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Objective: There is a growing importance for the home-based (HB) support services, and computerized cognitive training (CCT) has been reported as an effective intervention for cognitive impairment. However, there is still a need for further verification of the effect of HB-CCT. This study aimed to determine the effectiveness of HB-CCT on the cognitive function of community-dwelling adults with mild cognitive impairment (MCI) as well as safety in its use. Methods: Fifty community-dwelling adults with MCI were included, of which 25 each were randomized to either HB-CCT or control groups. Evaluations of comprehensive cognition, memory, attention, language, executive function, and depression were performed before and after the intervention, including three times a week for eight weeks in the intervention group and eight weeks apart with no intervention in the control group. Results: In baseline and post-evaluation comparisons, the HB-CCT group showed significant improvements, while the control group did not show significant changes. Statistically significant variations were noted between the HB-CCT and control groups in all post-intervention evaluations relative to baseline. Additionally, no side effects were observed. Conclusion: Beneficial effects on cognition and depression were noted in the intervention group compared with the control group, suggesting that HB-CCT may be a positive tool for cognitive improvement in adults with MCI.

Exposure to particulate matter (PM), especially PM2.5, is known to exacerbate asthma, posing a significant public health risk. This study investigated the asthma-reducing effects of photobiomodulation (PBM) in a mice model mimicking allergic airway inflammation exacerbated by PM2.5 exposure. The mice received sensitization with ovalbumin (OVA) and were subsequently treated with PM2.5 at a dose of 0.1 mg/kg every 3 days, for 9 times over 3 weeks during the challenge. PBM, using a 610 nm wavelength LED, was applied at 1.7 mW/cm2 to the respiratory tract via direct skin contact for 20 min daily for 19 days. Results showed that PBM significantly reduced airway hyperresponsiveness, plasma immunoglobulin E (IgE) and OVA-specific IgE, airway inflammation, T-helper type 2 cytokine, histamine and tryptase in bronchoalveolar lavage fluid (BALF), and goblet cell hyperplasia in PM2.5-exposed asthmatic mice. Moreover, PBM alleviated subepithelial fibrosis by reducing collagen deposition, airway smooth muscle mass, and expression of fibrosis-related genes. It mitigated reactive oxygen species generation, oxidative stress, endoplasmic reticulum stress, apoptotic cell death, ferroptosis, and modulated autophagic signals in the asthmatic mice exposed to PM2.5. These findings suggest that PBM could be a promising intervention for PM2.5-induced respiratory complications in patients with allergic asthma.

Background Information on the long‐term prognosis in patients with isolated thalamic stroke is sparse. We report the functional outcomes of patients with thalamic stroke up to 24 months from the KOSCO (Korean Stroke Cohort for Functioning and Rehabilitation) study. Methods and Results Isolated thalamic stroke was defined as the presence of lesions solely in the thalamus, excluding cases with lesions in other brain parenchyma areas apart from the thalamus, as identified by brain magnetic resonance imaging or computed tomography scans. The Fugl‐Meyer Assessment, the Functional Ambulatory Category, the Korean Mini‐Mental State Examination, the American Speech‐Language‐Hearing Association National Outcome Measurement System Swallowing Scale, and the short version of the Korean Frenchay Aphasia Screening Test were used to assess physical impairment. The Functional Independence Measure and modified Rankin Scale were used to assess functional outcomes. All measurements were conducted up to 24 months poststroke. A total of 297 patients were included, consisting of 235 with ischemic and 62 with hemorrhagic stroke. Except for the Functional Ambulatory Category and Functional Independence Measure, all physical impairments showed significant improvement up to 3 months poststroke (P

Long-term changes in caregiver burden should be clarified considering that extended post-stroke disability can increase caregiver stress. We assessed long-term changes in caregiver burden severity and its predictors. This study was a retrospective analysis of the Korean Stroke Cohort for Functioning and Rehabilitation. Patients with an acute first-ever stroke were enrolled from August 2012 to May 2015. Data were collected at 6 months and 6 years after stroke onset. The caregiver burden was measured with a subjective caregiver burden questionnaire based on the Korean version of the Caregiver Burden Inventory. The caregivers’ characteristics and patients’ clinical and functional status were also examined at each follow-up. A high caregiver burden, which suggests a risk of burnout, was reported by 37.9% and 51.7% of caregivers at 6 months and 6 years post-stroke, respectively. Both the caregiver burden total score and proportion of caregivers at risk of burnout did not decrease between 6 months and 6 years. The patients’ disability (OR = 11.60; 95% CI 1.58–85.08; p = 0.016), caregivers’ self-rated stress (OR = 0.03; 95% CI 0.00–0.47; p = 0.013), and caregivers’ quality of life (OR = 0.76; 95% CI 0.59–0.99; p = 0.042) were burden predictors at 6 months. At 6 years, only the patients’ disability (OR = 5.88; 95% CI 2.19–15.82; p < 0.001) and caregivers’ psychosocial stress (OR = 1.26; 95% CI 1.10–1.44; p = 0.001) showed significance. Nearly half of the caregivers were at risk of burnout, which lasted for 6 years after stroke onset. The patients’ disability and caregivers’ stress were burden predictors in both subacute and chronic phases of stroke. The findings suggest that consistent interventions, such as emotional support or counseling on stress relief strategies for caregivers of stroke survivors, may reduce caregiver burden. Further research is needed to establish specific strategies appropriate for Korean caregivers to alleviate their burden in caring for stroke patients.

