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© 2019 Elsevier Inc. The concentration of a number of trace elements (Ag, Al, As, B, Ba, Be, Bi, Cd, Cr, Co, Cu, Fe, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Sm, Sr, Sn, Tl, Ti, V and Zn) were determined in 42 commercialized denim garments (jeans and shirts), being dermal exposure subsequently assessed. Migration experiments with artificial acid and basic sweat were also conducted to determine the release of these elements, as well as indigo dye. In a similar way than for the total content, Mg (124 and 99.4 µg/g) and Mn (27.1 and 7.20 µg/g) showed the highest concentrations in both artificial sweat, acid and basic, respectively. Indigo dye migrated at levels ranged from 3.22 to 7.76 mg/g, being higher in dark than in light blue fabrics. The levels of trace elements and indigo were analysed according to materials of fabric, colour, brand, and eco-labelling. Using total content and migrations rates, dermal exposure to trace elements for adult men, women and teenagers were calculated under the two sweat extractions. Non-carcinogenic and carcinogenic risks due to dermal exposure to the elements here analysed in cloths were assessed. Both risks were in the limits of safe to according to international regulations. However, the maximum exposure to Sb reached a hazard quotient (HQ) of 0.3 in clothes partially made of polyester. Despite some authors have established that indigo is an agonist of the aril receptor, health risks due to exposure to indigo dye were not calculated due the lack of toxicological data.

The coelomycetous fungi are difficult to properly identify from their phenotypic characterization and their role as etiologic agents of human infections is not clear. We studied the species distribution of these fungi among clinical isolates that had been collected and stored over a ten-year period in two European reference laboratories (France and Spain). We identified phenotypically and molecularly 97 isolates by sequencing the D1-D2 fragment of the 28S nrRNA (LSU) gene and we provided the in vitro antifungal susceptibility pattern of seven antifungals against 46 isolates. Species of the orders Pleosporales and Glomerellales were present in both collections, and Botryosphaeriales and Diaporthales only in the French one. The most prevalent species were Medicopsis romeroi, Neocucurbitaria keratinophila, Neocucurbitaria unguis-hominis and Paraconiothyrium cyclothyrioides, which had been recovered primarily from superficial tissues. The Didymellaceae was the most common family represented, with 27 isolates distributed into five genera. Most of the isolates tested were susceptible to antifungals, and only the geometric mean (GM) and minimal inhibitory concentration (MIC) values of itraconazole and caspofungin had higher values. This study provides a good picture of the great diversity of coelomycetous fungi in the European clinical context, and the basis for future studies on this interesting but neglected group of fungi.Copyright © 2019 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

© The Author(s) 2019. Background. Whether antibiotic treatment of asymptomatic bacteriuria (AB) can prevent acute graft pyelonephritis (AGP) in kidney transplant (KT) recipients has not been elucidated. Methods. In this multicenter, open-label, nonblinded, prospective, noninferiority, randomized controlled trial, we compared antibiotic treatment with no treatment for AB in KT recipients in the first year after transplantation when urinary catheters had been removed. The primary endpoint was the occurrence of AGP. Secondary endpoints included bacteremic AGP, cystitis, susceptibility of urine isolates, graft rejection, graft function, graft loss, opportunistic infections, need for hospitalization, and mortality. Results. We enrolled 205 KT recipients between 2013 and 2015. AB occurred in 41 (42.3%) and 46 (50.5%) patients in the treatment and no treatment groups, respectively. There were no differences in the primary endpoint in the intention-to-treat population (12.2% [5 of 41] in the treatment group vs 8.7% [4 of 46] in the no treatment group; risk ratio, 1.40; 95% confidence interval, 0.40-4.87) or the per-protocol population (13.8% [4 of 29] in the treatment group vs 6.7% [3 of 45] in the no treatment group; risk ratio, 2.07, 95% confidence interval, 0.50-8.58). No differences were found in secondary endpoints, except for antibiotic susceptibility. Fosfomycin (P = .030), amoxicillin-clavulanic (P < .001) resistance, and extended-spectrum ß-lactamase production (P = .044) were more common in KT recipients receiving antibiotic treatment for AB. Conclusions. Antibiotic treatment of AB was not useful to prevent AGP in KT recipients and may increase antibiotic resistance. However, our findings should be regarded with caution, due to the small sample size analyzed.

Since 1998, a monitoring program is periodically performed to assess the environmental and human health impact of air chemicals potentially emitted by a hazardous waste incinerator (HWI) located in Constantí (Catalonia, Spain). In 2017, samples of hair were collected from 94 schoolchildren (aged 10-13 years) living nearby and the levels of 11 trace elements (As, Be, Cd, Cr, Hg, Mn, Ni, Pb, Sn, Tl and V) were determined. The concentrations showed the following descending order: Pb > Hg > Ni > Sn > Mn > Cr. In turn, As, Be and Tl were not detected, while Cd and V were found only in a few samples. Some metal levels were significantly, positively correlated. Some significant differences were also noticed according to the gender and the specific zone of residence. Finally, the levels of trace elements showed fluctuations through time. Cr and Pb showed a significant decrease in comparison to the concentrations obtained in the baseline study (1998). According to the current results, metal emissions from the HWI are not relevant in terms of human health impact since their levels were similar and even lower than those reported in other contaminated areas.

Background: Glucose-regulated protein 78/Binding immunoglobulin protein (GRP78/BiP) is a protein associated with endoplasmic reticulum stress and is upregulated by metabolic alterations at the tissue-level, such as hypoxia or glucose deprivation, and it is hyper-expressed in fat tissue of obese individuals. Objective: To investigate the role of the GRP78/BiP level as a metabolic and vascular disease biomarker in patients with type 2 diabetes (DM), obesity and metabolic syndrome (MS). Methods: Four hundred and five patients were recruited, of whom 52.5% were obese, 72.8% had DM, and 78.6% had MS. The intimae media thickness (cIMT) was assessed by ultrasonography. The plasma GRP78/BiP concentration was determined, and its association with metabolic and vascular parameters was assessed. Circulating GRP78/BiP was also prospectively measured in 30 DM patients before and after fenofibrate/niacin treatment and 30 healthy controls. Results: In the cross-sectional study, the GRP78/BiP level was significantly higher in the patients with obesity, DM, and MS. Age-, gender- and BMI-adjusted GRP78/BiP was directly associated with LDL-cholesterol, non-HDL-cholesterol, triglycerides, apoB, and cIMT. GRP78/BiP was positively associated to carotid plaque presence in the adjusted model, irrespective of obesity, DM and MS. In the prospective study, nicotinic acid treatment produced a significant reduction in the GRP78/BiP levels that was not observed with fenofibrate. Conclusions: GRP78/BiP plasma concentrations are increased in patients with both metabolic derangements and subclinical atherosclerosis. GRP78/BiP could be a useful marker of metabolic and cardiovascular risk.

