bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of the bioaccumulation factor to screen chemicals for bioaccumulation potential
Authors: Costanza Jed , Lynch David G. , Boethling Robert S. , Arnot Jon A.
Published: July 2012

The fish bioconcentration factor (BCF), as calculated from controlled laboratory tests, is commonly used in chemical management programs to screen chemicals for bioaccumulation potential. The bioaccumulation factor (BAF), as calculated from field-caught fish, is more ecologically relevant because it accounts for dietary, respiratory, and dermal exposures. The BCFBAF™ program in the U.S. Environmental Protection Agency's Estimation Programs Interface Suite (EPI Suite™ Ver 4.10) screening-level tool includes the Arnot-Gobas quantitative structure–activity relationship model to estimate BAFs for organic chemicals in fish. Bioaccumulation factors can be greater than BCFs, suggesting that using the BAF rather than the BCF for screening bioaccumulation potential could have regulatory and resource implications for chemical assessment programs. To evaluate these potential implications, BCFBAF was used to calculate BAFs and BCFs for 6,034 U.S. high- and medium-production volume chemicals. The results indicate no change in the bioaccumulation rating for 86% of these chemicals, with 3% receiving lower and 11% receiving higher bioaccumulation ratings when using the BAF rather than the BCF. All chemicals that received higher bioaccumulation ratings had log KOW values greater than 4.02, in which a chemical's BAF was more representative of field-based bioaccumulation than its BCF. Similar results were obtained for 374 new chemicals. Screening based on BAFs provides ecologically relevant results without a substantial increase in resources needed for assessments or the number of chemicals screened as being of concern for bioaccumulation potential. Environ. Toxicol. Chem. 2012; 31: 2261–2268. © 2012 SETAC
Oxytetracycline interactions at the soil–water interface: Effects of environmental surfaces on natural transformation and growth inhibition of Azotobacter vinelandii
Authors: Goetsch Heather E. , Mylon Steven E. , Butler Shane , Zilles Julie L. , Nguyen Thanh H.
Published: July 2012

The mechanism of oxytetracycline (OTC) adsorption to a silty clay loam soil was investigated using sorption isotherm experiments, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction spectroscopy (XRD). Sorption data fit well to a cation-exchange capacity sorption model. Spectroscopic data indicate that the interactions between oxytetracycline and silty clay loam soil were primarily through electrostatic interactions between the protonated dimethylamino group of OTC and the negatively charged moieties on the surface of the soil. Based on XRD results, OTC adsorption appeared to inhibit the ethylene glycol solvation of the expandable clay minerals, suggesting that OTC had diffused into the clay interlayer space. The presence of adsorbed OTC did not significantly affect the transformation frequency of the soil bacterium Azotobacter vinelandii with plasmid DNA (soil alone 3 × 106 ± 4 × 106 and soil with adsorbed OTC 4 × 106 ± 0.5 × 106). Growth was inhibited by adsorbed OTC, although a greater mass of adsorbed OTC was required to achieve the same degree of inhibition as the system of dissolved OTC alone. These results suggest that the interactions of tetracyclines at the soil–water interface will affect the growth of sensitive microorganisms in soil microbial communities. Environ. Toxicol. Chem. 2012; 31: 2217–2224. © 2012 SETAC
Transcriptional responses in Enchytraeus albidus (Oligochaeta): Comparison between cadmium and zinc exposure and linkage to reproduction effects
Authors: Novais Sara C. , De Coen Wim , Amorim Mónica J.B.
Published: July 2012

Metal ecotoxicity to soil organisms (for example, in enchytraeids) has been addressed mainly by assessing effects on survival and reproduction, but very little is known about the underlying molecular mechanisms of responses. The main purpose of the present study was to assess and compare the transcriptional responses of Enchytraeus albidus to an essential (Zn) and a nonessential (Cd) metal. Exposure was performed with two concentrations with a known effect on reproduction (effective concentration for 50% [EC50] and 90% [EC90]) at three time points (2, 4, and 8 d). Results showed that transcriptional responses were influenced by exposure duration but, independently of that, the mechanisms of response to Cd and Zn were consistently different. Both metals affected pathways related to the regulation of gene expression, calcium homeostasis, and cellular respiration. Mechanisms of toxicity that were exclusively associated with Cd exposures were the inhibition of DNA repair and the impairment of ubiquitin-mediated proteolysis. The microarray for E. albidus was a useful tool for detecting molecular pathways affected by metal exposures. Transcriptional responses strongly correlated with known mechanisms of Cd and Zn responses in other organisms, suggesting cross-species conserved mechanisms of action. It should be highlighted not only that the authors could retrieve mechanistic information but also that genes responded within 2 to 8 d of exposure. This represents an additional advantage of using such molecular endpoints as a complement to the traditional, more time-consuming endpoints. Environ. Toxicol. Chem. 2012; 31: 2289–2299. © 2012 SETAC
Influence of humic acid on the uptake of aqueous metals by the killifish Fundulus heteroclitus
Authors: Dutton Jessica , Fisher Nicholas S.
Published: July 2012

