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.

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.

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.

[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.

[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.

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.

IFN-beta treatment modulates the CD28/CTLA-4-mediated pathway for IL-2 production in patients with relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system probably mediated by Th1 lymphocytes. IFN-beta is an established therapy for relapsing MS patients, although the mechanisms underlying its efficacy are yet to be well characterized. We determined IL-2 production, CD25 expression and T-cell proliferation from relapsing-remitting MS patients before and three months after starting therapy. A decrease in the percentage of CD80-induced IL-2-producing cells was observed after in vivo IFN-beta treatment. These data support that one of the immunomodulatory effects of IFN-beta treatment in MS may be a limitation of the autoimmune response modifying the CD80:CD28/CTLA-4 pathway.

Metallothionein expression in the central nervous system of multiple sclerosis patients.

Multiple sclerosis (MS) is a major chronic demyelinating and inflammatory disease of the central nervous system (CNS) in which oxidative stress likely plays a pathogenic role in the development of myelin and neuronal damage. Metallothioneins (MTs) are antioxidant proteins induced in the CNS by tissue injury, stress and some neurodegenerative diseases, which have been postulated to play a neuroprotective role. In fact, MT-I+II-deficient mice are more susceptible to developing experimental autoimmune encephalomyelitis (EAE), and treatment of Lewis rats with Zn-MT-II reduces EAE severity. We show here that, as in EAE, MT-I+II proteins were expressed in brain lesions of MS patients. Cells expressing MT-I+II were mainly astrocytes and activated monocytes/macrophages. Interestingly, the levels of MT-I+II were slightly increased in the inactive MS lesions in comparison with the active lesions, suggesting that MTs may be important in disease remission.

Increased demyelination and axonal damage in metallothionein I+II-deficient mice during experimental autoimmune encephalomyelitis.

Metallothioneins I+II (MT-I+II) are antioxidant, neuroprotective factors. We previously showed that MT-I+II deficiency during experimental autoimmune encephalomyelitis (EAE) leads to increased disease incidence and clinical symptoms. Moreover, the inflammatory response of macrophages and T cells, oxidative stress, and apoptotic cell death during EAE were increased by MT-I+II deficiency. We now show for the first time that demyelination and axonal damage are significantly increased in MT-I+II deficient mice during EAE. Furthermore, oligodendroglial regeneration, growth cone formation, and tissue repair including expression of trophic factors were significantly reduced in MT-I+II-deficient mice during EAE. Accordingly, MT-I+II have protective and regenerative roles in the brain.

[Transcranial Doppler velocimetry in normotensive puerperal women]. / Velocimetría Doppler transcraneal en puérperas normotensas.

OBJECTIVES: To know transcranial Doppler (TCD) normal values in postpartum normotensive women. To evaluate the effect of different variables on cerebral blood flow velocity. PATIENTS AND METHODS: TCD examination was carried out in 100 postpartum normotensive women. Six intracranial arteries were evaluated. Different variables such as arterial pressure, hematocrit and clinical data related to pregnancy and delivery were recorded. A descriptive analysis of qualitative variables was made and the mean and standard deviation of each quantitative variable was calculated. We compared mean velocities (MV) by each side, and assessed the correlation between cerebral blood flow velocity and arterial pressure, hematocrit and the rest of variables. RESULTS: Mean and standard deviations of MV were: right MCA 73.10 14.33; left MCA 75.68 15.84; right ACA 57.61 12.92; left ACA 60.14 14.35; right PCA 42.77 9.28; left PCA 45.54 9.58. Statically significant higher values of MV in the left hemispheric arteries were found. The other analysed variables did not modify the MV values. CONCLUSIONS: In postpartum normotensive women MV values were higher in the left hemisphere. The knowledge of normal puerperium values for TCD is useful to identify cerebral hemodynamic pathological states such those in postpartum eclampsia and postpartum cerebral angiopathy.

Expression of chemokine receptors in the different clinical forms of multiple sclerosis.

Chemokines and their receptors are important in the trafficking of peripheral leukocytes into the central nervous system, a major event in the pathogenesis of multiple sderosis (MS). Evidence based on clinical, pathological and magnetic resonance imaging grounds supports some divergence between forms of MS with relapses [relapsing-remitting (RR) and secondary progressive (SP)] and the primary progressive (PP) form. To elucidate whether different pathogenic mechanisms are involved in PPMS, we compared membrane expression of a group of CC and CXC chemokine receptors (CCR1, CCR5, CXCR3, CXCR4) in peripheral blood of 68 MS patients (25 PPMS, 23 SPMS and 20 RRMS) and 26 healthy controls. We found a significant increase in surface expression of CCR5 in CD4+, CD8+, CD19+ and CD14+ cells as well as an increased percentage of CXCR3 and CXCR4 in CD14+ cells in MS patients compared to controls. Increased levels of CXCL10 (IP-10) and CCL5 (RANTES) in cerebrospinal fluid were also observed in a subgroup of MS patients. These results support that chemokines and their receptors are involved in the pathogenesis of MS However, a pattem of chemokine-chemokine receptor expression characteristic of each clinical form of the disease failed to be observed.