Neuroprotective Effect of Sterculia setigera Leaves Hydroethanolic Extract.

Plants are a valuable source of information for pharmacological research and new drug discovery. The present study aimed to evaluate the neuroprotective potential of the leaves of the medicinal plant Sterculia setigera. In vitro, the effect of Sterculia setigera leaves dry hydroethanolic extract (SSE) was tested on cultured cerebellar granule neurons (CGN) survival when exposed to hydrogen peroxide (H2O2) or 6-hydroxydopamine (6-OHDA), using the viability probe fluorescein diacetate (FDA), a lactate dehydrogenase (LDH) activity assay, an immunocytochemical staining against Gap 43, and the quantification of the expression of genes involved in apoptosis, necrosis, or oxidative stress. In vivo, the effect of intraperitoneal (ip) injection of SSE was assessed on the developing brain of 8-day-old Wistar rats exposed to ethanol neurotoxicity by measuring caspase-3 activity on cerebellum homogenates, the expression of some genes in tissue extracts, the thickness of cerebellar cortical layers and motor coordination. In vitro, SSE protected CGN against H2O2 and 6-OHDA-induced cell death at a dose of 10 µg/mL, inhibited the expression of genes Casp3 and Bad, and upregulated the expression of Cat and Gpx7. In vivo, SSE significantly blocked the deleterious effect of ethanol by reducing the activity of caspase-3, inhibiting the expression of Bax and Tp53, preventing the reduction of the thickness of the internal granule cell layer of the cerebellar cortex, and restoring motor functions. Sterculia setigera exerts neuroactive functions as claimed by traditional medicine and should be a good candidate for the development of a neuroprotective treatment against neurodegenerative diseases.

Non-pharmacological interventions for traumatic brain injury.

Heterogeneity and variability of symptoms due to the type, site, age, sex, and severity of injury make each case of traumatic brain injury (TBI) unique. Considering this, a universal treatment strategy may not be fruitful in managing outcomes after TBI. Most of the pharmacological therapies for TBI aim at modifying a particular pathway or molecular process in the sequelae of secondary injury rather than a holistic approach. On the other hand, non-pharmacological interventions such as hypothermia, hyperbaric oxygen, preconditioning with dietary adaptations, exercise, environmental enrichment, deep brain stimulation, decompressive craniectomy, probiotic use, gene therapy, music therapy, and stem cell therapy can promote healing by modulating multiple neuroprotective mechanisms. In this review, we discussed the major non-pharmacological interventions that are being tested in animal models of TBI as well as in clinical trials. We evaluated the functional outcomes of various interventions with an emphasis on the links between molecular mechanisms and outcomes after TBI.

Electroacupuncture Promotes Nerve Regeneration and Functional Recovery Through Regulating lncRNA GAS5 Targeting miR-21 After Sciatic Nerve Injury.

Although the benefits of electroacupuncture (EA) for peripheral nerve injury (PNI) are well accepted in clinical practice, the underlying mechanism remains incompletely elucidated. In our study, we observed that EA intervention led to a reduction in the expression of the long non-coding RNA growth-arrest-specific transcript 5 (GAS5) and an increased in miR-21 levels within the injured nerve, effectively promoting functional recovery and nerve regeneration following sciatic nerve injury (SNI). In contrast, administration of adeno-associated virus expressing GAS5 (AAV-GAS5) weakened the therapeutic effect of EA. On the other hand, both silencing GAS5 and introducing a miR-21 mimic prominently enhanced the proliferation activity and migration ability of Schwann cells (SCs), while also inhibiting SCs apoptosis. On the contrary, inhibition of SCs apoptosis was found to be mediated by miR-21. Additionally, overexpression of GAS5 counteracted the effects of the miR-21 mimic on SCs. Moreover, SCs that transfected with the miR-21 mimic promoted neurite growth in hypoxia/reoxygenation-induced neurons, which might be prevented by overexpressing GAS5. Furthermore, GAS5 was found to be widely distributed in the cytoplasm and was negatively regulated by miR-21. Consequently, the targeting of GAS5 by miR-21 represents a potential mechanism through which EA enhances reinnervation and functional restoration following SNI. Mechanistically, the GAS5/miR-21 axis can modulate the proliferation, migration, and apoptosis of SCs while potentially influencing the neurite growth of neurons.

