[Show abstract][Hide abstract] ABSTRACT: Objectives: To evaluate the mobile health applications (apps) developed by a single tertiary hospital in Korea with a particular focus on quality and patient safety. Methods: Twenty-three mobile health apps developed by Asan Medical Center were selected for analysis after exclusion of the apps without any relationship with healthcare or clinical workflow, the apps for individual usage, and the mobile Web apps. Two clinical informaticians independently evaluated the apps with respect to the six aims for quality improvement suggested by the United States Institute of Medicine. All discrepancies were resolved after discussion by the two reviewers. The six aims observed in the apps were reviewed and compared by target users. Results: Eleven apps targeted patients, the other 12 were designed for healthcare providers. Among the apps for patients, one app also had functions for healthcare providers. 'My cancer diary' and 'My chart in my hand' apps matched all the six aims. Of the six aims, Timeliness was the most frequently observed (20 apps), and Equity was the least observed (6 apps). Timeliness (10/11 vs. 10/12) and Patient safety (10/11 vs. 9/12) were frequently observed in both groups. In the apps for patients, Patient-centered-ness (10/11 vs. 2/12) and Equity (6/11 vs. 0/12) were more frequent but Efficiency (5/11 vs. 10/12) was less frequent. Conclusions: Most of the six aims were observed in the apps, but the extent of coverage varied. Further studies, evaluating the extent to which they improve quality are needed.
Healthcare Informatics Research 10/2015; 21(4):299-306. DOI:10.4258/hir.2015.21.4.299
[Show abstract][Hide abstract] ABSTRACT: A series of fluorophenyl and pyridine analogues of 1 and 2 were synthesized as ring-truncated deguelin surrogates and evaluated for their HIF-1α inhibition. Their structure-activity relationship was systematically investigated based on the variation of the linker B-region moiety. Among the inhibitors, compound 25 exhibited potent HIF-1α inhibition in a dose-dependent manner and significant antitumor activity in H1299 with less toxicity than deguelin. It also inhibited in vitro hypoxia-mediated angiogenic processes in HRMECs. The docking study indicates that 25 occupied the C-terminal ATP-binding pocket of HSP90 in a similar mode as 1, which implies that the anticancer and antiangiogenic activities of 25 are derived from HIF-1α destabilization by binding to the C-terminal ATP-binding site of hHSP90.
European Journal of Medicinal Chemistry 10/2015; 104:157-164. DOI:10.1016/j.ejmech.2015.09.033 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: On page 6029, S.‐Y. Lee, S.‐Y. Lee, and co‐workers present cellulose nanofibril/multiwall carbon nanotube‐based hetero‐nanonet paper batteries as 1D material‐mediated cell architectures to enable ultrahigh energy density and shape versatility far beyond those achievable with conventional battery technologies. Benefiting from 3D bicontinuous electron/ion transport pathways and exceptional mechanical compliance, the hetero‐nanonet paper batteries provide unprecedented improvements in the electrochemical reaction kinetics, energy density, and origami foldability.
[Show abstract][Hide abstract] ABSTRACT: Intracellular amyloid beta (Aβ) has been implicated in neuronal cell death in Alzheimer's disease (AD). Intracellular Aβ also contributes to tight junction breakdown of retinal pigment epithelium (RPE) in age-related macular degeneration (AMD). Although Aβ is predominantly secreted from neuronal cells, the mechanism of Aβ transport into RPE remains to be fully elucidated. In this study, we demonstrated that intracellular Aβ was found concomitantly with the breakdown of tight junction in RPE after subretinal injection of Aβ into the mouse eye. We also presented evidence that receptor for advanced glycation end products (RAGE) contributed to endocytosis of Aβ in RPE. siRNA-mediated knockdown of RAGE prevented intracellular Aβ accumulation as well as subsequent tight junction breakdown in RPE. In addition, we found that RAGE-mediated p38 MAPK signaling contributed to endocytosis of Aβ. Blockade of RAGE/p38 MAPK signaling inhibited Aβ endocytosis, thereby preventing tight junction breakdown in RPE. These results implicate that intracellular Aβ contributes to the breakdown of tight junction in RPE via the RAGE/p38 MAPK-mediated endocytosis. Thus, we suggest that RAGE could be a potential therapeutic target for intracellular Aβ induced outer BRB breakdown in AMD.
[Show abstract][Hide abstract] ABSTRACT: Objective:
The influence of high-dose statin therapy on the serial stent healing process has not been fully investigated. Using optical coherence tomography, the effect of high-dose statin therapy on stent strut coverage was evaluated in drug-eluting stent-treated patients.
