DIETARY HABITS AND CARDIOVASCULAR DISEASE

BACKGROUND AND AIM: Diet, in particular dietary fats, and cardiovascular disease (CVD) are closely related. Dietary fats might be captured by measuring blood fatty acid profiles. The role of diet as well as the role of blood fatty acid (FA) levels, in CVD aetiology is still uncertain. Aims of this thesis were to investigate in a large cohort of 60-year-old Swedish men and women: 1) The association between self-reported dietary intake, with a specific focus on foods rich in fat, and selected serum cholesterol ester FAs (Project I); 2) The relation between self-reported intake of specific types of dietary fats (primary aim) and fruit and vegetables (secondary aim) and incident of CVD and all-cause mortality (Project II); 3) The relation between serum cholesterol FAs, with a specific focus on polyunsaturated FAs (PUFA)eicosapentaenoic acid (EPA), docosaesaenoic acid (DHA), linoleic (LA) and linolenic (ALA) acid and incident CVD and all-cause mortality (Project III). METHODS: Data collected between 1997 and 1998 from 4,232 individuals (2,039 men and 2,139 women) aged 60, randomly selected from Stockholm County were used. The participants were followed regarding incident CVD up to 31st December 2012 using national registers yielding 359 incident CVD cases and 595 deaths. From nutritional data, collected by questionnaires, we created: 1) five diet scores reflecting intake of saturated fats in general, and fats from dairy, fish, processed meat and vegetable oils and margarines (Project I, II) 2) binary variables classifying study participants into exposed and unexposed and evaluating 16 specific dietary factors (Project II). Gas chromatography was used to assess 13 FAs in serum cholesterol esters (Project I, III). Association between each diet score and specific FAs was assessed by percentile differences (PD) with 95% confidence intervals (CI) at the 10th, 25th, 50th, 75th, and 90th percentile of each FA across levels of diet scores using quantile regression (Project I). Crude and adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% CI in the association between specific self-reported dietary fats (diet scores and single dietary items), fruit and vegetables intake (Project II) and serum PUFA (Project III) and incidence of CVD and all-causes mortality. RESULTS: In men and women combined, fish intake was associated with high serum proportions of EPA (50thPD=31.41, 95% CI= 27.77; 35.05) and DHA (50thPD=10 1951, 95% CI= 9.40; 11.62). Vegetable fat intake was associated with high serum proportion of total PUFA (50thPD 36.34, 95% CI= 22.77;49.92) and low proportion of total SFA (50thPD=\uf02d11.33, 95%CI= \uf02d14.92;\uf02d7.73). (Project I) In women, an increased risk of CVD was related to high consumption of spread butter or margarine ( 6510g/day vs <10g/day), HR=1.49, CI=1.02 ; 2.20, and oily potatoes ( 652 times/week vs <2time/week), HR=2.00, CI=1.11;3.60. In men, an increased risk of early death was related to the consumption of butter (vs margarine), HR=1.28, CI=1.01; 1.62, high consumption of spread butter or margarine, HR=1.57, CI=1.23; 2.02 and egg consumption 654 times/week (vs <4times/week), HR=1.53, CI=1.15;2.02. In men, daily intake of fruits (vs <1time/day) was inversely related to early death, HR=0.75, CI=0.60; 0.94. (Project II) High serum EPA and DHA proportions were inversely associated with CVD in women (for EPA HR= 0.79, 95% CI 0.64; 0.97; for DHA HR= 0.74 0.61; 0.89) but not in men. Inverse associations with early death were also noted in men for high serum EPA proportion, HR=0.82, 95% CI 0.71;0.95; and DHA proportion, HR= 0.82, 95%CI= 0.71;0.94, and in women for high serum EPA proportion, HR=0.79, 95%CI= 0.65;0.96, and DHA proportion, HR= 0.78, 95% CI= 0.66;0.93. High serum ALA proprotion was associated with moderately increased of CVD incidence, HR= 1.16, 95% CI=1.02;1.32 in women whereas high serum LA proportion was associated with reduced all-cause mortality in men, HR= 0.73 95% CI=0.64;0.83. (Project III). CONCLUSION: Based on our results, self-reported intake of fish and vegetable fats was clearly associated with serum PUFA. High intake of specific foods and not fats in general may have negative effects on CVD for women and all-causes mortality for men, whereas fruit may reduce mortality only in men. Similarly serum EPA, DHA and LA were protective for CVD and all-causes mortality with gender difference whereas serum ALA might be associated with increased of CVD in only women

Estilos de aprendizaje de los estudiantes de medicina veterinaria de la Universidad Nacional de Rosario, Argentina

