Els Qüestionaris com a recurs docent en l'aprenentatge autònom. Resultats d'una prova pilot en un curs de Química bàsica.

En aquest article es presenten uns nous qüestionaris on line dissenyats per millorar la comprensió dels continguts de l"assignatura Química Bàsica II i, alhora, propiciar el treball autònom dels estudiants. En el grup pilot que ha disposat dels qüestionaris, els resultats acadèmics dels estudiants que els han realitzat diverses vegades han estat millors que els dels alumnes que no els han utilitzat amb regularitat. Els resultats acadèmics del grup pilot també ha estat millor que els de cursos anteriors

Seminal Microbiota of Idiopathic Infertile Patients and Its Relationship With Sperm DNA Integrity

Oxidative stress; Seminal microbiome; Sperm dna damageEstrés oxidativo; Microbioma seminal; Daño en el ADN de los espermatozoidesEstrès oxidatiu; Microbioma seminal; Dany a l'ADN dels espermatozoidesThe development of new biomarkers for human male infertility is crucial to improve the diagnosis and the prognosis of this disease. Recently, seminal microbiota was shown to be related to sperm quality parameters, suggesting an effect in human fertility and postulating it as a biomarker candidate. However, its relationship to sperm DNA integrity has not been studied yet. The aim of the present study is to characterize the seminal microbiota of a western Mediterranean population and to evaluate its relationship to sperm chromatin integrity parameters, and oxidative stress. For that purpose, 14 samples from sperm donors and 42 samples from infertile idiopathic patients were obtained and were analyzed to assess the composition of the microbiota through full-length 16S rRNA gene sequencing (Illumina MiSeq platform). Microbial diversity and relative abundances were compared to classic sperm quality parameters (macroscopic semen parameters, motility, morphology and concentration), chromatin integrity (global DNA damage, double-stranded DNA breaks and DNA protamination status) and oxidative stress levels (oxidation-reduction potential). The seminal microbiota observed of these samples belonged to the phyla Firmicutes, Proteobacteria, Actinobacteria and Bacteroidetes. The most abundant genera were Finegoldia, Peptoniphilus, Anaerococcus, Campylobacter, Streptococcus, Staphylococcus, Moraxella, Prevotella, Ezakiella, Corynebacterium and Lactobacillus. To our knowledge, this is the first detection of Ezakiella genus in seminal samples. Two clusters of microbial profiles were built based on a clustering analysis, and specific genera were found with different frequencies in relation to seminal quality defects. The abundances of several bacteria negatively correlate with the sperm global DNA fragmentation, most notably Moraxella, Brevundimonas and Flavobacterium. The latter two were also associated with higher sperm motility and Brevundimonas additionally with lower oxidative-reduction potential. Actinomycetaceae, Ralstonia and Paenibacillus correlated with reduced chromatin protamination status and increased double-stranded DNA fragmentation. These effects on DNA integrity coincide in many cases with the metabolism or enzymatic activities of these genera. Significant differences between fertile and infertile men were found in the relative presence of the Propionibacteriaceae family and the Cutibacterium, Rhodopseudomonas and Oligotropha genera, which supports its possible involvement in male fertility. Our findings sustain the hypothesis that the seminal microbiome has an effect on male fertility.This research was funded by the European Regional Development Fund and Instituto de Salud Carlos III (Economy, Industry and Competitiveness Ministry, Madrid, Spain; Project PI14/00119) and Generalitat de Catalunya (2017SGR1796). Supported by the European Union’s Horizon 2020 Research and Innovation scheme under the Marie Skłodowska-Curie grant agreement No. 801342 (Tecniospring INDUSTRY; TECSPR-19-1-0003, to JR-M)

Elevated pulse pressure and cardiovascular risk associated in Spanish population attended in primary care: IBERICAN study

