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BackgroundMedical degree students often express great satisfaction toward their mentoring experience and share the impression that it has contributed significantly to their personal and professional development. Mentoring can contribute to a more comprehensive and integral preparation of the student for professional life, promoting critical reflection, but studies are needed which focus on effectiveness in achieving educational objectives by means of an appropriate methodology.MethodsThis pilot study aims to evaluate the formative impact on students' attitudes towards suffering and death and their perception of the role of mentors in an innovative mentoring program for undergraduate students through a quasi-experimental design.Between October 2019 and March 2020, 2nd-year medical students were invited to participate in a mentoring program made up of 5 mentors, randomly assigned to each student by Microsoft Excel's randomization function. A validated and adapted scale was used to measure students' perception of their mentors (CECA Scale) and the mentoring program, while another two validated scales were used to measure attitudes toward suffering (Brief Humanising Scale) and death (Bugen Scale).ResultsOf the 109 students invited to participate (79% female and 21% male), 20 agreed to participate in the intervention group and 24 in the control group. CECA was scored with medians of 6 (the highest score). The Brief Humanising Scale returned no statistically significant differences between the groups. The Bugen Scale showed significant differences after intervention in 80% of the items directly related to the educational objectives. ConclusionsStudents' perception of mentors and mentoring has been optimal. Students' attitude toward suffering was not improved, although attitudes toward death were. Long-term, mixed studies are needed to obtain a higher degree of evidence.

Summary Background Many antiseptics have been used to treat wounds. Aim To compare the microbicidal efficacy of ClHO (Clortech®) with other antiseptics used on wounds, healthy skin and mucous membranes. Methods The microbicidal efficacy of 13 antiseptic products on eight micro-organisms (three Gram-positive; three Gram-negative; two yeasts) inoculated on organic germ-carriers was studied. In addition, the loss of efficacy against Staphylococcus aureus and Pseudomonas aeruginosa with biofilm was assessed with the six best-performing products. Findings Chlorhexidine (1%) had the highest microbicidal effect at 1 min. At 5 min, 500 and 1500 mg/L ClHO showed similar, or better, activity than the other antiseptics studied. The ClHO concentration of 300 mg/L achieved this same efficacy at 10 min. The product that lost the most efficacy due to biofilm was 1% chlorhexidine, while 1% PVP-I and ClHO at either 300 or 500 mg/L were moderately affected by biofilm. The most effective in the presence of biofilm was ClHO at 1500 mg/L. Conclusions ClHO at medium–low concentrations (300 or 500 mg/L) is a good antiseptic that can be used on wounds and mucous membranes for 5–10 min. Lower concentrations of ClHO, as well as of the other antiseptics studied, were less effective or more altered by the biofilm. ClHO at a concentration of 1500 mg/L is very effective in the presence or absence of biofilm that can be used on healthy skin for 5 min.

To determine the functional recovery, active reincorporation, and anteroposterior and rotational stability of patients undergoing anterior cruciate ligament (ACL) reconstruction using arthroscopy techniques with simple-bundle (SB) or double-bundle (DB). The following databases were searched: PubMed, Embase (Elsevier platform), the Cochrane Central Register of Controlled Trials (Wiley platform), Web of Science, and CINAHL. Level I and II studies involving anterior cruciate ligament arthroscopy were included in the search. Records were screened by title and abstract and assessed the risk of bias of selected studies. Meta-analyses using RevMan 5.3 software were conducted on the following outcomes: knee functionality, objective measurements of knee stability, rotational knee stability and knee anterior stability, sports reincorporation, and subjective assessments. Twenty-four studies of patients undergoing ACL reconstruction were included in the qualitative and quantitative synthesis (1707 patients) for Lysholm score, Subjective International Knee Documentation Committee (IKDC) score, Tegner score, KT-1000/2000, Lachman test, Objective IKDC score, and Pivot-Shift test. A return to pre-injury level showed a significant decrease in the Lysholm score (mean difference, − 0.99; 95% CI − 1.71 to − 0.40; P = 0.007) and Tegner score (mean difference, − 0.07; 95% CI, − 0.13 to − 0.01; P = 0.02) at DB reconstruction, similar to the knee functionality outcome of the subjective IKDC score (mean difference − 1.42; 95% CI − 2.46 to − 0.38; P = 0.007). There is no clear or significant difference in clinical stability and knee function or in sports incorporation with the true difference occurring in the subjective assessment.

