Predicción de riesgo cardiovascular y periodontitis en pacientes con síndrome coronario agudo, Holguín 2020 / Cardiovascular Risk Prediction and Periodontitis in Patients with Acute Coronary Syndrome, Holguín 2020

Introducción : La predicción del riesgo cardiovascular favorece la prevención de eventos cardiovasculares. Objetivo : Estimar el riesgo cardiovascular y determinar la condición periodontal de pacientes con síndrome coronario agudo. Método : Se realizó un estudio transversal en 60 sujetos admitidos en la Unidad de Cuidados Coronarios del Hospital Provincial Vladimir Ilich Lenin, con diagnóstico de síndrome coronario agudo, que a su vez cumplieron con los criterios de inclusión. Se tuvieron en cuenta los principios de ética médica, se empleó el índice Periodontal de Russell y se determinó el riesgo cardiovascular según las Tablas de Predicción de Riesgo Cardiovascular aprobadas para Cuba. Se evaluaron las variables incluidas en dichas tablas. Resultados : El infarto agudo de miocardio se presentó en el 58,3 por ciento. El 55,0 por ciento eran del sexo masculino, 35,0 por ciento se encontraban en el grupo de edad de 55 a 64 años. En relación con la condición periodontal, el 76,7 por ciento presentó periodontitis. Según los factores de riesgo explorados la adicción tabáquica estuvo presente en el 71,7 por ciento y la hipertensión arterial en el 65,0 por ciento de los sujetos. El 25,0 por ciento de los pacientes con riesgo cardiovascular bajo presentaba periodontitis. Conclusiones : Según las tablas de predicción de riesgo cardiovascular empleadas, más de la mitad de los pacientes con síndrome coronario agudo presentaron riesgo cardiovascular bajo o moderado, sin embargo, la mayoría de estos presentaban periodontitis(AU)

Introduction : Prediction of cardiovascular risk favors prevention of cardiovascular events. Objective : To estimate cardiovascular risk and determine the periodontal condition of patients with acute coronary syndrome. Methods : A cross-sectional study was carried out with 60 subjects admitted to the coronary care unit at Hospital General Docente Vladimir Ilich Lenin, with a diagnosis of acute coronary syndrome and, in turn, meeting with the inclusion criteria. The principles of medical ethics were taken into account, the Russell's Periodontal Index was used, and cardiovascular risk was determined according to the cardiovascular risk prediction tables approved for Cuba. The variables included in these tables were evaluated. Results : Acute myocardial infarction occurred in 58.3 percent of the patients. 55.0 percent were male, and 35.0 percent were in the age group 55-64 years. Regarding their periodontal condition, 76.7 percent presented periodontitis. According to the explored risk factors, tobacco addiction was present in 71.7 percent, while arterial hypertension was present in 65.0 percent of the subjects. 25.0 percent of the patients with low cardiovascular risk had periodontitis. Conclusions : According to the used cardiovascular risk prediction tables, more than half of the patients with acute coronary syndrome presented low or moderate cardiovascular risk; however, most of these had periodontitis(AU)

Competencias informacionales en estudiantes de doctorado del sector de la salud en la provincia Holguín, Cuba / Informational competence in doctoral students in the health sector in Holguin province, Cuba

Introducción: Las competencias informacionales han sido reconocidas como de gran importancia en la educación doctoral. No se conocen las percepciones de doctorandos del sector de la salud en la provincia Holguín en relación con las competencias informacionales. Objetivo: Valorar las percepciones de doctorandos del sector de la salud en la provincia Holguín relacionadas con las competencias informacionales. Materiales y Métodos: Se realizó un estudio exploratorio que partió de un universo de 32 y que incluyó a 24 doctorandos del sector de la salud en la provincia Holguín que completaron el cuestionario ALFINVES sobre competencias informacionales en una versión en español. Resultados: Se obtuvo que las respuestas dadas a las preguntas en cuanto al conocimiento, alcanzaron puntuaciones entre 7,59 y 8,66 puntos. En el ámbito de las habilidades, los ítems que menor puntuación obtuvieron fueron los correspondientes al uso de índices para localizar la información y el empleo de sistemas de gestión de bibliografía. Mientras tanto, los ítems de menor puntuación en lo concerniente con las actitudes, correspondieron a la aprobación del tema de investigación de conjunto con el tutor y al conocimiento de los fundamentos del derecho de autor y la propiedad intelectual. Conclusiones: Se comprobó que los estudiantes de doctorado del sector de la salud en la provincia Holguín tienen autopercepciones altas de las competencias informacionales, desde las perspectivas del conocimiento, habilidades y actitudes, aunque se identificaron aspectos susceptibles a mejoramiento(AU)

Introduction: Informational competence is of great importance in doctoral education. The perceptions of doctoral students in the health sectorin Holguin province (SSHo) with respect to informational competence are not known. Objective: To assess the perceptions of doctoral students in the SSHo in relation to their informational competencies. Material and Methods: An exploratory study was carried out on a universe of 32 students that included 24 SSHo doctoral students who completed the study questionnaire. A Spanish version of the ALFINVES questionnaire was used to assess informational competencies. Results: The answers given to the questions related to knowledge reached scores between 7,59 and 8,66 points. In the area of skills, the items with the lowest scores were the use of indexes to locate information and the use of bibliographic management systems. Meanwhile, the items with the lowest scores relating to attitudes corresponded to the approval of the research topic in conjunction with their tutors, and the knowledge of the basics of copyright and intellectual property. Conclusions: It was found that SSHo doctoral students have high self-perceptions of their informational competencies from the perspectives of knowledge, skills, and attitudes; however, aspects susceptible to improvement were identified(AU)

Validez y confiabilidad de dos instrumentos para evaluar la adherencia al tratamiento en pacientes quemados / Validity and reliability of two instruments to assess adherence to treatment in burn patients

