and the chromatographic program. • Method validation tests followed the acceptance criteria guidelines in the NIOSH Manual of Analytical Methods. • CHMC levels were measured in workers exposed to coumaphos during livestock treatment. © 2025

BACKGROUND: Previous studies have demonstrated associations of persistent organic pollutants (POPs) with sex-related hormones; however, findings were inconsistent. Sex-specific impacts and pathways through which adiposity influences associations are not completely understood. We sought to evaluate sex-specific associations of POPs serum concentration with sex-related hormones and to explore pathways through which adiposity may modify associations. METHODS: We studied 1,073 men and 716 postmenopausal women participating in the "Persistent Organic Pollutants, Endogenous Hormones, and Diabetes in Latinos" ancillary study which is a subcohort of the "Hispanic Community Health Study/Study of Latinos." We use baseline examination data collected from 2008-2011 to investigate associations between eight organochlorine pesticides (OCPs), five polychlorinated biphenyls (PCB) groups, sum of polybrominated diphenyl ethers and polybrominated biphenyl 153 on sex hormone binding globulin (SHBG) and various sex-related hormone levels. We examined associations cross-sectionally using linear and logistic regression models adjusted for complex survey design and confounders. RESULTS: PCBs and select OCPs were associated with increased SHBG in women and decreased estradiol (E2) and/or bioavailable E2 in men. For instance, per quartile increase in serum concentrations of ∑PCBs and oxychlordane were associated with decreased levels of E2 (β=-6.36 pmol/L; 95% CI:-10.7,-2.02 and β=-5.08 pmol/L; 95% CI:-8.11,-2.05) and bioavailable E2 (β=-4.48 pmol/L; 95% CI:-7.22,-1.73 and β=-4.23 pmol/L; 95% CI:-6.17,-2.28), respectively, in men, and increased levels of SHBG (β=7.25 nmol/L; 95% CI:2.02,12.8 and β=9.42 nmol/L; 95% CI:4.08,15.0), respectively, in women. p,p'-DDT and β-HCCH, and o,p'-DDT were also associated with decreased testosterone (T) and bioavailable T (ng/dL) levels in men. Adiposity modified associations in men, revealing stronger inverse associations of PCBs, PBDEs, and several OCPs with LH, SHBG, E2, bioavailable E2, T, and the ratios of LH to FSH and E2 to T in those with below median body mass index and waist-to-hip ratio. CONCLUSION: Distinct patterns of hormone dysregulation with increasing POPs serum concentration were identified in men and post-menopausal women. In men but less so in postmenopausal women, adiposity modified associations of POPs serum concentration with sex-related hormones.

BACKGROUND: Diabetes affects millions of people in the United States and poses significant health and economic challenges, but it can be prevented or managed through health behavior changes. Such changes might be aided by voice-activated personal assistants (VAPAs), which offer interactive and real-time assistance through features such as reminders, or obtaining health information. However, there are little data on interest and acceptability of integrating VAPAs into programs such as the National Diabetes Prevention Program (National DPP) or diabetes, self-management, education, and support (DSMES) services. METHODS: We conducted individual and small-group semi-structured interviews of National DPP and DSMES staff and program participants. We used rapid-turnaround qualitative thematic analysis to identify emerging themes using an adapted version of the Consolidated Framework for Implementation Research (CFIR). RESULTS: Nearly all program participants and staff had prior experience with VAPAs, but not in the context of these programs. Most program participants felt confident in their ability to use VAPAs but were concerned about their privacy and security. Program staff were optimistic about the feasibility of integrating VAPAs into existing programs given their ability to support healthy habit formation, but staff were less optimistic about using VAPAs to share health information. Program staff also felt that additional resources to support VAPA use would help ensure that VAPAs would not create an extra burden on staff and program participants. IMPLICATIONS: Integrating VAPAs as a resource to enhance mobile applications already in use shows potential to support health behavior change. Future research should include how this technology could be further optimized to enhance utility.

We compared the number of Aedes aegypti females per trap and the number of detections of this mosquito species per week during 8 wk in 3 types of autocidal gravid traps, the Centers for Disease Control and Prevention (CDC) Autocidal Gravid Ovitrap (AGO), Biogents Gravid Aedes Trap (GAT), and Singapore Gravitrap (SGT), in central Puerto Rico. These traps use the same principles for attracting gravid Ae. aegypti females as traditional ovitraps, such as dark colors, standing water, and decomposing plant materials. The traps differ in size, AGO being the biggest and SGT the smallest. Average captures of female Ae. aegypti per trap per week were 11.1, 7.2, and 1.7 in AGO, GAT, and SGT traps, respectively, a pattern consistent with the sizes of the traps. These results indicated that GAT traps and SGT traps captured 35.5% and 84.7% fewer females of Ae. aegypti, respectively, than AGO traps. Although Ae. aegypti was present in all 20 sites during the 8 wk of observations, AGO, GAT, and SGT traps did not catch specimens in 1, 9, and 58 out of 160 observations per trap type (trap-wk), respectively. Trap failures were 1, 6, and 1 for the AGO, GAT, and SGT traps, respectively. Despite the absence of females of Ae. aegypti at some sites and weeks in each of the traps, all 3 traps were able to detect the presence of this mosquito at each of the 20 sites during the 8 wk of observations and could be used for Ae. aegypti surveillance.

