Publications by authors named "Jieun Park"

44 Publications

The impact of organic extracts of seasonal PM on primary human lung epithelial cells and their chemical characterization.

Environ Sci Pollut Res Int 2021 Jun 20. Epub 2021 Jun 20.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, 101 Daehakno, Jongno-gu, Seoul, 03080, Korea.

Lung epithelial cells serve as the first line of defense against various inhaled pollutant particles. To investigate the adverse health effects of organic components of fine particulate matter (PM) collected in Seoul, South Korea, we selected 12 PM samples from May 2016 to January 2017 and evaluated the effects of organic compounds of PM on inflammation, cellular aging, and macroautophagy in human lung epithelial cells isolated directly from healthy donors. Organic extracts of PM specifically induced neutrophilic chemokine and interleukin-8 expression via extracellular signal-regulated kinase activation. Moreover, PM significantly increased the expression of aging markers (p16, p21, and p27) and activated macroautophagy. Average mass concentrations of organic and elemental carbon had no significant correlations with PM effects. However, polycyclic aromatic hydrocarbons and n-alkanes were the most relevant components of PM that correlated with neutrophilic inflammation. Vegetative detritus and residential bituminous coal combustion sources strongly correlated with neutrophilic inflammation, aging, and macroautophagy activation. These data suggest that the chemical composition of PM is important for determining the adverse health effects of PM. Our study provides encouraging evidence to regulate the harmful components of PM in Seoul.
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http://dx.doi.org/10.1007/s11356-021-14850-1DOI Listing
June 2021

Acetazolamide-eluting biodegradable tubular stent prevents pancreaticojejunal anastomotic leakage.

J Control Release 2021 Jul 10;335:650-659. Epub 2021 Jun 10.

Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Division of Hepatobiliary Pancreas Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea; Asan Medical Institute of Convergence Science and Technology (AMIST), Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea. Electronic address:

Postoperative pancreatic fistula at the early stage can lead to auto-digestion, which may delay the recovery of the pancreaticojejunal (PJ) anastomosis. The efficacy and safety of an acetazolamide-eluting biodegradable tubular stent (AZ-BTS) for the prevention of self-digestion and intra-abdominal inflammatory diseases caused by pancreatic juice leakage after PJ anastomosis in a porcine model were investigated. The AZ-BTS was successfully fabricated using a multiple dip-coating process. Then, the drug amount and release profile were analyzed. The therapeutic effects of AZ were examined in vitro using two kinds of pancreatic cancer cell lines, AsPC-1 and PANC-1. The efficacy of AZ-BTS was assessed in a porcine PJ leakage model, with animals were each assigned to a leakage group, a BTS group and an AZ-BTS group. The overall mortality rates in these three groups were 44.4%, 16.6%, and 0%, respectively. Mean α-amylase concentrations were significantly higher in the leakage and BTS groups than in the AZ-BTS group on day 2-5 (p < 0.05 each all). The luminal diameters and areas of the pancreatic duct were significantly larger in the leakage group than in the BTS and AZ-BTS groups (p < 0.05 each all). These findings indicate that AZ-BTS can significantly suppress intra-abdominal inflammatory diseases caused by pancreatic juice leakage and also prevent late stricture formation at the PJ anastomotic site in a porcine model.
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http://dx.doi.org/10.1016/j.jconrel.2021.06.010DOI Listing
July 2021

Tanc2-mediated mTOR inhibition balances mTORC1/2 signaling in the developing mouse brain and human neurons.

Nat Commun 2021 05 11;12(1):2695. Epub 2021 May 11.

Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, Korea.

mTOR signaling, involving mTORC1 and mTORC2 complexes, critically regulates neural development and is implicated in various brain disorders. However, we do not fully understand all of the upstream signaling components that can regulate mTOR signaling, especially in neurons. Here, we show a direct, regulated inhibition of mTOR by Tanc2, an adaptor/scaffolding protein with strong neurodevelopmental and psychiatric implications. While Tanc2-null mice show embryonic lethality, Tanc2-haploinsufficient mice survive but display mTORC1/2 hyperactivity accompanying synaptic and behavioral deficits reversed by mTOR-inhibiting rapamycin. Tanc2 interacts with and inhibits mTOR, which is suppressed by mTOR-activating serum or ketamine, a fast-acting antidepressant. Tanc2 and Deptor, also known to inhibit mTORC1/2 minimally affecting neurodevelopment, distinctly inhibit mTOR in early- and late-stage neurons. Lastly, Tanc2 inhibits mTORC1/2 in human neural progenitor cells and neurons. In summary, our findings show that Tanc2 is a mTORC1/2 inhibitor affecting neurodevelopment.
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http://dx.doi.org/10.1038/s41467-021-22908-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113471PMC
May 2021

Memristive Behavior of Mixed Oxide Nanocrystal Assemblies.

ACS Appl Mater Interfaces 2021 May 3;13(18):21635-21644. Epub 2021 May 3.

Department of Mechanical and Industrial Engineering, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States.

Recent advances in memristive nanocrystal assemblies leverage controllable colloidal chemistry to induce a broad range of defect-mediated electrochemical reactions, switching phenomena, and modulate active parameters. The sample geometry of virtually all resistive switching studies involves thin film layers comprising monomodal diameter nanocrystals. Here we explore the evolution of bipolar and threshold resistive switching across highly ordered, solution-processed nanoribbon assemblies and mixtures comprising BaZrO (BZO) and SrZrO (SZO) nanocrystals. The effects of nanocrystal size, packing density, and A-site substitution on operating voltage ( and ) and switching mechanism were studied through a systematic comparison of nanoribbon heterogeneity (i.e., BZO-BZO vs BZO-SZO) and monomodal vs bimodal size distributions (i.e., small-small and small-large). Analysis of the current-voltage response confirms that tip-induced, trap-mediated space-charge-limited current and trap-assisted tunneling processes drive the low- and high-resistance states, respectively. Our results demonstrate that both smaller nanocrystals and heavier alkaline earth substitution decrease the onset voltage and improve stability and state retention of monomodal assemblies and bimodal nanocrystal mixtures, thus providing a base correlation that informs fabrication of solution-processed, memristive nanocrystal assemblies.
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http://dx.doi.org/10.1021/acsami.1c03722DOI Listing
May 2021

Correlative Light and Electron Microscopy Using Frozen Section Obtained Using Cryo-Ultramicrotomy.

