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Introduction: Computer-aided design has become an important tool to develop novel pesticides based on natural lead compounds. Tenuazonic acid (TeA), a typical representative of the natural tetramic acid family, was patented as a potential bioherbicide. However, its herbicidal efficacy is still not up to the ideal standard of commercial products. Objectives: We aim to find new TeA’s derivatives with improved potency. Methods: Molecular docking was used to build ligand-acceptor interaction models, design and screen new derivatives. Phytotoxicity, oxygen evolution rate, chlorophyll fluorescence and herbicidal efficacy were determined to estimate biological activity of compounds. Results: With the aid of a constructed molecular model of natural lead molecule TeA binding to the QB site in Arabidopsis D1 protein, a series of derivatives differing in the alkyl side chain were designed and ranked according to free energies. All compounds are stabilized by hydrogen bonding interactions between their carbonyl oxygen O2 and D1-Gly256 residue; moreover, hydrogen bond distance is the most important factor for maintaining high binding affinity. Among 54 newly designed derivatives, D6, D13 and D27 with better affinities than TeA were screened out and synthesized to evaluate their photosynthetic inhibitory activity and herbicidal efficacy. Analysis of structure-activity relationship indicated that D6 and D13 with sec-pentyl and sec-hexyl side chains, respectively, were about twice more inhibitory of PSII activity and effective as herbicide than TeA with a sec-butyl side chain. Conclusion: D6 and D13 are promising compounds to develop TeA-derived novel PSII herbicides with superior performance.

Background: Walnut production (Juglans regia) generates a large amount of waste, mainly comprised of husk and shell. The two by-products have several bioactive compounds, mainly phenolic compounds with antioxidant activity. Given the above, this work seeks to establish productive and adequate conditions for the recovery of compounds with antioxidant activity (juglone among them) from such discards to use the extract as a bioherbicide. Results: Temperature and extraction solvent (type of solvent and use of hydroalcoholic mixtures) are relevant factors on phenolic compounds’ (TPC, Folin-Ciocalteu method) recovery and antioxidant activity (AA, DPPH method), observing values from 2 to 17 mg GAE/g shell and 0.5 and 23 mg GAE/g husk, and 3 to 28 mg TE/g shell and 0.2–36 mg TE/g husk for TPC and AA, respectively. Using 50°C and ethanol as extraction solvent, 14,000 µmol TE/100 g of ORAC activity was obtained for both shell and husk. This value increased when a hydroalcoholic mixture was used. Juglone was recovered only from the husk at 166 mg/100 g. The bioherbicidal potential of the extract was evaluated; a phytotoxic effect and a lower plantar density when applying the product to broad-leaf weeds were observed. Conclusions: In conclusion, the walnut process’s residues have a high potential to be used under the circular economy concept in the agri-food sector by obtaining products with high added value.How to cite: Soto-Maldonado C, Caballero-Valdés E, Santis-Bernal J, et al. Potential of solid wastes from the walnut industry: Extraction conditions to evaluate the antioxidant and bioherbicidal activities. Electron J Biotechnol 2022;58. https://doi.org/10.1016/j.ejbt.2022.04.005

Resumen: Esta guía de recomendaciones para el TR de donante vivo (TRDV) es un documento elaborado con el patrocinio de la Sociedad Española de Nefrología, la Sociedad Española de Trasplantes y la Organización Nacional de Trasplantes que actualiza la calidad de la evidencia disponible para ofrecer el mejor tratamiento de la insuficiencia renal crónica cuando se disponga de un donante vivo potencial. El objetivo principal de esta guía es proporcionar a los profesionales con responsabilidad en los estudios previos del donante vivo y del receptor trasplantado, las mejores herramientas para tomar decisiones en beneficio del donante vivo y del receptor del trasplante.Además, en el contexto actual del TR, el donante vivo debe recuperar el protagonismo que alcanzó en un pasado reciente. Para ello, las nuevas modalidades de donación HLA y/o ABO incompatible, así como la donación cruzada disponibles en diversos centros con experiencia en TRDV, son oportunidades adicionales para el tratamiento de enfermos renales que tienen un donante incompatible.Los buenos resultados en supervivencia del paciente y del injerto están ampliando las circunstancias de aceptación de donantes vivos de riñón, incluyendo donantes de mayor edad y otros con algunos condicionantes que incluyen antecedentes o alteraciones límite que, cuando son evaluados con criterios objetivos, pueden aportar un numero adicional de trasplantes.No se ha obviado en esta guía que el TRDV puede representar algún riesgo para el que dona. Estos problemas que pueden aparecer a corto o largo plazo tienen que ser objeto principal de valoración previa a la donación y presentados al potencial donante para que en ejercicio de su autonomía los asuma o rechace. La experiencia acumulada en los últimos años ha permitido avanzar en el análisis de riesgos para preservar la salud de los donantes, aspecto que debe estar siempre presente en los responsables de programas de TRDV cuando se procede al estudio de idoneidad de un potencial donante.Finalmente, esta guía ha sido estructurada para facilitar la toma de decisiones con recomendaciones y sugerencias ante incertidumbres derivadas de los resultados en los exhaustivos estudios predonación. Y todo ello, con el objetivo de que el consentimiento informado que debe certificar la calidad de los estudios y la información proporcionada a donante y receptor, alcancen las mayores garantías posibles. Abstract: This guide for living donor renal transplantation (LDRT) has been prepared with the sponsorship of the Spanish Society of Nephrology (SEN), the Spanish Transplant Society (SET), and the Spanish National Transplant Organization (ONT). It updates evidence to offer the best chronic renal failure treatment when a potential living donor is available. The core aim of this guide is to supply clinicians who evaluate living donors and transplant recipients with the best decision-making tools, to optimise their outcomes.Moreover, the role of living donors in the current RT context should recover the level of importance it had until recently. To this end the new forms of incompatible HLA and/or ABO donation, as well as the paired donation which is possible in several hospitals with experience in LDRT, offer additional ways to treat renal patients with an incompatible donor.Good results in terms of patient and graft survival have expanded the range of circumstances under which living renal donors are accepted. Older donors are now accepted, as are others with factors that affect the decision, such as a borderline clinical history or alterations, which when evaluated may lead to an additional number of transplantations.This guide does not forget that LDRT may lead to risk for the donor. Pre-donation evaluation has to centre on the problems which may arise over the short or long-term, and these have to be described to the potential donor so that they are able to take them into account. Experience over recent years has led to progress in risk analysis, to protect donors’ health. This aspect always has to be taken into account by LDRT programmes when evaluating potential donors.Finally, this guide has been designed to aid decision-making, with recommendations and suggestions when uncertainties arise in pre-donation studies. Its overarching aim is to ensure that informed consent is based on high quality studies and information supplied to donors and recipients, offering the strongest possible guarantees.

Little information is currently available on the occurrence and genetic diversity of pathogenic and commensal protist species in captive and semi-captive non-human primates (NHP) resident in zoological gardens or sanctuaries in low- and medium-income countries. In this molecular-based study, we prospectively collected individual faecal samples from apparently healthy NHP at the Abidjan Zoological Garden (AZG) in Côte d’Ivoire, the Tacugama Sanctuary (TS) in Sierra Leone, and the Quistococha Zoological Garden (QZG) in Peru between November 2018 and February 2020. We evaluated for the presence of pathogenic (Cryptosporidium spp., Entamoeba histolytica, Giardia duodenalis, Blastocystis sp., Enterocytozoon bieneusi, Balantioides coli) and commensal (Entamoeba dispar, Troglodytella abrassarti) protist species using PCR methods and Sanger sequencing. Giardia duodenalis was the most prevalent species found (25.9%, 30/116), followed by Blastocystis sp. (22.4%, 26/116), and E. dispar (18.1%, 21/116). We detected E. bieneusi (4.2%, 1/24) and T. abrassarti (12.5%, 3/24) only on NHP from AZG. Cryptosporidium spp., E. histolytica, and B. coli were undetected at the three sampling sites investigated here. Sequence analyses revealed the presence of zoonotic sub-assemblages BIII (n = 1) in AZG and BIV (n = 1) in TS within G. duodenalis. We identified Blastocystis subtype ST3 (100%, 6/6) in AZG, ST1 (80.0%, 12/15), ST2 (6.7%, 1/15), and ST3 (13.3%, 2/15) in TS, and ST2 (80.0%, 4/5) and ST3 (20.0%, 1/5) in QZG. The only E. bieneusi isolate detected here was identified as zoonotic genotype CAF4. Our PCR-based data indicate that potentially pathogenic protist species including G. duodenalis, Blastocystis sp., E. bieneusi, and B. coli are present at variable rates in the three NHP populations investigated here. The identification of zoonotic genotypes within these species indicates that human-NHP transmission is possible, although the extent and directionality of these events need to be elucidated in future molecular surveys.