El objetivo del trabajo fue identificar los estilos de aprendizaje predominantes de los estudiantes de medicina veterinaria y determinar si existen diferencias en las preferencias cognitivas entre los alumnos del ciclo de formación básica y superior de la carrera. Para ello se encuestaron 76 estudiantes de la Universidad Nacional de Rosario (Argentina), aplicando el inventario de estilos de aprendizaje de Felder y Silverman, que valora la preferencia hacia los estilos activo o reflexivo (tipo de procesamiento), sensorial o intuitivo (tipo de percepción), visual o verbal (tipo de representación) y secuencial o global (tipo de comprensión). Las preferencias cognitivas de los estudiantes encuestados de ambos ciclos de formación se orientaron hacia lo activo, sensorial, visual y secuencial. Sin embargo, en el ciclo básico se hallaron diferencias estadísticamente significativas en los estilos de procesamiento y percepción según año de ingreso. Así, los estudiantes con dos o más años de trayectoria en la carrera presentaron mayores grados de preferencia por los estilos activo y sensorial que los ingresantes. Estos resultados apoyan la hipótesis de diferencias cognitivas en el aprendizaje. En este estudio se comprobó que la mayor parte de los estudiantes analizados prefieren aprender mediante los estilos activo, sensorial, visual y secuencial. Además, existe una profundización de estas preferencias a medida que permanecen más años en la carrera. La evaluación de las características psicológicas del alumnado permitiría el diseño de clases adecuadas a sus necesidades educativas facilitando la construcción de conocimientos en la universidad

I Jornada de expertos en ictiosis

On June 22, 2012 the First Symposium of Ichthyosis Experts in Spain was held at the Hospital Niño de Jesús in Madrid. It was a one-day symposium for dermatologists, pediatricians, and physicians-in-training interested in this disease, as well as for other health care professionals involved in the care of patients with ichthyosis. The aim of the meeting was to try to structure the care of ichthyosis patients in Spain. As happens in other rare diseases, because of the low prevalence of ichthyosis and the absence of designated referral centers, the number of patients treated in each center is very low and few dermatologists have any real clinical experience with this condition or know how to order diagnostic genetic tests. This article summarizes the presentations given at the symposium and is intended as a reference for anyone interested in the subject.El día 22 de junio de 2012 se celebró en el Hospital Niño Jesús la I Jornada de expertos en ictiosis, una jornada monográfica dirigida a dermatólogos, pediatras y médicos en formación interesados en esta enfermedad, así como al resto de profesionales sanitarios que participan en su atención. El objetivo de la l Jornada de expertos en ictiosis fue intentar estructurar la atención de los pacientes con ictiosis en España. Como ocurre con el resto de las enfermedades raras, su escasa prevalencia y la ausencia de centros de referencia formales diluyen el número de pacientes atendidos en cada centro, y pocos dermatólogos tienen verdadera experiencia clínica o conocen la manera de solicitar diagnóstico genético. En este artículo se resumen las ponencias expuestas en la Jornada para consulta de aquellas personas interesadas en el tema.Pathophysiology of Keratinization Disorders / Ángela Hernández . -- Extracutaneous Manifestations of Ichthyosis / Antonio Torrelo . -- New Clinical Classification of the Ichthyoses / Raúl de Lucas . -- Use of Histologic Diagnosis in Ichthyosis / Fernando Casco . -- Genetic Diagnosis of Ichthyosis / Rogelio González Sarmiento . -- The Multidisciplinary Approach in Ichthyosis: Psychological Care / José Luis Pedreira Massa . -- Collodion Baby and Congenital Erythroderma: Clinical Management and Course / Heiko Traupe . -- Treatment of Ichthyosis / Heiko Traupe . -- Lessons Learned from Experience / Pablo de Unamuno . -- Looking Towards the Future: Humanized Models of Ichthyosis and other Hyperkeratotic Disorders / Fernando Larcher, Marcela del Río . -- What Patients Need / The Leader ship Team of the Spanish Ichthyosis Association . -- Conclusions / Ángela HernándezPublicad

Skin gene therapy for acquired and inherited disorders

The rapid advances associated with the Human Genome Project combined with the development of proteomics technology set the bases to face the challenge of human gene therapy. Different strategies must be evaluated based on the genetic defect to be corrected. Therefore, the re-expression of the normal counterpart should be sufficient to reverse phenotype in single-gene inherited disorders. A growing number of candidate diseases are being evaluated since the ADA deficiency was selected for the first approved human gene therapy trial (Blaese et al., 1995). To cite some of them: sickle cell anemia, hemophilia, inherited immune deficiencies, hyper-cholesterolemia and cystic fibrosis. The approach does not seem to be so straightforward when a polygenic disorder is going to be treated. Many human traits like diabetes, hypertension, inflammatory diseases and cancer, appear to be due to the combined action of several genes and environment. For instance, several wizard gene therapy strategies have recently been proposed for cancer treatment, including the stimulation of the immune system of the patient (Xue et al., 2005), the targeting of particular signalling pathways to selectively kill cancer cells (Westphal and Melchner, 2002) and the modulation of the interactions with the stroma and the vasculature (Liotta, 2001; Liotta and Kohn, 2001).Our work is supported by grants SAF-2004-07717 from Ministerio de Ciencia y Tecnología (Spain) and LSHG-512073 from UE to M. Del Rio, LSHG-503447 from UE to J.L. Jorcano and LSHG-512102 from UE to F. Larcher. We express our gratitude to Dr. Y. Gache, Dr. F. Spirito and Dr. G. Meneguzzi for providing EM pictures to illustrate this work

Preclinical corrective gene transfer in Xeroderma pigmentosum human skin stem cells

