Gestational PBDE Concentrations, Persistent Externalizing, and Emerging Internalizing Behaviors in Adolescents: The HOME Study.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental chemicals used as flame retardants in commercial and consumer products. Gestational PBDE concentrations are associated with adverse behaviors in children; however, the persistence of these associations into adolescence remains understudied. OBJECTIVE: We estimated the association of gestational PBDE serum concentrations with early adolescent self- and caregiver-reported behaviors at age 12 years and determined the consistency with previously observed associations in childhood with caregiver-reported behaviors in a prospective pregnancy and birth cohort. METHODS: We measured maternal serum concentrations of five individual PBDE congeners and created a summary exposure variable (∑5BDE: -28, -47, -99, -100 and -153) during pregnancy. At age 12 years, we assessed behaviors for 237 adolescents using self- and caregiver-reports with the Behavioral Assessment System for Children-3 (BASC3). We used multivariable linear regression models to estimate covariate-adjusted associations of lipid standardized, log10-transformed gestational PBDE concentrations with BASC3 scores. We obtained estimates and 95% confidence intervals through a bootstrapping approach. We evaluated potential effect measure modification (EMM) of adolescent sex by examining sex-stratified regression models and estimating the EMM p-values. RESULTS: Gestational PBDE concentrations were positively associated with adolescent-reported BASC3 composite indices for inattention & hyperactivity (BDE-28, -47, -99, -100, ∑5BDE), internalizing problems (BDE-28, -47, -99), functional impairment (BDE-28, ∑5BDE), and emotional symptoms (BDE-28). Gestational PBDE concentrations were positively associated with caregiver-reported BASC3 composite indices for externalizing problems (BDE-28, -47, -99, -100, -153, ∑5BDE) and behavioral symptoms (BDE-99). For caregiver reported behaviors, we observed stronger associations with gestational BDE concentrations among males, especially for executive functioning (BDE-28, -47, -99, -100, ∑5BDE). DISCUSSION: Gestational PBDE serum concentrations were associated with self-reported internalizing and externalizing behavior problems in early adolescence. Caregiver-reported externalizing behaviors recognized during childhood remain associated with gestational PBDE concentrations and persist into early adolescence. Internalizing behaviors were less recognized by caregivers.

Hybrid capture-based next-generation sequencing of new and old world Orthohantavirus strains and wild-type Puumala isolates from humans and bank voles.

Orthohantaviruses, transmitted primarily by rodents, cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome in the Americas. These viruses, with documented human-to-human transmission, exhibit a wide case-fatality rate, 0.5-40 %, depending on the virus species, and no vaccine or effective treatment for severe Orthohantavirus infections exists. In Europe, the Puumala virus (PUUV), carried by the bank vole Myodes glareolus, causes a milder form of HFRS. Despite the reliance on serology and PCR for diagnosis, the three genomic segments of Swedish wild-type PUUV have yet to be completely sequenced. We have developed a targeted hybrid-capture method aimed at comprehensive genomic sequencing of wild-type PUUV isolates and the identification of other Orthohantaviruses. Our custom-designed panel includes >11,200 probes covering the entire Orthohantavirus genus. Using this panel, we sequenced complete viral genomes from bank vole lung tissue, human plasma samples, and cell-cultured reference strains. Analysis revealed that Swedish PUUV isolates belong to the Northern Scandinavian lineage, with nucleotide diversity ranging from 2.8 % to 3.7 % among them. Notably, no significant genotypic differences were observed between the viral sequences from reservoirs and human cases except in the nonstructural protein. Despite the high endemicity of PUUV in Northern Sweden, these are the first complete Swedish wild-type PUUV genomes and substantially increase our understanding of PUUV evolution and epidemiology. The panel's sensitivity enables genomic sequencing of human samples with viral RNA levels reflecting the natural progression of infection and underscores our panel's diagnostic value, and could help to uncover novel Orthohantavirus transmission routes.

Endocrine disrupting chemical mixture exposure and risk of papillary thyroid cancer in U.S. military personnel: A nested case-control study.

