Huntingtin CAG repeats in neuropathologically confirmed tauopathies: Novel insights.

Previous studies have suggested a relationship between the number of CAG triplet repeats in the HTT gene and neurodegenerative diseases not related to Huntington's disease (HD). This study seeks to investigate whether the number of CAG repeats of HTT is associated with the risk of developing certain tauopathies and its influence as a modulator of the clinical and neuropathological phenotype. Additionally, it aims to evaluate the potential of polyglutamine staining as a neuropathological screening. We genotyped the HTT gene CAG repeat number and APOE-ℰ isoforms in a cohort of patients with neuropathological diagnoses of tauopathies (n=588), including 34 corticobasal degeneration (CBD), 98 progressive supranuclear palsy (PSP) and 456 Alzheimer's disease (AD). Furthermore, we genotyped a control group of 1070 patients, of whom 44 were neuropathologic controls. We identified significant differences in the number of patients with pathological HTT expansions in the CBD group (2.7%) and PSP group (3.2%) compared to control subjects (0.2%). A significant increase in the size of the HTT CAG repeats was found in the AD compared to the control group, influenced by the presence of the Apoliprotein E (APOE)-ℰ4 isoform. Post-mortem assessments uncovered tauopathy pathology with positive polyglutamine aggregates, with a slight predominance in the neostriatum for PSP and CBD cases and somewhat greater limbic involvement in the AD case. Our results indicated a link between HTT CAG repeat expansion with other non-HD pathology, suggesting they could share common neurodegenerative pathways. These findings support that genetic or histological screening for HTT repeat expansions should be considered in tauopathies.

Image-guided programming deep brain stimulation improves clinical outcomes in patients with Parkinson's disease.

Deep brain stimulation (DBS) is an effective treatment for patients with Parkinson's disease (PD). However, some patients may not respond optimally to clinical programming adjustments. Advances in DBS technology have led to more complex and time-consuming programming. Image-guided programming (IGP) could optimize and improve programming leading to better clinical outcomes in patients for whom DBS programming is not ideal due to sub-optimal response. We conducted a prospective single-center study including 31 PD patients with subthalamic nucleus (STN) DBS and suboptimal responses refractory to clinical programming. Programming settings were adjusted according to the volumetric reconstruction of the stimulation field using commercial postoperative imaging software. Clinical outcomes were assessed at baseline and at 3-month follow-up after IGP, using motor and quality of life (QoL) scales. Additionally, between these two assessment points, follow-up visits for fine-tuning amplitude intensity and medication were conducted at weeks 2, 4, 6, and 9. After IGP, twenty-six patients (83.9%) experienced motor and QoL improvements, with 25.8% feeling much better and 38.7% feeling moderately better according to the patient global impression scale. Five patients (16.1%) had no clinical or QoL changes after IGP. The MDS-UPDRS III motor scale showed a 21.9% improvement and the DBS-IS global score improved by 41.5%. IGP optimizes STN-DBS therapy for PD patients who are experiencing suboptimal clinical outcomes. These findings support using IGP as a standard tool in clinical practice, which could save programming time and improve patients' QoL.

Effects of peppermint oil inhalation on vertical jump performance in elite young professional soccer players: A double-blinded randomized crossover study.

Aims: To evaluate peppermint essential oil (PEO) inhalation's effect on young soccer athletes' motor performance. Methods: A randomized crossover design was used to test the effect of the PEO. Eleven U-17 soccer players were evaluated into two conditions (PEO and Placebo - PLA). The players were tested in squat jump and countermovement jump and inhaled PEO or PLA and 10 min later performed the physical tests again. A mixed ANOVA was performed to test the hypotheses. Results: Main effects were found for the time in jumping height in the CMJ (p = 0.037). No main and interaction effects were found in the SJ variables. Conclusion: From the results, decrease CMJ performance acutely, both conditions presented decrease in JH, but based in effect size, PLA decrease is higher (more sample size for corroborate this) possibly due to improvements in the eccentric yielding sub-phase, where mentioned phase could be reflecting neural changes (required experimental verification). The PEO could be the interest in trainers for use before of match or in the half-time for minimize the decreased of physical performance by the rest.

