[Guillain-Barre syndrome and thrombocytopenia after SARS-CoV-2 vaccination with Moderna. A case report]. / Síndrome de Guillain-Barré y trombocitopenia tras la vacunación contra el SARS-CoV-2 con Moderna. Descripción de un caso.

INTRODUCTION: The massive vaccination against the SARS-CoV-2 virus has demonstrated to be one of the major measures for the reduction of the morbidity and mortality that this virus causes. However, during the last months the administration of the vaccine has been also associated with some rare, but life-threatening, adverse effects. CASE REPORT: In this article we describe the case of a patient that developed a Guillain-Barre syndrome and an Idiopathic thrombocytopenic purpura nine days after the vaccination with the third dose for the SARS-CoV-2 virus (Moderna). He had received previously two doses of the AstraZeneca vaccine. Moreover, the patient was positive for auto-antibodies anti-SSA/Ro60 and auto-antibodies IgG anti-GM1 and IgG anti-GM3. DISCUSSION: Even though it is not possible to stablish a clear relation of causality between the administration of the vaccine booster for SARS-CoV-2 and the diseases developed by the patient, the association of two concomitant autoimmune processes is remarkable. As well as the positivity for the auto-antibodies anti-SSA/Ro60, which have been described in the bibliography in cases of SARS-CoV-2 infection.

TITLE: Síndrome de Guillain-Barré y trombocitopenia tras la vacunación contra el SARS-CoV-2 con Moderna. Descripción de un caso.Introducción. La vacunación masiva contra el virus SARS-CoV-2 constituye una de las principales estrategias en la reducción de la morbimortalidad que presenta dicho virus. No obstante, a lo largo de los últimos meses, su administración también se ha relacionado con diversos efectos adversos raros, pero potencialmente graves. Caso clínico. En el presente artículo describimos el caso de un paciente que desarrolló un síndrome de Guillain-Barré y una púrpura trombocitopénica idiopática nueve días después de la vacunación con la tercera dosis contra el virus SARS-CoV-2 (Moderna), con dos dosis previas de AstraZeneca. Adicionalmente, destaca la presencia de positividad para autoanticuerpos anti-SSA/Ro60 y para anticuerpos inmunoglobulina G anti-GM1 e inmunoglobulina G anti-GM3. Conclusión. Aunque no es posible establecer una relación de causalidad entre la administración del booster de la vacuna y el desarrollo de la enfermedad, es destacable la asociación de dos procesos autoinmunes concomitantes, junto con la positividad en los autoanticuerpos anti-SSA/Ro60, lo cual se ha descrito en la bibliografía en casos de infección del virus SARS-CoV-2.

Síndrome de Guillain-Barré y trombocitopenia tras la vacunación contra el SARS-CoV-2 con Moderna. Descripción de un caso / Guillain-Barré syndrome and thrombocytopenia after SARS-CoV-2 vaccination with Moderna. A case report

Introducción: La vacunación masiva contra el virus SARS-CoV-2 constituye una de las principales estrategias en la reducción de la morbimortalidad que presenta dicho virus. No obstante, a lo largo de los últimos meses, su administración también se ha relacionado con diversos efectos adversos raros, pero potencialmente graves. Caso clínico: En el presente artículo describimos el caso de un paciente que desarrolló un síndrome de Guillain-Barré y una púrpura trombocitopénica idiopática nueve días después de la vacunación con la tercera dosis contra el virus SARS-CoV-2 (Moderna), con dos dosis previas de AstraZeneca. Adicionalmente, destaca la presencia de positividad para autoanticuerpos anti-SSA/Ro60 y para anticuerpos inmunoglobulina G anti-GM1 e inmunoglobulina G anti-GM3. Conclusión: Aunque no es posible establecer una relación de causalidad entre la administración del booster de la vacuna y el desarrollo de la enfermedad, es destacable la asociación de dos procesos autoinmunes concomitantes, junto con la positividad en los autoanticuerpos anti-SSA/Ro60, lo cual se ha descrito en la bibliografía en casos de infección del virus SARS-CoV-2.(AU)

Introduction: The massive vaccination against the SARS-CoV-2 virus has demonstrated to be one of the major measures for the reduction of the morbidity and mortality that this virus causes. However, during the last months the administration of the vaccine has been also associated with some rare, but life-threatening, adverse effects. Case report: In this article we describe the case of a patient that developed a Guillain-Barré syndrome and an Idiopathic thrombocytopenic purpura nine days after the vaccination with the third dose for the SARS-CoV-2 virus (Moderna). He had received previously two doses of the AstraZeneca vaccine. Moreover, the patient was positive for auto-antibodies anti-SSA/Ro60 and auto-antibodies IgG anti-GM1 and IgG anti-GM3. Discussion: Even though it is not possible to stablish a clear relation of causality between the administration of the vaccine booster for SARS-CoV-2 and the diseases developed by the patient, the association of two concomitant autoimmune processes is remarkable. As well as the positivity for the auto-antibodies anti-SSA/Ro60, which have been described in the bibliography in cases of SARS-CoV-2 infection.(AU)

