Ginkgo biloba extract ameliorates skin fibrosis in a bleomycin-induced mouse model of systemic sclerosis.

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by skin and internal organ fibrosis and obliterative vasculopathy. Few effective treatments are currently available for fibrosis in SSc, therefore, demand persists for novel therapies. Although use of Ginkgo biloba extract (GBE) has been reported to improve blood circulation and alleviate liver and lung fibrosis, its effect on skin fibrosis in SSc remains unclear. In this study, the effects and underlying mechanisms of GBE on skin fibrosis in bleomycin (BLM)-induced mouse model of SSc was investigated. GBE significantly reduced dermal thickness and protein levels of profibrotic factors in the BLM-induced SSc mouse model. Moreover, GBE inhibited the gene expression of profibrotic factors, such as COL1A1, α-SMA, and connective tissue growth factor (CTGF), in fibroblasts by suppressing transforming growth factor (TGF)-ß signaling. Furthermore, GBE inhibited the transdifferentiation of adipocytes into myofibroblasts. Thus, our findings suggest that GBE is a promising therapeutic candidate for the treatment of SSc.

Ultrasonographic Contrast and Therapeutic Effects of Hydrogen Peroxide-Responsive Nanoparticles in a Rat Model with Sciatic Neuritis.

Purpose: Peripheral nerve damage lacks an appropriate diagnosis consistent with the patient's symptoms, despite expensive magnetic resonance imaging or electrodiagnostic assessments, which cause discomfort. Ultrasonography is valuable for diagnosing and treating nerve lesions; however, it is unsuitable for detecting small lesions. Poly(vanillin-oxalate) (PVO) nanoparticles are prepared from vanillin, a phytochemical with antioxidant and anti-inflammatory properties. Previously, PVO nanoparticles were cleaved by H2O2 to release vanillin, exert therapeutic efficacy, and generate CO2 to increase ultrasound contrast. However, the role of PVO nanoparticles in peripheral nerve lesion models is still unknown. Herein, we aimed to determine whether PVO nanoparticles can function as contrast and therapeutic agents for nerve lesions. Methods: To induce sciatic neuritis, rats were administered a perineural injection of carrageenan using a nerve stimulator under ultrasonographic guidance, and PVO nanoparticles were injected perineurally to evaluate ultrasonographic contrast and therapeutic effects. Reverse transcription-quantitative PCR was performed to detect mRNA levels of pro-inflammatory cytokines, ie, tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2. Results: In the rat model of sciatic neuritis, PVO nanoparticles generated CO2 bubbles to increase ultrasonographic contrast, and a single perineural injection of PVO nanoparticles suppressed the expression of tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2, reduced the expression of F4/80, and increased the expression of GAP43. Conclusion: The results of the current study suggest that PVO nanoparticles could be developed as ultrasonographic contrast agents and therapeutic agents for nerve lesions.

RNF213 variant and autophagic impairment: A pivotal link to endothelial dysfunction in moyamoya disease.

Moyamoya disease (MMD) is closely associated with the Ring Finger Protein 213 (RNF213), a susceptibility gene for MMD. However, its biological function remains unclear. We aimed to elucidate the role of RNF213 in the damage incurred by human endothelial cells under oxygen-glucose deprivation (OGD). We analyzed autophagy in peripheral blood mononuclear cells (PBMCs) derived from patients carrying either RNF213 wildtype (WT) or variant (p.R4810K). Subsequently, human umbilical vein endothelial cells (HUVECs) were transfected with RNF213 WT (HUVECWT) or p.R4810K (HUVECR4810K) and exposed to OGD for 2 h. Immunoblotting was used to analyze autophagy marker proteins, and endothelial function was analyzed by tube formation assay. Autophagic vesicles were observed using transmission electron microscopy. Post-OGD exposure, we administered rapamycin and cilostazol as potential autophagy inducers. The RNF213 variant group during post-OGD exposure (vs. pre-OGD) showed autophagy inhibition, increased protein expression of SQSTM1/p62 (p < 0.0001) and LC3-II (p = 0.0039), and impaired endothelial function (p = 0.0252). HUVECR4810K during post-OGD exposure (versus pre-OGD) showed a remarkable increase in autophagic vesicles. Administration of rapamycin and cilostazol notably restored the function of HUVECR4810K and autophagy. Our findings support the pivotal role of autophagy impaired by the RNF213 variant in MMD-induced endothelial cell dysfunction.

