Using PM2.5 concentrations to estimate the health burden from solid fuel combustion, with application to Irish and Scottish homes

Background: This study estimates the potential population health burden from exposure to combustion-derived particulate air pollution in domestic settings in Ireland and Scotland. Methods: The study focused on solid fuel combustion used for heating and the use of gas for cooking. PM2.5 (particulate matter with an aerodynamic diameter < 2.5 μm) was used as the pollutant mixture indicator. Measured PM2.5 concentrations in homes using solid fuels were adjusted for other sources of PM2.5 by subtracting PM2.5 concentrations in homes using gas for cooking but not solid fuel heating. Health burden was estimated for exposure indoors 6 pm - midnight, or all day (24-hour), by combining estimated attributable annual PM2.5 exposures with (i) selected epidemiological functions linking PM2.5 with mortality and morbidity (involving some re-scaling from PM10 to PM2.5, and adjustments ‘translating’ from concentrations to exposures) and (ii) on the current population exposed and background rates of morbidity and mortality. Results: PM2.5 concentrations in coal and wood burning homes were similar to homes using gas for cooking, used here as a baseline (mean 24-hr PM2.5 concentrations 8.6 μg/m3) and so health impacts were not calculated. Concentrations of PM2.5 in homes using peat were higher (24-hr mean 15.6 μg/m3); however, health impacts were calculated for the exposed population in Ireland only; the proportion exposed in Scotland was very small. The assessment for winter evening exposure (estimated annual average increase of 2.11 μg/m3 over baseline) estimated 21 additional annual cases of all-cause mortality, 55 of chronic bronchitis, and 30,100 and 38,000 annual lower respiratory symptom days (including cough) and restricted activity days respectively. Conclusion: New methods for estimating the potential health burden of combustion-generated pollution from solid fuels in Irish and Scottish homes are provided. The methodology involves several approximations and uncertainties but is consistent with a wider movement towards quantifying risks in PM2.5 irrespective of source. Results show an effect of indoor smoke from using peat (but not wood or coal) for heating and cooking; but they do not suggest that this is a major public health issue

Pelvic pain symptoms and endometriosis characteristics in relation to oxidative stress among adolescents and adults with and without surgically-confirmed endometriosis [version 1; peer review: 2 approved]

Background: While the majority of reproductive-aged females will experience pelvic pain during their lives, biological mechanisms underlying pelvic pain are not well understood. We investigated associations between pelvic pain symptoms and oxidative stress among people with and without surgically-confirmed endometriosis. Methods: Using an enzyme-linked immunosorbent assay, we measured 8-Hydroxy-2’-deoxyguanosine (8-OHdG) in urine samples and corrected for creatinine levels in 434 surgically-confirmed endometriosis participants compared to 605 participants never diagnosed with endometriosis. At enrollment, participants reported details of their pelvic pain symptoms. Linear regression was used to compute geometric mean (GM) creatinine-corrected 8-OHdG levels with 95% confidence intervals (CI) among all participants and those with and without endometriosis separately, adjusting for potential confounders. Interactions by surgically-confirmed endometriosis status were tested by Wald statistics. Results: No trends in 8-OHdG were observed among those with or without endometriosis for severity or frequency of dysmenorrhea, acyclic pelvic pain, dyspareunia or pain with bowel movements. Among endometriosis participants, lower 8-OHdG levels were observed for participants with any white, blue/black, or brown lesions (GM=76.7 versus 82.9 ng/mg; p=0.10), which was primarily driven by lower levels of 8-OHdG for any blue/black lesions (GM=72.8 versus 81.6 ng/mg; p=0.05). Conclusion: While no associations were observed between 8-OHdG and pelvic pain symptoms, future research is needed to assess how other pathways of oxidative damage, e.g. through proteins or lipids, may affect endometriosis-associated symptoms. Additionally, further research is needed to understand differences in oxidative stress among endometriosis lesion sub-phenotypes

Mosaic fungal individuals have the potential to evolve within a single generation

Although cells of mushroom-producing fungi typically contain paired haploid nuclei (n + n), most Armillaria gallica vegetative cells are uninucleate. As vegetative nuclei are produced by fusions of paired haploid nuclei, they are thought to be diploid (2n). Here we report finding haploid vegetative nuclei in A. gallica at multiple sites in southeastern Massachusetts, USA. Sequencing multiple clones of a single-copy gene isolated from single hyphal filaments revealed nuclear heterogeneity both among and within hyphae. Cytoplasmic bridges connected hyphae in field-collected and cultured samples, and we propose nuclear migration through bridges maintains this nuclear heterogeneity. Growth studies demonstrate among- and within-hypha phenotypic variation for growth in response to gallic acid, a plant-produced antifungal compound. The existence of both genetic and phenotypic variation within vegetative hyphae suggests that fungal individuals have the potential to evolve within a single generation in response to environmental variation over time and space

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

Reproductive and Hormonal Factors in Relation to Ovarian Cancer Risk and Survival

