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ABSTRACTDuring the 2022–2023 season, the Region of Murcia (an autonomous community of Spain) introduced the influenza vaccination campaign in children aged 24–59 months with the live-attenuated influenza nasal spray vaccine. To expand coverage, a pilot study was conducted to include the 3- to 4-year population in 24 public schools. The aim of the study was to assess the experiences of parents and teachers involved in the project. This was a psychosocial qualitative study in which information was collected from a cohort of 23 parents and 17 teachers who attended three and two focus group sessions, respectively. A high degree of satisfaction with the school-located influenza vaccination program was consistently reported. The teachers reported creating a friendly environment and acting as companions to support children in the absence of their parents. They also considered the intranasal route, which avoids intramuscular puncture, as a facilitating element that turned the vaccination process into a kind of game. Parents emphasized the importance of vaccination to protect their children, and secondarily, to ensure protection of the family nucleus. Some parents who had their children already vaccinated in the health care center reported preference for the school setting, probably selecting this option in the future. The availability of school-based influenza vaccination promoted greater equity in accessing the vaccine and facilitated family reconciliation. To optimize coverage and minimize potential reluctance, providing the necessary information to parents both before and after vaccination was considered. School-located influenza vaccination was feasible and is a valuable strategy to be implemented in future campaigns.

Context: In 14 districts of the valley of Ica-Peru, Vitis vinifera L. plants are cultivated that produce grapes for consumption as table grapes and raisins (dried grapes); at the same time, for the production of wines and Piscos. Aims: To determine the levels of abamectin and emamectin in grapes of Vitis vinifera L from a district of the Valley of Ica-Peru. Methods: 30 lots (30 kg) of Moscatel grape variety V. vinifera L. were collected from six countryside (artisanal and organic cultivation) of the San Juan Bautista district. The extraction of abamectin (ABM) and emamectin benzoate (EMB) from the grapes was carried out with acetonitrile; it was quantified by means of Liquid Chromatography coupled to Mass Spectrometry (HPLC-MS). The maximum permissible limit values (MRL) were established at 0.010 ppm for both insecticides. Results: The determined levels of abamectin and emamectin in grapes were 0.0012-0.015 ppm and 0.0013-0.013 ppm, respectively. Values higher than the maximum permissible limits of abamectin were found in batches A2 (0.0102 ppm), C1 (0.015 ppm), C5 (0.0113 ppm), and F2 (0.012 ppm); emamectin benzoate in lots B1 (0.0113 ppm), B4 (0.013 ppm) and C4 (0.012 ppm). Using the Shapiro-Wilk, Anderson Darling and Student’s t tests, it was found that the global means of the values of the two insecticides in grapes are lower than the MRL. According to the global analysis of variance, the means of the concentrations of both insecticides were not different between the six sampling zones (countryside). Conclusions: The insecticides abamectin and emamectin are below the maximum permissible limit values (0.010 ppm) in Moscatel grapes of Vitis vinifera L., so the residual effect would not have implications for human health.

Este trabajo analiza cómo los 10 bancos españoles adheridos a los Principios de Banca Responsable comunican sus acciones en sus reportes anuales y, con ello, su nivel de transparencia y si existe relación con su reputación. Se ha utilizado una metodología cualitativa aplicando el análisis de contenido analizando los criterios de calidad de la información relacionada con la RSE que identifica la ISO 26000. Los resultados muestran que existen diferencias entre bancos y ninguno de ellos alcanza el cumplimiento en todas las variables de la ISO 26000; no obstante, la mayoría de ellos se encuentran en un nivel medio de cumplimiento. Los criterios peor abordados por los bancos son los de proporcionar información “equilibrada” y “accesible”. Asimismo, el estudio muestra que la validez de la información facilitada, en términos de relevancia para los grupos de interés, es escasa. En cuanto a la reputación de los bancos, se observa que la implementación de los PRB no ha sido significativa para la construcción de confianza y reputación entre sus stakeholders, pero sí ha favorecido su evolución positiva. En cuanto a la reputación, se observa la evolución del ranking Merco de los últimos 5 años, y se comparan las puntuaciones anteriores a la implementación de los PRB y las posteriores. Cabe destacar que la evolución sólo ha sido positiva en el caso de 1 banco, lo que parece indicar que la implementación de los PRB no ha sido significativa para la construcción de reputación de los bancos entre sus stakeholders.

In this randomized phase II study (GEM-KyCyDex, clinicaltrials gov. Identifier: NCT03336073), the combination of weekly carfilzomib 70 mg/m2, cyclophosphamide and dexamethasone (KCd) was compared to carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM) after 1-3 prior lines (PL). One hundred and ninety-seven patients were included and randomized 1:1 to receive KCd (97 patients) or Kd (100 patients) in 28-day cycles until progressive disease or unacceptable toxicity occurred. Patient median age was 70 years, and the median number of PL was one (range, 1-3). More than 90% of patients had previously been exposed to proteasome inhibitors, approximetely 70% to immunomodulators, and approximetely 50% were refractory to their last line (mainly lenalidomide) in both groups. After a median follow-up of 37 months, median progression-free survival (PFS) was 19.1 and 16.6 months in KCd and Kd, respectively (P=0.577). Of note, in the post hoc analysis of the lenalidomide-refractory population, the addition of cyclophosphamide to Kd resulted in a significant benefit in terms of PFS: 18.4 versus 11.3 months (hazard ratio =1.7, 95% confidence interval: 1.1-2.7; P=0.043). The overall response rate and the percentage of patients who achieved complete response was around 70% and 20% in both groups. The addition of cyclophosphamide to Kd did not result in any safety signal, except for severe infections (7% vs. 2%). In conclusion, the combination of cyclophosphamide with Kd 70 mg/m2 weekly does not improve outcomes as compared with Kd alone in RRMM after 1-3 PL, but a significant benefit in PFS was observed with the triplet combination in the lenalidomide-refractory population. The administration of weekly carfilzomib 70 mg/m2 was safe and convenient, and, overall, the toxicity was manageable in both arms.