Biofluid-based Biomarkers in Traumatic Brain Injury: A Narrative Review.

Traumatic brain injury (TBI) is a complex condition characterized by a multifaceted pathophysiology. It presents significant diagnostic and prognostic challenges in clinical settings. This narrative review explores the evolving role of biofluid biomarkers as essential tools in the diagnosis, prognosis, and treatment of TBI. In recent times, preclinical and clinical trials utilizing these biofluid biomarkers have been actively pursued internationally. Among the biomarkers for nerve tissue proteins are neuronal biomarkers like neuronal specific enolase and ubiquitin C-terminal hydrolase L1; astroglia injury biomarkers such as S100B and glial fibrillary acidic protein; axonal injury and demyelination biomarkers, including neurofilaments and myelin basic protein; new axonal injury and neurodegeneration biomarkers like total tau and phosphorylated tau; and others such as spectrin breakdown products and microtubule-associated protein 2. The interpretation of these biomarkers can be influenced by various factors, including secretion from organs other than the injury site and systemic conditions. This review highlights the potential of these biomarkers to transform TBI management and emphasizes the need for continued research to validate their efficacy, refine testing platforms, and ultimately improve patient care and outcomes.

Identification of VWA5A as a novel biomarker for inhibiting metastasis in breast cancer by machine-learning based protein prioritization.

Distant metastasis is the leading cause of death in breast cancer (BC). The timing of distant metastasis differs according to subtypes of BCs and there is a need for identification of biomarkers for the prediction of early and late metastasis. To identify biomarker candidates whose abundance level can discriminate metastasis types, we performed a high-throughput proteomics assay using tissue samples from BCs with no metastasis, late metastasis, and early metastasis, processed data with machine learning-based feature selection, and found that low VWA5A could be responsible for shorter duration of metastasis-free interval. Low expression of VWA5A gene in METABRIC cohort was associated with poor survival in BCs, especially in hormone receptor (HR)-positive BCs. In-vitro experiments confirmed tumor suppressive effect of VWA5A on BCs in HR+ and triple-negative BC cell lines. We found that expression of VWA5A can be assessed by immunohistochemistry (IHC) on archival tissue samples. Decreasing nuclear expression of VWA5A was significantly associated with advanced T stage and lymphatic invasion in consecutive BCs of all subtypes. We discovered lower expression of VWA5A as the potential biomarker for metastasis-prone BCs, and our results support the clinical utility of VWA5A IHC, as an adjunctive tools for prognostication of BCs.

Therapeutic efficacy and safety of home-based portable laser irradiation on patients with wrist pain: a single-blinded randomized controlled trial.

The purpose of this study is to confirm the effect of small, portable low-level laser therapy (light sources in square configuration: 830 nm GaAs diode 3.2 mW at the center, 4 × 650 nm InGaAIP diodes over the corners) treatment in reducing and enhancing hand function in patients with wrist pain. This study was a prospective, randomized, sham-controlled, and home-based self-therapy trial. A total of thirty subjects with wrist pain were enrolled. All participants received low-level laser therapy on painful area at the wrist. The experimental group (n = 15) received laser stimulation, while the control group (n = 15) received sham stimulation using identical equipment that generated only a red light without the laser output. Both groups self-treated for 30 min a day, 5 days per week for 3 weeks, total of 15 sessions. The primary outcome was assessed using a visual analogue scale (VAS) for wrist pain from 0 (painless) to 10 (extreme pain). The secondary outcomes were measured with patient-rated wrist evaluation (PRWE), grip strength, lateral, palmar, and tip pinch strength. Measures were taken before and after treatment. A total of thirty participants provided outcome data. After the intervention, both groups showed a significant decrease in VAS score, from 4.93 to 3.67 in experimental group, from 5.53 to 4.00 in control group (the experiment group: p = 0.020, the control group: p = 0.003). The experimental group showed a significant improvement in function scale score (p = 0.012), the control group did not. Lateral and pinch strength was significantly improved in the experimental group (p = 0.017) and in the control group (p = 0.034) respectively. There were no side effects in the patients. Medical laser irradiation is a portable and easy-to-use laser irradiator without side effects. Clinical Trial Registration number: KCT0006604.

