Impact of Fluoride on Associations between Free Sugars Intake and Dental Caries in US Children.

OBJECTIVE: Dental caries is the most prevalent chronic disease in US children, with the highest burden among Black and Hispanic youth. Sugars are a primary risk factor, but few studies have specifically measured intakes of free sugars and related this to dental caries or explored the extent to which water fluoride mitigates the cariogenicity of free sugars. Furthermore, the cariogenicity of certain free sugars sources, such as extruded fruit and vegetable products, is unclear. METHODS: Using cross-sectional data on 4,906 children aged 2 to 19 y in the US National Health and Nutrition Examination Survey 2013-2016, we examined associations of free sugars intake with counts of decayed or filled primary tooth surfaces (dfs) and decayed, missing, or filled permanent surfaces (DMFS) in negative binomial regressions. Stratified models examined these associations in children with home water fluoride above or below the Centers for Disease Control and Prevention (CDC)-recommended level of 0.7 ppm. RESULTS: Free sugars accounted for 16.4% of energy, primarily contributed by added sugars. In adjusted models, a doubling in the percentage of energy from free sugars was associated with 22% (95% confidence interval [CI], 1%-47%) greater dfs among children aged 2 to 8. A doubling in energy from added sugars was associated with 20% (95% CI, 1%-42%) greater dfs and 10% (95% CI, 2%-20%) greater DMFS in children aged 6 to 19 y. Beverages were the most important source of added sugars associated with increased caries. Other free sugars were not associated with dfs or DMFS. Associations between free sugars and caries were diminished among children with home water fluoride of 0.7 ppm or greater. CONCLUSIONS: Free sugars intake, especially in the form of added sugars and specifically in sweetened beverages, was associated with higher dental caries. Water fluoride exposures modify these associations, reducing caries risk in the primary dentition of children whose home water meets recommended fluoride levels. KNOWLEDGE TRANSFER STATEMENT: Intake of free sugars, especially in the form of added sugars and specifically in beverages, was associated with higher dental caries in US children in this study. Water fluoride exposure at CDC-recommended levels protected against caries, especially in the primary dentition. These findings suggest that household water fluoridation at CDC-recommended levels protects against the cariogenic potential of free and added sugars during childhood.

A Prospective Cohort Study of Bisphenol A Exposure from Dental Treatment.

Laboratory studies show that bisphenol A (BPA) leaches from bisphenol A-glycidyl methacrylate (bisGMA)-based dental materials. We aimed to quantify the extent to which children are exposed to BPA from dental treatment with bisGMA materials, by amount of treatment and type of sedation. We hypothesized that posttreatment urinary BPA (uBPA) concentrations would be higher among patients with more surfaces treated with bisGMA-based materials and among patients receiving general anesthesia compared with pretreatment concentrations. We conducted a prospective cohort study in 211 children, 4 to 12 y old, who had no prior resin-based dental treatment. We measured uBPA concentrations twice before treatment and at 2 d and 1, 4, and 16 wk posttreatment. We abstracted treatment data (surfaces treated) from the chart. We generated descriptive statistics and compared pre- and posttreatment uBPA concentrations using generalized estimating equations. Participants were 51% female, 46% non-White, and 74% publicly insured. The median age was 6 y. The mean number of tooth surfaces exposed to BisGMA materials (composites/sealants) was 7.5 (SD 5.3). Overall, uBPA concentrations were 86% higher (95% confidence interval [CI] 42% to 143%, P < 0.001) at 2 d posttreatment compared with pretreatment concentrations. The uBPA concentrations 2 d posttreatment versus pretreatment tended to be higher (112%, 95% CI 53% to 194%) among those receiving treatment on >4 surfaces than those receiving treatment on ≤4 surfaces (50%, 95% CI -2% to 130%). Two days after treatment, uBPA was significantly higher than pretreatment concentrations in children receiving nitrous oxide but not in those receiving general anesthesia. Among all findings, uBPA concentrations returned to baseline by 4 wk. Children experience short-term increases in BPA from dental treatment. The impact of relatively high, short-term BPA exposure on child health is unknown. Given the widespread use of BisGMA-based dental materials and that chronic low-dose BPA exposure may adversely affect child health, strategies that minimize BPA exposure could potentially improve child health.

