Effects of Folinic Acid Administration on Lower Limb Ischemia/Reperfusion Injury in Rats

Surgery under ischemic conditions, lasting up to 3 h, is routinely performed in orthopedic surgery, causing undesirable injury due to ischemia-reperfusion syndrome, with short and medium-term functional repercussions. To date, there is no established prophylactic treatment. In this work we evaluated folinic acid (FA) in a rodent model of lower limb ischemia-reperfusion (IRI-LL). 36 male WAG rats underwent 3 h of lower limb ischemia. In the saline group, rats received intraperitoneal administration of saline (used as vehicle for treatment). In the experimental group, rats were pretreated with FA (2.5 mg/kg) before the end of ischemia. After ischemia, animals were sacrificed at 3 h, 24 h or 14 days (for biochemical determination (Na+, K+, Cl-, urea, creatinine, CK, LDH, ALP, ALT, and AST), pathological assessment, or functional study using the rotarod test; respectively). Another six animals were used to establish the reference values. The prophylactic administration of FA significantly reduced the elevation of biochemical markers, especially those that most directly indicate muscle damage (CK and LDH). In addition, it also improved direct tissue damage, both in terms of edema, weight, PMN infiltrate and percentage of damaged fibers. Finally, the administration of FA allowed the animals to equal baseline values in the rotarod test; what did not occur in the saline group, where pre-ischemia levels were not recovered. Following 3 h of lower limb ischemia, FA minimizes the increase of CK and LDH, as well as local edema and leukocyte infiltration, allowing a faster recovery of limb functionality. Therefore, it could be considered as a prophylactic treatment when tourniquet is used in clinics.This research received funding from the University of The Basque Country UPV/EHU (grant reference GIU19/088)

Prediction Accuracy of Serial Lung Ultrasound in COVID-19 Hospitalized Patients (Pred-Echovid Study)

The value of serial lung ultrasound (LUS) in patients with COVID-19 is not well defined. In this multicenter prospective observational study, we aimed to assess the prognostic accuracy of serial LUS in patients admitted to hospital due to COVID-19. The serial LUS protocol included two examinations (0–48 h and 72–96 h after admission) using a 10-zones sequence, and a 0 to 5 severity score. Primary combined endpoint was death or the need for invasive mechanical ventilation. Calibration (Hosmer–Lemeshow test and calibration curves), and discrimination power (area under the ROC curve) of both ultrasound exams (SCORE1 and 2), and their difference (DIFFERENTIAL-SCORE) were performed. A total of 469 patients (54.2% women, median age 60 years) were included. The primary endpoint occurred in 51 patients (10.9%). Probability risk tertiles of SCORE1 and SCORE2 (0–11 points, 12–24 points, and ≥25 points) obtained a high calibration. SCORE-2 showed a higher discrimination power than SCORE-1 (AUC 0.72 (0.58–0.85) vs. 0.61 (0.52–0.7)). The DIFFERENTIAL-SCORE showed a higher discrimination power than SCORE-1 and SCORE-2 (AUC 0.78 (0.66–0.9)). An algorithm for clinical decision-making is proposed. Serial lung ultrasound performing two examinations during the first days of hospitalization is an accurate strategy for predicting clinical deterioration of patients with COVID-19

Una modificación al método de Kudoh para el cultivo de M. Tuberculosis

The adition of trisodium phophate 4.3% (Na3PO4. 12H2O 10 g. in 100 ml. of destiled watter) in equal parts to sputum for 24 hours, before the inoculation by the swab technique of Kudoh in modified Ogawa, substantially disminishes the contamination rate without altering the viability of M. tuberculosis, and facilitates the impregnation of the sputum in the swab.La adición al esputo de una cantidad igual de fosfato trisódico al 4.3% (Na3P04. 12H20 10 g. en 100 ml. de agua destilada) durante 24 horas previa a la siembra por el método del escobillón de Kudoh en medio modificado de Ogawa, disminuye notoriamente la contaminación de los cultivos, sin alterar la vitalidad del M. tuberculosis y facilita la homogenización del escobillón

Body mass index interacts with a genetic-risk score for depression increasing the risk of the disease in high-susceptibility individuals

