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Electromechanical-assisted gait training may be an effective intervention to promote motor recovery after brain injury. However, many studies still have difficulties in clarifying the difference between electromechanical-assisted gait training and conventional gait training. To evaluate the effectiveness of electromechanical-assisted gait training compared to that of conventional gait training on clinical walking function and gait symmetry of stroke patients. We randomly assigned patients with stroke ( n  = 144) to a control group (physical therapist-assisted gait training) and an experimental group (electromechanical gait training). Both types of gait training were done for 30 min each day, 5 days a week for 4 weeks. The primary endpoint was the change in functional ambulatory category (FAC). Secondary endpoints were clinical walking functions and gait symmetries of swing time and step length. All outcomes were measured at baseline (pre-intervention) and at 4 weeks after the baseline (post-intervention). FAC showed significant improvement after the intervention, as did clinical walking functions, in both groups. The step-length asymmetry improved in the control group, but that in the experimental group and the swing-time asymmetry in both groups did not show significant improvement. In the subgroup analysis of stroke duration of 90 days, FAC and clinical walking functions showed more significant improvement in the subacute group than in the chronic group. However, gait symmetries did not show any significant changes in either the subacute or the chronic group. Electromechanically assisted gait training by EXOWALK was as effective as conventional gait training with a physiotherapist. Although clinical walking function in the subacute group improved more than in the chronic group, gait asymmetry did not improve for either group after gait training. Trial registration : KCT0003411 Clinical Research Information Service (CRIS), Republic of Korea.

Background Physical activity (PA) is an important risk factor associated with health outcomes. However, the relationship between PA and kidney function decline in older adults remains unclear. We examined the influence of PA on kidney function decline and mortality in community-dwelling older adults. Methods Adults aged ≥ 65 years with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m 2 who had available health checkup data from 2009 to 2010 were included. The cohort was followed annually through December 2015 for anthropometric, sociodemographic, and medical information including outcomes and biennially for laboratory information from the health checkup. We divided these patients into three groups according to self-reported PA (Inactive group: no leisure-time PA, Active group: vigorous activity for at least 80 min/week or a sum of moderate-intensity activity and walking for at least 300 min/week, Low-active group: level of PA between the definitions of the other two groups). Associations between the intensity of PA and death, cardiovascular death, and ≥ 50% eGFR decline were investigated. Results Among 102,353 subjects, 32,984 (32.23%), 54,267 (53.02%), and 15,102 (14.75%) were classified into the inactive, low-active, and active groups, respectively. The active group was younger, contained a higher proportion of men, and had higher frequencies of hypertension, diabetes mellitus, drinking, and smoking than the other groups. The active group had significantly lower incidence rates of mortality, cardiovascular mortality, and kidney function decline than the other groups (all p  < 0.001). The active group also showed lower all-cause (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.70–0.82) and cardiovascular mortality (HR, 0.64; 95% CI, 0.53–0.78) and protection against ≥ 50% eGFR decline (HR, 0.81; 95% CI, 0.68–0.97) compared with the inactive group in the fully adjusted Cox proportional hazards regression model. Conclusions High PA was an independent modifiable lifestyle factor for reducing mortality and protecting against declines in kidney function in older adults.

Recent reports using a breathing simulator system have suggested that mesh nebulizers provide more effective medication delivery than jet nebulizers. In this study, the performances of jet and mesh nebulizers were evaluated by comparing their aerosol drug delivery efficiencies in mice. We compared four home nebulizers: two jet nebulizers (PARI BOY SX with red and blue nozzles), a static mesh nebulizer (NE-U22), and a vibrating mesh nebulizer (NE-SM1). After mice were exposed to salbutamol aerosol, the levels of salbutamol in serum and lung were estimated by enzyme linked immunoassay (ELISA). The residual volume of salbutamol was the largest at 34.6% in PARI BOY SX, while the values for NE-U22 and NE-SM1 mesh nebulizers were each less than 1%. The salbutamol delivery efficiencies of NE-U22 and NE-SM1 were higher than that of PARI BOY SX, as the total delivered amounts of lung and serum were 39.9% and 141.7% as compared to PARI BOY SX, respectively. The delivery efficiency of the mesh nebulizer was better than that of the jet nebulizer. Although the jet nebulizer can generate smaller aerosol particles than the mesh nebulizer used in this study, the output rate of the jet nebulizer is low, resulting in lower salbutamol delivery efficiency. Therefore, clinical validation of the drug delivery efficiency according to nebulizer type is necessary to avoid overdose and reduced drug wastage.