The role of humic acids, over a concentration range of 0 to 20 mg L−1, was investigated in the uptake of three metals (Cd, Cr, and Hg—as both inorganic Hg [Hg(II)] and methylmercury [MeHg]) and a metalloid (As) from the aqueous phase by the killifish (Fundulus heteroclitus). Cadmium uptake showed no relationship with humic acid concentration, whereas Cr, Hg(II), and MeHg uptake showed an inverse relationship, and As uptake increased with increasing humic acid concentration. Concentration factors were >1 for Cd, Hg(II), and MeHg at all humic acid concentrations, indicating killifish were more enriched in the metal than the experimental media, whereas As and Cr generally had concentration factors <1 at the end of a 72-h exposure. The uptake of As and Cr reached steady state within the 72-h exposure, whereas uptake of Cd, Hg(II), and MeHg did not. Uptake rate constants (kus; ml g−1 d−1) were highest for MeHg (91–3,936), followed by Hg(II), Cd, and Cr, and lowest for As (0.17–0.29). Dissection data revealed that the gills generally had the highest concentration of all metals under all humic acid treatments. The present study concludes that changes in humic acid concentration can influence the accumulation of aqueous metals in killifish and should be considered when modeling metal bioaccumulation. Environ. Toxicol. Chem. 2012; 31: 2225–2232. © 2012 SETAC
Dissolved organic carbon modulates the effects of copper on olfactory-mediated behaviors of chinook salmon
Authors: Kennedy Christopher J. , Stecko Pierre , Truelson Bob , Petkovich David
Published: July 2012

The modulation of Cu effects on olfactory-mediated behaviors by dissolved organic carbon (DOC) and Fe was examined in juvenile chinook salmon. Chinook were exposed to several concentrations of Cu, DOC, and Fe alone or in combination in a flow-through system for either 4 d (acute exposure) or 14 d (subchronic exposure) and tested for their ability to detect and avoid the odorant L-histidine in an avoidance/preference trough assay. In both acute and subchronic exposures, Cu inhibited the ability of fish to detect this amino acid in a concentration-dependent manner, and Cu toxicity (olfactory inhibition) decreased with increasing DOC concentration. In both acute and subchronic experiments including DOC, Cu-induced olfactory inhibition decreased in a linear fashion with increasing DOC concentration, although the modulation was lower in subchronic exposures. The protective effect of DOC on Cu olfactory inhibition was reduced only slightly in the presence of Fe, indicating that other metals can potentially affect the modulation of the olfactory inhibition of Cu through competition for DOC binding sites. The results of the present study clearly show the amelioration by DOC of the effects of Cu on juvenile chinook salmon olfaction at a behavioral level. These data further indicate that DOC concentrations should be considered when evaluating the potential impact of Cu on fish olfaction. Environ. Toxicol. Chem. 2012; 31: 2281–2288. © 2012 SETAC
Effects of road deicer (NaCl) and amphibian grazers on detritus processing in pond mesocosms
Authors: Van Meter Robin J. , Swan Christopher M. , Trossen Carrie A.
Published: July 2012

Road deicers have been identified as potential stressors in aquatic habitats throughout the United States, but we know little regarding associated impacts to ecosystem function. A critical component of ecosystem function that has not previously been evaluated with respect to freshwater salinization is the impact on organic matter breakdown. The purpose of this study was to evaluate cumulative effects of road deicers and tadpole grazers on leaf litter breakdown rate (g d−1) and microbial respiration (mg O2 g leaf−1 h−1). To test this interaction, in May 2008 the authors added dry leaf litter (Quercus spp.) to forty 600-L pond mesocosms and inoculated each with algae and zooplankton. In a full-factorial design, they manipulated a realistic level of road salt (ambient or elevated at 645 mg L−1 Cl−) and tadpole (Hyla versicolor) presence or absence. The elevated chloride treatment reduced microbial respiration by 24% in the presence of tadpoles. The breakdown of leaf litter by tadpoles occurred 9.7% faster under ambient chloride conditions relative to the elevated chloride treatment. Results of the present study suggest that the microbial community is directly impacted by road deicers and heavy tadpole grazing under ambient conditions limits microbial capacity to process detritus. Road salts and tadpoles interact to limit microbial respiration, but to a lesser extent leaf mass loss rate, thereby potentially restricting energy flow from detrital sources in pond ecosystems. Environ. Toxicol. Chem. 2012; 31: 2306–2310. © 2012 SETAC
Response of biomarkers in amphibian larvae to in situ exposures in a fruit-producing region in North Patagonia, Argentina
Authors: Rosenbaum Enrique A. , Duboscq Leonardo , Soleño Jimena , Montagna Cristina M. , Ferrari Ana , Venturino Andrés
Published: July 2012

The authors evaluated biomarker responses in caged larvae of the amphibian Rhinella arenarum in water channels during fruit production season and compared them with those elicited by a transient exposure to azinphos methyl (AzM) (0.02–2 mg/L; 4 h), the main pesticide applied in the Alto Valle region, Patagonia, Argentina, taking into account the maximum environmental concentration detected in superficial water (22.5 µg/L). The traditional biomarkers of organophosphate exposure, acetylcholinesterase (AChE) and carboxylesterase, were inhibited in tadpoles after one week of exposure in channels potentially receiving pesticide drift, whereas the antioxidant glutathione (GSH) and the detoxifying activity of GSH S-transferase (GST) were induced. In a two-week monitoring study, AChE activity was induced in larvae exposed at the agricultural site, and carboxylesterase showed an inhibition followed by return to control values, suggesting an exposure–recovery episode. Antioxidant glutathione levels were first depleted and then surpassed control levels, whereas GST activity was continuously induced. These responses were mimicked in the laboratory by 2 mg/L AzM-pulse exposure, which notably exceeds the expected environmental concentrations. The results draw attention to the complexity of responses after pesticide exposure, strongly depending on exposure time-concentration and recovery periods, among other possible factors, and support the necessity of the integrated use of biomarkers to assess exposure episodes in agricultural areas. Environ. Toxicol. Chem. 2012; 31: 2311–2317. © 2012 SETAC
Effects of environmental lead contamination on cattle in a lead/zinc mining area: Changes in cattle immune systems on exposure to lead in vivo and in vitro
Authors: Ikenaka Yoshinori , Nakayama Shouta M.M. , Muroya Taro , Yabe John , Konnai Satoru , Darwish Wageh Sobhy , Muzandu Kaampwe , Choongo Kennedy , Mainda Geoffrey , Teraoka Hiroki , Umemura Takashi , Ishizuka Mayumi
Published: July 2012