A Systematic Review of Exposure to Bisphenol A from Dental Treatment.

INTRODUCTION: Dental composite restorations and dental sealants containing bisphenol A glycidyl methacrylate (BisGMA) are commonly used materials in dentistry. Bisphenol A (BPA) is used to manufacture BisGMA and can be a by-product in BisGMA-based dental materials. BPA is an endocrine-disrupting chemical that may affect reproductive, psychological, cognitive, and endocrine-related health. We conducted a systematic review of clinical studies that measured urinary BPA (uBPA) concentrations before and after dental treatment to evaluate the extent to which individuals are exposed to BPA from dental treatment. METHODS: Eligibility included studies that measured uBPA concentrations before and after dental treatment with any type of resin-based dental material. We searched PubMed, Cochrane, Web of Science, Virtual Health Library, Science Direct, ProQuest, and Clinical Trials with no date or language restrictions to identify published studies. We summarized eligible studies across participant characteristics, amount of treatment, and time of follow-up measures. Because methods of measuring uBPA varied, our primary outcome was the direction and percentage change between baseline and 24 h posttreatment and at later time points as available. RESULTS: We identified 1,190 abstracts and 7 eligible studies: 4 in children and 3 in adults. In all studies, BPA concentrations increased 24 h after treatment. The 2 studies with the largest sample sizes found statistically significant increases >40% in uBPA concentrations at 24 h posttreatment (both P values <0.01). The 1 study to examine uBPA concentrations beyond 1 mo posttreatment found that concentrations returned to baseline by 14 d after treatment and remained at baseline 6 mo after treatment. CONCLUSIONS: Our findings suggest that uBPA concentrations increase 24 h after dental treatment. One study showed that uBPA concentrations return to baseline by 14 d. Additional research is needed to determine the magnitude of change from pre- to post-dental treatment and the trajectory of uBPA concentrations posttreatment. KNOWLEDGE TRANSFER STATEMENT: BPA is an endocrine-disrupting chemical that may have negative human health effects. Our findings suggest that urinary BPA concentrations increase in the short term after dental treatment. The extent to which such an increase may affect the health of patients remains an open question, particularly since there are no established thresholds for safety or harm related to BPA exposure.

Androgenic and estrogenic indices in human newborns and infants: the MIREC-ID study.

Prenatal sex steroid exposure plays an important role in determining child development. Yet, measurement of prenatal hormonal exposure has been limited by the paucity of newborn/infant data and the invasiveness of fetal hormonal sampling. Here we provide descriptive data from the MIREC-ID study (n=173 girls; 162 boys) on a range of minimally invasive physical indices thought to reflect prenatal exposure to androgens [anogenital distances (AGDs); penile length/width, scrotal/vulvar pigmentation], to estrogens [vaginal maturation index (VMI) - the degree of maturation of vaginal wall cells] or to both androgens/estrogens [2nd-to-4th digit ratio (2D:4D); areolar pigmentation, triceps/sub-scapular skinfold thickness, arm circumference]. VMI was found to be associated with triceps skinfold thickness (ß=0.265, P=0.005), suggesting that this marker may be sensitive to estrogen levels produced by adipose tissue in girls. Both estrogenic and androgenic markers (VMI: ß=0.338, P=0.031; 2D:4D - right: ß=-0.207, P=0.040; left: ß=-0.276, P=0.006; AGD-fourchette - ß=0.253, P=0.036) were associated with areolar pigmentation in girls, supporting a role for the latter as an index of both androgen and estrogen exposure. We also found AGD-penis (distance from the anus to the penis) to be associated with scrotal pigmentation (ß=0.290, P=0.048), as well as right arm circumference (ß=0.462, P<0.0001), supporting the notion that these indices may be used together as markers of androgen exposure in boys. In sum, these findings support the use of several physical indices at birth to convey a more comprehensive picture of prenatal exposure to sex hormones.

