Maternal periconceptional exposure to drinking water disinfection by-products and neural tube defects in offspring.

BACKGROUND: Associations between maternal periconceptional exposure to disinfection by-products (DBPs) in drinking water and neural tube defects (NTDs) in offspring are inconclusive, limited in part by exposure misclassification. METHODS: Maternal interview reports of drinking water sources and consumption from the National Birth Defects Prevention Study were linked with DBP concentrations in public water system monitoring data for case children with an NTD and control children delivered during 2000-2005. DBPs analyzed were total trihalomethanes, the five most common haloacetic acids combined, and individual species. Associations were estimated for all NTDs combined and selected subtypes (spina bifida, anencephaly) with maternal periconceptional exposure to DBPs in public water systems and with average daily periconceptional ingestion of DBPs accounting for individual-level consumption and filtration information. Mixed effects logistic regression models with maternal race/ethnicity and educational attainment at delivery as fixed effects and study site as a random intercept were applied. RESULTS: Overall, 111 case and 649 control children were eligible for analyses. Adjusted odds ratios for maternal exposure to DBPs in public water systems ranged from 0.8-1.5 for all NTDs combined, 0.6-2.0 for spina bifida, and 0.7-1.9 for anencephaly; respective ranges for average daily maternal ingestion of DBPs were 0.7-1.1, 0.5-1.5, and 0.6-1.8. Several positive estimates (≥1.2) were observed, but all confidence intervals included the null. CONCLUSIONS: Using community- and individual-level data from a large, US, population-based, case-control study, we observed statistically nonsignificant associations between maternal periconceptional exposure to total and individual DBP species in drinking water and NTDs and subtypes.

Use of a human skin in vitro model to investigate the influence of 'every-day' clothing and skin surface decontamination on the percutaneous penetration of organophosphates.

UNLABELLED: Organophosphates (OPs) are widely used in agriculture. Many studies have investigated the capability of personal protective equipment (PPE) to reduce chemical exposure; however, investigations into the protective effect of 'every-day' clothing are rare. The purpose of this study was to investigate the protective effect of 'every-day' clothing against dermal exposure and to measure early decontamination of skin following exposure to chlorpyrifos and dichlorvos. Using human skin in vitro, absorption of (14)C-labelled chlorpyrifos (500 ng/cm(2)), was shown to be significantly reduced when applied to clothed skin (cotton shirt), regardless of application vehicle (isopropanol (IPA) or propylene glycol (PG)). The majority of applied dose was retained within the clothing after 4 h exposure. Significant reduction in absorption of chlorpyrifos (in PG) was seen through clothed skin when supplemented with skin decontamination at 4 h, compared with clothed skin decontaminated after 24 h, however, this was not observed with IPA. Absorption of dichlorvos (5 µg/cm(2)) was greater through unclothed skin than chlorpyrifos for all vehicles (IPA, isopropyl myristate (IPM) and PG). Significant reduction in absorption was observed when decontaminating clothed skin at 30 min, compared with decontamination at 24 h (post-exposure) for all vehicles. RESULT: indicate that 'every-day' clothing is effective at reducing exposure to chemicals in contact with skin. Washing the skin surface immediately following removal of exposed clothing can further reduce exposure, depending on the properties of the chemical and vehicle applied.

Percutaneous absorption and distribution of organophosphates (chlorpyrifos and dichlorvos) following dermal exposure and decontamination scenarios using in vitro human skin model.

