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Background: Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery. Design: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (e.g., severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The two independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the two co-primary outcomes. Summary: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery. Population Health Research Institute

We report two rare and infrequent cases, one of a patient with a Cognard type V tentorial dural fistula diagnosed at the beginning as a trunk glioma in a patient with gait disturbance. And another with a Guillian Barré syndrome with tetraparesis secondary to a tentorial dural arteriovenous fistula.

Dialogic popular education developed by La Verneda-Sant Martí School for Adults in Spain, influenced by the work of Paulo Freire, has had a range of significant social and educational impacts. Starting with an emancipatory approach to eradicate oppression, this dialogic popular education resisted and has transformed aspects of the Spanish educational sphere despite ongoing hindrances and difficulties. This article presents a path of events, a history of interventions and findings from research on how dialogic popular education has affected and changed educational practices as well as how research is approached elsewhere in Europe. In addition, it presents ways in which a radical commitment to social change can be combined with scientific standards in the pursuit of achieving a better society for all.

La ansiedad dental es la sensación de aprensión sobre el tratamiento dental, que se asocia con un pobre estado de salud bucal; ya que es señalada por muchos pacientes como un motivo para no acudir de forma regular al dentista. De tal forma que los padres del paciente pediátrico tienen un rol muy importante en la atención odontológica, ya que son ellos quienes finalmente toman la decisión de llevar al niño a su cita dental y deciden a qué edad deben hacerlo. El origen del problema viene del desconocimiento del paciente pediátrico sobre lo que ocurrirá en la consulta, y en ocasiones pueden llegar a ser los mismos padres de familia quienes transmiten esa emoción a los hijos. Si el dentista es consciente del nivel de ansiedad de su paciente, entonces puede tomar medidas para ayudar a aliviar la ansiedad durante el tratamiento odontológico. El dentista debe estar comprometido en ayudar al paciente infantil a aprender las formas de manejar este comportamiento. Por ello es necesario generar un lazo de confianza con el paciente pediátrico desde la primera cita; el uso de técnicas y recomendaciones para la disminución de la ansiedad.

Tumor organoids are three-dimensional (3D) ex vivo tumor models that recapitulatethe biological key features of the original primary tumor tissues. Patient-derivedtumor organoids have been used in translational cancer research and can beapplied to assess treatment sensitivity and resistance, cell-cell interactions, and tumorcell interactions with the tumor microenvironment. Tumor organoids are complexculture systems that require advanced cell culture techniques and culture mediawith specific growth factor cocktails and a biological basement membrane thatmimics the extracellular environment. The ability to establish primary tumor cultureshighly depends on the tissue of origin, the cellularity, and the clinical featuresof the tumor, such as the tumor grade. Furthermore, tissue sample collection,material quality and quantity, as well as correct biobanking and storage are crucialelements of this procedure. The technical capabilities of the laboratory are also crucialfactors to consider. Here, we report a validated SOP/protocol that is technically andeconomically feasible for the culture of ex vivo tumor organoids from fresh tissuesamples of pancreatic adenocarcinoma origin, either from fresh primary resectedpatient donor tissue or patient-derived xenografts (PDX). The technique describedherein can be performed in laboratories with basic tissue culture and mouse facilitiesand is tailored for wide application in the translational oncology field.

We aimed to determine the presence of SARS-CoV-2 RNA in indoor and outdoor size-segregated aerosol samples (PM10-2.5, PM2.5). Five outdoor daily samples were collected between November and December 2020 in an urban/industrial area with relatively high PM10 levels (Maliaño, Santander, Spain) by using a PM impactor (air flowrate of 30 L/min). In a non-hospital indoor sampling surveillance context, 8 samples in classrooms and 6 samples in the central library-Paraninfo of the University of Cantabria (UC) were collected between April and June 2021 by using personal PM samplers (air flowrate of 3 L/min). Lastly, 8 samples in the pediatric nasopharyngeal testing room at Liencres Hospital, 6 samples from different single occupancy rooms of positive patients, and 2 samples in clinical areas of the COVID plant of the University Hospital Marqués de Valdecilla (HUMV) were collected between January and May 2021. N1, N2 genes were used to test the presence of SARS-CoV-2 RNA by RT-qPCR. SARS-CoV-2 positive detection was only obtained from one fine fraction (PM2.5) sample, corresponding to one occupancy room, where a patient with positive PCR and cough was present. Negative results found in other sampling areas such as the pediatric nasopharyngeal testing rooms should be interpreted in terms of air sampling volume limitation and good ventilation. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This research was developed in the framework of the project “Contaminación atmosférica y COVID-19: ¿Qué podemos aprender de esta pandemia?” selected in the Extraordinary BBVA Foundation grant call for SARS-CoV-2 and COVID-19 research proposals, within the area of ecology and veterinary science.