Introduction: Elevated pulse pressure (ePP) is an independent marker of cardiovascular risk (CVR) in people older than 60, and a functional marker of subclinical target organ damage (sTOD) which can predict cardiovascular events in patients with hypertension (HTN), regardless of sTOD. Objective: To evaluate the prevalence of ePP in adult population seen in primary care and its association with other vascular risk factors, sTOD and with cardiovascular disease (CVD). Materials and methods: Observational multicentre study conducted in Spain (8,066 patients, 54.5% women) from the prospective cohort study IBERICAN recruited in Primary Care. Pulse pressure (PP) was defined as the difference between the systolic blood pressure (SBP) and the diastolic blood pressure (DBP) ≥60 mmHg. Adjusted (for age and sex) ePP prevalence were determined. Bivariate and multivariate analyses of the possible variables associated with ePP were carried out. Results: The mean of PP was 52.35 mmHg, and was significantly higher (p < 0.001) in patients with HTN (56.58 vs. 48.45 mmHg) The prevalence of ePP adjusted for age and sex was 23.54% (25.40% men vs. 21.75% women; p < 0.0001). The ePP prevalence rates increased linearly with age (R2= 0.979) and were significantly more frequent in population aged ≥65 than in population aged <65 (45.47% vs. 20.98%; p < 0.001). HTN, left ventricular hypertrophy, low estimated glomerular filtration rate, alcohol consumption, abdominal obesity, and CVD were independently associated with ePP. 66.27% of patients with ePP had a high or very high CVR, as compared with 36.57% of patients without ePP (OR: 3.41 [95% CI 3.08–3.77]). Conclusions: The ePP was present in a quarter of our sample, and it was increased with the age. Also, the ePP was more frequent in men, patients with HTN, other TOD (as left ventricular hypertrophy or low estimated glomerular filtration rate) and CVD; because of this, the ePP was associated a higher cardiovascular risk. In our opinion, the ePP is an importer risk marker and its early identification lets to improve better diagnostic and therapeutic management

TMT-Based Proteomic Analysis of Human Spermatozoa from Unexplained Recurrent Miscarriage Patients before and after Oral Antioxidant Treatment

Recently, sperm quality and the presence of double-stranded breaks (DSB) has been pointed out as a possible cause of recurrent miscarriage, and the use of antioxidants has expanded as a treatment for male infertility. The aim of the present study was to analyze the proteomic effects of antioxidants on sperm from RM patients with high incidence of DSB. Proteomic analysis was performed using a tandem mass tag labeling technique, and subsequently compared with the PANTHER database for DEPs, and the STRING database for protein-protein interactions (PPI). Differentially expressed proteins (DEPs) both before and after antioxidant oral treatment were identified. PPI involving DEPs clustered into networks related to cell metabolism, cytoskeleton, and DNA damage. Results show that the sperm proteomic profiles before and after antioxidant treatment do not significantly differ from each other. However, some DEPs found after the antioxidant treatment shifted towards a DEPs profile typical of fertile donors. This indirect measurement suggests an improvement caused by antioxidants on the expression of several proteins. Among them were proteins involved in sperm DNA remodeling (LMO7, MMP28, BNC2, H2B, and PRDM2). The results presented here represent the first approach in the analysis and repair of the proteomic change caused by antioxidants in recurrent miscarriage patients, elucidating biomarkers that may be useful for the diagnosis and further sperm selection in this type of patient. Further studies should be conducted to validate the usefulness of these biomarkers in larger study groups

Seminal Microbiota of Idiopathic Infertile Patients and Its Relationship With Sperm DNA Integrity

The development of new biomarkers for human male infertility is crucial to improve the diagnosis and the prognosis of this disease. Recently, seminal microbiota was shown to be related to sperm quality parameters, suggesting an effect in human fertility and postulating it as a biomarker candidate. However, its relationship to sperm DNA integrity has not been studied yet. The aim of the present study is to characterize the seminal microbiota of a western Mediterranean population and to evaluate its relationship to sperm chromatin integrity parameters, and oxidative stress. For that purpose, 14 samples from sperm donors and 42 samples from infertile idiopathic patients were obtained and were analyzed to assess the composition of the microbiota through full-length 16S rRNA gene sequencing (Illumina MiSeq platform). Microbial diversity and relative abundances were compared to classic sperm quality parameters (macroscopic semen parameters, motility, morphology and concentration), chromatin integrity (global DNA damage, double-stranded DNA breaks and DNA protamination status) and oxidative stress levels (oxidation-reduction potential). The seminal microbiota observed of these samples belonged to the phyla Firmicutes, Proteobacteria, Actinobacteria and Bacteroidetes. The most abundant genera were Finegoldia, Peptoniphilus, Anaerococcus, Campylobacter, Streptococcus, Staphylococcus, Moraxella, Prevotella, Ezakiella, Corynebacterium and Lactobacillus. To our knowledge, this is the first detection of Ezakiella genus in seminal samples. Two clusters of microbial profiles were built based on a clustering analysis, and specific genera were found with different frequencies in relation to seminal quality defects. The abundances of several bacteria negatively correlate with the sperm global DNA fragmentation, most notably Moraxella, Brevundimonas and Flavobacterium. The latter two were also associated with higher sperm motility and Brevundimonas additionally with lower oxidative-reduction potential. Actinomycetaceae, Ralstonia and Paenibacillus correlated with reduced chromatin protamination status and increased double-stranded DNA fragmentation. These effects on DNA integrity coincide in many cases with the metabolism or enzymatic activities of these genera. Significant differences between fertile and infertile men were found in the relative presence of the Propionibacteriaceae family and the Cutibacterium, Rhodopseudomonas and Oligotropha genera, which supports its possible involvement in male fertility. Our findings sustain the hypothesis that the seminal microbiome has an effect on male fertility

