RESUMEN

The ring nematode genus Xenocriconemella De Grisse and Loof, 1965 comprises only one nominal species, Xenocriconemella macrodora (Taylor, 1936) De Grisse and Loof, 1965. The initial objective of the present study was to investigate the morphological-morphometric and molecular diversity of 28 X. macrodora populations in the Iberian Peninsula associated with tree forests (mainly Quercus spp.). However, a detailed integrative taxonomic analysis (morphological-morphometric and molecular data) from each population and analysis of this data using principal component analysis (PCA) for morphometric data (including these 28 populations and other 25 X. macrodora populations around the world) and molecular and phylogenetic species delimitation methods revealed that X. macrodora forms a species complex. This species complex is composed by species that are morphometricly and morphologically similar, but clearly different at the molecular level. Three new species are described applying integrative taxonomy, namely as Xenocriconemella iberica sp. nov., Xenocriconemella paraiberica sp. nov. and Xenocriconemella pradense sp. nov. However, the molecular diversity of this species in USA and Italy confirmed that additional species are likely present in this species complex, and the diversity of this group may be higher than expected. The study of X. macrodora topotypes can clarify the position of this species using molecular markers under an integrative approach.

RESUMEN

Parasitic nematodes of millipedes from Nigeria are molecularly characterized for the first time. During nematode surveys on live giant African millipedes from several localities in Nigeria, 4 species of rhigonematids were identified by application of integrative taxonomical approaches (morpho-anatomy and molecular markers), including Brumptaemilius sp., Gilsonema gabonensis, Obainia pachnephorus, and Rhigonema disparovis. The results of morphometric and molecular analyses of D2-D3 28S, ITS, partial 18S rRNA, and cytochrome oxidase c subunit 1 (COI) gene sequences further characterized the rhigonematid species, and clearly separated them from other related species. Phylogenetic relationships based on 28S and 18S rRNA genes suggest that genera within Ransomnematoidea (Ransomnema, Heth, Carnoya, Brumptaemilius, Cattiena, Insulanema, Gilsonema) and Rhigonematoidea (Rhigonema, Obainia, Xystrognathus, Trachyglossoides, Ichthyocephaloides) clustered rather closer than could be expected in view of their morphological differences. Phylogenetic relationships based on ITS and COI are congruent with those of other ribosomal genes; however, they are not conclusive due to the scarcity of available sequences of these genes for these genera in NCBI.

Asunto(s)

Escarabajos , Parásitos , Espirúridos , Animales , Filogenia , Nigeria , ARN Ribosómico 18S/genética

RESUMEN

Melatonin has been shown to have an antinociceptive effect and its administration could enhance the antinociceptive effect of other drugs. This study assessed the antinociceptive effects of melatonin in combination with paracetamol and N-palmitoylethanolamide (PEA) using the formalin test in mice. Melatonin, paracetamol, and PEA were administered intraplantarly (paw) alone or combined to mice. A concentration-response curve was generated to determine the concentration needed to reach 30% of the maximal antinociceptive effect (EC30). Melatonin, paracetamol and PEA induced a concentration-dependent antinociceptive effect in both phases of the formalin test, being PEA more potent (EC30 = 7.4±0.2 mg/paw) than melatonin (EC30 = 20.5±3.1 mg/paw) or paracetamol (EC30 = 41.8±2.6 mg/paw). Combinations of melatonin with paracetamol or PEA also induced a concentration-dependent antinociceptive effect in the formalin test. Isobolographic analysis showed that melatonin interacts synergistically with either paracetamol or PEA to reduce formalin-induced inflammatory pain. However, the experimental values of EC30 were significantly smaller than those calculated theoretically.

Asunto(s)

Acetaminofén , Melatonina , Acetaminofén/farmacología , Amidas , Analgésicos/farmacología , Animales , Relación Dosis-Respuesta a Droga , Etanolaminas , Formaldehído , Melatonina/farmacología , Ratones , Ácidos Palmíticos

Asunto(s)

Infección Hospitalaria , Infecciones por Klebsiella , Meningitis , Humanos , Klebsiella pneumoniae , Infección Hospitalaria/tratamiento farmacológico , Ceftazidima/uso terapéutico , Compuestos de Azabiciclo/uso terapéutico , Combinación de Medicamentos , Antibacterianos/uso terapéutico , beta-Lactamasas/genética , Pruebas de Sensibilidad Microbiana , Infecciones por Klebsiella/tratamiento farmacológico , Proteínas Bacterianas