RESUMEN Introducción: La adherencia terapéutica constituye uno de los principales problemas de las intervenciones en salud. Una de las poblaciones en las que se evidencian dificultades en la adherencia al tratamiento es en los pacientes quemados. Objetivo: Determinar la validez y confiabilidad de dos instrumentos para la evaluación de la adherencia al tratamiento y sus dimensiones influyentes en pacientes quemados hospitalizados. Métodos: Desde el enfoque cuantitativo se realizó un estudio transversal, en el periodo comprendido de enero de 2017 a diciembre de 2019. Se establecieron como variables de la investigación la adherencia al tratamiento y los factores influyentes en la adherencia al tratamiento. Se utilizó el criterio de expertos, la prueba piloto y por último se aplicaron los dos cuestionarios a 90 pacientes quemados. Resultados: Ambos instrumentos demostraron tener validez de contenido. La fiabilidad test-retest del instrumento para evaluar la adherencia terapéutica fue considerable y significativa, mientras que la consistencia interna fue aceptable. En el instrumento que evalúa las dimensiones influyentes en la adherencia terapéutica la fiabilidad fue muy fuerte y la consistencia buena. Conclusiones: Los dos instrumentos elaborados para la evaluación de la adherencia terapéutica en pacientes quemados hospitalizados, presentaron validez de contenido y confiabilidad.

ABSTRACT Introduction: Therapeutic adherence constitutesone of tema in problems of health interventions. One of the populations in which difficulties in adherence to treatment are evidence disburn patients. Objective: To determine the validity and reliability of two instruments for the evaluation of adherence to treatment and the irinfluential dimensions in hospitalized burn patients. Methods: From the quantitative approach, a cross-sectional study was conducted, in the period from January 2017 to December 2019. Adherence to treatment and influencing adherence to treat ment were established as research variables. Expert judgment wasused, the pilot test and finally the two question naireswere applied to 90 burn patients. Results: Both instruments proved to have content validity. The test-retestreliability of the instrument to evaluate therapeuticad herence was considerable and significant, whilethe internal consistency was acceptable. Reliability was very strong and consistency good in the instrument that evaluates the influencing dimensions in therapeutic adherence. Conclusions: The two instruments developed forthe evaluation of therapeutic adherence in hospitalized burn patients present content validity and reliability.

Aproximación a la ingesta nutricional en pacientes con Ataxia Espinocerebelosa tipo 2 / An approach to nutritional intake in patients with Spinocerebellar Ataxia type 2

Introducción: La Ataxia Espinocerebelosa tipo 2 (SCA2) es una enfermedad neurodegenerativa y hereditaria. No se ha realizado ningún estudio para la caracterización de la ingesta nutricional en pacientes cubanos con SCA2. Objetivo: Comprobar la reproducibilidad y fiabilidad del método de recordatorio de 24 horas para la evaluación de la ingesta nutricional en pacientes cubanos con SCA2, y obtener una caracterización preliminar de la misma en estos pacientes. Material y Métodos: Se realizó un estudio transversal con test-retest que incluyó 35 pacientes con diagnóstico de SCA2. Se empleó el cuestionario dietético de recordatorio de 24 horas incorporado al sistema CERES+. Resultados: Se obtuvieron correlaciones altamente significativas entre la primera y segunda mediciones para la ingesta estimada de energía, nutrientes y según grupos de alimentos. En la mayoría de los elementos relativos a la ingesta estimada de energía y nutrientes, y en todos los grupos de alimentos, se obtuvieron coeficientes de correlación intraclase (0,75. Se obtuvieron diferencias significativas entre pacientes de sexo masculino o femenino en cuanto a la ingesta de proteínas, carbohidratos, cobalamina, hierro, sodio y cinc. Se obtuvo un incremento en la ingesta de sodio y una disminución en la ingesta de ácido fólico y cobre, con respecto a las recomendaciones de ingesta nutricional diaria para la población cubana. Conclusiones: Se comprobó la elevada reproducibilidad y fiabilidad del cuestionario dietético recordatorio de 24 horas para la evaluación de la ingesta nutricional en pacientes con SCA2 y se logró una caracterización preliminar de la ingesta nutricional en estos pacientes(AU)

Introduction: Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative and inherited disorder. No study has been conducted to characterize nutritional intake in Cuban SCA2 patients. Objective: To test the reproducibility and reliability of the 24-hour dietary recall method for the assessment of nutritional intake in Cuban patients with SCA2, as well as to obtain a preliminary characterization of nutritional intake in these patients. Material and Methods: A cross-sectional test-retest study was conducted on 35 SCA2 patients. The 24-hour dietary recall questionnaire in the CERES+ system was used. Results: Highly significant correlations between the first and second measurements were obtained for energy and nutrients intake, and according to food groups. Intraclass correlation coefficients higher than 0.75 were obtained for energy and most of the nutrients and according to food groups. Significant differences were obtained between male and female patients in terms of proteins, carbohydrates, cobalamin, iron, sodium, and zinc intake. An increase in sodium intake and a decrease in folic acid and copper intake were obtained. SCA2 patients showed increased sodium intake, and decreased folic acid and copper intake relative to nutritional intake recommendations for the Cuban population. Conclusions: The 24-hour recall dietary questionnaire is reproducible and reliable for the assessment of nutritional intake in SCA2 patients. Preliminary characterization of nutritional intake in SCA2 patients was obtained(AU)

Enfermedad renal crónica y pronóstico de pacientes con COVID-19 / Chronic kidney disease and prognosis of COVID-19 patients

