Consensus statement of the Spanish Society of Neurology on the treatment of multiple sclerosis and holistic patient management in 2023.

The last consensus statement of the Spanish Society of Neurology's Demyelinating Diseases Study Group on the treatment of multiple sclerosis (MS) was issued in 2016. Although many of the positions taken remain valid, there have been significant changes in the management and treatment of MS, both due to the approval of new drugs with different action mechanisms and due to the evolution of previously fixed concepts. This has enabled new approaches to specific situations such as pregnancy and vaccination, and the inclusion of new variables in clinical decision-making, such as the early use of high-efficacy disease-modifying therapies (DMT), consideration of the patient's perspective, and the use of such novel technologies as remote monitoring. In the light of these changes, this updated consensus statement, developed according to the Delphi method, seeks to reflect the new paradigm in the management of patients with MS, based on the available scientific evidence and the clinical expertise of the participants. The most significant recommendations are that immunomodulatory DMT be started in patients with radiologically isolated syndrome with persistent radiological activity, that patient perspectives be considered, and that the term "lines of therapy" no longer be used in the classification of DMTs (> 90% consensus). Following diagnosis of MS, the first DMT should be selected according to the presence/absence of factors of poor prognosis (whether epidemiological, clinical, radiological, or biomarkers) for the occurrence of new relapses or progression of disability; high-efficacy DMTs may be considered from disease onset.

Influencia del estrés oxidativo en la evolución de la aterosclerosis carotídea / Influence of oxidative stress on the progression of carotid atherosclerosis

Introducción y objetivo: el estrés oxidativo (EO) ha demostrado clara influencia en el desarrollo de las placas de ateroma por daños provocados en endotelio vascular. El objetivo de este trabajo es realizar un estudio de los principales marcadores de estrés oxidativo en pacientes con enfermedad aterosclerótica de la arteria carótida como signo de vulnerabilidad, analizar la implicación de la situación redox y el estado metabólico mitocondrial en patología aterosclerótica de la arteria carótida y su relación con clínica neurológica. Pacientes y métodos: se estudiaron las placas de ateroma obtenidas de pacientes intervenidos de endarectomía carotídea (asintomáticos y sintomáticos) en el Servicio de Angiología del Hospital Clínico Universitario de Valladolid en el año 2020. Se recogieron variables clínicas y demográficas y la existencia de sintomatología neurológica. Las características anatómicas y hemodinámicas se estudiaron mediante estudio eco Doppler y angiografía mediante tomografía computarizada en el preoperatorio. Se analizaron placas de ateroma como estimadores del grado de peroxidación lipídica que reflejaron el estado redox. Se ha estimado un tamaño muestral de 45 muestras en cada grupo, con una tasa de pérdidas de seguimiento del 5 %. Se estudiaron las diferencias entre los grupos mediante χ2 y la t de Student para determinar relación entre el potencial redox con las características morfológicas de placa de ateroma. Se utilizó el programa estadístico SPSS 27.0, aceptando como significativo un valor p < 0,05. Resultados: las placas de ateroma calcificadas mostraron mayor capacidad antioxidante con respecto a las placas de ateroma no calcificadas en el parámetro ABTS: 2,2-ácino-bis(ácido 3-etilbenzotiazolina-6-sulfónico) (2635,08 frente a 2803,28). La relación es estadísticamente significativa (p = 0,007)...(AU)

