Structure of the type VI secretion system contractile sheath.

Bacteria use rapid contraction of a long sheath of the type VI secretion system (T6SS) to deliver effectors into a target cell. Here, we present an atomic-resolution structure of a native contracted Vibrio cholerae sheath determined by cryo-electron microscopy. The sheath subunits, composed of tightly interacting proteins VipA and VipB, assemble into a six-start helix. The helix is stabilized by a core domain assembled from four ß strands donated by one VipA and two VipB molecules. The fold of inner and middle layers is conserved between T6SS and phage sheaths. However, the structure of the outer layer is distinct and suggests a mechanism of interaction of the bacterial sheath with an accessory ATPase, ClpV, that facilitates multiple rounds of effector delivery. Our results provide a mechanistic insight into assembly of contractile nanomachines that bacteria and phages use to translocate macromolecules across membranes.

Structure of Hsp90-p23-GR reveals the Hsp90 client-remodelling mechanism.

Hsp90 is a conserved and essential molecular chaperone responsible for the folding and activation of hundreds of 'client' proteins1-3. The glucocorticoid receptor (GR) is a model client that constantly depends on Hsp90 for activity4-9. GR ligand binding was previously shown to nr inhibited by Hsp70 and restored by Hsp90, aided by the co-chaperone p2310. However, a molecular understanding of the chaperone-mediated remodelling that occurs between the inactive Hsp70-Hsp90 'client-loading complex' and an activated Hsp90-p23 'client-maturation complex' is lacking for any client, including GR. Here we present a cryo-electron microscopy (cryo-EM) structure of the human GR-maturation complex (GR-Hsp90-p23), revealing that the GR ligand-binding domain is restored to a folded, ligand-bound conformation, while being simultaneously threaded through the Hsp90 lumen. In addition, p23 directly stabilizes native GR using a C-terminal helix, resulting in enhanced ligand binding. This structure of a client bound to Hsp90 in a native conformation contrasts sharply with the unfolded kinase-Hsp90 structure11. Thus, aided by direct co-chaperone-client interactions, Hsp90 can directly dictate client-specific folding outcomes. Together with the GR-loading complex structure12, we present the molecular mechanism of chaperone-mediated GR remodelling, establishing the first, to our knowledge, complete chaperone cycle for any Hsp90 client.

Structure of Hsp90-Hsp70-Hop-GR reveals the Hsp90 client-loading mechanism.

Maintaining a healthy proteome is fundamental for the survival of all organisms1. Integral to this are Hsp90 and Hsp70, molecular chaperones that together facilitate the folding, remodelling and maturation of the many 'client proteins' of Hsp902. The glucocorticoid receptor (GR) is a model client protein that is strictly dependent on Hsp90 and Hsp70 for activity3-7. Chaperoning GR involves a cycle of inactivation by Hsp70; formation of an inactive GR-Hsp90-Hsp70-Hop 'loading' complex; conversion to an active GR-Hsp90-p23 'maturation' complex; and subsequent GR release8. However, to our knowledge, a molecular understanding of this intricate chaperone cycle is lacking for any client protein. Here we report the cryo-electron microscopy structure of the GR-loading complex, in which Hsp70 loads GR onto Hsp90, uncovering the molecular basis of direct coordination by Hsp90 and Hsp70. The structure reveals two Hsp70 proteins, one of which delivers GR and the other scaffolds the Hop cochaperone. Hop interacts with all components of the complex, including GR, and poises Hsp90 for subsequent ATP hydrolysis. GR is partially unfolded and recognized through an extended binding pocket composed of Hsp90, Hsp70 and Hop, revealing the mechanism of GR loading and inactivation. Together with the GR-maturation complex structure9, we present a complete molecular mechanism of chaperone-dependent client remodelling, and establish general principles of client recognition, inhibition, transfer and activation.

Structural basis of mitochondrial receptor binding and constriction by DRP1.

