Publications by authors named "H Kang"

12,326 Publications

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The longer the antithyroid drug is used, the lower the relapse rate in Graves' disease: a retrospective multicenter cohort study in Korea.

Endocrine 2021 Apr 15. Epub 2021 Apr 15.

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

Purpose: Current literature suggests 12-18 months of antithyroid drug (ATD) treatment for patients with Graves' disease, but the risk of relapse is high. Although some studies reported better outcomes of long-term ATD treatment, recent data that suggest the optimal treatment duration are limited.

Methods: We performed a multicenter retrospective cohort study of 908 patients newly diagnosed with Graves' disease between 2006 and 2013. The relapse rate according to ATD treatment duration was analyzed.

Results: After initial ATD treatment, 338 patients (37.2%) had relapsed. The relapse rate according to ATD treatment duration was 42.4% at 1 year, 38.5% at 2 years, 33.8% at 3 years, 31.7% at 4 years, 30.2% at 5 years, 27.8% at 6 years, and 19.1% at more than 6 years, respectively, demonstrating a significant decreasing trend (p = 0.003). In a multivariable Cox regression analysis, ATD treatment duration was an independent risk factor for relapse (p = 0.043).

Conclusions: The longer that ATD therapy is used, the lower the relapse rate is in patients with Graves' disease. Long-term ATD treatment may be considered in Graves' patients who do not show complications or an economic burden from hyperthyroidism.
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http://dx.doi.org/10.1007/s12020-021-02725-xDOI Listing
April 2021

Molecular risk markers related to local tumor recurrence at histological margin-free endoscopically resected early gastric cancers: A pilot study.

Pathol Res Pract 2021 Apr 5;222:153434. Epub 2021 Apr 5.

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

Local recurrences in early gastric cancers (EGCs) after complete endoscopic submucosal dissection (ESD) remain problematic. Here, we investigated the spatially sequential molecular changes in various cancer-related proteins along the axis of the histologically clear but recurrent resection margins (TRM) to determine the appropriate tumor-free margin distance and potential molecular risk markers related to local recurrence. Five eligible patients with recurrent EGCs after complete ESD were selected from 548 EGC patients. The specimens, including recurrent resection margin axis, were divided into 5 zones. Digital spatial profiling assay was performed to quantify the expression level of 31 cancer-related proteins along each zone. p-Chk1 level was significantly reduced in TRM zone than non-recurrent resection margin. The expression of p44/42 ERK and p-Chk1 were significantly decreased along the lateral axis of the recurrent resection margin, with no significance toward the normal zone, which may suggest that p44/42 ERK and p-Chk1 may be involved in the recurrent side compared to non-recurrent margin. Although we could not evaluate more than 5.5 mm, the significant linear decreases in p44/42 ERK and p-Chk1 were maintained until at least 5.5 mm from the tumor zone in the TRM direction. We estimated the possible margin distance using scatterplots and linear regression analyses, which also showed the estimated distance more than 5.5 mm. In conclusion, the p-Chk1 and p44/42 ERK may be potential candidates of molecular risk markers that may be related to the local recurrence after complete ESD, and a tumor-free distance of 5.5 mm is not enough for safety margin.
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http://dx.doi.org/10.1016/j.prp.2021.153434DOI Listing
April 2021

Renal clearable zwitterionic near-infrared fluorophores for potential clinical translation.

Angew Chem Int Ed Engl 2021 Apr 15. Epub 2021 Apr 15.

Massachusetts General Hospital, Radiology, 149 13th Street, 02129, Boston, UNITED STATES.

Near-infrared (NIR) fluorescence imaging has advanced medical imaging and image-guided interventions during the past three decades. However, despite major advances in imaging instrumentation, only a few dyes are currently available in the clinic. Previously, we reported two zwitterionic NIR fluorophores, ZW800-1A and ZW800-1C, which significantly improved the poor performance of the FDA-approved indocyanine green. However, ZW800-1A is not stable in serum and ZW800-1C induces severe stacking in aqueous media. To solve such dilemmas, ZW800-PEG was designed by introducing a flexible yet stable thiol PEG linker. ZW800-PEG shows high solubility in both aqueous and organic solvents, thus improving renal clearance with minimal binding to serum proteins during systemic circulation. The sulfide group on the meso position of the heptamethine core improves serum stability and physicochemical properties including the maximum emission wavelength shift to 800 nm, enabling the use of ZW800-PEG for image-guided interventions and augmenting photothermal therapy.
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http://dx.doi.org/10.1002/anie.202102640DOI Listing
April 2021

Diversity of microbial community and its metabolic potential for nitrogen and sulfur cycling in sediments of Phu Quoc island, Gulf of Thailand.

