Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was success in 66 participants transitioned to enteral therapy.

Eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis has been reported in several southern U.S. states and Hawai'i. We present the first locally acquired human cases of A. cantonensis meningoencephalitis in three children in Florida, occurring between June 2021 and January 2022. Clinicians should be attuned to this possible diagnosis in this region.

The antiviral drug tecovirimat* has been used extensively to treat U.S. mpox cases since the start of a global outbreak in 2022. Mutations in the mpox viral protein target (F13 or VP37) that occur during treatment can result in resistance to tecovirimat(†) (1,2). CDC and public health partners have conducted genetic surveillance of monkeypox virus (MPXV) for F13 mutations through sequencing and monitoring of public databases. MPXV F13 mutations associated with resistance have been reported since 2022, typically among severely immunocompromised mpox patients who required prolonged courses of tecovirimat (3-5). A majority of patients with infections caused by MPXV with resistant mutations had a history of tecovirimat treatment; however, spread of tecovirimat-resistant MPXV was reported in California during late 2022 to early 2023 among persons with no previous tecovirimat treatment (3). This report describes a second, unrelated cluster of tecovirimat-resistant MPXV among 18 persons with no previous history of tecovirimat treatment in multiple states.

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.

Nipah virus (NiV) causes near-annual outbreaks of fatal encephalitis and respiratory disease in South Asia with a high mortality rate (∼70%). Since there are no approved therapeutics for NiV disease in humans, the WHO has designated NiV and henipaviral diseases priority pathogens for research and development. We generated a new recombinant green fluorescent reporter NiV of the circulating Bangladesh genotype (rNiV-B-ZsG) and optimized it alongside our previously generated Malaysian genotype reporter counterpart (rNiV-M-ZsG) for antiviral screening in primary-like human respiratory cell types. Validating our platform for rNiV-B-ZsG with a synthetic compound library directed against viral RNA-dependent RNA polymerases, we identified a hit compound and confirmed its sub-micromolar activity against wild-type NiV, green fluorescent reporter, and the newly constructed bioluminescent red fluorescent double reporter (rNiV-B-BREP) NiV. We furthermore demonstrated that rNiV-B-ZsG and rNiV-B-BREP viruses showed pathogenicity comparable to wild-type NiV-B in the Syrian golden hamster model of disease, supporting additional use of these tools for both pathogenesis and advanced pre-clinical studies in vivo.

BACKGROUND: The 2022 mpox outbreak disproportionately affected gay, bisexual, and other men who have sex with men (GBMSM). Mpox cases continue to be reported nationally. Vaccination is a tool to prevent the spread of and serious disease from mpox. To understand mpox vaccine uptake and hesitancy, a virtual focus group with unvaccinated GBMSM was conducted. METHODS: In November 2022, a 60-minute, virtual focus group was conducted within an artificial intelligence (AI) platform that engages participants in chat-based conversation. The AI system uses machine learning and natural language processing to analyze and provide results immediately to the moderator. Descriptive frequencies, cross-tabulations and qualitative themes were analyzed. RESULTS: Fifty-one GBMSM ages 18-55 participated, of whom 12 had attempted to get the mpox vaccine. The top barriers in accessing the vaccine included challenges in scheduling appointments (4/12), available vaccine locations (3/12), and transportation (2/12). Nine participants reported not wanting the vaccine and 22 were undecided; Of these, 15 (4/9 and 11/22, respectively) said they did not think they needed the vaccine due to low perceived risk or monogamy.. Among the undecided, after receiving health messaging about mpox, 12/22 said the messaging made them reconsider getting the vaccine. CONCLUSION: During an outbreak, many unvaccinated GBMSM who may be at increased risk for mpox either wanted the vaccine or, with appropriate health messaging, may be open to getting the vaccine. Messaging about mpox vaccine efficacy, potential side effects, and how to access the vaccine may improve vaccine uptake especially as cases continue to occur.

