Publications by authors named "Sung Eun Kim"

637 Publications

Enhanced osteogenic differentiation of alendronate-conjugated nanodiamonds for potential osteoporosis treatment.

Biomater Res 2021 Sep 23;25(1):28. Epub 2021 Sep 23.

Biomedical and Chemical Engineering, Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro Wonmi-gu, Gyeonggi-do, 14662, Bucheon-si, Republic of Korea.

Background: Alendronate (Alen) is promising material used for bone-targeted drug delivery due to its high bone affinity and therapeutic effects on bone diseases. In addition, Alen can enhance the osteogenic differentiation of osteoblastic cell. Recently, nanodiamonds (NDs) with hardness, non-toxicity, and excellent biocompatibility are employed as promising materials for carrier systems and osteogenic differentiation. Therefore, we prepared Alen-conjugated NDs (Alen-NDs) and evaluated their osteogenic differentiation performances.

Methods: Alen-NDs were synthesized using DMTMM as a coupling reagent. Morphological change of Mouse calvaria-derived preosteoblast (MC3T3-E1) treated with Alen-NDs was observed using the confocal microscope. The osteogenic differentiation was confirmed by cell proliferation, alkaline phosphatase (ALP), calcium deposition, and real-time polymerase chain reaction assay.

Results: Alen-NDs were prepared to evaluate their effect on the proliferation and differentiation of osteoblastic MC3T3-E1 cells. The Alen-NDs had a size of about 100 nm, and no cytotoxicity at less than 100 μg/mL of concentration. The treatment of NDs and Alen-NDs reduced the proliferation rate of MC3T3-E1 cells without cell death. Confocal microscopy images confirmed that the treatment of NDs and Alen-NDs changed the cellular morphology from a fibroblastic shape to a cuboidal shape. Flow cytometry, alkaline phosphatase (ALP) activity, calcium deposition, and real-time polymerase chain reaction (RT-PCR) confirmed the higher differentiation of MC3T3-E1 cells treated by Alen-NDs, compared to the groups treated by osteogenic medium and NDs. The higher concentration of Alen-ND treated in MC3T3-E1 resulted in a higher differentiation level.

Conclusions: Alen-NDs can be used as potential therapeutic agents for osteoporosis treatment by inducing osteogenic differentiation.
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http://dx.doi.org/10.1186/s40824-021-00231-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461989PMC
September 2021

Amino acids and mechanistic target of rapamycin regulate the fate of live engulfed cells.

FASEB J 2021 Oct;35(10):e21909

Cell Biology Program, Sloan Kettering Institute for Cancer Research, New York, New York, USA.

Metabolic stress contributes to the regulation of cell death in normal and diseased tissues. While different forms of cell death are known to be regulated by metabolic stress, how the cell engulfment and killing mechanism entosis is regulated is not well understood. Here we find that the death of entotic cells is regulated by the presence of amino acids and activity of the mechanistic target of rapamycin (mTOR). Amino acid withdrawal or mTOR inhibition induces apoptosis of engulfed cells and blocks entotic cell death that is associated with the lipidation of the autophagy protein microtubule-associated protein light chain 3 (LC3) to entotic vacuoles. Two other live cell engulfment programs, homotypic cell cannibalism (HoCC) and anti-CD47 antibody-mediated phagocytosis, known as phagoptosis, also undergo a similar vacuole maturation sequence involving LC3 lipidation and lysosome fusion, but only HoCC involves mTOR-dependent regulation of vacuole maturation and engulfed cell death similar to entosis. We further find that the regulation of cell death by mTOR is independent of autophagy activation and instead involves the 4E-BP1/2 proteins that are known regulators of mRNA translation. Depletion of 4E-BP1/2 proteins can restore the mTOR-regulated changes of entotic death and apoptosis rates of engulfed cells. These results identify amino acid signaling and the mTOR-4E-BP1/2 pathway as an upstream regulation mechanism for the fate of live engulfed cells formed by entosis and HoCC.
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http://dx.doi.org/10.1096/fj.202100870RDOI Listing
October 2021

Intrinsic Thalamic Network in Temporal Lobe Epilepsy With Hippocampal Sclerosis According to Surgical Outcomes.

Front Neurol 2021 27;12:721610. Epub 2021 Aug 27.

Department of Neurology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, South Korea.

The aim of this study was to identify the differences of intrinsic amygdala, hippocampal, or thalamic networks according to surgical outcomes in temporal lobe epilepsy (TLE) patients with hippocampal sclerosis (HS). We enrolled 69 pathologically confirmed TLE patients with HS. All patients had pre-operative three-dimensional T1-weighted MRI using a 3.0 T scanner. We obtained the structural volumes of the amygdala nuclei, hippocampal subfields, and thalamic nuclei. Then, we investigated the intrinsic networks based on volumes of these structures using structural covariance and graph theoretical analysis. Of the 69 TLE patients with HS, 21 patients (42.1%) had poor surgical outcomes, whereas 40 patients (57.9%) had good surgical outcomes. The volumes in the amygdala nuclei, hippocampal subfields, and thalamic nuclei were not different according to surgical outcome. In addition, the intrinsic amygdala and hippocampal networks were not different between the patients with poor and good surgical outcomes. However, there was a significant difference in the intrinsic thalamic network in the ipsilateral hemisphere between them. The eccentricity and small-worldness index were significantly increased, whereas the characteristic path length was decreased in the patients with poor surgical outcomes compared to those with good surgical outcomes. We successfully demonstrated significant differences in the intrinsic thalamic network in the ipsilateral hemisphere between TLE patients with HS with poor and good surgical outcomes. This result suggests that the pre-operative intrinsic thalamic network can be related with surgical outcomes in TLE patients with HS.
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http://dx.doi.org/10.3389/fneur.2021.721610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429827PMC
August 2021

Spectrum of Ictal-Interictal Continuum: The Significance of 2HELPS2B Score and Background Suppression.

J Clin Neurophysiol 2021 Sep 6. Epub 2021 Sep 6.

Department of Neurology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea; Neurology Unit, Department of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; and Department of Neurology, CHA Ilsan Medical Center, Ilsan, Republic of Korea.

Purpose: The aims of this study were to identify (1) the spectrum of ictal-interictal continuum (IIC) using the two dimensions of 2HELPS2B score and background suppression and (2) the response to subsequent anti-seizure drugs depends on the spectrum of IIC.

Methods: The study prospectively enrolled 62 patients with IIC on EEG. The diagnosis of nonconvulsive status epilepticus was attempted with Salzburg criteria as well as clinical and neuroimaging data. IICs were dichotomized into patients with nonconvulsive status epilepticus and coma-IIC. The 2HELPS2B score was evaluated as the original proposal. The suppression ratio was analyzed with Persyst software.

