OBJECTIVE: The diagnostic criteria of lymphatic vascular invasion have not been standardized. Our investigation assesses the factors associated with lymphatic vascular invasion positive tumors and the impact of lymphatic vascular invasion on overall survival for patients with non-small cell lung cancer undergoing (bi)lobectomy with an adequate node dissection. METHODS: The National Cancer Database was queried from the years 2010 to 2015 to find surgical patients who underwent lobectomy with at least 10 lymph nodes examined (adequate node dissection) and with known lymphatic vascular invasion status. Paired t tests were used to distinguish differences between the patients with and without lymphatic vascular invasion in their specimen. Multivariable analysis was used to determine factors associated with overall survival. Propensity score matching adjusting for overall survival factors was used to determine the lymphatic vascular invasion's overall survival impact by grade, histology, p-T/N/overall stage, and tumor size. RESULTS: Lymphatic vascular invasion status was reported in 91.6% and positive in 23.4% of 28,842 eligible patients. Academic medical centers, institutions with populations more than 1,000,000, and the mid-Atlantic region reported higher rates of lymphatic vascular invasion positive tumors as well as overall survival compared with other cancer centers. Lymphatic vascular invasion was independently associated with a significant decrement in overall survival as per multivariable analysis and propensity score matching. Propensity score matching demonstrated that lymphatic vascular invasion was associated with a significant decrement in overall survival for all histologies, tumor grades, tumor sizes, and stages, except for more advanced pathologic stages T3/III/N2 and larger tumors greater than 4 cm for which overall survival was trending worse with lymphatic vascular invasion positive. CONCLUSIONS: Lymphatic vascular invasion positive varies based on hospital location/type and population, but it was associated with a decrement in overall survival that was independent of pathologic T/N/overall stage, histology, and tumor grade. Lymphatic vascular invasion must be standardized and considered as a staging variable and should be considered as a sole determinant for prognosis, especially for those with earlier-stage and smaller tumors.

While influenza A virus (IAV) antigenic drift has been documented globally, in experimental animal infections, and in immunocompromised hosts, positive selection has generally not been detected in acute infections. This is likely due to challenges in distinguishing selected rare mutations from sequencing error, a reliance on cross-sectional sampling, and/or the lack of formal tests of selection for individual sites. Here, we sequenced IAV populations from 346 serial, daily nasal swabs from 143 individuals collected over three influenza seasons in a household cohort. Viruses were sequenced in duplicate, and intrahost single nucleotide variants (iSNVs) were identified at a 0.5% frequency threshold. Within-host populations exhibited low diversity, with >75% mutations present at <2% frequency. Children (0-5 years) had marginally higher within-host evolutionary rates than adolescents (6-18 years) and adults (>18 years, 4.4 × 10(-6) vs. 9.42 × 10(-7) and 3.45 × 10(-6), P < .001). Forty-five iSNVs had evidence of parallel evolution but were not over-represented in HA and NA. Several increased from minority to consensus level, with strong linkage among iSNVs across segments. A Wright-Fisher approximate Bayesian computational model identified positive selection at 23/256 loci (9%) in A(H3N2) specimens and 19/176 loci (11%) in A(H1N1)pdm09 specimens, and these were infrequently found in circulation. Overall, we found that within-host IAV populations were subject to genetic drift and purifying selection, with only subtle differences across seasons, subtypes, and age strata. Positive selection was rare and inconsistently detected.

BACKGROUND: COVID-19 convalescent plasma (CCP) remains a treatment option for immunocompromised patients; however, the current FDA qualification threshold of ≥200 BAU/mL of spike antibody appears to be relatively low. We evaluated the levels of binding (bAb) and neutralizing antibodies (nAb) on serial samples from repeat blood donors who were vaccinated and/or infected to inform criteria for qualifying CCP from routinely collected plasma components. METHODS: Donors were categorized into four groups: (1) infected, then vaccinated, (2) vaccinated then infected during the delta, or (3) omicron waves, (4) vaccinated without infection. IgG Spike and total Nuclecapsid bAb were measured, along with S variants and nAb titers using reporter viral particle neutralization. RESULTS: Mean S IgG bAb peaks after infection alone were lower than after primary and booster vaccinations, and higher after delta and omicron infection in previously vaccinated donors. Half-lives for S IgG ranged from 34 to 66 days after first infection/vaccination events and up to 108 days after second events. The levels of S IgG bAb and nAb were similar across different variants, except for omicron, which were lower. Better correlations of nAb with bAb were observed at higher levels (hybrid immunity) than at the current FDA CCP qualifying threshold. DISCUSSION: Routine plasma donations from donors with hybrid immunity had high S bAb and potent neutralizing activity for 3-6 months after infection. In donations with high (>4000 BAU/mL) S IgG, >95% had high nAb titers (>500) against ancestral and variant S, regardless of COVID-19 symptoms. These findings provide the basis for test-based criteria for qualifying CCP from routine blood donations.

