Two-dimensional hydrogenated buckled gallium arsenide: an ab initio study.

First-principles calculations have been carried out to investigate the stability, structural and electronic properties of two-dimensional (2D) hydrogenated GaAs with three possible geometries: chair, zigzag-line and boat configurations. The effect of van der Waals interactions on 2D H-GaAs systems has also been studied. These configurations were found to be energetic and dynamic stable, as well as having a semiconducting character. Although 2D GaAs adsorbed with H tends to form a zigzag-line configuration, the energy differences between chair, zigzag-line and boat are very small which implies the metastability of the system. Chair and boat configurations display a [Formula: see text]-[Formula: see text] direct bandgap nature, while pristine 2D-GaAs and zigzag-line are indirect semiconductors. The bandgap sizes of all configurations are also hydrogen dependent, and wider than that of pristine 2D-GaAs with both PBE and HSE functionals. Even though DFT-vdW interactions increase the adsorption energies and reduce the equilibrium distances of H-GaAs systems, it presents, qualitatively, the same physical results on the stability and electronic properties of our studied systems with PBE functional. According to our results, 2D buckled gallium arsenide is a good candidate to be synthesized by hydrogen surface passivation as its group III-V partners 2D buckled gallium nitride and boron nitride. The hydrogenation of 2D-GaAs tunes the bandgap of pristine 2D-GaAs, which makes it a potential candidate for optoelectronic applications in the blue and violet ranges of the visible electromagnetic spectrum.

Gut dysbiosis and neuroimmune responses to brain infection with Theiler's murine encephalomyelitis virus.

Recent studies have begun to point out the contribution of microbiota to multiple sclerosis (MS) pathogenesis. Theiler's murine encephalomyelitis virus induced demyelinating disease (TMEV-IDD) is a model of progressive MS. Here, we first analyze the effect of intracerebral infection with TMEV on commensal microbiota and secondly, whether the early microbiota depletion influences the immune responses to TMEV on the acute phase (14 dpi) and its impact on the chronic phase (85 dpi). The intracranial inoculation of TMEV was associated with a moderate dysbiosis. The oral administration of antibiotics (ABX) of broad spectrum modified neuroimmune responses to TMEV dampening brain CD4+ and CD8+ T infiltration during the acute phase. The expression of cytokines, chemokines and VP2 capsid protein was enhanced and accompanied by clusters of activated microglia disseminated throughout the brain. Furthermore, ABX treated mice displayed lower levels of CD4+ and CD8+T cells in cervical and mesenteric lymph nodes. Increased mortality to TMEV was observed after ABX cessation at day 28pi. On the chronic phase, mice that survived after ABX withdrawal and recovered microbiota diversity showed subtle changes in brain cell infiltrates, microglia and gene expression of cytokines. Accordingly, the surviving mice of the group ABX-TMEV displayed similar disease severity than TMEV mice.

Expression of semaphorin 3A, semaphorin 7A and their receptors in multiple sclerosis lesions.

BACKGROUND: Studies in multiple sclerosis (MS) and in experimental models point to a critical role of semaphorin (sema)3A and sema7A in MS pathogenesis. OBJECTIVE: The objective of this paper is to characterise the expression of sema3A, sema7A, and their receptors in MS lesions. METHODS: We included 44 demyelinating lesions from MS patients, 12 lesions with acute cerebral infarct, 11 lesions with progressive multifocal leucoencephalopathy and 10 non-neurological control patients. MS lesions were classified according to inflammatory activity and all samples were immunostained for sema3A, sema7A, neuropilin 1 (Np-1), α1-integrin, and ß1-integrin. RESULTS: In MS-damaged white matter sema3A and Np-1 were both detected in microglia/macrophages, whereas reactive astrocytes expressed only sema3A. Otherwise, sema7A, α1-integrin and ß1-integrin were observed in reactive astrocytes, and microglia/macrophages only expressed ß1-integrin. The expression of sema3A, sema7A and their receptors is more relevant in MS than in other demyelinating diseases. Sema3A and sema7A expression correlated with the inflammatory activity of the MS lesions, suggesting their involvement in the immunological process that takes place in MS. CONCLUSIONS: The expression pattern of sema3A, sema7A and their receptors in MS lesions suggests that both molecules contribute to create a negative environment for tissue regeneration, influencing the ability to regenerate the damaged tissue.

