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Background: While the number of peritoneal dialysis (PD) patients has decreased by 14.4% from 2006 to 2016, the number of hemodialysis (HD) patients has sharply increased, by 237.2%, in the same period, leading to an increase in the total medical cost. We analyzed the effects of the changes in PD use rates for dialysis patients in Korea on the healthcare budget using budget impact analysis (BIA). Methods: The analysis modeled the influence of the increase in dialysis for the target population, changes in modality use rate, and/or changes in costs per patient-year on total medical cost for patients on dialysis, using the National Health Insurance Service (NHI) claims data. We developed 8 scenarios according to the changing PD use rate. Results: In scenarios 1 - 4 (increase in PD patients by 6%, 13%, 20%, and 50% of non-diabetic prevalent HD patients under 65), 5-year budget savings ranged from $47 million to $394 million (0.9% - 7.3% of the end-stage renal disease [ESRD] budget). In scenarios 5 - 8 (increase in incident PD patients by 20%, 50%, 70%, and 100% of non-diabetic patients under 65), 5-year savings ranged from $25 million to $74 million (0.5% - 1.4% of the ESRD budget). In all scenarios, budget savings were higher as PD patients increased, showing a gradually growing trend. Conclusion: In all scenarios from the payer's perspective, savings could be achieved through an increase in PD use. Selecting PD for ESRD patients without different expected clinical outcomes between HD and PD would be beneficial to the NHI budget., (Copyright © 2019 International Society for Peritoneal Dialysis.)

Streptozotocin (STZ) is widely used to induce diabetic rodent models. It is specifically toxic to pancreatic beta cells and causes severe destruction and dysfunction. We investigated the effect of 1-palmitoyl-2-linoleoyl-3-acetyl- rac -glycerol (PLAG) on an STZ-induced diabetic mouse model. PLAG attenuated the glucose increase and maintained serum insulin at levels similar to those seen with control mice. In pancreatic beta cell line INS-1, STZ-induced cell apoptosis and intracellular reactive oxygen species (ROS) generation were significantly reduced to nearly normal levels after PLAG treatment. Glucose transporter 2 (GLUT2) localization analyses and glucose uptake assays showed that PLAG accelerated GLUT2 internalization, which ameliorated excessive entry of glucose, as well as STZ. STZ-induced cytotoxic effects were significantly reduced in PLAG-treated groups. The biological activity of PLAG was further confirmed in GLUT2-silenced cells, and the specificity of PLAG was verified using its derivative 1-palmitoyl-2-linoleoyl-3-hydroxyl- rac -glycerol (PLH). Our results suggest that PLAG may be a useful agent for protecting beta cells in the setting of excessive glucose influx., (Copyright © 2019 Kim et al.)

A synthesis of (+)-xylogiblactone A has been achieved from t -butyl 2-methylbuta-2,3-dienoate in a linear three-step sequence. The key elements of the synthesis include a kinetic resolution of racemic 2-silyoxyaldehyde through the allenoate γ-addition to yield the γ-adduct as a single isomer and the subsequent gold catalysis to form the butenolide core. For a general method, the kinetic resolution of several racemic 2-silyloxyaldehydes is also performed to provide products in high levels of stereoselectivity with unusual anti -Felkin-Anh addition fashion.

A fixed-dose combination of inhaled corticosteroid and long-acting beta agonist (ICS/LABA) may increase the risk of pneumonia in patients with chronic airway diseases including chronic obstructive pulmonary disease and asthma. Although lung deposition of ICS/LABA is dependent on the inhaler device and inhalation technique, there have been few studies comparing the risk for pneumonia according to the type of device used to deliver ICS/LABA in real-world practice. A retrospective cohort study was performed using the National Health Insurance Database of the Korean Health Insurance Review & Assessment Service. New users who began ICS/LABA were selected and followed-up 180 days after ICS/LABA initiation. The risk for pneumonia requiring emergency room (ER) visit or admission was compared according to inhaler device used-pressurized metered-dose inhaler (pMDI) or dry powder inhaler (DPI)-after individual exact matching (1:5). Among the eligible cohort of 245,477 new ICS/LABA users, 7,942 patients who used pMDI only were matched with 39,690 patients who used DPI only. The incidence of pneumonia was higher in the pMDI group (1.6%) than the DPI group (1.1%); the adjusted hazard ratio (HR) for pneumonia was 1.6 (95% CI 1.3-2.0; p < 0.0001). In subgroup analyses, a significantly higher risk for pneumonia was found in the pMDI group compared with the DPI group regardless of the presence of history of pneumonia (HR 1.7 [95% CI 1.2-2.3]; p = 0.002), COPD (HR 1.6 [95% CI 1.2-2.0]; p = 0.0007), or asthma (HR 1.6 [95% CI 1.2-2.2]; p = 0.0008). In analyses of real-world data, pMDI users incurred a higher risk for pneumonia requiring hospitalization or ER visit compared with DPI users.