Background:Mesenchymal stem cells (MSCs) can be used for a wide range of therapeutic applications because of not only their differentiation potential but also their ability to secrete bioactive factors. Recently, several studies have suggested the use of human embryonic stem cell-derived MSCs (hE-MSCs) as an alternative for regenerative cellular therapy due to mass production of MSCs from a single donor.Methods:We generated hE-MSCs from embryonic stem cell lines, SNUhES3, and analyzed immune properties of these cells. Also, we evaluated the in-vivo therapeutic potential of hE-MSCs in immune-mediated inflammatory skin disease. Results:The cell showed the suppression of immunity associated with allogenic peripheral blood mononuclear cells in mixed lymphocyte response assay. We also detected that cytokines and growth factor related to the immune response were secreted from these cells. To assessed the in-vivo therapeutic potential of hE-MSCs in immune-mediated inflammatory skin disease, we used imiquimod (IMQ)-induced skin psoriasis mouse model. The score of clinical skin was significantly reduced in the hE-MSCs treated group compared with control IMQ group. In histological analysis, the IMQ-induced epidermal thickness was significantly decreased by hE-MSCs treatment. It was correlated with splenomegaly induced by IMQ which was also improved in the hE-MSCs. Moreover, IMQ-induced inflammatory cytokines; Th1 cytokines (TNF-α, IFN-α, IFN-γ,and IL-27) and Th17 cytokines (IL-17A and IL-23), in the serum and skin showed marked inhibition by hE-MSCs.Conclusion:These results suggested that hE-MSCs have a potency of immune modulation in psoriasis, which might be the key factor for the improved psoriasis.

Background High-intensity repetitive task-specific practice might be the most effective strategy to promote motor recovery after stroke, and electromechanical-assisted gait training represents one of the treatment options. However, there is still difficulty in clarifying the difference between conventional gait training and electromechanically assisted gait training. Methods The study is a multicenter, randomized, parallel-group clinical trial for stroke patients. Three clinical research centers in Korea (Dongguk University Ilsan Hospital, Chungnam National University Hospital, and Seoul National University Bundang Hospital) will participate in the clinical trial and 144 stroke patients will be registered. Enrolled patients are assigned to two groups, an experimental group and a control group, according to a randomization table. In addition, patients are treated for half an hour (one session) five times a week for 4 weeks. Both groups carry out basic rehabilitation (central nervous system development therapy and strength exercise) and the experimental group executes robotic walking rehabilitation treatment, and the control group executes conventional gait rehabilitation treatment. The primary endpoint variable is the Functional Ambulation Category (FAC) that determines the degree of independent walking and is measured before, after, and after 4 weeks of treatment. Secondary endpoint variables are 11 variables that take into account motor function and range, measured at the same time as the primary endpoint variable. Discussion There are still insufficient data on the effectiveness of electromechanical-assisted gait training for stroke patients and large-scale research is lacking. Thus, the research described here is a large-scale study of stroke patients that can supplement the limitations mentioned in other previous studies. In addition, the clinical studies described here include physical epidemiological analysis parameters that can determine walking ability. The results of this study can lead to prove the generalizable effectiveness and safety of electromechanical-assisted gait training with EXOWALK®. Trial registration Clinical Research Information Service (CRIS), Republic of Korea KCT0003411, Registered on 30 October 2018