Introduction and objective: oxidative Stress (OS) has proven to have a clear impact on the development of atherosclerotic plaques due to the damage it causes to vascular endothelium. The aim of this study is to conduct a research on key oxidative stress markers in patients with carotid artery atherosclerotic disease as a sign of vulnerability, analyze the implications of the redox status and mitochondrial metabolic state in carotid artery atherosclerotic disease, and its relationship with neurological clinical presentation. Patients and methods: atherosclerotic plaques obtained from carotid endarterectomy patients (both asymptomatic and symptomatic) performed the Department of Angiology, Vascular and Endovascular Surgery of Hospital Clinico Universitario de Valladolid, Spain in 2020 will be examined. The clinical-demographic variables and the presence of neurological symptoms will be recorded. Anatomical and hemodynamic characteristics will be studied using Doppler ultrasound and coronary computed tomography angiography (CCTA) preoperatively. Atherosclerotic plaques will be analyzed as estimators of the degree of lipid peroxidation showing the redox state. A sample size of 45 speciments from each group has been estimated with a loss to follow-up rate of 5 %. Inter-group differences will be studied using the chi-square and Student’s t tests to establish the relationship between redox potential and morphological characteristics of the atheromatous plaque. SPSS 27.0 statistical software will be used, with a significance level set at p < 0.05. Results: calcified atherosclerotic plaques showed higher antioxidant capacity compared to non-calcified plaques in the ABTS parameter (2,2-azino-bis(3-ethylbenzthioziozline-6-sulfonic)) (2635.08 vs 2803.28), with statistically significant relationship (p = 0.007). They also exhibited greater antioxidant defense when analyzing catalase activity (160.73 vs 175.13) and SOD activity (1.11 vs 1.49) (p = 0.049)...(AU)

A step towards rational design of carbon nanobelts with tunable electronic properties.

Belt-shaped aromatic compounds are among the most attractive classes of radial π-conjugated nanocarbon molecules with unique physical and chemical properties. In this work, we computationally studied a number of all-carbon and heteroatom-bridged nanobelts, as well as their inclusion complexes with fullerene C60. Our results provide a useful guide for modulating the electronic properties of the nanobelts. An in-depth analysis of the ground and excited state properties of their complexes has allowed us to establish structure-property relationships and propose simple principles for the design of nanobelts with improved electron-donating properties suitable for photovoltaic applications.

Widening the landscape of transcriptional regulation of green algal photoprotection.

Availability of light and CO2, substrates of microalgae photosynthesis, is frequently far from optimal. Microalgae activate photoprotection under strong light, to prevent oxidative damage, and the CO2 Concentrating Mechanism (CCM) under low CO2, to raise intracellular CO2 levels. The two processes are interconnected; yet, the underlying transcriptional regulators remain largely unknown. Employing a large transcriptomic data compendium of Chlamydomonas reinhardtii's responses to different light and carbon supply, we reconstruct a consensus genome-scale gene regulatory network from complementary inference approaches and use it to elucidate transcriptional regulators of photoprotection. We show that the CCM regulator LCR1 also controls photoprotection, and that QER7, a Squamosa Binding Protein, suppresses photoprotection- and CCM-gene expression under the control of the blue light photoreceptor Phototropin. By demonstrating the existence of regulatory hubs that channel light- and CO2-mediated signals into a common response, our study provides an accessible resource to dissect gene expression regulation in this microalga.

Light-independent regulation of algal photoprotection by CO2 availability.

Photosynthetic algae have evolved mechanisms to cope with suboptimal light and CO2 conditions. When light energy exceeds CO2 fixation capacity, Chlamydomonas reinhardtii activates photoprotection, mediated by LHCSR1/3 and PSBS, and the CO2 Concentrating Mechanism (CCM). How light and CO2 signals converge to regulate these processes remains unclear. Here, we show that excess light activates photoprotection- and CCM-related genes by altering intracellular CO2 concentrations and that depletion of CO2 drives these responses, even in total darkness. High CO2 levels, derived from respiration or impaired photosynthetic fixation, repress LHCSR3/CCM genes while stabilizing the LHCSR1 protein. Finally, we show that the CCM regulator CIA5 also regulates photoprotection, controlling LHCSR3 and PSBS transcript accumulation while inhibiting LHCSR1 protein accumulation. This work has allowed us to dissect the effect of CO2 and light on CCM and photoprotection, demonstrating that light often indirectly affects these processes by impacting intracellular CO2 levels.

Aromaticity controls the excited-state properties of host-guest complexes of nanohoops.

π-Conjugated organic molecules have exciting applications as materials for batteries, solar cells, light-emitting diodes, etc. Among these systems, antiaromatic compounds are of particular interest because of their smaller HOMO-LUMO energy gap compared to aromatic compounds. A small HOMO-LUMO gap is expected to facilitate charge transfer in the systems. Here we report the ground and excited-state properties of two model nanohoops that are nitrogen-doped analogs of recently synthesized [4]cyclodibenzopentalenes - tetramers of benzene-fused aromatic 1,4-dihydropyrrolo[3,2-b]pyrrole ([4]DHPP) and antiaromatic pyrrolo[3,2-b]pyrrole ([4]PP). Their complexes with C60 fullerene show different behavior upon photoexcitation, depending on the degree of aromaticity. [4]DHPP acts as an electron donor, whereas [4]PP is a stronger electron acceptor than C60. The ultrafast charge separation combined with the slow charge recombination that we found for [4]PP⊃C60 indicates a long lifetime of the charge transfer state.

