Publications by authors named "Hye-In Kim"

122 Publications

Surgeon Volume and Long-Term Oncologic Outcomes in Patients with Medullary Thyroid Carcinoma.

Ann Surg Oncol 2021 Jul 8. Epub 2021 Jul 8.

Division of Breast and Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Surgery is the most important curative treatment for medullary thyroid carcinoma (MTC). The relationship between surgeon volume (the number of surgeries performed) and short-term surgical outcomes, such as increased postoperative complication or costs, is well established. This study evaluated whether surgeon volume influenced long-term oncologic outcomes.

Methods: We retrospectively reviewed 246 patients diagnosed with MTC after initial thyroid surgery from 1995 to 2019. After exclusion, 194 patients were eligible for inclusion in the study. Surgeons were categorized as low/intermediate volume (fewer than 100 operations per year) or high volume (at least 100 operations per year).

Results: Of the 194 included patients, 60 (30.9%) developed disease recurrence, and 9 (4.6%) died of MTC during the median follow-up of 92.5 months. Having a low/intermediate-volume surgeon was associated with high disease recurrence (log-rank test, p < 0.001). After adjustment for age, sex, tumor type (sporadic versus hereditary), primary tumor size, presence of central lymph node metastasis (LNM), presence of lateral LNM, extrathyroidal extension, and positive resection margin, surgeon volume was a significant factor for disease recurrence (hazard ratio 2.28, p = 0.004); however, cancer-specific survival was not affected by surgeon volume (hazard ratio 4.16, p = 0.115).

Conclusions: Surgeon volume is associated with long-term oncologic outcome. MTC patients will be able to make the best decisions for their treatment based on the results of this study.
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http://dx.doi.org/10.1245/s10434-021-10383-6DOI Listing
July 2021

Tumor Volume Doubling Time in Active Surveillance of Papillary Thyroid Microcarcinoma: A Multicenter Cohort Study in Korea.

Thyroid 2021 Jul 6. Epub 2021 Jul 6.

Asan Medical Center, University of Ulsan College of Medicine, Endocrinology & Metabolism, 388-1 Pungnap-dong, Songpa-gu, Seoul, Korea (the Republic of), 138-736;

Background: Some papillary thyroid microcarcinomas (PTMCs) may progress with tumor enlargement or development of new lymph node (LN) metastasis during active surveillance (AS). This study evaluated the relevant predictors of disease progression, especially new cervical LN metastasis.

Methods: This was a long-term follow-up study conducted using a previous multicenter cohort of AS in Korea. After excluding 54 (14.2%) patients with a short follow-up duration, 326 PTMC patients were evaluated for tumor kinetics, including changes in tumor volume (TV) and TV doubling time (TVDT).

Results: During a median follow-up duration of 4.9 years, 17 (5.2%, 95% confidence intervals [CI] 2.7%-7.6%) patients showed a maximal diameter increase of ≥3 mm after a median 4.0 years of follow-up, while 9 (2.8%, 95% CI 1.0%-4.5%) showed newly developed LN metastasis after a median 2.2 years of follow-up. New cervical LN metastasis occurred exclusively of a maximal diameter increase of ≥3 mm. The prevalence of new development of LN metastasis was higher in patients with TVDT <5 years (7.4%) than in those with TV ≥50% (3.2%). Furthermore, only TVDT <5 years was significantly associated with LN metastasis (P = 0.002). In univariate and multivariate analyses, TVDT <5 years was an independent risk factor for disease progression with respect to new development of LN metastasis (hazard ratio [HR] = 6.51, CI 1.73-24.50; P = 0.002) and tumor enlargement (HR = 20.89, CI 5.78-75.48; P < 0.001). Finally, 86 (22.6%) patients underwent delayed surgery, and the most common reason was anxiety.

Conclusions: TVDT <5 years is the best predictor of disease progression during AS in terms of new LN metastasis development as well as tumor enlargement. Determination of TVDT in the early phase of AS could help in predicting disease progression for the precise tailoring of the follow-up intensity of AS and in determining if early surgical intervention is needed.
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http://dx.doi.org/10.1089/thy.2021.0094DOI Listing
July 2021

"CHicable" and "Clickable" Copolymers for Network Formation and Surface Modification.

Langmuir 2021 06 18;37(21):6510-6520. Epub 2021 May 18.

Laboratory for Chemistry and Physics of Interfaces, Department of Microsystems Engineering (IMTEK), University of Freiburg, Georges-Köhler-Allee 103, 79110 Freiburg, Germany.

In this study, we present the generation of novel, multifunctional polymer networks through a combination of C,H-insertion cross-linking (CHic) and click chemistry. To this, copolymers consisting of hydrophilic ,-dimethylacrylamide as matrix component and repeat units containing azide moieties, as well as benzophenone or anthraquinone groups, are generated. The benzophenone or anthraquinone groups allow photo-cross-linking, surface attachment or covalent immobilization of adjacent (bio)molecules through CHic reactions. The azide moieties either can react with available alkynes through conventional click reactions or can be activated to form nitrenes, which can also undergo CHic reactions. By choosing appropriate reaction conditions, the same polymer can be used to follow very different reaction paths, opening up a plethora of choices for the generation of functional polymer networks. In the exemplary presented case ("CHic-Click"), irradiation of the copolymers with UV-A light (λ = 365 nm) leads to cross-linking (network formation) and surface attachment simultaneously. The azide units remain intact during this cross-linking step, and alkyne-modified (bio)molecules can be bound through click reactions. Biofunctionalization of the polymer network with alkynylated streptavidin, followed by application of biotin-conjugated antibody and a model analyte, highlights the potential of these surface architectures as a toolbox which can be adapted for diverse bioanalytical applications.
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http://dx.doi.org/10.1021/acs.langmuir.1c00669DOI Listing
June 2021

CD11b Deficiency Exacerbates Methicillin-Resistant -Induced Sepsis by Upregulating Inflammatory Responses of Macrophages.

Immune Netw 2021 Apr 26;21(2):e13. Epub 2021 Feb 26.

Department of Biomedical Science, College of Natural Science, Hallym University, Chuncheon 24252, Korea.