First and second trimester urinary metabolic profiles and fetal growth restriction: an exploratory nested case-control study within the infant development and environment study.

BACKGROUND: Routine prenatal care fails to identify a large proportion of women at risk of fetal growth restriction (FGR). Metabolomics, the comprehensive analysis of low molecular weight molecules (metabolites) in biological samples, can provide new and earlier biomarkers of prenatal health. Recent research has suggested possible predictive first trimester urine metabolites correlating to fetal growth restriction in the third trimester. Our objective in this current study was to examine urinary metabolic profiles in the first and second trimester of pregnancy in relation to third trimester FGR in a US population from a large, multi-center cohort study of healthy pregnant women. METHODS: We conducted a nested case-control study within The Infant Development and the Environment Study (TIDES), a population-based multi-center pregnancy cohort study. We identified 53 cases of FGR based on the AUDIPOG [Neonatal growth - AUDIPOG [Internet]. [cited 29 Nov 2016]. Available from: http://www.audipog.net/courbes_morpho.php?langue=en ] formula for birthweight percentile considering maternal height, age, and prenatal weight, as well as infant sex, gestational age, and birth rank. Cases were matched to 106 controls based on study site, maternal age (± 2 years), parity, and infant sex. NMR spectroscopy was used to assess concentrations of four urinary metabolites that have been previously associated with FGR (tyrosine, acetate, formate, and trimethylamine) in first and second trimester urine samples. We fit multivariate conditional logistic regression models to estimate the odds of FGR in relation to urinary concentrations of these individual metabolites in the first and second trimesters. Exploratory analyses of custom binned spectroscopy results were run to consider other potentially related metabolites. RESULTS: We found no significant association between the relative concentrations of each of the four metabolites and odds of FGR. Exploratory analyses did not reveal any significant differences in urinary metabolic profiles. Compared with controls, cases delivered earlier (38.6 vs 39.8, p < 0.001), and had lower birthweights (2527 g vs 3471 g, p < 0.001). Maternal BMI was similar between cases and controls. CONCLUSIONS: First and second trimester concentrations of urinary metabolites (acetate, formate, trimethylamine and tyrosine) did not predict FGR. This inconsistency with previous studies highlights the need for more rigorous investigation and data collection in this area before metabolomics can be clinically applied to obstetrics.

Anogenital distance in newborn daughters of women with polycystic ovary syndrome indicates fetal testosterone exposure.

Polycystic ovary syndrome (PCOS) affects ~7% of reproductive age women. Although its etiology is unknown, in animals, excess prenatal testosterone (T) exposure induces PCOS-like phenotypes. While measuring fetal T in humans is infeasible, demonstrating in utero androgen exposure using a reliable newborn biomarker, anogenital distance (AGD), would provide evidence for a fetal origin of PCOS and potentially identify girls at risk. Using data from a pregnancy cohort (The Infant Development and Environment Study), we tested the novel hypothesis that infant girls born to women with PCOS have longer AGD, suggesting higher fetal T exposure, than girls born to women without PCOS. During pregnancy, women reported whether they ever had a PCOS diagnosis. After birth, infant girls underwent two AGD measurements: anofourchette distance (AGD-AF) and anoclitoral distance (AGD-AC). We fit adjusted linear regression models to examine the association between maternal PCOS and girls' AGD. In total, 300 mother-daughter dyads had complete data and 23 mothers reported PCOS. AGD was longer in the daughters of women with a PCOS diagnosis compared with daughters of women with no diagnosis (AGD-AF: ß=1.21, P=0.05; AGD-AC: ß=1.05, P=0.18). Results were stronger in analyses limited to term births (AGD-AF: ß=1.65, P=0.02; AGD-AC: ß=1.43, P=0.09). Our study is the first to examine AGD in offspring of women with PCOS. Our results are consistent with findings that women with PCOS have longer AGD and suggest that during PCOS pregnancies, daughters may experience elevated T exposure. Identifying the underlying causes of PCOS may facilitate early identification and intervention for those at risk.

