Publications by authors named "Jae-Yong Park"

465 Publications

Genetic Polymorphisms in Activating Transcription Factor 3 Binding Site and the Prognosis of Early-Stage Non-Small Cell Lung Cancer.

Oncology 2021 Feb 24:1-9. Epub 2021 Feb 24.

Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background: Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery.

Methods: A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated.

Results: Among those SNPs, HAX1 rs11265425T>G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00-1.69, p = 0.05), and ME3 rs10400291C>A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46-0.95, p = 0.03). Regarding HAX1 rs11265425T>G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding ME3 rs10400291C>A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher HAX1 promoter activity than T allele. HAX1 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, ME3 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes.

Conclusions: In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, HAX1 rs11265425T>G and ME3 rs10400291C>A are associated with the clinical outcomes of patients in surgically resected NSCLC.
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http://dx.doi.org/10.1159/000514131DOI Listing
February 2021

Prognostic significance of genetic variants in GLUT1 in stage III non-small cell lung cancer treated with radiotherapy.

Thorac Cancer 2021 Jan 31. Epub 2021 Jan 31.

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

Background: To examine the impact of polymorphisms of glucose transporter 1 (GLUT1) gene on the prognosis of patients with stage III non-small cell lung cancer (NSCLC) who received radiotherapy.

Methods: Five single nucleotide polymorphisms (SNPs) (rs4658C>G, rs1385129G>A, rs3820589A>T, rs3806401A>C and rs3806400C>T) in GLUT1 gene were evaluated in 90 patients with pathologically confirmed stage III NSCLC. A total of 21 patients were treated with radiotherapy alone, 25 with sequential chemoradiotherapy, and 44 with concurrent chemoradiotherapy. The association of the genetic variations of five SNPs with overall survival (OS) and progression-free survival (PFS) was analyzed.

Results: Two SNPs (rs1385129 and rs3806401) were significant risk factors for OS. Three SNPs (rs1385129, rs3820589 and rs3806401) were in linkage disequilibrium. In Cox proportional hazard models, GAA haplotype was a good prognostic factor for OS (hazard ratio [HR] = 0.57, 95% confidence interval [CI]: 0.39-0.81, p = 0.002) and PFS (HR = 0.68, 95% CI: 0.47-0.99, p = 0.043), compared to variant haplotypes. The GAA/GAA diplotype was observed in 46.7% of patients; these patients showed significantly better OS (HR = 0.38, 95% CI: 0.22-0.65, p < 0.001) and PFS (HR = 0.51, 95% CI: 0.31-0.85, p = 0.009) compared to those with other diplotypes.

Conclusions: These results suggest that polymorphisms of GLUT1 gene could be used as a prognostic marker for patients with stage III NSCLC treated with radiotherapy.
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http://dx.doi.org/10.1111/1759-7714.13851DOI Listing
January 2021

Impact of immune checkpoint gene CD155 Ala67Thr and CD226 Gly307Ser polymorphisms on small cell lung cancer clinical outcome.

Sci Rep 2021 Jan 19;11(1):1794. Epub 2021 Jan 19.

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea.

This study was conducted to investigate the impact of genetic variants of immune checkpoint genes on the treatment outcome in small cell lung cancer (SCLC). In the present study, 261 platinum doublet-treated SCLC patients were enrolled. A total of 96 polymorphisms in 33 immune checkpoint-related genes were selected, and their association with chemotherapy response and survival outcomes were analyzed. Among the polymorphisms studied, CD155 rs1058402G > A (Ala67Thr, A67T) and CD226 rs763361C > T (Gly307Ser, G307S) were significantly associated with SCLC treatment outcome. The rs1058402G > A had a worse chemotherapy response and overall survival (under a dominant model, adjusted odds ratio [aOR] = 0.52, 95% confidence interval [CI] = 0.27-0.99, P = 0.05; adjusted hazard ratio [aHR] = 1.55, 95% CI = 1.12-2.14, P = 0.01, respectively). The rs763361C > T had better chemotherapy response and overall survival (under a dominant model, aOR = 2.03, 95% CI = 1.10-3.75, P = 0.02; aHR = 0.69, 95% CI = 0.51-0.94, P = 0.02, respectively). When the rs1058402GA/AA and rs763361CC genotypes were combined, the chemotherapy response and overall survival were significantly decreased as the number of bad genotypes increased (aOR = 0.52, 95% CI = 0.33-0.81, Ptrend = 0.004; aHR = 1.48, 95% CI = 1.19-1.84, Ptrend = 4 × 10, respectively). The 3-D structural model showed that CD155 A67T created a new hydrogen bond and structural change on CD155. These changes resulted in extending the distance and losing the hydrogen bonds between CD155 and CD226, thus weakening CD155/CD226 binding activity. In conclusion, CD155 rs1058402G > A and CD226 rs763361C > T may be useful for predicting the clinical outcomes of SCLC patients after chemotherapy.
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http://dx.doi.org/10.1038/s41598-021-81260-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815735PMC
January 2021

ANO1 regulates the maintenance of stemness in glioblastoma stem cells by stabilizing EGFRvIII.

Oncogene 2021 Feb 15;40(8):1490-1502. Epub 2021 Jan 15.

Radiation Therapeutics Development Team, Division of Radiation Cancer Science, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.