El siguiente trabajo, amparado en la Lingüística Contrastiva, estudia la interferencia del chino mandarín en la producción de preguntas totales en español a partir de enunciados de estudiantes y profesores chinos del departamento de español de la Universidad de Estudios Extranjeros de Guangxi, en el sur de China. Para analizar la supuesta interferencia se ha realizado un trabajo de campo.

The hexavalent vaccines DT3aP-HBV-IPV/Hib and DT2aP-HBV-IPV-Hib are routinely used for primary immunization of infants against diphtheria, tetanus, pertussis, hepatitis B virus, poliomyelitis, and Haemophilus influenzae type b. A recent publication showed that after primary immunization with these vaccines, the odds ratios of adverse reactions (ARs) were significantly lower for DT3aP-HBV-IPV/Hib than for DT2aP-HBV-IPV-Hib. Our aim is to understand the impact of the various reactogenicity profiles at country level by comparing the ARs induced by one dose of DT3aP-HBV-IPV/Hib versus DT2aP-HBV-IPV-Hib in the primary infant immunization course. A mathematical projection tool was developed to simulate vaccination of infants with both vaccines in six countries: Austria, the Czech Republic, France, Jordan, Spain, and the Netherlands. Proportions of three local and five systemic ARs of interest for both vaccines were based on findings from a previous meta-analysis of ARs in infants. The absolute risk reductions calculated ranged from 3.0% (95% confidence interval [CI]: 2.8%–3.2%) for “Swelling at the injection site, any grade” to 10.0% (95% CI: 9.5%–10.5%) for “Fever, any grade.” The difference in occurrence of the AR “Fever, any grade” between vaccines in 2020 ranged from over 7,000 in Austria to over 62,000 in France. Over 5 years, this would amount to a reduction of over 150,000 ARs in Austria and over 1.4 million ARs in France when using DT3aP-HBV-IPV/Hib instead of DT2aP-HBV-IPV-Hib. In conclusion, the estimated numbers of ARs following hexavalent vaccination in six countries showed that vaccination of infants with DT3aP-HBV-IPV/Hib could lead to fewer ARs than vaccination with DT2aP-HBV-IPV-Hib.

Epilepsy is a neurological disorder characterized by spontaneous recurrent seizures. While 20% to 30% of epilepsy cases are untreatable with Anti-Epileptic Drugs, some of these cases can be addressed through surgical intervention. The success of such interventions greatly depends on accurately locating the epileptogenic tissue, a task achieved using diagnostic techniques like Stereotactic Electroencephalography (SEEG). SEEG utilizes multi-modal fusion to aid in electrode localization, using pre-surgical resonance and post-surgical computer tomography images as inputs. To ensure the absence of artifacts or misregistrations in the resultant images, a fusion method that accounts for electrode presence is required. We proposed an image fusion method in SEEG that incorporates electrode segmentation from computed tomography as a sampling mask during registration to address the fusion problem in SEEG. The method was validated using eight image pairs from the Retrospective Image Registration Evaluation Project (RIRE). After establishing a reference registration for the MRI and identifying eight points, we assessed the method’s efficacy by comparing the Euclidean distances between these reference points and those derived using registration with a sampling mask. The results showed that the proposed method yielded a similar average error to the registration without a sampling mask, but reduced the dispersion of the error, with a standard deviation of 0.86 when a mask was used and 5.25 when no mask was used.

Las actividades de fomento de la cultura científica se han convertido en una práctica habitual de las instituciones de investigación, que destinan presupuesto y recursos humanos a este objetivo. Cada vez más personal científico y técnico incorpora esta misión a sus tradicionales tareas de investigación y formación. Sin embargo, mientras la investigación y la docencia cuentan con indicadores establecidos, las actividades de divulgación siguen estando consideradas como un ejercicio extraordinario, pocas veces reconocido institucionalmente. En este sentido, el uso de unos indicadores de cultura científica contribuiría a favorecer un cambio de mentalidad y a la obtención de datos objetivos sobre los que orientar las acciones de comunicación social de la ciencia. En este contexto, el Consejo Superior de Investigaciones Científicas (CSIC), a través de su Vicepresidencia Adjunta de Cultura Científica, se ha propuesto analizar las actividades desarrolladas en esta línea, entre 2011 y 2019, en relación a los siguientes indicadores: 1) la inversión económica; 2) el personal dedicado a cultura científica; 3) el número y tipo de actividades; y 4) el público al que se llega. Entre las principales conclusiones, destaca que el CSIC cuenta con una masa crítica más o menos estable de unas 200 personas que se dedican a tareas de cultura científica. Cada año se realizan alrededor de 15.000 actividades (presenciales y no presenciales) en las que se implican alrededor de 3.000 trabajadoras y trabajadores del CSIC. Cada año participan cerca de un millón y medio de personas de manera presencial.

International outlook constitutes, together with teaching, research, and knowledge transfer, one of the university core missions. Spain remains as a preferred destination for outbound mobilities, which constitutes an opportunity in terms of international rankings. Vice-Rectorates are designing strategies to retain this flow of international students, as well as to promote outbound mobilities. The present piece of research is a qualitative study based on Deyo's Qualitative Social Constructionist Inquiry (2018), a semi-structured interview. Such design was supervised by experts and approved by the Ethics Committee of Social Studies. Results address the viewpoints of 17 international coordinators of the Universidad de Castilla-La Mancha, based on four different campuses. The sample was made in terms of convenience, as it is the authors' institution. Questions concentrate on coordinators' understanding of the goals and needs of study abroad programmes, together with the needs of international students, their main challenges, and the role of the three communicative subcompetences of the Common European Framework of Reference for Languages on these programmes, and more specifically their connection with the Theory of Identity Development (Chickering and Reisser, 1993), to help determine the strengths and weaknesses of such mobilities. Results reveal important information in relation to both the role of international coordinator and the effects these exchanges have on the students. Considering the former aspect, the answers evinced that this job post requires more attention in terms of training, tasks specification, recognition, and assistance. Regarding the latter, the responses highlight multiple benefits derived from these exchanges; in particular, the development of personal and social abilities to be more independent to solve problems, to collaborate with other people from different backgrounds, to communicate in a foreign language, and to expand their worldview. Nonetheless, the answers also show that this experience could be further enriched by academic, social, and emotional support for the students. In this line, the study suggests a set of recommendations and seeks for alternative instances to reach the goals of international exchange, such as excellence, equity, or education innovation (European Commission, 2021) by means of virtual exchange in COIL programmes such as eTwinning.