Int J Mol Sci 2021 Apr 20;22(8). Epub 2021 Apr 20.

Integrative Research Support Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.

Immuno-electron microscopy (Immuno-EM) is a powerful tool for identifying molecular targets with ultrastructural details in biological specimens. However, technical barriers, such as the loss of ultrastructural integrity, the decrease in antigenicity, or artifacts in the handling process, hinder the widespread use of the technique by biomedical researchers. We developed a method to overcome such challenges by combining light and electron microscopy with immunolabeling based on Tokuyasu's method. Using cryo-sectioned biological specimens, target proteins with excellent antigenicity were first immunolabeled for confocal analysis, and then the same tissue sections were further processed for electron microscopy, which provided a well-preserved ultrastructure comparable to that obtained using conventional electron microscopy. Moreover, this method does not require specifically designed correlative light and electron microscopy (CLEM) devices but rather employs conventional confocal and electron microscopes; therefore, it can be easily applied in many biomedical studies.
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http://dx.doi.org/10.3390/ijms22084273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074315PMC
April 2021

Removal of Cr by Modified Biochar Derived from Corn Husk.

J Nanosci Nanotechnol 2021 07;21(7):3965-3970

School of Environmental Engineering, University of Seoul, Seoul, 02504, Republic of Korea.

In this study, the physicochemical properties of modified biochar using different methods, such as physical (CO₂, steam) and chemical (KOH and H₃PO₄) methods, were estimated by X-ray diffraction, N₂ adsorption-desorption, field-emission scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy, and Fourier transform infrared spectroscopy. The performance of chars was evaluated using a Cr adsorption performance test. Among various chars modified in this study, CHC-P modified by H₃PO₄ showed the highest chromium adsorption efficiency. The adsorption efficiency was affected by the high nano-porosity, large surface area, and surface oxygen-containing functional groups.
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http://dx.doi.org/10.1166/jnn.2021.19185DOI Listing
July 2021

Cardiac arrest caused by contralateral tension pneumothorax during one-lung ventilation: - A case report.

Anesth Pain Med (Seoul) 2020 Jan;15(1):78-82

Department of Anesthesiology and Pain Medicine, College of Medicine, Hallym University, Chuncheon, Korea.

Background: Tension pneumothorax on the contralateral lung during one-lung ventilation (OLV) can be life-threatening if not rapidly diagnosed and managed. However, diagnosis is often delayed because the classic signs of tension pneumothorax are similar to clinical manifestations commonly observed during OLV.

Case: We report a case of contralateral tension pneumothorax in a patient undergoing right upper lobectomy during OLV. The patient suffered from sudden cardiac arrest and was assisted by extra-corporeal membrane oxygenation.

Conclusions: Contralateral pneumothorax during OLV is rare but can occur at any time. Therefore, anesthesiologists should consider this critical complication.
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http://dx.doi.org/10.17085/apm.2020.15.1.78DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713858PMC
January 2020

Effects of etomidate use in ICU patients on ventilator therapy: a study of 12,526 patients in an open database from a single center.

Korean J Anesthesiol 2021 Aug 25;74(4):300-307. Epub 2020 Nov 25.

Department of Anesthesiology and Pain Medicine, Dongguk University Ilsan Hospital, Goyang, Korea.

Background: There is a debate regarding the safety of etomidate. We evaluated the effects of etomidate on mortality in a large cohort of critical care patients.

Methods: This retrospective matched-cohort study was performed using the Medical Information Mart for Intensive Care version 3 (MIMIC-III) database. Among 12,526 adult patients who were prescribed etomidate or propofol on the first day of mechanical ventilation, 625 patients administered etomidate were statistically matched with 6,250 patients administered propofol. The primary outcome measures were all-cause in-hospital mortality, 48-hour survival, cardiovascular morbidity, and infectious morbidity. Logistic regression analysis with stepwise selection of variables was performed to examine the dose-mortality relationship of etomidate.

Results: All-cause in-hospital mortality was 1.84 times higher in the etomidate cohort (OR, 1.84; 98.75% CI, 1.42, 2.37). Compared to the propofol cohort, the etomidate cohort showed 57% lower odds of 48-hour survival (0.43 [0.27, 0.73]), no difference in odds of cardiovascular morbidity (0.86 [0.66, 1.12]), and 1.77 times higher odds of infectious morbidity (1.77 [1.35, 2.31]). Additionally, the odds of mortality increased by 1.36 times per 0.1 mg/kg of etomidate (1.36 [95% CI: 1.23, 1.49]).

Conclusions: Etomidate is a poor choice as a hypnotic drug on the first day of mechanical ventilation, as it is associated with a dose-dependent increase in all-cause mortality, and does not improve survival for the first 48 h.
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http://dx.doi.org/10.4097/kja.20509DOI Listing
August 2021

Microporous Organic Polymers: A Synthetic Platform for Engineering Heterogeneous Carbocatalysts.

ChemSusChem 2021 Jan 17;14(2):624-631. Epub 2020 Nov 17.

School of Polymer Science and Engineering and Alan G. MacDiarmid Energy Research Institute, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Korea.

