De la microbiota como “cisne negro”: El extraño caso de los amiloides bacterianos y la neurodegeneración / Microbiota as a ‘black swan’: The extrange case of bacterial amyloids and neurodegeneration

La microbiota humana es la compleja comunidad de microorganismos que colonizan nuestros epitelios, con especial presencia en el intestino grueso. Investigaciones recientes vinculan a la microbiota con diversas patologías, entre las cuales aquí me ocuparé de las enfermedades neurodegenerativas. Metabolitos generados por las bacterias de nuestra microbiota tienen propiedades moduladoras de la inflamación, interaccionado con receptores específicos en el epitelio intestinal, permeando el tejido subyacente y abriéndose paso hacia los vasos sanguíneos, alcanzando así el sistema nervioso central (SNC). Por otra parte, proteínas con el potencial de agregar ordenadamente en forma de amiloides, secretadas por las bacterias para construir la matriz que entreteje las biopelículas que les permiten persistir en el intestino, pueden utilizar para llegar al SNC una vía alternativa: las terminaciones parasimpáticas del nervio vago, propagándose como priones (amiloides infectivos), lo que constituye el denominado “eje intestino-cerebro”. Una vez en el SNC, los amiloides bacterianos pueden promover la agregación de proteínas amiloidogénicas implicadas en neurodegeneración (α-sinucleína, Tau, Ab, Sod1). En este artículo se revisan y ponderan algunas de las recientes evidencias experimentales que, principalmente en sistemas modelo animales, asignan un papel central para la microbiota en la etiología de las enfermedades neurodegenerativas, así como los estudios realizados en el laboratorio del autor que han conducido al desarrollo de un sistema modelo mínimo, exclusivamente bacteriano, que recapitula aspectos moleculares esenciales de una enfermedad neurodegenerativa.(AU)

The human microbiota is the complex community of microorganisms that colonize our epithelia, with a special presence in the large intestine. Recent research links the microbiota to various pathologies, among which I will focus here on neurodegenerative diseases. Metabolites generated by the bacteria of our microbiota have inflammation-modulating properties, interacting with specific receptors in the intestinal epithelium, permeating the underlying tissue and making their way into the blood vessels, thus reaching the central nervous system (CNS). On the other hand, proteins with the potential to aggregate in the form of amyloids, secreted by bacteria to build the matrix that interweaves the biofilms that allow them to persist in the intestine, can use an alternative route to reach the CNS: the parasympathetic endings of the vagus nerve, spreading as prions (infective amyloids), in what is known as the “gut-brain axis”. Once in the CNS, bacterial amyloids can promote aggregation of amyloidogenic proteins involved in neurodegeneration (α-synuclein, Tau, Ab, Sod1). This article reviews and discusses some of the recent experimental evidence that, mainly in animal model systems, assigns a central role for the microbiota in the aetiology of neurodegenerative diseases, as well as the studies performed in the laboratory of the author that have led to the development of a minimal, exclusively bacterial model system that recapitulates essential molecular aspects of a neurodegenerative disease.(AU)

Thermal insulation impact on overheating vulnerability reduction in Mediterranean dwellings.

Heat waves are expected to increase the use of air conditioning (AC), deriving in higher energy consumption. This research aims to determine whether thermal insulation is an effective retrofit strategy for tackling overheating. Four occupied dwellings in southern Spain were monitored: two houses built prior to any thermal criteria and two with current thermal standards. Thermal comfort is assessed considering adaptive models and user patterns for the operation of AC and natural ventilation. Results show that a high level of insulation combined with a proper use of night-time natural ventilation can increase thermal comfort hours under heat waves, lasting 2-5 times longer than in poorly-insulated houses and with up to 2 °C temperature difference at nights. Long-term effectiveness of insulation under extreme heat presents a better thermal performance, especially in intermediate floors. Yet, the activation of AC usually occurs with indoor temperatures of 27-31 °C, regardless of the envelope's solution.

Experimental optical trapping with frozen waves.