BACKGROUND: Alcohol-exposed pregnancies, which can lead to fetal alcohol spectrum disorders (FASDs), is one of the most common preventable causes of lifelong intellectual and developmental disabilities in the U.S. Healthcare teams can play a critical role in preventing FASDs; however, they are currently unprepared to do so. Training can remediate this problem. This article explores the different approaches to the education and training of healthcare providers around FASD prevention used by six Centers for Disease Control (CDC)-funded programs, and how they have been adapted to (1) the specific needs of the healthcare professionals and/or the clinical setting and (2) the challenges posed by the COVID-19 pandemic. METHODS: This article offers an in-depth description and comparison of the models utilized by the programs described, detailing the challenges of each model as well as the adaptations made. Interdisciplinary collaboration and review highlights these models and offers a variety of solutions and lessons learned that can be implemented in similar practice settings and/or educational initiatives. RESULTS: Based on organizational structure (i.e., national organization, educational institution, and clinical settings) and program purpose, different methods were employed for FASD education. Some programs were focused on FASD prevention through staff training and alcohol screening and brief intervention/clinical intervention and others were focused on broadscale professional education and awareness. Improvements were made on an ongoing basis as challenges related to COVID-19, staff shortages, and patient and clinician discomfort were identified, resulting in modifications to content and delivery modality (e.g., online forums and use of social media). CONCLUSION: FASD prevention education is wrought with a variety of challenges related to stigma, discomfort, and misinformation, which these programs encountered in a variety of ways.

BACKGROUND: Following California's statewide law prohibiting the sale of flavoured tobacco products, some cigarette brands introduced new variants advertised as non-menthol, yet featuring design and text commonly found in menthol cigarette marketing. METHODS: Data are from the February-May 2023 wave of the Tobacco Epidemic Evaluation Network (TEEN+) national probability-based survey (aged 13-25 years). Respondents (N=10 217) were shown images of two (of four) 'new non-menthol' brand ads or packaging and two comparators ('classic' non-menthol and menthol cigarette brands). Respondents reported expected taste of each (no or any minty/menthol taste; 'don't know'). Multinomial regression models tested associations between predictors (age, gender identity, race and ethnicity, perceived financial situation, smoking status) and expectation of minty/menthol taste. RESULTS: Younger age was associated with expectations of minty/menthol taste, controlling for covariates. Respondents aged 13-17 years had greater odds of expecting minty/menthol taste than no minty/menthol taste for all tested new non-menthol brands (Camel Crush Oasis adjusted OR (aOR): 1.30, p<0.05; Camel Crisp aOR: 1.47, p<0.001; Kool Non-Menthol Blue aOR: 1.27, p<0.05; Kool Non-Menthol Green aOR: 1.43, p<0.01), compared to respondents aged 21 and older. Respondents aged 18-20 years had greater odds of reporting minty/menthol expectancies than no minty/menthol expectancies for Camel Crush Oasis (aOR: 1.35, p<0.05) and Kool Non-Menthol Green (aOR: 1.29, p<0.05) compared to those aged 21-25 years. Compared to non-Hispanic white respondents, non-Hispanic Asian respondents had greater odds of expecting minty/menthol taste than no minty/menthol taste for Camel Crush Oasis (aOR: 1.89, p<0.01), Kool Non-Menthol Blue (aOR: 1.88, p<0.01) and Kool Non-Menthol Green (aOR: 1.72, p<0.05). DISCUSSION: Younger age was associated with expectations of new non-menthol cigarettes having a minty/menthol taste. Results raise concerns regarding the potential appeal of these products to youth and young adults.

OBJECTIVE: To summarize the principles and application of phototherapy consistent with the current 2022 American Academy of Pediatrics "Clinical Practice Guideline Revision for the Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation." METHODS: Relevant literature was reviewed regarding phototherapy devices in the United States, specifically those that incorporate blue to blue-green light-emitting diode, fluorescent, halogen, or fiberoptic light sources, and their currently marketed indications. RESULTS: The efficacy of phototherapy devices varies widely because of nonstandardized use of light sources and configurations and irradiance meters. In summary, the most effective and safest devices have the following characteristics: (1) incorporation of narrow band blue-to-green light-emitting diode lamps (∼460-490 nm wavelength range; 478 nm optimal) that would best overlap the bilirubin absorption spectrum; (2) emission of irradiance of at least 30 µW/cm2/nm (in term infants); and (3) illumination of the exposed maximal body surface area of an infant (35% to 80%). Furthermore, accurate irradiance measurements should be performed using the appropriate irradiance meter calibrated for the wavelength range delivered by the phototherapy device. CONCLUSIONS: With proper administration of effective phototherapy to an infant without concurrent hemolysis, total serum or plasma bilirubin concentrations will decrease within the first 4 to 6 hours of initiation safely and effectively.