To date, there has been little research investigating low-level human exposure to chemicals, and so the aim of this study was to examine the percutaneous penetration of organophosphates (dichlorvos and chlorpyrifos) using low-level exposure scenarios in vitro. Dermal absorption of chlorpyrifos applied in different vehicles was measured at 0, 4, 8 and 24 h, after dose application for 4 and 24 h exposure (finite dose, 500 ng/cm(2)) in isopropanol (IPA), isopropyl myristate (IPM) and propylene glycol (PG). Dichlorvos was applied to the skin for 24 h (infinite dose, 1 mg/cm(2) and 10 mg/cm(2); finite dose, 5 µg/cm(2)) using the same vehicles. Human skin was mounted in flow through diffusion cells with minimum essential medium eagle pH 7.4 (supplemented with 2% BSA) as receptor fluid. Following exposure, the skin surface dose was removed by tissue swabbing, the stratum corneum removed by sequential tape stripping, and the skin digested prior to scintillation counting (chlorpyrifos), or GC/MS analysis (dichlorvos). The dermal absorption of chlorpyrifos was the greatest following application in PG (19.5% of dose), when compared with absorption from the IPA and IPM vehicles (10.3% and 1.9% absorbed respectively). However, dichlorvos showed greater dermal absorption than chlorpyrifos from all vehicles used, with greatest absorption from the IPA vehicle (38.6% absorbed). Although dichlorvos exhibited a short lag time (0.6 h from IPA and IP vehicles, and 0.4 h from PG), chlorpyrifos displayed greater propensity to accumulate in the stratum corneum and epidermis/dermis. These results demonstrate that prompt skin surface decontamination would be required for both dichlorvos and chlorpyrifos (and chemicals with similar properties) in the event of skin contact. The magnitude of the skin reservoir formed with chlorpyrifos was time dependent, therefore, prompt decontamination of this and similar chemicals would be required to reduce delayed systemic absorption.

Wavelet-based analysis of surface mechanomyographic signals from subjects with differences in myosin heavy chain isoform content.

The purpose of this study was to use a wavelet analysis designed specifically for surface mechanomyographic (MMG) signals to determine if the % myosin heavy chain (MHC) isoform content affected the shape of the MMG frequency spectrum during isometric muscle actions. Five resistance-trained (mean +/- SD age = 23.2 +/-3.7 yrs), five aerobically-trained (mean +/- SD age = 32.6 +/- 5.2 yrs), and five sedentary (mean +/- SD age = 23.4 +/- 4.1 yrs) men performed isometric muscle actions of the dominant leg extensors at 20%, 40%, 60%, 80%, and 100% of the maximum voluntary contraction (MVC). Surface MMG signals were detected from the vastus lateralis during each muscle action and processed with the MMG wavelet analysis. In addition, muscle biopsies were taken from the vastus lateralis and analyzed for % MHC isoform content. The results showed that there were distinct differences among the three groups of subjects for % MHC isoform content. These differences were not manifested, however, in the isometric force-related changes in the total intensity of the MMG signal in each wavelet band. It is possible that factors such as the thicknesses of the subcutaneous adipose tissue and/or iliotibial band reduced the potential influence of differences in % MHC isoform content on the MMG signal.

Regional distribution of Ginkgo biloba-induced c-Fos immunoreactivity.

A growing literature supports the notion that Ginkgo biloba has cognitive enhancing and anxiolytic properties; however, its effects on neuronal populations have yet to be characterized. The present study used c-Fos immunoreactivity (Fos-IR) to characterize functional activity in selected brain regions following administration of a standardized Ginkgo biloba extract. Because Ginkgo is typically consumed orally, Exp 1 sought to identify patterns of neural activity induced by oral administration. To ensure that the alterations in functional neural activity observed in Exp 1 were not simply due to novel gustatory experience, Exp 2 characterized patterns of Fos-IR following intraperitoneal administration of Ginkgo. Rats were habituated to handling and experimental conditions. In Exp 1, rats self-administered 150 mg/kg Ginkgo or vehicle alone (strawberry jam) orally. In Exp 2, rats were injected with Ginkgo (2.5 or 25 mg/kg, i.p.) or vehicle (0.3% gum Arabic). Animals were anaesthetized and perfused transcardially. Brains were sectioned, immunostained using a c-Fos antibody, then the number of labelled cells was quantified microscopically in selected brain regions. In both experiments Ginkgo increased Fos-IR in numerous brain regions including the insular cortex and amygdala. Intraperitoneal administration induced Fos-IR in some additional regions including the nucleus accumbens and dentate gyrus. Results provide important preliminary data serving to identify several candidate neural sites involved in the cognitive enhancing and anxiolytic effects of Ginkgo biloba.

