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Prior epidemiological studies investigating the association between delivery mode (i.e., vaginal birth and cesarean section [C-section]) and autism spectrum disorder (ASD) and intellectual disability (ID) risk have reported mixed findings. This study examined ASD and ID risks associated with primary and repeat C-section within diverse US regions. During even years 2000-2016, 8-years-olds were identified with ASD and/or ID and matched to birth records [ASD only (N = 8566, 83.6% male), ASD + ID (N = 3445, 79.5% male), ID only (N = 6158, 60.8% male)] using the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network methodology. The comparison birth cohort (N = 1,456,914, 51.1% male) comprised all births recorded in the National Center for Health Statistics corresponding to birth years and counties in which surveillance occurred. C-section rates in the birth cohort demonstrated significant regional variation with lowest rates in the West. Overall models demonstrate increased odds of disability associated with primary and repeat C-section. Adjusted models, stratified by region, identified significant variability in disability likelihood associated with repeat C-section: increased odds occurred for all case groups in the Southeast, for ASD only and ID only in the Mid-Atlantic, and no case groups in the West. Regional variability in disability risk associated with repeat C-section coincides with differences in birth cohorts' C-section rates. This suggests increased likelihood of disability is not incurred by the procedure itself, but rather C-section serves as a proxy for exposures with regional variability that influence fetal development and C-section rates., (© 2024 International Society for Autism Research and Wiley Periodicals LLC.)

Herein, we describe a general hydrodefunctionalization protocol of alcohols and amines through a common isonitrile intermediate. To cleave the relatively inert C-NC bond, we leveraged dual hydrogen atom transfer (HAT) and photoredox catalysis to generate a nucleophilic boryl radical, which readily forms an imidoyl radical intermediate from the isonitrile. Rapid β-scission then accomplishes defunctionalization. This method has been applied to the hydrodefunctionalization of both amine and alcohol-containing pharmaceuticals, natural products, and biomolecules. We extended this approach to the reduction of carbonyls and olefins to their saturated counterparts, as well as the hydrodecyanation of alkyl nitriles. Both experimental and computational studies demonstrate a facile β-scission of the imidoyl radical, and reconcile differences in reactivity between nitriles and isonitriles within our protocol., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Objective: Our objectives with this study were to describe the frequency of selected cooccurring health conditions and individualized education program (IEP) services and post-high school transition planning for adolescents with autism spectrum disorder and identify disparities by sex, intellectual ability, race or ethnicity, and geographic area., Methods: The study sample included 1787 adolescents born in 2004 who were identified as having autism through a health and education record review through age 16 years in 2020. These adolescents were part of a longitudinal population-based surveillance birth cohort from the Autism and Developmental Disabilities Monitoring Network from 2004 to 2020 in 5 US catchment areas., Results: Attention deficit hyperactivity disorder (47%) and anxiety (39%) were the most common cooccurring health conditions. Anxiety was less commonly identified for those with intellectual disability than those without. It was also less commonly identified among Black adolescents compared with White or Hispanic adolescents. There was wide variation across Autism and Developmental Disabilities Monitoring Network sites in the provision of school-based IEP services. Students with intellectual disability were less likely to receive school-based mental health services and more likely to have a goal for postsecondary independent living skills compared with those without intellectual disability. A total of 37% of students did not participate in standardized testing., Conclusions: We identified disparities in the identification of cooccurring conditions and school-based IEP services, practices, and transition planning. Working with pediatric health and education providers, families, and adolescents with autism will be important to identify contributing factors and to focus efforts to reduce disparities in the supports and services adolescents with autism have access to and receive., (Copyright © 2024 by the American Academy of Pediatrics.)

The purinoceptor P2X 7 R is a promising therapeutic target for tauopathies, including Alzheimer's disease (AD). Pharmacological inhibition or genetic knockdown of P2X 7 R ameliorates cognitive deficits and reduces pathological tau burden in mice that model aspects of tauopathy, including mice expressing mutant human frontotemporal dementia (FTD)-causing forms of tau. However, disagreements remain over which glial cell types express P2X 7 R and therefore the mechanism of action is unresolved. Here, we show that P2X 7 R protein levels increase in human AD post-mortem brain, in agreement with an upregulation of P2RX7 mRNA observed in transcriptome profiles from the AMP-AD consortium. P2X 7 R protein increases mirror advancing Braak stage and coincide with synapse loss. Using RNAScope we detect P2RX7 mRNA in microglia and astrocytes in human AD brain, including in the vicinity of senile plaques. In cultured microglia, P2X 7 R activation modulates the NLRP3 inflammasome pathway by promoting the formation of active complexes and release of IL-1β. In astrocytes, P2X 7 R activates NFκB signalling and increases production of the cytokines CCL2, CXCL1 and IL-6 together with the acute phase protein Lcn2. To further explore the role of P2X 7 R in a disease-relevant context, we expressed wild-type or FTD-causing mutant forms of tau in mouse organotypic brain slice cultures. Inhibition of P2X 7 R reduces insoluble tau levels without altering soluble tau phosphorylation or synaptic localisation, suggesting a non-cell autonomous role of glial P2X 7 R on pathological tau aggregation. These findings support further investigations into the cell-type specific effects of P2X 7 R-targeting therapies in tauopathies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the reliability and reproducibility of an artificial intelligence (AI) software in identifying cephalometric points on lateral cephalometric radiographs considering four settings of brightness and contrast., Methods and Materials: Brightness and contrast of 30 lateral cephalometric radiographs were adjusted into four different settings. Then, the control examiner (ECont), the calibrated examiner (ECal), and the CEFBOT AI software (AIs) each marked 19 cephalometric points on all radiographs. Reliability was assessed with a second analysis of the radiographs 15 days after the first one. Statistical significance was set at p < 0.05., Results: Reliability of landmark identification was excellent for the human examiners and the AIs regardless of the type of brightness and contrast setting (mean intraclass correlation coefficient >0.89). When ECont and ECal were compared for reproducibility, there were more cephalometric points with significant differences on the x-axis of the image with the highest contrast and the lowest brightness, namely N( p = 0.033), S( p = 0.030), Po( p < 0.001), and Pog'( p = 0.012). Between ECont and AIs, there were more cephalometric points with significant differences on the image with the highest contrast and the lowest brightness, namely N( p = 0.034), Or( p = 0.048), Po( p < 0.001), A( p = 0.042), Pog'( p = 0.004), Ll( p = 0.005), Ul( p < 0.001), and Sn( p = 0.001)., Conclusions: While the reliability of the AIs for cephalometric landmark identification was rated as excellent, low brightness and high contrast seemed to affect its reproducibility. The experienced human examiner, on the other hand, did not show such faulty reproducibility; therefore, the AIs used in this study is an excellent auxiliary tool for cephalometric analysis, but still depends on human supervision to be clinically reliable.