Progression of Retinal Ganglion Cell and Nerve Fiber Layer Loss in Spinocerebellar Ataxia 3 Patients.

Spectral domain optical coherence tomography (SD-OCT) allows noninvasive measurements of retinal neuron layers. Here, we evaluate the relationship between clinical features and anatomical SD-OCT measurements in patients with spinocerebellar ataxia type 3 (SCA3) and how they change with time. A retrospective review was conducted on SCA3 patients. Clinical variables such as disease duration, number of CAG repeats, and the Scale for the Assessment and Rating of Ataxia (SARA) score were correlated with SD-OCT measurements, including retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, macular volume (MV), and central macular thickness (CMT). Seventeen SCA3 patients with an average follow-up of 44.9 months were recruited. Clinical features with significant baseline correlations with SD-OCT measurements included disease duration (CMT r = - 0.590; GCC r = - 0.585), SARA score (CMT r = - 0.560; RNFL r = - 0.390), and number of CAG repeats (MV r = - 0.552; RNFL r = - 0.503; GCC r = - 0.493). The annual rate of change of the SARA score during follow-up was associated with that of both the MV (r = - 0.494; p = 0.005) and GCC thickness (r = - 0.454; p = 0.012). High disability (stages 2 and 3) was independently inversely associated with the annual change in MV (ß coefficient - 17.09; p = 0.025). This study provides evidence of an association between clinical features and objective anatomical measurements obtained by SD-OCT in SCA3 patients. MV and GCC thickness could serve as potential biomarkers of disease severity, as their rates of decrease seem to be related to a worsening in the SARA score. These findings highlight the potential of SD-OCT as a noninvasive tool for assessing disease severity and progression in SCA3 patients.

Behavior of female judo weight divisions on approach and grip phases in different judo rules: The top 20 athletes from the 2016 and 2020 Olympic cycles.

In judo combat, the approach and gripping phases play a crucial role in determining victory, and it is believed that they can be influenced by the current rules. The objective of this study was to compare the technical-tactical actions executed by female judokas in the approach and gripping subphases during international competitions held in the 2016 and 2020 Olympic cycles, which featured different rules. We analyzed 1332 combat videos from the top 20 female judo athletes in the world rankings. These videos were equally distributed across weight divisions in the 2016 and 2020 Olympic cycles (48 kg = 132; 52 kg = 72; 57 kg = 109; 63 kg = 96; 70 kg = 69; 78 kg = 106; >78 kg = 82; total = 666 combats per cycle). The athletes in the 2020 cycle spent more time executing approach actions without contact with the judogi (formless: 2020 = 26.9; 2016 = 21.3 s; p < 0.001) and less time attempting grips (2020 = 24.6; 2016 = 31.2 s; p < 0.001) than the 2016 athletes. Additionally, the 2020 athletes spent less time on one-handed grips (left collar: 2020 = 7.1; 2016 = 7.9 s; p = 0.017; right sleeve: 2020 = 4.6; 2016 = 5.6 s; p = 0.018; left sleeve: 2020 = 4.7; 2016 = 5.2 s; p = 0.031) compared to the 2016 athletes. In both Olympic cycles, athletes devoted the most time to traditional grips (left collar right sleeve: 2016 = 12.3 ± 19.9; 2020 = 12.2 ± 17.5; right collar left sleeve: 2016 = 11.5 ± 20.6; 2020 = 12.3 ± 19.9 s). Differences in the approach subphases between Olympic cycles had varying impacts on different weight divisions (formless = 52 kg, 57 kg, 78 kg; right anteroposterior = 52 kg, 57 kg, 70 kg; grip attempts = 57 kg, 63 kg, 70 kg, 78 kg, >78 kg; p < 0.05), as did changes in grip types (right collar; left collar; left sleeve = 70 kg; right sleeve = >78 kg; right dorsal = 63 kg; left dorsal = 63 kg, 78 kg; right collar left sleeve = 48 kg, 52 kg; right dorsal left sleeve = 78 kg; right dorsal left collar = 48 kg, 70 kg; right dorsal left dorsal = 48 kg, 63 kg; p < 0.05). There were notable technical-tactical shifts in the behavior of female athletes between the Olympic cycles with different rules, and these findings should be taken into account for specialized training in female judo.