Graves ophthalmopathy (GO) is an autoimmune disorder and the most frequent extrathyroidal manifestation of Graves' disease. GO is an inflammatory process leading to an increased volume of the extraocular muscles and orbital connective and adipose tissues associated with multiple histopathological changes. Despite recent progress in the understanding of its pathogenesis, GO often remains a major diagnostic and therapeutic challenge. It has become increasingly important to classify patients into categories based on disease severity and activity. Low doses of radiotherapy (RT) have demonstrated a benefit in the treatment of moderate-to-severe GO with very few side effects. New RT techniques deliver a more conformal dose distribution to the target and decrease the dose to normal healthy tissue minimizing the risk of side effects. In this review we briefly analyzed the pathogenesis of GO and discussed the most relevant therapeutic approaches, with particular emphasis in the new RT technics. Appropriately designed and powered clinical studies are necessary to determine the most effective treatment with the lowest risk of side effects.

Insulin resistance (IR) and impaired glucose tolerance (IGT) are the first manifestations of diet-induced metabolic alterations leading to Type 2 diabetes, while hypertension is the deadliest risk factor of cardiovascular disease. The roles of dietary fat and fructose in the development of IR, IGT, and hypertension are controversial. We tested the long-term effects of an excess of fat or sucrose (fructose/glucose) on healthy male Wistar-Kyoto (WKY) rats. Fat affects IR and IGT earlier than fructose through low-grade systemic inflammation evidenced by liver inflammatory infiltration, increased levels of plasma IL-6, PGE2, and reduced levels of protective short-chain fatty acids without triggering hypertension. Increased populations of gut Enterobacteriales and Escherichia coli may contribute to systemic inflammation through the generation of lipopolysaccharides. Unlike fat, fructose induces increased levels of diacylglycerols (lipid mediators of IR) in the liver, urine F2-isoprostanes (markers of systemic oxidative stress), and uric acid, and triggers hypertension. Elevated populations of Enterobacteriales and E. coli were only detected in rats given an excess of fructose at the end of the study. Dietary fat and fructose trigger IR and IGT in clearly differentiated ways in WKY rats: early low-grade inflammation and late direct lipid toxicity, respectively; gut microbiota plays a role mainly in fat-induced IR, and hypertension is independent of inflammation-mediated IR. The results provide evidence that suggests that the combination of fat and sugar is potentially more harmful than fat or sugar alone when taken in excess.

Multi-target-directed ligands (MTDLs) offer new hope for the treatment of multifactorial complex diseases such as Alzheimer's Disease (AD). Herein, we present compounds aimed at targeting the NMDA and the P2X7 receptors, which embody a different approach to AD therapy. On one hand, we are seeking to delay neurodegeneration targeting the glutamatergic NMDA receptors; on the other hand, we also aim to reduce neuroinflammation, targeting P2X7 receptors. Although the NMDA receptor is a widely recognized therapeutic target in treating AD, the P2X7 receptor remains largely unexplored for this purpose; therefore, the dual inhibitor presented herein¿which is open to further optimization¿represents the first member of a new class of MTDLs

The metabolic alterations associated with obesity include mineral dysregulation. Essential trace elements are nutrients with a relevant function in a large number of cellular processes and multiple roles in the correct functioning of metabolic enzymes. Paraoxonase-1 (PON1) is an antioxidant and anti-inflammatory enzyme that is compromised in obesity. In the present study, the potential alterations in trace elements in morbidly obese women were assessed in relation to serum PON1 activity and concentration, as well as to other obesity-related comorbidities such as diabetes mellitus and fatty liver. We recruited 41 morbidly obese women and 51 control individuals. The serum concentrations of 30 elements, PON1 paraoxonase and lactonase activities, and PON1 concentration were measured. We observed significant alterations in the levels of As, Ba, Cu, Ca, Fe, Mg, Na, Se, Sr, and Zn in obese women; some of them (As, Ca, Cr, Cu, Mg, and Se) being significantly correlated with serum PON1 values. The most relevant changes were observed in the concentrations of As, Sr and Mg, the last of which was also significantly associated with diabetes mellitus. The current results raise the possibility that increased ingestion and/or storage of a number of trace elements may be factors predisposing to obesity-related comorbidities and metabolic alterations.Copyright © 2018 Elsevier GmbH. All rights reserved.

Previously to the modernization of the municipal solid waste incinerator (MSWI) of Campdorà (Girona, Catalonia, Spain) two sampling campaigns (2015 and 2016) were conducted. In each campaign, 8 soil and 4 air samples (PM10 and total particle phase and gas phase) were collected. The levels of As, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Sn, Tl and V, and PCDD/Fs were analysed at different distances and wind directions around the MSWI. Environmental levels of trace elements and PCDD/Fs were used to assess exposure and health risks (carcinogenic and non-carcinogenic) for the population living around the facility. In soils, no significant differences were observed for trace elements and PCDD/Fs between both campaigns. In air, significant higher levels of As, Cd, Co, Mn, Ni, Pb, Tl and V were detected in 2016. Regarding soil levels, only Cd (distances) and As, Cu, Mn, and Ni (wind directions) showed significant differences. No differences were noted in the concentrations of trace elements and PCDD/Fs in air levels with respect to distances and directions to the MSWI. No differences were registered in air levels (elements and PCDD/Fs) between points influenced by MSWI emissions and background point. However some differences in congener profile were noted regarding from where back-trajectories come from (HYSPLIT model results), pointing some influence of Barcelona metropolitan area. The concentrations of trace elements and PCDD/Fs were similar -or even lower- than those reported around other MSWIs in Catalonia and various countries. Non-carcinogenic risks were below the safety limit (HQ<1). In turn, carcinogenic risks due to exposure to trace elements and PCDD/Fs were in acceptable ranges, according to national and international standard regulations.Copyright © 2018 Elsevier B.V. A

© 2018 Elsevier Ltd Organophosphorus pesticides – and in particular chlorpyrifos (CPF) – are extensively used worldwide. They mainly exert their toxicity by targeting the cholinergic system. Several studies suggested that the gene coding for apolipoprotein E (apoE), which is a risk factor for several diseases, can also confer different vulnerability to toxic insults. This study was aimed at assessing the long-term effects of postnatal exposure to CPF on learning and memory as well as the expression levels of several genes involved in cholinergic neurotransmission in mice. Both male and female apoE4-TR and C57BL/6 mice were exposed to either 0 or 1 mg/kg/day of CPF by oral gavage using a micropipette on postnatal days 10–15. At 9 months, they were tested in a Morris Water Maze (MWM) and the gene expression in the frontal cortex and hippocampus was evaluated. Our results show that, in males, CPF had an effect on the spatial retention, while in females, it altered the expression levels of nicotinic receptors. Furthermore, apoE4-TR mice performed the worst during the MWM retention and presented low expression levels in a considerable number of cholinergic genes. Taken together, the current results reveal long-term effects in mice nine months after postnatal exposure to CPF, which are modulated by sex and apoE4 genotype.