Glioblastoma multiforme (GBM) or glioblastoma is the most deadly malignant brain tumor in adults. GBM is difficult to treat mainly due to the presence of glioblastoma stem cells (GSCs). Epidermal growth factor receptor variant III (EGFRvIII) has been linked to stemness and malignancy of GSCs; however, the regulatory mechanism of EGFRvIII is largely unknown. Here, we demonstrated that Anoctamin-1 (ANO1), a Ca-activated Cl channel, interacts with EGFRvIII, increases its protein stability, and supports the maintenance of stemness and tumor progression in GSCs. Specifically, shRNA-mediated knockdown and pharmacological inhibition of ANO1 suppressed the self-renewal, invasion activities, and expression of EGFRvIII and related stem cell factors, including NOTCH1, nestin, and SOX2 in GSCs. Conversely, ANO1 overexpression enhanced the above phenomena. Mechanistically, ANO1 protected EGFRvIII from proteasomal degradation by directly binding to it. ANO1 knockdown significantly increased survival in mice and strongly suppressed local invasion of GSCs in an in vivo intracranial mouse model. Collectively, these results suggest that ANO1 plays a crucial role in the maintenance of stemness and invasiveness of GSCs by regulating the expression of EGFRvIII and related signaling molecules, and can be considered a promising therapeutic target for GBM treatment.
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http://dx.doi.org/10.1038/s41388-020-01612-5DOI Listing
February 2021

AEG-1 Regulates TWIK-1 Expression as an RNA-Binding Protein in Astrocytes.

Brain Sci 2021 Jan 11;11(1). Epub 2021 Jan 11.

Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.

AEG-1, also called MTDH, has oncogenic potential in numerous cancers and is considered a multifunctional modulator because of its involvement in developmental processes and inflammatory and degenerative brain diseases. However, the role of AEG-1 in astrocytes remains unknown. This study aimed to investigate proteins directly regulated by AEG-1 by analyzing their RNA expression patterns in astrocytes transfected with scramble shRNA and AEG-1 shRNA. AEG-1 knockdown down-regulated TWIK-1 mRNA. Real-time quantitative PCR (qPCR) and immunocytochemistry assays confirmed that AEG-1 modulates TWIK-1 mRNA and protein expression. Electrophysiological experiments further revealed that AEG-1 further regulates TWIK-1-mediated potassium currents in normal astrocytes. An RNA immunoprecipitation assay to determine how AEG-1 regulates the expression of TWIK-1 revealed that AEG-1 binds directly to TWIK-1 mRNA. Furthermore, TWIK-1 mRNA stability was significantly increased upon overexpression of AEG-1 in cultured astrocytes ( < 0.01). Our findings show that AEG-1 serves as an RNA-binding protein to regulate TWIK-1 expression in normal astrocytes.
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http://dx.doi.org/10.3390/brainsci11010085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827766PMC
January 2021

Etiological Distribution and Morphological Patterns of Granulomatous Pleurisy in a Tuberculosis-prevalent Country.

J Korean Med Sci 2021 Jan 4;36(1):e10. Epub 2021 Jan 4.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.

The cause of epithelioid granulomatous inflammation varies widely depending on the affected organ, geographic region, and whether the granulomas morphologically contain necrosis. Compared with other organs, the etiological distribution and morphological patterns of pleural epithelioid granulomas have rarely been investigated. We evaluated the final etiologies and morphological patterns of pleural epithelioid granulomatous inflammation in a tuberculosis (TB)-prevalent country. Of 83 patients with pleural granulomas, 50 (60.2%) had confirmed TB pleurisy (TB-P) and 29 (34.9%) had probable TB-P. Four patients (4.8%) with non-TB-P were diagnosed. With the exception of microbiological results, there was no significant difference in clinical characteristics and granuloma patterns between the confirmed TB-P and non-TB-P groups, or between patients with confirmed and probable TB-Ps. These findings suggest that most pleural granulomatous inflammation (95.2%) was attributable to TB-P in TB-endemic areas and that the granuloma patterns contributed little to the prediction of final diagnosis compared with other organs.
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http://dx.doi.org/10.3346/jkms.2021.36.e10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781852PMC
January 2021

[Esophageal Involvement of Behcet's Disease].

Korean J Gastroenterol 2020 12;76(6):337-339

Department of Pathology, Chung-Ang University College of Medicine, Seoul, Korea.

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http://dx.doi.org/10.4166/kjg.2020.149DOI Listing
December 2020

Spadin Modulates Astrocytic Passive Conductance via Inhibition of TWIK-1/TREK-1 Heterodimeric Channels.

Int J Mol Sci 2020 Dec 17;21(24). Epub 2020 Dec 17.

School of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, Seoul 02841, Korea.

Astrocytes, the most abundant cell type in the brain, are non-excitable cells and play critical roles in brain function. Mature astrocytes typically exhibit a linear current-voltage relationship termed passive conductance, which is believed to enable astrocytes to maintain potassium homeostasis in the brain. We previously demonstrated that TWIK-1/TREK-1 heterodimeric channels mainly contribute to astrocytic passive conductance. However, the molecular identity of astrocytic passive conductance is still controversial and needs to be elucidated. Here, we report that spadin, an inhibitor of TREK-1, can dramatically reduce astrocytic passive conductance in brain slices. A series of gene silencing experiments demonstrated that spadin-sensitive currents are mediated by TWIK-1/TREK-1 heterodimeric channels in cultured astrocytes and hippocampal astrocytes from brain slices. Our study clearly showed that TWIK-1/TREK-1-heterodimeric channels can act as the main molecular machinery of astrocytic passive conductance, and suggested that spadin can be used as a specific inhibitor to control astrocytic passive conductance.
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http://dx.doi.org/10.3390/ijms21249639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765948PMC
December 2020

Hard-Soled Shoe Versus Short Leg Cast for a Fifth Metatarsal Base Avulsion Fracture: A Multicenter, Noninferiority, Randomized Controlled Trial.

J Bone Joint Surg Am 2021 Jan;103(1):23-29

Department of Orthopedic Surgery, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea.