The Republic of Zambia is rich in mineral resources, such as zinc (Zn) and lead (Pb), and mining is a key industry in Zambia. A previous study of Pb pollution in Kabwe, one of the main mining areas, found that soil was contaminated with high levels of toxic metals over a substantial area. In the present study, the authors focus on toxic metal pollution in cattle, one of the most important domestic animals in Zambia. Blood samples from cattle in Kabwe and a control area (Lusaka) were tested for toxic metal content. They also measured mRNA expression of metal-responsive proteins and cytokines in white blood cells using real-time reverse transcriptase polymerase chain reaction. In the present in vitro study, The authors cultured peripheral blood mononuclear cells (PBMCs) from cattle, exposing them to Pb acetate for 24 h and analyzing mRNA expression of metal-responsive proteins and selected cytokines. Lead concentrations in cattle blood from Kabwe were significantly greater than those from Lusaka, as were the mRNA expressions of metallothionein-2 (MT-2), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-6, and inducible nitric oxide synthase (iNOS). The present in vitro study demonstrated that Pb exposure led to an increase in the expressions of MT-2, TNF-α, IL-1β, and iNOS, similar to those found in vivo. These results indicate the possibility of immune system modulations in cattle from the Kabwe area. Environ. Toxicol. Chem. 2012; 31: 2300–2305. © 2012 SETAC
Comparison of human exposure pathways in an urban brownfield: Reduced risk from paving roads
Authors: James Kyle , Farrell Richard E. , Siciliano Steven D.
Published: July 2012

Risk assessments often do not quantify the risk associated with soil inhalation. This pathway generally makes a negligible contribution to the cumulative risk, because soil ingestion is typically the dominant exposure pathway. Conditions in northern or rural centers in Canada characterized by large areas of exposed soil, including unpaved roads, favor the resuspension of soil particles, making soil inhalation a relevant risk pathway. The authors determined and compared human exposure to metals and polycyclic aromatic hydrocarbons (PAHs) from soil ingestion and inhalation and analyzed the carcinogenic and noncarcinogenic risks before and after roads were paved in a northern community. To determine the inhalation exposure, three size fractions of airborne particulate matter were collected (total suspended particulates [TSP], particulate matter with an aerodynamic diameter less than 10 µm [PM10], and particulate matter with an aerodynamic diameter less than 2.5 µm [PM2.5]) before and after roads were paved. Road paving reduced the concentration of many airborne contaminants by 25 to 75%, thus reducing risk. For example, before paving, the carcinogenic risk associated with inhalation of Cr was 3.4 excess cancers per 100,000 people exposed, whereas after paving, this risk was reduced to 1.6 in 100,000. Paving roads reduced the concentrations of total suspended particulates (TSP; p < 0.1) and PM10 (p < 0.05) but not PM25. Consequently, the ingestion of inhaled soil particles was substantially reduced. The authors conclude that resuspended soil is likely an important source of risk for many northern communities and that paving roads is an effective method of reducing risk from the inhalation of soil particles. Environ. Toxicol. Chem. 2012; 31: 2423–2430. © 2012 SETAC
Nutritional status of community‐dwelling older people with dementia: associations with individual and family caregivers' characteristics
Authors: Rullier Laetitia , Lagarde Alexia , Bouisson Jean , Bergua Valérie , Barberger‐Gateau Pascale
Published: July 2012

Objective

The objective of this study was to explore the associations of individual characteristics of both older people with dementia and family caregivers with the nutritional status of older people with dementia.

Methods

This cross‐sectional study comprising 56 community‐dwelling older persons with dementia and 56 family caregivers was conducted at home by a psychogerontologist working for a community gerontological center. Older people with dementia were assessed with Mini mental state examination, Instrumental Activities of Daily Living, Activities of Daily Living (ADL), and NeuroPsychiatric Inventory (NPI) and family caregivers with the Burden Interview (Zarit scale), the State‐Trait Anxiety Inventory, the Center for Epidemiologic Studies Depression Scale, and the emotional impact measure of NPI. For both, nutritional status was evaluated using the Mini Nutritional Assessment (MNA).

Results

Among older people with dementia, 58.9% were at risk of malnutrition and 23.2% presented a poor nutritional status, and among the family caregivers, 32.1% and 5.4%, respectively. The MNA score of older people with dementia was strongly and inversely associated with the ADL score and was strongly and positively associated with the MNA score of family caregiver. These two factors significantly explained 32% of variation of MNA score of older people with dementia.