The conceptual, bottom-up design of functional carbon materials from microporous organic polymers was investigated. Owing to their structural rigidity and synthetic flexibility, the porous polymers streamlined the thermal carbonization process while excluding the need for exogenous additives or extra synthesis procedures and allowed for simultaneous elemental engineering of the resultant carbonaceous materials. As designed, heteroatoms such as nitrogen and sulfur could be uniformly incorporated into the carbon matrices from the microporous polymers during thermal carbonization with a concomitant change in the macroscopic properties of the materials. In particular, doping with sulfur atoms could provide reactive sites, thereby conferring superior catalytic performance to the carbon materials. This study demonstrates expansion of the capability of microporous polymers as a functional carbon source and advances the synthetic concept for carbonaceous materials.
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http://dx.doi.org/10.1002/cssc.202002348DOI Listing
January 2021

Stress in Caregivers and Children with a Developmental Disorder Who Receive Rehabilitation.

Children (Basel) 2020 Sep 15;7(9). Epub 2020 Sep 15.

Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

This study aimed to evaluate the stress levels of caregivers and children with developmental disorders who were receiving rehabilitation treatment. The relationships between stress levels and factors such as early rehabilitation and home rehabilitation were quantified.

Methods: This study was conducted in children with development disorders, aged from 1.5 years to 18 years, who were undergoing rehabilitation. The Korean version of the Child Behavior Checklist (K-CBCL) and the Adult Self-Report (K-ASR) were used to evaluate stress levels in children and caregivers, respectively.

Results: Questionnaires were provided to 150 caregivers who agreed to participate. However, only 76 copies of the K-CBCL and 75 copies of the K-ASR were collected. The mean K-CBCL and K-ASR scores were in the normal range. The K-CBCL score correlated positively with the K-ASR score ( value < 0.5). K-CBCL externalizing problems score correlated positively with the age at the start of rehabilitation, and the K-CBCL and K-ASR externalizing problems scores correlated negatively with home treatment delivered by caregivers.

Conclusions: Stress levels of children and caregivers were closely related. Home rehabilitation provided by caregivers reduced stress in both caregivers and children. Early rehabilitation did not impart additional psychological burden on caregivers or children.
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http://dx.doi.org/10.3390/children7090136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552633PMC
September 2020

Redundant Trojan horse and endothelial-circulatory mechanisms for host-mediated spread of Candida albicans yeast.

PLoS Pathog 2020 08 10;16(8):e1008414. Epub 2020 Aug 10.

Department of Molecular & Biomedical Sciences, University of Maine, Orono, Maine, United States of America.

The host innate immune system has developed elegant processes for the detection and clearance of invasive fungal pathogens. These strategies may also aid in the spread of pathogens in vivo, although technical limitations have previously hindered our ability to view the host innate immune and endothelial cells to probe their roles in spreading disease. Here, we have leveraged zebrafish larvae as a model to view the interactions of these host processes with the fungal pathogen Candida albicans in vivo. We examined three potential host-mediated mechanisms of fungal spread: movement inside phagocytes in a "Trojan Horse" mechanism, inflammation-assisted spread, and endothelial barrier passage. Utilizing both chemical and genetic tools, we systematically tested the loss of neutrophils and macrophages and the loss of blood flow on yeast cell spread. Both neutrophils and macrophages respond to yeast-locked and wild type C. albicans in our model and time-lapse imaging revealed that macrophages can support yeast spread in a "Trojan Horse" mechanism. Surprisingly, loss of immune cells or inflammation does not alter dissemination dynamics. On the other hand, when blood flow is blocked, yeast can cross into blood vessels but they are limited in how far they travel. Blockade of both phagocytes and circulation reduces rates of dissemination and significantly limits the distance of fungal spread from the infection site. Together, this data suggests a redundant two-step process whereby (1) yeast cross the endothelium inside phagocytes or via direct uptake, and then (2) they utilize blood flow or phagocytes to travel to distant sites.
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http://dx.doi.org/10.1371/journal.ppat.1008414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447064PMC
August 2020

Risk factors for and clinical outcomes of carbapenem non-susceptible gram negative bacilli bacteremia in patients with acute myelogenous leukemia.

BMC Infect Dis 2020 Jun 9;20(1):404. Epub 2020 Jun 9.

Department of Internal Medicine, Seoul National University College of Medicine, Daehak-ro 101, Jongro-gu, Seoul, 03080, Republic of Korea.

Background: Carbapenem is frequently used when gram negative bacilli (GNB) bacteremia is detected especially in neutropenic patients. Consequently, appropriate treatment could be delayed in GNB bacteremia cases involving organisms which are not susceptible to carbapenem (carba-NS), resulting in a poor clinical outcomes. Here, we explored risk factors for carba-NS GNB bacteremia and its clinical outcomes in patients with acute myelogenous leukemia (AML) that underwent chemotherapy.

Methods: We reviewed all GNB bacteremia cases that occurred during induction or consolidation chemotherapy, over a 15-year period, in a tertiary-care hospital.

Results: Among 489 GNB bacteremia cases from 324 patients, 45 (9.2%) were carba-NS and 444 (90.8%) were carbapenem susceptible GNB. Independent risk factors for carba-NS GNB bacteremia were: carbapenem use at bacteremia onset (adjusted odds ratio [aOR]: 91.2; 95% confidence interval [95%CI]: 29.3-284.1; P < 0.001); isolation of carbapenem-resistant Acinetobacter baumannii (aOR: 19.4, 95%CI: 3.4-112.5; P = 0.001) in the prior year; and days from chemotherapy to GNB bacteremia (aOR: 1.1 per day, 95%CI: 1.1-1.2; P < 0.001). Carba-NS bacteremia was independently associated with in-hospital mortality (aOR: 6.6, 95%CI: 3.0-14.8; P < 0.001).