Macrophages are important for the first line of defense against microbial pathogens. Integrin CD11b, which is encoded by , is expressed on the surface of macrophages and has been implicated in adhesion, migration, and cell-mediated cytotoxicity. However, the functional impact of CD11b on the inflammatory responses of macrophages upon microbial infection remains unclear. Here, we show that CD11b deficiency resulted in increased susceptibility to sepsis induced by methicillin-resistant (MRSA) infection by enhancing the pro-inflammatory activities of macrophages. Upon infection with MRSA, the mortality of knockout mice was significantly higher than that of control mice, which is associated with increased production of TNF-α and IL-6. In response to MRSA, both bone marrow-derived macrophages and peritoneal macrophages lacking CD11b produced elevated amounts of pro-inflammatory cytokines and nitric oxide. Moreover, CD11b deficiency upregulated IL-4-induced expression of anti-inflammatory mediators such as IL-10 and arginase-1, and an immunomodulatory function of macrophages to restrain T cell activation. Biochemical and confocal microscopy data revealed that CD11b deficiency augmented the activation of NF-κB signaling and phosphorylation of Akt, which promotes the functional activation of macrophages with pro-inflammatory and immunoregulatory phenotypes, respectively. Overall, our experimental evidence suggests that CD11b is a critical modulator of macrophages in response to microbial infection.
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http://dx.doi.org/10.4110/in.2021.21.e13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099615PMC
April 2021

Korean red ginseng induces extrinsic and intrinsic apoptotic pathways in MCF-7 breast cancer cells and MCF-10A non-malignant breast cells.

J Obstet Gynaecol Res 2021 May 13. Epub 2021 May 13.

Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: Among non-hormonal treatments, herbal products are frequently used by women. Korean red ginseng (KRG) is one of the popular herbal medicines. KRG could be one option for relieving menopausal symptoms. However, there are still concerns about the safety for long-term use. In order to be used for alleviating menopausal symptoms, the safety of KRG on breast must be ensured. The purpose of this study was to investigate the effects of KRG on breast cells.

Methods: MCF-7 and MCF-10A cells were treated with different concentrations of KRG extracts for 48 h. Cell viability was evaluated by MTT assay, and apoptosis by flow cytometry. The expression of apoptosis-related proteins was determined by western blot analysis and estrogen receptor (ER) affinity by ER binding assay.

Results: KRG extract inhibited growth and induced apoptosis of both MCF-7 and MCF-10A cells in dose-dependent manner. KRG extract increased the expression of pro-apoptotic proteins BAX, BAK, and BAD and decreased the expression of anti-apoptotic proteins Bcl-2 and Bcl-XL in both cells. The expressions of Fas and FasL were increased in lower doses, but decreased in higher doses in both cells. Activities of caspase-3, -8 and -9 increased in MCF-10A, while caspase-8 and -9 showed increase in MCF-7. Competition of KRG to E was significant in MCF-7 as KRG dose increased, whereas ER binding was hardly shown in MCF-10.

Conclusion: KRG induced apoptosis via extrinsic and intrinsic pathway in MCF-7 breast cancer cells and MCF-10A non-malignant cells. KRG may be safely used with regard to breast cancer risk in postmenopausal women to reduce the vasomotor symptoms.
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http://dx.doi.org/10.1111/jog.14826DOI Listing
May 2021

Predictive Factors of Conception and the Cumulative Pregnancy Rate in Subfertile Couples Undergoing Timed Intercourse With Ultrasound.

Front Endocrinol (Lausanne) 2021 15;12:650883. Epub 2021 Apr 15.

Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.

The aim of this study was to determine predictive factors for pregnancy and assess the cumulative pregnancy rate (CPR) and live birth rate (CLBR) in subfertile couples undergoing timed intercourse (TI) using ultrasound. This retrospective cohort study included 285 women (854 cycles) who started TI with ultrasound between January 2017 and October 2019. The overall clinical pregnancy rate was 28.1% (80/285) per couple and 9.4% (80/854) per cycle. Pregnant women had a higher body mass index (BMI), higher percentage of irregular menstrual cycles, a shorter duration of subfertility, lower serum follicle-stimulating hormone levels, and higher anti-Müllerian hormone levels than non-pregnant women. A longer duration of subfertility (≥24 months <12 months; odds ratio: 0.193; 95% confidence interval: 0.043-0.859) and endometriosis ( ovulatory factors; odds ratio: 0.282; 95% confidence interval: 0.106-0.746) as causes of subfertility were unfavorable factors that independently affected clinical pregnancy. In subgroup analysis, old age ≥ 35 years [ < 35 years; odds ratio: 0.279; 95% confidence interval: 0.083-0.938), a longer duration of infertility ≥24 months ( <24 months; odds ratio: 0.182; 95% confidence interval: 0.036-0.913) and a higher BMI ≥ 25 kg/m( >25 kg/m; odds ratio: 3.202; 95% confidence interval: 1.020-10.046) in couples with ovulatory factor and a longer duration of infertility ≥24 months ( <24 months; odds ratio: 0.185; 95% confidence interval: 0.042-0.819) in couples with non-ovulatory factors were significant independent predictive factors for pregnancy. No significant differences were found in the cycle characteristics between pregnant and non-pregnant women. The CPR substantially increased during the first three cycles and significantly increased until the sixth cycle. No significant increase was observed in the CPR after the sixth cycle. The CLBRs substantially increased during the first three cycles and significantly increased until the fourth cycle. No significant increase was observed in the CLBRs after the fifth cycle. When comparing CPRs and CLBRs according to subfertile causes, CRPs was significantly different and CLBRs was different with borderline significance. Our findings may indicate that women with a longer duration of subfertility or subfertility due to endometriosis have poor outcomes during TI with ultrasound. Women who failed to achieve conception by the fourth or fifth cycle of TI with ultrasound may be encouraged to consider advancing to the next treatment strategy.
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http://dx.doi.org/10.3389/fendo.2021.650883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082069PMC
April 2021

Surface Activity and Emulsifying Effect of Non-Toxic Starch Nanocrystal.

J Nanosci Nanotechnol 2021 07;21(7):4051-4054

Department of Pharmaceutical Engineering, Inje University, Gimhae 50834, Republic of Korea.

The purpose of this study is to investigate the surface activity of starch nanocrystals (SNC), material derived from starch, and confirm their usefulness as a surfactant. In order to evaluate the surface activity, the surface tension change of suspended SNC solution via the Wilhelmy plate method was measured and the values were compared with various synthetic surfactants. The effect of SNC as emulsifier was evaluated on emulsion formation and physical stability. The surface tension of the SNC-dispersed solution was decreased while its concentration was increased. When the 5.0% (w/v) of SNC was added, the surface tension was decreased from 70.3 to 49.5 mN/m. It was confirmed that the physical stability of the emulsion prepared by adding the SNC was improved compared to that of surface inactivity material (PEG 400). The phase separation was observed within 1 hour after preparation of the emulsion containing PEG 400, but the emulsion containing SNC was stable for 5 hours or more. To summarize this study, SNC, a natural-derived and non-toxic material, exhibits sufficient surface activity, thereby confirming the possibility of being applied to the food and pharmaceutical industry.
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http://dx.doi.org/10.1166/jnn.2021.19174DOI Listing
July 2021

Ovotesticular Disorder of Sex Development in Korean Children: A Single-Center Analysis over a 30-Year Period.