ABSTRACT Introduction: 46,XX Congenital adrenal hyperplasia (CAH) remains the first cause of genital virilization and current surgical techniques aim to restore female aspect of genitalia while preserving dorsal neurovascular bundle but not at the expense of not preserving erectile tissue. We aim to report our experience with a new surgical technique for clitoroplasty, completely preserving corporeal bodies, neurovascular bundles without dismembering the clitoris, in four patients with over a year follow up. Materials and Methods: After IRB approval four patients with 46,XX CAH and Prader 5 and 3 external genitalia, underwent feminizing genitoplasty. Complete preservation of erectile tissue was accomplished without a need to dissect dorsal neurovascular bundle. Glans size allowed no need for glanular reduction and there was no need to dismember the corporeal bodies. Results: Four patients 12 to 24-months-old underwent complete corporeal preservation clitoroplasty (CCPC), mean age was 18.5 months, mean follow up was 10.25 months. Vaginoplasty was performed in all patients with partial urogenital mobilization (PUM) and Urogenital Sinus flap (UF), only one severely virilized patient required a parasagittal pre-rectal approach to mobilize the vagina. We had no complications until last follow up. Conclusion: To our knowledge, we are introducing the concept of CCPC without the need of disassembling the corporeal bodies, neurovascular bundle and glans. It stands as a new alternative for feminizing genitoplasty with complete preservation of erectile tissue and no dissection of neurovascular bundle. Although there is still lacking long-term follow-up, it represents a new step in conservative reconfiguration of the external virilized female genitalia.

El presente artículo sistematiza los resultados de una investigación científica relacionada con el valor del acompañamiento andragógico en el ejercicio docente. Tuvo como objetivo analizar las transformaciones en las prácticas pedagógicas de los maestros, producidas en virtud de un modelo de acompañamiento. El problema estudiado está representado en la carencia de procesos de formación y seguimiento suficientes y efectivos hacia los maestros del ciclo de primaria, reflejado en los bajos resultados en materia de aprendizajes en este nivel. Se empleó la metodología Investigación Acción Pedagógica (IAP) desde el modelo propuesto por Restrepo (2006) en tres fases: deconstrucción, reconstrucción de la práctica y validación de la efectividad de la práctica, tomando como población de estudio a los maestros de la básica primaria de una sede educativa en la ciudad de Montería (Colombia). Los resultados de este estudio develan que la naturaleza representacional del docente está directamente ligada a su desempeño; sus creencias, percepciones y concepciones determinan su accionar en el aula; entretanto, su autonomía y colaboración le permiten reflexionar y liderar la de transformación de su práctica. Finalmente, se concluye que el acompañamiento de un andragogo toma fuerza en la formación del profesorado para avanzar en el mejoramiento continuo de su ejercicio docente, fortaleciendo a su vez, el trabajo colaborativo y el aprendizaje entre pares. Palabras clave: Saber pedagógico; enseñanza; prácticas pedagógicas; reflexión docente; andragogía; investigación acción pedagógica.

Abstract Background Patients with cancer have been shown to have a higher risk of clinical severity and mortality compared to non-cancer patients with COVID-19. Patients with hematologic malignancies typically are known to have higher levels of immunosuppression and may develop more severe respiratory viral infections than patients with solid tumors. Data on COVID-19 in patients with hematologic malignancies are limited. Here we characterize disease severity and mortality and evaluate potential prognostic factors for mortality. Methods In this population-based registry study, we collected de-identified data on clinical characteristics, treatment and outcomes in adult patients with hematologic malignancies and confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection within the Madrid region of Spain. Our case series included all patients admitted to 22 regional health service hospitals and 5 private healthcare centers between February 28 and May 25, 2020. The primary study outcome was all-cause mortality. We assessed the association between mortality and potential prognostic factors using Cox regression analyses adjusted for age, sex, comorbidities, hematologic malignancy and recent active cancer therapy. Results Of 833 patients reported, 697 were included in the analyses. Median age was 72 years (IQR 60–79), 413 (60%) patients were male and 479 (69%) and 218 (31%) had lymphoid and myeloid malignancies, respectively. Clinical severity of COVID-19 was severe/critical in 429 (62%) patients. At data cutoff, 230 (33%) patients had died. Age ≥ 60 years (hazard ratios 3.17–10.1 vs 2 comorbidities (1.41 vs ≤ 2), acute myeloid leukemia (2.22 vs non-Hodgkin lymphoma) and active antineoplastic treatment with monoclonal antibodies (2·02) were associated with increased mortality; conventional chemotherapy showed borderline significance (1.50 vs no active therapy). Conversely, Ph-negative myeloproliferative neoplasms (0.33) and active treatment with hypomethylating agents (0.47) were associated with lower mortality. Overall, 574 (82%) patients received antiviral therapy. Mortality with severe/critical COVID-19 was higher with no therapy vs any antiviral combination therapy (2.20). Conclusions In this series of patients with hematologic malignancies and COVID-19, mortality was associated with higher age, more comorbidities, type of hematological malignancy and type of antineoplastic therapy. Further studies and long-term follow-up are required to validate these criteria for risk stratification.

