Publications by authors named "O Jung Kwon"

3,522 Publications

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Exon junction complex dependent mRNA localization is linked to centrosome organization during ciliogenesis.

Nat Commun 2021 Mar 1;12(1):1351. Epub 2021 Mar 1.

Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, Paris, France.

Exon junction complexes (EJCs) mark untranslated spliced mRNAs and are crucial for the mRNA lifecycle. An imbalance in EJC dosage alters mouse neural stem cell (mNSC) division and is linked to human neurodevelopmental disorders. In quiescent mNSC and immortalized human retinal pigment epithelial (RPE1) cells, centrioles form a basal body for ciliogenesis. Here, we report that EJCs accumulate at basal bodies of mNSC or RPE1 cells and decline when these cells differentiate or resume growth. A high-throughput smFISH screen identifies two transcripts accumulating at centrosomes in quiescent cells, NIN and BICD2. In contrast to BICD2, the localization of NIN transcripts is EJC-dependent. NIN mRNA encodes a core component of centrosomes required for microtubule nucleation and anchoring. We find that EJC down-regulation impairs both pericentriolar material organization and ciliogenesis. An EJC-dependent mRNA trafficking towards centrosome and basal bodies might contribute to proper mNSC division and brain development.
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http://dx.doi.org/10.1038/s41467-021-21590-wDOI Listing
March 2021

A choreography of centrosomal mRNAs reveals a conserved localization mechanism involving active polysome transport.

Nat Commun 2021 Mar 1;12(1):1352. Epub 2021 Mar 1.

Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France.

Local translation allows for a spatial control of gene expression. Here, we use high-throughput smFISH to screen centrosomal protein-coding genes, and we describe 8 human mRNAs accumulating at centrosomes. These mRNAs localize at different stages during cell cycle with a remarkable choreography, indicating a finely regulated translational program at centrosomes. Interestingly, drug treatments and reporter analyses reveal a common translation-dependent localization mechanism requiring the nascent protein. Using ASPM and NUMA1 as models, single mRNA and polysome imaging reveals active movements of endogenous polysomes towards the centrosome at the onset of mitosis, when these mRNAs start localizing. ASPM polysomes associate with microtubules and localize by either motor-driven transport or microtubule pulling. Remarkably, the Drosophila orthologs of the human centrosomal mRNAs also localize to centrosomes and also require translation. These data identify a conserved family of centrosomal mRNAs that localize by active polysome transport mediated by nascent proteins.
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http://dx.doi.org/10.1038/s41467-021-21585-7DOI Listing
March 2021

SGK1 inhibition in glia ameliorates pathologies and symptoms in Parkinson disease animal models.

EMBO Mol Med 2021 Mar 1:e13076. Epub 2021 Mar 1.

Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea.

Astrocytes and microglia are brain-resident glia that can establish harmful inflammatory environments in disease contexts and thereby contribute to the progression of neuronal loss in neurodegenerative disorders. Correcting the diseased properties of glia is therefore an appealing strategy for treating brain diseases. Previous studies have shown that serum/ glucocorticoid related kinase 1 (SGK1) is upregulated in the brains of patients with various neurodegenerative disorders, suggesting its involvement in the pathogenesis of those diseases. In this study, we show that inhibiting glial SGK1 corrects the pro-inflammatory properties of glia by suppressing the intracellular NFκB-, NLRP3-inflammasome-, and CGAS-STING-mediated inflammatory pathways. Furthermore, SGK1 inhibition potentiated glial activity to scavenge glutamate toxicity and prevented glial cell senescence and mitochondrial damage, which have recently been reported as critical pathologic features of and therapeutic targets in Parkinson disease (PD) and Alzheimer disease (AD). Along with those anti-inflammatory/neurotrophic functions, silencing and pharmacological inhibition of SGK1 protected midbrain dopamine neurons from degeneration and cured pathologic synuclein alpha (SNCA) aggregation and PD-associated behavioral deficits in multiple in vitro and in vivo PD models. Collectively, these findings suggest that SGK1 inhibition could be a useful strategy for treating PD and other neurodegenerative disorders that share the common pathology of glia-mediated neuroinflammation.
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http://dx.doi.org/10.15252/emmm.202013076DOI Listing
March 2021

Measurement of Tryptase and CC16/Albumin in Nasal Lavage Fluid as a Screening Tool of Allergic Rhinitis.

Am J Rhinol Allergy 2021 Feb 25:1945892421998260. Epub 2021 Feb 25.

Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Korea.

Background: There is no trial to make a diagnostic tool of allergic rhinitis (AR) utilizing biomarkers from nasal fluid. Base on previous studies, we selected following five biomarkers in nasal fluids that represent the characteristics of allergic reactions: tryptase, eosinophil cationic protein (ECP), interleukin 5 (IL-5), Clara cell protein 16 (CC16) and CC16-to-albumin ratio.

Objective: This study aimed to identify biomarkers in nasal discharge that may be used in biosensors to diagnose AR as an additional diagnostic tool.

Methods: Patients showed rhinorrhea and tested positive on allergic skin and specific immunoglobulin E (IgE) tests were included in the AR group. The non-AR group included individuals no dominant nasal symptoms and tested negative on allergy tests. Nasal lavage fluid samples were collected from all participants. Biomarkers in the samples were quantified using enzyme-linked immunosorbent assay.

Results: Forty-five patients with AR and 28 non-AR subjects were enrolled in this study. Comparing the concentrations of biomarkers, the concentrations of tryptase and IL-5 were significantly higher in the AR group than in the NAR group. And CC16 level and CC16-to-albumin ratio were significantly lower in the AR group. In the combination of tryptase or CC16-to-albumin ratio, the sensitivity was 90.7% and the specificity was 64.3% ( = 0.013).

Conclusion: The combination of "tryptase or CC16-to-albumin" could be used as a screening tool for AR. Although this diagnostic method could not replace conventional diagnostic tools, we could consider the method we proposed as an additional screening tool for patients who could not undergo allergy tests.
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http://dx.doi.org/10.1177/1945892421998260DOI Listing
February 2021

Outcomes of inhaled amikacin-containing multidrug regimens for Mycobacterium abscessus pulmonary disease.

