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The design of transplantable scaffolds for tissue regeneration requires gaining precise control of topographical properties. Here, we propose a methodology to fabricate hierarchical multiscale scaffolds with controlled hydrophilic and hydrophobic properties by employing capillary force lithography in combination with plasma modification. Using our method, we fabricated biodegradable biomaterial (i.e., polycaprolactone (PCL))-based nitrogen gas (N-FN) and oxygen gas plasma-assisted flexible multiscale nanotopographic (O-FMN) patches with natural extracellular matrix-like hierarchical structures along with flexible and controlled hydrophilic properties. In response to multiscale nanotopographic and chemically modified surface cues, the proliferation and osteogenic mineralization of cells were significantly promoted. Furthermore, the O-FMN patch enhanced regeneration of the mineralized fibrocartilage tissue of the tendon–bone interface and the calvarial bone tissue in vivo in rat models. Overall, the PCL-based O-FMN patches could accelerate soft- and hard-tissue regeneration. Thus, our proposed methodology was confirmed as an efficient approach for the design and manipulation of scaffolds having a multiscale topography with controlled hydrophilic property.

Objective To compare a center-based cardiac rehabilitation (CR) program with a home-based CR program in terms of improving obesity related index and cardiopulmonary exercise capacity after the completing a phase II CR program. Methods In this study, there were seventy-four patients with acute myocardial infarction after percutaneous coronary intervention who were analyzed. Patients with mild to moderate risk (ejection fraction >40%) were included in the group. The patients underwent an exercise tolerance test by measurement of the modified Bruce protocol at three assessment points. Those in the center-based CR group participated in a 4-week training program with electrocardiography monitoring of the patient's progress and results, while those patients who were in the home-based CR group underwent self-exercise training. We measured the obesity related indices such as body mass index, fat free mass index (FFMI), and cardiopulmonary exercise capacity including peak oxygen consumption (VO2max), metabolic equivalents (METs), heart rate, resting systolic blood pressure and the diastolic blood pressure of the participants and noted the results. Results Of the 74 patients, 25 and 49 participated in the center-based and home-based CR programs, respectively. Both groups showed significant improvement in VO2max and METs at 1-month and 6-month follow-up. However, FFMI was significantly improved only in the center-based CR group after 1 month of the phase II CR. Conclusion Both groups identified in the study showed significant improvement of VO2max and METs at 1-month and 6-month follow-up. However, there was no significant difference in the intergroup analysis. A significant improvement of FFMI was seen only in the center-based CR group after phase II CR.

Anodal transcranial direct current stimulation (tDCS) is a painless noninvasive method that reportedly improves cognitive function in Alzheimer’s disease (AD) by stimulating the brain. However, its underlying mechanism remains unclear. Thus, the present study investigates the cognitive effects in a 5xFAD AD mouse model using electrophysiological and pathological methods. We used male 5xFAD C57BL/6J and male C57BL/6J wild-type mice; the dementia model was confirmed through DNA sequencing. The verified AD and wild-type mice were randomly assigned into four groups of five mice each: an induced AD group receiving tDCS treatment (Stim-AD), an induced AD group not receiving tDCS (noStim-AD), a non-induction group receiving tDCS (Stim-WT), and a non-induction group not receiving tDCS (noStim-WT). In the Stim group, mice received tDCS in the frontal bregma areas at an intensity of 200 µA for 20 min. After 2 weeks of treatment, we decapitated the mice, removed the hippocampus from the brain, confirmed its neuronal activation through excitatory postsynaptic potential (EPSP) recording, and performed molecular experiments on the remaining tissue using western blots. EPSP significantly increased in the Stim-AD group compared to that in the noStim-AD, which was comparable to that in the non-induced groups, Stim-WT and noStim-WT. There were no significant differences in cyclic amp-response element binding protein (CREB), phosphorylated CREB (pCREB), and Brain-derived neurotrophic factor (BDNF) levels in the Stim-AD group compared to those in the noStim-AD group. This study demonstrated that a tDCS in both frontal lobes of a transgenic 5xFAD mouse model affects long-term potentiation, indicating possible enhancement of cognitive function.

