Functional interplay between arginyl-tRNA synthetases and arginyltransferase

Protein arginylation, mediated by arginyltransferase ATE1, is a posttranslational modification of emerging biological importance that consists of transfer of the amino acid Arg to protein and peptide substrates. ATE1 utilizes charged tRNAArg as the donor of the arginyl group, which depends on the activity of Arg-tRNA synthetases (RARS) and is also utilized in translation. The mechanisms that regulate the functional balance between ATE1, RARS and translation are unknown. Here we addressed the functional interplay between these mechanisms using intracellular arginylation sensor in cell lines with overexpression or deletion of ATE1 and RARS isoforms. We find that arginylation levels depend on the physiological state of the cells but are not directly affected by translation activity or availability of RARS isoforms. However, displacement of RARS from the multi-synthetase complex leads to an increase in intracellular arginylation independently of RARS enzymatic activity. This effect is accompanied by ATE1 redistribution into the cytosol. Our results provide the first comprehensive analysis of the interdependence between translation, arginyl-tRNA synthesis, and arginylation.

Neighbourhood cohesion and territorial cohesion: in search for conceptual integrity

Neighbourhood cohesion is a concept describing the residents’ sense of community, engagement in acts of neighbouring, and attractiveness of living in the neighbourhood. Since 2000’s the term ‘cohesion’ has also been used in geography and in spatial policy to represent the distribution of functions and opportunities in space. The two approaches seem be complementary, but they lack consistency and appropriate conceptual framework. This paper aims at developing an integrated methodological framework which will include both social and spatial aspects of cohesion at the local level. Its empirical content refers to studies conducted in 2017–2019 in five locations in Poland. Three methods of spatial analysis are presented depicting various aspects of territorial cohesion of a neighbourhood: functional balance, accessibility of facilities and match between supply and demand. Such approach enables effective measurement and comparison of neighbourhoods representing various settlement types. The results show that the highest levels of cohesion were obtained for large cities where the density of amenities is the highest, and the lowest levels were noted in suburban settlements which confirms their malfunctioning character. The paper concludes with a critical revision of the concept of neighbourhood cohesion which can serve as a guideline for local urban policy.

Effect of Using Wii Balance Board on Functional Balance of Children With Ataxic Cerebral Palsy

Objective: Ataxic cerebral palsy accounts for 5%-10% of the population with cerebral palsy. This palsy is characterized by poor balance and coordination, clumsiness, and involuntary tremor. As a result, balance training is one of the essential parts of the rehabilitation programs for children with ataxic cerebral palsy. Wii Balance Board (WBB) is an efficient tool for balance training in children with different physical problems, including cerebral palsy. This study aims to assess the effect of WBB-based balance training on functional balance and the persistence of its effect two months after the intervention in children with ataxic cerebral palsy. Materials & Methods: This is a single-case study with a pre-test, post-test and follow-up design conducted on 3 children (2 girls and 1 boy) with ataxic cerebral palsy (Mean±SD age=10.56±1.09 years). They were classified at levels I and II of the gross motor function classification system. They received conventional occupational therapy three sessions per week, each for 45 minutes in the baseline and follow-up phases. In the intervention phase, each session consisted of 25 minutes of routine rehabilitation followed by 20 minutes of WBB-based balance training for 3 months (12 hours). The changes were evaluated by the Pediatric Balance Scale (PBS) and Timed Up And Go (TUG) test, three times in the baseline phase, three times in the intervention phase (at the end of 12th, 24th, and 36th sessions), and two times in the follow-up phase (one and two months after the intervention). Assessments were done by a pediatric occupational therapist who was unaware of the study process. Finally, the results were analyzed using the Percentage of Nonoverlapping Data (PND), 2 Standard Deviations (2SD), Hedges’s g, and the visual analysis method. Results: The results of the PBS and TUG test showed the improvement of functional balance in all children in the intervention phase and maintained in the follow-up phase. The PND of PBS and TUG test results was 100% for all children, indicating that balance training by the WBB improved functional balance in the intervention and follow-up phases compared to the baseline. Hedeges’ g value for all participants was more than 0.8, indicating a significant difference between the baseline and follow-up phases. The 2SD results showed a significant increase in the PBS score and a significant reduction in the TUG test duration in all children. Furthermore, the visual analysis revealed a significant improvement in the functional balance of all children in the intervention phase and the stability of these changes in the follow-up phase. Conclusion: Balance training by the WBB is an effective method for improving the functional balance of children with ataxic cerebral palsy. Further studies are needed using a larger sample size to confirm its effectiveness.

