ApTOLL: A new therapeutic aptamer for cytoprotection and (re)myelination after multiple sclerosis.

BACKGROUND AND PURPOSE: ApTOLL is an aptamer selected to antagonize toll-like receptor 4 (TLR4), a relevant actor for innate immunity involved in inflammatory responses in multiple sclerosis (MS) and other diseases. The currently available therapeutic arsenal to treat MS is composed of immunomodulators but, to date, there are no (re)myelinating drugs available in clinics. In our present study, we studied the effect of ApTOLL on different animal models of MS. EXPERIMENTAL APPROACH: The experimental autoimmune encephalomyelitis (EAE) model was used to evaluate the effect of ApTOLL on reducing the inflammatory component. A more direct effect on oligodendroglia was studied with the cuprizone model and purified primary cultures of murine and human oligodendrocyte precursor cells (OPCs) isolated through magnetic-activated cell sorting (MACS) from samples of brain cortex. Also, we tested these effects in an ex vivo model of organotypic cultures demyelinated with lysolecithin (LPC). KEY RESULTS: ApTOLL treatment positively impacted the clinical symptomatology of mice in the EAE and cuprizone models, which was associated with better preservation plus restoration of myelin and oligodendrocytes in the demyelinated lesions of animals. Restoration was corroborated on purified cultures of rodent and human OPCs. CONCLUSION AND IMPLICATIONS: Our findings reveal a new therapeutic approach for the treatment of inflammatory and demyelinating diseases such as MS. The molecular nature of the aptamer exerts not only an anti-inflammatory effect but also neuroprotective and remyelinating effects. The excellent safety profile demonstrated by ApTOLL in animals and humans opens the door to future clinical trials in MS patients.

The Delfos Platform: A Conceptual Model-Based Solution for the Enhancement of Precision Medicine.

The use in the clinical practice of the vast amount of genomic data generated by current sequencing technologies constitutes a bottleneck for the progress of Precision Medicine (PM). Various problems inherent to the genomics domain (i.e., dispersion, heterogeneity, discrepancies, lack of standardization, and data quality issues) remain unsolved. In this paper, we present the Delfos platform, a conceptual model-based solution developed following a rigorous methodological and ontological background, whose main aim is to minimize the impact of these problems when transferring the research results to clinical practice. This paper presents the SILE method that provides methodological support for the Delfos platform, the Conceptual Schema of the Genome that provides a shared understanding of the domain, and the technological architecture behind the implementation of the platform. This paper also exemplifies the use of the Delfos platform through two use cases that involve the study of the DNA variants associated with the risk of developing Dilated Cardiomyopathies and Neuroblastoma.

Pandemic Grief and Suicidal Ideation in Latin American Countries: A Network Analysis.

This study aimed to characterize the network structure of pandemic grief symptoms and suicidal ideation in 2174 people from eight Latin American countries. Pandemic grief and suicidal ideation were measured using the Pandemic Grief Scale and a single item, respectively. Network analysis provides an in-depth characterization of symptom-symptom interactions within mental disorders. The results indicated that, "desire to die," "apathy" and "absence of sense of life" are the most central symptoms in a pandemic grief symptom network; therefore, these symptoms could be focal elements for preventive and treatment efforts. Suicidal ideation, the wish to die, and the absence of meaning in life had the strongest relationship. In general, the network structure did not differ among the participating countries. It identifies specific symptoms within the network that may increase the likelihood of their co-occurrence and is useful at the therapeutic level.

Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS).

BACKGROUND: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. METHODS: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. RESULTS: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). CONCLUSIONS: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients.