We report, to the best of our knowledge, the first optical trapping experimental demonstration of microparticles with frozen waves. Frozen waves are an efficient method to model longitudinally the intensity of nondiffracting beams obtained by superposing copropagating Bessel beams with the same frequency and order. Based on this, we investigate the optical force distribution acting on microparticles of two types of frozen waves. The experimental setup of holographic optical tweezers using a spatial light modulator has been assembled and optimized. The results show that it is possible to obtain greater stability for optical trapping using frozen waves. The significant enhancement in trapping geometry from this approach shows promising applications for optical tweezers micromanipulations over a broad range.

Non-alcoholic fatty liver in hereditary fructose intolerance.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation affecting >5% of the liver volume that is not explained by alcohol abuse. It is known that fructose gives rise to NAFLD and it has been recently described that the ingestion of fructose in low amounts in aldolase B deficient mice is associated with the development of fatty liver. Therefore, it is reasonable that patients with HFI (Hereditary Fructose Intolerance) present fatty liver at diagnosis, but its prevalence in patients treated and with adequate follow-up is not well documented in the literature. The aim of this study is to analyze the association between HFI and NAFLD in treated patients. METHODS: A cross-sectional observational study was conducted. The population comprised 16 genetically diagnosed HFI patients aged from 3 years to 48 and in dietary treatment of fructose, sorbitol and sacarose exclusion at least for two years. Blood samples were obtained for analytical studies and anthropometric measurements of each patient were performed. RESULTS: Patients presented a Body Mass Index (BMI) of 17.9 ± 2.9 kg/m2. The HOMA index and Quick index were in normal range for our population. The S-adenosyl-methionine (SAM)/S-adenosyl-l-homocysteine (SAH) ratio was increased in the patients in whom this analysis was performed. By imaging techniques it was observed that 9 of the 16 patients presented fatty liver (7 by hepatic MRI). Of these 9 patients, only 3 presented hepatomegaly. 7 of 9 patients affected by the c.448G > C mutation had fatty infiltration, of which three of them presented in addition hepatomegaly. CONCLUSIONS: There is a high prevalence of fatty liver in HFI patients and it is not related to obesity and insulin resistance. The diagnosis of fatty liver in HFI patients and, above all, the identification of new therapeutic approaches, can positively impact the quality of life of these patients.

Cuidados enfermeros en Atención Primaria ante el síndrome cardiorrenal crónico con compromiso cerebrovascular / Nursing care at primary care for chronic cardiorenal syndrome with cerebrovascular involvement

La función cardiaca y la función renal están íntimamente asociadas, ya que el corazón y los riñones llevan a cabo la regulación hemodinámica del organismo. Cuando se producen alteraciones de forma bidireccional en ambos órganos se activa una serie de mecanismos compensadores que provocan un efecto nocivo de uno de ellos sobre el otro. Es lo que se conoce como síndrome cardiorrenal. Actualmente se dispone de protocolos de Enfermería estandarizados para el manejo de la insuficiencia cardiaca y para la insuficiencia renal; no obstante, es necesario ampliar la información para entender de forma óptima la relación cardiorrenal y aplicar la mejor evidencia científica a los cuidados. Por ello se expone un caso clínico abordado desde Atención Primaria, con el desarrollo de un plan de cuidados elaborado una vez identificados los diagnósticos de Enfermería que se han derivado de la valoración enfermera siguiendo el modelo de las 14 necesidades básicas de Virginia Henderson

Cardiac function and renal function are closely related, because the heart and the kidneys carry out the hemodynamic regulation of the body. When there are bidirectional alterations in both organs, a series of compensating mechanisms are activated, which cause harmful effects of one over the other. This is known as Cardiorenal Syndrome. There are current standard Nursing protocols available for the management of heart failure and renal impairment; however, it is necessary to increase information for an optimal understanding of the cardiorenal interaction, and to apply the best scientific evidence into care. To this aim, we present a case record addressed at Primary Care, with the development of a plan of care prepared after the Nursing diagnoses were identified, derived from nursing assessment following the model of the 14 Basic Needs of Virginia Henderson

Atención prestada por un Centro de Urgencias de Atención Primaria en el atentado terrorista de 2017 en Barcelona (España) / Care provided by a primary care emergency center in the terrorist attack of 2017 in Barcelona (Spain)