J Pediatr Adolesc Gynecol 2021 Mar 2. Epub 2021 Mar 2.

Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Women's Life Science, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Study Objective: To present clinical features that characterize ovotesticular disorder of sex development (OT-DSD) in the Korean population. Among the patient cohort who were initially suspected to have OT-DSD, the actual OT-DSD patients and those of other disorder of sex development were compared.

Design: Retrospective medical chart review of patients who were initially suspected to have OT-DSD from 1984 to 2018 on the basis of clinical examination.

Setting: Tertiary care university hospital.

Participants: Of 26 patients with initial diagnosis of OT-DSD, 3 were excluded because of incomplete records, and finally, 23 patients were subjected to analysis. Various examinations were performed before the surgical confirmation of gonad histopathology.

Interventions: Medical records were reviewed for clinical, anatomical, biochemical, and cytogenic characteristics, gender assignment, medical treatment, and histopathologic diagnosis.

Main Outcome Measures: Characteristics of OT-DSD in a Korean population.

Results: Among 23 patients suspected to have OT-DSD, 13/23 (56.5%) were diagnosed as OT-DSD after histopathologic confirmation. Of the remaining 10 patients, 5/23 (21.7%) were diagnosed with mixed gonadal dysgenesis, 3 with Turner variant, 1 with 46,XX disorder of sex development, and 1 with Mayer-Rokitansky-Küster-Hauser syndrome. Among the 13 OT-DSD cases, 9 patients presented with the 46,XX karyotype, 1 with the 46,XY, and 3 with the 46,XX/XY karyotype. Nine patients were assigned as male and 4 as female at birth. The most common gonad histology was ovotestis 10/26 (38%), followed by ovary and testis.

Conclusion: OT-DSD is one of the rarest disorders with various clinical presentations. A patient with ambiguous genitalia must be examined with a multidisciplinary approach with clinical suspicion for OT-DSD. Standardized procedure of evaluation and treatment is crucial.
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http://dx.doi.org/10.1016/j.jpag.2021.02.105DOI Listing
March 2021

Comparison of the clinical characteristics of community-acquired acute pyelonephritis between male and female patients.

J Infect Chemother 2021 Jul 25;27(7):1013-1019. Epub 2021 Feb 25.

Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, South Korea. Electronic address:

Background: Community-acquired acute pyelonephritis (CA-APN) is relatively rare in men. This study aimed to compare the clinical characteristics of CA-APN between male and female patients.

Methods: We prospectively collected the clinical and microbiological data of hospitalized CA-APN patients aged ≥19 years in South Korea from March 2010 to February 2011 in 11 hospitals and from September 2017 to August 2018 in 8 hospitals. Only the first episodes of APN of each patient during the study period were included.

Results: From 2010 to 2011, 573 patients from 11 hospitals were recruited, and from 2017 to 2018, 340 patients were recruited from 8 hospitals. Among them, 5.9% (54/913) were male. Male patients were older (66.0 ± 15.2 vs. 55.3 ± 19.0 years, P < 0.001), had a higher Charlson comorbidity index (1.3 ± 1.5 vs. 0.7 ± 1.2, P = 0.027), and had a higher proportion of structural problems in the urinary tract (40.7% vs. 6.1%, P < 0.001) than female patients. Moreover, the total duration of antibiotic treatment was longer (21.8 ± 17.8 d vs. 17.3 ± 9.4 d, P = 0.001) and the proportion of carbapenem usage was higher (24.1% vs. 9.5%, P = 0.001) in men than in women. Male patients were hospitalized for longer durations than female patients (median, 10 d vs. 7 d, P < 0.001).

Conclusions: Male CA-APN patients were older and had more comorbidities than female CA-APN patients. In addition, male patients received antibiotic treatment for a longer duration than female patients.
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http://dx.doi.org/10.1016/j.jiac.2021.02.014DOI Listing
July 2021

Exome Sequencing of 21 Bardet-Biedl Syndrome (BBS) Genes to Identify Obesity Variants in 6,851 American Indians.

Obesity (Silver Spring) 2021 04 22;29(4):748-754. Epub 2021 Feb 22.

Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, USA.

Objective: In an ongoing effort to identify the genetic variation that contributes to obesity in American Indians, known Bardet-Biedl syndrome (BBS) genes were analyzed for an effect on BMI and leptin signaling.

Methods: Potentially deleterious variants (Combined Annotation Dependent Depletion score > 20) in BBS genes were identified in whole-exome sequence data from 6,851 American Indians informative for BMI. Common variants (detected in ≥ 10 individuals) were analyzed for association with BMI; rare variants (detected in < 10 individuals) were analyzed for mean BMI of carriers. Functional assessment of variants' effect on signal transducer and activator of transcription 3 (STAT3) activity was performed in vitro.

Results: One common variant, rs59252892 (Thr549Ile) in BBS9, was associated with BMI (P = 0.0008, β = 25% increase per risk allele). Among rare variants for which carriers had severe obesity (mean BMI > 40 kg/m ), four were in BBS9. In vitro analysis of BBS9 found the Ile allele at Thr549Ile had a 20% increase in STAT3 activity compared with the Thr allele (P = 0.01). Western blot analysis showed the Ile allele had a 15% increase in STAT3 phosphorylation (P = 0.006). Comparable functional results were observed with Ser545Gly and Val209Leu but not Leu665Phe and Lys810Glu.

Conclusions: Potentially functional variants in BBS genes in American Indians are reported. However, functional evidence supporting a causal role for BBS9 in obesity is inconclusive.
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http://dx.doi.org/10.1002/oby.23115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048836PMC
April 2021

Changes in the Expression of TBP-2 in Response to Histone Deacetylase Inhibitor Treatment in Human Endometrial Cells.

Int J Mol Sci 2021 Jan 31;22(3). Epub 2021 Jan 31.

Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.