INTRODUCTION: An error grid compares measured versus reference glucose concentrations to assign clinical risk values to observed errors. Widely used error grids for blood glucose monitors (BGMs) have limited value because they do not also reflect clinical accuracy of continuous glucose monitors (CGMs). METHODS: Diabetes Technology Society (DTS) convened 89 international experts in glucose monitoring to (1) smooth the borders of the Surveillance Error Grid (SEG) zones and create a user-friendly tool-the DTS Error Grid; (2) define five risk zones of clinical point accuracy (A-E) to be identical for BGMs and CGMs; (3) determine a relationship between DTS Error Grid percent in Zone A and mean absolute relative difference (MARD) from analyzing 22 BGM and nine CGM accuracy studies; and (4) create trend risk categories (1-5) for CGM trend accuracy. RESULTS: The DTS Error Grid for point accuracy contains five risk zones (A-E) with straight-line borders that can be applied to both BGM and CGM accuracy data. In a data set combining point accuracy data from 18 BGMs, 2.6% of total data pairs equally moved from Zones A to B and vice versa (SEG compared with DTS Error Grid). For every 1% increase in percent data in Zone A, the MARD decreased by approximately 0.33%. We also created a DTS Trend Accuracy Matrix with five trend risk categories (1-5) for CGM-reported trend indicators compared with reference trends calculated from reference glucose. CONCLUSION: The DTS Error Grid combines contemporary clinician input regarding clinical point accuracy for BGMs and CGMs. The DTS Trend Accuracy Matrix assesses accuracy of CGM trend indicators.

IMPORTANCE: Uncontrolled hypertension is a major contributor to cardiovascular disease (CVD) in the US. OBJECTIVE: To determine the prevalence of hypertension control cascade outcomes (hypertension awareness, treatment recommendations, and medication use) among individuals with uncontrolled hypertension to inform action across cascade levels. DESIGN, SETTING, AND PARTICIPANTS: This weighted cross-sectional study used January 2017 to March 2020 National Health and Nutrition Examination Survey (NHANES) data from noninstitutionalized adults aged 18 years or older in the US with uncontrolled hypertension. Data analysis occurred from January to February 2024. EXPOSURE: Calendar year of response to the NHANES survey. MAIN OUTCOMES AND MEASURES: Mean blood pressure (BP) was computed using up to 3 measurements. Uncontrolled hypertension was defined as systolic BP of 130 mm Hg or greater or diastolic BP of 80 mm Hg or greater, regardless of medication use. Outcomes included patient awareness of hypertension, treatment recommendations, and medication use. To estimate population totals by subgroup, the age-standardized proportion of each outcome was multiplied by the estimated number of adults with uncontrolled hypertension. RESULTS: The study included 3129 US adults with uncontrolled hypertension (1675 male [weighted percentage, 52.3%]; 775 aged 18 to 44 years [weighted percentage, 29.4%]; 1306 aged 45 to 64 years [weighted percentage, 41.4%]; 1048 aged 65 years or older [weighted percentage, 29.2%]), resulting in a population estimate of 100.4 million adults (weighted percentage, 83.7%) with uncontrolled hypertension. More than one-half of study participants (57.8 million adults [weighted percentage, 57.6%]) were unaware that they had hypertension, and of the 35.0 million who were aware and met criteria for antihypertensive medication, 24.8 million (weighted percentage, 70.8%) took the medication but had hypertension that remained uncontrolled. These negative outcomes in the hypertension control cascade occurred across demographic groups, with notably high prevalence among younger adults and individuals engaged in health care. Among an estimated 30.1 million adults aged 18 to 44 years with hypertension, 10.4 of 11.3 million females (weighted percentage, 91.8%) and 17.7 million of 18.8 million males (weighted percentage, 94.3%) had uncontrolled hypertension. Of the 10.4 million females, 7.2 million (weighted percentage, 68.8%) were unaware of their hypertension status, and of the 17.7 million males, 12.0 million (weighted percentage, 68.1%) were unaware. Additionally, 9.9 of 13.0 million adults with uncontrolled hypertension (weighted percentage, 75.7%) reported no health care visits in the past year and were unaware. Conversely, among 70.6 million adults with uncontrolled hypertension reporting 2 or more health care visits, approximately one-half (36.6 million [weighted percentage, 51.8%]) were unaware. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, more than 50% of adults with uncontrolled hypertension in the US were unaware of their hypertension and were untreated, and 70.8% of those who were treated had hypertension that remained uncontrolled. These findings have serious implications for the nation's overall health given the association of hypertension with increased risk for CVD.

Nucleocapsid antibody assays can be used to estimate SARS-CoV-2 infection prevalence in regions implementing spike-based COVID-19 vaccines. However, poor sensitivity of nucleocapsid antibody assays in detecting infection after vaccination has been reported. We derived a lower cutoff for identifying previous infections in a large blood donor cohort (N = 142,599) by using the Ortho VITROS Anti-SARS-CoV-2 Total-N Antibody assay, improving sensitivity while maintaining specificity >98%. We validated sensitivity in samples donated after self-reported swab-confirmed infections diagnoses. Sensitivity for first infections in unvaccinated donors was 98.1% (95% CI 98.0-98.2) and for infection after vaccination was 95.6% (95% CI 95.6-95.7) based on the standard cutoff. Regression analysis showed sensitivity was reduced in the Delta compared with Omicron period, in older donors, in asymptomatic infections, <30 days after infection, and for infection after vaccination. The standard Ortho N antibody threshold demonstrated good sensitivity, which was modestly improved with the revised cutoff.