Health-related direct-to-consumer genetic tests: a public health assessment and analysis of practices related to Internet-based tests for risk of thrombosis.

BACKGROUND: Recent years have seen increased concern about direct-to-consumer (DTC) genetic testing (i.e., the sale and use of genetic tests without involving a health care provider). Numerous professional organizations have developed policies in this area. However, little systematic evidence exists to inform public policy about these tests. METHODS: We conducted a systematic search to identify genetic tests that are sold DTC without involving a health care provider. We evaluated the practices of companies offering DTC genetic tests for risk of thrombosis using criteria from multiple sources and a minimal set of key practices. RESULTS: We identified 84 instances of currently available health-related DTC genetic tests sold on 27 Web sites; the most common were for pharmacogenomics (12), risk of thrombosis (10), and nutrigenomics (10). For the DTC genetic tests for risk of thrombosis, we found low adherence to recommendations. Online information was frequently incomplete and had low agreement with professional recommendations. CONCLUSION: Our findings document the rapid growth in the availability of health-related DTC genetic tests and highlight the need to improve the delivery of DTC genetic tests. A major implication of this study is the need for the scientific and medical community to develop consistent recommendations to increase their impact.

A decade of public health genomics in the United States: centers for disease control and prevention 1997-2007.

Since 1997, the Centers for Disease Control and Prevention (CDC) has collaborated with numerous partners to develop and chart the course of the multidisciplinary field of public health genomics in the USA and globally. During this period, CDC has developed major initiatives for the appropriate integration of genomics into public health research, policy and programs. In this paper, we review briefly the progress in public health genomics made over the past decade in the USA, including population research, the human genome epidemiology network (HuGENet(TM)), the evaluation of genomic applications in practice and prevention (EGAPP), the family history public health initiative, and efforts in building the public health genomics capacity. We also outline a vision for public health genomics for the next decade.

Mutations in JARID1C are associated with X-linked mental retardation, short stature and hyperreflexia.

BACKGROUND: Mutations in the JARID1C (Jumonji AT-rich interactive domain 1C) gene were recently associated with X-linked mental retardation (XLMR). Mutations in this gene are reported to be one of the relatively more common causes of XLMR with a frequency of approximately 3% in males with proven or probable XLMR. The JARID1C protein functions as a histone 3 lysine 4 (H3K4) demethylase and is involved in the demethylation of H3K4me3 and H3K4me2. METHODS: Mutation analysis of the JARID1C gene was conducted in the following cohorts: probands from 23 XLMR families linked to Xp11.2, 92 males with mental retardation and short stature, and 172 probands from small XLMR families with no linkage information. RESULTS: Four novel mutations consisting of two missense mutations, p.A77T and p.V504M, and two frame shift mutations, p.E468fsX2 and p.R1481fsX9, were identified in males with mental retardation. Two of the mutations, p.V504M and p.E468fsX2, are located in the JmjC domain of the JARID1C gene where no previous mutations have been reported. Additional studies showed that the missense mutation, p.V504M, was a de novo event on the grandpaternal X chromosome of the family. Clinical findings of the nine affected males from the four different families included mental retardation (100%), short stature (55%), hyperreflexia (78%), seizures (33%) and aggressive behaviour (44%). The degree of mental retardation consisted of mild (25%), moderate (12%) and severe (63%). CONCLUSION: Based on the clinical observations, male patients with mental retardation, short stature and hyperreflexia should be considered candidates for mutations in the JARID1C gene.

The influence of muscle fiber type composition on the patterns of responses for electromyographic and mechanomyographic amplitude and mean power frequency during a fatiguing submaximal isometric muscle action.

