Effects of Transcranial Direct Current Stimulation on Long-term Motor Learning and Retention

Programa Oficial de Doutoramento en Enxeñaría Civil . 5011V01[Abstract] Optimizing the teaching-learning process is essential throughout life. Non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) seem to be an option for optimizing the motor learning curve. This thesis aims to study the effects of tDCS on motor learning, including the retention of a motor. The first randomized controlled study explored the effects of applying tDCS before, during, or after motor practice on retention of the practiced skill in 100 participants. After a single session, similar performance changes were observed in all groups, with no significant differences in the choice reaction time task. In the second randomized controlled study, we examined the effects of tDCS on typing performance in 63 participants. Participants performed a structured program of 23 intervention sessions across 3.5-month: 20, 15-min typing practice and 3 evaluations (pre, middle, post). tDCS group performed better motor performance in the rapid learning phase compared to the sham and control groups. However, these differences dissipated from session 11th. In conclusion, tDCS appears to be a safe stimulation method when administered over multiple sessions in healthy young adults but failed to enhance motor skill acquisition and retention compared with a sham control group.Resumen] Optimizar el proceso de enseñanza-aprendizaje es fundamental durante la vida. La estimulación transcraneal por corriente directa (tDCS) podría optimizar la curva de aprendizaje motor. El objetivo de la tesis fue estudiar los efectos de la tDCS sobre el aprendizaje, incluyendo la fase de retención. El primer estudio controlado aleatorio exploró los efectos de la aplicación de la tDCS antes, durante, o después, de la práctica sobre la retención en 100 participantes. Después de una sesión, se observaron cambios de rendimiento similares en todos los grupos en una tarea de tiempos de reacción aleatorios. En el segundo estudio controlado aleatorio, examinamos los efectos de la tDCS sobre el rendimiento mecanográfico. Los 63 participantes realizaron un programa estructurado durante 3.5-meses que incluía 20 prácticas y 3 evaluaciones (pre-, media- y post-intervención). El grupo tDCS obtuvo un mejor rendimiento en la fase rápida del aprendizaje en comparación con el grupo placebo y el grupo control, aunque estas diferencias se disiparon desde la sesión 11 en adelante. En conclusión, la tDCS parece ser segura aplicada en sesiones múltiples en adultos jóvenes y sanos, pero no eficaz para mejorar el aprendizaje de habilidades motoras en comparación con los grupos control y placebo.[Resumo] Optimizar o proceso de ensino-aprendizaxe é fundamental durante a vida. A estimulación transcraneal de corrente continua (tDCS) podería optimizar a curva de aprendizaxe motora. O obxectivo da tese foi estudar os efectos do tDCS na aprendizaxe, incluída a fase de retención. O primeiro estudo controlado aleatorizado explorou os efectos da aplicación de tDCS antes, durante ou despois da práctica sobre a retención en 100 participantes. Despois dunha sesión, observáronse cambios de rendemento similares en todos os grupos nunha tarefa aleatoria de tempos de reacción. No segundo estudo controlado aleatorizado, examinamos os efectos do tDCS no rendemento da dixitación. Os 63 participantes completaron un programa estruturado de 3.5-meses que incluía 20 prácticas e 3 avaliacións (pre-, media- e post-intervención). O grupo tDCS funcionou mellor na fase rápida de aprendizaxe en comparación co grupo placebo e o grupo control, aínda que estas diferenzas disipáronse a partir da sesión 11. En conclusión, o tDCS parece ser seguro cando se aplica en varias sesións en adultos novos sans, pero non é efectivo para mellorar a aprendizaxe das habilidades motoras en comparación cos grupos control e placeb

Improving motor skills and psychosocial behaviors in children with autism spectrum disorder through an adapted judo program

[Abstract] Introduction: This study aimed to investigate the long-term effects of an adapted judo program on the motor skills and psychosocial abilities of children with Autism Spectrum Disorder (ASD). Methods: All participants had been diagnosed with ASD and were assessed twice, one time at the start of the intervention and again 6 months later, with the Test of Gross Motor Development (TGMD-3) and the Gilliam Autism Rating Scale-Third Edition (GARS-3). A one-way repeated measures MANOVA was carried out in order to evaluate these assessments, and a mediation analysis was done to determine the relationship between them. Results: The experimental group significantly improved (p < 0.05) from the pre-test to the post-test for several subtests of the TGMD-3 and the GARS-3. Conclusion: The study shows that participation in an adapted judo program clearly helps to improve the motor skills and psychosocial behaviors of children with ASD

The Mediating Role of Vision in the Relationship Between Proprioception and Postural Control in Older Adults, as Compared to Teenagers and Younger and Middle-Aged Adults