Conclusions

These findings confirm the value of investigating nutritional deficiencies in dementia within the caregiving dyad and suggest that the functional status of older people with dementia and the nutritional status of family caregivers should be carefully assessed. Copyright © 2012 John Wiley & Sons, Ltd.
A randomized controlled trial of pretransplant antiviral therapy to prevent recurrence of hepatitis C after liver transplantation
Authors: Everson Gregory T. , Terrault Norah A. , Lok Anna S. , Rodrigo Del R. , Brown Robert S. , Saab Sammy , Shiffman Mitchell L. , Al-Osaimi Abdullah M.S. , Kulik Laura M. , Gillespie Brenda W. , Everhart James E.
Published: July 2012

Hepatitis C virus (HCV) infection recurs in liver recipients who are viremic at transplantation. We conducted a randomized, controlled trial to test the efficacy and safety of pretransplant pegylated interferon alpha-2b plus ribavirin (Peg-IFN-α2b/RBV) for prevention of post-transplant HCV recurrence. Enrollees had HCV and were listed for liver transplantation, with either potential living donors or Model for End-Stage Liver Disease upgrade for hepatocellular carcinoma. Patients with HCV genotypes (G) 1/4/6 (n = 44/2/1) were randomized 2:1 to treatment (n = 31) or untreated control (n = 16); HCV G2/3 (n=32) were assigned to treatment. Overall, 59 were treated and 20 were not. Peg-IFN-α2b, starting at 0.75 μg/kg/week, and RBV, starting at 600 mg/day, were escalated as tolerated. Patients assigned to treatment versus control had similar baseline characteristics. Combined virologic response (CVR) included pretransplant sustained virologic response and post-transplant virologic response (pTVR), defined as undetectable HCV RNA 12 weeks after end of treatment or transplant, respectively. In intent-to-treat analyses, 12 (19%) assigned to treatment and 1 (6%) assigned to control achieved CVR (

P

= 0.29); per-protocol values were 13 (22%) and 0 (0%) (

P

= 0.03). Among treated G1/4/6 patients, 23 of 30 received transplant, of whom 22% had pTVR; among treated G2/3 patients 21 of 29 received transplant, of whom 29% had pTVR. pTVR was 0%, 18%, and 50% in patients treated for <8, 8-16, and >16 weeks, respectively (

P

= 0.01). Serious adverse events (SAEs) occurred with similar frequency in treated versus untreated patients (68% versus 55%;

P

= 0.30), but the number of SAEs per patient was higher in the treated group (2.7 versus 1.3;

P

= 0.003).

Conclusion :

Pretransplant treatment with Peg-IFN-α2b/RBV prevents post-transplant recurrence of HCV in selected patients. Efficacy is higher with >16 weeks of treatment, but treatment is associated with increased risk of potentially serious complications.
Estrogen-Sensitive PTPRO Expression Represses Hepatocellular Carcinoma Progression by Control of STAT3
Authors: Hou Jiajie , Xu Juan , Jiang Runqiu , Wang Youjing , Chen Chen , Deng Lei , Huang Xingxu , Wang Xuehao , Sun Beicheng
Published: July 2012

Protein tyrosine phosphatase receptor type O (PTPRO), one of the receptor types of phosphotyrosine phosphatases (PTP), was recently described as a tumor suppressor in various kinds of cancers. We aimed to clarify the role of PTPRO in hepatocellular carcinoma (HCC). It was demonstrated in 180 pairs (120 male and 60 female) of clinical HCC specimens that the PTPRO level was significantly reduced, as compared with adjacent tissue, and the PTPRO level in male adjacent tissue was lower than in female. We further found that estrogen receptor alpha (ERα) could up-regulate PTPRO expression as a transcription factor. Moreover, an

in vitro

study showed that cell proliferation was inhibited and apoptosis was promoted in PTPRO-transduced HCC cell lines, whereas an

in vivo

study represented that tumor number and size was increased in

ptpro

−/− mice. As a result of its tumor-suppressive position, PTPRO was proved to down-regulate signal transducers and activators of transcription (STAT3) activity dependent on Janus kinase 2 (JAK2) and phosphoinositide 3-kinase (PI3K) dephosphorylation. Conclusions: PTPRO expression results in pathological deficiency and gender bias in HCC, which could be attributed to ERα regulation. The suppressive role of PTPRO in HCC could be ascribed to STAT3 inactivation.
High-mobility group box 1 (HMGB1)-toll-like receptor (TLR)4-interleukin (IL)-23-IL-17A axis in drug-induced damage-associated lethal hepatitis: Interaction of γδ T cells with macrophages
Authors: Wang Xuefu , Sun Rui , Wei Haiming , Tian Zhigang
Published: July 2012

Acetaminophen overdose causes acute liver inflammation with neutrophil infiltration; however, the mechanism of damage-associated inflammation has not been elucidated. In this study we found that the HMGB1-TLR4-IL-23-IL-17A axis played a crucial role in acetaminophen-induced infiltration of neutrophils and liver injury. Notably, interleukin (IL)-17A and IL-23 significantly increased after acetaminophen challenge. A neutralizing antibody against IL-17A attenuated the recruitment of neutrophils, accompanied by reduced liver injury. Only IL-17A+CD3+γδ T cell receptor (TCR)+ cells were significantly increased in the liver, and depletion of γδ T cells, but not CD4+ T cells or natural killer (NK)T cells significantly reduced IL-17A production, attenuated liver injury, and decreased the number of neutrophils in the liver. Furthermore, a neutralizing IL-23 p19 antibody or p40-deficiency significantly decreased the levels of IL-17A and infiltration of neutrophils. After in vitro stimulation, the percentage of IL-17A-producing γδ T cells and the levels of supernatant IL-17A from total hepatic lymphocytes or purified γδ T cells markedly increased in the presence with IL-23. Importantly, IL-23 and IL-17A were reduced after inhibition of macrophages and could not be induced in Toll-like receptor TLR4−/− mice after acetaminophen challenge. Meanwhile, serum high-mobility group box 1 (HMGB1), a damage-associated molecule released from necrotic hepatocytes, increased after acetaminophen challenge, and the HMGB1 inhibitor glycyrrhizin markedly reduced the production of IL-23 and IL-17A and the recruitment of hepatic neutrophils. HMGB1 stimulated the production of IL-23 by TLR4+/+ but not by TLR4−/− macrophages. Conclusion: The HMGB1-TLR4-IL-23 pathway in macrophages makes the generation of IL-17-producing γδ T cells, which mediates neutrophil infiltration and damage-induced liver inflammation. (Hepatology 2013)
Loss of SLC45A3 protein (prostein) expression in prostate cancer is associated with SLC45A3‐ERG gene rearrangement and an unfavorable clinical course
Authors: Perner Sven , Rupp Niels J. , Braun Martin , Rubin Mark A. , Moch Holger , Dietel Manfred , Wernert Nicolas , Jung Klaus , Stephan Carsten , Kristiansen Glen
Published: July 2012