Background and aimsThe burden hepatitis C infection in people with history or current drug use suppose a high risk of hepatic complications and transmission infectious disease. This population is poor linked to heath system and is difficult to achieve them and support treatment because they have high rates of lost follow-up. Our aim was to evaluate an intervention for the diagnosis and treatment of chronic hepatitis C and HIV in this population.MethodsSix-hundred and eighty-three people attended in Drugs and Addictions Centers (DAC) were asked to participate in health counseling and provide blood sample for test HCV, HIV, and syphilis from April 2019 to June 2020. Totally 556 subjects were surveyed and tested. All of them were assigned to a patient navigation program to improve health education and linking to the sanitary system. Hepatitis C infection patients were evaluated in an ampliated medical consult to evaluate hepatic stage with transient liver elastography and initiated Direct Acting Antivirals to achieve Sustained Viral Response.ResultsOf the 556 patients who agreed to participate in the study, 33 (5.9%) had active HCV infection. Of the 33 patients infected with HCV, three were lost to follow-up once the diagnosis of HCV infection was made. Twenty-eight patients (93.3%) completed treatment and 26 achieved Sustained Viral Response (78.8%). Of the 30 patients, seven (23.3%) had advanced fibrosis, and of these, four (16.6%) had liver cirrhosis. One of the cirrhotic patients had hepatic space-occupying lesions at the baseline evaluation and was diagnosed with hepatocarcinoma.ConclusionsOur study suggests that the implementation of strategies based on personalized intervention models can contribute to the control of HCV infection in DAC users.

Background/aim: Santander, the capital of Cantabria, Spain (172,000 inhabitants) is 7 km from an industrial emission source (IES) of Mn located in a 10,000 inhabitants town (Maliaño) (annual air Mn arithmetic mean = 231.8 ng/m3 ; reference WHO guideline = 150 ng/m3 ). Our objective was to compare the motor function of adult healthy volunteers living in both places. Methods: Cross-sectional study analyzing 130 consecutive participants. Exposure to Mn was assessed in terms of source distance from the IES, by Personal Environmental Monitors (PEMs) carried for 24 h by participants consisting of a portable impactor connected to a personal pump, and by biomarkers (blood, hair and fingernails). The impactor allowed the separation of fine (PM2.5) and coarse (PM10-2.5) particles and for each particle size in-vitro bioaccessibility tests with biologically active fluids were performed to separate the soluble (bio accessible) from the insoluble (non-bioaccessible) fraction. Mean Differences (MDs) adjusted for age, sex, and study level, were obtained for motor function tests results. Results: Regarding Grooved Pegboard, overall mean time to complete the test was 59.31 and 65.27 seconds (Standard Deviation = 10.11 and 11.69) for dominant and nondominant hands respectively. Statistically significant higher times (indicating worse function) were observed when living near the IES in both hands but MDs of only 1.22 and 2.05 seconds were obtained after adjusting for the predefined confounders (p = 0.373 and 0.221 respectively). Regarding Mn levels in their PEMs (in both bioaccessible and non-bioaccessible coarse&fine fractions) higher times were computed in participants with higher levels for the bioaccessible-fine fraction, with a MD that diminished but still yielded statistical significance after controlling for confounding: adjusted MD = 3.01 more seconds; 95%CI (0.44-5.38), p = 0.022. Poorer results were also observed for fingernails levels. Regarding Finger Tapping Test, no statistically significant differences were found with the exception of Mn fingernails levels. Conclusions: Our results suggest poorer motor function as assessed by Grooved Pegboard test in relation to "proximity to IES", "bioaccessible-fine fraction as determined by PEMs and "Mn fingernails levels". However, our findings were affected by confounding, and only the adjusted MD for the Mn bioaccessible-fine fraction remained of sufficient magnitude to maintain statistical significance. This work was supported by the Spanish Ministry of Science, Innovation and Universities through the CTM2017-82636-R Project. This funding source was not involved in the study design; data collection, analysis, or interpretation; the writing of the article; or the decision to submit for publication. Bohdana Markiv also thanks this Ministry for the PhD grant awarded, PRE2018-085152.

PurposeTo describe SARS-CoV-2 infection outcome in unvaccinated children and young adults with inborn errors of immunity (IEI) and to compare their specific acute and long-term immune responses with a sex-, age-, and severity-matched healthy population (HC).MethodsUnvaccinated IEI patients up to 22 years old infected with SARS-CoV-2 were recruited along with a cohort of HC. SARS-CoV-2 serology and ELISpot were performed in the acute phase of infection (up to 6 weeks) and at 3, 6, 9, and 12 months.ResultsTwenty-five IEI patients (median age 14.3 years, min.-max. range 4.5-22.8; 15/25 males; syndromic combined immunodeficiencies: 48.0%, antibody deficiencies: 16.0%) and 17 HC (median age 15.3 years, min.-max. range 5.4-20.0; 6/17 males, 35.3%) were included. Pneumonia occurred in 4/25 IEI patients. In the acute phase SARS-CoV-2 specific immunoglobulins were positive in all HC but in only half of IEI in whom it could be measured (n=17/25): IgG+ 58.8% (10/17) (p=0.009); IgM+ 41.2% (7/17)(p+ 52.9% (9/17)(p=0.003). Quantitative response (index) was also lower compared with HC: IgG IEI (3.1 ± 4.4) vs. HC (3.5 ± 1.5)(p=0.06); IgM IEI (1.9 ± 2.4) vs. HC (3.9 ± 2.4)(p=0.007); IgA IEI (3.3 ± 4.7) vs. HC (4.6 ± 2.5)(p=0.04). ELISpots positivity was qualitatively lower in IEI vs. HC (S-ELISpot IEI: 3/11, 27.3% vs. HC: 10/11, 90.9%; p=0.008; N-ELISpot IEI: 3/9, 33.3% vs. HC: 11/11, 100%; p=0.002) and also quantitatively lower (S-ELISpot IEI: mean index 3.2 ± 5.0 vs. HC 21.2 ± 17.0; p=0.001; N-ELISpot IEI: mean index 9.3 ± 16.6 vs. HC: 39.1 ± 23.7; p=0.004). As for long term response, SARS-CoV-2-IgM+ at 6 months was qualitatively lower in IEI(3/8, 37.5% vs. 9/10 HC: 90.0%; p=0.043), and quantitatively lower in all serologies IgG, M, and A (IEI n=9, 1.1 ± 0.9 vs. HC n=10, 2.1 ± 0.9, p=0.03; IEI n=9, 1.3 ± 1.5 vs. HC n=10, 2.9 ± 2.8, p=0.02; and IEI n=9, 0.6 ± 0.5 vs. HC n=10, 1.7 ± 0.8, p=0.002 –respectively) but there were no differences at remaining time points.ConclusionsOur IEI pediatric cohort had a higher COVID-19 pneumonia rate than the general age-range population, with lower humoral and cellular responses in the acute phase (even lower compared to the reported IEI serological response after SARS-CoV-2 vaccination), and weaker humoral responses at 6 months after infection compared with HC.