Objectives: Autism spectrum disorder (autism) is a heterogeneous condition that poses challenges in describing the needs of individuals with autism and making prognoses about future outcomes. We applied a newly proposed definition of profound autism to surveillance data to estimate the percentage of children with autism who have profound autism and describe their sociodemographic and clinical characteristics., Methods: We analyzed population-based surveillance data from the Autism and Developmental Disabilities Monitoring Network for 20 135 children aged 8 years with autism during 2000-2016. Children were classified as having profound autism if they were nonverbal, were minimally verbal, or had an intelligence quotient <50., Results: The percentage of 8-year-old children with profound autism among those with autism was 26.7%. Compared with children with non-profound autism, children with profound autism were more likely to be female, from racial and ethnic minority groups, of low socioeconomic status, born preterm or with low birth weight; have self-injurious behaviors; have seizure disorders; and have lower adaptive scores. In 2016, the prevalence of profound autism was 4.6 per 1000 8-year-olds. The prevalence ratio (PR) of profound autism was higher among non-Hispanic Asian/Native Hawaiian/Other Pacific Islander (PR = 1.55; 95 CI, 1.38-1.73), non-Hispanic Black (PR = 1.76; 95% CI, 1.67-1.86), and Hispanic (PR = 1.50; 95% CI, 0.88-1.26) children than among non-Hispanic White children., Conclusions: As the population of children with autism continues to change, describing and quantifying the population with profound autism is important for planning. Policies and programs could consider the needs of people with profound autism across the life span to ensure their needs are met., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: The author has disclosed no conflicts of interest.

Purpose: The objectives of this study were to describe child characteristics associated with later autism spectrum disorder (ASD) identification and the health status and educational transition plans of adolescents with ASD., Methods: Longitudinal population-based surveillance cohort from the Autism Developmental Disabilities Monitoring Network during 2002-2018 in five catchment areas in the United States. Participants included 3,148 children born in 2002 whose records were first reviewed for ASD surveillance in 2010., Results: Of the 1,846 children identified in the community as an ASD case, 11.6% were first identified after age 8 years. Children who were more likely to have ASD identified at older ages were Hispanic; were born with low birth weight; were verbal; had high intelligence quotient or adaptive scores; or had certain co-occurring neuropsychological conditions by age 8 years. By age 16 years, neuropsychological conditions were common with more than half of the adolescents with ASD having a diagnosis of attention-deficit/hyperactivity disorder or anxiety. Intellectual disability (ID) status was unchanged for the majority (>80%) of children from ages 8-16 years. A transition plan was completed for over 94% of adolescents, but disparities were observed in planning by ID status., Discussion: A high percentage of adolescents with ASD have co-occurring neuropsychological conditions, markedly higher than at age 8. While most adolescents had transition planning, this occurred less often for those with ID. Ensuring access to services for all people with ASD during adolescence and transition to adulthood may help to promote overall health and quality of life., (Published by Elsevier Inc.)

Objectives: The study objectives were to examine the contents of individualized education programs (IEPs) of adolescents with autism spectrum disorder (ASD), including postsecondary transition goals, services, and changes in special education classification over time., Methods: This study involved a longitudinal population-based surveillance cohort from the Autism Developmental Disabilities Monitoring Network from 2002 to 2018 in 3 catchment areas in the United States. The sample included 322 adolescents who were born in 2002, identified with ASD, and had an IEP available for review at ages 15-16 years., Results: We found that 297 (92%) adolescents with ASD had an IEP including a transition plan. Those without intellectual disability (ID) were more likely to have postsecondary education and employment goals and have those goals be to pursue higher education or competitive employment compared with those with ID. Forty-one percent of adolescents with ASD had a postsecondary living arrangement goal. Although 28% of adolescents with ASD received school-based mental health services, none of these adolescents were Black; additionally, 15% of those with ID received mental health services compared with 34% without ID. The percentage of adolescents with ASD served under an autism classification increased from 44% at age 8 years to 62% by age 16., Conclusions: We identified gaps and disparities in school-based postsecondary transition planning. Working with education partners, families, and adolescents will be important to identify what challenges contribute to these findings and what supports are needed to improve the equity and quality of the transition planning process for adolescents with ASD so they are prepared for adulthood., (Copyright © 2023 by the American Academy of Pediatrics.)

Purpose: The Metropolitan Atlanta Developmental Disabilities Surveillance Program tracks autism spectrum disorder (ASD) in selected counties within Georgia as part of the Autism and Developmental Disabilities Monitoring (ADDM) Network. ADDM Network analyses have historically found a higher prevalence of ASD in areas of higher socioeconomic status., Methods: We linked 2018 data from Centers for Disease Control and Prevention's Social Vulnerability Index (SVI) to two Metropolitan Atlanta Developmental Disabilities Surveillance Program counties by census tract, grouped census tracts into tertiles representing low, medium, and high social vulnerability, and calculated ASD prevalence for each tertile, overall and by each of four SVI themes., Results: We found that overall prevalence was higher in areas of low compared to high vulnerability for the socioeconomic status and transportation themes, and in areas of medium compared to high vulnerability for all themes. This pattern was consistent among males but varied for females and by race or ethnicity., Conclusions: Linking ASD prevalence to SVI metrics can improve the understanding of inequities among children with ASD in racial and ethnic minority groups or those living in low-resource settings. These methods can be applied to other ADDM Network surveillance sites and public health surveillance programs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Competing Interests: The author has disclosed no conflicts of interest.

Competing Interests: The author has disclosed no conflicts of interest.

