Correlation between cardiopulmonary metabolic energy cost and lower-limb muscle activity during inclined treadmill gait in older adults.

BACKGROUND: Inclined walking requires more cardiopulmonary metabolic energy and muscle strength than flat-level walking. This study sought to investigate changes in lower-limb muscle activity and cardiopulmonary metabolic energy cost during treadmill walking with different inclination grades and to discern any correlation between these two measures in older adults. METHODS: Twenty-four healthy older adults (n = 11 males; mean age: 75.3 ± 4.0 years) participated. All participants walked on a treadmill that was randomly inclined at 0% (condition 1), 10% (condition 2), and 16% (condition 3) for five minutes each. Simultaneous measurements of lower-limb muscle activity and cardiopulmonary metabolic energy cost during inclined treadmill walking were collected. Measured muscles included the rectus abdominis (RA), erector spinae (ES), rectus femoris (RF), biceps femoris (BF), vastus medialis (VM), tibialis anterior (TA), medial head of the gastrocnemius (GCM), and soleus (SOL) muscles on the right side. RESULTS: As compared with 0% inclined treadmill gait, the 10% inclined treadmill gait increased the net cardiopulmonary metabolic energy cost by 22.9%, while the 16% inclined treadmill gait increased the net cardiopulmonary metabolic energy cost by 44.2%. In the stance phase, as the slope increased, activity was significantly increased in the RA, RF, VM, BF, GCM, and SOL muscles. In the swing phase, As the slope increased activity was significantly increased in the RA, RF, VM, BF, and TA muscles. SOL muscle activity was most relevant to the change in cardiopulmonary metabolic energy cost in the stance phase of inclined treadmill walking. The relationship between the increase in cardiopulmonary metabolic energy cost and changes in muscle activity was also significant in the VM, GCM, and RF. CONCLUSION: This study demonstrated that changes in SOL, VM, GCM, and RA muscle activity had a significant relationship with cardiopulmonary metabolic energy cost increment during inclined treadmill walking. These results can be used as basic data for various gait-training programs and as an indicator in the development of assistive algorithms of wearable walking robots for older adults. TRIAL REGISTRATION: Clinical trials registration information: ClinicalTrials.gov Identifier: NCT04614857 (05/11/2020).

Wearable hip-assist robot modulates cortical activation during gait in stroke patients: a functional near-infrared spectroscopy study.

BACKGROUND: Gait dysfunction is common in post-stroke patients as a result of impairment in cerebral gait mechanism. Powered robotic exoskeletons are promising tools to maximize neural recovery by delivering repetitive walking practice. OBJECTIVES: The purpose of this study was to investigate the modulating effect of the Gait Enhancing and Motivating System-Hip (GEMS-H) on cortical activation during gait in patients with chronic stroke. METHODS: Twenty chronic stroke patients performed treadmill walking at a self-selected speed either with assistance of GEMS-H (GEMS-H) or without assistance of GEMS-H (NoGEMS-H). Changes in oxygenated hemoglobin (oxyHb) concentration in the bilateral primary sensorimotor cortex (SMC), premotor cortices (PMC), supplemental motor areas (SMA), and prefrontal cortices (PFC) were recorded using functional near infrared spectroscopy. RESULTS: Walking with the GEMS-H promoted symmetrical SMC activation, with more activation in the affected hemisphere than in NoGEMS-H conditions. GEMS-H also decreased oxyHb concentration in the late phase over the ipsilesional SMC and bilateral SMA (P < 0.05). CONCLUSIONS: The results of the present study reveal that the GEMS-H promoted more SMC activation and a balanced activation pattern that helped to restore gait function. Less activation in the late phase over SMC and SMA during gait with GEMS-H indicates that GEMS-H reduces the cortical participation of stroke gait by producing rhythmic hip flexion and extension movement and allows a more coordinate and efficient gait patterns. Trial registration NCT03048968. Registered 06 Feb 2017.

Anti-Fibrotic Effect of Human Wharton's Jelly-Derived Mesenchymal Stem Cells on Skeletal Muscle Cells, Mediated by Secretion of MMP-1.