Conslusion: Carba-NS organisms should be considered for antibiotic selection in AML patients having these risk factors.
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http://dx.doi.org/10.1186/s12879-020-05131-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282079PMC
June 2020

TGFam-Finder: a novel solution for target-gene family annotation in plants.

New Phytol 2020 09 5;227(5):1568-1581. Epub 2020 Jun 5.

Department of Plant Science, Plant Immunity Research Center, Plant Genomics and Breeding Institute, Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Korea.

Whole-genome annotation error that omits essential protein-coding genes hinders further research. We developed Target Gene Family Finder (TGFam-Finder), an alternative tool for the structural annotation of protein-coding genes containing target domain(s) of interest in plant genomes. TGFam-Finder took considerably reduced annotation run-time and improved accuracy compared to conventional annotation tools. Large-scale re-annotation of 50 plant genomes identified an average of 150, 166 and 86 additional far-red-impaired response 1, nucleotide-binding and leucine-rich-repeat, and cytochrome P450 genes, respectively, that were missed in previous annotations. We detected significantly higher number of translated genes in the new annotations using mass spectrometry data from seven plant species compared to previous annotations. TGFam-Finder along with the new gene models can provide an optimized platform for comprehensive functional, comparative, and evolutionary studies in plants.
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http://dx.doi.org/10.1111/nph.16645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496378PMC
September 2020

Foot Plantar Pressure Measurement System Using Highly Sensitive Crack-Based Sensor.

Sensors (Basel) 2019 Dec 13;19(24). Epub 2019 Dec 13.

Department of Mechanical Engineering, Ajou University, San 5, Woncheon-dong, Yeongtong-gu, Suwon 443-749, Korea.

Measuring the foot plantar pressure has the potential to be an important tool in many areas such as enhancing sports performance, diagnosing diseases, and rehabilitation. In general, the plantar pressure sensor should have robustness, durability, and high repeatability, as it should measure the pressure due to body weight. Here, we present a novel insole foot plantar pressure sensor using a highly sensitive crack-based strain sensor. The sensor is made of elastomer, stainless steel, a crack-based sensor, and a 3D-printed frame. Insoles are made of elastomer with Shore A 40, which is used as part of the sensor, to distribute the load to the sensor. The 3D-printed frame and stainless steel prevent breakage of the crack-based sensor and enable elastic behavior. The sensor response is highly repeatable and shows excellent durability even after 20,000 cycles. We show that the insole pressure sensor can be used as a real-time monitoring system using the pressure visualization program.
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http://dx.doi.org/10.3390/s19245504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960515PMC
December 2019

ATAD5 promotes replication restart by regulating RAD51 and PCNA in response to replication stress.

Nat Commun 2019 12 16;10(1):5718. Epub 2019 Dec 16.

Center for Genomic Integrity, Institute for Basic Science, Ulsan, Korea.

Maintaining stability of replication forks is important for genomic integrity. However, it is not clear how replisome proteins contribute to fork stability under replication stress. Here, we report that ATAD5, a PCNA unloader, plays multiple functions at stalled forks including promoting its restart. ATAD5 depletion increases genomic instability upon hydroxyurea treatment in cultured cells and mice. ATAD5 recruits RAD51 to stalled forks in an ATR kinase-dependent manner by hydroxyurea-enhanced protein-protein interactions and timely removes PCNA from stalled forks for RAD51 recruitment. Consistent with the role of RAD51 in fork regression, ATAD5 depletion inhibits slowdown of fork progression and native 5-bromo-2'-deoxyuridine signal induced by hydroxyurea. Single-molecule FRET showed that PCNA itself acts as a mechanical barrier to fork regression. Consequently, DNA breaks required for fork restart are reduced by ATAD5 depletion. Collectively, our results suggest an important role of ATAD5 in maintaining genome integrity during replication stress.
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http://dx.doi.org/10.1038/s41467-019-13667-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914801PMC
December 2019

Target-controlled infusion of dexmedetomidine effect-site concentration for sedation in patients undergoing spinal anaesthesia.

J Clin Pharm Ther 2020 Apr 5;45(2):347-353. Epub 2019 Dec 5.

Department of anesthesiology and pain medicine, Hallym University Sacred Heart Hospital, Hallym University School of Medicine, Anyang-si, Korea.

What Is Known And Objective: Dexmedetomidine has been a preferred sedative for patients undergoing regional anaesthesia and is mostly administered via conventional zero-order infusion. Recently, a pharmacokinetic-pharmacodynamic (PKPD) model of dexmedetomidine has been published, but no external validation has been reported in clinical trials. We aimed to administer target-controlled infusion (TCI) of dexmedetomidine at the effect-site concentration (Ce) to patients undergoing spinal anaesthesia and investigate the relationship between dexmedetomidine Ce and the sedative effects.

Methods: Forty-five patients scheduled for orthopaedic surgery received spinal anaesthesia with 0.5% bupivacaine. After confirmation of sensory block level, we initiated effect-site TCI of dexmedetomidine using Colin's model and assessed sedation levels using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale and bispectral index (BIS) with each stepwise increase in the dexmedetomidine Ce. We used a non-linear mixed-effects model to determine the PD relationships between the dexmedetomidine Ce and sedation level.

Results: The dexmedetomidine Ce associated with 50% probability (Ce ) of the MOAA/S scale ≤4, 3 and 2 was 0.57, 0.89 and 1.19 ng/mL, respectively. Mean dexmedetomidine Ce when BIS decreased ≤70 was 0.99 ± 0.15 ng/mL. As dexmedetomidine Ce increased, the MOAA/S scale decreased significantly (correlation coefficient [r] = -.832, P < .0001). BIS decreased significantly with increasing dexmedetomidine Ce (r = -.811, P < .0001) and decreasing MOAA/S scale (r = .838, P < .0001). The most common side effects were hypertension (26.67%) and bradycardia (20%).

