Adrenalectomía laparoscópica bilateral sincrónica: técnica quirúrgica y resultados perioperatorios en 13 años de experiencia / Synchronous bilateral laparoscopic adrenalectomy: Surgical technique and perioperative results of a 13-years’ experience

Introducción y objetivos: La cirugía laparoscópica se ha convertido en el abordaje estándar para el tratamiento de las glándulas suprarrenales. Debido a que la adrenalectomía bilateral sincrónica no se realiza con frecuencia, la evidencia sobre este procedimiento es limitada. Nuestro objetivo es reportar nuestra experiencia de 13 años con la adrenalectomía bilateral laparoscópica sincrónica, evaluando su viabilidad, seguridad y resultados perioperatorios.Pacientes y métodos: Un total de 23 pacientes consecutivos sometidos a adrenalectomía laparoscópica bilateral sincrónica entre 2007 y 2020 en un único centro académico fueron incluidos en el estudio. Las variables evaluadas fueron el tiempo quirúrgico, la pérdida media estimada de sangre, la conversión a cirugía abierta, las complicaciones postoperatorias, la mortalidad y la duración de la estancia postoperatoria.Resultados: El tiempo operatorio medio fue de 189,3±48,9min. La media de pérdida de sangre estimada fue de 163,0±201,3ml. No hubo conversiones a cirugía abierta. Cinco pacientes tuvieron complicaciones postoperatorias y 3 de estas fueron graves. Ningún paciente falleció durante el periodo perioperatorio. La mediana del tiempo de estancia postoperatoria fue de 3 días (rango 1-30). En el análisis patológico 15 pacientes tenían hiperplasia suprarrenal bilateral, 2 hiperplasia suprarrenal unilateral y un tumor benigno contralateral, uno hiperplasia suprarrenal unilateral y glándula contralateral normal, otro adenoma unilateral, 3 feocromocitomas bilaterales y uno mielolipoma bilateral.Conclusión: La adrenalectomía laparoscópica bilateral sincrónica es una técnica factible y segura. Se requiere un equipo multidisciplinar y experimentado que incluya anestesistas y endocrinólogos. (AU)

Introduction and objectives: Laparoscopic surgery is the standard approach for the treatment of adrenal glands. Bilateral synchronous adrenalectomy is rarely performed, and evidence about this procedure is limited. Our objective is to report our 13-year experience with synchronous laparoscopic bilateral adrenalectomy, evaluating its feasibility, safety, and perioperative outcomes.Patients and methods: A total of 23 consecutive patients undergoing synchronous bilateral laparoscopic adrenalectomy between 2007 and 2020 in a single academic center were included. Variables evaluated were operative time, estimated blood loss, conversion to open surgery, postoperative complications, mortality, and postoperative length of stay.Results: Mean operative time was 189.3±48.9min. Mean estimated blood loss was 163.0±201.3ml. There were no conversions to open surgery. Five patients had postoperative complications, three of those were major. No patient died in the perioperative period. Median postoperative length of stay was three days (range 1-30). At pathology analysis, 15 patients had bilateral adrenal hyperplasia, 2 unilateral adrenal hyperplasia and a contralateral benign tumor, 1 unilateral adrenal hyperplasia and a normal contralateral gland, 1 unilateral adenoma, 3 bilateral pheochromocytomas and 1 bilateral myelolipoma.Conclusion: Synchronous bilateral laparoscopic adrenalectomy is a feasible and safe technique. A multidisciplinary and experienced team involving anesthesiologists and endocrinologists is required. (AU)

Synchronous bilateral laparoscopic adrenalectomy: Surgical technique and perioperative results of a 13-years' experience.