Extracellular matrix (ECM) components play an important role in maintaining skeletal muscle function, but excessive accumulation of ECM components interferes with skeletal muscle regeneration after injury, eventually inducing fibrosis. Increased oxidative stress level caused by dystrophin deficiency is a key factor in fibrosis in Duchenne muscular dystrophy (DMD) patients. Mesenchymal stem cells (MSCs) are considered a promising therapeutic agent for various diseases involving fibrosis. In particular, the paracrine factors secreted by MSCs play an important role in the therapeutic effects of MSCs. In this study, we investigated the effects of MSCs on skeletal muscle fibrosis. In 2-5-month-old mdx mice intravenously injected with 1 × 105 Wharton's jelly (WJ)-derived MSCs (WJ-MSCs), fibrosis intensity and accumulation of calcium/necrotic fibers were significantly decreased. To elucidate the mechanism of this effect, we verified the effect of WJ-MSCs in a hydrogen peroxide-induced fibrosis myotubes model. In addition, we demonstrated that matrix metalloproteinase-1 (MMP-1), a paracrine factor, is critical for this anti-fibrotic effect of WJ-MSCs. These findings demonstrate that WJ-MSCs exert anti-fibrotic effects against skeletal muscle fibrosis, primarily via MMP-1, indicating a novel target for the treatment of muscle diseases, such as DMD.

Pressure Stimuli Improve the Proliferation of Wharton's Jelly-Derived Mesenchymal Stem Cells under Hypoxic Culture Conditions.

Mesenchymal stem cells (MSCs) are safe, and they have good therapeutic efficacy through their paracrine action. However, long-term culture to produce sufficient MSCs for clinical use can result in side-effects, such as an inevitable senescence and the reduction of the therapeutic efficacy of the MSCs. In order to overcome this, the primary culture conditions of the MSCs can be modified to simulate the stem cells' niche environment, resulting in accelerated proliferation, the achievement of the target production yield at earlier passages, and the improvement of the therapeutic efficacy. We exposed Wharton's jelly-derived MSCs (WJ-MSCs) to pressure stimuli during the primary culture step. In order to evaluate the proliferation, stemness, and therapeutic efficacy of WJ-MSCs, image, genetic, and Western blot analyses were carried out. Compared with standard incubation culture conditions, the cell proliferation was significantly improved when the WJ-MSCs were exposed to pressure stimuli. However, the therapeutic efficacy (the promotion of cell proliferation and anti-apoptotic effects) and the stemness of the WJ-MSCs was maintained, regardless of the culture conditions. Exposure to pressure stimuli is a simple and efficient way to improve WJ-MSC proliferation without causing changes in stemness and therapeutic efficacy. In this way, clinical-grade WJ-MSCs can be produced rapidly and used for therapeutic applications.

Training for Walking Efficiency With a Wearable Hip-Assist Robot in Patients With Stroke: A Pilot Randomized Controlled Trial.

Background and Purpose- The purpose of this study was to investigate the effects of gait training with a newly developed wearable hip-assist robot on locomotor function and efficiency in patients with chronic stroke. Methods- Twenty-eight patients with stroke with hemiparesis were initially enrolled, and 26 patients completed the randomized controlled trial (14 in the experimental and 12 in the control groups). The experimental group participated in a gait training program over a total of 10 sessions, including 5 treadmill sessions and 5 over-ground gait training sessions while wearing a hip-assist robot, the Gait Enhancing and Motivating System (GEMS, Samsung Advanced Institute of Technology, Suwon, Republic of Korea). The control group received gait training without Gait Enhancing and Motivating System. Primary outcome measured locomotor function and cardiopulmonary metabolic energy efficiency. Also, secondary outcome measured motor function and balance parameter. Results- Compared with the control group, the experimental group had significantly greater improvement in spatiotemporal gait parameters and muscle efforts after the training intervention (P<0.05). The net cardiopulmonary metabolic energy cost (mL·kg-1·min-1) was also reduced by 14.71% in the experimental group after the intervention (P<0.01). Significant group×time interactions were observed for all parameters (P<0.05). Cardiopulmonary metabolic efficiency was strongly correlated with gait symmetry ratio in the experimental group (P<0.01). Conclusions- Gait training with Gait Enhancing and Motivating System was effective for improving locomotor function and cardiopulmonary metabolic energy efficiency during walking in patients with stroke. These findings suggest that robotic locomotor training can be adopted for rehabilitation of patients with stroke with gait disorders. Clinical Trial Registration- URL: https://clinicaltrials.gov. Unique identifier: NCT02843828.