Assessment of the reproducibility of oligoclonal IgM band detection for its application in daily clinical practice.

BACKGROUND: The presence of oligoclonal IgM bands (OCMB) in cerebrospinal fluid (CSF) is an unfavourable prognostic marker in multiple sclerosis. There is no commercial test to investigate OCMB status. However, a sensitive and specific isoelectrofocusing (IEF) and western blot method was described. We aimed to study the inter-centre reproducibility of this technique, a necessary condition for a reliable test to be incorporated into clinical practice. METHODS: The presence of OCMB was analysed by IEF and western blot with prior reduction of pentameric IgM. We assayed the reproducibility of this test in a blinded multicentre study performed in 13 university hospitals. Paired-CSF and serum samples from 52 neurological patients were assayed at every centre. RESULTS: Global analysis rendered a concordance of 89.8% with a kappa value of 0.71. CONCLUSION: These data indicate that OCMB detection by means of IEF and western blot with IgM reduction shows a good interlaboratory reproducibility and thus can be used in daily clinical setting.

Anti-myelin antibodies play an important role in the susceptibility to develop proteolipid protein-induced experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. It is an autoimmune disorder in which activated T cells cross the blood-brain barrier (BBB) to initiate an inflammatory response that leads to demyelination and axonal damage. The key mechanisms responsible for disease initiation are still unknown. We addressed this issue in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. It is widely known that EAE manifests only in certain strains when immunized with myelin proteins or peptides. We studied the differential immune responses induced in two mouse strains that are susceptible or resistant to EAE induction when they are immunized with the 139-151 peptide of proteolipid protein, an encephalitogenic peptide capable of inducing EAE in the susceptible strain. The adequate combination of major histocompatibility complex alleles and myelin peptides triggered in susceptible mice a T helper type 17 (Th17) response capable of inducing the production of high-affinity anti-myelin immunoglobulin (Ig)G antibodies. These were not detected in resistant mice, despite immunization with the encephalitogenic peptide in junction with complete Freund's adjuvant and pertussis toxin, which mediate BBB disruption. These data show the pivotal role of Th17 responses and of high-affinity anti-myelin antibodies in EAE induction and that mechanisms that prevent their appearance can contribute to resistance to EAE.

Guía de uso adecuado de modelos animales para el desarrollo de terapias en esclerosis múltiple / Guidelines on the appropriate use of animal models for developing therapies in multiple sclerosis

Introducción. La búsqueda de terapias efectivas para la esclerosis múltiple (EM) y la definición de ventanas terapéuticas apropiadas, así como el establecimiento de mejores biomarcadores diagnósticos y pronósticos, continúan siendo un reto para investigadores tanto básicos como clínicos. El desarrollo y el método de evaluación de los estudios preclínicos en modelos animales podrían subyacer al hecho de que terapias eficaces en modelos animales fracasen en su aplicación clínica. Objetivo. Unificar la metodología en la aplicación de los modelos experimentales para la EM mediante la elaboración, por parte de grupos españoles expertos pertenecientes a la Red Española de Esclerosis Múltiple, de una guía de recomendaciones para los estudios preclínicos. Desarrollo. Se ha realizado una valoración detallada de los modelos experimentales adecuados y su aplicación en función del objetivo perseguido, incorporando estándares y criterios de calidad imprescindibles en un estudio preclínico. Conclusiones. El éxito traslacional en el avance terapéutico de la EM conlleva la adquisición de compromisos metodológicos en los modelos experimentales, de manera que se optimice la bondad y adecuación del modelo al estudio perseguido. Las recomendaciones establecidas en esta guía podrían ayudar a generar datos preclínicos de utilidad en la práctica clínica (AU)