Results: Forty-seven cases (75.8%) were nonconvulsive status epilepticus-IIC and 15 cases (24.2%) were coma-IIC. Multivariate analysis revealed that the 2HELPS2B score was the only significant variable dichotomizing the spectrum of IIC (odds ratio, 3.0; 95% confidence interval, 1.06-8.6; P = 0.03 for nonconvulsive status epilepticus-IIC). In addition, the suppression ratio was significantly negatively correlated with 2HELPS2B scores (Spearman coefficient = -0.37, P = 0.004 for left hemisphere and Spearman coefficient = -0.3, P = 0.02 for right hemisphere). Furthermore, patients with higher 2HELPS2B score (74% [14/19] in ≥2 points vs. 44% [14/32] in <2 points, P = 0.03 by χ2 test) and lower suppression ratio (62% [23/37] in ≤2.18 vs. 35% [6/17] in >2.18, P = 0.06 by χ2 test) seemed to be more responsive to subsequent anti-seizure drug.

Conclusions: The 2HELPS2B score and background suppression can be used to distinguish the spectrum of IIC and thereby predict the response to subsequent anti-seizure drug.
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http://dx.doi.org/10.1097/WNP.0000000000000894DOI Listing
September 2021

Diagnostic Performance of EUS-Guided Sampling in Indeterminate Radiological Diagnosis of Pancreatic Disease and Intra-Abdominal Lymphadenopathy.

J Clin Med 2021 Aug 27;10(17). Epub 2021 Aug 27.

Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Korea.

Background: Endoscopic ultrasound (EUS)-guided sampling has been widely used for pathologic diagnosis of pancreatic lesions and intra-abdominal lymphadenopathy. However, its effectiveness for diagnostic decision making in indeterminate radiological diagnosis has not been well determined.

Materials And Methods: From March 2012 to October 2015, 98 consecutive patients who underwent EUS-guided FNA for solid intra-abdominal lesions were retrospectively analyzed (100 procedures). The purpose of EUS-guided sampling was classified as (1) confirmation of a high-confidence radiological diagnosis (High-confidence group) or (2) decision making in the differential diagnostic dilemma for indeterminate radiological diagnosis (Indeterminate group). The accuracies of EUS-guided sampling according to the purpose were analyzed and then compared.

Results: Of the 100 procedures, 22 procedures (22%) came under the Indeterminate group, whereas 78 came under the High-confidence group. The accuracies did not differ between the Indeterminate and the High-confidence groups (86.4% vs. 88.5%, = 1.000). Clinical conditions that required EUS-guided sampling for indeterminate radiological diagnosis were (1) pancreatic cancer vs. benign disease ( = 8; e.g., pancreatic cancer vs. mass-forming pancreatitis), (2) recurrence of previous/pre-existing cancer vs. benign disease ( = 5; e.g., recurrent gastric cancer vs. reactive lymph node), (3) pathologic differentiation of presumed malignancy ( = 6; e.g., lymphadenopathies in the previous history of esophageal cancer and colon cancer), or (4) miscellaneous ( = 3; e.g., tuberculous lymphadenopathy vs. other condition).

Conclusions: EUS-guided sampling demonstrated an accuracy of 86.4% in the clinical setting of indeterminate radiological diagnosis, which was not different from that of the confirmation of high-confidence diagnosis.
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http://dx.doi.org/10.3390/jcm10173850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432008PMC
August 2021

Impact of HBeAg on Hepatocellular Carcinoma Risk During Oral Antiviral Treatment in Patients with Chronic Hepatitis B.

Clin Gastroenterol Hepatol 2021 Sep 6. Epub 2021 Sep 6.

Hospital U Puerta de Hierro, IDIPHIM CIBERehd, Madrid, Spain.

Background & Aims: Antiviral treatment from hepatitis B envelope antigen (HBeAg)-positive status may attenuate the integration of hepatitis B virus DNA into the host genome causing hepatocellular carcinoma (HCC). We investigated the impact of HBeAg status at the onset of antiviral treatment on the risk of HCC.

Methods: The incidence of HCC was evaluated in Korean chronic hepatitis B (CHB) patients who started entecavir or tenofovir in either HBeAg-positive or HBeAg-negative phase. The results in the Korean cohort were validated in a Caucasian PAGE-B cohort.

Results: A total of 9,143 Korean patients (mean age=49.2 years) were included: 49.1% were HBeAg-positive and 49.2% had cirrhosis. During follow-up (median=5.1 years), 916 patients (10.0%) developed HCC. Baseline HBeAg-positivity was not associated with the risk of HCC in the entire cohort or cirrhotic subcohort. However, in the non-cirrhotic subcohort, HBeAg-positivity was independently associated with a lower risk of HCC in multivariable (adjusted hazard ratio [aHR]=0.41, 95% confidence interval [CI]=0.26-0.66), propensity score matching (aHR=0.46, 95% CI=0.28-0.76), and inverse probability weighting analyses (aHR=0.44, 95% CI=0.28-0.70). In the Caucasian cohort (n=719, mean age=51.8 years, HBeAg-positive=20.3%, cirrhosis=34.8%), HBeAg-positivity was not associated with the risk of HCC either in the entire cohort or cirrhotic subcohort. In the non-cirrhotic subcohort, none of the HBeAg-positive group developed HCC, although the difference failed to reach statistical significance (aHR=0.21, 95% CI=0.00-1.67).

Conclusions: This multinational cohort study implies that HBeAg-positivity at the onset of antiviral treatment seems to be an independent factor associated with a lower risk of HCC in CHB patients without cirrhosis, but not in those with cirrhosis.
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http://dx.doi.org/10.1016/j.cgh.2021.09.001DOI Listing
September 2021

Injectable polymeric nanoparticle hydrogel system for long-term anti-inflammatory effect to treat osteoarthritis.

Bioact Mater 2022 Jan 7;7:14-25. Epub 2021 Jul 7.

Center for Biomaterials, Korea Institute of Science & Technology, Seoul, 02792, South Korea.

Treatment of osteoarthritis (OA) by administration of corticosteroids is a commonly used method in clinics using anti-inflammatory medicine. Oral administration or intra-articular injection of corticosteroids can reduce the pain and progress of cartilage degeneration, but they are usually insufficient to show local and long-term anti-inflammatory effects because of their fast clearance in the body. In this study, we suggest an injectable anti-OA drug depot system for sustained drug release that provides long-term effective therapeutic advantages. Amphiphilic poly(organophosphazene), which has temperature-dependent nanoparticle forming and sol-gel transition behaviors when dissolved in aqueous solution, was synthesized for triamcinolone acetonide (TCA) delivery. Because hydrophobic parts of the polymer can interact with hydrophobic parts of the TCA, the TCA was encapsulated into the self-assembled polymeric nanoparticles. The TCA-encapsulated polymeric nanoparticles (TePNs) were well dispersed in an aqueous solution below room temperature so that they can be easily injected as a sol state into an intra-articular region. However, the TePNs solution transforms immediately to a viscose 3D hydrogel like a synovial fluid in the intra-articular region via the conducted body temperature. An TCA release study showed sustained TCA release for six weeks. One-time injection of the TePN hydrogel system in an early stage of OA-induced rat model showed a great inhibition effect against further OA progression. The OA-induced knees completely recovered as a healthy cartilage without any abnormal symptoms.
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http://dx.doi.org/10.1016/j.bioactmat.2021.05.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377411PMC
January 2022

Fast and scalable earth texture synthesis using spatially assembled generative adversarial neural networks.