A wearable hip-assist robot reduces the cardiopulmonary metabolic energy expenditure during stair ascent in elderly adults: a pilot cross-sectional study.

BACKGROUND: Stair ascent is one of the most important and challenging activities of daily living to maintain mobility and independence in elderly adults. Recently, various types of wearable walking assist robots have been developed to improve gait function and metabolic efficiency for elderly adults. Several studies have shown that walking assist robots can improve cardiopulmonary metabolic efficiency during level walking in elderly. However, there is limited evidence demonstrating the effect of walking assist robots on cardiopulmonary metabolic efficiency during stair walking in elderly adults. Therefore, the aim of this study was to investigate the assistance effect of a newly developed wearable hip assist robot on cardiopulmonary metabolic efficiency during stair ascent in elderly adults. METHODS: Fifteen healthy elderly adults participated. The Gait Enhancing Mechatronic System (GEMS), developed by Samsung Electronics Co., Ltd., Korea, was used in the present study. The metabolic energy expenditure was measured using a K4b2 while participants performed randomly assigned two conditions consecutively: free ascending stairs without the GEMS or robot-assisted ascending stair with the GEMS. RESULTS: There were significant differences in the oxygen consumption per unit mass (ml/min/kg), metabolic power per unit mass (W/kg) and metabolic equivalents (METs) values between the GEMS and NoGEMS conditions. A statistically significant difference was found between the two conditions in net oxygen consumption and net metabolic power, with a reduction of 8.59% and 10.16% respectively in GEMS condition (p < 0.05). The gross oxygen consumption while climbing stairs under the GEMS and NoGEMS conditions was equivalent to 6.38 METs and 6.85 METs, respectively. CONCLUSION: This study demonstrated that the GEMS was helpful for reducing cardiopulmonary metabolic energy expenditure during stair climbing in elderly adults. The use of the GEMS allows elderly adults to climb stairs with less metabolic energy, therefore, they may experience more endurance in stair climbing while using the GEMS. TRIAL REGISTRATION: NCT03389165 , Registered 26 December 2017 - retrospectively registered.

Diagnosing bladder outlet obstruction using the penile cuff test in men with lower urinary tract symptoms.

AIM: The current standard diagnostic test to evaluate bladder outlet obstruction (BOO) is pressure-flow study (PFS). The penile cuff test (PCT) was introduced as a non-invasive alternative to PFS to determine the isovolumetric bladder pressure and also flow rate. The aim of the study was to evaluate the diagnostic accuracy and acceptability of the PCT, compared to those of PFS, in the assessment of BOO in men. METHODS: A total of 146 consecutive men with an International Prostate Symptom Score (IPSS) >12 and lower urinary tract symptoms (LUTS) for >6 months were included in this single-institution, prospective, diagnostic study. The primary outcome was to evaluate the diagnostic accuracy of PCT. Secondary outcomes included pain severity measured on a visual analog scale (VAS), procedure time, and adverse events. In addition, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were estimated. RESULTS: Based on the PFS results, the sensitivity of PCT was 89.7%, the PPV 54.2%, the specificity 71.8%, and the NPV 94.9%. The mean pain VAS for the PFS and PCT were 5.04 ± 2.17 and 1.83 ± 1.98, respectively (P < 0.0001). The mean procedure time for PCT (6.3 ± 0.6 min) was shorter than that of PFS (23.3 ± 2.2 min) (P < 0.0001). There were no adverse events reported during PCT. CONCLUSIONS: Given its high NPV, PCT may be an efficient screening test for BOO in men. In addition, PCT is advantageous over PFS with regard to its short procedure time and acceptable tolerability.

Age-related differences in muscle co-activation during locomotion and their relationship with gait speed: a pilot study.