The Korean Society of Radiology and the National Evidence-based Healthcare Collaborating Agency developed a primary imaging test for suspected traumatic thoracolumbar spine injury. This guideline was developed using an adaptation process involving collaboration between the development committee and the working group. The development committee, consisting of research methodology experts, established the overall plan and provided support on research methodology. The working group, composed of radiologists with expertise in musculoskeletal imaging, wrote the recommendation. The guidelines recommend that thoracolumbar spine computed tomography without intravenous contrast enhancement be the first-line imaging modality for diagnosing traumatic thoracolumbar spine injury in adults., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2019 The Korean Society of Radiology.)

Limited regenerative capacity of the nervous system makes treating traumatic nerve injuries with conventional polymer-based nerve grafting a challenging task. Consequently, utilizing natural polymers and biomimetic topologies became obvious strategies for nerve conduit designs. As a bioinspired natural polymer from a marine organism, mussel adhesive proteins (MAPs) fused with biofunctional peptides from extracellular matrix (ECM) were engineered for accelerated nerve regeneration by enhancing cell adhesion, proliferation, neural differentiation, and neurite formation. To physically promote contact guidance of neural and Schwann cells and to achieve guided nerve regeneration, MAP was fabricated into an electrospun aligned nanofiber conduit by introducing synthetic polymer poly(lactic-co-glycolic acid) (PLGA) to control solubility and mechanical property. In vitro and in vivo experiments demonstrated that the multi-dimensional tactics of combining adhesiveness from MAP, integrin-mediated interaction from ECM peptides (in particular, IKVAV derived from laminin α1 chain), and contact guidance from aligned nanofibers synergistically accelerated functional nerve regeneration. Thus, MAP-based multi-dimensional approach provides new opportunities for neural regenerative applications including nerve grafting. STATEMENT OF SIGNIFICANCE: Findings in neural regeneration indicate that a bioinspired polymer-based nerve conduit design should harmoniously constitute various factors, such as biocompatibility, neurotrophic molecule, biodegradability, and contact guidance. Here, we engineered three fusion proteins of mussel-derived adhesive protein with ECM-derived biofunctional peptides to simultaneously provide biocompatibility and integrin-based interactions. In addition, a fabrication of robust aligned nanofiber conduits containing the fusion proteins realized suitable biodegradability and contact guidance. Thus, our multi-dimensional strategy on conduit design provided outstanding biocompatibility, biodegradability, integrin-interaction, and contact guidance to achieve an accelerated functional nerve regeneration. We believe that our bioengineered mussel adhesive protein-based multi-dimensional strategy would offer new insights into the design of nerve tissue engineering biomaterials., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: Stakeholder engagement and community-engaged research (CEnR) are recognized as approaches necessary to promote health equity. Few studies have examined variations in stakeholder perspectives on research ethics despite the potential for meaningful differences. Our study examines the association between stakeholders' characteristics and their perception of the importance of 15 stakeholder-developed CEnR ethical statements., Design: Quantitative analysis of close-ended Delphi survey., Participants: We recruited a national, non-random, purposive sample of people who were eligible if they endorsed conducting CEnR in public health or biomedical fields. Participants were recruited from publicly available information, professional email distributions, and snowball sampling., Main Outcome Measures: We designed our close-ended Delphi survey from the results of 15 CEnR ethical statements, which were developed from a consensus development workshop with academic and community stakeholders., Results: 259 participants completed the Delphi survey. The results demonstrated that stakeholders' characteristics (affiliation, ethnicity, number of CEnR relationships, and duration of CEnR partnerships) were not associated with their perception of the importance of 15 ethical statements., Conclusions: The strong agreement among stakeholders on these broad, aspirational ethical statements can help guide partnerships toward ethical decisions and actions. Continued research about variability among stakeholders' ethics perspectives is needed to bolster the capacity of CEnR to contribute to health equity., Competing Interests: Competing Interests: None declared.

