Higher measured moisture in California homes with qualitative evidence of dampness.

Relationships between measured moisture and qualitative dampness indicators (mold odor, visible mold, visible water damage, or peeling paint) were evaluated using data collected from California homes in a prospective birth cohort study when the infants were 6 or 12 months of age (737 home visits). For repeated visits, agreement between observation of the presence/absence of each qualitative indicator at both visits was high (71-87%, P < 0.0001). Among individual indicators, musty odor and visible mold were most strongly correlated with elevated moisture readings. Measured moisture differed significantly between repeated visits in opposite seasons (P < 0.0001), and dampness increased with the number of indicators in a home. Linear mixed-effect models showed that 10-unit increases in maximum measured moisture were associated with the presence of 0.5 additional dampness indicators (P < 0.001). Bedroom (BR) walls were damper than living room (LR) walls in the same homes (P < 0.0001), although both average and maximum readings were positively correlated across room type (r = 0.75 and 0.67, respectively, both P < 0.0001). Exterior walls were significantly damper than interior walls (P < 0.0001 in both LRs and BRs), but no differences were observed between maximum wall readings and measurements at either window corners or sites of suspected dampness.

Next-generation DNA sequencing reveals that low fungal diversity in house dust is associated with childhood asthma development.

UNLABELLED: Dampness and visible mold in homes are associated with asthma development, but causal mechanisms remain unclear. The goal of this research was to explore associations among measured dampness, fungal exposure, and childhood asthma development without the bias of culture-based microbial analysis. In the low-income, Latino CHAMACOS birth cohort, house dust was collected at age 12 months, and asthma status was determined at age 7 years.The current analysis included 13 asthma cases and 28 controls. Next-generation DNA sequencing methods quantified fungal taxa and diversity. Lower fungal diversity (number of fungal operational taxonomic units) was significantly associated with increased risk of asthma development: unadjusted odds ratio(OR) 4.80 (95% confidence interval (CI) 1.04­22.1). Control for potential confounders strengthened this relationship. Decreased diversity within the genus Cryptococcus was significantly associated with increased asthma risk (OR 21.0, 95% CI 2.16­204). No fungal taxon (species, genus, class) was significantly positively associated with asthma development, and one was significantly negatively associated. Elevated moisture was associated with increased fungal diversity, and moisture/mold indicators were associated with four fungal taxa. Next-generation DNA sequencing provided comprehensive estimates of fungal identity and diversity, demonstrating significant associations between low fungal diversity and childhood asthma development in this community. PRACTICAL IMPLICATIONS: Early life exposure to low fungal diversity in house dust was associated with increased risk for later asthma developmen tin this low-income, immigrant community. No individual fungal taxon (species, genus, or class) was associated with asthma development, although exposure to low diversity within the genus Cryptococcus was associated with asthma development. Future asthma development studies should incorporate fungal diversity measurements, in addition to measuring individual fungal taxa. These results represent a step toward identifying the aspect(s) of indoor microbial populations that are associated with asthma development and suggest that understanding the factors that control diversity in the indoor environment may lead to public health recommendations for asthma prevention in the future.

A rapid questionnaire assessment of environmental exposures to pregnant women in the INTERGROWTH-21st Project.

Impaired fetal growth and preterm birth are the leading causes of neonatal and infant mortality worldwide and there is a growing scientific literature suggesting that environmental exposures during pregnancy may play a causal role in these outcomes. Our purpose was to assess the environmental exposure of the Fetal Growth Longitudinal Study (FGLS) participants in the multinational INTERGROWTH-21(st) Project. First, we developed a tool that could be used internationally to screen pregnant women for such exposures and administered it in eight countries on a subsample (n = 987) of the FGLS participants. The FGLS is a study of fetal growth among healthy pregnant women living in relatively affluent areas, at low risk of adverse pregnancy outcomes and environmental exposures. We confirmed that most women were not exposed to major environmental hazards that could affect pregnancy outcomes according to the protocol's entry criteria. However, the instrument was able to identify some women that reported various environmental concerns in their homes such as peeling paint, high residential density (>1 person per room), presence of rodents or cockroaches (hence the use of pesticides), noise pollution and safety concerns. This screening tool was therefore useful for the purposes of the project and can be used to ascertain environmental exposures in studies in which the primary aim is not focused on environmental exposures. The instrument can be used to identify subpopulations for more in-depth assessment, (e.g. environmental and biological laboratory markers) to pinpoint areas requiring education, intervention or policy change.