Chest 2021 Feb 20. Epub 2021 Feb 20.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address:

Background: Mycobacterium abscessus-pulmonary disease (MABS-PD) is challenging to treat due to its resistance to antibiotics.

Research Question: What are the outcomes of treatment-naïve MABS-PD patients treated with inhaled amikacin-containing multidrug regimens?

Study Design And Methods: We identified 82 treatment-naïve MABS-PD patients from a prospective observational cohort who were treated with regimens containing inhaled amikacin with or without clofazimine between March 2015 and June 2018 (ClinicalTrials.gov identifier: NCT00970801). During the initial phase, all patients received intravenous amikacin, imipenem (or cefoxitin) and oral azithromycin. Oral clofazimine was added in cases of (i) M. abscessus subspecies abscessus (here M. abscessus) or (ii) M. abscessus subspecies massiliense (here M. massiliense) with cavitary lesions. During the continuation phase, amikacin was changed from injection to inhalation form.

Results: Of 82 patients, 46 (56%) had M. massiliense-PD and 36 (44%) had M. abscessus-PD. Among 59 (72%) patients with nodular bronchiectatic disease, 23 (23/59) had a concurrent cavitary lesion. The remaining 23 (28%) patients had fibrocavitary disease. At 12 months after treatment initiation, cure was achieved in 53 (65%) patients; 42 (42/46, 91%) patients with M. massiliense-PD and 11 (11/36, 31%) patients with M. abscessus-PD (p<0.001). Symptomatic and radiological improvements were observed in 72 (88%) and 64 (78%) patients, respectively, with significantly greater improvement in M. massiliense-PD (96% vs 78% in symptom, p=0.047; 93% vs. 61% in computed tomography, p=0.002).

Interpretation: Inhaled amikacin with or without clofazimine in the regimen provides favorable treatment outcomes in M. massiliense-PD. However, more effective treatments are needed for M. abscessus-PD.
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http://dx.doi.org/10.1016/j.chest.2021.02.025DOI Listing
February 2021

Risk of osteoporotic fracture in older patients under antihypertensive treatment.

Eur J Prev Cardiol 2020 May 9. Epub 2020 May 9.

Cardiovascular Center, Seoul National University Bundang Hospital, Korea.

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http://dx.doi.org/10.1177/2047487320923054DOI Listing
May 2020

One-year outcomes of fixed-dosing Aflibercept therapy for pre treated and naive polypoidal choroidal vasculopathy patient.

BMC Ophthalmol 2021 Feb 18;21(1):94. Epub 2021 Feb 18.

Department of Ophthalmology, Nune Eye Hospital, Noon Bldg 404, Seonreung-ro Gangnam-gu, 06198, Seoul, Republic of Korea.

Background: Polypoidal choroidal vasculopathy (PCV) is a type of age-related macular degeneration that can cause permanent vision loss. The purpose of this paper was to report the one-year outcomes of fixed-dosing aflibercept therapy for the treatment of PCV.

Methods: This was a prospective, single-arm, interventional case series study of 25 PCV patients; 12 pre-treated and 13 treatment-naïve patients. The patients were treated and monitored for 12 months. Each patient was administered with an aflibercept (2.0 mg) injection every month for the first 3 months (the loading phase), and thereafter, once every 2 months. At every follow-up visit, best-corrected visual acuity (BCVA) test, fundus examination, and optical coherence tomography for measuring the central subfield macular thickness (CSMT) were performed. Fluorescein and indocyanine green angiography were conducted at baseline and at 4 and 12 months.

Results: After 12 months of aflibercept therapy, the mean BCVA of the patients significantly improved from 65.48 letters at baseline to 69.91 letters (p=0.001), and the CSMT significantly decreased from 406.92 um at baseline to 276.12 um (p< 0.001). Additionally, ten patients (40%) showed complete polyp regression. The treatment-naïve patients showed a statistically significant improvement in BCVA from 66.58 letters at baseline to 76.36 letters at 12 months, and a significant decrease in CSMT, from 462 to 243 um. In the pre-treated group, there was no change in BCVA (64.46 letters), and the decrease in CSMT from 356.08 to 303.69 um was not statistically significant.

Conclusions: The fixed-dosing aflibercept regimen is effective for treating patients with PCV and is more effective in treatment-naïve patients than in pre-treated patients.

Trial Registration: Clinical Research Information Service (CRiS), Republic of Korea. Identifer: KCT0005798, Registered: Jan 20, 2021. Retrospectively registered, URL: https://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=18546.
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http://dx.doi.org/10.1186/s12886-021-01829-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890830PMC
February 2021

Reliability Verification of Damping Capacity Assessment Through In Vitro Analysis of Implant Micromotion in Peri-implant Bone Loss Model.

Int J Oral Maxillofac Implants 2021 Jan-Feb;36(1):106-114

Purpose: This in vitro study aimed to determine the efficacy of a damping capacity assessment in evaluating the implant stability in a simulated peri-implant bone loss model.

Materials And Methods: The same type of implant was placed sequentially in 0.5-mm-depth increments in polyurethane bone of a constant density, resulting in 11 specimens with varying surrounding bone levels. The implant stability was evaluated by a damping capacity assessment consisting of six consecutive impacts in one set. The damping results, including the contact time and stability index, were measured by three repeated sets of stability tests for each specimen. All implant micromotions were recorded in real time using a laser scanning vibrometer during these stability tests. The micromotions were analyzed in terms of three parameters: maximum displacement, expected mobility, and vibration frequency. Additionally, two other stability indices were acquired three times each for reference. Pearson correlation analysis was used to confirm the correlations among all the variables; P < .05 was considered statistically significant.

Results: As the peri-implant bone level increased, the contact time results decreased gradually from 502 to 290 μs, and the stability index increased from 55 to 78. The implant micromotions of all specimens showed a damped sine waveform graph, which can be divided into impact displacement and self-vibration patterns by the contact end points. As the implant stability increased, these contact end points converged toward the third peak, the maximum displacement and expected mobility decreased, and the vibration frequency increased (ρ = -0.85, -0.88, and 0.99, respectively). Two other stability indices reflected the implant stability due to peri-implant bone loss. The statistical analysis indicated significant correlations among all measured variables; in particular, the three stability indices exhibited high correlations with each other (ρ = 0.99, -0.99, and -1.00, respectively).