BACKGROUND: The adequacy of biomarkers of potential harm (BOPH) for assessing tobacco products was explored based on their ability to distinguish tobacco use from non-use, change with cessation, and to show biological gradient. METHODS: The sample included individuals with biomarker data in Wave 1 of the Population Assessment of Tobacco Health (PATH) Study who never used tobacco, currently smoke cigarettes exclusively, used to smoke cigarettes exclusively (quit in past 12 months), currently use smokeless tobacco exclusively, and currently use e-cigarettes exclusively. We compared BOPH levels between groups and assessed the relationships between log-transformed biomarkers of exposure (BOE) [Total Nicotine Equivalents including seven nicotine metabolites (TNE-7), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanonol (NNAL), N-acetyl-S-(2-cyanoethyl)-L-cysteine (CYMA), 1-Hydroxypyrene (1-OHP), cadmium, and serum cotinine (SCOT)], and BOPH [high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), fibrinogen, soluble intercellular adhesion molecule-1 (sICAM-1) and 8-isoprostane]. RESULTS: Among people who smoke, both sICAM-1 and 8-isoprostane distinguished smoking from non-use and were associated with all six BOE. Among people who use smokeless tobacco, 8-isoprostane was associated with TNE-7 and NNAL whereas hs-CRP was associated with SCOT. Among people who use e-cigarettes, no associations between BOPH and BOE were observed. CONCLUSIONS: Both sICAM-1 and 8-isoprostane may be useful for assessing the use or changes in use of some tobacco products. Studies examining their predictive validity could further strengthen our understanding of these two biomarkers. IMPACT: We found that two BOPH, sICAM-1 and 8-isoprostane, may have utility in studies assessing the potential harm of tobacco use in absence of long-term epidemiological studies.

Sosuga virus (SOSV), a rare human pathogenic paramyxovirus, was first discovered in 2012 when a person became ill after working in South Sudan and Uganda. During an ecological investigation, several species of bats were sampled and tested for SOSV RNA and only one species, the Egyptian rousette bat (ERBs; Rousettus aegyptiacus), tested positive. Since that time, multiple other species have been sampled and ERBs in Uganda have continued to be the only species of bat positive for SOSV infection. Subsequent studies of ERBs with SOSV demonstrated that ERBs are a competent host for SOSV and shed this infectious virus while exhibiting only minor infection-associated pathology. Following the 2014 Ebola outbreak in West Africa, surveillance efforts focused on discovering reservoirs for zoonotic pathogens resulted in the capture and testing of many bat species. Here, SOSV RNA was detected by qRT-PCR only in ERBs captured in the Moyamba District of Sierra Leone in the central region of the country. These findings represent a substantial range extension from East Africa to West Africa for SOSV, suggesting that this paramyxovirus may occur in ERB populations throughout its sub-Saharan African range.

The purpose of this analysis is to describe HIV tests and associated outcomes for Asian people reached by the Centers for Disease Control and Prevention (CDC) HIV testing program. We analyzed CDC-funded HIV tests among Asian individuals in the United States, Puerto Rico, and the U.S. Virgin Islands (2014-2020). Of the 415,560 tests, the positivity of new diagnoses was higher among males (0.49%, aPR = 7.64) than females (0.06%), and in the West (0.42%, aPR = 1.15) than in the South (0.25%). In non-health care settings, positivity was highest among men who have sex with men (MSM; 0.87%) and transgender people (0.46%). Linkage to HIV medical care among Asian people was 87.5%, and 70.7% were interviewed for partner services. Our findings suggest that improvements are crucial, particularly for Asian MSM, in linkage to care and interview for partner services.

IMPORTANCE: The function-based eat, sleep, console (ESC) care approach substantially reduces the proportion of infants who receive pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS). This reduction has led to concerns for increased postnatal opioid exposure in infants who receive pharmacologic treatment. However, the effect of the ESC care approach on hospital outcomes for infants pharmacologically treated for NOWS is currently unknown. OBJECTIVE: To evaluate differences in opioid exposure and total length of hospital stay (LOS) for pharmacologically treated infants managed with the ESC care approach vs usual care with the Finnegan tool. DESIGN, SETTING, AND PARTICIPANTS: This post hoc subgroup analysis involved infants pharmacologically treated in ESC-NOW, a stepped-wedge cluster randomized clinical trial conducted at 26 US hospitals. Hospitals maintained pretrial practices for pharmacologic treatment, including opioid type, scheduled opioid dosing, and use of adjuvant medications. Infants were born at 36 weeks' gestation or later, had evidence of antenatal opioid exposure, and received opioid treatment for NOWS between September 2020 and March 2022. Data were analyzed from November 2022 to January 2024. EXPOSURE: Opioid treatment for NOWS and the ESC care approach. MAIN OUTCOMES AND MEASURES: For each outcome (total opioid exposure, peak opioid dose, time from birth to initiation of first opioid dose, length of opioid treatment, and LOS), we used generalized linear mixed models to adjust for the stepped-wedge design and maternal and infant characteristics. RESULTS: In the ESC-NOW trial, 463 of 1305 infants were pharmacologically treated (143/603 [23.7%] in the ESC care approach group and 320/702 [45.6%] in the usual care group). Mean total opioid exposure was lower in the ESC care approach group with an absolute difference of 4.1 morphine milligram equivalents per kilogram (MME/kg) (95% CI, 1.3-7.0) when compared with usual care (4.8 MME/kg vs 8.9 MME/kg, respectively; P = .001). Mean time from birth to initiation of pharmacologic treatment was 22.4 hours (95% CI, 7.1-37.7) longer with the ESC care approach vs usual care (75.4 vs 53.0 hours, respectively; P = .002). No significant difference in mean peak opioid dose was observed between groups (ESC care approach, 0.147 MME/kg, vs usual care, 0.126 MME/kg). The mean length of treatment was 6.3 days shorter (95% CI, 3.0-9.6) in the ESC care approach group vs usual care group (11.8 vs 18.1 days, respectively; P < .001), and mean LOS was 6.2 days shorter (95% CI, 3.0-9.4) with the ESC care approach than with usual care (16.7 vs 22.9 days, respectively; P < .001). CONCLUSION AND RELEVANCE: When compared with usual care, the ESC care approach was associated with less opioid exposure and shorter LOS for infants pharmacologically treated for NOWS. The ESC care approach was not associated with a higher peak opioid dose, although pharmacologic treatment was typically initiated later. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04057820.