Chemotherapy induces transient sex chromosomal and autosomal aneuploidy in human sperm.

Each year more than 20,000 children and young persons of reproductive age are exposed to known mutagens in the form of chemo- and/or radiotherapy for cancer in the States. As more of these treatments are effective there is growing concern that genetic defects are introduced in the germ cells of these young patients. It is well documented for male rodents that treatment with chemo- and radio-therapeutic agents before mating can cause genetic damage in the germ line, and the magnitude of heritable effects depends on the spermatogenic cell stage treated. Similar germinal effects are suspected to occur in humans but remain unproven. Hodgkin's disease (HD) is an example of a malignancy which is typically diagnosed during a patient's reproductive years. In our study we observed eight male HD patients who were treated with NOVP (Novanthrone, Oncovin, Vinblastine, Prednisone) chemotherapy. We evaluated sperm aneuploidy using multi-colour fluorescence in situ hybridization (FISH), and found approximately 5-fold increases in sperm with disomies, diploidies and complex genotypes involving chromosome X, Y and 8. Increases in sex chromosome aneuploidies arose from segregation errors at meiosis I as well as meiosis II. The aneuploidy effects were transient, however, declining to pretreatment levels within approximately 100 days after the end of the therapy. When compared with normal men, some HD patients showed higher proportions of certain sperm aneuploidy types even before their first therapy.

Determinants of organophosphorus pesticide urinary metabolite levels in pregnant women from the CHAMACOS cohort.

Organophosphosphorus pesticides (OPs) are widely used as insecticides in agriculture. Human exposure to OPs has been linked to adverse effects including poorer child neurodevelopment, reduced birth weight, altered serum hormone levels, and reduced semen quality. We measured six OP dialkyl phosphate (DAP) metabolites [three dimethyl alkylphosphates (DMs) and three diethyl alkylphosphates (DEs)] in urine samples collected two times during pregnancy (~13 and ~26 weeks gestation) from 594 women participating in the CHAMACOS birth cohort study and resided in an agricultural community in the United States (U.S.) between 1999 and 2000. Previous studies have shown these women have higher OP exposures compared with the general U.S. population. We examined bivariate associations between prenatal DAP metabolite levels and exposure determinants such as age, season, years living in the US, housing characteristics, fruit and vegetable consumption, occupation and residential proximity to agricultural fields. Final multivariable models indicated that season of urine collection was significantly associated (p < 0.01) with specific gravity-adjusted DM, DE and total DAP metabolites; samples collected in fall and winter had higher concentrations than those collected in spring-summer. Specific gravity-adjusted levels of DM and total DAP metabolites were significantly higher in women who had resided in the U.S. for 5 years or less (p < 0.05). Levels of DM metabolites also increased with daily fruit and vegetable servings (p < 0.01), and levels of DE metabolites were higher in residences with poorer housekeeping quality (p < 0.01) and in mothers that worked in agriculture (p < 0.05). These findings suggest that there are multiple determinants of OP exposure in pregnant women.

Sex ratio variations among the offspring of women with diabetes in pregnancy.