Braz J Microbiol 2021 Apr 15. Epub 2021 Apr 15.

Institute of Biotechnology, Vietnam Academy of Science and Technology, Hanoi, 10000, Vietnam.

Although Phu Quoc island, Gulf of Thailand possesses diverse marine and coastal ecosystems, biodiversity and metabolic capability of microbial communities remain poorly investigated. The aim of our study was to evaluate the biodiversity and metabolic potential of sediment microbial communities in Phu Quoc island. The marine sediments were collected from three different areas and analyzed by using 16S rRNA gene-based amplicon approach. A total of 1,143,939 reads were clustered at a 97% sequence similarity into 8,331 unique operational taxonomic units, representing 52 phyla. Bacteria and archaea occupied averagely around 86% and 14%, respectively, of the total prokaryotic community. Proteobacteria, Planctomycetes, Chloroflexi, and Thaumarchaeota were the dominant phyla in all sediments, which were involved in nitrogen and sulfur metabolism. Sediments harboring of higher nitrogen sources were found to coincide with increased abundance of archaeal phylum Thaumarchaeota. Predictive functional analysis showed high abundance prokaryotic genes associated with nitrogen cycling including nifA-Z, amoABC, nirA, narBIJ, napA, nxrAB, nrfA-K, nirBD, nirS, nirK, norB-Z, nlnA, ald, and ureA-J, based on taxonomic groups detected by 16S rRNA sequencing. Although the key genes involved in sulfur cycling were found to be at low to undetectable levels, the other genes encoding for sulfur-related biological processes were present, suggesting that alternative pathways may be involved in sulfur cycling at our study site. In conclusion, our study for the first time shed light on diversity of microbial communities in Phu Quoc island.
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http://dx.doi.org/10.1007/s42770-021-00481-8DOI Listing
April 2021

Dysregulated CRMP Mediates Circadian Deficits in a Drosophila Model of Fragile X Syndrome.

Neurosci Bull 2021 Apr 15. Epub 2021 Apr 15.

Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, China.

Fragile X syndrome (FXS) is the leading inherited cause of intellectual disability, resulting from the lack of functional fragile X mental retardation protein (FMRP), an mRNA binding protein mainly serving as a translational regulator. Loss of FMRP leads to dysregulation of target mRNAs. The Drosophila model of FXS show an abnormal circadian rhythm with disruption of the output pathway downstream of the clock network. Yet the FMRP targets involved in circadian regulation have not been identified. Here, we identified collapsing response mediator protein (CRMP) mRNA as a target of FMRP. Knockdown of pan-neuronal CRMP expression ameliorated the circadian defects and abnormal axonal structures of clock neurons (ventral lateral neurons) in dfmr1 mutant flies. Furthermore, specific reduction of CRMP in the downstream output insulin-producing cells attenuated the aberrant circadian behaviors. Molecular analyses revealed that FMRP binds with CRMP mRNA and negatively regulates its translation. Our results indicate that CRMP is an FMRP target and establish an essential role for CRMP in the circadian output in FXS Drosophila.
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http://dx.doi.org/10.1007/s12264-021-00682-zDOI Listing
April 2021

Correlates of Frailty in Community-Dwelling Older Adults with Cancer: 2017 Survey of Living Condition of Elderly Study in South Korea.

Authors:
Hyunwook Kang

Asia Pac J Oncol Nurs 2021 May-Jun;8(3):287-294. Epub 2021 Mar 12.

Department of Nursing, College of Nursing, Kangwon National University, Gangwon-do, Korea.

Objective: Frailty is prevalent among community-dwelling older adults with cancer and is associated with increased mortality and complications of treatments. However, evidence on the multiple factors influencing frailty in this population is scarce. This paper aimed to identify the demographic, sociobehavioral, and health status-related correlates of frailty in community-dwelling older adults with cancer.

Methods: This was a descriptive cross-sectional study using data from the fourth wave of the Living Condition of Elderly Study in South Korea conducted in 2017. Among the 10,299 individuals aged ≥65 years who participated in the survey, data of 391 individuals with cancer were analyzed. Frailty status (robust, prefrailty, and frailty) was assessed using the Korean version of the 5-item: Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight scale. We performed descriptive statistical analysis to report summary measures, and bivariate (-test, Chi-squared test, and analysis of variance) and multivariate regression analyses.

Results: Frailty and prefrailty were prevalent in 24.8% and 50.6% of the participants, respectively. The strongest correlate of frailty was a greater level of depression, followed by low levels of physical activity, dependency in instrumental activities of daily living, a greater number of comorbidities, an advanced age, a lower household income, and a widowed marital status.