Neuromuscular complications of the lower extremity after thrombectomy in a patient with superficial femoral artery occlusion: Case series.

BACKGROUND: Ischemia reperfusion (IR) injury may result in rhabdomyolysis and compartment syndrome when blood supply returns after thrombectomy for patients with acute limb ischemia. OBJECTIVE: We highlight the value of early diagnosis and treatment in post-thrombectomy patients with IR injuries in their lower legs. CASE DESCRIPTION: Two patients received thrombectomy due to left superficial femoral artery occlusion. Both patients complained of left calf pain during ambulation at the 1- and 3-day follow up post-thrombectomy, as well as a heating sensation, swelling, weakness, and sensory changes in the affected leg. For early diagnosis musculoskeletal ultrasounds were performed and in both cases revealed swelling and change of echogenicity in the left calf. To further diagnosis, magnetic resonance imaging of the left leg revealed limb IR-induced muscular injury and rhabdomyolysis, respectively. In both cases, an electrodiagnostic study revealed peripheral nerve injury in the left leg. Medications were provided for neuropathic pain control and early rehabilitation was performed to improve function. In both cases, patients reported during their follow-up that their pain and muscle weakness had improved. CONCLUSION: When post-thrombectomy calf pain occurs early evaluation and treatment should be performed to identify any potential IR injury.

The association between antibody responses and prolonged viable SARS-CoV-2 shedding in immunocompromised patients: a prospective cohort study.

Immunocompromised COVID-19 patients were prospectively enrolled from March to November 2022 to understand the association between antibody responses and SARS-CoV-2 shedding. A total of 62 patients were analyzed and the results indicated a faster decline in genomic and subgenomic viral RNA in patients with higher neutralizing and S1-specific IgG antibodies (both P < 0.001). Notably, high neutralizing antibody levels were associated with a significantly faster decrease in viable virus cultures (P = 0.04). Our observations suggest the role of neutralizing antibodies in prolonged virus shedding in immunocompromised patients, highlighting the potential benefits of enhancing their humoral immune response through vaccination or monoclonal antibody treatments.

Comparison of Ultrasound Contrast between H2O2-Responsive Nanoparticles and Microbubble Contrast According to Muscle Injury in Rat Models.