J Contam Hydrol 2021 Aug 12;243:103867. Epub 2021 Aug 12.

Civil and Environmental Engineering, University of Hawaii at Manoa, Honolulu, HI 96822, USA; Water Resources Research Center, University of Hawaii at Manoa, Hawaii, HI 96822, USA. Electronic address:

The earth texture with complex morphological geometry and compositions such as shale and carbonate rocks, is typically characterized with sparse field samples because of an expensive and time-consuming characterization process. Accordingly, generating arbitrary large size of the geological texture with similar topological structures at a low computation cost has become one of the key tasks for realistic geomaterial reconstruction and subsequent hydro-mechanical evaluation for science and engineering applications. Recently, generative adversarial neural networks (GANs) have demonstrated a potential of synthesizing input textural images and creating equiprobable geomaterial images for stochastic analysis of hydrogeological properties, for example, the feasibility of CO storage sites and exploration of unconventional resources. However, the texture synthesis with the GANs framework is often limited by the computational cost and scalability of the output texture size. In this study, we proposed a spatially assembled GANs (SAGANs) that can generate output images of an arbitrary large size regardless of the size of training images with computational efficiency. The performance of the SAGANs was evaluated with two and three dimensional (2D and 3D) rock image samples widely used in geostatistical reconstruction of the earth texture and Lattice-Boltzmann (LB) simulations were performed to compare pore-scale flow patterns and upscaled permeabilities of training and generated geomaterial images. We demonstrate SAGANs can generate the arbitrary large size of statistical realizations with connectivity and structural properties and flow characteristics similar to training images, and also can generate a variety of realizations even on a single training image. In addition, the computational time was significantly improved compared to standard GANs frameworks.
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http://dx.doi.org/10.1016/j.jconhyd.2021.103867DOI Listing
August 2021

Minimal and Maximal Extent of Band Ligation for Acute Variceal Bleeding during the First Endoscopic Session.

Gut Liver 2021 Aug 30. Epub 2021 Aug 30.

Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea.

Background/aims: The appropriate number of band ligations during the first endoscopic session for acute variceal bleeding is debatable. We aimed to compare the technical aspects of endoscopic variceal ligation (EVL) in patients with variceal bleeding according to the number of bands placed per session.

Methods: We retrospectively reviewed multicenter data from patients who underwent EVL for acute variceal bleeding. Patients were classified into minimal EVL (targeting only the foci with active bleeding or stigmata of recent bleeding) and maximal EVL (targeting potential bleeding sources in addition to the aforementioned targets) groups. The primary endpoint was 5-day treatment failure. The secondary endpoints were 30-day rebleeding, 30-day mortality, and intraprocedural adverse events.

Results: Minimal EVL was associated with lower rates of hypoxia and shock during EVL than maximal EVL (hypoxia, 0.9% vs 2.9%; shock, 1.3% vs 3.4%). However, treatment failure was higher in the minimal EVL group than in the maximal EVL group (odds ratio, 1.60; 95% confidence interval, 1.06 to 2.41). Age ≥60 years, Model for End-Stage Liver Disease score ≥15, Child-Turcotte-Pugh classification C, presence of hepatocellular carcinoma, and systolic blood pressure <90 mm Hg at initial presentation were also associated with treatment failure. In contrast, 30-day rebleeding and 30-day mortality did not differ between the minimal and maximal EVL groups.

Conclusions: Given that minimal EVL was associated with a high risk of treatment failure, maximal EVL may be a better option for variceal bleeding. However, the minimal EVL strategy should be considered in select patients because it does not affect 30-day rebleeding and mortality.
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http://dx.doi.org/10.5009/gnl20375DOI Listing
August 2021

Impaired cerebro-cerebellar white matter connectivity and its associations with cognitive function in patients with schizophrenia.

NPJ Schizophr 2021 Aug 12;7(1):38. Epub 2021 Aug 12.

Department of Psychiatry, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.

Schizophrenia is a complex brain disorder of unknown etiology. Based on the notion of "cognitive dysmetria," we aimed to investigate aberrations in structural white matter (WM) connectivity that links the cerebellum to cognitive dysfunction in patients with schizophrenia. A total of 112 participants (65 patients with schizophrenia and 47 healthy controls [HCs]) were enrolled and underwent diffusion tensor imaging. Between-group voxel-wise comparisons of cerebellar WM regions (superior/middle [MCP]/inferior cerebellar peduncle and pontine crossing fibers) were performed using Tract-Based Spatial Statistics. Cognitive function was assessed using the Trail Making Test Part A/B (TMT-A/B), Wisconsin Card Sorting Test (WCST), and Rey-Kim Memory Test in 46 participants with schizophrenia. WM connectivity, measured as fractional anisotropy (FA), was significantly lower in the MCP in participants with schizophrenia than in HCs. The mean FAs extracted from the significant MCP cluster were inversely correlated with poorer cognitive performance, particularly longer time to complete the TMB-B (r = 0.559, p < 0.001) and more total errors in the WCST (r = 0.442, p = 0.003). Our findings suggest that aberrant cerebro-cerebellar communication due to disrupted WM connectivity may contribute to cognitive impairments, a core characteristic of schizophrenia. Our results may expand our understanding of the neurobiology of schizophrenia based on the cerebro-cerebellar interconnectivity of the brain.
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http://dx.doi.org/10.1038/s41537-021-00169-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360938PMC
August 2021

Comparison of the Automated Fluorescent Immunoassay System With Roche Elecsys and Beckman Coulter Access 2 Assays for Anti-Müllerian Hormone Measurement.

Ann Lab Med 2022 Jan;42(1):47-53

I-dream Clinic, Department of Obstetrics and Gynecology, MizMedi Hospital, Seoul, Korea.

Background: Since 2017, automated assays have been used in most clinical laboratories for anti-Müllerian hormone (AMH) level measurement. We evaluated the analytical performance of the newly developed automated fluorescent immunoassay system (AFIAS) AMH assay (Boditech Med, Gangwon-do, Korea) in comparison with the Roche Elecsys and Beckman Coulter Access 2 AMH assays.

Methods: Analytical performance of the AFIAS AMH assay was assessed in terms of linearity, repeatability, and within-laboratory precision (CV%) using human recombinant AMH samples according to the Clinical and Laboratory Standards Institute (CLSI) guidelines EP05 and EP06. Using 293 serum samples collected from an infertility clinic, the AMH levels were compared across AFIAS, Elecsys, and Access 2 AMH assays according to the CLSI EP09 guidelines.