The common octopus (Octopus vulgaris) is nowadays the most demanded cephalopod species for human consumption. This species was also postulated for aquaculture diversification to supply its increasing demand in the market worldwide, which only relies on continuously declining field captures. In addition, they serve as model species for biomedical and behavioral studies. Body parts of marine species are usually removed before reaching the final consumer as by-products in order to improve preservation, reduce shipping weight, and increase product quality. These by-products have recently attracted increasing attention due to the discovery of several relevant bioactive compounds. Particularly, the common octopus ink has been described as having antimicrobial and antioxidant properties, among others. In this study, the advanced proteomics discipline was applied to generate a common octopus reference proteome to screen potential bioactive peptides from fishing discards and by-products such as ink. A shotgun proteomics approach by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) using an Orbitrap Elite instrument was used to create a reference dataset from octopus ink. A total of 1432 different peptides belonging to 361 non-redundant annotated proteins were identified. The final proteome compilation was investigated by integrated in silico studies, including gene ontology (GO) term enrichment, pathways, and network studies. Different immune functioning proteins involved in the innate immune system, such as ferritin, catalase, proteasome, Cu/Zn superoxide dismutase, calreticulin, disulfide isomerase, heat shock protein, etc., were found in ink protein networks. Additionally, the potential of bioactive peptides from octopus ink was addressed. These bioactive peptides can exert beneficial health properties such as antimicrobial, antioxidant, antihypertensive, and antitumoral properties and are therefore considered lead compounds for developing pharmacological, functional foods or nutraceuticals.

Chronic Lymphocytic Leukemia (CLL) is the most prevalent leukemia in Western countries and is notable for its variable clinical course. This variability is partly reflected by the mutational status of IGHV genes. Many CLL samples have been studied in recent years by next-generation sequencing. These studies have identified recurrent somatic mutations in NOTCH1, SF3B1, ATM, TP53, BIRC3 and others genes that play roles in cell cycle, DNA repair, RNA metabolism and splicing. In this study, we have taken a deep-targeted massive sequencing approach to analyze the impact of mutations in the most frequently mutated genes in patients with CLL enrolled in the REM (rituximab en mantenimiento) clinical trial. The mutational status of our patients with CLL, except for the TP53 gene, does not seem to affect the good results obtained with maintenance therapy with rituximab after front-line FCR treatment.

Casiopeinas are a family of copper(II) coordination compounds that have shown an important antineoplastic effect and low toxicity in normal cells. These compounds induce death cells by apoptosis through a catalytic redox process with endogenous reducing agents. Further studies included a structural variation, improving the activity and selectivity in cancer cells or other targets. In the present work we report the third generation, which contains a bioactive monocharged secondary ligand, as well as the design, synthesis, characterization and antiproliferative activity, of sixteen new copper(II) coordination compounds with curcumin or dimethoxycurcumin as secondary ligands. All compounds were characterized by elemental analysis, FTIR, UV-Vis, magnetic susceptibility, mass spectra with MALDI-flight time, cyclic voltammetry, electron paramagnetic resonance (EPR) spectroscopy and X-ray diffraction. Crystallization of two complexes was achieved in dimethylsulfoxide (DMSO) with polar solvent, and crystal data demonstrated that a square-based or square-base pyramid geometry are possible. A 1:1:1 stoichiometry (diimine: copper: curcuminoid) ratio and the possibility of a nitrate ion as a counterion were supported. 1H, 13C NMR spectra were used for the ligands. A sulforhodamine B assay was used to evaluate the cytotoxicity effect against two human cancer cell lines, SKLU-1 and HeLa. Electronic descriptors and redox potential were obtained by DFT calculations. Structure–activity relationships are strongly determined by the redox potential (E1/2) of copper(II) and molar volume (V) of the complexes. These compounds can be used as a template to open a wide field of research both experimentally and theoretically.

Under the Internet of Things paradigm, the emergence and use of a wide variety of connected devices and personalized telematics services have proliferated recently. As a result, along with the penetration of these devices in our daily lives, the users’ security and privacy have been compromised due to some weaknesses in connected devices and underlying applications. This article focuses on analyzing the security and privacy of such devices to promote safe Internet use, especially by young people. First, the connected devices most used by the target group are classified, and an exhaustive analysis of the vulnerabilities that concern the user is performed. As a result, a set of differentiated security and privacy issues existing in the devices is identified. The study reveals that many of these vulnerabilities are related to the fact that device manufacturers often prioritize functionalities and services, leaving security aspects in the background. These companies even exploit the data linked to the use of these devices for various purposes, ignoring users’ privacy rights. This research aims to raise awareness of severe vulnerabilities in devices and to encourage users to use them correctly. Our results help other researchers address these issues with a more global perspective.