Approach and results:
Sixty patients were randomly assigned to 2 groups according to the statin dose (atorvastatin 40 mg as high-dose statin therapy [n=29] versus pravastatin 20 mg as low-dose statin therapy [n=31]). Serial optical coherence tomographic evaluation post procedure and at the 3-month and 12-month follow-ups was performed in 50 patients with 54 stents (23 atorvastatin-treated patients versus 27 pravastatin-treated patients). The percentage of uncovered struts was defined as the ratio of uncovered struts/total struts. The primary end point was the percentage of uncovered struts at the 12-month follow-up. The secondary end point was the percentage of uncovered struts at the 3-month follow-up and the comparative percentage change (Δ) of uncovered struts at the 3- and 12-month follow-ups between the different dose statin therapies. The percentage of uncovered struts was 7.4% (range, 4.3%-10.4%) in atorvastatin-treated patients versus 10.6% (range, 5.7%-22.6%) in pravastatin-treated patients at the 3-month follow-up (P=0.13) and 1.3% (0.3%-3.8%) versus 2.5% (0.9%-9.7%), respectively, at the 12-month follow-up (P=0.01). The percentage Δ of uncovered struts from 3 to 12 months of follow-up was -7.9±8.5% in atorvastatin-treated patients versus -9.3±12.5% in pravastatin-treated patients (P=0.67).
This study suggested that high-dose statin therapy might provide a beneficial effect for the vascular healing process after drug-eluting stent implantation.
[Show abstract][Hide abstract] ABSTRACT: Forthcoming smart energy era is in strong pursuit of full-fledged rechargeable power sources with reliable electrochemical performances and shape versatility. Here, as a naturally abundant/environmentally friendly cellulose-mediated cell architecture strategy to address this challenging issue, a new class of hetero-nanonet (HN) paper batteries based on 1D building blocks of cellulose nanofibrils (CNFs)/multiwall carbon nanotubes (MWNTs) is demonstrated. The HN paper batteries consist of CNF/MWNT-intermingled heteronets embracing electrode active powders (CM electrodes) and microporous CNF separator membranes. The CNF/MWNT heteronet-mediated material/structural uniqueness enables the construction of 3D bicontinuous electron/ion transport pathways in the CM electrodes, thus facilitating electrochemical reaction kinetics. Furthermore, the metallic current collectors-free, CNF/MWNT heteronet architecture allows multiple stacking of CM electrodes in series, eventually leading to user-tailored, ultrathick (i.e., high-mass loading) electrodes far beyond those accessible with conventional battery technologies. Notably, the HN battery (multistacked LiNi0.5Mn1.5O4 (cathode)/multistacked graphite (anode)) provides exceptionally high-energy density (=226 Wh kg−1 per cell at 400 W kg−1 per cell), which surpasses the target value (=200 Wh kg−1 at 400 W kg−1) of long-range (=300 miles) electric vehicle batteries. In addition, the heteronet-enabled mechanical compliance of CM electrodes, in combination with readily deformable CNF separators, allows the fabrication of paper crane batteries via origami folding technique.
[Show abstract][Hide abstract] ABSTRACT: The eye is a small and enclosed organ which makes it an ideal target for gene therapy. Recently various strategies have been applied to gene therapy in retinopathies using non-viral and viral gene delivery to the retina and retinal pigment epithelium (RPE). Subretinal injection is the best approach to deliver viral vectors directly to RPE cells. Before the clinical trial of a gene therapy, it is inevitable to validate the efficacy of the therapy in animal models of various retinopathies. Thus, subretinal injection in mice becomes a fundamental technique for an ocular gene therapy. In this protocol, we provide the easy and replicable technique for subretinal injection of viral vectors to experimental mice. This technique is modified from the intravitreal injection, which is widely used technique in ophthalmology clinics. The representative results of RPE/choroid/scleral complex flat-mount will help to understand the efficacy of this technique and adjust the volume and titer of viral vectors for the extent of gene transduction.
[Show abstract][Hide abstract] ABSTRACT: Familial exudative vitreoretinopathy (FEVR) is a rare hereditary disorder characterized by the failure of peripheral retinal vascularization. The genes FZD4, LRP5, and TSPAN12 are known to be associated with the autosomal inheritance form of FEVR. In this study, we performed mutation screening for FZD4, LRP5, and TSPAN12 in patients with clinical diagnosis of FEVR. In patients with no mutation detected, sequencing analyses for ZNF408, a novel gene potentially related to FEVR, and two other genes related to retinal development, LGR4 and ATOH7, were performed.
Mutational studies were done in 51 unrelated patients with diagnosis of FEVR during 2008 to 2012 at the Seoul National University Hospital. These patients were screened previously for NDP gene and confirmed to be negative for mutations. Diagnosis of FEVR was established by ophthalmic examinations. Data collected from medical records included sex, age at diagnosis, clinical presentation, and angiographic findings.