Depression is strongly associated with obesity among other chronic physical diseases. The latest mega- and meta-analysis of genome-wide association studies have identified multiple risk loci robustly associated with depression. In this study, we aimed to investigate whether a genetic-risk score (GRS) combining multiple depression risk single nucleotide polymorphisms (SNPs) might have utility in the prediction of this disorder in individuals with obesity. A total of 30 depression-associated SNPs were included in a GRS to predict the risk of depression in a large case-control sample from the Spanish PredictD-CCRT study, a national multicentre, randomized controlled trial, which included 104 cases of depression and 1546 controls. An unweighted GRS was calculated as a summation of the number of risk alleles for depression and incorporated into several logistic regression models with depression status as the main outcome. Constructed models were trained and evaluated in the whole recruited sample. Non-genetic-risk factors were combined with the GRS in several ways across the five predictive models in order to improve predictive ability. An enrichment functional analysis was finally conducted with the aim of providing a general understanding of the biological pathways mapped by analyzed SNPs. We found that an unweighted GRS based on 30 risk loci was significantly associated with a higher risk of depression. Although the GRS itself explained a small amount of variance of depression, we found a significant improvement in the prediction of depression after including some non-genetic-risk factors into the models. The highest predictive ability for depression was achieved when the model included an interaction term between the GRS and the body mass index (BMI), apart from the inclusion of classical demographic information as marginal terms (AUC = 0.71, 95% CI = [0.65, 0.76]). Functional analyses on the 30 SNPs composing the GRS revealed an over-representation of the mapped genes in signaling pathways involved in processes such as extracellular remodeling, proinflammatory regulatory mechanisms, and circadian rhythm alterations. Although the GRS on its own explained a small amount of variance of depression, a significant novel feature of this study is that including non-genetic-risk factors such as BMI together with a GRS came close to the conventional threshold for clinical utility used in ROC analysis and improves the prediction of depression. In this study, the highest predictive ability was achieved by the model combining the GRS and the BMI under an interaction term. Particularly, BMI was identified as a trigger-like risk factor for depression acting in a concerted way with the GRS component. This is an interesting finding since it suggests the existence of a risk overlap between both diseases, and the need for individual depression genetics-risk evaluation in subjects with obesity. This research has therefore potential clinical implications and set the basis for future research directions in exploring the link between depression and obesity-associated disorders. While it is likely that future genome-wide studies with large samples will detect novel genetic variants associated with depression, it seems clear that a combination of genetics and non-genetic information (such is the case of obesity status and other depression comorbidities) will still be needed for the optimization prediction of depression in high-susceptibility individuals

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.Fil: Dalmasso, Maria Carolina. Gobierno de la Provincia de la Pampa. Ministerio Publico. Laboratorio de Genetica Forense.; Argentina. Universitat zu Köln; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Confluencia; ArgentinaFil: de Rojas, Itziar. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos Iii (isciii); EspañaFil: Moreno Grau, Sonia. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos Iii (isciii); EspañaFil: Tesi, Niccolo. Vrije Universiteit Amsterdam; Países Bajos. Delft University of Technology; Países BajosFil: Grenier Boley, Benjamin. Universite Lille; FranciaFil: Andrade, Victor. Universitat zu Köln; Alemania. Universitat Bonn; AlemaniaFil: Pedersen, Nancy L.. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Stringa, Najada. University of Amsterdam; Países BajosFil: Zettergren, Anna. University of Gothenburg; SueciaFil: Hernández, Isabel. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos Iii (isciii); EspañaFil: Montrreal, Laura. Universitat Internacional de Catalunya; EspañaFil: Antúnez, Carmen. Hospital Clínico Universitario Virgen de la Arrixaca; EspañaFil: Antonell, Anna. Universidad de Barcelona; EspañaFil: Tankard, Rick M.. Murdoch University; AustraliaFil: Bis, Joshua C.. University of Washington; Estados UnidosFil: Sims, Rebecca. Cardiff University; Reino UnidoFil: Bellenguez, Céline. Universite Lille; FranciaFil: Quintela, Inés. Universidad de Santiago de Compostela; EspañaFil: González Perez, Antonio. Centro Andaluz de Estudios Bioinformáticos; EspañaFil: Calero, Miguel. Instituto de Salud Carlos Iii (isciii); España. Fundación Reina Sofia; EspañaFil: Franco Macías, Emilio. Universidad de Sevilla; EspañaFil: Macías, Juan. Hospital Universitario de Valme; EspañaFil: Blesa, Rafael. Instituto de Salud Carlos Iii (isciii); España. Universitat Autònoma de Barcelona; EspañaFil: Cervera Carles, Laura. Instituto de Salud Carlos Iii (isciii); España. Universitat Autònoma de Barcelona; EspañaFil: Menéndez González, Manuel. Universidad de Oviedo; EspañaFil: Frank García, Ana. Instituto de Salud Carlos Iii (isciii); España. Universidad Autónoma de Madrid; España. Instituto de Investigacion del Hospital de la Paz.; España. Hospital Universitario La Paz; EspañaFil: Royo, Jose Luís. Universidad de Málaga; EspañaFil: Moreno, Fermin. Instituto de Salud Carlos Iii (isciii); España. Hospital Universitario Donostia; España. Instituto Biodonostia; EspañaFil: Huerto Vilas, Raquel. Hospital Universitari Santa Maria de Lleida; España. Institut de Recerca Biomedica de Lleida; EspañaFil: Baquero, Miquel. Hospital Universitari i Politècnic La Fe; Españ

