Executive Functioning and Language in a Pediatric Population with Autism Spectrum Disorders and Epilepsy: A Comparative Study.

In recent years, there has been an increase in the prevalence of comorbidity between ASD and epilepsy in the pediatric population. Children with ASD and epilepsy often exhibit greater impairments in executive functions such as cognitive flexibility, planning, inhibition, and emotional control, as well as in language dimensions such as phonology, semantics, morphosyntax, and pragmatics. These impairments can significantly impact their maturation and development. The aim of this study was to assess and compare the executive functioning and language skills of 150 participants, divided into three groups: one with ASD only, another with epilepsy only, and the third group with both ASD and epilepsy. The study utilized the Behavior Rating Inventory of Executive Function (BRIEF-2) and Neuropsychological Evaluation of Executive Functions in Children (ENFEN) to assess executive functions, and Clinical Evaluation of Language Fundamentals 5 (CELF-5) to evaluate language skills. The results indicated that participants with this comorbidity had lower scores in both executive functioning and language skills compared to children with only ASD or epilepsy. The presence of epilepsy significantly limits the executive and linguistic performance of children with ASD, negatively affecting language acquisition, functionality, and the ability to carry out basic life activities independently.

The Linguistic-Cognitive Profile in an Adult Population with Parkinson's Disease and Deep Brain Stimulation: A Comparative Study.

Introduction. Individuals with Parkinson's disease (PD) exhibit general impairments, particularly non-motor symptoms that are related to language, communication, and cognition processes. People with this disease may undergo a surgical intervention for the placement of a deep brain stimulation device, which improves their motor symptoms. However, this type of intervention leads to a decline in their linguistic and cognitive abilities that becomes increasingly noticeable as the disease progresses. Objective. The objective of this research was to compare the performance and linguistic-cognitive profile of individuals with Parkinson's disease who underwent deep brain stimulation treatment based on the stage of the disease. Method. A total of 60 participants who were diagnosed with PD by their reference hospital were selected. These participants were divided into three groups based on the stage of the disease that they were in, forming three groups: a Stage I group (n = 20), a Stage II group (n = 20), and a Stage III group (n = 20). The linguistic-cognitive profile was assessed using the MoCA, ACE-III, and MetAphas tests. The design of this study was established as a quasi-experimental, cross-sectional investigation, and statistical analysis was performed using MANOVA to compare the scores between the study groups. Results. The results indicate that individuals in Stage I exhibit better linguistic and cognitive performance compared to the other groups of participants in Stage II and Stage III, with statistically significant differences (p < 0.05). Conclusion. In conclusion, the progression of PD leads to significant linguistic and cognitive decline in individuals with this disease who have a deep brain stimulation device, greatly limiting the autonomy and quality of life for people with PD.

The Comprehension of Grammatical Structures in a Pediatric Population with ASD and Epilepsy: A Comparative Study.

Autism Spectrum Disorder (ASD) and epilepsy represent a comorbidity that negatively influences the proper development of linguistic competencies, particularly in receptive language, in the pediatric population. This group displays impairments in the auditory comprehension of both simple and complex grammatical structures, significantly limiting their performance in language-related activities, hampering their integration into social contexts, and affecting their quality of life. The main objective of this study was to assess auditory comprehension of grammatical structures in individuals with ASD and epilepsy and compare the results among the three groups. A non-experimental cross-sectional study was designed, including a total of 170 participants aged between 7 and 9 years, divided into three groups: a group with ASD, a group with epilepsy, and a comorbid group with both ASD and epilepsy (ASDEP). The comprehension of grammatical structures was assessed using the CEG and CELF-5 instruments. Statistical analyses included MANOVA and ANOVA to compare scores between groups to verify associations between study variables. The results indicate that the group with ASD and epilepsy performed worse compared to the ASD and epilepsy-only groups, respectively. Additionally, a significant and directly proportional association was observed among all variables within the measures of grammatical structure comprehension. The neurological damage caused by epilepsy in the pediatric population with ASD leads to difficulties in understanding oral language. This level of functioning significantly limits the linguistic performance of these children, negatively impacting their quality of life and the development of core language skills.