The purpose of this investigation was to examine the influence of muscle fiber type composition on the patterns of responses for electromyographic (EMG) and mechanomyographic (MMG) amplitude and mean power frequency (MPF) during a fatiguing submaximal isometric muscle action. Five resistance-trained (mean +/- SD age = 23.2 +/- 3.7 yrs) and five aerobically-trained (mean +/- SD age = 32.6 +/- 5.2 yrs) men volunteered to perform a fatiguing, 30-sec submaximal isometric muscle action of the leg extensors at 50% of the maximum voluntary contraction (MVC). Muscle biopsies from the vastus lateralis revealed that the myosin heavy chain (MHC) composition for the resistance-trained subjects was 59.0 +/- 4.2% Type IIa, 0.1 +/- 0.1% Type IIx, and 40.9 +/- 4.3% Type I. The aerobically-trained subjects had 27.4 +/- 7.8% Type IIa, 0.0 +/- 0.0% Type IIx, and 72.6 +/- 7.8% Type I MHC. The patterns of responses and mean values for absolute and normalized EMG amplitude and MPF during the fatiguing muscle action were similar for the resistance-trained and aerobically-trained subjects. The resistance-trained subjects demonstrated relatively stable levels for absolute and normalized MMG amplitude and MPF across time, but the aerobically-trained subjects showed increases in MMG amplitude and decreases in MMG MPE The absolute MMG amplitude and MPF values for the resistance-trained subjects were also greater than those for the aerobi-cally-trained subjects. These findings suggested that unlike surface EMG, MMG may be a useful noninvasive technique for examining fatigue-related differences in muscle fiber type composition.

Time series analysis of jaw muscle contraction and tissue deformation during mastication in miniature pigs.

Masticatory muscle contraction causes both jaw movement and tissue deformation during function. Natural chewing data from 25 adult miniature pigs were studied by means of time series analysis. The data set included simultaneous recordings of electromyography (EMG) from bilateral masseter (MA), zygomaticomandibularis (ZM) and lateral pterygoid muscles, bone surface strains from the left squamosal bone (SQ), condylar neck (CD) and mandibular corpus (MD), and linear deformation of the capsule of the jaw joint measured bilaterally using differential variable reluctance transducers. Pairwise comparisons were examined by calculating the cross-correlation functions. Jaw-adductor muscle activity of MA and ZM was found to be highly cross-correlated with CD and SQ strains and weakly with MD strain. No muscle's activity was strongly linked to capsular deformation of the jaw joint, nor were bone strains and capsular deformation tightly linked. Homologous muscle pairs showed the greatest synchronization of signals, but the signals themselves were not significantly more correlated than those of non-homologous muscle pairs. These results suggested that bone strains and capsular deformation are driven by different mechanical regimes. Muscle contraction and ensuing reaction forces are probably responsible for bone strains, whereas capsular deformation is more likely a product of movement.

Update on new developments in the study of human teratogens.

BACKGROUND AND METHODS: The purpose of this annual article is to highlight and briefly review new and significant information on agents that may be teratogenic in pregnant women. Various sources of on-line and printed information are given. RESULTS: The following topics have been discussed: 1) lithium medication: decreased estimate of risk; 2) cigarette smoking and genotype as contributors to oral-facial clefts and clubfoot; 3) trimethoprim; 4) methimazole syndrome?; 5) glucocorticoids and oral-facial clefts; 6) binge drinking; 7) fetal valproate syndrome; and 8) carbamazepine. CONCLUSIONS: We have highlighted several maternal exposures during pregnancy that are associated with small but increased rates of birth defects, generally only a few cases per 1,000 infants. These exposures include cigarette smoking, and treatment with lithium, trimethoprim, methimazole, or corticosteroids. This weak teratogenic effect was usually identified by the linkage of an uncommon treatment with an unusual birth defect outcome. The use of modern epidemiologic techniques, especially prospective multicenter studies that provide increased numbers, has helped to strengthen the evidence for these associations. We discuss how teratogenic risks that are small in comparison to the background risk can be presented to at-risk women and their doctors. We have briefly listed some elements that might be used in prioritizing further studies of suspected teratogenic exposures. Various existing methods for expressing the strength of evidence for human teratogenicity are also given.

Effective coding in birth defects surveillance.