Research shows that family involvement in learning activities at school improves students’ academic performance and social cohesion. This study analyses the impact of involving families through int...

Tissue engineered bone scaffolds are potential alternatives to bone allografts and autografts. Porous scaffolds based on triply periodic minimal surfaces (TPMS) are good candidates for tissue growth because they offer high surface-to-volume ratio, have tailorable stiffness, and can be easily fabricated by additive manufacturing. However, the range of TPMS scaffold types is extensive, and it is not yet clear which type provides the fastest cell or tissue growth while being sufficiently stiff to act as a bone graft. Nor is there currently an established methodology for TPMS bone scaffold design which can be quickly adopted by medical designers or biologists designing implants. In this study, we examine six TPMS scaffold types for use as tissue growth scaffolds and propose a general methodology to optimise their geometry. At the macro-scale, the optimisation routine ensures a scaffold stiffness within suitable limits for bone, while at the micro-scale it maximises the cell growth rate. The optimisation procedure also ensures the scaffold pores are of sufficient diameter to allow oxygen and nutrient delivery via capillaries. Of the examined TPMS structures, the Lidinoid and Split P cell types provide the greatest cell growth rates and are therefore the best candidates for bone scaffolds.

El presente texto forma parte del trabajo doctoral “Investigación-acción: la danza-escritura como posibilidad de auto-enuncación”. Para la parte práctica de la investigación se impartió el Taller de danza y escritura a manera de laboratorio. Lo que se presenta en este artículo es una parte del análisis de lo acontecido durante el taller. Se profundiza sobre el funcionamiento de la dramaturgia en el diseño de las sesiones, en la organización de los textos y danzas individuales y colectivos que se produjeron durante el laboratorio, así como en el ensamblaje de los materiales para su presentación ante un público. La dramaturgia es la herramienta articuladora para estudiar el proceso creativo en el que cada participante encontró un espacio para su propia enunciación y las resonancias que tuvo esta en el colectivo. Para abordar el análisis, se toman como punto de partida los planteamientos de André Lepecki sobre dramaturgia y los de Laurence Louppe sobre partitura. Abstract This text is part of the doctoral work "Research-action: dance-writing as a possibility of self-enunciation". For the practical part of the research, the Dance and writing workshop was given as a laboratory. What is presented in this article is a part of the analysis of what happened during the workshop. It delves into the operation of dramaturgy in the design of the sessions, in the organization of the individual and collective texts and dances that occurred during the laboratory, as well as in the assembly of the materials for presentation to an audience. Dramaturgy is the articulating tool to study the creative process in which each participant found a space for their own enunciation and the resonances that this had in the group. To address the analysis, the approaches of André Lepecki on dramaturgy and those of Laurence Louppe on score are taken as a starting point.

Background Candida auris is an emerging multidrug-resistant and highly virulent yeast that spreads easily among patients. Aims To describe the characteristics of candidemia caused by C. auris in the southeast of Spain (Autonomous Community of Valencia – ACV) through a 5-year population-based study. Methods An analysis of all the episodes of candidemia diagnosed in the ACV, with approximately 4,500,000 inhabitants, during 2013–2017, was done. Data were obtained from the Epidemiological Surveillance Valencian Network, a network that collects all the microbiological data from the hospitals in the study region. Results Based on the records, 1.9% of the isolates recovered from the positive blood cultures (corresponding to 1789 patients) were yeasts. This implies an annual rate of 7.09 cases/100,000 inhabitants. Of the 23 yeast species isolated, Candida albicans was the most frequent (37.3%), showing a higher frequency than Candida parapsilosis (28.4%) and Candida glabrata (15.6%) (p 500 beds (63.3% versus 36.7% in small hospitals) (p Conclusions The information about the local epidemiology of candidemia is essential in order to decide the best empirical treatment approach. This study reports the novel presence of C. auris in large hospitals. This pathogen has usually resistance to several antifungals and causes severe fungemia, so the results of this work reveal the need to monitor the presence of this species systematically.