INTRODUCTION AND OBJECTIVES: Laparoscopic surgery is the standard approach for the treatment of adrenal glands. Bilateral synchronous adrenalectomy is rarely performed, and evidence about this procedure is limited. Our objective is to report our 13-year experience with synchronous laparoscopic bilateral adrenalectomy, evaluating its feasibility, safety, and perioperative outcomes. PATIENTS AND METHODS: A total of 23 consecutive patients undergoing synchronous bilateral laparoscopic adrenalectomy between 2007 and 2020 in a single academic center were included. Variables evaluated were operative time, estimated blood loss, conversion to open surgery, postoperative complications, mortality, and postoperative length of stay. RESULTS: Mean operative time was 189.3 ±â€¯48.9 min. Mean estimated blood loss was 163.0 ±â€¯201.3 mL. There were no conversions to open surgery. Five patients had postoperative complications, three of those were major. No patient died in the perioperative period. Median postoperative length of stay was three days (range 1-30). At pathology analysis, 15 patients had bilateral adrenal hyperplasia, 2 unilateral adrenal hyperplasia and a contralateral benign tumor, 1 unilateral adrenal hyperplasia and a normal contralateral gland, 1 unilateral adenoma, 3 bilateral pheochromocytomas and 1 bilateral myelolipoma. CONCLUSION: Synchronous bilateral laparoscopic adrenalectomy is a feasible and safe technique. A multidisciplinary and experienced team involving anesthesiologists and endocrinologists is required.

Present and future of Spanish Military Telemedicine / Presente y futuro de la Telemedicina Militar Española. 25 años de la Unidad de Telemedicina en el Hospital Central de la Defensa «Gómez Ulla»

Telemedicine consists of the exchange of health information between healthcare professionals, and between healthcare professionals and patients, through the use of information and communications technologies (ICT). It is already considered an emerging technology in what is commonly called the «Productivity Plateau». It is also probably an exponential growth technology, in which the «trigger» for such growth will be a mixture of new technologies such as portable sensors/ wearables that detect multiple patient data (Blood Pressure, Heart Rate, Respiratory Rate, Glycaemia, Temperature, etc.), better communications (5G), augmented and mixed reality (augmented and virtual), artificial intelligence systems to improve diagnosis, etc. In Spain, Military Telemedicine is a pioneer in the field. The main mission is to provide remote health support to health professionals or military personnel deployed in Operations and remote or difficult-to-access locations. In 2021 the Spanish Telemedicine Unit at Central Defense Hospital «Gómez Ulla» will celebrate its 25Th anniversary. This article discusses the aforementioned aspects of telemedicine as an emerging technology and describes the current mission, organization and capabilities of Spanish military telemedicine, as well as its future

La Telemedicina consiste en el intercambio de información sanitaria entre profesionales sanitarios, o entre profesional sanitario y paciente, mediante el uso de las tecnologías de la información y comunicaciones (TIC). Se considera ya una tecnología emergente en el denominado «Plateau de productividad». Probablemente se trate de una tecnología de crecimiento exponencial, en la cual el «gatillo» para dicho crecimiento será una mezcla de diferentes tecnologías, como nuevos sensores portátiles que detecten múltiples datos de los pacientes (Tensión Arterial, Frecuencia cardiaca, Frecuencia respiratoria, Glucemia, Temperatura, etc), mejores comunicaciones (5G), realidad aumentada y mixta (aumentada y virtual), sistemas de inteligencia artificial para ayuda al diagnóstico, etc. En España, la Telemedicina Militar es pionera en este campo. Su misión fundamental es el apoyo y asesoramiento sanitario a distancia a personal sanitario y también no sanitario, tanto en Zona de Operaciones (ZO) como en situación de aislamiento y/o localización remota. En 2021 el Servicio de Telemedicina del Hospital Central de la Defensa «Gomez Ulla» celebrará su 25 aniversario. En el artículo se tratan los mencionados aspectos acerca de la Telemedicina como tecnología emergente y se describe la misión, organización y capacidades actuales de la Telemedicina Militar Española, así como sus perspectivas de futuro