Objective: To calculate, for the first time, the direct and social costs of transfusion-related adverse events in order to include them in the National Healthcare System's budget, calculation and studies. In Spain more than 1,500 patients yearly are diagnosed with such adverse events. Method: Blood transfusion-related adverse events recorded yearly in Spanish haemovigilance reports were studied retrospectively (2010-2015). The adverse events were coded according to the classification of Diagnosis-Related Groups. The direct healthcare costs were obtained from public information sources. The productivity loss (social cost) associated with adverse events was calculated using the human capital and hedonic salary methodologies. Results: In 2015, 1,588 patients had adverse events that resulted in direct health care costs (4,568,914€) and social costs due to hospitalization (200,724€). Three adverse reactions resulted in patient death (at a social cost of 1,364,805€). In total, the cost of blood transfusion-related adverse events was 6,134,443€ in Spain. For the period 2010-2015: the trends show a reduction in the total amount of transfusions (2 vs. 1.91 M€; -4.4%). The number of adverse events increased (822 vs. 1,588; +93%), as well as their related direct healthcare cost (3.22 vs. 4.57M€; +42%) and the social cost of hospitalization (110 vs 200M€; +83%). Mortality costs decreased (2.65 vs. 1.36M€; -48%). Discussion: This is the first time that the costs of post-transfusion adverse events have been calculated in Spain. These new figures and trends should be taken into consideration in any cost-effectiveness study or trial of new surgical techniques or sanitary policies that influence blood transfusion activities. Resumen: Objetivo: Calcular por primera vez los costes económicos y sociales relacionados con las reacciones adversas postransfusionales para actualizar estudios e incluirlos en los presupuestos del Sistema Nacional de Salud. En España, anualmente, más de 1500 pacientes sufren dichas reacciones adversas. Método: Se estudiaron retrospectivamente (periodo 2010-2015) las reacciones adversas a la transfusión recopiladas anualmente en los informes nacionales de hemovigilancia. Dichas reacciones se codificaron mediante clasificación de Grupos Relacionados con el Diagnóstico. Los costes directos sanitarios se obtuvieron de fuentes públicas de información. La pérdida en productividad (coste social) asociada a las reacciones adversas se contabilizó utilizando los métodos del capital humano y salarios hedónicos, respectivamente. Resultados: En el año 2015, en España, 1588 pacientes tuvieron reacciones adversas que derivaron en costes sanitarios (4.568.914 €) y costes sociales debido a hospitalización (200.724 €). Tres reacciones adversas resultaron en muerte del paciente (1.364.805 €). Como suma, el coste total de las reacciones adversas a la transfusión fue de 6.134.443 €. Periodo 2010-2015: la tendencia refleja una reducción en el número total de transfusiones (2 vs. 1,91 M€; -4,4%), un incremento en el número de reacciones adversas (822 vs. 1.588; +93%), en costes sanitarios (3,22 vs. 4,57M€; +42%) y en costes sociales (110 vs. 200M€; +83%), y un descenso en costes de mortalidad (2,65 vs. 1,36M€; -48%). Discusión: Por primera vez se han calculado en España los costes de las reacciones adversas a la transfusión. Los nuevos datos y tendencias deberían ser considerados en estudios de coste-eficiencia sobre técnicas quirúrgicas o políticas sanitarias con repercusión en actividades de transfusión sanguínea. Keywords: Adverse effects, Blood transfusion, Health care costs, Costs and cost analysis, Trends, Palabras clave: Reacciones adversas, Transfusión sanguínea, Costes de la atención en salud, Costes y análisis de costes, Tendencias

This paper describes the progress regarding the identification and quantification of potential wave energy in Atlántico state coast. The used methodology will serve as a starting point to establish the energetic potential in Colombia in this energy. The theoretical energetic potential estimated at the near shore in the Atlantic coast waves is approximately 1107 MW and this was possible with data that has been collected and processed since January 2016. We applied equations that take into account variables such as: significant wave height, period, sea water density, temperature and wind speed in the area. Also it is shown the progress of the near shore system design for the verification of the wave energetic potential consisting of a device which transforms kinetic energy of the sea waves into gravitational potential energy that is going to be used to move an alternating current generator.

El aguacate es uno de los frutos de importancia económica en Colombia que presenta pérdidas en post cosecha. El objetivo de esta investigación fue evaluar el efecto de un recubrimiento comestible a base de gelana de alto (GAA) y bajo acilo (GBA), sobre la calidad post cosecha del aguacate (Persea americana cv. "Hass"), almacenado durante nueve semanas. Para la elaboración de los recubrimientos, se utilizó un diseño factorial 2³, donde los factores fueron las concentraciones de GAA (0,30 y 0,60% p/v), GBA (0,30 y 0,60% p/v) y glicerol (GLI) (8,0 y 12% v/v); como agente antimicrobiano, se utilizó extracto acuoso de Toronjil (Melissa officinalis L), por ser un aditivo natural. Se evaluaron propiedades, como la firmeza, la pérdida de humedad, el pH y los sólidos solubles totales (SST), durante almacenamiento. Finalmente, para la estimación del periodo de vida útil, se empleó la ecuación de Monod Hinshelwood, previo modelado de los datos, con ayuda de la ecuación de Baranyi y Roberts. Los resultados indicaron que la aplicación de recubrimientos comestibles de goma gelana, conteniendo bajas concentraciones de glicerol, disminuye significativamente (P

Loss of half renal mass does not necessarily correspond to half of glomerular filtration rate (GFR), meaning that there is not an exact correlation between renal mass reduction and loss of renal function. The GFR is a necessary index for: diagnosis; follow-up of patients with renal injury; epidemiological controls; nephrotoxic drugs dose adjustment or renal elimination drugs; chronic renal disease stratification, etc.

The loss of half the renal mass does not necessarily imply half the Glomerular Filtration Rate (GFR), meaning that there is not an exact correlation between renal mass reduction and renal function loss. GFR is a necessary index for diagnosis and to establish chronic renal disease stages, followup of renal failure patients, epidemiological studies, adjustment of nephrotoxic drugs or renal excretion drugs, among other uses. This update briefly analyzes the principal methods used in order to estimate glomerular filtration, some of its strengths and weaknesses. The use of estimated GFR in epidemiological studies has contributed to generate a wide scale of controversies that instead of contributing to scientific progress, have produced endless discussions because of misleading argumentations and deviations for these calculations. Equations applied for estimating GFR in population studies, should be reconsidered, given their imperfection and the difficulty for clinicians, who are not specialists on the subject, to interpret the results.

Cancer is the second leading cause of death, after cardiovascular diseases. Different strategies have been developed to treat cancer; however, chemotherapy with cytotoxic agents is still the most widely used treatment approach. Nevertheless, drug resistance to available chemotherapeutic agents is still a serious problem, and the development of new active compounds remains a constant need. Taking advantage of the molecular hybridization approach, in the present work we designed, synthesized, and tested the cytotoxic activity of two hybrid compounds and seven derivatives based on the structure of combretastatin A-4 and 2,3-diphenyl-2H-indazole. Practical modifications of reported synthetic protocols for 2-pheny-2H-indazole and 2,3-dipheny-2H-indazole derivatives under microwave irradiation were implemented. The cytotoxicity assays showed that our designed hybrid compounds possess strong activity, especially compound 5, which resulted even better than the reference drug cisplatin against HeLa and SK-LU-1 cells (IC50 of 0.16 and 6.63 µM, respectively), and it had similar potency to the reference drug imatinib against K562 cells. Additionally, in silico and in vitro studies strongly suggest tubulin as the molecular target for hybrid compound 5.