u Purpose: To determine the effects of the intake of low-fat yoghurt supplemented with rooster comb extract (RCE) on muscle strength. Methods and results: 148 subjects, with mild knee pain, participated in a randomized, placebo-controlled, double-blind, and parallel study. Muscle strength, knee effusion, and pain perception were measured. C2C12 myoblasts were used to elucidate the mechanisms of action involved. RCE improved total work and mean power in men, and also peak torque in extension by 10%. RCE reduced synovial effusion by 11.8% and pain perception by 24.6%. Both RCE and HA increased myoblast proliferation by 29%, while RCE reduced myoblast differentiation by 36.2%, suggesting a beneficial role of RCE in muscle regeneration. Conclusions: Low-fat yoghurt supplemented with RCE improved muscle strength. This effect is partially explained by muscle regeneration enhancement, reduced synovial effusion, and reduced pain perception, which could exert a beneficial clinical impact on men affected by mild knee pain.

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Scope: The main findings of the “Virgin Olive Oil and HDL Functionality” (VOHF) study and other related studies on the effect of phenol-enriched virgin olive oil (VOO) supplementation on cardiovascular disease are integrated in the present work. Methods and results: VOHF assessed whether VOOs, enriched with their own phenolic compounds (FVOO) or with those from thyme (FVOOT), improve quantity and functionality of HDL. In this randomized, double-blind, crossover, and controlled trial, 33 hypercholesterolemic subjects received a control VOO (80 mg kg−1), FVOO (500 mg kg−1), and FVOOT (500 mg kg−1; 1:1) for 3 weeks. Both functional VOOs promoted cardioprotective changes, modulating HDL proteome, increasing fat-soluble antioxidants, improving HDL subclasses distribution, reducing the lipoprotein insulin resistance index, increasing endogenous antioxidant enzymes, protecting DNA from oxidation, ameliorating endothelial function, and increasing fecal microbial metabolic activity. Additional cardioprotective benefits were observed according to phenol source and content in the phenol-enriched VOOs. These insights support the beneficial effects of OO and PC from different sources. Conclusion: Novel therapeutic strategies should increase HDL-cholesterol levels and enhance HDL functionality. The tailoring of phenol-enriched VOOs is an interesting and useful strategy for enhancing the functional quality of HDL, and thus, it can be used as a complementary tool for the management of hypercholesterolemic individuals.

137-Cesium (137Cs) is one of the most important distributed radionuclides after a nuclear accident. Humans are usually co-exposed to various environmental toxicants, being Bisphenol-A (BPA) one of them. Exposure to IR and BPA in early life is of major concern, due to the higher vulnerability of developing organs. We evaluate the renal and hepatic effects of low doses of ionizing radiation (IR) and BPA. Sixty male mice (C57BL/6J) were randomly assigned to six experimental groups (n=10) and received a single subcutaneous dose of 0.9% saline solution, 137Cs and/or BPA on postnatal day 10: control, BPA (25 ?g/kgbw), Cs4000 (4000 Bq 137Cs/kgbw), Cs8000 (8000 Bq 137Cs/kgbw), BPA/Cs4000 and BPA/Cs8000. At the age of two months, urines (24h) and blood samples were collected from animals of each group to determine biochemical parameters. Finally, kidneys and liver were removed to quantify DNA damage (8-OHdG), as well as to determine CYP1A2 mRNA expression. Data suggest that both BPA and 137Cs induced renal and liver damage evidenced by oxidative stress. However, when there is a co-exposure, it seems that there are compensatory mechanisms that may reverse the damage induced by each toxic itself. Notwithstanding, more studies are necessary to better understand the synergistic mechanisms behind.Copyright © 2018 Elsevier Ltd. All rights reserved.

The taxonomy of the fungi that produce human infections and that develop asexual fruiting bodies in culture has become very complex. Recent molecular studies have produced dramatic changes in their classification. Currently, the coelomycetes traditionally included in Sphaeropsidales and Melanconiales are in fact distributed across at least three different classes of the Phylum Ascomycota. Approximately 1000 genera and 7000 species have been grouped in the classes Dothideomycetes, Leotiomycetes and Sordariomycetes and their proper identification can only be made by analysing their DNA sequences and comparing them with those corresponding to type strains available in the adequate databases. To facilitate this task for scientists and clinicians involved in the study of these complex, and every day more numerous taxa, we have updated the knowledge about the taxonomy of the commonest coelomycetes of clinical interest with the aim of improving their identification and antifungal treatment.© 2018 Blackwell Verlag GmbH.

The order Melanosporales comprises a large group of ascomycetes, most of them mycoparasites, characterized by the production of usually ostiolate, translucent ascomata, unitunicate asci, and unicellular, pigmented ascospores with germ pores or germ slits. The most studied taxa are Melanospora and Sphaerodes, but the boundaries with other morphologically closely related genera are not well resolved. In this study, the taxonomy of Melanospora and related taxa have been re-evaluated based on the analysis of nuclear rDNA, actin and elongation factor genes sequences of fresh isolates and numerous type and reference strains. The genus Melanospora has been restricted to species with ostiolate ascoma whose neck is composed of intermixed hyphae, and with a phialidic asexual morph. Microthecium has been re-established for species of Melanospora and Sphaerodes without a typical ascomatal neck or, if present, being short and composed of angular cells similar to those of the ascomatal wall, and usually producing bulbils. Three new genera have been proposed: Dactylidispora, possessing ascospores with a raised rim surrounding both terminal germ pores; Echinusitheca, with densely setose, dark ascomata; and Pseudomicrothecium, characterized by ascospores with indistinct germ pores. Dichotomous keys to identify the accepted genera of the Melanosporales, and keys to discriminate among the species of Melanospora and Microthecium, as well as a brief description of the accepted species of both genera, are also provided.

The genus Arcobacter comprises Campylobacter-related species, considered zoonotic emergent pathogens, the presence of which in water has been associated with fecal pollution. Discharges of fecal polluted water into the sea have been considered as one of the main reasons for the presence of Arcobacter in shellfish, and this may represent a risk for public health. In this study, the European Union shellfish food safety criteria based on levels of Escherichia colt were studied in relation to their capacity to predict the presence of Arcobacter species. In addition, the accumulation factor (AF) that measures the concentration ratio between the microbes present in the shellfish and in the water, was also studied for both bacteria. The results show that the presence of E. colt correlated with the presence of the potentially pathogenic species A butzleri and A. cryaerophilus. However, in 26.1% of the shell-fish samples (corresponding to those taken during summer months) E. coil failed to predict the presence of, for instance A. butzleri and A. skirrowii, among other species. In the rest of the samples a significant correlation between the concentration of E. coil and Arcobacter spp. (mussels and oyster; R-2 = 0.744) was found. This study indicates that the presence of E. coli can predict the presence of pathogenic Arcobacter species in shellfish samples harvested from water with temperatures lower than 26.2 degrees C. Consumption of shellfish collected at higher temperatures which may not be permissive to the growth of E. coil but does allow growth of Arcobacter spp., may represent a risk for consumers. (C) 2017 Elsevier B.V. All rights reserved.