BACKGROUND: Community-based management of acute malnutrition is an effective treatment model for severe acute malnutrition. However, sparse evidence exists on post-discharge outcomes and the sustainability of recovery. This study aimed to evaluate the risk and determinants of relapse following severe acute malnutrition recovery in high-burden settings. METHODS: This multi-country prospective cohort study followed children who had recovered from severe acute malnutrition and their non-malnourished peers in parallel for 6 months in Mali (nine sites), South Sudan (six sites), and Somalia (one site). Nutritional status was assessed by research staff at nutrition clinics monthly to obtain the proportion of children exposed to severe acute malnutrition who relapsed to acute malnutrition and the relative risk of developing acute malnutrition for exposed versus non-exposed (ie, previously non-malnourished) children. Exposed children were eligible if they had been discharged from community-based management of acute malnutrition programmes while aged 6-47 months. Non-exposed children were eligible if they had not had an episode of acute malnutrition in the previous year; non-exposed children were matched to exposed children by age, sex, and community. Acute malnutrition was defined as having a mid-upper arm circumference of less than 125 mm, a weight-for-height Z score of less than -2, or nutritional oedema. The primary outcome was the cumulative incidence of acute malnutrition at 6 months in the exposed and non-exposed cohorts. Relapse was defined as an episode of acute malnutrition among exposed children during the 6-month follow-up period. FINDINGS: Between April 9, 2021, and June 2, 2022, 2749 children were enrolled (1689 exposed and 1060 non-exposed). After 6 months, 30% (95% CI 25-34) of children previously exposed to severe acute malnutrition relapsed in Mali, 63% (95% CI 59-67) in South Sudan, and 22% (95% CI 19-25) in Somalia. Depending on the context, exposed children were 1·2-6·2 times more likely to have acute malnutrition compared with non-exposed children. Higher anthropometric measurements at discharge were protective against relapse; however, few other child-level or household-level factors at the time of discharge were associated with subsequent relapse. After discharge, children experiencing food insecurity or morbidity at time of follow-up were more likely to relapse than those who were not experiencing these factors. INTERPRETATION: Following severe acute malnutrition recovery, children have a significant risk of relapsing within 6 months, highlighting the particular vulnerability of this population. Although the community-based management of acute malnutrition model proves highly effective in saving lives, high relapse indicates the need for additional services during and following treatment to better sustain recovery. FUNDING: The United States Agency for International Development.

BACKGROUND: PFAS may impair bone health, but effects of PFAS exposure assessed during pregnancy and the perimenopause-life stages marked by rapidly changing bone metabolism-on later life bone health are unknown. METHODS: We studied 531 women in the Boston-area Project Viva cohort. We used multivariable linear, generalized additive, and mixture models to examine associations of plasma PFAS concentrations during early pregnancy [median (IQR) maternal age 32.9 (6.2) years] and midlife [age 51.2 (6.3)] with lumbar spine, total hip, and femoral neck areal bone mineral density (aBMD) and bone turnover biomarkersassessed in midlife. We examined effect modification by diet and physical activity measured at the time of PFAS exposure assessment and by menopausal status in midlife. RESULTS: Participants had higher PFAS concentrations during pregnancy [1999-2000; e.g., PFOA median (IQR) 5.4 (3.8) ng/mL] than in midlife [2017-2021; e.g. , PFOA: 1.5 (1.2) ng/mL]. Women with higher PFOA, PFOS and PFNA during pregnancy had higher midlife aBMD, especially of the spine [e.g., 0.28 (95% CI: 0.07, 0.48) higher spine aBMD T-score, per doubling of PFOA], with stronger associations observed among those with higher diet quality. In contrast, higher concentrations of all PFAS measured in midlife were associated with lower concurrent aBMD at all sites [e.g., -0.21 (-0.35, -0.07) lower spine aBMD T-score, per doubling of PFOA]; associations were stronger among those who were postmenopausal. The associations of several PFAS with bone resorption (loss) were also stronger among postmenopausal versus premenopausal women. DISCUSSION: Plasma PFAS measured during pregnancy versus in midlife had different associations with midlife aBMD. We found an adverse association of PFAS measured in midlife with midlife aBMD, particularly among postmenopausal women. Future studies with longer follow-up are needed to elucidate the effect of PFAS on bone health during the peri- and postmenopausal years.