Introducción: La COVID-19 ha desatado una emergencia en salud pública de carácter internacional, pues ha infescado y provocado muertes a millones de personas, desatando así una crisis humanitaria nunca antes vista. Las muertes por COVID-19 también se han asociado a la presencia de algunas enfermedades crónicas. Objetivo: Evaluar la asociación entre la enfermedad renal crónica y el peor pronóstico de pacientes con COVID-19. Métodos: Se realizó una búsqueda en las bases de datos PubMed, Scopus, EBSCO Host, Clinical Key, Hinari y Cochrane. Se consultaron artículos publicados hasta el 30 de abril de 2020. Se incluyeron artículos observacionales con información relevante respecto al desenlace de pacientes con COVID-19 y enfermedad renal crónica. Resultados: Fueron incluidos 13 artículos que resumen la información de 8207 pacientes, de los que 405 (4,9 por ciento) tenían enfermedad renal crónica. Se asoció la comorbilidad con un peor pronóstico en pacientes con COVID-19, con OR = 1,99 [IC 95 por ciento: 1,13-3,52; Z = 2,37; p = 0,02] y heterogeneidad I2 = 47 por ciento, (2 = 22,47 (p = 0,03). Al eliminar los estudios con mayor contribución a la heterogeneidad, se analizó información de 5924 pacientes y hubo una mayor asociación entre la enfermedad renal crónica y el peor pronóstico, con OR = 3,02 [IC 95 por ciento: 1,79-5,10; Z = 4,15; p < 0,0001] y heterogeneidad I2 = 0 por ciento, (2 = 3,78 (p = 0,88). Lo que se interpreta como que los pacientes con enfermedad renal crónica afectados con COVID-19 tienen una probabilidad tres veces mayor de presentar un peor pronóstico que la población general. Conclusiones: La enfermedad renal crónica empeora el pronóstico de los pacientes afectados con COVID-19(AU)

Introduction: COVID-19 has triggered a global public health emergency, for it has infected and caused the death of millions of people, thus unleashing an unprecedented humanitarian crisis. Deaths due to COVID-19 have also been associated to the presence of several chronic diseases. Objective: Evaluate the association between chronic kidney disease and the worst prognosis of COVID-19 patients. Methods: A search was conducted in the databases PubMed, Scopus, EBSCO Host, Clinical Key, Hinari and Cochrane for observational papers published before 30 April 2020 which contained relevant information about the outcome of patients with COVID-19 and chronic kidney disease. Results: A total 13 papers were included which summarize information about 8 207 patients, 405 (4.9 percent) of them with chronic kidney disease. Comorbidity was associated to a worse prognosis of COVID-19 patients, with OR = 1.99 [CI 95 percent: 1.13-3.52; Z = 2.37; p = 0.02] and heterogeneity I2 = 47 percent, (2 = 22.47 (p = 0.03). After deleting the studies with a greater contribution to heterogeneity, an analysis was conducted of the information about 5 924 patients, finding a greater association between chronic kidney disease and worst prognosis, with OR = 3.02 [CI 95 percent: 1.79-5.10; Z = 4.15; p < 0.0001] and heterogeneity I2 = 0 percent, (2 = 3.78 (p = 0.88). This implies that patients with chronic kidney disease affected by COVID-19 have three times as many chances of having a worse prognosis than the general population. Conclusions: Chronic kidney disease worsens the prognosis of COVID-19 patients(AU)

Relevancia del metabolismo del folato en el contexto de enfermedades neurodegenerativas / Relevance of folate metabolism in neurodegenerative disorders

Introducción: Varias enfermedades neurodegenerativas están asociadas a alteraciones en el metabolismo del folato, lo que tiene sustanciales implicaciones fisiopatológicas, clínicas y terapéuticas potenciales. Objetivo: Reflejar la relevancia del metabolismo del folato para enfermedades neurodegenerativas, destacando su significación fisiopatológica y clínica, y sus implicaciones terapéuticas. Material y métodos: Se consultaron las bases de datos especializadas en busca de artículos publicados hasta marzo de 2020. Se emplearon descriptores específicos y operadores booleanos. Se empleó la estrategia de búsqueda avanzada para la selección de los artículos, teniendo en cuenta la calidad metodológica o validez de los estudios. Desarrollo: Fueron identificadas evidencias de asociación entre alteraciones del metabolismo del folato y enfermedades neurodegenerativas. Se han identificado variantes en genes que codifican enzimas involucradas en el metabolismo del folato, y modificaciones en patrones de metilación de ADN, asociadas al riesgo o a la gravedad clínica de las enfermedades de Alzheimer, Parkinson, Huntington, Temblor Esencial y Ataxia Espinocerebelosa tipo 2. Fueron encontradas asociaciones entre enfermedades neurodegenerativas y alteraciones en los niveles de metabolitos del folato, y la frecuencia de micronúcleos. Se han realizado varios estudios observacionales o experimentales que indican que la suplementación con ácido fólico y vitaminas B6 y B12, tiene utilidad terapéutica potencial en el contexto de enfermedades neurodegenerativas. Conclusiones: El metabolismo del folato es de relevancia fisiopatológica, clínica y terapéutica para enfermedades neurodegenerativas. El uso de estrategias dirigidas a restaurar los niveles normales de folatos o de co-factores enzimáticos involucrados en el metabolismo del folato, o a reducir la acumulación de homocisteína, tiene potenciales aplicaciones terapéuticas en el contexto de estas enfermedades(AU)

Introduction: Several neurodegenerative disorders are associated with alterations in folate metabolism, having essential physiopathological, clinical and therapeutic implications. Objective: To assess the relevance of folate metabolism in neurodegenerative disorders, highlighting its physiopathological, clinical and therapeutic significance. Material and Methods: Specialized biomedical databases were searched for studies published up to March 2020. Descriptors and Boolean operators were used. Advanced search strategy was used for the selection of articles, taking into account the methodological quality and validity of the studies. Results: Strong evidence of the association between folate metabolism and neurodegenerative disorders were identified. Enzyme-coding genes involved in folate metabolism and epigenetic DNA modifications associated with increased risk or disease severity in Alzheimer´s, Parkinson´s, and Huntington´s diseases, Essential Tremor, and Spinocerebellar ataxia type 2 were also identified. Associations between neurodegenerative disorders and altered levels of folate metabolites and the frequency of micronuclei were found. A number of observational and experimental studies have demonstrated that the supplementation with folic acid and vitamin B6 and B12 has therapeutic potential in the context of neurodegenerative disorders. Conclusions: Folate metabolism is of physiopathological, clinical and therapeutic relevance for neurodegenerative disorders. The use of strategies to normalize folate levels or enzyme cofactors involved in folate metabolism or to reduce homocysteine levels has potential therapeutic applications for these disorders(AU)

Redox Imbalance Associates with Clinical Worsening in Spinocerebellar Ataxia Type 2.

