Effects of Transcranial Direct Current Stimulation on Clinical Features of Dizziness and Cortical Activation in a Patient with Vestibular Migraine.

BACKGROUND: Vestibular migraine (VM) is common migraine that occurs in patients with dizziness. Vestibular rehabilitation for managing VM generally remains unclear. Recently, it has been reported that transcranial direct current stimulation (tDCS) has positive effects in alleviating dizziness. This study investigated the effects of tDCS on dizziness and cortical activation in a patient with VM. METHODS: We recruited a male patient aged 31 years with no dizziness. The patient watched a video to induce dizziness using a virtual reality device. The study applied the intervention using tDCS for 4 weeks and measured 4 assessments: functional near-infrared spectroscopy (fNIRS), quantitative electroencephalography (qEEG), dizziness handicap inventory, and visual vertigo analog scale. RESULTS: We showed the activation in the middle temporal gyrus and inferior temporal gyrus (ITG) of the left hemisphere and in the superior temporal gyrus and ITG of the right hemisphere in the pre-intervention. After the intervention, the activation of these areas decreased. In the results of qEEG, excessive activation of C3, P3, and T5 in the left hemisphere and C4 in the right hemisphere before intervention disappeared after the intervention. CONCLUSIONS: This study indicated that tDCS-based intervention could be considered a viable approach to treating patients with vestibular dysfunction and dizziness caused by VM.

p300 nucleocytoplasmic shuttling underlies mTORC1 hyperactivation in Hutchinson-Gilford progeria syndrome.

The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth, metabolism and autophagy. Multiple pathways modulate mTORC1 in response to nutrients. Here we describe that nucleus-cytoplasmic shuttling of p300/EP300 regulates mTORC1 activity in response to amino acid or glucose levels. Depletion of these nutrients causes cytoplasm-to-nucleus relocalization of p300 that decreases acetylation of the mTORC1 component raptor, thereby reducing mTORC1 activity and activating autophagy. This is mediated by AMP-activated protein kinase-dependent phosphorylation of p300 at serine 89. Nutrient addition to starved cells results in protein phosphatase 2A-dependent dephosphorylation of nuclear p300, enabling its CRM1-dependent export to the cytoplasm to mediate mTORC1 reactivation. p300 shuttling regulates mTORC1 in most cell types and occurs in response to altered nutrients in diverse mouse tissues. Interestingly, p300 cytoplasm-nucleus shuttling is altered in cells from patients with Hutchinson-Gilford progeria syndrome. p300 mislocalization by the disease-causing protein, progerin, activates mTORC1 and inhibits autophagy, phenotypes that are normalized by modulating p300 shuttling. These results reveal how nutrients regulate mTORC1, a cytoplasmic complex, by shuttling its positive regulator p300 in and out of the nucleus, and how this pathway is misregulated in Hutchinson-Gilford progeria syndrome, causing mTORC1 hyperactivation and defective autophagy.

Impacts of Daily Life and Job Satisfaction on Social Participation of Persons with Visual Impairment.

Objective: This study is aimed at providing baseline data for improving the social participation of persons with visual impairment by verifying the impacts of daily life satisfaction and job satisfaction on their social participation. Methods: This study utilized data from the 5th survey of the 2nd wave of the Panel Survey of Employment for the Disabled (PSED) provided by the Korea Employment Agency for Persons with Disabilities (KEAD). Of the 511 persons with visual impairment who participated in the panel survey, 151 people who met the inclusion criteria were selected as the research subjects. This study compared social participation, job satisfaction, and daily life satisfaction, which were validated by experts' review, consulting, and research at the KEAD. Results: Daily life satisfaction and job satisfaction of persons with visual impairment had positive correlations with social participation. Job satisfaction had a statistically significant impact on social participation. Additionally, the stability of employment and monthly income were the variables affecting social participation. Conclusion: The result drawn in this study can be applied as basic data related to the social participation of people with visual impairment.

Physiotherapy strategies for functional improvement in a child with complicated hereditary spastic paraplegia: 1-year follow-up of a case report using a changing criterion design.