Background: The purpose of this study was to determine whether tolerated weight-bearing in a hard-soled shoe was noninferior to the use of a short leg cast for the treatment of a fifth metatarsal base avulsion fracture, as assessed with use of a 100-mm visual analog scale (VAS) for pain at 6 months after the fracture.

Methods: A total of 145 patients were assessed for eligibility. Of these, 96 patients were randomly assigned to either the hard-soled shoe group (46 patients) or the cast group (50 patients). The primary outcome measure was the mean difference on the 100-mm VAS between groups at 6 months after the fracture. Secondary outcome measures included the time to return to preinjury activity and patient-reported satisfaction. Analysis was performed according to both an intention-to-treat basis (i.e., patients were included in the assessment of their assigned treatment arm, even if they crossed over to the other treatment arm prior to completing the 6-month follow-up) and a per-protocol basis (i.e., patients who completed the 6-month follow-up were analyzed according to the treatment they received).

Results: At 6 months after the fracture, the mean 100-mm VAS was 8.6 ± 7.0 mm in the hard-soled shoe group and 9.8 ± 7.3 mm in the cast group (p = 0.41) according to intention-to-treat analysis. The mean difference in 100-mm VAS between the 2 groups was -1.3 mm (95% confidence interval, -4.3 to 1.8 mm). The upper limit of the 95% confidence interval did not exceed the noninferiority margin of 10 mm, indicating that treatment with the hard-soled shoe was noninferior to treatment with the short leg cast. The proportion of patients who reported satisfaction with their treatment was similar between the hard-soled shoe and cast groups (89.5% compared with 87.5%, respectively; p = 0.79), but the time to return to preinjury activity was significantly shorter in the hard-soled shoe group (37.2 ± 14.4 days compared with 43.0 ± 11.1 days in the cast group; p = 0.04). There were no cases of nonunion in either group.

Conclusions: Weight-bearing as tolerated in a hard-soled shoe for a fifth metatarsal base avulsion fracture was noninferior to the use of a short leg cast as assessed with use of a 100-mm VAS at 6 months after the fracture. Patient-reported satisfaction was similar between groups, but the time to return to preinjury activity was shorter in the hard-soled shoe group.

Level Of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.20.00777DOI Listing
January 2021

Effects of glycemic variability on the progression of diabetic retinopathy among patients with type 2 diabetes.

Retina 2020 Nov 23. Epub 2020 Nov 23.

Department of Internal Medicine, Sanggye Paik Hospital, Cardiovascular and Metabolic Disease Center, Inje University, Seoul, Korea.

Purpose: To evaluate the effects of glycemic variability on the progression of diabetic retinopathy (DR) among individuals with type 2 diabetes and to test the hypothesis that consistent glycemic control delays the progression of DR.

Methods: This retrospective study included 1125 participants with a follow-up period of more than 5 years and more than 20 glucose laboratory test results. The hazard ratio (HR) of ≥3 steps of progression on the Early Treatment Diabetic Retinopathy Study person scale and progression to proliferative diabetic retinopathy (PDR) were assessed.

Results: An increase in the HbA1c standard deviation (SD) was associated with a higher risk of ≥3 step progression (P<0.001) as well as progression to PDR (P<0.001). Not only mean HbA1c but also HbA1c standard deviation was associated with a lower risk of ≥3 steps of progression (P<0.001), as well as progression to PDR (P<0.001).

Conclusion: Achievable and consistent glycemic control may contribute to the delay in DR progression.
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http://dx.doi.org/10.1097/IAE.0000000000003049DOI Listing
November 2020

Helicobacter pylori-derived outer membrane vesicles stimulate interleukin 8 secretion through nuclear factor kappa B activation.

Korean J Intern Med 2020 Nov 27. Epub 2020 Nov 27.

Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.

Background/aims: Bacteria-derived outer membrane vesicles (OMVs) are commonly associated with various biological activities and functions. Helicobacter pylori-derived OMVs are thought to contribute to pathogenesis. This study aimed to investigate the effects of H. pylori-derived OMVs.

Methods: H. pylori strains were isolated from patients with gastritis, gastric ulcer, or gastric cancer using endoscopic biopsy. The U-937, AGS, and MKN-45 cell lines were exposed to H. pylori and H. pylori-derived OMVs. The expression of interleukin 8 (IL-8) messenger RNA (mRNA) was assessed using reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR, and IL-8 secretion was analyzed using enzyme-linked immunosorbent assay. Nuclear factor kappa B (NF-κB) activation was evaluated by Western blotting.

Results: H. pylori and H. pylori-derived OMVs induced the expression of IL-8 mRNA and protein. Importantly, the bacteria induced higher IL-8 mRNA and protein expression than the OMVs. IL-8 expression was induced to different levels in response to H. pylori-derived OMVs from hosts with different gastric diseases. Western blotting revealed the increased phosphorylation and reduced degradation of inhibitor of NF-κB alpha in cells exposed to OMVs.

Conclusions: H. pylori-derived OMVs may aid the development of various gastric diseases by inducing IL-8 production and NF-κB activation.
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http://dx.doi.org/10.3904/kjim.2019.432DOI Listing
November 2020

Clinical implication of minimal presence of solid or micropapillary subtype in early-stage lung adenocarcinoma.

Thorac Cancer 2021 Jan 24;12(2):235-244. Epub 2020 Nov 24.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.

Background: We investigated the clinical features and surgical outcomes of lung adenocarcinoma with minimal solid or micropapillary (S/MP) components, with a focus on stage IA.