Effect of supplementation with vitamins D3 and K2 on undercarboxylated osteocalcin and insulin serum levels in patients with type 2 diabetes mellitus: a randomized, double-blind, clinical trial.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are characterized by chronic hyperglycemia as a consequence of decreased insulin sensitivity, which contributes to bone demineralization and could also be related to changes in serum levels of osteocalcin and insulin, particularly when coupled with a deficiency in the daily consumption of vitamins D3 and K2. The objective of this study was to evaluate the effect of vitamin D3 and vitamin K2 supplements alone or in combination on osteocalcin levels and metabolic parameters in patients with T2DM. METHODS: A double-blind, randomized clinical trial was carried out in 40 patients aged between 30 and 70 years old for 3 months. Clinical and laboratory assessment was carried out at the beginning and at the end of the treatment. The patients were divided into three groups: (a) 1000 IU vitamin D3 + a calcinated magnesium placebo (n = 16), (b) 100 µg of Vitamin K2 + a calcinated magnesium placebo (n = 12), and (c) 1000 IU vitamin D3 + 100 µg vitamin K2 (n = 12). RESULTS: After treatment in the total studied population, a significant decrease in glycemia (p = 0.001), HOMA-IR (Homeostatic model assessment-insulin resistance) (p = 0.040), percentage of pancreatic beta cells (p < 0.001), uOC/cOC index and diastolic blood pressure (p = 0.030) were observed; in vitamin D3 group, differences in serum undercarboxylated osteocalcin (p = 0.026), undercarboxylated to carboxylated osteocalcin index (uOC/cOC) (p = 0.039) glucose (p < 0.001) and  % of functional pancreatic beta cells (p < 0.001) were demonstrated. In vitamin K2 group a significant decrease in glycemia (p = 0.002), HOMA-IR (p = 0.041), percentage of pancreatic beta cells (p = 0.002), and in cOC (p = 0.041) were observed, conversely cOC concentration was found high. Finally, in the vitamins D3 + K2 a significant decrease in glycemia (p = 0.002), percentage of pancreatic beta cells (p = 0.004), and in the uOC/cOC index (p = 0.023) were observed. CONCLUSION: Individual or combined supplementation with vitamins D3 and K2 significantly decreases the glucose levels and  % of functional pancreatic beta cells, while D3 and D3 + K2 treatments also induced a reduction in the uOC/cOC index. Only in the group with vitamin D3 supplementation, it was observed a reduction in undercarboxylated osteocalcin while vitamin K2 increased the carboxylated osteocalcin levels.Trial registration NCT04041492.

Multiplex polymerase chain reaction in combination with gel electrophoresis-inductively coupled plasma mass spectrometry: A powerful tool for the determination of gene copy number variations and gene expression changes.

During the last few years multiplex real-time or quantitative polymerase chain reaction PCR (qPCR) has become the method of choice for multiplex gene expression changes and gene copy number variations (CNVs) analysis. However, such determinations require the use of different fluorescent labels for the different amplified sequences, which increases significantly the costs of the analysis and limits the applicability of the technique for simultaneous amplification of many targets of interest in a single reaction. In this regard, the use of the coupling between gel electrophoresis (GE) separation with inductively coupled plasma mass spectrometry (ICP-MS) detection allows the label-free determination of multiplex PCR-amplified sequences (amplicons) by monitoring the P present in the DNA backbone. The quantitative dimension is obtained since under optimal and controlled multiplex PCR conditions the peak areas of the separated amplicons are directly proportional to the amount of DNA template in the original sample. Moreover, the calibration of the GE-ICP-MS system with a DNA ladder permits direct estimation of the size (bp) of the PCR products. The suitability of the proposed multiplex strategy has been evaluated addressing two different situations: determination of CNVs and gene expression changes in human ovarian cancer cells. In the first case, the results obtained for the simultaneous quantitation of CNVs of four genes (HER2, CCNE1, GSTM1, ACTB) on DNA obtained from OVCAR-3 cells were in accordance with the literature data, and also with the results obtained by conventional simplex qPCR. In the second case, multiplex gene expression changes of BAX, ERCC1 and CTR1 genes, using ACTB as constitutive gene, on A2780cis respect to A2780 cells, resistant and sensitive to cisplatin, respectively, provided the same information as single reaction reverse transcription (RT)-qPCR.

Genotoxic evaluation of poly(anhydride) nanoparticles in the gastrointestinal tract of mice.

Gantrez® AN 119-based NPs have been developed as oral drug carriers due to their strong bioadhesive interaction with components of the gastrointestinal mucosa and to their adaptable surface. The use of mannosamine to coat Gantrez® AN 119-based NPs results in a high mucus-permeable carrier, able to reach the gastrointestinal epithelium. Although their efficacy to transport a therapeutic agent has been demonstrated, their safety has not yet been thoroughly studied. They have proved to be non-cytotoxic, non-genotoxic and non-mutagenic in vitro; however, the in vivo toxicity profile has not yet been determined. In this study, the in vivo genotoxic potential of Gantrez® AN 119 NPs coated with mannosamine (GN-MA-NP) has been assessed using the in vivo comet assay in combination with the enzyme formamidopyrimidine DNA glycosylase in mice, following the OECD test guideline 489. To determine the relevant organs to analyse and the sampling times, an in vivo biodistribution study was also carried out. Results showed a statistically significant induction of DNA strand breaks and oxidized bases in the duodenum of animals exposed to 2000 mg/kg bw. However, this effect was not observed at lower doses (i.e. 500 and 1000 mg/kg which are closer to the potential therapeutic doses) or in other organs. In conclusion, GN-MA-NP are promising nanocarriers as oral drug delivery systems.