Mechanical Determinants of Sprinting and Change of Direction in Elite Female Field Hockey Players.

Profile determination in field hockey is critical to determining athletes' physical strengths and weaknesses, and is key in planning, programming, and monitoring training. This study pursued two primary objectives: (i) to provide descriptive data on sprinting, deceleration, and change of direction (COD) abilities and (ii) to elucidate the mechanical variables that influence sprint and COD performance in elite female field hockey players. Using radar and time-gate technology, we assessed performance and mechanical data from 30 m sprinting, deceleration, and COD tests for 26 elite female hockey players. A machine learning approach identified mechanical variables related to sprint and COD performance. Our findings offer a framework for athlete categorization and the design of performance-enhancing training strategies at the international level. Two pivotal mechanical variables-relative maximum horizontal force (F0) and maximum velocity (Vmax)-predominantly influence the times across all tested distances. However, the force-velocity profile (FVP) and horizontal deceleration do not influence the variance in the COD test outcomes. These insights can guide the design, adjustment, and monitoring of training programs, assisting coaches in decision making to optimize performance and mitigate injury risks for female hockey players.

Corrigendum: Effects of weight divisions in time-motion of female high-level Brazilian Jiu-jitsu combat behaviors.

[This corrects the article DOI: 10.3389/fpsyg.2023.1048642.].

Implementation of Exome Sequencing in Clinical Practice for Neurological Disorders.

Neurological disorders (ND) are diseases that affect the brain and the central and autonomic nervous systems, such as neurodevelopmental disorders, cerebellar ataxias, Parkinson's disease, or epilepsies. Nowadays, recommendations of the American College of Medical Genetics and Genomics strongly recommend applying next generation sequencing (NGS) as a first-line test in patients with these disorders. Whole exome sequencing (WES) is widely regarded as the current technology of choice for diagnosing monogenic ND. The introduction of NGS allows for rapid and inexpensive large-scale genomic analysis and has led to enormous progress in deciphering monogenic forms of various genetic diseases. The simultaneous analysis of several potentially mutated genes improves the diagnostic process, making it faster and more efficient. The main aim of this report is to discuss the impact and advantages of the implementation of WES into the clinical diagnosis and management of ND. Therefore, we have performed a retrospective evaluation of WES application in 209 cases referred to the Department of Biochemistry and Molecular Genetics of the Hospital Clinic of Barcelona for WES sequencing derived from neurologists or clinical geneticists. In addition, we have further discussed some important facts regarding classification criteria for pathogenicity of rare variants, variants of unknown significance, deleterious variants, different clinical phenotypes, or frequency of actionable secondary findings. Different studies have shown that WES implementation establish diagnostic rate around 32% in ND and the continuous molecular diagnosis is essential to solve the remaining cases.

Effects of weight divisions in time-motion of female high-level Brazilian Jiu-jitsu combat behaviors.

Coaches and psychologists can use time-motion analysis to elaborate specific interventions for female BJJ athletes, increasing specific training context and reducing unnecessary psychological and physical demands and injuries. Therefore, the present study aimed to analyze high-level BJJ female athletes in the 2020 Pan-American Games by comparing the weight categories on the time-motion analysis. The time-motion analysis (i.e., approach, gripping, attack, defensive actions, transition, mounting, guard, side control, and submissions) of 422 high-level female BJJ combats was divided and compared by weight category as follows: Rooster (n = 8), Light Feather (n = 18), Feather (n = 122), Light (n = 84), Middle (n = 74), Medium Heavy (n = 44), Heavy (n = 36), Super Heavy (n = 36), using p ≤ 0.05. The main results indicated that the Super heavyweight category [3.1 (5.8;119.9) s] had a shorter gripping time than other weight categories, p ≤ 0.05. In contrast, roosters [7.2 (3.5;64.6) s] had longer gripping, transition [14.0 (4.8;29.6) s], and attack time [76.2 (27.7, 93.2)] than the light feather, middlers, and heavier weight categories, p ≤ 0.05. These findings should be considered for the psychological interventions and training prescription.

A proof-of-concept study with SOM3355 (bevantolol hydrochloride) for reducing chorea in Huntington's disease.