The prevalence of allergic rhinitis (AR), an inflammatory disease, is gradually increasing. Studies have reported that moxibustion is effective for treating AR. Electric heating moxibustion (EM) was developed to offer adaptable heat stimulation without the generation of smoke. The objective of this study was to examine the possibility of EM in treating perennial allergic rhinitis (PAR) and to assess the feasibility of using this technique on a larger scale by comparing EM with acupuncture (AC). A randomized pilot study was conducted on 40 patients with PAR. Patients were randomly assigned to one of two treatment groups: EM or AC. The primary outcome measure was the change in the total nasal symptom score (TNSS) between before and after treatment. The secondary outcome measures were the changes in the rhinoconjunctivitis quality of life questionnaire (RQLQ), nasal endoscopy index for pattern identification, pattern identification questionnaire for AR, total serum immunoglobulin E (IgE), eosinophil count, and adverse effects (AEs). The results showed a statistically significant improvement in mean TNSS and RQLQ scores in both groups (p < 0.05), but no significant difference between the two groups. However, mean changes in itching and sneezing TNSS were significantly higher in the AC group. There was no significant difference in total serum IgE or eosinophil count before versus after treatment, nor was there any significant difference of three pattern subgroups between the two groups in the mean TNSS change. While the AC group reported two treatment-related AEs, there were no treatment-related AEs in the EM group. This trial provides evidence that EM isa safe alternative treatment for patients with PAR. ClinicalTrials.gov, NCT03342105. Registered on 14 November 2017. •Electric heating moxibustion treatment reduce symptoms and promoted quality of life of perennial allergic rhinitis patients.•No treatment-related adverse events were reported in the electric heating moxibustion group.•Our findings suggest that electric heating moxibustion can be considered as a safe alternative treatment.

KELCH-ECH-associated protein 1 (KEAP1) is an adaptor protein of Cullin 3 (CUL3) E3 ubiquitin ligase that targets a redox sensitive transcription factor, NF-E2-related factor 2 (NRF2). BRCA1-associated protein 1 (BAP1) is a tumor suppressor and deubiquitinase whose mutations increase the risk of several types of familial cancers. In the present study, we have identified that BAP1 deubiquitinates KEAP1 by binding to the BTB domain. Lentiviral transduction of BAP1 decreased the expression of NRF2 target genes, suppressed the migration and invasion, and sensitized cisplatin-induced apoptosis in human lung adenocarcinoma (LUAD) A549 cells. Examination of the lung tissues in KrasG12D/+ mice demonstrated that the level of Bap1 and Keap1 mRNAs progressively decreases during lung tumor progression, and it is correlated with NRF2 activation and the inhibition of oxidative stress. Supporting this observation, lentiviral transduction of BAP1 decreased the growth of A549 xenografts in athymic nude mice. Transcriptome analysis of human lung tissues showed that the levels of Bap1 mRNA are significantly higher in normal samples than LUAD samples. Moreover, the expression of Bap1 mRNA is associated with a better survival of LUAD patients. Together, our study demonstrates that KEAP1 deubiquitination by BAP1 is novel tumor suppressive mechanism of LUAD.

Behavioral and psychological symptoms of dementia are a major factor in the burden of care and medical expenses. Conventional pharmacological treatments do not exert a distinct effect on the benefits versus the risks. The herbal medicine woohwangchungsimwon is frequently prescribed for neuropsychiatric disorders. An effect of woohwangchungsimwon on behavioral and psychological symptoms of dementia has been previously reported; however, no clinical studies have been conducted. We aim to evaluate the efficacy and safety of woohwangchungsimwon combined with donepezil for alleviating these symptoms in probable Alzheimer’s disease. In this randomized, assessor-blinded, parallel-group clinical trial, 74 participants with probable Alzheimer’s disease will be divided via block randomization into a woohwangchungsimwon + donepezil combination group (n = 37) or a donepezil single group (n = 37). Participants will include patients under donepezil treatment for at least a month. We will perform the study for 24 weeks. The Neuro-Psychiatric Inventory subscale scores will be the primary outcome. Secondary outcomes will include cognitive function, dementia severity, physical function, quality of life, depression, anxiety, and insomnia. For safety evaluation, we will assess adverse reactions, measure vital signs, and conduct laboratory tests. This is the first trial aiming to confirm the efficacy and safety of woohwangchungsimwon combined with donepezil for alleviating behavioral and psychological symptoms of dementia. Its findings could provide a basis for their co-administration to control these symptoms in probable Alzheimer’s disease.