Introducción: el 17 de agosto de 2017 se produce en barcelona un atentado terrorista. una furgoneta arrolla a centenares de viandantes en las ramblas alrededor de las 5:00 pm. El centro de urgencias de atención primaria (cuap) ciutat-vella peracamps, que atiende generalmente entre 70 y 100 pacientes diarios, sobretodo de nivel III y IV, según el sistema español de triaje (set), está situado en las inmediaciones donde se produjo el atentado. Objetivo: determinar el perfil de la demanda y la respuesta de los servicios prestados en el cuap las primeras 24h después del atentado. Metodología: estudio cuantitativo, observacional y retrospectivo. Los datos fueron obtenidos de la trayectoria clínica informatizada de enfermería y de la historia clínica electrónica de los pacientes que acudieron en el ámbito temporal de dicho estudio. Resultados: en las primeras 24 horas, el cuap recibió un total de 70 pacientes, de los cuales 25 estuvieron relacionados de forma directa con el atentado. En cuanto a los niveles de triaje de enfermería, un 4% fueron de nivel I (n=1), un 40% fueron nivel III (n=10), y un 56% nivel IV (n=14). Conclusiones: no hubo una mayor demanda asistencial, pero sí un nivel de gravedad superior. En cuanto a los tiempos de asistencia tampoco se observa diferencia con otros días, pero se ha de considerar que se incrementó el número de personal sanitario, lo cual optimizó la asistencia

Introduction: on august 17, 2017, a terrorist attack takes place in barcelona. A van rolls over hundreds of pedestrians on the ramblas in barcelona around 5pm. The emergency center for primary care (cuap) ciutat-vella peracamps, which generally attends between 70 and 100 patients a day, above all at level III and IV, according to the spanish triage system (set); it's located close where the attack took place. Objective: determine the profile of the demand and the response of the services provided in the cuap the first 24 hours after the attack. Methodology: quantitative, observational and retrospective study. The data were obtained from the computerized clinical trajectory of nursing and the electronic clinical history of the patients who attended in the temporal scope of said study. Results: in the first 24 hours, the cuap received a total of 70 patients, which 25 were directly related to the attack. Regarding nursing triage levels, 4% were level i (n = 1), 40% were level iii (n = 10), and 56% level iv (n = 14). Conclusions: there was no greater demand for care, but a higher level of severity. Regarding the attendance times, there is no difference with other days, but it has to be considered that the number of health personnel increased, which optimized the assistance

Gestión de la calidad, un enfoque directivo para la seguridad del paciente / Quality management, a directive approach to patient safety

Hoy en día resulta imprescindible la implementación de sistemas de gestión de calidad en el entorno sanitario, sin embargo esto no es posible sin el apoyo de las direcciones de los centros sanitarios, puesto que son estas las que deben diseñar y trasladar las estrategias a los profesionales sanitarios. En este artículo se ha planteado el presentar la gestión de calidad desde las Direcciones de Enfermería, centrándose en las aplicaciones del ciclo de mejora continua, constituir grupos de mejora, implementar sistema de monitorización y la aplicación de modelos externos de calidad (como EFQM o ISO). Todo lo anterior y su implementación, redundará en la seguridad del paciente puesto que un adecuado sistema de gestión de calidad permitirá eliminar, reducir y mitigar los resultados adversos evitables, generados como consecuencia del proceso de atención, además de promocionar las prácticas seguras (AU)

Nowadays the implementation of effective quality management systems and external evaluation in healthcare is a necessity to ensure not only transparency in activities related to health but also access to health and patient safety. The key to correctly implementing a quality management system is support from the managers of health facilities, since it is managers who design and communicate to health professionals the strategies of action involved in quality management systems. This article focuses on nursing managers’ approach to quality management through the implementation of cycles of continuous improvement, participation of improvement groups, monitoring systems and external evaluation quality models (EFQM, ISO). The implementation of a quality management system will enable preventable adverse effects to be minimized or eliminated, and promote patient safety and safe practice by health professionals (AU)

Quality management, a directive approach to patient safety. / Gestión de la calidad, un enfoque directivo para la seguridad del paciente.

Nowadays the implementation of effective quality management systems and external evaluation in healthcare is a necessity to ensure not only transparency in activities related to health but also access to health and patient safety. The key to correctly implementing a quality management system is support from the managers of health facilities, since it is managers who design and communicate to health professionals the strategies of action involved in quality management systems. This article focuses on nursing managers' approach to quality management through the implementation of cycles of continuous improvement, participation of improvement groups, monitoring systems and external evaluation quality models (EFQM, ISO). The implementation of a quality management system will enable preventable adverse effects to be minimized or eliminated, and promote patient safety and safe practice by health professionals.

