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Department of Biomedical EngineeringHistone proteins are essential to the construction of chromatin fiber and controlling its conformational state for the regulation of gene expression. DNA wrapping over histone octamer forms a nucleosome as the basic unit of chromatin fiber and understanding how the nucleosome wrapping/positioning and the compaction of nucleosome arrays are controlled is the key to understanding epigenetic gene regulation. Each histone protein subunit has unstructured tail region, which is known as multiplexed target of epigenetic modification. But we still lack knowledge about the role of the tail regions and the effect of each epigenetic modification on the chromatin structure and dynamics. We developed magnetic tweezers combined with single molecule fluorescence imaging to measure the mechanical properties and dynamics of nucleosomes and chromatin fibers. By using histone proteins with deleted tail regions or with epigenetic modification at specific residues, we try to figure out their role in controlling chromatin structure and dynamics. We present preliminary results from the measurement of the chromatin compaction and nucleosome unwrapping dynamics.ope

Evaluation of a technology-enhanced, integrated community health and wellness program for seniors (HWePS): protocol of a non-randomized comparison trial

Background Healthy aging for all in the community is a shared public health agenda for countries with aging populations, but there is a lack of empirical evidence on community-wide preventive models that promote the health of older people residing in socially-disadvantaged communities. The Health and Wellness Program for Seniors (HWePS) is a technology-enhanced, multi-level, integrated health equity intervention model. This study evaluates the effect of the HWePS on the health and well-being of older adults residing in urban, low-income communities.  Methods/design HWePS is a prospective, non-randomized comparison trial conducted in an intervention and a control neighborhood (dong) in Seoul, South Korea, over 12 months. Older people who reside in the small areas and meet the inclusion/exclusion criteria are eligible to participate. The multi-level, multi-faceted HWePS intervention is a preventive community care model for older residents guided by the expanded chronic care model, the comprehensive health literacy intervention model, and the Systems for Person-centered Elder Care model along with health equity frameworks. HWePS consists of four components: a health literacy intervention based on individual and community needs assessments, personalized (self-)care management featuring nurse coaching and peer support, a healthy-living and healthy-aging community initiative, and information and communication technology (ICT) systems. The primary outcomes are self-reported health and health-related quality of life. Outcome assessors and data analysts are blinded to group assignment. Process evaluation will be also conducted. Discussion As a multi-level health equity project, HWePS has adopted a novel study design that simultaneously targets individual- and community-level factors known to contribute to health inequality in later life in the community. The study will provide insights into the effectiveness and implementation process of an integrated, multi-level, preventive community care model, which in turn can help improve the health outcomes of older residents and reduce disparities in underserved urban communities. Trial registration ISRCTN29103760. Registered 2 September 2021, https://www.isrctn.com/ISRCTN29103760This work was based on the Project to Empower Communities to Reduce Health Disparities, supported by the Korea Disease Control and Prevention Agency and the Seoul Metropolitan Government; the project was executed in Jungnang-gu (district) in Seoul. The funding sources had no role in the study design; data collection and management; writing the manuscript; or the decision to submit the manuscript for publication. The content is solely the responsibility of the authors and does not necessarily represent the ofcial views of the funding sources

Steering Algorithm for a Flexible Microrobot to Enhance Guidewire Control in a Coronary Angioplasty Application

Magnetically driven microrobots have been widely studied for various biomedical applications in the past decade. An important application of these biomedical microrobots is heart disease treatment. In intravascular treatments, a particular challenge is the submillimeter-sized guidewire steering; this requires a new microrobotic approach. In this study, a flexible microrobot was fabricated by the replica molding method, which consists of three parts: (1) a flexible polydimethylsiloxane (PDMS) body, (2) two permanent magnets, and (3) a micro-spring connector. A mathematical model was developed to describe the relationship between the magnetic field and the deformation. A system identification approach and an algorithm were proposed for steering. The microrobot was fabricated, and the models for steering were experimentally validated under a magnetic field intensity of 15 mT. Limitations to control were identified, and the microrobot was steered in an arbitrary path using the proposed model. Furthermore, the flexible microrobot was steered using the guidewire within a three-dimensional (3D) transparent phantom of the right coronary artery filled with water, to show the potential application in a realistic environment. The flexible microrobot presented here showed promising results for enhancing guidewire steering in percutaneous coronary intervention (PCI)

Development of a high-density piezoelectric micromachined ultrasonic transducer array based on patterned aluminum nitride thin film