Potential ecological and socio-economic effects of a novel megaherbivore introduction: the hippopotamus in Colombia

Introduced species can have strong ecological, social and economic effects on their non-native environment. Introductions of megafaunal species are rare and may contribute to rewilding efforts, but they may also have pronounced socio-ecological effects because of their scale of influence. A recent introduction of the hippopotamus Hippopotamus amphibius into Colombia is a novel introduction of a megaherbivore onto a new continent, and raises questions about the future dynamics of the socio-ecological system into which it has been introduced. Here we synthesize current knowledge about the Colombian hippopotamus population, review the literature on the species to predict potential ecological and socio-economic effects of this introduction, and make recommendations for future study. Hippopotamuses can have high population growth rates (7–11%) and, on the current trajectory, we predict there could be 400–800 individuals in Colombia by 2050. The hippopotamus is an ecosystem engineer that can have profound effects on terrestrial and aquatic environments and could therefore affect the native biodiversity of the Magdalena River basin. Hippopotamuses are also aggressive and may pose a threat to the many inhabitants of the region who rely upon the Magdalena River for their livelihoods, although the species could provide economic benefits through tourism. Further research is needed to quantify the current and future size and distribution of this hippopotamus population and to predict the likely ecological, social and economic effects. This knowledge must be balanced with consideration of social and cultural concerns to develop appropriate management strategies for this novel introduction

Over 200,000 kilometers of free-flowing river habitat in Europe is altered due to impoundments

European rivers are disconnected by more than one million man-made barriers that physically limit aquatic species migration and contribute to modification of freshwater habitats. Here, a Conceptual Habitat Alteration Model for Ponding is developed to aid in evaluating the effects of impoundments on fish habitats. Fish communities present in rivers with low human impact and their broad environmental settings enable classification of European rivers into 15 macrohabitat types. These classifications, together with the estimated fish sensitivity to alteration of their habitat are used for assessing the impacts of six main barrier types (dams, weirs, sluices, culverts, fords, and ramps). Our results indicate that over 200,000 km or 10% of previously free-flowing river habitat has been altered due to impoundments. Although they appear less frequently, dams, weirs and sluices cause much more habitat alteration than the other types. Their impact is regionally diverse, which is a function of barrier height, type and density, as well as biogeographical location. This work allows us to foresee what potential environmental gain or loss can be expected with planned barrier management actions in rivers, and to prioritize management actions

Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies

The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favoured development of epigenetic drugs. In this study, we design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of haematological neoplasia (acute myeloid leukaemia-AML, acute lymphoblastic leukaemia-ALL and diffuse large B-cell lymphoma-DLBCL) with the lead compound CM-272, inhibits cell proliferation and promotes apoptosis, inducing interferon-stimulated genes and immunogenic cell death. CM-272 significantly prolongs survival of AML, ALL and DLBCL xenogeneic models. Our results represent the discovery of first-in-class dual inhibitors of G9a/DNMTs and establish this chemical series as a promising therapeutic tool for unmet needs in haematological tumours.We particularly acknowledge the Biobank of the University of Navarra for its collaboration. We thank Dr Edorta Martínez de Marigorta and Dr Francisco Palacios from Departamento de Química Orgánica I, Facultad de Farmacia, Universidad del Pais Vasco for 13C NMR determination and Angel Irigoyen Barrio and Dr Ana Romo Hualde, from University of Navarra, for HRMS determination. Dr. Irene de Miguel Turrullols from Small Molecule Discovery Platform, CIMA, University of Navarra is acknowledged for NMR data interpretation. This work was funded by grants from Instituto de Salud Carlos III (ISCIII) PI10/01691, PI13/01469, PI14/01867, PI10/2983, TRASCAN (EPICA), CIBERONC, cofinanciacion FEDER, RTICC RD12/0036/0068, Fundació La Marató de TV3 (20132130-31-32) and ‘Fundación Fuentes Dutor’. B.P. is supported by a Sara Borrell fellowship CD13/00340 and X.A. is a Marie Curie researcher under contract ‘LincMHeM-330598’.S

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London