The 3¿UTR of the West Nile Virus genomic RNA is a potential antiviral target site

The protein coding-information only represents a small portion of the genetic load of a living organism. It is well established that essential information codes functional RNAs, called non-coding RNAs (ncRNAs), which play key roles in the essential biological processes of the cell life. Many mRNAs also act as truly ncRNAs besides being translated into proteins. Therefore, the repertoire of potential drug targets to fight diseases goes beyond proteins. Viral RNA genomes encode all the information for completion of the infectious cycle. They are multifunctional molecules, which act as replication templates and mRNAs. Further, defined structural domains in viral RNA genomes play key functions for the completion of the viral cycle and the regulation of the essential processes; these domains have also been involved in virulence. The West Nile Virus (WNV) genome consists in a single stranded RNA molecule, which contains a single ORF flanked by untranslated regions (UTRs). The 3¿UTR is required for efficient translation, but the mechanisms involved in this regulation are still obscure. In this work, we show evidences that the WNV-3¿UTR specifically recruits the 40S ribosomal subunit. We have localized two potential binding sites of the 40S. Binding of the 40S induced conformational changes in highly conserved structural domains within the WNV-3¿UTR. Functional assays support the hypothesis that recruitment of the 40S particle by the 3¿UTR is required for an efficient translation. Interfering with the 40S recruitment, by targeting the WNV-3¿UTR binding sites, constitutes a potential antiviral strategy by the development of new therapeutic compounds

Coordination between family doctors and the cardiologist: the result of clinical sessions in a primary health care centre

Introducción: La interacción entre médicos de familia (MF) y hospitalarios se considera indispensable para una atención de calidad. Objetivo: Evaluar los resultados de la realización de sesiones con el cardiólogo en un centro de salud. Métodos: Estudio descriptivo en un centro de salud Palma, Baleares, España. Presentación de casos clínicos al cardiólogo de referencia por los MF para la solución de problemas diagnóstico-terapéuticos. Registro de datos clínico-epidemiológicos, tipo de interconsulta, solución del cardiólogo, derivaciones evitadas. Resultados: Incluimos 99 pacientes de enero 2016-junio 2017, presentados por 14 MF. Motivos: 52,5% fueron posibles alteraciones electrocardiográficas. Problema: alteración electrocardiográfica solamente (39,1%), dolor torácico (9,1%), palpitaciones (9.1%), arritmias (8.1%). El 70,7% de casos se evitó que el paciente acudiera al servicio de cardiología. Conclusiones: la interconsulta cardiológica bimensual evita gran número de consultas presenciales y es altamente valorado por los MF.Introduction: The relationship between family doctors and the cardiologist in Primary Health Care (PHC) Team is important to ensure quality care. Objective: To assess the results of carrying out clinical sessions with the cardiologist in a PHC Centre. Methods: Descriptive study in a PHC Centre in Palma, Balearic Islands , Spain. Family doctors presented clinical cases to the cardiologist in order to solve diagnosis treatment problems. We registered clinical-epidemiology information, type of referral, cardiologist decision, and number of referrals to cardiology department avoided. Results: 99 patients were included from February 2016 to June 2017, who were presented by 14 family doctors. Cause of consultation: 52.5 % were EKG abnormalities. Problems: 39.1% were EKG doubts, 9.1% chest pain, 9.1% palpitations, 8.1% arrhythmia. A 70.7% of patients avoided being referred to the cardiology department. Conclusions: The bimonthly consultation avoids having to make a great amount of patient appointments at Hospital and is extremely appreciated by family doctors

Prosthetic shoulder joint infection by Cutibacterium acnes: does rifampin improve prognosis? a retrospective, multicenter, observational study.