Hemichorea/Hemiballism Associated with Hyperglycemia: Report of 20 Cases.

BACKGROUND: Hemichorea/hemiballism associated with nonketotic hyperglycemia is a well-recognized syndrome, but few case series have been reported in the literature. CASE REPORT: We describe 20 patients with hemichorea/hemiballism associated with hyperglycemia (9 males and 11 females) with mean age of 67.8 years. Ten patients had a previous diagnosis of type 2 diabetes mellitus, and one had type 1 diabetes mellitus. Six of them had documentation of poor diabetic control over at least the last 3 months. Nine patients had new-onset hyperglycemia with a diagnosis of diabetes mellitus made after discharge. Seventeen patients had unilateral chorea/ballism, while three had bilateral chorea/ballism. Eighteen cases had striatal hyperdensities on computed tomography (CT) and/or hyperintense signals on magnetic resonance imaging (MRI). The putamen was affected in all cases, and the caudate nucleus was involved in nine. DISCUSSION: Hemichorea/hemiballism associated with nonketotic hyperglycemia can be the presenting sign of diabetes mellitus in almost half of cases or can occur after a few months of poor glycemic control in patients with diagnosed diabetes. This case series is one of the largest to date and adds valuable information about clinical and neuroimaging features that are comparable with published data but also emphasize the role of adequate diabetes mellitus control.

Reply #1 to: Glycemic Choreoballism.

In Response To: Lee D, Ahn TB. Glycemic choreoballism. Tremor Other Hyperkinet Mov. 2016; 6. doi: 10.7916/D8QJ7HNF Original Article: Cosentino C, Torres L, Nuñez Y, et al. Hemichorea/hemiballism associated with hyperglycemia: report of twenty cases. Tremor Other Hyperkinet Mov. 2016; 6. doi: 10.7916/D8DN454P.

Systematic review: An approach to identifying health inequalities through case studies / Revisión sistemática: un enfoque para identificar desigualdades en salud a través de estudios de casos

Introduction: Health inequalities, among other factors, reflect the wellbeing level of a population. Interventions aimed at eliminating or preventing such inequalities require an understanding of their origins. Objective: To perform a systematic review to identify case studies reporting health inequalities worldwide. Methodology: Case reports, case studies and case series written in English, Spanish and Portuguese reporting health inequalities were included. Databases like Medline and EMBASE, and grey literature sources such as LILACS, OpenGrey, Google, and others were included. Results: Initially, the search produced 1272 articles. 139 articles were selected by their title, while, based on their abstract, 28 articles were chosen for full text reading. Finally, 23 articles were included. Gender difference was the most frequent factor in terms of health inequalities (23.2%), followed by socio economic condition (20%), belonging to a migrant population (13.3%), ethnic origin (13.3%), age (10%), geographic origin (3.3%), and others (16.6%). Discussion: This approach, which is based on reviewing case reports to study health inequalities, contrasts with the majority of the studies carried out in this field. This research proposes to study inequalities specific to population groups that suffer such inequalities within communities in a particular geographic area and are not able to access to optimal health services.

Introducción: las desigualdades en salud, entre otros factores, reflejan el nivel de bienestar de una población. Para realizar intervenciones dirigidas a eliminar o prevenir estas desigualdades es necesario comprender su origen. Objetivo: realizar una revisión sistemática para identificar estudios de casos en los que se reportan desigualdades en salud en todo el mundo. Metodología: en este estudio se incluyeron reportes de caso, estudios de casos y series de casos, escritos en inglés, español y portugués, en los que se informan desigualdades en salud. Se utilizaron bases de datos como Medline y EMBASE, así como fuentes de literatura gris como LILACS, OpenGrey, Google, entre otras. Resultados: la búsqueda inicial arrojó 1272 artículos; de los cuales se seleccionaron 139 por su título; luego, basándose en su resumen, se escogieron 28 para realizar una lectura completa. Finalmente se incluyeron 23 artículos. En términos de inequidad en salud, la diferencia de género fue el factor más frecuente (23.2%), seguido por condición socioeconómica (20%), pertenecer a una población migrante (13.3%), origen étnico (13.3%), edad (10%), origen geográfico (3.3%) y otros (16,6%). Discusión: este enfoque, que se basa en la revisión de reportes de caso para estudiar las desigualdades en salud, contrasta con la mayoría de estudios que se han realizado al respecto. En esta investigación se propone analizar las desigualdades en salud que son específicas a poblaciones que viven dentro de comunidades en un área geográfica en particular y que no tienen acceso a servicios óptimos de salud.