El incremento de las alteraciones auditivas en población infantil Una revisión sistemática de la literatura científica / The Increase of Hearing Disorders in the Child Population A systematic review of the scientific literature

El desarrollo del habla, el lenguaje, la comunicación, la cognición y otros aspectos en la infancia se ven profundamente influenciados por la audición. Cuando un niño presenta pérdida auditiva no detectada o no tratada, se reducen los estímulos y se dificulta el desarrollo de habilidades lingüísticas. La falta de atención temprana puede llevar a retrasos en el desarrollo del lenguaje, afectando la capacidad del niño para comprender y comunicarse. La hipoacusia pediátrica es un problema de salud pública que afecta a un porcentaje significativo de niños en todo el mundo. El aumento de la causa de la hipoacusia infantil en diferentes países se atribuye a factores como la falta de conciencia y educación sobre la importancia de la detección temprana, la disponibilidad y acceso limitados a servicios de detección y diagnóstico, la ausencia de programas de detección temprana en algunos países y la necesidad de contar con profesionales de la salud capacitados en el manejo de la audición pediátrica. Todo ello puede afectar áreas fundamentales del desarrollo, incluyendo el lenguaje y la comunicación, el desarrollo cognitivo, sensorial, motor y adaptativo. Por tanto, este trabajo tuvo el objetivo de llevar a cabo una revisión narrativa de la literatura científica sobre la situación de las alteraciones auditivas en la población pediátrica

The development of speech, language, communication, cognition, and other aspects in childhood is profoundly influenced by hearing. When a child experiences undetected or untreated hearing loss, stimuli are reduced, and the development of linguistic skills becomes challenging. The lack of early attention can lead to language development delays, affecting the child's ability to comprehend and communicate. Pediatric hearing loss is a public health issue that affects a significant percentage of children worldwide. The increasing prevalence of pediatric hearing loss in different countries is attributed to factors such as a lack of awareness and education about the importance of early detection, limited availability and access to screening and diagnostic services, the absence of early detection programs in some countries, and the need for trained healthcare professionals in pediatric audiology. All of this can impact fundamental areas of development, including language and communication, cognitive, sensory, motor, and adaptive development.Therefore, this work aimed to conduct a narrative review of the scientific literature on the status of auditory impairments in the pediatric population

The Influence of Sleep Disorders on Neurobiological Structures and Cognitive Processes in Pediatric Population with ASD and Epilepsy: A Systematic Review.

Autism Spectrum Disorder (ASD) and epilepsy are increasingly prevalent comorbidities in our society. These two disorders are often accompanied by other comorbidities, such as sleep disorders, significantly impacting the quality of life of individuals with ASD and epilepsy. To date, clinical approaches have primarily been descriptive in nature. Therefore, this study aimed to analyze the relationship between ASD, epilepsy, and sleep disorders, exploring neurobiological dysfunctions and cognitive alterations. A total of 22 scientific articles were selected using a systematic literature review following the criteria established using the PRISMA model. The selected articles were gathered from major databases: Medline, PubMed, PsycINFO, Google Scholar, and Web of Science. Inclusion criteria specified that study participants had an official diagnosis of ASD, the article precisely described the evaluation parameters used in the study participants, and individual characteristics of the sleep disorders of the study participants were specified. The results indicate, firstly, that the primary cause of sleep disorders in this population is directly linked to abnormal serotonin behaviors. Secondly, significant alterations in memory, attention, and hyperactivity were observed. In conclusion, sleep disorders negatively impact the quality of life and neurocognitive development of the pediatric population with ASD and epilepsy.

Emotional and behavioral alterations and their relationship with executive functioning in the pediatric population with autism spectrum disorder and epilepsy: a comparative study.

Introduction: The pediatric population with Autism Spectrum Disorder (ASD) and epilepsy presents behavioral and emotional alterations that hinder their correct developmental maturation as well as their integration in different contexts such as school, family or social. This population shows atypical behavioral and emotional patterns, with difficulties in emotional regulation, understanding of emotions, aggressiveness, or low frustration tolerance. They also present alterations in executive functions, which significantly influence the emotional and behavioral characteristics of this population. Research suggests that epilepsy worsens the emotional, behavioral, and executive functioning status. Objective: To explore differences in behavioral, emotional, and executive functioning profile in individuals with a diagnosis of ASD, epilepsy, and ASD with epilepsy. Method: In this quasi-experimental and cross-sectional study, a total of 170 participants were selected and distributed into three groups: a group of participants with ASD, a group with epilepsy, and a group of participants with ASD and epilepsy. The SENA, BASC-3, and ENFEN tests were administered to verify the behavioral, emotional, and executive functioning profile in the three groups. Results: The results indicate that individuals diagnosed with ASD and epilepsy present greater emotional, behavioral, and executive functioning alterations compared to those who only present ASD or epilepsy. Conclusion: Individuals with ASD and epilepsy present significant alterations in emotional, behavioral, and executive functioning processes, which hinder their adaptation to different contexts, as well as decreasing their quality of life and that of their family.