Histone deacetylase inhibitors (HDACi) induce apoptosis preferentially in cancer cells by caspase pathway activation and reactive oxygen species (ROS) accumulation. Suberoylanilide hydroxamic acid (SAHA), a HDACi, increases apoptosis via altering intracellular oxidative stress through thioredoxin (TRX) and TRX binding protein-2 (TBP-2). Because ROS accumulation, as well as the redox status determined by TBP-2 and TRX, are suggested as possible mechanisms for endometriosis, we queried whether SAHA induces apoptosis of human endometrial cells via the TRX-TBP-2 system in endometriosis. Eutopic endometrium from participants without endometriosis, and ectopic endometrium from patients with endometriosis, was obtained surgically. Human endometrial stromal cells (HESCs) and Ishikawa cells were treated with SAHA and cell proliferation was assessed using the CCK-8 assay. Real-time PCR and Western blotting were used to quantify TRX and TBP-2 mRNA and protein expression. After inducing oxidative stress, SAHA was applied. Short-interfering TRX (SiTRX) transfection was performed to see the changes after TRX inhibition. The mRNA and protein expression of TBP-2 was increased with SAHA concentrations in HESCs significantly. The mRNA TBP-2 expression was decreased after oxidative stress, upregulated by adding 2.5 μM of SAHA. The TRX/TBP-2 ratio decreased, apoptosis increased significantly, and SiTRX transfection decreased with SAHA. In conclusion, SAHA induces apoptosis by modulating the TRX/TBP-2 system, suggesting its potential as a therapeutic agent for endometriosis.
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http://dx.doi.org/10.3390/ijms22031427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866992PMC
January 2021

Transcriptome Profiling of Human Follicle Dermal Papilla Cells in response to Porphyra-334 Treatment by RNA-Seq.

Evid Based Complement Alternat Med 2021 13;2021:6637513. Epub 2021 Jan 13.

Anti-aging Research Institute of BIO-FD&C Co., Ltd., Incheon 21990, Republic of Korea.

Porphyra-334 is a kind of mycosporine-like amino acid absorbing ultraviolet-A. Here, we characterized porphyra-334 as a potential antiaging agent. An assay revealed that porphyra-334 dramatically promoted collagen synthesis in fibroblast cells. The effect of porphyra-334 on cell proliferation was dependent on the cell type, and the increase of cell viability by porphyra-334 was the highest in keratinocyte cells among the three tested cell types. An clinical test with 22 participants demonstrated the possible role of porphyra-334 in the improvement of periorbital wrinkles. RNA-sequencing using human follicle dermal papilla (HFDP) cells upon porphyra-334 treatment identified the upregulation of metallothionein- (MT-) associated genes, confirming the antioxidant role of porphyra-334 with MT. Moreover, the expression of genes involved in nuclear chromosome segregation and the encoding of components of kinetochores was upregulated by porphyra-334 treatment. Furthermore, we found that several genes associated with the hair follicle cycle, the hair follicle structure, the epidermal structure, and stem cells were upregulated by porphyra-334 treatment, suggesting the potential role of porphyra-334 in hair follicle growth and maintenance. In summary, we provided several new pieces of evidence of porphyra-334 as a potential antiaging cosmetic agent and elucidated the expression network in HFDP cells upon porphyra-334.
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http://dx.doi.org/10.1155/2021/6637513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817261PMC
January 2021

Gene expression profile of human follicle dermal papilla cells in response to Camellia japonica phytoplacenta extract.

FEBS Open Bio 2021 03 14;11(3):633-651. Epub 2021 Feb 14.

Anti-aging Research Institute of BIO-FD&C Co., Ltd., Incheon, Korea.

Camellia japonica L. is a flowering tree with several medicinal and cosmetic applications. Here, we investigated the efficacy of C. japonica placenta extract (CJPE) as a potential therapeutic agent for promotion of hair growth and scalp health by using various in vitro and in vivo assays. Moreover, we performed transcriptome analysis to examine the relative expression of human follicle dermal papilla cells (HFDPC) in response to CJPE by RNA-sequencing (RNA-seq). In vitro assays revealed upregulation of the expression of hair growth marker genes in HFDPC after CJPE treatment. Moreover, in vivo clinical tests with 42 adult female participants showed that a solution containing 0.5% CJPE increased the moisture content of the scalp and decreased the scalp's sebum content, dead scalp keratin, and erythema. Furthermore, RNA-seq analysis revealed key genes in HFDPC which are associated with CJPE. Interestingly, genes associated with lipid metabolism and cholesterol efflux were upregulated. Genes upregulated by CJPE are associated with several hormones, including parathyroid, adrenocorticotropic hormone, α-melanocyte-stimulating hormone (alpha-MSH), and norepinephrine, which are involved in hair follicle biology. Furthermore, some upregulated genes are associated with the regulation of axon guidance. In contrast, many genes downregulated by CJPE are associated with structural components of the cytoskeleton. In addition, CJPE suppressed genes associated with muscle structure and development. Taken together, this study provides extensive evidence that CJPE may have potential as a therapeutic agent for scalp treatment and hair growth promotion.
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http://dx.doi.org/10.1002/2211-5463.13076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931240PMC
March 2021

Diesel Exhaust Particulates Induce Neutrophilic Lung Inflammation by Modulating Endoplasmic Reticulum Stress-Mediated CXCL1/KC Expression in Alveolar Macrophages.

Molecules 2020 Dec 21;25(24). Epub 2020 Dec 21.

National Center for Efficacy Evaluation of Respiratory Disease Products, Korea Institute of Toxicology, 30 Baehak1-gil, Jeongeup 56212, Korea.

Diesel exhaust particulates (DEP) have adverse effects on the respiratory system. Endoplasmic reticulum (ER) abnormalities contribute to lung inflammation. However, the relationship between DEP exposure and ER stress in the respiratory immune system and especially the alveolar macrophages (AM) is poorly understood. Here, we examined ER stress and inflammatory responses using both in vivo and in vitro study. For in vivo study, mice were intratracheally instilled with 25, 50, and 100 μg DEP and in vitro AM were stimulated with DEP at 1, 2, and 3 mg/mL. DEP increased lung weight and the number of inflammatory cells, especially neutrophils, and inflammatory cytokines in bronchoalveolar lavage fluid of mice. DEP also increased the number of DEP-pigmented AM and ER stress markers including bound immunoglobulin protein (BiP) and CCAAT/enhancer binding protein-homologous protein (CHOP) were upregulated in the lungs of DEP-treated mice. In an in vitro study, DEP caused cell damage, increased intracellular reactive oxygen species, and upregulated inflammatory genes and ER stress-related BiP, CHOP, splicing X-box binding protein 1, and activating transcription factor 4 expressions in AM. Furthermore, DEP released the C-X-C Motif Chemokine Ligand 1 (CXCL1/KC) in AM. In conclusion, DEP may contribute to neutrophilic lung inflammation pathogenesis by modulating ER stress-mediated CXCL1/KC expression in AM.
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http://dx.doi.org/10.3390/molecules25246046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767360PMC
December 2020

Changes in Clinical Characteristics of Community-Acquired Acute Pyelonephritis and Antimicrobial Resistance of Uropathogenic in South Korea in the Past Decade.