The majority of prostate cancer harbors recurrent gene fusions involving ETS transcription factors, most commonly ERG. The second most common 5′ fusion partner after TMPRSS2 is SLC45A3. The aim of our study was to quantify the protein expression of ERG, TMPRSS2 and SLC45A3 in prostate cancer to assess for diagnostic or prognostic utility. Six hundred and forty consecutive prostate cancer cases in tissue microarray format were immunohistochemically analyzed for ERG, TMPRSS2 and SLC45A3 protein. Resultant protein expression data was correlated to the respective gene rearrangement status and clinico‐pathological parameters including PSA follow up times. ERG showed no expression in benign prostate glands. In cancer tissue, ERG protein expression showed a high rate of concordance with an underlying ERG rearrangement (91.5%). SLC45A3 showed a weaker expression in cancer as compared to benign tissue, which was pronounced in cases with SLC45A3‐ERG fusion. Importantly, SLC45A3 down regulation was significantly associated with shorter PSA‐free survival times. In contrast, TMPRSS2 was neither differentially expressed nor did it show a correlation between protein expression and rearrangement status. This study provides first evidence that the expression of SLC45A3 protein is down regulated through SLC45A3‐ERG fusion in prostate cancer. Moreover, these cases may represent a distinct molecular subclass of ERG rearranged prostate cancer with distinct clinical features. This study also confirms that ERG protein expression is predominantly found in prostate carcinomas with ERG gene rearrangement and does not occur in benign glands.
Influence of having a home garden on personal UVR exposure behavior and risk of cutaneous malignant melanoma in Denmark
Authors: Idorn Luise Winkel , Thieden Elisabeth , Philipsen Peter Alshede , Wulf Hans Christian
Published: July 2012

There is a need for more knowledge concerning the association of higher socioeconomic status (SES) with cutaneous malignant melanoma (CMM). Having a home garden is associated with a higher SES. We aimed to study the influence of having a home garden on UVR exposure behavior and risk of CMM. Register study: We collected information from Danish national registers about gender, age, type of home and CMM among persons aged 16–75 in 2002–2006. A total of 5,118 CMM cases were identified. Risk of CMM of the trunk was increased by 46% (p < 0.001, 95% confidence interval (CI): 31–63) and risk of CMM of the extremities by 34% (p < 0.001, 95% CI: 20–49) among people with home gardens. Dosimeter study: During a summer season 194 participants living in the Capital area, Denmark, equally distributed in homes with and without a garden, wore personal electronic UVR dosimeters measuring time‐stamped UVR doses continuously and filled in sun exposure diaries. While no difference was found in estimated yearly UVR dose between groups, participants with a home garden had more days exposing shoulders or upper body, and upper extremities outdoors than those without a garden (p = 0.026, age adjusted). People with a home garden are at increased risk of CMM of the trunk and extremities—body sites that seems to be exposed to a higher extent among people with home gardens. People with a higher SES are more likely to have a home garden. This may partly explain the well‐known association of higher SES with CMM incidence.
Stroma‐directed imatinib therapy impairs the tumor‐promoting effect of bone marrow‐derived mesenchymal stem cells in an orthotopic transplantation model of colon cancer
Authors: Shinagawa Kei , Kitadai Yasuhiko , Tanaka Miwako , Sumida Tomonori , Onoyama Mieko , Ohnishi Mayu , Ohara Eiji , Higashi Yukihito , Tanaka Shinji , Yasui Wataru , Chayama Kazuaki
Published: July 2012

Bone marrow‐derived mesenchymal stem cells (MSCs) are reported to contribute to formation of tumor‐promoting stromal cells. We reported recently that, in an orthotopic nude mice model of colon cancer, MSCs traveled to tumor stroma, where they differentiated into carcinoma‐associated fibroblast (CAF)‐like cells. We also found that CAFs express platelet‐derived growth factor receptor (PDGFR) at a high level and that imatinib therapy targeting PDGFR in CAFs inhibits growth and metastasis of human colon cancer. These findings led us to examine whether the tumor‐promoting effect of MSCs is impaired by blockade of PDGFR signaling achieved with imatinib. Orthotopic transplantation and splenic injection of human MSCs along with KM12SM human colon cancer cells, in comparison with transplantation of KM12SM cells alone, resulted in significantly greater promotion of tumor growth and liver metastasis. The KM12SM + MSC xenograft enhanced cell proliferation and angiogenesis and inhibited tumor cell apoptosis. When tumor‐bearing animals were treated with imatinib, there was no significant increase in primary tumor volume or total volume of liver metastases, despite the KM12SM+MSC xenograft, and survival in the mixed‐cell group was prolonged by imatinib treatment. Moreover, the ability of MSCs to migrate to tumor stroma was impaired, and the number of MSCs surviving in the tumor microenvironment was significantly decreased. In in vitro experiments, treatment with imatinib inhibited migration of MSCs. Our data suggest that blockade of PDGF signaling pathways influences the interaction between bone marrow‐derived MSCs and tumor cells in the tumor microenvironment and, hence, inhibits the progressive growth of colon cancer.
Macrophage migration inhibitory factor induces epithelial to mesenchymal transition, enhances tumor aggressiveness and predicts clinical outcome in resected pancreatic ductal adenocarcinoma
Authors: Funamizu Naotake , Hu Chaoxin , Lacy Curtis , Schetter Aaron , Zhang Geng , He Peijun , Gaedcke Jochen , Ghadimi Michael B. , Ried Thomas , Yfantis Harris G. , Lee Dong H. , Subleski Jeffrey , Chan Tim , Weiss Jonathan M. , Back Timothy C. , Yanaga Katsuhiko , Hanna Nader , Alexander H. Richard , Maitra Anirban , Hussain S. Perwez
Published: July 2012