Eficacia de un programa de entrenamiento en fortalezas personales para reducir la sintomatología ansiosa y depresiva en adolescentes / Efficacy of a personal strengths training program to reduce anxiety and depressive symptoms in adolescents

La literatura muestra la importancia de identificar experiencias que permitan a los adolescentes desarrollarse en el contexto escolar. Además, indica la escasa evidencia empírica existente con esta población. Por ello, en este estudio se pretende comparar la eficacia de un programa de intervención centrado en el entrenamiento en fortalezas personales, con respecto a otro programa basado en el entrenamiento de habilidades sociales y técnicas para reducir el estrés y un grupo control de lista de espera, para reducir la sintomatología ansiosa y depresiva en adolescentes. Los entrenamientos se aplicaron de forma colectiva y consistieron en 6 sesiones de intervención de dos horas cada una. Los participantes fueron 65 (33 chicos y 32 chicas) estudiantes de ESO (Educación Secundaria Obligatoria) con edades entre 13 y 17 años (M = 14.32 y DT = .89). Los resultados muestran que el programa de entrenamiento centrado en el desarrollo de fortalezas personales es eficaz para aumentar las fortalezas entrenadas además de ser más eficaz para disminuir la sintomatología que otro programa de entrenamiento y que la ausencia del mismo. Implantar de forma transversal en la escuela este tipo de programas podría ayudar a un desarrollo más completo y amplio de la persona adolescente. (AU)

The literature shows us the importance of identifying experiences that allow adolescents to develop in the school context, it also indicates the scant empirical evidence that exists in this population at school, therefore, this study aims to compare the effectiveness of a program of intervention, focused on training in personal strengths, with respect to another intervention program based on the training of social skills and techniques to reduce stress and a waiting list control group, to reduce the anxious and depressive symptoms of the/ as teenagers The trainings were applied collectively and consisted of 6 intervention sessions of two hours each. The participants were 65 (33 boys and 32 girls) ESO (Compulsory Secondary Education) students aged between 13 and 17 years (M = 14.32 and SD = .89). The results show that the training program focused on the development of personal strengths is effective in increasing the trained strengths, as well as being more effective in reducing symptoms than the other training program or the absence of it. Implementing this type of program across schools could help a more complete and comprehensive development of the adolescent. (AU)

Cold urticaria as a complication of cryotherapy in the treatment of viral warts.

Cryotherapy with liquid nitrogen has been established as the first-line treatment for pediatric patients with viral warts. Cold-induced urticaria (CU) is a rare skin reaction triggered by cold stimuli. We present the case of a pediatric patient with viral warts who developed CU after receiving cryotherapy.

Actividad y discapacidad en pacientes cubanos con artritis reumatoide como factores que influyen en la sexualidad

Introducción: La artritis reumatoide es una enfermedad autoinmune de carácter inflamatorio y crónico. La afectación en la esfera sexual es frecuente, compromete a ambos sexos y se relaciona con factores como el dolor, la discapacidad y el consumo de medicamentos. Esta afectación no ha sido suficientemente abordada en la literatura a pesar de su prevalencia, y en Cuba no se han reportado hasta el momento estudios relacionados sobre este tema de investigación. Objetivo: Determinar el impacto de la artritis reumatoide en la sexualidad y su relación en la actividad y la discapacidad. Métodos: Se realizó un estudio monocéntrico, transversal, descriptivo. Se incluyeron los pacientes con un diagnóstico de artritis reumatoide en el período comprendido de septiembre de 2019 a junio de 2021. Se utilizó el cuestionario Qualisex para evaluar el impacto de la artritis reumatoide en la sexualidad. Resultados: En el estudio doscientos veintiséis pacientes fueron incluidos, la media de edad fue de 53,38 años (DE ± 12,22) el 82,7 % fueron mujeres. Al responder el autocuestionario Qualisex el 73,9 % de los sujetos presentaron afectación en la sexualidad. No se estableció una relación significativa entre la afectación en la esfera sexual y el tiempo de evolución. A diferencia de los niveles altos de actividad y discapacidad. Conclusiones: En la población estudiada se presentó afectación en la sexualidad, no obstante, esta no se relacionó con el tiempo de evolución de la artritis reumatoide. Se encontró asociación entre la actividad de la enfermedad y la capacidad funcional con la afectación en la esfera sexual.