Antibiotics (Basel) 2020 Sep 18;9(9). Epub 2020 Sep 18.

Department of Internal Medicine, College of Medicine, Hanyang University, Seoul 04763, Korea.

This study examined changes in the clinical characteristics of community-acquired acute pyelonephritis (CA-APN) in South Korea between the period 2010-2011 and 2017-2018. We recruited all CA-APN patients aged ≥19 years who visited eight hospitals in South Korea from September 2017 to August 2018, prospectively. Data collected were compared with those from the previous study in 2010-2012, with the same design and participation from 11 hospitals. A total of 617 patients were enrolled and compared to 818 patients' data collected in 2010-2011. was the most common causative pathogen of CA-APN in both periods (87.3% vs. 86.5%, = 0.680). isolates showed significantly higher antimicrobial resistance against fluoroquinolone (32.0% vs. 21.6%, < 0.001), cefotaxime (33.6% vs. 8.3%, < 0.001), and trimethoprim/sulfamethoxazole (37.5% vs. 29.2%, = 0.013) in 2017-2018 than in 2010-2011. Total duration of antibiotic treatment increased from 16.55 ± 9.68 days in 2010-2011 to 19.12 ± 9.90 days in 2017-2018 ( < 0.001); the duration of carbapenem usage increased from 0.59 ± 2.87 days in 2010-2011 to 1.79 ± 4.89 days in 2010-2011 ( < 0.001). The median hospitalization was higher for patients in 2017-2018 than in 2010-2011 (9 vs. 7 days, < 0.001). In conclusion, antimicrobial resistance of to almost all antibiotic classes, especially third generation cephalosporin, increased significantly in CA-APN in South Korea. Consequently, total duration of antibiotic treatment, including carbapenem usage, increased.
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http://dx.doi.org/10.3390/antibiotics9090617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559700PMC
September 2020

A Fatal Case of Bacteremia Caused by Non-O1/O139.

Infect Chemother 2021 Jun 19;53(2):384-390. Epub 2020 Aug 19.

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

is a pathogen known to cause the waterborne epidemic disease cholera. Overall, O1 or O139 strains produce the cholera toxin that cause gastroenteritis, resulting in watery diarrhea. Most of the enterocolitis caused by can be easily treated with fluid therapy and conservative care. However, non-O1/O139 strains can cause extraintestinal infections, such as wound infection or sepsis, in immunocompromised patients. The clinical course of these infections is very similar to that of infection. We report about a 52-year-old man without previous underlying disease who was diagnosed with non-O1/O139 infection and died within 72 hours after admission to the intensive care unit.
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http://dx.doi.org/10.3947/ic.2020.0301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258294PMC
June 2021

Differing Associations between Fatty Liver and Dyslipidemia According to the Degree of Hepatic Steatosis in Korea.

J Lipid Atheroscler 2019 Sep 21;8(2):258-266. Epub 2019 Sep 21.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.

Objective: Fatty liver is associated with insulin resistance-related diseases, such as dyslipidemia, obesity, and type 2 diabetes. The aim of this study was to evaluate the association of dyslipidemia with fatty liver and assess the differences in these associations according to the degree of hepatic steatosis.

Methods: A total of 2,462 subjects (1,679 men and 783 women) who underwent a comprehensive health check-up (including abdominal computed tomography) from January 2010 to December 2013 were enrolled at Samsung Changwon Hospital Healthcare Center. The liver attenuation index (LAI), defined as the difference between mean hepatic and splenic attenuation, was used to assess the degree of hepatic steatosis. An LAI below 5 Hounsfield units was defined as fatty liver.

Results: We found that 32.2% of the study subjects had fatty liver. Serum low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG), and fasting blood glucose concentrations and glycated hemoglobin (HbA1c percentage) were significant greater in the fatty liver group compared with the non-fatty liver group, while serum high-density lipoprotein cholesterol (HDL-C) was significantly lower in the fatty liver group. Subjects with fatty liver had 1.7-fold greater risk of dyslipidemia than those without fatty liver after adjusting for age, sex, body mass index (BMI), and HbA1c. When individuals with fatty liver were analyzed by tertiles of LAI values, LDL-C, TG, fasting glucose, BMI, and HbA1c concentrations increased while HDL-C decreased with decreasing LAI tertiles. Compared with LAI tertile 3, the risk for dyslipidemia significantly increased with adjusted odds ratios of 1.42, and 1.81 in tertiles 2 and 1, respectively.

Conclusion: Fatty liver was significantly associated with dyslipidemia and this association varied according to the degree of hepatic steatosis.
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http://dx.doi.org/10.12997/jla.2019.8.2.258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379109PMC
September 2019

Exome Sequencing Identifies A Nonsense Variant in DAO Associated With Reduced Energy Expenditure in American Indians.

J Clin Endocrinol Metab 2020 11;105(11)

Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona.

Background: Obesity and energy expenditure (EE) are heritable and genetic variants influencing EE may contribute to the development of obesity. We sought to identify genetic variants that affect EE in American Indians, an ethnic group with high prevalence of obesity.

Methods: Whole-exome sequencing was performed in 373 healthy Pima Indians informative for 24-hour EE during energy balance. Genetic association analyses of all high-quality exonic variants (≥5 carriers) was performed, and those predicted to be damaging were prioritized.

Results: Rs752074397 introduces a premature stop codon (Cys264Ter) in DAO and demonstrated the strongest association for 24-hour EE, where the Ter allele associated with substantially lower 24-hour EE (mean lower by 268 kcal/d) and sleeping EE (by 135 kcal/d). The Ter allele has a frequency = 0.5% in Pima Indians, whereas is extremely rare in most other ethnic groups (frequency < 0.01%). In vitro functional analysis showed reduced protein levels for the truncated form of DAO consistent with increased protein degradation. DAO encodes D-amino acid oxidase, which is involved in dopamine synthesis which might explain its role in modulating EE.

Conclusion: Our results indicate that a nonsense mutation in DAO may influence EE in American Indians. Identification of variants that influence energy metabolism may lead to new pathways to treat human obesity.

Clinical Trial Registration Number: NCT00340132.
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http://dx.doi.org/10.1210/clinem/dgaa548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501742PMC
November 2020

scTyper: a comprehensive pipeline for the cell typing analysis of single-cell RNA-seq data.

BMC Bioinformatics 2020 Aug 4;21(1):342. Epub 2020 Aug 4.

Department of Physiology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea.