Biomarcadores pronósticos y de seguimiento en la polineuropatía desmielinizante inflamatoria crónica / Prognostic and monitoring biomarkers in chronic inflammatory demyelinating polyneuropathy

Introducción: La polineuropatía desmielinizante inflamatoria crónica (PDIC) es una entidad clínica con una variabilidad fenotípica muy importante tanto en el inicio como en la evolución. Por lo tanto, es importante disponer de biomarcadores objetivos para monitorizar la evolución. En esta revisión presentamos los biomarcadores clínicos, neurofisiológicos, de neuroimagen, y en la sangre y el líquido cefalorraquídeo (LCR) para el seguimiento y el pronóstico de la PDIC. Desarrollo: Se han desarrollado diferentes herramientas clínicas validadas para el seguimiento de la PDIC mediante la evaluación de la fuerza y la discapacidad. No obstante, falta determinar el mejor parámetro para monitorizar la marcha. El seguimiento mediante examen neurofisiológico también está ampliamente extendido, y la amplitud del compound muscle action potential es lo más utilizado. Más recientemente, se ha desarrollado la Motor Unit Number Index sum score, que es una técnica precisa y reproducible. El papel de la ecografía de nervio se encuentra en desarrollo, y se ha descrito correlación entre la evolución clínica y los hallazgos por ecografía. Se han descrito múltiples biomarcadores en sangre y el LCR, entre los que destacan los anticuerpos antinodales/paranodales, los neurofilamentos de cadena ligera, los niveles de inmunoglobulina G en el suero y los niveles de esfingomielina en el LCR. Asimismo, se han descrito variantes genéticas y citocinas relacionadas con el pronóstico y la respuesta a los tratamientos. Conclusiones: Uno de los retos más importante en el manejo de la PDIC es la monitorización de los cambios clínicos tras el inicio del tratamiento. La combinación de biomarcadores que permitan una comprensión exacta de la enfermedad es crucial para el manejo óptimo de la PDIC.(AU)

Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a clinical entity with significant phenotypic variability both in its onset and in its course. Therefore, it is important to have objective biomarkers with which to monitor its evolution. In this review we present clinical, neurophysiological, neuroimaging, blood and cerebrospinal fluid (CSF) biomarkers for the monitoring and prognosis of CIDP. Development: Different clinical tools have been developed and validated to monitor CIDP by assessing strength and disability. However, the best parameter for monitoring gait remains to be determined. Monitoring by neurophysiological examination is also widespread and the amplitude of the compound muscle action potential is the most commonly used. More recently, the Motor Unit Number Index sum score has been developed, which is an accurate and reproducible technique. The role of nerve ultrasonography is under development and a correlation between clinical evolution and ultrasound findings has been described. Multiple biomarkers have been described in blood and CSF, including antinodal/paranodal antibodies, neurofilament light chain, serum immunoglobulin G levels and CSF sphingomyelin levels. Genetic variants and cytokines associated with prognosis and response to treatment have also been described. Conclusions: One of the most important challenges in the management of CIDP is the monitoring of clinical changes after treatment initiation. The combination of biomarkers that allow an accurate understanding of the disease is crucial for the optimal management of CIDP.(AU)

[Prognostic and monitoring biomarkers in chronic inflammatory demyelinating polyneuropathy]. / Biomarcadores pronósticos y de seguimiento en la polineuropatía desmielinizante inflamatoria crónica.

INTRODUCTION: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a clinical entity with significant phenotypic variability both in its onset and in its course. Therefore, it is important to have objective biomarkers with which to monitor its evolution. In this review we present clinical, neurophysiological, neuroimaging, blood and cerebrospinal fluid (CSF) biomarkers for the monitoring and prognosis of CIDP. DEVELOPMENT: Different clinical tools have been developed and validated to monitor CIDP by assessing strength and disability. However, the best parameter for monitoring gait remains to be determined. Monitoring by neurophysiological examination is also widespread and the amplitude of the compound muscle action potential is the most commonly used. More recently, the Motor Unit Number Index sum score has been developed, which is an accurate and reproducible technique. The role of nerve ultrasonography is under development and a correlation between clinical evolution and ultrasound findings has been described. Multiple biomarkers have been described in blood and CSF, including antinodal/paranodal antibodies, neurofilament light chain, serum immunoglobulin G levels and CSF sphingomyelin levels. Genetic variants and cytokines associated with prognosis and response to treatment have also been described. CONCLUSIONS: One of the most important challenges in the management of CIDP is the monitoring of clinical changes after treatment initiation. The combination of biomarkers that allow an accurate understanding of the disease is crucial for the optimal management of CIDP.