When the photovoltaic (PV) and solar thermal energy (STE) systems, which share the rooftop area, are installed in the same building, a trade-off problem occurs in terms of the energy, economic, and environmental aspects, and thus, steps need to solve this problem. Therefore, this study aimed to develop a multi-criteria decision support system of the PV and STE systems using the multi-objective optimization algorithm. This system was developed in the following six steps: (i) database establishment; (ii) designing the variables of the PV and STE systems; (iii) development of the analysis engine of the PV and STE systems; (iv) environmental and economic assessment from the life cycle perspective; (v) integrated multi-objective optimization (iMOO) with a genetic algorithm; and (vi) establishment of a multi-criteria decision support system. To verify the robustness and reliability of the developed model, an analysis of "D" City Hall and "I" Airport as target facilities was performed. The optimal PV and STE systems that consider the energy, economic, and environmental aspects at the same time were determined with respect to the 1.23 × 10 15 and 1.05 × 10 16 installation scenarios, respectively, in terms of effectiveness. The iMOO scores of the existing PV and STE systems installed in "D" City Hall and "I" Airport were 0.358 and 0.346, respectively, whereas those of the optimal solutions were 0.249 and 0.280, showing score improvements. In terms of efficiency, the times required for determining the optimal solutions were 20 and 30 min, respectively. The developed model makes the final decision-maker to find the optimal solution in introducing the PV and STE systems in the early design phase at the same time., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Experimental analysis was conducted on the indoor air pollutant concentration using natural ventilation and filters. The study targeted two office rooms each of which was occupied by four people, and with the same outdoor environments. A non-woven fabric filter (room A) and an electrostatic filter (room B) were installed on the window frame, and the indoor air pollutant concentration and indoor climate factors were monitored based on the number of occupants and the occupants' activities. The results are as follows: (i) when the number of occupants in each room increased from 0.03-0.06 to 1.53-1.63, room A showed a 60% average PM 10 concentration increase while room B showed an opposite result (10% average PM 10 concentration decrease), meaning the electrostatic filter's lower resistance to flow contributed to better ventilation and also decreased the influence of the occupants on the indoor air pollutant concentration. A low correlation (0.323-0.350) between the CO 2 concentration and the occupants in room B also proved these results; (ii) while the average PM 10 concentration in room A was 9 μg/m 3 higher than that in room B, the average PM 2.5 concentration in room A was higher by only 0.2 μg/m 3 , which showing that much of the generated or resuspended indoor particulate matter was PM 10 ; and (iii) due to the more frequent heat transfer from outdoors to indoors, room B consumed 23% more heating energy. The results of this study are expected to be used as bases for the establishment of an appropriate management strategy that considers the indoor air pollutant concentration caused by the number of occupants and occupants' activities by combining natural ventilation and filters., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Connectivity and biophysical processes determine the functionality of neuronal networks. We, therefore, developed a real-time framework, called Neural Interactome , , to simultaneously visualize and interact with the structure and dynamics of such networks. Neural Interactome is a cross-platform framework, which combines graph visualization with the simulation of neural dynamics, or experimentally recorded multi neural time series, to allow application of stimuli to neurons to examine network responses. In addition, Neural Interactome supports structural changes, such as disconnection of neurons from the network (ablation feature). Neural dynamics can be explored on a single neuron level (using a zoom feature), back in time (using a review feature), and recorded (using presets feature). The development of the Neural Interactome was guided by generic concepts to be applicable to neuronal networks with different neural connectivity and dynamics. We implement the framework using a model of the nervous system of Caenorhabditis elegans ( C. elegans ) nematode, a model organism with resolved connectome and neural dynamics. We show that Neural Interactome assists in studying neural response patterns associated with locomotion and other stimuli. In particular, we demonstrate how stimulation and ablation help in identifying neurons that shape particular dynamics. We examine scenarios that were experimentally studied, such as touch response circuit, and explore new scenarios that did not undergo elaborate experimental studies.

Perivascular epithelioid cell tumor (PEComa) is a very rare mesenchymal tumor with a distinctive morphology and immunophenotype. PEComas usually harbor TSC2 alterations, although TFE3 translocations, which occur in MiT family translocation renal cell carcinoma and alveolar soft part sarcoma, are also possible. We recently experienced a case of PEComa with TFE3 expression arising in the breast. An 18-year-old female patient presented with a right breast mass. Histologically, the tumor consisted of epithelioid cells with alveolar structure and showed a diffuse strong expression of HMB45 and TFE3. TSC2 was preserved. Melan A and smooth muscle actin were negative. To our knowledge, this is the first Korean case of PEComa of the breast that intriguingly presented with TFE3 expression.