BACKGROUND: Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease presenting with redox imbalance. However, the nature and implications of redox imbalance in SCA2 physiopathology have not been fully understood. OBJECTIVE: The objective of this study is to assess the redox imbalance and its association with disease severity in SCA2 mutation carriers. METHODS: A case-control study was conducted involving molecularly confirmed SCA2 patients, presymptomatic individuals, and healthy controls. Several antioxidant parameters were assessed, including serum thiol concentration and the superoxide dismutase, catalase, and glutathione S-transferase enzymatic activities. Also, several prooxidant parameters were evaluated, including thiobarbituric acid-reactive species and protein carbonyl concentrations. Damage, protective, and OXY scores were computed. Clinical correlates were established. RESULTS: Significant differences were found between comparison groups for redox markers, including protein carbonyl concentration (F = 3.30; p = 0.041), glutathione S-transferase activity (F = 4.88; p = 0.009), and damage (F = 3.20; p = 0.045), protection (F = 12.75; p < 0.001), and OXY (F = 7.29; p = 0.001) scores. Protein carbonyl concentration was positively correlated with CAG repeat length (r = 0.27; p = 0.022), while both protein carbonyl concentration (r = -0.27; p = 0.018) and OXY score (r = -0.25; p = 0.013) were inversely correlated to the disease duration. Increasing levels of antioxidants and decreasing levels of prooxidant parameters were associated with clinical worsening. CONCLUSIONS: There is a disruption of redox balance in SCA2 mutation carriers which depends on the disease stage. Besides, redox changes associate with markers of disease severity, suggesting a link between disruption of redox balance and SCA2 physiopathology.

Body Mass Index Is Significantly Associated With Disease Severity in Spinocerebellar Ataxia Type 2 Patients.

BACKGROUND: Spinocerebellar ataxia type 2 is a progressive neurodegenerative disorder due to an unstable expansion of a CAG repeat in the ATXN2 gene. Although weight loss has been associated with disease progression in several neurodegenerative conditions, it has been barely assessed in patients with spinocerebellar ataxia type 2. OBJECTIVE: The objective of this study was to test whether body mass index is altered in patients with spinocerebellar ataxia type 2 with varying expansion sizes from early to late disease stages. METHODS: A cross-sectional case-control study was performed, which included 222 clinically and molecularly diagnosed patients and 214 sex- and age-matched healthy individuals. ATXN2 genotypes and sex were considered as risk factors. Clinical outcomes included the body mass index, age at onset, disease duration, Scale for the Assessment and Rating of Ataxia score, disease stage, dysphagia, and progression rate. Multiple linear regression models were generated. RESULTS: Body mass index was significantly decreased in male patients, but not in female patients, relative to control subjects. In addition to sex, body mass index was significantly associated with age at onset and progression rate. Conversely, body mass index, along with repeat length in ATXN2 expanded alleles and disease duration, was associated with Scale for the Assessment and Rating of Ataxia score. In addition, body mass index, along with the age at onset and the repeat length in ATXN2 normal and expanded alleles, has a significant influence on progression rate. CONCLUSIONS: Body mass index might be a useful biomarker of disease severity, particularly in male patients with spinocerebellar ataxia type 2 in the context of nutritional interventions or clinical trials assessing the efficacy of promising new drugs. © 2021 International Parkinson and Movement Disorder Society.

Atxn2-CAG100-KnockIn mouse spinal cord shows progressive TDP43 pathology associated with cholesterol biosynthesis suppression.

Large polyglutamine expansions in Ataxin-2 (ATXN2) cause multi-system nervous atrophy in Spinocerebellar Ataxia type 2 (SCA2). Intermediate size expansions carry a risk for selective motor neuron degeneration, known as Amyotrophic Lateral Sclerosis (ALS). Conversely, the depletion of ATXN2 prevents disease progression in ALS. Although ATXN2 interacts directly with RNA, and in ALS pathogenesis there is a crucial role of RNA toxicity, the affected functional pathways remain ill defined. Here, we examined an authentic SCA2 mouse model with Atxn2-CAG100-KnockIn for a first definition of molecular mechanisms in spinal cord pathology. Neurophysiology of lower limbs detected sensory neuropathy rather than motor denervation. Triple immunofluorescence demonstrated cytosolic ATXN2 aggregates sequestrating TDP43 and TIA1 from the nucleus. In immunoblots, this was accompanied by elevated CASP3, RIPK1 and PQBP1 abundance. RT-qPCR showed increase of Grn, Tlr7 and Rnaset2 mRNA versus Eif5a2, Dcp2, Uhmk1 and Kif5a decrease. These SCA2 findings overlap well with known ALS features. Similar to other ataxias and dystonias, decreased mRNA levels for Unc80, Tacr1, Gnal, Ano3, Kcna2, Elovl5 and Cdr1 contrasted with Gpnmb increase. Preterminal stage tissue showed strongly activated microglia containing ATXN2 aggregates, with parallel astrogliosis. Global transcriptome profiles from stages of incipient motor deficit versus preterminal age identified molecules with progressive downregulation, where a cluster of cholesterol biosynthesis enzymes including Dhcr24, Msmo1, Idi1 and Hmgcs1 was prominent. Gas chromatography demonstrated a massive loss of crucial cholesterol precursor metabolites. Overall, the ATXN2 protein aggregation process affects diverse subcellular compartments, in particular stress granules, endoplasmic reticulum and receptor tyrosine kinase signaling. These findings identify new targets and potential biomarkers for neuroprotective therapies.