Single-pollutant methods to evaluate associations between endocrine disrupting chemicals (EDCs) and thyroid cancer risk may not reflect realistic human exposures. Therefore, we evaluated associations between exposure to a mixture of 18 EDCs, including polychlorinated biphenyls (PCBs), brominated flame retardants, and organochlorine pesticides, and risk of papillary thyroid cancer (PTC), the most common thyroid cancer histological subtype. We conducted a nested case-control study among U.S. military servicemembers of 652 histologically-confirmed PTC cases diagnosed between 2000 and 2013 and 652 controls, matched on birth year, sex, race/ethnicity, military component (active duty/reserve), and serum sample timing. We estimated mixture odds ratios (OR), 95% confidence intervals (95% CI), and standard errors (SE) for associations between pre-diagnostic serum EDC mixture concentrations, overall PTC risk, and risk of histological subtypes of PTC (classical, follicular), adjusted for body mass index and military branch, using quantile g-computation. Additionally, we identified relative contributions of individual mixture components to PTC risk, represented by positive and negative weights (w). A one-quartile increase in the serum mixture concentration was associated with a non-statistically significant increase in overall PTC risk (OR = 1.19; 95% CI = 0.91, 1.56; SE = 0.14). Stratified by histological subtype and race (White, Black), a one-quartile increase in the mixture was associated with increased classical PTC risk among those of White race (OR = 1.59; 95% CI = 1.06, 2.40; SE = 0.21), but not of Black race (OR = 0.95; 95% CI = 0.34, 2.68; SE = 0.53). PCBs 180, 199, and 118 had the greatest positive weights driving this association among those of White race (w = 0.312, 0.255, and 0.119, respectively). Findings suggest that exposure to an EDC mixture may be associated with increased classical PTC risk. These findings warrant further investigation in other study populations to better understand PTC risk by histological subtype and race.

Organochlorine pesticides and risk of papillary thyroid cancer in U.S. military personnel: a nested case-control study.

BACKGROUND: The effects of organochlorine pesticide (OCP) exposure on the development of human papillary thyroid cancer (PTC) are not well understood. A nested case-control study was conducted with data from the U.S. Department of Defense Serum Repository (DoDSR) cohort between 2000 and 2013 to assess associations of individual OCPs serum concentrations with PTC risk. METHODS: This study included 742 histologically confirmed PTC cases (341 females, 401 males) and 742 individually-matched controls with pre-diagnostic serum samples selected from the DoDSR. Associations between categories of lipid-corrected serum concentrations of seven OCPs and PTC risk were evaluated for classical PTC and follicular PTC using conditional logistic regression, adjusted for body mass index category and military branch to compute odds ratios (OR) and 95% confidence intervals (CIs). Effect modification by sex, birth cohort, and race was examined. RESULTS: There was no evidence of associations between most of the OCPs and PTC, overall or stratified by histological subtype. Overall, there was no evidence of an association between hexachlorobenzene (HCB) and PTC, but stratified by histological subtype HCB was associated with significantly increased risk of classical PTC (third tertile above the limit of detection (LOD) vs.

Nanometa Live: a user-friendly application for real-time metagenomic data analysis and pathogen identification.

SUMMARY: Nanometa Live presents a user-friendly interface designed for real-time metagenomic data analysis and pathogen identification utilizing Oxford Nanopore Technologies' MinION and Flongle flow cells. It offers an efficient workflow and graphical interface for the visualization and interpretation of metagenomic data as it is being generated. Key features include automated BLAST validation, streamlined handling of custom Kraken2 databases, and a simplified graphical user interface for enhanced user experience. Nanometa Live is particularly notable for its capability to run without constant internet or server access once installed, setting it apart from similar tools. It provides a comprehensive view of taxonomic composition and facilitates the detection of user-defined pathogens or other species of interest, catering to both researchers and clinicians. AVAILABILITY AND IMPLEMENTATION: Nanometa Live has been implemented as a local web application using the Dash framework with Snakemake handling the data processing. The source code is freely accessible on the GitHub repository at https://github.com/FOI-Bioinformatics/nanometa_live and it is easily installable using Bioconda. It includes containerization support via Docker and Singularity, ensuring ease of use, reproducibility, and portability.

Novel strains of Culex flavivirus and Hubei chryso-like virus 1 from the Anopheles mosquito in western Kenya.