Conclusion: Within the limitations of this in vitro study, the implant stability measured by a damping capacity assessment was suitable for investigating the extent of implant micromotions, which were determined by 0.5-mm horizontal changes in the peri-implant bone level.
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http://dx.doi.org/10.11607/jomi.8168DOI Listing
February 2021

Clinical outcomes of post-stent intravascular ultrasound examination for chronic total occlusion intervention with drug-eluting stents.

EuroIntervention 2021 02 16. Epub 2021 Feb 16.

Division of Cardiology, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: Few studies have evaluated intravascular ultrasound (IVUS) use in chronic total occlusion (CTO) percutaneous coronary intervention (PCI).

Aims: In CTO-PCI, we aimed to (1) evaluate the clinical benefits of performing post-stent IVUS in preventing adverse clinical events, and (2) identify IVUS parameters and cut-off values for prediction of target-lesion revascularization (TLR)/reocclusion.

Methods: A total of 1,077 patients with 1077 CTO lesions treated with drug-eluting stents (DES) were included. Clinical outcomes during a median follow-up of 6.3 years were compared between subjects with or without post-stent IVUS using the inverse probability weighting method.

Results: Of 1,077 patients, post-stent IVUS was performed in 838 (77.8%) cases while the remaining 239 (22.2%) cases did not undergo. In the weighted population, the risk of TLR/reocclusion was significantly lower in subjects with post-stent IVUS (9.6% vs. 18.9%, hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.34-0.86, P=0.01), compared with those without post-stent IVUS. Cox-regression analysis showed that minimal stent area (MSA) measured by IVUS was the only parameter independently associated with TLR/reocculsion (HR, 0.78; 95% CI 0.64-0.95; P=0.01) and the optimal MSA cut-off value was 4.9 mm2 for prediction of TLR/reocclusion (area under the curve=0.632, P=0.001).

Conclusions: In CTO-PCI with DES, post-stent IVUS evaluation was associated with a lower risk of TLR/reocclusion. The final MSA was independently associated with TLR/reocclusion with a cut-off value of 4.9 mm2.
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http://dx.doi.org/10.4244/EIJ-D-20-00941DOI Listing
February 2021

High-Dose Steroid Dissolving Microneedle for Relieving Atopic Dermatitis.

Adv Healthc Mater 2021 Feb 15:e2001691. Epub 2021 Feb 15.

Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seoul, 08389, Republic of Korea.

Dissolving microneedles (DMN) supplemented with therapeutic molecules have been developed to enhance transdermal delivery efficiency of topically applied drugs in a minimally invasive manner. However, the dose of the drugs in DMN system is limited owing to the low solubility of drug. In fact, although triamcinolone acetonide (TA) is one of the most widely prescribed drugs for relieving atopic dermatitis (AD), its poor dissolving nature makes it difficult to design and fabricate DMN containing therapeutic dosage of TA. In this study, TA suspension is introduced to encapsulate therapeutic dosage of TA. Sonication and composition optimization of polymers is key to fabricate high dose TA-DMN to induce particle size reduction and dispersion stability of suspension, respectively. After confirming the physical performance of TA-DMN using the selected formulation in vitro, the anti-inflammatory effects of TA-DMN are evaluated in vivo using a mouse model affected with skin inflammation to mimic AD in humans. Herein, high-dose TA-DMN is presented as a candidate agent for relieving AD and, furthermore, for wide application in the treatment of skin inflammatory diseases in which high-dose steroid drugs are required.
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http://dx.doi.org/10.1002/adhm.202001691DOI Listing
February 2021

Double staining method for array tomography using scanning electron microscopy.

Appl Microsc 2020 Jun 22;50(1):14. Epub 2020 Jun 22.

Neural circuit research group, Korea Brain Research Institute, Daegu, South Korea.

Scanning electron microscopy (SEM) plays a central role in analyzing structures by imaging a large area of brain tissue at nanometer scales. A vast amount of data in the large area are required to study structural changes of cellular organelles in a specific cell, such as neurons, astrocytes, oligodendrocytes, and microglia among brain tissue, at sufficient resolution. Array tomography is a useful method for large-area imaging, and the osmium-thiocarbohydrazide-osmium (OTO) and ferrocyanide-reduced osmium methods are commonly used to enhance membrane contrast.Because many samples prepared using the conventional technique without en bloc staining are considered inadequate for array tomography, we suggested an alternative technique using post-staining conventional samples and compared the advantages.
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http://dx.doi.org/10.1186/s42649-020-00033-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818292PMC
June 2020

Clinical characteristics and treatment outcome of Candida tracheobronchitis.

Medicine (Baltimore) 2021 Feb;100(6):e24606

Division of Pulmonary Medicine and Allergy, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea.

Abstract: Although Candida species can cause invasive fungal diseases, such as disseminated infection and pneumonia, they rarely cause tracheobronchitis, which is often fatal.To identify the clinical characteristics of Candida tracheobronchitis, we retrospectively evaluated 8 patients who had pathologically proven Candida tracheobronchitis.Their median age was 64 (range: 51-70) years and 5 were females. Three patients had solid cancers and 5 had hematological malignancies. We classified tracheobronchitis into localized and diffuse types. Of the 8 patients, 5 had localized and 3 had diffuse tracheobronchitis. While all patients with diffuse tracheobronchitis had predisposing risk factors for invasive fungal disease, such as prolonged corticosteroid use, recent use of nucleoside analogues, or recent neutropenia (<500/m3), only 2 of the 5 with localized tracheobronchitis had predisposing risk factors. Four of the 5 patients with localized tracheobronchitis had loco-regional bronchial mucosal damage (e.g., radiation or photodynamic therapy). Although all 8 patients ultimately died, some improved with or without antifungal treatment. Two of the 5 patients (1 with localized and the other with diffuse tracheobronchitis) who received antifungal agents improved after treatment, and 1 patient with localized tracheobronchitis who did not receive antifungal treatment improved spontaneously. Two of the 3 patients with diffuse tracheobronchitis did not respond to antifungal treatment.Candida tracheobronchitis can present as both localized and diffuse types. While the former was influenced more by loco-regional mucosal damage, the latter was influenced more by the patient's immune status. The treatment outcomes were especially poor in patients with diffuse tracheobronchitis.
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http://dx.doi.org/10.1097/MD.0000000000024606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886430PMC
February 2021

Au@ZIF-8 SERS paper for food spoilage detection.