Relationship of epilepsy on the linguistic-cognitive profile of children with ASD: A systematic review of the literature.

Introduction: The prevalence of comorbidity between epilepsy and Autism Spectrum Disorder (ASD) in the pediatric age increased significantly in recent years. The onset of epilepsy negatively influences the abilities of the user with ASD. Thus, epilepsy will be a disabling factor that will reduce the cognitive-linguistic skills of users with ASD. The main objective of this work is to review the current scientific literature and to compare the relationship of epilepsy on the development of cognitive and linguistic skills of children with ASD. Methods: In this regard, a systematic search was carried out in the main sources (Medline, PubMed, WOS, ResearchGate and Google Scholar). 481 articles were identified, from which, after meeting the different inclusion and exclusion criteria, a total of 18 studies of relevance to the objectives of this work were selected. Results: The results reflect that, at a global level, epilepsy significantly influences the performance of cognitive- linguistic skills in people with ASD. Discussion: In conclusion, epilepsy in the ASD population leads to a reduction in cognitive and linguistic abilities, which respond to the different types of epilepsy and their location, significantly impacting the quality of life and basic activities of daily living of the user with ASD.

Insight into the antibacterial mechanism of Cu-enriched sol-gel coatings employing proteomics.

Advanced antibacterial biomaterials can help reduce the severe consequences of infections. Using copper compounds is an excellent option to achieve this goal; they offer a combination of regenerative and antimicrobial functions. In this study, new CuCl2-doped sol-gel coatings were developed and physicochemically characterised. Their osteogenic and inflammatory responses were tested in vitro using human osteoblasts and THP-1 macrophages. Their antibacterial effect was evaluated using Escherichia coli and Staphylococcus aureus. The Cu influence on the adsorption of human serum proteins was analysed employing proteomics. The materials released Cu2+ and were not cytotoxic. The osteoblasts in contact with these materials showed an increased ALP, BMP2 and OCN gene expression. THP-1 showed an increase in pro-inflammatory markers related to M1 polarization. Moreover, Cu-doped coatings displayed a potent antibacterial behaviour against E. coli and S. aureus. The copper ions affected the adsorption of proteins related to immunity, coagulation, angiogenesis, fibrinolysis, and osteogenesis. Interestingly, the coatings had increased affinity to proteins with antibacterial functions and proteins linked to the complement system activation that can lead to direct bacterial killing via large pore-forming complexes. These results contribute to our understanding of the antibacterial mechanisms of Cu-biomaterials and their interaction with biological systems.

Case report: Assessment of linguistic, cognitive, and sensory profile competencies in a child with ASD and epilepsy.

Introduction: Autism Spectrum Disorder (ASD) and epilepsy pose significant challenges for early diagnosis during childhood. Current scientific literature does not reflect robust action protocols that allow for a detailed screening of difficulties in this population, especially in areas such as language, cognition, and sensory profile. Additionally, detecting epilepsy before the age of 4 is established as a major current public health challenge in our society. Objective: The aim was to evaluate a patient exhibiting symptoms compatible with both ASD and epilepsy, determining the linguistic, cognitive, and sensory profile through a clinical assessment protocol. Furthermore, the objective included establishing a diagnosis of ASD. Method: This single-case study (N = 1) presents the evaluation of a 7-year-old patient with suspected ASD, experiencing a decline in linguistic and cognitive competencies following a documented epileptic episode. Evaluation was conducted using instruments such as CELF-5, PROLEC-R, WISC-V, ENFEN, PS-2, ADI-R, and ADOS-2. Results: Following assessment of language, cognition, sensory aspects, and behaviors associated with ASD, the diagnosis of ASD was confirmed in the patient, along with impairments in expressive and receptive language, executive functioning, and alterations in the sensory profile. Conclusion: Diagnosing ASD and epilepsy, as well as their evaluation, is a complex process requiring interdisciplinary assessment involving a detailed exploration of all functional competencies in individuals with this comorbidity. Future studies should focus on creating and improving existing protocols to develop optimal and effective evaluation strategies for assessing this population during childhood.