Surveillance of mosquito vectors is critical for early detection, prevention and control of vector borne diseases. In this study we used advanced molecular tools, such as DNA barcoding in combination with novel sequencing technologies to discover new and already known viruses in genetically identified mosquito species. Mosquitoes were captured using BG sentinel traps in Western Kenya during May and July 2019, and homogenized individually before pooled into groups of ten mosquitoes. The pools and individual samples were then used for molecular analysis and to infect cell cultures. Of a total of fifty-four (54) 10-pools, thirteen (13) showed cytopathic effect (CPE) on VeroB4 cells, eighteen (18) showed CPE on C6/36 cells. Eight (8) 10-pools out of the 31 CPE positive pools showed CPE on both VeroB4 and C6/36 cells. When using reverse transcriptase polymerase chain reaction (RT-PCR), Sanger sequencing and Twist Comprehensive Viral Research Panel (CVRP) (Twist Biosciences), all pools were found negative by RT-PCR when using genus specific primers targeting alphaviruses, orthobunyaviruses and virus specific primers towards o'nyong-nyong virus, chikungunya virus and Sindbis virus (previously reported to circulate in the region). Interestingly, five pools were RT-PCR positive for flavivirus. Two of the RT-PCR positive pools showed CPE on both VeroB4 and C6/36 cells, two pools showed CPE on C6/36 cells alone and one pool on VeroB4 cells only. Fifty individual mosquito homogenates from the five RT-PCR positive 10-pools were analyzed further for flavivirus RNA. Of these, 19 out of the 50 individual mosquito homogenates indicated the presence of flavivirus RNA. Barcoding of the flavivirus positive mosquitoes revealed the mosquito species as Aedes aegypti (1), Mansonia uniformis (6), Anopheles spp (3), Culex pipiens (5), Culex spp (1), Coquilletidia metallica (2) and Culex quinquefasciatus (1). Of the 19 flavivirus positive individual mosquitoes, five (5) virus positive homogenates were sequenced. Genome sequences of two viruses were completed. One was identified as the single-stranded RNA Culex flavivirus and the other as the double-stranded RNA Hubei chryso-like virus 1. Both viruses were found in the same Anopheles spp. homogenate extracted from a sample that showed CPE on both VeroB4 and C6/36 cells. The detection of both viruses in a single mosquito homogenate indicated coinfection. Phylogenetic analyses suggested that the Culex flavivirus sequence detected was closely related to a Culex flavivirus isolated from Uganda in 2008. All four Hubei chryso-like virus 1 segments clusters closely to Hubei chryso-like virus 1 strains isolated in Australia, China and USA. Two novel strains of insect-specific viruses in Anopheles mosquitoes were detected and characterized.

Bipolar Biogeographical Distribution of Parafrancisella Bacteria Carried by the Ciliate Euplotes.

Parafrancisella adeliensis, a Francisella-like endosymbiont, was found to reside in the cytoplasm of an Antarctic strain of the bipolar ciliate species, Euplotes petzi. To inquire whether Euplotes cells collected from distant Arctic and peri-Antarctic sites host Parafrancisella bacteria, wild-type strains of the congeneric bipolar species, E. nobilii, were screened for Parafrancisella by in situ hybridization and 16S gene amplification and sequencing. Results indicate that all Euplotes strains analyzed contained endosymbiotic bacteria with 16S nucleotide sequences closely similar to the P. adeliensis 16S gene sequence. This finding suggests that Parafrancisella/Euplotes associations are not endemic to Antarctica, but are common in both the Antarctic and Arctic regions.

Targeting the gut-lung axis by synbiotic feeding to infants in a randomized controlled trial.