RESUMEN

During nematode surveys in natural vegetation in Sierra Mágina, Jaén province, southern Spain, a Longidorus species closely resembling Longidorus carpetanensis was found, but application of integrative taxonomic approaches clearly demonstrated that it is a new species described herein as Longidorus maginicus n. sp. The new species is amphimictic, characterized by a moderately long body (4.2-5.2 mm); lip region anteriorly flattened, slightly separated from the rest of body by a depression, 9.0-11.0 µm wide and 3.5-6.0 µm high; amphidial fovea not lobed; relatively short odontostyle (61.0-70.5 µm); guiding ring located 23.5-27.0 µm from anterior end; vulva located at 42.0%-51.3% of body length; female tail 39.0-61.0 µm long, conoid, dorsally convex with rounded terminus (c' = 1.3-2.1), with two or three pairs of caudal pores; and males common (1:2 ratio males:females), with moderately long spicules (39.0-48.5 µm) and 1 + 6-9 ventromedian supplements and three juvenile developmental stages. According to the polytomous key, codes for the new species are (codes in parentheses are exceptions): A2-B1-C2-D2-E1-F2(3)-G2-H5(4)-I2-J1-K6. The results of molecular analysis of D2-D3 28S, internal transcribed spacer region, partial 18S rDNA, and cytochrome oxidase c subunit 1 (coxI) gene sequences further characterized the new species status, and separated it from L. carpetanensis and other related species.

Asunto(s)

Nematodos , Animales , Femenino , Masculino , Nematodos/genética , Filogenia , España

RESUMEN

It is now over 30 years since Demchenko and Ladokhin first posited the potential of the tryptophan red edge excitation shift (REES) effect to capture information on protein molecular dynamics. While there have been many key efforts in the intervening years, a biophysical thermodynamic model to quantify the relationship between the REES effect and protein flexibility has been lacking. Without such a model the full potential of the REES effect cannot be realized. Here, we present a thermodynamic model of the tryptophan REES effect that captures information on protein conformational flexibility, even with proteins containing multiple tryptophan residues. Our study incorporates exemplars at every scale, from tryptophan in solution, single tryptophan peptides, to multitryptophan proteins, with examples including a structurally disordered peptide, de novo designed enzyme, human regulatory protein, therapeutic monoclonal antibodies in active commercial development, and a mesophilic and hyperthermophilic enzyme. Combined, our model and data suggest a route forward for the experimental measurement of the protein REES effect and point to the potential for integrating biomolecular simulation with experimental data to yield novel insights.

RESUMEN

OBJECTIVES: During the last decade, some changes in the epidemiology of invasive infections have been reported; however, specific studies with patient-level data are scarce. The aim of this study was to describe and evaluate the epidemiologic changes in bloodstream infections (BSI) during the last decade in Andalucía, Spain. METHODS: Data from two prospective cohorts of BSI in adults with the same methodology performed 10 years apart in 11 hospitals (eight tertiary and three community) in Andalucía, Spain, were compared; the 2006-7 cohort study was performed between October 2006 and March 2007, and the 2016-17 cohort study was performed between October 2016 and March 2017. Population-based incidence rates were calculated and extrapolated for 1 year. Relative risk ratios were calculated between the 2 periods. Multivariate analyses were performed by logistic regression. RESULTS: Overall, 1262 episodes of BSI were included, 563 (44.6%) in 2006-7 and 699 (55.3%) in 2016-17. Multivariate models selected the following changes in patients' features in 2016-17, after controlling for type of acquisition: higher age (odds ratio (OR) = 1.02; 95% confidence interval [CI] 1.01-1.03), lower urinary catheter (OR = 0.37; 95% CI, 0.26-0.48) and lower Pitt score (OR = 0.76; 95% CI, 0.71-0.82). Adjusted estimations considering patients' features and exposure to procedures showed a reduction in coagulase-negative staphylococci (OR = 0.47; 95% CI, 0.32-0.69), and an increase in Proteus spp. (OR = 3.12; 95% CI, 1.18-8.23) and Candida spp. (OR = 3.01; 95% CI, 1.03-8.86). CONCLUSIONS: We found relevant epidemiologic changes in BSI in our area, including rates, frequency of acquisition types, changes in patient's profiles and aetiologic agents.