Huoxue Tongluo decoction combined with acupuncture in the treatment of lumbar disc herniation and its effect on JOA and VAS scores.

BACKGROUND: Lumbar disc herniation (LDH) is a common clinical disease of the skeletal system, and its prevalence has been on a rise. OBJECTIVE: To evaluate the efficacy of Huoxue Tongluo decoction plus acupuncture in the treatment of lumbar disc herniation and its effectiveness in improving the functional recovery of the patients' affected joints and mitigating their pain. METHODS: In this prospective study, 110 patients with lumbar disc herniation enrolled in our Hospital from June 2019 to June 2021 were collected and randomized to receive either conventional treatment (control group) or Huoxue Tongluo Decoction plus acupuncture (study group). RESULTS: Huoxue Tongluo Decoction plus acupuncture resulted in more rapid mitigation of lower extremity symptoms and lumbar symptoms versus conventional treatment (P< 0.05). Patients receiving traditional Chinese medicine (TCM) showed milder inflammatory responses than those with conventional medication, as evidenced by the lower serum concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and high-sensitivity C-reactive protein (hs-CRP) (P< 0.05). After treatment, the study group had higher Japanese Orthopedic Association (JOA) scores and lower visual analogue scale (VAS) scores than the control group (P< 0.05), suggesting that the combination of the herbal decoction and acupuncture provided better functional recovery of the affected joints and pain mitigation for the patients. Furthermore, the lower Pittsburgh sleep quality index (PSQI) scores in patients in the study group indicated better sleep quality of patients after TCM intervention than after conventional treatment (P< 0.05). Huoxue Tongluo Decoction plus acupuncture was associated with a significantly higher efficacy (94.55%) versus conventional treatment (80%) (P< 0.05). CONCLUSIONS: Huoxue Tongluo Decoction combined with acupuncture significantly offers a viable treatment alternative for lumbar disc herniation with promising treatment outcomes, mitigates patients' limb pain, and improves their lumbar function and sleep quality. Further trials are, however, required prior to general application in clinical practice.

Electroacupuncture for acute transverse myelitis following viral infection: A case report.

BACKGROUND: Electroacupuncture (EA) has a positive effect on neurological repair and functional recovery following spinal cord disease. However, evidence of its effectiveness in acute transverse myelitis (ATM) cases is limited. PATIENT PRESENTATION: A 48-year-old woman experienced headache and fever for 5 days, followed by a sudden onset of back pain, lower limb paralysis, and urinary and bowel dysfunction. The patient received intravenous medications. However, she did not experience improvement in clinical symptoms. She subsequently underwent acupuncture treatment. She regained walking ability and experienced improved bladder function and bowel control after 36 sessions of EA treatment. METHODS: CARE guidelines informed the case study report. The MRC and ICIQ-UI-SF scores were used to verify changes in lower-extremity muscle strength and urination after EA treatment. Qualitative information was collected using feedback tables. CONCLUSION: Pharmacological treatment for ATM lacks clear advantages because of its complex pathophysiological mechanisms. Hence, EA could be recommended as a promising treatment modality for ATM.

A novel approach to the immediate effects of electroacupuncture on dry eye: A case series.

INTRODUCTION: Dry eye disease (DED) is an inflammatory disorder that shares several features with autoimmune diseases. Research suggests that electroacupuncture (EA) is a promising alternative treatment option for this disorder; however, evidence of its immediate efficacy is limited. CASE PRESENTATION: Three patients were diagnosed with DED, and used artificial tears or anti-inflammatory drugs for long-term relief of eye symptoms. However, the cure rates were low, and the side effects were high. To improve ocular symptoms, quality of life, and physical and mental health, the patients sought alternative complementary therapies and received electroacupuncture therapy. All patients showed significant improvements in fatigue and dryness of the ocular surface after 3-4 days of treatment, and follow-up after 4 weeks showed no tendency for recurrence. No adverse reactions or unexpected events were observed during treatment. CONCLUSION: We propose an innovative electroacupuncture treatment aimed at fewer acupuncture points, shorter periods, and faster healing that improves the symptoms of patients with DED in the short term. Continuous current stimulation by anatomically positioned needles on both sides of the lacrimal gland and the creation of an electric field may improve the endogenous mechanisms of DED.