Micro- and nanoplastic particles (MNP) are omnipresent as either pollution or intentionally used in consumer products, released from packaging or even food. There is an exponential increase in the production of plastics. With the realization of bioaccumulation in humans, toxicity research is quickly expanding. There is a rapid increase in the number of papers published on the potential implications of exposure to MNP which necessitates a call for quality criteria to be applied when doing the research. At present, most papers on MNP describe the effects of commercially available polymer (mostly polystyrene) beads that are typically not the MNP of greatest concern. This is not a fault of the research community, necessarily, as the MNPs to which humans are exposed are usually not available in the quantities needed for toxicological research and innovations are needed to supply environmentally-relevant MNP models. In addition, like we have learned from decades of research with particulate matter and engineered nanomaterials, sample physicochemical characteristics and preparation can have major impacts on the biological responses and interpretation of the research findings. Lastly, MNP dosimetry may pose challenges as (1) we are seeing early evidence that plastics are already in the human body at quite high levels that may be difficult to achieve in acute in vitro studies and (2) plastics are already in the diets fed to preclinical models. This commentary highlights the pitfalls and recommendations for particle and fibre toxicologists that should be considered when performing and disseminating the research.

Hypertension in pregnancy (HP) includes eclampsia/preeclampsia, chronic hypertension, superimposed preeclampsia, and gestational hypertension. In the United States, HP prevalence doubled over the last three decades, based on birth certificate data. In 2019, the estimated percent of births with a history of HP varied from 10.1% to 15.9% for birth certificate data and hospital discharge records, respectively. The use of electronic medical records may result in identifying an additional third to half of undiagnosed cases of HP. Individuals with gestational hypertension or preeclampsia are at 3.5 times higher risk of progressing to chronic hypertension and from 1.7 to 2.8 times higher risk of developing cardiovascular disease (CVD) after childbirth compared with individuals without these conditions. Interventions to identify and address CVD risk factors among individuals with HP are most effective if started during the first 6 weeks postpartum and implemented during the first year after childbirth. Providing access to affordable health care during the first 12 months after delivery may ensure healthy longevity for individuals with HP. Average attendance rates for postpartum visits in the United States are 72.1%, but the rates vary significantly (from 24.9% to 96.5%). Moreover, even among individuals with CVD risk factors who attend postpartum visits, approximately 40% do not receive counseling on a healthy lifestyle. In the United States, as of the end of September 2023, 38 states and the District of Columbia have extended Medicaid coverage eligibility, eight states plan to implement it, and two states proposed a limited coverage extension from 2 to 12 months after childbirth. Currently, data gaps exist in national health surveillance and health systems to identify and monitor HP. Using multiple data sources, incorporating electronic medical record data algorithms, and standardizing data definitions can improve surveillance, provide opportunities to better track progress, and may help in developing targeted policy recommendations.

BACKGROUND: Approximately 13% of persons with HIV (PWH) are unaware of their status. To help end HIV, it is important to understand the relationship between the rates of HIV testing and undiagnosed HIV infection. SETTING: Ending the HIV in the U.S. (EHE) jurisdictions. METHODS: Using 2021 data from the National HIV Surveillance System and the National HIV Prevention Program Monitoring and Evaluation system, we calculated estimated rates of undiagnosed HIV infections per 100,000 population and rates of CDC-funded HIV tests per 1,000 population. We assessed the association between the two rates using Spearman's rank correlation. We also calculated a rank difference between the two rates for each EHE jurisdiction to help identify jurisdictions with greater unfilled needs for HIV testing. RESULTS: Overall, CDC-funded HIV tests per 1,000 population were positively associated with estimated rate of undiagnosed HIV infection per 100,000 population (rho=0.55, p<0.001). EHE jurisdictions with the greatest magnitude of negative rank differences (i.e., higher undiagnosed HIV infection per 100,000 population and lower CDC-funded HIV tests per 1,000 population) were Prince George's County, MD; Mecklenburg County, NC; Hudson County, NJ; Bronx County, NY, and Hamilton County, OH. CONCLUSIONS: In general, CDC-funded HIV testing is being conducted in jurisdictions with the greatest needs. However, we also found large discrepancies between CDC-funded HIV testing and undiagnosed HIV infection rates for some jurisdictions. These jurisdictions may want to identify barriers to their HIV testing services and expand their programs to ensure that all PWH in their jurisdictions are diagnosed.

BACKGROUND: Community Approaches to Reducing Sexually Transmitted Disease (CARS), a unique initiative of the US Centers for Disease Control and Prevention, promotes the use of community engagement to increase sexually transmitted disease (STD) prevention, screening, and treatment and to address locally prioritized STD-related social determinants of health within communities experiencing STD disparities, including youth, persons of color, and sexual and gender minorities. We sought to identify elements of community engagement as applied within CARS. METHODS AND MATERIALS: Between 2011 and 2018, we collected and analyzed archival and in-depth interview data to identify and explore community engagement across 8 CARS sites. Five to 13 interview participants (mean, 7) at each site were interviewed annually. Participants included project staff and leadership, community members, and representatives from local community organizations (e.g., health departments; lesbian, gay, bisexual, transgender, and queer-serving organizations; faith organizations; businesses; and HIV-service organizations) and universities. Data were analyzed using constant comparison, an approach to grounded theory development. RESULTS: Twelve critical elements of community engagement emerged, including commitment to engagement, partner flexibility, talented and trusted leadership, participation of diverse sectors, establishment of vision and mission, open communication, reducing power differentials, working through conflict, identifying and leveraging resources, and building a shared history. CONCLUSIONS: This study expands the community engagement literature within STD prevention, screening, and treatment by elucidating some of the critical elements of the approach and provides guidance for practitioners, researchers, and their partners as they develop, implement, and evaluate strategies to reduce STD disparities.