Introduction: The avoidance of asthma triggers, like tobacco smoke, facilitates asthma management. Reliance upon caregiver report of their child’s environmental tobacco smoke (ETS) exposure may result in information bias and impaired asthma management. This analysis aimed to characterize the chronicity of ETS exposure, assess the validity of caregiver report of ETS exposure, and investigate the relationship between ETS exposure and asthma attack. Methods: A secondary data analysis was performed on data from a longitudinal study of 162 children aged 7–12 years with asthma living in federally subsidized housing in three US cities (Boston, Cincinnati, and New Orleans). Data were collected at three time points over 1 year. Results: Over 90% of children were exposed to ETS (≥0.25 ng/ml of urine cotinine (UC)). Exposure was consistent over 1 year. Questionnaire data had a sensitivity of 28–34% using UC ≥0.25 ng/ml as the gold standard. High ETS exposure (UC ≥ 30 ng/ml) was significantly associated with asthma attack (aOR 2.97, 0.93–9.52, p = 0.07). Lower levels (UC 0.25–30 ng/ml) were not statistically significant (aOR 1.76, 0.71– 4.38, p = 0.22). No association was found using caregiver-reported ETS exposure. Conclusion: Relying on questionnaire data to assess children’s exposure to tobacco smoke may lead to substantial information bias. For children with asthma, incorrect characterization may substantially impact asthma morbidity. © The Author(s), 2024.

BACKGROUND: Tracking the emergence, introduction and spread of SARS-CoV-2 variants of concern are essential for informing public health strategies. In 2021, Cambodia faced two major epidemic waves of SARS-CoV-2 triggered by the successive rise of the Alpha and Delta variants. METHODS: Phylodynamic analysis of 1,163 complete SARS-CoV-2 genomes from Cambodia, along with global sequences, were conducted between February and September 2021 to infer viral introductions, molecular epidemiology and population dynamics. The relationship between epidemic trends and control strategies were evaluated. Bayesian phylogeographic reconstruction was employed to estimate and contrast the spatiotemporal dynamics of the Alpha and Delta variants over time. RESULTS: Here we reveal that the Alpha variant displays rapid lineage diversification, accompanied by the acquisition of a spike E484K mutation that coincides with the national implementation of mass COVID-19 vaccination. Despite nationwide control strategies and increased vaccination coverage, the Alpha variant was quickly displaced by Delta variants that exhibits a higher effective reproductive number. Phylogeographic inference indicates that the Alpha variant was introduced through south-central region of Cambodia, with strong diffusion rates from the capital of Phnom Penh to other provinces, while the Delta variant likely entered the country via the northern border provinces. CONCLUSIONS: Continual genomic surveillance and sequencing efforts, in combination with public health strategies, play a vital role in effectively tracking and responding to the emergence, evolution and dissemination of future emerging variants. | Tracking how SARS-CoV-2, the virus that causes COVID-19, changes over time is important for public health. In Cambodia, there were two major COVID-19 waves in 2021, driven by the Alpha and Delta variants. We analyzed 1,163 virus samples from Cambodia, plus samples from other places, to understand how these variants spread. We found that the Alpha variant quickly spread and changed as Cambodia started a mass vaccination campaign. Despite efforts to control it, the Delta variant, which spreads more easily, soon took over. The Alpha variant likely came into Cambodia from the south, while the Delta variant probably entered from the north. Monitoring these changes helps us respond better to future outbreaks. | eng

PURPOSE: To investigate differences in teen-reported and parent-reported lifetime prevalence estimates of traumatic brain injury (TBI) symptoms, TBI evaluation, and TBI diagnosis among a nationally representative sample of teenagers aged 12-17 years old and their parents. METHODS: Parent-reported data from the 2021 to 2022 National Health Interview Survey linked with teen-reported data from the National Health Interview Survey-Teen July 2021-December 2022 (n = 1,153) were analyzed. Lifetime prevalence estimates for TBI symptoms (e.g., selected symptoms as a result of a blow or jolt to the head), history of evaluation by health professional for TBI (i.e., TBI evaluation), and TBI diagnosis stratified by sociodemographic characteristics and reporter type were produced, and z-tests were conducted to test for differences. Concordance measures were calculated to assess agreement between teen and parent survey responses to TBI measures. RESULTS: Lifetime prevalence of TBI symptoms varied by reporter type across all sociodemographic characteristics with teen-report consistently producing higher estimates. Estimates of TBI evaluation varied by reporter type only among older teens, non-Hispanic teens, and teens who participated in sports; there was no difference for TBI diagnosis. Percent agreement between the 2 reporters ranged from 73% to 95%, prevalence-adjusted bias-adjusted kappa ranged from 0.45 to 0.90, and Cohen's kappa ranged from 0.22 to 0.63. DISCUSSION: There was general agreement for observable outcomes TBI evaluation and TBI diagnosis, but discordance existed in reports of TBI symptoms. These findings suggest that youth self-report of TBI symptoms may enhance surveillance efforts.