Biosens Bioelectron 2021 Feb 2;179:113063. Epub 2021 Feb 2.

Bionanotechnology Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, 34141, South Korea. Electronic address:

Putrescine and cadaverine are important volatile indicators for the evaluation of food spoilage. In this study, a metal-organic framework (MOF)-coated surface-enhanced Raman scattering (SERS) paper platform for the detection of putrescine and cadaverine is developed. Au@ zeolite imidazolate framework-8 (ZIF-8) SERS paper is fabricated by the coating of ZIF-8 layer on a Au nanoparticle-impregnated paper that is prepared by dry plasma reduction. The Au@ZIF-8 SERS paper is characterized by scanning electron microscope, energy-dispersive X-ray spectroscopy, X-ray diffraction, and N sorption isotherm. The ZIF-8 layer enables the accumulation of gaseous molecules and also provides enhancement of SERS signals. The fluorescence, SERS, and simulation results prove the improved detection ability of the Au@ZIF-8 platform for the volatile molecules. For the selective detection of putrescine and cadaverine, the Au@ZIF-8 SERS paper is functionalized with 4-mercatobenzaldehyde (4-MBA). The 4-MBA molecule acts as a Raman reporter and also a specific receptor for the volatile amine molecules. Using the intensity ratiometric detection of 4-MBA-functionalized Au@ZIF-8 SERS paper, putrescine and cadaverine are quantitatively detected with detection limits of 76.99 and 115.88 parts per billion, respectively. Furthermore, the detection of volatile amine molecules released from spoiled salmon, chicken, beef, and pork samples is demonstrated. It is anticipated that the MOF-coated SERS paper platforms will be applicable not only in food safety but other applications including disease diagnosis and environmental monitoring.
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http://dx.doi.org/10.1016/j.bios.2021.113063DOI Listing
February 2021

Correction to: Connectivity map-based drug repositioning of bortezomib to reverse the metastatic effect of GALNT14 in lung cancer.

Oncogene 2021 Feb 11. Epub 2021 Feb 11.

College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea.

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http://dx.doi.org/10.1038/s41388-021-01642-7DOI Listing
February 2021

Non-persistence with anti-platelet therapy and long-term mortality after ischemic stroke: A nationwide study.

PLoS One 2021 9;16(2):e0244718. Epub 2021 Feb 9.

Department of Family Medicine, Seoul National University Hospital, Seoul, Republic of Korea.

Background: We tried to investigate the effect of non-persistence with antiplatelets after ischemic stroke on long-term all-cause mortality (ACM).

Methods And Findings: We selected newly diagnosed ischemic stroke patients aged ≥20years who were newly treated with aspirin or clopidogrel from 2003-2010 Korean National Health Insurance Service-National Sample Cohort, a random sample of 2.2% of total population. Subjects were divided into two pairs of groups according to persistence with antiplatelets at 6 and 12 months: those who discontinued antiplatelets within 6 months (DA6M) and those who continued them for 6 or months or more (CA6M); and those who discontinued antiplatelets within 12 months (DA12M) and those who continued them for 12 months or more (CA12M). Those who died within 6 months among DA6M and those who died within 12 months among DA12M were excluded along with those with medication possession ratio<80% among CA6M and CA12M. Subjects were followed-up until death or December 31, 2013. Among 3,559 total subjects, DA6M were 1,080 and CA6M were 2,479 while, out of 3,628 total patients, DA12M were 1,434 and CA12M were 2,194. The risks of ACM [adjusted hazard ratio (aHR), 2.25; 95% confidence interval (CI), 1.94-2.61], cerebro-cardiovascular disease (CVD) death (aHR, 2.52; 95% CI, 1.96-3.24) and non-CVD death (aHR, 2.11; 95% CI, 1.76-2.64) of DA6M were all significantly increased compared to CA6M. DA12M also had significantly higher risks of ACM (aHR, 1.93; 95% CI, 1.65-2.25), CVD mortality (aHR, 2.13; 95% CI; 1.63-2.77) and non-CVD mortality (aHR, 1.83;95% CI 1.51-2.22) than DA12M but aHRs were lower than that between DA6M and CA6M. The difference rates of ACM, CVD death, and non-CVD death between non-persistent and persistent groups all continuously widened over time but the degree of difference was gradually decreased.

Conclusions: Maintaining antiplatelets for the first 12 months after ischemic stroke reduces long-term risks of both CVD death and non-CVD death.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244718PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872250PMC
February 2021

Changes in the bony alignment of the foot after tendo-Achilles lengthening in patients with planovalgus deformity.

J Orthop Surg Res 2021 Feb 8;16(1):118. Epub 2021 Feb 8.

Department of Orthopedic Surgery, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-Gu, Sungnam, Gyeonggi, 13620, Republic of Korea.

Background: This study was performed to investigate the change in the bony alignment of the foot after tendo-Achilles lengthening (TAL) and the factors that affect these changes in patients with planovalgus foot deformity.

Methods: Consecutive 97 patients (150 feet; mean age 10 years; range 5.1-35.7) with Achilles tendon contracture (ATC) and planovalgus foot deformity who underwent TAL were included. All patients underwent preoperative and postoperative weight-bearing anteroposterior (AP) or lateral (LAT) foot radiographics. Changes in AP talo-1st metatarsal angle, AP talo-2nd metatarsal angle, LAT talo-1st metatarsal angle, and calcaneal pitch angle and the factors affecting such changes after TAL were analyzed using lineal mixed model.

Results: There were no significant change in AP talo-1st metatarsal angle and AP talo-2nd metatarsal angle after TAL in patients with cerebral palsy (CP) (p = 0.236 and 0.212). However, LAT talo-1st metatarsal angle and calcaneal pitch angle were significantly improved after TAL (13.0°, p < 0.001 and 4.5°, p < 0.001). Age was significantly associated with the change in LAT talo-1st metatarsal angle after TAL (p = 0.028). The changes in AP talo-1st metatarsal angle, AP talo-2nd metatarsal angle, and calcaneal pitch angle after TAL were not significantly associated with the diagnosis (p = 0.879, 0.903, and 0.056). However, patients with CP showed more improvement in LAT talo-1st metatarsal angle (- 5.0°, p = 0.034) than those with idiopathic cause.