This study aimed to examine the physical activity and exercise status of stroke patients in the community after discharge and the need for community-based exercises. This study included 100 community-dwelling patients with stroke in South Korea. The survey investigated the self-assessment of health status and physical activity, demand for community-based exercise after discharge, quality of life, and social participation. Overall, 96% of the respondents recognized the need to exercise, and two-thirds exercised. The third who did not exercise cited disability (29%), lack of facilities (22%), and health concerns (13%); only 21% of participants had ever used a community exercise facility, and their satisfaction with the facility was low. The main reasons for not using community exercise facilities were concerns about accidents during exercise and accessibility issues. Among real-world community stroke patients, those who exercised regularly had higher EuroQol-5D and reintegration to normal living indices than those who did not exercise (p < 0.05). Although community-dwelling stroke patients were highly aware of the need for physical activity and exercise, few engaged in adequate exercise. This lack of engagement is directly linked to identifiable personal and socio-structural barriers. Addressing these barriers will improve the quality of life and social participation of patients with stroke.

Autonomic dysfunction is a common complication of acute stroke, which impairs functional outcomes and increases mortality. There is a lack of well-established knowledge regarding the influence of autonomic dysfunction in patients with acute stroke. This study aims to investigate the impact of the severity of autonomic dysfunction on functional outcomes in patients with acute stroke. A retrospective analysis was conducted at a single center, involving 22 patients diagnosed with acute stroke. The severity of autonomic dysfunction was evaluated based on the Composite Autonomic Scoring Scale (CASS). The modified Barthel Index, Berg Balance Scale, Functional Ambulatory Category, and modified Rankin Scale were designated as functional outcome measures. The impact of the severity of autonomic dysfunction on functional outcomes was analyzed using one-way analysis of covariance (ANCOVA). A statistically significant difference was observed between the initial and follow-up functional outcomes based on the severity of autonomic dysfunction. This study presents evidence that the severity of autonomic dysfunction influences functional prognosis in patients with acute stroke. The findings will serve as additional considerations for the rehabilitation of patients with acute stroke.

IntroductionRheumatoid arthritis (RA) is a chronic destructive inflammatory disease that afflicts over one percent of the world’s population. Current pharmacological treatments remain relatively ineffective. In this context, photobiomodulation (PBM) is a potential resource for the treatment of RA. This study investigates investigate the anti-arthritic effects and related mechanisms of PBM on fibroblast-like synoviocytes (FLSs) from RA patients and a mouse model of collagen-induced arthritis (CIA).MethodsThe RA-FLSs were irradiated with a light emitting diode (LED) at a wavelength of 610 nm for 20 min, and the corresponding power intensities were 5 and 10 mW/cm2. After the LED irradiation, cell viability, proliferation, migration, and invasion assays were performed. Male DBA/1J mice were used to establish an animal model of CIA. Light stimulation with 10 mW/cm2 was applied to the ankle joints via direct contact with the skin for 40 min, daily for 2 weeks.Results and DiscussionPBM significantly reduced tumor necrosis factor (TNF)-α-induced increase in proliferation, migration, and invasion in RA-FLSs, and downregulated the activation of nuclear factor-κappa B (NF-κB) and NLRP3 inflammasome by TNF-α. Moreover, PBM greatly inhibited the induction and development of CIA, resulting in the inhibition of synovial inflammation and cartilage degradation. PBM therapy decreased the serum levels of pro-inflammatory cytokines, while increasing the anti-inflammatory cytokines. PBM suppressed the translocation of NF-κB and activation of NLRP3 inflammasome in the ankle joint. Furthermore, PBM showed a more pronounced anti-arthritic effect when combined with methotrexate (MTX), a disease-modifying anti-rheumatic drug (DMARD). The results showed that the effectiveness of MTX + PBM in CIA is superior to that of either MTX or PBM and that both work synergistically. Therefore, PBM with LED may be a potential therapeutic intervention for against RA.

ObjectivesThe purpose of this study was to cluster long-term multifaceted functional recovery patterns and to establish prediction models for functional outcome in first-time stroke patients using unsupervised machine learning.MethodsThis study is an interim analysis of the dataset from the Korean Stroke Cohort for Functioning and Rehabilitation (KOSCO), a long-term, prospective, multicenter cohort study of first-time stroke patients. The KOSCO screened 10,636 first-time stroke patients admitted to nine representative hospitals in Korea during a three-year recruitment period, and 7,858 patients agreed to enroll. Early clinical and demographic features of stroke patients and six multifaceted functional assessment scores measured from 7 days to 24 months after stroke onset were used as input variables. K-means clustering analysis was performed, and prediction models were generated and validated using machine learning.ResultsA total of 5,534 stroke patients (4,388 ischemic and 1,146 hemorrhagic; mean age 63·31 ± 12·86; 3,253 [58.78%] male) completed functional assessments 24 months after stroke onset. Through K-means clustering, ischemic stroke (IS) patients were clustered into five groups and hemorrhagic stroke (HS) patients into four groups. Each cluster had distinct clinical characteristics and functional recovery patterns. The final prediction models for IS and HS patients achieved relatively high prediction accuracies of 0.926 and 0.887, respectively.ConclusionsThe longitudinal, multi-dimensional, functional assessment data of first-time stroke patients were successfully clustered, and the prediction models showed relatively good accuracies. Early identification and prediction of long-term functional outcomes will help clinicians develop customized treatment strategies.