Introduction. The advance in the achievement of effective therapies for multiple sclerosis (MS), the definition of appropriate therapeutic windows and to establish better diagnostic and prognostic biomarkers have become a challenging task for both researchers and clinicians. Some pitfalls in clinical trials might be related to lack of adequacy of the preclinical studies in MS experimental animal models Aim. To standardize the methodological protocols of experimental models by developing a set of guidelines for preclinical studies by groups of experts from REEM (Spanish Network for MS). Development. A guide with recommendations for the application of MS models including a detailed assessment of appropriate experimental models taking into account the objective of the study that has been presented. Standards and quality criteria necessary in a preclinical study have been included. Conclusions. Standardized animal models of MS are essential to increase the success of the preclinical findings in order to transfer them to the clinical practice (AU)

Utility of oligoclonal IgG band detection for MS diagnosis in daily clinical practice.

An early and accurate diagnosis of multiple sclerosis (MS) is very important, since it allows early treatment initiation, which reduces the activity of the disease. Oligoclonal IgG band (OCGB) detection is a good ancillary tool for MS diagnosis. However, it was argued that its usefulness was limited by the high interlaboratory variability. In the last years, different techniques for OCGB detection have appeared. We performed a blinded aleatorized multicenter study in 19 Spanish hospitals to assess the accuracy and reproducibility of OCGB detection in this new scenario. We studied cerebrospinal fluid (CSF) and serum samples from 114 neurological patients. Every hospital contributed to the study with triplicated pairs of CSF and serum samples of six patients and analyzed 18 different samples. Global analysis rendered a sensitivity of 92.1%, a specificity of 95.1% and a Kappa value of 0.81. This shows that current techniques for OCGB detection have good accuracy and a high interlaboratory reproducibility and thus, represent a good tool for MS diagnosis. When we analyzed separately the different techniques used for OCGB detection, the highest concordance was observed in western blot with alkaline phosphatase detection (kappa=0.91). This indicates that high sensitivity techniques improve the reproducibility of this assay.

Aplicación de metodología de marco lógico para el análisis del programa nacional de pesquisa y control del cáncer cervicouterino en Chile / Methodology of logical framework for the analysis of the program of control of cervical cancer in Chile

La metodología de marco lógico (MML) es una herramienta de gestión utilizada para el diseño, monitoreo y evaluación de proyectos y programas. Promovida por el Banco Mundial y usada por la Dirección de Presupuestos de Chile, desde 1997. Algunos de los actuales programas de salud de nuestro país, se remontan a épocas en que esta metodología no estaba en boga. En el presente trabajo, se analiza utilizando esta metodología, el Programa de Pesquisa y Control de Cáncer Cervicouterino, vigente en Chile desde 1987. Este método nos permitió detectar posibles áreas falentes, principalmente en la definición de la población objetivo, en la explicitación del presupuesto, en la coordinación de los diferentes niveles del programa y en la participación comunitaria. Se presentan algunas propuestas que podrían contribuir al mejor desarrollo de este programa.

The methodology of logical framework (LFW) is a management tools used to design and evaluation of projects and programs. Promoted by de World Bank and used by the Direction of Budgets of Chile, since 1997. The projects and programs on health force in our country, mostly, dating back to times when this me-thodology it was not in vogue. In this work, using this methodology, we analyze the Program of Control of Cervical Cancer in Chile, since 1987. This method allowed us to detect possible lack areas, mainly in the defnition of the target population, in the clarifcation of budget, in the coordination of the different levels of the program and the community participation. Finally, showed some proposals that could contribute to better development of this program.

Degeneración hepatocerebral adquirida / Acquired hepatocerebral degeneration

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Plasma chitotriosidase activity in multiple sclerosis.

A recent study has shown that chitotriosidase (Chit) may play a role in the pathogenesis of multiple sclerosis (MS). Plasma Chit activity was investigated in 219 untreated MS patients and 160 healthy controls (HC) by means of a fluorometric enzyme activity assay. Chit activity was also measured in a subgroup of 46 patients following treatment with interferon-beta (IFNbeta). Overall, plasma Chit activity was significantly increased in MS patients compared with HC, but no differences were observed between relapsing and progressive clinical forms. In addition, Chit activity was similar between patients during relapse and patients during clinical remission. Treatment with IFNbeta was associated with a significant increase in Chit activity compared with untreated patients in both responders and non-responders to treatment. Although these findings suggest a role of Chit in MS, our data do not support an association between plasma Chit activity and MS clinical course and clinical response to IFNbeta treatment.