Problem/condition: Autism spectrum disorder (ASD)., Period Covered: 2020., Description of System: The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance program that provides estimates of the prevalence of ASD among children aged 8 years. In 2020, there were 11 ADDM Network sites across the United States (Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin). To ascertain ASD among children aged 8 years, ADDM Network staff review and abstract developmental evaluations and records from community medical and educational service providers. A child met the case definition if their record documented 1) an ASD diagnostic statement in an evaluation, 2) a classification of ASD in special education, or 3) an ASD International Classification of Diseases (ICD) code., Results: For 2020, across all 11 ADDM sites, ASD prevalence per 1,000 children aged 8 years ranged from 23.1 in Maryland to 44.9 in California. The overall ASD prevalence was 27.6 per 1,000 (one in 36) children aged 8 years and was 3.8 times as prevalent among boys as among girls (43.0 versus 11.4). Overall, ASD prevalence was lower among non-Hispanic White children (24.3) and children of two or more races (22.9) than among non-Hispanic Black or African American (Black), Hispanic, and non-Hispanic Asian or Pacific Islander (A/PI) children (29.3, 31.6, and 33.4 respectively). ASD prevalence among non-Hispanic American Indian or Alaska Native (AI/AN) children (26.5) was similar to that of other racial and ethnic groups. ASD prevalence was associated with lower household income at three sites, with no association at the other sites.Across sites, the ASD prevalence per 1,000 children aged 8 years based exclusively on documented ASD diagnostic statements was 20.6 (range = 17.1 in Wisconsin to 35.4 in California). Of the 6,245 children who met the ASD case definition, 74.7% had a documented diagnostic statement of ASD, 65.2% had a documented ASD special education classification, 71.6% had a documented ASD ICD code, and 37.4% had all three types of ASD indicators. The median age of earliest known ASD diagnosis was 49 months and ranged from 36 months in California to 59 months in Minnesota.Among the 4,165 (66.7%) children with ASD with information on cognitive ability, 37.9% were classified as having an intellectual disability. Intellectual disability was present among 50.8% of Black, 41.5% of A/PI, 37.8% of two or more races, 34.9% of Hispanic, 34.8% of AI/AN, and 31.8% of White children with ASD. Overall, children with intellectual disability had earlier median ages of ASD diagnosis (43 months) than those without intellectual disability (53 months)., Interpretation: For 2020, one in 36 children aged 8 years (approximately 4% of boys and 1% of girls) was estimated to have ASD. These estimates are higher than previous ADDM Network estimates during 2000-2018. For the first time among children aged 8 years, the prevalence of ASD was lower among White children than among other racial and ethnic groups, reversing the direction of racial and ethnic differences in ASD prevalence observed in the past. Black children with ASD were still more likely than White children with ASD to have a co-occurring intellectual disability., Public Health Action: The continued increase among children identified with ASD, particularly among non-White children and girls, highlights the need for enhanced infrastructure to provide equitable diagnostic, treatment, and support services for all children with ASD. Similar to previous reporting periods, findings varied considerably across network sites, indicating the need for additional research to understand the nature of such differences and potentially apply successful identification strategies across states., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Problem/condition: Autism spectrum disorder (ASD)., Period Covered: 2020., Description of System: The Autism and Developmental Disabilities Monitoring Network is an active surveillance program that estimates prevalence and characteristics of ASD and monitors timing of ASD identification among children aged 4 and 8 years. In 2020, a total of 11 sites (located in Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin) conducted surveillance of ASD among children aged 4 and 8 years and suspected ASD among children aged 4 years. Surveillance included children who lived in the surveillance area at any time during 2020. Children were classified as having ASD if they ever received 1) an ASD diagnostic statement in an evaluation, 2) a special education classification of autism (eligibility), or 3) an ASD International Classification of Diseases (ICD) code (revisions 9 or 10). Children aged 4 years were classified as having suspected ASD if they did not meet the case definition for ASD but had a documented qualified professional's statement indicating a suspicion of ASD. This report focuses on children aged 4 years in 2020 compared with children aged 8 years in 2020., Results: For 2020, ASD prevalence among children aged 4 years varied across sites, from 12.7 per 1,000 children in Utah to 46.4 in California. The overall prevalence was 21.5 and was higher among boys than girls at every site. Compared with non-Hispanic White children, ASD prevalence was 1.8 times as high among Hispanic, 1.6 times as high among non-Hispanic Black, 1.4 times as high among Asian or Pacific Islander, and 1.2 times as high among multiracial children. Among the 58.3% of children aged 4 years with ASD and information on intellectual ability, 48.5% had an IQ score of ≤70 on their most recent IQ test or an examiner's statement of intellectual disability. Among children with a documented developmental evaluation, 78.0% were evaluated by age 36 months. Children aged 4 years had a higher cumulative incidence of ASD diagnosis or eligibility by age 48 months compared with children aged 8 years at all sites; risk ratios ranged from 1.3 in New Jersey and Utah to 2.0 in Tennessee. In the 6 months before the March 2020 COVID-19 pandemic declaration by the World Health Organization, there were 1,593 more evaluations and 1.89 more ASD identifications per 1,000 children aged 4 years than children aged 8 years received 4 years earlier. After the COVID-19 pandemic declaration, this pattern reversed: in the 6 months after pandemic onset, there were 217 fewer evaluations and 0.26 fewer identifications per 1,000 children aged 4 years than children aged 8 years received 4 years earlier. Patterns of evaluation and identification varied among sites, but there was not recovery to pre-COVID-19 pandemic levels by the end of 2020 at most sites or overall. For 2020, prevalence of suspected ASD ranged from 0.5 (California) to 10.4 (Arkansas) per 1,000 children aged 4 years, with an increase from 2018 at five sites (Arizona, Arkansas, Maryland, New Jersey, and Utah). Demographic and cognitive characteristics of children aged 4 years with suspected ASD were similar to children aged 4 years with ASD., Interpretation: A wide range of prevalence of ASD by age 4 years was observed, suggesting differences in early ASD identification practices among communities. At all sites, cumulative incidence of ASD by age 48 months among children aged 4 years was higher compared with children aged 8 years in 2020, indicating improvements in early identification of ASD. Higher numbers of evaluations and rates of identification were evident among children aged 4 years until the COVID-19 pandemic onset in 2020. Sustained lower levels of ASD evaluations and identification seen at a majority of sites after the pandemic onset could indicate disruptions in typical practices in evaluations and identification for health service providers and schools through the end of 2020. Sites with more recovery could indicate successful strategies to mitigate service interruption, such as pivoting to telehealth approaches for evaluation., Public Health Action: From 2016 through February of 2020, ASD evaluation and identification among the cohort of children aged 4 years was outpacing ASD evaluation and identification 4 years earlier (from 2012 until March 2016) among the cohort of children aged 8 years in 2020 . From 2016 to March 2020, ASD evaluation and identification among the cohort of children aged 4 years was outpacing that among children aged 8 years in 2020 from 2012 until March 2016. The disruptions in evaluation that coincided with the start of the COVID-19 pandemic and the increase in prevalence of suspected ASD in 2020 could have led to delays in ASD identification and interventions. Communities could evaluate the impact of these disruptions as children in affected cohorts age and consider strategies to mitigate service disruptions caused by future public health emergencies., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest.

Purpose: Autism spectrum disorder (ASD) prevalence information is necessary for identifying community needs such as addressing disparities in identification and services., Methods: Seven Autism and Developmental Disabilities Monitoring (ADDM) Network sites participated in a pilot project to link statewide health and education data to generate statewide and county-level prevalence estimates for a broader age range for their states for the first time., Results: Statewide prevalence of ASD for ages 3-21 years in 2018 ranged from 1.5% in Tennessee and Wisconsin to 2.3% in Arizona. The median county-level prevalence of ASD was 1.4% of residents ages 3-21 years. More boys than girls had ASD at all sites, and prevalence was lower among non-Hispanic Black, Hispanic, Asian/Pacific Islander, and American Indian/Alaska Native residents compared to non-Hispanic White residents at most sites. ASD prevalence estimates for children aged 8 years were similar to 2018 ADDM Network estimates that used record review to provide more in-depth information, but showed greater variation for children aged 4 years., Conclusions: Linkage of statewide data sets provides less detailed but actionable local information when more resource-intensive methods are not possible., (Published by Elsevier Inc.)

Objective: To assess the reliability of CEFBOT, an artificial intelligence (AI)-based cephalometry software, for cephalometric landmark annotation and linear and angular measurements according to Arnett's analysis., Methods: Thirty lateral cephalometric radiographs acquired with a Carestream CS 9000 3D unit (Carestream Health Inc., Rochester/NY) were used in this study. The 66 landmarks and the 10 selected linear and angular measurements of Arnett's analysis were identified on each radiograph by a trained human examiner (control) and by CEFBOT (RadioMemory Ltd., Belo Horizonte, Brazil). For both methods, landmark annotations and measurements were duplicated with an interval of 15 days between measurements and the intraclass correlation coefficient (ICC) was calculated to determine reliability. The numerical values obtained with the two methods were compared by a t -test for independent variables., Results: CEFBOT was able to perform all but one of the 10 measurements. ICC values > 0.94 were found for the remaining eight measurements, while the Frankfurt horizontal plane - true horizontal line (THL) angular measurement showed the lowest reproducibility (human, ICC = 0.876; CEFBOT, ICC = 0.768). Measurements performed by the human examiner and by CEFBOT were not statistically different., Conclusion: Within the limitations of our methodology, we concluded that the AI contained in the CEFBOT software can be considered a promising tool for enhancing the capacities of human radiologists.