Acortamiento de telómeros en enfermedades neurodegenerativas: implicaciones terapéuticas / Telomere attrition in neurodegenerative disorders: therapeutic implications

Introducción: Varias enfermedades neurodegenerativas están asociadas a la ocurrencia de acortamiento de los telómeros, y los convierten en biomarcadores y dianas terapéuticas potenciales. Objetivo: Reflejar la relevancia del acortamiento de los telómeros para enfermedades neurodegenerativas, y destacar sus implicaciones Material y métodos: Se realizó una revisión bibliográfica durante los meses de septiembre de 2019 a enero de 2020. Fueron consultadas bases de datos de referencia, con el uso de descriptores y operadores booleanos. La estrategia de búsqueda avanzada para la selección de los artículos fue empleada, teniendo en cuenta la calidad metodológica o validez de los estudios. Desarrollo: Fueron identificadas evidencias sólidas de asociación entre el acortamiento de los telómeros y las enfermedades de Alzheimer y Huntington, que sugieren un papel relevante de la biología de los telómeros en la fisiopatología de estas enfermedades. Las evidencias disponibles hasta el momento no permiten establecer la relevancia de la biología de los telómeros en la fisiopatología de la Enfermedad de Parkinson o de la esclerosis lateral amiotrófica. Se obtuvieron evidencias de la utilidad de terapias orientadas a la prevención del acortamiento de los telómeros para el tratamiento de enfermedades neurodegenerativas. Conclusiones: El acortamiento de los telómeros es de relevancia fisiopatológica y clínica para las enfermedades de Alzheimer y Huntington, mientras que existen evidencias insuficientes para establecer su importancia en la Enfermedad de Parkinson y la esclerosis lateral amiotrófica. El uso de estrategias para estimular la actividad de la telomerasa tiene potenciales aplicaciones terapéuticas en el contexto de enfermedades neurodegenerativas(AU)

Introduction: Several neurodegenerative disorders are associated with telomere attrition, turning telomeres into potential biomarkers and potential therapeutic targets. Objective: To assess the relevance of telomere attrition for neurodegenerative disorders, highlighting its therapeutic implications. Material and methods: A literature review was carried out from September 2019 to January 2020. Several databases were searched by using descriptors and Boolean operators. Advanced search strategy was used for the selection of articles, taking into account the methodological quality and validity of the studies. Results: Strong evidence for an association between telomere attrition and Alzheimer and Huntington diseases was obtained, suggesting a potential importance of telomere biology in the physiopathology of these diseases. Current evidence does not allow establishing the relevance of telomere attrition in the physiopathology of Parkinson´s disease or Amyotrophic Lateral Sclerosis. Evidence was obtained for the usefulness of therapies for the prevention of telomere attrition in the treatment of neurodegenerative disorders. Conclusions: Telomere attrition has physiopathological and clinical relevance in Alzheimer´s and Huntington´s diseases, though current evidence is not enough to establish its role in Parkinson's disease and Amyotrophic Lateral Sclerosis. Strategies that enhance telomerase activity have therapeutic potential in the context of neurodegenerative disorders(AU)

Potencial uso terapéutico del ARN de interferencia contra la COVID-19 / Potential therapeutic use of RNA interference against COVID-19

Introducción: El SARS-CoV-2 es el agente causal de la COVID-19, enfermedad respiratoria que ha causado miles de víctimas fatales a escala global, y para la cual no existe ninguna terapia curativa efectiva. Objetivo: Reflejar la relevancia potencial de la tecnología de ARN de interferencia (ARNi), como alternativa terapéutica contra la COVID-19. Material y métodos: Se consultaron las bases de datos especializadas en busca de artículos publicados hasta abril de 2020. Se emplearon descriptores específicos y operadores booleanos. Se empleó la estrategia de búsqueda avanzada para la selección de los artículos, teniendo en cuenta la calidad metodológica o validez de los estudios. Desarrollo: Fueron identificadas evidencias de aplicación a nivel experimental de la tecnología de ARNi contra el SARS-CoV. Se han diseñado y evaluado varios ARNs pequeños interferentes y ARNs pequeños con estructura en lazo, orientados al silenciamiento de genes esenciales del SARS-CoV, incluyendo aquellos que codifican las proteínas S, RdRp, M, E, N, 3a/3b y 7a/7b. Se comprobó la efectividad de los ARNi en el silenciamiento de sus genes diana. Aunque la mayoría de estas investigaciones se han realizado en sistemas in vitro, también se ha comprobado la utilidad terapéutica de la administración intranasal de ARNi en un modelo de SARS-CoV in vivo. Conclusiones: La tecnología de ARNi ha mostrado potencialidades como estrategia terapéutica contra el SARS-CoV en modelos celulares y animales. Dadas las similitudes a nivel genómico y en cuanto al proceso patogénico entre SARS-CoV y SARS-CoV-2, esta tecnología es potencialmente aplicable el tratamiento de la COVID-19(AU)