Effects of specific inspiratory muscle training combined with whole-body endurance training program on balance in COPD patients: Randomized controlled trial

Purpose This study aims to assess the effect of inspiratory muscle training (IMT) combined with endurance training (ET) on balance in patients with chronic obstructive pulmonary disease (COPD). Methods We studied 32 male patients (62 ± 6 years) with moderate to very severe COPD. They were randomly assigned to an experimental group (IMT+ET) n = 16 or a control group (ET) n = 16 with similar characteristics. The evaluations were carried out at inclusion and after eight weeks of the training period. Functional balance was assessed by the Berg Balance Scale (BBS), the Timed-up and Go (TUG), the Single Leg Stance test (SLS), and the Activities-specific Balance Confidence (ABC) scale. The strength of the inspiratory muscles (PImax) was assessed by maximal inspiratory mouth pressure. Functional exercise performance was assessed by the 6 minutes walking test (6MWT). IMT program consists in performing two daily sets of 30 inspirations with 50% of PImax increased by 10% every two weeks. ET program consists in performing 30 min treadmill exercise at 60% to 80% of the average speed achieved during the 6MWT three days per week. Results After the training period, the experimental group demonstrated greater improvements in BBS (IMT+ET vs. ET; p = 0.019), and in ABC (IMT+ET vs. ET; p = 0.014). However, no significant differences between groups were observed for TUG, SLS, and 6MWT. There was a significant difference between groups in PImax (IMT+ET vs. ET; p = 0.030). Significant moderate correlations were obtained between ΔPImax and ΔBBS for both groups (IMT+ET: r = 0.624, p = 0.010; ET r = 0.550, p = 0.027) as well as for ΔABC but only in the experimental group (IMT+ET: r = 0.550, p = 0.027). Conclusion Compared to ET alone, the results suggest that IMT combined with ET enhances inspiratory muscle function and functional balance according to BBS and ABC in patients with COPD. We suggest that inspiratory muscle training might be introduced as additional training to pulmonary rehabilitation programs aimed at improving balance in COPD patients. Trial registration The trial registry name: Clinical Trials; Registration number: NCT04084405; URL: https://clinicaltrials.gov/ct2/show/NCT04084405.

Efficacy of foot-ankle orthosis on balance for children with hemiplegic cerebral palsy: An observational study

Objectives: The aim of this study was to investigate the impact of ankle-foot orthoses (AFOs) on the balance and gait and to compare the effects of hinged AFOs with solid AFOs on balance in patients with cerebral palsy (CP). Patients and methods: Between January 2015 and January 2016, 19 hemiplegic children with CP (11 males, 8 females; mean age: 9.5±2.2 years; range, 6 to 15 years) and 23 sex- and age-matched controls (8 males, 15 females; mean age: 10±1.6 years; range, 6 to 13 years) were included in this study. All patients were using either solid or hinged AFO. Hemiplegic patients were attended to specific tests with orthoses and barefoot. Pediatric Balance Scale (PBS) and Five Times Sit to Stand Test (FTSST) were used for functional evaluation. The quantitative balance was evaluated using the device-assisted balance tests, Limits of Stability (LOS), Walk Across (WA), and Sit to Stand (STS) tests. Results: The control group had a better functional balance than the CP group (p<0.001 for PBS and p<0.001 for FTSST) and the CP group with AFO had a better balance than the barefoot (p=0.001 for PBS and p=0.009 for FTSST). Children with CP also showed a higher sway velocity in STS (p<0.001) than the control group. In patients with AFO, a decrease in the sway velocity in STS (p=0.037) and an increase in directional control in LOS (p=0.044) were observed, compared to barefoot. Conclusion: The AFO use offers a significant contribution to the functional balance in CP. Prescribing AFOs are usually required in ambulatory CP patients in combined with a well-designed standard physiotherapy.

Reducing the Cognitive Footprint of Brain Tumor Surgery

The surgical management of brain tumors is based on the principle that the extent of resection improves patient outcomes. Traditionally, neurosurgeons have considered that lesions in “non-eloquent” cerebrum can be more aggressively surgically managed compared to lesions in “eloquent” regions with more known functional relevance. Furthermore, advancements in multimodal imaging technologies have improved our ability to extend the rate of resection while minimizing the risk of inducing new neurologic deficits, together referred to as the “onco-functional balance.” However, despite the common utilization of invasive techniques such as cortical mapping to identify eloquent tissue responsible for language and motor functions, glioma patients continue to present post-operatively with poor cognitive morbidity in higher-order functions. Such observations are likely related to the difficulty in interpreting the highly-dimensional information these technologies present to us regarding cognition in addition to our classically poor understanding of the functional and structural neuroanatomy underlying complex higher-order cognitive functions. Furthermore, reduction of the brain into isolated cortical regions without consideration of the complex, interacting brain networks which these regions function within to subserve higher-order cognition inherently prevents our successful navigation of true eloquent and non-eloquent cerebrum. Fortunately, recent large-scale movements in the neuroscience community, such as the Human Connectome Project (HCP), have provided updated neural data detailing the many intricate macroscopic connections between cortical regions which integrate and process the information underlying complex human behavior within a brain “connectome.” Connectomic data can provide us better maps on how to understand convoluted cortical and subcortical relationships between tumor and human cerebrum such that neurosurgeons can begin to make more informed decisions during surgery to maximize the onco-functional balance. However, connectome-based neurosurgery and related applications for neurorehabilitation are relatively nascent and require further work moving forward to optimize our ability to add highly valuable connectomic data to our surgical armamentarium. In this manuscript, we review four concepts with detailed examples which will help us better understand post-operative cognitive outcomes and provide a guide for how to utilize connectomics to reduce cognitive morbidity following cerebral surgery.