Objective: To analyze the psychometric properties of the Child Development Assessment Questionnaire (QAD-PIPAS). Methods: This methodological study was comprised of two axes. The first one aimed to analyze the instrument's construct validity (discriminant and concurrent validity) and internal consistency, and the second one examined test-retest reliability, involving two different samples and procedures. For construct validity and internal consistency, the sample was recruited in Embu das Artes-SP, Brasilia-DF and Recife-PE during the immunization campaign in 2017, involving caregivers of 2005 children under 60 months of age (1295 under 36 and 710 from 37 to 59 months). For the test-retest analysis the sample consisted of 30 children aged 0–59 months old that attended daycare centers in Embu das Artes-SP in 2018. Results: Multivariate analyses of construct validity showed that the QAD-PIPAS was able to identify the association between the outcome (suspected child development delays) and expected risk and protective factors based on Nurturing Care Framework (OMS/UNICEF). A significant positive correlation was achieved between the scores of the QAD-PIPAS and CREDI in six of the eight age groups analyzed, with the most significant correlations being in the age groups from 25 to 30 and 31–36 months. Acceptable internal consistencies were identified in all age groups, with better performance above 36 months of age (Cronbach’s alpha between 0.61 to 0.80). We also found an adequate test-retest reliability (global Kappa 0.81). Conclusion: The QAD-PIPAS showed evidence of construct validity and reliability to be used in population studies involving children aged 0–59 months during multi-vaccination campaigns in Brazil.

Background: Prediabetes and type 2 Diabetes Mellitus (T2DM) are characterized by increased blood sugar concentration and insulin resistance. Although there are only a few reports of potential benefits of flaxseed’s consumption on different metabolic parameters, there is no evidence of its effect among people with these conditions. Objectives: The present systematic review and meta-analysis aimed to assess the effect of flaxseed supplementation on glycemic control variables and insulin resistance in prediabetes and T2DM. Methods: A literature search was conducted through PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science, to identify Randomized Control Trials (RCTs) that evaluated the effect of milled or ground flaxseed supplementation on fasting blood glucose, HbA1c, insulin concentrations, or HOMA-IR. The data were analyzed using Comprehensive Meta-Analysis (CMA) software version 3.3 in a fixed-effect model. Results: Seven studies were included in the systematic review and the meta-analysis, the results showed a significant reduction on fasting blood sugar (SMD: −0.392, 95% CI: −0.596, −0.187, p =

The platform economy (PE) has experienced its strongest period of growth since the emergence of the sharing economy (SE). Much work has been put into understanding the effects and antecedents of the PE, with particular emphasis on peers and consumer motivation, yet few studies have analysed the motivations of the service providers and even fewer its impact on individual and collective wellbeing. The aim of this paper is provide a better understanding of the decomposed beliefs that inform the attitudinal, social-normative and control factors that make up pro-PE behavioural intention (the intention to develop a PE initiative) in the context of digitisation and wellbeing, while making the platform the focus of analysis. In this study we adapt and extend the Decomposed Theory of Planned Behaviour (DTPB) and use partial least squares regression (PLS), a structural equation modelling technique, to analyse valid data collected from 127 PE organisations operating in Spain. The empirical results obtained demonstrate that the three antecedents for behavioural intention (perceived control, attitude and the subjective norm) have a positive effect on the intention to develop a PE initiative. The study also shows that PE micro-entrepreneurs are motivated by individual and collective wellbeing and not just financial gain. This contributes substantially to reconciling the PE with its origins, rooted in pro-solidarity and social concerns, and to framing wellbeing in a broader paradigm consisting of psychological and social factors, going beyond the economic considerations and interests contained in previous paradigms.

PytuTester is an open-source ventilator tester developed to help bio-engineers in the design and verification of new ventilator prototypes. A ventilator tester allows measuring the flow, pressure, volume, and oxygen concentration provided to the patient. During the global pandemic COVID-19, several open-source ventilators prototypes were developed; however, due to high cost and demand testers, they were not available. In this context, a low-cost tester was developed using a Raspberry Pi and medical-grade sensors for the test ventilators prototypes. This paper presents the design files, software interface, and validations tests. Our results indicate that the tester has good accuracy to evaluate the efficacy and performance of new prototypes. When tested on two ventilator designs developed in Paraguay, PytuTester reported flow profiles that were concordant with the industry-standard VT650 Gas Flow Analyzer. PytuTester was then field deployed to test several DIY ventilator designs in low-resource areas.

Summary: Mouse models enable the study of genetic factors affecting the complex pathophysiology of metabolic disorders. Here, we identify reductions in leptin levels, food intake, and obesity due to high-fat diet, accompanied by increased leptin sensitivity, in mice that harbor the E2a-Cre transgene within Obrq2, an obesity quantitative trait locus (QTL) that includes the leptin gene. Interestingly, loss of allograft inflammatory factor-1-like (AIF1L) protein in these transgenic mice leads to similar leptin sensitivity, yet marked reversal of the obesity phenotype, with accelerated weight gain and increased food intake. Transgenic mice lacking AIF1L also have low circulating leptin, which suggests that benefits of enhanced leptin sensitivity are lost with further impairment of leptin expression due to loss of AIF1L. Together, our results identify AIF1L as a genetic modifier of Obrq2 and leptin that affects leptin levels, food intake, and obesity during the metabolic stress imposed by HFD.

Purpose: To test the efficacy of runt-related transcription factor 1 (RUNX1) inhibition with topical nanoemulsion containing Ro5-3335 (eNano-Ro5) in experimental ocular neovascularization. Design: Preclinical experimental study. Participants: In vitro primary culture human retinal endothelial cell (HREC) culture. C57BL/6J 6- to 10-week-old male and female mice. Methods: We evaluated the effect of eNano-Ro5 in cell proliferation, cell toxicity, and migration of HRECs. We used an alkali burn model of corneal neovascularization and a laser-induced model of choroidal neovascularization to test in vivo efficacy of eNano-Ro5 in pathologic angiogenesis in mice. We used mass spectrometry to measure penetration of Ro5-3335 released from the nanoemulsion in ocular tissues. Main Outcome Measures: Neovascular area. Results: RUNX1 inhibition reduced cell proliferation and migration in vitro. Mass spectrometry analysis revealed detectable levels of the active RUNX1 small-molecule inhibitor Ro5-3335 in the anterior and posterior segment of the mice eyes. Topical treatment with eNano-Ro5 significantly reduced corneal neovascularization and improved corneal wound healing after alkali burn. Choroidal neovascularization lesion size and leakage were significantly reduced after treatment with topical eNano-Ro5. Conclusions: Topical treatment with eNano-Ro5 is an effective and viable platform to deliver a small-molecule RUNX1 inhibitor. This route of administration offers advantages that could improve the management and outcomes of these sight-threatening conditions. Topical noninvasive delivery of RUNX1 inhibitor could be beneficial for many patients with pathologic ocular neovascularization.

Summary: Remaining challenges in auricular cartilage tissue engineering include acquiring sufficient amounts of regeneration-competent cells and subsequent production of high-quality neocartilage. Progenitor cells are a resident subpopulation of native cartilage, displaying a high proliferative and cartilage-forming capacity, yet their potential for regenerative medicine is vastly understudied. In this study, human auricular cartilage progenitor cells were newly identified in healthy cartilage and, importantly, in microtia-impaired chondral remnants. Their cartilage repair potential was assessed via in vitro 3D culture upon encapsulation in a gelatin-based hydrogel, and subsequent biochemical, mechanical, and histological analyses. Auricular cartilage progenitor cells demonstrate a potent ability to proliferate without losing their multipotent differentiation ability and to produce cartilage-like matrix in 3D culture. As these cells can be easily obtained through a non-deforming biopsy of the healthy ear or from the otherwise redundant microtia remnant, they can provide an important solution for long-existing challenges in auricular cartilage tissue engineering.

