Expression of VE-cadherin in zebrafish embryos: a new tool to evaluate vascular development.

We have identified the zebrafish homologue of VE-cadherin and documented its expression in the developing vascular system. The zebrafish VE-cadherin gene is specifically expressed in the vascular endothelial cell lineage beginning with the differentiation and migration of angioblasts and persists throughout vasculogenesis, angiogenesis, and endocardium development. Staining zebrafish embryos by whole-mount in situ hybridization with the VE-cadherin probe provides a method to screen embryos for vascular defects. To illustrate this utility, we used VE-cadherin expression to demonstrate a conservation of vascular endothelial growth factor-A (VEGF-A) function. The morpholino antisense oligonucleotide knockdown of VEGF-A function in zebrafish embryos results in a loss of angiogenic blood vessels, as indicated by the lack of VE-cadherin expression in the intersegmental vasculature. This loss can be restored in embryos supplemented with either zebrafish or human VEGF-A, the latter indicating that genes crucial to angiogenesis have highly conserved functional activities in vertebrates.     

Collagen 1Alpha1 and transforming growth factor-beta polymorphisms in women with cervical insufficiency

OBJECTIVE: To estimate whether polymorphisms in the collagen 1Alpha1 gene (COL1Alpha1) and the transforming growth factor-beta gene (TGF-beta;1) are more common in women with cervical insufficiency than in those without the condition. METHODS: Medical, obstetric, and family histories and blood were obtained from women with (n=121) and those without (n=165) cervical insufficiency. DNA was extracted and purified by using commercial DNA isolation kits. Samples were analyzed for variants in two genes, the COL1A1 intron 1SP1 and TGF-beta Arg-25-Pro polymorphism, by using an allele-specific polymerase chain reaction assay. RESULTS: Thirty-four of 125 (27.2%) women with cervical insufficiency had at least one first-degree female relative affected. The frequency of the homozygous TT genotype in the COL1A1 gene was increased in women with a history of cervical insufficiency compared with controls (10.8% compared with 3.1%, P=.04). The TGF-beta polymorphisms (ArgPro and ProPro) also were increased in cases (38.3% compared with 14.6%, P<.001). CONCLUSION: Over one fourth of women with cervical insufficiency have a family history of cervical insufficiency, and the COL1A1 intron 1SP1 and TGF-beta Arg-25-Pro polymorphisms are associated with the condition. These observations suggest that, in part, cervical insufficiency is mediated by genetic factors. LEVEL OF EVIDENCE: II.     

Variation in Urinary Flow Rates According to Demographic Characteristics and Body Mass Index in NHANES: Potential Confounding of Associations between Health Outcomes and Urinary Biomarker Concentrations

Background:

Urinary analyte concentrations are affected both by exposure level and by urinary flow rate (UFR). Systematic variations in UFR with demographic characteristics or body mass index (BMI) could confound assessment of associations between health outcomes and biomarker concentrations.

Objectives:

We assessed patterns of UFR (milliliters per hour) and body weight–adjusted UFR (UFRBW; milliliters per kilogram per hour) across age, sex, race/ethnicity, and BMI category in the NHANES (National Health and Nutrition Examination Survey) 2009–2012 data sets.

Methods:

Geometric mean (GM) UFR and UFRBW were compared across age-stratified (6–11, 12–19, 20–39, 40–59, and ≥ 60 years) subgroups (sex, race/ethnicity, and BMI category). Patterns of analyte urinary concentration or mass excretion rates (nanograms per hour and nanograms per kilogram per hour BW) were assessed in sample age groups for case study chemicals bisphenol A and 2,5-dichlorophenol.

Results:

UFR increased from ages 6 to 60 years and then declined with increasing age. UFRBW varied inversely with age. UFR, but not UFRBW, differed significantly by sex (males > females after age 12 years). Differences in both metrics were observed among categories of race/ethnicity. UFRBW, but not UFR, varied inversely with BMI category and waist circumference in all age groups. Urinary osmolality increased with increasing BMI. Case studies demonstrated different exposure–outcome relationships depending on exposure metric. Conventional hydration status adjustments did not fully address the effect of flow rate variations.