BACKGROUND: Formula-fed infants are at increased risk of infections. Due to the cross-talk between the mucosal systems of the gastrointestinal and respiratory tracts, adding synbiotics (prebiotics and probiotics) to infant formula may prevent infections even at distant sites. Infants that were born full term and weaned from breast milk were randomized to prebiotic formula (fructo- and galactooligosaccharides) or the same prebiotic formula with Lactobacillus paracasei ssp. paracasei F19 (synbiotics) from 1 to 6 months of age. The objective was to examine the synbiotic effects on gut microbiota development. RESULTS: Fecal samples collected at ages 1, 4, 6, and 12 months were analyzed using 16S rRNA gene sequencing and a combination of untargeted gas chromatography-mass spectrometry/liquid chromatography-mass spectrometry. These analyses revealed that the synbiotic group had a lower abundance of Klebsiella, a higher abundance of Bifidobacterium breve compared to the prebiotic group, and increases in the anti-microbial metabolite d-3-phenyllactic acid. We also analyzed the fecal metagenome and antibiotic resistome in the 11 infants that had been diagnosed with lower respiratory tract infection (cases) and 11 matched controls using deep metagenomic sequencing. Cases with lower respiratory tract infection had a higher abundance of Klebsiella species and antimicrobial resistance genes related to Klebsiella pneumoniae, compared to controls. The results obtained using 16S rRNA gene amplicon and metagenomic sequencing were confirmed in silico by successful recovery of the metagenome-assembled genomes of the bacteria of interest. CONCLUSIONS: This study demonstrates the additional benefit of feeding specific synbiotics to formula-fed infants over prebiotics only. Synbiotic feeding led to the underrepresentation of Klebsiella, enrichment of bifidobacteria, and increases in microbial degradation metabolites implicated in immune signaling and in the gut-lung and gut-skin axes. Our findings support future clinical evaluation of synbiotic formula in the prevention of infections and associated antibiotic treatment as a primary outcome when breastfeeding is not feasible. TRIAL REGISTRATION: ClinicalTrials.gov NCT01625273 . Retrospectively registered on 21 June 2012.

Prenatal exposure to polybrominated diphenyl ethers and birth outcomes.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) were used as flame retardants and from their end-use products they can be released to accumulate within indoor environments. This may result in exposures to pregnant women with potential adverse effects on the developing fetus. While studies have shown associations between prenatal PBDE exposure and poor birth outcomes, research has mainly focused on birth weight and gestational age and may miss important indicators of newborn size. METHODS: The sample included a cohort of Dominican and African American mother-child pairs from New York City recruited from 1998 to 2006. PBDE congeners (BDE-47, BDE-99, BDE-100, and BDE-153) were measured in cord serum at birth and dichotomized into low (<80th percentile) and high (>80th percentile) categories. Weight, length, head circumference, and gestational age were measured at birth and the ponderal index (birth weight/length x 100), size for gestational age, and population-based z-scores were calculated (n = 305). Separate regression analyses were conducted to estimate associations between PBDEs or PBDE sum (ng/g lipid) and birth outcomes. Quantile g-computation was performed to estimate the effect of total PBDE mixture. We also assessed effect modification by sex and ethnicity. RESULTS: Adjusting for relevant covariates, the high exposure category of BDE-153 was associated with lower birth weight z-score (-0.25, 95% CI: -0.5, 0.0) and longer gestation (0.43 weeks, 95% CI: 0.07, 0.79). The high exposure category of BDE-99 was associated with lower birth length z-score (-0.55, 95% CI: -0.98, -0.12). There was a negative association between the overall PBDE mixture and birth length z-score (-0.10, 95% CI: -0.21, 0.00) per 1 quintile increase in PBDEs. There was no effect modification by sex or ethnicity. CONCLUSIONS: These results suggest that prenatal exposures to BDE-153, BDE-99, and total PBDE mixture are associated with birth outcomes in a cohort of Dominican and African American newborns.

Prenatal exposure to polybrominated diphenyl ethers and inattention/hyperactivity symptoms in mid to late adolescents.

Introduction: Prenatal exposure to polybrominated diphenyl ethers (PBDEs) has been associated with increased symptoms of attention deficit/hyperactivity disorder (ADHD) in early to middle childhood, as well as early adolescence. However, data are limited for the long-lasting impact of exposure on outcomes assessed across the entire adolescent period and the sex-specificity of such associations. Methods: We investigated the association between continuous natural-log-transformed cord plasma PBDE concentrations and ADHD rating scale 4th edition (ADHD-RS-IV) score from mid adolescence (approximately 11 years old) to late adolescence (approximately 17 years old). The study sample includes a subset (n = 219) of the African American and Dominican children enrolled in the Columbia Center for Children's Environmental Health Mothers and Newborns birth cohort. We used generalized estimating equations to account for the repeated measure of ADHD-RS scores. We examined interactions between exposure to PBDE and sex using cross-product terms and sex-stratified models. In addition, we used linear regression using an age-stratified sample as a sensitivity analysis. Results and Discussion: Associations between prenatal exposure and parents' reports of ADHD symptoms varied by sex (p-interaction <0.20), with positive relationships observed among girls but not boys from sex-stratified models. Our finding suggests prenatal exposure to PBDE may affect ADHD symptoms assessed during middle to late adolescence and the sex-specificity of such impact. Our results can be confirmed by future studies with larger and more diverse samples.

