Ozone exposure during early pregnancy and preterm birth: A systematic review and meta-analysis.

Exposure to ozone has been linked to reproductive outcomes, including preterm birth. In this systematic review, we summarize published epidemiologic cohort and case-control studies examining ozone exposures (estimated on a continuous scale) in early pregnancy (1st and 2nd trimesters (T1, T2)) and preterm birth using ratio measures, and perform a meta-analysis to evaluate the potential relationship between them. Studies were identified by searching PubMed and Web of Science, screened according to predefined inclusion/exclusion criteria, and evaluated for study quality. We extracted study data including effect estimates, confidence limits, study location, study years, ozone exposure assessment method, and mean or median ozone concentrations. Nineteen studies were identified and included, of which 18 examined T1 exposure (17 reported effect estimates), and 15 examined T2 exposure. Random effects meta-analysis was performed in the metafor package, R 3.5.3. The pooled OR (95% CI) for a 10 ppb increase in ozone exposure in T1 was 1.06 (1.03, 1.10) with a 95% prediction interval of 0.95, 1.19; for T2 it was 1.05 (1.02, 1.08) with a 95% prediction interval of 0.95, 1.16. Effect estimates for both exposure periods showed high heterogeneity. In meta-regression analyses of study characteristics, study location (continent) explained some (~20%) heterogeneity for T1 exposure studies, but no characteristic explained a substantial amount of heterogeneity for T2 exposure studies. Increased ozone exposure during early pregnancy is associated with preterm birth across studies.

A Case of Paraneoplastic Myoclonus Attributed to Non-Small Cell Lung Cancer.

Background: It is well known that myoclonus can be a paraneoplastic manifestation of underlying malignancy. Case Report: A 78-year-old male diagnosed with papillary variant non-small cell lung cancer (NSCLC) presented with tremulousness that rapidly evolved into severe, diffuse myoclonus with prominent palatal involvement requiring intubation. The generalized myoclonus resolved with on levetiracetam, chemotherapy and immune modulation. While low titer positive P/Q type calcium channel autoantibodies were detected, it's etiologic relevance is unclear. Discussion: This case highlights a rare neurologic paraneoplastic presentation of papillary NSCLC. It also illustrates the importance of monitoring airway safety when myoclonus is generalized. Highlights: A new, rare paraneoplastic presentation of papillary variant non-small cell lung adenocarcinoma is described. The patient presented with severe diffuse myoclonus with prominent palatal involvement without encephalitis that responded to a combination of chemotherapy, immune modulation, and levetiracetam. No clear causal antibody was found.

A systematic review of cardiovascular emergency department visits, hospital admissions and mortality associated with ambient black carbon.

BACKGROUND: Black carbon (BC) is a ubiquitous component of particulate matter (PM) emitted from combustion-related sources and is associated with a number of health outcomes. OBJECTIVES: We conducted a systematic review to evaluate the potential for cardiovascular morbidity and mortality following exposure to ambient BC, or the related component elemental carbon (EC), in the context of what is already known about the associations between exposure to fine particulate matter (PM2.5) and cardiovascular health outcomes. DATA SOURCES: We conducted a stepwise systematic literature search of the PubMed database and employed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting our results. STUDY ELIGIBILITY CRITERIA: Studies meeting inclusion criteria (i.e., include a quantitative measurement of BC or EC used to characterize exposure and an effect estimate of the association of the exposure metric with ED visits, hospital admissions, or mortality due to cardiovascular disease) were evaluated for risk of bias in study design and results. STUDY APPRAISAL AND SYNTHESIS METHODS: Risk of bias evaluations assess some aspects of internal validity of study findings based on study design, conduct, and reporting and identify potential issues related to confounding or other biases. RESULTS: The results of our systematic review demonstrate similar results for BC or EC and PM2.5; that is, a generally modest, positive association of each pollutant measurement with cardiovascular emergency department visits, hospital admissions, and mortality. There is no clear evidence that health risks are greater for either BC or EC when compared to one another, or when either is compared to PM2.5. LIMITATIONS: We were unable to adequately evaluate the role of copollutant confounding or differential spatial heterogeneity for BC or EC compared to PM2.5. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Overall, the evidence at present indicates that BC or EC is consistently associated with cardiovascular morbidity and mortality but is not sufficient to conclude that BC or EC is independently associated with these effects rather than being an indicator for PM2.5 mass. SYSTEMATIC REVIEW REGISTRATION NUMBER: Not available.