Ovarian cancer etiology is not fully elucidated and few modifiable risk factors have been identified. Ovarian cancer treatment has changed over time; however, survival is still poor. I investigated reproductive and hormonal factors in relation to ovarian cancer risk and survival. In the Nurses’ Health Study (NHS), NHSII and New England Case-Control Study (NECC), I evaluated reproductive and hormonal factors and incidence of ovarian cancer characterized by estrogen receptor-α (ERα) and progesterone receptor (PR) status using polytomous logistic regression. In the NHSII, I investigated oral contraceptive (OC) use and ovarian cancer risk using Cox proportional hazards models. In the NECC, I evaluated the association of pre-diagnostic reproductive and hormonal factors with overall survival and platinum resistance among ovarian cancer cases using Cox proportional hazards models. Postmenopausal status was associated with an increased risk of PR- tumors (OR: 2.07; 95%CI: 1.15-3.75; p-heterogeneity=0.01) and age at natural menopause was inversely associated with PR- tumors (OR, per 5yr: 0.77; 95%CI: 0.61-0.96; p-het=0.01). Increasing duration of postmenopause was differentially associated by PR status (p-het=0.0009). In OC analyses, OC use of 10 years of OC use (HR: 0.84; 95%CI: 0.51-1.39) compared to never use. The increased risk appeared to be driven by duration of mestranol use. In survival analyses, self-reported endometriosis was associated with a 29% (95%CI: 0.54-0.94) decreased risk of total death. Additionally, longer duration of hormone therapy (HT) was associated with a decreased risk of death (HR, ≥5yr vs. never: 0.70; 95%CI: 0.54-0.89). Further >5 years of HT use was associated with a decreased risk of platinum resistance. While our results need to be confirmed in other studies, they suggest that the development of ovarian tumors through hormonal pathways differs by menopausal status, the association between OC use and ovarian cancer differs between younger and older birth cohorts, and that various reproductive and hormonal factors are associated with ovarian cancer survival. These results may help in further understanding ovarian cancer etiology and providing recommendations for ovarian cancer prevention and survival

Indoor air pollution and health.

The number of deaths caused by smoking in the home could be comparable to the numbers of fatalities from road traffic collisions, according to new research led by NUI Galway and funded under the EPA’s STRIVE Research Programme. ‘Indoor Air Pollution and Health’ is a new in-depth study of air pollution in homes and shows that the concentration of particulate pollution in the homes of smokers who smoke indoors is six times higher than the World Health Organisation’s recommendation for general outdoor air quality. This research examined the health impacts of air pollution in homes. It presents new information on levels of indoor air pollutants in homes using solid fuels for heating or cooking and in homes that have a resident smoker. The report highlights the need for public health policy and research professionals to develop interventions to address this. The objective of the Indoor Air Pollution and Health (IAPAH) research project was to quantify the levels of Indoor Air Pollution (IAP) in Irish and Scottish homes where open combustion takes place, and provide an estimate of the potential health burden due to exposure to combustion derived air pollution in the home. IAP concentrations were measured in 100 homes in Ireland and Scotland

Oral contraceptive use by formulation and endometrial cancer risk among women born in 1947–1964: The Nurses’ Health Study II, a prospective cohort study

Oral contraceptives (OCs) have been associated with long-term lower endometrial cancer risk; relatively little is known about associations with more recent OC formulations and associations with longer-term risk. A total of 107,069 women from the Nurses' Health Study II recalled OC use from age 13 to baseline (1989); biennial questionnaires updated data on OC use until 2009. OCs were classified by estrogen and progestin type, dose, and potency based on reported brand. 864 incident endometrial cancer cases were identified through 2017. Multivariable Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals [95% CI] for the association of OC use with endometrial cancer risk. OC use was associated with lower endometrial cancer risk (ever use, HR 0.77 [95% CI 0.65-0.91]; &amp;gt;10 years of use, 0.43 [0.32-0.58] vs. never OC use). Inverse associations for duration were evident regardless of time since last use. Longer durations (&amp;gt; 5 years) of ethinyl estradiol (0.52 [0.41-0.67]) and second-generation progestins (0.43 [0.30-0.61]), both versus never use, were more strongly associated with lower risk than mestranol (0.66 [0.50-0.88], p-het = 0.01) and first-generation progestins (0.62 [0.49-0.78], p-het = 0.03). Inverse associations were generally observed for cross-classified cumulative average estrogen and progestin dose and potency (&amp;lt; vs. ≥ median; ever use vs. never OC use), with the exception of high estrogen and low progestin dose. OCs were associated with lower endometrial cancer risk, independent of time since last use. Use of ethinyl estradiol and second-generation progestins were more strongly inversely associated with risk compared with older formulations

Reproductive and hormonal factors in relation to survival and platinum resistance among ovarian cancer cases

Background: Ovarian cancer survival is poor, particularly for platinum-resistant cases. The previous literature on pre-diagnostic reproductive factors and ovarian cancer survival has been mixed. Therefore, we evaluated pre-diagnostic reproductive and hormonal factors with overall survival and, additionally, platinum-chemotherapy resistance. Methods: We followed 1649 invasive epithelial ovarian cancer cases who were enrolled between 1992 and 2008 for overall mortality within the New England Case-Control Study and abstracted chemotherapy data on a subset (n=449). We assessed pre-diagnostic reproductive and hormonal factors during in-person interviews. We calculated hazard ratios (HRs) using Cox-proportional hazards models. Results: We observed 911 all-cause deaths among 1649 ovarian cancer cases. Self-reported endometriosis and longer duration of hormone therapy use were associated with improved survival (HR: 0.72; 95% confidence interval (CI): 0.54–0.94 and HR, ⩾5 years vs never: 0.70; 95% CI: 0.55–0.90, respectively). Older age at menopause and menarche were associated with worse survival (HR, ⩽50 vs >50 years: 1.23; 95% CI: 1.03–1.46 and HR, 13 vs <13 years: 1.24; 95% CI: 1.06–1.44, respectively). We observed no association between oral contraceptive use, parity and tubal ligation, and overall survival. No significant associations were observed for any of the reproductive and hormonal factors and platinum resistance. Conclusions: These results suggest that pre-diagnostic exposures such as endometriosis and HT use may influence overall survival among ovarian cancer patients