Asunto(s)

Infecciones Bacterianas/epidemiología , Micosis/epidemiología , Sepsis/microbiología , Anciano , Infecciones Bacterianas/mortalidad , Femenino , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Mortalidad , Micosis/mortalidad , Estudios Prospectivos , Factores de Riesgo , Sepsis/epidemiología , Sepsis/mortalidad , España/epidemiología

RESUMEN

Deregulation of nutrient, hormonal, or neuronal signaling produces metabolic alterations that result in increased mitochondrial reactive oxygen species (ROS) production. The associations of the mitochondrial respiratory chain components into supercomplexes could have pathophysiological relevance in metabolic diseases, as supramolecular arrangements, by sustaining a high electron transport rate, might prevent ROS generation. In this review, the relationship between mitochondrial dysfunction and supercomplex arrangement of the mitochondrial respiratory chain components in obesity, insulin resistance, hepatic steatosis and diabetes mellitus is summarized and discussed.

Asunto(s)

Enfermedades Metabólicas/metabolismo , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Humanos

RESUMEN

Strawberry is affected by several pests and diseases. Neopamera bilobata is an emerging pest that has been reported by several strawberry growers, usually associated with catfacing symptoms in fruits. We evaluated intercropping garlic or Chinese chives on N. bilobata populations on strawberry crops grown in high tunnels in two experiments. In the first experiment, we evaluated N. bilobata populations on strawberry intercropping with garlic plants (three densities: 8, 16, 24 GP - garlic plant per plot) on the bags by taking 12 samples from December 2015 to April 2017. N. bilobata populations on strawberry were also assessed when Chinese chives were grown under the suspended wooden structures in which strawberry plants are grown ('undercropping') (14 samples), in two high tunnels, from November 2016 to March 2017. The number of nymphs and adults on 14 randomly selected fruits per plot were assessed. During the garlic intercropping experiment, the treatments of three densities of garlic reduced N. bilobata populations; however, the 24 GP treatment caused a greater reduction than the 8 GP treatment. Garlic densities reduced N. bilobata populations by 35, 50, and 64% for the 8, 16, and 24 GP treatments, respectively. Chinese chives cultivated under the structures reduced N. bilobata populations by 47%. The results suggest that intercropping garlic or undercropping Chinese chives are suitable tools to be tested in integrated pest management in strawberry crops.

Asunto(s)

Cebollino/crecimiento & desarrollo , Cadena Alimentaria , Fragaria , Ajo/crecimiento & desarrollo , Heterópteros/fisiología , Animales , Brasil , Producción de Cultivos/métodos , Fragaria/crecimiento & desarrollo , Herbivoria , Dinámica Poblacional

RESUMEN

Electron leakage from dysfunctional respiratory chain and consequent superoxide formation leads to mitochondrial and cell injury during ischemia and reperfusion (IR). In this work we evaluate if the supramolecular assembly of the respiratory complexes into supercomplexes (SCs) is associated with preserved energy efficiency and diminished oxidative stress in post-ischemic hearts treated with the antioxidant N-acetylcysteine (NAC) and the cardioprotective maneuver of Postconditioning (PostC). Hemodynamic variables, infarct size, oxidative stress markers, oxygen consumption and the activity/stability of SCs were compared between groups. We found that mitochondrial oxygen consumption and the activity of respiratory complexes are preserved in mitochondria from reperfused hearts treated with both NAC and PostC. Both treatments contribute to recover the activity of individual complexes. NAC reduced oxidative stress and maintained SCs assemblies containing Complex I, Complex III, Complex IV and the adapter protein SCAFI more effectively than PostC. On the other hand, the activities of CI, CIII and CIV associated to SCs assemblies were preserved by this maneuver, suggesting that the activation of other cardioprotective mechanisms besides oxidative stress contention might participate in maintaining the activity of the mitochondrial respiratory complexes in such superstructures. We conclude that both the monomeric and the SCs assembly of the respiratory chain contribute to the in vivo functionality of the mitochondria. However, although the ROS-induced damage and the consequent increased production of ROS affect the assembly of SCs, other levels of regulation as those induced by PostC, might participate in maintaining the activity of the respiratory complexes in such superstructures.

Asunto(s)

Acetilcisteína/farmacología , Antioxidantes/farmacología , Cardiotónicos/farmacología , Mitocondrias Cardíacas/efectos de los fármacos , Daño por Reperfusión Miocárdica/prevención & control , Animales , Transporte de Electrón/efectos de los fármacos , Complejo I de Transporte de Electrón/genética , Complejo I de Transporte de Electrón/metabolismo , Complejo III de Transporte de Electrones/genética , Complejo III de Transporte de Electrones/metabolismo , Complejo IV de Transporte de Electrones/genética , Complejo IV de Transporte de Electrones/metabolismo , Regulación de la Expresión Génica , Poscondicionamiento Isquémico/métodos , Mitocondrias Cardíacas/enzimología , Membranas Mitocondriales/efectos de los fármacos , Membranas Mitocondriales/enzimología , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/patología , Miocardio/enzimología , Miocardio/patología , Fosforilación Oxidativa/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Ratas , Ratas Wistar