Results: The AFIAS AMH assay results were linear across the measurement range of 0.420-72.386 pmol/L AMH, with repeatability of 6.341%. CV% of the AFIAS AMH assay for three levels of control, 1.786, 7.143, and 56.857 pmol/L, were 5.801%, 5.714%, and 6.228%, respectively. The results of the three AMH assays showed strong correlation: AFIAS and Elecsys [slope, 1.055 (95% confidence interval (CI), 1.022-1.088) and Spearman's rho, 0.978 (95% CI, 0.973-0.983)], Elecsys and Access 2 [slope, 0.813 (95% CI, 0.791-0.834) and Spearman's rho, 0.986 (95% CI, 0.983-0.989)], and AFIAS and Access 2 [slope, 0.836 (95% CI, 0.821-0.853) and Spearman's rho, 0.984 (95% CI, 0.980-0.988)].

Conclusions: The AFIAS AMH assay may be an alternative to the Roche Elecsys and Beckman Coulter Access 2 AMH assays.
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http://dx.doi.org/10.3343/alm.2022.42.1.47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8368231PMC
January 2022

Multifunctional Tannic Acid-Alendronate Nanocomplexes with Antioxidant, Anti-Inflammatory, and Osteogenic Potency.

Nanomaterials (Basel) 2021 Jul 13;11(7). Epub 2021 Jul 13.

Department of Orthopedic Surgery and Nano-Based Disease Control Institute, Korea University Guro Hospital, #148, Gurodong-ro, Guro-gu, Seoul 08308, Korea.

In the current study, we fabricated tannic acid-alendronate (TA-ALN) nanocomplexes (NPXs) via self-assembly. These TA-ALNs were characterized by dynamic light scattering, zeta potential, transmission electron microscopy, and FT-IR spectroscopy. The TA-ALNs were evaluated for antioxidant, anti-inflammatory, and osteogenesis-accelerating abilities in osteoblast-like cells (MC3T3-E1 cells). All TA-ALNs displayed nano-sized beads that were circular in form. Treatment with TA-ALN (1:0.1) efficiently removed reactive oxygen species in cells and protected osteoblast-like cells from toxic hydrogen peroxide conditions. Moreover, TA-ALN (1:0.1) could markedly decrease the mRNA levels of pro-inflammatory mediators in lipopolysaccharide-stimulated cells. Furthermore, cells treated with TA-ALN (1:1) exhibited not only significantly greater alkaline phosphatase activity and calcium collection, but also outstandingly higher mRNA levels of osteogenesis-related elements such as collagen type I and osteocalcin. These outcomes indicate that the prepared TA-ALNs are excellent for antioxidant, anti-inflammatory, and osteogenic acceleration. Accordingly, TA-ALN can be used latently for bone renovation and regeneration in people with bone fractures, diseases, or disorders.
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http://dx.doi.org/10.3390/nano11071812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308329PMC
July 2021

UDP-glucose pyrophosphorylase 2, a regulator of glycogen synthesis and glycosylation, is critical for pancreatic cancer growth.

Proc Natl Acad Sci U S A 2021 Aug;118(31)

Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA 94158;

UDP-glucose pyrophosphorylase 2 (UGP2), the enzyme that synthesizes uridine diphosphate (UDP)-glucose, rests at the convergence of multiple metabolic pathways, however, the role of UGP2 in tumor maintenance and cancer metabolism remains unclear. Here, we identify an important role for UGP2 in the maintenance of pancreatic ductal adenocarcinoma (PDAC) growth in both in vitro and in vivo tumor models. We found that transcription of UGP2 is directly regulated by the Yes-associated protein 1 (YAP)-TEA domain transcription factor (TEAD) complex, identifying UGP2 as a bona fide YAP target gene. Loss of UGP2 leads to decreased intracellular glycogen levels and defects in N-glycosylation targets that are important for the survival of PDACs, including the epidermal growth factor receptor (EGFR). These critical roles of UGP2 in cancer maintenance, metabolism, and protein glycosylation may offer insights into therapeutic options for otherwise intractable PDACs.
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http://dx.doi.org/10.1073/pnas.2103592118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346792PMC
August 2021

Existence and Significance of Internal Border Zone Infarcts with Accessory Lesions Located in the Anteromedial Temporal Lobe.

J Stroke Cerebrovasc Dis 2021 Jul 26;30(10):106004. Epub 2021 Jul 26.

Department of Neurology, UCLA Stroke Center, University of California, 635 Charles E. Young Drive South, Suite 225, Los Angeles, CA 90095, USA. Electronic address:

Objectives: To examine the existence and significance of internal border zone (IBZ) infarcts with accessory lesions in the anteromedial temporal lobe (ATL).

Materials And Methods: IBZ infarcts located at the corona radiata were selected based on diffusion-weighted imaging of 2535 consecutive patients with ischemic stroke and the presence of lesions in the ATL was identified. The Mann-Whitney U test, Student t-test, Pearson χ test, or Fisher exact test was used to analyze differences between the IBZ infarct groups with and without accessory lesions in the ATL.

Results: Thirty-six of 2535 patients (1.4%) had IBZ infarcts. The IBZ group with accessory lesions in the ATL (17 cases, 47.2%) showed a higher portion of occluded middle cerebral arteries than the IBZ group without accessory lesions in the ATL (p = 0.02). The initial National Institutes of Health Stroke Scale score (odds ratio, 2.03; 95% confidence interval, 1.04-3.99;   = 0.039) and progression after admission (odds ratio, 25.43; 95% confidence interval, 2.47-261.99; p = 0.007) were independently associated with poor prognosis in patients with IBZ infarcts. There were no differences in the progression rate and clinical outcomes, regardless of the presence of lesions in the ATL.

Conclusions: Our study suggests the existence of a distinct type of IBZ infarct characterized by accessory lesions in the ATL, which is associated with different arterial features but has a similar clinical course to IBZ infarcts without accessory lesions in the ATL.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.106004DOI Listing
July 2021

Analysis of Clinical Characteristics and Prognosis of Patients With Periocular Malignant Melanoma in Korea.

J Craniofac Surg 2021 Jul 20. Epub 2021 Jul 20.

Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul Department of Ophthalmology, Hospital, National Cancer Center, Gyeonggi-do, South Korea.

Objective: To report the clinical features of 20 patients with malignant melanoma and to evaluate the survival and prognosis of patients with malignant melanoma in Korea.

Methods And Analysis: The medical records of 20 patients with malignant melanoma treated between March 2004 and March 2020 were reviewed retrospectively. The demographic data, clinical characteristics, and outcomes were also reviewed. Outcome measures included local recurrence, metastasis, and tumor-related mortality. Prognostic factors associated with recurrence, metastasis, and survival were analyzed using a Cox proportional hazards model.

