Urinary Bisphenol A and Type-2 Diabetes in U.S. Adults: Data from NHANES 2003-2008

Bisphenol A (BPA) is found in plastics and other consumer products; exposure may lead to insulin resistance and development of type-2 diabetes mellitus (T2DM) through over-activation of pancreatic β-cells. Previous studies using data from the National Health and Nutrition Examination Survey (NHANES) showed an inconsistent association between prevalence of self-reported T2DM and urinary BPA. We used a different diagnosis method of T2DM (hemoglobin A1c (HbA1c)) with a larger subset of NHANES.We analyzed data from 4,389 adult participants who were part of a sub-study of environmental phenol measurements in urine from three NHANES cycles from 2003 to 2008. T2DM was defined as having a HbA1c ≥6.5% or use of diabetes medication. The weighted prevalence of T2DM was 9.2%. Analysis of the total sample revealed that a two-fold increase in urinary BPA was associated with an odds ratio (OR) of 1.08 of T2DM (95% confidence interval (CI), 1.02 to 1.16), after controlling for potential confounders. However, when we examined each NHANES cycle individually, we only found a statistically significant association in the 2003/04 cycle (n = 1,364, OR = 1.23 (95% CI, 1.07 to 1.42) for each doubling in urinary BPA). We found no association in either the NHANES cycle from 2005/06 (n = 1,363, OR = 1.05 (95% CI, 0.94 to 1.18)); or 2007/08 (n = 1,662, OR = 1.06 (95% CI, 0.91 to 1.23)). Similar patterns of associations between BPA and continuous HbA1c were also observed.Although higher urinary BPA was associated with elevated HbA1c and T2DM in the pooled analysis, it was driven by data from only one NHANES cycle. Additional studies, especially of a longitudinal design with repeated BPA measurements, are needed to further elucidate the association between BPA and T2DM

Assessment of Survivor Concerns (ASC): A newly proposed brief questionnaire

BACKGROUND: The purpose of this study was to design a brief questionnaire to measure fears about recurrence and health in cancer survivors. Research involving fear of recurrence has been increasing, indicating that it is an important concern among cancer survivors. METHODS: We developed and tested a six-item instrument, the Assessment of Survivor Concerns (ASC). Construct validity was examined in a multiple group confirmatory factor analysis (CFA) with 592 short-term and 161 long-term cancer survivors. Convergent and discriminant validity was examined through comparisons with the PANAS (Positive and Negative Affect Schedule) and the CES-D (Center for Epidemiologic Studies Depression) measures. RESULTS: CFA models for the ASC with short- and long-term survivors showed good fit, with equivalent structure across both groups of cancer survivors. Convergent and discriminant validity was also supported through analyses of the PANAS and CES-D. One item (children's health worry) did not perform as well as the others, so the models were re-run with the item excluded, and the overall fit was improved. CONCLUSION: The ASC showed excellent internal consistency and validity. We recommend the revised five-item instrument as an appropriate measure for assessment of cancer survivor worries

Minimum pricing of alcohol versus volumetric taxation:which policy will reduce heavy consumption without adversely affecting light and moderate consumers?

Background We estimate the effect on light, moderate and heavy consumers of alcohol from implementing a minimum unit price for alcohol (MUP) compared with a uniform volumetric tax. Methods We analyse scanner data from a panel survey of demographically representative households (n = 885) collected over a one-year period (24 Jan 2010–22 Jan 2011) in the state of Victoria, Australia, which includes detailed records of each household's off-trade alcohol purchasing. Findings The heaviest consumers (3% of the sample) currently purchase 20% of the total litres of alcohol (LALs), are more likely to purchase cask wine and full strength beer, and pay significantly less on average per standard drink compared to the lightest consumers (A$1.31 [95$2.21 [95% CI 2.10–2.31]). Applying a MUP of A$1 per standard drink has a greater effect on reducing the mean annual volume of alcohol purchased by the heaviest consumers of wine (15.78 LALs [95$393.60 [95% CI 374.19–413.00]) and beer ($108.26 [95$552.46 [95% CI 530.55–574.36] and $163.92 [95% CI 152.79–175.03], respectively). Both a MUP and uniform volumetric tax have little effect on changing the annual cost of wine and beer for light and moderate consumers, and likewise little effect upon their purchasing. Conclusions While both a MUP and a uniform volumetric tax have potential to reduce heavy consumption of wine and beer without adversely affecting light and moderate consumers, a MUP offers the potential to achieve greater reductions in heavy consumption at a lower overall annual cost to consumers

Bisphenol A and 17β-Estradiol Promote Arrhythmia in the Female Heart via Alteration of Calcium Handling