Passive surface acoustic wave (SAW) devices are attractive candidates for continuous wireless monitoring of corrosion in large infrastructures. However, acoustic loss in the aqueous medium and limited read range usually create challenges in their widespread use for monitoring large systems such as oil and gas (O&G) pipelines, aircraft, and processing plants. This paper presents the investigation of impedance-loaded reflective delay line (IL-RDL) SAW devices for monitoring metal corrosion under O&G pipeline-relevant conditions. Specifically, we studied the effect of change in resistivity of a reflector on the backscattered signal of an RDL and investigated an optimal range through simulation. This was followed by the experimental demonstrations of real-time monitoring of Fe film corrosion in pressurized (550 psi) humid CO(2) conditions. Additionally, remote monitoring of Fe film corrosion in an acidic solution inside a 70 m carbon steel pipe was demonstrated using guided waves. This paper also suggests potential ways to improve the sensing response of IL-RDLs.

Vaccine effectiveness (VE) studies utilizing the test-negative design are typically conducted in clinical settings, rather than community populations, leading to bias in VE estimates against mild disease and limited information on VE in healthy young adults. In a community-based university population, we utilized data from a large SARS-CoV-2 testing program to estimate relative VE of COVID-19 mRNA vaccine primary series and monovalent booster dose versus primary series only against symptomatic SARS-CoV-2 infection from September 2021 to July 2022. We used the test-negative design and logistic regression implemented via generalized estimating equations adjusted for age, calendar time, prior SARS-CoV-2 infection, and testing frequency (proxy for test-seeking behavior) to estimate relative VE. Analyses included 2,218 test-positive cases (59 % received monovalent booster dose) and 9,615 test-negative controls (62 %) from 9,066 individuals, with median age of 21 years, mostly students (71 %), White (56 %) or Asian (28 %), and with few comorbidities (3 %). More cases (23 %) than controls (6 %) had COVID-19-like illness. Estimated adjusted relative VE of primary series and monovalent booster dose versus primary series only against symptomatic SARS-CoV-2 infection was 40 % (95 % CI: 33-47 %) during the overall analysis period and 46 % (39-52 %) during the period of Omicron circulation. Relative VE was greater for those without versus those with prior SARS-CoV-2 infection (41 %, 34-48 % versus 33 %, 9 %-52 %, P < 0.001). Relative VE was also greater in the six months after receiving a booster dose (41 %, 33-47 %) compared to more than six months (27 %, 8-42 %), but this difference was not statistically significant (P = 0.06). In this relatively young and healthy adult population, an mRNA monovalent booster dose provided increased protection against symptomatic SARS-CoV-2 infection, overall and with the Omicron variant. University testing programs may be utilized for estimating VE in healthy young adults, a population that is not well-represented by routine VE studies.

Between September and November 2021, 5 snow leopards (Panthera uncia) and 1 lion (Panthera leo) were naturally infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) and developed progressive respiratory disease that resulted in death. Severe acute respiratory syndrome coronavirus 2 sequencing identified the delta variant in all cases sequenced, which was the predominant human variant at that time. The time between initial clinical signs and death ranged from 3 to 45 days. Gross lesions in all 6 cats included nasal turbinate hyperemia with purulent discharge and marked pulmonary edema. Ulcerative tracheitis and bronchitis were noted in 4 cases. Histologically, there was necrotizing and ulcerative rhinotracheitis and bronchitis with fibrinocellular exudates and fibrinosuppurative to pyogranulomatous bronchopneumonia. The 4 cats that survived longer than 8 days had fungal abscesses. Concurrent bacteria were noted in 4 cases, including those with more acute disease courses. Severe acute respiratory syndrome coronavirus 2 was detected by in situ hybridization using probes against SARS-CoV-2 spike and nucleocapsid genes and by immunohistochemistry. Viral nucleic acid and protein were variably localized to mucosal and glandular epithelial cells, pneumocytes, macrophages, and fibrinocellular debris. Based on established criteria, SARS-CoV-2 was considered a contributing cause of death in all 6 cats. While mild clinical infections are more common, these findings suggest that some SARS-CoV-2 variants may cause more severe disease and that snow leopards may be more severely affected than other felids.

The free-living thermophilic amoeba Naegleria fowleri (N. fowleri) causes the highly fatal disease primary amoebic meningoencephalitis. The environmental conditions that are favorable to the growth and proliferation of N. fowleri are not well-defined, especially in northern regions of the United States. In this study, we used culture-based methods and multiple molecular approaches to detect and analyzeN. fowleri and other Naegleria spp. in water, sediment, and biofilm samples from five hot spring sites in Grand Teton National Park, Wyoming, U.S.A. These results provide the first detections of N. fowleri in Grand Teton National Park and provide new insights into the distribution of pathogenic N. fowleri and other nonpathogenic Naegleria spp. in natural thermal water systems in northern latitudes. © 2024 The Authors. Published by American Chemical Society.