Xeroderma pigmentosum (XP) is a devastating disease associated with dramatic skin cancer proneness. XP cells are deficient in nucleotide excision repair (NER) of bulky DNA adducts including ultraviolet (UV)-induced mutagenic lesions. Approaches of corrective gene transfer in NER-deficient keratinocyte stem cells hold great hope for the long-term treatment of XP patients. To face this challenge, we developed a retrovirus-based strategy to safely transduce the wild-type XPC gene into clonogenic human primary XP-C keratinocytes. De novo expression of XPC was maintained in both mass population and derived independent candidate stem cells (holoclones) after more than 130 population doublings (PD) in culture upon serial propagation (> 10(40) cells). Analyses of retrovirus integration sequences in isolated keratinocyte stem cells suggested the absence of adverse effects such as oncogenic activation or clonal expansion. Furthermore, corrected XP-C keratinocytes exhibited full NER capacity as well as normal features of epidermal differentiation in both organotypic skin cultures and in a preclinical murine model of human skin regeneration in vivo. The achievement of a long-term genetic correction of XP-C epidermal stem cells constitutes the first preclinical model of ex vivo gene therapy for XP-C patients.F.L. was supported in part by grants PI081054 from ISCIII and PBIO-0306-2006 from Comunidad de Madrid (CAM). M.D.R. was supported by grant SAF2010-16976 from MICINN. The authors declared no conflict of interest

Time Trends of Acrylamide Exposure in Europe: Combined Analysis of Published Reports and Current HBM4EU Studies

More than 20 years ago, acrylamide was added to the list of potential carcinogens found in many common dietary products and tobacco smoke. Consequently, human biomonitoring studies investigating exposure to acrylamide in the form of adducts in blood and metabolites in urine have been performed to obtain data on the actual burden in different populations of the world and in Europe. Recognizing the related health risk, the European Commission responded with measures to curb the acrylamide content in food products. In 2017, a trans-European human biomonitoring project (HBM4EU) was started with the aim to investigate exposure to several chemicals, including acrylamide. Here we set out to provide a combined analysis of previous and current European acrylamide biomonitoring study results by harmonizing and integrating different data sources, including HBM4EU aligned studies, with the aim to resolve overall and current time trends of acrylamide exposure in Europe. Data from 10 European countries were included in the analysis, comprising more than 5500 individual samples (3214 children and teenagers, 2293 adults). We utilized linear models as well as a non-linear fit and breakpoint analysis to investigate trends in temporal acrylamide exposure as well as descriptive statistics and statistical tests to validate findings. Our results indicate an overall increase in acrylamide exposure between the years 2001 and 2017. Studies with samples collected after 2018 focusing on adults do not indicate increasing exposure but show declining values. Regional differences appear to affect absolute values, but not the overall time-trend of exposure. As benchmark levels for acrylamide content in food have been adopted in Europe in 2018, our results may imply the effects of these measures, but only indicated for adults, as corresponding data are still missing for children

Trends of Exposure to Acrylamide as Measured by Urinary Biomarkers Levels within the HBM4EU Biomonitoring Aligned Studies (2000–2021)

Acrylamide, a substance potentially carcinogenic in humans, represents a very prevalent contaminant in food and is also contained in tobacco smoke. Occupational exposure to higher concentrations of acrylamide was shown to induce neurotoxicity in humans. To minimize related risks for public health, it is vital to obtain data on the actual level of exposure in differently affected segments of the population. To achieve this aim, acrylamide has been added to the list of substances of concern to be investigated in the HBM4EU project, a European initiative to obtain biomonitoring data for a number of pollutants highly relevant for public health. This report summarizes the results obtained for acrylamide, with a focus on time-trends and recent exposure levels, obtained by HBM4EU as well as by associated studies in a total of seven European countries. Mean biomarker levels were compared by sampling year and time-trends were analyzed using linear regression models and an adequate statistical test. An increasing trend of acrylamide biomarker concentrations was found in children for the years 2014–2017, while in adults an overall increase in exposure was found to be not significant for the time period of observation (2000–2021). For smokers, represented by two studies and sampling for, over a total three years, no clear tendency was observed. In conclusion, samples from European countries indicate that average acrylamide exposure still exceeds suggested benchmark levels and may be of specific concern in children. More research is required to confirm trends of declining values observed in most recent years

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Implementation of effect biomarkers in human biomonitoring studies: A systematic approach synergizing toxicological and epidemiological knowledge

ReviewHuman biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2′-deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU confirms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better understand the public health implications of human exposure to environmental chemicals.Supported by the European Union's Horizon 2020 research and innovation program projects HBM4EU [grant number 733032]info:eu-repo/semantics/publishedVersio

A systematic approach synergizing toxicological and epidemiological knowledge

Funding Information: This work was supported by the European Union's Horizon 2020 research and innovation program projects HBM4EU [grant number 733032 ]. Authors acknowledge the editorial assistance of Richard Davies. Publisher Copyright: © 2023 The Author(s)Human biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2′-deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU confirms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better understand the public health implications of human exposure to environmental chemicals.publishersversionpublishe