RESUMEN

Introducción: Los programas de cribado prenatal de cromosomopatías requieren un software que permita el cálculo de riesgo. El software suele ser comercial y vinculado al proveedor de los reactivos bioquímicos. Exponemos los resultados del programa desde la implantación de un nuevo software no comercial y de carácter corporativo (siPACAC) y las mejoras en la gestión generadas tras su establecimiento. Material y método: Estudio observacional, retrospectivo efectuado sobre gestantes incluidas en el programa de cribado prenatal de cromosomopatías y estudiadas mediante cribado combinado del 1.ertrimestre durante los años 2013-2014. Se calcula la tasa de detección (TD) y la tasa de falsos positivos (TFP) para cada aneuploidía y para el conjunto de cromosomopatías. Se comparan los resultados con los obtenidos por el software empleado anteriormente (PRISCA). Incluimos el número de técnicas invasivas indicadas, realizadas y revocadas. Resultados: Se realizaron un total de 6.584 cribados. Cobertura del 95%. TD para trisomía 21 del 87% (TFP 3,2%). Para trisomías 18, 13 y síndrome de Turner las TD fueron del 100%. La TD global para todas las aneuploidías fue del 89% (TFP de 3,3%). Fueron indicadas 258 técnicas invasivas (203 efectuadas y 55 revocadas). Conclusión: Los resultados con siPACAC son, por lo menos, equiparables a los de PRISCA (TD 80% con TFP 4,6% para trisomía 21) y cumplen con los estándares de calidad publicados. Las mejoras de gestión incluyen la integración del proceso, la conectividad con otras aplicaciones, la gestión eficaz de incidencias, la independencia del proveedor de reactivos y bases de datos sólidas a nivel de comunidad autónoma. Además de suponer una reducción de técnicas invasivas por menor TFP. Se observa un aumento de revocaciones voluntarias (incremento diagnóstico no invasivo)

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Introduction: Prenatal screening programmes for chromosomal abnormalities require software that allows the calculation of risk. The software is often commercial and linked to the biochemical reagents supplier. We present the results of the programme from the implementation of a new non-commercial, corporate software (siPACAC) and management improvements generated after its introduction. Material and methods: Observational, retrospective study performed on pregnant women included in the Prenatal Screening Programme who underwent 1st trimester combined chromosomal screening during 2013 and 2014. The detection rate (TD) and false positive rate (TFP) for each aneuploidy and for all included chromosomal abnormalities was calculated. The results were compared with those obtained by the previously used software (PRISCA). We include the number of invasive techniques indicated, performed and refused. Results: A total of 6584 prenatal screenings were performed. The programme reached a coverage of 95%. The TD for trisomy 21 was 87% (TFP 3.2%). For trisomy 18, 13 and Turner's syndrome, the TDs were 100%. The overall TD for all aneuploidies was 89% (TFP 3.3%). A total of 258 invasive techniques were indicated (203 performed and 55 refused). Conclusion: SiPACAC's results are at least comparable to those of PRISCA (TD of 80% with a TFP of 4.6% for trisomy 21) and it meets quality standards published. Management improvements involve process integration, connectivity with other applications, effective management of incidents, independence from the reagent supplier, solid databases at autonomous community level, as well as reduction in invasive techniques due to lower TFP and increased voluntary refusals (increase in non-invasive diagnoses)

Asunto(s)

Humanos , Recién Nacido , Pruebas de Detección del Suero Materno/métodos , Trastornos de los Cromosomas/epidemiología , Diagnóstico Prenatal/métodos , Síndrome de Down/diagnóstico , Tamizaje Neonatal/métodos , Evaluación de Eficacia-Efectividad de Intervenciones , Ajuste de Riesgo/métodos , Estudios Retrospectivos