TITLE: Biomarcadores pronósticos y de seguimiento en la polineuropatía desmielinizante inflamatoria crónica.Introducción. La polineuropatía desmielinizante inflamatoria crónica (PDIC) es una entidad clínica con una variabilidad fenotípica muy importante tanto en el inicio como en la evolución. Por lo tanto, es importante disponer de biomarcadores objetivos para monitorizar la evolución. En esta revisión presentamos los biomarcadores clínicos, neurofisiológicos, de neuroimagen, y en la sangre y el líquido cefalorraquídeo (LCR) para el seguimiento y el pronóstico de la PDIC. Desarrollo. Se han desarrollado diferentes herramientas clínicas validadas para el seguimiento de la PDIC mediante la evaluación de la fuerza y la discapacidad. No obstante, falta determinar el mejor parámetro para monitorizar la marcha. El seguimiento mediante examen neurofisiológico también está ampliamente extendido, y la amplitud del compound muscle action potential es lo más utilizado. Más recientemente, se ha desarrollado la Motor Unit Number Index sum score, que es una técnica precisa y reproducible. El papel de la ecografía de nervio se encuentra en desarrollo, y se ha descrito correlación entre la evolución clínica y los hallazgos por ecografía. Se han descrito múltiples biomarcadores en sangre y el LCR, entre los que destacan los anticuerpos antinodales/paranodales, los neurofilamentos de cadena ligera, los niveles de inmunoglobulina G en el suero y los niveles de esfingomielina en el LCR. Asimismo, se han descrito variantes genéticas y citocinas relacionadas con el pronóstico y la respuesta a los tratamientos. Conclusiones. Uno de los retos más importante en el manejo de la PDIC es la monitorización de los cambios clínicos tras el inicio del tratamiento. La combinación de biomarcadores que permitan una comprensión exacta de la enfermedad es crucial para el manejo óptimo de la PDIC.

Controlling the off-center positions of anions through thermodynamics and kinetics in flexible perovskite-like materials.

Due to the network flexibility of their BX3 sub-lattice, a manifold of polymorphs with potential multiferroic applications can be found in perovskite-like ABX3 materials under different pressure and temperature conditions. The potential energy surface of these compounds usually presents equivalent off-center positions of anions connected by low energetic barriers. This feature facilitates a competition between the thermodynamic and kinetic control of the transitions from low to high symmetry structures, and explains the relationship between the rich polymorphism and network flexibility. In the rhombohedral phase of iron trifluoride, our first-principles electronic structure and phonon calculations reveal the factors that determine which of the two scenarios dominates the transition. At the experimentally reported rhombohedral-cubic transition temperature, the calculated fluorine displacements are fast enough to overcome forward and backward a barrier of less than 30 kJ mol-1, leading to an average structure with cubic symmetry. In addition, lattice strain effects observed in epitaxial growth and nanocrystallite experiments involving BX3 compounds are successfully mimicked by computing the phase stability of FeF3 under negative pressures. We predict a transition pressure at -1.8 GPa with a relative volume change around 5%, consistent with a first-order transition from the rhombohedral to the cubic structure. Overall, our study illustrates how, by strain tuning, either a thermodynamic or a kinetic pathway can be selected for this transformation.

Temperature and pressure-induced strains in anhydrous iron trifluoride polymorphs.

Various structural configurations of iron trifluoride appear at the nanoscale and macroscopic size, either in the amorphous or crystalline state. The specific atomic organization in these structures crucially alters the performance of FeF3 as an effective cathode in Li-ion batteries. Our detailed first-principles computational simulations examine the structural strains induced by temperature and stress on the four anhydrous polymorphs observed so far in FeF3 at ambient pressure. A wealth of data covering previous experimental results on their equilibrium structures and extending their characterization with new static and isothermal equations of state is provided. We inform on how porous apertures associated with the six-octahedra rings of the HTB and pyrochlore phases are modified under compressive and expansive strains. A quasi-auxetic behavior at low pressures for the ground state rhombohedral phase is detected, which is in concordance with its anomalous structural anisotropy. In contrast with the effect of temperature, this structure undergoes under negative pressure phase transitions to the other three polymorphs, indicating potential conditions where low-density FeF3 could show a better performance in technological applications.