Desmoid tumors are rare, aggressive fibroblastic soft tissue tumors. We report a case of a 20-year-old male with recurrence of desmoid tumor of the left shoulder after initial complete resection 3 years prior. Pathology revealed fibromatosis desmoid type. After complete resection of tumor at 17-year-old, no symptoms were reported after 3 years of first resection, when he developed numbness and weakness of the left upper extremity. Magnetic resonance imaging demonstrated an enlarging arteriovenous malformation at the left shoulder with possible recurrence. Excision was performed, and after tissue examination evidence of recurrent fibromatosis desmoid type was found without arteriovenous malformation. Recurrence after complete resection could be as high as 70%. Early recurrence recognition is essential as tumor growth before the infiltration of the aggressive tumor makes the resection more difficult and increases surgical risk of complications.

Background & Aims: Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure. Methods: SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated. Results: The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in ≥1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing ≥2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4. Conclusions: Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized. Lay summary: Although direct-acting antiviral medications effectively cure hepatitis C in most patients, sometimes treatment selects for resistant viruses, causing antiviral drugs to be either ineffective or only partially effective. Multidrug resistance is common in patients for whom DAA treatment fails. Older patients and patients with advanced liver diseases are more likely to select drug-resistant viruses. Collective efforts from international communities and governments are needed to develop an optimal approach to managing drug resistance and preventing the transmission of resistant viruses.

Aqueous rechargeable Zn–MnO2 batteries have been attracting increasing interest in recent years due to their relatively high energy density, non-toxicity, non-flammability, and low-cost. However, the battery chemistry still faces several challenges limiting the performance of some key performance indicators and preventing its commercial deployment. Among these, cycle stability and lifespan are important, especially for stationary energy applications, and require improvement. In this work, a spontaneous reaction between Zn metal and electrolytes evolving hydrogen and Zn ions is shown to drive the electrolyte pH towards alkaline conditions, which in turn hinders the reversible electrochemical reactions at both positive and negative electrodes. Proton release during the oxidation of a Mn2+ additive and promotion of the oxygen evolution reaction (OER) at the positive electrode by implementing a float-charging protocol (constant voltage at the end of the charging process) is proposed as a simple strategy to restore the initial pH. Using a pH indicator dissolved in the electrolyte and assembling the electrochemical cell in a spectrophotometer cuvette, the effect of floating voltage is evaluated in operando, allowing optimization of the floating voltage to enable the electrolyte pH to remain stable.

While visual assessment by a clinician is the standard of care for burn severity evaluations, new technologies at various stages of development are attempting to add objectivity to this practice by quantifying burn severity. Assessment accuracy generally improves after the burn injury has progressed, but early assessments that correctly identify superficial partial and deep partial burns have the potential to lead to more prompt treatments and shorter recovery times. To date, Spatial Frequency Domain Imaging (SFDI) has only been used in animal models of burns, but has shown the potential to categorize burns accurately at earlier time points. Here we examine the potential for SFDI to assess burn severity in clinical patients. We also utilize Laser Speckle Imaging (LSI), an FDA cleared non-invasive imaging technology that typically measures blood perfusion in order to evaluate burns in clinical patients. We present a case series of two patients, both with partial thickness burns of varying severity. Partial thickness burns are often difficult for clinicians to categorize based on visual appearance alone. SFDI and LSI were both performed on each patient at approximately 24 and 72 h after their respective burn incidents. Each technique was able to render spatially resolved information that enabled improved assessment accuracy for each burn. This represents the first publication of SFDI applied to clinical burn patients after being successfully utilized in animal models, and highlights the potential for SFDI as a feasible tool for the timely categorization of burn severity. Keywords: Burns, Clinical, Humans, Spatial Frequency Domain Imaging, Laser Speckle Imaging

Objective: Assessing the association between socioeconomic gradient and cognitive development among children of a Spanish birth cohort aged 5-6 years from a gender perspective. Method: Cognitive development was assessed on 525 children aged 5-6 years in the INMA-Valencia cohort, with the Global Cognitive Score (GCS) from McCarthy Scales of Children's Abilities. Information on social class, education level and employment was collected for both parents in addition to other sociodemographic factors, parental, family and child characteristics. The relationship between maternal and paternal socioeconomic gradient and cognitive development was assessed by linear regressions and comparing the variance explained by each indicator measured in the mother and father. Results: Maternal socioeconomic gradient indicators explained more variance on GCS than paternal. Maternal education and paternal social class had an important individual effect that stayed after adjusting by other parental, child and family determinants. In the multivariable analysis, maternal education, age and intelligence, paternal social class and the child's age and sex were significantly associated with cognitive development. Conclusions: Diverse socioeconomic gradient factors have an important influence on cognitive development, maternal education being the strongest determinant. Policies should be implemented to mitigate the negative effects of this gradient on child development. Resumen: Objetivo: Evaluar la asociación del gradiente socioeconómico y el desarrollo cognitivo en niños y niñas de una cohorte española a los 5-6 años de edad desde una perspectiva de género. Método: Se evaluó el desarrollo cognitivo en 525 niños/as de 5-6 años de la cohorte INMA-Valencia, mediante la Puntuación Global Cognitiva (PGC) de las Escalas McCarthy para niños y niñas. Se recogió información de ambos progenitores sobre clase social, nivel de estudios y empleo, además de otros factores sociodemográficos, características parentales, de la familia y del niño o la niña. La relación entre el gradiente socioeconómico materno y paterno y el desarrollo cognitivo se evaluó mediante modelos de regresión lineal y comparando la varianza explicada por cada uno de los indicadores medidos en la madre y en el padre. Resultados: Los indicadores de gradiente socioeconómico de la madre explicaron más varianza del índice de PGC que los del padre. La educación materna y la clase social paterna tuvieron un importante efecto individual, que se mantuvo tras ajustar por otros determinantes de los progenitores, del niño o de la niña, y del entorno familiar. En el análisis multivariante, la educación, la edad y la inteligencia maternas, la clase social paterna, y la edad y el sexo del infante se asociaron significativamente con el desarrollo cognitivo. Conclusiones: Distintos factores del gradiente socioeconómico tienen influencia en el desarrollo cognitivo, siendo la educación materna el determinante más fuerte. Deberían implementarse políticas para paliar los efectos negativos de este gradiente en el desarrollo infantil. Keywords: Cognitive development, Socio-economic gradient, Children, Parental education, Gender perspective, Palabras clave: Desarrollo cognitivo, Gradiente socioeconómico, Infancia, Educación parental, Perspectiva de género

This paper details the methodology and approach conducted to monitor the behaviour of twelve users interacting with their computers for fifty-five consecutive days without preestablished indications or restrictions. The generated dataset, called BEHACOM, contains for each user a set of features that models, in one-minute time windows, the usage of computer resources such as CPU or memory, as well as the activities registered by applications, mouse and keyboard. It has to be stated that the collected data have been treated in a privacy-preserving way during each phase of the collection and analysis. Together with the features and their explanation, we also detail the software used to gather and process the data. Finally, this article describes the data distribution of the BEHACOM dataset.

Objective: Chagas disease affects over six million people, but less than 1% are diagnosed and treated. Complicated diagnostic processes are a major barrier. Colombia’s previous diagnostic algorithm, using in-house tests, was difficult to scale up, creating significant access barriers for patients. A new algorithm using commercially manufactured immunoassays would potentially improve access, but these tests’ performance in Colombian patients with Chagas disease is not well known. Methods: We assessed seven commercially available assays. Samples (n = 501), 93.8% originating from Colombia, were characterized as positive or negative based on standard procedure at the National Reference Laboratory. Performance characteristics were calculated for individual assays and hypothetical test pairings, then compared to the existing algorithm. Results: Five of seven assays exhibited sensitivity >98% while six showed specificity >97%. A total antigen ELISA paired with a recombinant assay provided similar performance to the current diagnostic process. Six of six assays tested proved capable of detecting different Trypanosoma cruzi genetic lineages. Conclusions: The study indicated that several commercial assays accurately detect T. cruzi infection in Colombian patients. A simplified testing process with two commercial assays could perform comparably to the previous process, reducing cost and accessibility barriers and facilitating national scale-up. Keywords: Trypanosoma cruzi, Chagas disease, Enzyme-linked immunosorbent assays, Diagnostic barriers, Access to healthcare, Neglected tropical diseases (NTDs)