Background The effect of combined repetitive transcranial magnetic stimulation (rTMS) and scalp acupuncture stimulation (SAS) on middle cerebral artery occlusion (MCAO) mice has not yet been reported. The regulation of gene expression after combined stimulation remains unclear. Objective To analyze gene expression patterns through ribonucleic acid (RNA) sequencing. Methods Thirty-six 8-weeks-old C57BL/6J male mice weighing 50-60 grams were used for this experiment. The MCAO was induced with 60-min occlusion and subsequent reperfusion of the middle cerebral artery. Experimental mice were randomly assigned to four groups, with nine mice in each group, as follows: control group (no treatment), SAS group (10 minutes SAS), rTMS group (1 Hz rTMS), and combined group (1 Hz rTMS and SAS). Stimulation was performed from the 3rd day to the 7th day after the induction of MCAO. All mice were sacrificed, and brain tissues were taken from the motor area of the MCAO lesion. We analyzed their gene expression profiles using RNA sequencing technology. Results After stimulation, the grip strength increased in the SAS and rTMS group compared to the control and combined group. The nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) was the key up-regulated protein in the SAS group while src homologus and collagene gene (SHC) and p90 ribosomal protein S6 kinases (p90RSK) were key up-regulated proteins in the rTMS group. However, the C-terminal src kinase-homologous kinase (CHK) was down-regulated whereas p90RSK was up-regulated in the combined group based on the RNA sequencing analysis. Conclusions Each stimulation method showed different patterns with neurotrophin signaling pathway including NFκB, SHC, p90RSK, and CHK. These can be used in further mechanistic studies about gene expression related to neurorecovery.

Transcranial alternating current stimulation (tACS) is a neuromodulation procedure that is currently studied for the purpose of improving cognitive function in various diseases. A few studies have shown positive effects of tACS in Alzheimer’s disease (AD). However, the mechanism underlying tACS has not been established. The purpose of this study was to investigate the mechanism of tACS in five familial AD mutation (5xFAD) mouse models. We prepared twenty 4-month-old mice and divided them into four groups: wild-type mice without stimulation (WT-NT group), wild-type mice with tACS (WT-T group), 5xFAD mice without stimulation (AD-NT group), and 5xFAD mice with tACS (AD-T group). The protocol implemented was as follows: gamma frequency 200 μA over the bilateral frontal lobe for 20 min over 2 weeks. The following tests were conducted: excitatory postsynaptic potential (EPSP) recording, Western blot analysis (cyclic AMP response element-binding (CREB) proteins, phosphorylated CREB proteins, brain-derived neurotrophic factor, and parvalbumin) to examine the synaptic plasticity. The EPSP was remarkably increased in the AD-T group compared with in the AD-NT group. In the Western blot analysis, the differences among the groups were not significant. Hence, tACS can affect the long-lasting enhancement of synaptic transmission in mice models of AD.

Rationale: Spinal cord injury (SCI) patients who experience difficulties with independent walking use gait-assistive devices such as a cane, walker, or wheelchair. Few studies have explored gait patterns or cardiopulmonary function in chronic SCI patients after powered exoskeleton training. We investigated whether the cardiopulmonary function of a patient with an incomplete chronic cervical SCI and a hemiplegic gait pattern could be improved by walking training using a powered exoskeleton (Angelegs). Patient concerns: A 57-year-old male was diagnosed with an SCI at C3-C4. The right upper and lower limb motor functions differed when evaluated before entry into the program. Motor function was good in the right leg but poor in the left one. Before program entry, the patient could walk for about 10 m using a cane. He did not have a history of severe medical or psychological problems and was not cognitively impaired. Diagnosis: The patient was tetraplegia with incomplete SCI at C3-C4. Interventions: The patient was trained for 6 weeks using a powered exoskeleton. The training program consisted of sit-to-stand and stand-to-sit movements, maintenance of balanced standing for 5 minutes, and walking for 15 minutes. Outcomes: After 6 weeks of training, gait speed improved in the timed up-and-go test, and cardiac function was enhanced as measured by the metabolic equivalent and VO2 tests. Lessions: Walking training using a powered exoskeleton can facilitate the effective rehabilitation and improve the gait speed and cardiopulmonary function of patients with chronic SCIs or strokes.