Pushen capsule treatment promotes functional recovery after ischemic stroke.

BACKGROUND: As a leading cause of long-term disability, ischemic stroke urgently needs further research and drug development. Pushen capsule (Pushen) has been commonly applied in clinical treatment for relieving headaches, dizziness, and numbness. However, the effects of Pushen on ischemic stroke have not been revealed yet. PURPOSE: To assess the efficiency of Pushen in ischemic stroke and identify its potential therapeutic targets and active ingredients for treating ischemic stroke. STUDY DESIGN AND METHODS: Behavioural experiments, Triphenyltetrazolium chloride (TTC) staining, Magnetic resonance imaging (MRI), and immunofluorescence staining were performed to examine the efficiency of Pushen in stroke model mice. The potential mechanism and active ingredients of Pushen were assessed by transcriptome, 16S rDNA sequencing, metabonomics, and network pharmacology. Finally, the targets were validated by RT-PCR, chromatin immunoprecipitation (ChIP), ELISA, and molecular docking methods. RESULTS: Pushen had several effects on stroke model mice, including reducing the infarct volume, improving the blood‒brain barrier (BBB), and promoting functional restoration. Furthermore, the network pharmacology, LC-MS/MS, and molecular docking results revealed that tricin, quercetin, luteolin, kaempferol, and physcion were identified as the key active ingredients in Pushen that treated ischemic stroke. Mechanistically, these key ingredients could bind with the transcription factor c-Myc and thereby regulate the expression of Adora2a, Drd2, and Ppp1r1b, which are enriched in the cAMP signaling pathway. Additionally, Pushen improved the gut microbiota dysbiosis and reduced inosine levels in feces and serum, thereby reducing Adora2a expression in the brain. CONCLUSIONS: Our study confirmed that Pushen was effective for treating ischemic stroke and has promising clinical applications.

The potential of curcumin for treating spinal cord injury: a meta-analysis study.

INTRODUCTION: In this paper, we conducted a meta-analysis on the curcumin effect on functional recovery provided by the Basso, Beattie, Brenham (BBB) test for rats, and the Basso mouse scale (BMS) for mice after spinal cord injury (SCI) in animal models. METHOD: Data mining was performed, and the standard mean difference (SMD) between the treated and control (untreated) groups was calculated using the STATA software. Quality control and subgroup analysis were performed. RESULTS: The analysis includes 24 experimental studies that showed curcumin had a strong significance in improving functional recovery after SCI (SMD = 3.38; 95% CI: 2.54-4.22; p < 0.001). When curcumin was administered daily, it had a stronger effect than single-dose treatment or weekly administration. Despite the same effect in the follow-up time before and after 4 weeks post-injury, but later 9 weeks, curcumin had only a moderate effect. Curcumin also significantly reduced the expression of GFAP (Glial fibrillary acidic protein) marker compared to untreated groups. CONCLUSION: These findings suggest that daily administration of curcumin can be an effective approach to improving functional recovery after SCI.

Association between Baseline NIHSS Limb Motor Score and Functional Recovery after Stroke: Analysis Based on a Multicountry Dataset.

INTRODUCTION: Motor skills are the domains most often affected by stroke, but a comprehensive assessment of motor function is often impractical in the acute setting. It could be useful to have a brief simple tool allowing the stratification of patients at the time of inclusion in clinical studies. Hence, our primary objective was to evaluate whether the baseline NIH Stroke Scale limb motor score (b-NIHSS-LMS), obtained by summing the four motor items 5a to 6b of the NIHSS, is associated with functional recovery assessed by the modified Rankin Score (mRS). A secondary objective was to apply this new tool in the context of a clinical trial. METHODS: The analysed population considered for this research included subjects from a large published, double-blind, multicentre trial, randomised to receive either a combination of various herbal and non-herbal components (MLC601) or placebo, administered within 72 h after an acute ischaemic stroke of intermediate severity (defined by baseline NIH Stroke Scale [b-NIHSS] score of 8-14). Associations between b-NIHSS-LMS and favourable outcome, i.e., mRS 0-1 at month 3, were evaluated using logistic regression adjusted for baseline covariates and study treatment. RESULTS: The analysis included 533 subjects with an acute ischaemic stroke of intermediate severity assessed at month 3. Analyses showed that b-NIHSS-LMS was independently associated with a favourable outcome (OR 0.84; 95% confidence interval 0.76-0.92; p < 0.0003) at 3 months. Furthermore, in the clinical study considered, a selection of patients based upon a sufficient level of motor impairment at study entry (b-NIHSS-LMS ≥3) would result in the detection of a more pronounced and longer-lasting treatment effect. Indeed, ORs of treatment effect versus placebo in the selected subgroup (b-NIHSS-LMS ≥3) were statistically significant from months 3-24. DISCUSSION/CONCLUSIONS: As an independent association between b-NIHSS-LMS and functional recovery after an acute ischaemic stroke of intermediate severity was established in this study, we suggest that the b-NIHSS-LMS can be used as a stratification factor in large clinical trials to define a target population with poststroke motor impairments.