What Is New And Conclusion: We applied effect-site TCI of dexmedetomidine in patients undergoing spinal anaesthesia for the first time. Dexmedetomidine Ce correlated significantly with MOAA/S scale and BIS, and was 0.89 and 1.19 ng/mL for moderate and deep sedation, respectively.
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http://dx.doi.org/10.1111/jcpt.13085DOI Listing
April 2020

Lysosome-Rich Enterocytes Mediate Protein Absorption in the Vertebrate Gut.

Dev Cell 2019 10 29;51(1):7-20.e6. Epub 2019 Aug 29.

Department of Cell Biology, Duke University, Durham, NC 27710, USA; Regeneration Next Initiative, Duke University, Durham, NC 27710, United States. Electronic address:

The guts of neonatal mammals and stomachless fish have a limited capacity for luminal protein digestion, which allows oral acquisition of antibodies and antigens. However, how dietary protein is absorbed during critical developmental stages when the gut is still immature is unknown. Here, we show that specialized intestinal cells, which we call lysosome-rich enterocytes (LREs), internalize dietary protein via receptor-mediated and fluid-phase endocytosis for intracellular digestion and trans-cellular transport. In LREs, we identify a conserved endocytic machinery, composed of the scavenger receptor complex Cubilin/Amnionless and Dab2, that is required for protein uptake by LREs and for growth and survival of larval zebrafish. Moreover, impairing LRE function in suckling mice, via conditional deletion of Dab2, leads to stunted growth and severe protein malnutrition reminiscent of kwashiorkor, a devastating human malnutrition syndrome. These findings identify digestive functions and conserved molecular mechanisms in LREs that are crucial for vertebrate growth and survival.
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http://dx.doi.org/10.1016/j.devcel.2019.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783362PMC
October 2019

Analysis of the time-velocity curve in phase-contrast magnetic resonance imaging: a phantom study.

Comput Assist Surg (Abingdon) 2019 10 6;24(sup2):3-12. Epub 2019 Aug 6.

Department of Radiology, Kyungpook National University & Hospital , Daegu , Republic of Korea.

The aim of this study was to analyze the characteristics of time-velocity curve acquired by phase-contrast magnetic resonance imaging (PC-MRI) using an in-vitro flow model as a reference for hemodynamic studies. The time- velocity curves of the PC-MRI were compared with Doppler ultrasonography (US) and also compared with those obtained in the electromagnetic flowmeter. The correlation between techniques was analyzed using an electromagnetic flowmeter as a reference standard; the maximum, minimum, and average velocities, full-width at half-maximum (FWHM), and ascending gradient (AG) were measured from time-velocity curves. The correlations between an electromagnetic flowmeter and the respective measurement technique for the PC-MRI and Doppler US were found to be high (mean  > 0.9,  < 0.05). These results indicate that these measurement techniques are useful for measuring blood flow information and reflect actual flow. The PC-MRI was the best fit for the minimum velocity and FWHM, and the maximum velocity and AG were the best fit for Doppler US. The PC-MRI showed lower maximum velocity value and higher minimum velocity value than Doppler US. Therefore, PC-MRI demonstrates more obtuse time-velocity curve than Doppler US. In addition, the time- velocity curve of PC-MRI could be calibrated by introducing formulae that can convert each measurement value to a reference standard value within a 10% error. The PC-MRI can be used to estimate the Doppler US using this formula.
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http://dx.doi.org/10.1080/24699322.2019.1649066DOI Listing
October 2019

Regulation of PCNA cycling on replicating DNA by RFC and RFC-like complexes.

Nat Commun 2019 06 3;10(1):2420. Epub 2019 Jun 3.

Center for Genomic Integrity, Institute for Basic Science, Ulsan, 44919, Republic of Korea.

Replication-Factor-C (RFC) and RFC-like complexes (RLCs) mediate chromatin engagement of the proliferating cell nuclear antigen (PCNA). It remains controversial how RFC and RLCs cooperate to regulate PCNA loading and unloading. Here, we show the distinct PCNA loading or unloading activity of each clamp loader. ATAD5-RLC possesses the potent PCNA unloading activity. ATPase motif and collar domain of ATAD5 are crucial for the unloading activity. DNA structures did not affect PCNA unloading activity of ATAD5-RLC. ATAD5-RLC could unload ubiquitinated PCNA. Through single molecule measurements, we reveal that ATAD5-RLC unloaded PCNA through one intermediate state before ATP hydrolysis. RFC loaded PCNA through two intermediate states on DNA, separated by ATP hydrolysis. Replication proteins such as Fen1 could inhibit the PCNA unloading activity of Elg1-RLC, a yeast homolog of ATAD5-RLC in vitro. Our findings provide molecular insights into how PCNA is released from chromatin to finalize DNA replication/repair.
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http://dx.doi.org/10.1038/s41467-019-10376-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546911PMC
June 2019

FEP Encapsulated Crack-Based Sensor for Measurement in Moisture-Laden Environment.

Materials (Basel) 2019 May 9;12(9). Epub 2019 May 9.

Department of Mechanical Engineering, Ajou University, Suwon 16499, Korea.

Among many flexible mechanosensors, a crack-based sensor inspired by a spider's slit organ has received considerable attention due to its great sensitivity compared to previous strain sensors. The sensor's limitation, however, lies on its vulnerability to stress concentration and the metal layers' delamination. To address this issue of vulnerability, we used fluorinated ethylene propylene (FEP) as an encapsulation layer on both sides of the sensor. The excellent waterproof and chemical resistance capability of FEP may effectively protect the sensor from damage in water and chemicals while improving the durability against friction.
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http://dx.doi.org/10.3390/ma12091516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539873PMC
May 2019

A Ras destabilizer KYA1797K overcomes the resistance of EGFR tyrosine kinase inhibitor in KRAS-mutated non-small cell lung cancer.