Mitochondrial inheritance, genome maintenance and metabolic adaptation depend on organelle fission by dynamin-related protein 1 (DRP1) and its mitochondrial receptors. DRP1 receptors include the paralogues mitochondrial dynamics proteins of 49 and 51 kDa (MID49 and MID51) and mitochondrial fission factor (MFF); however, the mechanisms by which these proteins recruit and regulate DRP1 are unknown. Here we present a cryo-electron microscopy structure of full-length human DRP1 co-assembled with MID49 and an analysis of structure- and disease-based mutations. We report that GTP induces a marked elongation and rotation of the GTPase domain, bundle-signalling element and connecting hinge loops of DRP1. In this conformation, a network of multivalent interactions promotes the polymerization of a linear DRP1 filament with MID49 or MID51. After co-assembly, GTP hydrolysis and exchange lead to MID receptor dissociation, filament shortening and curling of DRP1 oligomers into constricted and closed rings. Together, these views of full-length, receptor- and nucleotide-bound conformations reveal how DRP1 performs mechanical work through nucleotide-driven allostery.

Improving Executive Function and Dual-Task Cost in Parkinson Disease: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Dual-task walking is challenging for people with Parkinson disease (PD). Gait performance worsens while executing dual tasks, possibly due to a decline in executive function (EF). This study aimed to investigate the effects of dual-task training on EF and dual-task cost (DTC) in people with PD and to explore whether training-induced changes in EF were associated with changes in DTC. METHODS: This study was a randomized controlled trial. A total of 28 people with PD participated. Participants were randomly assigned to the experimental group (dual-task training) and the control group (treadmill training). Both groups received a total of 16 training sessions during the 8 weeks. Assessments were conducted at baseline and postintervention. Primary outcomes included EF and dual-task cost. RESULTS: Significant time-by-group interactions were found in executive function and DTC. The experimental group showed significant improvement in frontal assessment battery (FAB), trail-making test (TMT) part A, Stroop color and word test (SCWT), and DTC on speed in cognitive dual-task walking. There was a moderate to high correlation between the change values of the FAB, TMT part A, SCWT, and the change values of DTC in cognitive dual-task walking. DISCUSSION AND CONCLUSIONS: Compared to treadmill training, dual-task training resulted in greater improvements in EF and DTC. Training-induced changes in EF were linked to changes in DTC when walking while performing a cognitive task but not when walking while performing a motor task. VIDEO ABSTRACT: For more insights from the authors Supplemental Digital Content available at http://links.lww.com/JNPT/A485.

High prevalence of diabetes in a regional Australian hospital highlights the need to prioritise inpatient diabetes care.

Regional centres have smaller workforces in acute diabetes care compared to their metropolitan counterparts. A cross-sectional audit performed at Albury Hospital identified a high prevalence (34%) of diabetes for inpatients compared with metropolitan centres. The high prevalence highlights the need for all healthcare services to consider appropriate resources for the management of diabetes in people admitted to hospital.

Outcomes of Head and Neck Microvascular Free Tissue Transfer for Advanced Cutaneous Squamous Cell Carcinoma: A Comparison of Solid Organ Transplant Recipients to Nontransplant Patients.

BACKGROUND: Patients with solid organ transplant (SOT) are at increased risk of developing aggressive cutaneous malignancies due to their immunosuppression, particularly cutaneous squamous cell carcinoma (cSCC). PURPOSE: There is limited data regarding SOT patients with locally advanced cSCC requiring radical surgery and microvascular free tissue transfer (MVFTT). Our objectives were to characterize outcomes in SOT patients and compare them with a non-SOT cohort. STUDY DESIGN: This is a retrospective cohort study of patients undergoing MVFTT for advanced cSCC of the head and neck between January 2016 and May 2020 at a tertiary referral center. Patients who underwent MVFTT as part of curative intent surgery for advanced cSCC during the study were considered for inclusion. Exclusion criteria included distant metastasis, palliative intent treatment, age less than 18 years, and lip primaries. PREDICTOR: The predictor variable was SOT status. A cohort of non-SOT patients was matched to the SOT cohort based on age, smoking status, tumor stage, and defect size. MAIN OUTCOME VARIABLES: The primary reconstructive outcome was the major surgical complications and secondary outcome measures included major medical complications and minor surgical complications. The primary oncologic outcome was overall survival and the secondary outcome was disease-specific survival. The primary predictor was transplant status. COVARIATES: Covariates included patient comorbidities, prior treatment, tumor stage, type of reconstruction, pathologic findings, and adjuvant therapy. ANALYSIS: Continuous and categorical variables were compared using Student's T test and Fisher's exact test. Survival was calculated using the Kaplan-Meier method and differences in survival between groups were calculated using the log-rank test. Statistical significance was set a priori at P ≤ .05. RESULTS: Fourteen SOT and 14 matched non-SOT patients met inclusion criteria. There was not a statistically significant difference in the rate of major surgical complications (7 vs 7%, P = .74) between the SOT and non-SOT cohorts. Rates of minor (21 vs 43%, P = .26) wound complications and medical complications (0 vs 14%, P = .24) were also similar between the SOT and non-SOT cohorts. Locoregional recurrences and distant metastasis were more common for SOT patients, though this was not statistically significant. Overall survival was significantly worse for SOT patients (21.7 vs 31.0 months, P = .04), though there was not a significant difference in disease-free survival (9.8 vs 31.0 months, P = .17). CONCLUSIONS AND RELEVANCE: MVFTT in the management of SOT patients with locally advanced head and neck cSCC demonstrates similar complication rates with non-SOT patients. While survival and oncologic outcomes are worse in the SOT cohort, aggressive surgical intervention with MVFTT can be performed with comparable complication rates to patients without a history of SOT.