Background: Nearly one in six children lived in war zones in 2023. Evidence-based psychosocial and parenting support has potential to mitigate negative impacts for parents and children co-exposed to war and displacement, especially in relation to mental health and harsh parenting reactions. In the current war in Ukraine, local mental health experts co-created and evaluated, with global experts, the effectiveness of psychosocial and parenting support groups, called 'Hope Groups' on improvements in mental health, positive parenting, and violence against children. This paper aimed to assess the effectiveness of psychosocial and parenting support groups, called 'Hope Groups,' on improvements in caregiver mental health, positive parenting, and prevention of violence against children, for families affected by the war in Ukraine, using a pre/post study design. Method(s): Participants (n = 577) included Ukrainian caregivers, 66% (381) of whom were parents and co-residing caregivers of children ages 0-17, while the remaining 34% were non-resident informal caregivers. Internally displaced, externally displaced, and those living at-home in war-torn regions were invited to groups by trained Ukrainian peer facilitators. Using a pre-post design, we compared individual level frequency measures at three time-points - baseline, midline, and endline, to assess changes in 4 mental health, and 9 parenting and child health outcomes. We analyzed these outcomes using paired t-tests to compare outcomes at baseline-to-midline (after 4-sessions) and baseline-to-endline (after 10-sessions), which estimated the mean changes in days per week and associated percent change, during the respective periods; we quantified uncertainties using bias-corrected and accelerated (BCa) bootstrapping with 95% uncertainty ranges for baseline-midline and baseline-endline estimates. We used this same approach for stratified analyses to assess potential effect modification by displacement status and facilitator type. We further used linear models to adjust for age and sex. Finding(s): Compared to baseline, every mental health, parenting, and child health outcome improved significantly at midline and endline. Mental health ratings showed endline reductions in depressive symptoms of 56.8% (95% CI: -59.0,-54.3; -1.8 days/week), and increases in hopefulness, coping with grief, and self-care, ranging from 62.0% (95% CI: 53.6,71.3; 2.2 days/week) to 77.0% (95% CI: 66.3,88.3; 2.2 days/week). Significant improvements in parenting and child health outcomes included monitoring children, reinforcing positive behavior, supporting child development, protecting child, nonviolent discipline, and child verbalizing emotions. By endline, emotional violence, physical violence, and child despondency had dropped by 57.7% (95% CI: -63.0%,-51.9; -1.3 days/week), 64.0% (95% CI: -79.0,-39.5; -0.22 days/week), and 51.9% (95% CI: -45.1,-57.9; -1.2 days/week), respectively. Outcomes stratified by displacement status remained significant across all groups, as did those according to facilitator type (lay versus professional). Interpretation(s): This study demonstrates preliminary evidence, using a brief survey and pre-post design as is appropriate for acute and early protracted emergency settings, of the feasibility and effectiveness of Hope Groups for war-affected Ukrainian caregivers, on improved mental health, positive parenting, and reduced violence against children. Copyright © 2024

Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. For the 2021-22 and 2022-23 influenza seasons, 26 forecasting teams provided national and jurisdiction-specific probabilistic predictions of weekly confirmed influenza hospital admissions for one-to-four weeks ahead. Forecast skill is evaluated using the Weighted Interval Score (WIS), relative WIS, and coverage. Six out of 23 models outperform the baseline model across forecast weeks and locations in 2021-22 and 12 out of 18 models in 2022-23. Averaging across all forecast targets, the FluSight ensemble is the 2(nd) most accurate model measured by WIS in 2021-22 and the 5(th) most accurate in the 2022-23 season. Forecast skill and 95% coverage for the FluSight ensemble and most component models degrade over longer forecast horizons. In this work we demonstrate that while the FluSight ensemble was a robust predictor, even ensembles face challenges during periods of rapid change.