A Mix of Natural Bioactive Compounds Reduces Fat Accumulation and Modulates Gene Expression in the Adipose Tissue of Obese Rats Fed a Cafeteria Diet.

Scientists are focusing on bioactive ingredients to counteract obesity. We evaluated whether a mix containing grape seed proanthocyanidin extract (GSPE), anthocyanins, conjugated linoleic acid (CLA), and chicken feet hydrolysate (CFH) could reduce body fat mass and also determined which mechanisms in the white adipose tissue (WAT) and the brown adipose tissue (BAT) were affected by the treatment. The mix or vehicle (VH) were administered for three weeks to obese rats fed a cafeteria (CAF) diet. Biometric measures, indirect calorimetry, and gene expression in WAT and BAT were analyzed as was the histology of the inguinal WAT (IWAT). The individual compounds were also tested in the 3T3-L1 cell line. The mix treatment resulted in a significant 15% reduction in fat (25.01 ± 0.91 g) compared to VH treatment (21.19 ± 1.59 g), and the calorimetry results indicated a significant increase in energy expenditure and fat oxidation. We observed a significant downregulation of Fasn mRNA and an upregulation of Atgl and Hsl mRNA in adipose depots in the group treated with the mix. The IWAT showed a tendency of reduction in the number of adipocytes, although no differences in the total adipocyte area were found. GSPE and anthocyanins modulated the lipid content and downregulated the gene and protein levels of Fasn compared to the untreated group in 3T3-L1 cells. In conclusion, this mix is a promising treatment against obesity, reducing the WAT of obese rats fed a CAF diet, increasing energy expenditure and fat oxidation, and modifying the expression of genes involved in lipid metabolism of the adipose tissue.

Consumption of out-of-season orange modulates fat accumulation, morphology and gene expression in the adipose tissue of Fischer 344 rats.

PURPOSE: According to the xenohormesis theory, animals receive signals from plants that give clues about the changing environment, and thus, depending on the season of the year, animals develop physiological changes to adapt in advance to the seasonal changes. Our objective was to study how the same fruit cultivated during two different seasons could affect the adipose tissue of rats. METHODS: Thirty-six Fischer 344 rats were acclimated for 4 weeks to long-day or short-day (SD) photoperiods. After adaptation, three groups (n = 6) from each photoperiod were supplemented either with orange from the northern (ON) or southern (OS) hemispheres harvested in the same month or a vehicle (VH) for 10 weeks. Biometric measurements, postprandial plasmatic parameters, gene expression of the inguinal white adipose tissue (IWAT) and brown adipose tissue (BAT), and the histology of the IWAT were analysed. RESULTS: The OSSD group increased its fat content compared to the VHSD, while the ON groups showed no biometric differences. The OS groups were further studied, and the IWAT showed increased levels of Pparγ gene expression and a higher percentage of larger adipocytes compared to the VH group. The BAT showed down-regulation of Lpl, Cpt1b and Pparα in the OSSD group compared to that in the VHSD group, suggesting an inhibition of BAT activity, however, Ucp1 gene expression was up-regulated. CONCLUSIONS: We observed a different effect from both fruits, with the OS promoting a phenotype prone to fat accumulation when consumed in an SD photoperiod, which might be explained by the xenohormesis theory.

Response to the photoperiod in the white and brown adipose tissues of Fischer 344 rats fed a standard or cafeteria diet.

Researchers are identifying new factors that contribute to the obesity epidemic, with changes in the photoperiod as one promising risk factor. To study the influence of the photoperiod on adipose tissue, Fischer 344 rats were treated for 14 weeks with a long day (18 h light:6 h dark; LD) or a short day (6 h light:18 h dark; SD) and fed a standard diet (STD). Biometric measures, postprandial plasmatic parameters, gene expression in the retroperitoneal white adipose tissue (RWAT) and brown adipose tissue (BAT) and histology of the RWAT were analyzed. A second experiment with the same conditions and analysis was performed for 11 weeks with rats fed a cafeteria diet (CAF). In the STD experiment, the SD increased triglycerides and showed a tendency to reduce fat compared to the LD. In the RWAT, genes implicated in adipogenesis, lipogenesis and lipolysis were down-regulated, and the histological results showed a higher percentage of small adipocytes in the SD without changes in their total number. In the CAF experiment, lipogenesis and adipogenesis gene expression was increased in the SD, while adipocytes were smaller and their number increased. Both experiments showed in the SD a decrease in the BAT expression of lipid uptake and ß-oxidation genes, while only the STD additionally showed a reduction in Ucp1 expression. In conclusion, the RWAT morphology and the expression of key genes for lipid metabolism in RWAT and BAT were influenced by the photoperiod; however, the changes observed in the RWAT were different depending on the diet.