Background. The typical methylation patterns associated with cancer are hypermethylation at gene promoters and global genome hypomethylation. Aberrant CpG island hypermethylation at promoter regions and global genome hypomethylation have not been associated with histological colorectal carcinomas (CRC) subsets. Using Illumina’s 450 k Infinium Human Methylation beadchip, the methylome of 82 CRCs were analyzed, comprising different histological subtypes: 40 serrated adenocarcinomas (SAC), 32 conventional carcinomas (CC) and 10 CRCs showing histological and molecular features of microsatellite instability (hmMSI‐H), and, additionally, 35 normal adjacent mucosae. Scores reflecting the overall methylation at 250 bp, 1 kb and 2 kb from the transcription starting site (TSS) were studied. Results. SAC has an intermediate methylation pattern between CC and hmMSI‐H for the three genome locations. In addition, the shift from promoter hypermethylation to genomic hypomethylation occurs at a small sequence between 250 bp and 1 Kb from the gene TSS, and an asymmetric distribution of methylation was observed between both sides of the CpG islands (N vs. S shores). Conclusion. These findings show that different histological subtypes of CRC have a particular global methylation pattern depending on sequence distance to TSS and highlight the so far underestimated importance of CpGs aberrantly hypomethylated in the clinical phenotype of CRCs., This work was supported by two grants from Instituto de Salud Carlos III, Ministerio de Sanidad, Spain and FEDER funds (refs: PI12-1232, PI18-0144) and another from the European Union’s Horizon 2020 research and innovation program (ref. 848098)

Introducción La crisis por COVID-19 supuso en marzo del 2020 el cierre de las universidades del país, con interrupción total de actividad presencial. Para afrontar el último cuatrimestre 2019/20 en confinamiento, nuestra Facultad de Medicina elaboró y aplicó un programa docente íntegramente online con un enfoque «autorregulativo» (enfocado en el aprendizaje autónomo del alumno). Este estudio presenta las opiniones de profesores y alumnos. Métodos Las características educativas del Programa online ante COVID-19 (POLAC), para primero y segundo cursos, estructuración, organización de la intervención y resultados académicos, han sido descritos en otro trabajo. Este estudio mediante encuestas online, explora opiniones de profesores y alumnos tras su desarrollo. Dos investigadores codificaron temática e independientemente las respuestas abiertas obtenidas, clasificándolas en categorías. Resultados Respondieron los ocho profesores implicados y un número variable por asignatura de alumnos, recibiéndose 234 cuestionarios (17%). Los alumnos destacan de positivo la optimización de recursos docentes utilizados, la utilidad de las herramientas online, especialmente autoevaluaciones y sistema de gestión de dudas. El desarrollo de las prácticas y aspectos propios de la presencialidad se destacaron como negativos. La dedicación de los profesores recibió comentarios, tanto positivos como negativos. Los profesores resaltaron la potenciación de la autonomía del alumno, la utilidad de las herramientas online y la necesidad adicional de presencialidad. Conclusión Globalmente, los comentarios positivos y negativos están en línea con las fortalezas y debilidades tanto de la enseñanza online como de enfoques docentes «autorregulativos». Se precisan estudios de diseños más robustos para comprobar el alcance real de estos resultados. post-print 333 KB

Assessment methods of surface disinfection based on international standards (Environmental Protection Agency, European Norms, etc) do not correspond to hospital reality. New evaluation methods of surfaces disinfection are proposed to choose the most suitable disinfectant to act against clinically relevant microorganisms detected on the surfaces of burn units. 1) "Immediate effect": 6 products were compared using a glass germ-carrier and 20 recently isolated microorganisms from different patients in the intensive care units. Disinfectants were applied with microfiber cloths. Log10 reductions were calculated for colony forming units produced after 15 minutes of disinfectant application. 2) "Residual effect": the glass germ-carriers were previously impregnated with one of the studied disinfectants. After a 30-minute wait period, they were then contaminated with 1 microorganism (from the 20 above-mentioned). After 15 minutes, the disinfectant was inhibited and the log10 reduction of colony forming units was assessed. The immediate effect (disinfection and microorganism dragging and transferring from the surface to the cloth) produced complete elimination of the inoculums for all products used except one (a diluted quaternary ammonium). The average residual effect found on the 20 microorganisms was moderate: 2 to 3 log10 colony forming unit reduction with chlorine dioxide or 0.5% chlorhexidine (and lower with the other products), obtaining surfaces refractory to recontamination, at least, during 30 minutes. Two tests should be performed before advising surface disinfectant: 1) direct effect and 2) residual efficacy. These characteristics should be considered when a new surface disinfectant is chosen. Chlorine dioxide has a similar or better direct effect than sodium hypochlorite and a similar residual effect than chlorhexidine.