RESUMEN

Introducción. El objetivo del presente trabajo es analizar los incidentes y agresiones ocurridos contra el personal sanitario en el área de acción del Servicio de Prevención Mancomunado de Grupo comparando los resultados de Atención Primaria (AP) con los de Atención Especializada (AE). Material y métodos. Se ha explotado la información disponible en la base de datos de ámbito regional Registro Madrileño de Agresiones y Conflicto Profesional Sanitario entre los años 2009 y 2014 que incluyen un total de 8.056 trabajadores, de los que 1.605 son de AP atendidos por el Servicio de Prevención Mancomunado de Grupo. Resultados. Se han registrado 1.262 incidencias, de las que el 61,2% tuvieron lugar en AE y el 38,8% en AP (32,2 notificaciones/100.000 habitantes o 12,88 incidentes/100 trabajadores en hospitales frente a 168,98 notificaciones/100.000 habitantes o 30,53 incidentes/100 trabajadores en AP). En AE es enfermería la que acumula más agresiones (47,4%), mientras que en AP son los facultativos (53,1%) (p<0,001). En AP el agresor suele ser el paciente (56,9%), mientras que en AE es el familiar o acompañante (45,3%) (p<0,001). Las agresiones en AE ocurren más frecuentemente en Urgencias (35,5%) en comparación con AP, donde el 63,9% ocurren en las consultas (p<0,001). Conclusiones. Aunque es difícil establecer comparaciones con otros estudios previos por las diferencias metodológicas existentes, se observa una mayor incidencia de agresiones en AP en comparación con la AE. Es necesario establecer mejoras en el Registro Madrileño de Agresiones y Conflictos destinadas a optimizar la calidad de los datos y la explotación con fines preventivos (AU)

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Introduction. The aim of this paper is perform an analysis on the incidents and attacks against medical personnel that occurred in the area covered by the Prevention Service Group, comparing the results in Primary Care (PC) with Hospital Care (HC). Material and methods. The information available in the database of the regional Madrid Register of Aggressions Conflict Health Worker between 2009 and 2014 was analysed. This included a total of 8,056 workers, of whom 1,605 were from PC. Results. A total of 1,262 incidents have been reported, of which 61.2% took place in HC and 38.8% in PC (32.2 notifications/100,000 inhabitants, or 12.88 incidents/100 hospital workers compared to 168.98 notifications/100,000 inhabitants, or 30.53 incidents/100 PC workers). Nurses in CP have a higher incidence of assaults (47.4%), while in HC it is the physicians (53.1%) (P<.001). In PC the aggressor is usually the patient (56.9%), while in HC it is the relative or companion (45.3%) (P<.001). HC aggressions occur more frequently in emergency departments (35.5%) compared with 63.9% in PC, where they occur in the consulting room (P<.001). Conclusions. Although it is difficult to make comparisons with previous studies due to methodological differences, a higher incidence of aggression in PC is observed compared with HC. It is necessary to establish improvements in Madrid Register of Aggressions and Conflicts, designed to optimise data quality and use them for preventive purposes (AU)

Asunto(s)

Humanos , Masculino , Femenino , Agresión , Personal de Salud/estadística & datos numéricos , Atención Primaria de Salud , Violencia Laboral/estadística & datos numéricos , 50230 , Conducta Social , Estudios Retrospectivos , Personal de Salud/clasificación , Personal de Salud/estadística & datos numéricos

RESUMEN

Introducción: El análisis de los falsos negativos (FN) detectados en programas de cribado prenatal para trisomía 21 (T21) mediante cribado combinado de primer trimestre (CC1.erT) puede ser una herramienta que ayude a mejorar los resultados finales y la calidad global de dichos programas. El objetivo es evaluar las características de FN para T21 y compararlas con los verdaderos positivos (VP) de nuestro programa. Material y métodos: Estudio retrospectivo (enero del 2005-diciembre del 2012). Se seleccionó a los CC1.erT con resultado VP o FN para T21, excluyéndose gestaciones múltiples. Edad y peso materno, edad gestacional (momento de extracción), medida de translucencia nucal (TN) en milímetros y múltiplos de mediana (MoM), concentración sérica y MoM corregido de β-HCG libre y PAPP-A y riesgo bioquímico fueron las variables analizadas. Análisis estadístico con el programa SPSS(R) 22. Resultados: En los FN las medianas para la edad materna, la TN (milímetros y MoM) y el riesgo bioquímico fueron menores, mientras que el peso materno fue superior, siendo todas estas diferencias estadísticamente significativas. En el resto de las variables no se encontró diferencia significativa. Conclusiones: La aparición de FN es multifactorial. Dadas las diferencias significativas encontradas en peso materno y TN, así como la significación límite en las diferencias del MoM de PAPP-A, es esencial disponer del peso correcto en el momento de la extracción y sobre todo asegurar la calidad en las medidas de TN y PAPP-A. La edad materna determina el riesgo previo, condicionando el resultado final, es significativo que nuestros FN aparezcan en gestantes más jóvenes