Background: Recent advances in single-cell RNA sequencing (scRNA-seq) technology have enabled the identification of individual cell types, such as epithelial cells, immune cells, and fibroblasts, in tissue samples containing complex cell populations. Cell typing is one of the key challenges in scRNA-seq data analysis that is usually achieved by estimating the expression of cell marker genes. However, there is no standard practice for cell typing, often resulting in variable and inaccurate outcomes.

Results: We have developed a comprehensive and user-friendly R-based scRNA-seq analysis and cell typing package, scTyper. scTyper also provides a database of cell type markers, scTyper.db, which contains 213 cell marker sets collected from literature. These marker sets include but are not limited to markers for malignant cells, cancer-associated fibroblasts, and tumor-infiltrating T cells. Additionally, scTyper provides three customized methods for estimating cell-type marker expression, including nearest template prediction (NTP), gene set enrichment analysis (GSEA), and average expression values. DNA copy number inference method (inferCNV) has been implemented with an improved modification that can be used for malignant cell typing. The package also supports the data preprocessing pipelines by Cell Ranger from 10X Genomics and the Seurat package. A summary reporting system is also implemented, which may facilitate users to perform reproducible analyses.

Conclusions: scTyper provides a comprehensive and user-friendly analysis pipeline for cell typing of scRNA-seq data with a curated cell marker database, scTyper.db.
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http://dx.doi.org/10.1186/s12859-020-03700-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430822PMC
August 2020

Modulation of oligonucleotide-binding dynamics on WS nanosheet interfaces for detection of Alzheimer's disease biomarkers.

Biosens Bioelectron 2020 Oct 20;165:112401. Epub 2020 Jun 20.

Department of Chemical Engineering, Hanyang University, Ansan, 426-791, Republic of Korea. Electronic address:

Non-covalent adsorption and desorption of oligonucleotides on two-dimensional nanosheets are widely employed to design nanobiosensors for the rapid optical detection of targets. A precise control over the weak interactions between nanosheet interfaces and oligonucleotides is crucial for a high-sensing performance. Herein, the interface of ultrathin WS nanosheets used as a fluorescence quencher was engineered by four different dextran polymers in an aqueous solution to control the adsorption kinetics and thermodynamics of the DNA probe. The WS nanosheets, functionalized by the carboxyl group-bearing dextran (CM-dex-WS) or the trimethylammonium-modified dextran (TMA-dex-WS), exhibited 3.6-fold faster adsorption rates of the fluorescein-labeled DNA probe (FAM-DNA), which led to the effective fluorescence quenching of FAM, compared to the nanosheets functionalized with pristine dextran (dex-WS) or the hydrophobic phenoxy groups-bearing dextran (PhO-dex-WS). Isothermal titration calorimetry measurements showed that the adsorption strength of FAM-DNA for CM-dex-WS was one order of magnitude greater than its hybridization energy for a target microRNA (miR-29a) that is well-known as an Alzheimer's disease (AD) biomarker, leading to the unfavorable desorption of the DNA probe from the surface. In contrast, TMA-dex-WS exhibited the proper adsorption strength of FAM-DNA, which was lower than its hybridization energy for miR-29a, leading to its favorable desorption from the nanosheet surface along with the noticeable restoration of the quenched fluorescence after its hybridization with miR-29a. Finally, the interface modulation of WS nanosheets allowed the selective and sensitive recognition of miR-29a against non-complementary RNA and single base-mismatched RNA in human serum via increases in target-specific fluorescence.
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http://dx.doi.org/10.1016/j.bios.2020.112401DOI Listing
October 2020

Pelvic malakoplakia presenting as endometrial cancer: a case report.

Obstet Gynecol Sci 2020 Jul 30;63(4):538-542. Epub 2020 Jun 30.

Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.

Malakoplakia is a rare granulomatous, inflammatory disease generally manifesting as ulcers of the urogenital tract, especially in the bladder, but it can occur in any part of the body. Because of its varied clinical presentations, malakoplakia is considered for differential diagnosis upon suspicion. The final diagnosis is confirmed by the presence of Michaelis-Gutmann bodies. We report a case of pelvic malakoplakia accompanied by left lower quadrant pain that was misdiagnosed as endometrial cancer with pelvic mass based on imaging studies. The patient underwent dilatation and curettage, and the pathology report revealed no malignancy. Because of persistent pain and septic shock, she underwent a debulking operation to remove the mass. Histopathologic examination revealed malakoplakia. For postoperative management, she received broad-spectrum antibiotics, but abdominal pelvic computerized tomography performed on postoperative day 9 revealed pelvic mass recurrence. To the best of our knowledge, this is the only rare case report of pelvic malakoplakia mimicking endometrial cancer.
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http://dx.doi.org/10.5468/ogs.19245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393746PMC
July 2020

Angiopoietin-like protein 3 governs LDL-cholesterol levels through endothelial lipase-dependent VLDL clearance.

J Lipid Res 2020 09 9;61(9):1271-1286. Epub 2020 Jul 9.

Regeneron Pharmaceuticals, Tarrytown, NY, USA

Angiopoietin-like protein (ANGPTL)3 regulates plasma lipids by inhibiting LPL and endothelial lipase (EL). ANGPTL3 inactivation lowers LDL-C independently of the classical LDLR-mediated pathway and represents a promising therapeutic approach for individuals with homozygous familial hypercholesterolemia due to mutations. Yet, how ANGPTL3 regulates LDL-C levels is unknown. Here, we demonstrate in hyperlipidemic humans and mice that ANGPTL3 controls VLDL catabolism upstream of LDL. Using kinetic, lipidomic, and biophysical studies, we show that ANGPTL3 inhibition reduces VLDL-lipid content and size, generating remnant particles that are efficiently removed from the circulation. This suggests that ANGPTL3 inhibition lowers LDL-C by limiting LDL particle production. Mechanistically, we discovered that EL is a key mediator of ANGPTL3's novel pathway. Our experiments revealed that, although dispensable in the presence of LDLR, EL-mediated processing of VLDL becomes critical for LDLR-independent particle clearance. In the absence of EL and LDLR, ANGPTL3 inhibition perturbed VLDL catabolism, promoted accumulation of atypical remnants, and failed to reduce LDL-C. Taken together, we uncover ANGPTL3 at the helm of a novel EL-dependent pathway that lowers LDL-C in the absence of LDLR.
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http://dx.doi.org/10.1194/jlr.RA120000888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469887PMC
September 2020

Characterization of Exome Variants and Their Metabolic Impact in 6,716 American Indians from the Southwest US.

Am J Hum Genet 2020 08 7;107(2):251-264. Epub 2020 Jul 7.