[A descriptive analysis of the demand for ambulatory neurological care in the health district of Huelva]. / Análisis descriptivo de la demanda de asistencia neurológica ambulatoria en un área sanitaria de Huelva.

INTRODUCTION: In recent years the demand for ambulatory neurological care has risen. Studying this situation can help to improve health care planning and the quality of the referrals from primary care. AIM: To analyse a number of variables involved in the first visits referred from primary care to neurology services. PATIENTS AND METHODS: We conducted a prospective, descriptive study in which data was consecutively collected about 500 new patients from primary care who had appointments for a visit to general neurology services in the health district of the province of Huelva. Demographic features, the reason for referral, initial diagnoses and the case resolution index were analysed. RESULTS: Mean age was 51 years old, and patients were predominantly female (63.4%). The most frequent diagnoses were headaches (42.8%) and cognitive impairment (12%). In 8.2% of cases the referred patients had no neurological pathology. Data showed that 40.2% were discharged after the first visit. CONCLUSIONS: The demographic characteristics and reasons for the visit were similar to those previously published on other regions in Spain. The high percentage of direct discharges translates into a poor selection of the patients referred from primary care. Improving the quality of referrals would make it possible to enhance the efficiency of ambulatory neurological care.

Análisis descriptivo de la demanda de asistencia neurológica ambulatoria en un área sanitaria de Huelva / A descriptive analysis of the demand for ambulatory neurological care in the health district of Huelva

Introducción. En los últimos años se ha incrementado la demanda de asistencia neurológica ambulatoria. Su estudio puede contribuir a mejorar la planificación sanitaria y la calidad de las derivaciones desde atención primaria. Objetivo. Analizar diversas variables de las primeras visitas remitidas desde atención primaria a las consultas de neurología. Pacientes y métodos. Estudio prospectivo descriptivo en el que se recogieron de forma consecutiva los datos de 500 pacientes nuevos procedentes de atención primaria citados en una consulta de neurología general en el área sanitaria de la provincia de Huelva. Se analizaron las características demográficas, el motivo de derivación, los diagnósticos iniciales y el índice de resolución de los casos. Resultados. La media de edad fue de 51 años, con un predominio femenino (63,4%). Los diagnósticos más frecuentes fueron las cefaleas (42,8%) y el deterioro cognitivo (12%). El 8,2% de los pacientes remitidos no tenía ninguna patología neurológica. El 40,2% fue dado de alta tras la primera visita. Conclusiones. Las características demográficas y los motivos de consulta son similares a los publicados previamente en otras comunidades españolas. El elevado porcentaje de altas directas traduce una escasa selección de los pacientes remitidos desde atención primaria. La mejora en la calidad de las derivaciones permitiría mejorar la eficiencia de la asistencia neurológica ambulatoria

Introduction. In recent years the demand for ambulatory neurological care has risen. Studying this situation can help to improve health care planning and the quality of the referrals from primary care. Aim.To analyse a number of variables involved in the first visits referred from primary care to neurology services. Patients and methods. We conducted a prospective, descriptive study in which data was consecutively collected about 500 new patients from primary care who had appointments for a visit to general neurology services in the health district of the province of Huelva. Demographic features, the reason for referral, initial diagnoses and the case resolution index were analysed. Results. Mean age was 51 years old, and patients were predominantly female (63.4%). The most frequent diagnoses were headaches (42.8%) and cognitive impairment (12%). In 8.2% of cases the referred patients had no neurological pathology. Data showed that 40.2% were discharged after the first visit. Conclusions. The demographic characteristics and reasons for the visit were similar to those previously published on other regions in Spain. The high percentage of direct discharges translates into a poor selection of the patients referred from primary care. Improving the quality of referrals would make it possible to enhance the efficiency of ambulatory neurological care

[Room tilt illusion: a rare symptom of migraine aura]. / Ilusión de inversión de la imagen visual: una manifestación excepcional de aura migrañosa.