Introduction: Rheumatoid arthritis is a chronic, inflammatory autoimmune disease. Disorders in the sexual sphere is frequent, it affects both sexes and it is related to factors such as pain, disability and medication consumption. This condition has not been sufficiently addressed in the literature despite its prevalence and in Cuba no studies related to the topic under study have been reported to date. Objective: To determine the impact of rheumatoid arthritis on sexuality and its relationship with activity and disability. Methods: A monocentric, cross-sectional and descriptive study was carried out on patients with a diagnosis of rheumatoid arthritis, from September 2019 to June 2021. The Qualisex questionnaire was used to evaluate the impact of rheumatoid arthritis on sexuality. Results: Two hundred twenty-six patients were included, the mean age was 53.38 years (SD ± 12.22) and 82.7% were women. When answering the Qualisex self-questionnaire, 73.9% of the subjects had effects in their sexuality. No significant relationship was established between the involvement in the sexual sphere and the time of evolution. Conclusions: The impact on sexuality in the studied population was not related to the duration of rheumatoid arthritis. On the other hand, an association was found between disease activity and functional capacity with effects in the sexual sphere.

Cross-cultural invariance of the Spanish version of the COVID-19 Assessment Scorecard to measure the perception of government actions against COVID-19 in Latin America.

OBJECTIVES: The present study aimed to evaluate the measurement invariance of a general measure of the perception of governmental responses to COVID-|19 (COVID-SCORE-10) in the general population of 13 Latin American countries. METHODS: A total of 5780 individuals from 13 Latin American and Caribbean countries selected by non-probabilistic snowball sampling participated. A confirmatory factor analysis was performed and the alignment method was used to evaluate invariance. Additionally, a graded response model was used for the assessment of item characteristics. RESULTS: The results indicate that there is approximate measurement invariance of the COVID-SCORE-10 among the participating countries. Furthermore, IRT results suggest that the COVID-SCORE-10 measures with good psychometric ability a broad spectrum of the construct assessed, especially around average levels. Comparison of COVID-SCORE-10 scores indicated that participants from Cuba, Uruguay and El Salvador had the most positive perceptions of government actions to address the pandemic. Thus, the underlying construct of perception of government actions was equivalent in all countries. CONCLUSION: The results show the importance of initially establishing the fundamental measurement properties and MI before inferring the cross-cultural universality of the construct to be measured.

Metabolic syndrome, adiposity, diet, and emotional eating are associated with oxidative stress in adolescents.

Background: Metabolic syndrome (MS), a condition related to adiposity and oxidative stress, can develop in adolescence, a critical stage in life that impacts health in adulthood. However, there is scarce scientific research about the relationship between lifestyle factors, emotion management, and oxidative stress in this phase of life. Aim: To analyze whether nutritional parameters, lifestyle factors, emotion management, and MS in adolescents are associated with oxidative stress measured by the biomarker 8-isoprostane. Methods: A cross-sectional study was carried out in 132 adolescents (48.5% girls, aged 12 ± 0.48 years) and data were collected on nutritional parameters (anthropometric measurements, biochemical analyzes, and blood pressure), lifestyle factors (physical activity, sleep, and diet), and emotion management (self-esteem, emotional eating, and mood). 8-isoprostane was analyzed in spot urine samples. The study population was categorized in three groups (healthy, at-risk, and with MS) using the International Diabetes Federation definition of MS in adolescents. To capture more complex interactions, a multiple linear regression was used to analyze the association between 8-isoprostane and the aforementioned variables. Results: Urinary 8-isoprostane levels were significantly higher in the MS group compared to the healthy group (1,280 ± 543 pg./mg vs. 950 ± 416 pg./mg respectively). In addition, univariable analysis revealed positive significant associations between 8-isoprostane and body mass index, waist circumference, waist-to-height ratio, body fat percentage, blood lipid profile and glucose, emotional eating, and refined cereal intake. Conversely, a negative significant association was found between 8-isoprostane and sleep duration and fish intake. The multiple linear regression analysis revealed associations between 8-isoprostane and LDL-c (ß = 0.173 value of p = 0.049), emotional eating (low ß = 0.443, value of p = 0.036; high ß = 0.152, value of p = 0.470), refined cereal intake (ß =0.191, value of p = 0.024), and fish intake (ß = -0.187, value of p = 0.050). Conclusion: The MS group, LDL-c, emotional eating, and high refined cereals and low fish intakes were associated with higher levels of oxidative stress in an adolescent population.

Assessment of Obsessive Thoughts About COVID-19 in 7 Latin American Countries: Structure and Measurement Invariance of the Obsession With COVID-19 Scale.

The present study aimed to evaluate the measurement invariance of the Obsession with COVID-19 Scale (OCS) among seven Latin American countries: Bolivia, Brazil, Cuba, El Salvador, Guatemala, Paraguay, and Uruguay. Although the OCS has been used in several countries and languages, there is a need for approaches that better integrate the cross-cultural equivalence of the scale. A total of 3185 people participated in the study. The results indicated the presence of a unidimensional structure and good reliability indices for the OCS in each country. The alignment method indicated that the OCS is an invariant measure of COVID-19 obsession among the populations of seven Latin American countries. The findings based on IRT analysis indicated that all OCS items had adequate discrimination and difficulty parameters. The findings contribute to the understanding of the internal structure of the scale in different countries at the same time, something that has been pending evaluation.

Effectiveness of gamification and game-based learning in Spanish adolescents with dyslexia: A longitudinal quasi-experimental research.

BACKGROUND: Gamification and game-based learning can provide motivating learning opportunities. The scientific literature suggests that these play strategies could be supportive tools for the learning of students with diagnosed dyslexia. AIMS: This study compares the effectiveness of an educational gamification and game-based learning (GBL) methodology versus a transmissive methodology for the improvement of reading processes and academic performance in the subject of Spanish Language and Literature in Spanish high school students with dyslexia. METHODS AND PROCEDURES: Longitudinal quasi-experimental research was conducted with control and experimental groups. Ninety students with a mean age of 14.22 years (SD = 0.95) participated in the study. The assessment instruments used were the PROLEC-SE reading process assessment battery and academic performance through subject grades. The intervention with the experimental group consisted of gamification and GBL of 15 one-hour sessions in which students' oral and written skills were worked with playful learning strategies. OUTCOMES AND RESULTS: The results indicate that the experimental group had statistically significant improvement in their reading skills (η2g = 0.616) and academic performance, albeit less in pseudoword speed, compared to the control group (η2g = 0.197). CONCLUSION AND IMPLICATIONS: The study highlights the usefulness of gamification and GBL as practical tools for meaningful learning in students with dyslexia.

Quiste dentígero en relación con tercer molar inferior retenido / A Dentigerous Cyst Related to Retained Lower Third Molar

Introducción: El quiste dentígero es un quiste odontogénico, casi siempre asociado a la corona de un diente retenido. Sus ubicaciones más frecuentes son la zona de tercer molar inferior y canino superior. Objetivo: Caracterizar la presentación de un quiste dentígero en un paciente adulto. Presentación de caso: Se presentó el caso de una paciente de 27 años de edad que acude a consulta por presentar sensación de opresión, dolor e inflamación en región de tercer molar inferior izquierdo. Al examen oral se observa tejido dentario en correspondencia con molar 38 parcialmente brotado con ligero edema de la mucosa a su alrededor. En radiografía panorámica se observa imagen radiolúcida en relación con cara mesial del 38 con discreto halo radiopaco, redondeada, compatible con un quiste dentígero. Conclusiones: Un diagnóstico a tiempo de estas lesiones constituye la clave para un tratamiento exitoso y menos invasivo, lo cual evitaría complicaciones mayores como la malignización, el crecimiento exagerado que puede ocasionar deformidad facial y la disfunción masticatoria permanente(AU)

Introduction: Dentigerous cyst is an odontogenic cyst, almost always associated with the crown of a retained tooth. Its most frequent locations are the areas of the lower third molar and the upper canine. Objective: To characterize the presentation of a dentigerous cyst in an adult patient. Case presentation: The case is presented of a 27-year-old female patient who came to the clinic with a sensation of pressure, pain and inflammation in the region of the lower left third molar. Oral examination permits to observe some dental tissue corresponding with molar 38 partially erupted with slight edema of the surrounding mucosa. Panoramic radiograph shows a radiolucent image related to the mesial side of 38, with a discrete radiopaque halo, rounded, compatible with a dentigerous cyst. Conclusions: A timely diagnosis of these lesions is the key to a successful and less invasive treatment, which would avoid major complications, such as malignization, the exaggerated growth that can cause facial deformity and permanent masticatory dysfunction(AU)

Metabolic switch from fatty acid oxidation to glycolysis in knock-in mouse model of Barth syndrome.

Mitochondria are central for cellular metabolism and energy supply. Barth syndrome (BTHS) is a severe disorder, due to dysfunction of the mitochondrial cardiolipin acyl transferase tafazzin. Altered cardiolipin remodeling affects mitochondrial inner membrane organization and function of membrane proteins such as transporters and the oxidative phosphorylation (OXPHOS) system. Here, we describe a mouse model that carries a G197V exchange in tafazzin, corresponding to BTHS patients. TAZG197V mice recapitulate disease-specific pathology including cardiac dysfunction and reduced oxidative phosphorylation. We show that mutant mitochondria display defective fatty acid-driven oxidative phosphorylation due to reduced levels of carnitine palmitoyl transferases. A metabolic switch in ATP production from OXPHOS to glycolysis is apparent in mouse heart and patient iPSC cell-derived cardiomyocytes. An increase in glycolytic ATP production inactivates AMPK causing altered metabolic signaling in TAZG197V . Treatment of mutant cells with AMPK activator reestablishes fatty acid-driven OXPHOS and protects mice against cardiac dysfunction.

Diet quality and nutrient density in pregnant women according to adherence to Mediterranean diet.

Background and aims: The dietary pattern followed during pregnancy, specifically healthy dietary patterns such as the Mediterranean diet, is a key factor in the mother's and the offspring's health. Pregnant women dietary intake is not enough to cover the micronutrient requirements of pregnancy, and higher adherence to the Mediterranean diet may improve dietary quality and nutritional density. The aim of the present study was to describe the dietary nutrient intake and diet quality during pregnancy and to evaluate whether a high adherence to Mediterranean diet was associated with a more adequate intake of micronutrients. Methods: This was a cross-sectional study with 1,356 pregnant women selected during the routine second trimester ultrasound scan (19-23 weeks' gestation). Energy and nutrient intake were calculated using a validated 151-item semi-quantitative food frequency questionnaire and nutrient density was estimated dividing the absolute nutrient intake by total energy intake. Adherence to the Mediterranean diet was evaluated with a 17-item Mediterranean diet adherence score. The criterion used for risk of inadequate nutrient intake has been set below two thirds (2/3) of the dietary reference intakes. The differences were assessed by multivariate linear regression models adjusted for confounders. Results: A significant proportion of pregnant women had an inadequate intake of macro and micronutrient that was lower in those with high adherence to the Mediterranean diet (≥12 points, n = 122, 19%), including calcium (the Mediterranean diet high adherence 2.5% vs. low adherence 26.7%, p < 0.001), magnesium (0% vs. 7.6%, p = 0.001), iron (24.5% vs. 74.1%, p < 0.001), and vitamin B9 (0% vs. 29.8%, p < 0.001), vitamin C (0% vs. 1.9%, p = 0.033), and vitamin D (61.5% vs. 92.8%, p < 0.001) intake. High adherence to Mediterranean diet was associated with higher intake of protein, monounsaturated fatty acids, fiber, vitamins (B1, B9, C, D), calcium, magnesium, iron, zinc, phosphor, potassium, essential fatty acids, and α-linolenic acid, and with a lower intake of α-linoleic acid and trans fatty acids as compared to low adherence to Mediterranean diet. Conclusion: High adherence to Mediterranean diet was associated with higher diet quality and lower proportion of inadequate micro and macronutrient intake. The Mediterranean diet promotion, particularly among pregnant women, may be a useful and public health strategy to avoid overweight and nutrient deficiencies.

Pathogenesis of spinal intramedullary lipomas: two case reports.