In this study, we identified 3 known mutations, 10 novel variants with high possibility of pathogenicity, and a whole gene deletion in a total of 18 unrelated patients of 51, resulting in 35.3% of patients being genetically confirmed as having FEVR. Among the patients with pathogenic mutations detected, FZD4 mutations accounted for the largest proportion of autosomal inheritance FEVR cases (13/18 patients, 72.2%), followed by LRP5 (4/18 patients, 22.2%) and TSPAN12 (1/18 patients, 5.6%). No pathogenic mutations were identified in ZNF408, LGR4, and ATOH7. A significant difference in FEVR stage and visual acuity was observed according to the gene involved, showing that patients with FZD4 mutations had milder phenotype.
Mutations of FZD4 accounted for the largest proportion, which could be directly applied to the testing strategy to start with screening for FZD4 mutations. Panel sequencing consisting of related genes would be an alternative choice for the diagnosis of FEVR. Also, genotype-phenotype correlation suggested in this study could be helpful in genetic counseling of the probands and their family members as well.
[Show abstract][Hide abstract] ABSTRACT: Anti-vascular endothelial growth factor (VEGF) agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondria-related genes, Ppargc1a and Ucp1, all of which are characteristics of “whitening” of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants.
PLoS ONE 07/2015; 10(7). DOI:10.1371/journal.pone.0134308 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: R-(-)-β-O-methylsynephrine (OMe-Syn) is a naturally occurring small molecule that was identified in a previous screen as an inhibitor of angiogenesis. In this study, we conducted two animal model experiments to investigate the in vivo antiangiogenic activity of OMe-Syn. OMe-Syn significantly inhibited angiogenesis in a transgenic zebrafish model as well as in a mouse retinopathy model. To elucidate the underlying mechanisms responsible for the antiangiogenic activity of OMe-Syn, we used phage display cloning to isolate potential OMe-Syn binding proteins from human cDNA libraries and identified nucleoporin 153 kDa (NUP153) as a primary binding partner of OMe-Syn. OMe-Syn competitively inhibited mRNA binding to the RNA-binding domain of NUP153. Furthermore, depletion of NUP153 in human cells or zebrafish embryos led to an inhibition of angiogenesis, in a manner similar to that seen in response to OMe-Syn treatment. These data suggest that OMe-Syn is a promising candidate for the development of a novel antiangiogenic agent and that inhibition of NUP153 is possibly responsible for the antiangiogenic activity of OMe-Syn.
International journal of biological sciences 07/2015; 11(9):1088-99. DOI:10.7150/ijbs.10603 · 4.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pericytes enveloping the endothelium play an important role in the physiology and pathology of microvessels, especially in vessel maturation and stabilization. However, our understanding of fundamental pericyte biology is limited by the lack of a robust in vitro model system that allows researchers to evaluate the interactions among multiple cell types in perfusable blood vessels. The present work describes a microfluidic platform that can be used to investigate interactions between pericytes and endothelial cells (ECs) during the sprouting, growth, and maturation steps of neovessel formation. A mixture of ECs and pericytes was attached to the side of a pre-patterned three dimensional fibrin matrix and allowed to sprout across the matrix. The effects of intact coverage and EC maturation by the pericytes on the perfused EC network were confirmed using a confocal microscope. Compared with EC monoculture conditions, EC-pericyte co-cultured vessels showed a significant reduction in diameter, increased numbers of junctions and branches and decreased permeability. In response to biochemical factors, ECs and pericytes in the platform showed the similar features with previous reports from in vivo experiments, thus reflect various pathophysiological conditions of in vivo microvessels. Taken together, these results support the physiological relevancy of our three-dimensional microfluidic culture system but also that the system can be used to screen drug effect on EC-pericyte biology.
PLoS ONE 07/2015; 10(7):e0133880. DOI:10.1371/journal.pone.0133880 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vascular integrity is important in maintaining homeostasis of brain microenvironments. In various brain diseases including Alzheimer’s disease, stroke, and multiple sclerosis, increased paracellular permeability due to breakdown of blood-brain barrier is linked with initiation and progression of pathological conditions. We developed a capacitance sensor array to monitor dielectric responses of cerebral endothelial cell monolayer, which could be utilized to evaluate the integrity of brain microvasculature. Our system measured real-time capacitance values which demonstrated frequency- and time-dependent variations. With the measurement of capacitance at the frequency of 100 Hz, we could differentiate the effects of vascular endothelial growth factor (VEGF), a representative permeability-inducing factor, on endothelial cells and quantitatively analyse the normalized values. Interestingly, we showed differential capacitance values according to the status of endothelial cell monolayer, confluent or sparse, evidencing that the integrity of monolayer was associated with capacitance values. Another notable feature was that we could evaluate the expression of molecules in samples in our system with the reference of real-time capacitance values. We suggest that this dielectric spectroscopy system could be successfully implanted as a novel in vitro assay in the investigation of the roles of paracellular permeability in various brain diseases.