Results: Among the 20 patients with periocular malignant melanoma, 4 (20%) showed local recurrence during follow-up (6.61 ± 6.36 years). The 1-, 5-, and 10-year recurrence rates were 5%, 10.3%, and 24.1%, respectively. 10 (50%) patients developed distant metastasis, mainly involving lung, brain, parotid gland and spine. The 1-, 5-, and 10-year rates of metastasis were 5%, 10.9%, and 35.7%, respectively. Significantly fewer metastases were detected following initial extensive surgical excision (P = 0.04). 8 (40%) patients died of malignant melanoma. The main risk factor for mortality was tumor thickness (HR: 3.88, P < 0.01). Based on Kaplan-Meier survival estimates, the 1-, 5-, and 10-year tumor-related survival rates were 75.8%, 55.6%, and 55.6%, respectively.

Conclusion: Tumor thickness is a significant prognostic factor affecting the survival rate. It is important to reduce the metastatic rate via extensive resection without leaving any residual tumor in the margin during surgery.
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http://dx.doi.org/10.1097/SCS.0000000000007800DOI Listing
July 2021

Physical multimorbidity and incident urinary incontinence among community-dwelling adults aged ≥50 years: findings from a prospective analysis of the Irish Longitudinal Study on Ageing.

Age Ageing 2021 Jul 17. Epub 2021 Jul 17.

Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, 08830 Barcelona, Spain.

Background: There are no prospective studies on the association between multimorbidity and urinary incontinence (UI), while mediators in this association are unknown. Thus, we aimed to (i) investigate the longitudinal association between multimorbidity and UI in a large sample of Irish adults aged ≥50 years and (ii) investigate to what extent physical activity, polypharmacy, cognitive function, sleep problems, handgrip strength and disability mediate the association.

Methods: Data on 5,946 adults aged ≥50 years old from the Irish Longitudinal Study on Aging were analysed. The baseline survey was conducted between 2009 and 2011 and follow-up after 2 years was conducted. Information on self-reported occurrence of UI in the past 12 months and lifetime diagnosis of 14 chronic conditions were obtained. Multivariable logistic regression and mediation analysis were conducted.

Results: After adjustment for potential confounders, compared to having no chronic conditions at baseline, having three (odds ratio [OR] = 1.79; 95% confidence interval [CI] = 1.30-2.48) and four or more (OR = 1.86; 95% CI = 1.32-2.60), chronic conditions were significantly associated with incident UI. Mediation analysis showed that polypharmacy, sleep problems and disability explained 22.7, 17.8 and 14.7% of the association between multimorbidity (i.e. two or more chronic conditions) and incident UI, respectively.

Conclusion: A greater number of chronic conditions at baseline were associated with a higher risk for incident UI at 2-year follow-up among adults aged ≥50 years in Ireland. Considering the effects of different medications on UI and improving sleep quality and disability among people aged ≥50 years with multimorbidity may reduce the incidence of UI.
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http://dx.doi.org/10.1093/ageing/afab151DOI Listing
July 2021

Effect of Number of Previous Antiseizure Medications on Efficacy and Tolerability of Adjunctive Brivaracetam for Uncontrolled Focal Seizures: Post Hoc Analysis.

Adv Ther 2021 07 21;38(7):4082-4099. Epub 2021 Jun 21.

UCB Pharma, 369 Gangnam-daero, Seocho-gu, Seoul, South Korea.

Introduction: The aim was to evaluate the efficacy and tolerability of adjunctive brivaracetam (BRV) in adults with severely drug-resistant focal seizures versus adults with less drug-resistant disease.

Methods: Data were pooled from patients with focal seizures on 1-2 concomitant antiseizure medications (ASMs) randomized to BRV 50, 100, 200 mg/day, or placebo in 3 phase 3 trials (N01252 [NCT00490035], N01253 [NCT00464269], and N01358 [NCT01261325]) with a 12-week treatment period. Outcomes were assessed in patients with ≥ 5 and 0-4 previous ASMs (stopped before trial drug initiation).

Results: In ≥ 5 previous ASMs subgroup (BRV 50, 100, 200 mg/day: n = 26, n = 137, n = 120; placebo: n = 151), percentage reduction over placebo in 28-day adjusted focal seizure frequency was 13.0% for 50 mg/day (p = 0.38), 18.1% for 100 mg/day (p = 0.006), 19.8% for 200 mg/day (p = 0.004), and 17.0% for all BRV-treated patients (p = 0.001). The 50% responder rate was 26.9%, 29.9%, 30.0%, and 29.7% for BRV 50, 100, 200, and 50-200 mg/day, respectively (placebo: 13.2%); odds ratios versus placebo were statistically significant (p < 0.05) for BRV 100, 200, and 50-200 mg/day. In 0-4 previous ASMs subgroup (BRV 50, 100, 200 mg/day: n = 135, n = 195, n = 129; placebo: n = 267), all BRV dosages showed statistically significant (1) percentage reduction over placebo in 28-day adjusted focal seizure frequency (21.4-28.7%); (2) differences from placebo in median percentage reduction in 28-day adjusted focal seizure frequency from baseline (35.5-45.9%; placebo: 21.3%); and (3) odds ratios versus placebo (favoring BRV) for 50% responder rates. In BRV-treated patients, treatment-emergent adverse event (TEAE) incidence (73.8% [217/294] vs. 64.6% [329/509]) and discontinuation due to TEAEs (10.5% vs. 4.5%) were higher in the ≥ 5 versus 0-4 previous ASMs subgroup; serious TEAEs were rare in both subgroups (≥ 5 previous ASMs: 3.1%; 0-4 previous ASMs: 2.9%).

Conclusion: Adjunctive BRV showed efficacy and was generally well tolerated in adults with focal seizures independent of the number of previous ASMs.
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http://dx.doi.org/10.1007/s12325-021-01816-5DOI Listing
July 2021

Low recurrence rate after endoscopic resection in non-ampullary duodenal lesions: A 16-year single-center retrospective study.

Medicine (Baltimore) 2021 Jun;100(23):e26267

Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea.

Abstract: Endoscopic resection (ER) for non-ampullary duodenal lesions (NADLs) is technically more difficult than lesions of the stomach. However, endoscopic treatment of duodenal lesions has been increasingly performed in recent years. This study aimed to evaluate the efficacy and safety of ER for NADLs.Patients who underwent ER for NADLs between 2004 and 2019 were retrospectively reviewed. Clinical and pathologic features of the lesions including the clinical outcomes and adverse events were analyzed.The study included 80 patients with NADLs. The mean age of patients was 59.3 years (22-80 years), the mean size of the lesion was 8.8 ± 7.0 mm, and the mean procedure time was 13.2 ± 11.2 min. Half (40/80) of the lesions were in the duodenal bulb including the superior duodenal angle. Final histological data showed 56 adenomas (70.5%), 13 Brunner gland tumors (16.2%), and 4 pyloric gland tumors (5.0%). The final diagnoses of 5 lesions after ER showed higher-grade dysplasia compared to pre-ER biopsy findings. The en bloc resection rate was 93.8% (75/80), and the complete resection rate with clear margins was 90.0% (72/80). Micro-perforation occurred in 2 of 80 patients and was successfully treated with conservative treatment. There were no cases of delayed bleeding. The mean follow-up period was 27.0 months (2-119 months) with no cases of recurrence.ER may be an effective treatment for NADLs with favorable long-term outcomes. However, the possibility of perforation complications should always be considered during ER.
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http://dx.doi.org/10.1097/MD.0000000000026267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202602PMC
June 2021

Evidence based guidelines for the treatment of Helicobacter pylori infection in Korea 2020.