Atención del Trastorno del Espectro Autista y epilepsia a través de Sistemas Aumentativos/Alternativos de Comunicación / Care of Autism Spectrum Disorder and Epilepsy through Augmentative/

El incremento de la prevalencia de los perfiles clínicos de personas con TEA y epilepsia en la etapa infantil ha aumentado en los últimos años, describiendo una problemática en su evaluación e intervención en las competencias lingüísticas. Esta población muestra graves alteraciones en el lenguaje expresivo que abarcan diferentes dimensiones de este como la fonología, la semántica, la morfosintaxis, la pragmática y la comprensión auditiva. Todo ello hace que estos usuarios muestren alteraciones significativas en su comunicación y expresión del lenguaje, lo que dificulta significativamente su autonomía y calidad de vida. Por ello, según la literatura científica, uno de los planes de intervención más efectivo que disponemos en la actualidad es el uso de los Sistemas Aumentativos y/o Alternativos de Comunicación (SAAC), los cuales han demostrado en esta población que permiten aumentar su capacidad comunicativa y resolver situaciones lingüísticas con éxito. Es por lo que los profesionales de la salud deben tener un plan de evaluación e intervención adecuado que permita solventar las necesidades comunicativas de las personas con TEA y epilepsia en la etapa infantil. Por ende, este trabajo tuvo el objetivo de reflexionar y proporcionar una revisión de la atención de la población infantil con TEA y epilepsia a través del uso de los SAACs. Para ello, se llevó a cabo una revisión narrativa de la literatura científica publicada hasta el momento, con la lectura de 51 artículos de investigación sobre la atención de la población infantil con TEA y epilepsia. Los resultados indicaron que el protocolo de evaluación para su implementación debe seguir una serie de pasos como son: Recogida de información, Valoración de la persona, Valoración del entorno cercano, Selección del vocabulario, Selección de los reforzadores, Análisis de los sistemas de comunicación, Toma de decisiones y Evaluación de la efectividad del sistema de comunicación. Asimismo, el uso de SAACs en este colectivo mejora de forma significativa la comunicación funcional en diferentes contextos y entornos. En conclusión, se debe llevar a cabo una atención multidisciplinar para mejorar las competencias lingüísticas de las personas con TEA y epilepsia.

The increasing prevalence of clinical profiles of individuals with ASD and epilepsy in childhood has grown in recent years, describing a challenge in their assessment and intervention in language competencies. This population exhibits severe impairments in expressive language that encompass various dimensions of language, such as phonology, semantics, morphosyntax, pragmatics, and auditory comprehension. All of this results in these individuals showing significant disruptions in their communication and language expression, significantly impacting their autonomy and quality of life. Therefore, according to scientific literature, one of the most effective intervention plans currently available is the use of Augmentative and Alternative Communication Systems (AAC), which have shown in this population to increase their communicative capacity and successfully address language-related situations. Hence, healthcare professionals should have an appropriate assessment and intervention plan to address the communication needs of children with ASD and epilepsy. Therefore, this work aimed to reflect on and provide a review of the care for children with ASD and epilepsy through the use of AACs. To achieve this, a narrative review of the scientific literature published up to now was conducted, with the reading of 51 research articles on the care of children with ASD and epilepsy. The results indicated that the assessment protocol for its implementation should follow a series of steps, including: Gathering information, Assessing the individual, Assessing the immediate environment, Selecting vocabulary, Choosing reinforcers, Analyzing communication systems, Making decisions, and Evaluating the effectiveness of the communication system. Furthermore, the use of AACs in this group significantly improves functional communication in various contexts and environments. In conclusion, a multidisciplinary approach should be taken to enhance the language competencies of individuals with ASD and epilepsy.

Implication of stem cells from adipose tissue in wound healing in obese and cancer patients.