Methods: We enrolled 506 patients with lung adenocarcinoma who underwent curative resection in this study. Clinical features and surgical outcomes were compared between the groups with and without the S/MP subtype (S/MP+ and S/MP-, respectively), and between the group with an S/MP proportion of ≤5% (S/MP5) and the S/MP-.

Results: The S/MP subtype was present in 247 patients (48.8%); 129 (25.5%) were grouped as the S/MP5 group. The S/MP+ and S/MP5 groups had larger tumors, higher frequency of lymph node metastasis, and more advanced stages of disease than the S/MP- group (P < 0.001, all comparisons). Pleural, lymphatic, and vascular invasions occurred more frequently in the S/MP+ and S/MP5 groups (P < 0.001, all comparisons for S/MP+ vs. S/MP-; P ≤ 0.01, all comparisons for S/MP5 vs. S/MP-). The S/MP+ and S/MP5 groups showed a shorter time to recurrence and cancer-related death than the S/MP- group(P < 0.001, both comparisons). For stage I, the presence or absence of the S/MP subtype defined prognostic subgroups better than the stage IA/IB classification. Notably, in the multivariate analysis, the minimal S/MP component was a significant predictor of recurrence, even in stage IA.

Conclusions: The presence of the minimal S/MP component was a significant predictor of poor prognosis after surgery, even in stage IA patients. Clinical trials to evaluate the advantages of adjuvant chemotherapy for this subset of patients and further investigations to understand underlying biological mechanisms of poor prognosis are needed.

Key Points: Significant findings of the study: We demonstrated that only minimal presence of solid or micropapillary component was profoundly associated with aggressive clinicopathological features and poor prognosis after complete resection even in stage IA lung adenocarcinoma.

What This Study Adds: Our results suggest that minimal presence of these subtypes is a strong prognostic factor which should be taken into account in the risk assessment for adjuvant chemotherapy in lung adenocarcinoma.
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http://dx.doi.org/10.1111/1759-7714.13754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812076PMC
January 2021

Heterotopic pancreas: the added value of endoscopic ultrasound with Computed Tomography for diagnosis.

Med Ultrason 2021 Feb 10;23(1):22-28. Epub 2020 Nov 10.

Department of Internal Medicine, Chung-Ang University Hospital, Seoul, South Korea.

Aims: To investigate the added value of endoscopic ultrasound (EUS) with computed tomography (CT) in distinguishing heterotopic pancreas (HP) from other pathologies, when gastroduodenal subepithelial tumors (SETs) are suspected on an upper endoscopic examination.

Material And Methods: We retrospectively included 54 consecutive patients with gastroduodenal SETs who had undergone both abdominal CT and EUS within a 3-month interval. All EUS, endoscopy, and CT images were reviewed and evaluated in a blinded manner by an endoscopist and a radiologist, respectively. Univariate and multivariate analyses were performed to identify EUS/CT findings related to HP. Diagnostic performance of CT only and CT combined with EUS was compared for distinguishing HP from other SETs.

Results: We included patients with HP (n=17; pathologically confirmed, n=6), gastrointestinal stromal tumor (GIST, n=24), and other pathologies (n=13). Multivariate logistic regression analyses revealed that irregular margin, origin from submucosal layer, internal microcystic-tubular structure, and oval shape were independent factors in diagnosing HP by EUS, whereas a micro-lobulating contour was the only significantly independent factor in CT. In assessments of diagnostic performance, CT combined with EUS showed significantly superior diagnostic performance in comparison with CT only (area under the curve, 0.961 vs. 0.833, p=0.028) in the consensus interpretation of an endoscopist and a radiologist.

Conclusions: CT combined with EUS with a comprehensive and complementary interpretation showed significant added value compared to CT only in diagnosing gastroduodenal HP.
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http://dx.doi.org/10.11152/mu-2704DOI Listing
February 2021

Highly transparent all-dielectric metasurface to block the near-infrared region of the solar spectrum.

Opt Express 2020 Oct;28(21):30466-30477

Blocking the near-infrared region (NIR) is indispensable for saving energy consumed to maintain the interior temperature in buildings. However, simultaneously enhancing transmission in visible light and blocking in the NIR remains challenging. Here, we theoretically demonstrate a transparent all-dielectric metasurface selectively blocking the NIR by using TiO nanocylinders and an indium tin oxide (ITO) layer. The ITO layer is implemented as a back reflector because ITO is transparent in visible light, whereas the ITO becomes a reflective material in the long-wavelength region (λ > 1500 nm). The designed metasurface exhibits high average transmittance of 70% in visible light and high solar energy rejection (SER) of 90% in the NIR. Furthermore, the blocking capability in the NIR of the designed metasurface is maintained over a wide range of an incident angle and polarization angle of light. Therefore, the metasurface gives a guideline for designing energy-saving applications.
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http://dx.doi.org/10.1364/OE.403559DOI Listing
October 2020

Gastric Gastrointestinal Stromal Tumor with Repeated Recurrence at the Anastomosis Site in a Very Elderly Patient.

Korean J Gastroenterol 2020 10;76(4):206-210

Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea.

Although high-risk gastrointestinal stromal tumors (GISTs) frequently recur, even after a complete resection and imatinib therapy, local recurrence at the suture line after complete resection is rare. The present case was an 88-year-old woman who was initially diagnosed with high-risk GIST without a distant metastasis. She underwent a complete surgical resection of the lesion and received adjuvant imatinib therapy for 18 months, which was discontinued due to severe drug-induced anemia. During the follow- up, an endoscopic examination performed 40 months after the initial surgery revealed local recurrence at the anastomosis site. Although a complete surgical resection was performed, repeated local recurrence was detected 18 months later, which progressed rapidly to metastatic disease. This paper reports a case of a completely resected gastric GIST with repeated local recurrence, despite the complete surgical resections and adjuvant imatinib therapy.
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http://dx.doi.org/10.4166/kjg.2020.76.4.206DOI Listing
October 2020

Loss of skeletal muscle mass during palliative chemotherapy is a poor prognostic factor in patients with advanced gastric cancer.