Among components of the consumer's perception of tomato fruit quality, texture is one of the most critical, being formed of a number of attributes that are difficult to evaluate and which change during fruit ripening and storage. The present work relates different textural parameters measured in a collection of traditional tomatoes from Madrid with the appreciation collected from consumer opinions. Texture traits were highly variable in studied tomatoes; they had strong environmental influence and they differed among genotypes. Great intrapopulational variability has been also detected, probably due to the heterogeneity of its fruit tissues and the intrapopulational diversity of studied landraces. Textural behavior of tomatoes affected the level of consumer appreciation. In general, consumers preferred firm fruits with soft skin, due to their low level of springiness and resilience. However, different taster groups have demonstrate how diversity appears to be necessary to satisfy different types of consumers. Among the three groups of consumers which have been identified in this study, the majority (83% of them) preferred local tomato varieties. In addition, heirloom tomatoes presented softer skins than the commercial hybrid reference (values of 0.29 ± 0.19 vs. 0.49 ± 0.12 kg regarding skin rupture force). That circumstance, which is involved in the post-harvest behavior, must be further considered in storage and commercialization.

Powdery mildew and rust fungi are major agricultural problems affecting many economically important crops and causing significant yield losses. These fungi are obligate biotrophic parasites that are completely dependent on their hosts for growth and reproduction. Biotrophy in these fungi is determined by the presence of haustoria, specialized fungal cells that are responsible for nutrient uptake and molecular dialogue with the host, a fact that undoubtedly complicates their study under laboratory conditions, especially in terms of genetic manipulation. RNA interference (RNAi) is the biological process of suppressing the expression of a target gene through double-stranded RNA that induces mRNA degradation. RNAi technology has revolutionized the study of these obligate biotrophic fungi by enabling the analysis of gene function in these fungal. More importantly, RNAi technology has opened new perspectives for the management of powdery mildew and rust diseases, first through the stable expression of RNAi constructs in transgenic plants and, more recently, through the non-transgenic approach called spray-induced gene silencing (SIGS). In this review, the impact of RNAi technology on the research and management of powdery mildew and rust fungi will be addressed.

Novel and sustainable approaches are required to curb the increasing threat of antimicrobial resistance (AMR). Within the last decades, antimicrobial peptides, especially bacteriocins, have received increased attention and are being explored as suitable alternatives to antibiotics. Bacteriocins are ribosomally synthesized antimicrobial peptides produced by bacteria as a self-preservation method against competitors. Bacteriocins produced by Staphylococcus, also referred to as staphylococcins, have steadily shown great antimicrobial potential and are currently being considered promising candidates to mitigate the AMR menace. Moreover, several bacteriocin-producing Staphylococcus isolates of different species, especially coagulase-negative staphylococci (CoNS), have been described and are being targeted as a good alternative. This revision aims to help researchers in the search and characterization of staphylococcins, so we provide an up-to-date list of bacteriocin produced by Staphylococcus. Moreover, a universal nucleotide and amino acid-based phylogeny system of the well-characterized staphylococcins is proposed that could be of interest in the classification and search for these promising antimicrobials. Finally, we discuss the state of art of the staphylococcin applications and an overview of the emerging concerns.

This study aimed to determine the prevalence and diversity of extended-spectrum β-lactamase (ESBL)-producing and multidrug-resistant (MDR) Escherichia coli and Klebsiella pneumoniae isolates from 136 broiler livers randomly purchased in 136 retail markets in Djelfa (Algeria). Isolation was performed on Hektoen agar and bacterial identification was carried out by API20E system and Maldi-TOF-MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry). Antimicrobial susceptibility was tested by the disk diffusion and agar dilution methods. Detection of ESBLs and other resistance and integron genes, phylogenetic grouping, and molecular typing was performed by PCR and sequencing. Seventy-eight isolates (one per positive sample) were recovered: 73 E. coli and 5 K. pneumoniae. Among E. coli, 86.3% of isolates were MDR. ESBL activity was revealed in eight E. coli and five K. pneumoniae isolates (rates of 5.9% and 3.7% in analyzed samples, respectively). ESBL genes detected among E. coli were as follows (number of isolates): blaCTX-M-15 (3), blaCTX-M-1 (3), blaCTX-M-55 (1), and blaSHV-12 (1); all ESBL-producing K. pneumoniae isolates carried the blaCTX-M-15 gene. ESBL-producing E. coli isolates were assigned to lineages (phylogroup/sequence type and number of isolates in parenthesis): A/ST48 (1), B1/ST6448 (1), B1/ST5087 (3), B1/ST23 (1), and B2/ST131 (two blaCTX-M-15 E. coli isolates). K. pneumoniae isolates were ascribed to sequence types ST2010 and ST3483. Regarding the 65 non-ESBL E. coli isolates, the most observed resistance genes were as follows: tet(A) (75%), blaTEM (57.1%), and sul2 (43.5%). Class1 integrons were revealed in seven non-ESBL E. coli isolates (10.7%) and two gene-cassette arrays were identified: dfrA1 and aadA1+dfrA1. Our study provides evidence that broiler-derived food from Center of Algeria constitutes a source of ESBL and/or MDR-producing Enterobacteriaceae, with detection of relevant ESBL genes and epidemic clones.