BACKGROUND: Muscle co-activation plays an important role in enhancing joint stability for movement regulation during motor learning activities. In normal aging, greater muscle co-activation is induced during gait in elderly adults. This study investigated age-related changes in muscle co-activation and spatio-temporal parameters during gait and identified the relationship between muscle co-activation and gait speed. METHODS: A total of 46 adult volunteers participated in this study in three age groups (15 young adults [8 males, 7 females; age, 24.27 ± 2.71], 15 middle-aged adults [8 males, 7 females; age, 53.71 ± 2.52], and 16 elderly adults [7 males, 9 females; age, 76.88 ± 3.48]). All participants underwent locomotion analysis using a Three-dimensional motion analysis system and 12-channel dynamic electromyography. RESULTS: The elderly adults showed significantly higher co-activation than the young and middle-aged adults during gait (p < 0.05). In contrast, elderly adults showed significantly lower trunk co-activation than the young and middle-aged adults (p < 0.05). Muscle co-activation was significantly correlated with gait speed by aging. Muscle co-activation of the trunk showed a significant positive correlation with gait speed based on age. However, muscle co-activation of the lower extremity showed a significant negative correlation with gait speed based on age. CONCLUSION: This finding demonstrated that less muscle co-activation of the trunk was related to locomotive instability in elderly adults. Therefore, clarification of the relationship between trunk co-activation and locomotor instability will be helpful for developing optimal rehabilitation of elderly people to prevent fall.

Gait performance and foot pressure distribution during wearable robot-assisted gait in elderly adults.

BACKGROUND: A robotic exoskeleton device is an intelligent system designed to improve gait performance and quality of life for the wearer. Robotic technology has developed rapidly in recent years, and several robot-assisted gait devices were developed to enhance gait function and activities of daily living in elderly adults and patients with gait disorders. In this study, we investigated the effects of the Gait-enhancing Mechatronic System (GEMS), a new wearable robotic hip-assist device developed by Samsung Electronics Co, Ltd., Korea, on gait performance and foot pressure distribution in elderly adults. METHODS: Thirty elderly adults who had no neurological or musculoskeletal abnormalities affecting gait participated in this study. A three-dimensional (3D) motion capture system, surface electromyography and the F-Scan system were used to collect data on spatiotemporal gait parameters, muscle activity and foot pressure distribution under three conditions: free gait without robot assistance (FG), robot-assisted gait with zero torque (RAG-Z) and robot-assisted gait (RAG). RESULTS: We found increased gait speed, cadence, stride length and single support time in the RAG condition. Reduced rectus femoris and medial gastrocnemius muscle activity throughout the terminal stance phase and reduced effort of the medial gastrocnemius muscle throughout the pre-swing phase were also observed in the RAG condition. In addition, walking with the assistance of GEMS resulted in a significant increase in foot pressure distribution, specifically in maximum force and peak pressure of the total foot, medial masks, anterior masks and posterior masks. CONCLUSION: The results of the present study reveal that GEMS may present an alternative way of restoring age-related changes in gait such as gait instability with muscle weakness, reduced step force and lower foot pressure in elderly adults. In addition, GEMS improved gait performance by improving push-off power and walking speed and reducing muscle activity in the lower extremities. TRIAL REGISTRATION: NCT02843828 .

Age-Related Locomotion Characteristics in Association with Balance Function in Young, Middle-Aged, and Older Adults.

The purpose of this study was to examine age-related gait characteristics and their associations with balance function in older adults. A total of 51 adult volunteers participated. All subjects underwent locomotion analysis using a 3D motion analysis and 12-channel dynamic electromyography system. Dynamic balance function was assessed by the Berg Balance Scale. Older adults showed a higher level of muscle activation than young adults, and there were significant positive correlations between increased age and activation of the trunk and thigh muscles in the stance and swing phase of the gait cycle. In particular, back extensor muscle activity was mostly correlated with the dynamic balance in older adults. Thus, back extensor muscle activity in walking may provide a clue for higher falling risk in older adults. This study demonstrates that the back extensor muscles play very important roles with potential for rehabilitation training to improve balance and gait in older adults.

Nervonic Acid Inhibits Replicative Senescence of Human Wharton's Jelly-Derived Mesenchymal Stem Cells.

Cellular senescence causes cell cycle arrest and promotes permanent cessation of proliferation. Since the senescence of mesenchymal stem cells (MSCs) reduces proliferation and multipotency and increases immunogenicity, aged MSCs are not suitable for cell therapy. Therefore, it is important to inhibit cellular senescence in MSCs. It has recently been reported that metabolites can control aging diseases. Therefore, we aimed to identify novel metabolites that regulate the replicative senescence in MSCs. Using a fecal metabolites library, we identified nervonic acid (NA) as a candidate metabolite for replicative senescence regulation. In replicative senescent MSCs, NA reduced senescence-associated ß-galactosidase positive cells, the expression of senescence-related genes, as well as increased stemness and adipogenesis. Moreover, in non-senescent MSCs, NA treatment delayed senescence caused by sequential subculture and promoted proliferation. We confirmed, for the first time, that NA delayed and inhibited cellular senescence. Considering optimal concentration, duration, and timing of drug treatment, NA is a novel potential metabolite that can be used in the development of technologies that regulate cellular senescence.