Objective: Early identification can improve outcomes for children with autism spectrum disorder (ASD). We sought to assess changes in early ASD identification over time and by co-occurring intellectual disability (ID) and race/ethnicity., Method: Using data for 2002-2016 from a biennial population-based ASD surveillance program among 8-year-old children in the United States, we defined identification as a child's earliest recorded ASD diagnosis or special education eligibility. Unidentified children had characteristics meeting the ASD surveillance case definition but no recorded identification by age 8 years. We calculated median age at identification among identified children, median age at identification including unidentified children, and cumulative incidence of identification by age 48 months., Results: ASD identification by age 48 months was 4 times (95% CI: 3.6-4.3) as likely in 2016 as in 2002, with the largest increases among children without ID. Median age at ASD identification among identified children decreased 3 months during this time. Children of every race/ethnicity were more likely to be identified over time. There were racial disparities stratified by ID: in 2016, Black and Hispanic children without ID were less likely to be identified with ASD than were White children (both groups risk ratio: 0.7; 95% CI: 0.5-0.8), but Black children were 1.5 times (95% CI: 1.3-1.9) as likely as White children to be identified with ASD and ID., Conclusion: Substantial progress has been made to identify more children with ASD early, despite minimal decrease in median age at diagnosis. Considerable disparities remain in early ASD identification by race/ethnicity and co-occurring intellectual disability., (Published by Elsevier Inc.)

Sensory features (i.e., atypical responses to sensory stimuli) are included in the current diagnostic criteria for autism spectrum disorder. Yet, large population-based studies have not examined these features. This study aimed to determine the prevalence of sensory features among autistic children, and examine associations between sensory features, demographics, and co-occurring problems in other areas. Analysis for this study included a sample comprised of 25,627 four- or eight-year-old autistic children identified through the multistate Autism and Developmental Disabilities Monitoring Network (2006-2014). We calculated the prevalence of sensory features and applied multilevel logistic regression modeling. The majority (74%; 95% confidence interval: 73.5%-74.5%) of the children studied had documented sensory features. In a multivariable model, children who were male and those whose mothers had more years of education had higher odds of documented sensory features. Children from several racial and ethnic minority groups had lower odds of documented sensory features than White, non-Hispanic children. Cognitive problems were not significantly related to sensory features. Problems related to adaptive behavior, emotional states, aggression, attention, fear, motor development, eating, and sleeping were associated with higher odds of having documented sensory features. Results from a large, population-based sample indicate a high prevalence of sensory features in autistic children, as well as relationships between sensory features and co-occurring problems. This study also pointed to potential disparities in the identification of sensory features, which should be examined in future research. Disparities should also be considered clinically to avoid reduced access to supports for sensory features and related functional problems. LAY SUMMARY: In a large, population-based sample of 25,627 autistic children, 74% had documented differences in how they respond to sensation. We also identified significant associations of sensory features with adaptive behavior and problems in other domains. Sensory features were less common among girls, children of color, and children of mothers with fewer years of education, suggesting potential disparities in identification., (© 2022 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the adenovirus-vectored COVID-19 vaccine (Janssen Biotech, Inc., a Janssen Pharmaceutical company, Johnson & Johnson), and on February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for its use as a single-dose primary vaccination in persons aged ≥18 years (1,2). On April 13, 2021, CDC and FDA recommended a pause in the use of Janssen COVID-19 vaccine after reports of thrombosis with thrombocytopenia syndrome (TTS), a rare condition characterized by low platelets and thrombosis, including at unusual sites such as the cerebral venous sinus (cerebral venous sinus thrombosis [CVST]), after receipt of the vaccine.* ACIP rapidly convened two emergency meetings to review reported cases of TTS, and 10 days after the pause commenced, ACIP reaffirmed its interim recommendation for use of the Janssen COVID-19 vaccine in persons aged ≥18 years, but included a warning regarding rare clotting events after vaccination, primarily among women aged 18-49 years (3). In July, after review of an updated benefit-risk assessment accounting for risks of Guillain-Barré syndrome (GBS) and TTS, ACIP concluded that benefits of vaccination with Janssen COVID-19 vaccine outweighed risks. Through ongoing safety surveillance and review of reports from the Vaccine Adverse Event Reporting System (VAERS), additional cases of TTS after receipt of Janssen COVID-19 vaccine, including deaths, were identified. On December 16, 2021, ACIP held an emergency meeting to review updated data on TTS and an updated benefit-risk assessment. At that meeting, ACIP made a recommendation for preferential use of mRNA COVID-19 vaccines over the Janssen COVID-19 vaccine, including both primary and booster doses administered to prevent COVID-19, for all persons aged ≥18 years. The Janssen COVID-19 vaccine may be considered in some situations, including for persons with a contraindication to receipt of mRNA COVID-19 vaccines., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Allison Lale reports personal fees from the Medical Library Association, outside the submitted work. No other potential conflicts of interest were disclosed.

Background: Pathological interactions between β-amyloid (Aβ) and tau drive synapse loss and cognitive decline in Alzheimer's disease (AD). Reactive astrocytes, displaying altered functions, are also a prominent feature of AD brain. This large and heterogeneous population of cells are increasingly recognised as contributing to early phases of disease. However, the contribution of astrocytes to Aβ-induced synaptotoxicity in AD is not well understood., Methods: We stimulated mouse and human astrocytes with conditioned medium containing concentrations and species of human Aβ that mimic those in human AD brain. Medium from stimulated astrocytes was collected and immunodepleted of Aβ before being added to naïve rodent or human neuron cultures. A cytokine, identified in unbiased screens of stimulated astrocyte media and in postmortem human AD brain lysates was also applied to neurons, including those pre-treated with a chemokine receptor antagonist. Tau mislocalisation, synaptic markers and dendritic spine numbers were measured in cultured neurons and organotypic brain slice cultures., Results: We found that conditioned medium from stimulated astrocytes induces exaggerated synaptotoxicity that is recapitulated following spiking of neuron culture medium with recombinant C-X-C motif chemokine ligand-1 (CXCL1), a chemokine upregulated in AD brain. Antagonism of neuronal C-X-C motif chemokine receptor 2 (CXCR2) prevented synaptotoxicity in response to CXCL1 and Aβ-stimulated astrocyte secretions., Conclusions: Our data indicate that astrocytes exacerbate the synaptotoxic effects of Aβ via interactions of astrocytic CXCL1 and neuronal CXCR2 receptors, highlighting this chemokine-receptor pair as a novel target for therapeutic intervention in AD., (© 2021. The Author(s).)