Advancements in Dentistry with Artificial Intelligence: Current Clinical Applications and Future Perspectives.

Artificial intelligence has been widely used in the field of dentistry in recent years. The present study highlights current advances and limitations in integrating artificial intelligence, machine learning, and deep learning in subfields of dentistry including periodontology, endodontics, orthodontics, restorative dentistry, and oral pathology. This article aims to provide a systematic review of current clinical applications of artificial intelligence within different fields of dentistry. The preferred reporting items for systematic reviews (PRISMA) statement was used as a formal guideline for data collection. Data was obtained from research studies for 2009-2022. The analysis included a total of 55 papers from Google Scholar, IEEE, PubMed, and Scopus databases. Results show that artificial intelligence has the potential to improve dental care, disease diagnosis and prognosis, treatment planning, and risk assessment. Finally, this study highlights the limitations of the analyzed studies and provides future directions to improve dental care.

Wax worm saliva and the enzymes therein are the key to polyethylene degradation by Galleria mellonella.

Plastic degradation by biological systems with re-utilization of the by-products could be a future solution to the global threat of plastic waste accumulation. Here, we report that the saliva of Galleria mellonella larvae (wax worms) is capable of oxidizing and depolymerizing polyethylene (PE), one of the most produced and sturdy polyolefin-derived plastics. This effect is achieved after a few hours' exposure at room temperature under physiological conditions (neutral pH). The wax worm saliva can overcome the bottleneck step in PE biodegradation, namely the initial oxidation step. Within the saliva, we identify two enzymes, belonging to the phenol oxidase family, that can reproduce the same effect. To the best of our knowledge, these enzymes are the first animal enzymes with this capability, opening the way to potential solutions for plastic waste management through bio-recycling/up-cycling.

Nitrogen-doped molecular bowls as electron donors in photoinduced electron transfer reactions.

In recent years, the chemistry of curved π-conjugated molecules has experienced a sharp rise. The inclusion of a heteroatom in the carbon network significantly affects its semiconducting properties. In this work, we computationally study the photoinduced electron transfer in a series of C60 fullerene complexes with experimentally established nitrogen-doped molecular bowls. Our results demonstrate that introducing nitrogen into pentagonal rings of the bowl-shaped π-conjugated molecules and extending the π-conjugation can modulate their electron-transfer properties. Among the studied complexes, the hub-NCor⊃C60 complex exhibits the most desirable combination of ultrafast charge separation and slow charge recombination, suggesting its potential use in photovoltaics.

Role of the gut microbiota in the development of various neurological diseases.

INTRODUCTION: In recent years, the scientific evidence supporting a relationship between the microbiota and various diseases has increased significantly; this trend has also been observed for neurological diseases. This has given rise to the concept of the gut-brain axis and the idea of a relationship between the gut microbiota and several neurological diseases whose aetiopathogenesis is yet to be clearly defined. DEVELOPMENT: We review the role of the gut microbiota in the gut-brain axis and analyse those neurological diseases in which alterations in the gut microbiota have been described as a result of human studies: specifically, Parkinson's disease, Alzheimer disease, amyotrophic lateral sclerosis, neuromyelitis optica, and multiple sclerosis. CONCLUSIONS: The body of evidence linking the gut microbiota to various neurological diseases has grown considerably. Several interesting studies show a relationship between the gut microbiota and Parkinson's disease, Alzheimer disease, neuromyelitis optica, and multiple sclerosis, whereas other controversial studies implicate it in amyotrophic lateral sclerosis. Many of these studies place considerable emphasis on modulation of inflammation, particularly by bacteria capable of producing short-chain fatty acids. Despite these encouraging results, many questions remain, and there is a need to demonstrate causality, determine the role of fungi or viruses, and research possible treatment through diet, probiotics, or faecal microbiota transplantation.