Objective To test the hypothesis that a longer duration of phase II cardiac rehabilitation is required to recover the exercise capacity of elderly patients compared to younger patients.Methods We retrospectively reviewed and analyzed the medical records of patients who were referred to our cardiac rehabilitation (CR) center and underwent percutaneous coronary intervention for acute myocardial infarction (AMI). A total of 70 patients were enrolled who underwent an exercise tolerance test (ETT) 3 weeks after the occurrence of an AMI (T0), 6 weeks after the first ETT (T1), and 12 weeks after the first ETT (T2). Patients older than 65 years were assigned to the elderly group (n=24) and those aged 65 years and younger to the younger group (n=46). Both groups performed center-based or home-based CR for 12 weeks (3 times per week and 1 session per day). Exercise intensity for each individual was based on the target heart rate calculated by the Karvonen formula. The change in maximal metabolic equivalents (METmax) of the two groups was measured at each assessment point (T0, T1, and T2) to investigate the recovery of exercise capacity.Results The younger group showed improvement in METmax between T0 and T1. However, METmax of the elderly group showed no significant improvement between T0 and T1. The exercise capacity, measured with METmax, of all groups showed improvement between T0 and T2.Conclusion Elderly patients with AMI need a longer duration of CR (>6 weeks) than younger patients with AMI.

Spinocerebellar ataxia (SCA) is a hereditary neurodegenerative disorder that presents as ataxia. Due to the decline in balance, patients with SCA often experience restricted mobility and a decreased quality of life. Thus, many studies have emphasized the importance of physiotherapies, including gait training, in SCA patients. However, few studies have examined the effectiveness of robotic gait training in SCA. Here, we report the therapeutic outcomes of exoskeleton-assisted gait training in a patient with SCA. A 23-year-old woman with SCA participated in a gait training program using a powered lower-limb robotic exoskeleton, ANGELLEGS. The 8-week training program consisted of standing training, weight-shifting exercises, and gait training. Several measures of general function, balance, gait, and cardiopulmonary function were applied before, after, and 4 weeks after the program. After the program, overall improvements were found on scales measuring balance and gait function, and these improvements remained at 4 weeks after the program. Cardiopulmonary function was also improved 4 weeks after the program. Robotic exoskeleton gait training can be a beneficial option for training balance, gait, and cardiopulmonary function in SCA.

Many studies about Electrical muscle stimulation (EMS) have been performed to determine the effectiveness of EMS. However, most studies enrolled only elderly patients. Moreover, only a few studies have verified the effect of a whole body (WB)-EMS suit on young healthy women. Thus, the main purpose of this study was to verify the physiological effects of exercise training with a WB-EMS suit in young women. During the study periods, 24 young women were randomly assigned into two groups: 1) the WB-EMS training group, and 2) the control. All participants in the two groups performed the same low-intensity resistance exercise three times a week for 6 weeks at a training center. Group 1 used an electric current for WB-EMS suit which was switched on during the exercise period. Outcome measures were body composition, body circumference of hips and abdomen, isokinetic muscle function of knees, balance functions, Magnetic resonance imaging (MRI)s, cardiopulmonary functions, and lipid profiles. All outcomes were measured before and after the exercise protocol over 6 weeks. A total of 23 young women (group 1, n=11; group 2, n=12) completed a 6-week exercise regimen. After exercise, we compared the differences before and after the exercise program in each group. There were significant differences (p≤0.05) in body circumference, cardiopulmonary function in group 1 and 2. In particular, group 1 that activated WB-EMS showed significant differences in the isokinetic muscle function on knee flexors and balance functions. The results of this study show that exercise with a WB-EMS suit can be considered as an effective exercise addition for young women.

