Spatial variations in the incidence of breast cancer and potential risks associated with soil dioxin contamination in Midland, Saginaw, and Bay Counties, Michigan, USA

<p>Abstract</p> <p>Background</p> <p>High levels of dioxins in soil and higher-than-average body burdens of dioxins in local residents have been found in the city of Midland and the Tittabawassee River floodplain in Michigan. The objective of this study is threefold: (1) to evaluate dioxin levels in soils; (2) to evaluate the spatial variations in breast cancer incidence in Midland, Saginaw, and Bay Counties in Michigan; (3) to evaluate whether breast cancer rates are spatially associated with the dioxin contamination areas.</p> <p>Methods</p> <p>We acquired 532 published soil dioxin data samples collected from 1995 to 2003 and data pertaining to female breast cancer cases (<it>n </it>= 4,604) at ZIP code level in Midland, Saginaw, and Bay Counties for years 1985 through 2002. Descriptive statistics and self-organizing map algorithm were used to evaluate dioxin levels in soils. Geographic information systems techniques, the Kulldorff's spatial and space-time scan statistics, and genetic algorithms were used to explore the variation in the incidence of breast cancer in space and space-time. Odds ratio and their corresponding 95% confidence intervals, with adjustment for age, were used to investigate a spatial association between breast cancer incidence and soil dioxin contamination.</p> <p>Results</p> <p>High levels of dioxin in soils were observed in the city of Midland and the Tittabawassee River 100-year floodplain. After adjusting for age, we observed high breast cancer incidence rates and detected the presence of spatial clusters in the city of Midland, the confluence area of the Tittabawassee, and Saginaw Rivers. After accounting for spatiotemporal variations, we observed a spatial cluster of breast cancer incidence in Midland between 1985 and 1993. The odds ratio further suggests a statistically significant (<it>α </it>= 0.05) increased breast cancer rate as women get older, and a higher disease burden in Midland and the surrounding areas in close proximity to the dioxin contaminated areas.</p> <p>Conclusion</p> <p>These findings suggest that increased breast cancer incidences are spatially associated with soil dioxin contamination. Aging is a substantial factor in the development of breast cancer. Findings can be used for heightened surveillance and education, as well as formulating new study hypotheses for further research.</p

Dioxin Induces Genomic Instability in Mouse Embryonic Fibroblasts

Ionizing radiation and certain other exposures have been shown to induce genomic instability (GI), i.e., delayed genetic damage observed many cell generations later in the progeny of the exposed cells. The aim of this study was to investigate induction of GI by a nongenotoxic carcinogen, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mouse embryonic fibroblasts (C3H10T1/2) were exposed to 1, 10 or 100 nM TCDD for 2 days. Micronuclei (MN) and expression of selected cancer-related genes were assayed both immediately and at a delayed point in time (8 days). For comparison, similar experiments were done with cadmium, a known genotoxic agent. TCDD treatment induced an elevated frequency of MN at 8 days, but not directly after the exposure. TCDD-induced alterations in gene expression were also mostly delayed, with more changes observed at 8 days than at 2 days. Exposure to cadmium produced an opposite pattern of responses, with pronounced effects immediately after exposure but no increase in MN and few gene expression changes at 8 days. Although all responses to TCDD alone were delayed, menadione-induced DNA damage (measured by the Comet assay), was found to be increased directly after a 2-day TCDD exposure, indicating that the stability of the genome was compromised already at this time point. The results suggested a flat dose-response relationship consistent with dose-response data reported for radiation-induced GI. These findings indicate that TCDD, although not directly genotoxic, induces GI, which is associated with impaired DNA damage response

Ultrafast all-optical switching by single photons

An outstanding goal in quantum optics is the realization of fast optical non-linearities at the single-photon level. Such non-linearities would allow for the realization of optical devices with new functionalities such as a single-photon switch/transistor or a controlled-phase gate, which could form the basis of future quantum optical technologies. While non-linear optics effects at the single-emitter level have been demonstrated in different systems, including atoms coupled to Fabry-Perot or toroidal micro-cavities, super-conducting qubits in strip-line resonators or quantum dots (QDs) in nano-cavities, none of these experiments so far has demonstrated single-photon switching on ultrafast timescales. Here, we demonstrate that in a strongly coupled QD-cavity system the presence of a single photon on one of the fundamental polariton transitions can turn on light scattering on a transition from the first to the second Jaynes-Cummings manifold with a switching time of 20 ps. As an additional device application, we use this non-linearity to implement a single-photon pulse-correlator. Our QD-cavity system could form the building-block of future high-bandwidth photonic networks operating in the quantum regime

In utero exposure to butyl benzyl phthalate induces modifications in the morphology and the gene expression profile of the mammary gland: an experimental study in rats