Problem/condition: Autism spectrum disorder (ASD)., Period Covered: 2018., Description of System: The Autism and Developmental Disabilities Monitoring Network is an active surveillance program that estimates ASD prevalence and monitors timing of ASD identification among children aged 4 and 8 years. This report focuses on children aged 4 years in 2018, who were born in 2014 and had a parent or guardian who lived in the surveillance area in one of 11 sites (Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin) at any time during 2018. Children were classified as having ASD if they ever received 1) an ASD diagnostic statement (diagnosis) in an evaluation, 2) a special education classification of ASD (eligibility), or 3) an ASD International Classification of Diseases (ICD) code. Suspected ASD also was tracked among children aged 4 years. Children who did not meet the case definition for ASD were classified as having suspected ASD if their records contained a qualified professional's statement indicating a suspicion of ASD., Results: For 2018, the overall ASD prevalence was 17.0 per 1,000 (one in 59) children aged 4 years. Prevalence varied from 9.1 per 1,000 in Utah to 41.6 per 1,000 in California. At every site, prevalence was higher among boys than girls, with an overall male-to-female prevalence ratio of 3.4. Prevalence of ASD among children aged 4 years was lower among non-Hispanic White (White) children (12.9 per 1,000) than among non-Hispanic Black (Black) children (16.6 per 1,000), Hispanic children (21.1 per 1,000), and Asian/Pacific Islander (A/PI) children (22.7 per 1,000). Among children aged 4 years with ASD and information on intellectual ability, 52% met the surveillance case definition of co-occurring intellectual disability (intelligence quotient ≤70 or an examiner's statement of intellectual disability documented in an evaluation). Of children aged 4 years with ASD, 72% had a first evaluation at age ≤36 months. Stratified by census-tract-level median household income (MHI) tertile, a lower percentage of children with ASD and intellectual disability was evaluated by age 36 months in the low MHI tertile (72%) than in the high MHI tertile (84%). Cumulative incidence of ASD diagnosis or eligibility received by age 48 months was 1.5 times as high among children aged 4 years (13.6 per 1,000 children born in 2014) as among those aged 8 years (8.9 per 1,000 children born in 2010). Across MHI tertiles, higher cumulative incidence of ASD diagnosis or eligibility received by age 48 months was associated with lower MHI. Suspected ASD prevalence was 2.6 per 1,000 children aged 4 years, meaning for every six children with ASD, one child had suspected ASD. The combined prevalence of ASD and suspected ASD (19.7 per 1,000 children aged 4 years) was lower than ASD prevalence among children aged 8 years (23.0 per 1,000 children aged 8 years)., Interpretation: Groups with historically lower prevalence of ASD (non-White and lower MHI) had higher prevalence and cumulative incidence of ASD among children aged 4 years in 2018, suggesting progress in identification among these groups. However, a lower percentage of children with ASD and intellectual disability in the low MHI tertile were evaluated by age 36 months than in the high MHI group, indicating disparity in timely evaluation. Children aged 4 years had a higher cumulative incidence of diagnosis or eligibility by age 48 months compared with children aged 8 years, indicating improvement in early identification of ASD. The overall prevalence for children aged 4 years was less than children aged 8 years, even when prevalence of children suspected of having ASD by age 4 years is included. This finding suggests that many children identified after age 4 years do not have suspected ASD documented by age 48 months., Public Health Action: Children born in 2014 were more likely to be identified with ASD by age 48 months than children born in 2010, indicating increased early identification. However, ASD identification among children aged 4 years varied by site, suggesting opportunities to examine developmental screening and diagnostic practices that promote earlier identification. Children aged 4 years also were more likely to have co-occurring intellectual disability than children aged 8 years, suggesting that improvement in the early identification and evaluation of developmental concerns outside of cognitive impairments is still needed. Improving early identification of ASD could lead to earlier receipt of evidence-based interventions and potentially improve developmental outcomes., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Problem/condition: Autism spectrum disorder (ASD)., Period Covered: 2018., Description of System: The Autism and Developmental Disabilities Monitoring (ADDM) Network conducts active surveillance of ASD. This report focuses on the prevalence and characteristics of ASD among children aged 8 years in 2018 whose parents or guardians lived in 11 ADDM Network sites in the United States (Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin). To ascertain ASD among children aged 8 years, ADDM Network staff review and abstract developmental evaluations and records from community medical and educational service providers. In 2018, children met the case definition if their records documented 1) an ASD diagnostic statement in an evaluation (diagnosis), 2) a special education classification of ASD (eligibility), or 3) an ASD International Classification of Diseases (ICD) code., Results: For 2018, across all 11 ADDM sites, ASD prevalence per 1,000 children aged 8 years ranged from 16.5 in Missouri to 38.9 in California. The overall ASD prevalence was 23.0 per 1,000 (one in 44) children aged 8 years, and ASD was 4.2 times as prevalent among boys as among girls. Overall ASD prevalence was similar across racial and ethnic groups, except American Indian/Alaska Native children had higher ASD prevalence than non-Hispanic White (White) children (29.0 versus 21.2 per 1,000 children aged 8 years). At multiple sites, Hispanic children had lower ASD prevalence than White children (Arizona, Arkansas, Georgia, and Utah), and non-Hispanic Black (Black) children (Georgia and Minnesota). The associations between ASD prevalence and neighborhood-level median household income varied by site. Among the 5,058 children who met the ASD case definition, 75.8% had a diagnostic statement of ASD in an evaluation, 18.8% had an ASD special education classification or eligibility and no ASD diagnostic statement, and 5.4% had an ASD ICD code only. ASD prevalence per 1,000 children aged 8 years that was based exclusively on documented ASD diagnostic statements was 17.4 overall (range: 11.2 in Maryland to 29.9 in California). The median age of earliest known ASD diagnosis ranged from 36 months in California to 63 months in Minnesota. Among the 3,007 children with ASD and data on cognitive ability, 35.2% were classified as having an intelligence quotient (IQ) score ≤70. The percentages of children with ASD with IQ scores ≤70 were 49.8%, 33.1%, and 29.7% among Black, Hispanic, and White children, respectively. Overall, children with ASD and IQ scores ≤70 had earlier median ages of ASD diagnosis than children with ASD and IQ scores >70 (44 versus 53 months)., Interpretation: In 2018, one in 44 children aged 8 years was estimated to have ASD, and prevalence and median age of identification varied widely across sites. Whereas overall ASD prevalence was similar by race and ethnicity, at certain sites Hispanic children were less likely to be identified as having ASD than White or Black children. The higher proportion of Black children compared with White and Hispanic children classified as having intellectual disability was consistent with previous findings., Public Health Action: The variability in ASD prevalence and community ASD identification practices among children with different racial, ethnic, and geographical characteristics highlights the importance of research into the causes of that variability and strategies to provide equitable access to developmental evaluations and services. These findings also underscore the need for enhanced infrastructure for diagnostic, treatment, and support services to meet the needs of all children., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Inflammatory bowel disease (IBD) is characterized by multiple alterations in cytokine expression and is a risk factor for colon cancer. The Omega class glutathione transferase GSTO1-1 regulates the release of the pro-inflammatory cytokines interleukin 1β (IL-1β) and interleukin 18 (IL-18) by deglutathionylating NEK7 in the NLRP3 inflammasome. When treated with azoxymethane and dextran sodium sulphate (AOM/DSS) as a model of IBD, Gsto1-/- mice were highly sensitive to colitis and showed a significant increase in the size and number of colon tumours compared with wild-type (WT) mice. Gsto1-/- mice treated with AOM/DSS had significantly lower serum IL-1β and IL-18 levels as well as significantly decreased interferon (IFN)-γ, decreased pSTAT1 and increased pSTAT3 levels in the distal colon compared with similarly treated WT mice. Histologically, AOM/DSS treated Gsto1-/- mice showed increased active chronic inflammation with macrophage infiltration, epithelial dysplasia and invasive adenocarcinoma compared with AOM/DSS treated WT mice. Thus, this study shows that GSTO1-1 regulates IL-1β and IL-18 activation and protects against colorectal cancer formation in the AOM/DSS model of IBD. The data suggest that while GSTO1-1 is a new target for the regulation of the NLRP3 inflammasome-associated cytokines IL-1β and IL-18 by small molecule inhibitors, there is a possibility that anti-inflammatory drugs targeting these cytokines may potentiate colon cancer in some situations., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The U.S. COVID-19 vaccination program began in December 2020, and ensuring equitable COVID-19 vaccine access remains a national priority.* COVID-19 has disproportionately affected racial/ethnic minority groups and those who are economically and socially disadvantaged (1,2). Thus, achieving not just vaccine equality (i.e., similar allocation of vaccine supply proportional to its population across jurisdictions) but equity (i.e., preferential access and administra-tion to those who have been most affected by COVID-19 disease) is an important goal. The CDC social vulnerability index (SVI) uses 15 indicators grouped into four themes that comprise an overall SVI measure, resulting in 20 metrics, each of which has national and state-specific county rankings. The 20 metric-specific rankings were each divided into lowest to highest tertiles to categorize counties as low, moderate, or high social vulnerability counties. These tertiles were combined with vaccine administration data for 49,264,338 U.S. residents in 49 states and the District of Columbia (DC) who received at least one COVID-19 vaccine dose during December 14, 2020-March 1, 2021. Nationally, for the overall SVI measure, vaccination coverage was higher (15.8%) in low social vulnerability counties than in high social vulnerability counties (13.9%), with the largest coverage disparity in the socioeconomic status theme (2.5 percentage points higher coverage in low than in high vulnerability counties). Wide state variations in equity across SVI metrics were found. Whereas in the majority of states, vaccination coverage was higher in low vulnerability counties, some states had equitable coverage at the county level. CDC, state, and local jurisdictions should continue to monitor vaccination coverage by SVI metrics to focus public health interventions to achieve equitable coverage with COVID-19 vaccine., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

