Author Correction: Elephant shark genome provides unique insights into gnathostome evolution.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Household Air Pollution and Child Lung Function: The Ghana Randomized Air Pollution and Health Study.

Rationale: The impact of a household air pollution (HAP) stove intervention on child lung function has been poorly described. Objectives: To assess the effect of a HAP stove intervention for infants prenatally to age 1 on, and exposure-response associations with, lung function at child age 4. Methods: The Ghana Randomized Air Pollution and Health Study randomized pregnant women to liquefied petroleum gas (LPG), improved biomass, or open-fire (control) stove conditions through child age 1. We quantified HAP exposure by repeated maternal and child personal carbon monoxide (CO) exposure measurements. Children performed oscillometry, an effort-independent lung function measurement, at age 4. We examined associations between Ghana Randomized Air Pollution and Health Study stove assignment and prenatal and infant CO measurements and oscillometry using generalized linear regression models. We used reverse distributed lag models to examine time-varying associations between prenatal CO and oscillometry. Measurements and Main Results: The primary oscillometry measure was reactance at 5 Hz, X5, a measure of elastic and inertial lung properties. Secondary measures included total, large airway, and small airway resistance at 5 Hz, 20 Hz, and the difference in resistance at 5 Hz and 20 Hz (R5, R20, and R5-20, respectively); area of reactance (AX); and resonant frequency. Of the 683 children who attended the lung function visit, 567 (83%) performed acceptable oscillometry. A total of 221, 106, and 240 children were from the LPG, improved biomass, and control arms, respectively. Compared with control, the improved biomass stove condition was associated with lower reactance at 5 Hz (X5 z-score: ß = -0.25; 95% confidence interval [CI] = -0.39, -0.11), higher large airway resistance (R20 z-score: ß = 0.34; 95% CI = 0.23, 0.44), and higher AX (AX z-score: ß = 0.16; 95% CI = 0.06, 0.26), which is suggestive of overall worse lung function. The LPG stove condition was associated with higher X5 (X5 score: ß = 0.16; 95% CI = 0.01, 0.31) and lower small airway resistance (R5-20 z-score: ß = -0.15; 95% CI = -0.30, 0.0), which is suggestive of better small airway function. Higher average prenatal CO exposure was associated with higher R5 and R20, and distributed lag models identified sensitive windows of exposure between CO and X5, R5, R20, and R5-20. Conclusions: These data support the importance of prenatal HAP exposure on child lung function. Clinical trial registered with www.clinicaltrials.gov (NCT01335490).

Household Air Pollution Interventions to Improve Health in Low- and Middle-Income Countries: An Official American Thoracic Society Research Statement.

Background: An estimated 3 billion people, largely in low- and middle-income countries, rely on unclean fuels for cooking, heating, and lighting to meet household energy needs. The resulting exposure to household air pollution (HAP) is a leading cause of pneumonia, chronic lung disease, and other adverse health effects. In the last decade, randomized controlled trials of clean cooking interventions to reduce HAP have been conducted. We aim to provide guidance on how to interpret the findings of these trials and how they should inform policy makers and practitioners.Methods: We assembled a multidisciplinary working group of international researchers, public health practitioners, and policymakers with expertise in household air pollution from within academia, the American Thoracic Society, funders, nongovernmental organizations, and global organizations, including the World Bank and the World Health Organization. We performed a literature search, convened four sessions via web conference, and developed consensus conclusions and recommendations via the Delphi method.Results: The committee reached consensus on 14 conclusions and recommendations. Although some trials using cleaner-burning biomass stoves or cleaner-cooking fuels have reduced HAP exposure, the committee was divided (with 55% saying no and 45% saying yes) on whether the studied interventions improved measured health outcomes.Conclusions: HAP is associated with adverse health effects in observational studies. However, it remains unclear which household energy interventions reduce exposure, improve health, can be scaled, and are sustainable. Researchers should engage with policy makers and practitioners working to scale cleaner energy solutions to understand and address their information needs.

Nonsurgical treatment of skin cancer with local delivery of bioadhesive nanoparticles.