Sci Rep 2020 10 19;10(1):17683. Epub 2020 Oct 19.

Division of Hemato-Oncology, Department of Internal Medicine, Chung-Ang University College of Medicine, 224-1 Heukseok-dong, Dongjak-gu, 06973, Seoul, South Korea.

Cancer causes muscle mass loss, which is associated with a poor prognosis. Chemotherapy may also reduce muscle mass. We investigated skeletal muscle mass change during palliative chemotherapy for advanced gastric cancer (AGC) and its association with treatment outcomes. We retrospectively reviewed 111 consecutive AGC patients who underwent first-line palliative chemotherapy. Skeletal muscle area was measured before and after chemotherapy at the third lumbar vertebra level using computed tomography scans. We compared skeletal muscle index (SMI), body mass index (BMI), and body weight changes to chemotherapy response and survival. The 80 male and 31 female patients' median age was 65 (range 31-87) years, and 46.8% had sarcopenia at baseline. Median pre-chemotherapy to post-chemotherapy SMI, BMI, and body weight decreases were - 4.5 cm/m (- 11.3%) (P < 0.001); - 0.7 kg/m (- 3.2%) (P < 0.001); and - 2.0 kg (- 3.5%) (P < 0.001), respectively. Median SMI decreases for patients with objective response, stable disease, and disease progression were - 4.0 cm/m (range - 20.1 ~ 9.5); - 4.5 cm/m (range - 19.8 ~ 0.8); and - 3.8 cm/m (range: - 17.6 ~ 0.1), respectively. Response to chemotherapy was not associated with SMI decrease (P = 0.463). In multivariable analysis, sarcopenia at baseline (HR 1.681; 95% CI 1.083-2.609, P = 0.021), decreased SMI (HR 1.620; 95% CI 1.041-2.520; P = 0.032) were significant poor prognostic factors for survival. Skeletal muscle mass decreased significantly during chemotherapy in AGC patients, but was not associated with chemotherapy response. Decreased SMI was a poor prognostic factor in AGC patients during first-line palliative chemotherapy.
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http://dx.doi.org/10.1038/s41598-020-74765-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573603PMC
October 2020

Laboratory and radiological discrimination between tuberculous and malignant pleural effusions with high adenosine deaminase levels.

Korean J Intern Med 2020 Sep 29. Epub 2020 Sep 29.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background/aims: Pleural fluid adenosine deaminase (ADA) levels are useful in discriminating tuberculous pleural effusions (TPEs) from malignant pleural effusions (MPEs). However, some patients with MPE exhibit high-ADA levels, which may mimic TPEs. There is limited data regarding the differential diagnosis between high-ADA MPE and high-ADA TPE. This study aimed to identify the predictors for distinguishing high-ADA MPEs from high-ADA TPEs.

Methods: Patients with TPE and MPE with pleural fluid ADA levels ≥40 IU/L were included in this study. Clinical, laboratory, and radiological data were compared between the two groups. Independent predictors and their diagnostic performance for high-ADA MPEs were evaluated using multivariate logistic regression analysis and receiver operating characteristic curve.

Results: A total of 200 patients (high-ADA MPE, n = 30, and high-ADA TPE, n = 170) were retrospectively included. In the multivariate analysis, pleural fluid ADA, pleural fluid carcinoembryonic antigen (CEA), and pleural nodularity were independent discriminators between high-ADA MPE and high-ADA TPE groups. Using pleural ADA level of 40-56 IU/L (3 points), pleural CEA level ≥6 ng/mL (6 points), and presence of pleural nodularity (3 points) for predicting high-ADA MPEs, a sum score ≥6 points yielded a sensitivity of 90%, specificity of 96%, positive predictive value of 82%, negative predictive value of 98%, and area under the receiver operating characteristic curve of 0.965.

Conclusions: A scoring system using three parameters may be helpful in guiding the differential diagnosis between high-ADA MPEs and high-ADA TPEs.
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http://dx.doi.org/10.3904/kjim.2020.246DOI Listing
September 2020

The Prevalence of Multidrug Resistance of and Its Impact on Eradication in Korea from 2017 to 2019: A Single-Center Study.

Antibiotics (Basel) 2020 Sep 27;9(10). Epub 2020 Sep 27.

Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul 06974, Korea.

Antimicrobial resistance is one of the major factors determining the efficacy of eradication therapy. This study aimed to estimate the recent prevalence of multidrug resistance of and its impact on eradication in Korea. A total of 174 patients were prospectively enrolled at Chung-Ang University Hospital from 2017 to 2019. strains were isolated from the gastric body and antrum. The minimum inhibitory concentrations of antibiotics were determined by the serial twofold agar dilution method. Eradication results were reviewed and analyzed in connection with antibiotic resistance. The prevalence of infection was 51.7% (90/174). The culture success rate was 77.8% (70/90). The resistance rates for clarithromycin, metronidazole, amoxicillin, tetracycline, levofloxacin, and moxifloxacin were 28.6% (20/70), 27.1% (19/70), 20.0% (14/70), 18.6% (13/70), 42.9% (30/70), and 42.9% (30/70), respectively. The multidrug resistance (resistance to two or more classes of antimicrobials) rate was 42.9% (30/70). Dual resistance to clarithromycin and metronidazole was confirmed in 8.6% (6/70). Eradication with a first-line treatment was successful in 75% (36/48), and those who received second-line treatment all achieved successful eradication. The rate of multidrug resistance is increasing, and standard triple therapy (STT) is no longer an acceptable first-line option for eradication in Korea.
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http://dx.doi.org/10.3390/antibiotics9100646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601770PMC
September 2020

CPNE1-mediated neuronal differentiation can be inhibited by HAX1 expression in HiB5 cells.