[Show abstract][Hide abstract] ABSTRACT: The objective of this research is to design a piezoelectric tile for harvesting energy from footsteps and to optimize the system for harvesting maximum energy. Because piezoelectric modules easily break when directly subjected to energy generated by human movements, we designed a tile that employs indirect energy transmission using springs and a tip mass. We aimed at matching the mechanical resonance frequency of the tile with that of the piezoelectric modules. The resonance frequency of a piezoelectric module with a 10-g tip mass was almost similar to the vibration frequency of the tile at 22.5 Hz when we dropped an 80-g steel ball from a 1-m height. We performed impedance matching and realized a matching value of 15 kΩ. Under these optimal mechanical and electrical conditions, we harvested 770-μW RMS and 55-mW peak output power.
Current Applied Physics 03/2015; 15(6). DOI:10.1016/j.cap.2015.02.009 · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and thus contributes to many vasoproliferative retinopathies including retinopathy of prematurity. Based on the importance of canonical transient receptor potential (TRPC) channels in VEGF signaling, we firstly evaluated the expression of TRPC channels in mouse retina by reverse transcriptase-polymerase chain reaction. All seven TRPC channels were expressed in mouse retina. TRPC4 channels were chosen for further analysis based on their upregulation on hypoxic retina according to the GEO database under the identifier GSE19886. Interestingly, TRPC4 suppression by intravitreal injection of siRNA against mTRPC4 significantly inhibited retinal neovascularization. To further investigate the effect of TRPC4 suppression on neovascularization, human retina microvascular endothelial cells (HRMECs) that are responsible for initiating neovascularization in response to increased VEGF in OIR retina were transfected with siRNA against TRPC4. As we have expected, suppression of TRPC4 effectively inhibited VEGF-induced migration and tube formation as well. Further evaluation on VEGF signaling pathway by western blot analysis of signaling molecules discovered that VEGF-induced activation of ERK, p38 MAPK and AKT signaling pathways were inhibited by suppression of TRPC4. These findings suggest that suppression of TRPC4 could be an alternative therapeutic option for VEGF-induced retinal neovascularization.
[Show abstract][Hide abstract] ABSTRACT: Pathologic angiogenesis induced by hypoxia is a hallmark of ischemic retinopathy including diabetic retinopathy and retinopathy of prematurity. These 2 diseases affect substantial number of working population and preterm babies, respectively, resulting in visual deterioration. It is essential for novel therapeutics for ischemic retinopathy to demonstrate the potency in reducing pathologic angiogenesis and the safety without definite toxicity on the retina and the whole body. In this review, we suggest a novel platform of integrative studies from in vitro to in vivo experiments on angiogenesis and toxicity with the aim of accelerating and facilitating the development of novel therapeutic agents for ischemic retinopathy. Robust in vitro and in vivo studies with bridging microfluidic and ex vivo systems help researchers to evaluate the efficacy and anticipate the toxicity of candidate drugs. We hope that novel therapeutic approach based on this platform will be developed in near future and reduce the incidence of vision loss from ischemic retinopathy.
[Show abstract][Hide abstract] ABSTRACT: To describe the clinical course of congenital aniridia and to evaluate prognostic factors for visual outcome after long-term follow-up.
The medical records of 120 eyes from 60 patients with congenital aniridia were retrospectively reviewed. The prevalence and clinical course of ophthalmic characteristics, systemic disease, refractive errors, and visual acuity were assessed. Prognostic factors for final visual outcomes were analyzed.
Aniridic keratopathy developed in 82 (69%) of 119 eyes. Macular hypoplasia was observed in 70 eyes of 35 patients (91%). Cataract was observed in 63 of 120 eyes (53%). Nystagmus was present in 41 patients (68% of 60 patients) at the initial visit but decreased in five patients (8% of 60 patients). Ocular hypertension was detected in 19 eyes (20% of 93 eyes), six (32% of 19 eyes) of which developed secondarily after cataract surgery. The mean changes in spherical equivalent and astigmatism during the follow-up period were -1.10 and 1.53 diopter, respectively. The mean final visual acuity was 1.028 logarithm of minimal angle of resolution. Nystagmus and ocular hypertension were identified as prognostic factors for poor visual outcome.
Identification of nystagmus and ocular hypertension was important to predict final visual outcome. Based on the high rate of secondary ocular hypertension after cataract surgery, careful management is needed.
Korean Journal of Ophthalmology 12/2014; 28(6):479-485. DOI:10.3341/kjo.2014.28.6.479