Demographic and dietary risk factors in relation to urinary metabolites of organophosphate flame retardants in toddlers.

Organophosphate flame retardants (OPFRs), including Tris (1,3-dichloro-isopropyl) phosphate (TDCPP), triphenyl phosphate (TPP), and isopropylated triphenyl phosphate (ITP), are increasingly used in consumer products because of the recent phase out of polybrominated diphenyl ether (PBDE) flame retardants. OPFRs have been widely detected in adults and have been linked to reproductive and endocrine changes in adult males. Carcinogenicity and damage to immunologic, neurologic and developmental systems have been observed in human cell lines. Young children are especially vulnerable to OPFR exposure, but little is known about exposure levels or exposure risk factors in this population. We examined parent-reported demographic and dietary survey data in relation to OPFR urinary metabolite concentrations in 15- to 18-month old toddlers (n = 41). OPFR metabolites were detected in 100% of subjects. The metabolite of TPP, diphenyl phosphate (DPP) was detected most commonly (100%), with TDCPP metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCPP), detected in 85-95% of samples, and ITP metabolite, monoisopropylphenyl phenyl phosphate (ip-DPP), detected in 81% of samples (n = 21). Toddlers of mothers earning <$10,000 annually had geometric mean DPP concentrations 66% higher (p = 0.05) than toddlers of mothers earning >$10,000/year (7.8 ng/mL, 95% CI 5.03, 12.11 and 4.69 ng/mL, 95% CI 3.65-6.04, respectively). While no dietary factors were significantly associated with OPFR metabolite concentrations, results suggested meat and fish consumption may be associated with higher DPP and BDCPP levels while increased dairy and fresh food consumption may be associated with lower DPP, BDCPP, and ip-DPP levels. Research with larger sample sizes and more detailed dietary data is required to confirm these preliminary findings.

SKP2 loss destabilizes EZH2 by promoting TRAF6-mediated ubiquitination to suppress prostate cancer.

EZH2 is crucial for the progression of prostate cancer (PCa) and castration-resistant prostate cancer (CRPC) through upregulation and activation of progenitor genes, as well as androgen receptor (AR)-target genes. However, the mechanisms by which EZH2 is regulated in PCa and CRPC remain elusive. Here we report that EZH2 is post-transcriptionally regulated by SKP2 in vitro in cultured cells and in vivo in mouse models. We observed aberrant upregulation of Skp2, Ezh2 and histone H3 lysine 27 trimethylation (H3K27me3) in both Pten null mouse embryonic fibroblasts (MEFs) and Pten null mouse prostate tissues. Loss of Skp2 resulted in a striking decrease of Ezh2 levels in Pten/Trp53 double-null MEFs and in prostate tumors of Pten/Trp53 double-null mutant mice. SKP2 knockdown decreased EZH2 levels in human PCa cells through upregulation of TRAF6-mediated and lysine(K) 63-linked ubiquitination of EZH2 for degradation. Ectopic expression of TRAF6 promoted the K63-linked ubiquitination of EZH2 to decrease EZH2 and H3K27me3 levels in PCa cells. In contrast, TRAF6 knockdown resulted in a reduced EZH2 ubiquitination with an increase of EZH2 and H3K27me3 levels in PCa cells. Furthermore, the catalytically dead mutant TRAF6 C70A abolished the TRAF6-mediated polyubiquitination of recombinant human EZH2 in vitro. Most importantly, a concurrent elevation of Skp2 and Ezh2 was found in CRPC tumors of Pten/Trp53 mutant mice, and expression levels of SKP2 and EZH2 were positively correlated in human PCa specimens. Taken together, our findings revealed a novel mechanism on EZH2 ubiquitination and an important signaling network of SKP2-TRAF6-EZH2/H3K27me3, and targeting SKP2-EZH2 pathway may be a promising therapeutic strategy for CRPC treatment.