In December 2020, two COVID-19 vaccines (Pfizer-BioNTech and Moderna) were authorized for emergency use in the United States for the prevention of coronavirus disease 2019 (COVID-19).* Because of limited initial vaccine supply, the Advisory Committee on Immunization Practices (ACIP) prioritized vaccination of health care personnel † and residents and staff members of long-term care facilities (LTCF) during the first phase of the U.S. COVID-19 vaccination program (1). Both vaccines require 2 doses to complete the series. Data on vaccines administered during December 14, 2020-January 14, 2021, and reported to CDC by January 26, 2021, were analyzed to describe demographic characteristics, including sex, age, and race/ethnicity, of persons who received ≥1 dose of COVID-19 vaccine (i.e., initiated vaccination). During this period, 12,928,749 persons in the United States in 64 jurisdictions and five federal entities § initiated COVID-19 vaccination. Data on sex were reported for 97.0%, age for 99.9%, and race/ethnicity for 51.9% of vaccine recipients. Among persons who received the first vaccine dose and had reported demographic data, 63.0% were women, 55.0% were aged ≥50 years, and 60.4% were non-Hispanic White (White). More complete reporting of race and ethnicity data at the provider and jurisdictional levels is critical to ensure rapid detection of and response to potential disparities in COVID-19 vaccination. As the U.S. COVID-19 vaccination program expands, public health officials should ensure that vaccine is administered efficiently and equitably within each successive vaccination priority category, especially among those at highest risk for infection and severe adverse health outcomes, many of whom are non-Hispanic Black (Black), non-Hispanic American Indian/Alaska Native (AI/AN), and Hispanic persons (2,3)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

As of September 21, 2020, the coronavirus disease 2019 (COVID-19) pandemic had resulted in 6,786,352 cases and 199,024 deaths in the United States.* Health care personnel (HCP) are essential workers at risk for exposure to patients or infectious materials (1). The impact of COVID-19 on U.S. HCP was first described using national case surveillance data in April 2020 (2). Since then, the number of reported HCP with COVID-19 has increased tenfold. This update describes demographic characteristics, underlying medical conditions, hospitalizations, and intensive care unit (ICU) admissions, stratified by vital status, among 100,570 HCP with COVID-19 reported to CDC during February 12-July 16, 2020. HCP occupation type and job setting are newly reported. HCP status was available for 571,708 (22%) of 2,633,585 cases reported to CDC. Most HCP with COVID-19 were female (79%), aged 16-44 years (57%), not hospitalized (92%), and lacked all 10 underlying medical conditions specified on the case report form † (56%). Of HCP with COVID-19, 641 died. Compared with nonfatal COVID-19 HCP cases, a higher percentage of fatal cases occurred in males (38% versus 22%), persons aged ≥65 years (44% versus 4%), non-Hispanic Asians (Asians) (20% versus 9%), non-Hispanic Blacks (Blacks) (32% versus 25%), and persons with any of the 10 underlying medical conditions specified on the case report form (92% versus 41%). From a subset of jurisdictions reporting occupation type or job setting for HCP with COVID-19, nurses were the most frequently identified single occupation type (30%), and nursing and residential care facilities were the most common job setting (67%). Ensuring access to personal protective equipment (PPE) and training, and practices such as universal use of face masks at work, wearing masks in the community, and observing social distancing remain critical strategies to protect HCP and those they serve., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

The Krebs cycle-derived metabolite itaconate is highly upregulated in inflammatory macrophages and exerts immunomodulatory effects through cysteine modifications on target proteins. The NLRP3 inflammasome, which cleaves IL-1β, IL-18, and gasdermin D, must be tightly regulated to avoid excessive inflammation. Here we provide evidence that itaconate modifies NLRP3 and inhibits inflammasome activation. Itaconate and its derivative, 4-octyl itaconate (4-OI), inhibited NLRP3 inflammasome activation, but not AIM2 or NLRC4. Conversely, NLRP3 activation was increased in itaconate-depleted Irg1 -/- macrophages. 4-OI inhibited the interaction between NLRP3 and NEK7, a key step in the activation process, and "dicarboxypropylated" C548 on NLRP3. Furthermore, 4-OI inhibited NLRP3-dependent IL-1β release from PBMCs isolated from cryopyrin-associated periodic syndrome (CAPS) patients, and reduced inflammation in an in vivo model of urate-induced peritonitis. Our results identify itaconate as an endogenous metabolic regulator of the NLRP3 inflammasome and describe a process that may be exploited therapeutically to alleviate inflammation in NLRP3-driven disorders., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Clinical guidelines recommend that primary care providers (PCPs) provide guidance and support to ensure a planned transition from pediatric to adult health care for adolescents, beginning at age 12 years (1). However, most adolescents do not receive the recommended health care transition planning (2). This is particularly concerning for adolescents with diagnosed mental, behavioral, and developmental disorders (MBDDs) (3), who account for approximately 20% of U.S. adolescents (4). Childhood MBDDs are linked to increased long-term morbidity and mortality; timely health care transition planning might mitigate adverse outcomes (5,6). CDC analyzed pooled, parent-reported data from the 2016 and 2017 National Survey of Children's Health (NSCH), comparing adolescents, aged 12-17 years, with and without MBDDs on a composite measure and specific indicators of recommended health care transition planning by PCPs. Overall, approximately 15% of adolescents received recommended health care transition planning: 15.8% (95% confidence interval [CI] = 14.1%-17.5%) of adolescents with MBDDs, compared with 14.2% (95% CI = 13.2%-15.3%) of adolescents without MBDDs. Relative to peers without MBDDs and after adjusting for age, adolescents with anxiety were 36% more likely to receive recommended health care transition planning, and those with depression were 69% more likely; adolescents with autism spectrum disorder (ASD) were 35% less likely to receive such transition planning, and those with developmental delay* were 25% less likely. Fewer than 20% of adolescents with MBDDs receiving current treatment met the transition measure. These findings suggest that a minority of adolescents with MBDDs receive recommended transition planning, indicating a potential missed public health opportunity to prevent morbidity and mortality in a population at high risk for health care disengagement (1). Improving access to comprehensive and coordinated programs and services, † as well as increasing provider training concerning adolescents' unique mental and physical health care needs (7), could help increase the number of adolescents benefiting from successful health care transitions (4)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Vaccination is the best way to prevent influenza; however, greater benefits could be achieved. To help guide research and policy agendas, we aimed to quantify the magnitude of influenza disease that would be prevented through targeted increases in vaccine effectiveness (VE) or vaccine coverage (VC)., Methods: For 3 influenza seasons (2011-12, 2015-16, and 2017-18), we used a mathematical model to estimate the number of prevented influenza-associated illnesses, medically attended illnesses, and hospitalizations across 5 age groups. Compared with estimates of prevented illness during each season, given observed VE and VC, we explored the number of additional outcomes that would have been prevented from a 5% absolute increase in VE or VC or from achieving 60% VE or 70% VC., Results: During the 2017-18 season, compared with the burden already prevented by influenza vaccination, a 5% absolute VE increase would have prevented an additional 1 050 000 illnesses and 25 000 hospitalizations (76% among those aged ≥65 years), while achieving 60% VE would have prevented an additional 190 000 hospitalizations. A 5% VC increase would have resulted in 785 000 fewer illnesses (56% among those aged 18-64 years) and 11 000 fewer hospitalizations; reaching 70% would have prevented an additional 39 000 hospitalizations., Conclusions: Small, attainable improvements in effectiveness or VC of the influenza vaccine could lead to substantial additional reductions in the influenza burden in the United States. Improvements in VE would have the greatest impact in reducing hospitalizations in adults aged ≥65 years, and VC improvements would have the largest benefit in reducing illnesses in adults aged 18-49 years., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Activated caspase-1 and caspase-11 induce inflammatory cell death in a process termed pyroptosis. Here we show that Prostaglandin E 2 (PGE 2 ) inhibits caspase-11-dependent pyroptosis in murine and human macrophages. PGE 2 suppreses caspase-11 expression in murine and human macrophages and in the airways of mice with allergic inflammation. Remarkably, caspase-11-deficient mice are strongly resistant to developing experimental allergic airway inflammation, where PGE 2 is known to be protective. Expression of caspase-11 is elevated in the lung of wild type mice with allergic airway inflammation. Blocking PGE 2 production with indomethacin enhances, whereas the prostaglandin E 1 analog misoprostol inhibits lung caspase-11 expression. Finally, alveolar macrophages from asthma patients exhibit increased expression of caspase-4, a human homologue of caspase-11. Our findings identify PGE 2 as a negative regulator of caspase-11-driven pyroptosis and implicate caspase-4/11 as a critical contributor to allergic airway inflammation, with implications for pathophysiology of asthma.