Chemical pressure-chemical knowledge: squeezing bonds and lone pairs within the valence shell electron pair repulsion model.

The valence shell electron pair repulsion (VSEPR) model is a demanding testbed for modern chemical bonding formalisms. The challenge consists in providing reliable quantum mechanical interpretations of how chemical concepts such as bonds, lone pairs, electronegativity, or hypervalence influence (or modulate) molecular geometries. Several schemes have been developed thus far to visualize and characterize these effects; however, to the best of our knowledge, no scheme has yet incorporated the analysis of the premises derived from the ligand close-packing (LCP) extension of the VSEPR model. Within the LCP framework, the activity of the lone pairs of the central atom and ligand-ligand repulsions constitute the two key features necessary to explain certain controversial molecular geometries that do not conform to the VSEPR rules. Considering the dynamical picture obtained when electron local forces at different nuclear configurations are evaluated from first-principles calculations, we investigate the chemical pressure distributions in a variety of molecular systems, namely, electron-deficient molecules (BeH2, BH3, BF3), several AX3 series (A: N, P, As; X: H, F, Cl), SO2, ethylene, SF4, ClF3, XeF2, and nonequilibrium configurations of water and ammonia. Our chemical pressure maps clearly reveal space regions that are totally consistent with the molecular and electronic geometries predicted by VSEPR and provide a quantitative correlation between the lone pair activity of the central atom and electronegativity of ligands, which are in agreement with the LCP model. Moreover, the analysis of the kinetic and potential energy contributions to the chemical pressure allows us to provide simple explanations on the connection between ligand electronegativity and electrophilic/nucleophilic character of the molecules, with interesting implications in their potential reactivity. NH3, NF3, SO2, BF3, and the inversion barrier of AX3 molecules are selected to illustrate our findings.

Consumption of Cherry out of Season Changes White Adipose Tissue Gene Expression and Morphology to a Phenotype Prone to Fat Accumulation.

The aim of this study was to determine whether the consumption of cherry out of its normal harvest photoperiod affects adipose tissue, increasing the risk of obesity. Fischer 344 rats were held over a long day (LD) or a short day (SD), fed a standard diet (STD), and treated with a cherry lyophilizate (CH) or vehicle (VH) (n = 6). Biometric measurements, serum parameters, gene expression in white (RWAT) and brown (BAT) adipose tissues, and RWAT histology were analysed. A second experiment with similar conditions was performed (n = 10) but with a cafeteria diet (CAF). In the STD experiment, Bmal1 and Cry1 were downregulated in the CHSD group compared to the VHSD group. Pparα expression was downregulated while Ucp1 levels were higher in the BAT of the CHSD group compared to the VHSD group. In the CAF-fed rats, glucose and insulin serum levels increased, and the expression levels of lipogenesis and lipolysis genes in RWAT were downregulated, while the adipocyte area increased and the number of adipocytes diminished in the CHSD group compared to the VHSD group. In conclusion, we show that the consumption of cherry out of season influences the metabolism of adipose tissue and promotes fat accumulation when accompanied by an obesogenic diet.

Spectral windows analysis method for monitoring anthropogenic radionuclides in real-time environmental gamma-ray scintillation spectrometry.

This paper proposes an analysis methodology based on the spectral windows technique aimed for environmental real-time gamma-ray spectra obtained with scintillation detectors. The method permits us to monitor activity concentrations of selected isotopes, such as anthropogenic radionuclides like 137Cs and 131I, by removing the Compton scattering plus other external contributions and resolving peak overlapping within any window. Activity concentrations are presented for 137Cs, 131I, 214Bi, and 214Pb when applying the method to a monitor using a LaBr3(Ce) detector. The method avoids false-positive and false-negative results of anthropogenic radionuclides in the presence of radiation from natural origins by obtaining activity concentrations that correspond to those obtained by a Gaussian fitting commercial software.