Evaluating potential response-modifying factors for associations between ozone and health outcomes: a weight-of-evidence approach.

BACKGROUND: Epidemiologic and experimental studies have reported a variety of health effects in response to ozone (O3) exposure, and some have indicated that certain populations may be at increased or decreased risk of O3-related health effects. OBJECTIVES: We sought to identify potential response-modifying factors to determine whether specific groups of the population or life stages are at increased or decreased risk of O3-related health effects using a weight-of-evidence approach. METHODS: Epidemiologic, experimental, and exposure science studies of potential factors that may modify the relationship between O3 and health effects were identified in U.S. Environmental Protection Agency's 2013 Integrated Science Assessment for Ozone and Related Photochemical Oxidants. Scientific evidence from studies that examined factors that may influence risk were integrated across disciplines to evaluate consistency, coherence, and biological plausibility of effects. The factors identified were then classified using a weight-of-evidence approach to conclude whether a specific factor modified the response of a population or life stage, resulting in an increased or decreased risk of O3-related health effects. DISCUSSION: We found "adequate" evidence that populations with certain genotypes, preexisting asthma, or reduced intake of certain nutrients, as well as different life stages or outdoor workers, are at increased risk of O3-related health effects. In addition, we identified other factors (i.e., sex, socioeconomic status, and obesity) for which there was "suggestive" evidence that they may increase the risk of O3-related health effects. CONCLUSIONS: Using a weight-of-evidence approach, we identified a diverse group of factors that should be considered when characterizing the overall risk of health effects associated with exposures to ambient O3.

Genome-wide association mapping of acute lung injury in neonatal inbred mice.

Reactive oxygen species (ROS) contribute to the pathogenesis of many acute and chronic pulmonary disorders, including bronchopulmonary dysplasia (BPD), a respiratory condition that affects preterm infants. However, the mechanisms of susceptibility to oxidant stress in neonatal lungs are not completely understood. We evaluated the role of genetic background in response to oxidant stress in the neonatal lung by exposing mice from 36 inbred strains to hyperoxia (95% O2) for 72 h after birth. Hyperoxia-induced lung injury was evaluated by using bronchoalveolar lavage fluid (BALF) analysis and pathology. Statistically significant interstrain variation was found for BALF inflammatory cells and protein (heritability estimates range: 33.6-55.7%). Genome-wide association mapping using injury phenotypes identified quantitative trait loci (QTLs) on chromosomes 1, 2, 4, 6, and 7. Comparative mapping of the chromosome 6 QTLs identified Chrm2 (cholinergic receptor, muscarinic 2, cardiac) as a candidate susceptibility gene, and mouse strains with a nonsynonymous coding single-nucleotide polymorphism (SNP) in Chrm2 that causes an amino acid substitution (P265L) had significantly reduced hyperoxia-induced inflammation compared to strains without the SNP. Further, hyperoxia-induced lung injury was significantly reduced in neonatal mice with targeted deletion of Chrm2, relative to wild-type controls. This study has important implications for understanding the mechanisms of oxidative lung injury in neonates.

Systematic review of the effects of black carbon on cardiovascular disease among individuals with pre-existing disease.

OBJECTIVES: Recent interest has developed in understanding the health effects attributable to different components of particulate matter. This review evaluates the effects of black carbon (BC) on cardiovascular disease in individuals with pre-existing disease using evidence from epidemiologic and experimental studies. METHODS: A systematic literature search was conducted to identify epidemiologic and experimental studies examining the relationship between BC and cardiovascular health effects in humans with pre-existing diseases. Nineteen epidemiologic and six experimental studies were included. Risk of bias was evaluated for each study. RESULTS: Evidence across studies suggested ambient BC is associated with changes in subclinical cardiovascular health effects in individuals with diabetes and coronary artery disease (CAD). Limited evidence demonstrated that chronic respiratory disease does not modify the effect of BC on cardiovascular health. CONCLUSIONS: Results in these studies consistently demonstrated that diabetes is a risk factor for BC-related cardiovascular effects, including increased interleukin-6 and ECG parameters. Cardiovascular effects were associated with BC in individuals with CAD, but few comparisons to individuals without CAD were provided in the literature.