Keratinocyte-derived carcinomas, including squamous cell carcinoma (SCC), comprise the most common malignancies. Surgical excision is the therapeutic standard but is not always clinically feasible, and currently available alternatives are limited to superficial tumors. To address the need for a nonsurgical treatment for nodular skin cancers like SCC, we developed a bioadhesive nanoparticle (BNP) drug delivery system composed of biodegradable polymer, poly(lactic acid)-hyperbranched polyglycerol (PLA-HPG), encapsulating camptothecin (CPT). Nanoparticles (NPs) of PLA-HPG are nonadhesive NPs (NNPs), which are stealthy in their native state, but we have previously shown that conversion of the vicinal diols of HPG to aldehydes conferred NPs the ability to form strong covalent bonds with amine-rich surfaces. Herein, we show that these BNPs have significantly enhanced binding to SCC tumor cell surfaces and matrix proteins, thereby significantly enhancing the therapeutic efficacy of intratumoral drug delivery. Tumor injection of BNP-CPT resulted in tumor retention of CPT at ∼50% at 10 d postinjection, while CPT was undetectable in NNP-CPT or free (intralipid) CPT-injected tumors at that time. BNP-CPT also significantly reduced tumor burden, with a portion (∼20%) of BNP-CPT-treated established tumors showing histologic cure. Larger, more fully established PDV SCC tumors treated with a combination of BNP-CPT and immunostimulating CpG oligodeoxynucleotides exhibited enhanced survival relative to controls, revealing the potential for BNP delivery to be used along with local tumor immunotherapy. Taken together, these results indicate that percutaneous delivery of a chemotherapeutic agent via BNPs, with or without adjuvant immunostimulation, represents a viable, nonsurgical alternative for treating cutaneous malignancy.

The p53-Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans.

The extant jawless vertebrates, represented by lampreys and hagfish, are the oldest group of vertebrates and provide an interesting genomic evolutionary pivot point between invertebrates and jawed vertebrates. Through genome analysis of one of these jawless vertebrates, the Japanese lamprey (Lethenteron japonicum), we identified all three members of the important p53 transcription factor family--Tp53, Tp63, and Tp73--as well as the Mdm2 and Mdm4 genes. These genes and their products are significant cellular regulators in human cancer, and further examination of their roles in this most distant vertebrate relative sheds light on their origin and coevolution. Their important role in response to DNA damage has been highlighted by the discovery of multiple copies of the Tp53 gene in elephants. Expression of lamprey p53, Mdm2, and Mdm4 proteins in mammalian cells reveals that the p53-Mdm2 interaction and the Mdm2/Mdm4 E3 ligase activity existed in the common ancestor of vertebrates and have been conserved for >500 million years of vertebrate evolution. Lamprey Mdm2 degrades human p53 with great efficiency, but this interaction is not blocked by currently available small molecule inhibitors of the human HDM2 protein, suggesting utility of lamprey Mdm2 in the study of the human p53 signaling pathway.

An antibody Fc engineered for conditional antibody-dependent cellular cytotoxicity at the low tumor microenvironment pH.

Despite the exquisite specificity and high affinity of antibody-based cancer therapies, treatment side effects can occur since the tumor-associated antigens targeted are also present on healthy cells. However, the low pH of the tumor microenvironment provides an opportunity to develop conditionally active antibodies with enhanced tumor specificity. Here, we engineered the human IgG1 Fc domain to enhance pH-selective binding to the receptor FcγRIIIa and subsequent antibody-dependent cellular cytotoxicity (ADCC). We displayed the Fc domain on the surface of mammalian cells and generated a site-directed library by altering Fc residues at the Fc-FcγRIIIa interface to support interactions with positively charged histidine residues. We then used a competitive staining and flow cytometric selection strategy to isolate Fc variants exhibiting reduced FcγRIIIa affinities at neutral pH, but physiological affinities at the tumor-typical pH 6.5. We demonstrate that antibodies composed of Fab arms binding the breast cell epithelial marker Her2 and the lead Fc variant, termed acid-Fc, exhibited an ∼2-fold pH-selectivity for FcγRIIIa binding based on the ratio of equilibrium dissociation constants Kd,7.4/Kd,6.5, due to a faster dissociation rate at pH 7.4. Finally, in vitro ADCC assays with human FcγRIIIa-positive natural killer and Her2-positive target cells demonstrated similar activities for anti-Her2 antibodies bearing the wild-type or acid-Fc at pH 6.5, but nearly 20-fold reduced ADCC for acid-Fc at pH 7.4, based on EC50 ratios. This work shows the promise of mammalian cell display for Fc engineering and the feasibility of pH-selective Fc activation to provide a second dimension of selective tumor cell targeting.