Background: Community-level health data are needed to identify and prioritize the most pressing health issues at the local level., Objectives: To conduct a community-driven probability health survey of disadvantaged Chicago communities in 2015-2016., Methods: A safety-net hospital completed questionnaire development and dissemination in close partnership with a Community Advisory Committee (CAC), so the data captured accurately reflected community priorities., Lessons Learned: The final survey sample included 1,543 adult interviews and proxy reports for 394 children, well below our original recruitment goal. Although ideal for area probability sampling, face-to-face surveys are challenging given declining response rates. Nevertheless, these data provide representative community-level data that is otherwise unavailable., Conclusions: Hyper-local data are especially critical for diverse and segregated cities such as Chicago. Lessons learned can be applied to future community surveys done by hospital systems, health departments, and community advocates to maximize the usefulness of findings.

The 2017-18 U.S. influenza season was notable for its high severity, with approximately 45 million illnesses and 810,000 influenza-associated hospitalizations throughout the United States (1). The purpose of the investigation reported here was to create a state-level estimate of the number of persons in Utah who became ill with influenza disease during this severe national seasonal influenza epidemic and to create a sustainable system for making timely updates in future influenza seasons. Knowing the extent of influenza-associated illness can help public health officials, policymakers, and clinicians tailor influenza messaging, planning, and responses for seasonal influenza epidemics or during pandemics. Using national methods and existing influenza surveillance and testing data, the influenza burden (number of influenza illnesses, medical visits for influenza, and influenza-associated hospitalizations) in Utah during the 2016-17 and 2017-18 influenza seasons was estimated. During the 2016-17 season, an estimated 265,000 symptomatic illnesses affecting 9% of Utah residents occurred, resulting in 125,000 medically attended illnesses and 2,700 hospitalizations. During the 2017-18 season, an estimated 338,000 symptomatic illnesses affecting 11% of Utah residents occurred, resulting in 160,000 medically attended illnesses and 3,900 hospitalizations. Other state or county health departments could adapt similar methods in their jurisdictions to estimate the burden of influenza locally and support prompt public health activities., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Mr. McCaffrey reports grants from the Council of State and Territorial Epidemiologists during the conduct of the study. Dr. Pavia reports personal fees from Antimicrobial Therapy Inc, WebMD, Genentech, Merck, and Sequirius outside the submitted work. No other potential conflicts of interest were disclosed.

CDC, the Food and Drug Administration, state and local health departments, and other public health and clinical stakeholders are investigating a national outbreak of electronic-cigarette (e-cigarette), or vaping, product use-associated lung injury (EVALI) (1). As of October 22, 2019, 49 states, the District of Columbia (DC), and the U.S. Virgin Islands have reported 1,604 cases of EVALI to CDC, including 34 (2.1%) EVALI-associated deaths in 24 states. Based on data collected as of October 15, 2019, this report updates data on patient characteristics and substances used in e-cigarette, or vaping, products (2) and describes characteristics of EVALI-associated deaths. The median age of EVALI patients who survived was 23 years, and the median age of EVALI patients who died was 45 years. Among 867 (54%) EVALI patients with available data on use of specific e-cigarette, or vaping, products in the 3 months preceding symptom onset, 86% reported any use of tetrahydrocannabinol (THC)-containing products, 64% reported any use of nicotine-containing products, and 52% reported use of both. Exclusive use of THC-containing products was reported by 34% of patients and exclusive use of nicotine-containing products by 11%, and for 2% of patients, no use of either THC- or nicotine-containing products was reported. Among 19 EVALI patients who died and for whom substance use data were available, 84% reported any use of THC-containing products, including 63% who reported exclusive use of THC-containing products; 37% reported any use of nicotine-containing products, including 16% who reported exclusive use of nicotine-containing products. To date, no single compound or ingredient used in e-cigarette, or vaping, products has emerged as the cause of EVALI, and there might be more than one cause. Because most patients reported using THC-containing products before symptom onset, CDC recommends that persons should not use e-cigarette, or vaping, products that contain THC. In addition, because the specific compound or ingredient causing lung injury is not yet known, and while the investigation continues, persons should consider refraining from the use of all e-cigarette, or vaping, products., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

