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Jimenez-Diaz I.,Institute Investigacion Biosanitaria Ibsgranada | Arrebola J.P.,Institute Investigacion Biosanitaria Ibsgranada | Arrebola J.P.,CIBER ISCIII | Arrebola J.P.,University of Granada | And 2 more authors.
Chemosphere | Year: 2015

Zearalenone (ZON) is a non-steroidal estrogenic mycotoxin produced by Fusarium species. The exposure risk to humans and animals is the consumption of contaminated food and animal feeds. It has been reported that ZON and some of its metabolites promote the development of hormone-dependent tumors. The aim of this case-control study was to estimate exposure to ZON and its five metabolites (α-zearalenol [α-ZOL], β-zearalenol [β-ZOL], α-zearalanol [zeranol, α-ZAL], β-zearalanol [teranol, β-ZAL] and zearalanone [ZAN]) by measuring urinary concentrations of these compounds, and to evaluate the risk of breast cancer related to this exposure. Chemical analyses were carried out by liquid-liquid extraction (LLE) and ultra-high performance liquid chromatography with tandem mass spectrometry detection (UHPLC-MS/MS). Statistical analyses were performed in order to determine the association between exposure to these compounds and the development of breast cancer. Crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by unconditional logistic regression to estimate the magnitude of the associations. The obtained results (adjusted OR. = 1.54, 95% CI. = 1.10-2.77) suggest a potential role of α-ZAL in the risk of developing breast cancer. © 2015 Elsevier Ltd.


Fernandez Mondejar E.,Hospital Universitario Virgen Of Las Nieves | Fernandez Mondejar E.,Institute Investigacion Biosanitaria Ibsgranada | Alvarez F.J.,University of Valladolid
Medicina Intensiva | Year: 2014

The mortality of trauma patients has improved significantly in recent decades due to a combination of factors: medical care, educational campaigns and structural changes. Generalization of out-of hospital emergence medical services and the hospital care in specific centers for traumatized has undoubtedly contributed to this decline, but other factors such as periodic campaigns to prevent workplace and traffic accidents, as well as improvements in the road network have played a key role.The challenge now is to continue to decrease mortality, for which is essential an analysis of the situation to detect potential areas of improvement.The application of diagnostic or therapeutic actions with scientific evidence is associated with lower mortality, but as in other areas of medicine, the application of scientific evidence in trauma patients is barely 50%. Moreover, nearly 90% of trauma deaths occur in the crash site or in the first 72. h of hospitalization, the vast majority as a result of injuries incompatible with life. In these circumstances it is clear that prevention is the most cost-effective activity. As medical practitioners, our role in prevention is mainly focused on the secondary prevention to avoid recidivism, for which it is necessary to identify risk factor (frequently alcohol, illegal drugs, psychotropic medication etc.) and implement a brief motivational intervention. This activity can reduce recidivism by nearly 50%. In Spain, the activity in this field is negligible therefore measures should be implemented for dissemination of secondary prevention in trauma. © 2014 Elsevier España, S.L. and SEMICYUC.


Jimenez-Diaz I.,Institute Investigacion Biosanitaria Ibsgranada | Jimenez-Diaz I.,University of Granada | Molina-Molina J.M.,Institute Investigacion Biosanitaria Ibsgranada | Molina-Molina J.M.,University of Granada | And 4 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2014