OBJECTIVE: Certain diseases such as obesity and cancer can cause impaired wound healing. Adipose tissue derived stem cells (ASCs) are a novel field of research. Many studies have evidenced their high degree of safety and potential for wound repair due to their immunomodulatory and tissue-regeneration properties. The purpose of this study is to determine the impact of obesity and cancer on the therapeutic potential of ASCs. MATERIALS AND METHODS: We isolated and characterized the phenotype, differentiation capacities, secretome, and in vitro migration capacities of ASCs. Furthermore, we analyze their capacity of in vitro migration associated with the plasma of the different patients. RESULTS: We observed that ASCs isolated from obese and cancer patients have the same phenotype, cell proliferation, and migration capacities as ASCs derived from healthy donors. However, they do not have the same differentiation potential and exhibit distinct profiles of both pro-inflammatory and regulatory secreted cytokines, which, together with the signals received from the bloodstream, could account for the impaired healing in patients with these diseases. CONCLUSIONS: We consider the ASCs from patients with either obesity or cancer are slightly altered, and this may be the cause of worse wound healing in these patients.

OBJETIVO: Enfermedades como la obesidad y el cáncer pueden alterar la cicatrización de las heridas. Las células madre derivadas del tejido adiposo (ASC) abren un nuevo campo de investigación ya que muchos estudios han demostrado su utilidad y alto grado de seguridad para la reparación de heridas debido a sus propiedades inmunomoduladoras y de regeneración tisular. El propósito de este estudio es determinar el impacto de la obesidad y el cáncer en el potencial terapéutico de las ASCs. MATERIAL Y MÉTODOS: Aislamos y caracterizamos el fenotipo, la capacidad de diferenciación, el secretoma y la capacidad de migración in vitro de las ASC. Asimismo, analizamos la capacidad de migración in vitro asociada al plasma de los diferentes pacientes. RESULTADOS: Observamos que las ASC aisladas de pacientes obesos y con cáncer tienen el mismo fenotipo, proliferación celular y capacidades de migración que las ASCaisladas de donantes sanos. Sin embargo, no tienen el mismo potencial de diferenciación y exhiben perfiles distintos de citoquinas secretadas tanto proinflamatorias como reguladoras. CONCLUSIONES: Consideramos que las ASC de pacientes con obesidad o cáncer están levemente alteradas. Esta puede ser la causa de una peor cicatrización de las heridas en este tipo de pacientes.

Comparative Analysis Between Mesenchymal Stem Cells From Subcutaneous Adipose Tissue and Omentum in Three Types of Patients: Cancer, Morbid Obese and Healthy Control.

Objective. The aims of this study are to compare 2 origins of adipose-derived mesenchymal stem cells (MSCs) (omentum and subcutaneous) from 2 pathologies (morbid obesity and cancer) vs healthy donors. Adipose tissue has revealed to be the ideal MSC source. However, in developing adipose-derived stem cells (ASCs) for clinical use, it is important to consider the effects of different fat depots and also the effect of donor variability. Methods. We isolated and characterized the membrane markers and differentiation capacities of ASCs obtained from patients with these diseases and different origin. During the culture period, we further analysed the cells' proliferation capacity in an in vitro assay as well as their secretome. Results. Adipose-derived stem cells isolated from obese and cancer patients have mesenchymal phenotype and similar cell proliferation as ASCs derived from healthy donors, some higher in cells derived from subcutaneous fat. However, cells from these 2 types of patients do not have the same differentiation potential, especially in cancer patients from omentum, and exhibit distinct secretion of both pro-inflammatory and regulatory cytokines, which could explain the differences in use due to origin as well as pathology associated with the donor. Conclusion. Subcutaneous and omentum ASCs are slightly different; omentum generates fewer cells but with greater anti-inflammatory capacity. Adipose-derived stem cells from patients with either obesity or cancer are slightly altered, which limits their therapeutic properties.

La llegada de los inhibidores biológicos para la prevención de la migraña / The arrival of biological inhibitors for preventing migraine