<p>Abstract</p> <p>Background</p> <p>Environmental estrogens are exogenous estrogen-mimicking compounds that can interfere with endogenous endocrine systems. Several of these endocrine disruptors have been shown to alter normal development and influence tumorigenesis in experimental models. N-butyl benzyl phthalate (BBP), a widely used plasticizer, is a well-known endocrine disruptor. The aim of this study was to elucidate the effect of prenatal exposure to BBP on the morphology, proliferative index, and genomic signature of the rat mammary gland at different ages.</p> <p>Methods</p> <p><it>In utero </it>exposure was performed by gavage of pregnant Sprague Dawley CD rats with 120mg or 500mg BBP/kg/day from day 10 post-conception to delivery. Female litters were euthanized at 21, 35, 50 and 100 days. The morphology and proliferative index of the mammary gland were studied from whole mount preparations and BrdU incorporation, respectively. Gene expression profile was assessed by microarrays. Several genes found differentially expressed and related to different functional categories were further validated by real time RT-PCR.</p> <p>Results</p> <p>Prenatal exposure of BBP induced delayed vaginal opening and changes in the post-natal mammary gland long after the end of the treatment, mainly by 35 days of age. Exposure to the high dose resulted in modifications in architecture and proliferative index of the mammary gland, mostly affecting the undifferentiated terminal end buds. Moreover, the expression profiles of this gland in the exposed rats were modified in a dose-dependent fashion. Analysis of functional categories showed that modified genes were related to immune function, cell signaling, proliferation and differentiation, or metabolism.</p> <p>Conclusions</p> <p>Our data suggest that <it>in utero </it>exposure to BBP induced a delayed pubertal onset and modified morphology of the mammary gland. These alterations were accompanied by modifications in gene expression previously associated with an increased susceptibility to carcinogenesis.</p

In Vivo Dioxin Favors Interleukin-22 Production by Human CD4+ T Cells in an Aryl Hydrocarbon Receptor (AhR)-Dependent Manner

The transcription factor aryl hydrocarbon receptor (AhR) mediates the effects of a group of chemicals known as dioxins, ubiquitously present in our environment. However, it is poorly known how the in vivo exposure to these chemicals affects in humans the adaptive immune response. We therefore assessed the functional phenotype of T cells from an individual who developed a severe cutaneous and systemic syndrome after having been exposed to an extremely high dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).T cells of the TCDD-exposed individual were studied for their capacity to produce cytokines in response to polyclonal and superantigenic stimulation, and for the expression of chemokine receptors involved in skin homing. The supernatants from T cells of the exposed individual contained a substantially increased amount of interleukin (IL)-22 but not of IL-17A, interferon (IFN)-γ or IL-10 when compared to nine healthy controls. In vitro experiments confirmed a direct, AhR-dependent, enhancing effect of TCDD on IL-22 production by CD4+ T cells. The increased production of IL-22 was not dependent on AhR occupancy by residual TCDD molecules, as demonstrated in competition experiments with the specific AhR antagonist CH-223191. In contrast, it was due to an increased frequency of IL-22 single producing cells accompanied by an increased percentage of cells expressing the skin-homing chemokine receptors CCR6 and CCR4, identified through a multiparameter flow cytometry approach. Of interest, the frequency of CD4+CD25(hi)FoxP3+ T regulatory cells was similar in the TCDD-exposed and healthy individuals.This case strongly supports the contention that human exposure to persistent AhR ligands in vivo induce a long-lasting effect on the human adaptive immune system and specifically polarizes CD4+ T cells to produce IL-22 and not other T cell cytokines with no effect on T regulatory cells

Classification of bipolar disorder in psychiatric hospital. a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>This study has explored the classification of bipolar disorder in psychiatric hospital. A review of the literature reveals that there is a need for studies using stringent methodological approaches.</p> <p>Methods</p> <p>480 first-time admitted patients to psychiatric hospital were found eligible and 271 of these gave written informed consent. The study sample was comprised of 250 patients (52%) with hospital diagnoses. For the study, expert diagnoses were given on the basis of a structured diagnostic interview (M.I.N.I.PLUS) and retrospective review of patient records.</p> <p>Results</p> <p>Agreement between the expert's and the clinicians' diagnoses was estimated using Cohen's kappa statistics. 76% of the primary diagnoses given by the expert were in the affective spectrum. Agreement concerning these disorders was moderate (kappa ranging from 0.41 to 0.47). Of 58 patients with bipolar disorder, only 17 received this diagnosis in the clinic. Almost all patients with a current manic episode were classified as currently manic by the clinicians. Forty percent diagnosed as bipolar by the expert, received a diagnosis of unipolar depression by the clinician. Fifteen patients (26%) were not given a diagnosis of affective disorder at all.</p> <p>Conclusions</p> <p>Our results indicate a considerable misclassification of bipolar disorder in psychiatric hospital, mainly in patients currently depressed. The importance of correctly diagnosing bipolar disorder should be emphasized both for clinical, administrative and research purposes. The findings questions the validity of psychiatric case registers. There are potential benefits in structuring the diagnostic process better in the clinic.</p