Background Electroacupuncture has been used for treatment in patients with overactive bladder. This study was conducted to evaluate the efficacy and safety of electroacupuncture for treating overactive bladder of postmenopausal women. Methods/design This is a multicenter, randomized controlled, parallel clinical trial. Two hundred ninety participants with overactive bladder syndrome will be recruited from Dongguk University Bundang Oriental Hospital and Cheonan Korean Medicine Hospital of Daejeon University and randomly allocated into one of two groups in a 1:1 ratio. One group will receive electroacupuncture (EA) and the other acupuncture (AC). The allocation will be concealed from both participants and assessors. The study period will be about 10 weeks, including 6 weeks of electroacupuncture or acupuncture treatment and a four week follow-up period. Both EA group and AT group will undergo acupuncture at 7 fixed points, and the EA group will undergo electronic stimulation at 6 points. The primary outcome will be the average number of micturitions per 24 h based on a 3-day bladder diary. The secondary outcome will comprise the 3-day bladder diary, the overactive bladder symptom score and the results of the King’s health questionnaire. Discussion The results of this trial will provide information regarding the efficacy and safety of electroacupuncture for treating overactive bladder in postmenopausal women. Trial registration ClinicalTrials.gov, NCT03260907 . Registered on 24 August 2017.

Background Human constitution, the fundamental basis of oriental medicine, is categorized into different patterns for a particular disease according to the physical, physiological, and clinical characteristics of the individuals. Obesity, a condition of metabolic disorder, is classified according to six patterns in oriental medicine, as follows: spleen deficiency syndrome, phlegm fluid syndrome, yang deficiency syndrome (YDS), food accumulation syndrome (FAS), liver depression syndrome (LDS), and blood stasis syndrome. In oriental medicine, identification of the disease pattern for individual obese patients is performed on the basis of differentiation in obesity syndrome index and, accordingly, personalized treatment is provided to the patients. The aim of the current study was to understand the obesity patterns in oriental medicine from the genomic point of view via determining the gene expression signature of obese patients using peripheral blood mononuclear cells as the samples. Methods The study was conducted in 23 South Korean obese subjects (19 female and four male) with BMI ≥25 kg/m 2 . Identification of oriental obesity pattern was based on the software-guided evaluation of the responses of the subjects to a questionnaire developed by the Korean Institute of Oriental Medicine. The expression profiles of genes were determined using DNA microarray and the level of transcription of genes of interest was further evaluated using quantitative real-time PCR (qRT-PCR). Results and conclusion Gene clustering analysis of the microarray data from the FAS, LDS, and YDS subjects exhibited disease pattern-specific upregulation of expression of several genes in a particular cluster. Further analysis of transcription of selected genes using qRT-PCR led to identification of specific genes, including prostaglandin endoperoxide synthase 2, G0/G1 switch 2, carcinoembryonic antigen-related cell adhesion molecule 3, cystein-serine-rich nuclear protein 1, and interleukin 8 receptor, alpha which were highly expressed in LDS obesity constitution. Our current study can be considered as a valuable contribution to the understanding of possible explanation for obesity pattern differentiation in oriental medicine. Further studies can address a novel possibility that the genomic and oriental empirical approaches can be combined and implemented in systematic and synergistic development of personalized medicine. This clinical trial was registered in Clinical Research Information Service of Korea National Institute of Health ( https://cris.nih.go.kr/cris/index.jsp ). Registration number: KCT0000387