En noviembre de 2019, se aprobaron para su financiación, en el Sistema Nacional de Salud, dos nuevos anticuerpos monoclonales para la prevención de la migraña crónica y episódica: el erenumab y el galcanezumab.1 La migraña es una de las enfermedades neurológicas más frecuentes, que produce discapacidad y reducción de la calidad de vida de quien la padece. Actualmente, el tratamiento estándar para su prevención se basa en medicamentos orales (betabloqueantes, topiramato, entre otros), que en su momento fueron desarrollados específicamente para el tratamiento de otras enfermedades (la depresión, la hipertensión y la epilepsia) los cuales pese a ser eficaces, no lo son para una gran proporción de quienes padece migraña. Esto, sumado a los efectos adversos que muchas veces presentan, provoca que haya una baja adherencia al tratamiento.1,2 Por ello, y gracias a nuevas investigaciones centradas en la fisiopatología de la migraña, se ha descubierto que el péptido relacionado con el gen de la calcitonina (CGRP, por sus siglas en inglés) tiene una función clave en su etiopatogenia. El CGRP, así como su receptor, se expresan tanto a nivel periférico como central, incluyendo la vía trigeminovascular. Durante los episodios de migraña, los niveles de CGRP se encuentran elevados, debido a que estos péptidos son liberados desde las terminaciones nerviosas del trigémino, produciendo vasodilatación de los vasos cerebrales y meníngeos con importante modulación neuronal del dolor. Además, el CGRP también es un potente vasodilatador arterial sistémico.3 Tras el descubrimiento de la importancia de este péptido se empezaron a desarrollar los llamados -gepants, antagonistas de CGRP de molécula pequeña, de administración oral. En un principio parecían cumplir con las expectativas de eficacia, pero empezaron a surgir problemas de hepatotoxicidad y se vieron obligados a interrumpir su desarrollo. Tras muchos años con la investigación y los ensayos clínicos en parada indefinida, actualmente se ha conseguido que las moléculas Rimegepant y Atogepant no muestren dicha hepatotoxicidad y se encuentran en fase 3 de ensayo clínico.4 Posteriormente, se desarrollaron los anti-CGRP, anticuerpos monoclonales dirigidos contra CGRP (galcanezumab, fremanezumab) o contra su receptor (erenumab).5 Erenumab ha demostrado una reducción de 50 por ciento o más del número de días migrañosos al mes en 50 por ciento de pacientes, que recibieron dosis de 140 mg, en comparación con 26,6 por ciento de pacientes del grupo placebo. Galcanezumab, por su parte, ha objetivado una reducción de 50 por ciento o más de días migrañosos en 62,3 por ciento de pacientes, frente al 38,6 por ciento de pacientes del grupo placebo. Como consecuencia, también se ha objetivado una menor necesidad de uso agudo de medicamentos.6,7 En cuanto a la tolerancia y la seguridad, se ha visto que son fármacos seguros, cuyos efectos adversos más frecuentes son los efectos locales, en el lugar de inyección del fármaco (prurito, eritema, dolor), siendo estos leves. También se ha visto que pueden producir nasofaringitis, infecciones de vías respiratorias altas y sinusitis. La frecuencia de estos efectos adversos es similar a la que se produce en el grupo placebo e inferior a la de los tratamientos preventivos convencionales. Además, estos anticuerpos monoclonales no presentan interacciones farmacológicas o hepatotoxicidad y, a diferencia de la mayoría de los anticuerpos, no suprimen la función inmune. Otro dato muy importante que se ha visto reflejado en los resultados es que, para la gran mayoría de los consumidores, el fármaco no produce taquifilaxia. No obstante, dichos efectos adversos pueden surgir con el tiempo y con el uso, debido a que disponemos de una experiencia limitada con estos fármacos y, por tanto, habrá que mantener una vigilancia activa.8 Asimismo, debido a que el CGRP es un vasodilatador arterial y se ve inhibido por los anti-CGRP, se podría ver afectado el sistema cardiovascular, provocando hipertensión arterial. Esto podría aumentar los factores de riesgo cardiovascular, aunque se ha informado que estos fármacos no son vasoconstrictores per se. Para observar y notificar esta posible variable, se está desarrollando un estudio de 5 años de duración, durante los cuales se cuantificará este riesgo cardiovascular y se observará si aumenta con el tratamiento a largo plazo con Erenumab. Con Galcanezumab no se ha realizado ningún estudio de esta índole, si bien sí se han realizado este tipo de estudios a menor escala y con menor duración, sin que se hayan notificado problemas cardiovasculares. Este posible efecto adverso deberá ser estudiado con mayor profundidad en el futuro.9 Estos anticuerpos monoclonales están indicados tanto en la migraña episódica como en la crónica, si hay fracaso de 3 o más tratamientos preventivos. Este tratamiento tendrá impacto en la mejora de la calidad de vida de aquella población refractaria y que no dispone de más opciones. Sobre todo, en los pacientes con migraña episódica de alta frecuencia, los cuales, en caso de fracaso del tratamiento preventivo, no pueden beneficiarse de la toxina botulínica, como así lo hacen los que padecen de migraña crónica.10,11 Ambos fármacos (galcanezumab y erenumab) se administran por vía subcutánea; de esta forma, aumenta la adherencia al tratamiento al ser administrada de forma mensual, estos anticuerpos tienen una vida media larga. También aumenta la adherencia al tratamiento el hecho de que haya una rápida respuesta a la terapia. En caso de pacientes que no respondan al tratamiento, si no se observa una reducción de la frecuencia y la gravedad de los síntomas entre 1 a 3 meses tras el inicio, la terapia debe suspenderse.12 El desarrollo de estos nuevos fármacos supone un antes y un después en el tratamiento de la migraña, se trata de los primeros fármacos que fijan la diana terapéutica en una de las claves de la fisiopatología de esta enfermedad. Debido a ello, existe una eficacia científicamente demostrada superior a la del tratamiento convencional. No obstante, como problema, tenemos el elevado precio de costo de los medicamentos, que supone el principal impedimento en su indicación como primera o segunda línea de prevención, debiendo cumplir con los criterios anteriormente descritos.13 Con la llegada de los inhibidores del CGRP se abren las puertas a continuar la investigación y comprensión de la fisiopatología de la migraña que, en parte, aún es desconocida para, si cabe, mejorar aún más la vida de cientos de millones de personas en el mundo que padecen esta incapacitante enfermedad(AU)