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.

Timing of prenatal phthalate exposure in relation to genital endpoints in male newborns.

Prior studies report that penile size and male anogenital distance (AGD), sensitive markers of androgen action in utero, may be shortened by prenatal exposure to certain phthalates, including diethylhexyl phthalate (DEHP), but no human study has investigated the importance of exposure timing in these associations. The aim of this study was to examine the significance of exposure timing on the action of prenatal phthalates in particular DEHP, on male infant penile size and AGD. In The Infant Development and the Environment Study (TIDES) we measured penile width (PW) as well as anoscrotal distance (AGDAS ) and anopenile distance (AGPAP ) in newborn males. We modeled these endpoints in relation to phthalate metabolite concentrations in maternal urine samples collected in each trimester (T1, T2, and T3) in a subset of TIDES mothers (N = 168). PW was inversely associated with T2 oxidized DEHP metabolites, mono-2-ethyl-5-oxohexyl (MEOHP, ß=-0.48; 95% confidence interval, -0.93, -0.02), MEHHP (-0.48; -0.92, -0.05), mono-2-ethyl-5-carboxypentyl (MECPP, -0.51; -1.01, -0.004), although no appreciable associations were seen between PW and T1 and T3 DEHP metabolite concentrations in this subset. Concentrations of DEHP metabolites in T1 urine samples were inversely related to male AGD. For example, in T1 samples in this subset of women mono-2-ethyl-5-hydroxyhexyl (MEHHP) was inversely associated with male AGDAP (ß = -1.73; 95% confidence interval, -3.45, 0.0004). However, no appreciable associations were seen between AGD measures and any DEHP metabolite in T2 and T3 samples. These data suggest that DEHP exposure is inversely associated with AGD and PW, with PW primarily associated with T2 exposure and AGD associations seen only for T1 exposure, but no associations were found between T3 DEHP metabolites and any of these genital endpoints. These findings are consistent with data on critical windows in rodent studies, supporting the biological plausibility of these associations in humans.

Burden of disease and costs of exposure to endocrine disrupting chemicals in the European Union: an updated analysis.

A previous report documented that endocrine disrupting chemicals contribute substantially to certain forms of disease and disability. In the present analysis, our main objective was to update a range of health and economic costs that can be reasonably attributed to endocrine disrupting chemical exposures in the European Union, leveraging new burden and disease cost estimates of female reproductive conditions from accompanying report. Expert panels evaluated the epidemiologic evidence, using adapted criteria from the WHO Grading of Recommendations Assessment, Development and Evaluation Working Group, and evaluated laboratory and animal evidence of endocrine disruption using definitions recently promulgated by the Danish Environmental Protection Agency. The Delphi method was used to make decisions on the strength of the data. Expert panels consensus was achieved for probable (>20%) endocrine disrupting chemical causation for IQ loss and associated intellectual disability; autism; attention deficit hyperactivity disorder; endometriosis; fibroids; childhood obesity; adult obesity; adult diabetes; cryptorchidism; male infertility, and mortality associated with reduced testosterone. Accounting for probability of causation, and using the midpoint of each range for probability of causation, Monte Carlo simulations produced a median annual cost of €163 billion (1.28% of EU Gross Domestic Product) across 1000 simulations. We conclude that endocrine disrupting chemical exposures in the EU are likely to contribute substantially to disease and dysfunction across the life course with costs in the hundreds of billions of Euros per year. These estimates represent only those endocrine disrupting chemicals with the highest probability of causation; a broader analysis would have produced greater estimates of burden of disease and costs.

First trimester phthalate exposure and anogenital distance in newborns.