Objective To investigate long-term and serial functional outcomes in ischemic stroke patients without diabetes with post-stroke hyperglycemia. Methods The Korean Stroke Cohort for Functioning and Rehabilitation (KOSCO) is a large, multi-center, prospective cohort study of stroke patients admitted to participating hospitals in nine areas of Korea. From KOSCO, ischemic stroke patients without diabetes were recruited and divided into two groups: patients without diabetes without (n=779) and with post-stroke hyperglycemia (n=223). Post-stroke hyperglycemia was defined as a glucose level >8 mmol/L. Functional assessments were performed 7 days and 3, 6, and 12 months after stroke onset. Results There were no significant differences in baseline characteristics between the groups, except in the age of onset and smoking. Analysis of the linear correlation between the initial National Institutes of Health Stroke Scale (NIHSS) score and glucose level showed no significant difference. Among our functional assessments, NIHSS, Fugl-Meyer Assessment (affected side), Functional Ambulatory Category, modified Rankin Scale, and Korean Mini-Mental State Examination (K-MMSE) showed statistically significant improvements in each group. All functional improvements except K-MMSE were significantly higher in patients without post-stroke hyperglycemia at 7 days and 3, 6, and 12 months. Conclusion The glucose level of ischemic stroke patients without diabetes had no significant correlation with the initial NIHSS score. The long-term effects of stress hyperglycemia showed worse functional outcomes in ischemic stroke patients without diabetes with post-stroke hyperglycemia.

It has been reported that lettuce and its bioactive compounds enhance the host immune system by acting as immune modulators. This study aimed to identify the immunological effect of fermented lettuce extract (FLE) on macrophages. To evaluate the efficacy of FLE in enhancing macrophage function, we measured and compared the levels of macrophage activation-related markers in FLE- and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Treatment with FLE activated RAW 264.7 macrophages, increased their phagocytic ability, and increased the production of nitric oxide (NO) and pro-inflammatory cytokine levels—similar to LPS. The effects of FLE on M1/M2 macrophage polarization were investigated by determining M1 and M2 macrophage transcript markers in mouse peritoneal macrophages. The FLE-related treatment of peritoneal macrophages enhanced the expression of M1 markers but reduced IL-4 treatment-induced M2 markers. After the generation of tumor-associated macrophages (TAMs), alterations in the levels of M1 and M2 macrophage markers were measured after treatment with FLE. The FLE-related treatment of TAMs increased the expression and production of pro-inflammatory cytokines and also led to the enhanced apoptosis of pancreatic cancer cells. These findings suggest that FLE may be useful for macrophage-targeted cancer therapy because of its ability to regulate the activation and polarization of macrophages in the tumor microenvironment.

To identify cancer/testis (CT) antigens and immunogenic proteins, immunoscreening of testicular and small-cell lung cancer cell line NCI-H889 cDNA libraries was performed using serum obtained from a small-cell lung cancer (SCLC) patient. We obtained 113 positive cDNA clones comprised of 74 different genes, designated KP-SCLC-1 through KP-SCLC-74. Of these genes, 59 genes were found to be related to cancers by EMBASE analysis. Three of these antigens, including KP-SCLC-29 (NOL4), KP-SCLC-59 (CCDC83), and KP-SCLC-69 (KIF20B), were CT antigens. RT-PCR and western blot analysis showed that NOL4 was frequently present in small-cell lung cancer cell lines (8/9, 8/9). In addition, NOL4 mRNA was weakly, or at a low frequency, or not detected in various cancer cell lines. Our results reveal that NOL4 was expressed at protein levels in small-cell lung cancer tissues (10/10) but not detected in lung adenocarcinoma and squamous cell carcinoma by immunohistochemical analysis. Serological response to NOL4 was also evaluated by western blot assay using NOL4 recombinant protein. A humoral response against NOL4 proteins was detected in 75% (33/44) of small-cell lung cancer patients and in 65% (13/20) of healthy donors by a serological western blot assay. These data suggest that NOL4 is a specific target that may be useful for diagnosis and immunotherapy in SCLC.

The potential of transcranial direct current stimulation (tDCS) as a non-invasive brain stimulation technique for treating pain has been studied. However, its effectiveness in patients with central post-stroke pain (CPSP) and the impact of lesion location remain unclear. This study investigated tDCS’s pain reduction effects in patients with CPSP. Twenty-two patients with CPSP were randomized into the tDCS or sham groups. The tDCS group received stimulation of the primary motor cortex (M1) for 20 min, five times weekly, for two weeks, and underwent evaluations at baseline, immediately after the intervention, and one week after the intervention. The tDCS group had no significant improvement compared to the sham group in pain, depression, and quality of life. Nevertheless, significant changes were identified within the tDCS group, and the pain trends appeared to be influenced by the lesion location. These findings provide important insights into the use of tDCS in patients with CPSP, which could inform further research and development of pain treatment options.

Abstract Photobiomodulation (PBM) has received attention due to its potential for improving tissue function and enhancing regeneration in stroke. A lightweight, compact, and simple system of miniaturized electronic devices consisting of packaged light‐emitting diodes (LEDs) that incorporates a flexible substrate for in vivo brain PBM in a mouse model is developed. Using this device platform, the preventive and therapeutic effects of PBM affixed to the exposed skull of mice in the photothrombosis and middle cerebral artery occlusion stroke model are evaluated. Among the wavelength range of 630, 850, and 940 nm LED array, the PBM with 630‐nm LED array is proved to be the most effective for reducing the infarction volume and neurological impairment after ischemic stroke. Moreover, the PBM with 630 nm LED array remarkably improves the capability of spatial learning and memory in the chronic poststroke phase, attenuates AIM2 inflammasome activation and inflammasome‐mediated pyroptosis, and modulates microglial polarization in the hippocampus and cortex 7 days following ischemic stroke. Thus, PBM may prevent tissue and functional damage in acute ischemic injury, thereby attenuating the development of cognitive impairment after stroke.