© 2018 Elsevier Inc. Particulate matter (PM) composition has a key role in a wide range of health outcomes, such as asthma, chronic obstructive pulmonary disease, lung cancer, cardiovascular disease, and death, among others. Montcada i Reixac, a municipality located in the Barcelona metropolitan area (Catalonia, Spain), for its location and orography, is an interesting case- study to investigate air pollution. The area is also characterized by the presence of different industrial emission sources, including a cement factory and a large waste management plant, as well as an intense traffic. In this study, PM 10 levels, trace elements, ions, and carbonaceous particles were determined for a long time period (2013–2016) in this highly polluted area. PM 10 samples were collected during six consecutive days in two campaigns (cold and warm) per year. A number of elements (As, Ba, Be, Bi, Ca, Cd, Ce, Co, Cr, Cs, Cu, Dy, Er, Eu, Fe, Ga, Gd, Ge, Hf, Hg, Ho, K, La, Li, Hg, Mg, Mn, Mo, Nb, Nd, Ni, Pb, Pr, Rb, Sb, Sc, Se, Sm, Sn, Sr, Tb, Th, Ti, Tl, U, V, W, Y, Yb, and Zr), ions (Cl - , SO 4 2- , NO 3 - , and NH 4 + ), and carbonaceous content (total carbon, organic plus elemental carbon, and CO 3 2- ), were analysed. These data were used to identify the PM 10 main components: mineral matter, sea spray, secondary inorganic aerosols, organic matter plus elemental carbon, trace elements or indeterminate fraction. Although a clear seasonality (cold vs. warm periods) was found, there were no differences between working days and weekends. Obviously, the cement plant influences the surrounding environment. However, no differences in trace elements related with the cement plant activity (Al, Ca, Ni and V) between weekdays and weekends were noted. However, some traffic-related elements (i.e

To evaluate if the dose equivalent to 2 Gy per fraction (EQD2)(?/?=3Gy) at 0.1 cm3, 1 cm3, and 2 cm3 of vagina in vaginal-cuff-brachytherapy (VBT) (high-dose-rate [HDR] 192Ir-source) ± external-beam-irradiation (EBRT) is associated with toxicity in post-operative endometrial carcinoma (P-EC).From June 2014 till November 2015, 67 consecutive P-EC patients underwent VBT ± EBRT; 44 patients received EBRT (median, 45 Gy; range, 44-50.4) + VBT (7 Gy), and 23 exclusive-VBT (6 Gy x 3 fractions). The upper 2.5 cm of vagina was delineated on computed tomography (CT). The active-length source was 2.5 cm, and the brachytherapy dose was prescribed at 5 mm from the applicator. D90, V100, and EQD2(?/?=3Gy) at 0.1 cm3, 1 cm3, and 2 cm3 of the most exposed part of the vagina were calculated. Vaginal toxicity assessment was completed with a LENT-SOMA-objective-criteria. Statistics were done with the use of ?2 and Student's-t test.The mean follow-up was 23.2 months (7.6-46.8). Median D90 was 7.8 Gy(?/?=3Gy). Late toxicity: 8 G1 and 9 G2. Median EQD2(?/?=3Gy) in vagina was 88.6 Gy (62.8-177.6) for 0.1 cm3, 72.4 Gy (57.1-130.4) for 1 cm3, and 69 Gy (53-113.4) for 2 cm3. Exclusive VBT vs. EBRT+VBT showed no differences in vaginal toxicity. There was no relationship between EQD2(?/?=3Gy) at 0.1 cm3 and 1 cm3 of vagina with G1-G2 toxicity (p = 0.62 and p = 0.58, respectively). G2 toxicity was related to EQD2(?/?=3Gy) at 2 cm3 (p = 0.03). EQD2(?/?=3Gy) > 68 Gy caused G2 late toxicity in 20.5% patients. All patients presenting G2 toxicity received > 68 Gy EQD2(?/?=3Gy).More than 68 Gy EQD2(?/?=3Gy) at 2 cm3 was related to G2 toxicity in P-EC-VBT. Further studies including larger number of patients are needed to confirm these results. Patients receiving these doses should be informed of the risk

In May 2016, a big fire occurred in an illegal landfill placed in Seseña (Toledo, Spain), where between 70,000 and 90,000 tons of tires had been accumulated during years. Just after the fire, and because of the increase of airborne PAHs, we found that cancer risks for the population living in the neighborhood of the landfill were 3-5 times higher than for the rest of inhabitants of Seseña. Some months after our initial (June 2016) study, two sampling campaigns (December 2016 and May 2017) were performed to assess the temporal trends of the environmental levels of PAHs, as well as to reassure that these chemicals did not pose any risk for the human health of Seseña inhabitants. In soils, the total concentrations of the 16 PAHs (December 2016), as well as the sum of the seven carcinogenic PAHs, showed values between 8.5 and 94.7 ng g-1 and between 1.0 and 42.3 ng g-1, respectively. In May 2017, a significant decrease (between 4 and 38 times) in the levels of PAHs in air was observed, with total concentrations ranging between 3.49 and 5.06 ng m-3. One year after the fire, the cancer risk at different zones of Seseña was similar, being lower than that found in June 2016, and negligible according to national and international agencies.

© Springer Nature Switzerland AG 2018. This paper proposes a novel approach based on conditional Generative Adversarial Networks (cGAN) for breast mass segmentation in mammography. We hypothesized that the cGAN structure is well-suited to accurately outline the mass area, especially when the training data is limited. The generative network learns intrinsic features of tumors while the adversarial network enforces segmentations to be similar to the ground truth. Experiments performed on dozens of malignant tumors extracted from the public DDSM dataset and from our in-house private dataset confirm our hypothesis with very high Dice coefficient and Jaccard index (>94% and >89%, respectively) outperforming the scores obtained by other state-of-the-art approaches. Furthermore, in order to detect portray significant morphological features of the segmented tumor, a specific Convolutional Neural Network (CNN) have also been designed for classifying the segmented tumor areas into four types (irregular, lobular, oval and round), which provides an overall accuracy about 72% with the DDSM dataset.