BACKGROUND: and Purpose: Hereditary spastic paraplegias (HSP) are a group of clinically diverse genetic disorders that share the neurologic symptom of difficulty in walking due to progressive serious muscle weakness and spasticity in the legs. This study describes a physiotherapy program for improving the functional ability of a child diagnosed with complicated HSP and reports the treatment results. METHODS: A 10-year-old boy with complicated HSP received a physiotherapy intervention that included strengthening of the leg muscles and treadmill training for 1 h per session, three to four times a week for 6 weeks. Outcome measures included sit-to-stand, 10-m walk, 1-min walk tests, and gross motor function measures (dimensions D and E). RESULTS: After the intervention, the sit-to-stand, 1-min walk, and 10-m walk test scores improved by 6.75 times, 2.57 m, and 0.05 m/s, respectively. Furthermore, the gross motor function measure dimensions D and E scores improved by 8% (46%-54%) and 5% (22%-27%), respectively. The gains in each parameter were maintained at the 3- and 6-month and 1-year follow-ups. CONCLUSION: These results suggest that structured physiotherapy programs can benefit the functional rehabilitation of children with complicated HSP.

Motor Imagery Combined With Physical Training Improves Response Inhibition in the Stop Signal Task.

Background: Motor imagery training has a similar effect to that of physical training on motor performance. The objective of this study was to investigate the short-term effectiveness of motor imagery training on response inhibition using the stop signal task (SST). Methods: Participants were divided into a physical training group (PT, n = 17), a motor imagery training group (MIT, n = 17), and a motor imagery combined with physical training group (MIPT, n = 17). All participants performed 10 SST training sessions over 5 days. Both stop signal reaction time (SSRT) and non-signal reaction time (NSRT) were measured before and after SST training. Results: There were significant interaction (time × group) and time effects, although the group effect was not statistically significant. Bonferroni post hoc analysis showed that MIPT group revealed a significantly greater change in SSRT than PT and MIT groups, while there was no significant difference between PT and MIT groups. SSRT significantly decreased after training in all groups. In NSRT, there was a significant effect of time, but there was no significant interaction effect (time × group) or group effect. Conclusion: Response inhibition could be enhanced via training, and it was most effective when motor imagery and physical training were combined. We demonstrate that motor imagery training significantly improves response inhibition and should be accompanied by physical training when performing SST.

The different autophagy degradation pathways and neurodegeneration.

The term autophagy encompasses different pathways that route cytoplasmic material to lysosomes for degradation and includes macroautophagy, chaperone-mediated autophagy, and microautophagy. Since these pathways are crucial for degradation of aggregate-prone proteins and dysfunctional organelles such as mitochondria, they help to maintain cellular homeostasis. As post-mitotic neurons cannot dilute unwanted protein and organelle accumulation by cell division, the nervous system is particularly dependent on autophagic pathways. This dependence may be a vulnerability as people age and these processes become less effective in the brain. Here, we will review how the different autophagic pathways may protect against neurodegeneration, giving examples of both polygenic and monogenic diseases. We have considered how autophagy may have roles in normal CNS functions and the relationships between these degradative pathways and different types of programmed cell death. Finally, we will provide an overview of recently described strategies for upregulating autophagic pathways for therapeutic purposes.

Vinexin contributes to autophagic decline in brain ageing across species.

Autophagic decline is considered a hallmark of ageing. The activity of this intracytoplasmic degradation pathway decreases with age in many tissues and autophagy induction ameliorates ageing in many organisms, including mice. Autophagy is a critical protective pathway in neurons and ageing is the primary risk factor for common neurodegenerative diseases. Here, we describe that autophagosome biogenesis declines with age in mouse brains and that this correlates with increased expression of the SORBS3 gene (encoding vinexin) in older mouse and human brain tissue. We characterise vinexin as a negative regulator of autophagy. SORBS3 knockdown increases F-actin structures, which compete with YAP/TAZ for binding to their negative regulators, angiomotins, in the cytosol. This promotes YAP/TAZ translocation into the nucleus, thereby increasing YAP/TAZ transcriptional activity and autophagy. Our data therefore suggest brain autophagy decreases with age in mammals and that this is likely, in part, mediated by increasing levels of vinexin.

Correlational study between online friendship network and internet game disorder among university students.

PURPOSE: The purpose of this study was to provide basic information about the analysis of the correlation between online friendship network and internet game disorder among university students. METHODS: Study subjects were 77 university students. For analysis of online friendship among them, social network analysis was performed and the analysis of degree, closeness, and betweenness centrality was measured. Assessment of internet game disorder was done using the Korean version of Internet Gaming Disorder Scale. RESULTS: As per the results, the positive correlation showed between in-closeness centrality and internet gaming disorder (IGD) and the negative correlation showed between out-closeness centrality and internet gaming disorder. CONCLUSIONS: Online friendship is considered to contribute to the changes of internet game disorder level. Thus, in the relationship between online friendship and internet game disorder, closeness centrality should be considered, and causal relation analysis should be performed in further studies.