Introduction: SARS-CoV-2 is the causal agent of COVID-19, a respiratory disease that has caused thousands of deaths globally for which there is no effective curative therapy. Objective: To demonstrate the potential relevance of RNA interference (RNAi) technology as a therapeutic alternative in the treatment of COVID-19. Materials and methods: Specialized biomedical databases were searched looking for studies published until April 2020. The search was carried out using descriptors and Boolean operators. Advanced search strategy was used for the selection of articles, taking into account the methodological quality and validity of the studies. Results: Evidence of experimental application of RNAi technology against SARS-CoV was identified. Several small interfering RNAs and small loop-structured RNAs oriented to the silencing of essential SARS-CoV genes including those encoding the S, RdRp, M, E, N, 3a/3b and 7a/7b proteins have been designed and evaluated. The effectiveness of RNAi for silencing its target genes was proven. Although most of these research studies have been conducted in in vitro systems, the therapeutic effectiveness of the intranasal administration of small RNA interference has also been proven in an in vivo SARS-CoV model. Conclusions: RNAi technology has demonstrated to be a potential therapeutic strategy against SARS-CoV in cellular and animal models. Given the similarities at the genomic level and in terms of the pathogenic process between SARS-CoV and SARS-CoV-2, this technology has a potential applicability for the treatment of COVID-19(AU)

Testosterone Levels Are Decreased and Associated with Disease Duration in Male Spinocerebellar Ataxia Type 2 Patients.

Spinocerebellar ataxia type 2 (SCA2) is a progressive neurodegenerative disorder due to an unstable expansion of a CAG repeat in the ATXN2 gene. Despite clinical and experimental evidence indicating the relevance of the gonadotropic axis to the prognosis and therapeutics for several late-onset neurodegenerative disorders, its functioning and association with disease severity have not been previously explored in SCA2. To assess serum levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), and their clinical relevance in SCA2 patients. A case-control study involving 94 Cuban SCA2 patients and 101 gender- and age-matched healthy controls was conducted. Testosterone, LH, and FSH serum levels were determined by radioimmunoassay or immunoradiometric assay systems. Clinical outcomes included age at onset, disease duration, Scale for the Assessment and Rating of Ataxia (SARA) score, and progression rate. Univariate general linear models were generated. Testosterone, LH, and FSH serum levels were significantly reduced in male SCA2 patients relative to control individuals. On average, there was a 35% reduction in testosterone levels in male patients versus male control individuals. Testosterone levels were associated with disease duration (r = 0.383; p = 0.025) and age at onset (r = 0.414; p = 0.011) in male SCA2 patients, but no association was observed between testosterone and CAG expansion size, SARA score, or progression rate. Testosterone levels might be a biomarker of disease progression in male SCA2 patients. Further studies are needed to explore the effects of low testosterone levels on non-motor symptoms, and to assess the potential of testosterone replacement therapy in male SCA2 patients.

Hereditary Ataxias in Cuba: A Nationwide Epidemiological and Clinical Study in 1001 Patients.

The prevalence estimations of hereditary ataxias are biased since most epidemiological studies are confined to isolated geographical regions and few nationwide studies are available. The study aims to assess the prevalence, distribution, and neurological features of the Cuban population with hereditary ataxias. A nationwide epidemiological study of hereditary ataxias was conducted in Cuba between March 2017 and June 2018. Patients were scheduled at the Cuban ataxia research center, various hospitals, or at their homes. Demographic and clinical variables were obtained through standardized questionnaires and validated clinical tools. Overall, 1001 patients were diagnosed with hereditary ataxias for a nationwide prevalence of 8.91 cases/100.000 inhabitants. Spinocerebellar ataxia type 2 (SCA2) was the commonest subtype, with highest prevalences at Holguín province (47.86/100.000), and a broad dissemination in the whole country. Most of neurological features were common between all SCA cohorts, but the frequencies of some of them varied between distinct subtypes. Within the SCA2 cohort, significant influences of long mutation size and higher disease duration over the muscle atrophy and oculomotor disorders were observed. Besides, higher disease durations were associated with resting tremor and dysphagia, whereas shorter disease durations were associated with hyperreflexia. The spreading of SCA2 to whole country and the documented raising of its prevalence set the rationales for higher-scope medical care and research strategies, supported in collaborative research networks. The wide epidemiological, clinical, and genetic characterization of this founder SCA2 population identifies this homogeneous cohort as an attractive source for the development of future clinical-genetic and therapeutic researches.

One­carbon metabolism factor MTHFR variant is associated with saccade latency in Spinocerebellar Ataxia type 2.

BACKGROUND: Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder due to a CAG-repeat expansion. This work is intended to identify modifiers of the clinical phenotype in SCA2, following up on recent genome-wide association analyses that demonstrated the prominent role of DNA-damage repair and methylation for the severity and progression of polyglutamine diseases. In particular, we assessed the impact of MTHFR as rate-limiting enzyme in DNA methylation pathways, which modulates cerebellar neurotransmission and motor neuron atrophy. METHODS: A sample of 166 Cuban SCA2 patients and of 130 healthy subjects from the same geographical and ethnic background was selected. The ATXN2 CAG repeat length was determined by PCR followed by polyacrylamide gel electrophoresis. Two amino acid substitutions known to decrease the enzyme activity of MTHFR, encoded by C677T and A1298C polymorphisms, were assessed by PCR/RFLP. RESULTS: No significant differences were observed for C677T or A1298C alleles or genotype frequencies between cases and controls, confirming that disease risk in SCA2 does not depend on MTHFR activity. However, MTHFR A1298C genotypes showed a significant association with saccade latency. CONCLUSIONS: \MTHFR A1298C polymorphism is associated with saccade latency in SCA2 patients, but not with disease risk, age at onset or maximal saccade velocity. These results provide evidence that folate-mediated one­carbon metabolism might be important in the physiopathology of SCA2.