Milk is a liquid food that possesses an important quantity of highly bioavailable macronutrients. In addition, it is readily accessible, as well as relatively inexpensive. Given that the knowledge of physicians about nutrition and food composition is deficient, in general, many of the dietary interventions recommended in diverse clinical settings lack a scientific basis. The aim of the present review was to produce a technical opinion that serves as a frame of reference to best sustain recommendations for consuming milk and dairy products as daily nutrition in the adult and older adult. The effects of milk and dairy products during the pediatric stage are not addressed in the present work. The Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Gerontología y Geriatría jointly discussed and analyzed topics dealing with the legal designation of milk, the classification and nutritional profile of cow's milk, its nutritional characteristics, its consumption in the adult, intolerance to cow's milk, and associations of milk consumption with digestive tract alterations and other conditions. Finally, certain aspects of milk consumption in the older adult and its relation to overall health are briefly discussed. Resumen: La leche es un alimento que tiene una importante cantidad de macronutrimentos de gran biodisponibilidad, accesible y de relativo bajo costo. El conocimiento de los médicos en general sobre nutrición y composición de los alimentos es deficiente por lo que muchas de las intervenciones dietéticas que tradicionalmente recomendamos en diversos escenarios clínicos carecen de sustento científico. El objetivo de esta revisión fue generar una opinión técnica que sirva como marco de referencia para sustentar de mejor forma la recomendación sobre el consumo de leche y productos lácteos en la nutrición diaria de adultos y adultos mayores. Los efectos de la leche y productos lácteos durante la etapa pediátrica salen del contexto del presente trabajo. La Asociación Mexicana de Gastroenterología y la Asociación Mexicana de Gerontología y Geriatría comentaron y analizaron de forma conjunta temas acerca de la denominación legal de la leche, clasificación y perfil nutrimental de la leche de vaca, sus características nutrimentales, su consumo en el adulto, intolerancia a la leche de vaca, asociaciones entre el consumo de leche y alteraciones del aparato digestivo y otras condiciones; finalmente, se mencionan de forma breve algunos aspectos sobre el consumo de leche en el adulto mayor y su relación con la salud. Keywords: Dairy products, Cow's milk, Diet, Adult, Older adult, Palabras clave: Lácteos, Leche de vaca, Alimentación, Adulto, Adulto mayor

Resumen: La leche es un alimento que tiene una importante cantidad de macronutrimentos de gran biodisponibilidad, accesible y de relativo bajo costo. El conocimiento de los médicos en general sobre nutrición y composición de los alimentos es deficiente por lo que muchas de las intervenciones dietéticas que tradicionalmente recomendamos en diversos escenarios clínicos carecen de sustento científico. El objetivo de esta revisión fue generar una opinión técnica que sirva como marco de referencia para sustentar de mejor forma la recomendación sobre el consumo de leche y productos lácteos en la nutrición diaria de adultos y adultos mayores. Los efectos de la leche y productos lácteos durante la etapa pediátrica salen del contexto del presente trabajo. La Asociación Mexicana de Gastroenterología y la Asociación Mexicana de Gerontología y Geriatría comentaron y analizaron de forma conjunta temas acerca de la denominación legal de la leche, clasificación y perfil nutrimental de la leche de vaca, sus características nutrimentales, su consumo en el adulto, intolerancia a la leche de vaca, asociaciones entre el consumo de leche y alteraciones del aparato digestivo y otras condiciones; finalmente, se mencionan de forma breve algunos aspectos sobre el consumo de leche en el adulto mayor y su relación con la salud. Abstract: Milk is a liquid food that possesses an important quantity of highly bioavailable macronutrients. In addition, it is readily accessible, as well as relatively inexpensive. Given that the knowledge of physicians about nutrition and food composition is deficient, in general, many of the dietary interventions recommended in diverse clinical settings lack a scientific basis. The aim of the present review was to produce a technical opinion that serves as a frame of reference to best sustain recommendations for consuming milk and dairy products as daily nutrition in the adult and older adult. The effects of milk and dairy products during the pediatric stage are not addressed in the present work. The Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Gerontología y Geriatría jointly discussed and analyzed topics dealing with the legal designation of milk, the classification and nutritional profile of cow's milk, its nutritional characteristics, its consumption in the adult, intolerance to cow's milk, and associations of milk consumption with digestive tract alterations and other conditions. Finally, certain aspects of milk consumption in the older adult and its relation to overall health are briefly discussed. Palabras clave: Lácteos, Leche de vaca, Alimentación, Adulto, Adulto mayor, Keywords: Dairy products, Cow's milk, Diet, Adult, Older adult

The World Health Organization launched a global initiative, known as aDSM (active TB drug safety monitoring and management) to better describe the safety profile of new treatment regimens for drug-resistant tuberculosis (TB) in real-world settings. However, comprehensive surveillance is difficult to implement in several countries.The aim of the aDSM project is to demonstrate the feasibility of implementing national aDSM registers and to describe the type and the frequency of adverse events (AEs) associated with exposure to the new anti-TB drugs.Following a pilot study carried out in 2016, official involvement of TB reference centres/countries into the project was sought and cases treated with bedaquiline- and/or delamanid-containing regimens were consecutively recruited. AEs were prospectively collected ensuring potential attribution of the AE to a specific drug based on its known safety profile.A total of 309 cases were fully reported from 41 centres in 27 countries (65% males; 268 treated with bedaquiline, 20 with delamanid, and 21 with both drugs) out of an estimated 781 cases the participating countries had committed to report by the first quarter of 2019. Keywords: Tuberculosis, MDR-TB, Adverse events, Monitoring, Delamanid, Bedaquiline

Two phase I clinical trials were conducted to evaluate, among other parameters, the humoral response elicited by a vascular endothelial growth factor (VEGF)-based therapeutic vaccine in cancer patients with advanced solid tumors. VEGF reduction was studied using an indirect methodology named as “Platelet VEGF”. This methodology is based on the estimation of VEGF within platelets by subtracting the plasma VEGF level from the serum level and dividing this by the platelet count, and then this latter expression is additionally corrected by the hematocrit. However, there is broad debate, whether serum or plasma VEGF or platelet-derived VEGF measurements is the most appropriate strategy to study the changes that occur on ligand bioavailability when patients are submitted to a VEGF-based immunotherapy.The current research is a retrospective study evaluating the changes on VEGF levels in serum and plasma as well as platelet-derived measurements. Changes in VEGF levels were related with the humoral response seen in cancer patients after an active immunotherapy with a VEGF-based vaccine. The present study indicates that “Platelet VEGF” is the most reliable methodology to investigate the effect of VEGF-based immunotherapies on ligand bioavailability. “Platelet VEGF” was associated with those groups of individuals that exhibited the best specific humoral response and the variation of “Platelet VEGF” showed the strongest negative correlation with VEGF-specific IgG antibody levels. This methodology will be very useful for the investigation of this VEGF-based vaccine in phase II clinical trials and could be applied to immunotherapies directed to other growth factors that are actively sequestered by platelets.

The term social bots refer to software-controlled accounts that actively participate in the social platforms to influence public opinion toward desired directions. To this extent, this data descriptor presents a Twitter dataset collected from October 4th to November 11th, 2019, within the context of the Spanish general election. Starting from 46 hashtags, the collection contains almost eight hundred thousand users involved in political discussions, with a total of 5.8 million tweets. The proposed data descriptor is related to the research article available at [1]. Its main objectives are: i) to enable worldwide researchers to improve the data gathering, organization, and preprocessing phases; ii) to test machine-learning-powered proposals; and, finally, iii) to improve state-of-the-art solutions on social bots detection, analysis, and classification. Note that the data are anonymized to preserve the privacy of the users. Throughout our analysis, we enriched the collected data with meaningful features in addition to the ones provided by Twitter. In particular, the tweets collection presents the tweets’ topic mentions and keywords (in the form of political bag-of-words), and the sentiment score. The users’ collection includes one field indicating the likelihood of one account being a bot. Furthermore, for those accounts classified as bots, it also includes a score that indicates the affinity to a political party and the followers/followings list.

The major controlling factors that determine the various mechanical properties of an elastomer system are type of chemical crosslinking and crosslink density of the polymer network. In this study, a catalytic amount of acrylonitrile butadiene copolymer (NBR) was used as a co-accelerator for the curing of polybutadiene (BR) elastomer. After the addition of this copolymer along with other conventional sulphur ingredients in polybutadiene compounds, a clear and distinct effect on the curing and other physical characteristics was noticed. The crosslinking density of BR was increased, as evidenced by rheometric properties, solid-state NMR and swelling studies. The vulcanization kinetics study revealed a substantial lowering of the activation energy of the sulphur crosslinking process when acrylonitrile butadiene copolymer was used in the formulation. The compounds were also prepared in the presence of carbon black and silica, and it was found that in the carbon black filled system the catalytic effect of the NBR was eminent. The effect was not only reflected in the mechanical performance but also the low-temperature crystallization behavior of BR systems was altered.