This retrospective, multicenter observational study aimed to describe the outcomes of surgical and medical treatment of C. acnes-related prosthetic joint infection (PJI) and the potential benefit of rifampin-based therapies. Patients with C. acnes-related PJI who were diagnosed and treated between January 2003 and December 2016 were included. We analyzed 44 patients with C. acnes-related PJI (median age, 67.5 years (IQR, 57.3-75.8)); 75% were men. The majority (61.4%) had late chronic infection according to the Tsukayama classification. All patients received surgical treatment, and most antibiotic regimens (43.2%) included β-lactam. Thirty-four patients (87.17%) were cured; five showed relapse. The final outcome (cure vs. relapse) showed a nonsignificant trend toward higher failure frequency among patients with previous prosthesis (OR: 6.89; 95% CI: 0.80-58.90) or prior surgery and infection (OR: 10.67; 95% IC: 1.08-105.28) in the same joint. Patients treated with clindamycin alone had a higher recurrence rate (40.0% vs. 8.8%). Rifampin treatment did not decrease recurrence in patients treated with β-lactams. Prior prosthesis, surgery, or infection in the same joint might be related to recurrence, and rifampin-based combinations do not seem to improve prognosis. Debridement and implant retention appear a safe option for surgical treatment of early PJI

The Different Microbial Etiology of Prosthetic Joint Infections According to Route of Acquisition and Time After Prosthesis Implantation, Including the Role of Multidrug-Resistant Organisms

The aim of our study was to characterize the etiology of prosthetic joint infections (PJIs)-including multidrug-resistant organisms (MDRO)-by category of infection. A multicenter study of 2544 patients with PJIs was performed. We analyzed the causative microorganisms according to the Tsukayama's scheme (early postoperative, late chronic, and acute hematogenous infections (EPI, LCI, AHI) and "positive intraoperative cultures" (PIC)). Non-hematogenous PJIs were also evaluated according to time since surgery: 12 months. AHIs were mostly caused by Staphylococcus aureus (39.2%) and streptococci (30.2%). EPIs were characterized by a preponderance of virulent microorganisms (S. aureus, Gram-negative bacilli (GNB), enterococci), MDROs (24%) and polymicrobial infections (27.4%). Conversely, coagulase-negative staphylococci (CoNS) and Cutibacterium species were predominant in LCIs (54.5% and 6.1%, respectively) and PICs (57.1% and 15.1%). The percentage of MDROs isolated in EPIs was more than three times the percentage isolated in LCIs (7.8%) and more than twice the proportion found in AHI (10.9%). There was a significant decreasing linear trend over the four time intervals post-surgery for virulent microorganisms, MDROs, and polymicrobial infections, and a rising trend for CoNS, streptococci and Cutibacterium spp. The observed differences have important implications for the empirical antimicrobial treatment of PJIs.Acknowledgments: This work was supported by the Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness (grant number PI15/1026) (Co-funded by European Regional Development Fund/European Social Fund "Investing in your future"). REIPI (Spanish Network for Research in Infectious Disease) is supported by the Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness, and by the European Development Regional Fund “A way to achieve Europe”

Multicentre, randomised, open-label, phase IV–III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial

SAFO study group and the Spanish Network for Research in Infectious Diseases (REIPI).[Introduction] Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia.[Methods] We will perform a superiority, randomised, open-label, phase IV–III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant).[Ethics and dissemination] Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders.[Trial registration number] The protocol has been approved by AEMPS with the Trial Registration Number EudraCT 2018-001207-37. ClinicalTrials.gov Identifier: NCT03959345; Pre-results.The SAFO trial is supported by a competitive grant awarded by the Fondo de Investigaciones Sanitarias at the Spanish government’s National Institute of Health Research, Instituto de Salud Carlos III (ISCIII), (FIS PI17/01116). This study was supported by Plan Nacional de I+D+i 2017–2021 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0005).Peer reviewe

Revisiting the epidemiology of bloodstream infections and healthcare-associated episodes: results from a multicentre prospective cohort in Spain (PRO-BAC Study)