Bacterial composition in Swedish raw drinking water reveals three major interacting ubiquitous metacommunities.

BACKGROUND: Surface raw water used as a source for drinking water production is a critical resource, sensitive to contamination. We conducted a study on Swedish raw water sources, aiming to identify mutually co-occurring metacommunities of bacteria, and environmental factors driving such patterns. METHODS: The water sources were different regarding nutrient composition, water quality, and climate characteristics, and displayed various degrees of anthropogenic impact. Water inlet samples were collected at six drinking water treatment plants over 3 years, totaling 230 samples. The bacterial communities of DNA sequenced samples (n = 175), obtained by 16S metabarcoding, were analyzed using a joint model for taxa abundance. RESULTS: Two major groups of well-defined metacommunities of microorganisms were identified, in addition to a third, less distinct, and taxonomically more diverse group. These three metacommunities showed various associations to the measured environmental data. Predictions for the well-defined metacommunities revealed differing sets of favored metabolic pathways and life strategies. In one community, taxa with methanogenic metabolism were common, while a second community was dominated by taxa with carbohydrate and lipid-focused metabolism. CONCLUSION: The identification of ubiquitous persistent co-occurring bacterial metacommunities in freshwater habitats could potentially facilitate microbial source tracking analysis of contamination issues in freshwater sources.

Genomic characterization of Francisella tularensis and other diverse Francisella species from complex samples.

Francisella tularensis, the bacterium that causes the zoonosis tularemia, and its genetic near neighbor species, can be difficult or impossible to cultivate from complex samples. Thus, there is a lack of genomic information for these species that has, among other things, limited the development of robust detection assays for F. tularensis that are both specific and sensitive. The objective of this study was to develop and validate approaches to capture, enrich, sequence, and analyze Francisella DNA present in DNA extracts generated from complex samples. RNA capture probes were designed based upon the known pan genome of F. tularensis and other diverse species in the family Francisellaceae. Probes that targeted genomic regions also present in non-Francisellaceae species were excluded, and probes specific to particular Francisella species or phylogenetic clades were identified. The capture-enrichment system was then applied to diverse, complex DNA extracts containing low-level Francisella DNA, including human clinical tularemia samples, environmental samples (i.e., animal tissue and air filters), and whole ticks/tick cell lines, which was followed by sequencing of the enriched samples. Analysis of the resulting data facilitated rigorous and unambiguous confirmation of the detection of F. tularensis or other Francisella species in complex samples, identification of mixtures of different Francisella species in the same sample, analysis of gene content (e.g., known virulence and antimicrobial resistance loci), and high-resolution whole genome-based genotyping. The benefits of this capture-enrichment system include: even very low target DNA can be amplified; it is culture-independent, reducing exposure for research and/or clinical personnel and allowing genomic information to be obtained from samples that do not yield isolates; and the resulting comprehensive data not only provide robust means to confirm the presence of a target species in a sample, but also can provide data useful for source attribution, which is important from a genomic epidemiology perspective.

Early exposure to flame retardants is prospectively associated with anxiety symptoms in adolescents: A prospective birth cohort study.