BACKGROUND: Although substance use rates among adolescents have decreased, drug overdose deaths among adolescents have increased since 2020, driven largely by illegally made fentanyl (IMF). This study explores substance use patterns and characteristics of adolescents who were assessed for substance use disorder (SUD) treatment to inform prevention and response strategies. METHODS: A convenience sample of adolescents aged 10-18 years assessed for SUD treatment from September 2017 to December 2021 was analyzed using the Comprehensive Health Assessment for Teens. The percentage of lifetime and past 30-day substance use was examined. Adolescent characteristics (e.g., demographics, history of overdoses or hospital visits due to drug/alcohol use) were analyzed by lifetime substances used. RESULTS: Among 5,377 assessments, most were male (58.7%), aged 16-18 years (50.5%), non-Hispanic White (43.1%), enrolled in school (87.3%), and living with their parent(s) (72.4%). The most commonly reported lifetime substances used were marijuana (68.0%), alcohol (54.2%), and prescription opioid misuse (13.6%). The most common past 30-day substance use combination was alcohol and marijuana (35.6%). The percentage of assessments indicating past-year overdoses or hospital visits due to drug/alcohol use was greatest among those who reported lifetime use of IMF (24.0%), followed by heroin (21.4%) and cocaine (15.3%). Overall, 2.3% reported lifetime IMF use and 0.6% thought IMF was causing them the most problems. CONCLUSIONS: Findings inform opportunities to address substance use and increased IMF-involved overdose among adolescents. Continued overdose prevention and response strategies such as evidence-based education campaigns, naloxone distribution and harm reduction efforts, and evidence-based SUD treatment expansion are needed.

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.

A laboratory colony of the southern green stink bug, Nezara viridula L. (Heteroptera: Pentatomidae) was used to evaluate the effect of two strains of Beauveria bassiana (Balsamo-Crivelli) Vuillemin (Hypocreales: Cordycipitaceae) on its growth and reproductive rates. Four concentrations (106, 107, 108, and 109 conidia g−1) of native (NI8) and commercial (GHA) entomopathogenic fungi alongside a water control were used. Cumulative oviposition and survival of nine groups (ten couple per group per concentration) were used to calculate the demographic parameters of this insect. Two computations were done based on total offspring (fertile and infertile eggs) and eggs with developed embryo (fertile eggs). Net reproductive rates (Ro) on insect sprayed with NI8 calculated based on total offspring showed a dose-dependent effect (72.55, 85.50, 58.15, and 37.60 females per newborn female) compared with water control (87.65). In populations sprayed with GHA, only the highest concentration (109 conidia g−1) was lower than control (27.15). The calculated Ro values based on fertile eggs were much lower as it was expected with 60.75, 61.45, 45.45, and 32.05 females per newborn female from lowest to highest concentrations of NI8 and 21.50 for GHA highest concentration compared with water control (78.45). These results demonstrated that both native and commercial strains affected embryo development, decreasing growth and reproductive rates of N. viridula populations. Further field testing is needed to evaluate the potential for in-field control. © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.

CrAssphages are human gut bacteriophages with potential use as an indicator of human fecal contamination in water and other environmental systems. We determined the prevalence and abundance of crAssphages in water, food, and fecal samples and compared these estimates with the prevalence of norovirus. Samples were tested using two crAssphage-specific qPCR assays (CPQ056 and TN201-203) and for norovirus using TaqMan realtime RT-PCR. CrAssphage was detected in 40% of human fecal specimens, 61% of irrigation water samples, 58.5% of stream water samples, and 68.5% of fresh leafy greens samples. Interestingly, across all sample categories, crAssphage concentrations were 2-3 log10 higher than norovirus concentrations. The correlation of detection of crAssphage and norovirus was significant for the irrigation water samples (r = 0.74, p = 7.4e-06). Sequences obtained from crAssphage positive samples from human fecal and stream water samples phylogenetically clustered with genotype I crAssphages, whereas sequences derived from irrigation water samples clustered differently from other genotypes. Our data show that crAssphages were prevalent in norovirus-positive water samples and in fresh leafy green samples, there was a strong correlation between the presence of crAssphage and norovirus. CrAssphage genomic copies were consistently higher than norovirus copies in all sample types. Overall, our findings suggest that crAssphages could be used as reliable indicators to monitor fecal-borne virus contamination within the food safety chain.