Unexpected nascent atmospheric emissions of three ozone-depleting hydrochlorofluorocarbons.

Global and regional atmospheric measurements and modeling can play key roles in discovering and quantifying unexpected nascent emissions of environmentally important substances. We focus here on three hydrochlorofluorocarbons (HCFCs) that are restricted by the Montreal Protocol because of their roles in stratospheric ozone depletion. Based on measurements of archived air samples and on in situ measurements at stations of the Advanced Global Atmospheric Gases Experiment (AGAGE) network, we report global abundances, trends, and regional enhancements for HCFC-132b ([Formula: see text]), which is newly discovered in the atmosphere, and updated results for HCFC-133a ([Formula: see text]) and HCFC-31 ([Formula: see text]ClF). No purposeful end-use is known for any of these compounds. We find that HCFC-132b appeared in the atmosphere 20 y ago and that its global emissions increased to 1.1 Gg⋅y-1 by 2019. Regional top-down emission estimates for East Asia, based on high-frequency measurements for 2016-2019, account for ∼95% of the global HCFC-132b emissions and for ∼80% of the global HCFC-133a emissions of 2.3 Gg⋅y-1 during this period. Global emissions of HCFC-31 for the same period are 0.71 Gg⋅y-1 Small European emissions of HCFC-132b and HCFC-133a, found in southeastern France, ceased in early 2017 when a fluorocarbon production facility in that area closed. Although unreported emissive end-uses cannot be ruled out, all three compounds are most likely emitted as intermediate by-products in chemical production pathways. Identification of harmful emissions to the atmosphere at an early stage can guide the effective development of global and regional environmental policy.

Table Correction: Effectiveness of eHealth Smoking Cessation Interventions: Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.2196/45111.].

Effects of Dual Task Training on Dual Task Gait Performance and Cognitive Function in Individuals With Parkinson Disease: A Meta-analysis and Meta-regression.

OBJECTIVE: To explore the effects of dual task (DT) training on DT gait performance and cognitive function in individuals with Parkinson disease (PD) and to examine factors that might influence the effects of DT training. DATA SOURCES: PubMed, Wiley Online Library, Cochrane Library, CINAHL, and Medline were searched for articles published from January 2006 to December 2021. STUDY SELECTION: Randomized controlled trials comparing DT training with usual care or general exercise were included. DATA EXTRACTION: The outcomes studied were DT gait parameters including speed, step and stride length, cadence, step and stride time variability, dual-task cost on gait speed, and Trail Making Tests presented as standardized mean differences (SMDs). The Grading of Recommendations, Assessment, Development, and Evaluation was used to evaluate the quality of evidence. DATA SYNTHESIS: Ten randomized controlled trials with 466 participants were included in the meta-analysis. The included studies presented, in general, with a low to high risk of bias. Meta-analyses used a random-effects model for all analyses. The meta-analysis showed the DT training effects on DT gait speed (SMD=0.825, P=.012), DT step and stride length (SMD=0.400, P=.015), Trail Making Tests-part A (TMT-A; SMD=0.533, P=.010), and Trail Making Tests-part B (SMD=0.516, P=.012) compared with the control group. Only the effect on TMT-A was maintained at the follow-up assessment. The results of meta-regression showed that participants with slower initial single task gait speed improved more after DT training on DT step and stride length. CONCLUSIONS: The DT training improved more in DT gait speed with moderate-quality evidence as compared with usual care or conventional physical training in individuals with PD. The beneficial effects of DT training on DT step and stride length, attention, and executive function were also demonstrated in this meta-analysis. Furthermore, the improvement in the DT walking step and stride length was related to the participant's initial single task gait speed.