Purpose: The objective of this study was to determine alterations in caloric balance, body composition, metabolites, and cytokines in athletes participating in the Yukon Arctic Ultra. Methods: Ten participants traveling on foot in the 2017 692-km event were recruited for the study. Measurements and samples were obtained at pre-event, 278 km (C1), 384 km (C2), and post-event. Body composition measurements were obtained using bioelectrical impedance analysis. Accelerometer devices were utilized to provide an estimation of caloric expenditure and dietary recalls provided assessments of caloric intake. Blood serum samples were collected, processed, and analyzed using enzyme-linked immunosorbent assays or nuclear magnetic resonance. Results were analyzed using linear mixed model, presented as means ± SD, and considered significant at p  < 0.05. Results: Participants (8 males, 2 females; age: 37 ± 10 years; body mass index: 24.4 ± 2.5 kg/m 2 ) were recruited. Four males and one female completed the entire event in 260 ± 19 h. Caloric intake/expenditure was 4,126 ± 1,115 kcal/day and 6,387 ± 781 kcal/day, respectively, indicating a caloric deficit of 2,261 ± 1,543 kcal/day. Total mass, body mass index, and fat mass were reduced at each time point of the event. Fat-free mass (FFM) was unchanged throughout the event. Follistatin was increased at C1 (1,715 ± 876 pg/ml) in comparison to baseline. Acetoacetate increased significantly at post-event (6.1 ± 1.5 mg/ml). Conclusions: Despite a pronounced caloric deficit and sustained activity under extreme cold conditions, FFM was preserved with an increase in serum follistatin and acetoacetate. Future studies should be directed at the role of nutrient strategies and/or training methods on the retention of FFM under these conditions.

A comprehensive understanding of the key microenvironmental signals regulating bone regeneration is pivotal for the effective design of bioinspired orthopedic materials. Here, we identified citrate as an osteopromotive factor and revealed its metabonegenic role in mediating citrate metabolism and its downstream effects on the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Our studies show that extracellular citrate uptake through solute carrier family 13, member 5 (SLC13a5) supports osteogenic differentiation via regulation of energy-producing metabolic pathways, leading to elevated cell energy status that fuels the high metabolic demands of hMSC osteodifferentiation. We next identified citrate and phosphoserine (PSer) as a synergistic pair in polymeric design, exhibiting concerted action not only in metabonegenic potential for orthopedic regeneration but also in facile reactivity in a fluorescent system for materials tracking and imaging. We designed a citrate/phosphoserine-based photoluminescent biodegradable polymer (BPLP-PSer), which was fabricated into BPLP-PSer/hydroxyapatite composite microparticulate scaffolds that demonstrated significant improvements in bone regeneration and tissue response in rat femoral-condyle and cranial-defect models. We believe that the present study may inspire the development of new generations of biomimetic biomaterials that better recapitulate the metabolic microenvironments of stem cells to meet the dynamic needs of cellular growth, differentiation, and maturation for use in tissue engineering., Competing Interests: Conflict of interest statement: J.Y. and The Pennsylvania State University have a financial interest in Acuitive Technologies, Inc. These interests have been reviewed by the University’s Institutional and Individual Conflict of Interest Committees and are currently being managed by the University.

Angiopoietin-like protein 2 has been proposed to be a key mediator linking obesity and insulin resistance. However, no detailed study of ANGPTL2 expression in human adipose tissues has yet been reported. To investigate the pattern and regulation of ANGPTL2 expression in human adipose tissues in obesity and its related diseases, we recruited 32 non-diabetic and 13 type 2 diabetic obese women and 32 normal-weight women. ANGPTL2 mRNA was expressed at a similar level in visceral and subcutaneous adipose tissues. Adipose tissue ANGPTL2 mRNA was much higher in obese patients. Adipose tissue ANGPTL2 mRNA and serum ANGPTL2 levels showed strong associations with metabolic parameters associated with insulin resistance. In adipose tissue, ANGPTL2 mRNA was closely correlated with the expression of genes involved in inflammation and ER stress. ANGPTL2 mRNA was principally expressed in adipocytes, and its expression was markedly higher in the adipocyte but non-adipocyte fraction of obese adipose tissues. Culture of human adipocytes under conditions mimicking the microenvironment of obese adipose tissue (especially, increased ER stress) stimulated ANGPTL2 gene expression and secretion. In addition, co-culture of adipocytes and macrophages suggested that ANGPTL2 excessively produced by adipocytes, may contribute inflammation and remodeling in obese adipose tissues, thereby promoting insulin resistance.