Objectives: In 2019, the Council of State and Territorial Epidemiologists ratified a multitiered standardized surveillance case definition (SSCD) for neonatal abstinence syndrome (NAS) to minimize variability in definitions across states. This evaluation of the tier 1 NAS SSCD aimed to identify common challenges and opportunities for enhancement to support consistent implementation of the definition. Methods: This mixed-methods analysis consisted of 3 virtual focus groups in March 2021 with site principal investigators, medical record abstractors, and data analysts (1 focus group each) from 4 jurisdictions piloting the tier 1 NAS SSCD. We analyzed focus group transcripts to create a codebook. We collected written reports in February 2022 from the 4 jurisdictions, conducted thematic analysis of focus group transcripts and written reports to identify themes, and collected surveillance data on infants identified with NAS born from January 2020 through December 2021 from the pilot sites. We analyzed surveillance data to further inform identified themes. We examined agreement among tier 1 classifications assigned independently by each pilot site and the Centers for Disease Control and Prevention to cases of NAS. Results: Three major themes emerged in the data: challenges abstracting data on withdrawal signs from the medical record, difficulty determining the time frame of prenatal substance exposure, and challenges assigning case classifications. In a comparison of tier 1 classifications assigned by the Centers for Disease Control and Prevention and the sites, 82.1% of cases in the dataset were concordant. Conclusions: We identified several opportunities to modify the SSCD to promote consistency and ease implementation across jurisdictions. Promoting consistent implementation supports comparability of NAS incidence estimates across jurisdictions, evaluation of prevention efforts, and allocation of resources to support families. © 2024, Association of Schools and Programs of Public Health.

[This corrects the article DOI: 10.3389/fcimb.2023.1067475.].

In support of the environmental justice (EJ) movement, researchers, activists, and policymakers often use environmental data to document evidence of the unequal distribution of environmental burdens and benefits along lines of race, class, and other socioeconomic characteristics. Numerous limitations, such as spatial or temporal discontinuities, exist with commonly used data measurement techniques, which include ground monitoring and federal screening tools. Satellite data is well poised to address these gaps in EJ measurement and monitoring; however, little is known about how satellite data has advanced findings in EJ or can help to promote EJ through interventions. Thus, this scoping review aims to (1) explore trends in study design, topics, geographic scope, and satellite datasets used to research EJ, (2) synthesize findings from studies that use satellite data to characterize disparities and inequities across socio-demographic groups for various environmental categories, and (3) capture how satellite data are relevant to policy and real-world impact. Following PRISMA extension guidelines for scoping reviews, we retrieved 81 articles that applied satellite data for EJ research in the United States from 2000 to 2022. The majority of the studies leveraged the technical advantages of satellite data to identify socio-demographic disparities in exposure to environmental risk factors, such as air pollution, and access to environmental benefits, such as green space, at wider coverage and with greater precision than previously possible. These disparities in exposure and access are associated with health outcomes such as increased cardiovascular and respiratory diseases, mental illness, and mortality. Research using satellite data to illuminate EJ concerns can contribute to efforts to mitigate environmental inequalities and reduce health disparities. Satellite data for EJ research can therefore support targeted interventions or influence planning and policy changes, but significant work remains to facilitate the application of satellite data for policy and community impact. © 2024 The Author(s). Published by IOP Publishing Ltd.

Substance use often begins during adolescence, placing youths at risk for fatal overdose and substance use disorders (SUD) in adulthood. Understanding the motivations reported by adolescents for using alcohol, marijuana, and other drugs and the persons with whom they use these substances could guide strategies to prevent or reduce substance use and its related consequences among adolescents. A cross-sectional study was conducted among adolescents being assessed for SUD treatment in the United States during 2014-2022, to examine self-reported motivations for using substances and the persons with whom substances were used. The most commonly reported motivation for substance use was "to feel mellow, calm, or relaxed" (73%), with other stress-related motivations among the top reasons, including "to stop worrying about a problem or to forget bad memories" (44%) and "to help with depression or anxiety" (40%); one half (50%) reported using substances "to have fun or experiment." The majority of adolescents reported using substances with friends (81%) or using alone (50%). These findings suggest that interventions related to reducing stress and addressing mental health concerns might reduce these leading motivations for substance use among adolescents. Education for adolescents about harm reduction strategies, including the danger of using drugs while alone and how to recognize and respond to an overdose, can reduce the risk for fatal overdose.