ObjectiveTo investigate the available evidence on early supported discharge (ESD) and transitional care (TC) delivery service in patients with cerebrovascular disease.MethodsA systematic literature search was conducted to collect all available evidence on the use of ESD and TC services. We included cluster-randomized pragmatic trials or randomized controlled trials (RCTs) that recruited patients with stroke or transient ischemic attack to receive either conventional care or any care service intervention that included rehabilitation or support provided by professional medical personnel with the aim of accelerating and supporting home discharge. Relevant data were electronically searched through international databases (Cochrane Library, EMBASE, and PubMed) and incorporated into a summary grid to investigate research outcomes and provide a narrative synthesis. Furthermore, we compared the outcomes in terms of length of hospital stay, patient and caregiver outcomes, and mortality through meta-analysis.ResultsWe identified and included a total of 20 publications of various original randomized studies. There were 18 studies conducted in western countries and 2 in eastern countries. The meta-analysis revealed a tendency that ESD or TC could decrease the length of hospital stay more than the usual care [standardized mean difference (SMD) −0.13; 95% confidence interval (CI) −0.31 to 0.04 days; P = 0.14]. Moreover, there was a tendency that ESD resulted in better activities of daily living (ADL) than usual care (SMD 0.29; 95% CI −0.04 to 0.61; P = 0.08). Patient outcome based on modified Rankin scale (mRS) score (SMD −0.11; 95% CI −0.38 to 0.17; P = 0.45] and mortality (odds ratio 0.80; 95% CI 0.56–1.17; P = 0.25) did not reveal any significant difference. The Caregiver Strain Index revealed no difference.ConclusionWe did not find a large effect size for the use of TC and ESD. When implementing the TC and ESD model from western to Asian countries, services should be prepared and implemented in accordance with national medical rehabilitation pathways for cerebrovascular disease.

Lettuce (Lactuca sativa L.) contains various bioactive compounds that can reduce the severity of inflammatory diseases. This study aimed to identify therapeutic effects and underlying mechanisms of fermented lettuce extract (FLE) containing stable nitric oxide (NO) on collagen-induced arthritis (CIA) in mice and fibroblast-like synoviocytes (MH7A line) from patients with rheumatoid arthritis (RA). DBA/1 mice were immunized with bovine type II collagen and orally administered FLE for 14 days. On day 36, mouse sera and ankle joints were collected for serological and histological analysis, respectively. Consuming FLE inhibited RA development, suppressing pro-inflammatory cytokine productions, synovial inflammation, and cartilage degradation. The therapeutic effects of FLE in CIA mice were similar to those of methotrexate (MTX), which is typically used to treat RA. In vitro, FLE suppressed the transforming growth factor-β (TGF-β)/Smad signaling pathway in MH7A cells. We also demonstrated that FLE inhibited TGF-β-induced cell migration, suppressed MMP-2/9 expression, inhibited MH7A cell proliferation, and increased the expression of autophagy markers LC3B and p62 in a dose-dependent manner. Our data suggest that FLE could induce autophagosome formations in the early of stages of autophagy while inhibiting their degradation in the later stages. In conclusion, FLE is a potential therapeutic agent for RA.

Objective To investigate longitudinal changes in language function in left-hemispheric ischemic stroke patients as well as factors that influence language recovery until 1 year after stroke onset. Methods We analyzed data from 235 patients with first-ever left-hemispheric ischemic stroke. All patients completed the Korean version of the Frenchay Aphasia Screening Test (K-FAST) at 7 days (T1), 3 months (T2), 6 months (T3), and 1 year (T4) after stroke onset. Repeated measures analysis of variance (ANOVA) was used to investigate changes in language function between time points. Subgroup analysis was performed according to the K-FAST scores at T1. Stroke lesion volume was assessed using diffusion tensor images, and involvement of language-related brain regions was examined. Multiple regression analysis was used to analyze factors influencing improvement of K-FAST score. Results The K-FAST scores at T1, T2, T3, and T4 differed significantly (p

Purpose: Community-dwelling stroke survivors have various unmet needs for rehabilitative management, but there is a lack of in-depth investigations on common health problems after stroke. Moreover, the association between unmet needs and health-related quality of life (HRQoL) has not been thoroughly investigated. This study aimed to investigate the unmet needs for rehabilitative management in common problems after stroke and their associations with HRQoL among community-dwelling stroke survivors.Methods: A face-to-face cross-sectional survey was conducted among community-dwelling stroke survivors visiting outpatient clinics of rehabilitation departments between June and October 2020 in three university-affiliated hospitals. Unmet needs for common problems after stroke were assessed across eight domains based on the post-stroke checklist: spasticity, dysphagia, communication, cognition, ambulation, pain/discomfort, anxiety/depression, and self-care. HRQoL was measured using the EuroQoL-5D three level (EQ-5D). The prevalence of unmet needs for rehabilitative management and their associations with the EQ-5D index were analyzed.Results: Among the 239 participants who responded to the survey, 63% (n = 150) were men. The mean age was 63 ± 13 years, and the mean duration of stroke onset was 55.6 months. Overall, 49% reported at least one unmet need, and the most frequently reported unmet needs were anxiety/depression (20.9%), self-care (20.9%), and pain/discomfort (18.0%). The highest proportion of unmet needs was in the anxiety/depression, communication, and cognition domains. Patients with unmet needs for cognition and pain/discomfort showed a significantly lower EQ-5D index, even after adjusting for age, sex, and modified Rankin scale scores. The total number of unmet needs was significantly correlated with a lower EQ-5D index (Pearson's r = −0.329, p < 0.001) in the multivariate linear regression model.Conclusions: Unmet rehabilitative needs are prevalent among community-dwelling stroke survivors, and the proportion of unmet needs was high among non-physical domains such as anxiety/depression. The number of unmet needs is an independent negative predictor of HRQoL. Systematic approaches to identify unmet needs and provide appropriate rehabilitative management are required in long-term stroke survivors.