Comorbilidades y gravedad clínica de la COVID-19: revisión sistemática y meta-análisis / Comorbidities and clinical severity of COVID-19: systematic review and meta-analysis

Introducción: La emergencia de la COVID-19 se ha convertido en un serio problema de salud a nivel mundial. La identificación de comorbilidades asociadas a la presentación clínica grave de la COVID-19, es de importancia para el adecuado abordaje terapéutico de los pacientes afectados. Objetivo: Evaluar el riesgo de COVID-19 con presentación clínica grave en pacientes con comorbilidades. Material y métodos: Se realizó una revisión sistemática y meta-análisis en bases de datos especializadas en busca de artículos publicados hasta el 20 de marzo de 2020, que aportaran información sobre la asociación entre la gravedad de la presentación clínica de la COVID-19 y comorbilidades. Se empleó la razón de probabilidades con un intervalo de confianza de 95 por ciento, y modelos de efectos fijos o aleatorios. Resultados: En el análisis fueron incluidos 13 estudios para un total de 99 817 pacientes. Se obtuvieron los efectos globales para la hipertensión arterial (RP: 4,05; IC 95 por ciento: 3,45-4,74), enfermedad cardiovascular (RP: 4,39; IC 95 por ciento: 3,29-5,87), Diabetes Mellitus (RP: 3,53; IC 95 por ciento: 2,79-4,47), hábito de fumar (RP: 2,87; IC 95 por ciento: 1,81-4,54), enfermedades respiratoria (RP: 2,73; IC 95 por ciento: 2,55-2,94), renal (RP: 5,60; IC 95 por ciento: 4,13-7,60) y hepática crónicas (RP: 1,98 (IC 95 por ciento: 1,08-3,64) e inmunodeficiencias (RP: 2,90; IC 95 por ciento: 2,06-4,09), en pacientes graves en comparación con pacientes no graves. Conclusiones: La enfermedad renal crónica, la enfermedad cardiovascular, la hipertensión arterial y la Diabetes Mellitus están entre las comorbilidades que mayor riesgo implican para una presentación clínica grave en pacientes con COVID-19, seguidas en importancia por las inmunodeficiencias, hábito de fumar, enfermedad respiratoria crónica y enfermedad hepática crónica(AU)

Introduction: The recent emergence of COVID-19 has become a serious global health problem. The identification of comorbidities associated with the clinical severity in COVID-19 patients is of paramount significance for the appropriate therapeutic approach of affected patients. Objective: To evaluate the risk of severe clinical presentation of COVID-19 in patients with comorbidities. Materials and methods: A systematic literature search and meta-analysis was conducted in specialized databases to obtain information from articles published until March 20, 2020. All relevant papers with information on the association between clinical severity and comorbidities were included. The odds ratio with 95 percent confidence interval and fixed or random effect models were used. Results: Thirteen studies were included for a total of 99 817 patients. Global effects were obtained for hypertension (OR: 4.05; 95 percent CI: 3.45-4.74), cardiovascular disease (OR: 4.39; 95 percent CI: 3.29-5.87), diabetes mellitus (OR: 3.53; 95 percent CI: 2.79-4.47), smoking (OR: 2.87; 95 percent CI: 1.81-4.54), chronic lung disease (OR: 2.73; 95 percent CI: 2.55-2.94), chronic kidney disease (OR: 5.60; 95 percent CI: 4.13-7.60), chronic liver disease (OR: 1.98; 95 percent CI: 1.08-3.64), and immunodeficiency (OR: 2.90; 95 percent CI: 2.06-4.09) in severe patients compared with non-severe patients. Conclusions: Chronic kidney disease, cardiovascular disease, hypertension and diabetes are among the comorbidities with the highest risk of severe clinical presentation in COVID-19 patients, followed in importance by immunodeficiency, smoking, chronic lung disease and chronic liver disease(AU)

Estilos de aprendizaje de preferencia entre estudiantes de Medicina en La Gambia / Learning styles proffered by medical students in The Gambia

Introducción: En las últimas tres décadas, la proposición de que los estudiantes aprenden siguiendo diferentes estilos se ha convertido en un prominente tema en pedagogía a nivel mundial. En La Gambia no se conoce cuáles son los estilos de aprendizaje en estudiantes de Medicina. Objetivo: Caracterizar los estilos de aprendizaje de preferencia en estudiantes de la Escuela de Medicina y Ciencias Afines de la Salud en La Gambia. Métodos: Se aplicó un diseño transversal mediante el cuestionario estandarizado VARK para la recolección de datos, cuyo análisis se realizó con el uso del software SPSS. Resultados: La mayoría de los estudiantes prefirieron variantes multimodales de aprendizaje; la variante bimodal se escogió con más frecuencia. No se obtuvieron asociaciones significativas entre las puntuaciones VARK y el sexo o la edad de los estudiantes (p > 0,05). Se alcanzaron diferencias significativas para las puntuaciones kinestésicas entre estudiantes de preclínica y clínica (p = 0,031). Además, se logró una asociación significativa con relación a las variantes unimodales preferidas entre los estudiantes de preclínica y clínica. No fueron encontradas diferencias significativas en cuanto al rendimiento académico entre estudiantes con preferencias unimodales o multimodales (p > 0,05). Conclusiones: La aplicación del cuestionario VARK permitió la identificación de los estilos preferidos de aprendizaje para modos particulares de presentación de la información en estudiantes de Medicina en La Gambia. Los estilos de aprendizaje difirieron entre los estudiantes, la mayoría de los cuales tuvieron preferencia por los estilos multimodales, que incluían la variante kinestésica. Estos hallazgos pudieran emplearse para mejorar la calidad de la enseñanza(AU)