Papel de la microbiota intestinal en el desarrollo de diferentes enfermedades neurológicas / Role of the gut microbiota in the development of various neurological diseases

Introducción: En los últimos años la producción científica acerca de la microbiota y su relación con diversas enfermedades se ha disparado, hecho que se ha observado también entre las enfermedades neurológicas. Fruto de estas investigaciones ha surgido el concepto del eje intestino-cerebro, así como la existencia de una relación entre la microbiota intestinal y diversas enfermedades neurológicas, muchasde ellas sin etiopatogenia claramente definida. Desarrollo: Se revisa la implicación de la microbiota intestinal en el eje intestino-cerebro, así como en aquellas enfermedades neurológicas en que se ha descrito una alteración en la microbiota intestinal en estudios llevados a cabo en humanos; concretamente enfermedad de Parkinson, enfermedad de Alzheimer, esclerosis lateral amiotrófica, neuromielitis óptica y esclerosis múltiple. Conclusiones: En la actualidad el cuerpo de evidencia que relaciona la microbiota intestinal y diversas enfermedades neurológicas está creciendo notablemente. Existen interesantes estudios que relacionan la microbiota intestinal con la enfermedad de Parkinson, el Alzheimer, la neuromielitis óptica y la esclerosis múltiple, así como estudios controvertidos acerca del papel de las bacterias intestinales en la esclerosis lateral amiotrófica. En muchas de estas relaciones tiene un importante peso el papel de la modulación de la inflamación, especialmente de aquellas bacterias capaces de producir ácidos grasos de cadena corta. Aún quedan muchos interrogantes por dilucidar, como realizar estudios diseñados para demostrar causalidad, determinar el papel de hongos o virus y los posibles tratamientos con dieta, probióticos o trasplante de heces. (AU)

Introduction: In recent years, the scientific evidence supporting a relationship between the microbiota and various diseases has increased significantly; this trend has also been observed for neurological diseases. This has given rise to the concept of the gut-brain axis and the idea of a relationship between the gut microbiota and several neurological diseases whose aetiopathogenesis is yet to be clearly defined. Development: We review the role of the gut microbiota in the gut-brain axis and analyse those neurological diseases in which alterations in the gut microbiota have been described as a result of human studies: specifically, Parkinson's disease, Alzheimer disease, amyotrophic lateral sclerosis, neuromyelitis optica, and multiple sclerosis. Conclusions: The body of evidence linking the gut microbiota to various neurological diseases has grown considerably. Several interesting studies show a relationship between the gut microbiota and Parkinson's disease, Alzheimer disease, neuromyelitis optica, and multiple sclerosis, whereas other controversial studies implicate it in amyotrophic lateral sclerosis. Many of these studies place considerable emphasis on modulation of inflammation, particularly by bacteria capable of producing short-chain fatty acids. Despite these encouraging results, many questions remain, and there is a need to demonstrate causality, determine the role of fungi or viruses, and research possible treatment through diet, probiotics, or faecal microbiota transplantation. (AU)

Impacto económico del tratamiento a largo plazo de la incontinencia fecal grave / Economic burden of long-term treatment of severe fecal incontinence

Objetivo Conocer el coste económico a largo plazo asociado al tratamiento de la incontinencia fecal grave mediante SNS frente al tratamiento conservador sintomático y la colostomía definitiva. Métodos Estudio descriptivo pormenorizado de los costes del proceso asistencial (intervenciones, consultas, dispositivos, pruebas complementarias, hospitalización, etc.) de 3 alternativas de tratamiento de la incontinencia fecal empleando herramientas de gestión y contabilidad analítica del propio Servicio de Salud con base en datos de actividad clínica. Se estimó, en cada caso, la frecuencia de uso de recursos sanitarios o la cantidad de productos dispensados en farmacias (medicación, pañales, material de ostomía, etc.). Se incluyeron costes derivados de situaciones adversas. Se incluyeron pacientes con incontinencia fecal grave, definida por una puntación superior a 9 en la escala de severidad de Wexner, en los que han fracasado los tratamientos de primera línea. Se emplearon datos de una cohorte consecutiva de 93 pacientes a los que se realizó una SNS entre los años 2002 y 2016; de pacientes intervenidos de colostomía definitiva (n=2); hernia paraestomal (n=3) y estenosis de colostomía (n=1). Resultados El coste medio acumulado en 10 años por paciente en cada alternativa fue: 10.972,9€ para el tratamiento sintomático (62% pañales); 17.351,57€ para la SNS (95,83% intervenciones; 81,6% dispositivos), y 25.858,54€ para la colostomía definitiva (70,4% material de ostomía) Conclusiones El manejo de la incontinencia fecal grave implica un gran impacto en términos económicos. La colostomía es la alternativa que más costes directos genera, seguida de la SNS y el tratamiento sintomático (AU)