Conclusion: This study showed that TAL can improve the bony alignment of the foot in patients with planovalgus and ATC. We recommend that physicians should consider this study's findings when planning operative treatment for such patients.
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http://dx.doi.org/10.1186/s13018-021-02272-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869243PMC
February 2021

Tumour necrosis factor inhibitor tapering in patients with ankylosing spondylitis at low disease activity: factors associated with flare.

Ther Adv Musculoskelet Dis 2021 21;13:1759720X20986732. Epub 2021 Jan 21.

Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-gu, Seoul 06273, Korea.

Background: To investigate factors associated with flare in patients with ankylosing spondylitis (AS) who tapered tumour necrosis factor inhibitors (TNFis) after achievement of low disease activity (LDA) with the standard dose of TNFis.

Methods: This retrospective cohort study included 101 patients with AS who tapered their first TNFis after achievement of LDA. The proportion of reduced standard doses of TNFi throughout the follow up in each patient was quantified using the time-averaged dose quotient (DQ). Clinical characteristics were compared between patients who did and did not experience flare after TNFi tapering. Multivariable Cox regression analysis was performed to identify factors associated with flare. Receiver operating characteristic curve analysis was performed to determine the cut-offs of these covariates that best predicted flare.

Results: Of the total 101 patients, 45 (44.6%) patients experienced flare after TNFi tapering. Compared with patients who did not experience flare, those who experienced flare had a shorter disease duration ( = 0.006), shorter LDA duration before TNFi tapering ( < 0.001) and lower time-averaged DQ ( < 0.001). In multivariable Cox regression analysis, the LDA duration [adjusted hazard ratio (HR): 0.944, 95% confidence interval (CI): 0.906-0.983,  = 0.006] and time-averaged DQ (adjusted HR: 0.978, 95% CI: 0.959-0.998,  = 0.032) were inversely associated with flare. The cut-off values of the LDA duration and time-averaged DQ that best predicted flares were <5.3 months and <60.6%, respectively.

Conclusion: Shorter LDA duration (cut-off value: 5.3 months) and lower time-averaged DQ (cut-off value: 60.6%) were associated with a higher risk of flare after tapering TNFi.
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http://dx.doi.org/10.1177/1759720X20986732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841669PMC
January 2021

Validation of soy isoflavone intake and its health effects: a review of the development of exposure biomarkers.

Nutr Res Pract 2021 Feb 5;15(1):1-11. Epub 2020 Aug 5.

Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03765, Korea.

Background/objectives: It is difficult to consistently demonstrate the health effects of soy isoflavones owing to the multitude of factors contributing to their bioavailability. To accurately verify these health effects, dietary isoflavone intake should be measured using a biologically active dose rather than an intake dose. This concept has been expanded to the development of new exposure biomarkers in nutrition research. This review aims to provide an overview of the development of exposure biomarkers and suggest a novel research strategy for identifying the health effects of soy isoflavone intake.

Materials/methods: We cover recent studies on the health effects of soy isoflavones focusing on isoflavone metabolites as exposure biomarkers.

Results: Compared to non-fermented soy foods, fermented soy foods cause an increased concentration of isoflavones in the biofluid immediately following ingestion. The correlation between exposure biomarkers in blood and urine and the food frequency questionnaire was slightly lower than that of corresponding 24-h dietary recalls. Urinary and blood isoflavone levels did not show a consistent association with chronic disease and cancer risk.

Conclusion: It is crucial to understand the variable bioavailabilities of soy isoflavones, which may affect evaluations of soy isoflavone intake in health and disease. Further studies on the development of valid exposure biomarkers are needed to thoroughly investigate the health effects of isoflavone.
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http://dx.doi.org/10.4162/nrp.2021.15.1.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838478PMC
February 2021

Effectiveness and Safety of Polydioxanone Thread Embedding Acupuncture Compared to Physical Therapy in the Treatment of Patients with Non-Specific Chronic Neck Pain: An Assessor-Blinded, Randomized, Controlled, Clinical Trial.

J Pain Res 2021 28;14:201-211. Epub 2021 Jan 28.

Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea.

Background: Thread embedding acupuncture (TEA) has recently been used as a conservative treatment method for non-specific chronic neck pain (CNP). The objective of this study was to evaluate the effectiveness and safety of TEA compared to physical therapy (PT) for treating patients with CNP.

Methods: A total of 128 patients diagnosed with CNP were randomly assigned to a TEA group and a PT group at a 1:1 ratio. The TEA group received four sessions of TEA, while the PT group received eight sessions of PT over 4 weeks. Outcomes were assessed using Neck Pain and Disability Scale (NPDS), clinically important difference (CID), cervical spinal angle, Beck Depression Inventory II (BDI-II), Beck Anxiety Inventory (BAI), Patient Global Impression of Change (PGIC), and EuroQol Five-Dimension (EQ-5D) at baseline and 5, 9, and 13 weeks.

Results: The TEA group showed significant improvement in NPDS compared to the PT group at 5, 9, and 13 weeks. Proportions of patients with decreased NPDS scores of more than 11.5 points (minimal CID) were significantly higher in the TEA group at 5, 9, and 13 weeks. There were significant differences between the two groups at 5, 9, and 13 weeks for BDI-II, and at 5 and 9 weeks for BAI. For EQ-5D, the TEA group showed significant improvement at 5, 9, and 13 weeks. There was no significant difference in cervical spinal angle between the two groups. For PGIC, better improvement was observed at 9 and 13 weeks in the TEA group. Adverse events associated with interventions were mostly temporary and mild.

Conclusion: For patients with CNP, TEA treatment was found to be more effective than PT treatment for improving their pain and dysfunction, quality of life, and psychological distress. Despite some post-treatment discomfort, TEA treatment can be considered as a useful treatment method for patients with CNP.

Trial Registration: This trial has been registered 5 April 2019 in Clinical Research Information Service of South Korea (CRIS- KCT0003720).
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http://dx.doi.org/10.2147/JPR.S276941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850897PMC
January 2021

Unified Approach to Furan Natural Products via Phosphine-Palladium Catalysis.