AIMS: The study's aim is to investigate the efficacy and safety of SOM3355 (bevantolol hydrochloride), a ß1 -adrenoreceptor antagonist with recently identified vesicular monoamine transporter type 2 inhibitory properties, as a repositioned treatment to reduce chorea in Huntington's disease (HD). METHODS: A randomized, placebo-controlled proof-of-concept study was performed in 32 HD patients allocated to 2 arms of 4 sequential 6-week periods each. Patients received placebo and SOM3355 at 100 and 200 mg twice daily in a crossover design. The primary endpoint was improvement by at least 2 points in the total maximal chorea score in any active drug period compared with the placebo period. RESULTS: The primary endpoint was met in 57.1% of the patients. Improvements ≥3, ≥4, ≥5 and ≥6 points vs. placebo treatment were observed in 28.6, 25.0, 17.9 and 10.7% of the patients, respectively. A mixed-model analysis found a significant improvement in the total maximal chorea score of -1.14 (95% confidence interval, -2.11 to -0.16; P = .0224) with 200 mg twice daily SOM3355 treatment compared with placebo treatment. These results were paralleled by Clinical and Patient Global Impression of Change ratings (secondary endpoints). An elevation in plasma prolactin levels by 1.7-1.9-fold was recorded (P < .005), probably reflecting the effect on the dopamine pathway, consistent with vesicular monoamine transporter type 2 inhibition. The most frequent adverse events during SOM3355 administration were mild to moderate. CONCLUSION: Within the limits of this study, the results suggest that SOM3355 reduces chorea in patients with HD and is well-tolerated. Larger studies are necessary to confirm its therapeutic utility as an antichoreic drug. EudraCT number: 2018-000203-16 and ClinicalTrials.gov Identifier: NCT03575676.

The effects of weight categories on the time-motion analysis of female high-level judo athletes between the 2016 and 2020 Olympic cycles.

This study compared the time of female judo combat phases in international competitions between two Olympic cycles (2016; 2020) according to weight divisions (48 kg = 132; 52 kg = 72; 57 kg = 109; 63 kg = 96; 70 kg = 69; 78 kg = 106; >78 kg = 82; total = 666 combats/cycle). The behaviors of 1,332 high-level female judo combats were randomly observed over two Olympic cycles (2016 = 666; 2020 = 666) from the top 20 athletes in the world ranking by weight division. We performed time-motion analysis according to the combat phase and sequential judo actions (approach, gripping, attack, defense, groundwork, pause, and effort: pause ratio) considering the moment when the combat ended (Regular time = RT; Golden score = GS). The weight division groups were compared between Olympic cycles (2016; 2020), and p < 0.05 was defined as significant. The main results showed that 2020 athletes spent less time in the gripping (p = 0.005), attack (p < 0.001), defense (p < 0.001), groundwork (p<0.001) and pause (p = 0.002) phases than 2016 athletes. However, compared by the end-of-combat, 2020 female athletes spent less time in all combat phases for RT combats (p < 0.001), and more time in the approach phase for GS combats (p < 0.05) than in 2016. The 2016 weight divisions showed a higher diversity in the effort: pause ratio (2.5:1-3.4:1), whereas the 2020 weight divisions had values closer to each other (2.8,1-3:1). Analyzing each weight division separately and by the end-of-combat, the main results showed that (p < 0.05): 48, 63, 70, and 78 kg reduced the time in almost every phase of RT combat (except for: 63 kg = gripping and attack; 70 kg = approach and groundwork; 78 kg = approach); 48 and 57 kg increased the groundwork time in GS combats whereas 78 kg decreased; 52 kg and 78 kg increased the GS approach time. The temporal behavior of the combats changed between the Olympic cycles with different rules. These data must be considered to understand the characteristics of each group and to prescribe specialized training in female judo.

Dynamic Stretching Increases the Eccentric Rate of Force Development, but not Jump Height in Female Volleyball Players.