In vitro evaluation of the genotoxicity of poly(anhydride) nanoparticles designed for oral drug delivery.

In the last years, the development of nanomaterials has significantly increased due to the immense variety of potential applications in technological sectors, such as medicine, pharmacy and food safety. Focusing on the nanodevices for oral drug delivery, poly(anhydride) nanoparticles have received extensive attention due to their unique properties, such as their capability to develop intense adhesive interactions within the gut mucosa, their modifiable surface and their biodegradable and easy-to-produce profile. However, current knowledge of the possible adverse health effects as well as, toxicological information, is still exceedingly limited. Thus, we investigated the capacity of two poly(anhydride) nanoparticles, Gantrez® AN 119-NP (GN-NP) and Gantrez® AN 119 covered with mannosamine (GN-MA-NP), and their main bulk material (Gantrez® AN 119-Polymer), to induce DNA damage and thymidine kinase (TK+/-) mutations in L5178Y TK+/- mouse lymphoma cells after 24h of exposure. The results showed that GN-NP, GN-MA-NP and their polymer did not induce DNA strand breaks or oxidative damage at concentrations ranging from 7.4 to 600µg/mL. Besides, the mutagenic potential of these nanoparticles and their polymer revealed no significant or biologically relevant gene mutation induction at concentrations up to 600µg/mL under our experimental settings. Considering the non-genotoxic effects of GN-NP and GN-MA-NP, as well as their exceptional properties, these nanoparticles are promising nanocarriers for oral medical administrations.

Evaluation of the cytotoxicity, genotoxicity and mucus permeation capacity of several surface modified poly(anhydride) nanoparticles designed for oral drug delivery.

The main concerns with drugs designed for oral administration are their inactivation or degradation in the harsh conditions of the gastrointestinal tract, their poor solubility through the gastrointestinal mucus gel layer, the poor intestinal epithelium permeability that limits their absorption, and their toxicity. In this context, poly(anhydride) nanoparticles are capable of protecting the drug from the harsh environment, reduce the drug's toxicity and, by virtue of surface modification, to enhance or reduce their mucus permeability and the bioadhesion to specific target cells. The copolymer between methyl vinyl ether and maleic anhydride (commercialized as Gantrez® AN 119) are part of the poly(anhydride) nanoparticles. These biocompatible and biodegradable nanoparticles (NPs) can be modified by using different ligands. Their usefulness as drug carriers and their bioadhesion with components of the intestinal mucosa have been described. However, their toxicity, genotoxicity and mucus permeation capacity has not been thoroughly studied. The aim of this work was to evaluate and compare the in vitro toxicity, cell viability and in vitro genotoxicity of the bioadhesive empty Gantrez® AN 119 NPs modified with dextran, aminodextran, 2-hydroxypropyl-ß-cyclodextrin, mannosamine and poly-ethylene glycol of different molecular weights. Results showed that, in general, coated NPs exhibit better mucus permeability than the bare ones, those coated with mannosamine being the most permeable ones. The NPs studied did not affect cell metabolism, membrane integrity or viability of Caco-2 cells at the different conditions tested. Moreover, they did not induce a relevant level of DNA strand breaks and FPG-sensitive sites (as detected with the comet assay).

Development of a neuroprotective peptide that preserves survival pathways by preventing Kidins220/ARMS calpain processing induced by excitotoxicity.