Conclusions: Community-dwelling older adults who had cancer and depression had the highest risk of frailty. Given the adverse impact of frailty on health outcomes in this population, health-care providers need to provide interventions incorporating the management of depression, physical activity, and comorbidities to prevent or manage frailty.
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http://dx.doi.org/10.4103/2347-5625.311130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8030589PMC
March 2021

A Home-Based Mobile Health Intervention to Replace Sedentary Time With Light Physical Activity in Older Cancer Survivors: Randomized Controlled Pilot Trial.

JMIR Cancer 2021 Apr 13;7(2):e18819. Epub 2021 Apr 13.

School of Public Health, Rutgers University, Piscataway, NJ, United States.

Background: Older cancer survivors are at risk of the development or worsening of both age- and treatment-related morbidity. Sedentary behavior increases the risk of or exacerbates these chronic conditions. Light-intensity physical activity (LPA) is more common in older adults and is associated with better health and well-being. Thus, replacing sedentary time with LPA may provide a more successful strategy to reduce sedentary time and increase physical activity.

Objective: This study primarily aims to evaluate the feasibility, acceptability, and preliminary efficacy of a home-based mobile health (mHealth) intervention to interrupt and replace sedentary time with LPA (standing and stepping). The secondary objective of this study is to examine changes in objective measures of physical activity, physical performance, and self-reported quality of life.

Methods: Overall, 54 cancer survivors (aged 60-84 years) were randomized in a 1:1:1 allocation to the tech support intervention group, tech support plus health coaching intervention group, or waitlist control group. Intervention participants received a Jawbone UP2 activity monitor for use with their smartphone app for 13 weeks. Tech support and health coaching were provided via 5 telephone calls during the 13-week intervention. Sedentary behavior and physical activity were objectively measured using an activPAL monitor for 7 days before and after the intervention.

Results: Participants included survivors of breast cancer (21/54, 39%), prostate cancer (16/54, 30%), and a variety of other cancer types; a mean of 4.4 years (SD 1.6) had passed since their cancer diagnosis. Participants, on average, were 70 years old (SD 4.8), 55% (30/54) female, 24% (13/54) Hispanic, and 81% (44/54) overweight or obese. Malfunction of the Jawbone trackers occurred in one-third of the intervention group, resulting in enrollment stopping at 54 rather than the initial goal of 60 participants. Despite these technical issues, the retention in the intervention was high (47/54, 87%). Adherence was high for wearing the tracker (29/29, 100%) and checking the app daily (28/29, 96%) but low for specific aspects related to the sedentary features of the tracker and app (21%-25%). The acceptability of the intervention was moderately high (81%). There were no significant between-group differences in total sedentary time, number of breaks, or number of prolonged sedentary bouts. There were no significant between-group differences in physical activity. The only significant within-group change occurred within the health coaching group, which increased by 1675 daily steps (95% CI 444-2906; P=.009). This increase was caused by moderate-intensity stepping rather than light-intensity stepping (+15.2 minutes per day; 95% CI 4.1-26.2; P=.008).

Conclusions: A home-based mHealth program to disrupt and replace sedentary time with stepping was feasible among and acceptable to older cancer survivors. Future studies are needed to evaluate the optimal approach for replacing sedentary behavior with standing and/or physical activity in this population.

Trial Registration: ClinicalTrials.gov NCT03632694; https://clinicaltrials.gov/ct2/show/NCT03632694.
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http://dx.doi.org/10.2196/18819DOI Listing
April 2021

Nicotinamide riboside, an NAD precursor, attenuates inflammation and oxidative stress by activating sirtuin 1 in alcohol-stimulated macrophages.

Lab Invest 2021 Apr 12. Epub 2021 Apr 12.

Department of Nutritional Sciences, University of Connecticut, Storrs, CT, USA.