This study presents the fabrication and characterization of a piezoelectric micromachined ultrasonic transducer (pMUT; radius: 40 μm) using a patterned aluminum nitride (AlN) thin film as the active piezoelectric material. A 20 x 20 array of pMUTs using a 1 μm thick AlN thin film was designed and fabricated on a 2 x 2 mm2 footprint for a high fill factor. Based on the electrical impedance and phase of the pMUT array, the electromechanical coefficient was ~1.7% at the average resonant frequency of 2.82 MHz in air. Dynamic displacement of the pMUT surface was characterized by scanning laser Doppler vibrometry. The pressure output while immersed in water was 19.79 kPa when calculated based on the peak displacement at the resonant frequency. The proposed AlN pMUT array has potential applications in biomedical sensing for healthcare, medical imaging, and biometrics. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.1

Variations in hip fracture inpatient care in Japan, Korea, and Taiwan: an analysis of health administrative data

Background Little is known about hip fracture inpatient care in East Asia. This study examined the characteristics of patients, hospitals, and regions associated with delivery of hip fracture surgeries across Japan, Korea, and Taiwan. We also analyzed and compared how the resource use and a short-term outcome of the care in index hospitals varied according to factors in the respective health systems. Methods We developed comparable, nationwide, individual-level health insurance claims datasets linked with hospital- and regional-level statistics across the health systems using common protocols. Generalized linear multi-level analyses were conducted on length of stay (LOS) and total cost of index hospitalization as well as inpatient death. Results The majority of patients were female and aged 75 or older. The standardized LOS of the hospitalization for hip fracture surgery was 32.5 (S.D. = 18.7) days in Japan, 24.7 (S.D. = 12.4) days in Korea, and 7.1 (S.D. = 2.9) days in Taiwan. The total cost per admission also widely varied across the systems. Hospitals with a high volume of hip fracture surgeries had a lower LOS across all three systems, while other factors associated with LOS and total cost varied across countries. Conclusion There were wide variations in resource use for hip fracture surgery in the index hospital within and across the three health systems with similar social health insurance schemes in East Asia. Further investigations into the large variations are necessary, along with efforts to overcome the methodological challenges of international comparisons of health system performance.This study was supported by an AXA Award (900-2017006) from the AXA Research Fund, Paris, France; the National Research Foundation of Korea (NO.419 999 0514025); the Ministry of Health, Labour and Welfare, Japan (19AA2007 and 20AA2005); and the Ministry of Education, Culture, Sports, Science and Technology, Japan (20H03907). The supporting organizations had no role in the study design, data collection and analysis, and interpretation of the data. The content is solely the responsibility of the authors and does not necessarily represent the official views of the supporting organizations and the funding sources

A Needle-Type Microrobot for Targeted Drug Delivery by Affixing to a Microtissue.

A needle-type microrobot (MR) for targeted drug delivery is developed to stably deliver drugs to a target microtissue (MT) for a given period time without the need for an external force after affixing. The MRs are fabricatedby 3D laser lithography and nickel (Ni)/titanium oxide (TiO2 ) layers are coated by physical vapor deposition. The translational velocity of the MR is 714 µm s-1 at 20 mT and affixed to the target MT under the control of a rotating magnetic field. The manipulability of the MR is shown by using both manual and automatic controls. Finally, drug release from the paclitaxel-loaded MR is characterized to determine the efficiency of targeted drug delivery. This study demonstrates the utility of the proposed needle-type MR for targeted drug delivery to MT with various flow rates in vitro physiological fluidic environments

Evaluation of a technology-enhanced integrated care model for frail older persons: protocol of the SPEC study, a stepped-wedge cluster randomized trial in nursing homes

Background Limited evidence exists on the effectiveness of the chronic care model for people with multimorbidity. This study aims to evaluate the effectiveness of an information and communication technology- (ICT-)enhanced integrated care model, called Systems for Person-centered Elder Care (SPEC), for frail older adults at nursing homes. Methods/Design SPEC is a prospective stepped-wedge cluster randomized trial conducted at 10 nursing homes in South Korea. Residents aged 65 or older meeting the inclusion/exclusion criteria in all the homes are eligible to participate. The multifaceted SPEC intervention, a geriatric care model guided by the chronic care model, consists of five components: comprehensive geriatric assessment for need/risk profiling, individual need-based care planning, interdisciplinary case conferences, person-centered care coordination, and a cloud-based information and communications technology (ICT) tool supporting the intervention process. The primary outcome is quality of care for older residents using a composite measure of quality indicators from the interRAI LTCF assessment system. Outcome assessors and data analysts will be blinded to group assignment. Secondary outcomes include quality of life, healthcare utilization, and cost. Process evaluation will be also conducted. Discussion This study is expected to provide important new evidence on the effectiveness, cost-effectiveness, and implementation process of an ICT-supported chronic care model for older persons with multiple chronic illnesses. The SPEC intervention is also unique as the first registered trial implementing an integrated care model using technology to promote person-centered care for frail older nursing home residents in South Korea, where formal LTC was recently introduced