Kinase D-interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS), has a central role in the coordination of receptor crosstalk and the integration of signaling pathways essential for neuronal differentiation, survival and function. This protein is a shared downstream effector for neurotrophin- and ephrin-receptors signaling that also interacts with the N-methyl-d-aspartate type of glutamate receptors (NMDARs). Failures in neurotrophic support and glutamate signaling are involved in pathologies related to excitotoxicity and/or neurodegeneration, where different components of these dynamic protein complexes result altered by a combination of mechanisms. In the case of Kidins220/ARMS, overactivation of NMDARs in excitotoxicity and cerebral ischemia triggers its downregulation, which contributes to neuronal death. This key role in neuronal life/death decisions encouraged us to investigate Kidins220/ARMS as a novel therapeutic target for neuroprotection. As the main mechanism of Kidins220/ARMS downregulation in excitotoxicity is proteolysis by calpain, we decided to develop cell-penetrating peptides (CPPs) that could result in neuroprotection by interference of this processing. To this aim, we first analyzed in detail Kidins220/ARMS cleavage produced in vitro and in vivo, identifying a major calpain processing site in its C-terminal region (between amino acids 1669 and 1670) within a sequence motif highly conserved in vertebrates. Then, we designed a 25-amino acids CPP (Tat-K) containing a short Kidins220/ARMS sequence enclosing the identified calpain site (amino acids 1668-1681) fused to the HIV-1 Tat protein basic domain, able to confer membrane permeability to attached cargoes. Transduction of cortical neurons with Tat-K reduced Kidins220/ARMS calpain processing in a dose- and time-dependent manner upon excitotoxic damage and allowed preservation of the activity of pERK1/2 and pCREB, signaling molecules central to neuronal survival and functioning. Importantly, these effects were associated to a significant increase in neuronal viability. This Kidins220/ARMS-derived peptide merits further research to develop novel neuroprotective therapies for excitotoxicity-associated pathologies.

Toxicity evaluation of nanocarriers for the oral delivery of macromolecular drugs.

Oral administration is the most commonly used and accepted route for drug administration. However, two of the main concerns are the poor intestinal epithelium permeability and rapid degradation, which limit absorption of drugs. In this context, nanocarriers have shown great potential for oral drug delivery. Nevertheless, special importance should be given to the possible toxic effect of these nanocarriers, such as their bioaccumulation in different tissues of the body, as well as, the different physicochemical parameters influencing their properties and so their potential toxic effect. This review describes first some aspects related to the behavior of nanosystems within the gastrointestinal tract and then some aspects of nanotoxicology and its evaluation, including the most popular techniques and approaches used for in vitro and in vivo toxicity studies. It also reviews the physicochemical characteristics of polymeric nanoparticles that may influence the development of toxicological effects, and finally it summarizes the toxicity results that have been published regarding polymeric nanocarriers.

Colaboración multidisciplinaria en el tratamiento de un niño de 5 años de edad con desnutrición / Multidisciplinary colaboration in the treatment of a 5 year old boy with malnutrition

Objetivo: El presente artículo describe el tratamiento multidisciplinario de un niño de 5 años de edad con desnutrición, alimentación selectiva, inapetencia e hiperrespuesta a los estí- mulos orales y táctiles. Se utilizó una intervención basada en una estrecha colaboración entre un pediatra, una dietetistanutricionista y una terapeuta ocupacional para afrontar el problema de alimentación. Se presenta una descripción de los 4 meses y medio de tratamiento y 2 meses de seguimiento. Método: Se analizaron las entrevistas con la familia y las notas de evolución en pediatría, nutrición y terapia ocupacional. Se presenta la progresión hacia los objetivos nutricionales, de aceptación de alimentos y de participación activa en el proceso de alimentación. Resultados: La normalización del estado nutricional se documenta mediante el seguimiento del índice de masa corporal y de datos antropométricos por parte del pediatra y de la nutricionista. La mejora en la participación en las comidas y en la aceptación de una mayor cantidad y variedad de alimentos se documenta mediante entrevistas con los padres y observaciones directas en las sesiones de terapia ocupacional. La mejora en las respuestas al estímulo oral y táctil se documenta mediante un cuestionario estandarizado (Sensory Profile). Conclusión: Este caso clínico contribuye a la evidencia existente sobre la utilización de un enfoque multidisciplinario en los casos de niños con desnutrición y rechazo a la alimentación. La consideración de problemas sensoriales como factor subyacente al problema de alimentación ha sido clave en la mejoría nutricional de este niño. Asimismo, este caso clínico contribuye a la evidencia sobre el uso de la terapia ocupacional basada en el enfoque de la integración sensorial de la Dra. Ayres para abordar la relación entre el procesamiento sensorial, la conducta y el desempeño ocupacional (AU)