AIMS: It has long been hypothesized that natural selection would favour a reproductive strategy biased towards females under adverse circumstances in order to maximize the number of surviving grandchildren. An excess of daughters in women with Type 1 diabetes and a greater likelihood of gestational diabetes in women carrying male fetuses have also been reported. This study aims to compare the sex ratio across categories of maternal glycaemia. METHODS: Among 288,009 mother-infant pairs delivering at Kaiser Permanente Northern California in 1996-2008, sex ratios were calculated for the following categories: pregravid diabetes, gestational diabetes, mild pregnancy hyperglycaemia (defined as an abnormal screening but normal diagnostic test for gestational diabetes) and normoglycaemia. Odds ratios for delivering a male were estimated with logistic regression; normoglycaemic pregnancies comprised the reference. RESULTS: Women with pregravid diabetes delivered the fewest males (ratio male/female = 1.01), followed by women with normoglycaemic pregnancies and those with an abnormal screening only (both sex ratios = 1.05); women with gestational diabetes delivered the most males (sex ratio = 1.07). Odds ratio estimates suggested the same pattern, but none attained statistical significance. CONCLUSIONS: The crude sex ratios in this cohort suggest a possible gradient by category of maternal glycaemia. Women with gestational diabetes, a condition characterized by excessive fuel substrates, appear to deliver more males. Women with pregravid diabetes delivered the fewest males, possibly reflecting the unfavourable state of chronic disease.

Fungi and pollen exposure in the first months of life and risk of early childhood wheezing.

BACKGROUND: Many studies have found that the risk of childhood asthma varies by month of birth, but few have examined ambient aeroallergens as an explanatory factor. A study was undertaken to examine whether birth during seasons of elevated ambient fungal spore or pollen concentrations is associated with risk of early wheezing or blood levels of Th1 and Th2 type cells at 24 months of age. METHODS: 514 children were enrolled before birth and followed to 24 months of age. Early wheezing was determined from medical records, and Th1 and Th2 type cells were measured in peripheral blood using flow cytometry. Ambient aeroallergen concentrations were measured throughout the study period and discrete seasons of high spore and pollen concentrations were defined. RESULTS: A seasonal pattern was observed, with birth in autumn to winter (the spore season) associated with increased odds of early wheezing (adjusted odds ratio 3.1; 95% confidence interval 1.3 to 7.4). Increasing mean daily concentrations of basidiospores and ascospores in the first 3 months of life were associated with increased odds of wheeze, as were increasing mean daily concentrations of total and specific pollen types. Levels of Th1 cells at age 24 months were positively associated with mean spore concentrations and negatively associated with mean pollen concentrations in the first 3 months of life. CONCLUSIONS: Children with higher exposure to spores and pollen in the first 3 months of life are at increased risk of early wheezing. This association is independent of other seasonal factors including ambient levels of particulate matter of aerodynamic diameter

The association of folate, zinc and antioxidant intake with sperm aneuploidy in healthy non-smoking men.

BACKGROUND: Little is known about the effect of paternal nutrition on aneuploidy in sperm. We investigated the association of normal dietary and supplement intake of folate, zinc and antioxidants (vitamin C, vitamin E and beta-carotene) with the frequency of aneuploidy in human sperm. METHODS: Sperm samples from 89 healthy, non-smoking men from a non-clinical setting were analysed for aneuploidy using fluorescent in situ hybridization with probes for chromosomes X, Y and 21. Daily total intake (diet and supplements) for zinc, folate, vitamin C, vitamin E and beta-carotene was derived from a food frequency questionnaire. Potential confounders were obtained from a self-administered questionnaire. RESULTS: After adjusting for covariates, men with high folate intake (>75th percentile) had lower frequencies of sperm with disomies X, 21, sex nullisomy, and a lower aggregate measure of sperm aneuploidy (P

Prenatal phthalate exposure and 8-isoprostane among Mexican-American children with high prevalence of obesity.