Regeneron Genetics Center, Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA. Electronic address:

Applying exome sequencing to populations with unique genetic architecture has the potential to reveal novel genes and variants associated with traits and diseases. We sequenced and analyzed the exomes of 6,716 individuals from a Southwestern American Indian (SWAI) population with well-characterized metabolic traits. We found that the SWAI population has distinct allelic architecture compared to populations of European and East Asian ancestry, and there were many predicted loss-of-function (pLOF) and nonsynonymous variants that were highly enriched or private in the SWAI population. We used pLOF and nonsynonymous variants in the SWAI population to evaluate gene-burden associations of candidate genes from European genome-wide association studies (GWASs) for type 2 diabetes, body mass index, and four major plasma lipids. We found 19 significant gene-burden associations for 11 genes, providing additional evidence for prioritizing candidate effector genes of GWAS signals. Interestingly, these associations were mainly driven by pLOF and nonsynonymous variants that are unique or highly enriched in the SWAI population. Particularly, we found four pLOF or nonsynonymous variants in APOB, APOE, PCSK9, and TM6SF2 that are private or enriched in the SWAI population and associated with low-density lipoprotein (LDL) cholesterol levels. Their large estimated effects on LDL cholesterol levels suggest strong impacts on protein function and potential clinical implications of these variants in cardiovascular health. In summary, our study illustrates the utility and potential of exome sequencing in genetically unique populations, such as the SWAI population, to prioritize candidate effector genes within GWAS loci and to find additional variants in known disease genes with potential clinical impact.
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http://dx.doi.org/10.1016/j.ajhg.2020.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413855PMC
August 2020

Optimization of Hydroxypropyl Methylcellulose and Dextrin in Development of Dried Nanosuspension for Poorly Water-Soluble Drug.

J Nanosci Nanotechnol 2020 09;20(9):5813-5818

Department of Pharmaceutical Engineering, Inje University, Gimhae 50834, Republic of Korea.

The purpose of this study is to identify the effects of a stabilizer and matrix former in the development of a celecoxib dried nanosuspension (DNS) for high dissolution rate and drug loading. Tween 80 and Hydroxypropyl Methylcellulose (HPMC) were used as stabilizers in the bead-milling process and dextrin was used as the matrix former in the spray-drying. Various nanosuspensions (NS) were prepared by varying the ratio of HPMC and dextrin, and the physicochemical properties of each formulation were evaluated for particle size, morphology, drug loading, crystallinity, redispersibility, physical stability and dissolution rate. HPMC efficiently stabilized the NS system and reduced the particle size of NS. The mean particle size of the NS with 0.5% HPMC (w/v) was the smallest (248 nm) of all formulations. Dextrin has been shown to inhibit the increase of particle size efficiently, which is known to occur frequently when NS is being solidified. As the dextrin increased in DNS, the dissolution rates of reconstituted NS were significantly improved. However, it was confirmed that more than the necessary amount of dextrin in DNS reduced the dissolution and drug loading. The dissolution of celecoxib in DNS prepared at the ratio (drug:dextrin, 1:2.5) was almost the highest. The dissolution of optimal formulation was 95.8% at 120 min, which was 2.0-fold higher than that of NS dried without dextrin. In conclusion, these results suggest that the formulation based on Tween 80, HPMC and dextrin may be an effective option for DNS to enhance its dissolution and in vivo oral absorption.
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http://dx.doi.org/10.1166/jnn.2020.17659DOI Listing
September 2020

Anti-Aging Effects of (Edelweiss) Callus Culture Extract Through Transcriptome Profiling.

Genes (Basel) 2020 02 21;11(2). Epub 2020 Feb 21.

Anti-Aging Research Institute of BIO-FD&C Co., Ltd., Incheon 21990, Korea.

Edelweiss () in the family is a wildflower that grows in rocky limestone places. Here, we investigated the efficacy of edelweiss callus culture extract ( callus culture extract; LACCE) using multiple assays from to as well as transcriptome profiling. Several assay results showed the strong antioxidant activity of LACCE in response to UVB treatment. Moreover, LACCE suppressed inflammation and wrinkling; however, moisturizing activity was increased by LACCE. The clinical test demonstrated that constant application of LACCE on the face and skin tissues improved anti-periorbital wrinkles, skin elasticity, dermal density, and skin thickness compared with the placebo. The RNA-Sequencing results showed at least 16.56% of human genes were expressed in keratinocyte cells. LACCE up-regulated genes encoding several KRT proteins; DDIT4, BNIP3, and IGFBP3 were involved in the positive regulation of the developmental process, programmed cell death, keratinization, and cornification forming skin barriers, which provide many advantages in the human skin. By contrast, down-regulated genes were stress-responsive genes, including metal, oxidation, wounding, hypoxia, and virus infection, suggesting LACCE did not cause any harmful stress on the skin. Our comprehensive study demonstrated LACCE is a promising agent for anti-aging cosmetics.
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http://dx.doi.org/10.3390/genes11020230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074254PMC
February 2020

IL-10 Expression-Inducing Gut Bacteria Alleviate High-Fat Diet-Induced Obesity and Hyperlipidemia in Mice.

J Microbiol Biotechnol 2020 Apr;30(4):599-603

Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, Kyung Hee University, Seoul.

In the present study, we examined the effects of interleukin (IL)-10 expression-inducing bacteria HP1, HP2, and HP3 on high-fat diet (HFD)-induced obesity and liver steatosis in mice. Oral gavage of HP1, HP2, and HP3 reduced HFD-induced bodyweight gain, triglycerides, and total cholesterol levels in the blood and liver. They also suppressed HFD-induced colitis and the fecal δ,γ-Proteobacteria population. Of the tested bacteria, HP2, which most potently inhibited IL-10 expression, also suppressed HFD-induced bodyweight gain, liver steatosis, and colitis most effectively. These findings suggest that IL-10 expression-inducing gut bacteria can suppress obesity and liver steatosis.
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http://dx.doi.org/10.4014/jmb.1912.12014DOI Listing
April 2020

The success rate of radioactive iodine therapy for Graves' disease in iodine-replete area and affecting factors: a single-center study.

Nucl Med Commun 2020 Mar;41(3):212-218

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul.

Objective: Initial treatment options for Graves' disease include antithyroid drugs, radioactive iodine (RAI), and surgery. Because of similar effects of three modalities, initial treatment preferences differ by country to country. In Korea, iodine-replete area, RAI was used as a second-line option. For these reasons, the RAI success rate in Korea might differ from other countries.

Methods: A total of 247 patients were enrolled. The primary outcome was cumulative success rate in the first year, and the secondary outcome was factors that affected the success. Delayed response, which included patients who attained successful RAI during the follow-up, after the first year without further RAI, and factors that affected the delayed response were reviewed.