BACKGROUND: Anxiety disorders emerge during childhood and adolescence and are frequently preceded by subsyndromal anxiety symptoms. Environmental toxicants, including gestational polybrominated diphenyl ether (PBDE) exposure, are associated with neuropsychiatric sequelae; however, the role of PBDEs as risk factors for anxiety in adolescence is unclear. METHODS: Using data from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort enrolled from 2003 to 2006, we investigated the relationship between gestational serum PBDE concentrations and anxiety symptoms in adolescents (N = 236). We measured five PBDE congeners (PBDE-28, -47, -99, -100, and -153) at 16 ± 3 weeks of gestation and calculated their sum (∑PBDE). We assessed self-reported anxiety symptoms using the Screen for Child Anxiety Related Emotional Disorders (SCARED) and depressive symptoms using the Children's Depression Inventory (CDI-2) at age 12 years. We estimated the associations of maternal PBDE concentrations with child anxiety and depressive symptoms using multivariable linear regression and modified Poisson regression. Covariates included child sex, maternal race, maternal age at delivery, maternal marital status, maternal education, and household income at the 12-year study visit as well as maternal depressive and anxiety symptoms. Sensitivity analyses were performed to control for maternal lead and mercury at delivery. RESULTS: After adjusting for predetermined covariates, each doubling in maternal PBDE concentrations was associated with increased SCARED scores (e.g., for ∑PBDE, SCARED total score, ß = 1.6 95% confidence interval [CI]: 0.3-2.9, p = .019) and a nonsignificant increase in depressive symptoms (e.g., for CDI total score, ß = .8, 95% CI: -0.2-1.8, p = .11). CONCLUSIONS: Gestational serum PBDE concentrations just before mid-pregnancy and during a period of active cortical and limbic neurogenesis, synaptogenesis and myelogenesis may be a risk factor for developing anxiety symptoms in early adolescence.

Prenatal exposure to polybrominated diphenyl ethers and BMI Z-scores from 5 to 14 years.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are flame-retardant compounds widely used in household products until phase out in 2004. PBDEs are endocrine disruptors and are suggested to influence signaling related to weight control. Prenatal exposures to PBDEs may alter childhood adiposity, yet few studies have examined these associations in human populations. METHODS: Data were collected from a birth cohort of Dominican and African American mother-child pairs from New York City recruited from 1998 to 2006. PBDE congeners BDE-47, - 99, - 100, and - 153 were measured in cord plasma (ng/µL) and dichotomized into low (< 80th percentile) and high (>80th percentile) exposure categories. Height and weight were collected at ages 5, 7, 9, 11, and an ancillary visit from 8 to 14 years (n = 289). Mixed-effects models with random intercepts for participant were used to assess associations between concentrations of individual PBDE congeners or the PBDE sum and child BMI z-scores (BMIz). To assess associations between PBDEs and the change in BMIz over time, models including interactions between PBDE categories and child age and (child age)2 were fit. Quantile g-computation was used to investigate associations between BMIz and the total PBDE mixture. Models were adjusted for baseline maternal covariates: ethnicity, age, education, parity, partnership status, and receipt of public assistance, and child covariates: child sex and cord cholesterol and triglycerides. RESULTS: The prevalence of children with obesity at age 5 was 24.2% and increased to 30% at age 11. Neither cord levels of individual PBDEs nor the total PBDE mixture were associated with overall BMIz in childhood. The changes in BMIz across childhood were not different between children with low or high PBDEs. Results were similar when adjusting for postnatal PBDE exposures. CONCLUSIONS: Prenatal PBDE exposures were not associated with child growth trajectories in a cohort of Dominican and African American children.

Co-Occurrence of Francisella, Spotted Fever Group Rickettsia, and Midichloria in Avian-Associated Hyalomma rufipes.

The migratory behavior of wild birds contributes to the geographical spread of ticks and their microorganisms. In this study, we aimed to investigate the dispersal and co-occurrence of Francisella and spotted fever group Rickettsia (SFGR) in ticks infesting birds migrating northward in the African-Western Palaearctic region (AWPR). Birds were trapped with mist nests across the Mediterranean basin during the 2014 and 2015 spring migration. In total, 575 ticks were collected from 244 birds. We screened the ticks for the species Francisella tularensis, the genus Francisella, and SFGR by microfluidic real-time PCR. Confirmatory analyses and metagenomic sequencing were performed on tick samples that putatively tested positive for F. tularensis during initial screenings. Hyalomma rufipes was the most common tick species and had a high prevalence of Francisella, including co-occurrence of Francisella and SFGR. Metagenomic analysis of total DNA extracted from two H. rufipes confirmed the presence of Francisella, Rickettsia, and Midichloria. Average nucleotide identity and phylogenetic inference indicated the highest identity of the metagenome-assembled genomes to a Francisella-like endosymbiont (FLE), Rickettsia aeschlimannii, and Midichloria mitochondrii. The results of this study suggest that (i) FLE- and SFGR-containing ticks are dispersed by northbound migratory birds in the AWPR, (ii) H. rufipes likely is not involved in transmission of F. tularensis in the AWPR, and (iii) a dual endosymbiosis of FLEs and Midichloria may support some of the nutritional requirements of H. rufipes.