MIF is a proinflammatory cytokine and is implicated in cancer. A higher MIF level is found in many human cancer and cancer‐prone inflammatory diseases, including chronic pancreatitis and pancreatic cancer. We tested the hypothesis that MIF contributes to pancreatic cancer aggressiveness and predicts disease outcome in resected cases. Consistent with our hypothesis we found that an elevated MIF mRNA expression in tumors was significantly associated with poor outcome in resected cases. Multivariate Cox‐regression analysis further showed that MIF is independently associated with patients' survival (HR = 2.26, 95% CI = 1.17–4.37, p = 0.015). Mechanistic analyses revealed that MIF overexpression decreased E‐cadherin and increased vimentin mRNA and protein levels in pancreatic cancer cell lines, consistent with the features of epithelial‐to‐mesenchymal transition (EMT). Furthermore, MIF‐overexpression significantly increased ZEB1/2 and decreased miR‐200b expression, while shRNA‐mediated inhibition of MIF increased E‐cadherin and miR‐200b expression, and reduced the expression of ZEB1/2 in Panc1 cells. Re‐expression of miR‐200b in MIF overexpressing cells restored the epithelial characteristics, as indicated by an increase in E‐cadherin and decrease in ZEB1/2 and vimentin expression. A reduced sensitivity to the chemotherapeutic drug, gemcitabine, occurred in MIF‐overexpressing cells. Indicative of an increased malignant potential, MIF over‐expressing cells showed significant increase in their invasion ability in vitro, and tumor growth and metastasis in an orthotopic xenograft mouse model. These results support a role of MIF in disease aggressiveness, indicating its potential usefulness as a candidate target for designing improved treatment in pancreatic cancer.
Oncogenic mutations in extramammary Paget's disease and their clinical relevance
Authors: Kang Zhihua , Xu Feng , Zhang Qiao‐an , Wu Zhiyuan , Zhang Xinju , Xu Jinhua , Luo Yan , Guan Ming
Published: July 2012

Extramammary Paget's disease (EMPD) is a rare cutaneous malignant neoplasm. The genetic alterations underlying its pathogenesis have less been described. Therefore, we analyzed the possible mutations in the KRAS, HRAS, NRAS, BRAF, ARAF, RAF1, PIK3CA, AKT1, CTNNB1 and APC genes as well as methylation and expression of CDH1 in 144 EMPD cases and 42 matched normal skin tissues. A distinct mutation profile was identified in EMPDs with 27 (19%) cases mutant for RAS and RAF genes and 50 (35%) cases harboring oncogenic mutations in PIK3CA and AKT1. Moreover, a mutually exclusive pattern was observed in the genetic variants in these two signaling pathways. No mutation was detected in CTNNB1 and APC genes. High prevalence of low expression and hypermethylation of CDH1 gene was detected in 33 and 48% of the EMPD cases, respectively. Furthermore, PIK3CA and AKT1 mutations were significantly correlated with CDH1 hypermethylation which could explain why the majority of EMPD cases with mutant PIK3CA and AKT1 were invasive. Our study demonstrates that genetic variants associated with constitutive activation of RAS/RAF and PI3K/AKT pathways are involved in the pathogenesis of EMPD. This may represent novel therapeutic targets for this skin cancer.
A novel RT‐PCR method for quantification of human papillomavirus transcripts in archived tissues and its application in oropharyngeal cancer prognosis
Authors: Gao Ge , Chernock Rebecca D. , Gay Hiram A. , Thorstad Wade L. , Zhang Tian R. , Wang Hongwei , Ma Xiao‐Jun , Luo Yuling , Lewis James S. , Wang Xiaowei
Published: July 2012

Oropharyngeal squamous cell carcinoma (SCC) is strongly associated with human papillomavirus (HPV) infection, which is distinctively different from most other head and neck cancers. However, a robust quantitative reverse transcription PCR (RT‐qPCR) method for comprehensive expression profiling of HPV genes in routinely fixed tissues has not been reported. To address this issue, we have established a new real‐time RT‐PCR method for the expression profiling of the E6 and E7 oncogenes from 13 high‐risk HPV types. This method was validated in cervical cancer and by comparison with another HPV RNA detection method (in situ hybridization) in oropharyngeal tumors. In addition, the expression profiles of selected HPV‐related human genes were also analyzed. HPV E6 and E7 expression profiles were then analyzed in 150 archived oropharyngeal SCC samples and compared with other variables and with patient outcomes. Our study showed that RT‐qPCR and RNA in situ hybridization were 100% concordant in determining HPV status. HPV transcriptional activity was found in most oropharyngeal SCC (81.3%), a prevalence that is higher than in previous studies. Besides HPV16, three other HPV types were also detected, including 33, 35 and 18. Furthermore, HPV and p16 had essentially identical expression signatures, and both HPV and p16 were prognostic biomarkers for the prediction of disease outcome. Thus, p16 mRNA or protein expression signature is a sensitive and specific surrogate marker for HPV transcriptional activity (all genotypes combined).
Italian mediterranean index and risk of colorectal cancer in the Italian section of the EPIC cohort
Authors: Agnoli Claudia , Grioni Sara , Sieri Sabina , Palli Domenico , Masala Giovanna , Sacerdote Carlotta , Vineis Paolo , Tumino Rosario , Giurdanella Maria Concetta , Pala Valeria , Berrino Franco , Mattiello Amalia , Panico Salvatore , Krogh Vittorio
Published: July 2012