Effectiveness of eHealth Smoking Cessation Interventions: Systematic Review and Meta-Analysis.

BACKGROUND: Rapid advancements in eHealth and mobile health (mHealth) technologies have driven researchers to design and evaluate numerous technology-based interventions to promote smoking cessation. The evolving nature of cessation interventions emphasizes a strong need for knowledge synthesis. OBJECTIVE: This systematic review and meta-analysis aimed to summarize recent evidence from randomized controlled trials regarding the effectiveness of eHealth-based smoking cessation interventions in promoting abstinence and assess nonabstinence outcome indicators, such as cigarette consumption and user satisfaction, via narrative synthesis. METHODS: We searched for studies published in English between 2017 and June 30, 2022, in 4 databases: PubMed (including MEDLINE), PsycINFO, Embase, and Cochrane Library. Two independent reviewers performed study screening, data extraction, and quality assessment based on the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework. We pooled comparable studies based on the population, follow-up time, intervention, and control characteristics. Two researchers performed an independent meta-analysis on smoking abstinence using the Sidik-Jonkman random-effects model and log risk ratio (RR) as the effect measurement. For studies not included in the meta-analysis, the outcomes were narratively synthesized. RESULTS: A total of 464 studies were identified through an initial database search after removing duplicates. Following screening and full-text assessments, we deemed 39 studies (n=37,341 participants) eligible for this review. Of these, 28 studies were shortlisted for meta-analysis. According to the meta-analysis, SMS or app text messaging can significantly increase both short-term (3 months) abstinence (log RR=0.50, 95% CI 0.25-0.75; I2=0.72%) and long-term (6 months) abstinence (log RR=0.77, 95% CI 0.49-1.04; I2=8.65%), relative to minimal cessation support. The frequency of texting did not significantly influence treatment outcomes. mHealth apps may significantly increase abstinence in the short term (log RR=0.76, 95% CI 0.09-1.42; I2=88.02%) but not in the long term (log RR=0.15, 95% CI -0.18 to 0.48; I2=80.06%), in contrast to less intensive cessation support. In addition, personalized or interactive interventions showed a moderate increase in cessation for both the short term (log RR=0.62, 95% CI 0.30-0.94; I2=66.50%) and long term (log RR=0.28, 95% CI 0.04-0.53; I2=73.42%). In contrast, studies without any personalized or interactive features had no significant impact. Finally, the treatment effect was similar between trials that used biochemically verified or self-reported abstinence. Among studies reporting outcomes besides abstinence (n=20), a total of 11 studies reported significantly improved nonabstinence outcomes in cigarette consumption (3/14, 21%) or user satisfaction (8/19, 42%). CONCLUSIONS: Our review of 39 randomized controlled trials found that recent eHealth interventions might promote smoking cessation, with mHealth being the dominant approach. Despite their success, the effectiveness of such interventions may diminish with time. The design of more personalized interventions could potentially benefit future studies. TRIAL REGISTRATION: PROSPERO CRD42022347104; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=347104.

Incidence of Post-denosumab Rebound Hypercalcaemia in Bony-Metastatic Breast Cancer.