There is wide-spread human exposure to bisphenol A (BPA), a ubiquitous estrogenic endocrine disruptor that has been implicated as having potentially harmful effects on human heart health. Higher urine BPA concentrations have been shown to be associated with cardiovascular diseases in humans. However, neither the nature nor the mechanism(s) of BPA action on the heart are understood. leak suppressed estrogen-induced triggered activities. The rapid response of female myocytes to estrogens was abolished in an estrogen receptor (ER) β knockout mouse model. leak. Our study provides the first experimental evidence suggesting that exposure to estrogenic endocrine disrupting chemicals and the unique sensitivity of female hearts to estrogens may play a role in arrhythmogenesis in the female heart

Lack of observational evidence for quantum structure of space-time at Plank scales

It has been noted (Lieu & Hillmann, 2002) that the cumulative affect of Planck-scale phenomenology, or the structure of space-time at extremely small scales, can be lead to the loss of phase of radiation emitted at large distances from the observer. We elaborate on such an approach and demonstrate that such an effect would lead to an apparent blurring of distant point-sources. Evidence of the diffraction pattern from the HST observations of SN 1994D and the unresolved appearance of a Hubble Deep Field galaxy at z=5.34 lead us to put stringent limits on the effects of Planck-scale phenomenology.Comment: 12 pages, 3 figures, accepter for ApJ

Tranilast increases vasodilator response to acetylcholine in rat mesenteric resistance arteries through increased EDHF participation

Background and Purpose: Tranilast, in addition to its capacity to inhibit mast cell degranulation, has other biological effects, including inhibition of reactive oxygen species, cytokines, leukotrienes and prostaglandin release. In the current study, we analyzed whether tranilast could alter endothelial function in rat mesenteric resistance arteries (MRA). Experimental Approach: Acetylcholine-induced relaxation was analyzed in MRA (untreated and 1-hour tranilast treatment) from 6 month-old Wistar rats. To assess the possible participation of endothelial nitric oxide or prostanoids, acetylcholineinduced relaxation was analyzed in the presence of L-NAME or indomethacin. The participation of endothelium-derived hyperpolarizing factor (EDHF) in acetylcholine-induced response was analyzed by preincubation with TRAM-34 plus apamin or by precontraction with a high K+ solution. Nitric oxide (NO) and superoxide anion levels were measured, as well as vasomotor responses to NO donor DEA-NO and to large conductance calcium-activated potassium channel opener NS1619. Key Results: Acetylcholine-induced relaxation was greater in tranilast-incubated MRA. Acetylcholine-induced vasodilation was decreased by L-NAME in a similar manner in both experimental groups. Indomethacin did not modify vasodilation. Preincubation with a high K+ solution or TRAM-34 plus apamin reduced the vasodilation to ACh more markedly in tranilastincubated segments. NO and superoxide anion production, and vasodilator responses to DEA-NO or NS1619 remained unmodified in the presence of tranilast. Conclusions and Implications: Tranilast increased the endothelium-dependent relaxation to acetylcholine in rat MRA. This effect is independent of the nitric oxide and cyclooxygenase pathways but involves EDHF, and is mediated by an increased role of small conductance calcium-activated K+ channelsThis study was supported by Ministerio de Ciencia e Innovación (SAF 2009-10374), Ministerio de Economía y Competitividad (SAF 2012-38530), and Fundación Mapfre. F.E. Xavier is recipient of research fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brazil

Fetal Programming of Adult Glucose Homeostasis in Mice

BACKGROUND: Emerging evidence suggests that dietary soy and phytoestrogens can have beneficial effects on lipid and glucose metabolism. We have previously shown that male mice fed from conception to adulthood with a high soy-containing diet had reduced body weight, adiposity and a decrease in glucose intolerance, an early marker of insulin resistance and diabetes. OBJECTIVES: The purpose of this study was to identify the precise periods of exposure during which phytoestrogens and dietary soy improve lipid and glucose metabolism. Since intrauterine position (IUP) has been shown to alter sensitivity to endocrine disruptors, we also investigated whether the combination of IUP and fetal exposure to dietary phytoestrogens could potentially affect adult metabolic parameters. METHODS: Male outbred mice (CD-1) were allowed ad libitum access to either a high soy-containing diet or a soy-free diet either during gestation, lactation or after weaning. Adiposity and bone mass density was assessed by dual x-ray absorptiometry. Glucose tolerance was assessed by a glucose tolerance test. Blood pressure was examined by the tail-cuff system. RESULTS: Here we show that metabolic improvements are dependent on precise windows of exposure during life. The beneficial effects of dietary soy and phytoestrogens on adiposity were apparent only in animals fed post-natally, while the improvements in glucose tolerance are restricted to animals with fetal exposure to soy. Interestingly, we observed that IUP influenced adult glucose tolerance, but not adiposity. Similar IUP trends were observed for other estrogen-related metabolic parameters such as blood pressure and bone mass density. CONCLUSION: Our results suggest that IUP and fetal exposure to estrogenic environmental disrupting compounds, such as dietary phytoestrogens, could alter metabolic and cardiovascular parameters in adult individuals independently of adipose gain