We propose an approach to represent neuronal network dynamics as a probabilistic graphical model (PGM). To construct the PGM, we collect time series of neuronal responses produced by the neuronal network and use singular value decomposition to obtain a low-dimensional projection of the time-series data. We then extract dominant patterns from the projections to get pairwise dependency information and create a graphical model for the full network. The outcome model is a functional connectome that captures how stimuli propagate through the network and thus represents causal dependencies between neurons and stimuli. We apply our methodology to a model of the Caenorhabditis elegans somatic nervous system to validate and show an example of our approach. The structure and dynamics of the C. elegans nervous system are well studied and a model that generates neuronal responses is available. The resulting PGM enables us to obtain and verify underlying neuronal pathways for known behavioural scenarios and detect possible pathways for novel scenarios.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'., (© 2018 The Author(s).)

Purpose: This review aimed to evaluate the effectiveness of telemonitoring (TM) in the management of children and adolescents with asthma., Methods: We searched Ovid-MEDLINE, Ovid-EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), CINAHL (Cumulative Index to Nursing and Allied Health Literature), and 5 domestic databases to identify randomized controlled trials (RCTs) published through December 2017. Two reviewers independently selected relevant studies, assessed methodological quality and extracted data. We performed a meta-analysis of TM versus usual care and summarized the intervention characteristics of included studies., Results: Of the 3,095 articles identified, 8 RCTs (9 articles) were included in this review. The type of TM intervention of included studies was varying across studies (transmitted data, transmission frequency, data review, etc.). The pooled asthma control score was not significantly different between TM and usual care (standardized mean difference 0.04, 95% confidence interval (CI) -0.20~0.28). Another pooled analysis demonstrated no statistically significant difference in asthma exacerbation between TM and usual care (odds ratio 0.95, 95% CI 0.43~2.09). Overall, the pooled results from these studies revealed that TM did not lead to clinically significant improvements in health outcomes, but some studies in our analysis suggested that TM increased patient medication adherence and intervention adherence., Conclusion: The current evidence base does not demonstrate any differences between TM intervention and usual care, but TM intervention might be considered a promising strategy for the delivery of self-management support for children and adolescents with asthma. Further well-designed studies are needed to assess the effects on clinical outcomes., Competing Interests: The authors declared no conflict of interest., (© 2018 Korean Society of Nursing Science.)

Tissue adhesives play an important role in surgery to close wounds, seal tissues, and stop bleeding, but existing adhesives are costly, cytotoxic, or bond weakly to tissue. Inspired by the water-resistant adhesion of plant-derived tannins, we herein report a new family of bioadhesives derived from a facile, one-step Michael addition of tannic acid and gelatin under oxidizing conditions and crosslinked by silver nitrate. The oxidized polyphenol groups of tannic acid enable wet tissue adhesion through catecholamine-like chemistry, while both tannic acid and silver nanoparticles reduced from silver nitrate provide antimicrobial sources inherent within the polymeric network. These tannin-inspired gelatin bioadhesives are low-cost and readily scalable and eliminate the concerns of potential neurological effect brought by mussel-inspired strategy due to the inclusion of dopamine; variations in gelatin source (fish, bovine, or porcine) and tannic acid feeding ratios resulted in tunable gelation times (36 s-8 min), controllable degradation (up to 100% degradation within a month), considerable wet tissue adhesion strengths (up to 3.7 times to that of fibrin glue), excellent cytocompatibility, as well as antibacterial and antifungal properties. The innate properties of tannic acid as a natural phenolic crosslinker, molecular glue, and antimicrobial agent warrant a unique and significant approach to bioadhesive design., Statement of Significance: This manuscript describes the development of a new family of tannin-inspired antimicrobial bioadhesives derived from a facile, one-step Michael addition of tannic acid and gelatin under oxidizing conditions and crosslinked by silver nitrate. Our strategy is new and can be easily extended to other polymer systems, low-cost and readily scalable, and eliminate the concerns of potential neurological effect brought by mussel-inspired strategy due to the inclusion of dopamine. The tannin-inspired gelatin bioadhesives hold great promise for a number of applications in wound closure, tissue sealant, hemostasis, antimicrobial and cell/drug delivery, and would be interested to the readers from biomaterials, tissue engineering, and drug delivery area., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Streptozotocin (STZ) acts specifically on pancreatic beta cells, inducing cell destruction and cell dysfunction, resulting in diabetes. Many studies have reported that nuclear factor-erythroid 2-related factor 2 (Nrf2), a main regulator of antioxidant expression, prevents and improves diabetes-related diseases. In this study, we investigated the antidiabetic effect of the newly discovered Nrf2 activator, HX-1171, in the STZ-induced diabetic mouse model. HX-1171 enhanced insulin secretion by reducing STZ-induced cell apoptosis, and decreased intracellular reactive oxygen species (ROS) generation by upregulating the expression of antioxidant enzymes through Nrf2 activation in INS-1 pancreatic beta cells. In STZ-induced diabetic mice, HX-1171 administration significantly lowered blood glucose levels and restored blood insulin levels. In the STZ-only injected mice, the pancreatic islets showed morphological changes and loss of function, whereas the HX-1171-treated group was similar to that of the control group. These results suggest that HX-1171 may be developed as a promising therapeutic agent for diabetes-related diseases., Competing Interests: CONFLICTS OF INTEREST The authors have declared no conflicts of interest.