Denosumab reduces incidence of skeletal related events in patients with bony-metastatic breast cancer, however cessation is associated with a rebound phenomenon which, rarely, has been associated with hypercalcaemia. We aimed to identify the incidence of post-denosumab cessation rebound hypercalcaemia amongst patients with breast cancer-related bony metastases. We performed a single-centre retrospective cohort analysis to determine the incident of rebound hypercalcaemia amongst patients treated with antiresorptive agents for bony metastatic breast cancer between 2016-2020. 22,320 outpatient encounters were reviewed, which identified 97 patients with bonymetastatic disease treated with antiresorptive therapy. Of the 21 patients who had denosumab ceased, six (28.6%) developed hypercalcaemia. Interval between last denosumab dose and onset of hypercalcaemia was a median 7.5 (range 2-13) months. There was a significant difference in both denosumab treatment duration as well as total treatment dose exposure between patients who developed hypercalcaemia post-denosumab cessation (median 41 months, 40 doses) and those who remained normocalcaemic (median 10 months, 5 doses), p = 0.009. In our study, hypercalcaemia occurred between two and thirteen months after denosumab cessation. Greater denosumab treatment duration as well as total denosumab dose exposure was associated with higher risk of hypercalcaemia after denosumab cessation. Hormonal therapy or previous bisphosphonate treatment was not seen to impact upon development of hypercalcaemia. Rebound hypercalcaemia is a rare but important diagnosis to consider in patients experiencing hypercalcaemia after denosumab cessation.

Comparing different montages of transcranial direct current stimulation on dual-task walking and cortical activity in chronic stroke: double-blinded randomized controlled trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation to modulate cortical activity for improving motor function. However, the different tDCS applications for modulating cortical activity and dual task gait performance in chronic stroke have not yet been investigated. This study investigated the effects of different tDCS applications on dual task gait performance and contralesional M1 activation in chronic stroke. METHODS: Forty-eight participants were randomized to anodal, bilateral, cathodal, and sham tDCS groups. Each group received 20 min of tDCS stimulation, except the sham group. Gait performance was measured by GaitRite system during cognitive dual task (CDT) walking, motor dual task (MDT) walking, and single walking (SW). Contralesional M1 activity of unaffected tibialis anterior (TA) was measured using transcranial magnetic stimulation (TMS). Intragroup difference was analyzed by Wilconxon sign ranks test with Bonferroni correction, and Kruskal-Wallis one-way analysis of variance by ranks was used for intergroup comparisons, followed by post-hoc Mann-Whitney U tests with Bonferroni correction. RESULTS: The bilateral tDCS (p = 0.017) and cathodal tDCS (p = 0.010) improved the CDT walking speed more than sham group. The bilateral tDCS (p = 0.048) and cathodal tDCS (p = 0.048) also improved the MDT walking speed more than sham group. Furthermore, bilateral tDCS (p = 0.012) and cathodal tDCS (p = 0.040) increased the silent period (SP) more than the anodal and sham group. Thus, one-session of bilateral and cathodal tDCS improved dual task walking performance paralleled with increasing contralesional corticomotor inhibition in chronic stroke. CONCLUSIONS: Our results indicate that one-session of bilateral and cathodal tDCS increased contralesional corticomotor inhibition and improved dual task gait performance in chronic stroke. TRIAL REGISTRATION: Thai Clinical Trials Registry (TCTR20180116001). Registered prospectively on 16th Jan, 2018 at http://www.thaiclinicaltrials.org .

Multiarea Brain Activation and Gait Deterioration During a Cognitive and Motor Dual Task in Individuals With Parkinson Disease.

BACKGROUND AND PURPOSE: In people with Parkinson disease (PD), gait performance deteriorating during dual-task walking has been noted in previous studies. However, the effects of different types of dual tasks on gait performance and brain activation are still unknown. The purpose of this study was to investigate cognitive and motor dual-task walking performance on multiarea brain activity in individuals with PD. METHODS: Twenty-eight participants with PD were recruited and performed single walking (SW), walking while performing a cognitive task (WCT), and walking while performing a motor task (WMT) at their self-selected speed. Gait performance including walking speed, stride length, stride time, swing cycle, temporal and spatial variability, and dual-task cost (DTC) was recorded. Brain activation of the prefrontal cortex (PFC), premotor cortex (PMC), and supplementary motor areas (SMA) were measured using functional near-infrared spectroscopy during walking. RESULTS: Walking performance deteriorated upon performing a secondary task, especially the cognitive task. Also, a higher and more sustained activation in the PMC and SMA during WCT, as compared with the WMT and SW, in the late phase of walking was found. During WMT, however, the SMA and PMC did not show increased activation compared with during SW. Moreover, gait performance was negatively correlated with PMC and SMA activity during different walking tasks. DISCUSSION AND CONCLUSIONS: Individuals with mild to moderate PD demonstrated gait deterioration during dual-task walking, especially during WCT. The SMA and PMC were further activated in individuals with PD when performing cognitive dual-task walking.Supplemental Digital Content is Available in the Text.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A383 ).