Epilepsia mioclónica en el síndrome de Down y en la enfermedad de Alzheimer / Myoclonic epilepsy in Down syndrome and Alzheimer disease

Introducción: Los pacientes con síndrome de Down (SD) presentan una demencia tipo Alzheimer (EA) asociada a la edad. Ambas patologías, con una base neuropatológica común, han sido asociadas a la epilepsia mioclónica de inicio tardío (LOMEDS). Esta entidad presenta alteraciones electroencefalográficas características en forma de descargas generalizadas de polipunta-onda. Método: Presentamos una serie de 11 pacientes con el diagnóstico de SD o EA que desarrollaron crisis epilépticas mioclónicas o tónico-clónicas generalizadas. En todos ellos, se realizó un seguimiento clínico y estudios de neuroimagen y poligrafía EEG. Resultados: En todos los casos, el deterioro cognitivo avanzó rápidamente tras el comienzo de la epilepsia, produciendo un incremento en el grado de dependencia. El hallazgo más común en el EEG fue un enlentecimiento de la actividad cerebral con ritmos theta y delta; además, en 8 pacientes se objetivaron descargas intercríticas generalizadas de polipunta-onda. En los estudios de neuroimagen se encontró atrofia cerebral cortical. El fármaco más eficaz en esta serie fue el levetiracetam. Conclusiones: La asociación de epilepsia generalizada al SD de edad avanzada supone un epifenómeno en la evolución que marca un agravamiento rápidamente progresivo de las funciones cognitivas y motoras. Presenta unas características electroclínicas bien definidas y se comporta como una epilepsia mioclónica progresiva, que probablemente se relaciona con los cambios estructurales que caracterizan el parecido evolutivo del SD con la enfermedad de Alzheimer. El reconocimiento de este síndrome es importante, dado que tiene repercusiones pronósticas y requiere un tratamiento adecuado

Introduction: Patients with Down syndrome (DS) who exhibit Alzheimer disease (AD) are associated with age. Both diseases with a common neuropathological basis have been associated with late-onset myoclonic epilepsy (LOMEDS). This entity presents electroencephalogram features as generalized polyspike-wave discharges. Method. We present a series of 11 patients with the diagnosis of DS or AD who developed myoclonic seizures or generalized tonic-clonic seizures. In all cases, clinical and neuroimaging studies and polygraph EEG monitoring was performed. Results: In all cases, cognitive impairment progressed quickly after the onset of epilepsy causing an increase in the degree of dependence. The most common finding in the EEG was a slowing of brain activity with theta and delta rhythms, plus intercritical generalized polyspike-waves were objectified in eight patients. In neuroimaging studies was found cerebral cortical atrophy. The most effective drug in this series was the levetiracetam. Conclusions: The association of generalized epilepsy with elderly DS represents an epiphenomenon in evolution which is associated with a progressive deterioration of cognitive and motor functions. This epilepsy has some electroclinical characteristics and behaves as progressive myoclonic epilepsy, which is probably related to the structural changes that characterize the evolutionary similarity of DS with AD. Recognition of this syndrome is important, since it has prognostic implications and requires proper treatment

Myoclonic epilepsy in Down syndrome and Alzheimer disease. / Epilepsia mioclónica en el síndrome de Down y en la enfermedad de Alzheimer.

INTRODUCTION: Patients with Down syndrome (DS) who exhibit Alzheimer disease (AD) are associated with age. Both diseases with a common neuropathological basis have been associated with late-onset myoclonic epilepsy (LOMEDS). This entity presents electroencephalogram features as generalized polyspike-wave discharges. METHOD: We present a series of 11 patients with the diagnosis of DS or AD who developed myoclonic seizures or generalized tonic-clonic seizures. In all cases, clinical and neuroimaging studies and polygraph EEG monitoring was performed. RESULTS: In all cases, cognitive impairment progressed quickly after the onset of epilepsy causing an increase in the degree of dependence. The most common finding in the EEG was a slowing of brain activity with theta and delta rhythms, plus intercritical generalized polyspike-waves were objectified in eight patients. In neuroimaging studies was found cerebral cortical atrophy. The most effective drug in this series was the levetiracetam. CONCLUSIONS: The association of generalized epilepsy with elderly DS represents an epiphenomenon in evolution which is associated with a progressive deterioration of cognitive and motor functions. This epilepsy has some electroclinical characteristics and behaves as progressive myoclonic epilepsy, which is probably related to the structural changes that characterize the evolutionary similarity of DS with AD. Recognition of this syndrome is important, since it has prognostic implications and requires proper treatment.