Colorectal cancer is among the commonest cancers worldwide. Dietary factors have been linked to colorectal cancer risk, however, few studies have evaluated the relationship between a priori dietary patterns and colorectal cancer risk. We evaluated the effect of adherence to a Mediterranean dietary pattern, as measured by the Italian Mediterranean Index, on the risk of colorectal cancer in the 45,275 participants of the Italian section of the EPIC study who completed a dietary questionnaire. Hazard ratios (HRs) with 95% confidence intervals (CIs) for colorectal cancer in relation to categories of Italian Mediterranean Index score were estimated by multivariate Cox models adjusted for known risk factors, on the whole cohort, on men and women and according to cancer subsite. During a mean follow‐up of 11.28 years, 435 colorectal cancer cases were identified. The Italian Mediterranean Index was inversely associated with colorectal cancer risk (HR: 0.50; 95% CI: 0.35–0.71 for the highest category compared to the lowest, P‐trend: 0.043). Results did not differ by sex. Highest Italian Mediterranean Index score was also significantly associated with reduced risks of any colon cancer (HR: 0.54, 95% CI: 0.36–0.81), distal colon cancer (HR: 0.44, 95% CI: 0.26–0.75) and rectal cancer (HR: 0.41, 95% CI: 0.20–0.81), but not of proximal colon cancer. These findings suggest that adherence to a Mediterranean diet (as measured by the Italian Mediterranean Index) protects against colorectal cancer in general but not against cancer developing in the proximal colon.
Biocompatibility of an experimental MTA sealer implanted in the rat subcutaneous: Quantitative and immunohistochemical evaluation
Authors: Viana Viola Naiana , Maria Guerreiro‐Tanomaru Juliane , Ferreira da Silva Guilherme , Sasso‐Cerri Estela , Tanomaru‐Filho Mario , Cerri Paulo Sérgio
Published: July 2012

The tissue reaction promoted by an experimental mineral trioxide aggregate sealer (MTAS) in the rat subcutaneous was evaluated by morphological and morphometric analyses. In the animals from each group (n = 20), polyethylene tubes filled with MTAS, Portland cement (PC) or MTA were implanted in the dorsal subcutaneous. In the control group, empty tubes were implanted. After 7, 14, 30, and 60 days, the specimens were fixed and embedded in paraffin. In the HE‐stained sections, the numerical density of inflammatory cells (IC) in the capsule was evaluated and statistical analyses performed (p ≤ 0.05). The expression of osteopontin (OPN) was evaluated by immunohistochemistry. The von Kossa method for detection of calcified structures was also performed. A moderate inflammatory process in the capsule was seen in all groups, at 7 and 14 days. At 60 days, significant reduction in the number of IC was verified in comparison to initial periods; however, significant differences were not verified among the groups. OPN immunolabeling was observed in the fibroblasts cytoplasm of the capsule next to the implants. Structures von Kossa‐positive were observed in the capsule adjacent to all materials implanted at 7, 14, and 30 days. The results strongly indicate that MTAS presents biocompatibility similarly to MTA and PC. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Extension of the CHARMM general force field to sulfonyl‐containing compounds and its utility in biomolecular simulations
Authors: Yu Wenbo , He Xibing , Vanommeslaeghe Kenno , MacKerell Alexander D.
Published: July 2012

Presented is an extension of the CHARMM General Force Field (CGenFF) to enable the modeling of sulfonyl‐containing compounds. Model compounds containing chemical moieties such as sulfone, sulfonamide, sulfonate, and sulfamate were used as the basis for the parameter optimization. Targeting high‐level quantum mechanical and experimental crystal data, the new parameters were optimized in a hierarchical fashion designed to maintain compatibility with the remainder of the CHARMM additive force field. The optimized parameters satisfactorily reproduced equilibrium geometries, vibrational frequencies, interactions with water, gas phase dipole moments, and dihedral potential energy scans. Validation involved both crystalline and liquid phase calculations showing the newly developed parameters to satisfactorily reproduce experimental unit cell geometries, crystal intramolecular geometries, and pure solvent densities. The force field was subsequently applied to study conformational preference of a sulfonamide based peptide system. Good agreement with experimental IR/NMR data further validated the newly developed CGenFF parameters as a tool to investigate the dynamic behavior of sulfonyl groups in a biological environment. CGenFF now covers sulfonyl group containing moieties allowing for modeling and simulation of sulfonyl‐containing compounds in the context of biomolecular systems including compounds of medicinal interest. © 2012 Wiley Periodicals, Inc.
Preparation and Characterization of Sulfonated Polyacrylamide from Polyacrylonitrile for Proton Conductive Membranes
Authors: Touheed Azra , Maab Husnul
Published: July 2012