Relationship between lower limb muscle activity and cortical activation among elderly people during walking: Effects of fast speed and cognitive dual task.

Objective: Gait is a complex behavior that involves not only the musculoskeletal system, but also higher-order brain functions, including cognition. This study was performed to investigate the correlation between lower limb muscle activity and cortical activation during treadmill walking in two groups of elderly people: the young-old (aged 65-74 years) and the old-old (aged 75-84 years). Methods: Thirty-one young-old and 31 old-old people participated in this study. All participants were sequentially subjected to three gait conditions on a treadmill: (1) comfortable walking, (2) fast walking, and (3) cognitive dual-task walking. During treadmill walking, the activity of the lower limb muscles was measured using a surface electromyography system, and cortical activation was measured using a functional near-infrared spectroscopy system. The correlation between muscle activity and cortical activation during treadmill walking was analyzed and compared between the two groups. Results: During comfortable walking, lower extremity muscle activity had a strong correlation with cortical activation, especially in the swing phase; this was significantly stronger in the young-old than the old-old. During fast walking, the correlations between lower limb muscle activity and cortical activation were stronger than those during comfortable walking in both groups. In cognitive dual-task walking, cortical activation in the frontal region and motor area was increased, although the correlation between muscle activity and cortical activation was weaker than that during comfortable walking in both groups. Conclusion: The corticomotor correlation differed significantly between the old-old and the young-old. These results suggest that gait function is compensated by regulating corticomotor correlation as well as brain activity during walking in the elderly. These results could serve as a basis for developing gait training and fall prevention programs for the elderly.

Wharton's Jelly-Derived Mesenchymal Stem Cells with High Aurora Kinase A Expression Show Improved Proliferation, Migration, and Therapeutic Potential.

Mesenchymal stem cells (MSCs) are effective therapeutic agents that contribute to tissue repair and regeneration by secreting various factors. However, donor-dependent variations in MSC proliferation and therapeutic potentials result in variable production yields and clinical outcomes, thereby impeding MSC-based therapies. Hence, selection of MSCs with high proliferation and therapeutic potentials would be important for effective clinical application of MSCs. This study is aimed at identifying the upregulated genes in human Wharton's jelly-derived MSCs (WJ-MSCs) with high proliferation potential using mRNA sequencing. Aurora kinase A (AURKA) and dedicator of cytokinesis 2 (DOCK2) were selected as the upregulated genes, and their effects on proliferation, migration, and colony formation of the WJ-MSCs were verified using small interfering RNA (siRNA) techniques. mRNA expression levels of both the genes were positively correlated with the proliferation capacity of WJ-MSCs. Moreover, AURKA from human WJ-MSCs regulated the antiapoptotic effect of skeletal muscle cells by upregulating the chemokine (C motif) ligand (XCL1); this was further confirmed in the mdx mouse model. Taken together, the results indicated that AURKA and DOCK2 can be used as potential biomarkers for proliferation and migration of human WJ-MSCs. In particular, human WJ-MSCs with high expression of AURKA might have therapeutic efficacy against muscle diseases, such as Duchenne muscular dystrophy (DMD).

Analysis of Factors Affecting Neutralizing Antibody Production after COVID-19 Vaccination Using Newly Developed Rapid Point-of-Care Test.