Humans can be exposed to mycotoxins through the diet. Evaluation of exposure levels to mycotoxins can be performed by direct determination in urine. The present work proposes a sensitive ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of zearalenone (ZON) and its five metabolites (α-zearalenol [α-ZOL], β-zearalenol [β-ZOL], α-zearalanol [zeranol, α-ZAL], β-zearalanol [teranol, β-ZAL] and zearalanone [ZAN]) in human urine samples. The method involves the enzymatic hydrolysis of the samples, extraction of the analytes using liquid-liquid extraction (LLE) with ethyl acetate/formic acid (99:1 v/v) and a cleanup step using hexane, prior to their quantification by UHPLC-MS/MS, using an electrospray ionization (ESI) interface in the negative mode. Zearalenone-d6 (ZON-d6) was used as surrogate. The limits of detection and the limits of quantification ranged from 0.03 to 0.3ngmL-1 and from 0.1 to 1.0ngmL-1, respectively. The method was validated using matrix-matched calibration and a spike recovery assay. Recovery rates for spiked samples ranged from 96% to 104%, with relative standard deviations lower than 8.5%. This method was satisfactorily applied to 42 urine samples from Tunisian women for the determination of zearalenone and its five metabolites. © 2014 Elsevier B.V.


PubMed | Institute Investigacion Biosanitaria Ibsgranada, University of Granada and CIBER ISCIII
Type: | Journal: The Science of the total environment | Year: 2016

Bisphenol A (BPA), benzophenones and parabens are commonly used in the production of polycarbonate plastics, as UV-filters and as antimicrobial preservatives, respectively, and they are thought to exhibit endocrine disrupting properties. Exposure to these compounds remains poorly characterized in developing countries, despite the fact that certain behaviors related to westernization have the potential to influence exposure. The aim of this pilot study was to measure urinary concentrations of BPA, six different benzophenones and four parabens in 34 Tunisian women. In addition, we identified some socio-demographic and dietary predictors of exposure to these compounds. Chemical analyses were carried out by dispersive liquid-liquid microextraction (DLLME) and ultra-high performance liquid chromatography with tandem mass spectrometry detection (UHPLC-MS/MS). Detection frequencies of methylparaben (MP), ethylparaben (EP) and propylparaben (PP) ranged between 67.6 and 94.1%. Butylparaben (BP) was found in 38.2% of the analyzed samples; BPA in 64.7%; and benzophenone-1 (BP-1) and benzophenone-3 (BP-3) were detected in 91.2 and 64.7% of the analyzed samples, respectively. Urinary geometric mean concentrations of MP, EP, PP, and BP were 30.1, 1.4, 2.0 and 0.5ngmL(-1), respectively. Geometric mean concentrations of BPA, BP-1, and BP-3 were 0.4, 1.3 and 1.1ngmL(-1), respectively. Our results suggest that Tunisian women are widely exposed to BPA, parabens and some benzophenones. Further studies on the general Tunisian population are needed in order to assess the levels of exposure to these compounds and to identify sources of exposure and population groups at higher risk.


Arrebola J.P.,University of Granada | Arrebola J.P.,CIBER ISCIII | Fernandez M.F.,University of Granada | Fernandez M.F.,CIBER ISCIII | And 6 more authors.
Environmental Research | Year: 2015

The aim of this study was to assess the influence of adipose tissue concentrations of a group of persistent organic pollutants (POPs) on the risk of hypertension in an adult cohort of residents of Granada (Southern Spain) over a 10-year follow-up. No chemical was significantly associated with the risk of hypertension in the overall population or when models were stratified by sex or median age. However, we found positive associations between log-transformed POP concentrations and hypertension risk in participants with body mass index (BMI) above the median value of 26.3kg/m2, which were statistically significant for hexachlorobenzene (HR=1.26, 95% CI=1.03-1.56), β-hexachlorocyclohexane (HR=1.25, 95% CI=1.03-1.51), and polychlorinated biphenyl congeners -138 (HR=1.32, 95% CI=1.04-1.69) and -153 (HR=1.36, 95% CI=1.00-1.84). Inverse associations were observed in the subgroup with BMI≤26.3kg/m2, but none was statistically significant. More research and a longer follow-up period are warranted to verify these associations and elucidate the role of obesity as a potential effect modifier. Given the elevated worldwide frequency of POP exposure and hypertension, the public health impact of this relationship may be substantial. © 2015 Elsevier Inc.