Macrophages play an essential role in alcohol-induced inflammation and oxidative stress. We investigated the effects of nicotinamide riboside (NR), a natural nicotinamide adenine dinucleotide (NAD) precursor, on alcohol-induced inflammation and oxidative stress in macrophages. NR significantly decreased ethanol-induced inflammatory gene expression, with a concomitant decrease in nuclear translocation of nuclear factor κB p65 in RAW 264.7 macrophages and mouse bone marrow-derived macrophages (BMDMs). In macrophages incubated with ethanol or acetaldehyde, NR abolished the accumulation of cellular reactive oxygen species. Ethanol decreased sirtuin 1 (SIRT1) expression and activity, and cellular NAD level while inducing pro-inflammatory gene expression. However, NR markedly attenuated the changes. SIRT1 inhibition augmented ethanol-induced inflammatory gene expression, but its activation elicited opposing effects. Also, ethanol did not alter glycolysis but increased glycolytic capacity, glycolytic reserve, and non-glycolytic acidification, with concomitant increases in hypoxia-induced factor 1α expression and activity, phosphorylation of pyruvate dehydrogenase, and extracellular lactate levels. Interestingly, ethanol increased mitochondrial respiration and ATP production but decreased maximal respiration and spare respiration capacity. The latter was linked to decreases in mitochondrial copy numbers. NR abolished the ethanol-induced metabolic changes in the glycolytic and oxidative phosphorylation pathways in RAW 264.7 macrophages. In conclusion, NR exerts anti-inflammatory and antioxidant properties by abrogating the inhibitory effects of ethanol on the SIRT1 pathway by increasing Sirt1 expression and its activator, NAD. Also, SIRT1 activation and normalization of ethanol-induced changes in NAD/NADH ratios by NR are likely crucial to counteract the changes in energy phenotypes of macrophages exposed to ethanol.
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http://dx.doi.org/10.1038/s41374-021-00599-1DOI Listing
April 2021

Hepatoid thymic carcinoma: a case report of a rare subtype of thymic carcinoma.

J Pathol Transl Med 2021 Apr 14. Epub 2021 Apr 14.

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

Hepatoid thymic carcinoma is an extremely rare subtype of primary thymus tumor resembling "pure" hepatoid adenocarcinomas with hepatocyte paraffin 1 (Hep-Par-1) expression. A 53-year-old man presented with voice change and a neck mass. Multiple masses involving the thyroid, cervical and mediastinal lymph nodes, and lung were detected on computed tomography. Papillary thyroid carcinoma was confirmed by biopsy, and the patient underwent neoadjuvant chemoradiation therapy. However, the anterior mediastinal mass was enlarged after the treatment whereas the multiple masses in the thyroid and neck decreased in size. Microscopically, polygonal tumor cells formed solid sheets or trabeculae resembling hepatocytes and infiltrated remnant thymus. The tumor cells showed immunopositivity for cytokeratin 7, cytokeratin 19, and Hep-Par-1 and negativity for α-fetoprotein. Possibilities of germ cell tumor, squamous cell carcinoma, and metastasis of thyroid papillary carcinoma were excluded by immunohistochemistry. This report on the new subtype of thymic carcinoma is the third in English literature thus far.
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http://dx.doi.org/10.4132/jptm.2021.03.10DOI Listing
April 2021

The Dopaminergic Neuronal System Regulates the Inflammatory Status of Mouse Lacrimal Glands in Dry Eye Disease.

Invest Ophthalmol Vis Sci 2021 Apr;62(4):14

Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.

Purpose: Comparison of the parasympathetic and sympathetic neurons, including the dopaminergic neural system, in dry eye (DE)-induced pathophysiology has not been elucidated well. This study investigated the presence of dopamine receptors (DRs) and their functional roles in the lacrimal glands (LGs) of DE-induced mice.

Methods: After DE was induced in B6 mice for 2 weeks, the expression of tyrosine hydroxylase (TH), dopamine, and DRs (DR1, DR2, etc.) in the LGs and corneas were measured by quantitative RT-PCR, immunoblot, and ELISA. Using flow cytometry and ELISA, immune cell infiltration and inflammatory cytokine expression were determined in DE-induced LGs with or without DR blockers, SCH-23390 (DR1i), or melperone (DR2i). Corneal erosion scores were also investigated.

Results: The mRNA and protein levels of TH significantly increased in DE-induced LGs. The dopamine concentration of LGs was 9.51 pmol in DE (versus naive: 1.39 pmol; P < 0.001). Both DR1 and DR2 mRNA expression were significantly enhanced in desiccating stress compared with those in naive (3.7- and 2.1-fold, P < 0.001). Interestingly, DR1 and DR2 immunostaining patterns stained independently in DE-induced LGs. CD3+ and CD19+ cell infiltration was significantly increased by DR2i (P < 0.001) but not by DR1i. Furthermore, IFN-γ, IL-17, and TNF-α were significantly upregulated by DR2i compared with the blow-only condition. The severity of corneal erosion and inflammation was also aggravated by DR2i.

Conclusions: Upregulation of DR1 and DR2 was observed in DE-induced mouse LGs. As the inflammatory conditions are aggravated by the inhibition of DRs, especially DR2, their activity may be an important factor preserving ocular surface homeostasis.
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http://dx.doi.org/10.1167/iovs.62.4.14DOI Listing
April 2021

n -methyladenosine mrna methylation is important for salt stress tolerance in arabidopsis.