Biochem Biophys Res Commun 2020 Dec 18;533(3):319-324. Epub 2020 Sep 18.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea. Electronic address:

We previously demonstrated that CPNE1 induces neuronal differentiation and identified two binding proteins of CPNE1 (14-3-3γ and Jab1) as potential regulators of CPNE1-mediated neuronal differentiation in hippocampal progenitor cells. To better understand the cellular processes in which CPNE1 participates in neuronal differentiation, we here carried out a yeast two-hybrid screening to find another CPNE1 binding protein. Among the identified proteins, HCLS1-related protein X-1 (HAX1) directly interacts with CPNE1. Immunostaining experiments showed that a fraction of CPNE1 and HAX1 co-localized in the cytosol, particularly in the plasma membrane. In addition, the physical interaction as well as the specific binding regions between CPNE1 and HAX1 were confirmed in vitro and in vivo. Moreover, AKT phosphorylation, Tuj1 (neuronal marker protein) expression, and neurite outgrowth are all reduced in CPNE1/HAX1 overexpressing cells compared to CPNE1 only overexpressing HiB5 cells. Conversely, the HAX1 mutant that does not bind to CPNE1 was unable to inhibit the CPNE1-mediated neuronal differentiation. Together these results indicate that HAX1 is a binding partner of CPNE1 and CPNE1-mediated neuronal differentiation is negatively affected through the binding of HAX1, especially its N-terminal region, with CPNE1.
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http://dx.doi.org/10.1016/j.bbrc.2020.09.037DOI Listing
December 2020

Emerging roles of 14-3-3γ in the brain disorder.

BMB Rep 2020 Nov;53(10):500-511

School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 02708, Korea.

14-3-3 proteins are mostly expressed in the brain and are closely involved in numerous brain functions and various brain disorders. Among the isotypes of the 14-3-3 proteins, 14-3-3γ is mainly expressed in neurons and is highly produced during brain development, which could indicate that it has a significance in neural development. Furthermore, the distinctive levels of temporally and locally regulated 14-3-3γ expression in various brain disorders suggest that it could play a substantial role in brain plasticity of the diseased states. In this review, we introduce the various brain disorders reported to be involved with 14-3-3γ, and summarize the changes of 14-3-3γ expression in each brain disease. We also discuss the potential of 14-3-3γ for treatment and the importance of research on specific 14-3-3 isotypes for an effective therapeutic approach. [BMB Reports 2020; 53(10): 500-511].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607152PMC
November 2020

Anti-glioma effects of 2-aminothiophene-3-carboxamide derivatives, ANO1 channel blockers.

Eur J Med Chem 2020 Dec 8;208:112688. Epub 2020 Aug 8.

KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea; Chemical Kinomics Research Center, Korea Institute of Science and Technology, 5 Hwarangro 14-gil, Seongbuk-gu, Seoul, 02792, Republic of Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. Electronic address:

Anoctamin1 (ANO1), a calcium-activated chloride ion channel (CaCC), is associated with various physiological functions including cancer progression and metastasis/invasion. ANO1 has been considered as a promising target for cancer therapeutics as ANO1 is over-expressed in a variety of cancers including glioblastoma (GBM) and inhibition of ANO1 has been reported to suppress cell proliferation, migration and invasion in GBM. GBM is one of the most common and aggressive cancers with poor prognosis with median survival for 15 months. Lack of effective treatment options against GBM emphasizes urgent necessity of effective GBM therapeutics. In an effort to discover potent and selective ANO1 inhibitors capable of inhibiting GBM cells, we have designed and synthesized a series of new 2-aminothiophene-3-carboxamide derivatives and performed SAR studies using both fluorescent cellular membrane potential assay and whole-cell patch-clamp recording. We observed that among these substances, 9c and 10q strongly suppress ANO1 channel activities and possess remarkable selectivity over ANO2. Unique structural feature of 10q, a cyclopentane-fused thiophene-3-carboxamide derivative, is the presence of benzoylthiourea functionality which dramatically contributes to activity. Both 9c and 10q suppress more strongly proliferation of GBM cells than four reference compounds including 3, Ani-9 and are also capable of inhibiting much more strongly colony formation than reference compounds in both 2D colony formation assay and 3D soft agar assay using U251 glioma cells. In addition, 9c and 10q suppress far more strongly migration/invasion of GBM cells than reference compounds. We, for the first time, found that the combination of ANO1 inhibitor (9c or 3) and temozolomide (TMZ) brings about remarkable synergistic effects in suppressing proliferation of GBM cells. Our study may provide an insight into designing selective and potent ANO1 inhibitors aiming at GBM treatment.
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http://dx.doi.org/10.1016/j.ejmech.2020.112688DOI Listing
December 2020

Genetic Variants in One-Carbon Metabolism Pathway Predict Survival Outcomes of Early-Stage Non-Small Cell Lung Cancer.

Oncology 2020 13;98(12):897-904. Epub 2020 Aug 13.

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background: This study was conducted to investigate the association between genetic variants in one-carbon metabolism and survival outcomes of surgically resected non-small cell lung cancer (NSCLC).

Methods: We genotyped 41 potentially functional variants of 19 key genes in the one-carbon metabolism pathway among 750 NSCLC patients who underwent curative surgery. The association between genetic variants and overall survival (OS)/disease-free survival (DFS) were analyzed.