Association between malaria and household air pollution interventions in a predominantly rural area of Ghana.

BACKGROUND: Though anecdotal evidence suggests that smoke from HAP has a repellent effect on mosquitoes, very little work has been done to assess the effect of biomass smoke on malaria infection. The study, therefore, sought to investigate the hypothesis that interventions to reduce household biomass smoke may have an unintended consequence of increasing placental malaria or increase malaria infection in the first year of life. METHODS: This provides evidence from a randomized controlled trial among 1414 maternal-infant pairs in the Kintampo North and Kintampo South administrative areas of Ghana. Logistic regression was used to assess the association between study intervention assignment (LPG, Biolite or control) and placental malaria. Finally, an extended Cox model was used to assess the association between study interventions and all episodes of malaria parasitaemia in the first year of infant's life. RESULTS: The prevalence of placental malaria was 24.6%. Out of this, 20.8% were acute infections, 18.7% chronic infections and 60.5% past infections. The study found no statistical significant association between the study interventions and all types of placental malaria (OR = 0.88; 95% CI 0.59-1.30). Of the 1165 infants, 44.6% experienced at least one episode of malaria parasitaemia in the first year of life. The incidence of first and/or only episode of malaria parasitaemia was however found to be similar among the study arms. CONCLUSION: The findings suggest that cookstove interventions for pregnant women and infants, when combined with additional malaria prevention strategies, do not lead to an increased risk of malaria among pregnant women and infants.

Long-Term Air Pollution Exposure and COVID-19 Mortality: A Patient-Level Analysis from New York City.

Rationale: Risk factors for coronavirus disease (COVID-19) mortality may include environmental exposures such as air pollution. Objectives: To determine whether, among adults hospitalized with PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), long-term air pollution exposure is associated with the risk of mortality, ICU admission, or intubation. Methods: We performed a retrospective analysis of SARS-CoV-2 PCR-positive patients admitted to seven New York City hospitals from March 8, 2020, to August 30, 2020. The primary outcome was mortality; secondary outcomes were ICU admission and intubation. We estimated the annual average fine particulate matter (particulate matter ⩽2.5 µm in aerodynamic diameter [PM2.5]), nitrogen dioxide (NO2), and black carbon (BC) concentrations at patients' residential address. We employed double robust Poisson regression to analyze associations between the annual average PM2.5, NO2, and BC exposure level and COVID-19 outcomes, adjusting for age, sex, race or ethnicity, hospital, insurance, and the time from the onset of the pandemic. Results: Among the 6,542 patients, 41% were female and the median age was 65 (interquartile range, 53-77) years. Over 50% self-identified as a person of color (n = 1,687 [26%] Hispanic patients; n = 1,659 [25%] Black patients). Air pollution exposure levels were generally low. Overall, 31% (n = 2,044) of the cohort died, 19% (n = 1,237) were admitted to the ICU, and 16% (n = 1,051) were intubated. In multivariable models, a higher level of long-term exposure to PM2.5 was associated with an increased risk of mortality (risk ratio, 1.11 [95% confidence interval, 1.02-1.21] per 1-µg/m3 increase in PM2.5) and ICU admission (risk ratio, 1.13 [95% confidence interval, 1.00-1.28] per 1-µg/m3 increase in PM2.5). In multivariable models, neither NO2 nor BC exposure was associated with COVID-19 mortality, ICU admission, or intubation. Conclusions: Among patients hospitalized with COVID-19, a higher long-term PM2.5 exposure level was associated with an increased risk of mortality and ICU admission.

Successful Medical Management of an Acute Traumatic Sternal Luxation in a Cat.