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Introduction: Analysis of false negatives (FN) detected in Prenatal Screening Programme for trisomy 21 (T21) by First Trimester Combined Screening (CC1°T) could be a tool to help improve the final results and the overall quality of these programmes. The objective is to evaluate the characteristics of the FN cases for T21 and compare them with the true positives (TP). Material and methods: A retrospective study (January 2005 - December 2012). FN and TP results for CC1°T were selected, excluding multiple gestations. The analyzed variables were maternal age and weight, gestational age (at the time of biochemical testing), nuchal translucency (NT) measurement in millimeters and in Multiples of Medians (MoM), serum concentrations and corrected MoM of free β-HCG and PAPP-A and biochemical risk. Statistical analysis was carried out with SPSS(R)22 software. Results: Median maternal age, median NT (in millimeters and in MoM) and median biochemical risk were lower in FN cases, however, maternal weight was higher, all these differences were statistically significant. We did not find significant differences in the rest of variables. Conclusions: The occurrence of FN is caused by multiple factors. We found significant differences in maternal weight and NT, as well as borderline significance in differences of MoM of PAPP-A, therefore, it is essential to use the correct weight at the time of biochemical testing and, most important, ensure the quality of NT and PAPP-A measurement. Maternal age determines the previous risk and final result; so it is significant that our FN cases appeared in younger pregnant

Asunto(s)

Humanos , Diagnóstico Prenatal/métodos , Síndrome de Down/diagnóstico , Ultrasonografía Prenatal , Reacciones Falso Negativas , Sensibilidad y Especificidad , Tamizaje Masivo/métodos , Estudios Retrospectivos , Mejoramiento de la Calidad

RESUMEN

INTRODUCTION: The aim of this paper is perform an analysis on the incidents and attacks against medical personnel that occurred in the area covered by the Prevention Service Group, comparing the results in Primary Care (PC) with Hospital Care (HC). MATERIAL AND METHODS: The information available in the database of the regional Madrid Register of Aggressions Conflict Health Worker between 2009 and 2014 was analysed. This included a total of 8,056 workers, of whom 1,605 were from PC. RESULTS: A total of 1,262 incidents have been reported, of which 61.2% took place in HC and 38.8% in PC (32.2 notifications/100,000 inhabitants, or 12.88 incidents/100 hospital workers compared to 168.98 notifications/100,000 inhabitants, or 30.53 incidents/100 PC workers). Nurses in CP have a higher incidence of assaults (47.4%), while in HC it is the physicians (53.1%) (P<.001). In PC the aggressor is usually the patient (56.9%), while in HC it is the relative or companion (45.3%) (P<.001). HC aggressions occur more frequently in emergency departments (35.5%) compared with 63.9% in PC, where they occur in the consulting room (P<.001). CONCLUSIONS: Although it is difficult to make comparisons with previous studies due to methodological differences, a higher incidence of aggression in PC is observed compared with HC. It is necessary to establish improvements in Madrid Register of Aggressions and Conflicts, designed to optimise data quality and use them for preventive purposes.

Asunto(s)

Agresión , Personal de Salud/estadística & datos numéricos , Violencia Laboral/estadística & datos numéricos , Adulto , Bases de Datos como Asunto , Servicio de Urgencia en Hospital , Femenino , Hospitales/estadística & datos numéricos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Atención Primaria de Salud/estadística & datos numéricos , España

RESUMEN

Our aim was to evaluate the killer cell immunoglobulin-like receptors (KIRs) as a marker for the development of thrombocytopenia secondary to Peg-interferon (IFN) therapy in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients. Patients were naive to HCV treatment, receiving a first course of Peg-IFN/Ribavirin combination therapy. Total platelet count (cells ml-1) was determined at each visit, determining platelet decline from baseline to weeks 1, 2, 4, 8 and 12 after starting therapy. The end point of the study was development of thrombocytopenia, defined as a platelet count of <1 50 000 cells ml-1. Fifty-eight HIV/HCV co-infected patients were included in the study, of whom 20 (34.4%) developed thrombocytopenia. The absence of KIR2DS2 was associated with higher and faster rate of thrombocytopenia (54.2% vs 22.5%; P=0.012; 6.6 vs 10.3 weeks; P=0.008). The absence of KIR2DS2 was associated with a greater decline in platelet count and development of thrombocytopenia during Peg-IFN treatment in HIV/HCV co-infected patients.