BACKGROUND: Prolonged exposure to hyperoxia can lead to hyperoxic acute lung injury (HALI) in preterm neonates. Vitamin D (VitD) stimulates lung maturation and acts as an anti-inflammatory agent. Our objective was to determine if VitD provides a dose-dependent protective effect against HALI by reducing inflammatory cytokine expression and improving alveolarization and lung function in neonatal mice. METHODS: C57BL/6 mouse neonates were randomized and placed in room air or hyperoxic (85% O(2)) conditions for 6 days. Control, low (5 ng/neonate) and high (25 ng/neonate) doses of VitD were administered daily beginning at day 2 via oral gavage. Lung tissue was analyzed for edema, changes in pulmonary structure and function, and inflammatory cytokine expression. RESULTS: Neonatal mice treated with VitD in hyperoxic conditions had improved weight gain, reduced pulmonary edema and increased alveolar surface area compared to untreated pups in hyperoxia. No significant changes in cytokine expression were observed between untreated and VitD neonates. While changes in surfactant protein mRNA expression were impacted by hyperoxia and VitD administration, no significant changes in alveolar type II cell percentages were observed. At 3 weeks, mice in hyperoxia treated with VitD had greater lung compliance, diminished airway reactivity and improved weight gain. CONCLUSIONS: High dose VitD significantly limited harmful effects of HALI. These results suggest that supplementation of VitD to neonatal mice during hyperoxia exposure provides both short-term and long-term protective benefits against HALI.

INTRODUCTION: Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) experience cognitive problems with attention, information processing speed, working memory, learning efficiency, and executive function. Commonly, patients report worsening of cognitive symptoms over time after physical and/or cognitive challenges. To determine, monitor, and manage longitudinal decrements in cognitive function after such exposures, it is important to be able to screen for cognitive dysfunction and changes over time in clinic and also remotely at home. The primary objectives of this paper were: (1) to determine whether a brief computerized cognitive screening battery will detect differences in cognitive function between ME/CFS and Healthy Controls (HC), (2) to monitor the impact of a full-day study visit on cognitive function over time, and (3) to evaluate the impact of exercise testing on cognitive dysfunction. METHODS: This cognitive sub-study was conducted between 2013 and 2019 across seven U.S. ME/CFS clinics as part of the Multi-Site Clinical Assessment of ME/CFS (MCAM) study. The analysis included 426 participants (261 ME/CFS and 165 HC), who completed cognitive assessments including a computerized CogState Brief Screening Battery (CBSB) administered across five timepoints (T0-T4) at the start of and following a full day in-clinic visit that included exercise testing for a subset of participants (182 ME/CFS and 160 HC). Exercise testing consisted of ramped cycle ergometry to volitional exhaustion. The primary outcomes are performance accuracy and latency (performance speed) on the computerized CBSB administered online in clinic (T0 and T1) and at home (T2-T4). RESULTS: No difference was found in performance accuracy between ME/CFS and HCs whereas information processing speed was significantly slower for ME/CFS at most timepoints with Cohen's d effect sizes ranging from 0.3-0.5 (p < 0.01). The cognitive decline over time on all CBSB tasks was similar for patients with ME/CFS independent of whether exercise testing was included in the clinic visit. CONCLUSION: The challenges of a clinic visit (including cognitive testing) can lead to further cognitive deficits. A single short session of intense exercise does not further reduce speed of performance on any CBSB tasks.

On April 24, 2023, the American Samoa Department of Health (ASDoH) declared a public health emergency amid concern about a possible measles outbreak given low 2-dose vaccination coverage at the time. ASDoH had received two positive measles immunoglobulin (Ig) M test results after Flag Day festivities 1 week earlier from vaccinated children. ASDoH performed active case finding, took actions to mitigate transmission, and requested technical assistance from CDC. ASDoH implemented a vaccination campaign to improve suboptimal coverage. Confirmatory molecular testing of specimens from these initial persons under investigation (PUIs) was not possible, but subsequent testing of specimens from additional PUIs by Hawaii State Laboratories Division and CDC ruled out measles. In settings with low measles prevalence, measles antibody testing results have low positive predictive value and can lead to difficulties with interpreting results. Testing for additional pathogens revealed a variety of viruses known to cause common childhood viral exanthems. Both molecular and serologic testing should be performed for all suspected measles cases. To decrease the probability of false-positive IgM results, testing should be reserved for cases that meet the Council of State and Territorial Epidemiologists measles case definition, especially those in persons with no evidence of immunity and with a history of recent international travel. In addition, maintaining high measles vaccination coverage can prevent future outbreaks.