Oxidative stress has been linked to many obesity-related conditions among children including cardiovascular disease, diabetes mellitus and hypertension. Exposure to environmental chemicals such as phthalates, ubiquitously found in humans, may also generate reactive oxygen species and subsequent oxidative stress. We examined longitudinal changes of 8-isoprostane urinary concentrations, a validated biomarker of oxidative stress, and associations with maternal prenatal urinary concentrations of phthalate metabolites for 258 children at 5, 9 and 14 years of age participating in a birth cohort residing in an agricultural area in California. Phthalates are endocrine disruptors, and in utero exposure has been also linked to altered lipid metabolism, as well as adverse birth and neurodevelopmental outcomes. We found that median creatinine-corrected 8-isoprostane concentrations remained constant across all age groups and did not differ by sex. Total cholesterol, systolic and diastolic blood pressure were positively associated with 8-isoprostane in 14-year-old children. No associations were observed between 8-isoprostane and body mass index (BMI), BMI Z-score or waist circumference at any age. Concentrations of three metabolites of high molecular weight phthalates measured at 13 weeks of gestation (monobenzyl, monocarboxyoctyl and monocarboxynonyl phthalates) were negatively associated with 8-isoprostane concentrations among 9-year olds. However, at 14 years of age, isoprostane concentrations were positively associated with two other metabolites (mono(2-ethylhexyl) and mono(2-ethyl-5-carboxypentyl) phthalates) measured in early pregnancy. Longitudinal data on 8-isoprostane in this pediatric population with a high prevalence of obesity provides new insight on certain potential cardiometabolic risks of prenatal exposure to phthalates.

An assessment of dioxin exposure across gestation and lactation using a PBPK model and new data from Seveso.

On July 10, 1976, an explosion at a chemical plant in Seveso, Italy, released up to 30kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-the most potent dioxin congener. Twenty years later, the Seveso Women's Health Study (SWHS) initiated a follow-up assessment of a cohort of female Seveso residents. Researchers collected serial blood, measured for TCDD levels, and recorded information about the women's medical history after the explosion. The study's aims were to: 1) modify the human PBPK model for TCDD (Emond et al. 2004; Emond et al. 2005; NCEA-USEPA, 2010) to include repetitive gestation and lactation; 2) simulate TCDD blood concentrations during different life stages including pregnancy and lactation, under different exposure scenarios; and 3) use this PBPK model to compare the influence of gestation and lactation on elimination of TCDD. After optimization of the model, it was assessed using data from the SWHS cohort. The 23 women in Subcohort A, were 4-39years old and in Subcohort B, the 18 women were 3-17years old when the explosion occurred. The model accurately predicted the blood concentrations during the 20years post-exposure, including periods of pregnancy and lactation. The model was also used to analyze the contribution of gestation and lactation to the mother's elimination of TCDD. The results suggest that gestation and lactation do not significantly impact TCDD blood elimination. Future efforts will focus on using additional data to evaluate the PBPK model and improving the mathematical descriptions of lactation and multiple gestations.

Dichlorodiphenyltrichloroethane exposure and anogenital distance in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) birth cohort study, South Africa.

Dichlorodiphenyltrichloroethane (DDT) is used for malaria control by 10 countries, nine of which are in Africa. Technical DDT contains various isomers with 65-80% insecticidal p,p'-DDT and 15-21% o,p'-DDT, an estrogenic chemical, while the persistent metabolite of p,p'-DDT, dichlorodiphenyldichloroethylene (p,p'-DDE), is an antiandrogen. In utero antiandrogenic exposure reduces anogenital distance in animal models and the anal position index in a single study. This study examined the associations between mother's serum DDT and DDE levels at delivery and anogenital distance in their children at birth and age 1 year. Data were collected as part of the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE), a birth cohort study located in rural South Africa. DDT and DDE concentrations were measured in blood samples collected from 752 mothers at delivery. Anogenital distance measurements, taken at birth (n = 671) and age 1 year (n = 674), included anofourchette and anoclitoral distances in girls, and anoscrotal and anopenile lengths in boys. We also measured anococcygeal and coccyx-fourchette distances in girls, while in boys, we measured anococcygeal and coccyx-scrotal distances as well as penile length and penile width. The anal position index is calculated for both sexes as anoscrotal/coccyx-scrotal in boys and anofourchette/coccyx-fourchette in girls. We found no associations between p,p'-DDT/-DDE or o,p'-DDT and anogenital distance measurements at birth in either boys or girls. At 1 year, o,p'-DDE was negatively associated with anofourchette in girls (ß =-1.32 mm, 95% confidence interval (CI) = -2.27, -0.38) and positively associated with penile width in boys (ß = 0.30 mm, 95% CI = 0.00, 0.60). The results do not suggest an overt antiandrogenic or estrogenic effect on anogenital distance after long-term DDT exposure. These weak associations may be due to chance.