Programa de coordinación en el Máster Universitario en Física y Tecnología de los Láseres

Memoria ID-042. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2010-2011.El proyecto ha pretendido desarrollar un programa integral de coordinación en la titulación de Máster en Física y Tecnología de los Láseres. Desde que se implantó el máster en el curso 2006-07 se han llevado a cabo tareas de coordinación de forma continua con el objeto de subsanar problemas detectados. Durante la ejecución de este proyecto se ha intentado sistematizar el proceso de coordinación y documentar las actuaciones realizadas

Declaración de Chinchón: decálogo sobre eldulcorantes sin y bajos en calorías (ESBC)

Multidisciplinary experts in the areas of nutrition and health met in Chinchón, Madrid, on November 25-26, 2013 under the auspices of the Fundación para la Investigación Nutricional (Nutrition Research Foundation) and with the collaboration of the Madrid Regional Government’s Health Ministry, the International Sweeteners Association and the Carlos III Health Institute CIBER of Physiopathology of Obesity and Nutrition. They analyzed the current status of scientific knowledge on low- and no-calorie sweeteners (LNCS) and developed a consensus Decalogue on their use; this constitutes the Chinchón Declaration. Sweeteners, including sugar, represent a subject of undeniable interest and are currently a popular topic, although areas relating to their safety and benefits remain unknown to segments of academia and the general public. The nature of LNCS makes them vulnerable to biased and even contradictory information. They are food additives that are broadly used as sugar substitutes to sweeten foods, medicines and food supplements when non-nutritional or non-caloric alternatives are needed. The Chinchón Decalogue is the outcome of a meeting for reflection and consensus by a group of experts with backgrounds in different scientific disciplines (toxicology, clinical nutrition, community nutrition, physiology, food science, public health, pediatrics, endocrinology and nutrition, nursing, pharmaceutical care and food legislation). The Decalogue includes different aspects of LNCS related to regulation, use, benefits and safety. In general, benefits of LNCS have been traditionally neglected in comparison with the tendency for emphasising unexisting or unproven possible risks. The need to strengthen research on LNCS in Spain was emphasized, as well as the need to educate both professionals and the publicExpertos de carácter multidisciplinar de las áreas de conocimiento de la nutrición y la salud reunidos en Chinchón, Madrid, los días 25 y 26 de noviembre de 2013 , bajo los auspicios de la Fundación para la Investigación Nutricional y con la colaboración de la Consejería de Sanidad del Gobierno de la Comunidad de Madrid, la International Sweeteners Association y el CIBER de Fisiopatología de la Obesidad y la Nutrición del Instituto de Salud Carlos III, analizaron el estado actual del conocimiento científico en torno a los Edulcorantes sin y bajos en calorías (ESBC) y desarrollaron un Decálogo sobre su uso que constituye la Declaración de Chinchón. Los edulcorantes, incluido el azúcar, constituyen un elemento de indudable interés y actualidad, aunque no exento de desconocimiento por algunos sectores tanto académicos como de la población en general. La propia naturaleza de los ESBC los hace susceptibles de informaciones tergiversadas e incluso contradictorias. Son aditivos alimentarios ampliamente utilizados como sustitutivos del azúcar para endulzar alimentos, medicamentos y complementos alimenticios cuando se persiguen fines no nutritivos. El Decálogo de Chinchón es fruto de una reunión de reflexión y consenso por parte de un grupo de expertos procedentes de distintas disciplinas científicas (toxicología, nutrición clínica, nutrición comunitaria, fisiología, bromatología, salud pública, atención primaria, pediatría, endocrinología y nutrición, enfermería, atención farmacéutica y legislación alimentaria). El decálogo incluye diferentes aspectos de los EBSC relacionados con la legislación, uso, beneficios y seguridad. En general, los beneficios de los EBSC han sido tradicionalmente desatendidos en comparación con la tendencia de destacar posibles riesgos inexistentes o que no han sido probados. Hace especial hincapié en la necesidad de fortalecer la investigación de los EBSC en España, así como la necesidad de formar en este ámbito a los profesionales y a los consumidores en genera