Arsenic (As) uptake by plants is mainly carried out as arsenate (As(V)), whose chemical analogy with phosphate is largely responsible for its elevated toxicity. Arsenate is known to stimulate reactive oxygen species (ROS) formation in plants that provoke oxidative stress. This manuscript reports the results of a hydroponics study using rice (Oryza sativa L.) seedlings as a test plant, where the effects of increasing arsenate concentrations (0–10 mg L−1) on both lipid and protein oxidation, as well as As accumulation and speciation in plant roots and shoots were examined. Plant yield was negatively affected by increasing As concentration. Accumulation in plant roots was higher than in shoots at low arsenate doses (0.5–2.5 mg L−1), while root to shoot transport was drastically enhanced at the highest doses (5 and 10 mg L−1). Moreover, As(V) was the dominating species in the shoots and As(III) in the roots. Rice leaves in the 10 mg As L−1 treatment showed the highest lipid peroxidation damage (malondialdehyde concentration), whilst protein oxidation was not remarkably influenced by As dose. Lipid peroxidation seems to be therefore conditioned by As accumulation in rice plants, particularly by the presence of high As(V) concentrations in the aerial part of the plants as a consequence of unregulated translocation from roots to shoots above a threshold concentration (1.25–2.5 mg L−1) in the growing media. These results provide relevant information regarding As(V) toxic concentrations for rice plants, highlight the importance of major As species analysis in plant tissues regarding As toxicity and contribute to better understand plants response to elevated As concentrations in the growing media.

Summary: Diabetic kidney disease (DKD) increases the risk for mortality and is the leading cause of end-stage renal disease. Treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2i) attenuates the progression of DKD, especially in patients with advanced kidney disease. Herein, we show that in diabetes, mTORC1 activity is increased in renal proximal tubule cells (RPTCs) along with enhanced tubule-interstitial fibrosis; this is prevented by SGLT2i. Constitutive activation of mTORC1 in RPTCs induces renal fibrosis and failure and abolishes the renal-protective effects of SGLT2i in diabetes. On the contrary, partial inhibition of mTORC1 in RPTCs prevents fibrosis and the decline in renal function. Stimulation of mTORC1 in RPTCs turns on a pro-fibrotic program in the renal cortex, whereas its inhibition in diabetes reverses the alterations in gene expression. We suggest that RPTC mTORC1 is a critical node that mediates kidney dysfunction in diabetes and the protective effects of SGLT2i by regulating fibrogenesis.

Platelet lysate has attracted attention for different biomedical applications, including biological processes where cellular proliferation and migration have been altered. Spectroscopic properties of a platelet lysate obtained from human platelets were performed in order to be incorporated in polymeric nanoparticles and then into a PluronicⓇ F127 hydrogel, intended for wound healing (more details can be found at https://doi.org/10.1016/j.ejps.2020.105231 [1]). The platelet lysate (PL) was assessed by ultraviolet, infrared and circular dichroism spectroscopy. The developed hydrogel was also analyzed by infrared spectroscopy to evaluate if the PluronicⓇ F127 structure was maintained when the nanoparticles or platelet lysate-loaded nanoparticles were included. The sol-gel transition temperature of the hydrogel was determined through its thermal behavior and by dynamic light scattering.

Background: The use of novel materials as an artificial extracellular matrix for stem cell growth is a current strategy of increasing interest for regenerative medicine. Here, we prepare thermal-remolded membrane scaffolds from poly(3-hydroxybutyrate) grafted with 2-amino-ethyl methacrylate hydrochloride. However, it is unclear whether these membranes are useful for tissue engineering. Results: The mechanical properties, tribology, and morphology of the dense membranes were assessed. The results show that tensile strain at break and roughness of the compressed membrane decrease with increasing graft degree. Moreover, graft copolymer membranes showed lower resistance to scratching, greater degree of swelling and higher brittleness than un-grafted P(3HB) films. Thus, it effectively supports the growth of dermal fibroblast, as demonstrated by epifluorescence microscopy. Conclusions: It is concluded that the developed membrane can be properly used in is the restoration of skin tissue.How to cite: González-Torres M, Sánchez-Sánchez R, Solís-Rosales SG, et al. Poly(3-hydroxybutyrate) graft copolymer dense membranes for human mesenchymal stem cell growth. Electron J Biotechnol 2018, 34; https://doi.org/10.1016/j.ejbt.2018.05.007. Keywords: Artificial extracellular matrix, Dense membranes, Membrane scaffolds, Mesenchymal, Methacrylate, Regenerative medicine, Scaffolds, Stem cell growth, Stem cell growth, Thermal properties, Thermal-remolded

Summary: The linear ubiquitin chain assembly complex (LUBAC) participates in inflammatory and oncogenic signaling by conjugating linear ubiquitin chains to target proteins. LUBAC consists of the catalytic HOIP subunit and two accessory subunits, HOIL-1L and SHARPIN. Interactions between the ubiquitin-associated (UBA) domains of HOIP and the ubiquitin-like (UBL) domains of two accessory subunits are involved in LUBAC stabilization, but the precise molecular mechanisms underlying the formation of stable trimeric LUBAC remain elusive. We solved the co-crystal structure of the binding regions of the trimeric LUBAC complex and found that LUBAC-tethering motifs (LTMs) located N terminally to the UBL domains of HOIL-1L and SHARPIN heterodimerize and fold into a single globular domain. This interaction is resistant to dissociation and plays a critical role in stabilizing trimeric LUBAC. Inhibition of LTM-mediated HOIL-1L/SHARPIN dimerization profoundly attenuated the function of LUBAC, suggesting LTM as a superior target of LUBAC destabilization for anticancer therapeutics. : Fujita et al. report a crystal structure of the trimeric LUBAC core and show that motifs in HOIL-1L and SHARPIN fold into a single domain critical for LUBAC stabilization. The authors also develop an inhibitor of this interaction that destabilizes LUBAC and kills cancer cells. Keywords: linear ubiquitin chains, LUBAC, LUBAC-tethering motif, HOIP, HOIL-1L, SHARPIN, ubiquitin-like domain, ubiquitin-associated domain, cancer

Purpose: Vitreomacular traction (VMT) is a relatively common ocular disorder that may distort the foveal structure causing visual symptoms. The influence of ocular massage (OM) on this condition has not been considered yet. We aim to report clinical and OCT features of VMT release associated with OM. Observations: A 70-year-old woman complained about blurred vision and metamorphopsia in her right eye for one month. Her best-corrected visual acuity (BCVA) was 20/50. Macular OCT showed focal VMT in this eye. Moderate intensity, digital OM was performed by an ophthalmologist. However, the traction was still present. The patient was instructed to perform the same OM every 8 hours at home herself. Four days later she indicated disappearance of metamorphopsia, her BCVA increased to 20/25 and OCT showed VMT release with 39-μm foveal thinning. Conclusions and importance: OM may be useful for focal VMT release. Keywords: Vitreomacular traction, Adhesion, OCT, Ocular massage, Release

Objective: Poor fetal nutrition increases the risk of type 2 diabetes in the offspring at least in part by reduced embryonic β-cell growth and impaired function. However, it is not entirely clear how fetal nutrients and growth factors impact β-cells during development to alter glucose homeostasis and metabolism later in life. The current experiments aimed to test the impact of fetal nutrients and growth factors on endocrine development and how these signals acting on mTOR signaling regulate β-cell mass and glucose homeostasis. Method: Pancreatic rudiments in culture were used to study the role of glucose, growth factors, and amino acids on β-cell development. The number and proliferation of pancreatic and endocrine progenitor were assessed in the presence or absence of rapamycin. The impact of mTOR signaling in vivo on pancreas development and glucose homeostasis was assessed in models deficient for mTOR or Raptor in Pdx1 expressing pancreatic progenitors. Results: We found that amino acid concentrations, and leucine in particular, enhance the number of pancreatic and endocrine progenitors and are essential for growth factor induced proliferation. Rapamycin, an mTORC1 complex inhibitor, reduced the number and proliferation of pancreatic and endocrine progenitors. Mice lacking mTOR in pancreatic progenitors exhibited hyperglycemia in neonates, hypoinsulinemia and pancreatic agenesis/hypoplasia with pancreas rudiments containing ductal structures lacking differentiated acinar and endocrine cells. In addition, loss of mTORC1 by deletion of raptor in pancreatic progenitors reduced pancreas size with reduced number of β-cells. Conclusion: Together, these results suggest that amino acids concentrations and in particular leucine modulates growth responses of pancreatic and endocrine progenitors and that mTOR signaling is critical for these responses. Inactivation of mTOR and raptor in pancreatic progenitors suggested that alterations in some of the components of this pathway during development could be a cause of pancreatic agenesis/hypoplasia and hyperglycemia. Keywords: Nutrients, mTOR, Rapamycin, Pancreas, Development, Islets, β-cells

The data presented in this article are related to the research article entitled “Establishment of Aedes aegypti (L.) in mountainous regions in Mexico: Increasing number of population at risk of mosquito-borne disease and future climate conditions” (M. Equihua, S. Ibáñez-Bernal, G. Benítez, I. Estrada-Contreras, C.A. Sandoval-Ruiz, F.S. Mendoza-Palmero, 2016) [1]. This article provides presence records in shapefile format used to generate maps of potential distribution of Aedes aegypti with different climate change scenarios as well as each of the maps obtained in raster format. In addition, tables with values of potential distribution of the vector as well as the average values of probability of presence including data of the mosquito incidence along the altitudinal range.