This study analyzed how the relationships of adolescent students with their peers, the educational community, and their families, as well as their attitudes to school violence, influences becoming ...

Titanate nanotubes (NTs) were synthesised by the hydrothermal method and later calcined at temperatures between 100–500°C. The calcined NTs were characterised and evaluated in the physicochemical adsorption of the safranin dye and photocatalytic degradation of caffeine. The materials calcined at low temperatures displayed a tubular structure and the H2Ti3O7 crystalline phase, which was transformed into anatase nanoparticles at 400°C. The NTs treated at 100°C showed the highest adsorption capacity (94%). Safranin was adsorbed through an ion-exchange mechanism, following the Langmuir isotherm and a pseudo-second-order kinetic model. While NTs calcined at lower temperatures were better for adsorption, the photocatalytic degradation of caffeine increased in samples calcined at higher temperatures with a maximum removal of 72%. The photocatalytic behaviour of the NT samples confirmed that the crystalline anatase structure in conjunction with structural OH groups enhanced the photocatalytic activity. The addition of isopropanol as a scavenger confirmed the important role played by the •OH radicals in the photocatalytic process. NTs calcined at 300°C were efficient for both adsorption and photocatalytic processes. Due to its efficiency, this sample was reused after dye adsorption for the photocatalytic degradation of caffeine under visible light due to its enhanced absorbance in the visible region. This research work shows the potential of NTs for wastewater purification.

Aims: To perform the molecular characterization of 23 Staphylococcus aureus isolates from pigs with signs of infections recovered in Spanish farms during 2018–2019. Methods and Results: The antimicrobial resistance pattern and virulence profile were determined. The molecular typing was performed by different molecular techniques. The transferability of the cfr gene was assessed by conjugation and its genetic environment was determined by PCR mapping. In all, 21 isolates were methicillin-resistant S. aureus (MRSA) carrying the mecA gene (SCCmecV or non-typeable SCCmec), whereas the remaining two were methicillin-susceptible (MSSA). All but one MRSA isolates (n = 20) belonged to the CC398, being the spa t011 the most prevalent (n = 11). The remaining MRSA and the two MSSA isolates were ascribed to ST9/CC9. The S. aureus isolates exhibited resistance to (number of resistant isolates): β-lactamics (21), erythromycin and/or clindamycin (20), aminoglycosides (7), tetracycline (22), fluoroquinolones (14), chloramphenicol (5) and linezolid (1). The S. aureus isolates did not carry any of the virulence genes studied. One MRSA belonging to the CC398 showed linezolid resistance mediated by the cfr gene. The cfr gene was co-located with fexA in the Tn558 variant previously reported in the S. aureus plasmid pSCFS7. Conclusions: Two major livestock-associated genetic lineages were detected among pigs with signs of infection in Spain. The presence of the cfr gene among LA-MRSA-CC398 is of great concern not only for veterinary medicine, but also for humans in close contact. Significance and Impact of the Study: This work describes the molecular characterization of S. aureus isolates recovered from pigs with signs of infection and we report, as far as we know, the first description of MRSA-CC9 from pigs in Spain. Moreover, the detection of a MRSA-CC398 isolate carrying the multiresistance cfr gene highlights the need for continuous surveillance and awareness of LA-MRSA.

The increase in penicillin susceptibility among Staphylococcus aureus (SA-PenOver a 2.5 years period, all SA isolates from bacteraemia in one hospital were analysed. For all isolates, antimicrobial susceptibility profile, beta-lactam resistance genes (blaZ, mecA) and Panton-Valentine leucocidine encoding-genes were studied. For SA-PenAmong 84 patients with SA bacteraemia (35.7% MRSA and 64.3% MSSA), 77 were analysed; 22.2% of MSSA isolates were PenA high prevalence of MRSA/SA and MSSA-Pen

Introduction The increase in penicillin susceptibility among Staphylococcus aureus (SA-PenS) might have therapeutic relevance. We aimed to study the current situation in our environment. Material and methods Over a 2.5 years period, all SA isolates from bacteraemia were analysed. For all isolates, antimicrobial susceptibility profile, beta-lactam resistance genes (blaZ, mecA) and Panton-Valentine leucocidine encoding-genes were studied. For SA-PenS-blaZnegative isolates, spa-type, MLST and the presence of other resistance genes were studied. Results Among 84 patients with SA bacteraemia (35.7% MRSA and 64.3% MSSA), 77 were analysed; 22.2% of MSSA isolates were PenS and blaZnegative (Pen-MIC ≤0.03 µg/mL) corresponding to 14.3% of the total SA. In MSSA-PenS-blaZnegative isolates, eight spa-types corresponding to seven clonal complexes were detected. Conclusion A high prevalence of MRSA/SA and MSSA-PenS-blaZnegative/MSSA was detected in blood cultures. Pen-MIC ≤0,3 µg/mL corresponded to MSSA-PenS-blaZnegative. This situation raises therapeutic options which should be further evaluated in larger studies and clinical trials.