Introduction: Early supported discharge (ESD) is a transitional care model aimed at facilitating post-acute stroke patients' discharge to home. Previous studies have demonstrated that ESD provides equivalent patient and caregiver outcomes with superior cost-effectiveness compared to conventional rehabilitation (CR). This study intends to examine the feasibility of ESD in Korea.Methods and Analysis: This study is designed as a multicenter assessor-blinded, randomized controlled trial. Ninety post-acute stroke patients with mild to moderate disability (modified Rankin Scale 1–3) will be recruited from three university hospitals (30 patients per hospital) in Korea and allocated to either the ESD group or the CR group in a 1:1 ratio. Patients in the ESD group will receive individualized discharge planning and goal setting, a 4-week home-based rehabilitation program, and liaison service to community-based resources by a multidisciplinary team. Patients in the CR group will receive rehabilitation practices according to their current hospital policy.Outcomes: The primary outcome is the Korean version of the modified Barthel Index, and the primary endpoint was post-onset 3 months. Clinical outcomes, patient/caregiver reported outcomes, and socioeconomic outcomes will be measured at baseline, 1 month after discharge, 2 months after discharge, and 3 months after onset.Discussion: The efficacy and cost-effectiveness of ESD can vary according to the healthcare system and sociocultural aspects. To establish ESD as an alternative transitional care model for post-acute stroke patients in Korea, its feasibility needs to be examined in prior. This study will add evidence on the applicability of ESD in Korea.Ethical Considerations: The study protocol was reviewed and approved by the Institutional Review Board of Seoul National University Bundang Hospital (IRB number B-2012/654-308). The study protocol was registered at ClinicalTrials.gov (Identifier NCT04720820). Disseminations will include submission to peer-reviewed journals and presentations at conferences.

BackgroundBrain disorders are gradually becoming the leading cause of death worldwide. However, the lack of knowledge of brain disease’s underlying mechanisms and ineffective neuropharmacological therapy have led to further exploration of optimal treatments and brain monitoring techniques.ObjectiveThis study aims to review the current state of brain disorders, which utilize transcranial electrical stimulation (tES) and daily usable noninvasive neuroimaging techniques. Furthermore, the second goal of this study is to highlight available gaps and provide a comprehensive guideline for further investigation.MethodA systematic search was conducted of the PubMed and Web of Science databases from January 2000 to October 2020 using relevant keywords. Electroencephalography (EEG) and functional near-infrared spectroscopy were selected as noninvasive neuroimaging modalities. Nine brain disorders were investigated in this study, including Alzheimer’s disease, depression, autism spectrum disorder, attention-deficit hyperactivity disorder, epilepsy, Parkinson’s disease, stroke, schizophrenia, and traumatic brain injury.ResultsSixty-seven studies (1,385 participants) were included for quantitative analysis. Most of the articles (82.6%) employed transcranial direct current stimulation as an intervention method with modulation parameters of 1 mA intensity (47.2%) for 16–20 min (69.0%) duration of stimulation in a single session (36.8%). The frontal cortex (46.4%) and the cerebral cortex (47.8%) were used as a neuroimaging modality, with the power spectrum (45.7%) commonly extracted as a quantitative EEG feature.ConclusionAn appropriate stimulation protocol applying tES as a therapy could be an effective treatment for cognitive and neurological brain disorders. However, the optimal tES criteria have not been defined; they vary across persons and disease types. Therefore, future work needs to investigate a closed-loop tES with monitoring by neuroimaging techniques to achieve personalized therapy for brain disorders.

Membrane-free stem cell extract (MFSCE) of human adipose tissues possesses various biological activities. However, the effects of MFSCE on blood–brain barrier dysfunction and brain damage are unknown. In this study, we determined the role of MFSCE in an ischemic stroke mouse model. Mice were treated with MFSCE once daily for 4 days and 1 h before ischemic damage. Experimental ischemia was induced by photothrombosis. Pretreatment with MFSCE reduced infarct volume and edema and improved neurological, as well as motor functions. Evans blue leakage and water content in the brain tissue were reduced by MFSCE pretreatment relative to those in the vehicle group. MFSCE increased the expression of the tight junction proteins zonula occludens 1 and claudin-5, as well as vascular endothelial-cadherin, but decreased that of matrix metalloproteinase 9. Notably, MFSCE treatment decreased cell death and the level of NOD-like receptor protein 3 inflammasome, consistent with the downregulated expression of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 in the ischemic brain. These effects might have occurred via the suppression of the expression of Toll-like receptor 4 and activation of nuclear factor-κB. The results highlighted the potential of MFSCE treatment as a novel and preventive strategy for patients at a high risk of ischemic stroke.