Diagnósticos fonoaudiológicos y síntomas no motores en pacientes con Enfermedad de Parkinson / Phonoaudiological diagnoses and non-motor symptoms in patients with Parkinson's disease

Objetivo: Este estudio descriptivo se orientó a conocer el perfil clínico-epidemiológico de la Enfermedad de Parkinson (EP) y la coexistencia entre síntomas no motores (SNM) y diagnósticos fonoaudiológicos (DF). Método: La muestra estuvo conformada por 34 personas con Parkinson idiopático (26 hombres y 8 mujeres), cuyas historias clínicas fueron analizadas para describir la coexistencia de DF, como la hipofonía, la disprosodia, la disartria y la disfagia, con síntomas no motores, tales como: trastornos gastrointestinales, depresión, trastornos del sueño y deterioro cognitivo. Resultados: Los resultados señalan que las personas con Parkinson tenían edades entre los 25 a los 86 años. En cuanto a la fase, se clasificaron en: estadio I el 11,7%, II el 17,6%, III el 47%, IV el 14,7% y V el 8,8%. El 47% de los pacientes llegó al servicio de Fonoaudiología en una etapa avanzada de la EP. Los SNM más frecuentes fueron trastornos del sueño (67,6%), depresión (58,8%), alteraciones gastrointestinales (29,4%) y deterioro cognitivo (15%). Los DF se distribuyeron así: disprosodia (38%), hipofonía (33%), disartria (18%) y disfagia (11%). Discusión: se observa una alta frecuencia tanto de SNM (como la depresión y los trastornos del sueño), como de SF (especialmente disprosodia e hipofonía). Esta sintomatología provoca, por una parte, la reducción del deseo de relacionarse socialmente y por otro, dificultades para hacerse entender al presentar un volumen de voz reducido o prosodia (además de trastornos de la melodía, inflexiones, marcadores paralingüísticos) de la expresión oral del lenguaje. Conclusión: los trastornos del sueño y la depresión podrían tener un impacto negativo significativo en las funciones fonoaudiológico de las personas con Parkinson.