(1) Objective: To investigate the factors that affect rates of neutralizing antibody production and duration after vaccination using the newly developed SARS-CoV-2 POCT. (2) Methods: The production of immunoglobulin and neutralizing antibody in clinical subjects who completed various vaccines was analyzed using the POCT, the semi-quantitative was interpreted by measurement application, and the quantified neutralizing antibody titers were using the ELISA. (3) Results: According to the clinical performance analysis of the POCT, the clinical sensitivity and the specificity were 96.8% (90/93) and 97.7% (167/171), respectively, for the S1 RBD IgG antibody. The clinical sensitivity was 92.22% (83/90), and the clinical specificity was 100.00% (174/174) for neutralizing antibodies. Factors influencing antibody production were analyzed using the whole blood of the five types of second-completed vaccinators (N = 736, 20−80 years old). General and neutralizing antibody and showed significant differences in age (p < 0.0001), vaccine type (p < 0.0001), inoculation interval (p < 0.0001), pain score (p < 0.0001), diabetes (p < 0.0001), and hypertension (p = 0.002). The gender (p = 0.021) and chronic fatigue (p = 0.02) did not show the significance. (4) Conclusions: An acquisition of immunoglobulin and neutralizing antibody varies according to vaccine type, age, days after vaccination, pain degree after vaccination, and underlying diseases. The POCT used in this study will be utilized for clinical recommendations such as deciding whether to receive additional vaccines through the immediate rapid determination of neutralizing antibody generation in the clinical site.

Exposure of Mesenchymal Stem Cells to an Alzheimer's Disease Environment Enhances Therapeutic Effects.

Mesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of Alzheimer's disease (AD). Previous studies suggested that the coculture of human MSCs with AD in an in vitro model reduced the expression of amyloid-beta 42 (Aß42) in the medium as well as the overexpression of amyloid-beta- (Aß-) degrading enzymes such as neprilysin (NEP). We focused on the role of primed MSCs (human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) exposed to an AD cell line via a coculture system) in reducing the levels of Aß and inhibiting cell death. We demonstrated that mouse groups treated with naïve MSCs and primed MSCs showed significant reductions in cell death, ubiquitin conjugate levels, and Aß levels, but the effects were greater in primed MSCs. Also, mRNA sequencing data analysis indicated that high levels of TGF-ß induced primed-MSCs. Furthermore, treatment with TGF-ß reduced Aß expression in an AD transgenic mouse model. These results highlighted AD environmental preconditioning is a promising strategy to reduce cell death and ubiquitin conjugate levels and maintain the stemness of MSCs. Further, these data suggest that human WJ-MSCs exposed to an AD environment may represent a promising and novel therapy for AD.

Wharton's Jelly-Derived Mesenchymal Stem Cells Reduce Fibrosis in a Mouse Model of Duchenne Muscular Dystrophy by Upregulating microRNA 499.

The aim of this study was to evaluate the therapeutic effects and mechanisms of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) in an animal model of Duchenne muscular dystrophy (DMD). Mdx mice (3-5 months old) were administered five different doses of WJ-MSCs through their tail veins. A week after injection, grip strength measurements, creatine kinase (CK) assays, immunohistochemistry, and western blots were performed for comparison between healthy mice, mdx control mice, and WJ-MSC-injected mdx mice. WJ-MSCs exerted dose-dependent multisystem therapeutic effects in mdx mice, by decreasing CK, recovering normal behavior, regenerating muscle, and reducing apoptosis and fibrosis in skeletal muscle. We also confirmed that miR-499-5p is significantly downregulated in mdx mice, and that intravenous injection of WJ-MSCs enhanced its expression, leading to anti-fibrotic effects via targeting TGFßR 1 and 3. Thus, WJ-MSCs may represent novel allogeneic "off-the-shelf" cellular products for the treatment of DMD and possibly other muscle disorders.

Can the Penile Cuff Test Predict the Outcome of Holmium Laser Enucleation of the Prostate for Benign Prostatic Obstruction?

OBJECTIVE: To determine whether the penile cuff test can predict surgical outcomes prior to Holmium laser enucleation of the prostate for benign prostatic obstruction. METHODS: Men scheduled to undergo Holmium laser enucleation of the prostate were enrolled in this study, and all patients underwent the penile cuff test prior to and 3 months after surgery. Patients were categorized as obstructed, nonobstructed, or uncertain by nomogram. Surgical outcomes were assessed by evaluating changes in their international prostate symptom score, quality of life index, and maximum flow rate preoperatively and 3 months postoperatively. The proportion of patients with good outcomes was compared among nomogram-classified groups, and postoperative changes in position on the nomogram were assessed. RESULTS: A total of 125 patients were analyzed. After surgery, the overall treatment efficacy and symptomatic treatment efficacy were not different between obstructed and nonobstructed patients. However, the maximum flow rate and quality of life score were significantly higher after surgery in obstructed patients compared to nonobstructed patients. After surgery, 75.7% of patients with obstruction and 63.6% of patients categorized as uncertain for obstruction transitioned to the nonobstructed group, while 77.3% of nonobstructed patients remained in the nonobstructed group. CONCLUSION: The penile cuff test can be used in patients with bladder outlet obstruction to predict good functional outcome and improved quality of life following treatment with Holmium laser enucleation. After Holmium laser enucleation of the prostate, the majority of patients were classified as nonobstructed.