Conclusions:

UFR and UFRBW exhibit systematic variations with age, sex, race/ethnicity, and BMI category. These variations can confound assessments of potential exposure–health outcome associations based on urinary concentration. Analyte excretion rates are valuable exposure metrics in such assessments.

Citation:

Hays SM, Aylward LL, Blount BC. 2015. Variation in urinary flow rates according to demographic characteristics and body mass index in NHANES: potential confounding of associations between health outcomes and urinary biomarker concentrations. Environ Health Perspect 123:293–300; http://dx.doi.org/10.1289/ehp.1408944     

The major cockroach allergen Bla g 4 binds tyramine and octopamine

Bla g 4 is a male cockroach specific protein and is one of the major allergens produced by Blattella germanica (German cockroach). This protein belongs to the lipocalin family that comprises a set of proteins that characteristically bind small hydrophobic molecules and play a role in a number of processes such as: retinoid and pheromone transport, prostaglandin synthesis and mammalian immune response. Using NMR and isothermal titration calorimetry we demonstrated that Bla g 4 binds tyramine and octopamine in solution. In addition, crystal structure analysis of the complex revealed details of tyramine binding. As tyramine and octopamine play important roles in invertebrates, and are counterparts to vertebrate adrenergic transmitters, we speculate that these molecules are physiological ligands for Bla g 4. The nature of binding these ligands to Bla g 4 sheds light on the possible biological function of the protein. In addition, we performed a large-scale analysis of Bla g 4 and Per a 4 (an allergen from American cockroach) homologs to get insights into the function of these proteins. This analysis together with a structural comparison of Blag 4 and Per a 4 suggests that these proteins may play different roles and most likely bind different ligands.     

Complications with Outpatient Angiography and Interventional Procedures

Purpose: To prospectively identify the complications, and rates of complication, in outpatient angiography and interventional procedures. Methods: There were 1050 consecutive patients, 646 men and 404 women, aged 17–89 years, with a total of 1239 procedures studied in a 2-year period, 1997 to 1999. Results: There were 560 cases of aorto-femoral angiography, resulting in 124 complications (22%), with pain or hematoma in 110. There were 206 cases of neck and cerebral angiography, resulting in 51 complications (25%), with pain and hematoma in 34, transient ischemic attack in 2 and cerebrovascular accident in 1. There were 197 interventional procedures, with 177 being balloon dilatations, resulting in 68 complications (35%), with 2 having hematomas and 1 having hematoma/abscess requiring active treatment. There were 276 cases having various "other" procedures (e.g., renal angiography), resulting in 65 complications (24%), with pain and hematoma in 61. No procedure-related death occurred. Eighteen cases (1.5%) had significant complications, with contrast allergy in eight. Conclusion: Outpatient angiography and intervention are relatively safe, with low significant complication rates.     

CSHCN in Texas: Meeting the Need for Specialist Care

Objective: Assuring the sufficiency and suitability of systems of care and services for children with special health care needs (CSHCN) presents a challenge to Texas providers, agencies, and state Title V programs. To meet the need for specialist care, referrals from primary care doctors are often necessary. The objective of this study was to describe the factors associated with the need for specialist care and problems associated with obtaining referrals in Texas. Methods: Bivariate and multivariate analyses were performed using the National Survey of Children with Special Health Care Needs (NS-CSHCN) weighted sample for Texas (n = 719,014) to identify variables associated with the need for specialist care and problems obtaining referrals for specialist care. Results: Medical need of the CSHCN and sensitivity to family values/customs was associated with greater need for specialist care, and Hispanic ethnicity and lower maternal education were associated with less need. Medical need, amount of time spent with doctors and sensitivity to values/customs, living in a large metropolitan statistical area, and lack of medical information were associated with problems obtaining a specialist care referral. Conclusions: Findings revealed some similarities and differences with meeting the need for specialist care when comparing Texas results to other studies. In Texas, aspects of customer satisfaction variables, especially doctors’ sensitivity to family values/customs and parents’ not receiving enough information on medical problems, were significantly associated with problems obtaining specialist referrals. Findings indicate a need to further research relationships and communication among doctors, CSHCN, and their families.     