© 2018 The authors and IOS Press. Breast density is a crucial factor to follow-up the relapse of breast cancer in mammograms and the risk of local recurrence after conservative surgery and/or radiotherapy. Accurate breast density estimation with visual assessment is still a challenge due to faint contrast and significant variations in background fatty tissues in mammograms. The important key of breast density estimation is to properly detect the dense tissues in a mammographic image. Thus, this paper presents an automatic deep breast density segmentation using conditional Generative Adversarial Networks (cGAN) that consist of two successive deep networks: generator and discriminator. The generator network learns the mapping from the input mammogram to the output binary mask detection the area of the dense tissues. In turn, the discriminator learns a loss function to train this mapping by comparing the ground-truth and the predicted mask under observing the input mammogram as a condition. The performance of the proposed model was evaluated on the public INbreast mammographic datasets. The proposed model can segment the dense regions with overall recall, precision and F-score about 95%, 92%, and 93%, respectively, outperforming state-of-the-art of breast density segmentation. The proposed model can segment more than 40 images with a size of 512×512 per second on a recent GPU.

The aims of this study were to investigate changes in energy balance-associated metabolites associated with radiotherapy in patients with breast cancer, and to relate these changes to the clinical and pathological response-to-treatment. We studied 151 women with breast cancer who received radiotherapy following surgical excision of the tumor. Blood was obtained before and after the irradiation procedure. The control group was composed of 44 healthy women with a similar age distribution to that of the patients. We analyzed the concentrations of metabolites involved in glycolysis, citric acid cycle and amino acid metabolism using targeted quantitative metabolomics. Post-surgery, pre-radiotherapy, patients had major alterations in the serum concentrations of products of glycolysis, citric acid cycle and amino acid metabolism. The strongest alterations were decreases in serine, leucine and isoleucine concentrations. Alterations in metabolite levels were partially, or totally, reversed after irradiation; the concentrations of serine, leucine and isoleucine approached equivalence to those of the control group. Estrogen receptor-positive patients were those with lower concentrations, while triple negative patients had higher concentrations of these amino acids. The normalization of the amino acids serine, leucine and isoleucine concentrations could be clinically relevant because the normalization of these energy-balance metabolites would suggest that residual micro-metastatic disease had been effectively diminished by the radiotherapy, and may be an indicator of its efficacy.

Alterations in the circulating levels of trace elements have been observed in breast cancer (BC) patients. However, the relationships between these alterations and the metabolic and clinical consequences of BC are unknown. The treatment-of-choice of BC is surgery followed by radiation therapy (RT). The present study was aimed at investigating: 1) the concentrations of several trace elements in BC patients, and their relationships with the intrinsic molecular subtypes of tumors; 2) the toxicological effect of RT. We studied 49 women with BC who were scheduled to receive RT following excision of the tumor. Plasma samples were obtained before and after the irradiation procedure. The control group was composed of 49 healthy women. Patients had significantly lower pre-RT concentrations of B, Cu, and Zn, and significantly higher concentrations of Sr than the control group. Irradiation was associated with a striking increase in plasma B concentrations, while Cu, Fe, Sr and Zn concentrations were not significantly different from pre-RT levels, albeit Sr and Zn showed non-significant trends towards increases. The plasma concentrations of B, Cu, Fe, Sr, and Zn were associated with the tumor expression of hormone receptors, epidermal growth factor receptor 2, Ki67 antigen, as well as dermatitis and asthenia, all of which represent the main toxicological responses to RT.Copyright © 2018 Elsevier Ltd. All rights reserved.

Mucormycosis is an emerging opportunistic fungal infection. Increasing immunocompromization, widespread use of antibacterial and antifungal agents (such as voriconazole prophylaxis), carcinomas, transplantation and lifestyle diseases such as diabetes are the main contributors to this situation. The predominant clinical manifestations of mucormycosis vary from host to host, with rhino-orbital-cerebral, pulmonary, cutaneous, and gastrointestinal infections being the most common. In India, the prevalence of mucormycosis is approximately 0.14 cases/1000 population, which is about 70 times the worldwide-estimated rate for mucormycosis. The present study was undertaken over a period of five years (January 2009-December 2014) to determine the prevalence of mucormycosis. The samples suspected of mucormycosis were examined by direct KOH wet mount and cultured on Sabouraud's dextrose agar without actidione and on blood agar as per standard mycological techniques. Histopathological correlation was done for most of the cases. Antifungal susceptibility testing was performed by the EUCAST reference method. We identified a total of 82 cases of mucormycosis out of a total of 6365 samples received for mycological culture and examination during the said time period. Out of these, 56 were male patients and 27 were females. Most common presentation was rhino-orbito-cerebral (37), followed by cutaneous (25), pulmonary (14), oral cavity involvement (4) and gastrointestinal (2). The most common risk factors were diabetes and intramuscular injections. The fungi isolated were Rhizopus arrhizus (17), Apophysomyces variabilis (12), R. microsporus (9), Lichtheimia ramosa (8), Saksenaea erythrospora (5), Syncephalastrum racemosus (4), R. homothallicus (2), Rhizomucor pusillus (1), Mucor irregularis

With new radiotherapy techniques, treatment delivery is becoming more complex and accordingly, these treatment techniques require dosimetry audits to test advanced aspects of the delivery to ensure best practice and safe patient treatment.This review of novel methodologies for dosimetry audits for advanced radiotherapy techniques includes recent developments and future techniques to be applied in dosimetry audits. Phantom-based methods (i.e. phantom-detector combinations) including independent audit equipment and local measurement equipment as well as phantom-less methods (i.e. portal dosimetry, transmission detectors and log files) are presented and discussed. Methodologies for both conventional linear accelerator (linacs) and new types of delivery units, i.e. Tomotherapy, stereotactic devices and MR-linacs, are reviewed.Novel dosimetry audit techniques such as portal dosimetry or log file evaluation have the potential to allow parallel auditing (i.e. performing an audit at multiple institutions at the same time), automation of data analysis and evaluation of multiple steps of the radiotherapy treatment chain. These methods could also significantly reduce the time needed for audit and increase the information gained. However, to maximise the potential, further development and harmonisation of dosimetry audit techniques are required before these novel methodologies can be applied.

Background and purpose: It is known that intensity-modulated radiotherapy plans that are highly complex might be less accurate in dose calculation and treatment delivery. Multiple complexity metrics have been proposed, but the relationships between them have not been thoroughly investigated. This study investigated these relationships in multi-institutional comparisons of treatment plans, where plans from multiple treatment planning systems (TPSs) are typically evaluated.Materials and methods: A program was developed to compute several complexity indices and provide analysis of dynamic plan parameters. This in-house software was used to analyse plans from a recent multi-institutional audit. Additionally, 100 clinical volumetric modulated arc therapy (VMAT) plans from two institutions using different TPSs were analysed.Results: All plans produced satisfactory pre-treatment verification results and, hence, complexity metrics could not be used to predict plans failing QA. Regarding the relationship among complexity indices, some very strong correlations were found (r > 0.9 with p < 0.01). However, some relevant discrepancies between complexity indices were obtained, even with negative correlation coefficients (r similar to-0.6) which were expected to be positive. These discrepancies could be explained because each complexity index focused on different features of the plan and different TPSs prioritised modulation of different plan parameters.Conclusions: Some complexity indices provided similar information and can be considered equivalent. However, indices that focused on different plan parameters yielded different results and it was unclear which complexity index should be used. Careful consideration should be given to the use of complexity metrics in multi-institutional