Background: Vascular cognitive impairment (VCI) refers to all cognitive disorders caused by cerebrovascular disorders. For the treatment, many types of pharmacologic and nonpharmacologic treatments are used but their underlying mechanisms and effects are unclear. Regarding nonpharmacologic treatment, electroacupuncture (EA), transcranial direct current stimulation (tDCS), and computerized cognitive rehabilitation treatment (CCRT) are effective. Here, we report the protocol for a randomized controlled trial of the effect and safety of combination therapy of EA or tDCS and CCRT in patients with VCI. Methods: This study will be a prospective, outcome assessor-blinded, parallel-arm, randomized controlled clinical trial. Participants with cognitive impairment caused by stroke after 3 months of onset (n = 45) will be randomly assigned to a CCRT, combination therapy with EA and computerized cognitive rehabilitation treatment, or combination therapy with tDCS and computerized cognitive rehabilitation treatment group. All groups will receive treatment 3 times per week for 8 weeks, giving a total of 24 treatments. The CCRT group will perform a training task like shopping, calculating, and others and involving computerized cognitive assessment and brain training system (RehaCom) for 30 minutes. The combination therapy with EA and computerized cognitive rehabilitation treatment group will receive EA using 8 acupuncture points – baekhoe, sinjeong, both sides of pungji, 4 sites of sishencong – and will be applied using an EA stimulator and receive CCRT for 30 minutes at the same time. The combination therapy with tDCS and computerized cognitive rehabilitation treatment group will receive tDCS treatment and receive CCRT for 30 minutes at the same time. The primary outcome will be evaluated using the Lowenstein occupational therapy cognitive assessment, while other scales assessing walking ability, activities of daily living, and quality of life are considered secondary outcome measures. Outcomes will be evaluated before intervention, at the end of intervention 8 weeks after the first intervention, and 4 weeks after completion of the intervention program. Discussion: This study aims to examine the effect and safety of combination therapy with EA or tDCS and CCRT in patients with VCI. This study can be useful in developing new treatment technologies using collaborative research with combined traditional Korean and conventional medicines. Trial registration: This trial has been registered with cris.nih.go.kr (registration number, KCT 0003644 Registered 01 April 2019, http://cris.nih.go.kr).

Background. Significant proportion of rotator cuff tears (RCTs) in clinical field are of a kind of repairable tear wherein the degree of fatty infiltration is of Goutallier stage 1 or stage 2. Therefore, the animal model, showing similar fatty infiltration, seems preferable for researches. The purpose of this study is to find out the proper time frame in which there is Goutallier stage 1 or stage 2 fatty infiltration in the rabbit RCT model for the research of repairable RCT in humans. Methods. Supraspinatus tendon tears were created in forty male New Zealand white rabbits at their right shoulder (n= 8 for each group), and a sham operation on the left shoulder. Rabbits were divided into five groups (2nd, 4th, 6th, 8th, and 12th weeks). Specimens were harvested from the central portion of the supraspinatus muscle for haematoxylin and eosin (H &E) staining, followed by histological and Goutallier grading evaluation. Results are expressed as mean ± standard deviation by Sigma Plot software (version 7.0). Results. At two weeks, mainly lipoblasts were observed around the muscle fibers, and at four weeks these lipoblasts were replaced by mature adipocytes with fatty infiltration amount (2.13 ± 0.35). The degree of muscle atrophy was (1.50 ± 0.53) at four weeks compared to sham group (0.88 ± 0.64) with significant difference (p < 0.05). The inflammatory process appeared as two phases. At two weeks, it was increased with grading value (1.88 ± 0.35). However, in the four-week group, it showed a sharp decrease (0.50 ± 0.53). At six weeks, inflammation reappeared to increase (1.13 ± 0.83). Then, a gradual decline appeared at eight weeks (0.88 ± 0.83) and at 12 weeks (0.50 ± 0.92). Conclusions. At two and four weeks, both fat distribution in rabbit supraspinatus muscles and Goutallier grading scale mostly appeared as grade 2. Therefore, we can consider four weeks to be a suitable period for making a repairable RCT animal model for the human research, considering the early acute tissue reaction at 2 weeks after the tendon tears.