A 5 yr old indoor-outdoor domestic longhair red tabby cat presented for evaluation of a 1-day history of hiding, urinating and defecating outside the litterbox, and vocalizing when picked up. Physical examination revealed significant pain on palpation of the caudal sternum where an approximately 8 × 6 cm contusion was noted. Sedated thoracic radiographs revealed a luxated fifth intersternebral joint with the sixth sternebra being cranioventrally displaced (along with the seventh and eight sternebrae) to the level of the mid fourth sternebra. There were sharply marginated, short oblique fractures of the distal sixth costal cartilages bilaterally with mild dorsal displacement of the distal segment. The sternal luxation was palpated more aggressively once the patient was sedated and deemed to be stable. Because of the stability of the luxation and absence of sternebral fractures, conservative medical management in the form of analgesics and rest was instituted. Repeat thoracic radiographs 2 wk after presentation revealed an unchanged sternal luxation. Twelve months after presentation, the patient presented for an unrelated lameness and, in that timeframe, has exhibited no sequelae to the sternal luxation, which still palpates stable and is radiographically unchanged.

The seahorse genome and the evolution of its specialized morphology.

Seahorses have a specialized morphology that includes a toothless tubular mouth, a body covered with bony plates, a male brood pouch, and the absence of caudal and pelvic fins. Here we report the sequencing and de novo assembly of the genome of the tiger tail seahorse, Hippocampus comes. Comparative genomic analysis identifies higher protein and nucleotide evolutionary rates in H. comes compared with other teleost fish genomes. We identified an astacin metalloprotease gene family that has undergone expansion and is highly expressed in the male brood pouch. We also find that the H. comes genome lacks enamel matrix protein-coding proline/glutamine-rich secretory calcium-binding phosphoprotein genes, which might have led to the loss of mineralized teeth. tbx4, a regulator of hindlimb development, is also not found in H. comes genome. Knockout of tbx4 in zebrafish showed a 'pelvic fin-loss' phenotype similar to that of seahorses.

Prenatal lead exposure and childhood lung function: Influence of maternal cortisol and child sex.

INTRODUCTION: Maternal hypothalamic-pituitary-adrenal (HPA) axis disruption in pregnancy may contribute to the programming of childhood respiratory disease and may modify the effect of chemical toxins, like lead (Pb), on lung development. Child sex may further modify these effects. We sought to prospectively examine associations between maternal HPA axis disruption, prenatal Pb and childhood lung function and explore potential effect modification by maternal cortisol and child sex on the association between prenatal Pb and lung function outcomes. MATERIALS AND METHODS: Analyses included 222 mothers and children enrolled in a longitudinal birth cohort study in Mexico City. Maternal diurnal salivary cortisol was assessed in pregnancy; cortisol awakening response (CAR) and diurnal slope were calculated. Blood Pb was measured during the second trimester of pregnancy. Post-bronchodilator lung function was tested at ages 8-11 years. Associations were modeled using generalized linear models with interaction terms, adjusting for covariates. RESULTS: A higher (flatter) diurnal slope was associated with lower FEV1/FVC ratio (ß: 0.433, 95%CI [-0.766, -0.101]). We did not find any main effect associations between prenatal Pb and lung function outcomes. We report an interaction between Pb and cortisol in relation to FEV1/FVC and FEF25-75% (pinteraction<0.05 for all). Higher prenatal Pb was associated with reduced FEV1/FVC only in children whose mothers had a high CAR. Higher prenatal Pb was also associated with reduced FEV1/FVC and FEF25-75% in mothers with a flatter diurnal slope. A 3-way interaction between prenatal Pb, CAR and sex on FEV1/FVC, indicated that boys born to women with high CAR and higher prenatal Pb levels had lower FEV1/FVC ratios (pinteraction = 0.067). CONCLUSIONS: Associations between prenatal Pb and childhood lung function were modified by disrupted maternal cortisol in pregnancy and child sex. These findings underscore the need to consider complex interactions to fully elucidate effects of prenatal Pb exposure on childhood lung function.

Youth mental health-related presentations at a quaternary centre: Who comes, What are their needs, and Can we meet their needs.