Introduction: In the last three decades, the proposition that students learn by following different styles has become a prominent topic in pedagogy worldwide. In The Gambia, learning styles in medical students are not known. Objective: To characterize the learning styles preferred by the students of the School of Medicine and Allied Health Sciences of The Gambia. Methods: A cross-sectional design was applied using the standardized VARK questionnaire for data collection, the analysis of which was performed using the SPSS software. Results: Most students preferred multimodal variants of learning; the bimodal variant was chosen more frequently. No significant associations were obtained between VARK scores and the sex or age of the students (p>0.05). Significant differences were reached for kinesthetic scores between preclinical and clinical students (p=0.031). In addition, a significant association was achieved in relation to the preferred unimodal variants among preclinical and clinical students. No significant differences were found regarding academic performance among students with unimodal or multimodal preferences (p>0.05). Conclusions: The application of the VARK questionnaire allowed the identification of preferred learning styles for particular ways of presenting information among medical students in The Gambia. Learning styles differed among students, most of whom had a preference for multimodal styles, which included the kinesthetic variant. These findings could be used to improve the quality of teaching(AU)

Relevancia de componentes del eje hipotálamo-hipófisis-gonadal en la fisiopatología de proteinopatías del sistema nervioso / Relevance of components of the hypothalamic-pituitary-gonadal axis in the pathophysiology of proteinopathies of the nervous system

RESUMEN Introducción: Varias proteinopatías del sistema nervioso están asociadas a la ocurrencia de alteraciones en componentes del eje hipotálamo-hipófisis-gonadal. Objetivo: Reflejar la relevancia de componentes del eje hipotálamo-hipófisis-gonadal en la fisiopatología de proteinopatías del sistema nervioso. Material y Métodos: Se realizó una revisión bibliográfica durante los meses de enero de 2018 a diciembre de 2018. Fueron consultadas bases de datos de referencia, con el uso de descriptores y operadores booleanos. La estrategia de búsqueda avanzada para la selección de los artículos fue empleada, teniendo en cuenta la calidad metodológica o validez de los estudios. Desarrollo: Fueron identificaron alteraciones del funcionamiento normal del eje hipotálamo-hipófisis-gonadal en varias proteinopatías del sistema nervioso. Las alteraciones más frecuentemente reportadas fueron el incremento en los niveles de gonadotropinas, principalmente de la hormona luteinizante, en la enfermedad de Alzheimer, y la disminución de los niveles de testosterona en las enfermedades de Alzheimer, Parkinson, Huntington y Esclerosis Lateral Amiotrófica, con el consiguiente agravamiento del fenotipo clínico. Se obtuvieron evidencias de naturaleza preliminar, que fundamentan la posible ocurrencia de disfunción hipotalámica en pacientes con ataxias espinocerebelosas. Conclusiones: Aun cuando existen evidencias que demuestran la existencia de un vínculo entre la fisiopatología de proteinopatías del sistema nervioso y alteraciones en componentes del eje hipotálamo-hipófisis-gonadal, se requerirán estudios más extensos e integrales para confirmar estas asociaciones y para caracterizar los mecanismos moleculares implicados.

ABSTRACT Introduction: Several proteinopathies of the nervous system are associated with disturbances in components of the hypothalamic-pituitary-gonadal axis. Objective: To assess the relevance of components of the hypothalamic-pituitary-gonadal axis in the pathophysiology of proteinopathies of the nervous system. Material and Methods: A literature review was carried out from January to December 2018. Several databases were searched by using descriptors and Boolean operators. Advanced search strategy was used for the selection of articles, taking into account the methodological quality and validity of the studies. Results: Disturbances of the normal function of the hypothalamic-pituitary-gonadal axis were identified in proteinopathies of the nervous system. The most frequently reported disturbances were the increase in gonadotropin levels, mainly in luteinizing hormone in Alzheimer´s disease, and the decrease in testosterone levels in Alzheimer´s, Parkinson´s and Huntington´s diseases, and Amyotrophic Lateral Sclerosis, with the resulting worsening of the clinical phenotype. Preliminary evidence was obtained, which was pointing to a possible hypothalamic dysfunction in Spinocerebellar ataxia patients. Conclusions: Even when evidences were gathered supporting a link between the pathophysiology of proteinopathies of the nervous system and disturbances in components of the hypothalamic-pituitary-gonadal axis, deeper and more comprehensive studies will be needed to confirm these associations and to characterize the underlying molecular mechanisms.

Aplicaciones de terapias de reemplazo celular al tratamiento de enfermedades poliglutamínicas / Applications of cell replacement therapies to the treatment of poly-glutamine diseases

Se realizó una revisión de la literatura especializada con el objetivo de evaluar el estado del arte en cuanto a la aplicación de terapias de reemplazo celular en enfermedades poliglutamínicas. Se consultaron las bases de datos HighWire y PubMed, con el uso de descriptores y operadores booleanos. Se recuperaron 84 artículos sobre la temática, publicados en revistas con un factor de impacto promedio de 5,42. Se discuten los estudios experimentales y pre-clínicos realizados con relación a terapias de reemplazo celular en enfermedades poliglutamínicas. Se demuestra la efectividad del uso de células madre de distintas fuentes en el mejoramiento de la función motora en modelos experimentales de enfermedades poliglutamínicas. Se revela la necesidad de realizar estudios multicéntricos a mediano y largo plazos, para la evaluación de los efectos terapéuticos de las terapias de reemplazo celular en enfermedades poliglutamínicas.

A review of the specialized literature was carried out with the aim of evaluating the state of the art regarding the application of cell replacement therapies in polyglutamine diseases. The HighWire and PubMed databases were consulted, with the use of Boolean descriptors and operators. 84 articles were retrieved on the subject, published in journals with an average impact factor of 5.42. The experimental and pre-clinical studies carried out in relation to cell replacement therapies in polyglutamine diseases are discussed. The effectiveness of the use of stem cells from different sources in the improvement of motor function in experimental models of polyglutamine diseases is demonstrated. The need to perform multicenter studies in the medium and long term is revealed, for the evaluation of the therapeutic effects of cell replacement therapies in polyglutamine diseases.