Romero I.,Hospital Universitario Virgen Of Las Nieves | Romero I.,Institute Investigacion Biosanitaria IbsGranada | Garrido F.,Hospital Universitario Virgen Of Las Nieves | Garrido F.,Institute Investigacion Biosanitaria IbsGranada | And 3 more authors.
Cancer Research | Year: 2014

The aim of any anticancer treatment is to avoid, control, or eliminate disseminated tumor cells. Clinical and experimental evidence has revealed that metastases can remain in a latency state, that is, metastasis dormancy. Three mechanisms are thought to be involved in cancer dormancy: cellular dormancy, angiogenic dormancy, and immune-mediated dormancy. Here, we review the mechanisms and cells involved in immune-mediated cancer dormancy and discuss current and future immunotherapeutic strategies. Recent results indicate that the immune system can restrain disseminated cancer cells, promoting their permanent dormancy. CD8+ T lymphocytes play a relevant role in maintaining immune equilibrium with metastatic dormant cells, and MHC class I surface expression on tumor cells may also be involved. Natural killer (NK) cells have an activator function that triggers a cytotoxic T lymphocyte (CTL) response. Furthermore, immune dormancy promotes cancer cell growth arrest and angiogenic control. Immunotherapeutic interventions in metastatic dormancy may help to control or eradicate cancer disease. Treatments that activate or increase the CTL immune response or reverse cancer cell-induced CTL immunosuppression might be useful to restrain or destroy metastatic cells. These objectives may be achieved by recovering or increasing MHC class I surface expression on cancer cells or even by activating NK cells. Immune-mediated metastasis dormancy provides an opportunity for targeting cancer in novel immune treatments. ©2014 AACR.


PubMed | CIBER ISCIII, University of Granada and Institute Investigacion Biosanitaria Ibsgranada
Type: Journal Article | Journal: Bioelectromagnetics | Year: 2016

The relationship between exposure to electromagnetic fields from non-ionizing radiation and adverse human health effects remains controversial. We aimed to explore the association of environmental radiofrequency-electromagnetic fields (RF-EMFs) exposure with neurobehavioral function of children. A subsample of 123 boys belonging to the Environment and Childhood cohort from Granada (Spain), recruited at birth from 2000 through 2002, were evaluated at the age of 9-11 years. Spot electric field measurements within the 100kHz to 6GHz frequency range, expressed as both root mean-square (S(RMS) and maximum power density (S(MAX)) magnitudes, were performed in the immediate surrounds of childres dwellings. Neurocognitive and behavioral functions were assessed with a comprehensive battery of tests. Multivariate linear and logistic regression models were used, adjusting for potential confounders. All measurements were lower than reference guideline limits, with median S(RMS) and S(MAX) values of 285.94 and 2759.68W/m(2), respectively. Most of the cognitive and behavioral parameters did not show any effect, but children living in higher RF exposure areas (above median S(RMS) levels) had lower scores for verbal expression/comprehension and higher scores for internalizing and total problems, and obsessive-compulsive and post-traumatic stress disorders, in comparison to those living in areas with lower exposure. These associations were stronger when S(MAX) values were considered. Although some of our results may suggest that low-level environmental RF-EMF exposure has a negative impact on cognitive and/or behavior development in children; given limitations in the study design and that the majority of neurobehavioral functioning tasks were not affected, definitive conclusions cannot be drawn.


PubMed | University of Granada, Copenhagen University and Institute Investigacion Biosanitaria Ibsgranada
Type: | Journal: Environmental research | Year: 2015