Objective: This descriptive study was aimed at understanding the clinical-epidemiological profile of Parkinson's disease (PD) and the coexistence between non-motor symptoms (NMS) and phonoaudiological diagnoses (PD). Methods: The sample comprised 34 people with idiopathic Parkinson's (26 men and 8 women). Their clinical histories were analysed to describe the coexistence of PD, such as hypophonia, dysprosody, dysarthria and dysphagia, with non-motor symptoms, such as gastrointestinal disorders, depression, sleep disorders and cognitive impairment. Results: The results indicate that people with Parkinson's are between the ages of 25 and 86. In terms of phase, they were classified as: stage I 11.7%, II 17.6%, III 47%, IV 14.7% and V 8.8%. 47% of patients reached the Speech Therapy service at an advanced stage of PD. The most frequent NMS were sleep disorders (67.6%), depression (58.8%), gastrointestinal disorders (29.4%) and cognitive impairment (15%). The PD were distributed as follows: dysprosody (38%), hypophonia (33%), dysarthria (18%) and dysphagia (11%). Discussion: a high frequency of both NMS (such as depression and sleep disorders) and PD (especially dysprosody and hypophonia) is observed. This symptomatology causes a reduction in the desire to relate socially, and difficulties in making oneself understood by presenting a reduced voice volume or prosody (in addition to melody of speech disorders, inflections, paralinguistic markers) of the oral language expression. Conclusion: sleep disorders and depression could have a significant negative impact on the speech and hearing functions of people with Parkinson's.

Detection of KRAS G12D in colorectal cancer stool by droplet digital PCR.

AIM: To assess KRAS G12D mutation detection by droplet digital PCR (ddPCR) in stool-derived DNA from colorectal cancer (CRC) patients. METHODS: In this study, tumor tissue and stool samples were collected from 70 patients with stage I-IV CRC diagnosed by preoperative biopsy. KRAS mutational status was determined by pyrosequencing analysis of DNA obtained from formalin-fixed paraffin-embedded (FFPE) tumor tissues. The KRAS G12D mutation was then analyzed by ddPCR in FFPE tumors and stool-derived DNA from patients with this point mutation. Wild-type (WT) tumors, as determined by pyrosequencing, were included as controls; analysis of FFPE tissue and stool-derived DNA by ddPCR was performed for these patients as well. RESULTS: Among the total 70 patients included, KRAS mutations were detected by pyrosequencing in 32 (45.71%), whereas 38 (54.29%) had WT tumors. The frequency of KRAS mutations was higher in left-sided tumors (11 located in the right colon, 15 in the left, and 6 in the rectum). The predominant point mutation was KRAS G12D (14.29%, n = 10), which was more frequent in early-stage tumors (I-IIA, n = 7). In agreement with pyrosequencing results, the KRAS G12D mutation was detected by ddPCR in FFPE tumor-derived DNA, and only a residual number of mutated copies was found in WT controls. The KRAS G12D mutation was also detected in stool-derived DNA in 80% of all fecal samples from CRC patients with this point mutation. CONCLUSION: ddPCR is a reliable and sensitive method to analyze KRAS G12D mutation in stool-derived DNA from CRC patients, especially at early stages. This non-invasive approach is potentially applicable to other relevant biomarkers for CRC management.

Heart valve tissue engineering: how far is the bedside from the bench?

Heart disease, including valve pathologies, is the leading cause of death worldwide. Despite the progress made thanks to improving transplantation techniques, a perfect valve substitute has not yet been developed: once a diseased valve is replaced with current technologies, the newly implanted valve still needs to be changed some time in the future. This situation is particularly dramatic in the case of children and young adults, because of the necessity of valve growth during the patient's life. Our review focuses on the current status of heart valve (HV) therapy and the challenges that must be solved in the development of new approaches based on tissue engineering. Scientists and physicians have proposed tissue-engineered heart valves (TEHVs) as the most promising solution for HV replacement, especially given that they can help to avoid thrombosis, structural deterioration and xenoinfections. Lastly, TEHVs might also serve as a model for studying human valve development and pathologies.

Exosomes Derived from Breast Cancer Cells, Small Trojan Horses?

Exosomes are small extracellular vesicles secreted to the extracellular environment by several cell types, including tumor cells. It has been demonstrated that exosomes have an important role in intercellular communication, but they have recently been implicated in various tumor processes, including the oncogenic transformation of cells in the tumor microenvironment, tumor drug resistance, and the transport of tumor factors. Tumors appear to use exosomes to dialogue with and transform neighboring cells to create an ideal environment for their growth and expansion. On the other hand, the structure and function of exosomes may make them useful in cancer diagnosis and prognosis, because they contain molecules that could serve as biomarkers, including oncogenes, miRNAs, and certain proteins. They have the ability to travel via body fluids, from which they could be isolated and used to transport drugs to specific targets. This review aims to provide an update on the role of exosomes derived from breast cancer cells.