The NLRP3 inflammasome is a cytosolic complex sensing phagocytosed material and various damage-associated molecular patterns, triggering production of the pro-inflammatory cytokines interleukin-1 beta (IL)-1β and IL-18 and promoting pyroptosis. Here, we characterize glutathione transferase omega 1-1 (GSTO1-1), a constitutive deglutathionylating enzyme, as a regulator of the NLRP3 inflammasome. Using a small molecule inhibitor of GSTO1-1 termed C1-27, endogenous GSTO1-1 knockdown, and GSTO1-1 -/- mice, we report that GSTO1-1 is involved in NLRP3 inflammasome activation. Mechanistically, GSTO1-1 deglutathionylates cysteine 253 in NIMA related kinase 7 (NEK7) to promote NLRP3 activation. We therefore identify GSTO1-1 as an NLRP3 inflammasome regulator, which has potential as a drug target to limit NLRP3-mediated inflammation., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Breastfeeding confers substantial health benefits to women and infants. While disparities in breastfeeding persist in the United States, the extent of these disparities at the local level is unclear. This study aimed to identify local level and racial/ethnic breastfeeding disparities within Chicago. A community-based representative survey including questions on breastfeeding was conducted in Chicago. We estimated the proportion of women who breastfed their last child for any length of time and who breastfed at 6 months by neighborhood and maternal characteristics. We performed Rao-Scott corrected chi-squared tests to analyze factors hypothesized to be associated with breastfeeding. Between March 2015 and September 2016, 641 women with at least one live birth completed the survey. We found no differences by community area in the breastfeeding initiation or breastfeeding for at least 6 months. Puerto Rican women had the lowest prevalence of breastfeeding initiation and continuation at 6 months in contrast to Mexican women who reported the highest prevalence of these practices. We found breastfeeding disparities between Puerto Rican and Mexican Hispanic subgroups. Policies and programs aimed at increasing breastfeeding should prioritize groups that are least likely to initiate breastfeeding or most likely to breastfeed for a limited duration.

Infectious human papillomavirus 16 (HPV16) L1/L2 pseudovirions were found to remain largely intact during vesicular transport to the nucleus. By electron microscopy, capsids with a diameter of 50 nm were clearly visible within small vesicles attached to mitotic chromosomes and to a lesser extent within interphase nuclei, implying nuclear disassembly. By confocal analysis, it was determined that nuclear entry of assembled L1 is dependent upon the presence of the minor capsid protein, L2, but independent of encapsidated DNA. We also demonstrate that L1 nuclear localization and mitotic chromosome association can occur in vivo in the murine cervicovaginal challenge model of HPV16 infection. These findings challenge the prevailing concepts of PV uncoating and disassembly. More generally, they document that a largely intact viral capsid can enter the nucleus within a transport vesicle, establishing a novel mechanism by which a virus accesses the nuclear cellular machinery. IMPORTANCE Papillomaviruses (PVs) comprise a large family of nonenveloped DNA viruses that include HPV16, among other oncogenic types, the causative agents of cervical cancer. Delivery of the viral DNA into the host cell nucleus is necessary for establishment of infection. This was thought to occur via a subviral complex following uncoating of the larger viral capsid. In this study, we demonstrate that little disassembly of the PV capsid occurs prior to nuclear delivery. These surprising data reveal a previously unrecognized viral strategy to access the nuclear replication machinery. Understanding viral entry mechanisms not only increases our appreciation of basic cell biological pathways but also may lead to more effective antiviral interventions., (Copyright © 2019 American Society for Microbiology.)

Background: Frailty is associated with increased risk of mortality and decline in functional status among older adults. Older adults are at increased risk of severe disease from acute respiratory illness (ARIs), but ARI effects on frailty status among older adults are not well understood. We evaluated how ARIs affect short-term frailty status among community-dwelling adults aged ≥65 years in Nakhon Phanom, Thailand., Methods: During May 2015 to May 2017, older adults were contacted weekly to identify ARIs as part of a community-based longitudinal cohort study. Each participant's frailty status was assessed at baseline and every 6 months using the Vulnerable Elders Survey-13 (VES-13). We selected cohort participants with an ARI and compared them with a sample of participants without an ARI matched on age, sex, influenza vaccination status, and most recent VES-13 score. For these matched cohort members, an additional VES-13 was recorded at 3-4 weeks after the ARI episode date., Results: Of 3220 cohort study participants, 114 participants with an ARI and 111 comparison participants without an ARI were selected for the matched cohort; three comparison participants were matched to two ARI cases. We found no statistically significant difference between ARI and non-ARI participants in modified VES-13 score 3-4 weeks post-episode (cases = 0.90, controls = 0.63, P = 0.07). Only two ARI episodes required hospitalization., Conclusions: Primarily mild ARIs did not affect short-term frailty status among community-dwelling older adults in Thailand. As few cases of severe ARI were detected, the contribution of severe ARI to changes in frailty requires further investigation., (© 2019 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. Keegan McCaffrey reports grants from the Council of State and Territorial Epidemiologists during the course of the study. No other potential conflicts of interest were disclosed.

Pollution has led to a decline of benthic invertebrate biodiversity of Narragansett Bay, raising questions about effects on ecosystem functions and services including shellfish production, energy flow to fishes, and biogeochemical cycles. Changes in community composition and taxonomic distinctness (biodiversity) were calculated from the 1950s-when quantitative benthic invertebrate data first became available-to 2015. Change in community composition of the bay was correlated with changes in dissolved inorganic nitrogen, dissolved oxygen, and sediment contaminants. A mid-bay reference site showed moderate changes in community composition but no change in biodiversity. In contrast, a more impacted site in the upper bay showed substantial differences in community composition over time and a decline in taxonomic distinctness. Bay-wide, as inputs of some stressors such as nutrients and sediment contaminants have declined, there are signs of recovery of benthic biodiversity but other stressors such as temperature and watershed development are increasing., (Published by Elsevier Ltd.)

The endogenous metabolite itaconate has recently emerged as a regulator of macrophage function, but its precise mechanism of action remains poorly understood. Here we show that itaconate is required for the activation of the anti-inflammatory transcription factor Nrf2 (also known as NFE2L2) by lipopolysaccharide in mouse and human macrophages. We find that itaconate directly modifies proteins via alkylation of cysteine residues. Itaconate alkylates cysteine residues 151, 257, 288, 273 and 297 on the protein KEAP1, enabling Nrf2 to increase the expression of downstream genes with anti-oxidant and anti-inflammatory capacities. The activation of Nrf2 is required for the anti-inflammatory action of itaconate. We describe the use of a new cell-permeable itaconate derivative, 4-octyl itaconate, which is protective against lipopolysaccharide-induced lethality in vivo and decreases cytokine production. We show that type I interferons boost the expression of Irg1 (also known as Acod1) and itaconate production. Furthermore, we find that itaconate production limits the type I interferon response, indicating a negative feedback loop that involves interferons and itaconate. Our findings demonstrate that itaconate is a crucial anti-inflammatory metabolite that acts via Nrf2 to limit inflammation and modulate type I interferons.

Objectives: To investigate local-level adult influenza and pneumococcal vaccination disparities to inform targeted interventions., Methods: Questions on influenza and pneumococcal vaccination uptake were included in a door-to-door community-based representative survey conducted in 10 Chicago, Illinois, neighborhoods in 2015 and 2016. A total of 1543 adults completed the survey, including 172 adults aged 65 years or older. We calculated adult influenza (≥ 18 years) and pneumococcal (≥ 65 years) vaccination coverage by community area and respondent characteristics., Results: We observed significant differences in pneumococcal vaccination coverage between community areas (range = 18%-91%). Influenza vaccination coverage differed by gender, age, insurance coverage, acculturation, and confidence or trust in physician. Non-Hispanic Blacks were more likely to be vaccinated when they had higher confidence or trust in their physician (45% vs 20%; P < .01). Mexicans who reported less acculturation were more likely to be vaccinated than were Mexicans who were more acculturated (41% vs 27%; P = .02)., Conclusions: Striking disparities between neighborhoods and racial/ethnic groups in adult influenza and pneumococcal vaccination coverage highlight the need for improved local-level immunization coverage data.