Clinical and genomic characterisation of a fatal Puumala orthohantavirus case with low levels of neutralising antibodies.

BACKGROUND: Orthohantaviruses are rodent-borne emerging viruses that cause haemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome in America. Transmission between humans have been reported and the case-fatality rate ranges from 0.4% to 40% depending on virus strain. There is no specific and efficient treatment for patients with severe HFRS. Here, we characterised a fatal case of HFRS and sequenced the causing Puumala orthohantavirus (PUUV). METHODS: PUUV RNA and virus specific neutralising antibodies were quantified in plasma samples from the fatal case and other patients with non-fatal PUUV infection. To investigate if the causing PUUV strain was different from previously known strains, Sanger sequencing was performed directly from the patient's plasma. Biopsies obtained from autopsy were stained for immunohistochemistry. RESULTS: The patient had approximately tenfold lower levels of PUUV neutralising antibodies and twice higher viral load than was normally seen for patients with less severe PUUV infection. We could demonstrate unique mutations in the S and M segments of the virus that could have had an impact on the severity of infection. Due to the severe course of infection, the patient was treated with the bradykinin receptor inhibitor icatibant to reduce bradykinin-mediated vessel permeability and maintain vascular circulation. CONCLUSIONS: Our data suggest that bradykinin receptor inhibitor may not be highly efficient to treat patients that are at an advanced stage of HFRS. Low neutralising antibodies and high viral load at admission to the hospital were associated with the fatal outcome and may be useful for future predictions of disease outcome.

A nested case-control study of serum polychlorinated biphenyls and papillary thyroid cancer risk among U.S. military service members.

BACKGROUND AND OBJECTIVES: Although polychlorinated biphenyls (PCBs) were banned decades ago, populations are continuously exposed to PCBs due to their persistence and bioaccumulation/biomagnification in the environment. Results from limited epidemiologic studies linking PCBs to thyroid cancer have been inconclusive. This study aimed to investigate the association between individual PCBs and PCB mixture and papillary thyroid cancer (PTC), the most common thyroid cancer histologic subtype. METHODS: We carried out a nested case-control study including 742 histologically confirmed PTC cases diagnosed in 2000-2013 and 742 individually matched controls among U.S. military service members. Pre-diagnostic serum samples that were collected on average nine years before PTC diagnosis were used to measure PCB congeners by gas chromatography isotope dilution high resolution mass spectrometry (GC/ID-HRMS). Conditional logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression were employed to estimate the association between single PCB congeners as well as their mixture and PTC. RESULTS: Four PCB congeners (PCB-74, PCB-99, PCB-105, PCB-118) had significant associations and dose-response relationships with increased risk of PTC in single congener models. When considering the effects from all measured PCBs and their potential interactions in the BKMR model, PCB-118 showed positive trends of association with PTC. Increased exposure to the PCB congeners as a mixturewas also associated with an increased risk of PTC in the WQS model, with the mixture dominated by PCB-118, followed by PCB-74 and PCB-99. One PCB congener, PCB-187, showed an inverse trend of association with PTC in the mixture analysis. DISCUSSION: This study suggests that exposure to certain PCBs as well as a mixture of PCBs were associated with an increased risk of PTC. The observed association was mainly driven by PCB-118, and to a lesser extent by PCB-74 and PCB-99. The findings warrant further investigation.

Alphacoronavirus in a Daubenton's Myotis Bat (Myotis daubentonii) in Sweden.

The ongoing COVID-19 pandemic has stimulated a search for reservoirs and species potentially involved in back and forth transmission. Studies have postulated bats as one of the key reservoirs of coronaviruses (CoVs), and different CoVs have been detected in bats. So far, CoVs have not been found in bats in Sweden and we therefore tested whether they carry CoVs. In summer 2020, we sampled a total of 77 adult bats comprising 74 Myotis daubentonii, 2 Pipistrellus pygmaeus, and 1 M. mystacinus bats in southern Sweden. Blood, saliva and feces were sampled, processed and subjected to a virus next-generation sequencing target enrichment protocol. An Alphacoronavirus was detected and sequenced from feces of a M. daubentonii adult female bat. Phylogenetic analysis of the almost complete virus genome revealed a close relationship with Finnish and Danish strains. This was the first finding of a CoV in bats in Sweden, and bats may play a role in the transmission cycle of CoVs in Sweden. Focused and targeted surveillance of CoVs in bats is warranted, with consideration of potential conflicts between public health and nature conservation required as many bat species in Europe are threatened and protected.