The aim of this study was to assess the influence of adipose tissue concentrations of a group of persistent organic pollutants (POPs) on the risk of hypertension in an adult cohort of residents of Granada (Southern Spain) over a 10-year follow-up. No chemical was significantly associated with the risk of hypertension in the overall population or when models were stratified by sex or median age. However, we found positive associations between log-transformed POP concentrations and hypertension risk in participants with body mass index (BMI) above the median value of 26.3kg/m(2), which were statistically significant for hexachlorobenzene (HR=1.26, 95% CI=1.03-1.56), -hexachlorocyclohexane (HR=1.25, 95% CI=1.03-1.51), and polychlorinated biphenyl congeners -138 (HR=1.32, 95% CI=1.04-1.69) and -153 (HR=1.36, 95% CI=1.00-1.84). Inverse associations were observed in the subgroup with BMI26.3kg/m(2), but none was statistically significant. More research and a longer follow-up period are warranted to verify these associations and elucidate the role of obesity as a potential effect modifier. Given the elevated worldwide frequency of POP exposure and hypertension, the public health impact of this relationship may be substantial.


PubMed | Hospital Universitario Virgen Of Las Nieves and Institute Investigacion Biosanitaria Ibsgranada
Type: | Journal: Cancer immunology, immunotherapy : CII | Year: 2017

Most tumor cells derive from MHC-I-positive normal counterparts and remain positive at early stages of tumor development. T lymphocytes can infiltrate tumor tissue, recognize and destroy MHC class I (MHC-I)-positive cancer cells (permissive phase I). Later, MHC-I-negative tumor cell variants resistant to T-cell killing emerge. During this process, tumors first acquire a heterogeneous MHC-I expression pattern and finally become uniformly MHC-I-negative. This stage (phase II) represents a non-permissive encapsulated structure with tumor nodes surrounded by fibrous tissue containing different elements including leukocytes, macrophages, fibroblasts, etc. Molecular mechanisms responsible for total or partial MHC-I downregulation play a crucial role in determining and predicting the antigen-presenting capacity of cancer cells. MHC-I downregulation caused by reversible (soft) lesions can be upregulated by TH1-type cytokines released into the tumor microenvironment in response to different types of immunotherapy. In contrast, when the molecular mechanism of the tumor MHC-I loss is irreversible (hard) due to a genetic defect in the gene/s coding for MHC-I heavy chains (chromosome 6) or beta-2-microglobulin (B2M) (chromosome 15), malignant cells are unable to upregulate MHC-I, remain undetectable by cytotoxic T-cells, and continue to grow and metastasize. Based on the tumor MHC-I molecular analysis, it might be possible to define MHC-I phenotypes present in cancer patients in order to distinguish between non-responders, partial/short-term responders, and likely durable responders. This highlights the need for designing strategies to enhance tumor MHC-I expression that would allow CTL-mediated tumor rejection.


PubMed | University of Alicante, CSIC - Institute of Refrigeration, Biomedical Research Institute Sant Pau and Institute Investigacion Biosanitaria Ibsgranada
Type: Journal Article | Journal: Gaceta sanitaria | Year: 2015

To analyse gender inequalities in research on public health and epidemiology in Spain for the period 2007-2014.A descriptive study was conducted by sex of leadership positions in the Centre for Biomedical Research Network (CIBER), especially in the subject area of epidemiology and public health (CIBERESP) in 2014; scientific societies of public health (SESPAS) and epidemiology (SEE) 2009-2014; research projects requested (13,320) and financed (4,699), and monetary amounts of calls for Strategic Action in Health (AES), 2007-2013.Women were clearly under-represented in positions of leadership and in research excellence in public health (CIBER), with a predominance of men in decision-making positions. Although research projects led by women in AES increased slightly between 2007 and 2013, among proposed projects this figure was less than 50%, with the exception of the public health commission. The gender gap was even greater in funded projects. Projects led by men were more likely to be funded, representing 29% in public health. There was also a persistence of horizontal gender segregation in positions of scientific recognition in the SESPAS and SEE Congresses.The overrepresentation of male leaders in public health research in Spain can be understood as an indicator and a consequence of androcentrism in scientific societies and professional groups. This sexist situation threatens the existence of innovative products and services from a gender perspective that respond to the needs and demands of society as a whole. More women are needed in research incorporating this perspective.

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