Asunto(s)

Interferón-alfa/uso terapéutico , Receptores KIR/metabolismo , Trombocitopenia/tratamiento farmacológico , Trombocitopenia/metabolismo , Adulto , Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Coinfección/metabolismo , Quimioterapia Combinada/métodos , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/metabolismo , Humanos , Masculino , Recuento de Plaquetas/métodos , Ribavirina/uso terapéutico

RESUMEN

Ceramide accumulation in mitochondria has been associated with reperfusion damage, but the underlying mechanisms are not clearly elucidated. In this work we investigate the role of sphingomyelinases in mitochondrial ceramide accumulation, its effect on reactive oxygen species production, as well as on mitochondrial function by using the sphingomyelinase inhibitor, tricyclodecan-9-yl-xanthogenate (D609). Correlation between neutral sphingomyelinase (nSMase) activity and changes in ceramide content were performed in whole tissue and in isolated mitochondria from reperfused hearts. Overall results demonstrated that D609 treatment attenuates cardiac dysfuncion, mitochondrial injury and oxidative stress. Ceramide was accumulated in mitochondria, but not in the microsomal fraction of the ischemic-reperfused (I/R) group. In close association, the activity of nSMase increased, whereas glutathione (GSH) levels diminished in mitochondria after reperfusion. On the other hand, reduction of ceramide levels in mitochondria from I/R+D609 hearts correlated with diminished nSMase activity, coupling of oxidative phosphorylation and with mitochondrial integrity maintenance. These results suggest that mitochondrial nSMase activity contributes to compartmentation and further accumulation of ceramide in mitochondria, deregulating their function during reperfusion.

Asunto(s)

Ceramidas/metabolismo , Mitocondrias Cardíacas/metabolismo , Proteínas Mitocondriales/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Fosforilación Oxidativa , Esfingomielina Fosfodiesterasa/metabolismo , Animales , Hidrocarburos Aromáticos con Puentes/farmacología , Glutatión/metabolismo , Proteínas Mitocondriales/antagonistas & inhibidores , Daño por Reperfusión Miocárdica/patología , Norbornanos , Ratas , Esfingomielina Fosfodiesterasa/antagonistas & inhibidores , Tiocarbamatos , Tionas/farmacología

RESUMEN

We analysed the efficacy and safety of switching from a regimen based on nonnucleoside reverse transcriptase inhibitors (NNRTI) or integrase inhibitors (INI) to ABC/3TC + RPV in virologically suppressed HIV-infected patients. This multicentre, retrospective study comprised asymptomatic HIV-infected patients who switched from 2 NRTI + NNRTI or 2 NRTI + INI to ABC/3TC + RPV between February 2013 and December 2013; all had undetectable HIV viral load prior to switching. Efficacy and safety, and changes in lipids and cardiovascular risk (CVR) were analysed at 48 weeks. Of 85 patients (74.1 % men, mean age 49.5 years), 83 (97.6 %) switched from a regimen based on NNRTI (EFV 74, RPV 5, ETV 2, NVP 2), and 45 (53 %) switched from TDF/FTC to ABC/3TC. The main reasons for switching were toxicity (58.8 %) and convenience (29.4 %). At 48 weeks, 78 (91.8 %) patients continued taking the same regimen; efficacy was 88 % by intention to treat, and 96 % by per protocol. Two patients were lost to follow-up and five ceased the new regimen (4 due to adverse effects and 1 virologic failure). Mean CD4 cell counts increased (744 vs. 885 cells/µL; p = 0.0001), and there were mean decreases in fasting total cholesterol (-15.9 mg/dL; p < 0.0001) and LDL-cholesterol (-11.0 mg/dL; p < 0.004), with no changes in HDL-cholesterol, triglycerides, total cholesterol:HDL-cholesterol ratio, and CVR. ABC/3TC + RPV is effective and safe in virologically-suppressed patients on antiretroviral therapy (ART). Forty-eight weeks after switching the lipid profile improved with decreases in total and LDL cholesterol.

Asunto(s)

Fármacos Anti-VIH/uso terapéutico , Didesoxinucleósidos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Lamivudine/uso terapéutico , Rilpivirina/uso terapéutico , Adulto , Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Didesoxinucleósidos/efectos adversos , Combinación de Medicamentos , Sustitución de Medicamentos , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/transmisión , Humanos , Lamivudine/efectos adversos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Rilpivirina/efectos adversos , Resultado del Tratamiento , Carga Viral

RESUMEN

Increased dosage of methyl-CpG-binding protein-2 (MeCP2) results in a dramatic neurodevelopmental phenotype with onset at birth. We generated induced pluripotent stem cells (iPSCs) from patients with the MECP2 duplication syndrome (MECP2dup), carrying different duplication sizes, to study the impact of increased MeCP2 dosage in human neurons. We show that cortical neurons derived from these different MECP2dup iPSC lines have increased synaptogenesis and dendritic complexity. In addition, using multi-electrodes arrays, we show that neuronal network synchronization was altered in MECP2dup-derived neurons. Given MeCP2 functions at the epigenetic level, we tested whether these alterations were reversible using a library of compounds with defined activity on epigenetic pathways. One histone deacetylase inhibitor, NCH-51, was validated as a potential clinical candidate. Interestingly, this compound has never been considered before as a therapeutic alternative for neurological disorders. Our model recapitulates early stages of the human MECP2 duplication syndrome and represents a promising cellular tool to facilitate therapeutic drug screening for severe neurodevelopmental disorders.