Cardiovascular conditions are significant contributors to morbidity and mortality among pregnant and postpartum women.1 | | We used data from the MarketScan Commercial Claims and Encounters database to identify women 12 to 55 years of age who delivered from 2017 to 2019. Delivery hospitalizations and cardiovascular diagnoses and procedures (ie, conditions) were identified using International Classification of Diseases-10th Revision-Clinical Modification codes. Cardiovascular conditions included acute heart failure or pulmonary edema; acute myocardial infarction; arrhythmia; conduction disorders; cardiac arrest, ventricular fibrillation, or ventricular flutter; cardiomyopathy; congenital heart and great artery defects; conversion of cardiac rhythm; endocarditis, myocarditis, or pericarditis; hypertensive heart disease; ischemic heart disease; nonrheumatic valve disorders; pulmonary heart disease; rheumatic heart disease; and other heart diseases and complications. We calculated the prevalence of hospitalizations with any cardiovascular condition in the year postpartum. Among these patients, we calculated the prevalence of cardiovascular conditions at delivery hospitalization and the frequency of postpartum hospitalizations. For postpartum hospitalizations with cardiovascular conditions, we calculated timing relative to delivery hospitalization and the prevalence (95% CI) of specific cardiovascular conditions by timing since delivery hospitalization (early postpartum [1–42 days] vs late postpartum [43–365 days]), accounting for clustering at the patient level. The data were collected and statistically deidentified. The data are also compliant with the conditions set forth in sections 164.514(a) and 164.51(b)(1)(ii) of the Health Insurance Portability and Accountability Act of 1996 Privacy Rule; therefore, approval from an Institutional Review Board was not sought.

Children with chronic illnesses report being bullied by peers, yet little is known about bullying among children with heart conditions. Using 2018-2020 National Survey of Children's Health data, the prevalence and frequency of being bullied in the past year (never; annually or monthly; weekly or daily) were compared between children aged 6-17 years with and without heart conditions. Among children with heart conditions, associations between demographic and health characteristics and being bullied, and prevalence of diagnosed anxiety or depression by bullying status were examined. Differences were assessed with chi-square tests and multivariable logistic regression using predicted marginals to produce adjusted prevalence ratios and 95% confidence intervals. Weights yielded national estimates. Of 69,428 children, 2.2% had heart conditions. Children with heart conditions, compared to those without, were more likely to be bullied (56.3% and 43.3% respectively; adjusted prevalence ratio [95% confidence interval] = 1.3 [1.2, 1.4]) and bullied more frequently (weekly or daily = 11.2% and 5.3%; p < 0.001). Among children with heart conditions, characteristics associated with greater odds of weekly or daily bullying included ages 9-11 years compared to 15-17 years (3.4 [2.0, 5.7]), other genetic or inherited condition (1.7 [1.0, 3.0]), ever overweight (1.7 [1.0, 2.8]), and a functional limitation (4.8 [2.7, 8.5]). Children with heart conditions who were bullied, compared to never, more commonly had anxiety (40.1%, 25.9%, and 12.8%, respectively) and depression (18.0%, 9.3%, and 4.7%; p < 0.01 for both). Findings highlight the social and psychological needs of children with heart conditions.

These recommendations from the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations for anthrax vaccine adsorbed (AVA) (CDC. Use of anthrax vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2000;49:1-20; CDC. Use of anthrax vaccine in response to terrorism: supplemental recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2002;51:1024-6) and reflect the status of anthrax vaccine supplies in the United States. This statement 1) provides updated information on anthrax epidemiology; 2) summarizes the evidence regarding the effectiveness and efficacy, immunogenicity, and safety of AVA; 3) provides recommendations for pre-event and preexposure use of AVA; and 4) provides recommendations for postexposure use of AVA. In certain instances, recommendations that did not change were clarified. No new licensed anthrax vaccines are presented. Substantial changes to these recommendations include the following: 1) reducing the number of doses required to complete the pre-event and preexposure primary series from 6 doses to 5 doses, 2) recommending intramuscular rather than subcutaneous AVA administration for preexposure use, 3) recommending AVA as a component of postexposure prophylaxis in pregnant women exposed to aerosolized Bacillus anthracis spores, 4) providing guidance regarding preexposure vaccination of emergency and other responder organizations under the direction of an occupational health program, and 5) recommending 60 days of antimicrobial prophylaxis in conjunction with 3 doses of AVA for optimal protection of previously unvaccinated persons after exposure to aerosolized B. anthracis spores.

BACKGROUND: A guideline panel convened by the American Dental Association Council on Scientific Affairs, American Dental Association Science and Research Institute, University of Pittsburgh School of Dental Medicine, and Center for Integrative Global Oral Health at the University of Pennsylvania conducted a systematic review and meta-analyses and formulated evidence-based recommendations for the pharmacologic management of acute dental pain after 1 or more simple and surgical tooth extractions and the temporary management of toothache (that is, when definitive dental treatment not immediately available) associated with pulp and furcation or periapical diseases in children (< 12 years). TYPES OF STUDIES REVIEWED: The authors conducted a systematic review to determine the effect of analgesics and corticosteroids in managing acute dental pain. They used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence and the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework to formulate recommendations. RESULTS: The panel formulated 7 recommendations and 5 good practice statements across conditions. There is a small beneficial net balance favoring the use of nonsteroidal anti-inflammatory drugs alone or in combination with acetaminophen compared with not providing analgesic therapy. There is no available evidence regarding the effect of corticosteroids on acute pain after surgical tooth extractions in children. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Nonopioid medications, specifically nonsteroidal anti-inflammatory drugs like ibuprofen and naproxen alone or in combination with acetaminophen, are recommended for managing acute dental pain after 1 or more tooth extractions (that is, simple and surgical) and the temporary management of toothache in children (conditional recommendation, very low certainty). According to the US Food and Drug Administration, the use of codeine and tramadol in children for managing acute pain is contraindicated.