A review of the diet, nutrients, and supplementation potential for the outcome augmentation in surgical treatment of peripheral nerve injuries.

Objective: Although the studies have shown the beneficial effects of diet, nutrition, and supplementation as an independent treatment modality, their roles are underestimated in the treatment of peripheral nerve injuries. This is in great part due to the development of efficient nerve repair techniques, combined with physical treatment and stimulation. To achieve the best possible functional recovery diet, nutrition, and supplementation should be implemented within a multidisciplinary approach. The aim of the study is to provide insight into the potentially beneficial effects of diet, nutrients, and supplementation, in the limitation of nerve damage and augmentation of the functional recovery after surgery in a review of human and animal studies. Methods: The data relating to the diet, nutrients, and supplementation effects on peripheral nerve injuries and their treatment was extracted from the previously published literature. Results: General balanced diet as well as obesity influence the initial nerve features prior to the injury. In the period following the injury, neuroprotective agents demonstrated beneficial effects prior to surgery, and immediately after the injury, while those potentiating nerve regeneration may be used after the surgical repair to complement the physical treatment and stimulation for improved functional recovery. Conclusions: Standardized diet, nutrition, and supplementation recommendations and protocols may be of great importance for better nerve regeneration and functional recovery as a part of the multidisciplinary approach to achieve the best possible results in surgically treated patients with peripheral nerve injuries in the future.

Ginsenoside Rg1 promotes remyelination and functional recovery in demyelinating disease by enhancing oligodendrocyte precursor cells-mediated myelin repair.

BACKGROUND: Inefficient differentiation of oligodendrocyte precursor cells (OPCs) is one of the significant pathological obstacles of myelin repair and provides an essential therapeutic target against behavioral dysfunction in various neurodegenerative diseases, especially in secondary progressive multiple sclerosis (SPMS). Ginsenoside Rg1 (Rg1) has traditionally been recognized as a protector of neuronal damages, preventing its degeneration. PURPOSE: We investigated the effects of Rg1 on myelin regeneration-mediated by OPCs and its therapeutic significance in SPMS. METHODS: A cuprizone (CPZ) model was established and then administered with Rg1 specific for evaluations of functional recovery and remyelination. In vitro, the primary mouse OPCs were isolated and cultured for examining their ability of myelin repair. Furthermore, a chronic experimental autoimmune encephalomyelitis (EAE) model was utilized to assess the therapeutic value on SPMS. RESULTS: We found that Rg1 promoted functional recovery of the demyelinated mice, including spatial memory, motor function, and anxiety-like behavior. Histologically, Rg1 enhanced myelin-genesis as proven by myelin staining and microstructures of myelin observed by transmission electron microscope. Furthermore, Rg1 significantly increased Olig2+ oligodendrocyte lineage cells in callosum, implying that the pro-remyelination effect of Rg1 was closely correlated to the enhanced differentiation of OPCs. We further demonstrated that Rg1 increased the survival and proliferation of OPCs as well as induced maturation in oligodendrocytes (OLs). Molecular analysis showed that Rg1 transduced the pro-differentiation signaling programmed by the GSK3ß/ß-Catenin pathway. Notably, relying on its pro-remyelination effects, Rg1 ameliorated severity and histopathology of EAE disease. CONCLUSION: By paving the way for OPCs differentiation, Rg1 could maintain the integrity of myelin and is a promising candidate for functional recovery in demyelinating diseases.