Objective: This article describes the multidisciplinary treatment of a 5 year old child with malnutrition, selective feeding, lack of appetite and sensory over-responsiveness to oral and tactile stimuli. An intervention based on a close collaboration between a pediatrician, a dietician-nutritionist and an occupational therapist was used to treat the feeding problem. A description of the 4 and half months of treatment and a 2 month follow-up is presented. Methods: Interviews with the family and pediatric, nutrition and occupational therapy progress notes are analyzed. Progress towards nutritional objectives, acceptance of food and active participation in the feeding process is presented. Results: The normalization of the nutritional status is documented through monitoring of body mass and anthropometric data by the pediatrician and nutritionist. Improvement in meal participation and acceptance of a greater amount and variety of foods is documented through interviews with parents and direct observations in the occupational therapy sessions. The improvement in oral and tactile sensory reactivity is documented using a standardized questionnaire (Sensory Profile). Conclusion: This clinical case report contributes to the existing evidence on the use of a multidisciplinary approach in the treatment of children with malnutrition and refusal to feed. Consideration of sensory issues as an underlying factor to the feeding problem has been instrumental in the nutritional improvement of this child. This clinical case also contributes to the evidence on the use of occupational therapy based on Dr. Ayres sensory integration approach in addressing the relationship between (AU)

Separating the contributions of the volume change upon mixing, permittivity contrast and molecular interactions in the excess relative permittivity of liquid mixtures.

The excess relative permittivity of binary systems is separated into three parts. The excess molar volume is the basis for estimating the volume-change contribution. It is proposed to evaluate the electrical permittivity of liquid mixtures, which is solely due to the composition and the relative permittivities of pure components, named permittivity contrast contribution, using the classic local field approach in the case of point-dipoles contained in Lorentz's spherical cavities embedded in the corresponding ideal mixture. The effect of molecular interactions is simply estimated by the difference required to make up experimental excess relative permittivities. This analysis has been applied to 16 binary aqueous organic and organic-organic systems and the estimated values for the contribution of molecular interactions provide interesting insights into the molecular arrangement of these liquid mixtures and the suitability of solvents for determining solute dipole moments.

Life in the unthinking depths: energetic constraints on encephalization in marine fishes.

Several hypotheses have been proposed to explain the limitation of brain size in vertebrates. Here, we test three hypotheses of brain size evolution using marine teleost fishes: the direct metabolic constraints hypothesis (DMCH), the expensive tissue hypothesis and the temperature-dependent hypothesis. Our analyses indicate that there is a robust positive correlation between encephalization and basal metabolic rate (BMR) that spans the full range of depths occupied by teleosts from the epipelagic (< 200 m), mesopelagic (200-1000 m) and bathypelagic (> 4000 m). Our results disentangle the effects of temperature and metabolic rate on teleost brain size evolution, supporting the DMCH. Our results agree with previous findings that teleost brain size decreases with depth; however, we also recover a negative correlation between trophic level and encephalization within the mesopelagic zone, a result that runs counter to the expectations of the expensive tissue hypothesis. We hypothesize that mesopelagic fishes at lower trophic levels may be investing more in neural tissue related to the detection of small prey items in a low-light environment. We recommend that comparative encephalization studies control for BMR in addition to controlling for body size and phylogeny.

Situación funcional tras un ictus y experiencia acumulada de una unidad de ictus / Functional outcome of stroke and the cumulative experience of a stroke unit

Objetivo: Los pacientes con un ictus tienen más probabilidades de supervivencia e independencia si son atendidos en una unidad de ictus. La información disponible en nuestro entorno acerca de la influencia del aprendizaje sobre estos resultados es escasa. Analizamos la situación funcional y mortalidad en nuestros pacientes en función de la experiencia acumulada en una unidad de ictus. Pacientes y métodos: Estudio de cohortes retrospectivo de pacientes ingresados en una unidad de ictus. Diferenciamos 2 grupos según el año de ingreso: grupo A (julio 2007-diciembre 2009) y grupo B (enero 2010-diciembre 2011), analizando la evolución precoz en función de la puntuación en la escala de ictus del National Institute of Health y la mortalidad al alta y la situación funcional a medio plazo en función de la mortalidad y estado funcional según la escala Rankin a los 3 meses. Resultados: Se incluyó a 1.070 pacientes. No se obtuvo diferencias entre los grupos ni en la evolución favorable (68,3% vs. 63,9), ni en la mortalidad tanto hospitalaria (5,1% vs. 6,6%), como a los 90 días (12,8% vs. 13,1%), siendo mayor el porcentaje de independientes a los 90 días en el grupo B (56,3% vs. 65,5%: p = 0,03). El análisis multivariante ajustado por subtipo de ictus y tratamiento fibrinolítico mantuvo la asociación entre la independencia y el período de ingreso. Conclusiones: La probabilidad de independencia funcional de nuestros pacientes aumentó con la experiencia acumulada de nuestra Unidad de Ictus sin observarse diferencias en la mortalidad