Lead and hyperactivity revisited. An investigation of nondisadvantaged children.

The purposes of this study were to examine whether hyperactive children had elevated lead levels, to assess whether lead levels were associated with poor psychometric performance in hyperactive children, and to replicate previous reports of hyperactive children with perinatal insult having lower lead levels than those with normal perinatal history. Hyperactive, learning-disabled children and normal siblings were studied. The hyperactive children had higher chelated urine lead levels than their own siblings. Other contrasts were not significant. Cognitive performances and lead levels were weakly associated in the hyperactive sample. Contrary to previous reports, lead levels and perinatal complications were not negatively correlated. These results support the notion that lead levels are weakly associated with hyperactive disorders.

HIV serology in artificially inseminated lesbians.

The purpose of this investigation was to examine the risks of HIV transmission from artificial insemination in a sample of lesbians residing in California and inseminated between 1979 and 1987. This population was selected because lesbians are considered to be at low risk for HIV infection, and have traditionally used semen from men engaging in high-risk behaviors, namely, homosexual men. Each of the 98 participants had blood drawn for the HIV antibody test (ELISA) and completed a questionnaire inquiring about her sexual, health, and reproductive history, including detailed information about her inseminations (e.g., vaginal vs. uterine, fresh vs. frozen semen, sexual orientation, and antibody status of donor). One-half of the women had homosexual or bisexual donors, many of whom resided in the San Francisco Bay area; most of these inseminations were with fresh semen. The women reported a marked decline in the use of homosexual donors after 1982 and a corresponding increase in the use of donations from sperm banks and health practitioners. Based on the women's reports, as many as 11 women may have received semen from an infected donor. However, none of the 98 women tested seropositive. We attribute our negative findings to the change to low-risk donors in the years when HIV became more prevalent in the population, and to the potentially lower rates of infectivity with artificial insemination than with heterosexual intercourse. Nevertheless, we recommend that women continue to follow the CDC guidelines for screening donors prior to artificial insemination.

Olfactory lateralization and identification in right hemisphere lesion and control patients.

This study investigated olfactory lateralization and identification in right hemisphere lesion and control patients. Significant group differences were found for olfactory and trigeminal lateralization and identification on unilateral and double simultaneous stimulation. In the control group, significantly greater than chance accuracy was found for lateralization and identification, whereas in the lesion group, significantly greater than chance accuracy was found for identification but not for lateralization. Olfactory detection thresholds were found not to be significantly different between the groups.

Odor perception in temporal lobe epilepsy patients with and without temporal lobectomy.

The investigation employed monorhinic (single nostril) olfactory testing to decide whether patients with unilateral anterior temporal lobe resection (N = 16) and patients with unoperated temporal lobe epilepsy (N = 18) have impaired ability to detect, remember, and identify odors. A shape memory task accompanied the odor memory task for comparison. The lobectomy patients showed a minor bilateral depression of absolute sensitivity but still fell within the clinically normal range. The lobectomy patients showed impairment of odor recognition memory but strictly via the nostril ipsilateral to the resected lobe. A similar ipsilateral-contralateral asymmetry characterized the performance of these patients in odor identification. In that case, however, performance via the contralateral nostril showed some impairment too. Nonsurgery patients also exhibited some impairment in odor identification, but bilaterally. Finally, both groups of patients fell somewhat below normals in recognition memory for amorphous shapes. The various results implied that temporal lobe epilepsy alone takes some toll on olfactory information processing and that temporal lobe resection exacerbates the problem, but only on the side of surgery.

Olfactory functioning in temporal lobectomy patients.

Seventeen patients who received unilateral excision of the temporal lobe for intractable epilepsy were compared to 46 normal controls on a battery of tests of olfactory functioning. Tests included quality discrimination, immediate and delayed recognition memory, matching an odor to its visually or haptically presented source, and verbal identification of odors and the function of stimulus objects. In spite of clinically normal absolute sensitivity, the patients performed significantly worse than controls on all tests of olfactory functioning. There were no significant differences in performance between dominant and non-dominant lobectomy patients. Likely explanations for the uniformly impaired performance of patients include deficits in quality discrimination and minor lapses of attention.