espanolIntroduccion. La crisis por la COVID-19 supuso en marzo de 2020 el cierre de las universidades del pais, con interrupcion total de la actividad presencial. Este estudio presenta el diseno, el desarrollo y los resultados generales de una formacion totalmente en linea con un enfoque docente ‘autorregulativo’ (enfocado al aprendizaje autonomo del alumno), que una escuela de Medicina realizo durante los meses de confinamiento (ultimo cuatrimestre del curso 2019/2020). Sujetos y metodos. Se describen las caracteristicas educativas del Programa OnLine Ante COVID-19 para los cursos de primero y segundo de Medicina, estructuracion, organizacion de la intervencion, utilizacion de las herramientas y plataformas. Se comparan los resultados academicos del grupo de alumnos en los que se interviene con alumnos del curso anterior. Resultados. De 14 asignaturas participaron 10, y 111-158 (primer curso) y 110-139 (segundo curso) alumnos. La plataforma utilizada fue Moodle. Las sesiones sincronas fueron 49. El 83,7% de alumnos realizo autoevaluaciones. Se realizaron tres foros/asignatura. Se expusieron mas de 500 dudas y hubo 107 tutorias. Los resultados de los examenes finales (global de las asignaturas) mostraron un 17,7% mas de aptos y un 11,1% menos de no aptos respecto al curso anterior. Conclusiones. El programa en su diseno (enfoque centrado en el alumno) y desarrollo (completamente en linea) se mostro viable para el desarrollo del aprendizaje ‘autorregulativo’ no presencial. El uso de herramientas en linea habituales, una estructura academica centralizada y una organizacion en modulos semanales son elementos que han podido contribuir a su viabilidad y aplicacion inmediata. Son necesarios nuevos estudios para comprobar el alcance real de este tipo de enfoques educativos EnglishIntroduction. The Covid-19 crisis led to the closure of the country’s universities in March 2020, with total interruption of face-to-face activity. This study presents the design, development and general results of a totally online training with a ‘self-regulatory’ teaching approach, which a School of Medicine carried out during lockdown months (2019/20 last semester). Subjects and methods. The educational features of OnLine Program Because Covid19 (POLAC) for the 1st and 2nd medicine years are described, the structure and organization of the intervention. Use of tools and web-programs and comparison of academic results between the group of these students with students from previous year. Results. Ten out of 14 subjects participated and between 111-158 (1st) and 110-139 (2nd) students. Moodle web-program. Synchronous sessions: 49, self-evaluations carried out by 83.7% students. Forums: 3 forums / subject. Exposed doubts > 500; Tutorials: 107; Results of the final exams (global of subjects): a 17.7% of increase in the number of ‘pass’ grades and a 11.1% of decrease of ‘not pass’ grades regarding previous year. Conclusions. The design (student-centered approach) and development (completely online) of the POLAC is practicable for the development of non-face-to-face ‘self-regulatory’ learning. Using common online tools, a centralized academic structure, and an organization in weekly units are elements that may contribute to viability and immediate implementation. New studies are needed to verify the real scope of this type of instructional approaches

Objective: To determine whether there was any association between resistance to antibiotics and decreased susceptibility to antiseptics and disinfectants and their importance in clinical practice. Methods: We studied a large number of microorganisms isolated from ICU patients (high percentage of cases of antibiotic resistance). The antibiogram (Kirby-Bauer) was determined and, in parallel, the bactericidal effect was assessed by two methods, according to the product used: 1) Effect on rough material (endodontic files) in 10 min, using five disinfectants; 2) Effect on a skin equivalent (sterile cotton cloth) in 30 sec, for two alcohol solutions. A predictive equation of the bactericidal effects versus microorganisms’ antibiogram was obtained by multivariate methods. Results: Bactericidal efficacy was very similar for all the products with the exception of 1% povidone-iodine. Within each product there were no significant differences between the three groups of microorganisms: “Enterobacteria”, “Non Fermentative Gram Negative Bacteria” and “cocci”. Multivariate study only obtained one significant equation: 1% chlorhexidine resistance was directly correlated with aztreonam resistance (OR = 2.16), while resistance to imipenem and to phosphomycin acted as protection factors (OR < 1). Conclusion: There is no necessary to change the indications for antiseptics or disinfectants in ICUs, except if aztreonam resistance is high. In which caseis better to use greater concentration than 1% of Chlorhexidine.