Sci Rep 2019 01 24;9(1):648. Epub 2019 Jan 24.

Translational Research Center for Protein Function Control, Yonsei University, Seoul, Korea.

The epidermal growth factor receptor (EGFR) inhibitors such as erlotinib and gefitinib are widely used for treatment of non-small cell lung cancer (NSCLC), but they have shown limited efficacy in an unselected population of patients. The KRAS mutations, which are identified in approximately 20% of NSCLC patients, have shown to be associated with the resistance to the EGFR tyrosine kinase inhibitors (TKIs). Currently, there is no clinically available targeted therapy which can effectively inhibit NSCLC tumors harboring KRAS mutations. This study aims to show the effectiveness of KYA1797K, a small molecule which revealed anti-cancer effect in colorectal cancer by destabilizing Ras via inhibiting the Wnt/β-catenin pathway, for the treatment of KRAS-mutated NSCLC. While erlotinib fail to have anti-transforming effect in NSCLC cell lines harboring KRAS mutations, KYA1797K effectively inhibited the Ras-ERK pathway in KRAS-mutant NSCLC cell lines. As a result, KYA1797K treatment suppressed the growth and transformation of KRAS mutant NSCLC cells and also induced apoptosis. Furthermore, KYA1797K effectively inhibited Kras-driven tumorigenesis in the Kras mouse model by suppressing the Ras-ERK pathway. The destabilization of Ras via inhibition of the Wnt/β-catenin pathway is a potential therapeutic strategy for KRAS-mutated NSCLC that is resistant to EGFR TKI.
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http://dx.doi.org/10.1038/s41598-018-37059-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345925PMC
January 2019

A small molecule approach to degrade RAS with EGFR repression is a potential therapy for KRAS mutation-driven colorectal cancer resistance to cetuximab.

Exp Mol Med 2018 11 20;50(11):1-12. Epub 2018 Nov 20.

Translational Research Center for Protein Function Control, Yonsei University, Seoul, Korea.

Drugs targeting the epidermal growth factor receptor (EGFR), such as cetuximab and panitumumab, have been prescribed for metastatic colorectal cancer (CRC), but patients harboring KRAS mutations are insensitive to them and do not have an alternative drug to overcome the problem. The levels of β-catenin, EGFR, and RAS, especially mutant KRAS, are increased in CRC patient tissues due to mutations of adenomatous polyposis coli (APC), which occur in 90% of human CRCs. The increases in these proteins by APC loss synergistically promote tumorigenesis. Therefore, we tested KYA1797K, a recently identified small molecule that degrades both β-catenin and Ras via GSK3β activation, and its capability to suppress the cetuximab resistance of KRAS-mutated CRC cells. KYA1797K suppressed the growth of tumor xenografts induced by CRC cells as well as tumor organoids derived from CRC patients having both APC and KRAS mutations. Lowering the levels of both β-catenin and RAS as well as EGFR via targeting the Wnt/β-catenin pathway is a therapeutic strategy for controlling CRC and other types of cancer with aberrantly activated the Wnt/β-catenin and EGFR-RAS pathways, including those with resistance to EGFR-targeting drugs attributed to KRAS mutations.
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http://dx.doi.org/10.1038/s12276-018-0182-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244225PMC
November 2018

Global gene expression profiling for fruit organs and pathogen infections in the pepper, Capsicum annuum L.

Sci Data 2018 06 5;5:180103. Epub 2018 Jun 5.

Interdisciplinary Program in Agricultural Genomics, Seoul National University, Seoul 08826, Korea.

Hot pepper (Capsicum annuum) is one of the most consumed vegetable crops in the world and useful to human as it has many nutritional and medicinal values. Genomic resources of pepper are publically available since the pepper genomes have been completed and massive data such as transcriptomes have been deposited. Nevertheless, global transcriptome profiling is needed to identify molecular mechanisms related to agronomic traits in pepper, but limited analyses are published. Here, we report the comprehensive analysis of pepper transcriptomes during fruit ripening and pathogen infection. For the ripening, transcriptome data were obtained from placenta and pericarp at seven developmental stages. To reveal global transcriptomic landscapes during infection, leaves at six time points post-infection by one of three pathogens (Phytophthora infestans, Pepper mottle virus, and Tobacco mosaic virus P0 strain) were profiled. The massive parallel transcriptome profiling in this study will serve as a valuable resource for detection of molecular networks of fruit development and disease resistance in Capsicum annuum.
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http://dx.doi.org/10.1038/sdata.2018.103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987667PMC
June 2018

Functional Communication Profiles in Children with Cerebral Palsy in Relation to Gross Motor Function and Manual and Intellectual Ability.

Yonsei Med J 2018 Jul;59(5):677-685

Department of Rehabilitation Medicine, Severance Hospital, Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Korea.

Purpose: The aim of the present study was to investigate communication function using classification systems and its association with other functional profiles, including gross motor function, manual ability, intellectual functioning, and brain magnetic resonance imaging (MRI) characteristics in children with cerebral palsy (CP).

Materials And Methods: This study recruited 117 individuals with CP aged from 4 to 16 years. The Communication Function Classification System (CFCS), Viking Speech Scale (VSS), Speech Language Profile Groups (SLPG), Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), and intellectual functioning were assessed in the children along with brain MRI categorization.