A Backward Walking Training Program to Improve Balance and Mobility in Children with Cerebral Palsy.

BACKGROUND: We studied the effects of motor tasks using backward walking training on balance and gait functions of children with cerebral palsy. This was a single-blinded, randomized controlled trial with a crossover design conducted at a single facility. METHODS: Among 12 children with cerebral palsy, the forward (FWG) (n = 6) and backward walking groups (BWG) (n = 6) underwent training three times a week for 4 weeks, 40 min a day. After a 6-week break, the crossover training was conducted. Functional walking variables were measured. Time-Up-and-Go (TUG) test, Figure-8 Walk Test (FW8T), and Pediatric Balance Scale (PBS) were used for measuring balance. RESULTS: Both groups showed significant improvement in walking speed, stride length, and step length. The BWG demonstrated significant improvement in walking speed (p < 0.05) compared with the FWG. The TUG test, FW8T, and PBS showed significant improvement. After the 4-week intervention, both groups displayed a remarkable decrease in TUG duration and FW8T. Both groups also exhibited improvement in the PBS; more so in the BWG. CONCLUSIONS: Backward walking training with motor dual tasks could be a more effective interventional approach than forward walking training to improve balance and walking functions of children with spastic hemiplegia.

Ultrasound Measurement of the Transverse Abdominis, Internal Oblique, and External Oblique Muscles Associated with Forward Head Posture and Reduced Cranio-Vertebral Angle.

BACKGROUND Abnormal posture can affect the alignment of the cervical spine, which can lead to various physical problems. There are many ways to solve the problem by limiting the area around the neck to restore abnormal neck condition. However, there is a need to look at these problems from an enlarged perspective through the relationship between the cervical spine and trunk. This study aimed to investigate the significance of the thickness of the transverse abdominis, internal oblique, and external oblique muscles in patients with forward head posture and reduced cranio-vertebral angle. MATERIAL AND METHODS We included 24 healthy adult males in their 20s without lower back pain. The cranio-vertebral angle (CVA) in all the subjects was measured with the help of pictures taken in the sagittal plane using a digital camera. The thickness of muscles, including transverse abdominis (TrA), internal oblique (IO), and external oblique (EO), was measured using a diagnostic ultrasound device. Pearson's correlation analysis was used to identify the correlation between the variables measured. RESULTS CVA showed a statistically significant correlation with TrA thickness (r=0.506/p=0.012), and among the abdominal muscles, there was a significant correlation between IO and EO thickness (r=0.663/p=0.000). CONCLUSIONS A reduced CVA due to FHP was significantly associated with reduced TrA thickness. Therefore, increasing the bulk of the abdominal muscles with restoration of the abnormal CVA is a potential treatment approach and requires further study.

Glucose starvation induces autophagy via ULK1-mediated activation of PIKfyve in an AMPK-dependent manner.

Autophagy is an essential catabolic process induced to provide cellular energy sources in response to nutrient limitation through the activation of kinases, like AMP-activated protein kinase (AMPK) and ULK1. Although glucose starvation induces autophagy, the exact mechanism underlying this signaling has yet to be elucidated. Here, we reveal a role for ULK1 in non-canonical autophagy signaling using diverse cell lines. ULK1 activated by AMPK during glucose starvation phosphorylates the lipid kinase PIKfyve on S1548, thereby increasing its activity and the synthesis of the phospholipid PI(5)P without changing the levels of PI(3,5)P2. ULK1-mediated activation of PIKfyve enhances the formation of PI(5)P-containing autophagosomes upon glucose starvation, resulting in an increase in autophagy flux. Phospho-mimic PIKfyve S1548D drives autophagy upregulation and lowers autophagy substrate levels. Our study has identified how ULK1 upregulates autophagy upon glucose starvation and induces the formation of PI(5)P-containing autophagosomes by activating PIKfyve.

Lysosome positioning and mTOR activity in Lowe syndrome.