STUDY QUESTION: Is first trimester phthalate exposure associated with anogenital distance (AGD), a biomarker of prenatal androgen exposure, in newborns? SUMMARY ANSWER: Concentrations of diethylhexyl phthalate (DEHP) metabolites in first trimester maternal urine samples are inversely associated with AGD in male, but not female, newborns. WHAT IS KNOWN ALREADY: AGD is a sexually dimorphic measure reflecting prenatal androgen exposure. Prenatal phthalate exposure has been associated with shorter male AGD in multiple animal studies. Prior human studies, which have been limited by small sample size and imprecise timing of exposure and/or outcome, have reported conflicting results. STUDY DESIGN, SIZE, DURATION: The Infant Development and the Environment Study (TIDES) is a prospective cohort study of pregnant women recruited in prenatal clinics in San Francisco, CA, Minneapolis, MN, Rochester, NY and Seattle, WA in 2010-2012. Participants delivered 787 infants; 753 with complete data are included in this analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Any woman over 18 years old who was able to read and write English (or Spanish in CA), who was <13 weeks pregnant, whose pregnancy was not medically threatened and who planned to deliver in a study hospital was eligible to participate. Analyses include all infants whose mothers provided a first trimester urine sample and who were examined at or shortly after birth. Specific gravity (SpG) adjusted concentrations of phthalate metabolites in first trimester urine samples were examined in relation to genital measurements. In boys (N = 366), we obtained two measures of anogenital distance (AGD) (anoscrotal distance, or AGDAS and anopenile distance, AGDAP) as well as penile width (PW). In girls (N = 373), we measured anofourchette distance (AGDAF) and anoclitoral distance (AGDAC). We used multivariable regression models that adjusted for the infant's age at exam, gestational age, weight-for-length Z-score, time of day of urine collection, maternal age and study center. MAIN RESULTS AND THE ROLE OF CHANCE: Three metabolites of DEHP were significantly and inversely associated with both measures of boys' AGD. Associations (ß, 95% confidence interval (CI)) between AGDAS and (log10) SpG-adjusted phthalate concentrations were: -1.12 (-2.16, -0.07) for mono-2-ethylhexyl phthalate (MEHP), -1.43, (-2.49, -0.38) for mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and -1.28 (-2.29, -0.27) for mono-2-ethyl-5-hydroxyhexyl (MEHHP). Associations were of similar magnitude for AGDAP. Associations were weaker and not statistically significant for PW. No other phthalate metabolites were associated with any genital measurement in boys. No phthalate metabolites were associated with either AGD measure in girls. LIMITATIONS, REASONS FOR CAUTION: Exposure assessment was based on a single first trimester urine sample, which may have introduced exposure misclassification. In addition, significant between-center differences suggest that this measurement is difficult to standardize. WIDER IMPLICATIONS OF THE FINDINGS: Our findings are consistent with multiple rodent studies and most human studies which were far smaller. The data we report here suggest that even at current low levels, environmental exposure to DEHP can adversely affect male genital development resulting in reproductive tract changes that may impact reproductive health later in life. These findings have important implications for public policy since most pregnant women are exposed to this ubiquitous chemical. STUDY FUNDING/COMPETING INTERESTS: Funding for TIDES was provided by the following grants from the National Institute of Environmental Health Sciences: R01ES016863-04 and R01 ES016863-02S4. The authors report no conflict of interest.

Latent factor regression models for grouped outcomes.

We consider regression models for multiple correlated outcomes, where the outcomes are nested in domains. We show that random effect models for this nested situation fit into a standard factor model framework, which leads us to view the modeling options as a spectrum between parsimonious random effect multiple outcomes models and more general continuous latent factor models. We introduce a set of identifiable models along this spectrum that extend an existing random effect model for multiple outcomes nested in domains. We characterize the tradeoffs between parsimony and flexibility in this set of models, applying them to both simulated data and data relating sexually dimorphic traits in male infants to explanatory variables.

Laparoscopic vertical sleeve gastrectomy after open gastric banding in a patient with situs inversus totalis.