A Magnetically Controlled Soft Microrobot Steering a Guidewire in a Three-Dimensional Phantom Vascular Network

Magnetically actuated soft robots may improve the treatment of disseminated intravascular coagulation. Significant progress has been made in the development of soft robotic systems that steer catheters. A more challenging task, however, is the development of systems that steer sub-millimeter-diameter guidewires during intravascular treatments; a novel microrobotic approach is required for steering. In this article, we develop a novel, magnetically actuated, soft microrobotic system, increasing the steerability of a conventional guidewire. The soft microrobot is attached to the tip of the guidewire, and it is magnetically steered by changing the direction and intensity of an external magnetic field. The microrobot is fabricated via replica molding and features a soft body made of polydimethylsiloxane, two permanent magnets, and a microspring. We developed a mathematical model mapping deformation of the soft microrobot using a feed-forward approach toward steering. Then, we used the model to steer a guidewire. The angulation of the microrobot can be controlled from 21.1° to 132.7° by using a magnetic field of an intensity of 15 mT. Steerability was confirmed by two-dimensional in vitro tracking. Finally, a guidewire with the soft microrobot was tested by using a three-dimensional (3D) phantom of the coronary artery to verify steerability in 3D space

Revealing the Role of Histone Tails in Controlling Nucleosome Assembly and Chromatin Compaction

Histone proteins are essential to the construction of chromatin fiber and controlling its conformational state for the regulation of gene expression. DNA wrapping over histone octamer forms a nucleosome as the basic unit of chromatin fiber and understanding how the nucleosome wrapping/positioning and the compaction of nucleosome arrays are controlled is the key to understanding epigenetic gene regulation. Each histone protein subunit has unstructured tail region, which is known as multiplexed target of epigenetic modification. But we still lack knowledge about the role of the tail regions and the effect of each epigenetic modification on the chromatin structure and dynamics. We developed magnetic tweezers combined with single molecule fluorescence imaging to measure the mechanical properties and dynamics of nucleosomes and chromatin fibers. By using histone proteins with deleted tail regions or with epigenetic modification at specific residues, we try to figure out their role in controlling chromatin structure and dynamics. We present preliminary results from the measurement of the chromatin compaction and nucleosome unwrapping dynamics

Fabrication of a two-dimensional piezoelectric micromachined ultrasonic transducer array using a top-crossover-to-bottom structure and metal bridge connections

A new design methodology and fabrication process for two-dimensional (2D) piezoelectric micromachined ultrasonic transducer (pMUT) arrays using a top-crossover-to-bottom (TCTB) structure was developed. Individual sensing and actuation of pMUT elements from a small number of connection lines was enabled by the TCTB structure, and the parasitic coupling capacitance of the array was significantly reduced as a result. A 32 × 32 pMUT array with a TCTB structure was fabricated, resulting in 64 connection lines over an area of 4.8 × 4.8 mm2. The top electrodes for each pMUT element were re-connected by metal bridging after bottom-electrode etching caused them to become disconnected. A deep reactive ion etching process was used to compactify the array. Each pMUT element was a circular-shaped K31-type ultrasonic transducer using a 1 μm thick sol-gel lead zirconate titanate (PZT: Pb1.10 Zr0.52 Ti0.48) thin film. To characterize a single element in the 2D pMUT array, the resonant frequency and coupling coefficient of 20 pMUT elements were averaged to 3.85 MHz and 0.0112, respectively. The maximum measured ultrasound intensity in water, measured at a distance of 4 mm, was 4.6 μW cm-2 from a single pMUT element driven by a 5 Vpp sine wave at 2.22 MHz. Potential applications for development of a TCTB-arranged 2D pMUT array include ultrasonic medical imaging, ultrasonic communication, ultrasonic range-finding and handwriting input systems. © 2013 IOP Publishing Ltd.1