Effective coding is critical to data collected by birth defects surveillance programs because subsequent use of the data depends on storage and retrieval of cases using codes. Hence, careful consideration needs to be given to the coding process. The primary goal of coding is to accurately, completely, and concisely represent infants with birth defects. Coding procedures need to accommodate the objectives of the surveillance program; for example, programs that focus on research may require different coding procedures from those that focus on linking infants to services. Several challenges exist in coding birth defects, including the need to distinguish infants with multiple defects and syndromes from those with isolated defects, and the need for strategies to code suspected defects for which confirmation is not available. Selection of a coding system by a birth defects surveillance program is central to the utility of the data collected. Most programs use a modification of the International Statistical Classification of Diseases and Related Health Problems-based (ICD) systems. This paper addresses ICD-based systems and the modifications used by many birth defects surveillance programs and presents examples of the problems in interpreting birth defects data because of inappropriate coding.

Folic acid supplementation and risk for imperforate anus in China.

Maternal consumption of folic acid before pregnancy and during early pregnancy is associated with a reduced risk for some birth defects. Whether folic acid can reduce the risk for imperforate anus is unknown. As part of a public health campaign conducted in China from 1993 through 1995, the outcomes of pregnancies of > or =20 weeks' gestation were evaluated among women using folic acid supplements. The women were asked to take one pill containing 400 microg of folic acid (without other vitamins) every day from the time of their premarital examination until the end of their first trimester of pregnancy. Rates of imperforate anus and risk ratios for imperforate anus among the offspring of these women were calculated according to folic acid use. Among the offspring of women who took folic acid and women who did not take folic acid, 20 and 30 infants with imperforate anus were identified, respectively. The rate of imperforate anus was 3.1 per 10,000 among the offspring of women who did not take folic acid and 1.6 per 10,000 among the offspring of women who took folic acid; adjusted for maternal age, the risk ratio was 0.59 (95% confidence interval: 0.33, 1.07). Daily maternal consumption of 400 microg of folic acid before and during early pregnancy may reduce the risk for imperforate anus.

Mortality associated with congenital heart defects in the United States: trends and racial disparities, 1979-1997.

BACKGROUND: Surgical series and some population-based studies have documented a decrease in mortality from heart defects. Recent population-based data for the United States are lacking, however. We examined population-based data for patterns, time trends, and racial differences of mortality from heart defects for the United States from 1979 through 1997. METHODS AND RESULTS: We examined the multiple-cause mortality files compiled by the National Center for Health Statistics of the CDC from all death certificates filed in the United STATES: From these data, we derived death rates (deaths per 100 000 population) by the decedent's age, race, year of death, and heart defect type. We also analyzed age at death as an indirect indicator of survival. From 1979 through 1997, mortality from heart defects (all ages) declined 39%, from 2.5 to 1.5 per 100 000 population; among infants, the decline was 39%, or 2.7% per year. In 1995 to 1997, heart defects contributed to 5822 deaths per year. Of these deaths, 51% were among infants and 7% among children 1 to 4 years old. Mortality was on average 19% higher among blacks than among whites; this gap does not appear to be closing. Age at death increased for most heart defects, although less among blacks than among whites. CONCLUSIONS: Mortality from heart defects is declining in the United States, although it remains a major cause of death in infancy and childhood. Age at death is increasing, suggesting that more affected persons are living to adolescence and adulthood. The racial discrepancies should be investigated to identify opportunities for prevention.

Risk for birth defects among premature infants: a population-based study.

OBJECTIVE: To investigate the relationship between prematurity and birth defects. STUDY DESIGN: In a population-based cohort study, infants with birth defects were ascertained through the Metropolitan Atlanta Congenital Defects Program, a surveillance system with active methods of ascertainment. Gestational age data were obtained from birth certificates of liveborn, singleton infants with and without birth defects born in the 5-county metropolitan Atlanta area. RESULTS: Among 264,392 infants with known gestational ages born between 1989 and 1995, 7738 were identified as having birth defects (2.93%). Premature infants (<37 weeks' gestation) were more than two times as likely to have birth defects than term infants (37-41 weeks) (risk ratio = 2.43; 95% CI 2.30-2.56). This relationship was evident for several categories of birth defects. The rate of birth defects varied by gestational age categories, with the highest risk in the 29- to 32-week gestational age category (risk ratio = 3.37). CONCLUSIONS: The risk for birth defects is increased in premature infants. Awareness of this relationship is important for clinicians caring for premature infants. The morbidity and mortality associated with a particular defect may be significantly altered by the presence of prematurity. Further study of this association may provide insight into the etiology of these relatively common problems.