Additive manufacturing (AM) is increasingly gaining a presence in the pharmaceutical industry, specifically in the reconfiguration of drug delivery systems wherein new products are being developed for administering pharmaceuticals inside the body, and drug testing systems wherein complex tissues are created to analyze medical treatments. This paper proposes a novel methodology of Competitive Technology Intelligence (CTI) to uncover the evolution of new drug delivery products where additive manufacturing is present. Using the multiple linear regression analysis and hype cycle model as a conceptual basis, we processed data from scientific papers and patents indexed by Scopus and PatSnap for the period of 2004-2019. The outcomes of this study can create a relevant knowledge base for decision-making on introducing novel technologies such as AM. Industrial and academic communities are devoting important efforts toward the advancement of AM in the health industry, especially pharmaceuticals. It is expected that this technology will bring new solutions to address fundamental global health problems. However, this technology is still in its very early stage. Therefore, investments should focus on research and development (R&D) to build a solid foundation for commercialization in the next decade.

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) is an important clinical problem. In 2005, a livestock-associated MRSA clone was described, named CC398, being mostly associated with pigs, and causing colonization and infection in pigs and in related humans. The prevalence of these strains in food-producing pigs raised concerns about the possibility of MRSA-CC398 being a foodborne pathogen. The objective of this study was to investigate the presence of S. aureus and MRSA in 141 carcasses of pigs at three slaughterhouses of Portugal, discarded from the food chain by signs of infection, and to characterize the recovered isolates. Methods: S. aureus isolates were identified by matrix-assisted laser desorption/ionization time-of-flight and they were typed (spa, CC398-clone, and SCCmec). The study of antibiotic resistance and virulence genes, and the detection of immune evasion cluster genes and prophages were performed by PCR and sequencing. Results: Twenty-eight S. aureus were obtained from 141 samples (one/sample, 19.9%), being 22 MRSA and 6 methicillin-susceptible S. aureus (MSSA). All MRSA strains were typed as CC398 and were ascribed to three spa types (t011, t108, and t1451). The SCCmec detected differed according to the spa types of MRSA isolates (SCCmecV: t011 and t108; SCCmecIVa: t1451). The MSSA strains were classified as spa-t1491-ST1-CC1. All the strains contained a wide range of antimicrobial resistance genes, the resistance to tetracycline being the prevalent one. In contrast, the strains contained only a few virulence genes. Among the 6 integrases of phages tested, three were detected: Sφ1, Sφ2, and Sφ7, with variations between MRSA and MSSA strains. Conclusions: MRSA-CC398 is not only a habitual pig colonizer but also an opportunistic pathogen in these animals, and must be controlled at the level of producers and slaughterhouses because of its impact on public health.

Le combat entre le regime syrien et ses opposants s’est en partie joue sur un plan interpretatif et discursif. Loin d’etre anodins, les termes et les expressions employes, ainsi que les cadrages des evenements proposes par les differents acteurs de la crise revolutionnaire, sont porteurs de significations sociales et politiques situees. L’objectif de cet article est de les analyser en contextualisant les moments de leur emergence et en evoquant l’imaginaire collectif avec lesquels ils font resonance. Il montre tout d’abord la forte pregnance du local, malgre le travail d’alignement permanent qui cherche a les unifier et les universaliser ; ensuite, leur resonance avec des recits historiques qui facilitent leur diffusion et les inscrivent dans la longue duree ; enfin, leur articulation avec une realite du terrain changeante. La production langagiere des acteurs de la crise participe ainsi a la construction de cette derniere pour en devenir une partie constitutive fondamentale.

Tetracycline resistance (Tet

La adopción de las tecnologías de la información y la comunicación en contextos educativos ha cambiado la concepción de los roles de los maestros y de los aprendices, la relación entre ellos y las prácticas educativas. Esto conduce a que nociones como el aprendizaje autorregulado cobren relevancia en la forma en la que los alumnos aprenden en este tipo de mediación y que se resalte la influencia que tiene el acompañamiento del docente en ello. Por tanto, se llevó a cabo una investigación cualitativa que, a través de entrevistas semiestructuradas y del análisis de foros de interacción de tres tutores, identificara las prácticas que fomentan el aprendizaje autorregulado en ambientes virtuales en el contexto de una universidad a distancia. A partir del análisis interpretativo, se encontró que para los participantes, el rol de los docentes se centra en promover la motivación y aquellos elementos que ayudan a generarla y sostenerla, como la autoeficacia. Adicionalmente, se define como categoría emergente la empatía, la cual permite que el profesor sea cercano al educando, identifique las necesidades de este último y promueva tanto la motivación como el interés en el aprendizaje.