Regulating insulin and leptin levels using a protein tyrosine phosphatase 1B (PTP1B) inhibitor is an attractive strategy to treat diabetes and obesity. Glycyrrhetinic acid (GA), a triterpenoid, may weakly inhibit this enzyme. Nonetheless, semisynthetic derivatives of GA have not been developed as PTP1B inhibitors to date. Herein we describe the synthesis and evaluation of two series of indole- and N-phenylpyrazole-GA derivatives (4a–f and 5a–f). We measured their inhibitory activity and enzyme kinetics against PTP1B using p-nitrophenylphosphate (pNPP) assay. GA derivatives bearing substituted indoles or N-phenylpyrazoles fused to their A-ring showed a 50% inhibitory concentration for PTP1B in a range from 2.5 to 10.1 µM. The trifluoromethyl derivative of indole-GA (4f) exhibited non-competitive inhibition of PTP1B as well as higher potency (IC50 = 2.5 µM) than that of positive controls ursolic acid (IC50 = 5.6 µM), claramine (IC50 = 13.7 µM) and suramin (IC50 = 4.1 µM). Finally, docking and molecular dynamics simulations provided the theoretical basis for the favorable activity of the designed compounds.

Indazole is an important scaffold in medicinal chemistry. At present, the progress on synthetic methodologies has allowed the preparation of several new indazole derivatives with interesting pharmacological properties. Particularly, the antiprotozoal activity of indazole derivatives have been recently reported. Herein, a series of 22 indazole derivatives was synthesized and studied as antiprotozoals. The 2-phenyl-2H-indazole scaffold was accessed by a one-pot procedure, which includes a combination of ultrasound synthesis under neat conditions as well as Cadogan’s cyclization. Moreover, some compounds were derivatized to have an appropriate set to provide structure-activity relationships (SAR) information. Whereas the antiprotozoal activity of six of these compounds against E. histolytica, G. intestinalis, and T. vaginalis had been previously reported, the activity of the additional 16 compounds was evaluated against these same protozoa. The biological assays revealed structural features that favor the antiprotozoal activity against the three protozoans tested, e.g., electron withdrawing groups at the 2-phenyl ring. It is important to mention that the indazole derivatives possess strong antiprotozoal activity and are also characterized by a continuous SAR.

Candidiasis, caused by yeasts of the genus Candida, is the second cause of superficial and mucosal infections and the fourth cause of bloodstream infections. Although some antifungal drugs to treat candidiasis are available, resistant strains to current therapies are emerging. Therefore, the search for new candicidal compounds is certainly a priority. In this regard, a series of indazole and pyrazole derivatives were designed in this work, employing bioisosteric replacement, homologation, and molecular simplification as new anticandidal agents. Compounds were synthesized and evaluated against C. albicans, C. glabrata, and C. tropicalis strains. The series of 3-phenyl-1H-indazole moiety (10a–i) demonstrated to have the best broad anticandidal activity. Particularly, compound 10g, with N,N-diethylcarboxamide substituent, was the most active against C. albicans and both miconazole susceptible and resistant C. glabrata species. Therefore, the 3-phenyl-1H-indazole scaffold represents an opportunity for the development of new anticandidal agents with a new chemotype.

BACKGROUND: Induction schedules in acute myeloid leukemia (AML) are based on combinations of cytarabine and anthracyclines. The choice of the anthracycline employed has been widely studied in multiple clinical trials showing similar complete remission rates. MATERIALS AND METHODS: Using an ex vivo test we have analyzed if a subset of AML patients may respond differently to cytarabine combined with idarubicin, daunorubicin or mitoxantrone. Bone marrow (BM) samples of 198 AML patients were incubated for 48 hours in 96 well plates, each well containing different drugs or drug combinations at different concentrations. Ex vivo drug sensitivity analysis was made using the PharmaFlow platform maintaining the BM microenvironment. Drug response was evaluated as depletion of AML blast cells in each well after incubation. Annexin V-FITC was used to quantify the ability of the drugs to induce apoptosis, and pharmacological responses were calculated using pharmacokinetic population models. RESULTS: Similar dose-respond graphs were generated for the three anthracyclines, with a slight decrease in EC50 with idarubicin (p=1.462E-06), whereas the interpatient variability of either drug was large. To identify those cases of selective sensitivity to anthracyclines, potency was compared, in terms of area under the curve. Differences in anthracycline monotherapy potency greater than 30% from 3 pairwise comparisons were identified in 28.3% of samples. Furthermore, different sensitivity was detected in 8.2% of patients comparing combinations of cytarabine and anthracyclines. DISCUSSION: A third of the patients could benefit of the use of this test in the first line induction therapy selection, although it should be confirmed in a clinical trial specifically designed.

This paper presents a hybrid grasshopper optimization algorithm using a novel decoder and local search to solve instances of the open vehicle routing problem with capacity and distance constraints. The algorithm’s decoder first defines the number of vehicles to be used and then it partitions the clients, assigning them to the available routes. The algorithm performs a local search in three neighborhoods after decoding. When a new best solution is found, every route is locally optimized by solving a traveling salesman problem, considering the depot and clients in the route. Three sets containing a total of 30 benchmark problems from the literature were used to test the algorithm. The experiments considered two cases of the problem. In the first, the primary objective is to minimize the total number of vehicles and then the total distance to be traveled. In the second case, the total distance traveled by the vehicles is minimized. The obtained results showed the algorithm’s proficient performance. For the first case, the algorithm was able to improve or match the best-known solutions for 21 of the 30 benchmark problems. For the second case, the best-known solutions for 18 of the 30 benchmark problems were found or improved by the algorithm. Finally, a case study from a real-life problem is included.