While several equivalent alternatives are available in the bariatric algorithm, more recently the laparoscopic sleeve gastrectomy (SG) has been gaining traction as an effective means of weight loss in patients with morbid obesity. We present the case of a 39-year-old woman with situs inversus totalis, who was taken to the operating room for laparoscopic SG. The patient had previously undergone a failed open gastric banding procedure 20 months earlier. Awareness of the inherited condition before performing the operation allows for advanced planning and preparation. Subsequent modifications to the standard trocar placement help make the procedure more technically feasible. To our knowledge, this is the first published report of a laparoscopic SG after open gastric banding in a patient with situs inversus totalis. After encountering the initial disorientation, we believe experienced laparoscopic surgeons can perform this procedure successfully and safely.

Measurement and correlates of ano-genital distance in healthy, newborn infants.

Ano-genital distance (AGD) is a sexually dimorphic trait that is a well established reproductive toxicity endpoint in animals. In male animals, a shortened AGD is associated with a variety of genital abnormalities including hypospadias and cryptorchidism. Consensus on the anatomical definition of AGD in humans remains to be established and few data exist on the determinants and normal variance in the general population. We implemented a standardized anthropometric protocol to measure AGD, ano-scrotal distance (ASD), and ano-fourchette distance (AFD) in 169 (82 male, 87 female) infants in the University of Washington newborn nursery in 2008. We collected data on the following characteristics: weight, length, and occipital head circumference, race and relevant gestational complications. Using linear regression modelling, we examined AGD/ASD/AFD for sexual dimorphism, normal population variance and predictors of the measurement in infants. The mean male and female AGD measurements were 52.0 mm (SD +/- 5.5) and 37.2 mm (SD +/- 3.7). The mean ASD and AFD were 23.0 mm (SD +/- 3.8) and 15.1 mm (SD +/- 2.9). Weight, length, occipital head circumference and gestational age were associated with AGD (p < 0.05). Weight and length were the most important correlates to AGD. We confirmed previous findings that AGD is a sexually dimorphic measurement that is most strongly predicted by infant weight. The application of this measurement to clinically relevant outcomes remains to be explored in further depth.

Exploiting inherent parallelisms for accelerating linear Hough transform.

Accelerating Hough transform in hardware has been of interest due its popularity in real-time capable image processing applications. In most existing linear Hough transform architectures, an m xm edge map is serially read for processing, resulting in a total computation time of at least m(2) cycles. In this paper, we propose a novel parallel Hough transform computation method called the Additive Hough transform (AHT), wherein the image is divided using a k x k grid to reduce the total computation time by a factor of k(2). We have also proposed an efficient implementation of the AHT consisting of a look-up table (LUT) and two-operand adder arrays for every angle. Techniques to condense the LUT size have also been proposed to further reduce area utilization by as much as 50%. Our investigations based on employing an 8 x 8 grid shows a 1000 x speedup compared to existing architectures for a range of image sizes. Area-time trade-off analysis has been presented to demonstrate that the area-time product of the proposed AHT-based implementation is at least 43% lower than other implementations reported in the literature. We have also included and characterized a hierarchical addition step in order to generate a global accumulation space equivalent to that of the conventional HT. It is shown that the proposed implementation with the hierarchical addition step remains superior to other methods in terms of both performance and area-time product metrics. Finally, we show that the proposed solution is equally efficient when applied on rectangular images.

Maternal and infant urinary phthalate metabolite concentrations: are they related?