Background: Mental health issues are increasingly prevalent across Canada, reflected in rising presentations to emergency departments. To effectively address the needs of children and youth seeking mental health-related care in the emergency department and to judiciously use scarce mental health-related resources, we need to better identify the specific areas of psychosocial needs and accessibility of associated services. Objective: To describe the types and severity of paediatric mental health-related presentations evaluated at a quaternary paediatric emergency department, and to explore the accessibility of community mental health-related resources. Methods: We conducted a retrospective cohort study of children and youth presenting to a quaternary paediatric emergency department who were assessed using HEARTSMAP, a validated mental health assessment and management tool. We reported the proportion who sought care for a psychiatric, social, or youth health-related mental health complaint. We contacted community mental health-related resources for their estimated wait times to determine accessibility. Results: Of 1,530 paediatric emergency presentations, 98.8% of patients had psychiatric issues (40.1% were severe), 78.0% of patients had social issues (17.1% were severe), and 71.5% had youth health issues (18.1% were severe). We contacted 123 community mental health-related resources. Community youth health and social services were somewhat accessible, with 50.0% and 38.7%, respectively, able to intake youth within a week of referral. Community psychiatric programs were least accessible, with 59.3% having wait times greater than 1 month. Conclusions: Many psychiatric concerns presenting in paediatric emergency departments have complex psychosocial challenges requiring non-psychiatric support. A need exists for improved accessibility to community psychiatric programs.

Multi-omics profiling of a CHO cell culture system unravels the effect of culture pH on cell growth, antibody titer, and product quality.

A robust monoclonal antibody (mAb) bioprocess requires physiological parameters such as temperature, pH, or dissolved oxygen to be well-controlled as even small variations in them could potentially impact the final product quality. For instance, pH substantially affects N-glycosylation, protein aggregation, and charge variant profiles, as well as mAb productivity. However, relatively less is known about how pH jointly influences product quality and titer. In this study, we investigated the effect of pH on culture performance, product titer, and quality profiles by applying longitudinal multi-omics profiling, including transcriptomics, proteomics, metabolomics, and glycomics, at three different culture pH set points. The subsequent systematic analysis of multi-omics data showed that pH set points differentially regulated various intracellular pathways including intracellular vesicular trafficking, cell cycle, and apoptosis, thereby resulting in differences in specific productivity, product titer, and quality profiles. In addition, a time-dependent variation in mAb N-glycosylation profiles, independent of pH, was identified to be mainly due to the accumulation of mAb proteins in the endoplasmic reticulum disrupting cellular homeostasis over culture time. Overall, this multi-omics-based study provides an in-depth understanding of the intracellular processes in mAb-producing CHO cell line under varied pH conditions, and could serve as a baseline for enabling the quality optimization and control of mAb production.

Data-driven discovery of mid-pregnancy immune markers associated with maternal lifetime stress: results from an urban pre-birth cohort.

Changes to the maternal inflammatory milieu may be a mechanism through which maternal psychosocial stress is transmitted to the fetus. Research investigating a limited number of immune markers may miss important signals. We take a proteomics approach to investigate maternal lifetime stress and 92 biomarkers of immune system status. Participants were enrolled in an urban, dual-site (Boston, n = 301 and New York City, n = 110) pregnancy cohort. We measured maternal lifetime history of stress and trauma using the validated Life Stressor Checklist-Revised (LSC-R). We measured a panel of 92 immune-related proteins in mid-pregnancy serum using proximity extension assay technology. We leveraged the dual-site study design to perform variable selection and inference within the cohort. First, we used LASSO to select immune markers related to maternal stress among Boston mothers. Then, we performed OLS regression to examine associations between maternal stress and LASSO-selected proteins among New York City mothers. LASSO regression selected 19 immune proteins with non-null coefficients (CCL11, CCL23, CD244, CST5, CXCL1, CXCL5, CXCL10, CX3CL1, FGF-23, IL-5, IL-7, IL-10, IL-17C, MCP-2, MMP-1, SLAMF1, ST1A1, TNF-ß, and TWEAK). Of these, only the chemotactic cytokine CX3CL1 (i.e. fractalkine) was significantly associated with maternal stress among the validation sample (percent change in LSC-R score per 1% increase in relative fractalkine expression: 0.74, 95% confidence interval: 0.19, 1.28). Expanding research suggests fractalkine plays an important role in many aspects of pregnancy and fetal development and is stress-sensitive. We found that maternal lifetime history of stress and trauma was significantly associated with elevated serum fractalkine levels during pregnancy.