Periconceptional folic acid use can often prevent neural tube defects (NTDs). Variants of genes involved in folate metabolism in mothers and children have been associated with occurrence of NTDs. We identified Irish families with individuals affected by neural tube defects. In these families, we observed that neural tube defects and birth defects overall occurred at a higher rate in the maternal lineage compared with the paternal lineage. The goal of this study was to look for evidence for genetic effects that could explain the discrepancy in the occurrence of these birth defects in the maternal vs. paternal lineage. We genotyped blood samples from 322 individuals from NTD-affected Irish families, identified through their membership in spina bifida associations. We looked for differences in distribution in maternal vs. paternal lineages of five genetic polymorphisms: the DHFR 19 bp deletion, MTHFD1 1958G>A, MTHFR 1298A>C, MTHFR 677C>T, and SLC19A1 80A>G. In addition to looking at genotypes individually, we determined the number of genotypes associated with decreased folate metabolism in each relative ("risk genotypes") and compared the distribution of these genotypes in maternal vs. paternal relatives. Overall, maternal relatives had a higher number of genotypes associated with lower folate metabolism than paternal relatives (p = 0.017). We expected that relatives would share the same risk genotype as the individuals with NTDs and/or their mothers. However, we observed that maternal relatives had an over-abundance of any risk genotype, rather than one specific genotype. The observed genetic effects suggest an epigenetic mechanism in which decreased folate metabolism results in epigenetic alterations related to the increased rate of NTDs and other birth defects seen in the maternal lineage. Future studies on the etiology of NTDs and other birth defects could benefit from including multigenerational extended families, in order to explore potential epigenetic mechanisms.

BACKGROUND: Between October 2016 and March 2019, Lynn Community Health Center in Massachusetts implemented a targeted latent TB infection testing and treatment (TTT) program, increasing testing from a baseline of 1,200 patients tested to an average of 3,531 patients tested, or 9% of the population per year.METHODS: We compared pre-implementation TTT, represented by the first two quarters of implementation data, to TTT, represented by 12 quarters of data. Time, diagnostic, and laboratory resources were estimated using micro-costing. Other cost and testing data were obtained from the electronic health record, pharmaceutical claims, and published reimbursement rates. A Markov cohort model estimated future health outcomes and cost-effectiveness from a societal perspective in 2020 US dollars. Monte Carlo simulation generated 95% uncertainty intervals.RESULTS: The TTT program exhibited extended dominance over baseline pre-intervention testing and had an incremental cost-effectiveness ratio (ICER) of US$52,603 (US$22,008â-"US$95,360). When compared to baseline pre-TTT testing, the TTT program averted an estimated additional 7.12 TB cases, 3.49 hospitalizations, and 0.16 deaths per lifetime cohort each year.CONCLUSIONS: TTT was more cost-effective than baseline pre-implementation testing. Lynn Community Health Centerâ-™s experience can help inform other clinics considering expanding latent TB infection testing.

Pollen allergies pose a considerable global public health concern. Allergy risk can vary significantly within plant families, yet some key pollen allergens can only be identified to family level by current optical methods. Pollen information with greater taxonomic resolution is therefore required to best support allergy prevention and self-management. We used environmental DNA (eDNA) metabarcoding to deepen taxonomic insights into the seasonal composition of airborne pollen in cool temperate Australia, a region with high rates of allergic respiratory disease. In Hobart, Tasmania, we collected routine weekly air samples from December 2018 until October 2020 and sequenced the internal transcribed spacer 2 (ITS2) and chloroplastic tRNA-Leucine tRNA-Phenylalanine intergenic spacer (trnL-trnF) regions in order to address the following questions: a) What is the genus-level diversity of known and potential aeroallergens in Hobart, in particular, in the families Poaceae, Cupressaceae and Myrtaceae? b) How do the atmospheric concentrations of these taxa change over time, and c) Does trnL-trnF enhance resolution of biodiversity when used in addition to ITS2? Our results suggest that individuals in the region are exposed to temperate grasses including Poa and Bromus in the peak grass pollen season, however low levels of exposure to the subtropical grass Cynodon may occur in autumn and winter. Within Cupressaceae, both metabarcodes showed that exposure is predominantly to pollen from the introduced genera Cupressus and Juniperus. Only ITS2 detected the native genus, Callitris. Both metabarcodes detected Eucalyptus as the major Myrtaceae genus, with trnL-trnF exhibiting primer bias for this family. These findings help refine our understanding of allergy triggers in Tasmania and highlight the utility of multiple metabarcodes in aerobiome studies.