Maternal morbidity and perinatal outcomes among pregnant women with respiratory hospitalizations during influenza season

OBJECTIVES: A population-based assessment of maternal and perinatal morbidity related to respiratory illness during influenza season among pregnant women has not been published. The objectives of this investigation were to describe and quantify the impact of respiratory hospitalization during pregnancy on serious maternal and perinatal morbidity. STUDY DESIGN: A matched cohort study using an administrative database of pregnant women enrolled in the Tennessee Medicaid population to determine pregnancy outcomes associated with respiratory hospitalizations during influenza season. Pregnant women aged 15 to 44 years with a respiratory hospitalization during influenza seasons 1985-1993 were matched by gestational age and presence of comorbidity with pregnant control subjects without a respiratory hospitalization. RESULTS: During the eight influenza seasons studied, 293 women with singleton pregnancies had respiratory disease hospitalizations (5.1:1000). Women with asthma had high rates of such hospitalization (59.7:1000). Compared with matched controls, women with respiratory hospitalizations had similar modes of delivery, delivery length of stay, and episodes of preterm labor. The prevalence of prematurity and low birth weight among infants born to such women was likewise similar between the two groups. CONCLUSION: In this population of pregnant women, those with asthma accounted for half of all respiratory-related hospitalizations during influenza seasons, with 6% of pregnant women with asthma requiring respiratory hospitalization during influenza season, (odds ratio 10.63, 95% CI, 8.18-13.83, compared with women without a medical comorbidity). We detected no significant increase in adverse perinatal outcomes associated with respiratory hospitalizations during influenza season.     

Dioxin risks in perspective: past,present, and future

The United States Environmental Protection Agency (USEPA) and other U.S. and international agencies have focused extensive efforts on the evaluation of the potential health risks of exposures to chlorinated dioxins (PCDDs), furans (PCDFs), and related dioxin-like polychlorinated biphenyls (PCBs). Extensive regulatory efforts over the past 20 years have also been made to control emissions of these compounds and thus to reduce exposures in the general population. This paper reviews the available information on temporal trends in emissions, environmental levels, intake levels through foods, and human body burdens of dioxins. This paper also provides an overview and comparison of recent hazard assessments for dioxins from U.S. and international agencies. Available data on emissions, environmental and food levels, and human body burdens of dioxins in the general population indicate a several-fold reduction in exposures and body burdens in the general population over the three decades from 1970 to 2000. U.S. and international hazard assessments concur on certain aspects, but disagree on fundamental issues including the likelihood of a threshold for carcinogenic dose-response and the degree of safety factors needed in deriving a protective exposure limit. These disagreements have significant consequences for interpreting the potential health risks of current background dioxin exposure levels. However, whatever the degree of health risk that may be associated with current background exposures, the general population is experiencing several-fold lower exposures, and, therefore, lower health risks, currently compared to 30 years ago. In light of the dramatic declines in exposure already observed, further efforts to reduce exposures through attempts to control emissions or food levels should be carefully evaluated to understand the likely efficacy of the efforts and the relative costs and benefits.     

Hepatic P450 Enzyme Activity, Tissue Morphology and Histology of Mink (Mustela vison) Exposed to Polychlorinated Dibenzofurans

Dose- and time-dependent effects of environmentally relevant concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQ) of 2,3,7,8-tetrachlorodibenzofuran (TCDF), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or a mixture of these two congeners on hepatic P450 enzyme activity and tissue morphology, including jaw histology, of adult ranch mink were determined under controlled conditions. Adult female ranch mink were fed either TCDF (0.98, 3.8, or 20 ng TEQ_TCDF/kg bw/day) or PeCDF (0.62, 2.2, or 9.5 ng TEQ_PeCDF/kg bw/day), or a mixture of TCDF and PeCDF (4.1 ng TEQ_TCDF/kg bw/day and 2.8 ng TEQ_PeCDF/kg bw/day, respectively) for 180 days. Doses used in this study were approximately eight times greater than those reported in a parallel field study. Activities of the cytochrome P450 1A enzymes, ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-deethylase (MROD) were significantly greater in livers of mink exposed to TCDF, PeCDF, and a mixture of the two congeners; however, there were no significant histological or morphological effects observed. It was determined that EROD and MROD activity can be used as sensitive biomarkers of exposure to PeCDF and TCDF in adult female mink; however, under the conditions of this study, the response of EROD/MROD induction occurred at doses that were less than those required to cause histological or morphological changes.