Objective: Patients with acute stroke are more likely to survive and achieve independence if they are treated in a stroke unit. Available information in our setting is scarce. We analyse the outcomes of our patients on the basis of cumulative experience in a stroke unit. Patients and methods: A retrospective cohort study of patients admitted to a stroke unit. We differentiate between two groups according to the year of admission: group A (July 2007-December 2009) and group B (January 2010-December 2011), analysing early outcome based on the score on the National Institute of Health stroke salce and mortality at discharge, and medium-term outcome in terms of mortality and functional status according to the modified Rankin scale at three months. Results: A total 1070 patients were included. There were no differences between groups with respect to favourable outcome (68.3% vs 63.9), hospital mortality (5.1% vs 6.6%), or 90-day mortality (12.8% vs 13.1%). The percentage of patients who were independent at 90 days was greater in group B (56.3% vs 65.5%, P = .03). In the multivariate analysis adjusted for stroke subtype and fibrinolytic therapy, the association between patient independence and admission period remained present. Conclusions: The probability of functional independence in our patients increased alongside accumulated experience in our stroke unit with no differences in mortality

Functional outcome of stroke and the cumulative experience of a stroke unit.

OBJECTIVE: Patients with acute stroke are more likely to survive and achieve independence if they are treated in a stroke unit. Available information in our setting is scarce. We analyse the outcomes of our patients on the basis of cumulative experience in a stroke unit. PATIENTS AND METHODS: A retrospective cohort study of patients admitted to a stroke unit. We differentiate between two groups according to the year of admission: group A (July 2007-December 2009) and group B (January 2010-December 2011), analysing early outcome based on the score on the National Institute of Health stroke scale and mortality at discharge, and medium-term outcome in terms of mortality and functional status according to the modified Rankin scale at three months. RESULTS: A total 1070 patients were included. There were no differences between groups with respect to favourable outcome (68.3% vs 63.9), hospital mortality (5.1% vs 6.6%), or 90-day mortality (12.8% vs 13.1%). The percentage of patients who were independent at 90 days was greater in group B (56.3% vs 65.5%, P=.03). In the multivariate analysis adjusted for stroke subtype and fibrinolytic therapy, the association between patient independence and admission period remained present. CONCLUSIONS: The probability of functional independence in our patients increased alongside accumulated experience in our stroke unit with no differences in mortality.

Dipole moments of isomeric alkoxyalcohols in cyclohexane. Comparison of Hedestrand and Fröhlich procedures with a new formula.

Limiting dipole moments of four isomeric alkoxyalcohols dissolved in cyclohexane at 298.15 K were determined from measurements of the relative permittivity of at least 17 dilute solutions up to solute mole fraction of 0.03. In addition, 5 to 7 data points were obtained up to a mole fraction of 0.1. A stepwise dilution device ensured dielectric measurements to be performed in highly dilute solutions with accurately determined concentrations. Densities of these solutions and refractive indices of the pure liquids were independently measured. Limiting dipole moments were calculated using Hedestrand's equation and an improved method of implementing Fröhlich's equation, which circumvents extrapolation difficulties referred to in the literature. A new formula, based on the one-liquid approach for extending the Onsager-Kirkwood-Fröhlich equation to liquid mixtures, is introduced and shown to yield a reliable and robust procedure for estimating dipole moments of polar molecules dissolved in non-polar solvents. Limiting dipole moment values for 2-tert-butoxyethanol (2.31 D), 1-propoxypropan-2-ol (2.14 D), 2-butoxyethanol (2.14 D) and 2-isobutoxyethanol (2.08 D) are recommended. The relative order of these values appears to determine the order of hydrophilicity of these four alkoxyalcohols as suggested by their recently reported limiting partial molar volumes and isentropic compressions in aqueous solutions.