Korean J Intern Med 2021 07 8;36(4):807-838. Epub 2021 Jun 8.

Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea.

Helicobacter pylori infection is one of the most common infectious diseases worldwide. H. pylori is responsible for substantial gastrointestinal morbidity with a high disease burden. Since the revision of the H. pylori Clinical Practice Guidelines in 2013 in Korea, the eradication rate of H. pylori has gradually decreased with the use of a clarithromycin based triple therapy. According to a nationwide randomized controlled study by the Korean College of Helicobacter and Upper Gastrointestinal Research released in 2018, the intention-to-treat eradication rate was only 63.9%, which was mostly due to increased antimicrobial resistance to clarithromycin. The clinical practice guidelines for treatment of H. pylori were updated based on evidence-based medicine from a meta-analysis conducted on a target group receiving the latest level of eradication therapy. The draft recommendations developed based on the meta-analysis were finalized after expert consensus on three recommendations regarding the indication for treatment and eight recommendations on the treatment itself. These guidelines were designed to provide clinical evidence for the treatment of H. pylori to patients, nurses, medical school students, policymakers, and clinicians. These may differ from current medical insurance standards, and will be revised if more evidence emerges in the future.
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http://dx.doi.org/10.3904/kjim.2020.701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273819PMC
July 2021

Determination of the duration of glucocorticoid therapy in type 1 autoimmune pancreatitis: A systematic review and meta-analysis.

Pancreatology 2021 May 31. Epub 2021 May 31.

Department of Internal Medicine, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea.

Background: The indications for maintenance glucocorticoid therapy (MGT) and its duration after initial remission of type 1 autoimmune pancreatitis (AIP) remain controversial. In contrast to the Japanese treatment protocol, the Mayo protocol does not recommend MGT after initial remission. This study aimed to evaluate the relapse rate in patients with type 1 AIP according to the duration of glucocorticoid therapy.

Methods: We conducted a systematic literature review up until November 30, 2020, and identified 40 studies reporting AIP relapse rates. The pooled relapse rates were compared between groups according to the protocol and duration of glucocorticoids (routine vs. no MGT; glucocorticoids ≤6 months vs. 6-12 months vs. 12-36 months vs. ≥ 36 months). The pooled rates of adverse events related to glucocorticoids were also evaluated.

Results: Meta-analysis indicated calculated pooled relapse rates of 46.6% (95% confidence interval (CI), 38.9-54.3%) with glucocorticoids for ≤ 6 months, 44.3% (95% CI, 38.8-49.8%) for 6-12 months, 34.1% (95% CI, 28.6-39.7%) for 12-36 months, and 27.0% (95% CI, 23.4-30.6%) for ≥ 36 months. The rate of relapse was also significantly lower in patients with routine-use protocol of MGT (31.2%; 95% CI, 27.5-34.8%) than in patients with no MGT protocol (44.1%; 95% CI, 35.8-52.4%). Adverse events were comparable between groups.

Conclusions: The rate of relapse tended to decrease with extended durations of glucocorticoid therapy up to 36 months. Clinicians may decide the duration of glucocorticoids according to patient condition, including comorbidities and risk of relapse.
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http://dx.doi.org/10.1016/j.pan.2021.05.303DOI Listing
May 2021

Progression Rates by Age, Sex, Treatment, and Disease Activity by AASLD and EASL Criteria: Data for Precision Medicine.

Clin Gastroenterol Hepatol 2021 Jun 2. Epub 2021 Jun 2.

Department of Internal Medicine, Saga University Hospital, Saga, Japan.

Background & Aims: Antiviral treatment criteria are based on disease progression risk, and hepatocellular carcinoma (HCC) surveillance recommendations for patients with chronic hepatitis B (CHB) without cirrhosis is based on an annual incidence threshold of 0.2%. However, accurate and precise disease progression estimate data are limited. Thus, we aimed to determine rates of cirrhosis and HCC development stratified by age, sex, treatment status, and disease activity based on the 2018 American Association for the Study of Liver Diseases and 2017 European Association for the Study of the Liver guidelines.

Methods: We analyzed 18,338 patients (8914 treated, 9424 untreated) from 6 centers from the United States and 27 centers from Asia-Pacific countries. The Kaplan-Meier method was used to estimate annual progression rates to cirrhosis or HCC in person-years.

Results: The cohort was 63% male, with a mean age of 46.19 years, with baseline cirrhosis of 14.3% and median follow up of 9.60 years. By American Association for the Study of Liver Diseases criteria, depending on age, sex, and disease activity, annual incidence rates ranged from 0.07% to 3.94% for cirrhosis, from 0.04% to 2.19% for HCC in patients without cirrhosis, and from 0.40% to 8.83% for HCC in patients with cirrhosis. Several subgroups of patients without cirrhosis including males younger than 40 years of age and females younger than 50 years of age had annual HCC risk near or exceeding 0.2%. Similar results were found using European Association for the Study of the Liver criteria.

Conclusion: There is great variability in CHB disease progression rates even among "lower-risk" populations. Future CHB modeling studies, public health planning, and HCC surveillance recommendation should be based on more precise disease progression rates based on sex, age, and disease activity, plus treatment status.
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http://dx.doi.org/10.1016/j.cgh.2021.05.062DOI Listing
June 2021

Blinatumomab-related pneumatosis intestinalis in a pediatric patient with relapsed acute lymphoblastic leukemia: A case report.

J Oncol Pharm Pract 2021 May 30:10781552211015776. Epub 2021 May 30.

Department of Pediatrics, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea.

Introduction: Pneumatosis intestinalis is characterized by air in the subserosal or submucosal layer of the intestine, with the severity ranging from mild and asymptomatic to symptomatic with serious conditions such as intestinal ischemia and perforation requiring surgery. Although several etiologies, including those from conventional chemotherapy agents and molecular target agents, have been suggested, blinatumomab-related pneumatosis intestinalis is quite rare.