Effectiveness of Modified Vaccinia Ankara-Bavaria Nordic Vaccination in a Population at High Risk of Mpox: A Spanish Cohort Study

Background: With over 7,500 cases notified since April 2022, Spain has experienced the highest incidence of mpox in Europe. From July 12th onwards, the Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN) smallpox vaccine was offered as pre-exposure prophylaxis for individuals at high-risk of mpox, including those receiving pre-exposure prophylaxis for HIV (HIV-PrEP). Our aim was to assess the effectiveness of one dose of MVA-BN vaccine as pre-exposure against mpox virus (MPXV) infection in persons on HIV-PrEP. Methods: We conducted a national retrospective cohort study between July 12 and December 12, 2022. Individuals ≥18 years, receiving HIV-PrEP as of July 12 and with no previous MPXV infection or vaccination were eligible. Each day, we matched individuals receiving a first dose of MVA-BN vaccine and unvaccinated controls of the same age group and region. We used a Kaplan-Meier estimator and calculate risk ratios (RR) and vaccine effectiveness (VE = 1-RR). Results: We included 5,660 matched pairs, with a median follow-up of 62 days (interquartile range 24-97). Mpox cumulative incidence was 5.6 per 1,000 (25 cases) in unvaccinated and 3.5 per 1,000 (18 cases) in vaccinated. No effect was found during days 0-6 post-vaccination (VE -38.3; 95% confidence interval (95%CI): -332.7; 46.4), but VE was 65% in ≥7 days (95%CI 22.9; 88.0) and 79% in ≥14 days (95%CI 33.3; 100.0) post-vaccination. Conclusions: One dose of MVA-BN vaccine offered protection against mpox in a most-at-risk population shortly after the vaccination. Further studies need to assess the VE of a second dose and the duration of protection over time.S

Effectiveness of a strategy that uses educational games to implement clinical practice guidelines among Spanish residents of family and community medicine (e-EDUCAGUIA project):A clinical trial by clusters

This study was funded by the Fondo de Investigaciones Sanitarias FIS Grant Number PI11/0477 ISCIII.-REDISSEC Proyecto RD12/0001/0012 AND FEDER Funding.Background: Clinical practice guidelines (CPGs) have been developed with the aim of helping health professionals, patients, and caregivers make decisions about their health care, using the best available evidence. In many cases, incorporation of these recommendations into clinical practice also implies a need for changes in routine clinical practice. Using educational games as a strategy for implementing recommendations among health professionals has been demonstrated to be effective in some studies; however, evidence is still scarce. The primary objective of this study is to assess the effectiveness of a teaching strategy for the implementation of CPGs using educational games (e-learning EDUCAGUIA) to improve knowledge and skills related to clinical decision-making by residents in family medicine. The primary objective will be evaluated at 1 and 6months after the intervention. The secondary objectives are to identify barriers and facilitators for the use of guidelines by residents of family medicine and to describe the educational strategies used by Spanish teaching units of family and community medicine to encourage implementation of CPGs. Methods/design: We propose a multicenter clinical trial with randomized allocation by clusters of family and community medicine teaching units in Spain. The sample size will be 394 residents (197 in each group), with the teaching units as the randomization unit and the residents comprising the analysis unit. For the intervention, both groups will receive an initial 1-h session on clinical practice guideline use and the usual dissemination strategy by e-mail. The intervention group (e-learning EDUCAGUIA) strategy will consist of educational games with hypothetical clinical scenarios in a virtual environment. The primary outcome will be the score obtained by the residents on evaluation questionnaires for each clinical practice guideline. Other included variables will be the sociodemographic and training variables of the residents and the teaching unit characteristics. The statistical analysis will consist of a descriptive analysis of variables and a baseline comparison of both groups. For the primary outcome analysis, an average score comparison of hypothetical scenario questionnaires between the EDUCAGUIA intervention group and the control group will be performed at 1 and 6months post-intervention, using 95% confidence intervals. A linear multilevel regression will be used to adjust the model. Discussion: The identification of effective teaching strategies will facilitate the incorporation of available knowledge into clinical practice that could eventually improve patient outcomes. The inclusion of information technologies as teaching tools permits greater learning autonomy and allows deeper instructor participation in the monitoring and supervision of residents. The long-term impact of this strategy is unknown; however, because it is aimed at professionals undergoing training and it addresses prevalent health problems, a small effect can be of great relevance. Trial registration: ClinicalTrials.gov: NCT02210442.Publisher PDFPeer reviewe

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