A method for the regioselective asymmetric aldol addition of 2-alkyl allenoates with aldehydes to provide an α- or γ-adduct depending on the aldehyde pair is reported. In most cases, except enals, a mixture of a chiral bromoborane with 2-alkyl allenoates in the presence of iPr 2 NEt can react with aldehydes to provide efficient γ-addition products as single isomers containing axial and central chirality. On the other hand, observations indicate that enals undergo α-addition to yield highly functionalized adducts, including an α-carbon quaternary center in high levels of diastereo- and enantioselectivity.

Objectives: The association between low skeletal muscle mass and left ventricular diastolic dysfunction (LVDD), a predictor of future heart failure, is largely unexplored. We investigated the relationship between relative muscle mass and LVDD., Methods: We conducted a cross-sectional study in 67,106 Koreans who underwent an echocardiography as part of a comprehensive health examination between January 2012 and December 2014. Skeletal muscle mass index (SMI) [SMI (%)=total skeletal muscle mass (kg)/body weight (kg)×100] was estimated using a bioelectrical impedance analyzer. The presence of LVDD was determined using echocardiographic findings., Results: In 67,106 participants, 19,232 subjects (28.7%) and 1553 subjects (2.3%) had LVDD and left ventricular (LV) hypertrophy, respectively. SMI was positively associated with E/A ratio and septal E', whereas E/E' ratio and LV mass index were negatively associated with SMI. Lower SMI was associated with increased presence of LVDD. In a multivariable-adjusted model controlling for potential confounders including physical activity, insulin resistance, and LV mass, the odds ratios for LVDD in SMI quartiles 1, 2, and 3 compared with quartile 4 were 2.11 (1.97-2.25), 1.79 (1.68-1.90), and 1.45 (1.36-1.55), respectively (P for trend<0.001)., Conclusions: In a large sample of young and middle-aged Korean adults, low relative muscle mass was independently associated with increased risk of LVDD, indicating an independent role of skeletal muscle mass in the pathogenesis of LVDD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We investigated the association between the use of inhaled bronchodilators and the risk of AMI. A nested case-control study using the nationwide insurance claims database was conducted. Overall, 11,054 AMI cases and 47,815 matched (up to 1:5) controls were identified from 1,036,119 subjects without acute major cardiovascular events in the past year. Long-acting and short-acting β-agonists (LABAs and SABAs) were associated with increase in the risk of AMI, although an inhaled corticosteroid combined with a long-acting β-agonist was not. Long-acting muscarinic antagonists (LAMAs) in a dry powder inhaler (DPI) were significantly associated with reduced risk of AMI, while LAMAs in a soft mist inhaler (SMI) didn't decrease the risk of it. In hypertensive or diabetic patients, LAMAs in a DPI were associated with reduced risk of AMI, but LABAs were associated with increased risk. Among the β-blocker users, the reduction of AMI risk by LAMAs was the most significant. In conclusions, inhaled β-agonists were associated with increase in the risk of AMI, while LABAs accompanied by ICSs were not associated with increase in the risk of AMI. LAMAs in a DPI use were associated with lower risk of AMI.