Most therapeutic candidates for treating attention-deficit hyperactivity disorder (ADHD) have focused on modulating the dopaminergic neurotransmission system with neurotrophic factors. Regulation of this system by transcranial direct current stimulation (tDCS) could contribute to the recovery of cognitive symptoms observed in patients with ADHD. Here, male spontaneously hypertensive rats (SHR) were subjected to consecutive high-definition tDCS (HD-tDCS) (20 min, 50 μA, current density 63.7 A/m2, charge density 76.4 kC/m2) over the prefrontal cortex. This treatment alleviated cognitive deficits, with an increase in tyrosine hydroxylase and vesicular monoamine transporter two and significantly decreased plasma membrane reuptake transporter (DAT). HD-tDCS application increased the expression of several neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF), and activated hippocampal neurogenesis. Our results suggest that anodal HD-tDCS over the prefrontal cortex may ameliorate cognitive dysfunction via regulation of DAT and BDNF in the mesocorticolimbic dopaminergic pathways, and therefore represents a potential adjuvant therapy for ADHD.

Mild cognitive impairment (MCI) is the clinical precursor of Alzheimer's disease (AD), which is considered the most common neurodegenerative disease in the elderly. Some MCI patients tend to remain stable over time and do not evolve to AD. It is essential to diagnose MCI in its early stages and provide timely treatment to the patient. In this study, we propose a neuroimaging approach to identify MCI using a deep learning method and functional near-infrared spectroscopy (fNIRS). For this purpose, fifteen MCI subjects and nine healthy controls (HCs) were asked to perform three mental tasks: N-back, Stroop, and verbal fluency (VF) tasks. Besides examining the oxygenated hemoglobin changes (ΔHbO) in the region of interest, ΔHbO maps at 13 specific time points (i.e., 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, and 65 s) during the tasks and seven temporal feature maps (i.e., two types of mean, three types of slope, kurtosis, and skewness) in the prefrontal cortex were investigated. A four-layer convolutional neural network (CNN) was applied to identify the subjects into either MCI or HC, individually, after training the CNN model with ΔHbO maps and temporal feature maps above. Finally, we used the 5-fold cross-validation approach to evaluate the performance of the CNN. The results of temporal feature maps exhibited high classification accuracies: The average accuracies for the N-back task, Stroop task, and VFT, respectively, were 89.46, 87.80, and 90.37%. Notably, the highest accuracy of 98.61% was achieved from the ΔHbO slope map during 20–60 s interval of N-back tasks. Our results indicate that the fNIRS imaging approach based on temporal feature maps is a promising diagnostic method for early detection of MCI and can be used as a tool for clinical doctors to identify MCI from their patients.

Assessment of functional independence and residual disability is very important for measuring treatment outcome after stroke. The modified Rankin Scale (mRS) and the modified Barthel Index (MBI) are commonly used scales to measure disability or dependence in activities of daily living (ADL) of stroke survivors. Lack of consensus regarding MBI score categories has caused confusion in interpreting stroke outcomes. The purpose of this study was to identify the optimal corresponding MBI and modified Rankin scale (mRS) grades for categorization of MBI. The Korean versions of the MBI (K-MBI) and mRS were collected from 5,759 stroke patients at 3 months after onset of stroke. The sensitivity and specificity were calculated at K-MBI score cutoffs for each mRS grade to obtain optimally corresponding K-MBI scores and mRS grades. We also plotted receiver operating characteristic (ROC) curves of sensitivity and specificity and determined the area under the curve (AUC). The K-MBI cutoff points with the highest sum of sensitivity and specificity were 100 (sensitivity 0.940; specificity 0.612), 98 (sensitivity 0.904; specificity 0.838), 94 (sensitivity 0.885; specificity 0.937), 78 (sensitivity 0.946; specificity, 0.973), and 55 (sensitivity 937; specificity 0.986) for mRS grades 0, 1, 2, 3, and 4, respectively. From this result, the K-MBI cutoff score range for each mRS grade can be obtained. For mRS grade 0, the K-MBI cutoff score is 100, indicating no associated score range. For mRS grades 1, 2, 3, 4, and 5, the K-MBI score ranges is from 99 to 98, 97 to 94, 93 to 78, 77 to 55, and under 54, respectively.The AUC for the ROC curve was 0.791 for mRS grade 0, 0.919 for mRS grade 1, 0.970 for mRS grade 2, 0.0 for mRS grade 3, and 0.991 for mRS grade 4. The K-MBI cutoff score ranges for representing mRS grades were variable; mRS grades 0, 1, and 2 had narrow K-MBI score ranges, while mRS grades 3, 4, and 5 exhibited broad K-MBI score ranges. mRS grade seemed to sensitively differentiate mild residual disability of stroke survivors, whereas K-MBI provided more specific information of the functional status of stroke survivors with moderate to severe residual impairment.