Combination of contrast with stress echocardiography: A practical guide to methods and interpretation

Contrast echocardiography has an established role for enhancement of the right heart Doppler signals, the detection of intra-cardiac shunts, and most recently for left ventricular cavity opacification (LVO). The use of intravenously administered micro-bubbles to traverse the myocardial microcirculation in order to outline myocardial viability and perfusion has been the source of research studies for a number of years. Despite the enthusiasm of investigators, myocardial contrast echocardiography (MCE) has not attained routine clinical use and LV opacification during stress has been less widely adopted than the data would support. The purpose of this review is to facilitate an understanding of the involved imaging technologies that have made this technique more feasible for clinical practice, and to guide its introduction into the practice of the non-expert user

Critical evaluation of key evidence on the human health hazards of exposure to bisphenol A

Despite the fact that more than 5000 safety-related studies have been published on bisphenol A (BPA), there seems to be no resolution of the apparently deadlocked controversy as to whether exposure of the general population to BPA causes adverse effects due to its estrogenicity. Therefore, the Advisory Committee of the German Society of Toxicology reviewed the background and cutting-edge topics of this BPA controversy. The current tolerable daily intake value (TDI) of 0.05 mg/kg body weight [bw]/day, derived by the European Food Safety Authority (EFSA), is mainly based on body weight changes in two- and three-generation studies in mice and rats. Recently, these studies and the derivation of the TDI have been criticized. After having carefully considered all arguments, the Committee had to conclude that the criticism was scientifically not justified; moreover, recently published additional data further support the reliability of the two-and three-generation studies demonstrating a lack of estrogen-dependent effects at and below doses on which the current TDI is based. A frequently discussed topic is whether doses below 5 mg/ kg bw/day may cause adverse health effects in laboratory animals. Meanwhile, it has become clear that positive results from some explorative studies have not been confirmed in subsequent studies with higher numbers of animals or a priori defined hypotheses. Particularly relevant are some recent studies with negative outcomes that addressed effects of BPA on the brain, behavior, and the prostate in rodents for extrapolation to the human situation. The Committee came to the conclusion that rodent data can well be used as a basis for human risk evaluation. Currently published conjectures that rats are insensitive to estrogens compared to humans can be refuted. Data from toxicokinetics studies show that the half-life of BPA in adult human subjects is less than 2 hours and BPA is completely recovered in urine as BPA-conjugates. Tissue deconjugation of BPA-glucuronide and -sulfate may occur. Because of the extremely low quantities, it is only of minor relevance for BPA toxicity. Biomonitoring studies have been used to estimate human BPA exposure and show that the daily intake of BPA is far below the TDI for the general population. Further topics addressed in this article include reasons why some studies on BPA are not reproducible; the relevance of oral versus non-oral exposure routes; the degree to which newborns are at higher systemic BPA exposure; increased BPA exposure by infusions in intensive care units; mechanisms of action other than estrogen receptor activation; and the current regulatory status in Europe, as well as in the USA, Canada, Japan, New Zealand, and Australia. Overall, the Committee concluded that the current TDI for BPA is adequately justified and that the available evidence indicates that BPA exposure represents no noteworthy risk to the health of the human population, including newborns and babies

Brain structural and functional asymmetry in human situs inversus totalis

Magnetic resonance imaging was used to investigate brain structural and functional asymmetries in 15 participants with complete visceral reversal (situs inversus totalis, SIT). Language-related brain structural and functional lateralization of SIT participants, including peri-Sylvian gray and white matter asymmetries and hemispheric language dominance, was similar to those of 15 control participants individually matched for sex, age, education, and handedness. In contrast, the SIT cohort showed reversal of the brain (Yakovlevian) torque (occipital petalia and occipital bending) compared to the control group. Secondary findings suggested different asymmetry patterns between SIT participants with (n = 6) or without (n = 9) primary ciliary dyskinesia (PCD, also known as Kartagener syndrome) although the small sample sizes warrant cautious interpretation. In particular, reversed brain torque was mainly due to the subgroup with PCD-unrelated SIT and this group also included 55% left handers, a ratio close to a random allocation of handedness. We conclude that complete visceral reversal has no effect on the lateralization of brain structural and functional asymmetries associated with language, but seems to reverse the typical direction of the brain torque in particular in participants that have SIT unrelated to PCD. The observed differences in asymmetry patterns of SIT groups with and without PCD seem to suggest that symmetry breaking of visceral laterality, brain torque, and language dominance rely on different mechanisms