Lowe syndrome is a rare, developmental disorder caused by mutations in the phosphatase, OCRL. A study in this issue of EMBO Reports shows that OCRL is required for microtubule nucleation and that mutations in this protein lead to an inability to activate mTORC1 signaling and consequent cell proliferation in the presence of nutrients. These defects are the result of impaired microtubule-dependent lysosomal trafficking to the cell periphery and are independent of OCRL phosphatase activity.

Social interaction changes in people with intellectual disabilities through the application of equine-assisted intervention in Korea.

This study aims to provide basic information about the social interaction changes in people with intellectual disabilities through the application of equine-assisted intervention (EAI) in Korea. The subjects were 12 people with intellectual disabilities residing in a residential care facility in Korea. EAI was applied and consisted of communal activities and horseback riding. The intervention was conducted for 60 minutes each session, two sessions a week for 12 weeks. To determine the psychological aspects of the social interaction changes after the study cohort participated in the EAI, their social interaction anxiety, social phobia, and social avoidance and distress were measured. Their social interaction anxiety was measured using the Korean-Social Interaction Anxiety Scale (K-SIAS), and their social phobia was measured using the Korean-Social Phobia Scale (K-SPS). To measure their social avoidance and distress, the Korean-Social Avoidance and Distress scale (K-SADS) was used. The social interaction anxiety, social phobia, and social avoidance and distress results showed a continuous decrease after the application of EAI. Thus, the application of EAI, including communal activities and horseback riding, should be considered for people with intellectual disabilities in order to decrease their social interaction anxieties, phobias, and social avoidance and distress.

Pelvic Belt Wearing during Exercise Improves Balance of Patients with Stroke: A Randomized, Controlled, Preliminary Trial.

OBJECTIVES: To investigate whether wearing a pelvic belt during a trunk stability exercise program positively affects balance in patients with stroke. MATERIALS AND METHODS: Twenty-four patients with stroke were randomly allocated to the experimental or control group and performed a 60-min general physical therapy and an additional 30-min trunk stability exercise (five times/week for 6 weeks). Those in the experimental and control groups performed the trunk stability exercises with and without wearing the pelvic belt, respectively. RESULTS: The experimental group showed a significantly greater magnitude of improvements in balance than the control group (Postural Assessment Scale for Stroke: +18.3%, F (1, 22)=14.350, p=.001, η2=.395; Berg Balance Scale: +11%, F (1, 22)=19.062, p=.000, η2=.464; Timed Up and Go Test: -10.5%, F (1, 22)=8.562, p=.008, η2=.280; center of pressure path length with eyes open: -15.1%, F (1, 22)=6.770, p=.016, η2=.235; center of pressure path length with eyes closed: -19.5%, F (1, 22)=9.256, p=.006, η2=.296; center of pressure path velocity with eyes open: -22.6%, F (1, 22)=37.747, p=.000, η2=.632; center of pressure path velocity with eyes closed: -13.9%, F (1, 22)=6.511, p=.018, η2=.228, respectively). CONCLUSIONS: Wearing a pelvic belt while performing trunk stability exercise programs could be a more effective approach for improving balance in patients with stroke.

Effect of posture control training using virtual reality program on sitting balance and trunk stability in children with cerebral palsy.

OBJECTIVE: We aimed to determine whether the posture control training in the sitting posture using virtual reality (VR) training program affects sitting balance and trunk stability in children with spastic cerebral palsy (CP). METHODS: The experiment was conducted for 4 weeks by randomly allocating 20 children with CP. The experimental group (n = 10) performed balance training in the sitting position using a VR training program, and the control group (n = 10) performed arm reach training in the sitting position. To evaluate static and dynamic sitting balance and trunk stability, the Wii Balance Board and Balancia software, the modified functional reach test, and the Korean version of the Trunk Control Measurement Scale were used. RESULTS: There were significant differences between the two groups in the changes in speed and postural swing distance before and after training (p < 0.05). The mFRT measurement showed significant differences in all directions before and after training between the two groups (p < 0.05). However, there was no significant difference between the two groups in the K-TCMS score. CONCLUSIONS: Posture control training in the sitting position using a VR training program was found to be more effective in improving the sitting balance and trunk stability of children with CP.

α-Catenin levels determine direction of YAP/TAZ response to autophagy perturbation.