Polyacrylonitrile (PAN) was sulfonated and the membranes prepared were then characterized by the FTIR‐ATR, Elemental Analyzer EA, TGA, DSC, SEM, Tensile, Water uptake and Impedance tests. FTIR‐ATR spectra show the substitution of the sulfonic group (SO3) to the main stem of the chain and also the hydrolysis of the cyanide group to amide group confirm the conversion of polyacrylonitrile to sulfonated polyacrylamide. Increase in water uptake property as compared to pure PAN also confirms the sulfonation process has occurred. Thermal properties also confirm the enhancement of the materials after sulfonation reaction.
Microwave‐assisted Synthesis of Flower‐like Structure ϵ‐MnO2 as Cathode for Lithium Ion Batteries
Authors: Li Dan , Du Guodong , Wang Jieqiang , Guo Zaiping , Chen Zhixin , Liu Huakun
Published: July 2012

Nanostructured flower‐like ϵ‐MnO2 and α‐MnO2 nanowires were prepared by the microwave‐assisted hydrothermal method at 110 °C and 140 °C. The ϵ‐nanoflowers are about 500 nm in size and are composed of petals about 100 nm in length, while the α‐nanowires are 20‐30 μm in diameter and about 1 mm in length. The ϵ‐MnO2 demonstrates higher initial discharge capacity, while the α‐MnO2 shows greater cycling stability in different voltage ranges. Both phases of MnO2 show better cycling performance in ethylene carbonate (EC)/diethyl carbonate electrolyte (DEC) than in EC/dimethyl carbonate (DMC) electrolyte. The ϵ‐MnO2 sample delivered a discharge capacity of 116.2 mAh g−1 for up to 100 cycles, indicating that it is a promising cathode material for lithium ion batteries.
Preparation and Characterization of Fe‐substituted Li3V2(PO4)3 Cathodes for Li‐ion Batteries
Authors: Wu She‐hung , Chen Mao‐Sung , Pang Wei Kong , Liu Fan‐Ping
Published: July 2012

In this study, Li3V2(1‐x)Fe3x(PO4)3 (0 ≤ x ≤ 0.09) powders are prepared via a solution method and heattreated at 700 °C for 8 hours. The chemical composition, morphology, crystalline structure, and valence of iron in the prepared samples were investigated with ICP, SEM, XRD, and EXAFS. The effects of Fe‐substitution for vanadium sites on the electrochemical properties as cathode materials for lithium ion batteries are studied with capacity retention study and incremental capacity analysis. In addition to the monoclinic Li3V2(PO4)3 phase, olivine LiFePO4 is also observed when x ≥ 0.03. The valence of iron in the prepared powders is predominately 3+ at low substitution level (x ≤ 0.05), while the ratio of the Fe2+ to Fe3+ increases abruptly when the substitution level is higher than x = 0.07. Among the prepared samples, Li3V1.86Fe0.21(PO4)3 shows the best cycling performance at rates higher than 1C. It demonstrates discharge capacities of 141.2 mAh/g for second cycle and 126 mAh/g after 30 cycles at 5C rate.
MR assessment of regional myocardial mechanics
Authors: Simpson Robin M. , Keegan Jennifer , Firmin David N.
Published: July 2012

Regional myocardial function can be measured by several MR techniques including tissue tagging, phase velocity mapping, and more recently, displacement encoding with stimulated echoes (DENSE) and strain encoding (SENC). Each of these techniques was developed separately and has undergone significant change since its original implementation. As a result, in the current literature, the common features and the differences between the techniques and what they measure are often unclear and confusing. This review article delivers an extensively referenced introductory text which clarifies the current methodology from the starting point of the Bloch equations. By doing this in a consistent way for each method, the similarities and differences between them are highlighted. In addition, their capabilities and limitations are discussed, together with their relative advantages and disadvantages. While the focus is on sequence design and development, the principal parameters measured by each technique are also summarized, together with brief results, with the reader being directed to the extensive literature on data processing and clinical applications for more detail. J. Magn. Reson. Imaging 2013;37:576–599. © 2012 Wiley Periodicals, Inc.
Hepatitis C viremia and genotype distribution among a sample of nonmedical prescription drug users exposed to HCV in rural Appalachia
Authors: Young April M. , Crosby Richard A. , Oser Carrie B. , Leukefeld Carl G. , Stephens Dustin B. , Havens Jennifer R.
Published: July 2012

Research has demonstrated that hepatitis C (HCV) genotype distribution varies geographically and demographically. This exploratory study examines HCV viremia, viral concentration, and genotype distribution among anti‐HCV positive, rural Appalachian nonmedical prescription drug users. The study population was randomly selected from a pool of 200 anti‐HCV positive participants in a longitudinal study. Those randomly chosen were representative of the overall pool in terms of demographics, drug use, and other risk behaviors. Participants were tested serologically for HCV RNA, viral concentration, and genotype, and interview‐administered questionnaires examined behavioral and demographic characteristics. Of the 81 participants, 69% tested RNA positive, 59% of which had viral loads exceeding 800,000 IU/ml. Approximately 66% of the RNA positive sample had genotype 1a; types 2b (16%) and 3a (13%) were less common. RNA positive participants were not significantly different than RNA negative participants demographically or behaviorally. Likewise, with the exception of education, genotype 1 participants were not significantly different than those with genotype 2 or 3. The prevalence of active HCV infection highlights a need for prevention and treatment in this population. However, the predominance of genotype 1 may present challenges due to its association with decreased responsiveness to drug treatment, although the novel class of direct‐acting antivirals such as telaprevir and boceprevir offer new hope in this regard. The prevalence of genotype 1 may also foreshadow heightened burden of hepatocellular carcinoma and elevated healthcare expenditures. More research is needed to characterize HCV infection and genotype in this population. J. Med. Virol. 84:1376–1387, 2012. © 2012 Wiley Periodicals, Inc.