Bionimbus: a cloud for managing, analyzing and sharing large genomics datasets.

BACKGROUND: As large genomics and phenotypic datasets are becoming more common, it is increasingly difficult for most researchers to access, manage, and analyze them. One possible approach is to provide the research community with several petabyte-scale cloud-based computing platforms containing these data, along with tools and resources to analyze it. METHODS: Bionimbus is an open source cloud-computing platform that is based primarily upon OpenStack, which manages on-demand virtual machines that provide the required computational resources, and GlusterFS, which is a high-performance clustered file system. Bionimbus also includes Tukey, which is a portal, and associated middleware that provides a single entry point and a single sign on for the various Bionimbus resources; and Yates, which automates the installation, configuration, and maintenance of the software infrastructure required. RESULTS: Bionimbus is used by a variety of projects to process genomics and phenotypic data. For example, it is used by an acute myeloid leukemia resequencing project at the University of Chicago. The project requires several computational pipelines, including pipelines for quality control, alignment, variant calling, and annotation. For each sample, the alignment step requires eight CPUs for about 12 h. BAM file sizes ranged from 5 GB to 10 GB for each sample. CONCLUSIONS: Most members of the research community have difficulty downloading large genomics datasets and obtaining sufficient storage and computer resources to manage and analyze the data. Cloud computing platforms, such as Bionimbus, with data commons that contain large genomics datasets, are one choice for broadening access to research data in genomics.

Roger Kornberg y la RNApol II: el mecanismo de síntesis del ácido ribonucleico desvelado al medio siglo de Severo Ochoa y su polinucleótido fosforilasa / Roger Kornberg and RNApol II: unveiling the mechanism of ribonucleic acid synthesis half a century after Severo Ochoa and his polynucleotide phosphorylase

El premio Nobel de Química, en su edición de 2006, ha sido otorgado al Profesor Roger Kornberg, del Departamento de Biología Estructural de la californiana Universidad de Stanford. El Profesor Kornberg ha desarrollado durante años un exhaustivo y riguroso trabajo sobre el complejo de proteínas responsable de la síntesis del ARN mensajero en las células eucarióticas, la RNA polimerasa II. Aplicando metodologías biofísicas, en particular la cristalografía de rayos-X, su trabajo muestra cómo diez de las doce subunidades proteicas del enzima se coordinan para separar las dos hebras de la molécula de ADN, reconocer el primer ribonucleótido que debe incorporarse sobre el molde de la cadena que ha de ser transcrita y catalizar la polimerización de sucesivos nucleótidos con gran fidelidad y procesividad. Cerca de medio siglo después de que Severo Ochoa realizase la primera síntesis bioquímica del ARN en un tubo de ensayo, el trabajo del ahora galardonado desentraña, en sus detalles más íntimos, el funcionamiento de la maquinaria macromolecular esencial para la expresión de los genes

The Nobel Prize in Chemistry 2006 has been awarded to Prof. Roger Kornberg, Head of the Department of Structural Biology, Stanford CA, USA. Prof. Kornberg has been leading along years an exhaustive and rigorous research effort on RNApol II, the protein complex responsible for the synthesis of messenger RNA in eukaryotic cells. By means of biophysical approaches, X-ray crystallography in particular, his work shows how ten of the twelve protein subunits of the whole enzyme are coordinated in order to melt the two DNA strands, recognize the first ribonucleotide to be incorporated on the template chain to be transcribed and catalyze polymerization of successive nucleotide building blocks with astonishing fidelity and processivity. Nearly half a century after the pioneering in vitro synthesis of RNA by Severo Ochoa, the work now awarded unveils, with a wealth of intimate details, the function of the macromolecular machinery essential for gene expression

Evaluation of quality of life following treatment with etoricoxib in patients with arthritis or low-back pain: an open label, uncontrolled pilot study in Mexico.