PROBAC REIPI/GEIH-SEIMC/SAEI Group.The epidemiology of bloodstream infections (BSIs) is dynamic as it depends on microbiological, host and healthcare system factors. The aim of this study was to update the information regarding the epidemiology of BSIs in Spain considering the type of acquisition. An observational, prospective cohort study in 26 Spanish hospitals from October 2016 through March 2017 including all episodes of BSI in adults was performed. Bivariate analyses stratified by type of acquisition were performed. Multivariate analyses were performed by logistic regression. Overall, 6345 BSI episodes were included; 2510 (39.8%) were community-acquired (CA), 1661 (26.3%) were healthcare-associated (HCA) and 2056 (32.6%) hospital-acquired (HA). The 30-day mortality rates were 11.6%, 19.5% and 22.0%, respectively. The median age of patients was 71 years (interquartile range 60–81 years) and 3656 (58.3%; 95% confidence interval 57.1–59.6%) occurred in males. The proportions according to patient sex varied according to age strata. Escherichia coli (43.8%), Klebsiella spp. (8.9%), Staphylococcus aureus (8.9%) and coagulase-negative staphylococci (7.4%) were the most frequent pathogens. Multivariate analyses confirmed important differences between CA and HCA episodes, but also between HCA and HA episodes, in demographics, underlying conditions and aetiology. In conclusion, we have updated the epidemiological information regarding patients’ profiles, underlying conditions, frequency of acquisition types and aetiological agents of BSI in Spain. HCA is confirmed as a distinct type of acquisition.This work was financed by grants from Plan Nacional de I+D+i 2013–2016, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades [PI16/01432] and the Spanish Network for Research in Infectious Diseases (REIPI) [RD16/0016/0001; RD16/0016/0008], co‐financed by the European Development Regional Fund ‘A way to achieve Europe’, Operative program Intelligent Growth 2014–2020

Daptomycin plus Fosfomycin versus Daptomycin Alone for Methicillin-Resistant Staphylococcus 2 aureus Bacteremia and Endocarditis. A Randomized Clinical Trial

Background We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. Methods A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. Results Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93-1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018). Conclusions Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events

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

Artificial intelligence within the interplay between natural and artificial computation:Advances in data science, trends and applications

Artificial intelligence and all its supporting tools, e.g. machine and deep learning in computational intelligence-based systems, are rebuilding our society (economy, education, life-style, etc.) and promising a new era for the social welfare state. In this paper we summarize recent advances in data science and artificial intelligence within the interplay between natural and artificial computation. A review of recent works published in the latter field and the state the art are summarized in a comprehensive and self-contained way to provide a baseline framework for the international community in artificial intelligence. Moreover, this paper aims to provide a complete analysis and some relevant discussions of the current trends and insights within several theoretical and application fields covered in the essay, from theoretical models in artificial intelligence and machine learning to the most prospective applications in robotics, neuroscience, brain computer interfaces, medicine and society, in general.BMS - Pfizer(U01 AG024904). Spanish Ministry of Science, projects: TIN2017-85827-P, RTI2018-098913-B-I00, PSI2015-65848-R, PGC2018-098813-B-C31, PGC2018-098813-B-C32, RTI2018-101114-B-I, TIN2017-90135-R, RTI2018-098743-B-I00 and RTI2018-094645-B-I00; the FPU program (FPU15/06512, FPU17/04154) and Juan de la Cierva (FJCI-2017–33022). Autonomous Government of Andalusia (Spain) projects: UMA18-FEDERJA-084. Consellería de Cultura, Educación e Ordenación Universitaria of Galicia: ED431C2017/12, accreditation 2016–2019, ED431G/08, ED431C2018/29, Comunidad de Madrid, Y2018/EMT-5062 and grant ED431F2018/02. PPMI – a public – private partnership – is funded by The Michael J. Fox Foundation for Parkinson’s Research and funding partners, including Abbott, Biogen Idec, F. Hoffman-La Roche Ltd., GE Healthcare, Genentech and Pfizer Inc

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial

Introduction: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. Methods: We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). Ethics and dissemination: Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders