Mutant Huntingtin Is Cleared from the Brain via Active Mechanisms in Huntington Disease.

Huntington disease (HD) is a neurodegenerative disease caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene. Therapeutics that lower HTT have shown preclinical promise and are being evaluated in clinical trials. However, clinical assessment of brain HTT lowering presents challenges. We have reported that mutant HTT (mHTT) in the CSF of HD patients correlates with clinical measures, including disease burden as well as motor and cognitive performance. We have also shown that lowering HTT in the brains of HD mice results in correlative reduction of mHTT in the CSF, prompting the use of this measure as an exploratory marker of target engagement in clinical trials. In this study, we investigate the mechanisms of mHTT clearance from the brain in adult mice of both sexes to elucidate the significance of therapy-induced CSF mHTT changes. We demonstrate that, although neurodegeneration increases CSF mHTT concentrations, mHTT is also present in the CSF of mice in the absence of neurodegeneration. Importantly, we show that secretion of mHTT from cells in the CNS followed by glymphatic clearance from the extracellular space contributes to mHTT in the CSF. Furthermore, we observe secretion of wild type HTT from healthy control neurons, suggesting that HTT secretion is a normal process occurring in the absence of pathogenesis. Overall, our data support both passive release and active clearance of mHTT into CSF, suggesting that its treatment-induced changes may represent a combination of target engagement and preservation of neurons.SIGNIFICANCE STATEMENT: Changes in CSF mutant huntingtin (mHTT) are being used as an exploratory endpoint in HTT lowering clinical trials for the treatment of Huntington disease (HD). Recently, it was demonstrated that intrathecal administration of a HTT lowering agent leads to dose-dependent reduction of CSF mHTT in HD patients. However, little is known about how HTT, an intracellular protein, reaches the extracellular space and ultimately the CSF. Our findings that HTT enters CSF by both passive release and active secretion followed by glymphatic clearance may have significant implications for interpretation of treatment-induced changes of CSF mHTT in clinical trials for HD.

Cerebrospinal fluid mutant huntingtin is a biomarker for huntingtin lowering in the striatum of Huntington disease mice.

Huntington disease (HD) is a neurodegenerative disease caused by a trinucleotide repeat expansion in the HTT gene encoding an elongated polyglutamine tract in the huntingtin (HTT) protein. Expanded mutant HTT (mHTT) is toxic and leads to regional atrophy and neuronal cell loss in the brain, which occurs earliest in the striatum. Therapeutic lowering of mHTT in the central nervous system (CNS) has shown promise in preclinical studies, with multiple approaches currently in clinical development for HD. Quantitation of mHTT in the cerebrospinal fluid (CSF) is being used as a clinical pharmacodynamic biomarker of target engagement in the CNS. We have previously shown that the CNS is a major source of mHTT in the CSF. However, little is known about the specific brain regions and cell types that contribute to CSF mHTT. Therefore, a better understanding of the origins of CSF mHTT and whether therapies targeting mHTT in the striatum would be expected to be associated with significant lowering of mHTT in the CSF is needed. Here, we use complementary pharmacological and genetic-based approaches to either restrict expression of mHTT to the striatum or selectively deplete mHTT in the striatum to evaluate the contribution of this brain region to mHTT in the CSF. We show that viral expression of a mHTT fragment restricted to the striatum leads to detectable mHTT in the CSF. We demonstrate that targeted lowering of mHTT selectively in the striatum using an antisense oligonucleotide leads to a significant reduction of mHTT in the CSF of HD mice. Furthermore, using a transgenic mouse model of HD that expresses full length human mHTT and wild type HTT, we show that genetic inactivation of mHTT selectively in the striatum results in a significant reduction of mHTT in the CSF. Taken together, our data supports the conclusion that the striatum contributes sufficiently to the pool of mHTT in the CSF that therapeutic levels of mHTT lowering in the striatum can be detected by this measure in HD mice. This suggests that CSF mHTT may represent a pharmacodynamic biomarker for therapies that lower mHTT in the striatum.

An Open Hardware Design for Internet of Things Power Quality and Energy Saving Solutions.

An important challenge for our society is the transformation of traditional power systems to a decentralized model based on renewable energy sources. In this new scenario, advanced devices are needed for real-time monitoring and control of the energy flow and power quality (PQ). Ideally, the data collected by Internet of Thing (IoT) sensors should be shared to central cloud systems for online and off-line analysis. In this paper openZmeter (oZm) is presented as an advanced low-cost and open-source hardware device for high-precision energy and power quality measurement in low-voltage power systems. An analog front end (AFE) stage is designed and developed for the acquisition, conditioning, and processing of power signals. This AFE can be stacked on available quadcore embedded ARM boards. The proposed hardware is capable of adapting voltage signals up to 800 V AC/DC and currents up to thousands of amperes using different probes. The oZm device is described as a fully autonomous open-source system for the computation and visualization of PQ events and consumed/generated energy, along with full details of its hardware implementation. It also has the ability to send data to central cloud management systems. Given the small size of the hardware design and considering that it allows measurements under a wide range of operating conditions, oZm can be used both as bulk metering or as metering/submetering device for individual appliances. The design is released as open hardware and therefore is presented to the community as a powerful tool for general usage.

Goal Orientations of Secondary School Students and Their Intention to Practise Physical Activity in Their Leisure Time: Mediation of Physical Education Importance and Satisfaction.

The aim of this study was to analyse the mediating role of Physical Education importance and satisfaction/fun between the dispositional goal orientations of secondary school students and their intention to partake in leisure time physical activity. The research design was descriptive, cross-sectional, and non-randomized. In total, 2102 secondary school students participated (Mage = 14.87; SD = 1.39) (1024 males; 1078 females). The scales used were the Perception of Success Questionnaire, Importance of Physical Education, Satisfaction with Physical Education, and Intention to Participate in Leisure Time Physical Activity. Structural equation models with the latent variables were also calculated. The results highlight that Physical Education satisfaction/fun has a mediating effect between task orientation and the intention to practice physical activity during leisure time.

Mediation of academic self-efficacy between emotional intelligence and academic engagement in physical education undergraduate students.

The aim of this study was to analyze academic self-efficacy as a mediator between emotional intelligence and academic engagement. A non-experimental, cross-sectional, correlational-causal study was designed in which 1,164 Mexican students participated (Mage = 21.21; SD = 3.26) (30.0% female; 69.6% male; 0.4% other). The scales of emotional intelligence, academic self-efficacy and academic engagement were used, and a structural equation analysis with latent variables was conducted. The results obtained demonstrate that emotional clarity and repair have a positive and direct effect on academic self-efficacy. In addition, emotional repair predicts behavioral and emotional engagement. It was also found that academic self-efficacy is an excellent mediator between emotional clarity and repair, and the dimensions of academic engagement, as it substantially improves behavioral and emotional engagement while decreasing behavioral and emotional disaffection.

Analysis of Academic Psychological Variables, Physical Education, and Physical Activity Levels of Mexican Students.

Physical inactivity is a current worldwide, and especially Mexican adolescents. Therefore, this study has the following objectives: (i) to analyze the PA-LT pattern of Mexican adolescents; (ii) to analyze whether there are differences in emotional intelligence, basic psychological needs, academic motivation, self-esteem, and academic satisfaction according to the PA-LT pattern; (iii) to analyze the relationship between emotional intelligence, basic psychological needs, academic motivation, self-esteem, and academic satisfaction. A total of 748 secondary school students participated, of which 374 were girls (Mean age = 13.99; SD = 0.30) and 374 boys (Mean age = 14.02; SD = 0.33). The questionnaire comprised the following scales: IE, NPB-ESC, EMA, EA, and SIE. The main results obtained show that none of the girls stick to any active physical activity pattern during their spare time. In addition, physically active boys obtained better scores in emotional clarity, emotional repair, perception of academic competence, perception of social relationships, extrinsic motivation, intrinsic motivation, self-esteem, and satisfaction with school.

Mediating effect of social interaction anxiety between emotional intelligence and life satisfaction in physical education students: post-COVID-19 study.

The aim of this research is to analyze the effect of social interaction anxiety on satisfaction with life mediated by emotional intelligence. The research design was descriptive, cross-sectional, and non-randomized. In total, 1,164 Mexican physical education students participated (Mage = 21.21; SD = 3.26; 30.0% female; 69.6% male; 0.4% other). The scales used were the Social Interaction Anxiety Scale, Trait Meta-Mood Scale and Satisfaction with Life and a structural equation analysis with latent variables was conducted. The results highlight that it can be asserted that emotional clarity and repair had a mediating effect between social interaction anxiety and satisfaction with life, as they did decrease the negative effects of social interaction anxiety on satisfaction with life. In addition, social interaction anxiety had a direct and positive effect on emotional attention and a negative effect on emotional clarity and repair.

Psychometric properties of the learning perception questionnaire in Mexican's students.

The aim of this study is to analyze the psychometric properties of the learning perception questionnaire (CPA) presented in this research. It was administered to a total of 1496 students in Baja California and Nuevo León, of the total sample, 748 were girls (Mage = 14.0, SD = 0.3), and 748 boys (Age = 14.1, SD = 0.3). The analyses support the hypothesized theoretical model of origin, presenting an acceptable internal consistency and temporal stability. The model fit data was excellent; furthermore, the examined model meets the convergent validity requirements. External validity was explored by examining the predictive relationship of the scale studied with Satisfaction with School. The CPA has a strong predictive relationship with student satisfaction/fun in class, while it is negative with boredom. Thus, the higher the perception of learning, the less likely that students will be bored in class. It is concluded, therefore, that the CPA scale is a proven instrument and that it serves to assess the perception of key learning by secondary school students.

Relation between Physical Fitness Components and the Occurrence and Subjective Intensity of Back Pain in Secondary School Adolescents.

Despite the well documented benefits of physical fitness (PF) on general health, its role in back pain (BP) is still unclear. The objective of this study was to assess the association between different PF profiles and BP in a sample of adolescents. The study assessed PF and BP in a sample of 919 youth (age = 15.5 ± 1.3 years) from North and South Tyrol. A total of 531 participants (57.8%) reported no BP, whereas 4.7% (n = 43) reported severe BP. A two-step cluster analysis detected three main groups: the "less fit", with significantly lower scores in all PF tests (p < 0.001); the "strong sprinters", with higher speed and muscular strength than the others (p < 0.001); and the "flexible marathoners", with higher flexibility and cardiorespiratory fitness (p < 0.001). The "flexible marathoners" showed significantly better BP scores than the "less fit" (p = 0.029). Cardiorespiratory fitness and trunk flexibility are potential preventive components of BP in adolescents. Since the decline in flexibility starts very early in life, it is recommended to put a particular emphasis on this component of PF. The role of other components of PF should be further investigated in the future.

Influence of Teaching Styles on the Learning Academic Confidence of Teachers in Training.

The objective of this research was to analyze the mediation of academic engagement and the satisfaction of basic needs between teaching styles and academic confidence amongst teachers during initial training. The research design was observational, descriptive, cross-sectional, and non-randomized. In total, 920 university students in initial teacher training participated (61.85% women) (Mage = 24.73; SD = 5.34). The scales of interpersonal teaching styles, the satisfaction of basic psychological needs, academic engagement, and academic confidence were used, and a structural equation analysis with latent variables was carried out. The results highlight the important mediating role played by the satisfaction of basic psychological needs between the autonomous support style and the academic confidence of the trainee teachers. This research also highlights the importance, both for teachers and researchers, of using an autonomous support style, as well as the creation of a context for encouraging the satisfaction of basic psychological needs, to promote academic confidence in initial teacher training programs at university.

Erratum: Rodríguez-Medellín, R., et al. Mexican Validation of the Engagement and Disaffection in Physical Education Scale. Int. J. Environ. Res. Public Health 2020, 17, 1821.

The authors wish to add the following correction to their paper published in International Journal of Environmental Research and Public Health [...].

Satisfaction, Enjoyment and Boredom with Physical Education as Mediator between Autonomy Support and Academic Performance in Physical Education.