[Abstract] The aim of this study is to analyze the mediating role of vision in the relationship between conscious lower limb proprioception (dominant knee) and bipedal postural control (with eyes open and closed) in older adults, as compared with teenagers, younger adults and middle-aged adults. Methods: The sample consisted of 119 healthy, physically active participants. Postural control was assessed using the bipedal Romberg test with participants’ eyes open and closed on a force platform. Proprioception was measured through the ability to reposition the knee at 45_, measured with the Goniometer Pro application’s goniometer. Results: The results showed an indirect relationship between proprioception and postural control with closed eyes in all age groups; however, vision did not mediate this relationship. Conclusions: Older adults outperformed only teenagers on the balance test. The group of older adults was the only one that did not display differences with regard to certain variables when the test was done with open or closed eyes. It seems that age does not influence performance on proprioception tests. These findings help us to optimize the design of training programs for older adults and suggest that physical exercise is a protective factor against age-related decline.This research recieved funding from Aristos Campus Mundus 2018 proyect. ID: ACM20180

Splice donor site sgRNAs enhance CRISPR/Cas9-mediated knockout efficiency

[EN]CRISPR/Cas9 allows the generation of knockout cell lines and null zygotes by inducing site-specific double-stranded breaks. In most cases the DSB is repaired by non-homologous end joining, resulting in small nucleotide insertions or deletions that can be used to construct knockout alleles. However, these mutations do not produce the desired null result in all cases, but instead generate a similar, functionally active protein. This effect could limit the therapeutic efficiency of gene therapy strategies based on abrogating oncogene expression, and therefore needs to be considered carefully. If there is an acceptable degree of efficiency of CRISPR/Cas9 delivery to cells, the key step for success lies in the effectiveness of a specific sgRNA at knocking out the oncogene, when only one sgRNA can be used. This study shows that the null effect could be increased with an sgRNA targeting the splice donor site (SDS) of the chosen exon. Following this strategy, the generation of null alleles would be facilitated in two independent ways: the probability of producing a frameshift mutation and the probability of interrupting the canonical mechanism of pre-mRNA splicing. In these contexts, we propose to improve the loss-of-function yield driving the CRISPR system at the SDS of critical exons

MGRN1 as a Phenotypic Determinant of Human Melanoma Cells and a Potential Biomarker

Mahogunin Ring Finger 1 (MGRN1), a ubiquitin ligase expressed in melanocytes, interacts with the α melanocyte-stimulating hormone receptor, a well-known melanoma susceptibility gene. Previous studies showed that MGRN1 modulates the phenotype of mouse melanocytes and melanoma cells, with effects on pigmentation, shape, and motility. Moreover, MGRN1 knockdown augmented the burden of DNA breaks in mouse cells, indicating that loss of MGRN1 promoted genomic instability. However, data concerning the roles of MGRN1 in human melanoma cells remain scarce. We analyzed MGRN1 knockdown in human melanoma cells. Transient MGRN1 depletion with siRNA or permanent knockdown in human melanoma cells by CRISPR/Cas9 caused an apparently MITF-independent switch to a more dendritic phenotype. Lack of MGRN1 also increased the fraction of human cells in the S phase of the cell cycle and the burden of DNA breaks but did not significantly impair proliferation. Moreover, in silico analysis of publicly available melanoma datasets and estimation of MGRN1 in a cohort of clinical specimens provided preliminary evidence that MGRN1 expression is higher in human melanomas than in normal skin or nevi and pointed to an inverse correlation of MGRN1 expression in human melanoma with patient survival, thus suggesting potential use of MGRN1 as a melanoma biomarker.This research was funded by grant SAF2018_RTI2018-094929-B-I00 financed by FEDER/Ministerio de Ciencia e Innovación—Agencia Estatal de Investigación (Spain) (to C.J.-C. and J.C.G.-B.), and by grant UPV/EHU GIU20/035 (to S.A and M.D.B.)