Results: With the antibiograms and MIC-dilutions for every bacteria and biocide, the bivariate analysis found that only 4.7% of the antibiotic-biocide pairs showed a significant correlation (p < 0.05%) between antibiotic resistance and decreased susceptibility to the disinfectant or antiseptic, 8.3% showed a significant inverse correlation, and the rest no correlation. Multivariate analysis of the above variables (controlling the effects of the type of microorganism and disinfectant or antiseptic used), showed that overall fit of the equation was very poor, since R 2 = 0.032. Conclusion: In a large sample of different bacteria genera there was no significant correlation between antibiotic resistance and decreased susceptibility to disinfectants and antiseptics, except in 4.7% of the antibiotic-biocide pairs. List of abbreviations: OPA: Ortho-phthalaldehyde; NFGNB: Non Fermentative Gram Negative Bacteria; ROC: Receiver Operating Characteristics; COR: Correlations with p < 0.05; Cor: Correlations with p between 0.05 and 0.1; SXT: Sulfamethoxazole trimethoprim; CPH: Cephalothin; LEVO: Levofloxacin; IPM: Imipenem; TOB: Tobramycin; CAZ: Ceftazidime; GM: Gentamicin; AN: Amikacin; FO: Phosphomycin; TZP: Tazobactam; ATM: Aztreonam; TEC: Teicoplanin

Inhibition of extracellular matrix (ECM) degradation may represent a mechanism for cardiac protection against ischemia. Extracellular matrix metalloproteinase inducer (EMMPRIN) is highly expressed in response to acute myocardial infarction (AMI), and induces activation of several matrix metalloproteinases (MMPs), including gelatinases MMP-2 and MMP-9. We targeted EMMPRIN with paramagnetic/fluorescent micellar nanoparticles conjugated with the EMMPRIN binding peptide AP-9 (NAP9), or an AP-9 scrambled peptide as a negative control (NAPSC). We found that NAP9 binds to endogenous EMMPRIN in cultured HL1 myocytes and in mouse hearts subjected to ischemia/reperfusion (IR). Injection of NAP9 at the time of or one day after IR, was enough to reduce progression of myocardial cell death when compared to CONTROL and NAPSC injected mice (infarct size in NAP9 injected mice: 32%±6.59 vs 46%±9.04 or NAPSC injected mice: 48%±7.64). In the same way, cardiac parameters were recovered to almost healthy levels (LVEF NAP9 63% ± 7.24 vs CONTROL 42% ± 4.74 or NAPSC 39% ± 6.44), whereas ECM degradation was also reduced as shown by inhibition of MMP-2 and MMP-9 activation. Cardiac magnetic resonance (CMR) scans have shown a signal enhancement in the left ventricle of NAP9 injected mice with respect to non-injected, and to mice injected with NAPSC. A positive correlation between CMR enhancement and Evans-Blue/TTC staining of infarct size was calculated (R:0.65). Taken together, these results point to EMMPRIN targeted nanoparticles as a new approach to the mitigation of ischemic/reperfusion injury., Ministerio de Economía y Competitividad, Instituto de Salud Carlos III

Cardiovascular diseases are the leading cause of death in developed countries. The aetiology is currently multifactorial, thus making them very difficult to prevent. Preclinical models of atherothrombotic diseases, including vulnerable plaque-associated complications, are now providing significant insights into pathologies like atherosclerosis, and in combination with the most recent advances in new non-invasive imaging technologies, they have become essential tools to evaluate new therapeutic strategies, with which can forecast and prevent plaque rupture. Positron emission tomography (PET)/computed tomography imaging is currently used for plaque visualisation in clinical and pre-clinical cardiovascular research, albeit with significant limitations. However, the combination of PET and magnetic resonance imaging (MRI) technologies is still the best option available today, as combined PET/MRI scans provide simultaneous data acquisition together with high quality anatomical information, sensitivity and lower radiation exposure for the patient. The coming years may represent a new era for the implementation of PET/MRI in clinical practice, but first, clinically efficient attenuation correction algorithms and research towards multimodal reagents and safety issues should be validated at the preclinical level.