BACKGROUND: Spinal lipomas not associated with dysraphism are rare and have an unknown natural history. In this report, we describe two cases; they showed recurrence during long-term follow-up, which makes us doubt a benign malformative etiology. CASE REPORTS: Two patients, a 19-year-old South American woman and a 14-year-old boy with spinal lipomas, underwent surgical resection. The lipomas were not associated with dysraphism and were located in the cervicothoracic and craniocervical junctions. In both cases, we decided to operate due to clinical progression; the former had a progressive natural course, and the latter experienced clinical worsening after recurrence from previous surgeries. The surgery took place with the assistance of neurophysiological monitoring and intraoperative ultrasound; a partial resection and medullary decompression were done, following the more recent recommendations. DISCUSSION: The natural history of these lesions is currently unknown due to their rarity and the heterogeneity in the long-term follow-up of previously reported cases. Although previous reports describe good outcomes after surgical resection, long follow-ups, especially in young subjects, may show differences in these outcomes with progression and recurrence. We contribute to this last piece of evidence by describing two more cases of progression and recurrence. LESSONS: Long-term close follow-up should be done in young subjects with spinal lipomas, as they are more prone to an aggressive course. Metabolism and hormonal changes may be behind this progression. Reoperation must be considered if neurological decline is detected.

Relationship Between Fear of COVID-19, Conspiracy Beliefs About Vaccines and Intention to Vaccinate Against COVID-19: A Cross-National Indirect Effect Model in 13 Latin American Countries.

The present study explored the predictive capacity of fear of COVID-19 on the intention to be vaccinated against COVID-19 and the influence in this relationship of conspiracy beliefs as a possible mediating psychological variable, in 13 Latin American countries. A total of 5779 people recruited through non-probabilistic convenience sampling participated. To collect information, we used the Fear of COVID-19 Scale, Vaccine conspiracy beliefs Scale-COVID-19 and a single item of intention to vaccinate. A full a priori Structural Equation Model was used; whereas, cross-country invariance was performed from increasingly restricted structural models. The results indicated that, fear of COVID-19 positively predicts intention to vaccinate and the presence of conspiracy beliefs about COVID-19 vaccines. The latter negatively predicted intention to vaccinate against COVID-19. Besides, conspiracy beliefs about COVID-19 vaccines had an indirect effect on the relationship between fear of COVID-19 and intention to vaccinate against COVID-19 in the 13 countries assessed. Finally, the cross-national similarities of the mediational model among the 13 participating countries are strongly supported. The study is the first to test a cross-national mediational model across variables in a large number of Latin American countries. However, further studies with other countries in other regions of the world are needed.

Virus-Specific T Cells From Cryopreserved Blood During an Emergent Virus Outbreak for a Potential Off-the-Shelf Therapy.

During the first outbreak of an emergent virus, methods need to be developed to rapidly establish suitable therapies for patients with high risk of severe disease caused by the pathogen. Considering the importance of the T-cell response in controlling viral infections, adoptive cell therapy with virus-specific T cells has been used as a safe and effective antiviral prophylaxis and treatment for immunocompromised patients. The main objective of this study was to establish an effective and safe method to cryostore whole blood as starting material and to adapt a T-cell activation and expansion protocol to generate an off-the-shelf antiviral therapeutic option. Additionally, we studied how memory T-cell phenotype, clonality based on T-cell receptor, and antigen specificity could condition characteristics of the final expanded T-cell product. Twenty-nine healthy blood donors were selected from a database of convalescent plasma donors with a confirmed history of SARS-CoV-2 infection. Blood was processed using a fully automated, clinical-grade, and 2-step closed system. Eight cryopreserved bags were advanced to the second phase of the protocol to obtain purified mononucleated cells. We adapted the T-cell activation and expansion protocol, without specialized antigen-presenting cells or presenting molecular structures, in a G-Rex culture system with IL-2, IL-7, and IL-15 cytokine stimulation. The adapted protocol successfully activated and expanded virus-specific T cells to generate a T-cell therapeutic product. We observed no major impact of post-symptom onset time of donation on the initial memory T-cell phenotype or clonotypes resulting in minor differences in the final expanded T-cell product. We showed that antigen competition in the expansion of T-cell clones affected the T-cell clonality based on the T-cell receptor ß repertoire. We demonstrated that good manufacturing practice of blood preprocessing and cryopreserving is a successful procedure to obtain an initial cell source able to activate and expand without a specialized antigen-presenting agent. Our 2-step blood processing allowed recruitment of the cell donors independently of the expansion cell protocol timing, facilitating donor, staff, and facility needs. Moreover, the resulting virus-specific T cells could be also banked for further use, notably maintaining viability and antigen specificity after cryopreservation.