The present study aimed to analyze the effect of static and dynamic stretching exercises on the rate of force development (RFD) during the eccentric braking phase and jump height in a countermovement jump (CMJ) in female volleyball players. Thirty female volleyball players were randomly distributed in a static stretching (n = 10; SG), a dynamic stretching, and (n = 10; DG) a control group (n = 10; CG). A force plate and a 3D analysis system were employed to detect the eccentric braking phase during the CMJ. The RFD was analyzed in RFD (RFDi) intervals and the accumulated RFD (RFDa), and normalized to body mass. The SG experienced a likely small decrease in the RFDa (mean difference -17.4 N/s/kg) and a likely small decrease in the RFDi (mean difference -19.1 N/s/kg). Contrarily, the DG showed a likely small increase in the RFDa (mean difference 31.2 N/s/kg) and a most likely small increase in the RFDi (mean difference 34.8 N/s/kg). The effect of both static and dynamic stretching on jump height was trivial. Practitioners should consider utilizing dynamic stretching exercises instead of static stretching before a competition in female volleyball players. Further research is needed in order to find complementary strategies during the warm-up that could increase jump height.

Delineating apathy profiles in Huntington's disease with the short-Lille Apathy Rating Scale.

INTRODUCTION: Apathy, a prevalent feature in neurological disorders including Huntington's disease (HD), is characterized by a reduction in goal-directed behavior across cognitive, auto-activation (i.e., self-activating thoughts/behavior), and emotional domains. Nonetheless, current diagnostic criteria are incapable of distinguishing multidimensional apathy profiles. Meanwhile, the short-Lille Apathy Rating Scale (LARS-s) bears potential as an operative diagnostic tool to disentangle apathy dimensions in clinical practice. The present study thereby examines the psychometric properties and factor structure of the LARS-s to tap into apathy profiles and their underlying neural correlates in HD. METHODS: Forty HD individuals were scanned and evaluated for apathy using the LARS-s, assessed for reliability and validity in HD, and the short-Problem Behavior Assessment (PBA-s). To study the dimensional structure of apathy, principal component analysis (PCA) of the LARS-s was implemented. Resulting factors were associated with gray matter volume through whole-brain voxel-based morphometry. RESULTS: The LARS-s demonstrated satisfactory psychometric properties, sharing convergent validity with PBA-s apathy and discriminant validity against depression. PCA resulted in three factors representative of apathy profiles across cognitive, auto-activation, and emotional domains. Anatomically, global apathy was significantly related with large-scale motor, cognitive, and limbic networks. Exploratory analyses of apathy profiles revealed correspondence between each factor and distinct cortical and subcortical nodes. CONCLUSION: The LARS-s is capable of capturing the multidimensional spectrum of apathy. At the same time, apathy profiles in HD are underpinned by functionally diverse neural networks. Such findings promote the continued study of apathy domains to pinpoint personalized therapeutic targets in neurologic disorders in addition to HD.

Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias.

Our clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits are known. The patients were evaluated using standardised clinical assessments of ataxia and MDs. First, NBIA genes were analysed by Sanger sequencing and 59 patients achieved a diagnosis, including the detection of the founder mutation PANK2 p.T528M in Romani people. Then, we used a custom panel MovDisord and/or exome sequencing; 29 cases were solved with a great genetic heterogeneity (34 different mutations in 23 genes). Three patients presented brain iron deposits with Fe-sensitive MRI sequences and mutations in FBXO7, GLB1, and KIF1A, suggesting an NBIA-like phenotype. Eleven patients showed very early-onset ataxia and CA with cortical hyperintensities caused by mutations in ITPR1, KIF1A, SPTBN2, PLA2G6, PMPCA, and PRDX3. The novel variants were investigated by structural modelling, luciferase analysis, transcript/minigenes studies, or immunofluorescence assays. Our findings expand the phenotypes and the genetics of MDs and ataxias with early-onset CA and cortical hyperintensities and highlight that the abnormal brain iron accumulation or early cerebellar gliosis may resembling an NBIA phenotype.

Training at moderate altitude improves submaximal but not maximal performance-related parameters in elite rowers.