An open-label study was undertaken at multiple centers in Mexico to assess the impact of treatment with etoricoxib - a selective cyclo-oxygenase-2 (COX-2) inhibitor - on quality of life (QoL) and pain relief among patients with osteoarthritis (OA), rheumatoid arthritis (RA) or chronic low-back pain (CLBP). The study involved 191 adult patients (aged > 18 years old) who had used non-selective non-steroidal antiinflammatory drugs (NSAIDs) for the treatment of OA, RA or CLBP during the month prior to study enrolment. After discontinuation of prior therapy, patients were treated with etoricoxib 60 mg for OA and CLBP,or 90 mg for RA once daily for 2 weeks. Patient and physician questionnaires were used to collect information about drug treatments, patients' QoL (Short Form-8 Health Survey [SF8] and EQ-5D VAS), patients' pain assessment, and physicians' and patients' satisfaction with treatment at baseline and at follow-up visits. Relative to prior NSAID use, etoricoxib use was associated with improvements in all SF-8 QoL domains and component scores as well as in measures of pain and physical functioning. Current pain was reduced from 59.1 mm (0-100mm VAS) at baseline to 27.1mm at follow-up and the physical component score of the SF-8 improved from 33.3 to 46.3 (on a scale from 0 to100). At follow-up, 91% of patients were satisfied with the pain control provided by etoricoxib compared with 34% who were satisfied with the pain control provided by previous NSAIDs. Among physicians, 93% reported satisfaction with the analgesic effect, 95% with the anti-inflammatory profile, and 82% with the side-effect profile of etoricoxib relative to pre-study NSAID treatment. During etoricoxib therapy, use of concomitant medications was reduced. The results of this study are limited due to the lack of a control group, the un-blinded design, and the small number of patients. Large naturalistic trials are needed to confirm the results.

Uso de tirofiban en angioplastia coronaria de alto riesgo / Tirofiban for hight risk coronary angioplasty

Los eventos cardíacos adversos posterior a angioplastia coronaria pueden ser hasta del 15 por ciento, los medicamentos antiplaquetarios reducen estas complicaciones, el tirofíban produce un bloqueo selectivo de los receptores de GP IIblIIa en la plaqueta. Nuestro propósito es mostrar el uso del tirofíban usado como terapia adjunta a angioplastia coronaria en pacientes considerado de alto riesgo, y analizar a aparición de eventos cardíacos mayores (MACE) intrahospitalarios y a tres meses. Se tomaron todas las angioplastias en las cuales se usó el medicamento (n: 170) desde enero de 1999 hasta marzo del 2000; describiendo en ellas la indicación, aparición de eventos adversos, mortalidad, complicaciones, y se realizó un seguimiento telefónico a tres meses. Se usó tirofíban en el 11.2 por ciento de todas las angioplastias en el período estudiado, el 73 por ciento fueron hombres con edad promedio 52 años; el 83.5 por ciento tenían factores de riesgo para enfermedad coronaria; la presentación clínica fue 42 por ciento con IAM Q (4.7 por ciento en choque cardiogénico) 13 por ciento IAM no Q, 31.2 por ciento anginas inestables, 11 por ciento anginas estables y 2.8 por ciento isquemia silente. Se trataron 235 vasos, lesiones complejas (Tipo B2 y C) 884.2 por ciento; el uso del medicamento fue electivo (Primario) 53.5 por ciento. Se implantaron 13 Stents por vaso. La mortalidad intrahospitalaria fue 2.35 por ciento (tres pacientes en choque cardiogénico y uno por hemorragia vía digestiva); no se requirieron procedimientos de revascularización urgentes y sólo hubo un IAM no Q. Se realizó seguimiento a tres meses en 91.2 por ciento, la necesidad de revascularizar el vaso tratado fue del 7.08 por ciento (10 pacientes con PTCA y uno con cirugía de RVM). En este grupo se muestra el uso de tirofiban adjunto a la angioplastia como una estrategia segura con bajas complicaciones isquémicas y mortalidad intrahospitalarias y a tres meses