Shall we play together? Game-based learning for engagement and classroom climate in Spanish socially deprived communities.

Purpose: The purpose of this study is to analyze the effects of a game-based learning (GBL) program on the classroom climate and engagement of high schools in socially deprived communities in Spain. Methods: The study included 277 students from two secondary schools located in Southern Spain, situated in Zones in Need of Social Transformation. Sampling was non-probabilistic and accidental, based on the accessibility of the school and the willingness of the management and teaching staff to participate in the GBL program. The study employed a control group and two experimental groups (cooperative games group only and cooperative and competitive games group) to compare pre-test and post-test data in both groups. The Brief Class Climate Scale and Engagement Inventory, validated in academic literature, were used as assessment instruments. Results: The study used a series of ANOVA tests to compare the experimental groups with the control group. The results indicated statistically significant changes in all study variables. In all cases, the experimental groups demonstrated greater benefits than the control group. Discussion and conclusion: The study findings reveal that games can provide significant benefits to students, regardless of whether they are cooperative or competitive. The study provides evidence of the benefits of GBL in high schools located in socially deprived communities in Spain.

Huge variability in restrictions of mobilization for patients with aneurysmal subarachnoid hemorrhage - A European survey of practice.

Introduction: One of the major goals of neurointensive care is to prevent secondary injuries following aSAH. Bed rest and patient immobilization are practiced in order to decrease the risk of DCI. Research question: To explore the current practices in place concerning the management of patients with aSAH, specifically, protocols and habits regarding restrictions of mobilization and HOB positioning. Material and methods: A survey was designed, modified, and approved by the panel of the Trauma & Critical Care section of the EANS to cover the practice of restrictions of patient mobilization and HOB positioning in patients with aSAH. Results: Twenty-nine physicians from 17 countries completed the questionnaire. The majority (79.3%) stated that non-secured aneurysm and the presence of an EVD were the factors related to the establishment of restriction of mobilization. The average duration of the restriction varied widely ranging between 1 and 21 days. The presence of an EVD (13.8%) was found to be the main reason to recommend restriction of HOB elevation. The average duration of restriction of HOB positioning ranged between 3 and 14 days. Rebleeding or complications related to CSF over-drainage were found to be related to these restrictions. Discussion and conclusion: Restriction of patient mobilization regimens vary widely in Europe. Current limited evidence does not support an increased risk of DCI rather the early mobilization might be beneficial. Large prospective studies and/or the initiative of a RCT are needed to understand the significance of early mobilization on the outcome of patients with aSAH.

IDH3γ functions as a redox switch regulating mitochondrial energy metabolism and contractility in the heart.

Redox signaling and cardiac function are tightly linked. However, it is largely unknown which protein targets are affected by hydrogen peroxide (H2O2) in cardiomyocytes that underly impaired inotropic effects during oxidative stress. Here, we combine a chemogenetic mouse model (HyPer-DAO mice) and a redox-proteomics approach to identify redox sensitive proteins. Using the HyPer-DAO mice, we demonstrate that increased endogenous production of H2O2 in cardiomyocytes leads to a reversible impairment of cardiac contractility in vivo. Notably, we identify the γ-subunit of the TCA cycle enzyme isocitrate dehydrogenase (IDH)3 as a redox switch, linking its modification to altered mitochondrial metabolism. Using microsecond molecular dynamics simulations and experiments using cysteine-gene-edited cells reveal that IDH3γ Cys148 and 284 are critically involved in the H2O2-dependent regulation of IDH3 activity. Our findings provide an unexpected mechanism by which mitochondrial metabolism can be modulated through redox signaling processes.