Ultrasound contrast agents are clinically used for diagnosis of internal organs, but ultrasound contrast agents are rarely applied clinically in musculoskeletal disorders. Our study aims to comparatively analyze the differences between ultrasonographic images through peri-injury injection of the clinically used microbubble and researched nanoparticle contrast agents in various muscular injury models. To compare contrast-enhanced images in different muscle injury models, we prepared groups of rats with sham, laceration, punch, contusion, and toxin injection injuries. We measured H2O2 levels using the Amplex Red assay by extracting tissue from the damaged area. As comparative contrast agents, SonoVue®, a commercially available microbubble contrast agent, and poly(vanillinoxalte) (PVO) nanoparticles, which are H2O2-responsive nanoparticles, were used. The difference in contrast between the two contrast agents was recorded as an ultrasound movie, and J-image software 1.53p was used to quantify and analyze the maximum and minimum echogenicity values of the images after contrast enhancement. In the Amplex red assay for the highest H2O2 level in each muscle injury model, the maximum level showed 24 h after the modeling. In the sham rats, PVO injection showed no increased echogenicity except at the needle insertion site, but SonoVue® injection showed increased echo signal throughout the injected muscle immediately after injection. One day after the preparation of the lesion, PVO and SonoVue® were injected into the lesion site and ultrasound was performed on the lesion site. After the injection of PVO nanoparticles, contrast enhancement was observed at the lesion site immediately. SonoVue® injections, on the other hand, showed a widespread pattern of echo signals and an increase in echo retention only at the lesion site over time, but this was not clear. There were statistically significant differences between the highest and lowest echogenicity in PVO and SonoVue® contrast-enhanced images in all models. Contrast enhancement lasted more than 3 h in the PVO injection, but disappeared within 3 h in the SonoVue® injection. PVO nanoparticles showed the possibility of physiologic contrast by CO2 generated by conjugation with H2O2 generated by muscle injuries, and SonoVue® injection observed the possibility of microbubble contrast as a contrast agent with a pooling effect that lasts longer on the lesion. Further research is needed to investigate the use of various ultrasound contrast agents, including nanoparticles, in musculoskeletal disorders, as well as the potential for further utilities of microbubble contrast agents.

Interactions between Polygenetic Variants and Lifestyle Factors in Hypothyroidism: A Hospital-Based Cohort Study.

Hypothyroidism is a prevalent endocrine disorder and is associated with a variety of metabolic disturbances. This study aimed to investigate the polygenic variants associated with hypothyroidism risk and the interaction of polygenic risk scores (PRS) with dietary patterns in influencing disease risk in 56,664 participants aged >40 in a hospital-based cohort. The participants were classified as having hypothyroidism (n = 870) diagnosed by a physician and no hypothyroidism (n = 55,794). Genetic variants associated with hypothyroidism were identified using a genome-wide association study (GWAS). Genetic variants interacting with each other were selected using a generalized multifactor dimensionality reduction analysis, and the PRS generated was evaluated for interaction with lifestyle parameters. Coffee, alcohol, meat intake, and a Korean balanced diet were inversely associated with hypothyroidism risk, as were selenium, copper, and manganese intakes. White blood cell (WBC) counts and serum alkaline phosphatase and triglyceride concentrations were positively associated with hypothyroidism risk, as were osteoporosis and thyroid cancer. The GMDR analysis generated a three-single nucleotide polymorphism (SNP) model comprising dual oxidase-1 (DUOX1)_rs1648314; thyroid-stimulating hormone receptor (TSHR)_rs75664963; and major histocompatibility complex, class-II, DQ Alpha-1 (HLA-DQA1)_rs17426593. The PRS derived from the three- and seven-SNP models were associated with a 2.11- and 2.32-fold increase in hypothyroidism risk, respectively. Furthermore, the PRS from the three-SNP model showed interactions with WBC counts, wherein the positive association with hypothyroidism risk was more pronounced in participants with low WBC counts than those with high WBC counts (≥4 × 109 /L). Dietary patterns, such as the plant-based diet (PBD) and the Western-style diet (WSD), along with smoking status, exhibited interactions with the PRS, influencing hypothyroidism risk. In participants with a high PRS, those in the high-PBD, low-WSD, and smoker groups had a higher proportion of hypothyroidism than those in the low-PBD, high-WSD, and non-smoker groups. In conclusion, genetic variants related to immunity and thyroid hormone secretion were linked to hypothyroidism risk, and their PRS interacted with PBD and WSD intake and smoking status. These results contribute to a better understanding of hypothyroidism and its prevention strategies for precision medicine intervention.

Ipsilateral Motor Evoked Potentials in a Preschool-age Child With Traumatic Brain Injury: A Case Report.