PURPOSE: Racial discrimination targeting Asians in the United States has increased sharply since the COVID-19 pandemic. Despite a well-established link with mental/physical health outcomes, little is known about how racial discrimination relates to interpersonal violence, particularly in adolescents. To address this gap in knowledge, we examined cross-sectional and longitudinal (1-year follow-up) associations between racial discrimination and interpersonal violence perpetration and victimization in Asian American adolescents in a large US city. METHODS: Data from Waves 3 (2020) and 4 (2021) of a randomized clinical trial of a school-based violence prevention program were examined. We limited our sample to participants who identified as Asian American (n = 344; 48.3% female; Mean(age) = 14.6 years at Wave 3). RESULTS: At Wave 3, 26.5% of the adolescents reported experiencing some form of racial discrimination, including 18.3% experiencing verbal harassment due to race and 16.0% reporting inequitable treatment due to race. Relative to their nonvictimized counterparts, adolescents who experienced racial discrimination were more likely to report being a victim of bullying and teen dating violence cross-sectionally and being a bullying victim longitudinally. Moreover, those who experienced racial discrimination reported more bullying and teen dating violence perpetration concurrently, as well as more dating violence perpetration 1 year later. DISCUSSION: In the understudied population of Asian American adolescents, we found that experiencing racial discrimination contributes to both interpersonal violence victimization and perpetration. Youth violence prevention could include strategies addressing racial discrimination.

THIS REPORT UPDATES PREVIOUS CDC GUIDELINES AND RECOMMENDATIONS ON PREFERRED PREVENTION AND TREATMENT REGIMENS REGARDING NATURALLY OCCURRING ANTHRAX. ALSO PROVIDED ARE A WIDE RANGE OF ALTERNATIVE REGIMENS TO FIRST-LINE ANTIMICROBIAL DRUGS FOR USE IF PATIENTS HAVE CONTRAINDICATIONS OR INTOLERANCES OR AFTER A WIDE-AREA AEROSOL RELEASE OF: Bacillus anthracis spores if resources become limited or a multidrug-resistant B. anthracis strain is used (Hendricks KA, Wright ME, Shadomy SV, et al.; Workgroup on Anthrax Clinical Guidelines. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014;20:e130687; Meaney-Delman D, Rasmussen SA, Beigi RH, et al. Prophylaxis and treatment of anthrax in pregnant women. Obstet Gynecol 2013;122:885-900; Bradley JS, Peacock G, Krug SE, et al. Pediatric anthrax clinical management. Pediatrics 2014;133:e1411-36). Specifically, this report updates antimicrobial drug and antitoxin use for both postexposure prophylaxis (PEP) and treatment from these previous guidelines best practices and is based on systematic reviews of the literature regarding 1) in vitro antimicrobial drug activity against B. anthracis; 2) in vivo antimicrobial drug efficacy for PEP and treatment; 3) in vivo and human antitoxin efficacy for PEP, treatment, or both; and 4) human survival after antimicrobial drug PEP and treatment of localized anthrax, systemic anthrax, and anthrax meningitis. CHANGES FROM PREVIOUS CDC GUIDELINES AND RECOMMENDATIONS INCLUDE AN EXPANDED LIST OF ALTERNATIVE ANTIMICROBIAL DRUGS TO USE WHEN FIRST-LINE ANTIMICROBIAL DRUGS ARE CONTRAINDICATED OR NOT TOLERATED OR AFTER A BIOTERRORISM EVENT WHEN FIRST-LINE ANTIMICROBIAL DRUGS ARE DEPLETED OR INEFFECTIVE AGAINST A GENETICALLY ENGINEERED RESISTANT: B. anthracis strain. In addition, these updated guidelines include new recommendations regarding special considerations for the diagnosis and treatment of anthrax meningitis, including comorbid, social, and clinical predictors of anthrax meningitis. The previously published CDC guidelines and recommendations described potentially beneficial critical care measures and clinical assessment tools and procedures for persons with anthrax, which have not changed and are not addressed in this update. In addition, no changes were made to the Advisory Committee on Immunization Practices recommendations for use of anthrax vaccine (Bower WA, Schiffer J, Atmar RL, et al. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices, 2019. MMWR Recomm Rep 2019;68[No. RR-4]:1-14). The updated guidelines in this report can be used by health care providers to prevent and treat anthrax and guide emergency preparedness officials and planners as they develop and update plans for a wide-area aerosol release of B. anthracis.

Many government agencies and expert groups have estimated a dose-rate of perfluorooctanoate (PFOA) that would protect human health. Most of these evaluations are based on the same studies (whether of humans, laboratory animals, or both), and all note various uncertainties in our existing knowledge. Nonetheless, the values of these various, estimated, safe-doses vary widely, with some being more than 100,000 fold different. This sort of discrepancy invites scrutiny and explanation. Otherwise what is the lay public to make of this disparity? The Steering Committee of the Alliance for Risk Assessment (2022) called for scientists interested in attempting to understand and narrow these disparities. An advisory committee of nine scientists from four countries was selected from nominations received, and a subsequent invitation to scientists internationally led to the formation of three technical teams (for a total of 24 scientists from 8 countries). The teams reviewed relevant information and independently developed ranges for estimated PFOA safe doses. All three teams determined that the available epidemiologic information could not form a reliable basis for a PFOA safe dose-assessment in the absence of mechanistic data that are relevant for humans at serum concentrations seen in the general population. Based instead on dose-response data from five studies of PFOA-exposed laboratory animals, we estimated that PFOA dose-rates 10–70 ng/kg-day are protective of human health. © 2023 Elsevier Inc.