Results: Among the 41 single-nucleotide polymorphisms (SNPs) analyzed, 4 SNPs (MTHFD1L rs6919680T>G and rs3849794T>C, MTR rs2853523C>A, and MTHFR rs4846049G>T) were significantly associated with survival outcomes. MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (adjusted hazard ratio [aHR] = 0.73, 95% confidence interval [CI] = 0.54-0.99, p = 0.04) and worse OS (aHR = 2.14, 95% CI = 1.13-4.07, p = 0.02), respectively. MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.41, 95% CI = 1.08-1.83, p = 0.01; and aHR = 1.97, 95% CI = 1.10-3.53, p = 0.02, respectively). When the patients were divided according to histology, the associations were significant only in squamous cell carcinoma (SCC), but not in adenocarcinoma (AC). In SCC, MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (aHR = 0.64, 95% CI = 0.41-1.00, p = 0.05) and worse OS (aHR = 2.77, 95% CI = 1.11-6.91, p = 0.03), respectively, and MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.73, 95% CI = 1.17-2.56, p = 0.01; and aHR = 2.78, 95% CI = 1.12-6.88, p = 0.03, respectively).

Conclusions: Our results suggest that the genetic variants in the one-carbon metabolism pathway could be used as biomarkers for predicting the clinical outcomes of patients with early-stage NSCLC.
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http://dx.doi.org/10.1159/000509658DOI Listing
December 2020

Expression of key regulatory genes in necroptosis and its effect on the prognosis in non-small cell lung cancer.

J Cancer 2020 11;11(18):5503-5510. Epub 2020 Jul 11.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Accumulating evidence suggests that necroptosis, or programmed necrotic cell death, may play a significant role in cancer. We evaluated the expression of key molecules in necroptosis and their association with clinical features and prognosis in NSCLC. A total of 253 NSCLC patients (96 squamous cell carcinoma [SCC] cases and 157 adenocarcinoma [AC] cases) who underwent curative resection were included. Tumor tissues and corresponding normal tissues were investigated for relative mRNA expression levels of , , and . Difference in disease free survival (DFS) was analyzed according to the expression levels of these molecules in tumor tissues. NSCLC tissues had significantly lower expression of , , and than normal tissues ( = 1 x 10, = 8 x 10, and = 4 x 10, respectively). In subgroup analysis, SCCs had significantly lower , , and expression ( = 5 x 10, = 3 x 10, = 1 x 10, respectively), and ACs had significantly lower and expression ( = 0.01 and = 6 x 10, respectively) than normal tissues. Low expression of , , and in tumors was associated with a worse DFS (HR = 1.71, = 0.01; HR = 1.53, = 0.04; and HR = 1.53, = 0.04, respectively) in a multivariate analysis. In SCC, none of the , , and expression was significantly associated with DFS. However, in AC, low expression of , , and was significantly associated with worse DFS (HR = 1.67, = 0.03; HR = 1.70, = 0.03; and HR = 1.81, = 0.02, respectively). Key regulatory genes in necroptosis, , , and , were downregulated in NSCLC, and their lower expression in NSCLC may be used to predict early recurrence after curative resection, especially in AC.
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http://dx.doi.org/10.7150/jca.46172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391199PMC
July 2020

Effect of genetic variation in Notch regulator DTX1 on SCLC prognosis compared with the effect on NSCLC prongosis.

Thorac Cancer 2020 Sep 22;11(9):2698-2703. Epub 2020 Jul 22.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea.

Deltex-1 (DTX1) is a negative regulator of the Notch signaling pathway. Here, we investigated the clinical effect of DTX1 rs1732786A > G, which is associated with better prognosis in patients with early-stage non-small cell lung cancer (NSCLC), in 261 patients with small cell lung cancer (SCLC). DTX1 rs1732786A > G was associated with a significantly worse chemotherapy response and lower overall survival in the codominant model (odds ratio = 0.42, 95% confidence interval [CI]: 0.26-0.66, P = 2 × 10 ; hazard ratio = 1.47, 95% CI: 1.17-1.84, P = 0.001, respectively). An in vitro luciferase assay was performed, and the 1732786G allele demonstrated significantly higher promoter activity than the 1732786A allele (P = 2 × 10 ). In summary, DTX1 rs1732786A > G was associated with poor prognosis in patients with SCLC as opposed to patients with NSCLC. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: DTX1 rs1732786A > G was associated with better prognosis in patients with early-stage non-small cell lung cancer (NSCLC) in our previous study. WHAT THIS STUDY ADDS: DTX1 rs1732786A > G was associated with a significantly worse chemotherapy response and lower overall survival in small cell lung cancer (SCLC).
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http://dx.doi.org/10.1111/1759-7714.13566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471053PMC
September 2020

Clinical Impact of N-Terminal Prohormone of Brain Natriuretic Peptide on Patients Hospitalized with Community-Acquired Pneumonia.

Am J Med Sci 2020 10 2;360(4):383-391. Epub 2020 Jun 2.

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

Background: Risk stratification is important for the management of community-acquired pneumonia (CAP). The present study aimed to investigate the clinical impact of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) on prognosis and to identify clinical characteristics associated with NT-proBNP elevation in CAP patients.

Methods: This retrospective study included patients hospitalized for CAP at a tertiary referral center and who underwent measurement plasma NT-proBNP levels. Based on 30-day mortality, patients (n = 1,821) were divided into 2 groups, survivors (n = 150) and nonsurvivors (n = 1,671), and clinical and laboratory findings were compared.