Secondary amenorrhea attributed to occlusion of microperforate transverse vaginal septum.

OBJECTIVE: To present a case of secondary amenorrhea after occlusion of microperforate transverse vaginal septum. DESIGN: Case report. SETTING: Academic teaching hospital. PATIENT(S): A 19-year-old woman with new onset of irregular menses and pelvic pain, with history of menarche at age 14. INTERVENTION(S): Surgical evaluation and treatment, including laparoscopy, hysteroscopy, and excision of septum, followed by repeat surgery with lysis of adhesions due to agglutination of the area previously excised. MAIN OUTCOME MEASURE(S): Awareness of the possibility of secondary amenorrhea occurring due to septal scarring of a perforate transverse vaginal septum. RESULT(S): Imaging revealed a hematometra and hematocolpos. Examination revealed a transverse vaginal septum. Ultrasound scans and magnetic resonance imaging revealed an enlarged uterus and an endometrial cavity and cervix distended with fluid and debris. Examination under anesthesia revealed a septum approximately 5 mm thick, which was revealed to be benign fibromuscular tissue with chronic nonspecific inflammation. CONCLUSION(S): This case demonstrates the evolution from a microperforate transverse vaginal septum with regular menses for over 4 years to an occluded septum. Although transverse vaginal septa causing amenorrhea are usually diagnosed at menarche, perforate septa have been shown to lead to hypomenorrhea, dysmenorrhea, dyspareunia, infertility, and issues with vaginal childbirth. We present a case in which a perforate transverse vaginal septum led to secondary amenorrhea.

Case of accessory ovary in the round ligament with associated endometriosis.

The phenomenon of accessory ovary, initially described in 1864, is extremely rare. We report a case of an accessory ovary in a round ligament with endometriosis. At the time of laparoscopy a firm 2- to 3-cm mass was noted within the round ligament with a normal ovary visualized. Dissection and removal of the mass was performed. Histopathology revealed ovarian stroma and dense connective tissue with endometriosis. This case fulfills the criteria established in 1959 for accessory ovary and is the first case of an accessory ovary reported within the round ligament. A unique finding with the accessory ovary in this case is the presence of endometriosis. No reported cases exist of endometriosis within an accessory ovary. This information may be pertinent for evaluation of dysmenorrhea when no endometrial implants are present, or with the persistence or recurrence of endometriosis and pain after a bilateral salpingo-oophorectomy.

Case of sisters with complete androgen insensitivity syndrome and discordant Müllerian remnants.

OBJECTIVE: Presentation of complete androgen insensitivity in two members of the same family with differing residual Müllerian tissue. DESIGN: Case report. SETTING: Rural hospital setting. PATIENT(S): Two siblings with 46,XY karyotype and female phenotype presented at different points in time with primary amenorrhea. Laparoscopy of sister 1 revealed bilateral elongated gonads and remnants of uterine tissue. Laparoscopy of sister 2 demonstrated both gonads, but no uterus was identified. INTERVENTION(S): Sister 1: bilateral gonadectomy and hysterectomy. Sister 2: bilateral gonadectomy. MAIN OUTCOME MEASURE(S): Gonadectomy for cancer prophylaxis, counseling in affected/unaffected family members. RESULT(S): Sister 1: pathology revealed portions of immature testicles and fragments of smooth muscle. Sister 2: pathology reported two testicular and epididymal-like structures with benign Sertoli cell adenomas entirely in testicular parenchyma. CONCLUSION(S): This case demonstrates the presentation and laparoscopic photos of complete androgen insensitivity syndrome discovered in two siblings. Both girls are genotypically male, but differ in the presence of vestigial Müllerian tissue. This case demonstrates that siblings with androgen resistance may express varying amounts of Müllerian tissue.