We report the realization of novel symmetry-protected Dirac fermions in a surface-doped two-dimensional (2D) semiconductor, black phosphorus. The widely tunable band gap of black phosphorus by the surface Stark effect is employed to achieve a surprisingly large band inversion up to ∼0.6  eV. High-resolution angle-resolved photoemission spectra directly reveal the pair creation of Dirac points and their movement along the axis of the glide-mirror symmetry. Unlike graphene, the Dirac point of black phosphorus is stable, as protected by space-time inversion symmetry, even in the presence of spin-orbit coupling. Our results establish black phosphorus in the inverted regime as a simple model system of 2D symmetry-protected (topological) Dirac semimetals, offering an unprecedented opportunity for the discovery of 2D Weyl semimetals.

We present a highly adaptable design platform for multi-responsive, multilayered composite nanoparticles (MC-NPs) with fine-tunable functional layers. A flexible disulfide-linked nanogel template is obtained by a controlled in-situ gelation method, enabling a high degree of control over each successive layer. From this template, we optimize "smart" biomaterials with biofunctional surfaces, tunable drug release kinetics, and magnetic or pH-responsive functionality, fabricated into MC-NPs for targeted drug release and periosteum-mimetic structures for controlled rhBMP-2 release towards bone tissue formation in-vivo . Such a versatile platform for the design of MC-NPs is a powerful tool that shows considerable therapeutic potential in clinical fields such as oncology and orthopedics.

Efficient sunlight-driven water-splitting devices can be achieved by using an optically and energetically well-matched pair of photoelectrodes in a tandem configuration. The key for maximizing the photoelectrochemical efficiency is the use of a highly transparent front photoelectrode with a band gap below 2.0 eV. Herein, we propose two-dimensional (2D) photonic crystal (PC) structures consisting of a CuFeO 2 -decorated microsphere monolayer, which serve as self-light-harvesting architectures allowing for amplified light absorption and high transparency. The photocurrent densities are evaluated for three CuFeO 2 2D PC-based photoelectrodes with microspheres of different sizes. The optical analysis confirmed the presence of a photonic stop band that generates slow light and at the same time amplifies the absorption of light. The 410 nm sized CuFeO 2 -decorated microsphere 2D PC photocathode shows an exceptionally high visible light transmittance of 76.4% and a relatively high photocurrent of 0.2 mA cm -2 at 0.6 V vs a reversible hydrogen electrode. The effect of the microsphere size on the carrier collection efficiency was analyzed by in situ conductive atomic force microscopy observation under illumination. Our novel synthetic method to produce self-light-harvesting nanostructures provides a promising approach for the effective use of solar energy by highly transparent photocathodes.

Kinks near the Fermi level observed in angle-resolved photoemission spectroscopy (ARPES) have been widely accepted to represent electronic coupling to collective excitations, but kinks at higher energies have eluded a unified description. We identify the mechanism leading to such kink features by means of ARPES and tight-binding band calculations on σ bands of graphene, where anomalous kinks at energies as high as ∼4  eV were reported recently [Phys. Rev. Lett. 111, 216806 (2013)]. We found that two σ bands show a strong intensity modulation with abruptly vanishing intensity near the kink features, which is due to sublattice interference. The interference induced local singularity in the matrix element is a critical factor that gives rise to apparent kink features, as confirmed by our spectral simulations without involving any coupling to collective excitations.

Although copper-based chalcopyrite materials such as CuInS2 have been considered promising photocathodes for solar water splitting, the fabrication route for a nanostructure with vertical orientation has not yet been developed. Here, a fabrication route for vertically aligned CuInS2 nanorod arrays from an aqueous solution using anodic aluminum oxide template-assisted growth and transfer is presented. The nanorods exhibit a phase-pure CuInS2 chalcopyrite structure and cathodic photocurrent response without co-catalyst loading. Small particles of CdS and ZnS were conformally decorated onto CuInS2 nanorods using a successive ion layer adsorption and reaction method. With surface modification of CdS/ZnS, the photoelectrochemical properties of CuInS2 nanorod arrays are enhanced via flat-band potential shift, as determined by analyses of onset potential and Mott-Schottky plots.

Synthesis of terminal allenes via a copper-catalyzed decarboxylative coupling reaction was developed. Aryl alkynyl carboxylic acid, paraformaldehyde, and dicyclohexylamine were reacted with CuI (20 mol %) in diglyme at 100 °C for 2 h to produce the terminal allene in moderate to good yields. The method showed good functional group tolerance.