Novel species of fungi described in this study include those from various countries as follows: Australia, Chaetopsina eucalypti on Eucalyptus leaf litter, Colletotrichum cobbittiense from Cordyline stricta × C. australis hybrid, Cyanodermella banksiae on Banksia ericifolia subsp. macrantha, Discosia macrozamiae on Macrozamia miquelii, Elsinoë banksiigena on Banksia marginata, Elsinoë elaeocarpi on Elaeocarpus sp., Elsinoë leucopogonis on Leucopogon sp., Helminthosporium livistonae on Livistona australis, Idriellomyces eucalypti (incl. Idriellomyces gen. nov.) on Eucalyptus obliqua, Lareunionomyces eucalypti on Eucalyptus sp., Myrotheciomyces corymbiae (incl. Myrotheciomyces gen. nov., Myrotheciomycetaceae fam. nov.), Neolauriomyces eucalypti (incl. Neolauriomyces gen. nov., Neolauriomycetaceae fam. nov.) on Eucalyptus sp., Nullicamyces eucalypti (incl. Nullicamyces gen. nov.) on Eucalyptus leaf litter, Oidiodendron eucalypti on Eucalyptus maidenii, Paracladophialophora cyperacearum (incl. Paracladophialophoraceae fam. nov.) and Periconia cyperacearum on leaves of Cyperaceae, Porodiplodia livistonae (incl. Porodiplodia gen. nov., Porodiplodiaceae fam. nov.) on Livistona australis, Sporidesmium melaleucae (incl. Sporidesmiales ord. nov.) on Melaleuca sp., Teratosphaeria sieberi on Eucalyptus sieberi, Thecaphora australiensis in capsules of a variant of Oxalis exilis.Brazil, Aspergillus serratalhadensis from soil, Diaporthe pseudoinconspicua from Poincianella pyramidalis, Fomitiporella pertenuis on dead wood, Geastrum magnosporum on soil, Marquesius aquaticus (incl. Marquesius gen. nov.) from submerged decaying twig and leaves of unidentified plant, Mastigosporella pigmentata from leaves of Qualea parviflorae, Mucor souzae from soil, Mycocalia aquaphila on decaying wood f

© 2018 American Society for Bone and Mineral Research. Type 2 diabetes (T2DM) is associated with a reduced life expectancy. The latest published evidence suggests an increased risk of fractures among T2DM patients. We conducted a population-based cohort study to determine the impact of mortality as a competing risk in the study of the association between T2DM and hip fracture rates. Participants were all diagnosed T2DM patients registered in the Sistema de Información para el Desarrollo de la Investigación en Atención Primaria (SIDIAP) database aged 65 years and older; up to two non-T2DM were matched by age, sex, and primary care facility. We used Cox regression models to estimate cause-specific hazard ratio (HR) of death or hip fracture according to T2DM status. Fine and Gray models were then fitted to estimate the subhazard ratio (SHR) of hip fracture while accounting for competing risk with death and to estimate the probability of hip fracture within 5 years. A total of 55,891 T2DM and 103,093 matched non-T2DM patients were observed for a median of 8 years. Mortality was 48.8 per 1000 person years (py) in T2DM, and 33.8 per 1000 py in non-T2DM; hip fracture rates were 6.0 per 1000 py and 4.9 per 1000 py, respectively. Cox models confirmed a significant association for death and hip fracture: HR 1.51 (95% CI, 1.48 to 1.55), and HR 1.32 (95% CI, 1.24 to 1.40), respectively. Accounting for death as a competing event (Fine-Gray models), the association between T2DM and hip fracture risk remained statistically significant (SHR 1.15; 95% CI, 1.09 to 1.21) and the probability of a hip fracture within 5 years was 2.3% for TD2M and 1.9% for non-TD2M patients compared to 2.6% and 2.1% respectively using Kaplan-Meier (KM) estimates. T2DM patients have a 50% increased mortality

Resveratrol (RSV) has been described as a potent antioxidant, anti-steatotic, and antitumor compound, and it has also been identified as a potent autophagy inducer. On the other hand, quercetin (QCT) is a dietary flavonoid with known antitumor, anti-inflammatory and antidiabetic effects. Additionally, QCT increases autophagy. To study the hypothetical synergistic effect of both compounds, we tested the combined effect of QCT and RSV on the autophagy process in HepG2 cells METHODS AND RESULTS: Autophagy was studied by western blotting, real-time RT-PCR, and cellular staining. Our results clearly indicate a bifunctional molecular effect of RSV. Both polyphenols were individually able to promote autophagy. Strikingly, when RSV was combined with QCT, it promoted a potent reduction of QCT-induced autophagy and influenced pro-apoptotic signaling. Conclusion: RSV acts differentially on the autophagic process depending on the cellular energetic state. We further characterized the molecular mechanisms related to this effect, and we observed that AMP-activated protein kinase (AMPK) phosphorylation, heme oxygenase 1 (HO-1) downregulation, lysosomal membrane permeabilization (LMP) and Zinc (Zn2+ ) dynamics could be important modulators of such RSV-related effects and could globally represent a promising strategy to sensitize cancer cells to QCT treatment. This article is protected by copyright. All rights reserved.

This study considered the physiological modulation of liver proteins due to the supplementation with fish oils under two dietary backgrounds: standard or high in fat and sucrose (HFHS), and their combination with grape polyphenols. By using a quantitative proteomics approach, we showed that the capacity of the supplements for regulating proteins depended on the diet; namely, 10 different proteins changed into standard diets, while 45 changed into the HFHS diets and only scarcely proteins were found altered in common. However, in both contexts, fish oils were the main regulatory force, although the addition of polyphenols was able to modulate some fish oils' effects. Moreover, we demonstrated the ability of fish oils and their combination with grape polyphenols in improving biochemical parameters and reducing lipogenesis and glycolysis enzymes, enhancing fatty acid beta-oxidation and insulin signaling and ameliorating endoplasmic reticulum stress and protein oxidation when they are included in an unhealthy diet.