The SDF1-CXCR4 Axis Is Involved in the Hyperbaric Oxygen Therapy-Mediated Neuronal Cells Migration in Transient Brain Ischemic Rats.

Neurogenesis is a physiological response after cerebral ischemic injury to possibly repair the damaged neural network. Therefore, promoting neurogenesis is very important for functional recovery after cerebral ischemic injury. Our previous research indicated that hyperbaric oxygen therapy (HBOT) exerted neuroprotective effects, such as reducing cerebral infarction volume. The purposes of this study were to further explore the effects of HBOT on the neurogenesis and the expressions of cell migration factors, including the stromal cell-derived factor 1 (SDF1) and its target receptor, the CXC chemokine receptor 4 (CXCR4). Thirty-two Sprague-Dawley rats were divided into the control or HBO group after receiving transient middle cerebral artery occlusion (MCAO). HBOT began to intervene 24 h after MCAO under the pressure of 3 atmospheres for one hour per day for 21 days. Rats in the control group were placed in the same acrylic box without HBOT during the experiment. After the final intervention, half of the rats in each group were cardio-perfused with ice-cold saline followed by 4% paraformaldehyde under anesthesia. The brains were removed, dehydrated and cut into serial 20µm coronal sections for immunofluorescence staining to detect the markers of newborn cell (BrdU+), mature neuron cell (NeuN+), SDF1, and CXCR4. The affected motor cortex of the other half rats in each group was separated under anesthesia and used to detect the expressions of brain-derived neurotrophic factor (BDNF), SDF1, and CXCR4. Motor function was tested by a ladder-climbing test before and after the experiment. HBOT significantly enhanced neurogenesis in the penumbra area and promoted the expressions of SDF1 and CXCR4. The numbers of BrdU+/SDF1+, BrdU+/CXCR4+, and BrdU+/NeuN+ cells and BDNF concentrations in the penumbra were all significantly increased in the HBO group when compared with the control group. The motor functions were improved in both groups, but there was a significant difference between groups in the post-test. Our results indicated that HBOT for 21 days enhanced neurogenesis and promoted cell migration toward the penumbra area in transient brain ischemic rats. HBOT also increased BDNF expression, which might further promote the reconstructions of the impaired neural networks and restore motor function.

Effects of square-stepping exercise on executive function in individuals with Parkinson's disease: A randomized controlled pilot study.

With the aging population, the incidence of Parkinson's disease (PD) increases over time. In this study, a popular and interesting exercise called the square-stepping exercise (SSE) was chosen as an intervention for people with PD. The purpose of the study was to investigate the effects of SSE on cognitive function, especially executive function. Twenty-eight participants were recruited and randomly assigned to the experimental group (n=14) or the control group (n=14). The duration of the intervention for both groups was 8 weeks, twice a week. The outcomes, including the trail making test, the digit span task, the Montreal cognitive assessment, and the Parkinson's disease questionnaire, were evaluated before the intervention, after the intervention, and at 1-month follow-up. The results showed that executive function improved significantly on the digit span task after SSE training. Consequently, SSE could be an effective intervention to improve executive function in people with PD.

Effects of transcranial direct current stimulation followed by exercise on neuropathic pain in chronic spinal cord injury: a double-blinded randomized controlled pilot trial.