Maximal oxygen consumption (V̇O2max), physiological thresholds, and hemoglobin mass are strong predictors of endurance performance. High values of V̇O2max, maximal aerobic power (MAP), and power output at anaerobic thresholds are key variables in elite rowers. Endurance athletes often use altitude training as a strategy to improve performance. However, no clear evidence exists that training at natural altitude enhances sea-level performance in elite rowers. This study aimed to evaluate the effect of altitude training on rowing-performance parameters at sea level. The study was conducted on eleven rowers (Six females, five males) from the Chilean National Team during a 3-week moderate altitude training (∼2,900 m. a.s.l.) under the live high-train high (LHTH) model. It included a rowing ergometer maximal incremental test and blood analysis (pre and post-altitude). Gas exchange analysis was performed to measure V̇O2max, ventilatory thresholds (VTs) and rowing economy/efficiency (ECR/GE%). LHTL training improves performance-related variables at sea level (V̇Emax: 3.3% (95% CI, 1.2-5.5); hemoglobin concentration ([Hb]): 4.3% (95% CI, 1.7-6.9); hematocrit (%): 4.5% (95% CI, 0.9-8.2); RBC (red blood cells) count: 5.3% (95% CI, 2.3-8.2); power at VT2: 6.9% (95% CI, 1.7-12.1), V̇EVT2: 6.4% (95% CI, 0.4-12.4); power at VT1: 7.3% (95% CI, 1.3-13.3), V̇EVT1: 8.7% (95% CI, 1.6-15.8)) and economy/efficiency-related variables (ECRVT2: 5.3% (95% CI, -0.6 to -10.0); GE(%): 5.8% (95% CI, 0.8-10.7)). The LHTH training decreased breathing economy at MAP (-2.8% (95% CI, 0.1-5.6)), pVT2 (-9.3% (95% CI, -5.9 to -12.7)), and pVT1 (-9.3% (95% CI, -4.1 to -14.4)). Non-significant changes were found for V̇O2max and MAP. This study describes the effects of a 3-week moderate altitude (LHTH training) on performance and economy/efficiency-related variables in elite rowers, suggesting that it is an excellent option to induce positive adaptations related to endurance performance.

Effects of plyometric training on softer vs. Harder surfaces on jump-related performance in rugby sevens players.

This study aimed to compare jump-related performance after plyometric training on harder vs. softer surfaces in rugby sevens players. Fourteen players were randomly assigned to the harder surface group (H-G, n = 7) and softer surface group (S-G, n = 7). Three times per week, in the morning, the players performed plyometric training on different surfaces and strength training. Before and after the 4-week intervention period, squat jump (SJ), countermovement jump (CMJ), and CMJ with arms (CMJA) tests were performed to measure vertical jump displacement (d), rate of force development (r), and power (p). The main results indicated a significant improvement in S-G for CMJd (∆% = +8.2%; p = 0.029; ES = 0.59) and for CMJAp (∆% = +8.7%; p = 0.035; ES = 0.44). These improvements were significant compared to H-G for CMJAd (F1,12 = 8.50; p = 0.013; η p 2 = 0.41; ES = 0.83) and CMJAp (F1,12 = 7.69; p = 0.017; η p 2 = 0.39; ES = 0.79). This study reveals that performance related to the counter movement jump with arms on softer surfaces after 4-week plyometric training improved vertical jump displacement and lower body power in rugby sevens players.

Concussion vs. resignation by submission: Technical-tactical behavior analysis considering injury in mixed martial arts.

This research study verified the technical-tactical actions during the mixed martial arts (MMA) fights to generate serious enough injury to stop the MMA round, determining technical-tactical potential risk factors for injury in official MMA combats, according to Concussion or Resignation per Submission. A total of 990 rounds with concussions and 627 resignations per submission were considered with severe injury (i.e., a fight ended by a doctor or referee). All injuries were diagnosed and managed by attending ringside physicians during the MMA fights and rounds and had a continuous technical-tactical behavior analysis, p ≤ 0.05. The leading cause of concussion was due to head trauma (~90%), with higher dependence on head strikes scored actions. Comparisons between Concussion and Resignation per Submission combats demonstrated differences between distance head strikes actions [13(6,25) vs. 9(4,18) frequencies], clinch head strikes actions [1(0;4) vs. 1(0;3) frequencies], ground head strikes actions [1(0;8) vs. 2(0;10) frequencies] and takedowns actions [0(0;1) vs. 1(0;2) frequencies]. This information may provide significant evidence regarding the doctor stoppage in concussion combats and when it could be called by officials supervising MMA.