Introduction Find out the long-term economic cost associated with the treatment of severe fecal incontinence by SNS versus symptomatic conservative treatment and definitive colostomy. Methods Detailed descriptive study of the costs of the healthcare process (interventions, consultations, devices, complementary tests, hospitalization, etc.) of 3 treatment alternatives for fecal incontinence using analytical accounting tools of the Health Service based on clinical activity data. The frequency of use of health resources or the quantity of products dispensed in pharmacies (medication, diapers, ostomy material, etc.) was estimated in each case. Costs derived from adverse situations were included. Patients with severe fecal incontinence, defined by a score greater than 9 on the Wexner severity scale, in whom first-line treatments had failed, were included. Data from a consecutive cohort of 93 patients who underwent an SNS between 2002 and 2016 were used; patients who underwent definitive colostomy (n=2); parastomal hernia (n=3), and colostomy stenosis (n=1). Results The mean cumulative cost in 10 years per patient in each alternative was: € 10,972.9 symptomatic treatment (62% diapers); € 17,351.57 SNS (95.83% interventions; 81.6% devices); € 25,858.54 definitive colostomy (70.4% ostomy material and accessories). Conclusions Management of severe fecal incontinence implies a great burden in economic terms. The colostomy is the alternative that generates the most direct cost, followed by SNS and symptomatic treatment (AU)

Dissociation between individual differences in self-reported pain intensity and underlying fMRI brain activation.

Pain is an individual experience. Previous studies have highlighted changes in brain activation and morphology associated with within- and interindividual pain perception. In this study we sought to characterize brain mechanisms associated with between-individual differences in pain in a sample of healthy adolescent and adult participants (N = 101). Here we show that pain ratings varied widely across individuals and that individuals reported changes in pain evoked by small differences in stimulus intensity in a manner congruent with their pain sensitivity, further supporting the utility of subjective reporting as a measure of the true individual experience. Furthermore, brain activation related to interindividual differences in pain was not detected, despite clear sensitivity of the Blood Oxygenation Level-Dependent (BOLD) signal to small differences in noxious stimulus intensities within individuals. These findings suggest fMRI may not be a useful objective measure to infer reported pain intensity.

Economic burden of long-term treatment of severe fecal incontinence.

INTRODUCTION: Find out the long-term economic cost associated with the treatment of severe fecal incontinence by SNS versus symptomatic conservative treatment and definitive colostomy. METHODS: Detailed descriptive study of the costs of the healthcare process (interventions, consultations, devices, complementary tests, hospitalization, etc.) of 3 treatment alternatives for fecal incontinence using analytical accounting tools of the Health Service based on clinical activity data. The frequency of use of health resources or the quantity of products dispensed in pharmacies (medication, diapers, ostomy material, etc.) was estimated in each case. Costs derived from adverse situations were included. Patients with severe fecal incontinence, defined by a score greater than 9 on the Wexner severity scale, in whom first-line treatments had failed, were included. Data from a consecutive cohort of 93 patients who underwent an SNS between 2002 and 2016 were used; patients who underwent definitive colostomy (n=2); parastomal hernia (n=3); and colostomy stenosis (n=1). RESULTS: The mean cumulative cost in 10 years per patient in each alternative was: € 10,972.9 symptomatic treatment (62% diapers); € 17,351.57 SNS (95.83% interventions; 81.6% devices); € 25,858.54 definitive colostomy (70.4% ostomy material and accessories). CONCLUSIONS: Management of severe fecal incontinence implies a great burden in economic terms. The colostomy is the alternative that generates the most direct cost, followed by SNS and symptomatic treatment.