The purpose of this study was to analyze the mediating effect of satisfaction/enjoyment and boredom between the perception of autonomy support and academic performance in physical education. The sample consisted of 374 girls (Mage = 13.99; SD = 0.30) and 374 boys (Mage = 14.02; SD = 0.33) from the state of Nuevo León, Mexico. The instruments used were the Questionnaire for Autonomy Support in Physical Education (CAA-EF), Sport Satisfaction Intrinsic in Physical Education (SSI-EF) and the physical education performance of the students. The instrument's validity tests were analyzed using confirmatory procedures. Descriptive, reliability, and validity analyses were carried out for each instrument, and the mediating effect was examined; a mediation analysis was performed using the PROCESS V.3.5 macro. The main results revealed that autonomy support is not a direct indicator of physical education performance, but rather that students must feel satisfied with physical education for there to exist a forecast for a positive physical education performance. Satisfaction with physical education was found to have a mediating effect between autonomy support and physical education performance. However, boredom did not have a mediating effect between autonomy support and the student's performance in physical education class.

Analysis of Misbehaviors and Satisfaction With School in Secondary Education According to Student Gender and Teaching Competence.

Effective classroom management is a critical teaching skill and a key concern for educators. Disruptive behaviors disturb effective classroom management and can influence school satisfaction if the teacher does not have the competencies to control them. Two objectives were set in this work: to understand the differences that exist in school satisfaction, disruptive behaviors, and teaching competencies according to the gender of the students; and to analyze school satisfaction and disruptive student behaviors based on perceived teaching competence. A non-probabilistic and convenience sample selection process was employed, based on the subjects that we were able to access. 758 students participated (male = 45.8%) from seven public secondary schools in the Murcia Region (Spain). The age range was between 13 and 18 years (M = 15.22; DT = 1.27). A questionnaire composed of the following scales was used: Competencies Evaluation Scale for Teachers in Physical Education, School Satisfaction and Disruptive Behaviors in Physical Education. Mixed Linear Models performed with the SPSS v.23 was used for statistical analyses. The results revealed statistically significant differences based on gender and physical education teaching competencies. In conclusion, the study highlights that physical education teacher skills influence disruptive behaviors in the classroom, and that this is also related to school satisfaction. Furthermore, it highlights that boys showed higher levels of negative behaviors than girls.

Psychometric Properties of the Interpersonal Styles Questionnaire for Physical Education in a Mexican Sample.

During physical education classes, one of the contextual factors that can influence motivation is the teacher's interpersonal style. The aim of this study was to analyze the psychometric properties, structure, and factorial invariance across gender of the physical education teachers' Interpersonal Styles Questionnaire of Sonora, Mexico. The participants were 500 students (50.8% boys, 49.2% girls) aged between 9 and 13 years old (mean age (Mage) = 10.72; standard deviation (SD) = 0.74) from different elementary schools of Sonora, Mexico. In terms of measuring the teacher's interpersonal styles, the short version of the Learning Climate Questionnaire was used to measure autonomy support, whereas the Teacher Controllingness Scale was used to measure controlling style. The results support the structure and factorial invariance across gender groups of the Mexican version of the Interpersonal Styles Questionnaire for Physical Education (Cuestionario de Estilos Interpersonales en la Educación Física (CEI-EF, by its initials in Spanish)). In conclusion, the CEI-EF is a valid and reliable instrument that can be used to assess the teachers' interpersonal styles and draw comparisons between groups of boys and girls.

Mexican Validation of the Engagement and Disaffection in Physical Education Scale.

To date, no instrument adapted and validated that measures engagement and disaffection in the physical education class has been found, which limits the generation of knowledge of this area in Mexico. The aims of this study were to translate and adapt the engagement and disaffection scale to the context of physical education in Mexico and to examine its reliability, structure (two and four factors), and factorial invariance by gender in Mexican fifth- and sixth-grade elementary school students. A total of 1470 students participated (50.6% boys) with ages between 10 and 14 years (mean (M) = 10.56; standard deviation (SD) = 0.77) from federal (89.3%) and state (10.7%) elementary schools. Two factorial structures were tested (with four factors and two factors). The fit indexes of both models were satisfactory, and the factorial saturations were significant. The differences between the fit indexes of both models were irrelevant; therefore, the two-factor model was considered more suitable. The total strict invariance by gender was confirmed, and the reliabilities of the engagement and disaffection scale were acceptable. The Mexican version of the course engagement and disaffection scale in physical education is valid and useful to measure these constructs in the context of physical education in Mexico.