Case Report: An 11-year-old girl with history of B-cell ALL presented with bone marrow relapse 3 years after completion of initial chemotherapy. Reinduction chemotherapy and blinatumomab as post-reinduction consolidation were initiated. On day 28 of blinatumomab therapy, pneumatosis intestinalis from the ascending colon to the hepatic flexure was found incidentally on abdominal computed tomography.Management and outcome: After withholding blinatumomab therapy for 1 month, pneumatosis intestinalis improved significantly without abnormal gastrointestinal symptoms. Blinatumomab was resumed and safely completed. The computed tomography performed 4 months later showed complete resolution of pneumatosis intestinalis. The patient has been in good condition for over 1 year to date.

Discussion: To our knowledge, this is the first case report of pneumatosis intestinalis after blinatumomab therapy in a pediatric patient with relapsed precursor B-cell acute lymphoblastic leukemia. Herein, we highlight the importance of early detection of pneumatosis intestinalis through imaging follow-up during blinatumomab therapy.
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http://dx.doi.org/10.1177/10781552211015776DOI Listing
May 2021

Gene Environment Interactions in the Etiology of Neural Tube Defects.

Front Genet 2021 10;12:659612. Epub 2021 May 10.

Department of Molecular and Cellular Biology, Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX, United States.

Human structural congenital malformations are the leading cause of infant mortality in the United States. Estimates from the United States Center for Disease Control and Prevention (CDC) determine that close to 3% of all United States newborns present with birth defects; the worldwide estimate approaches 6% of infants presenting with congenital anomalies. The scientific community has recognized for decades that the majority of birth defects have undetermined etiologies, although we propose that environmental agents interacting with inherited susceptibility genes are the major contributing factors. Neural tube defects (NTDs) are among the most prevalent human birth defects and as such, these malformations will be the primary focus of this review. NTDs result from failures in embryonic central nervous system development and are classified by their anatomical locations. Defects in the posterior portion of the neural tube are referred to as meningomyeloceles (spina bifida), while the more anterior defects are differentiated as anencephaly, encephalocele, or iniencephaly. Craniorachischisis involves a failure of the neural folds to elevate and thus disrupt the entire length of the neural tube. Worldwide NTDs have a prevalence of approximately 18.6 per 10,000 live births. It is widely believed that genetic factors are responsible for some 70% of NTDs, while the intrauterine environment tips the balance toward neurulation failure in at risk individuals. Despite aggressive educational campaigns to inform the public about folic acid supplementation and the benefits of providing mandatory folic acid food fortification in the United States, NTDs still affect up to 2,300 United States births annually and some 166,000 spina bifida patients currently live in the United States, more than half of whom are now adults. Within the context of this review, we will consider the role of maternal nutritional status (deficiency states involving B vitamins and one carbon analytes) and the potential modifiers of NTD risk beyond folic acid. There are several well-established human teratogens that contribute to the population burden of NTDs, including: industrial waste and pollutants [e.g., arsenic, pesticides, and polycyclic aromatic hydrocarbons (PAHs)], pharmaceuticals (e.g., anti-epileptic medications), and maternal hyperthermia during the first trimester. Animal models for these teratogens are described with attention focused on valproic acid (VPA; Depakote). Genetic interrogation of model systems involving VPA will be used as a model approach to discerning susceptibility factors that define the gene-environment interactions contributing to the etiology of NTDs.
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http://dx.doi.org/10.3389/fgene.2021.659612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143787PMC
May 2021

Effect of body mass index on peak growth hormone level after growth hormone stimulation test in children with short stature.

Ann Pediatr Endocrinol Metab 2021 May 12. Epub 2021 May 12.

Department of Pediatrics, Seoul St. Mary's hospital, Catholic University, Korea, Seoul, Korea.

Purpose: The aim of this study is to evaluate the effect of body mass index (BMI) on peak serum growth hormone (GH) level after GH stimulation test in children with short stature.

Methods: Data was obtained from retrospective medical records review of those who visited the pediatric endocrine clinic at St. Vincent's hospital of Catholic university for short stature from January 2010 to June 2019. A total 115 children (66 boys and 49 girls) whose height was less than 3 percentiles according to age and sex underwent GH stimulation test.

Results: Of 115 subjects, 47 were diagnosed with GH deficiency (GHD) and 68 were diagnosed with idiopathic short stature (ISS). In patients with GHD, weight standard deviation score (SDS) (P < 0.001) and BMI SDS (P ≤ 0.001) were higher and free thyroxine (T4) level (P = 0.012) was lower than those in the ISS group. In total subjects, peak serum GH level after GH stimulation test showed negative correlations with weight SDS (r = -0.465, P < 0.001), BMI SDS (r = -0.398, P < 0.001), thyroid stimulating hormone (r = -0.248, P = 0.008) and a positive correlation with free T4 (r = 0.326, P < 0.001). In multiple regression analysis, BMI SDS (P = 0.003) was negatively associated with peak serum GH level in GH stimulation test after adjusting for age, sex, pubertal status and type of pharmacological stimulus.

Conclusion: BMI SDS influence peak serum GH level after GH stimulation test. We should consider BMI factor when interpreting of results of GH stimulation test.
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http://dx.doi.org/10.6065/apem.2040246.123DOI Listing
May 2021

Comparison of postoperative outcomes between early and delayed surgery for pediatric nasal fractures.

Arch Craniofac Surg 2021 Apr 20;22(2):93-98. Epub 2021 Apr 20.

Department of Plastic and Reconstructive Surgery, Daegu Catholic University School of Medicine, Daegu, Korea.

Background: Pediatric nasal fractures, unlike adult nasal fractures, are treated surgically as early as 7 days after the initial trauma. However, in some cases, a week or more elapses before surgery, and few studies have investigated the consequences of delayed surgery for pediatric nasal fractures. The purpose of this study was to evaluate the postoperative outcomes of pediatric nasal fractures according to the time interval between the initial trauma and surgery.

Methods: The records of pediatric patients under 12 years old who underwent closed reduction of nasal bone fracture from March 2012 to February 2020 were reviewed. The interval between trauma and surgery was divided into within 7 days (early reduction) and more than 7 days (delayed reduction). Postoperative results were classified into five grades (excellent, good, moderate, poor, and very poor) based on the degree of reduction shown on computed tomography.

Results: Ninety-eight patients were analyzed, of whom 51 underwent early reduction and 47 underwent delayed reduction. Forty-two (82.4%) of the 51 patients in the early reduction group showed excellent results, and nine (17.6%) showed good results. Thirty-nine (83.0%) of the 47 patients in the delayed reduction group showed excellent results and eight (17.0%) showed good results. No statistically significant difference in outcomes was found between the two groups (chi-square test p= 0.937). However, patients without septal injury were significantly more likely to have excellent postoperative outcomes (chi-square test p< 0.01).

Conclusion: No statistically significant difference was found in the outcomes of pediatric nasal fractures between the early and delayed reduction groups. Successful surgical results were found even in patients who received delayed reduction (more than 7 days after trauma).
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http://dx.doi.org/10.7181/acfs.2021.00122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107460PMC
April 2021

Tannylated Calcium Carbonate Materials with Antacid, Anti-Inflammatory, and Antioxidant Effects.