Understanding the Role of Persistent Organic Pollutants and Stress in the Association between Proximity to the World Trade Center Disaster and Birth Outcomes.

Fetal growth is affected by exposure to both prenatal stress and environmental contaminants. The attacks on the World Trade Center (WTC) resulted in exposure to chemicals and psychological stress amongst New York City residents. We measured prenatal maternal stress and exposure to persistent organic pollutants (polybrominated diphenyl ethers, polychlorinated biphenyls, and polychlorinated dibenzo-p-dioxins (PCDDs)) in 108 participants from a Columbia University WTC birth cohort. Principal component (PC) analyses were conducted to characterize the mixture of exposure to the three groups of chemicals. We evaluated the associations between geographical exposures (proximity to the WTC disaster) and both chemical exposures (PCs) and stress (demoralization). We then evaluated the effect these exposures (PCs and stress) had on previously reported associations between geographical WTC exposure and birth outcomes (birth weight and birth length) in this study population to understand their individual roles in the observed associations. Geographical exposure via proximity to the WTC was associated with the PC reflecting higher PCDD exposure (PC3) (ß = 0.60, 95% CI: 0.03, 1.18 for living/working within 2 miles of the WTC; and ß = 0.73, 95% CI = 0.08, 1.38 for living within 2 miles of WTC). Previously reported reductions in birth weight and length associated with WTC proximity (ß = -215.2, 95% CI: -416.2, -14.3 and ß = -1.47, 95% CI: -2.6, -0.34, respectively) were attenuated and no longer significant for birth weight (ß = -156.4, 95% CI: -358.2, 45.4) after adjusting for PC3, suggesting that PCDDs may act as partial mediators in this previously observed association. The results of this study can help focus future research on the long-term health effects of these prenatally exposed populations.

Gestational exposure to polybrominated diphenyl ethers and social skills and problem behaviors in adolescents: The HOME study.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are persistent environmental pollutants used as flame retardants. Gestational PBDE exposure has been associated with a variety of behavior problems in children, but little is known about its impact into adolescence, particularly on social skills, which are important for achieving social competence, establishing identity, and forming lasting relationships. OBJECTIVE: We investigated associations between gestational exposure to PBDEs and social skills and problem behaviors in early adolescence in a longitudinal pregnancy and birth cohort in Cincinnati, Ohio (recruited 2003-2006). METHODS: We measured maternal serum concentrations of five PBDE congeners during gestation. At age 12, we measured social skills and problem behaviors scores for 243 adolescents using self- and caregiver-report on the Social Skills Improvement System (SSiS). We used multivariable linear regression models to estimate associations between maternal PBDE concentrations and SSiS scores, controlling for potential covariates. We report associations for the five congeners and a summary exposure variable (∑5BDE: the sum of BDE- 28, 47, 99, 100, and 153, n = 197). RESULTS: We found sex-specific associations of ∑5BDE concentrations with adolescent-reported Problem Behaviors (∑5BDE × sex pint = 0.02) and caregiver-reported Social Skills (∑5BDE × sex pint = 0.02). In sex-stratified models, log10 transformed data revealed increased maternal ∑5BDE concentration among males was associated with decreased caregiver-reported Social Skills composite score (ß = -10.2, 95% CI: -19.5, -1.0), increased adolescent-reported Problem Behaviors composite score (ß = 12.1, 95% CI: 5.4, 18.8), and increased caregiver-reported Problem Behaviors composite score (ß = 6.2, 95% CI: 0.7, 11.7). Further analysis on SSiS subscales revealed similar patterns in significant associations among males. There were no statistically significant associations in stratified models among females despite higher ∑5BDE exposure (Female GM=40.15 ng/g lipid, GSE=1.10; Male GM=35.30 ng/g lipid, GSE=1.09). DISCUSSION: We found gestational PBDE exposure in males was associated with poorer behavioral outcomes, extending previous findings among this cohort into early adolescence.