Litio para el tratamiento de la esclerosis lateral amiotrófica: mucho ruido para nada / Lithium for treatment of amyotrophic lateral sclerosis: much ado about nothing

Introducción: El litio fue propuesto en 2008 como un candidato eficaz en el tratamiento de ELA tras reportarse que era capaz de retrasar el deterioro funcional en un 40% y que ninguno de los 16 pacientes tratados con una combinación de litio más riluzole falleció durante un periodo de seguimiento de 15 meses. Los excelentes resultados de este estudio piloto despertaron una gran expectativa en pacientes, familiares, asociaciones de enfermos y comunidad científica. Consecuencia directa de esta noticia fue la puesta en marcha de numerosos ensayos clínicos en fase ii. Muchos de los pacientes, que no pudieron ser incluidos en estos estudios, utilizaron todos sus recursos para acceder a este fármaco mediante uso compasivo. Objetivos: Evaluar la eficacia del litio en ELA mediante un metaanálisis de la información reportada en 12 de estos estudios. Se analiza su calidad metodológica. Material y métodos: Se realizaron búsquedas en MEDLINE, EMBASE y Registros Cochrane del Grupo de Enfermedades Neuromusculares, ClinicalTrials.gov y EudraCT (enero de 1996-agosto de 2012). Resultados: Hasta la fecha disponemos de información de más de 1.100 pacientes tratados con litio. Lamentablemente los resultados obtenidos no confirman el efecto positivo descrito en el estudio piloto y sugieren que este fármaco es ineficaz para detener la progresión de la enfermedad. Dos ensayos tuvieron que ser suspendidos antes del plazo previsto por ineficacia del fármaco y por numerosos efectos adversos. En un estudio publicado recientemente se descarta también cualquier posibilidad de un mínimo efecto. Conclusiones: Hay evidencia de que el litio no ofrece beneficios a corto plazo en ELA. Al comparar el grupo de pacientes tratados con litio + riluzole con el grupo control tratado con riluzole no se observan diferencias estadísticamente significativas en las tasas de deterioro funcional o de deterioro de la función respiratoria ni tampoco en la supervivencia. No hay tampoco evidencia de que sea superior al placebo

Introduction: Lithium was proposed in 2008 as an effective candidate in the treatment of ALS after a report claimed that it was able to delay functional deterioration by 40% and that none of the 16 patients treated with a combination of lithium plus riluzole had died during a 15-month follow-up period. The excellent results of this pilot study engendered considerable optimism among patients, their families, patients’ associations, and the scientific community. This report sparked numerous phase ii clinical trials. Many patients who were not included in these studies used all resources at their disposal to access the drug as treatment under a compassionate use programme. Objectives: To evaluate the effectiveness of lithium in ALS using a meta-analysis of the information reported in 12 studies which were examined for methodological quality. Material and methods: Searches were performed using MEDLINE, EMBASE, the Cochrane Neuromuscular Disease Group Trials Register, ClinicalTrials.gov, and EudraCT (January 1996-August 2012). Results: To date, we have information on more 1100 patients treated with lithium. Unfortunately, the results do not confirm the positive effect described in the pilot study, which suggests that this drug is not effective at slowing disease progression. Two trials had to be suspended before the scheduled completion date due to the ineffectiveness of the drug as well as numerous adverse effects. A recently published study also ruled out any possible modest effect. Conclusions: There is evidence to suggest that lithium has no short-term benefits in ALS. A comparison of the group of patients treated with lithium + riluzole and the control group treated with riluzole alone showed no statistically significant differences in rates of functional decline, deterioration of respiratory function, or survival time. Furthermore, there was no evidence that it was more effective than the placebo

Computer simulations of 3C-SiC under hydrostatic and non-hydrostatic stresses.

The response of 3C-SiC to hydrostatic pressure and to several uni- and bi-axial stress conditions is thoroughly investigated using first principles calculations. A topological interpretation of the chemical bonding reveals that the so-called non-covalent interactions enhance only at high pressure while the nature of the covalent Si-C bonding network keeps essentially with the same pattern. The calculated low compressibility agrees well with experimental values and is in concordance with the high structural stability of this polymorph under hydrostatic pressure. Under uniaxial [001] stress, the c/a ratio shows a noticeable drop inducing a closure of the band gap and the emergence of a metallic state around 40 GPa. This behavior correlates with a plateau of the electron localization function exhibiting a roughly constant and non-negligible value surrounding CSi4 and SiC4 covalent bonded units.

Proanthocyanidins in health and disease.

Proanthocyanidins (PAs) are the most abundant flavonoids in the human diet. Several epidemiological studies connect PA consumption and health benefits and the designation of PAs as healthy compounds started at the early stages of the 20th century. The beneficial health properties of PAs are attributed to their conjugated and colonic metabolites. Therefore, gut microbial compositions can determine the effectiveness of PAs. Reciprocally, dietary polyphenols can act as prebiotics. Recently, it has also been described that PAs modulate the circadian rhythm. Biochemical and epigenetic mechanisms, including the modulation of microRNAs, allow PAs to modulate cell functionality. PA effects in metabolic diseases are also reviewed.