The nature of unilateral neglect in the olfactory sensory system.

This study investigated two major theories of unilateral neglect utilizing the ipsilaterally innervated olfactory sense. The sensory theory states that unilateral neglect is due to a diminished or attenuated sensory input. The representational theory states that unilateral neglect is due to a disordered internal representation, which is not dependent on sensory input. Results of the study revealed that right hemisphere lesion patients with left unilateral neglect failed to respond to their left contralateral nostril on olfactory double simultaneous stimulation, consistent with the representational theory because the left nostril has no direct sensory input to the right hemisphere.

Workshop on perinatal exposure to dioxin-like compounds. II. Reproductive effects.

This summary report focuses on current studies on reproductive effects reported at the workshop on Perinatal Exposure to Dioxin-like Compounds and supporting data noted in the discussion. Recent laboratory studies have suggested that altered development (e.g., low birth weight, spontaneous abortion, congenital malformation) and reproductive health (e.g., fertility, sex organ development, reproductive behavior) may be among the most sensitive end points when examining the effects of dioxinlike compounds. Thus, future research should target the reproductive health of both males and females exposed postnatally and prenatally. Studies in humans are needed and are on-going. In animal models, postnatal exposure to dioxin or dioxinlike compounds has been associated with abnormal spermatogenesis and abnormal testicular morphology and size in males and with reduced fertility and endometriosis in females. In utero exposure may also produce profound reproductive consequences in both males and females including delays in sexual maturation, abnormalities in development of sexual organs, and abnormal sexual behavior. The mechanism by which dioxin-like compounds cause reproductive effects is not well delineated.

Association of prenatal maternal or postnatal child environmental tobacco smoke exposure and neurodevelopmental and behavioral problems in children.

We review the potential neurodevelopmental and behavioral effects of children's prenatal and/or postnatal exposure to environmental tobacco smoke (ETS). Children's exposure to ETS has been assessed in epidemiologic studies as a risk factor for a variety of behavioral and neurodevelopmental problems including reduced general intellectual ability, skills in language and auditory tasks, and academic achievement, and behavioral problems such as hyperactivity and decreased attention spans. We review 17 epidemiologic studies that have attempted to separate the effects of maternal active smoking during pregnancy from passive ETS smoke exposure by the pregnant mother or the child. Based on the available data, we found that ETS exposure could cause subtle changes in children's neurodevelopment and behavior. However, studies to date are difficult to interpret because of the unknown influence of uncontrolled confounding factors, imprecision in measurements of smoking exposure, and collinearity of pre- and postnatal maternal smoking. Although some evidence suggests that maternal smoking during pregnancy may be associated with deficits in intellectual ability and behavioral problems in children, the impact of prenatal or postnatal ETS exposure remains less clear.

Possible risk of endometriosis for Seveso, Italy, residents: an assessment of exposure to dioxin.

A recent study by Rier et al. showed that rhesus monkeys exposed daily for 4 years to 5 or 25 ppt of dioxin in food develop endometriosis, with incidence and severity related to dose. We aimed to determine whether the total time-integrated dioxin exposure of a human population could be comparable to that of Rier's monkeys. We selected a sample of residents of Seveso, Italy, who were acutely exposed to high levels of dioxin following an accident in 1976. We conducted a toxicokinetic analysis which takes into account species and exposure differences in dose and timing between humans and monkeys. The area under the time-concentration curve for dioxin in fat, which corresponds to cumulative exposure over time, ranges for some of the most heavily exposed Seveso residents from approximately 1.7 x 10(6) ppt-days to 1.1 x 10(8) ppt-days. These values exceed in all cases the values for the monkeys exposed to 25 ppt or 5 ppt. Given their exposure, the Seveso population should be an ideal epidemiologic cohort to rule out or confirm whether exposure to dioxin leads to an increased risk of endometriosis in humans.