STUDY DESIGN: Double-blinded randomized controlled pilot trial. OBJECTIVES: The present study aimed to investigate the effects of multiple sessions of tDCS followed by exercise on neuropathic pain and brain activity in individuals with chronic SCI. SETTING: Rehabilitation center in Taipei, Taiwan. METHODS: Twelve individuals with neuropathic pain after SCI were randomized into the experimental (real) or control (sham) tDCS group. All participants received 12 sessions of real or sham tDCS, and moderate upper body exercises over 4-6 weeks. Pain intensity, characters of pain, self-rating change of pain, brain activity, and quality of life were assessed at pre, posttest, and 4-week follow-up. RESULTS: The between-group differences (95% CI) of pain intensity at posttest and at 4-week follow-up were -2.2/10 points (-3.0 to 1.0, p = 0.060) and -2.0/10 points (-5.0 to -0.4, p = 0.035), respectively. The between-group differences of paresthesia/dysesthesia pain character were -2.0/10 points (-3.2 to 1.0, p = 0.053) at posttest and -2.3/10 points (-5.0 to 2.5, p = 0.054) at follow-up. No significant changes in brain activity and quality of life were noted at post-intervention and follow-up in both groups. CONCLUSIONS: The multiple sessions of anodal tDCS combined with moderate upper body exercise were feasible for individuals with neuropathic pain after spinal cord injury. However, the analgesic effect was not superior to exercise alone after 12 sessions of intervention, and the beneficial effect was observed at 4-week follow-up.

Effects of square-stepping exercise on motor and cognitive function in older adults - A systematic review and meta-analysis.

OBJECTIVES: To document the effects of square-stepping exercise (SSE) on motor and cognitive function in older adults. METHODS: Five online databases were searched in May 2021. Controlled studies published from 2006 to May 2021 were included. The experimental group received SSE alone or SSE combined with other exercise(s), whereas the control group received no training or other exercise(s). Motor and cognitive outcomes included balance, fall risk, agility, endurance, gait speed, flexibility, muscle strength, reaction time, global cognitive function, memory, and executive function. RESULTS: Ten articles with a total of 920 participants were included. Static balance (p=0.0009), dynamic balance (p=0.0008), fall risk (p<0.00001), and agility (p=0.02) improved more in the intervention group than in the control group. However, SSE did not seem to exert beneficial effects on cognitive function. CONCLUSION: In older adults, SSE provided beneficial effects on motor function, including static and dynamic balance, risk of falls, and agility. However, positive effects on cognitive function were not observed and require further investigation.

Feasibility and effectiveness of interactive stepping exercise on community-dwelling older adults: A pilot randomized controlled trial.

Recently, the interactive stepping exercise (ISE) was developed on the basis of square stepping exercise. The aim of this study was to examine the feasibility and effectiveness of ISE on executive function and gait variability among community-dwelling older adults. Fourteen participants were recruited and randomly assigned to the experimental group (n=7) or control group (n=7) and received ISE or home exercise program, respectively, three times a week for 12 weeks. The outcomes included retention rate, attendance rate, Trail Making Test, and dual-task walking. The results showed that participants had high retention and attendance rate for the ISE intervention. Moreover, significant improvement in the part A of Trail Making Test and stride length variability during cognitive dual-task walking after 12-week ISE intervention. The current results suggested that ISE is a feasible and effective intervention on executive function and gait variability in community-dwelling older adults.

Muscle activation and intermuscular coherence during forward and backward pedaling.

The purpose of this study was to investigate muscle activity and intermuscular coherence of the rectus femoris (RF) and biceps femoris (BF) during forward (FW) and backward (BW) pedaling. Sixteen healthy volunteers performed FW and BW pedaling in 30, 45, and 60 revolutions per minute (RPM), while electromyographic (EMG) signals of the RF and BF were recorded bilaterally to determine integral EMG and intermuscular coherence. BW pedaling showed a statistically significant larger EMG activity on the left BF (P = 0.023) in 30 RPM; on the left BF (P = 0.01), right BF (P = 0.05), and right RF (P = 0.006) in 45 RPM, and on the left BF (P = 0.014) and right RF (P = 0.011) in 60 RPM than FW pedaling. In 45 RPM, higher coherence was demonstrated on the left leg (P = 0.011) during the left flexor and right extensor phases and on the right leg (P = 0.043) during the right flexor and left extensor phases in BW compared with FW pedaling. In 60 RPM, higher coherence was observed on both legs (left, P = 0.037; right, P < 0.001) during the left flexor and right extensor phases in BW compared with FW pedaling. Our results suggest that BW pedaling increased the muscle activity of both biarticular muscles and intermuscular coherence.