Lithium for treatment of amyotrophic lateral sclerosis: much ado about nothing. / Litio para el tratamiento de la esclerosis lateral amiotrófica: mucho ruido para nada.

INTRODUCTION: Lithium was proposed in 2008 as an effective candidate in the treatment of ALS after a report claimed that it was able to delay functional deterioration by 40% and that none of the 16 patients treated with a combination of lithium plus riluzole had died during a 15-month follow-up period. The excellent results of this pilot study engendered considerable optimism among patients, their families, patients' associations, and the scientific community. This report sparked numerous phase ii clinical trials. Many patients who were not included in these studies used all resources at their disposal to access the drug as treatment under a compassionate use programme. OBJECTIVES: To evaluate the effectiveness of lithium in ALS using a meta-analysis of the information reported in 12 studies which were examined for methodological quality. MATERIAL AND METHODS: . Searches were performed using MEDLINE, EMBASE, the Cochrane Neuromuscular Disease Group Trials Register, ClinicalTrials.gov, and EudraCT (January 1996-August 2012). RESULTS: To date, we have information on more 1100 patients treated with lithium. Unfortunately, the results do not confirm the positive effect described in the pilot study, which suggests that this drug is not effective at slowing disease progression. Two trials had to be suspended before the scheduled completion date due to the ineffectiveness of the drug as well as numerous adverse effects. A recently published study also ruled out any possible modest effect. CONCLUSIONS: There is evidence to suggest that lithium has no short-term benefits in ALS. A comparison of the group of patients treated with lithium+riluzole and the control group treated with riluzole alone showed no statistically significant differences in rates of functional decline, deterioration of respiratory function, or survival time. Furthermore, there was no evidence that it was more effective than the placebo.

Gpr116 Receptor Regulates Distinctive Functions in Pneumocytes and Vascular Endothelium.

Despite its known expression in both the vascular endothelium and the lung epithelium, until recently the physiological role of the adhesion receptor Gpr116/ADGRF5 has remained elusive. We generated a new mouse model of constitutive Gpr116 inactivation, with a large genetic deletion encompassing exon 4 to exon 21 of the Gpr116 gene. This model allowed us to confirm recent results defining Gpr116 as necessary regulator of surfactant homeostasis. The loss of Gpr116 provokes an early accumulation of surfactant in the lungs, followed by a massive infiltration of macrophages, and eventually progresses into an emphysema-like pathology. Further analysis of this knockout model revealed cerebral vascular leakage, beginning at around 1.5 months of age. Additionally, endothelial-specific deletion of Gpr116 resulted in a significant increase of the brain vascular leakage. Mice devoid of Gpr116 developed an anatomically normal and largely functional vascular network, surprisingly exhibited an attenuated pathological retinal vascular response in a model of oxygen-induced retinopathy. These data suggest that Gpr116 modulates endothelial properties, a previously unappreciated function despite the pan-vascular expression of this receptor. Our results support the key pulmonary function of Gpr116 and describe a new role in the central nervous system vasculature.

Dietary proanthocyanidins modulate BMAL1 acetylation, Nampt expression and NAD levels in rat liver.

Metabolism follows circadian rhythms, which are driven by peripheral clocks. Clock genes in the liver are entrained by daytime meals and food components. Proanthocyanidins (PAs), the most abundant flavonoids in the human diet, modulate lipid and glucose metabolism. The aim of this study was to determine whether PAs could adjust the clock system in the liver. Male Wistar rats were orally gavaged with 250 mg grape seed proanthocyanidin extract (GSPE)/kg body weight at zeitgeber time (ZT) 0 (light turned on), at ZT12 (light turned off), or before a 6 hour jet-lag and sacrificed at different times. The 24 hour rhythm of clock-core and clock-controlled gene expression indicated that nicotinamide phosphoribosyltransferase (Nampt) was the most sensitive gene to GSPE. However, Nampt was repressed or overexpressed after GSPE administration at ZT0 or ZT12, respectively. NAD levels, which are controlled by Nampt and also exhibit circadian rhythm, decreased or increased according to Nampt expression. Moreover, the ratio of acetylated Bmal1, that directly drives Nampt expression, only increased when GSPE was administered at ZT12. Therefore, GSPE modulated the clock system in the liver, suggesting that PAs can regulate lipid and glucose metabolism by adjusting the circadian rhythm in the liver.