Associations of killer cell immunoglobulin- like receptor genes with rheumatoid arthritis.

OBJECTIVE: Rheumatoid Arthritis (RA) is an autoimmune and chronic inflammatory disease of unknown etiology. Killer cell immunoglobulin-like receptors are expressed on the surface of natural killer cells and CD28null T-cells, both present in synovial membrane of RA. Therefore we evaluated the associations of KIR genes with RA. METHODS: 16 KIR genes were genotyped in 100 healthy subjects (HS) and 100 RA patients from Western Mexico using PCR-SSP. Differences in KIR genotypes and gene frequencies were assessed using the X^{2} test. RESULTS: Gene frequency of KIR2DL3 was lower in RA than in HS (p= 0.0019), whereas KIR2DL2 and KIR2DS2 were higher in RA than HS (p =0.0004 and p = 0.0487, respectively). In addition were identified 38 genotypes (from G1-G38) in both studied groups, and the genotype frequencies of G1, G6 and G14 showed significant differences (p =0.0001, p =0.0208 and p =0.0300, respectively). CONCLUSIONS: The presence of KIR2DL2, KIR2DS2 and absence of KIR2DL3 are associated with RA. Moreover, two genotypes BX are associated with RA. These results suggest that KIRs can be involved in RA susceptibility.

The ACTN3 R577X polymorphism is associated with inflammatory myopathies in a Mexican population.

BACKGROUND: The ACTN3 gene encodes the fast muscle protein α-actinin-3. The ACTN3 R577X polymorphism is a premature stop codon and results in absence of α-actinin-3 in 577XX homozygotes. The aim of this study was to determine the ACTN3 genotype in idiopathic inflammatory myopathies (IIMs). METHODS: We performed ACTN3 genotyping on 27 patients with dermatomyositis (DM), 10 with polymyositis (PM), and 85 healthy subjects. Muscle enzyme levels of creatine phosphokinase (CPK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were recorded at the time of diagnosis and recruitment. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the allele frequency was analysed. RESULTS: A total of 36% of healthy subjects had the ACTN3 577XX polymorphism (α-actinin-3 deficiency), 18% had the 577RR (homozygous wild type) genotype, and 46% 577RX (heterozygous). In DM/PM, 70% had the ACTN3 577XX polymorphism, 6% RR, and 24% RX [odds ratio (OR) 4.12, 95% confidence interval (CI) 1.67-10.33, p < 0.001]. In healthy subjects, the R allele was present in 41% and the X allele in 59% compared to 18% and 82%, respectively, in the IIM group (OR 3.21, 95% CI 1.57-6.66, p < 0.001). Thus, the ACTN3 577X allele seemed to increase the risk of developing IIM, and DM in particular, although this was not related to severity of expression of the phenotype. CONCLUSIONS: The ACTN3 577X allele appeared to increase the risk of developing IIM; 70% of IIM patients were deficient in α-actinin-3. By contrast, ACTN3 577XX patients seemed to have less severe disease as reflected in lower muscle enzyme levels.

E2F4 plays a key role in Burkitt lymphoma tumorigenesis.

Sporadic Burkitt lymphoma (sBL) is a rapidly growing B-cell non-Hodgkin's lymphoma whose treatment requires highly aggressive therapies that often result severely toxic. Identification of proteins whose expression or function is deregulated in sBL and play a role in its formation could facilitate development of less toxic therapies. We have previously shown that E2F1 expression is deregulated in sBL. We have now investigated the mechanisms underlying E2F1 deregulation and found that the E2F sites in its promoter fail to repress its transcriptional activity in BL cells and that the transcriptional repressor E2F4 barely interacts with these sites. We also have found that E2F4 protein levels, but not those of its mRNA, are reduced in sBL cell lines relative to immortal B-cell lines. E2F4 protein expression is also decreased in 24 of 26 sBL tumor samples from patients compared with control tissues. Our data demonstrate that enforced E2F4 expression in BL cells not only diminishes E2F1 levels, but also reduces selectively the tumorigenic properties and proliferation of BL cells, while increasing their accumulation in G(2)/M. Our results therefore point to E2F4 as a target for developing novel and less toxic treatments for sBL.