Aspergillus versicolor is ubiquitous in the environment and is particularly abundant in damp indoor spaces. Exposure to Aspergillus species, as well as other environmental fungi, has been linked to respiratory health outcomes, including asthma, allergy, and even local or disseminated infection. However, the pulmonary immunological mechanisms associated with repeated exposure to A. versicolor have remained relatively uncharacterized. Here, A. versicolor was cultured and desiccated on rice then placed in an acoustical generator system to achieve aerosolization. Mice were challenged with titrated doses of aerosolized conidia to examine deposition, lymphoproliferative properties, and immunotoxicological response to repeated inhalation exposures. The necessary dose to induce lymphoproliferation was identified, but not infection-like pathology. Further, it was determined that the dose was able to initiate localized immune responses. The data presented in this study demonstrate an optimized and reproducible method for delivering A. versicolor conidia to rodents via nose-only inhalation. Additionally, the feasibility of a long-term repeated exposure study was established. This experimental protocol can be used in future studies to investigate the physiological effects of repeated pulmonary exposure to fungal conidia utilizing a practical and relevant mode of delivery. In total, these data constitute an important foundation for subsequent research in the field.

West Nile virus (WNV) is the leading cause of mosquito-borne illness in the continental United States (CONUS). Spatial heterogeneity in historical incidence, environmental factors, and complex ecology make prediction of spatiotemporal variation in WNV transmission challenging. Machine learning provides promising tools for identification of important variables in such situations. To predict annual WNV neuroinvasive disease (WNND) cases in CONUS (2015-2021), we fitted 10 probabilistic models with variation in complexity from naïve to machine learning algorithm and an ensemble. We made predictions in each of nine climate regions on a hexagonal grid and evaluated each model's predictive accuracy. Using the machine learning models (random forest and neural network), we identified the relative importance and variation in ranking of predictors (historical WNND cases, climate anomalies, human demographics, and land use) across regions. We found that historical WNND cases and population density were among the most important factors while anomalies in temperature and precipitation often had relatively low importance. While the relative performance of each model varied across climatic regions, the magnitude of difference between models was small. All models except the naïve model had non-significant differences in performance relative to the baseline model (negative binomial model fit per hexagon). No model, including the ensemble or more complex machine learning models, outperformed models based on historical case counts on the hexagon or region level; these models are good forecasting benchmarks. Further work is needed to assess if predictive capacity can be improved beyond that of these historical baselines.

BACKGROUND: The nutritional status of children with cystic fibrosis (CF), as assessed by their body mass index percentile (BMIp), is a critical determinant of long-term health outcomes. While the intestinal microbiome plays an important role in nutrition, little is known regarding the relationship of the microbiome and BMIp in children with CF. METHODS: Pediatric patients (< 18 years old) with CF and healthy comparison patients (HCs) were enrolled in the study and stool samples obtained. BMIp was categorized as Green Zone (BMIp > 50th), Yellow Zone (BMIp 25th-49th) and Red Zone (BMIp < 25th). Intestinal microbiome assessment was performed via 16S rRNA gene sequencing; microbial richness, diversity, and differential species abundance were assessed. RESULTS: Stool samples were collected from 107 children with CF and 50 age-matched HCs. Compared to HCs, children with CF were found to have lower bacterial richness, alpha-diversity, and a different microbial composition. When evaluating them by their BMIp color zone, richness and alpha-diversity were lowest in those in the Red Zone. In addition, an unclassified amplicon sequence variant (ASV) of Blautia, a known butyrate-producing anaerobe, was of lowest abundance in children in the Red Zone. CONCLUSION: Children with CF have a dysbiotic intestinal microbiome with specific changes that accompany changes in BMIp. Longitudinal assessments of the microbiome and its metabolic activities over time are needed to better understand how improvements in the microbiome may improve nutrition and enhance long-term survival in children with CF.

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.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.