Marburg virus disease, caused by Marburg and Ravn orthomarburgviruses, emerges sporadically in sub-Saharan Africa and is often fatal in humans. The natural reservoir is the Egyptian rousette bat (ERB), which sheds virus in saliva, urine, and feces. Frugivorous ERBs discard test-bitten and partially eaten fruit, potentially leaving infectious virus behind that could be consumed by other susceptible animals or humans. Historically, 8 of 17 known Marburg virus disease outbreaks have been linked to human encroachment on ERB habitats, but no linkage exists for the other 9 outbreaks, raising the question of how bats and humans might intersect, leading to virus spillover. We used micro‒global positioning systems to identify nightly ERB foraging locations. ERBs from a known Marburg virus‒infected population traveled long distances to feed in cultivated fruit trees near homes. Our results show that ERB foraging behavior represents a Marburg virus spillover risk to humans and plausibly explains the origins of some past outbreaks.

In early 2022, a cluster of monkeypox virus (MPXV) infection (mpox) cases were identified within the UK with no prior travel history to MPXV-endemic regions. Subsequently, case numbers exceeding 80,000 were reported worldwide, primarily affecting gay, bisexual, and other men who have sex with men (GBMSM). Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individuals at high-risk to provide protection and limit the spread of MPXV. We have developed a comprehensive array of ELISAs to study poxvirus-induced antibodies, utilising 24 MPXV and 3 Vaccinia virus (VACV) recombinant antigens. Panels of serum samples from individuals with differing Smallpox-vaccine doses and those with prior MPXV infection were tested on these assays, where we observed that one dose of Smallpox vaccination induces a low number of antibodies to a limited number of MPXV antigens but increasing with further vaccination doses. MPXV infection induced similar antibody responses to diverse poxvirus antigens observed in Smallpox-vaccinated individuals. We identify MPXV A27 as a serological marker of MPXV-infection, whilst MPXV M1 (VACV L1) is likely IMVANEX-specific. Here, we demonstrate analogous humoral antigen recognition between both MPXV-infected or Smallpox-vaccinated individuals, with binding to diverse yet core set of poxvirus antigens, providing opportunities for future vaccine (e.g., mRNA) and therapeutic (e.g., mAbs) design.

BACKGROUND: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). METHODS: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. RESULTS: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. CONCLUSIONS: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. FUNDING: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]). | Salmonella Typhi (Typhi) is a type of bacteria that causes typhoid fever. More than 110,000 people die from this disease each year, predominantly in areas of sub-Saharan Africa and South Asia with limited access to safe water and sanitation. Clinicians use antibiotics to treat typhoid fever, but scientists worry that the spread of antimicrobial-resistant Typhi could render the drugs ineffective, leading to increased typhoid fever mortality. The World Health Organization has prequalified two vaccines that are highly effective in preventing typhoid fever and may also help limit the emergence and spread of resistant Typhi. In low resource settings, public health officials must make difficult trade-off decisions about which new vaccines to introduce into already crowded immunization schedules. Understanding the local burden of antimicrobial-resistant Typhi and how it is spreading could help inform their actions. The Global Typhoid Genomics Consortium analyzed 13,000 Typhi genomes from 110 countries to provide a global overview of genetic diversity and antimicrobial-resistant patterns. The analysis showed great genetic diversity of the different strains between countries and regions. For example, the H58 Typhi variant, which is often drug-resistant, has spread rapidly through Asia and Eastern and Southern Africa, but is less common in other regions. However, distinct strains of other drug-resistant Typhi have emerged in other parts of the world. Resistance to the antibiotic ciprofloxacin was widespread and accounted for over 85% of cases in South Africa. Around 70% of Typhi from Pakistan were extensively drug-resistant in 2020, but these hard-to-treat variants have not yet become established elsewhere. Variants that are resistant to both ciprofloxacin and ceftriaxone have been identified, and azithromycin resistance has also appeared in several different variants across South Asia. The Consortium’s analyses provide valuable insights into the global distribution and transmission patterns of drug-resistant Typhi. Limited genetic data were available fromseveral regions, but data from travel-associated cases helped fill some regional gaps. These findings may help serve as a starting point for collective sharing and analyses of genetic data to inform local public health action. Funders need to provide ongoing supportto help fill global surveillance data gaps. | eng

BACKGROUND: Prenatal ethylene oxide exposure may have adverse effects on fetal development. We examined the relationships between ethylene oxide hemoglobin (Hb) adduct levels and offspring's size at birth in a prospective European mother-child study. METHODS: This study included 1106 singletons from the NewGeneris project (2006-2010) with ethylene oxide Hb adducts measured in cord blood. We examined the relationships between adduct levels and offspring's size at birth among all infants and separately among infants of nonsmokers, using linear regression models for birth weight and birth head circumference and logarithmic binomial regression models for small for gestational age. We examined potential interactions between CYP2E1 single nucleotide polymorphisms in cord blood and the effects of ethylene oxide Hb adduct levels on offspring birth size. RESULTS: Higher quartiles of adduct levels as a measure of exposure were associated with decreasing birth weight and head circumference in the overall population. Compared to infants in the lowest quartile, those in the highest quartile exhibited lower birth weight (-70.73 g, 95% confidence interval = -141.16, -0.30) and reduced head circumference (-0.30 cm, 95% confidence interval = -0.58, -0.02). We observed similar, albeit less pronounced, patterns among infants of nonsmokers. There was no evidence of an association between ethylene oxide Hb adducts and risk of small for gestational age, nor consistent evidence of an interaction with CYP2E1 polymorphisms on the association between EO Hb adduct levels and offspring's size at birth. CONCLUSION: Results suggest that higher ethylene oxide Hb adduct levels in cord blood are associated with a reduction in offspring birth size.