Introducción: El linaje CC398 se asocia con cepas de Staphylococcus aureus resistente a meticilina (SARM) relacionadasepidemiológicamente con el ganado (CC398 clado animal) que pueden causar infecciones en humanos, especialmenteen aquellos ligados al sector porcino. Recientemente ha emergido, fundamentalmente en cepas invasivas en pacientessin relación con animales, la variante SASM-CC398 que constituye un clado de posible origen humano.El objetivo de este trabajo es el análisis de los genomas completos de cepas CC398 (SASM y SARM), procedentes dehumanos, cerdos, cigüeñas y aguas para el estudio de características determinantes de los clados animal y humano.Material y Métodos: Se estudiaron las secuencias completas de 23 aislados de S. aureus del linaje CC398 (18 SASM, 5SARM), obtenidos de distintos orígenes. Mediante el programa Geneius Prime se analizaron los SNPs que permiten suasignación a los clados animal o humano, la presencia y localización del fago Sa3 portador del gen scn del IEC, la isla depatogenicidad de origen porcino (SAPIpig), tipado agr, spa y MLST, el resistoma, variantes de blaZ, polimorfismos enPBPs y otros genes relacionados con la resistencia a beta-lactámicos.Resultados: Se asignaron 14 cepas al clado humano (todos SASM) y el resto al clado animal (5 SARM, 4 SASM). Todas lascepas del clado humano presentaban el gen scn, además de 4 del clado animal (2 SARM, 2 SASM). Se detectaron 9 spa-tipos distintos, 4 característicos del clado animal (t011, t899, t1197, t4358) y 5 del clado humano (t571, t1451, t3625,t6606, t13938). Los agr detectados fueron tipo I (n=22) y tipo II (n=1, SARM de agua y clado animal). La SAPIpig selocalizó en 6 cepas, todas ellas del clado animal y una cepa scn-positivo. El fago portador del sistema IEC se insertó endos posiciones diferentes del gen hlB en 17 de las 18 cepas scn-positivas; en la cepa restante el fago Sa3 se insertó enotra posición. Se han detectado dos variantes del gen blaZ en las cepas CC398: A (4 cepas, 2 de ellas con alotipo 2), B (14cepas, 9 alotipos diferentes). Se han detectado distintos polimorfismos en los genes de las PBPs. Los genes erm(T) ycadD (asociados con resistencia a eritromicina y cadmio, respectivamente) se detectaron de forma conjunta en todas lascepas del clado humano. El gen tet(M) (asociado con resistencia a la tetraciclina) se detectó en todas las cepas del cladoanimal.Conclusiones: 1) Todas las cepas asociadas al clado humano fueron SASM, y contenían los genes scn, erm(T) y cadD. 2)Las cepas SARM fueron todas de origen animal y albergaban el gen tet(M). 3) Dos cepas SARM del clado animalcontenían el IEC lo que supone un grave problema de salud pública ya que poseen una ventaja para colonizar y/oinfectar seres humanos. 4) La presencia conjunta de erm(T) y cadD puede ser marcador de cepas del clado humano. 5) Elgen hlB se encuentra truncado debido a la inserción de un bacteriófago portador del IEC.

Respect for different sexual options and orientations prevents the occurrence of hate crimes against lesbian, gay, bisexual, trans and intersex (LGTBI) persons for this reason. Our aim was to review the legislation that protects the rights of LGTBI people and to quantify the victimization rates of hate crimes based on sexual identity and orientation. A retrospective observational study was conducted across all regions of Spain from 2011?2021. The laws on LGTBI rights in each region were identified. Hate crime victimization data on sexual identity and orientation were collected in annual rates per 100,000 inhabitants, annual percentage change and average change during the study period to assess the trend. The regulatory development of laws against discrimination against LGTBI individuals is heterogeneous across regions. Overall, in Spain there is an upward trend in the number of hate crime victimizations motivated by sexual identity or orientation. The effectiveness of data collection, thanks to better training and awareness of police forces regarding hate crimes and the processes of data cleansing and consolidation contributes to a greater visibility of hate crimes against LGTBI people. Project Nextval 2019/14 funded by Fundación Instituto de Investigación Marqués de Valdecilla

Background/aim: In the Santander Bay (Cantabria, northern Spain), a ferromanganese alloy plant is located. Our objective was to characterize the Mn personal exposure of adult healthy volunteers living in this highly Mn exposed region, and to determine its association with a poorer cognitive function. Methods: Cross-sectional study analyzing 130 consecutive participants. Cognitive function was assessed by Stroop Color Word, Verbal Fluency tests, Trail Making Test (TMT), Digit Span (WAIS III) and Rey Osterrieth Complex Figure (ROCF) tests and crude scores were standardized according to NEURONORMA norms. Exposure to Mn was assessed in terms of source distance, by Personal Environmental Monitors (PEMs) allowing the separation of fine (PM2.5) and coarse (PM10-2.5) particles (obtaining the bioaccessible fraction by in-vitro bioaccessibility tests), and by biomarkers (blood, hair and fingernails). Age, sex, study level and number of years of residence were predefined as confounding variables and adjusted Mean Differences (MDs) were obtained. Results: Statistically significant lower scores (negative MDs) in all test were observed when living near the industrial emission source, after adjusting for the predefined variables. Regarding PEMs results, statistically significant lower scores in all Stroop parts were obtained in participants with higher levels of Total Mn in All fractions (PM10). For Verbal Fluency tests, negative MDs were obtained for both bioaccessible fractions. Digit Span Backward scores were lower for those with higher levels in the bioaccessible coarse fraction, and negative MDs were also observed for the ROCF Delayed part and the non-bioaccessible fine fraction. As regards to Mn in fingernails, adjusted MDs of -1.60; 95%CI (-2.57 to -0.64) and -1.45; 95%CI (-2.29 to -0.61) for Digit Span Forward and Backward parts were observed. Conclusions: Our results support an association between poorer cognitive function and environmental airborne Mn exposure. This work was supported by the Spanish Ministry of Science, Innovation and Universities through the CTM2017-82636-R Project. This funding source was not involved in the study design; data collection, analysis, or interpretation; the writing of the article; or the decision to submit for publication.