INTRODUCTION: Room tilt illusion is a distorted perception of the spatial distribution of objects due to complex rotations in different planes. This distortion usually occurs in the vertical plane and is usually associated to vertebrobasilar ischemia. The etiology of the phenomenon varies greatly and only rarely corresponds to migraine aura. CASE REPORT: Since youth, a sixty-year-old woman had frequent episodes of room tilt illusion in the horizontal plane. These lasted from 30 minutes to 2 hours and were always followed by frontal headache fulfilling criteria for migraine (computerized tomography and magnetic resonance imaging) were normal. Visual symptoms and headache disappeared following treatment with flunarizine. DISCUSSION: Room tilt illusion might be a rare symptom of migraine aura. In this setting a functional depression of neurons from the posterior parietal cortex may occur, possibly mediated by chemical factors.

Ilusión de inversión de la imagen visual: una manifestación excepcional de aura migrañosa / Room tilt illusion: a rare symptom of migraine aura

Introducción. La ilusión de inversión de la imagen visual consiste en una percepción alterada de la situación de los objetos que se produce por rotaciones completas en los distintos planos del espacio. Esta alteración es más frecuente en el plano vertical y se asocia sobre todo a isquemia vertebrobasilar. La etiología del fenómeno es muy diversa y sólo excepcionalmente corresponde a un aura migrañosa. Caso clínico. Mujer de 60 años que desde su juventud presenta episodios de inversión visual en el plano horizontal, de 30 min a 2 h de duración, que siempre se siguen de una cefalea bifrontal con criterios de migraña. Los estudios de neuroimagen (tomografía computarizada y resonancia magnética craneal) fueron normales. Tanto los síntomas visuales como la cefalea desaparecieron al instaurar tratamiento con flunarizina. Discusión. La ilusión de inversión de la imagen visual puede ser una manifestación infrecuente de aura migrañosa. El mecanismo fisiopatológico consiste en una depresión funcional neuronal transitoria de la corteza parietal posterior, posiblemente mediada por factores químicos

Introduction. Room tilt illusion is a distorted perception of the spatial distribution of objects due to complex rotations in different planes. This distortion usually occurs in the vertical plane and is usually associated to vertebrobasilar ischemia. The etiology of the phenomenon varies greatly and only rarely corresponds to migraine aura. Case report. Since youth, a sixty-year-old woman had frequent episodes of room tilt illusion in the horizontal plane. These lasted from 30 minutes to 2 hours and were always followed by frontal headache fulfilling criteria for migraine (computerized tomography and magnetic resonance imaging) were normal. Visual symptoms and headache disappeared following treatment with flunarizine. Discussion. Room tilt illusion might be a rare symptom of migraine aura. In this setting a functional depression of neurons from the posterior parietal cortex may occur, possibly mediated by chemical factors

[Cerebral calcifications: a clue for a diagnostic process in a nonspecific clinical case]. / Calcificaciones cerebrales típicas como orientación de cuadro clínico inespecífico.

Coeliac disease is a gluten sensitive enteropathy, autoimmune in origin, which has been traditionally regarded as a gastrointestinal disease. Years later it has been reported an extraintestinal affection. A huge number of neurological syndromes of unknown cause had been initially described in association with coeliac disease, with total or partial response to a gluten free-diet. A specific kind of occipital cerebral calcifications in relation to coeliac disease has been also described, and sometimes it means the existence of a syndrome called "Gobby's Syndrome". We show a patient with a mild unknown coeliac disease, a woman who had occipital cerebral calcifications in a TAC cerebral, which was made because of her intractable migraines and that it lead to the diagnosis. The migraine disappeared after a gluten free-diet, like similar cases reported by literature. The fact of existing neurological symptoms associated to coeliac diseases opens a therapeutic window of opportunity because they would respond to a gluten free-diet.