Radix Astragalus Polysaccharide Accelerates Angiogenesis by Activating AKT/eNOS to Promote Nerve Regeneration and Functional Recovery.

Peripheral nerve injury (PNI) results in loss of neural control and severe disabilities in patients. Promoting functional nerve recovery by accelerating angiogenesis is a promising neuroprotective treatment strategy. Here, we identified a bioactive Radix Astragalus polysaccharide (RAP) extracted from traditional Chinese medicine (TCM) as a potent enhancer of axonal regeneration and remyelination. Notably, RAP promoted functional recovery and delayed gastrocnemius muscle atrophy in a rat model of sciatic nerve crush injury. Further, RAP treatment may induce angiogenesis in vivo. Moreover, our in vitro results showed that RAP promotes endothelial cell (EC) migration and tube formation. Altogether, our results show that RAP can enhance functional recovery by accelerating angiogenesis, which was probably related to the activation of AKT/eNOS signaling pathway, thereby providing a polysaccharide-based therapeutic strategy for PNI.

Guhong injection promotes post-stroke functional recovery via attenuating cortical inflammation and apoptosis in subacute stage of ischemic stroke.

BACKGROUND: As a leading cause of death and disability, alternative therapies for stroke are still limited by its complicated pathophysiological manifestations. Guhong injection (GHI), consisting of safflower aqueous extract and aceglutamide, has been widely applied for the clinical treatment of cerebrovascular diseases, especially ischemic stroke and post-stroke recovery, in China. Recently, a series of studies have reported the positive effect of GHI against cerebral ischemia/reperfusion injury via targeting various molecular mechanisms. However, questions remain on whether treatment with GHI contributes to better functional recovery after stroke and if so, the potential mechanisms and active substances. PURPOSE: The aim of this work was to explore the potential therapeutic possibilities of GHI for the neurological and behavioral recovery after stroke and to investigate the underlying molecular mechanisms as well as active substances. METHODS: The neural and motor deficits as well as cortical lesions after GHI treatment were investigated in a mouse model of transient ischemic stroke. Based on the substance identification of GHI, network pharmacology combined with an experimental verification method was used to systematically decipher the biological processes and signaling pathways closely related to GHI intervention in response to post-stroke functional outcomes. Subsequently, ingenuity pathway analysis (IPA) analysis was performed to determine the anti-stroke active substances targeting to the hub targets involved in the significant molecular pathways regulated by GHI treatment. RESULTS: Therapeutically, administration of GHI observably ameliorated the post-stroke recovery of neural and locomotor function as well as reduced infarct volume and histopathological damage to the cerebral cortex in subacute stroke mice. According to 26 identified or tentatively characterized substances in GHI, the compound-target-pathway network was built. Bioinformatics analysis suggested that inflammatory and apoptotic pathways were tightly associated with the anti-stroke effect of GHI. Based on protein-protein interaction network analysis, the hub targets (such as NF-κB p65, TNF-α, IL-6, IL-1ß, Bax, Bcl-2, and Caspase-3) involved in inflammation and apoptosis were selected. On the one hand, immunofluorescence and ELISA results showed that GHI (10 ml/kg) treatment obviously reduced NF-κB p65 nuclear translocation as well as decreased the abnormally elevated concentrations of proinflammatory cytokines (TNF-α, IL-6, and IL-1ß) in damaged cortex tissues. On the other hand, GHI (10 ml/kg) treatment significantly downregulated the number of TUNEL-positive apoptotic cells in ischemic cortex and effectively restored the abnormal expression of Bax, Bcl-2, and Caspase-3. Based on the results of IPA, hydroxysafflor yellow A, baicalin, scutellarin, gallic acid, syringin, chlorogenic acid, kaempferol, kaempferol-3-O-ß-rutinoside, and rutin acted synergistically on core targets, which could be considered as the active substances of GHI. CONCLUSION: Overall, the current findings showed that the beneficial action of GHI on improving post-stroke functional recovery of subacute stroke mice partly via the modulation of cortical inflammation and apoptosis. These findings not only provide a reliable reference for the clinical application of GHI, but also shed light on a promising alternative therapeutic strategy for ischemic stroke patients.

The Effects of Mindfulness-Based Stress Reduction Training on Hope, Psychological Well-Being, and Functional Recovery in Patients with Schizophrenia.