Angew Chem Int Ed Engl 2021 Feb 2. Epub 2021 Feb 2.

University of California Los Angeles, Chemistry and Biochemistry, UNITED STATES.

Polyalkyl furans are widespread in Nature, often performing important biological roles. Despite a plethora of methods for the synthesis of tetrasubstituted furans, the construction of tetraalkyl furans remains non-trivial. The prevalence of alkyl groups in bioactive furan natural products, combined with the desirable bioactivities of tetraalkyl furans, calls for a general synthetic protocol for polyalkyl furans. This paper describes a Michael-Heck approach, using sequential phosphine-palladium catalysis, for the preparation of various polyalkyl furans from readily available precursors. The versatility of this method is illustrated by the total syntheses of nine distinct polyalkylated furan natural products belonging to different classes, namely the furanoterpenes rosefuran, sesquirosefuran, and mikanifuran; the marine natural products plakorsins A, B, and D and plakorsin D methyl ester; and the furan fatty acids 3D5 and hydromumiamicin.
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http://dx.doi.org/10.1002/anie.202015232DOI Listing
February 2021

Correlation between 3D scanner image and MRI for tracking volume changes in head and neck cancer patients.

J Appl Clin Med Phys 2021 Feb 1. Epub 2021 Feb 1.

Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea.

Introduction: We investigated the correlation between optical surface imaging using a three-dimensional (3D) scanner and magnetic resonance imaging (MRI) for suggesting feasibility in the clinical process of tracking volume changes in head and neck patients during radiation treatment.

Methods: Ten patients were divided into two groups depending on the location of their tumor (i.e., right or left side). With weekly imaging data, the change in volume based on MRI was evaluated during the treatment course. Four volumes of interest (VOIs) were calculated on the 3D surface image of the facial and cervical areas using an optical 3D scanner, and the correlation between volumetric parameters were analyzed.

Results: The target volume changed significantly overall for both groups. The changes parotid volume reduced by up to 3.8% and 28.0% for groups A (right side) and B (left side), respectively. In Group A, VOI 1 on the facial area and VOI 3 on the cervical area decreased gradually during the treatment course by up to 3.3% and 10.7%, respectively. In Group B, only VOI 4 decreased gradually during the treatment course and reduced by up to 9.2%. In group A, the change in target volume correlated strongly with right-side parotid, VOI 1, and VOI 3, respectively. The parotid also showed strong correlations with VOIs (P < 0.01). The weight loss was strongly correlated with either PTV or parotid without statistical significance (P > 0.05). In group B (left side), the change in target volume correlated strongly with each volumetric parameter, including weight loss. For individual patient, PTV showed more correlation with VOIs on the cervical area than VOIs on the facial area.

Conclusions: An optical 3D scanner can be applied to track changes in volume without radiation exposure during treatment and the optical surface image correlated with MRI.
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http://dx.doi.org/10.1002/acm2.13181DOI Listing
February 2021

CardioNet: a manually curated database for artificial intelligence-based research on cardiovascular diseases.

BMC Med Inform Decis Mak 2021 Jan 28;21(1):29. Epub 2021 Jan 28.

Division of Cardiology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olumpicro 43gil, Songpagu, Seoul, 05505, Republic of Korea.

Background: Cardiovascular diseases (CVDs) are difficult to diagnose early and have risk factors that are easy to overlook. Early prediction and personalization of treatment through the use of artificial intelligence (AI) may help clinicians and patients manage CVDs more effectively. However, to apply AI approaches to CVDs data, it is necessary to establish and curate a specialized database based on electronic health records (EHRs) and include pre-processed unstructured data.

Methods: To build a suitable database (CardioNet) for CVDs that can utilize AI technology, contributing to the overall care of patients with CVDs. First, we collected the anonymized records of 748,474 patients who had visited the Asan Medical Center (AMC) or Ulsan University Hospital (UUH) because of CVDs. Second, we set clinically plausible criteria to remove errors and duplication. Third, we integrated unstructured data such as readings of medical examinations with structured data sourced from EHRs to create the CardioNet. We subsequently performed natural language processing to structuralize the significant variables associated with CVDs because most results of the principal CVD-related medical examinations are free-text readings. Additionally, to ensure interoperability for convergent multi-center research, we standardized the data using several codes that correspond to the common data model. Finally, we created the descriptive table (i.e., dictionary of the CardioNet) to simplify access and utilization of data for clinicians and engineers and continuously validated the data to ensure reliability.

Results: CardioNet is a comprehensive database that can serve as a training set for AI models and assist in all aspects of clinical management of CVDs. It comprises information extracted from EHRs and results of readings of CVD-related digital tests. It consists of 27 tables, a code-master table, and a descriptive table.

Conclusions: CardioNet database specialized in CVDs was established, with continuing data collection. We are actively supporting multi-center research, which may require further data processing, depending on the subject of the study. CardioNet will serve as the fundamental database for future CVD-related research projects.
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http://dx.doi.org/10.1186/s12911-021-01392-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842077PMC
January 2021

A Simple Route of Printing Explosive Crystalized Micro-Patterns by Using Direct Ink Writing.

Micromachines (Basel) 2021 Jan 21;12(2). Epub 2021 Jan 21.

Department of Chemistry, Institute of Biological Interfaces, Sogang University, Seoul 04107, Korea.

The production of energetic crystalized micro-patterns by using one-step printing has become a recent trend in energetic materials engineering. We report a direct ink writing (DIW) approach in which micro-scale energetic composites composed of 1,3,5-trinitro-1,3,5-triazinane (RDX) crystals in selected ink formulations of a cellulose acetate butyrate (CAB) matrix are produced based on a direct phase transformation from organic, solvent-based, all-liquid ink. Using the formulated RDX ink and the DIW method, we printed crystalized RDX micro-patterns of various sizes and shapes on silicon wafers. The crystalized RDX micro-patterns contained single crystals on pristine Si wafers while the micro-patterns containing dendrite crystals were produced on UV-ozone (UVO)-treated Si wafers. The printing method and the formulated all-liquid ink make up a simple route for designing and printing energetic micro-patterns for micro-electromechanical systems.
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http://dx.doi.org/10.3390/mi12020105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911122PMC
January 2021

Tuning the hierarchical pore structure of graphene oxide through dual thermal activation for high-performance supercapacitor.