Preclinical studies with glioblastoma brain organoid co-cultures show efficient 5-ALA photodynamic therapy

Abstract: Background: The high recurrence of glioblastoma (GB) that occurs adjacent to the resection cavity within two years of diagnosis urges an improvement of therapies oriented to GB local control. Photodynamic therapy (PDT) has been proposed to cleanse infiltrating tumor cells from parenchyma to ameliorate short long-term progression-free survival. We examined 5-aminolevulinic acid (5-ALA)- mediated PDT effects as therapeutical treatment and determined optimal conditions for PDT efficacy without causing phototoxic injury to the normal brain tissue. Methods: We used a platform of Glioma Initiation Cells (GICs) infiltrating cerebral organoids with two different glioblastoma cells, GIC7 and PG88. We measured GICs-5-ALA uptake and PDT/5-ALA activity in dose-response curves and the efficacy of the treatment by measuring proliferative activity and apoptosis. Results: 5-ALA (50 and 100  g/mL) was applied, and the release of protoporphyrin IX (PpIX) fluorescence measures demonstrated that the emission of PpIX increases progressively until its stabilization at 24 h. Moreover, decreased proliferation and increased apoptosis corroborated the effect of 5-ALA/PDT on cancer cells without altering normal cells. Conclusions: We provide evidence about the effectiveness of PDT to treat high proliferative GB cells in a complex in vitro system, which combines normal and cancer cells and is a useful tool to standardize new strategic therapies

Trends in Adherence to the Mediterranean Diet in Spanish Children and Adolescents across Two Decades.

Unhealthy dietary habits determined during childhood may represent a risk factor to many of the chronic non-communicable diseases (NCDs) in adulthood. Mediterranean Diet (MD) adherence in children and adolescents (8–16 years) living in Spain was investigated using the KIDMED questionnaire in a comparative analysis of two cross-sectional nationwide representative studies: enKid (1998–2000, n = 1001) and PASOS (2019–2020, n = 3540). Taking into account the educational level of pupils, as well as the characteristics of the place of living, a significant association was found between a KIDMED score ≥ 8 (optimal MD adherence) and primary education as well as residency in an area of <50,000 inhabitants, while living in the southern regions was associated with non-optimal MD adherence (p < 0.001). Participants of the 2019–2020 study showed an increase in the consumption of dairy products (31.1% increase), pasta/rice (15.4% increase), olive oil (16.9% increase), and nuts (9.7% increase), as well as a decreased sweets and candies intake (12.6% reduction). In contrast, a significantly lower MD adherence was found when comparing the 2019–2020 (mean ± SE: 6.9 ± 0.04) and the 1998–2000 study (7.37 ± 0.08); p < 0.001), due to less consumption of fish (20.3% reduction), pulse (19.4% reduction), and fruits (14.9% reduction), and an increased intake of commercial goods/pastries or fast-food intake (both 19.4% increase). The lowest adherence was recorded for adolescents also in the most recent study, where 10.9% of them presented a KIDMED score ≤ 3. This study shows that eating habits are deteriorating among Spanish children and adolescents. Such findings point out the urgency of undertaking strong measures to promote the consumption of healthy, sustainable, and non-ultra-processed food, such as those available in an MD, not only at a scientific and academic level, but also at a governmental onePartial funding for open access charge: Universidad de Málag

Estrategias metodológicas enfocadas a la mejora del aprendizaje en estudiantes con diversidad

Diseño y desarrollo de estrategias metodológicas que faciliten el aprendizaje de los estudiantes en general y que permitan a los estudiantes con diversidad funcional la integración y participación en el proceso de aprendizaje, que refuercen su inclusión y que favorezcan la adquisición de competencias

Determinants of adherence to the Mediterranean diet in Spanish children and adolescents: the PASOS study

[Abstract]: A progressive shift away from traditional healthy dietary patterns, such as the Mediterranean diet (MedDiet), has been observed in recent decades. The aim of this study was to assess determinants of optimal adherence to the MedDiet in Spanish children and adolescents. A cross-sec-tional analysis was included in the PASOS nationwide representative study in Spain. Participants were 3607 children and adolescents; 8–16 years old. Primary and secondary outcome measures of weight and height were measured. Adherence to the MedDiet, physical activity, and sedentary behavior in children and adolescents, as well as parental physical activity and dietary habits, were assessed. Optimal adherence to the MedDiet was observed in 45.5% of primary school students and 34.8% of secondary school students (OR: 0.65; 95%CI: 0.56–0.75). Optimal adherence to the MedDiet was higher in children/adolescents meeting daily recommended moderate and vigorous physical activity (OR: 2.39, 95%CI: 1.97–2.89) and in those meeting daily recommended screen time on week-days (OR: 2.05, 95%CI: 1.77–2.38) and weekends (OR: 1.76, 95%CI: 1.48–2.10). Participants with optimal adherence to the MedDiet were more likely to have mothers with a high-level education and high-tercile of SDQS, mothers who never smoked or were former smokers, and mothers who met the recommended physical activity and screen time. It can be concluded that a low prevalence of optimal adherence to the MedDiet was found among current Spanish children and adolescents. Optimal adherence to the MedDiet was associated with reaching the recommendations on physical activity and screen time, with the highest maternal educational level, and healthier maternal life-style