Product design is one of the most important factors to introduce the circular economy model. In this discipline, the decisions made influence the whole life cycle of the product, since the raw material obtaining to the end of life of the product. Product engineering uses resources, both technical and material to create products. In this way, among all stages that product design encompasses, most relevant and significant decisions are taken during the conceptual stage, when changes can more easily be introduced. On the other hand, creativity plays an important role in introducing new features in products (as circularity is) in a new way. To implement in a proper manner these new functionalities in the products the concepts have to be evaluated. There are methods for assessing novelty and for assessing circularity, but in the case of circularity they are focused on products that have already been developed. Moreover, these methods do not assess circularity in a holistic way, as they only cover some of the aspects that the circular economy encompasses. This work intends to fill the gap that currently exists in the tools for evaluating product concepts by designing a metric, CN_Con, that measures the circularity and the novelty of conceptual proposals as a whole. The metric works according the product functions and analysing the novelty, the strategies for durability and for extending the useful life of the product that the concepts use. It also assesses the raw material and the end of life of the materials with which the concepts are designed. The development of CN_Con will help to implement the circular economy paradigm while encouraging creative design solutions. Funding for open access charge: CRUE-Universitat Jaume I

Within the literature devoted to studying the influence of environment factors on people’s creativity, the majority analyzed these factors as isolated elements and assess individual’s creativity in general. The aim of this work is to analyze the influence of some of these environmental factors on the design outcomes in terms of creativity, considering the potential emotion it can cause (relaxation or arousal). An experiment was developed to test the results generated in different settings combining environment factors that enhance creativity, in which designers were asked to develop different creative concepts. Different colors and music were combined in order to set arousing and relaxing environments. Results point to differences in the creativity parameters, according to the environment in which designers worked.

El presente trabajo indaga en prácticas que asociamos al liderazgo pedagógico (LP) yliderazgo para la justicia social (LJS) en Uruguay a partir de un estudio exploratoriode las Unidades Coordinadoras Departamentales de Integración Educativa (UCDIE).Tomando algunas competencias que hacen a los liderazgos mencionados y la informaciónrecabada en una serie de entrevistas, se ensaya un esbozo del saber hacer dedichas unidades. Uno de los interrogantes que guían la investigación es el siguiente:¿Responden los perfiles de coordinación de las UCDIE a las características del liderazgopedagógico y de la justicia social? Las UCDIE son las encargadas de potenciar, a nivel departamental y local, una políticaque apunta a la coordinación metodológica y a la continuidad educativa entre lossubsistemas de la Administración Nacional de Educación Pública (ANEP), así como dedesplegar estrategias y generar acuerdos territoriales en pro de favorecer el derechoa la educación.

Mutant KRAS is present in over 90% of pancreatic as well as 30-40% of lung and colorectal cancers and is one of the most common oncogenic drivers. Despite decades of research and the recent emergence of isoform-specific KRASG12C-inhibitors, most mutant KRAS isoforms, including the ones frequently associated with pancreatic ductal adenocarcinoma (PDAC), cannot be targeted directly. Moreover, targeting single RAS downstream effectors induces adaptive mechanisms leading to tumor recurrence or resistance. We report here on the combined inhibition of SHP2, a non-receptor tyrosine phosphatase upstream of KRAS, and ERK, a serine/threonine kinase and a key molecule downstream of KRAS in PDAC. This combination shows synergistic anticancer activity in vitro, superior disruption of the MAPK pathway, and significantly increased apoptosis induction compared to single-agent treatments. In vivo, we demonstrate good tolerability and efficacy of the combination. Concurrent inhibition of SHP2 and ERK induces significant tumor regression in multiple PDAC mouse models. Finally, we show evidence that 18F-FDG PET scans can be used to detect and predict early drug responses in animal models. Based on these compelling results, we will investigate this drug combination in a clinical trial (SHERPA, SHP2 and ERK inhibition in pancreatic cancer, NCT04916236), enrolling patients with KRAS-mutant PDAC.

SummaryIn pancreatic cancer, emerging evidence suggests that PPAR-δ overexpression is associated with tumor progression and metastasis, but a mechanistic link is still missing. Here we now show that PPAR-δ acts as the integrating upstream regulator for the metabolic rewiring, which is preceding the subsequent initiation of an invasive/metastatic program. Specifically, paracrine and metabolic cues regularly found in the metastasis-promoting tumor stroma consistently enhance, via induction of PPAR-δ activity, the glycolytic capacity and reserve of pancreatic cancer cells, respectively, accompanied by decreased mitochondrial oxygen consumption. Consequently, genetic or pharmacological inhibition of PPAR-δ results in reduced invasiveness and metastasis. Mechanistically, PPAR-δ acts by shifting the MYC/PGC1A balance towards MYC, enhancing metabolic plasticity. Targeting MYC similarly prevents the metabolic switch and subsequent initiation of invasiveness. Therefore, our data demonstrate that PPAR-δ is a key initiator for the metabolic reprogramming in pancreatic cancer, thereby acting as a checkpoint for the phenotypic change towards invasiveness. These findings provide compelling evidence for a novel treatment strategy to combat pancreatic cancer progression.