Environmental mixtures and children's health: identifying appropriate statistical approaches.

PURPOSE OF REVIEW: Biomonitoring studies have shown that children are constantly exposed to complex patterns of chemical and nonchemical exposures. Here, we briefly summarize the rationale for studying multiple exposures, also called mixture, in relation to child health and key statistical approaches that can be used. We discuss advantages over traditional methods, limitations and appropriateness of the context. RECENT FINDINGS: New approaches allow pediatric researchers to answer increasingly complex questions related to environmental mixtures. We present methods to identify the most relevant exposures among a high-multitude of variables, via shrinkage and variable selection techniques, and identify the overall mixture effect, via Weighted Quantile Sum and Bayesian Kernel Machine regressions. We then describe novel extensions that handle high-dimensional exposure data and allow identification of critical exposure windows. SUMMARY: Recent advances in statistics and machine learning enable researchers to identify important mixture components, estimate joint mixture effects and pinpoint critical windows of exposure. Despite many advantages over single chemical approaches, measurement error and biases may be amplified in mixtures research, requiring careful study planning and design. Future research requires increased collaboration between epidemiologists, statisticians and data scientists, and further integration with causal inference methods.

Elephant shark genome provides unique insights into gnathostome evolution.

The emergence of jawed vertebrates (gnathostomes) from jawless vertebrates was accompanied by major morphological and physiological innovations, such as hinged jaws, paired fins and immunoglobulin-based adaptive immunity. Gnathostomes subsequently diverged into two groups, the cartilaginous fishes and the bony vertebrates. Here we report the whole-genome analysis of a cartilaginous fish, the elephant shark (Callorhinchus milii). We find that the C. milii genome is the slowest evolving of all known vertebrates, including the 'living fossil' coelacanth, and features extensive synteny conservation with tetrapod genomes, making it a good model for comparative analyses of gnathostome genomes. Our functional studies suggest that the lack of genes encoding secreted calcium-binding phosphoproteins in cartilaginous fishes explains the absence of bone in their endoskeleton. Furthermore, the adaptive immune system of cartilaginous fishes is unusual: it lacks the canonical CD4 co-receptor and most transcription factors, cytokines and cytokine receptors related to the CD4 lineage, despite the presence of polymorphic major histocompatibility complex class II molecules. It thus presents a new model for understanding the origin of adaptive immunity.

The genomic substrate for adaptive radiation in African cichlid fish.

Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.

Prenatal particulate air pollution and newborn telomere length: Effect modification by maternal antioxidant intakes and infant sex.

BACKGROUND: Evidence links gestational exposure to particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5) with changes in leukocyte telomere length in cord blood with some studies showing sex-specific effects. PM2.5 exposure in utero increases oxidative stress, which can impact telomere biology. Thus, maternal antioxidant intakes may also modify the particulate air pollution effects. METHODS: We examined associations among prenatal PM2.5 exposure and newborn relative leukocyte telomere length (rLTL), and the modifying effects of maternal antioxidant intake and infant sex. We estimated daily PM2.5 exposures over gestation using a validated spatiotemporally resolved satellite-based model. Maternal dietary and supplemental antioxidant intakes over the prior three months were ascertained during the second trimester using the modified Block98 food frequency questionnaire; high and low antioxidant intakes were categorized based on a median split. We employed Bayesian distributed lag interaction models (BDLIMs) to identify both sensitive windows of exposure and cumulative effect estimates for prenatal PM2.5 exposure on newborn rLTL, and to examine effect modification by maternal antioxidant intakes. A 3-way interaction between PM2.5, maternal antioxidant intake and infant sex was also explored. RESULTS: For the main effect of PM2.5, BDLIMs identified a sensitive window at 12-20 weeks gestation for the association between increased prenatal PM2.5 exposure and shorter newborn rLTL and a cumulative effect of PM2.5 over gestation on newborn telomere length [cumulative effect estimate (CEE) = -0.29 (95% CI -0.49 to -0.10) per 1µg/m3 increase in PM2.5]. In models examining maternal antioxidant intake effects, BDLIMs found that children born to mothers reporting low antioxidant intakes were most vulnerable [CEE of low maternal antioxidant intake = -0.31 (95% CI -0.55 to -0.06) vs high maternal antioxidant intake = -0.07 (95% CI -0.34 to 0.17) per 1µg/m3 increase in PM2.5]. In exploratory models examining effect modification by both maternal antioxidant intakes and infant sex, the cumulative effect remained significant only in boys whose mothers reported low antioxidant intakes [CEE = -0.38 (95% CI -0.80 to -0.004)]; no sensitive windows were identified in any group. CONCLUSIONS: Prenatal PM2.5 exposure in mid-gestation was associated with reduced infant telomere length. Higher maternal antioxidant intakes mitigated these effects.