The factors regulating cellular identity are critical for understanding the transition from health to disease and responses to therapies. Recent literature suggests that autophagy compromise may cause opposite effects in different contexts by either activating or inhibiting YAP/TAZ co-transcriptional regulators of the Hippo pathway via unrelated mechanisms. Here, we confirm that autophagy perturbation in different cell types can cause opposite responses in growth-promoting oncogenic YAP/TAZ transcriptional signalling. These apparently contradictory responses can be resolved by a feedback loop where autophagy negatively regulates the levels of α-catenins, LC3-interacting proteins that inhibit YAP/TAZ, which, in turn, positively regulate autophagy. High basal levels of α-catenins enable autophagy induction to positively regulate YAP/TAZ, while low α-catenins cause YAP/TAZ activation upon autophagy inhibition. These data reveal how feedback loops enable post-transcriptional determination of cell identity and how levels of a single intermediary protein can dictate the direction of response to external or internal perturbations.

Autophagy regulation by acetylation-implications for neurodegenerative diseases.

Posttranslational modifications of proteins, such as acetylation, are essential for the regulation of diverse physiological processes, including metabolism, development and aging. Autophagy is an evolutionarily conserved catabolic process that involves the highly regulated sequestration of intracytoplasmic contents in double-membrane vesicles called autophagosomes, which are subsequently degraded after fusing with lysosomes. The roles and mechanisms of acetylation in autophagy control have emerged only in the last few years. In this review, we describe key molecular mechanisms by which previously identified acetyltransferases and deacetylases regulate autophagy. We highlight how p300 acetyltransferase controls mTORC1 activity to regulate autophagy under starvation and refeeding conditions in many cell types. Finally, we discuss how altered acetylation may impact various neurodegenerative diseases in which many of the causative proteins are autophagy substrates. These studies highlight some of the complexities that may need to be considered by anyone aiming to perturb acetylation under these conditions.

mTORC2 Assembly Is Regulated by USP9X-Mediated Deubiquitination of RICTOR.

The mechanistic target of rapamycin complex 2 (mTORC2) controls cell metabolism and survival in response to environmental inputs. Dysregulation of mTORC2 signaling has been linked to diverse human diseases, including cancer and metabolic disorders, highlighting the importance of a tightly controlled mTORC2. While mTORC2 assembly is a critical determinant of its activity, the factors regulating this event are not well understood, and it is unclear whether this process is regulated by growth factors. Here, we present data, from human cell lines and mice, describing a mechanism by which growth factors regulate ubiquitin-specific protease 9X (USP9X) deubiquitinase to stimulate mTORC2 assembly and activity. USP9X removes Lys63-linked ubiquitin from RICTOR to promote its interaction with mTOR, thereby facilitating mTORC2 signaling. As mTORC2 is central for cellular homeostasis, understanding the mechanisms regulating mTORC2 activation toward its downstream targets is vital for our understanding of physiological processes and for developing new therapeutic strategies in pathology.

Effects of white noise in walking on walking time, state anxiety, and fear of falling among the elderly with mild dementia.

OBJECTIVE: This study aimed to analyze the effects of white noise in walking on the walking time, state anxiety, and fear of falling of the elderly with mild dementia. METHODS: Subjects were 32 elderlies with mild dementia, and they divided into experimental group and control group, respectively. In the experimental group, walking program with white noise was applied 3 times a week for 4 weeks. White noise was provided by white noise generator in walking program. In the control group, walking program only was applied. To measure the effect of white noise in walking among the subjects, the walking time, state anxiety, and fear of falling were measured. Walking time was measured by Timed Up and Go test. State anxiety related in walking was measured by Korean version of State-Trait Anxiety Inventory. Fear of falling was used by Korean Falls Efficacy Scale. RESULTS: The results of walking time showed the increase in both groups, but the statistically significant difference was not shown. However, the results of state anxiety and fear of falling showed decrease and the statistically significant difference was shown (p < .01). In comparative analysis, the statistically significant difference in the results of gate velocity between groups was not shown. However, in the results of state anxiety and fear of falling the statistically significant difference between groups was shown (p < .01). CONCLUSIONS: White noise in walking should be induced positively to decrease the state anxiety and fear of falling in walking among elderly with mild dementia. Thus, in their environment, to decrease of state anxiety and fear of falling occurring in walking, the application of white noise in walking situation should be considered to apply for them.

Erratum: Author Correction: Mendelian neurodegenerative disease genes involved in autophagy.

[This corrects the article DOI: 10.1038/s41421-020-0158-y.].