We study the orientation dependence of the reconstructed deceleration parameter as a function of redshift. We use the Union 2 and Loss datasets, and the well known preferred axis discussed in the literature, and find the best fit reconstructed deceleration parameter. Our results show that a low redshift transition of the reconstructed q(z) is clearly absent in one direction and amazingly sharp in the opposite one. We discuss the possibility that such behavior can be associated to large scale structures affecting the data.

Objetivo: Analizar el estado de salud percibida, y otros indicadores relacionados con la salud, en personas adultas de Granada que se encuentran en un proceso de desahucio de su vivienda habitual, de alquiler o en propiedad, en comparación con la salud de la población general andaluza. Métodos: Estudio transversal mediante encuesta administrada por personal entrenado que incluye instrumentos de la Encuesta Andaluza de Salud 2011 para la medición de variables de salud física y mental, y de hábitos relacionados con la salud. Se han comparado los resultados con los obtenidos sobre la población general andaluza mediante la Encuesta Andaluza de Salud. Se ha realizado un análisis bivariado utilizando la prueba de ji al cuadrado, y un análisis multivariado mediante regresión logística. Resultados: Se ha obtenido una muestra total de 205 personas en proceso de desahucio. El 59,5% (122) son mujeres y el 40,5% (83) hombres. Presentan una mayor probabilidad de tener una salud deficiente (odds ratio [OR]: 12,63; intervalo de confianza del 95% [IC95%]: 8,74-18,27), enfermedad cardiovascular (OR: 3,08; IC95%:1,54-6,16) o consumir tabaco (OR: 1,68; IC95%: 1,21-2,33), en comparación con la población general andaluza. La mayoría de los indicadores analizados muestran un peor resultado para las mujeres que experimentan un proceso de desahucio. Conclusiones: Nuestros resultados indican que las personas afectadas por un proceso de desahucio en Granada y su área metropolitana, en el actual contexto de crisis, expresan una peor salud en relación a la población general andaluza. Es necesario seguir investigando sobre la salud y los desahucios, desde diferentes aproximaciones metodológicas, para una mejor comprensión de este problema.

Antecedentes: La prevalencia del sobrepeso y la obesidad están aumentando de manera importante. México ocupa uno de los primeros lugares a nivel mundial y se estima que más del 70% de nuestra población adulta está afectada. Las afecciones asociadas a la obesidad son múltiples y el aparato digestivo no es la excepción. Objetivo: Investigar la prevalencia de síntomas gastrointestinales en personas con sobrepeso y obesidad en una muestra representativa de la población mexicana. Métodos: Se realizó un estudio epidemiológico en 1,139 voluntarios, quienes se dividieron de acuerdo a su índice de masa corporal en 3 grupos: A: peso normal, B: sobrepeso, y C: obesidad, y se investigaron la prevalencia, la intensidad y la recurrencia de 14 síntomas gastrointestinales comunes mediante una encuesta dirigida. Se realizó un análisis comparativo con medidas de frecuencia y asociación, utilizando el paquete estadístico EPIDAT 3.1. Resultados: La prevalencia de síntomas se incrementó con el aumento de peso; 8 de ellos (meteorismo, ardor epigástrico, regurgitaciones, flatulencia, plenitud posprandial tardía, plenitud precoz, pirosis y vómitos recurrentes) resultaron ser más prevalentes, más intensos y más frecuentes en personas obesas que en quienes tienen peso normal, con diferencias estadísticamente significativas (p = 0.0001). Conclusiones: Los individuos con sobrepeso y obesidad tienen más síntomas gastrointestinales que aquellos con peso normal; al agrupar los síntomas más frecuentes, se observó que predominaron aquellos que son característicos de dispepsia, enfermedad por reflujo y mayor producción de gases intestinales.

Background: Early and accurate risk prediction is an unmet clinical need in patients with infective endocarditis (IE). The aim of this study was to determine the value of B-type natriuretic peptide (BNP) levels obtained on admission for the prediction of in-hospital death in IE patients. Methods: Between 2009 and 2011, consecutive patients with IE diagnosed using the revised Duke criteria and admitted to the emergency department were evaluated prospectively. BNP levels were measured on admission. Death during hospitalization was the primary endpoint. Results: Among 104 consecutive patients with IE and with available BNP levels, 34 (32.7%) died in hospital. BNP levels were significantly higher in patients who died as compared to survivors (709.0 pg/ml vs. 177.5 pg/ml, p

Objetivos: Analizar la variabilidad poblacional del tratamiento quirúrgico del cáncer de mama, tanto en régimen de ingreso como ambulatorio, mediante cirugía conservadora más radioterapia y cirugía no conservadora, y estimar el coste de oportunidad asociado a la utilización de una u otra. Métodos: Estudio observacional de las variaciones geográficas en las tasas estandarizadas de cirugía conservadora y no conservadora realizadas en 199 áreas de salud españolas durante 2008-2009. Los costes se calcularon de manera indirecta, mediante All-Patients Diagnosis Related Groups (AP-DRG) y de manera directa a partir de costes registrados por la Red Española de Costes Hospitalarios (RECH). Resultados: Las tasas estandarizadas de cirugía conservadora y no conservadora por cada 10.000 mujeres fueron 6,84 y 4,35, respectivamente, con un rango de variación entre áreas de 2,95 y 3,11. En el año 2009, el 9% de la cirugía conservadora se realizó mediante cirugía mayor ambulatoria, pero más de un tercio de las áreas no registraron ninguna intervención de este tipo. Según RECH, el coste medio de la cirugía conservadora fue de 7078 €, y el de la cirugía no conservadora fue de 6161 €. Utilizando AP-DRG, estos costes fueron de 9036 € y 8526 €, respectivamente. Sin embargo, el coste de oportunidad de la cirugía conservadora resultó inferior al coste de la cirugía no conservadora, a partir de un 46% de utilización de cirugía mayor ambulatoria según RECH o un 23% según AP-DRG. Conclusiones: La cirugía conservadora realizada mediante cirugía mayor ambulatoria se perfila como la opción con menor coste de oportunidad en el tratamiento quirúrgico del cáncer de mama, a partir de cierto umbral, cuando ambas, conservadora y no conservadora, son de elección.

Objetivo: Analizar la percepción de la población española sobre la importancia de los factores de riesgo de cáncer. Métodos: La base de datos analizada fue OncoBarómetro 2010. Se realizaron modelos de regresión logística para analizar la importancia que la población atribuye al tabaco, el alcohol, el sol, la alimentación, el peso, las enfermedades de transmisión sexual, la historia familiar, la exposición a radiaciones, el contacto con sustancias nocivas y la contaminación atmosférica. Las respuestas fueron recogidas en una escala de 0 a 10, y dicotomizadas en importancia baja (0-6) y alta (7-10). La medida de asociación utilizada fue la razón de prevalencia (RP). Resultados: El tabaco ocupa el primer lugar en importancia percibida alta (83,1%), mientras que el peso (26,5%) se encuentra en último lugar. La probabilidad de percibir importantes los factores de riesgo estudiados es menor en los hombres (RP sol: 0,87; RP enfermedad de trasmisión sexual: 0,78) y mayor en las personas que han recibido recomendaciones preventivas de los profesionales (RP alcohol: 1,11; RP sol: 1,18; RP dieta: 1,31; RP peso: 1,92). Conocer algún síntoma de la enfermedad y un temor extremo al cáncer se asocian a la percepción del tabaco como un importante factor de riesgo. Una alta percepción de vulnerabilidad hacia la enfermedad hace que se perciba la exposición a sustancias nocivas, la contaminación y el tabaco como factores de riesgo importantes. Conclusiones: Es necesario dar a conocer la asociación del cáncer con el sobrepeso y las enfermedades de transmisión sexual. Las recomendaciones dadas por los/las profesionales sanitarios para prevenir el cáncer son clave para ampliar nuestra concienciación sobre los factores de riesgo.