Prenatal Household Air Pollution Is Associated with Impaired Infant Lung Function with Sex-Specific Effects. Evidence from GRAPHS, a Cluster Randomized Cookstove Intervention Trial.

RATIONALE: Approximately 2.8 billion people are exposed daily to household air pollution from polluting cookstoves. The effects of prenatal household air pollution on lung development are unknown. OBJECTIVES: To prospectively examine associations between prenatal household air pollution and infant lung function and pneumonia in rural Ghana. METHODS: Prenatal household air pollution exposure was indexed by serial maternal carbon monoxide personal exposure measurements. Using linear regression, we examined associations between average prenatal carbon monoxide and infant lung function at age 30 days, first in the entire cohort (n = 384) and then stratified by sex. Quasi-Poisson generalized additive models explored associations between infant lung function and pneumonia. MEASUREMENTS AND MAIN RESULTS: Multivariable linear regression models showed that average prenatal carbon monoxide exposure was associated with reduced time to peak tidal expiratory flow to expiratory time (ß = -0.004; P = 0.01), increased respiratory rate (ß = 0.28; P = 0.01), and increased minute ventilation (ß = 7.21; P = 0.05), considered separately, per 1 ppm increase in average prenatal carbon monoxide. Sex-stratified analyses suggested that girls were particularly vulnerable (time to peak tidal expiratory flow to expiratory time: ß = -0.003, P = 0.05; respiratory rate: ß = 0.36, P = 0.01; minute ventilation: ß = 11.25, P = 0.01; passive respiratory compliance normalized for body weight: ß = 0.005, P = 0.01). Increased respiratory rate at age 30 days was associated with increased risk for physician-assessed pneumonia (relative risk, 1.02; 95% confidence interval, 1.00-1.04) and severe pneumonia (relative risk, 1.04; 95% confidence interval, 1.00-1.08) in the first year of life. CONCLUSIONS: Increased prenatal household air pollution exposure is associated with impaired infant lung function. Altered infant lung function may increase risk for pneumonia in the first year of life. These findings have implications for future respiratory health. Clinical trial registered with www.clinicaltrials.gov (NCT 01335490).

Association of meniscal injury to joint space width on standard tibial plateau leveling osteotomy lateral radiographic projections of the canine stifle.

Up to 70% of dogs with cranial cruciate ligament tears have concurrent meniscal injury, and these injuries can increase the risk of developing osteoarthritis and persistent lameness. Studies assessing joint space width on knee radiographs in people have indicated associations between joint space width and meniscal injuries. The aim of this prospective analytical study was to determine if there was an association between stifle joint space width on three different radiographic projections (the standard tibial plateau leveling osteotomy projections and a standing lateral projection) and meniscal injuries identified at surgery in dogs. There was a significant association between dogs with a meniscal tear and the corresponding joint space width on standard tibial plateau leveling osteotomy lateral radiographic projections (P-value = .0028). Based on receiver operator characteristic curve analysis, joint space widths measuring less than 3.43 mm may indicate a meniscal tear, with a corresponding 89.5% specificity and 40.5% sensitivity in dogs weighing 31 kg. Joint space narrowing is seen with meniscal tears in dogs, and radiography may be a noninvasive way to identify meniscal tears prior to surgery.