The following article proposes a revision of dramatic creation strategies present in the play Gota d’água (1975) by Chico Buarque and Paulo Pontes. Firstly, it will provide a comparative exercise with Medea by Euripides (431 BC) in order to account for the transculturation processes from the European referent. Then, the manner in which authors make use of epic-brechtian resources is analyzed to finally develop an interpretation proposal that links the 1975 play to the political and social situation in Brazil during the military dictatorship.

Este trabajo de percepción ambiental se originó con el fin de determinar la relación entre los guías de turismo de tres localidades de las bahías de Huatulco (La Entrega, San Agustín y Maguey) y el uso que hacen del recurso natural; es decir, el arrecife de coral situado en estas playas. Se diseñaron entrevistas enfocadas en tres diferentes apartados: saber qué conocen, cómo actúan y qué valoran los guías de turismo respecto de los servicios naturales que ofrece el arrecife de coral. Los resultados arrojaron que la percepción ambiental que los guías de turismo de las tres localidades tienen es totalmente diferente; mientras que los guías de las localidades La Entrega y San Agustín muestran un interés en la conservación del recurso, los de la localidad de Maguey están poco interesados en su cuidado. Por último, se busca analizar la posibilidad de la creación de una estrategia de educación ambiental para equilibrar la relación sociedad –naturaleza de este ecosistema marino y la actividad turística que se realiza en él.

Se evaluó la influencia de la separación de electrodos sobre la producción de electricidad y la eliminación de materia orgánica en celdas de combustible microbianas usando agua residual. Para ello se construyeron tres celdas de geometría semejante pero con diferente volumen. En promedio, se obtuvo una eficiencia de eliminación de materia orgánica del 71%. La duración del ciclo fue de 0.97 días para la celda de 40 mL, 1.03 días para la celda de 80 mL y 5.93 días para la celda de 120 mL. El aumento de distancia entre los electrodos (4, 8 y 12 cm) no causó un efecto negativo en la generación de electricidad, pues en la mayor separación (celda de 120 mL) se alcanzó un voltaje máximo de 660 mV, mientras que para las celdas de 40 y 80 mL fue de 540 mV y 532 mV, respectivamente. La densidad de potencia máxima se presentó en la celda con separación de 12 cm (408 mW/m2). Sin embargo, se observó que la potencia volumétrica disminuyó a medida que aumentó la separación entre los electrodos.

Objetivo. Presentar un caso de diagnóstico prenatal de ambigüedad genital, con la posterior confirmación posnatal de pseudohermafroditismo masculino. Describir los rasgos más importantes de ultrasonido obstétrico en las malformaciones genitales y realizar una revisión de la literatura que permita al lector un abordaje fácil a este tipo de literatura. Métodos. Se realizó la evaluación prenatal en un embarazo de 22 semanas de una madre de 38 años y se observó un feto con genitales externos ambiguos y posible hipospadias. La paciente entró en el programa de vigilancia fetal y se realizaron ecografías periódicas y un estrecho control prenatal. Durante la etapa posnatal se realizó la evaluación clínica, hormonal y genética del recién nacido. Posteriormente, se hizo estimulación con testosterona y se observó una respuesta favorable con mejor caracterización de los genitales externos: aumento del grosor del pene y pigmentación del escroto. Resultados. Se le realizó el diagnóstico prenatal de genitales ambiguos, hipospadias, apéndice preauricular izquierdo; se le ofreció a la madre determinar el cariotipo prenatal, a lo cual se negó. El diagnóstico de pseudohermafroditismo masculino fue realizado al relacionar los hallazgos ecográficos encontrados prenatalmente, con los hallazgos descritos en el examen físico, el estudio de cariotipo 46 XY y los marcadores hormonales en la etapa posnatal. Conclusiones. El diagnóstico prenatal de alteraciones de la diferenciación sexual del feto no es siempre fácil. Comprende un estudio minucioso, cuidadoso y multidisciplinario de las posibles causas de la alteración para lograr determinar de la mejor manera las acciones terapéuticas en beneficio del desarrollo biopsicosexual del individuo afectado por este tipo de patología.

Las masas abdominales en niños, en su gran mayoría, se originan del parénquima renal. Al momento del estudio de dichas lesiones, la aproximación radiológica es fundamental. Por lo tanto, el conocer a profundidad las características y las manifestaciones clínicas y radiológicas de cada una de las patologías es de vital importancia. Por lo general, el médico siempre tendrá dificultad para el diagnóstico por la similitud entre las diferentes lesiones en cuanto a comportamiento y apariencia radiológica. En el presente artículo se busca caracterizar mejor cada una de las patologías tomando como base un caso clínico.

Chagas, or American trypanosomiasis, remains an important public health problem in developing countries. In the last decade, trans-sialidase has become a pharmacological target for new anti-Chagas drugs. In this work, the aims were to design and find a new series of benzoic acid derivatives as trans-sialidase (TS) inhibitors and anti-trypanosomal agents. Three compounds (14, 18, and 19) sharing a para-aminobenzoic acid moiety showed more potent trypanocidal activity than the commercially available drugs nifurtimox and benznidazole in both strains: the lysis concentration of 50% of the population (LC50) was