Results: Very strong relationships were noted among the VSS, CFCS, and SLPG, although these three communication systems provide complementary information, especially for children with mid-range communication impairment. These three communication classification systems were strongly related with the MACS, but moderately related with the GMFCS. Multiple logistic regression analysis indicated that manual ability and intellectual functioning were significantly related with VSS and CFCS function, whereas only intellectual functioning was significantly related with SLPG functioning in children with CP. Communication function in children with a periventricular white matter lesion (PVWL) varied widely. In the cases with a PVWL, poor functioning was more common on the SLPG, compared to the VSS and CFCS.

Conclusion: Very strong relationships were noted among three communication classification systems that are closely related with intellectual ability. Compared to gross motor function, manual ability seemed more closely related with communication function in these children.
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http://dx.doi.org/10.3349/ymj.2018.59.5.677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990683PMC
July 2018

Reactive oxygen species (ROS) activity of ambient fine particles (PM) measured in Seoul, Korea.

Environ Int 2018 08 16;117:276-283. Epub 2018 May 16.

Center for Healthy Environment Education & Research, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea. Electronic address:

Substantial increase in level of particulate matter has raised concerns in South Korea recently. Ambient particulate matter is classified as Group I carcinogen (IARC, 2013) and multiple epidemiological studies has demonstrated adverse health effects due to exposure of particulate matter. Fine particulate matter (PM) which has a diameter <2.5 μm is likely to penetrate deeply into lung and is known to be eliciting adverse health effects. A number of epidemiological studies have been conducted on adverse health effects of PM-related diseases and mortality rate, yet particulate matter (PM)-induced reactive oxygen species (ROS) activity at the cellular level has not been actively studied in Korea. This study assessed PM-induced oxidative potential by exposure of collected ambient PM samples to the rat alveolar macrophage cell line. The characteristics of PM in Korea were further characterized by linking chemical constituents and contributing sources to ROS. PM mass concentration during the cold season was relatively higher than mass concentration during the warm season and chemical constituents except for Secondary Organic Carbon (SOC) and SO which both showed similar trends in both the cold and cold seasons. The concentration of crustal elements was especially high during the cold season which can be an indication of long range transport of Asian dust. Water soluble organic carbon and water soluble transition metals (Cr and Zn) were also shown to be correlated to oxidative potential and metals such as As and V were shown to have a high contribution to ROS activity according to stepwise multiple linear regression. Principal Component Analysis (PCA) results identified six factors that can be interpreted as soil, mobile, industry, secondary inorganic aerosol, secondary organic aerosol and oil combustion. Moreover, through Principal Component Regression (PCR), industry, soil, mobile and SIA were shown to be statistically significant sources in a relation to ROS activity.
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http://dx.doi.org/10.1016/j.envint.2018.05.018DOI Listing
August 2018

Functional analysis of cell-free RNA using mid-trimester amniotic fluid supernatant in pregnancy with the fetal growth restriction.

Medicine (Baltimore) 2018 Jan;97(2):e9572

Department of Obstetrics and Gynecology, CHA Bundang Medical Center, CHA University, Seongnam Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University Genetic Laboratory, CHA Gangnam Medical Center, CHA University, Seoul, Korea.

The prediction and monitoring of fetal growth restriction (FGR) fetuses has become with the use of ultrasound. However, these tools lack the fundamental evidence for the growth of fetus with FGR excluding pathogenic factors.Amniotic fluid samples were obtained from pregnant women for fetal karyotyping and genetic diagnosis at 16 to 19 weeks of gestation. For this study, 15 FGR and 9 control samples were selected, and cell-free fetal RNA was isolated from each supernatant of the amniotic fluid for microarray analysis.In this study, 411 genes were differentially expressed between the FGR and control group. Of these genes, 316 genes were up-regulated, while 95 genes were down-regulated. In terms of gene ontology, the up-regulated genes were highly related to metabolic process as well as protein synthesis, while the down-regulated genes were related to receptor activity and biological adhesion. In terms of tissue-specific expression, the up-regulated genes were involved in various organs while down-regulated genes were involved only in the brain. In terms of organ-specific expression, many genes were enriched for B-cell lymphoma, pancreas, eye, placenta, epithelium, skin, and muscle. In the functional significance of gene, low-density lipoprotein receptor-related protein 10 (LRP10) was significantly increased (6-fold) and insulin-like growth factor (IGF-2) was dramatically increased (17-fold) in the FGR cases.The results show that the important brain-related genes are predominantly down-regulated in the intrauterine growth restriction fetuses during the second trimester of pregnancy. This study also suggested possible genes related to fetal development such as B-cell lymphoma, LRP10, and IGF-2. To monitor the fetal development, further study may be needed to elucidate the role of the genes identified.
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http://dx.doi.org/10.1097/MD.0000000000009572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943846PMC
January 2018

Comparisons of severity classification systems for oropharyngeal dysfunction in children with cerebral palsy: Relations with other functional profiles.

Res Dev Disabil 2018 Jan 7;72:248-256. Epub 2017 Dec 7.

Department of Rehabilitation Medicine, Severance Hospital, Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

This study aimed to investigate the relationships between various classification systems assessing the severity of oropharyngeal dysphagia and communication function and other functional profiles in children with cerebral palsy (CP). This is a prospective, cross-sectional, study in a university-affiliated, tertiary-care hospital. We recruited 151 children with CP (mean age 6.11 years, SD 3.42, range 3-18yr). The Eating and Drinking Ability Classification System (EDACS) and the dysphagia scales of Functional Oral Intake Scale (FOIS), Swallow Function Scales (SFS), and Food Intake Level Scale (FILS) were used. The Communication Function Classification System (CFCS) and Viking Speech Scale (VSS) were employed to classify communication function and speech intelligibility, respectively. The Pediatric Evaluation of Disability Inventory (PEDI) with the Gross Motor Function Classification System (GFMCS) and the Manual Ability Classification System (MACS) level were also assessed. Spearman correlation analysis to investigate the associations between measures and univariate and multivariate logistic regression models to identify significant factors were used. Median GMFCS level of participants was III (interquartile range II-IV). Significant dysphagia based on EDACS level III-V was noted in 23 children (15.2%). There were strong to very strong relationships between the EDACS level with the dysphagia scales. The EDACS presented strong associations with MACS, CFCS, and VSS, a moderate association with GMFCS level, and a moderate to strong association with each domain of the PEDI. In multivariate analysis, poor functioning in EDACS were associated with poor functioning in gross motor and communication functions.
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http://dx.doi.org/10.1016/j.ridd.2017.12.002DOI Listing
January 2018

Neuroprotective effect of Ruminococcus albus on oxidatively stressed SH-SY5Y cells and animals.