PURPOSE:To determine the comparability of choroidal thickness (ChT) measurements using swept source (SS) and spectral domain (SD) optical coherence tomography (OCT) devices in patients with pachychoroid diseases. METHODS:Patients with pachychoroid diseases were recruited. OCT scans were performed sequentially with a Cirrus HD OCT 5000 and Plex Elite 9000. Images were analyzed by two independent observers. Each image was independently measured twice by each observer to determine the intraobserver repeatability. RESULTS:A total of 55 eyes were included. The average ChT of the subfoveal area using SS-OCT and SD-OCT was 430.5 ± 68.1 and 428.5 ± 57.9 μm, respectively, which did not show a significant result as the main effect in the repeated-measure analysis of variance (P = 0.067). Using SS-OCT, the intraobserver intraclass correlation coefficient (ICC) of both observers was > 0.950 at every measured point, and the interobserver coefficient of repeatability (CR) of the subfoveal area was 45.1 μm (95% confidence interval (CI), 40.8-49.4). Using SD-OCT, the intraobserver ICC of both observers was > 0.800, and the interobserver CR of the subfoveal area was 71.2 μm (95% CI, 64.4-78.0). Additionally, the intraobserver and interobserver CRs showed significantly better repeatability in SS-OCT than SD-OCT in F-test. In patients with ChT ≥ 400 μm, the interobserver CRs of SS-OCT and SD-OCT were 48.4 (95% CI, 42.6-54.2) and 95.2 μm (95% CI, 83.9-106.6), respectively. In patients with a subfoveal active lesion, the interobserver CRs were 44.5 (95% CI, 37.6-51.4) and 100.1 μm (95% CI, 84.6-115.5), respectively. CONCLUSIONS:Although the ChT measurements were comparable between SS-OCT and SD-OCT devices in pachychoroid diseases, SD-OCT showed low reliability in patients with ChT ≥ 400 μm and subfoveal active lesions. SS-OCT would be therefore more suitable for observation and follow-up of choroidal structures in pachychoroid diseases.

PurposeTo determine the repeatability of superficial vessel density measurements using Spectral domain Ocular coherence tomography angiography(SD-OCTA) in patients diagnosed with retinal vein occlusion(RVO).DesignProspective observational study.SubjectsPatients who visited our retinal clinic from August 2017 to August 2018, diagnosed with RVO were recruited for the study.MethodsTwo consecutive 3×3 mm pattern scans were performed using the Cirrus HD-OCT 5000 along with AngioPlex software (Carl Zeiss Meditec) in each eye by single skilled examiner. All scans were analyzed using en face OCTA images to measure vessel density (VD) automatically. For further analysis of the effect of central macular thickness(CMT), eyes were divided into two groups according to CMT of 400μm (Group 1: CMT > 400μm, Group 2: CMT < 400μm). To identify factors affecting the repeatability of VD measurements, linear regression analyses were conducted for the coefficient of variation (CV) of VD by investigating demographics and ocular variables.Main outcome measuresThe intraclass correlation coefficient (ICC), coefficient of variation (CV) of VD measurements.ResultsA total of 57 eyes from 57 patients were examined: 35 eyes with BRVO and 22 eyes with CRVO. In all 57 eyes with RVO, the ICC and CV of the full VD(VD of 3mm diameter circle) were 0.800 and 10.61%, respectively. Univariate analyses showed that the mean CMT (B, 0.001; p 400μm) were 0.348 and 22.55% respectively. In group 2 (CMT < 400μm), the ICC and CV of the full VD were 0.910 and 7.76%, respectively.ConclusionsThe repeatability of VD measurement in eyes with RVO was reasonably comparable to previous studies. Repeatability of VD measurement was significantly affected by central macular thickness.

Oxidative stress and inflammation are key pathways responsible for the pathogenesis of asthma. Aquatic exercise (AE) has been proven to elicit a variety of biological activities such as anti-oxidant and anti-inflammatory effects. However, although proper forms of AE provide beneficial health effects, incorrect forms and types of AE are potentially injurious to health. Several studies have investigated AE, but the relationship between types of AE and asthma has not been fully elucidated. This study evaluated the effects of two types of AE according to resistance on ovalbumin (OVA)-induced allergic airway inflammation in mice. BALB/c mice were subjected to OVA sensitization and challenge, and then to different types of AE including, walking and swimming, in a pool filled with water to a height of 2.5 and 13 cm for 30 min, respectively. AE reduced OVA-induced eosinophilic inflammation, airway hyperresponsiveness, and serum immunoglobulin E level. AE significantly inhibited increases in interleukin (IL)-4, IL-5, IL-13, histamine, leukotriene D4, and tryptase levels in bronchoalveolar lavage fluid (BALF). AE also effectively suppressed mucus formation, lung fibrosis, and hypertrophy of airway smooth muscle within the lung tissues. This exercise markedly reduced the levels of malondialdehyde while increased glutathione and superoxide dismutase (SOD) activity in lung tissues. Furthermore, AE significantly decreased tumor necrosis factor-α, IL-6 levels, and prostaglandin E2 production in BALF. The inhibitory effects of swimming on the levels of biomarkers related to oxidative stress and inflammation were greater than that of walking. These effects may have occurred through upregulation of NF-E2-related factor 2/heme oxygenase-1 signaling and suppression of mitogen-activated protein kinase/nuclear factor-κB pathway. Cumulative results from this study suggest that AE might be beneficial in mitigating the levels of biomarkers related to oxidative stress and inflammation. Thus, this therapy represents a crucial non-pharmacological intervention for treatments of allergic airway inflammation.

