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Descripción del curso El objetivo general de esta asignatura es capacitar a futuros profesionales e investigadores relacionados con el campo de Ciencias de la Salud con las herramientas y habilidades necesarias y suficientes para poner en práctica técnicas proteo-inmunológicas que sean resolutivas en el estudio de parásitos en un laboratorio. Objetivos específicos - Conocer algunas de las herramientas necesarias para el estudio proteico e inmunológico de parásitos causantes de enfermedades tropicales. - Adquirir las habilidades necesarias por parte del alumno para el manejo de dichas técnicas en investigación básica y/o aplicada, búsqueda y mejoras de técnicas para el diagnóstico, etc

Mutagenic and genotoxic potential of pure Cylindrospermopsin by a battery of in vitro tests

Cylindrospermopsin (CYN) is a cyanobacterial toxin with an increasing world-wide occurrence. The main route of human exposure is through the ingestion of contaminated food and water. The European Food Safety Authority has identified the need to further characterize the toxicological profile of cyanotoxins and in this regard the genotoxicity is a key toxicological effect. The data available in the scientific literature show contradictory results. Thus, the aim of this study was to investigate the mutagenic and genotoxic effects of pure CYN using a battery of different in vitro assays including: the bacterial reverse-mutation assay in Salmonella typhimurium (Ames test) (0–10 μg/mL), the mammalian cell micronucleus (MN) test (0–1.35 μg/mL and 0–2 μg/mL in absence or presence of S9 fraction, respectively) and the mouse lymphoma thymidine-kinase assay (MLA)(0–0.675 μg/mL) on L5178YTk ± cells, and the standard and enzyme-modified comet assays (0–2.5 μg/mL) on Caco-2 cells. Positive results were obtained only when the metabolic fraction S9 was employed in the MN test, suggesting pro-genotoxic properties of CYN. Also, DNA damage was not mediated by oxidative stress as CYN did not induced changes in the modified comet assay. These data could contribute to a better risk assessment of this cyanotoxin.Ministerio de Economía y Competitividad (AGL2015-64558-R, MINECO/FEDER, U

In vitro toxicological assessment of an organosulfur compound from Allium extract: Cytotoxicity, mutagenicity and genotoxicity studies

Garlic (Allium sativum) and onion (Allium cepa) are being used in the food industry as flavoring but also for their antimicrobial activities. These activities are mainly derived from the organosulfur compounds (OSCs). Propyl propane thiosulfinate (PTS) is an OSC with potential use in the active packaging, but its safety should be guaranteed before being commercialized. The aim of this work was to investigate for the first time the cytotoxicity of PTS as well as its in vitro mutagenic/genotoxic potential using the following battery of genotoxicity tests:(1)the bacterial reverse-mutation assay in S. typhimurium (Ames test, OECD 471, 1997); (2) the micronucleus test (MN, OECD 487, 2016); (3) the mouse lymphoma thymidine-kinase assay (MLA, OECD 476, 2015), and (4) the comet assay (standard and modified with restriction enzymes). The results revealed that PTS was not mutagenic neither in the Ames test nor in MLA. However, genotoxic effects were recorded in the MN test on mammalian cells (L5178YTk+/−cells) after PTS exposure at the highest concentration tested (17.25 μM) without S9, and also its metabolites (+S9, from 20 μM). Moreover, in the comet assay, PTS induced DNA breaks damage in Caco-2 cells at the highest concentration tested (280 μM) but it did not induce oxidative DNA damage.Spanish Ministry of Scienceand Innovation (AGL2012-38357-C02-01) co-financed by FEDER fundsJunta de Andalucía (AGR-7252

Targeting the Gut Microbiota of Vertically HIV-Infected Children to Decrease Inflammation and Immunoactivation: A Pilot Clinical Trial

Aims: Children with HIV exhibit chronic inflammation and immune dysfunction despite antiretroviral therapy (ART). Strategies targeting persistent inflammation are needed to improve health in people living with HIV. The gut microbiota likely interacts with the immune system, but the clinical implications of modulating the dysbiosis by nutritional supplementation are unclear. Methods: Pilot, double-blind, randomized placebo-controlled trial in which 24 HIV-infected on ART were randomized to supplementation with a daily mixture of symbiotics, omega-3/6 fatty acids and amino acids, or placebo four weeks, in combination with ART. We analyzed inflammatory markers and T-cell activation changes and their correlations with shifts in fecal microbiota. Results: Twenty-four HIV-infected children were recruited and randomized to receive a symbiotic nutritional supplement or placebo. Mean age was 12 ± 3.9 years, 62.5% were female. All were on ART and had HIV RNA < 50/mL. We did not detect changes in inflammatory (IL-6, IL-7, IP-10), microbial translocation (sCD14), mucosal integrity markers (IFABP, zonulin) or the kynurenine to tryptophan ratio, or changes in markers of the adaptive immune response in relation to the intervention. However, we found correlations between several key bacteria and the assessed inflammatory and immunological parameters, supporting a role of the microbiota in immune modulation in children with HIV. Conclusions: In this exploratory study, a four-week nutritional supplementation had no significant effects in terms of decreasing inflammation, microbial translocation, or T-cell activation in HIV-infected children. However, the correlations found support the interaction between gut microbiota and the immune system

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

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Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030