Sci Rep 2017 11 6;7(1):14520. Epub 2017 Nov 6.

Department of Public Health Science (Brain Korea 21 PLUS program), Graduate School, Korea University, Seoul, 136-701, Republic of Korea.

Recent evidence shows that the gut microbiota has an important role in gut-brain crosstalk and is linked to neuronal disorders. The aim of this study was to investigate the effects of intestinal Ruminococcus albus with probiotic potential on neuroprotection in oxidatively stressed SH-SY5Y neuroblastoma cells and animals. To investigate these effects, conditioned medium was prepared using Caco-2 cells cultured with heat-killed R. albus (CRA-CM). Caco-2 cells cultured with heat-killed R. albus showed increased BDNF expression and BDNF protein levels increased in CRA-CM. CRA-CM up-regulated the protein expression levels of SRF, C-fos and CDK2. In addition, CRA-CM protected SH-SY5Y cells from HO-induced cell death. CRA-CM significantly decreased the Bax/Bcl-2 ratio in oxidatively stressed SH-SY5Y cells. Animal experiments showed that oral administration of heat-killed R. albus for 15 days attenuated the oxidative stress induced by sodium arsenate. Treatment with heat-killed R. albus reduced the level of ROS, and the levels of SOD and GSH increased in oxidatively stressed brains. In conclusion, the secretome prepared from Caco-2 cells cultured with heat-killed R. albus might promote neuronal proliferation through the activation of cell proliferation-related proteins, and heat-killed R. albus protects neurons from oxidative damage by reducing ROS levels and increasing SOD and GSH levels.
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http://dx.doi.org/10.1038/s41598-017-15163-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674049PMC
November 2017

New reference genome sequences of hot pepper reveal the massive evolution of plant disease-resistance genes by retroduplication.

Genome Biol 2017 11 1;18(1):210. Epub 2017 Nov 1.

Department of Plant Science, Plant Genomics and Breeding Institute, Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, 08826, South Korea.

Background: Transposable elements are major evolutionary forces which can cause new genome structure and species diversification. The role of transposable elements in the expansion of nucleotide-binding and leucine-rich-repeat proteins (NLRs), the major disease-resistance gene families, has been unexplored in plants.

Results: We report two high-quality de novo genomes (Capsicum baccatum and C. chinense) and an improved reference genome (C. annuum) for peppers. Dynamic genome rearrangements involving translocations among chromosomes 3, 5, and 9 were detected in comparison between C. baccatum and the two other peppers. The amplification of athila LTR-retrotransposons, members of the gypsy superfamily, led to genome expansion in C. baccatum. In-depth genome-wide comparison of genes and repeats unveiled that the copy numbers of NLRs were greatly increased by LTR-retrotransposon-mediated retroduplication. Moreover, retroduplicated NLRs are abundant across the angiosperms and, in most cases, are lineage-specific.

Conclusions: Our study reveals that retroduplication has played key roles for the massive emergence of NLR genes including functional disease-resistance genes in pepper plants.
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http://dx.doi.org/10.1186/s13059-017-1341-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664825PMC
November 2017

Nutrition knowledge and Mediterranean diet adherence in the southeast United States: Validation of a field-based survey instrument.

Appetite 2017 04 23;111:166-176. Epub 2016 Dec 23.

Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL 36849, USA. Electronic address:

The Mediterranean diet (MD) can reduce chronic disease risk and is a recommended diet for prevention and management of diabetes. Adherence to the MD in the southeast United States where obesity and diabetes are highly prevalent is unknown. The purpose of the present study was to: 1) construct a survey instrument relevant to the general population integrating both MD related nutrition knowledge and adherence questions from previously validated instruments, and 2) assess MD related nutrition knowledge and adherence in a sample population in the southest United States. Adherance was assessed using the validated short MD Adherence Screener (MEDAS). A MD nutrition knowledge (MDNK) questionnaire was developed from previously validated general nutrition knowledge questionnaires and was validated using 127 university students enrolled in three courses with varying levels of nutrition education. Cronbach's α for internal validity of MDNK was acceptable for a short questionnaire (0.653). Test-retest reliability was established (r = 0.853). Field validation of the three-part survey instrument (MEDAS, MDNK and demographic questions) was subsequently performed in 230 adults shopping at supermarkets and farmers markets in eastern Alabama. Total MDNK and MEDAS scores were significantly higher in students with formal nutrition education and in patrons of farmers markets. Greater MD adherence, assessed by dividing MEDAS scores into thirds, was found with increasing formal nutrition education in university students (p = 0.002) and in farmers market participants (p < 0.001). There was a weak but significant association between MDNK and MEDAS scores within university students and participants in the field. Together, the MDNK-MEDAS survey instrument is an effective tool for assessing baseline knowledge and adherence and can be used to target nutritional interventions to improve MD adherence for prevention and management of diabetes and other chronic disease.
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http://dx.doi.org/10.1016/j.appet.2016.12.029DOI Listing
April 2017
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