El objetivo del Consenso Mexicano de Hipertensión Portal fue desarrollar un documento guía para facilitar la práctica clínica en eventos clave del paciente con hipertensión portal y sangrado variceal. El panel de expertos incluyó gastroenterólogos, hepatólogos y endoscopistas mexicanos distinguidos por su trayectoria profesional. El documento exploró temas de interés en los siguientes módulos: profilaxis preprimaria y primaria, hemorragia variceal aguda y profilaxis secundaria. El manejo del sangrado variceal ha mejorado notablemente en años recientes. La información actual indica que el manejo general del paciente cirrótico con sangrado variceal se debe realizar por un equipo multidisciplinario, lo que tiene un papel importante en el desenlace final. Se recomienda combinar la terapia farmacológica y endoscópica en el manejo inicial; los fármacos vasoactivos se deben iniciar cuanto antes ante la sospecha de sangrado de origen variceal y mantenerse durante 5 días. Después de estabilizar al paciente, se realizará la endoscopia diagnóstica de urgencia por un endoscopista calificado, y se dará el tratamiento endoscópico variceal correspondiente. La profilaxis con antibiótico se debe considerar como parte integral del tratamiento, iniciarse desde el ingreso hospitalario y mantenerse durante 5 días. En caso de falla terapéutica, las terapias de rescate se deben iniciar de inmediato; tomando en cuenta que las terapias de derivación mediante radiolgía de intervención son muy efectivas en el control del sangrado variceal refractario. Estas guías están basadas en la mejor evidencia disponible sobre hipertensión portal, y están dirigidas a lograr una mayor eficacia clínica.

El menor tiempo empleado en diagnosticar y tratar las enfermedades incide tanto en el bienestar del enfermo como en la calidad asistencial. En este trabajo se plantea el estudio de los tiempos de demora que intervienen en el diagnóstico del cáncer. Material y métodos: Se ha utilizado el método epidemiológico descriptivo y el análisis estadístico valorando: media, mediana, moda y desviación estándar, para medir los diferentes tiempos de demora. Los datos proceden de un registro hospitalario de cáncer, en el que habitualmente se recogen esos tiempos. Resultados: El mayor tiempo de demora entre los períodos considerados se estima que es el transcurrido entre los primeros síntomas y la fecha del diagnóstico de sospecha, que se estima en 96 días. Los restantes períodos de tiempo estudiados presentan una demora de alrededor de 26 días de mediana. Conclusiones: Es importante la actitud del médico de atención primaria, ya que habitualmente es quien se encuentra con los síntomas precoces, así como con los factores de riesgo persistentes en las personas. Por tanto, desempeña un papel muy importante en el diagnóstico precoz, a la vez que en la educación sanitaria de los pacientes.

Con la introducción en 1953 de la circulación extracorpórea (CEC) se inició la historia de la cirugía cardíaca abierta, y las lesiones regurgitantes valvulares pudieron ser tratadas. En 1965 Kay diseñó una estrategia novedosa para reparar la insuficiencia tricúspide (IT), pero no fue realmente hasta 1972 cuando de Vega describió su técnica de anuloplastia, definiéndola como selectiva, regulable y permanente. Por esta misma época, Carpentier inventó el anillo que lleva su nombre, y probablemente todo parecía indicar que al menos la enfermedad adquirida de la válvula tricúspide (VT) estaba en camino de ser quirúrgicamente resuelta. En este medio siglo, y después de múltiples autoplastias de sutura y múltiples anillos, completos, incompletos, rígidos, flexibles e incluso tridimensionales, puede parecer que aquel entusiasmo se ha desvanecido. Es posible que ni el exceso de certeza inicial ni la desconfianza de la actualidad sean unas actitudes lógicas, porque probablemente la incógnita pueda despejarse aplicando la teoría de las manzanas y las peras.

Objetivo: El hospital de día supone una alternativa asistencial a la hospitalización convencional. Durante el año 2009 se realizó un análisis del funcionamiento y la rentabilidad del hospital de día del Hospital Clínico de Valladolid, España. Expresamos la rentabilidad como la prestación de una idéntica cobertura sanitaria a un menor coste generado respecto a la hospitalización convencional y cumpliendo unos indicadores de calidad. Métodos: Estudio de tipo retrospectivo, transversal, observacional y descriptivo, sobre la información obtenida de cada paciente atendido en el hospital de día, entre el 1 de enero y el 31 de diciembre de 2009. Se determinaron cuatro indicadores de calidad: la determinación de la cancelación de sesiones, la tasa de reacciones transfusionales, el índice de ambulatorización y el índice de satisfacción. El ahorro estimado de cada proceso atendido resulta de la diferencia del coste medio por proceso en hospitalización menos el coste medio del proceso en hospital de día. Resultados: La patología más prevalente fueron las enfermedades sistémicas y del tejido conectivo, que representan el 25,4%; de ellas, el 17,1% corresponde a artritis reumatoide. La satisfacción global de los pacientes es del 93%, la cancelación de sesiones y la tasa de reacciones transfusionales fue del 0%, y el índice de ambulatorización de un 26%. Los costes del hospital de día representan el 8,6% de los costes generados en la hospitalización convencional, con un ahorro de 78.390,69 euros. Conclusión: El hospital de día es rentable, debido al ahorro generado respecto a la hospitalización convencional, a la vez que consigue unos adecuados índices de calidad.Objective: Day hospitals are an alternative to conventional hospital care. We analyzed the functioning and profitability of the day hospital of Hospital Clínico de Valladolid, Spain, in 2009. Profitability is expressed as the provision of identical health coverage at a lower cost than that generated by conventional hospital care and with adequate quality indicators. Methods: We performed a retrospective, observational and descriptive study of the information obtained on each patient attended in the day hospital from January 1 to December 31, 2009. We studied four quality indicators: cancellation of meetings, the rate of transfusion reactions, the out-patient rate and the satisfaction index. The estimated savings for each process was calculated as the difference in the average cost of hospitalization minus the average cost of the process in the day hospital. Results: The most frequent diseases were systemic and connective tissue diseases, accounting for 25.4% of the processes treated; of these, 17.1% corresponded to rheumatoid arthritis. Patient satisfaction was 93%. Meetings cancellations and the rate of transfusion reactions were 0%. The out-patient rate was 26%. Day hospital costs were 8.6% of conventional hospital costs, with savings of 78,390.69 euros. Conclusion: The day hospital is cost effective due to savings compared with conventional hospitalization and has a satisfactory quality index.

La aparición de una insuficiencia valvular mitral funcional en el seno de una miocardiopatía isquémica o dilatada es un signo de mal pronóstico con una elevada mortalidad y morbilidad y una reducción significativa de la esperanza de vida. La válvula mitral es anatómicamente normal, sin lesiones orgánicas en sus estructuras, por lo que el mecanismo de la regurgitación valvular se explica por los cambios en la geometría que sufre el ventrículo izquierdo. La miocardiopatía isquémica produce un remodelado del ventrículo que pierde su configuración normal, produciéndose una separación de ambos músculos papilares que traccionan de los velos ocasionando un déficit de coaptación y la aparición de la insuficiencia valvular. Probablemente, el tratamiento quirúrgico es la única opción terapéutica adecuada para corregir la regurgitación valvular y normalizar el pronóstico de estos pacientes. Se han diseñado diversas estrategias quirúrgicas encaminadas a reparar la lesión valvular, por una parte, y a normalizar la geometría ventricular, por otra. No obstante, en la actualidad aún no disponemos de una solución quirúrgica definitiva que pueda ser considerada el «patrón oro».