Sci Rep 2021 Jan 22;11(1):2063. Epub 2021 Jan 22.

Department of Chemical and Biomolecular Engineering, Yonsei University, Yonsei-ro 50, Seodaemun-gu, Seoul, 120-749, Republic of Korea.

Herein, we introduce a simple method to prepare hierarchical graphene with a tunable pore structure by activating graphene oxide (GO) with a two-step thermal annealing process. First, GO was treated at 600 °C by rapid thermal annealing in air, followed by subsequent thermal annealing in N. The prepared graphene powder comprised abundant slit nanopores and micropores, showing a large specific surface area of 653.2 m/g with a microporous surface area of 367.2 m/g under optimized conditions. The pore structure was easily tunable by controlling the oxidation degree of GO and by the second annealing process. When the graphene powder was used as the supercapacitor electrode, a specific capacitance of 372.1 F/g was achieved at 0.5 A/g in 1 M HSO electrolyte, which is a significantly enhanced value compared to that obtained using activated carbon and commercial reduced GO. The performance of the supercapacitor was highly stable, showing 103.8% retention of specific capacitance after 10,000 cycles at 10 A/g. The influence of pore structure on the supercapacitor performance was systematically investigated by varying the ratio of micro- and external surface areas of graphene.
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http://dx.doi.org/10.1038/s41598-021-81759-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822934PMC
January 2021

Clinical Characteristics and Treatment Outcomes of De Novo Nonconvulsive Status Epilepticus: A Retrospective Study.

J Clin Neurol 2021 Jan;17(1):26-32

Department of Neurology, Nowon Eulji Medical Center, Eulji University, Seoul, Korea.

Background And Purpose: Nonconvulsive status epilepticus (NCSE) is challenging to diagnose. This study aimed to describe and classify the clinical features and electroencephalography (EEG) findings of patients with de novo NCSE and to correlate them with clinical outcomes.

Methods: We retrospectively reviewed the medical and EEG records of patients admitted to our institution with altered mentation and EEG abnormalities from January 1, 2013 to December 31, 2018. We evaluated premorbid modified Rankin Scale (mRS) scores, underlying disorders, precipitating factors, clinical manifestations, laboratory tests, and outcomes after a 3-month follow-up. Patients who met the Salzburg Consensus Criteria for NCSE were categorized into good-outcome and poor-outcome groups. A good outcome was defined as 1) clinical and electrographic seizures ceasing after treatment, and 2) an mRS score of ≤2 or remaining unchanged during the 3-month follow-up. A poor outcome was defined as 1) death, 2) seizures continuing despite treatment, or 3) a follow-up mRS score of ≥3 in a patient with a premorbid mRS score of ≤2, or a follow-up mRS score that increased in a patient with a premorbid mRS score of ≥3.

Results: The 48 included patients comprised 37 categorized into the good-outcome group and 11 into the poor-outcome group. The presence of acute metabolic disturbances was significantly correlated with poor outcome (=0.036), while the other analyzed variables were not significantly correlated with outcomes.

Conclusions: Acute metabolic disturbances in NCSE are associated with poor outcomes. Adequate treatment of underlying reversible disorders alongside controlling seizures is critical for patients with NCSE.
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http://dx.doi.org/10.3988/jcn.2021.17.1.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840313PMC
January 2021

Arsenic adsorption on two types of powdered and beaded coal mine drainage sludge adsorbent.

Chemosphere 2021 Jan 11;272:129560. Epub 2021 Jan 11.

School of Civil, Environmental, and Architectural Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea. Electronic address:

The aim of this study was to evaluate the performance of a new adsorbent in terms of beading the sludge generated from coal mine drainage or arsenic removed from water is treated by electro-purification (EP) and chemical-precipitation (CP) methods. Batch experiments were conducted to study the influence of experimental parameters such as pH and temperature, as well as the mechanism of arsenic adsorption with the new adsorbent. The porosity of coal mine drainage sludge (CMDS)-beaded adsorbent made of chitosan and alginate was optimized by adding NaHCO powder to generate CO gas during the preparation process. Two types of adsorbents, beaded EP Najeon CMDS (BCMDS-NJ) and beaded CP Yeongdong CMDS (BCMDS-YD), were prepared by heating. The specific surface areas of the powdered adsorbents CMDS-NJ and CMDS-YD were 104 and 231 m g, respectively. The prepared beaded adsorbents BCMDS-NJ and BCMDS-YD had good porosity and specific surface areas of 16.8 and 21.2 m g, respectively. The X-ray diffraction results showed that the structure was goethite (aragonite) and schwertmannite. The pseudo second-order, intra-particle, and Langmuir models were used to explain the adsorption process. The q values of As(III) with BCDMS-NJ and BCMDS-YD adsorbents are 4.31 and 4.58 mg g, respectively and those of AS(V) are 9.31 and 10.93 mg g, respectively. The adsorption capacity for As(III) increased with increasing pH, whereas that for As(V) decreased. The activation energy was 8 kJ mol or more. The mechanism of adsorption of arsenic using a beaded adsorbent was chemical adsorption followed by diffusion. The results of the present study suggest that new adsorbents can be effectively utilized for arsenic removal from water.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129560DOI Listing
January 2021

An Accelerated Wound-Healing Surgical Suture Engineered with an Extracellular Matrix.

Adv Healthc Mater 2021 Jan 18:e2001686. Epub 2021 Jan 18.

Department of Chemistry and Institute of Biological Interfaces, Sogang University, 35-Baekbeom-ro, Mapo-gu, Seoul, 04107, Republic of Korea.