Prediction of the Satisfaction With the Student Life, Based on Teaching Competence and Satisfaction With the School.

The aim of this article was to assess how students evaluate the professional personality competence of physical education teachers in high school and its relation to student satisfaction and student satisfaction with life itself. In line with these aims, this study was completed as a cross-sectional study, which was carried out in a group of 890 physical education students. Of the study group, 50.3% were female and 49.7% were male. The average age was 15.49 years for females (SD 1.79) and 15.00 years for males (SD 2.00). We used a questionnaire featuring the Physical Education Teacher Competence, Intrinsic Satisfaction Classroom Scale, and Satisfaction with Life Scale. The results are presented as descriptive statistics, correlations, and a structural equation modeling analysis showing students' perceived competence, predicted self-determined satisfaction, which in turn corresponds to life satisfaction.

The Relationships between High School Subjects in terms of School Satisfaction and Academic Performance in Mexican Adolescents.

Adolescents' academic performance and the way it is related to their subjective wellbeing are issues of great interest across educational systems. The purpose of this study was to ascertain how satisfaction with high school subjects can predict school satisfaction and academic performance in Mexican students. The sample consisted of 457 high school students in the Baja California and Nuevo León states in Mexico (247 boys, 210 girls); their mean age being 14.10 (SD = 0.84). We used a questionnaire featuring a subject satisfaction scale, an intrinsic school satisfaction scale, and one related to academic grades. We used descriptive analyses, correlations, and structural regression models. In terms of results, the high satisfaction and academic performance levels in physical education, Spanish and English are worth highlighting. Geography and history are the most relevant predictors of academic grades, while Spanish predicts school satisfaction and physical education predicts boredom. In conclusion, satisfaction with mathematics, Spanish, and English are strong predictors of satisfaction (SATF), and the latter in turn predicts Mexican high school students' academic performance.

Motivational Regulations Across the Stages of Change for Exercise in the General Population of Monterrey (Mexico).

Few studies have examined exercise adherence in the Mexican population using self-determination theory proposals and the stages of change model. The objectives of this study were:(a) to translate and adapt the Behavioral Regulation in Exercise Questionnaire-3 (BREQ-3) to Mexican Spanish and examine its internal consistency and factorial structure (six dimensions); and (b) to analyse variations in behavioral regulations using the stages of change model. This study included 530 participants between 11 and 76 years old who lived in the metropolitan area of the city of Monterrey, Nuevo Leon, Mexico. The Mexican version of the BREQ-3 presented an acceptable six-factor model that agrees with the theory and has good internal consistency. Results showed that the less self-determined regulations (i.e., external and amotivation) predominated in the first stages of change (i.e., pre-contemplation and contemplation) and decreased in the last stages (i.e., action and maintenance); by contrast, the more self-determined regulations (i.e., intrinsic, integrated, and identified) predominated in the last stages (i.e., action and maintenance) and were lower in the first stages (i.e., pre-contemplation and contemplation). Linking these two theoretical constructs contributes to understanding physical exercise adherence.

Habituation Training Improves Locomotor Performance in a Forced Running Wheel System in Rats.

Increasing evidence supports that physical activity promotes mental health; and regular exercise may confer positive effects in neurological disorders. There is growing number of reports that requires the analysis of the impact of physical activity in animal models. Exercise in rodents can be performed under voluntary or forced conditions. The former presents the disadvantage that the volume and intensity of exercise varies from subject to subject. On the other hand, a major challenge of the forced training protocol is the low level of performance typically achieved within a given session. Thus, the aim of the present study was to evaluate the effectiveness of gradual increasing of the volume and intensity (training habituation protocol) to improve the locomotor performance in a forced running-wheel system in rats. Sprague-Dawley rats were randomly assigned to either a group that received an exercise training habituation protocol, or a control group. The locomotor performance during forced running was assessed by an incremental exercise test. The experimental results reveal that the total running time and the distance covered by habituated rats was significantly higher than in control ones. We conclude that the exercise habituation protocol improves the locomotor performance in forced running wheels.