Energy cost of walking in low lumbar myelomeningocele.

The aim of this study was to determine whether it is more efficient for adolescents with low lumbar myelomeningocele (MM) to walk with a reciprocal or a swing-through gait pattern. Energy measurements for subjects with MM were compared for reciprocal and swing-through gait and also with an able-bodied control group. The rate of oxygen consumption (in milliliters per kilogram per minute) was higher for both the reciprocal and swing-through conditions compared with the control group, but there was no difference in the rate of consumption between the two modes of walking. Walking velocities (in meters per minute) were slower for both the reciprocal and swing-through conditions compared with the control group, with reciprocal walking significantly slower than swing-through gait. Oxygen cost (in milliliters per kilogram per meter) was higher for both the reciprocal and the swing-through conditions compared with the control group. Oxygen cost was higher for reciprocal walking than for swing-through gait. Swing-through gait proved to be the more efficient walking pattern in this group of subjects with MM.

Maternal multivitamin use and orofacial clefts in offspring.

BACKGROUND: Cleft lip with or without cleft palate (CLP) and cleft palate alone (CP) affect approximately 1 in 1000 infants and 1 in 2,500 infants, respectively. Studies of the relation between orofacial clefts and multivitamins or folic acid have been inconsistent. METHODS: We used data from a population-based case-control study involving 309 nonsyndromic cleft-affected births (222 with CLP, 87 with CP) and 3,029 control births from 1968 to 1980 to evaluate the relation between regular multivitamin use and the birth prevalence of orofacial clefts. RESULTS: We found a 48% risk reduction for CLP (odds ratio = 0.52, 95% confidence interval = 0.34-0.80) among mothers who used multivitamins during the periconceptional period or who started multivitamin use during the first postconceptional month, after controlling for several covariates. The risk reduction for CP was less than those for CLP (odds ratio = 0.81, 95% confidence interval = 0.44-1.52); however, a small number of CP cases limited interpretation. No risk reductions for CLP or CP were found for women who began multivitamin use in the second or third month after conception. CONCLUSIONS: The magnitude of the risk reduction in our study is comparable to those of other recent studies; our study does not support the contention that only large dosages of folic acid are needed to prevent orofacial clefts. More studies are needed to test the effects of multivitamins and varying dosages of folic acid on the recurrence and/or occurrence of orofacial clefts to provide information needed to determine possible prevention strategies. Published 2001 Wiley-Liss, Inc.

Relative kinematics of the rib cage and abdomen during speech and nonspeech behaviors of 15-month-old children.

Speech motor control emerges in the neurophysiologic context of widely distributed, powerful coordinative mechanisms, including those mediating respiratory function. It is unknown, however, whether developing children are able to exploit the capabilities of neural circuits controlling homeostasis for the production of speech and voice. Speech and rest breathing were investigated in eleven 15-month-old children using inductance plethysmography (Respitrace). Rib cage and abdominal kinematics were studied using a time-varying correlational index of thoracoabdominal coupling (i.e., reflecting the synchrony of movement of the rib cage and abdomen) as well as simple classification of the moment-to-moment kinematic relationship of these two functional components (i.e., concurrent expansion or compression, or oppositional movement). Results revealed markedly different patterns of movement for rest breathing and speech breathing, although within types of vocalization (nonspeech vocalization, babbling, true word production) no differences were apparent. Whereas rest breathing was characterized by tight coupling of rib cage and abdominal movement (average correlation coefficients usually exceeded .90), speech breathing exhibited weak coupling (the correlation coefficient ranged widely, but averaged about .60). Furthermore, speech production by these toddlers included the occurrence of both rib cage and abdominal paradoxing, which are observed infrequently in adult speakers. These results fail to support the suggestion that speech emerges from the extant coordinative organization of rest breathing. Rather, even in its earliest stages breathing for speech and voice exhibits kinematic properties distinct from those of other observed behaviors.