Background. Adipose tissue is an endocrine organ that could play a role in tumor progression via its secreted adipokines. The role of adipose-derived fatty acid-binding protein (FABP) 4 and FABP5 in breast cancer is presently under study, but their circulating levels in this pathology are poorly known. We analyzed the blood concentrations of FABP4 and FABP5 in breast cancer patients to determine whether there is an association between them and breast cancer. Materials and Methods. We studied 294 women in the oncology department with a family history of breast cancer; 198 of the women had breast cancer, and 96 were healthy controls. The levels of FABP4, FABP5, lipid profile, standard biochemical parameter, and high-sensitivity C-reactive protein (hsCRP) were determined. We analyzed the association of FABP4 and FABP5 with breast cancer, while adjusting for demographic, anthropometric, and biochemical parameters. Results. Breast cancer patients had a 24.8% (p < .0001) and 11.4% (p < .05) higher blood concentration of FABP4 and FABP5, respectively. Fatty acid-binding protein 4 was positively associated with age, body mass index (BMI), FABP5, very-low-density lipoprotein cholesterol (VLDLc), non-highdensity lipoprote in cholesterol (non-HDLc), Apolipoprotein B 100 (ApoB100), triglycerides, glycerol, glucose, and hsCRP (p < .05), and was negatively associated with HDLc (p < .005) in breast cancer patients. Fatty acid-binding protein 5 was positively associated with BMI, FABP4, VLDLc, triglycerides, glycerol, and hsCRP (p < .05), and was negatively associated with HDLc and Apolipoprotein AI (ApoAI) (p < .05) in breast cancer patients. Using a logistic regression analysis and adjusting for age, BMI, hsCRP, non-HDLc, and triglycerides, FABP4 was independently associated with bre

ω-3 Polyunsaturated fatty acids (PUFAs) reduce risk factors for cardiovascular diseases (CVD) and other pathologies that involve low-grade inflammation. They have recently been shown to exert complementary functional effects with proanthocyanidins. As the reduction of health-promoting gut bacteria such as lactobacilli and bifidobacteria has been linked to a number of alterations in the host, the aim of this study was to determine whether PUFAs and proanthocyanidins also cooperate in maintaining well-balanced microbiota. To this end, rats were supplemented for 6 months with eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) 1:1 (16.6 g/kg feed); proanthocyanidin-rich grape seed extract (GSE, 0.8 g/kg feed); or both. Plasma adiponectin, cholesterol, and urine nitrites were measured. Gut bacterial subgroups were evaluated in fecal DNA by qRT-PCR. Short-chain fatty acids (SCFAs) were determined in feces by gas chromatography. Body and adipose tissue weights were found to be higher in the animals given ω-3 PUFAs, while their energy intake was lower. Plasma cholesterol was lower in ω-3 PUFA supplemented groups, while adiponectin and urine nitrites were higher. ω-3 PUFAs reduced the population of Lactobacillales and L. acidophilus after 6 months of supplementation. GSE significantly reduced L. plantarum and B. longum. The combination of ω-3 PUFAs and GSE maintained the health-promoting bacteria at levels similar to those of the control group. Acetic acid was increased by the ω-3 PUFA individual supplementation, while the combination with GSE kept this value similar to the control value. In conclusion, while individual supplementations with ω-3 PUFAs or GSE modify the populations of Lactobacillus, Bifidobacterium and microbial products (SCFAs), their combination maintains t

The levels of 16 polycyclic aromatic hydrocarbons (PAHs) were determined in 8 passive air samples (PAS) and 6 lichen transplants (Ramalina fastigiata) deployed for a period of 2 months in different zones of Tarragona County (Catalonia, Spain), an area with an important number of chemical and petrochemical industries. The accumulated amount of the sum of the 16 PAHs ranged between 1363 to 7866 ng/sample in air samples. The highest concentration was found in the neighborhood of Puigdelfí (village of Perafort), in the vicinity of a big oil refinery and well under the potential influence of the petrochemical emissions. In lichen samples, the sum of the 16 PAHs ranged between 247 and 841 ng/g (dry weight), being the greatest value also observed in Puigdelfí. Data on the levels and profiles of PAHs in both passive monitoring methods were compared. A significant positive linear correlation was found between the concentrations of low molecular weight PAHs in lichens and the amounts accumulated in passive air samples (R?=?0.827, P?

This study aimed at evaluating the potential impact of a cement plant after 4 years of the employment of alternative fuel. In June 2015, concentrations of PCDD/Fs and metals were determined in soils, vegetation and air in order to measure potential changes with respect to previous surveys before (July 2011) and after (June 2013) the employment of alternative fuel. Risks to human health were also assessed. In soils, metal levels were similar to those observed in June 2013 (p > 0.05). In comparison with July 2011, the increment was only statistically significant for As and Cd (p < 0.05). A notable increase in levels of PCDD/Fs was noted when current levels in soils (1.14 ng WHO-TEQ per kg) were compared with those observed in July 2011 (0.37 ng WHO-TEQ per kg) (p > 0.05) and June 2013 (0.41 ng WHO-TEQ per kg) (p < 0.05). This increase was mainly caused by the increase in PCDD/F levels at one sampling site, which showed the heterogeneity of PCDD/F levels in soils, possibly as a result of different point emissions over the years. On the other hand, temporal trends in levels of metals and PCDD/Fs in vegetation showed a clear decrease, which indicated that the particle fraction of these pollutants would potentially be removed from leaf surfaces by wash-off. In air, levels were similar to those found in previous surveys. The results of PCA showed that the change in fuel had not affected the environmental profiles of metals and PCDD/Fs around the cement plant. The exposure of the population living in the surroundings of the plant was measured and it was shown that diet was the major contributor for both metals and PCDD/Fs, with percentages of over 97%, the only exceptions being As and Pb, for which dietary intake accounted for 43% and 71% of the total exposure, respectively. En

Studies evaluating the relationship between soluble transferrin receptor (sTfR), a biomarker inversely related to body iron stores, and risk of type 2 diabetes mellitus (T2DM) are scarce and inconclusive. Furthermore, sTfR concentrations have been observed to be significantly higher in obese than in nonobese individuals. Therefore, the aim of this study was to assess the relationship between sTfR and the risk of T2DM in obese and nonobese subjects.A nested case-control study of 153 cases of newly diagnosed diabetic subjects, 73 obese and 80 nonobese, and 306 individually matched controls, 138 obese and 166 nonobese, who did not develop T2DM for a median 6-year follow-up (interquartile range: 3·9-6·5) was conducted using data from the PREvention with MEDiterranean Diet (PREDIMED) cohort (http://www.controlled-trials.com/ISRCTN35739639). Cases and controls were matched for age (? 67 vs. > 67 years), gender, dietary intervention group and BMI (? 27 vs. > 27 kg/m2 ).Waist circumference is the main determinant of sTfR concentrations in the whole sample (? = 0·476, P < 0·001), in the obese (? = 0·802, P < 0·001) and the nonobese (? = 0·455, P = 0·003). Furthermore, sTfR is directly associated with the risk of T2DM in obese individuals (OR = 2·79; 95% CI: 1·35-5·77, P = 0·005) and inversely associated in nonobese individuals (OR = 0·40; 95% CI: 0·20-0·79, P = 0·015).The association between sTfR levels and risk of T2DM in a population at high cardiovascular risk depend on the presence or absence of obesity. While in nonobese subjects elevated sTfR levels are associated with a decreased risk of developing T2DM, in obese subjects the risk increases. This suggests that obesity alters the relationship between sTfR and T2DM incidence.© 2017 Stichting European Society for Clinical In