Innovative Distribution Priorities for the Medical Devices Industry in the Fourth Industrial Revolution.

PURPOSE: This study aimed to set priorities for improving the medical device distribution structure and to suggest an innovative improvement plan for the distribution structure using the analytic hierarchy process (AHP) method, focusing on stakeholders in the medical device industry. METHODS: This study conducted a survey with 35 specialists using the AHP method, which is a multiple-criteria decisionmaking methodology, in order to set priorities for improvement plans to address the problems faced by the medical device distribution structure. RESULTS: The AHP analysis showed that supply stability was the most important factor, followed by greater transparency, efficiency, smart supply, and cost reduction. CONCLUSIONS: It is necessary to establish a stable supply system and manage crises through supply stability, as well as to provide opportunities for fair trade through greater transparency. As steps towards those goals, we propose establishing a unique device identification system, an information disclosure system, online distribution, and a group purchasing organization system in Korea.

Potent effect of the MDM2 inhibitor AMG232 on suppression of glioblastoma stem cells.

Testing new ways to identify untapped opportunities for glioblastoma therapies remains highly significant. Amplification and overexpression of MDM2 gene is frequent in glioblastoma and disrupting the MDM2-p53 interaction is a promising strategy to treat the cancer. RG7112 is the first-in class inhibitor and recently discovered AMG232 is the most potent MDM2 inhibitor known to date. Here, we compared the effects of these two clinical MDM2 inhibitors in six glioblastoma cell lines and ten patient-derived glioblastoma stem cells. Targeted sequencing of the TP53, MDM2 genes and whole transcriptome analysis were conducted to verify genetic status associated with sensitivity and resistance to the drugs. Although TP53 wild-type glioblastoma cell lines are similarly sensitive to AMG232 and RG7112, we found that four TP53 wild-type out of ten patient-derived glioblastoma cells are much more sensitive to AMG232 than RG7112 (average IC50 of 76 nM vs. 720 nM). Among these, 464T stem cells containing MDM2 gene amplification were most sensitive to AMG232 with IC50 of 5.3 nM. Moreover, AMG232 exhibited higher selectivity against p53 wild-type cells over p53 mutant stem cells compared to RG7112 (average selectivity of 512-fold vs. 16.5-fold). Importantly, we also found that AMG232 is highly efficacious in three-dimensional (3D) tumor spheroids growth and effectively inhibits the stemness-related factors, Nestin and ZEB1. Our data provide new evidence that glioblastoma stem cells have high susceptibility to AMG232 suggesting the potential clinical implications of MDM2 inhibition for glioblastoma treatment. These will facilitate additional preclinical and clinical studies evaluating MDM2 inhibitors in glioblastoma and direct further efforts towards developing better MDM2-targeted therapeutics.

Volumetric Analysis of 3-D-Cultured Colonies in Wet Alginate Spots Using 384-Pillar Plate.

The volumetric analysis of three-dimensional (3-D)-cultured colonies in alginate spots has been proposed to increase drug efficacy. In a previously developed pillar/well chip platform, colonies within spots are usually stained and dried for analysis of cell viability using two-dimensional (2-D) fluorescent images. Since the number of viable cells in colonies is directly related to colony volume, we proposed the 3-D analysis of colonies for high-accuracy cell viability calculation. The spots were immersed in buffer, and the 3-D volume of each colony was calculated from the 2-D stacking fluorescent images of the spot with different focal positions. In the experiments with human gastric carcinoma cells and anticancer drugs, we compared cell viability values calculated using the 2-D area and 3-D volume of colonies in the wet and dried alginate spots, respectively. The IC50 value calculated using the 3-D volume of the colonies (9.5 µM) was less than that calculated in the 2-D area analysis (121.5 µM). We observed that the colony showed a more sensitive drug response regarding volume calculated from the 3-D image reconstructed using several confocal images than regarding colony area calculated in the 2-D analysis.