Indazole is considered a very important scaffold in medicinal chemistry. It is commonly found in compounds with diverse biological activities, e.g., antimicrobial and anti-inflammatory agents. Considering that infectious diseases are associated to an inflammatory response, we designed a set of 2H-indazole derivatives by hybridization of cyclic systems commonly found in antimicrobial and anti-inflammatory compounds. The derivatives were synthesized and tested against selected intestinal and vaginal pathogens, including the protozoa Giardia intestinalis, Entamoeba histolytica, and Trichomonas vaginalis; the bacteria Escherichia coli and Salmonella enterica serovar Typhi; and the yeasts Candida albicans and Candida glabrata. Biological evaluations revealed that synthesized compounds have antiprotozoal activity and, in most cases, are more potent than the reference drug metronidazole, e.g., compound 18 is 12.8 times more active than metronidazole against G. intestinalis. Furthermore, two 2,3-diphenyl-2H-indazole derivatives (18 and 23) showed in vitro growth inhibition against Candida albicans and Candida glabrata. In addition to their antimicrobial activity, the anti-inflammatory potential for selected compounds was evaluated in silico and in vitro against human cyclooxygenase-2 (COX-2). The results showed that compounds 18, 21, 23, and 26 display in vitro inhibitory activity against COX-2, whereas docking calculations suggest a similar binding mode as compared to rofecoxib, the crystallographic reference.

Se realizó un estudio para determinar el efecto de la actividad física aeróbica controlada en el peso, la grasa corporal, la masa libre de grasa y la distribución de la grasa corporal, en 16 mujeres sedentarias, con edades entre 55 y 70 años, clínicamente libres de enfermedad cardiovascular. Las mujeres, seleccionadas de un grupo de voluntarias del municipio de Caldas en Antioquia, Colombia, se sometieron a un programa de actividad física, entre el 60 y el 85% de la frecuencia cardíaca máxima (FCmax), de 60 minutos de duración, tres veces por semana, durante 4 meses. Al inicio y al final se les tomaron las medidas antropométricas: peso corporal, perímetros y pliegues cutáneos; antes y después del programa, para estimar los cambios en el peso, la composición corporal, a partir de los indicadores: peso corporal total (PCT), peso corporal en grasa (PCG), peso corporal libre de grasa (PCLG), área grasa del brazo (AGB), área grasa del muslo (AGM), área grasa de la pierna (AGP), área magra del brazo (AMB), área magra del muslo (AMM), área magra de la pierna (AMP), sumatoria de pliegues del tronco (SPTr), sumatoria pliegues de las extremidades (SPExt) y la razón entre el perímetro de la cintura y el de la cadera (PCi/PCa). Se registró además la ingesta de alimentos mediante encuesta de recordatorio de consumo, combinada con la frecuencia semicuantitativa, para calcular el consumo diario de Kilocalorías (Kcal). Se observaron cambios estadísticamente significativos, utilizando la prueba no paramétrica del signo-rango de Wilcoxon, entre el inicio y el final del programa para todos los indicadores antes menciona- dos excepto para el AMM y el PCi/ Pca. La ingesta energética al inicio y al final se utilizó como variable de control y se comprobó su correlación mediante el coeficiente de Pearson. De éste estudio se concluye que la actividad física aeróbica controlada mejoró la composición corporal, al disminuir los depósitos de grasa y aumentar la masa corporal libre de grasa, en este grupo de mujeres.

Background Imatinib, given concurrently or alternating with chemotherapy, has improved the response and survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) but relapses are still frequent. The aim of this study was to evaluate the feasibility and results of giving imatinib concurrently with intensive chemotherapy, stem cell transplantation and post-transplant imatinib maintenance therapy in patients with newly diagnosed Ph+ ALL.Design and Methods This was a phase II study of patients with newly diagnosed Ph+ ALL given standard chemotherapy, together with imatinib (400 mg/day) until stem cell transplantation, followed by imatinib maintenance therapy for all patients regardless of the molecular status of the disease.Results Of the 30 patients included, 27 (90%) achieved complete remission, one was resistant to treatment and two died during induction therapy. The percentages of major and complete molecular responses were 86% and 21% after induction, and 81% and 65% after consolidation, respectively. Similar results were observed assessing minimal residual disease by flow cytometry. Of the 27 patients who achieved complete remission, 21 underwent stem cell transplantation (16 allogeneic, 5 autologous). Imatinib (400 mg/day) could be administered after transplantation for a median of 3.9 months in 12 patients, although it was interrupted in 10 patients (in 2 cases because of side effects of the drug). Nine patients relapsed, four before and five after stem cell transplantation and eight patients died of transplant-related causes. With a median follow-up of 4.1 years, the probabilities (95% CI) of disease-free and overall survival were 30% (15% to 45%) and 30% (16% to 45%), respectively.Conclusions These results confirm that imatinib is an effective first-line treatment for adult Ph+ ALL when given concurrently with chemotherapy, making stem cell transplantation feasible in a high proportion of patients. However, post-transplantation imatinib administration was limited, mainly because of transplantation-derived complications rather than drug-specific toxicity.

Los óxidos de metales como circonio(IV), hierro(III) y titanio(IV), al adicionarles el ión sulfato y/o cationes con alto número de oxidación, aumentan notablemente sus características ácidas alcanzando, algunos de ellos, una acidez mayor que la del ácido sulfúrico puro. Esta característica los potencia como catalizadores promisorios en reacciones de isomerización, alquilación, craqueo de alcanos, entre otros, en remplazo de los catalizadores ácidos tradicionales como el sulfúrico y el fluorhídrico, que son bastante corrosivos y generan contaminación ambiental. En el presente trabajo se sintetizaron óxidos de circonio sulfatados, a diferentes niveles de concentración del ión sulfato. La adición del ión sulfato se realizó desde el inicio de la reacción de precipitación, lo cual difiere de los métodos tradicionales en los cuales el sulfato se adiciona al hidróxido seco por impregnación. Algunas muestras se doparon con los cationes cerio(IV), antimonio(V) y tungsteno(VI) para analizar su efecto en las propiedades ácidas. La caracterización muestra que los materiales sintetizados tienen una mayor adsorción del ión sulfato en la superficie del hidróxido con respecto a los preparados por impregnación, el producto inicial es amorfo y los cationes dopantes no alteran considerablemente las propiedades ácidas de los óxidos sulfatados.