Results: In multivariate analysis, blood levels of NT-proBNP (>942.5 pg/mL), albumin (<3.3 g/dL), and troponin I (>0.018 ng/mL) independently predicted 30-day mortality. Of these blood biomarkers, NT-proBNP exhibited the highest C-statistic, followed by albumin. NT-proBNP level/CURB-65 score and NT-proBNP level/pneumonia severity index (PSI) class exhibited significantly higher C-statistics than CURB-65 score and PSI class alone, respectively. The 3-test combinations of CURB-65 score/NT-proBNP level/albumin level and PSI class/NT-proBNP level/albumin level exhibited significantly higher C-statistics than the 2-test combinations. NT-proBNP elevation was associated with increased age, heart disease and chronic kidney disease and NT-proBNP levels only weakly or moderately correlated with other blood biomarkers.

Conclusions: NT-proBNP level was a useful marker for the prediction of 30-day mortality in patients hospitalized with CAP, and provided additional prognostic value to PSI or CURB-65 alone.
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http://dx.doi.org/10.1016/j.amjms.2020.05.042DOI Listing
October 2020

AlGaN Deep-Ultraviolet Light-Emitting Diodes with Localized Surface Plasmon Resonance by a High-Density Array of 40 nm Al Nanoparticles.

ACS Appl Mater Interfaces 2020 Aug 29;12(32):36339-36346. Epub 2020 Jul 29.

Department of Materials Science and Engineering, Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang 37673, Korea.

We present a remarkable improvement in the efficiency of AlGaN deep-ultraviolet light-emitting diodes (LEDs) enabled by the coupling of localized surface plasmon resonance (LSPR) mediated by a high-density array of Al nanoparticles (NPs). The Al NPs with an average diameter of ∼40 nm were uniformly distributed near the AlGaN/AlGaN multiple quantum well active region for coupling 285 nm emission by block copolymer lithography. The internal quantum efficiency is enhanced by 57.7% because of the decreased radiative recombination lifetime by the LSPR. As a consequence, the AlGaN LEDs with an array of Al NPs show 33.3% enhanced electroluminescence with comparable electrical properties to those of reference LEDs without Al NPs.
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http://dx.doi.org/10.1021/acsami.0c08916DOI Listing
August 2020

Effect of Schroth Rehabilitation Exercise Program on Scoliometer Readings, Lumbar Lordosis and Calcaneal Valgus Angle in Patients with Idiopathic Scoliosis.

Iran J Public Health 2020 Apr;49(4):808-809

Department of Physical Education, Busan National University of Education, Busan 47503, South Korea.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283169PMC
April 2020

Effect of intravitreal ceftazidime injection on endogenous klebsiella pneumoniae endophthalmitis, a single center case series.

Medicine (Baltimore) 2020 May;99(22):e20521

Department of Ophthalmology Sanggye Paik Hospital, Inje University of Korea, College of Medicine, Seoul, Republic of Korea.

To report long-term outcomes of intravitreal ceftazidime injection in patients with endogenous Klebsiella pneumoniae endophthalmitis (EKPE).This was a retrospective observational case study, including 7 eyes from 6 patients with EKPE. The medical records from January 2010 to December 2018 were reviewed.Diagnosis of EKPE was made based on the finding of endophthalmitis with concurrent systemic infection and positive blood culture result. All patients received tap and intravitreal ceftazidime injection base on the results of antibiotics sensitivity test. Visual acuity ranged from no light perception to 20/60 at initial visit, and the final visual acuity was 20/20. Two eyes underwent evisceration after intravitreal injection.Intravitreal ceftazidime injection showed favorable results in patients with EKPE.
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http://dx.doi.org/10.1097/MD.0000000000020521DOI Listing
May 2020

Discovery of a Novel Mutation in DNA Gyrase and Changes in the Fluoroquinolone Resistance of over a 14-Year Period: A Single Center Study in Korea.

Antibiotics (Basel) 2020 May 27;9(6). Epub 2020 May 27.

Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul 06974, Korea.

The efficacy of fluoroquinolone-based eradication therapy largely depends on the fluoroquinolone resistance of . The aim of this study was to investigate the changes in the primary resistance rate of to fluoroquinolone and the mechanism of resistance in Korea. A total of 153 strains and 48 strains of were isolated at a tertiary hospital in 2005/2006 and 2017/2018, respectively. The minimum inhibitory concentrations (MICs) of fluoroquinolone were determined by the serial 2-fold agar dilution method. DNA sequences in the quinolone resistance-determining regions of were analyzed in resistant strains. Subsequent natural transformation study was performed to determine the association between gyrase mutation and resistance. The resistance rates increased from 19.0% (29/153) to 43.8% (21/48) both for levofloxacin and moxifloxacin. The MIC values for resistant strains increased from 2-8 µg/mL to 4-16 µg/mL over time. Mutation of was detected in 93.1% (27/29) and 100% (21/21) among the resistant strains in both periods, respectively. A novel Gly-85 mutation of was found and confirmed to be associated with fluoroquinolone resistance. Fluoroquinolone resistance rate of has markedly increased over time in Korea. The resistance is mostly due to the point mutation of . Fluoroquinolone-containing regimens should be carefully selected in Korea, considering the increasing fluoroquinolone resistance.
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http://dx.doi.org/10.3390/antibiotics9060287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345123PMC
May 2020

Corrigendum to "The Motoric Types of Delirium and Estimated Blood Loss during Perioperative Period in Orthopedic Elderly Patients".

Biomed Res Int 2020 9;2020:8753817. Epub 2020 May 9.

Department of Orthopaedic Surgery, Hallym University Sacred Heart Hospital College of Medicine, Hallym University, Anyang-si, Republic of Korea.

[This corrects the article DOI: 10.1155/2018/9812041.].
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http://dx.doi.org/10.1155/2020/8753817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243023PMC
May 2020