A suture is a ubiquitous medical device to hold wounded tissues together and support the healing process after surgery. Surgical sutures, having incomplete biocompatibility, often cause unwanted infections or serious secondary trauma to soft or fragile tissue. In this research, UV/ozone (UVO) irradiation or polystyrene sulfonate acid (PSS) dip-coating is used to achieve a fibronectin (FN)-coated absorbable suture system, in which the negatively charged moieties produced on the suture cause fibronectin to change from a soluble plasma form into a fibrous form, mimicking the actions of cellular fibronectin upon binding. The fibrous fibronectin coated on the suture can be exploited as an engineered interface to improve cellular migration and adhesion in the region around the wounded tissue while preventing the binding of infectious bacteria, thereby facilitating wound healing. Furthermore, the FN-coated suture is found to be associated with a lower friction between the suture and the wounded tissue, thus minimizing the occurrence of secondary wounds during surgery. It is believed that this surface modification can be universally applied to most kinds of sutures currently in use, implying that it may be a novel way to develop a highly effective and safer suture system for clinical applications.
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http://dx.doi.org/10.1002/adhm.202001686DOI Listing
January 2021

Antiviral activity of lambda-carrageenan against influenza viruses and severe acute respiratory syndrome coronavirus 2.

Sci Rep 2021 01 12;11(1):821. Epub 2021 Jan 12.

Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), 141 Gajeongro, Yuseong, Daejeon, 34114, Republic of Korea.

Influenza virus and coronavirus, belonging to enveloped RNA viruses, are major causes of human respiratory diseases. The aim of this study was to investigate the broad spectrum antiviral activity of a naturally existing sulfated polysaccharide, lambda-carrageenan (λ-CGN), purified from marine red algae. Cell culture-based assays revealed that the macromolecule efficiently inhibited both influenza A and B viruses with EC values ranging from 0.3 to 1.4 μg/ml, as well as currently circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with an EC value of 0.9 ± 1.1 μg/ml. No toxicity to the host cells was observed at concentrations up to 300 μg/ml. Plaque titration and western blot analysis verified that λ-CGN reduced expression of viral proteins in cell lysates and suppressed progeny virus production in culture supernatants in a dose-dependent manner. This polyanionic compound exerts antiviral activity by targeting viral attachment to cell surface receptors and preventing virus entry. Moreover, its intranasal administration to mice during influenza A viral challenge not only alleviated infection-mediated reductions in body weight but also protected 60% of mice from virus-induced mortality. Thus, λ-CGN could be a promising antiviral agent for preventing infection with several respiratory viruses.
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http://dx.doi.org/10.1038/s41598-020-80896-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804421PMC
January 2021

A Prosthetic Socket with Active Volume Compensation for Amputated Lower Limb.

Sensors (Basel) 2021 Jan 8;21(2). Epub 2021 Jan 8.

Daegu Research Center for Medical Devices, Korea Institute of Machinery and Materials, Daegu 42994, Korea.

Typically, the actual volume of the residual limb changes over time. This causes the prosthesis to not fit, and then pain and skin disease. In this study, a prosthetic socket was developed to compensate for the volume change of the residual limb. Using an inflatable air bladder, the proposed socket monitors the pressure in the socket and keeps the pressure distribution uniform and constant while walking. The socket has three air bladders on anterior and posterior tibia areas, a latching type 3-way pneumatic valve and a portable control device. In the paper, the mechanical properties of the air bladder were investigated, and the electromagnetic analysis was performed to design the pneumatic valve. The controller is based on a hysteresis control algorithm with a closed loop, which keeps the pressure in the socket close to the initial set point over a long period of time. In experiments, the proposed prosthesis was tested through the gait simulator that can imitate a human's gait cycle. The active volume compensation of the socket was successfully verified during repetitive gait cycle using the weight loads of 50, 70, and 90 kg and the residual limb model with a variety of volumes. It was confirmed that the pressure of the residual limb recovered to the initial state through the active control. The pressure inside the socket had a steady state error of less than 0.75% even if the volume of the residual limb was changed from -7% to +7%.
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http://dx.doi.org/10.3390/s21020407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827594PMC
January 2021

Mesenchymal stem cells genetically engineered to express platelet-derived growth factor and heme oxygenase-1 ameliorate osteoarthritis in a canine model.

J Orthop Surg Res 2021 Jan 11;16(1):43. Epub 2021 Jan 11.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, South Korea.

Background: Mesenchymal stem cells (MSCs) are used for the treatment of osteoarthritis (OA), and MSC genetic engineering is expected to enhance cartilage repair. Here, we aimed to investigate the effect of MSCs overexpressing platelet-derived growth factor (PDGF) or heme oxygenase-1 (HO-1) in chondrocytes and synovial cells with an OA phenotype and assess the in vivo efficacy of intra-articular injections of these MSCs in canine OA models.

Methods: Canine adipose-derived MSCs were transfected with canine PDGF (PDGF-MSCs) or HO-1 (HO-1-MSCs) using lentiviral vectors. Canine chondrocytes or synovial cells were stimulated with lipopolysaccharide (LPS) to mimic the inflammatory OA model and then co-cultured with MSCs, PDGF-MSCs, or HO-1-MSCs for 24 h and 72 h. The mRNA levels of pro-inflammatory, extracellular matrix-degradative/synthetic, or pain-related factors were measured after co-culture by real-time PCR. Furthermore, a surgery-induced canine OA model was established and the dogs were randomized into four groups: normal saline (n = 4), MSCs (n = 4), PDGF-MSCs (n = 4), and HO-1-MSCs (n = 4). The OA symptoms, radiographic OA severity, and serum matrix metallopeptidase (MMP)-13 levels were assessed before and 10 weeks after treatment, to evaluate the safety and efficacy of the modified MSCs.

Results: PDGF or HO-1 overexpression significantly reduced the expression of pro-inflammatory factors, MMP-13, and nerve growth factor elicited by LPS and increased that of aggrecan and collagen type 2 in chondrocytes (P < 0.05). In addition, the expression of aggrecanases was significantly downregulated in synovial cells, whereas that of tissue inhibitor of metalloproteinases was upregulated (P < 0.05). Furthermore, the co-cultured MSCs highly expressed genes that contributed to the maintenance of joint homeostasis (P < 0.05). In vivo studies showed that OA symptoms improved after administration of all MSCs. Also, PDGF-MSCs significantly improved limb function and reduced pain (P < 0.05). The results of the radiographic assessment and serum MMP-13 levels did not vary significantly compared to those of the control.

Conclusions: Genetically modifying PDGF and HO-1 in MSCs is an effective strategy for treating OA, suggesting that PDGF-MSCs can be novel therapeutic agents for improving OA symptoms.
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http://dx.doi.org/10.1186/s13018-020-02178-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802278PMC
January 2021