This study tested the effects of mindfulness-based stress reduction (MBSR) training on multiple outcomes in patients with schizophrenia. We compared MBSR, psychoeducation, and control groups in a randomized controlled research design. Outcome measures assessed hope, psychological wellbeing, and functional recovery over three time points in 137 participants. The results of this study indicate that MBSR training was more effective in terms of increasing the level of hope, psychological well-being, and functional recovery of schizophrenia patients when compared with psychoeducation and control patients.

Effect of Neurorepair for Motor Functional Recovery Enhanced by Total Saponins From Trillium tschonoskii Maxim. Treatment in a Rat Model of Focal Ischemia.

Trillium tschonoskii Maxim. (TTM), is a perennial herb from Liliaceae, that has been widely used as a traditional Chinese medicine treating cephalgia and traumatic hemorrhage. The present work was designed to investigate whether the total saponins from Trillium tschonoskii Maxim. (TSTT) would promote brain remodeling and improve gait impairment in the chronic phase of ischemic stroke. A focal ischemic model of male Sprague-Dawley (SD) rats was established by permanent middle cerebral artery occlusion (MCAO). Six hours later, rats were intragastrically treated with TSTT (120, 60, and 30 mg/kg) and once daily up to day 30. The gait changes were assessed by the CatWalk-automated gait analysis system. The brain tissues injuries, cerebral perfusion and changes of axonal microstructures were detected by multimodal magnetic resonance imaging (MRI), followed by histological examinations. The axonal regeneration related signaling pathways including phosphatidylinositol 3-kinases (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3 (GSK-3)/collapsin response mediator protein-2 (CRMP-2) were measured by western blotting. TSTT treatment significantly improved gait impairment of rats. MRI analysis revealed that TSTT alleviated tissues injuries, significantly improved cerebral blood flow (CBF), enhanced microstructural integrity of axon and myelin sheath in the ipsilesional sensorimotor cortex and internal capsule. In parallel to MRI findings, TSTT preserved myelinated axons and promoted oligodendrogenesis. Specifically, TSTT interventions markedly up-regulated expression of phosphorylated GSK-3, accompanied by increased expression of phosphorylated PI3K, AKT, but reduced phosphorylated CRMP-2 expression. Taken together, our results suggested that TSTT facilitated brain remodeling. This correlated with improving CBF, encouraging reorganization of axonal microstructure, promoting oligodendrogenesis and activating PI3K/AKT/GSK-3/CRMP-2 signaling, thereby improving poststroke gait impairments.

Therapeutic Potential of Complementary and Alternative Medicines in Peripheral Nerve Regeneration: A Systematic Review.

Despite the progressive advances, current standards of treatments for peripheral nerve injury do not guarantee complete recovery. Thus, alternative therapeutic interventions should be considered. Complementary and alternative medicines (CAMs) are widely explored for their therapeutic value, but their potential use in peripheral nerve regeneration is underappreciated. The present systematic review, designed according to guidelines of Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols, aims to present and discuss the current literature on the neuroregenerative potential of CAMs, focusing on plants or herbs, mushrooms, decoctions, and their respective natural products. The available literature on CAMs associated with peripheral nerve regeneration published up to 2020 were retrieved from PubMed, Scopus, and Web of Science. According to current literature, the neuroregenerative potential of Achyranthes bidentata, Astragalus membranaceus, Curcuma longa, Panax ginseng, and Hericium erinaceus are the most widely studied. Various CAMs enhanced proliferation and migration of Schwann cells in vitro, primarily through activation of MAPK pathway and FGF-2 signaling, respectively. Animal studies demonstrated the ability of CAMs to promote peripheral nerve regeneration and functional recovery, which are partially associated with modulations of neurotrophic factors, pro-inflammatory cytokines, and anti-apoptotic signaling. This systematic review provides evidence for the potential use of CAMs in the management of peripheral nerve injury.