To the best of our knowledge, the upper age limit at which post-neonatal cerebral palsy (CP) can manifest remains uncertain. This uncertainty is attributed to the lack of objective parameters for assessing the developing brain. In a previous study, we reported that an ipsilateral corticospinal projection associated with brain injury, as manifested in the paretic hand of a CP patient, had never been observed in individuals aged > 2 years. In this case report, we present an instance of ipsilateral motor evoked potential (iMEP) in a girl whose traumatic brain injury occurred at the age of 4 years. This case is the oldest in which brain injury occurred and iMEP was maintained. In conclusion, iMEP can be a valuable indicator of motor system plasticity in the developing brain.

Clinical Practice Guideline for Stroke Rehabilitation in Korea-Part 1: Rehabilitation for Motor Function (2022).

This clinical practice guideline (CPG) is the fourth edition of the Korean guideline for stroke rehabilitation, which was last updated in 2016. The development approach has been changed from a consensus-based approach to an evidence-based approach using the Grading of Recommendations Assessment Development and Evaluation (GRADE) method. This change ensures that the guidelines are based on the latest and strongest evidence available. The aim is to provide the most accurate and effective guidance to stroke rehabilitation teams, and to improve the outcomes for stroke patients in Korea. Fifty-five specialists in stroke rehabilitation and one CPG development methodology expert participated in this development. The scope of the previous clinical guidelines was very extensive, making it difficult to revise at once. Therefore, it was decided that the scope of this revised CPG would be limited to Part 1: Rehabilitation for Motor Function. The key questions were selected by considering the preferences of the target population and referring to foreign guidelines for stroke rehabilitation, and the recommendations were completed through systematic literature review and the GRADE method. The draft recommendations, which were agreed upon through an official consensus process, were refined after evaluation by a public hearing and external expert evaluation.

Effects of Home Based Serious Game Training (Brain Talk™) in the Elderly With Mild Cognitive Impairment: Randomized, a Single-Blind, Controlled Trial.

Mild cognitive impairment (MCI) increases with aging society. Serious games may be effective in improving cognitive function in patients with MCI; however, research on their effects remains insufficient. This study aimed to confirm the efficacy and safety of cognitive rehabilitation training using a serious game (Brain Talk™) for the elderly with MCI. Twenty-four elderly individuals with MCI were randomized into study and control groups. The study group received 12 training sessions (30 min/session, 3 times/week), whereas the control group did not receive training. Blinded evaluations were conducted before and after the training and four weeks after the training. The primary outcome measures were the Korean Mini-Mental State Examination (K-MMSE) and K-MoCA (Korean Montreal Cognitive Assessment). Secondary outcome measures were the Semantic Verbal Fluency Task (SVFT), Trail-Making Test-B, and 2-back test. In the study group, the K-MMSE, K-MoCA, and SVFT scores after finishing the training and 4 weeks after training showed a significant increase; however, there was no significant change in the control group. No significant differences were observed between the two groups. Cognitive function significantly improved in the study group after training. Home-based serious games are considered helpful in improving cognitive function.

Short-Term Effectiveness of Oral Nirmatrelvir/Ritonavir Against the SARS-CoV-2 Omicron Variant and Culture-Positive Viral Shedding.

BACKGROUND: Information on the effectiveness of nirmatrelvir/ritonavir against the omicron is limited. The clinical response and viral kinetics to therapy in the real world need to be evaluated. METHODS: Mild to moderate coronavirus disease 2019 (COVID-19) patients with risk factors for severe illness were prospectively enrolled as a treatment group with nirmatrelvir/ritonavir therapy versus a control group with supportive care. Serial viral load and culture from the upper respiratory tract were evaluated for seven days, and clinical responses and adverse reactions were evaluated for 28 days. RESULTS: A total of 51 patients were analyzed including 40 in the treatment group and 11 in the control group. Faster symptom resolution during hospitalization (P = 0.048) was observed in the treatment group. Only minor adverse reactions were reported in 27.5% of patients. The viral load on Day 7 was lower in the treatment group (P = 0.002). The viral culture showed a positivity of 67.6% (25/37) vs. 100% (6/6) on Day 1, 0% (0/37) vs. 16.7 (1/6) on Day 5, and 0% (0/16) vs. 50.0% (2/4) on Day 7 in the treatment and control groups, respectively. CONCLUSIONS: Nirmatrelvir/ritonavir against the omicron was safe and resulted in negative viral culture conversion after Day 5 of treatment with better symptomatic resolution.