Results: The cumulative success rate in the first year was 62.8%. Higher RAI activity [odds ratio (OR) 2.56, P = 0.02], longer disease duration (OR 0.43, P = 0.01), larger goiter (OR 0.31, P = 0.01), and higher post-RAI fT4 (fT4 between upper normal limit (UNL) to 1.5 × UNL; OR 0.24; P < 0.01, 1.5 × UNL<; OR 0.08; P < 0.01) were associated with RAI success. Twenty-seven patients showed delayed response, and goiter size (P < 0.05), pre-RAI TSH receptor Ab (TRAb) level (P < 0.01) and post-RAI fT4 (P < 0.01) were associated.

Conclusion: The success rate of the first RAI in Korea was lower than that in other countries. Delayed response was observed in patients with smaller goiter, low pre-RAI TRAb, and low post-RAI fT4. In these patients, clinical follow-up with monitoring could be an option, and decision of optimal timing of first RAI is crucial.
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http://dx.doi.org/10.1097/MNM.0000000000001138DOI Listing
March 2020

Improved survival after early detection of asymptomatic distant metastasis in patients with thyroid cancer.

Sci Rep 2019 12 10;9(1):18745. Epub 2019 Dec 10.

Division of Endocrinology & Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

The incidence of thyroid cancer (TC) has been increasing in many countries and concerns about overdiagnosis are also widely shared. However, early detection may be helpful in some high-risk TC patients, such as those with initial distant metastasis. We conducted this study to evaluate the usefulness of early detection in TC patients with initial distant metastasis. We retrospectively reviewed the clinical data of 13,249 TC patients, and found 127 patients with initial distant metastasis. Enrolled patients were divided into two groups according to the diagnostic periods; before and after 2004, when the early detection of TC by ultrasonography began in earnest in Korea. Patients were also divided into two groups according to the presence of symptoms. Prior to 2004, 33 patients (1.7% of TC patients) were diagnosed with TC with initial distant metastasis and 16 (48.5%) of them died. After 2004, 94 patients (0.8% of TC patients) were diagnosed with TC with initial distant metastasis and 29 (30.9%) of them died. Prior to 2004, the disease-specific death rates were similar between the asymptomatic and symptomatic groups (46.2% vs. 50.0%, P = 0.566). Conversely, after 2004, the asymptomatic group showed a significantly lower disease-specific death rate as compared with that of the symptomatic groups (17.2% vs. 60.0%; P < 0.001). Early detection had a significant positive impact on survival outcomes only after 2004, especially in asymptomatic TC patients with initial distant metastasis.
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http://dx.doi.org/10.1038/s41598-019-55370-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904730PMC
December 2019

Fermented red ginseng and ginsenoside Rd alleviate ovalbumin-induced allergic rhinitis in mice by suppressing IgE, interleukin-4, and interleukin-5 expression.

J Ginseng Res 2019 Oct 7;43(4):635-644. Epub 2019 Mar 7.

Neurobiota Research Center and Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.

Background: To increase the pharmacological effects of red ginseng (RG, the steamed root of Meyer), RG products modified by heat process or fermentation have been developed. However, the antiallergic effects of RG and modified/fermented RG have not been simultaneously examined. Therefore, we examined the allergic rhinitis (AR)-inhibitory effects of water-extracted RG (wRG), 50% ethanol-extracted RG (eRG), and bifidobacteria-fermented eRG (fRG) in vivo.

Methods: RBL-2H3 cells were stimulated with phorbol 12-myristate-13-acetate/A23187. Mice with AR were prepared by treatment with ovalbumin. Allergic markers IgE, tumor necrosis factor-α, interleukin (IL)-4, and IL-5 were assayed in the blood, bronchoalveolar lavage fluid, nasal mucosa, and colon using enzyme-linked immunosorbent assay. Mast cells, eosinophils, and Th2 cell populations were assayed using a flow cytometer.

Results: RG products potently inhibited IL-4 expression in phorbol 12-myristate-13-acetate/A23187-stimulated RBL-2H3 cells. Of tested RG products, fRG most potently inhibited IL-4 expression. RG products also alleviated ovalbumin-induced AR in mice. Of these, fRG most potently reduced nasal allergy symptoms and blood IgE levels. fRG treatment also reduced IL-4 and IL-5 levels in bronchoalveolar lavage fluid, nasal mucosa, and reduced mast cells, eosinophils, and Th2 cell populations. Furthermore, treatment with fRG reduced IL-4, IL-5, and IL-13 levels in the colon and restored ovalbumin-suppressed Bacteroidetes and Actinobacteria populations and ovalbumin-induced Firmicutes population in gut microbiota. Treatment with ginsenoside Rd significantly alleviated ovalbumin-induced AR in mice.

Conclusion: fRG and ginsenoside Rd may alleviate AR by suppressing IgE, IL-4, IL-5, and IL-13 expression and restoring the composition of gut microbiota.
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http://dx.doi.org/10.1016/j.jgr.2019.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823749PMC
October 2019

The impact of infection control cost reimbursement policy on central line-associated bloodstream infections.

Am J Infect Control 2020 05 31;48(5):560-565. Epub 2019 Oct 31.

Department of Infection Control, Daegu Fatima Hospital, Daegu, Republic of Korea.

Background: In September 2016, the Korean National Health Insurance Service began reimbursing infection control (IC) costs on the condition that a certain number of doctors and full-time nurses for IC be allocated to supported hospitals. We analyzed the impact of the IC cost reimbursement policy on central line-associated bloodstream infections (CLABSIs).

Methods: A before-and-after study that analyzed the CLABSI rate trends between preintervention (January 2016 to February 2017) and intervention (March to December 2017) periods using autoregression time series analysis was performed in intensive care units (ICUs) at a 750-bed, secondary care hospital in Daegu, Republic of Korea. The enhanced IC team visited ICUs daily, monitored the implementation of CLABSI prevention bundles, and educated all personnel involved in catheter insertion and maintenance from March 2017.

Results: Autoregressive analysis revealed that the CLABSI rates per month in the preintervention and intervention periods were -0.256 (95% confidence interval, -0.613 to 0.101; P = .15) and -0.602 (95% confidence interval, -0.972 to -0.232; P = .008), respectively. The rates of compliance with maximal barrier precautions significantly improved from the preintervention (36.2%) to the intervention (77.9%) period (χ² test, P < .001).

Conclusions: The IC cost reimbursement policy accelerated the decline in CLABSI rates significantly in monitored ICUs. A nationwide study to evaluate the effectiveness of the IC cost reimbursement policy for various health care-associated infections is warranted.
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http://dx.doi.org/10.1016/j.ajic.2019.09.002DOI Listing
May 2020
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