Black phosphorus consists of stacked layers of phosphorene, a two-dimensional semiconductor with promising device characteristics. We report the realization of a widely tunable band gap in few-layer black phosphorus doped with potassium using an in situ surface doping technique. Through band structure measurements and calculations, we demonstrate that a vertical electric field from dopants modulates the band gap, owing to the giant Stark effect, and tunes the material from a moderate-gap semiconductor to a band-inverted semimetal. At the critical field of this band inversion, the material becomes a Dirac semimetal with anisotropic dispersion, linear in armchair and quadratic in zigzag directions. The tunable band structure of black phosphorus may allow great flexibility in design and optimization of electronic and optoelectronic devices., (Copyright © 2015, American Association for the Advancement of Science.)

Background/objectives: There have been controversies about whether inhaled bronchodilators could increase the risk of clinically important tachyarrhythmias. We investigated the association between inhaled bronchodilators and the development of tachyarrhythmias, including atrial fibrillation and other paroxysmal tachyarrhythmias in real practice., Methods: We conducted a nested case-control study with the use of the nationwide insurance claims database of the Health Insurance Review and Assessment Service (Seoul, Republic of Korea). Overall, 3312 cases with newly developed tachyarrhythmias including atrial fibrillation and other paroxysmal tachyarrhythmias and 9732 matched (up to 1:5) controls were identified from 545,508 subjects without acute major cardiovascular events in the past year between January 1, 2011 and December 31, 2011. Conditional logistic regression analysis adjusted by comorbidities, cardiovascular drugs and healthcare utilization was performed., Results: In various multivariate models, the use of inhaled long-acting muscarinic antagonists (LAMAs) or long-acting inhaled β2 agonists (LABAs) was significantly associated with tachyarrhythmias. Statistically significant effects of LAMAs on tachyarrhythmias were found only in the non-users of β-blockers. We did not find a statistically significant difference in the impact of a LABA without a LAMA vs a LAMA without a LABA (aOR, 0.93; 95% CI, 0.74-1.18), or a multiplicative or additive interaction between a LABA and a LAMA., Conclusions: Inhaled LAMAs and LABAs were significantly and comparably associated with an increased risk of tachyarrhythmias., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Phosphate regulating gene with homologies to endopeptidases on the X-chromosome (PHEX) is a common cause of X-linked hypophosphatemic (XLH) rickets. Diverse PHEX gene mutations have been reported; however, gene mutations in sporadic rickets are less common than in XLH rickets. Herein, we describe a 50-year-old female patient with sporadic hypophosphatemic rickets harboring a novel splicing-site mutation in the PHEX gene (c.663+1G>A) at the exon 5-intron 5 boundary. The patient had recently suffered from right thigh pain and an aggravated waddling gait. She also presented with very short stature, generalized bone pain, and muscle weakness. Despite low serum phosphate levels, her phosphate reabsorption rate was lower than normal. Additionally, her 1,25-dihydroxyvitamin D3 concentration was lower than normal, although FGF23 level was normal. After treatment with alfacalcidol and elemental phosphate, her rachitic symptoms subsided, and callus formation was observed in the fracture site on the right femur.

To identify factors associated with plasma exchange response in neuromyelitis optica (NMO) spectrum disorders, the clinical and magnetic resonance imaging (MRI) features of 31 NMO-IgG-positive patients receiving plasma exchange for steroid-resistant exacerbations were analyzed. Functional improvement was observed in 65% of the patients. A lower baseline Expanded Disability Status Scale score was associated with favorable response (p = 0.040). Patients without cord atrophy had a higher success rate than patients with atrophy (p = 0.016). Levels of NMO-IgG did not differ between responders and non-responders before and after plasma exchange. In conclusion, a minimal pre-existing disability is the primary determinant of the effectiveness of plasma exchange.

Eeny, meeny, miny ... enaminones! Lactams and imides have been shown to consistently provide enantioselectivities substantially higher than other substrate classes previously investigated in the palladium-catalyzed asymmetric decarboxylative allylic alkylation. Several new substrates have been designed to probe the contributions of electronic, steric, and stereoelectronic factors that distinguish the lactam/imide series as superior alkylation substrates (see scheme). These studies culminated in marked improvements on carbocyclic allylic alkylation substrates., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In a variation of the classical Ugi reaction, an acid promoted reaction between imines and isocyanides forms both 3-aminoindoles and substituted indoxyls. A recently reported triflyl phosphoramide is shown to be critical to obtain high yields under mild conditions.