Objetivo: Los objetivos de este estudio fueron estimar las tasas de frecuentación a los servicios de urgencias hospitalarios (SUH) del Sistema Nacional de Salud (SNS) por áreas de salud, el porcentaje de ingresos, las razones estandarizadas de utilización de urgencias y analizar la relación con los recursos hospitalarios. Métodos: Estudio ecológico combinando información de diversas fuentes (Encuesta de Establecimientos Sanitarios con Régimen de Internado 2006 y Conjunto Mínimo de Datos Básicos 2006) para estimar la frecuentación a los SUH y el porcentaje de ingresos asociado en 164 áreas de salud de 14 comunidades autónomas (CC.AA.). Resultados: Los 35,3 millones de habitantes de las 164 áreas de salud incluidas realizaron 16,2 millones de visitas (45,7 por 100 habitantes) a los SUH del SNS, y de ellos ingresaron algo más de 2 millones (12,6%). Excluyendo el 5% de áreas extremas por cada cola, la frecuentación osciló entre 31,6 y 78,7 urgencias/100 habitantes y el porcentaje de ingresos entre el 7,6% y el 27,9%. Estas diferencias apenas se atenuaron al estandarizar. El factor CC.AA. explicó un 29% de la varianza en frecuentación y un 82% en ingresos. La frecuentación no se asoció al volumen poblacional de camas o médicos de plantilla, aunque sí al de médicos de urgencias, hospitales de menor tamaño y no docentes. Conclusiones: Las áreas de salud del SNS mantienen una gran variabilidad en frecuentación a urgencias e ingresos por urgencias, que parece asociarse a un uso diferencial por problemas de menor entidad.Objective: The aims of this study were to estimate the rate of hospital emergency services (HES) visits per health area, the associated percentage of admissions and the standardized HES utilization ratio, and to analyze their relationship with hospital resources. Methods: We performed an ecological study that combined information from distinct sources (Survey of Health Care Hospitalization Establishments 2006 and Minimum Data Set 2006) to estimate the rate of HES visits and the percentage of associated emergency admissions in 164 health areas in 14 autonomous communities (AC). Results: Among 35.3 million inhabitants in the 164 areas examined, there were 16.2 million visits to the HES (45.75 per 100 inhabitants); more than 2 million (12.6%) were hospitalized. Excluding 5% of extreme areas, rates oscillated between 31.60 and 78.69 HES visits/100 inhabitants, and the percentage of admissions was between 7.6% and 27.9%. These differences were not attenuated after standardization. The AC factor explained 29% of variance in HES visits and 82% of variance in admissions. The rate of visits was not associated with the number of beds or staff physicians but did correlate with the number HES doctors, and smaller and non-teaching hospitals. Conclusions: There is wide variability in the rates of HES visits and emergency admissions in the different areas of the Spanish National Health System. This variability seems to be associated with a differential use for minor problems.

Este trabajo presenta una visión complementaria respecto a las últimas experiencias y avances en la evaluación económica de medicamentos en el mercado español. El contexto europeo y los recientes cambios normativos parecen favorecer la incorporación de la evaluación económica como una herramienta básica en el proceso de toma de decisiones sobre financiación pública de medicamentos. Sin embargo, aún persisten dudas sobre si el apoyo gubernamental será claro y explícito y sobre el papel que desempeñarán los decisores regionales y otros agentes sanitarios en este proceso.This article presents a complementary view of the latest experiences and advances in the economic evaluation of medicines in the Spanish market. The European context and recent normative changes seem to favour the incorporation of economic evaluation of medicines as a basic tool in the decision-making process of public funding of drugs. However, some doubts remain about whether government support for economic evaluation of medicines will be open and explicit and about the role that regional decision-makers and other health actors will play in this process.

Objetivos: Identificar y priorizar los temas de investigación en los servicios sanitarios, adoptando una perspectiva orientada a satisfacer las necesidades de la población cubierta por el Sistema Nacional de Salud. Material y método: Reunión de 13 expertos estructurada con una técnica grupal mixta, desarrollada en 2 fases consecutivas: grupo nominal y método Delphi. Se identificaron prioridades de investigación en servicios de salud que fueron puntuadas de la siguiente manera: de 7 a 9, muy relevante; de 4 a 6, relevancia intermedia, y de 1 a 3, poco o nada relevante. Los resultados fueron ordenados en función de su puntuación mediana y su dispersión. Resultados: Se identificaron 53 temas de investigación. Se clasificaron como prioritarios los temas relacionados con estrategias para mejorar la efectividad de la atención sanitaria, la información a los pacientes, la calidad y la seguridad de la atención, la equidad y la accesibilidad de los servicios, y la sostenibilidad del sistema sanitario. El consenso entre estos temas fue muy alto: sólo 4 ítems obtuvieron una dispersión reseñable (intervalo intercuartílico (IQ) ≥ 2). En un rango de prioridad intermedia se situaron los temas relacionados con las mejoras organizativas del sistema, las mejoras en productividad y eficiencia, y los recursos humanos y equipamientos. El disenso en este caso fue muy alto: el 59% de los ítems obtuvo un IQ ≥ 2. Conclusiones: Aún con diversas limitaciones, se ofrece una referencia de prioridades para los investigadores españoles en servicios de salud y, también, una referencia para los financiadores y los usuarios de esta modalidad de investigación.Objectives: The aim of the present paper was to identify and prioritise health services research issues, from the perspective of Spanish NHS enrollees' health needs. Methods: 13 experts attended to a structured consensual meeting by using a two-phase process, sharing both Nominal Group and Delphi Technique features. Health Services Research Priorities were identified and scored (7 to 9, high relevance; 4 to 6 mild relevance and 1 to 3, low or no relevance). Results were sorted regarding the median score and its dispersion. Results: 53 research issues were identified. Strategies to improve effectiveness in health care, information to patients, health care quality and safety, equity, access and sustainability were considered of high priority and high consensus; just 4 items had remarkable dispersion (Intercuartile interval (ICI) ≥ 2). Organizational improvement, productivity and efficiency enhancement, workforce and equipments were classified of mild priority. Additionally, this group of items reached very low consensus: 59% of them reached ICI ≥ 2. Conclusions: Our approach offers reference about priorities to Spanish health services researchers, and also, orientation to financers and users of this kind of research, though several limitations have been described.

La reparación valvular es considerada actualmente como el tratamiento quirúrgico electivo de la insuficiencia mitral cuando la anatomía valvular es favorable. La anuloplastia mitral provee los mejores resultados en la enfermedad degenerativa, con una mortalidad hospitalaria < 1% y supervivencia actuarial del 90 y 80% a los 5 y 10 años, respectivamente; la mayoría de pacientes permanecen libres de reoperación e insuficiencia mitral residual (90% a los 10 años). Esta técnica no resulta tan satisfactoria en la enfermedad reumática, y aunque hemos obtenido resultados satisfactorios, otros autores presentan incidencia elevada de reoperación por disfunción mitral. La disfunción valvular mitral postoperatoria a largo plazo (20 años) es significativamente mayor en pacientes menores de 20 años (26,8 vs 4,5%). La enfermedad congénita de la válvula mitral constituye un grupo heterogéneo, debiendo considerarse la anuloplastia como una parte de la reconstrucción valvular, siendo preciso tratar quirúrgicamente el resto de anomalías congénitas asociadas. En estos casos, la mortalidad hospitalaria oscila entre 1-10%, con una incidencia de reoperación por disfunción valvular a largo plazo de 20-50%, dependiendo del tipo de cardiopatía congénita. La cirugía reparadora en la insuficiencia mitral isquémica sigue constituyendo motivo de controversia por la complejidad de los mecanismos que la ocasionan. En estos pacientes, la anuloplastia soluciona parcialmente la regurgitación, al aumentar la zona de coaptación de los velos, pero no logra corregir las alteraciones en la movilidad valvular ni los cambios geométricos del aparato subvalvular. En el 25% de los pacientes operados reaparece una insuficiencia mitral, por lo que se recomienda utilizar un anillo restrictivo con objeto de incrementar la coaptación valvular. Recientemente, en estos casos se emplea la anuloplastia asimétrica, que corrige el defecto de la región posterolateral del anillo y válvula. La anuloplastia en pacientes con miocardiopatía dilatada e insuficiencia cardíaca terminal, propuesta por Bolling, ha dado resultados satisfactorios, con mejoría de la clase funcional NY HA, disminución de la hospitalización y supervivencia al año del 84%, a pesar de que a los 5 años sobreviven menos de la mitad de los pacientes. En resumen, la anuloplastia mitral debe considerarse como parte de la cirugía reparadora, siendo necesario individualizar su utilización de forma que, para cada paciente, la reconstrucción valvular «completa» requerirá un determinado modelo de prótesis anular y de técnicas reparadoras asociadas. Debemos evitar, de este modo, generalizar el tratamiento quirúrgico como hemos venido haciendo incorrectamente durante años.