Comparison of intermittent pneumatic compression device and compression stockings for workers with leg edema and pain after prolonged standing: a prospective crossover clinical trial.

BACKGROUND: During prolonged standing, insufficient calf muscle pumping accompanies venous stasis and hypertension in the lower legs, resulting in valve dysfunction, venous wall problems, and sub-sequent inflammation. Compression therapy, which includes medical compression stockings (MCS) and mechanical intermittent pneumatic compression (IPC), is one of the most effective therapeutic interventions for treating chronic venous diseases. This study aimed to compare the therapeutic effect among resting, IPC and MCS alone, and IPC with MCS in long-standing workers (> 8 h daily). METHODS: This crossover trial was conducted with 39 participants with complaints of leg edema and pain whose work involved standing for more than 8 h daily. Four treatment protocols were established for each visit as follows: protocol A (not wear MCS during work and rest without IPC after work), protocol B (wear MCS during work and rest without IPC after work), protocol C (not wear MCS during work and treat with IPC after work), and protocol D (wear MCS during work and treat with IPC after work). The primary outcome was the visual analogue scale (VAS) score for leg pain. The secondary outcomes were leg volume (mL), circumference (cm), extracellular fluid/total body fluid (ECF/TBF), and extracellular water/total body water (ECW/TBW) through bioelectrical impedance analysis. Outcomes were assessed before work (T0), after work (T1), and 60 min after intervention (T2). RESULTS: All four protocols had significantly increased leg pain after work (T0-1) but improved 60 min after intervention (T1-2), particularly protocol C (decreased VAS by 1.9). When leg swelling was compared at T0 and T1, protocols A and C showed significant increases in leg volume and circumference, indicating significant work-induced edema, whereas protocols B and D showed no change or even a decrease. After interventions, leg volume and circumference significantly decreased in protocols A and C, although protocols B and C did not show significant improvement. The ECF/TBF and ECW/TBW of all protocols decreased after interventions. CONCLUSIONS: Leg pain and edema after prolonged standing (T1-T2) in adults were safely and effectively improved by both IPC alone and IPC with MCS. Although the use of MCS during the workday did not show improvement in leg pain immediately after work (T0-T1), both MCS with resting and MCS with IPC decreased leg pain at T1-T2 and prevented leg edema at T0-T1. TRIAL REGISTRATION: This trial protocol was registered at the Clinical Research Information Service (KCT0005383, the date of first registration: 08/09/2020).

Recovery of brachial plexus injury after bronchopleural fistula closure surgery based on electrodiagnostic study: A case report and review of literature.

BACKGROUND: Axillary thoracotomy and muscle flap are muscle- and nerve-sparing methods among the surgical approaches to bronchopleural fistula (BPF). However, in patients who are vulnerable to a nerve compression injury, nerve injury may occur. In this report, we present a unique case in which the brachial plexus (division level), suprascapular, and long thoracic nerve injury occurred after BPF closure surgery in a patient with ankylosing spondylitis and concomitant multiple joint contractures. CASE SUMMARY: A 52-year-old man with a history of ankylosing spondylitis with shoulder joint contractures presented with right arm weakness and sensory impairment immediately after axillary thoracotomy and latissimus dorsi muscle flap surgery for BPF closure. During the surgery, the patient was positioned in a lateral decubitus position with the right arm hyper-abducted for approximately 6 h. Magnetic resonance imaging and ultrasound revealed subclavius muscle injury or myositis with brachial plexus (BP) compression and related neuropathy. An electrodiagnostic study confirmed the presence of BP injury involving the whole-division level, long thoracic, and suprascapular nerve injuries. He was treated with medication, physical therapy, and ultrasound-guided injections. Ultrasound-guided steroid injection at the BP, hydrodissection with 5% dextrose water at the BP and suprascapular nerve, and intra-articular steroid and hyaluronidase injection at the glenohumeral joint were performed. On postoperative day 194, the pain and arm weakness were resolved, and a follow-up electrodiagnostic study showed marked improvement. CONCLUSION: Clinicians should consider the possibilities of multiple nerve injuries in patients with joint contracture, and treat each specific therapeutic target.