Asunto(s)

Proteína 2 de Unión a Metil-CpG/genética , Proteína 2 de Unión a Metil-CpG/fisiología , Red Nerviosa/metabolismo , Diferenciación Celular , Dendritas/metabolismo , Dosificación de Gen/fisiología , Duplicación de Gen/genética , Estudios de Asociación Genética , Humanos , Células Madre Pluripotentes Inducidas , Masculino , Neurogénesis , Neuronas

RESUMEN

Fitness of a single species is often measured in terms of the number of viable offspring produced. We explore the relationship between the number of ovarioles and the size of females in five species of Simuliidae in two páramo regions of Colombia. Individuals of seven species of female blackflies that landed on animals were collected from mules in the Ucumarí Regional Park (RPNU) and from cattle in the Chingaza Natural National Park (ChNNP). The ovarioles of the five most abundant species were dissected out and counted, and a one-factor ANOVA was performed to explore differences in the mean number of ovarioles produced by different female size categories. Simulium ignescens Roubaud and S. ignescens-like species were collected in RPNU and S. ignescens, Simulium muiscorum Bueno et al, Simulium cormonsi Wygodzinsky and Simulium pautense Coscarón & Takaoka, in ChNNP. In addition, we also analyzed the Pearson product-moment correlation between the mean number of ovarioles per blackfly and female size within species using those which more than 20 individuals were collected. Ovarioles were meroistic-polytrophic type. A multiple range test (least significant difference) indicated that the largest size group had the largest mean number of ovarioles per female. In the other size groups, there were approximately equal numbers of ovarioles per female. Pearson's correlation coefficient was separately measured and indicated a 50% correlation between female size and ovariole number in S. ignescens. Although ovariole number is probably a genetically driven feature, other environmental and physiological conditions, including infections, can influence the number of eggs.

Asunto(s)

Simuliidae/anatomía & histología , Estructuras Animales/anatomía & histología , Animales , Tamaño Corporal , Colombia , Femenino , Geografía

RESUMEN

PURPOSE: Hepatitis C virus (HCV) viral relapse (VR) after end-of-treatment response (ETR) in human immunodeficiency virus (HIV) co-infected patients is observed in as many as one in three co-infected patients. The aim of the study was to identify baseline risk factors for VR in HIV/HCV co-infected patients treated with pegylated interferon plus ribavirin (PEG-INF/RBV). METHODS: A total of 212 Caucasian HIV-infected patients with chronic hepatitis C naïve for PEG-INF/RBV were followed prospectively. Patients were included in this prospective study if they had completed a full course of therapy with an ETR. We assessed the relationship between VR rate and potential predictors of relapse. RESULTS: Of the patients followed, 130 (61.3 %) attained ETR and 103 (79.2 %) achieved sustained virological response (SVR). Consequently, 27 (20.8 %) showed VR. Patients who relapsed were more often male (p = 0.036), carried the non-CC rs14158 genotype in the low-density lipoprotein receptor (LDLr) gene (p = 0.039), had higher baseline HCV RNA levels (p = 0.012), body mass index (BMI) ≥ 25 kg/m(2) (p = 0.034), significant liver fibrosis (p < 0.001), had been diagnosed with acquired immunodeficiency syndrome (AIDS)-defining criteria in the past (p = 0.001) and bore the HCV genotypes 1/4 (p = 0.046) when compared with SVR patients. The IL28B genotype was not associated with relapse. Multivariate binary logistic regression showed that high baseline HCV RNA, significant liver fibrosis, HCV genotypes 1/4, being overweight and being diagnosed with AIDS-defining criteria in the past were independently associated with relapse. CONCLUSIONS: Our study shows that VR can be accurately predicted in HIV/HCV co-infected patients on the basis of risk factors which can be identified before treatment.

Asunto(s)

Antivirales/uso terapéutico , Coinfección , Infecciones por VIH , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Quimioterapia Combinada , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Hepacivirus/genética , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Recurrencia , Factores de Riesgo , Resultado del Tratamiento , Carga Viral