Background. The incidence of septic arthritis of the shoulder joint is increasing as the population ages. The prevalence of shoulder infection is also increasing because of the growing use of arthroscopy and expansion of procedures in the shoulder. However, cultures do not always identify all microorganisms, even in symptomatic patients. The incidence of negative cultures ranges from 0% to 25%. Few studies have reported clinical features and treatment outcomes of culture-negative shoulder infections. This cohort study addresses culture-negative shoulder joint infections in nonarthroplasty patients. This study aimed to compare clinical characteristics and treatment outcomes of patients with culture-negative results to those with culture-positive results. Our hypothesis was that culture-negative infections would have more favorable outcomes than culture-positive infections.Methods. We retrospectively reviewed data of 36 patients (17 culture-negative and 19 culture-positive) with shoulder infections between June 2004 and March 2015. The minimum follow-up duration was 1.2 years (mean, 5 ± 3.8 years; range, 1.2-11 years). We assessed preoperative demographic data and characteristics, laboratory markers, imaging and functional scores, intraoperative findings, and postoperative findings of both groups.Results. Culture-negative patients (17/36, 47.2%) had a significantly lower occurrence of repeated surgical debridement (culture-negative vs. culture-positive: 1.2 ± 0.4 vs. 2.4 ± 1.7,p= 0.002) without osteomyelitis. In the multiple logistic regression analysis, the presence of osteomyelitis [odds ratio (OR) = 9.7, 95% confidence interval (CI): 1.0-91.8,p=0.04)] and the number of surgical debridements (OR = 5.3, 95% CI: 1.3-21.6,p=0.02) were significantly associated with culture-positive infections.Conclusions. Culture-negative infections without osteomyelitis are less severe than culture-positive infections. Culture-negative infections can be controlled more easily and are not necessarily a negative prognostic factor for shoulder joint infections.

Objective: This study investigated the effect of regular swimming exercise according to the duration-intensity on neurocognitive function in a cerebral infarction rat model.Methods: Forty male Spra...

Background Exercise intensity is a particularly important determinant of physiological responses to exercise training in patients with acute myocardial infarction. Heart rate (HR) is commonly used as a practical way of prescribing and monitoring exercise as specific intensities based on a linear relationship between the percentage of maximum HR (%HR max ) and the percentage of maximum oxygen consumption (%VO 2max ) regardless of age, gender, or exercise mode. Objective To examine the change in variability in the correlation between %HR max and %VO 2max after acute myocardial infarction. Design Retrospective study. Setting Regional cardio-cerebrovascular center at a tertiary hospital. Patients A total of 66 patients were enrolled who were referred for cardiac rehabilitation (CR) after percutaneous intervention, and who had reached stage 3 of the modified Bruce Protocol (mBP) on an exercise tolerance test (ETT). Methods There were 54 men and 12 women with an average age of 56.7 ± 9.48 years, ejection fraction (EF) of 56.4% ± 8.89%, and body mass index (BMI) of 24.73 ± 2.86 kg/m 2 . All patients participated in a 4-week outpatient CR program and underwent ETT with a gas analyzer to determine maximal heart rate and maximal oxygen consumption before CR and 1 month, 3 months, and 6 months after CR. Main Outcome Measurements VO 2max and HR max were defined as the highest values attained during the ETT. The HR and VO 2 values at each stage of the mBP were expressed as percentages of their maximum. %HR max and %VO 2max were calculated at each stage of the mBP. Results The maximum METs and VO 2max significantly improved at 1 month after CR, but not significantly at 3 and 6 months after CR. The correlation between VO 2max and HR max progressively changed in a favorable manner during CR. The relationship between %HR max and %VO 2max indicated a coefficient of variation before and 1, 3, and 6 months after of 0.800, 0.826, 0.832, and 0.880, respectively. Conclusions This study showed that the %HR max correlates better with the %VO 2max in the late-stage post-AMI than in the initial stage. We should therefore set and monitor the exercise intensity using maximal oxygen consumption in the early stage of exercise training after onset of acute myocardial infarction. Level of Evidence IV