Extracellular matrix metalloproteinase inducer EMMPRIN, is highly expressed in patients with acute myocardial infarction (AMI), and induces activation of several matrix metalloproteinases (MMPs), including MMP-9 and MMP-13. To prevent Extracellular matrix degradation and cardiac cell death we targeted EMMPRIN with paramagnetic/fluorescent micellar nanoparticles with an EMMPRIN binding peptide AP9 conjugated (NAP9), or an AP9 scramble peptide as a negative control (NAPSC). NAP9 binds to endogenous EMMPRIN as detected by confocal microscopy of cardiac myocytes and macrophages incubated with NAP and NAPSC in vitro, and in vivo in mouse hearts subjected to left anterior descending coronary artery occlusion (IV injection 50mγ/Kg NAP9 or NAP9SC). Administration of NAP9 at the same time or 1 hour after AMI reduced infarct size over a 20% respect to untreated and NAPSC injected mice, recovered left ventricle ejection fraction (LVEF) similar to healthy controls, and reduced EMMPRIN downstream MMP9 expression. In magnetic resonance scans of mouse hearts 2 days after AMI and injected with NAP9, we detected a significant gadolinium enhancement in the left ventricle respect to non-injected mice and to mice injected with NAPSC. Late gadolinium enhancement assays exhibited NAP9-mediated left ventricle signal enhancement as early as 30 minutes after nanoprobe injection, in which a close correlation between the MRI signal enhancement and left ventricle infarct size was detected. Taken together, these results point EMMPRIN targeted nanoprobes as a new tool for the treatment of AMI.

Summary Microbial contamination of hospital surfaces may be a source of infection for hospitalized patients. We evaluated the efficacy of Glosair™ 400 against two American Type Culture Collection strains and 18 clinical isolates, placed on glass germ-carriers. Carriers were left to air-dry for 60min and then exposed to a cycle before detection of any surviving micro-organisms. Antibiotic-susceptible Gram-negative bacilli were less susceptible (although not significantly) to this technique than resistant Gram-negative bacilli or Gram-positive cocci and yeasts (3, 3.4 and 4.6 log 10 reduction, respectively). In conclusion, in areas that had not been cleaned, aerosolized hydrogen peroxide obtained >3 log 10 mean destruction of patients' micro-organisms.

Short communication.-- et al., Bluetongue (BT) is a climate change-related emerging infectious disease in Europe. Outbreaks of serotypes 1, 2, 4, 6, 8, 9, 11, and 16 are challenging Central and Western Europe since 1998. Measures to control or eradicate bluetongue virus (BTV) from Europe have been implemented, including movement restrictions and vaccination of domestic BTV-susceptible ruminants. However, these measures are difficult to apply in wild free-ranging hosts of the virus, like red deer (Cervus elaphus), which could play a role in the still unclear epidemiology of BT in Europe. We show for the first time that BTV RNA can be detected in European red deer blood for long periods, comparable to those of domestic ruminants, after experimental infection with BTV-1 and BTV-8. BTV RNA was detected in experimentally infected red deer blood up to the end of the study (98¿112 dpi). BTV-specific antibodies were found in serum both by enzyme-linked immunosorbent assay (ELISA) and virus neutralization (VNT) from 8 to 12 dpi to the end of the study, peaking at 17¿28 dpi. Our results indicate that red deer can be infected with BTV and maintain BTV RNA for long periods, remaining essentially asymptomatic. Thus, unvaccinated red deer populations have the potential to be a BT reservoir in Europe, and could threaten the success of the European BTV control strategy. Therefore, wild and farmed red deer should be taken into account for BTV surveillance, and movement restrictions and vaccination schemes applied to domestic animals should be adapted to include farmed or translocated red deer., We acknowledge the funding from JCCM PAI08-0287-8502, the Government of Scotland, and INIA-MARM CC08-020 (additional support to CISA). Caterina Falconi had a grant from the Government of Sardinia.

The use of alcohol-based hand rubs serves to reduce hospital-acquired infections. Many products of this type are now on offer and it is essential to know how to rank their efficacy. A sequence of tests is proposed here to compare any given new alcohol-based solution against the reference solution (60% 2-iso-propyl-alcohol) with 30 s of contact time: (i) in vitro (with pig skin as carrier) testing of >30 species of microorganism; (ii) in vitro assessment of residual efficacy (after 30 min of drying); (iii) in vivo study of transient microbiota (modification of the EN 1500 standard procedure) using four ATCC strains; (iv) in vivo study of resident hand microbiota. After performing the in vitro evaluation of seven alcohol-based hand rubs, the two most efficacious (chlorhexidine-quac-alcohol and mecetronium-alcohol) were chosen and studied, comparatively with the reference solution (60% iso-propyl alcohol), in vitro (for chemical sustainability on the skin) and in vivo (against transient and resident microbiota). Chlorhexidine-quac-alcohol proved to be significantly superior to mecetronium-alcohol or the reference solution in all tests, except against resident microbiota for which the improvement was not statistically significant.