Aggravation of dysphagia after surgical removal of anterior cervical osteophytes: a case report.

Dysphagia induced by anterior cervical osteophytes (ACOs) is frequently reported in older individuals. Surgical resection of ACOs is considered when conservative treatment fails, but its effectiveness is controversial owing to side effects after surgery. We present the case of a 78-year-old man who complained of progressive dysphagia that started 10 months previously. A videofluoroscopic swallow study (VFSS) showed prominent ACOs along C2-C6, which translocated the upper hypopharynx anteriorly, impinging the lumen and impairing epiglottic folding and laryngeal closure. Aspiration of a soft diet was observed. Despite conservative therapy, the symptoms persisted, and ACO resection surgery was performed. Unexpectedly, the patient's dysphagia worsened immediately post-surgery. A VFSS on postoperative day (POD) 2 showed improvement in epiglottic folding. However, prevertebral soft tissue swelling and dysfunction of opening of the upper esophageal sphincter newly arose. Laryngeal aspiration was observed during 5 cc and a large amount of liquid swallowing trials. The patient was provided a modified diet and rehabilitative dysphagia therapy. A VFSS on PODs 6 and 14 showed a gradual improvement in the prevertebral soft tissue swelling. This report suggests that a serial VFSS is effective for evaluating the different mechanisms of dysphagia and for devising an appropriate treatment plan.

Home-Based Transcranial Direct Current Stimulation to Enhance Cognition in Stroke: Randomized Controlled Trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a promising tool for improving poststroke cognitive function. Home-based rehabilitation is increasingly required for patients with stroke, and additional benefits are expected if supplemented with remotely supervised tDCS (RS-tDCS). We evaluated the cognitive improvement effect and feasibility of RS-tDCS in patients with chronic stroke. METHODS: Twenty-six patients with chronic stroke and cognitive impairment (Korean version of the Montreal Cognitive Assessment [K-MoCA] score <26) were randomized into real and sham RS-tDCS groups and underwent concurrent computerized cognitive training and RS-tDCS. Patients and caregivers underwent training to ensure correct tDCS self-application, were monitored, and treated 5 d/wk for 4 weeks. We investigated several cognition tests including K-MoCA, Korean version of the Dementia Rating Scale-2, Korean-Boston Naming Test, Trail Making Test, Go/No Go, and Controlled Oral Word Association Test at the end of the training sessions and one month later. Repeated-measures ANOVA was used for comparison between the groups and within each group. The adherence rate of the appropriate RS-tDCS session was also investigated. RESULTS: In within-group comparison, unlike the sham group, the real group showed significant improvement in K-MoCA (Preal=0.004 versus Psham=0.132), particularly in patients with lower baseline K-MoCA (K-MoCA10-17; Preal=0.001 versus Psham=0.835, K-MoCA18-25; Preal=0.060 versus Psham=0.064) or with left hemispheric lesions (left; Preal=0.010 versus Psham=0.454, right; Preal=0.106 versus Psham=0.128). In between-group comparison, a significant difference was observed in K-MoCA in the lower baseline K-MoCA subgroup (K-MoCA10-17; Ptime×group=0.048), but no significant difference was found in other cognitive tests. The adherence rate of successful application of the RS-tDCS was 98.4%, and no serious adverse effects were detected. CONCLUSIONS: RS-tDCS is a safe and feasible rehabilitation modality for poststroke cognitive dysfunction. Specifically, RS-tDCS is effective in patients with moderate cognitive decline. Additionally, these data demonstrate the potential to enhance home-based cognitive training, although significant differences were not consistently found in between-group comparisons; therefore, further larger studies are needed. REGISTRATION: URL: https://cris.nih.go.kr; Unique identifier: KCT0003427.