The present pilot study was aimed at conducting a comparative analysis of the level of activation in the prefrontal cortex among a normal elderly group and amnestic and nonamnestic mild cognitive impairment (MCI) groups and investigating the presence of neural compensatory mechanisms according to types of MCI and different cognitive tasks. We performed functional near-infrared spectroscopy (fNIRS) along with cognitive tasks, including two-back test, Korean color word Stroop test, and semantic verbal fluency task (SVFT), to investigate hemodynamic response and the presence of neural compensation and neuroplasticity in the prefrontal cortex of patients with amnestic and nonamnestic MCI compared with a healthy elderly group. During the two-back test, there was no significant difference in the bilateral region-of-interest (ROI) analysis in the three groups. During the Stroop test, right-sided hyperactivation compared to the left side during the task was shown in the nonamnestic MCI and normal groups with statistical significance. Mean acc∆HbO2 on the right side was highest in the nonamnestic MCI group (0.30 μM) followed by the normal group (0.07 μM) and the amnestic MCI group (-0.10 μM). Otherwise, intergroup ROI analysis of acc∆HbO2 in these activated right sides showed no significant difference. During the VFT test, there was no significant difference in the bilateral region-of-interest analysis in the three groups. The highest mean acc∆HbO2 was shown in the normal group (0.79 μM) followed by the nonamnestic MCI group (0.52 μM) and the amnestic MCI group (0.21 μM). Otherwise, there was no significant difference between groups. The hemodynamic response during fNIRS showed different findings according to MCI types and cognitive tasks. Among the three tasks, the Stroop test showed results that were suggestive of neural compensatory mechanisms in the prefrontal cortex in nonamnestic MCI.

Electroacupuncture (EA) therapy via alternating current stimulation on the scalp over the motor cortex is used for the treatment of brain disorders. Perinatal hypoxia-ischemia (HI), a brain injury in newborns, leads to long-term neurologic complications. Here, we investigated whether EA could promote functional improvements and neurogenesis in a neonatal HI rat model. A neonatal HI rat model was induced by permanent ligation of the left carotid artery in postnatal day 7 pups. EA for neonatal HI rats was performed at 2 Hz (1, 3, or 5 mA; 20 min) from 4–6 weeks after birth. HI rats undergoing EA had improved motor and memory function, with the greatest improvement after 3 mA EA. The corpus callosum was significantly thicker and showed a significant increase in proliferating astrocytes in the 3 mA EA group. We observed proliferating cells and a greater number of newly developed neurons and astrocytes in the subventricular zone and dentate gyrus of the 3 mA EA group than in those of the HI group. These results suggest that EA promotes functional improvements following neonatal HI assault via the proliferation and differentiation of neural stem cells. This effect was the strongest after 3 mA EA, suggesting that this is the optimal treatment dose.

Robotic mirror therapy (MT), which allows movement of the affected limb, is proposed as a more effective method than conventional MT (CMT). To improve the rehabilitation effectiveness of post-stroke patients, we developed a sensory stimulation-based continuous passive motion (CPM)-MT system with two different operating protocols, that is, asynchronous and synchronous modes. To evaluate their effectiveness, we measured brain activation through relative and absolute power spectral density (PSD) changes of electroencephalogram (EEG) mu rhythm in three cases with CMT and CPM-MT with asynchronous and synchronous modes. We also monitored changes in muscle fatigue, which is one of the negative effects of the CPM device, based on median power frequency (MPF) and root mean square (RMS). Relative PSD was most suppressed when subjects used the CPM-MT system under synchronous control: 22.11%, 15.31%, and 16.48% on Cz, C3, and C4, respectively. The absolute average changes in MPF and RMS were 1.59% and 9.78%, respectively, with CPM-MT. Synchronous mode CPM-MT is the most effective method for brain activation, and muscle fatigue caused by the CPM-MT system was negligible. This study suggests the more effective combination rehabilitation system for MT by utilizing CPM and magnetic-based MT task to add action execution and sensory stimulation compared with CMT.

Repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) has been used for the modulation of stroke patients’ motor function. Recently, more challenging approaches have been studied. In this study, simultaneous stimulation using both rTMS and tDCS (dual-mode stimulation) over bilateral primary motor cortices (M1s) was investigated to compare its modulatory effects with single rTMS stimulation over the ipsilesional M1 in subacute stroke patients. Twenty-four patients participated; 12 participants were assigned to the dual-mode stimulation group while the other 12 participants were assigned to the rTMS-only group. We assessed each patient’s motor function using the Fugl-Meyer assessment score and acquired their resting-state fMRI data at two times: prior to stimulation and 2 months after stimulation. Twelve healthy subjects were also recruited as the control group. The interhemispheric connectivity of the contralesional M1, interhemispheric connectivity between bilateral hemispheres, and global efficiency of the motor network noticeably increased in the dual-mode stimulation group compared to the rTMS-only group. Contrary to the dual-mode stimulation group, there was no significant change in the rTMS-only group. These data suggested that simultaneous dual-mode stimulation contributed to the recovery of interhemispheric interaction than rTMS only in subacute stroke patients. This trial is registered with NCT03279640.

In this paper, a theory for detection of the absolute concentrations of oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbR) from hemodynamic responses using a bundled-optode configuration in functional near-infrared spectroscopy (fNIRS) is proposed. The proposed method is then applied to the identification of two fingers (i.e., little and thumb) during their flexion and extension. This experiment involves a continuous-wave-type dual-wavelength (760 and 830 nm) fNIRS and five healthy male subjects. The active brain locations of two finger movements are identified based on the analysis of the t- and p-values of the averaged HbOs, which are quite distinctive. Our experimental results, furthermore, revealed that the hemodynamic responses of two-finger movements are different: The mean, peak, and time-to-peak of little finger movements are higher than those of thumb movements. It is noteworthy that the developed method can be extended to 3-dimensional fNIRS imaging.