OBJECTIVES: The condition of the home is a strong predictor of exposure to environmental contaminants, with low-income households being particularly vulnerable. Therefore, improving housing standards is a priority. Housing built to "green" standards, with improved building methods and materials, has been suggested to reduce contaminants. However, evidence is limited as to which contaminants are reduced. The Green Housing Study was conducted to address this issue. The study hypothesis was that housing built using green components has lower concentrations of environmental contaminants compared to conventional housing. METHODS: A repeated-measures, 12-month cohort study was performed in three U.S. cities. Data were collected in the home at three time points throughout a year. The level of contaminants were estimated using air samples for particulate matter and black carbon, dust samples for aeroallergens and pesticides, and resident or study staff reporting evidence of mold. To investigate source(s) of PM(2.5) and black carbon, multivariable models using stepwise variable selection were developed. RESULTS: In adjusted generalized estimating equations (GEE) models, black carbon concentration (μg/m(3)) (β = -0.22, 95% CI = -0.38 to -0.06, p = 0.01), permethrin (OR = 0.28, 95% CI = 0.15-0.49, p < 0.0001), and reported mold (OR = 0.29, 95% CI = 0.13-0.68, p = 0.003) were significantly lower in green homes. Cockroach antigen was also lower in green homes (OR = 0.59, 95% CI = 0.33-1.08, p = 0.09), although not statistically significant. We found that 68% of PM(2.5) was explained by dwelling type and smoking and 42% of black carbon was explained by venting while cooking and use of a gas stove. CONCLUSIONS: This study provides quantitative data suggesting benefits of incorporating green building practices on the level of numerous environmental contaminants known to be associated with health. Occupant behavior, particularly smoking, is an important contributor to indoor air pollution.

BACKGROUND: Nonmedical use (NMU) of prescription psychotherapeutic drugs (PPD) may increase risk for significant morbidity and mortality in the overdose crisis. OBJECTIVE: This study examines sources of PPD using real-world data from adolescents and adults reporting past 30-day NMU of PPDs. METHODS: A convenience sample of individuals aged ≥10 years assessed for substance use disorders (SUD) treatment was analyzed using the 2014-2022 National Addictions Vigilance Intervention and Prevention Program datasets. PPD include prescription opioids, prescription tranquilizers/sedatives, and prescription stimulants. RESULTS: Overall, among assessments of adolescents aged 10-18 years (N = 1991) and young adults aged 19-24 years (N = 15,166), "family/friend" (46.08-47.41 %) and "dealer" (33.82-42.71 %) were the most common sources. Among assessments of adults aged ≥25 years (N = 89,225), "own prescription" was the most common source and increased in frequency as age increased. Across all age groups, "family/friend" was the most frequent source for all drug classes (41.96-48.76 %) except for nonmedically used buprenorphine/methadone, for which "own prescription" was the most common source (51.85 %) among adults. CONCLUSIONS: Our study demonstrates heterogeneity in sources of nonmedically used PPD across age groups. Tailored prevention strategies for different age groups and improving timely access to medical care to ensure proper treatment of chronic medical conditions including SUD are needed.

Potential acute and chronic human health effects associated with exposure to cyanobacteria and cyanotoxins, including respiratory symptoms, are an understudied public health concern. We examined the relationship between estimated cyanobacteria biomass and the frequency of respiratory-related hospital visits for residents living near Green Bay, Lake Michigan, Wisconsin during 2017-2019. Remote sensing data from the Cyanobacteria Assessment Network was used to approximate cyanobacteria exposure through creation of a metric for cyanobacteria chlorophyll-a (Chl(BS)). We obtained counts of hospital visits for asthma, wheezing, and allergic rhinitis from the Wisconsin Hospital Association for ZIP codes within a 3-mile radius of Green Bay. We analyzed weekly counts of hospital visits versus cyanobacteria, which was modelled as a continuous measure (Chl(BS)) or categorized according to World Health Organization's (WHO) alert levels using Poisson generalized linear models. Our data included 2743 individual hospital visits and 114 weeks of satellite derived cyanobacteria biomass indicator data. Peak values of Chl(BS) were observed between the months of June and October. Using the WHO alert levels, 60% of weeks were categorized as no risk, 19% as Vigilance Level, 15% as Alert Level 1, and 6% as Alert Level 2. In Poisson regression models adjusted for temperature, dewpoint, season, and year, there was no association between Chl(BS) and hospital visits (rate ratio [RR] [95% Confidence Interval (CI)] = 0.98 [0.77, 1.24]). There was also no consistent association between WHO alert level and hospital visits when adjusting for covariates (Vigilance Level: RR [95% CI] 0.88 [0.74, 1.05], Alert Level 1: 0.82 [0.67, 0.99], Alert Level 2: 0.98 [0.77, 1.24], compared to the reference no risk category). Our methodology and model provide a template for future studies that assess the association between cyanobacterial blooms and respiratory health.