Calcificaciones cerebrales típicas como orientación de cuadro clínico inespecífico / Cerebral calcifications: a clue for a diagnostic process in a inespecific clinical case

La enfermedad celíaca es una enteropatía por sensibilidad al gluten de origen autoinmune, considerada clásicamente como enfermedad exclusivamente gastrointestinal. Posteriormente se han puesto de manifiesto manifestaciones extraintestinales. Un número importante de síndromes neurológicos catalogados de idiopáticos al inicio, han sido descritos en el contexto de enfermedad celiaca, presentando respuesta total o parcial tras dieta sin gluten. Se ha descrito asociado a enfermedad celiaca un tipo muy característico de calcificaciones cerebrales occipitales, que a veces forma parte de un síndrome específico llamado síndrome de Gobby. Presentamos una paciente con enfermedad celiaca oligosintomática, que presentaba las peculiares calcificaciones cerebrales que fueron halladas tras realización de una prueba de imagen al presentar migraña rebelde a tratamiento, y que orientaron hacia su diagnóstico. La migraña mejoró sustancialmente tras realizar dieta sin gluten, como en otros casos descritos en la literatura. El hecho de que existan manifestaciones neurológicas asociadas a enfermedad celiaca hace posible la reversibilidad de las mismas tras dieta exenta de gluten

Coeliac disease is a gluten sensitive enteropathy, autoimmune in origin, which has been traditionally regarded as a gastrointestinal disease. Years later it has been reported an extraintestinal affection. A huge number of neurological syndromes of unknown cause had been initially described in association with coeliac disease, with total or parcial response to a gluten free-diet. A specific kind of occipital cerebral calcifications in relation to coeliac disease has been also described, and sometimes it means the existence of a syndrom called “Gobby´s Syndrom”. We show a patient with a mild unknown coeliac disease, a woman who had occipital cerebral calcifications in a TAC cerebral, which was made because of her wild migraine and that it leaded the diagnosis. The migraine disappeared after a gluten free-diet, like similar cases reported by literature. The fact of existing neurological symtoms associated to coeliac diseases opens a therapeutc window of opportunity because they would repond to a gluten free-diet

Time-course expression of CNS inflammatory, neurodegenerative tissue repair markers and metallothioneins during experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis (MS). EAE and MS are characterized by CNS inflammation, demyelination and neurodegeneration. The inflammatory response occurring within the CNS leads to glial activation, dysfunction and death, as well as axonal damage and neurological deficit. Although the pathogenic mechanisms involved in EAE/MS are not well understood, accumulating data suggest that oxidative stress plays a major role in lesion development, and contributes to axonal dysfunction and degeneration. Metallothionein-I and -II are anti-inflammatory, neuroprotective, antioxidant proteins expressed during EAE and MS, in which they might play a protective role. The present study aimed to describe the expression profile of a group of inflammatory, neurodegenerative and tissue repair markers as well as metallothioneins during proteolipid protein-induced EAE, and to establish the time-relationships these molecules had during EAE. Interestingly, we found two marker expression profiles. In the first, marker expression increased as clinical signs worsened and reverted to baseline expression during recovery; in the second, marker expression increased at a later point during relapse, peaked at highest clinical score, and remained elevated throughout recovery. Of note, metallothionein expression was found to be related to the second profile, which would suggest that metallothionein proteins are implicated in the clinical recovery of EAE and perhaps these antioxidant proteins may provide therapeutic benefits in MS.

A new case of semicircular lipoatrophy associated with repeated external microtraumas and review of the literature.

We present a new case of semicircular lipoatrophy whose lesions disappeared after 2 months of avoiding a repeated trauma in that area. It seems that this is the only associated aetiological factor, and this entity is perhaps a consequence of certain postural habits. The repeated microtraumas would damage the fatty tissue giving rise to the histopathological findings described, which are compatible with traumatic panniculitis. In conclusion, repeated microtraumas may be the aetiological factor in these cutaneous lesions. Other data in favour of this hypothesis are the disappearance of the lesions after avoiding the mechanical trauma, the fact that there were other affected people at work, and that this factor has also been identified in the majority of cases reported previously.