Motor organization of unilateral polymicrogyria associated with ipsilateral brainstem atrophy - a case report.

BACKGROUND: Polymicrogyria refers to the disruption of normal cerebral cortical development late in neuronal migration or in early cortical organization. Although patients with polymicrogyria feature relatively favorable motor outcomes, polymicrogyric lesions accompanied by extensive unilateral hemispheric atrophy and ipsilateral brainstem atrophy may induce poorer motor outcomes. This study is the first to employ transcranial magnetic stimulation (TMS) and diffusion tensor imaging (DTI) to characterize changes to motor organization and white matter tracts induced by polymicrogyria. CASE PRESENTATION: We document a case of a 16-year-old female with left hemiplegic unilateral polymicrogyria associated with ipsilateral brainstem atrophy. Magnetic resonance imaging (MRI) of the brain revealed unilateral polymicrogyria to have affected anterior cortical areas, including the perisylvian region on the right side. The right halves of the brain and brainstem were significantly smaller than the left halves. Although our patient was found to exhibit cortical dysplasia of the right frontoparietal and sylvian fissure areas and a decreased number of fibers in the corticospinal tract (CST) of the affected side on DTI, the connectivity of the CST was preserved up to the motor cortex. We also measured the cross-sectional area of the CST at the level of the pons. In TMS, contralateral motor evoked potentials (MEPs) were evoked from both hands, but the ipsilateral MEPs were evoked only from the left hand. The left hand featured a long duration, polyphasic pattern of contralateral MEPs. DISCUSSION AND CONCLUSION: TMS revealed that the concurrent bilateral projections to the paretic hand from the affected and unaffected hemispheres and contralateral MEPs in the paretic hand were polyphasic, indicating delayed electrophysiological maturation or a pathologic condition of the corticospinal motor pathways. In DTI, the cross-sectional area of the CST at the level of the pons on the affected side was smaller than that on the unaffected side. These DTI findings reveal an inadequate CST volume. Despite extensive brain malformation and ipsilateral brainstem atrophy, our patient had less severe motor dysfunction and presented with involuntary mirror movements. Mirror movements in the paretic hand are considered to indicate ipsilateral corticospinal projections from the unaffected hemisphere and may suggest favorable motor outcomes in early brain injury.

Proteomics Analysis of Antitumor Activity of Agrimonia pilosa Ledeb. in Human Oral Squamous Cell Carcinoma Cells.

Oral cancer is a malignant neoplasm of oral cavity. It accounts for approximately 5% of all malignant tumors. Approximately 97% of all oral cancers are squamous cell carcinomas, followed by adenocarcinomas, and rarely malignant melanomas. It occurs particularly in males (twice as common in males than in females) of middle age (above 40 years). Agrimonia pilosa Ledeb. has traditionally been known for its effective antitumor activity and is currently used in China for cancer therapy. A. pilosa Ledeb. has been traditionally used for the treatment of abdominal pain, sore throat, headache, blood discharge, parasitic infections, and eczema in Korea and other Asian countries. Most studies on A. pilosa Ledeb. are related to the leaves and a few investigated the roots of the plant. However, detailed mechanisms of antitumor activity of A. pilosa Ledeb. have not been fully elucidated. Furthermore, to date, there have been no reports on the antitumor effect of A. pilosa Ledeb. in oral squamous cells. In this study, we used proteomic technology to observe changes in proteins related to anticancer activity of A. pilosa Ledeb. and identified target proteins among altered proteins to reveal the underlying mechanism of action.