Transcranial electrostimulation with special waveforms enhances upper-limb motor function in patients with chronic stroke: a pilot randomized controlled trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) and intermittent theta burst stimulation (iTBS) were both demonstrated to have therapeutic potentials to rapidly induce neuroplastic effects in various rehabilitation training regimens. Recently, we developed a novel transcranial electrostimulation device that can flexibly output an electrical current with combined tDCS and iTBS waveforms. However, limited studies have determined the therapeutic effects of this special waveform combination on clinical rehabilitation. Herein, we investigated brain stimulation effects of tDCS-iTBS on upper-limb motor function in chronic stroke patients. METHODS: Twenty-four subjects with a chronic stroke were randomly assigned to a real non-invasive brain stimulation (NIBS; who received the real tDCS + iTBS output) group or a sham NIBS (who received sham tDCS + iTBS output) group. All subjects underwent 18 treatment sessions of 1 h of a conventional rehabilitation program (3 days a week for 6 weeks), where a 20-min NIBS intervention was simultaneously applied during conventional rehabilitation. Outcome measures were assessed before and immediately after the intervention period: Fugl-Meyer Assessment-Upper Extremity (FMA-UE), Jebsen-Taylor Hand Function Test (JTT), and Finger-to-Nose Test (FNT). RESULTS: Both groups showed improvements in FMA-UE, JTT, and FNT scores after the 6-week rehabilitation program. Notably, the real NIBS group had greater improvements in the JTT (p = 0. 016) and FNT (p = 0. 037) scores than the sham NIBS group, as determined by the Mann-Whitney rank-sum test. CONCLUSIONS: Patients who underwent the combined ipsilesional tDCS-iTBS stimulation with conventional rehabilitation exhibited greater impacts than did patients who underwent sham stimulation-conventional rehabilitation in statistically significant clinical responses of the total JTT time and FNT after the stroke. Preliminary results of upper-limb functional recovery suggest that tDCS-iTBS combined with a conventional rehabilitation intervention may be a promising strategy to enhance therapeutic benefits in future clinical settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04369235. Registered on 30 April 2020.

Effectiveness of pulmonary rehabilitation in COVID-19 respiratory failure patients post-ICU.

INTRODUCTION: Some COVID-19 patients develop respiratory failure requiring admission to intensive care unit (ICU). We aim to evaluate the effects of pulmonary rehabilitation (PR) post-ICU in COVID-19 patients. METHODS: Twenty-one COVID-19 patients were evaluated pre- and post-PR and compared retrospectively to a non-COVID-19 group of 21 patients rehabilitated after ICU admission due to respiratory failure. RESULTS: PR induced greater 6-min walking distance improvement in COVID-19 patients (+205 ± 121 m) than in other respiratory failure patients post-ICU (+93 ± 66 m). The sooner PR was performed post-ICU, the better patients recovered. CONCLUSIONS: PR induced large functional improvements in COVID-19 patients post-ICU although significant physical and psychosocial impairments remained post-PR.

Aggressive nutrition therapy in malnutrition and sarcopenia.

Aggressive nutrition therapy is essential to improve nutrition and function in patients with malnutrition and sarcopenia. Malnutrition and sarcopenia negatively affect functional recovery and activities of daily living. Nutrition improvement is associated with better functional recovery. Target energy intake in aggressive nutrition therapy is defined as total energy expenditure (TEE) plus the amount of energy accumulated. The amount of energy accumulation per 1 kg of body weight is generally 7500 kcal. If the goal is to gain 1 kg of weight over 30 d, TEE + 250 kcal is the target daily energy intake. Aggressive nutrition therapy is implemented using a rehabilitation nutrition care process, which consists of five steps: assessment and diagnostic reasoning, diagnosis, goal setting, intervention, and monitoring. Aggressive nutrition therapy sets clear goals using the Specific, Measurable, Achievable, Relevant, and Time-bound principles. The application and effect of aggressive nutrition therapy differs depending on the etiology and condition of malnutrition. Precachexia, short bowel syndrome, and older people with mild to moderate dementia are indications for aggressive nutrition therapy. Nevertheless, aggressive nutrition therapy is usually contraindicated in cases of refractory cachexia, acute disease or injury with severe inflammation, and bedridden patients with severe dementia and reduced activity. Aggressive nutrition therapy should be combined with aggressive exercise and rehabilitation. Enhanced nutritional therapy combined with rehabilitation in patients with cerebrovascular disease, hip fracture, or acute disease is recommended in the 2018 clinical practice guidelines for rehabilitation nutrition. Further evidence for aggressive nutrition therapy is however required.