BACKGROUND: Phthalates are synthetic chemicals that are ubiquitous in our society and may have adverse health effects in humans. Detectable concentrations of phthalate metabolites have been found in adults and children, but no studies have examined the relationship between maternal and infant phthalate metabolite concentrations. OBJECTIVE: We investigated the relationship between maternal and infant urinary phthalate metabolite concentrations. METHODS: We measured nine phthalate metabolites in urine samples from 210 mother/infant pairs collected on the same study visit day (1999-2005) and obtained demographic history from questionnaires. Using multivariate linear regression analyses, we examined the degree to which maternal urine phthalate metabolite concentration predicted infant phthalate metabolite concentration. All analyses were adjusted for infant age, creatinine concentration, and race. RESULTS: Correlation coefficients between phthalate metabolite concentrations in the urine of mothers and their infants were generally low but increased with decreasing age of infant. In multivariate analyses, mother's phthalate metabolite concentrations were significantly associated with infants' concentrations for six phthalate metabolites: monobenzyl phthalate, monoethyl phthalate, monoisobutyl phthalate, and three metabolites of di(2-ethylhexyl) phthalate: mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-hydroxy-hexyl) phthalate, and mono(2-ethyl-5-oxo-hexyl) phthalate (p-values for all coefficients <0.05). DISCUSSION: Mother's urine phthalate metabolite concentration is significantly associated with infant urine phthalate metabolite concentration for six phthalate metabolites. It is plausible that shared exposures to phthalates in the immediate surrounding environment accounted for these relationships, but other unidentified sources may also contribute to infants' phthalate exposures. This study indicates the importance of further identifying infant phthalate exposures that may be distinct from maternal exposures in order to decrease overall infant phthalate exposures.

Spontaneous bowel perforation after ventriculoperitoneal shunt surgery: case report and a review of 45 cases.

BACKGROUND: Ventriculoperitoneal shunt surgery is the most widely used procedure in the treatment of hydrocephalus. However, this invasive procedure has been associated with several delayed abdominal complications. Perforation of the bowel is a very rare complication occurring in less than 0.1% of cases. Although infrequent, this delayed complication can be fatal if it goes unrecognized. CASE DESCRIPTION: This report presents an adult patient who had undergone ventriculoperitoneal shunt surgery and later presented with rectal protrusion of the shunt tube after asymptomatic perforation of the bowel wall. The shunt was removed without complication and the patient remained asymptomatic. CONCLUSIONS: Forty-five similar cases have been reported in the literature. The information provided within this report examines the case at hand, as well as provides an analysis of the literature as it relates to bowel perforation through symptomatic presentation, diagnosis, cultures, management with or without laparotomy, and outcome.

A general method for the synthesis of 3'-sulfhydryl and phosphate group containing oligonucleotides.

The syntheses are described of polymer supports useful for the synthesis of 3'-partially protected sulfhydryl, free sulfhydryl or phosphate group containing oligonucleotides. The supports are compatible with established phosphoramidite chemistry of oligonucleotide synthesis giving rise to oligonucleotides with terminal 3'-partially protected sulfhydryl, free sulfhydryl or phosphate function during final deprotection. Crosslinking of the thiol group containing oligonucleotide to sulfhydryl group specific fluorescent probes was carried out with high selectivity, in high yields under mild conditions. 3-Aminopropylated Controlled Pore Glass (CPG) was succinylated with succinic anhydride followed by the reaction with S-(2-thio-5-nitropyridyl)-2-mercaptoethanol in the presence of dicyclohexylcarbodiimide (DCC). The resultant polymer support was reacted with 4,4'-dimethoxytrityloxyalkanthiol 5(a - c) to yield the derivatized polymer supports 5(a - c). The support 5a directly leads to oligonucleotide-3'-phosphate on deprotection with ammonical DTT at 55 degrees C while the supports 5b and 5c lead to oligonucleotide-3'-thiols or partially protected 3'-sulfhydryl group containing oligonucleotides during final deprotection.

A spectrophotometric method for the estimation of polymer-supported sulfhydryl groups.

A sensitive and simple method is described for the quantitative determination of free sulfhydryl (-SH) groups on polymer supports. The method includes the reaction of 4,4'-dimethoxytrityloxy-S-(2-thio-5-nitropyridyl)-2-mercapto ethane (DTNPME) with polymer-supported sulfhydryl groups. After removal of excess reagent through washing, a weighed quantity of the polymer support is treated with perchloric acid to release the 4,4'-dimethoxytrityl cation from the polymer support into the solution. The dimethoxytrityl cation (lambda max = 498 nm, epsilon 498 = 70,000/M) is then quantified spectrophotometrically. A comparative study of the reagent DTNPME with 2,2'-dithiobis(5-nitropyridine) is also described.