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

Department of Systems Biotechnology, Chung-Ang University, Gyeonggi 17546, Korea.

Calcium carbonate (CaCO)-based materials have received notable attention for biomedical applications owing to their safety and beneficial characteristics, such as pH sensitivity, carbon dioxide (CO) gas generation, and antacid properties. Herein, to additionally incorporate antioxidant and anti-inflammatory functions, we prepared tannylated CaCO (TA-CaCO) materials using a simple reaction between tannic acid (TA), calcium (Ca), and carbonate (CO) ions. TA-CaCO synthesized at a molar ratio of 1:75 (TA:calcium chloride (CaCl)/sodium carbonate (NaCO)) showed 3-6 μm particles, comprising small nanoparticles in a size range of 17-41 nm. The TA-CaCO materials could efficiently neutralize the acid solution and scavenge free radicals. In addition, these materials could significantly reduce the mRNA levels of pro-inflammatory factors and intracellular reactive oxygen species, and protect chondrocytes from toxic hydrogen peroxide conditions. Thus, in addition to their antacid property, the prepared TA-CaCO materials exert excellent antioxidant and anti-inflammatory effects through the introduction of TA molecules. Therefore, TA-CaCO materials can potentially be used to treat inflammatory cells or diseases.
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http://dx.doi.org/10.3390/ijms22094614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124724PMC
April 2021

Octreotide inhibits secretion of IGF-1 from orbital fibroblasts in patients with thyroid-associated ophthalmopathy via inhibition of the NF-κB pathway.

PLoS One 2021 22;16(4):e0249988. Epub 2021 Apr 22.

Department of Ophthalmology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Purpose: We investigated the effect of octreotide, a long-acting somatostatin (SST) analogue, on IGF-1 secretion and its possible mechanism of action in orbital fibroblasts (OFs) from patients with thyroid-associated ophthalmopathy (TAO).

Materials And Methods: OFs were isolated from the orbital fat of patients with TAO or healthy individuals. The expression level of insulin-like growth factor (IGF)-1, at the protein and mRNA level, was determined with ELISA and quantitative RT-PCR, respectively. The expression pattern of somatostatin receptor (SSTR) 2, which has the highest affinity for octreotide, was examined by flow cytometry. The activity of NF-κB pathway was determined by examining the levels of phosphorylation of IKKα/β and p65, and degradation of IκB via western blot analysis, and by measuring the activity of NF-kB-dependent luciferase via transfection with plasmids containing luciferase and NF-κB binding site.

Results: OFs from patients with TAO showed significantly higher levels of IGF-1 secretion and NF-κB activity even in the absence of stimulation, compared to those from controls. Treatment with octreotide reduced the level of IGF-1 secretion in OFs from patients with TAO, but not in OFs from controls. OFs from patients with TAO expressed higher levels of SSTR2 on the cell surface, compared to controls. In addition, the expression of IGF-1 at the protein and mRNA level was dependent on the activity of NF-κB pathway in OFs from patients with TAO. Furthermore, treatment with octreotide reduced on the activity of NF-κB pathway in OFs from patients with TAO.

Conclusion: OFs from patients with TAO showed significantly higher levels of IGF-1 secretion via up-regulation of NF-κB activity. Treatment with octreotide inhibited the secretion of IGF-1 by reducing the NF-κB pathway in OFs, which expressed higher levels of SSRT2 on the cell surface, from patients with TAO.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249988PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062018PMC
September 2021

Computer-aided detection and abnormality score for the outer retinal layer in optical coherence tomography.

Br J Ophthalmol 2021 Apr 19. Epub 2021 Apr 19.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore

Background: To develop computer-aided detection (CADe) of ORL abnormalities in the retinal pigmented epithelium, interdigitation zone and ellipsoid zone via optical coherence tomography (OCT).

Methods: In this retrospective study, healthy participants with normal ORL, and patients with abnormality of ORL including choroidal neovascularisation (CNV) or retinitis pigmentosa (RP) were included. First, an automatic segmentation deep learning (DL) algorithm, CADe, was developed for the three outer retinal layers using 120 handcraft masks of ORL. This automatic segmentation algorithm generated 4000 segmentations, which included 2000 images with normal ORL and 2000 (1000 CNV and 1000 RP) images with focal or wide defects in ORL. Second, based on the automatically generated segmentation images, a binary classifier (normal vs abnormal) was developed. Results were evaluated by area under the receiver operating characteristic curve (AUC).

Results: The DL algorithm achieved an AUC of 0.984 (95% CI 0.976 to 0.993) for individual image evaluation in the internal test set of 797 images. In addition, performance analysis of a publicly available external test set (n=968) had an AUC of 0.957 (95% CI 0.944 to 0.970) and a second clinical external test set (n=1124) had an AUC of 0.978 (95% CI 0.970 to 0.986). Moreover, the CADe highlighted well normal parts of ORL and omitted highlights in abnormal ORLs of CNV and RP.

Conclusion: The CADe can use OCT images to segment ORL and differentiate between normal ORL and abnormal ORL. The CADe classifier also performs visualisation and may aid future physician diagnosis and clinical applications.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317817DOI Listing
April 2021

Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis.

J Korean Med Sci 2021 Apr 12;36(14):e90. Epub 2021 Apr 12.

Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Korea.

Background: Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades. However, the involvement of S100B and RAGE in cholestasis-induced liver fibrosis remains unclear. In this study, we investigated S100B and RAGE expression during liver fibrosis in mice that underwent common bile duct ligation (BDL).

Methods: BDL was performed in 10-week-old male C57BL/6J mice with sham control (n = 26) and BDL (n = 26) groups. Expression levels of S100B, RAGE and fibrotic markers in the livers from both groups at week 1 and 3 after BDL were examined by western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Liver fibrotic changes were examined by histological and ultrastructural analysis.

Results: Histological staining with Sirius Red and the evaluation of the messenger RNA expression of fibrotic markers showed noticeable periportal fibrosis and bile duct proliferation. S100B was mainly present in bile duct epithelial cells, and its expression was upregulated in proportion to the ductular reaction during fibrogenesis by BDL. RAGE expression was also increased, and interestingly, triple immunofluorescence staining and transmission electron microscopy showed that both S100B and RAGE were expressed in proliferating bile duct epithelial cells and activated hepatic stellate cells (HSCs) of the BDL livers. In addition, in rat HSCs (HSC-T6), treatment with recombinant S100B protein significantly increased fibrotic markers in a dose-dependent manner, and RAGE small interfering RNA (siRNA) suppressed S100B-stimulated upregulation of fibrotic markers compared with cells treated with scramble siRNA and S100B.

Conclusion: These findings suggest that the increased expression of S100B and RAGE and the interaction between S100B and RAGE may play an important role in ductular reaction and liver fibrosis induced by BDL.
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http://dx.doi.org/10.3346/jkms.2021.36.e90DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042478PMC
April 2021
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