PBDEs (congeners 28, 47, 99, 100, 153, 154, 183, 209), HBCD (?, ?, ?), emerging brominated flame retardants (PBEB, HBB and DBDPE), dechloranes (Dec 602, 603, 604, syn- and anti-DP), TBBPA, 2,4,6-TBP and MeO-PBDEs (8 congeners) were analysed in commercial seafood samples from European countries. Levels were similar to literature and above the environmental quality standards (EQS) limit of the Directive 2013/39/EU for PBDEs. Contaminants were found in 90.5% of the seafood samples at n.?d.-356 ng/g lw (n.?d.-41.1 ng/g ww). DBDPE was not detected and 2,4,6-TBP was detected only in mussels, but at levels comparable to those of PBDEs. Mussel and seabream were the most contaminated species and the Mediterranean Sea (FAO Fishing Area 37) was the most contaminated location. The risk assessment revealed that there was no health risk related to the exposure to brominated flame retardants via seafood consumption. However, a refined risk assessment for BDE-99 is of interest in the future. Moreover, the cooking process concentrated PBDEs and HBB.Copyright © 2016 Elsevier Ltd. All rights reserved.

Encouraging adolescents to adopt healthy lifestyles can be challenging. The aim of the "Som la Pera" study was to engage adolescents by applying new strategies to increase both their fruit and vegetable consumption and their physical activity (PA) while reducing their sedentary behavior.In disadvantaged neighborhoods of Reus (Spain), two high schools were randomly assigned to the intervention (n?=?170 adolescents 13- to 16-year-olds) and two were assigned to the control group (n?=?223 adolescents 13- to 16-year-olds). The intervention, which lasted 12 months and spanned 2 academic years (2013-2015), used social marketing (SM) to improve healthy choices. The peer-led strategy involved 5 adolescents who designed and implemented 10 activities as challenges for their 165 school-aged peers. The control group received no intervention. To assess self-reported lifestyles in both groups, the Health Behavior in School-Aged Children Survey was used at baseline and end of study.After 12 months, intervention adolescents showed an increase of 28.9% in ?1 fruit/day (p?

This study was aimed at evaluating the potential impact of a cement plant after 4 years of alternative fuel implementation. In June 2015, concentrations of PCDD/Fs and metals were determined in soil, herbage and air in order to evaluate the potential changes with respect to previous surveys before (July 2011) and after (June 2013) alternative fuel implementation. Human health risks were also assessed. In soils, metal levels were similar to those obtained in June 2013 (p>0.05). In comparison with July 2011 the increment was only statistically significant for As and Cd (p<0.05). A notable increase of PCDD/Fs was noted when current levels in soils (1.14 ng WHO-TEQ/kg) were compared with those obtained in July 2011 (0.37 ng WHO-TEQ/kg) (p>0.05) and June 2013 (0.41 ng WHO-TEQ/kg) (p<0.05). This increase was mainly caused by the increment of PCDD/Fs in one sampling site, showing the heterogeneity of PCDD/F levels in soils possibly as a result of different punctual emissions along years. On the other hand, temporal trends of metals and PCDD/Fs in herbage showed a clear decrease indicating that the particle fraction of those pollutants would be potentially removed from leaf surfaces by wash off. In air, levels were similar to those found in previous surveys. Results of the PCA analysis showed that the change of fuel had not affected environmental profiles of metals and PCDD/Fs around cement plant. The exposure for the population living in the surroundings of the plant was evaluated showing that diet was the major contributor for both, metals and PCDD/Fs, with percentages over 97%, being the only exception As and Pb for which the dietary intake accounted for 43 and 71% of the total exposure, respectively. Environmental non-cancer and cancer risks were within the limi

The neurotrophin brain-derived neurotrophic factor (BDNF) acts via tropomyosin-related kinase B receptor (TrkB) to regulate synapse maintenance and function in the neuromuscular system. The potentiation of acetylcholine (ACh) release by BDNF requires TrkB phosphorylation and Protein Kinase C (PKC) activation. BDNF is secreted in an activity-dependent manner but it is not known if pre- and/or postsynaptic activities enhance BDNF expression in vivo at the neuromuscular junction (NMJ). Here, we investigated whether nerve and muscle cell activities regulate presynaptic conventional PKC (cPKCα and βI) via BDNF/TrkB signaling to modulate synaptic strength at the NMJ. To differentiate the effects of presynaptic activity from that of muscle contraction, we stimulated the phrenic nerve of rat diaphragms (1 Hz, 30 min) with or without contraction (abolished by µ-conotoxin GIIIB). Then, we performed ELISA, Western blotting, qRT-PCR, immunofluorescence and electrophysiological techniques. We found that nerve-induced muscle contraction: (1) increases the levels of mature BDNF protein without affecting pro-BDNF protein or BDNF mRNA levels; (2) downregulates TrkB.T1 without affecting TrkB.FL or p75 neurotrophin receptor (p75) levels; (3) increases presynaptic cPKCα and cPKCβI protein level through TrkB signaling; and (4) enhances phosphorylation of cPKCα and cPKCβI. Furthermore, we demonstrate that cPKCβI, which is exclusively located in the motor nerve terminals, increases activity-induced acetylcholine release. Together, these results show that nerve-induced muscle contraction is a key regulator of BDNF/TrkB signaling pathway, retrogradely activating presynaptic cPKC isoforms (in particular cPKCβI) to modulate synaptic function. These results indicate that a decrease in neuromuscula

Review DOI: 10.1371/journal.pone.0178860 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0178860 Filiació URV: SI, Previous research has associated schizophrenia with an inability to activate behavioural intentions facilitated by counterfactual thinking (CFT) as a step to improving performance. Consequently, these findings suggest that rehabilitation strategies will be entirely ineffective. To extend previous research, we evaluated the influence of CFT in the activation of behavioural intentions using a novel sequential priming paradigm in the largest sample of subjects explored to date. Method: The main variables assessed were: answer to complete a target task (wrong or correctly), and percentage gain in the reaction time (RT) to complete a target task correctly depending on whether the prime was a counterfactual or a neutral-control cue. These variables were assessed in 37 patients with schizophrenia and 37 healthy controls. Potential associations with clinical status and socio-demographic characteristics were also explored. Results: When a counterfactual prime was presented, the probability of giving an incorrect answer was lower for the entire sample than when a neutral prime was presented (OR 0.58; CI 95% 0.42 to 0.79), but the schizophrenia patients showed a higher probability than the controls of giving an incorrect answer (OR 3.89; CI 95% 2.0 to 7.6). Both the schizophrenia patients and the controls showed a similar percentage gain in RT to a correct answer of 8%. Conclusions: Challenging the results of previous research, our findings suggest a normal activation of behavioural intentions facilitated by CFT in schizophrenia. Nevertheless, the patients showed more difficulty than the controls with the task, adding support to the concept of CFT as