Plant J 2021 Apr 12. Epub 2021 Apr 12.

Jiangsu Key Laboratory of Phylogenomics and Comparative Genomics, School of Life Sciences, Jiangsu Normal University, Jiangsu Province, Xuzhou, 221116, China.

As the most abundant internal modification in mRNA, N -methyladenosine (m A) methylation of RNA is emerging as a new layer of epitranscriptomic gene regulation in cellular processes, including embryo development, flowering time control, microspores generation, and fruit-ripening, in plants. However, the cellular role of m A in plant response to environmental stimuli remains largely unexplored. In this study, we show that m A methylation plays an important role in salt stress tolerance in Arabidopsis. All mutants of m A writer components, including MTA, MTB, VIRILIZER (VIR), and HAKAI, displayed salt-sensitive phenotypes in an m A-dependent manner. The vir mutant, in which the m A level was most highly reduced, exhibited salt-hypersensitive phenotypes. Analysis of m A methylome in the vir mutant revealed a transcriptome-wide loss of m A modification in the 3'UTR. We further demonstrated that VIR-mediated m A methylation modulates reactive oxygen species homeostasis by negatively regulating the mRNA stability of several salt stress negative regulators, including ATAF1, GI, and GSTU17, via affecting 3'UTR lengthening linked to alternative polyadenylation. Our results highlight the important role played by epitranscriptomic mRNA methylation in the salt stress response of Arabidopsis and indicate a strong link between m A methylation and 3'UTR length and mRNA stability during stress adaptation.
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http://dx.doi.org/10.1111/tpj.15270DOI Listing
April 2021

Computed tomography-based visual assessment of chronic obstructive pulmonary disease: comparison with pulmonary function test and quantitative computed tomography.

J Thorac Dis 2021 Mar;13(3):1495-1506

Department of Internal Medicine and Environmental Health Center, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea.

Background: Chronic obstructive pulmonary disease (COPD) has variable subtypes involving mixture of large airway inflammation, small airway disease, and emphysema. This study evaluated the relationship between visually assessed computed tomography (CT) subtypes and clinical/imaging characteristics.

Methods: In total, 452 participants were enrolled in this study between 2012 and 2017. Seven subtypes were defined by visual evaluation of CT images using Fleischner Society classification: normal, paraseptal emphysema (PSE), bronchial disease, and centrilobular emphysema (trace, mild, moderate and confluent/advanced destructive). The differences in several variables, including clinical, laboratory, spirometric, and quantitative CT features among CT-based visual subtypes, were compared using the chi-square tests and one-way analysis of variance.

Results: Subjects who had PSE had better forced expiratory volume in 1 second (FEV1) (P=0.03) percentage and higher lung density (P<0.05) than those with moderate to confluent/advanced destructive centrilobular emphysema. As the visual grade of centrilobular emphysema worsened, pulmonary function declined and modified Medical Research Council, COPD assessment test (CAT) score, and quantitative assessment (emphysema index and air trapping) increased. The bronchial subtype was associated with higher body mass index (BMI), better lung function and higher lung density. Participants with trace emphysema showed a rapid increase in functional small airway disease.

Conclusions: Classifying subtypes using visual CT imaging features can reflect heterogeneity and pathological processes of COPD.
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http://dx.doi.org/10.21037/jtd-20-3041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024830PMC
March 2021

Clinical significance of microbial colonization identified by initial bronchoscopy in patients with lung cancer requiring chemotherapy.

J Thorac Dis 2021 Mar;13(3):1306-1314

Division of Infectious Disease, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: There are limited data on the association between bronchial colonization and respiratory infections in people with lung cancer requiring cytotoxic chemotherapy. We investigated whether bronchial colonization in initial bronchoscopy specimens can predict the development of pneumonia after chemotherapy in patients with lung cancer.

Methods: Four hundred thirteen patients with lung cancer included in the Catholic Medical Center lung cancer registry were enrolled from March 2015 to August 2018. Demographic data, microbiology results, development of pneumonia after chemotherapy, and clinical information about lung cancer were analyzed retrospectively.

Results: A total of 206 lung cancer patients treated with chemotherapy were included in the analysis. Forty patients (19.4%) had positive results for the bronchial washing culture during the initial evaluation of lung cancer. The most common organisms were (n=14) and (n=6) in the surveillance culture, and (n=12) and (n=8) at the time of pneumonia development. Eighty-nine patients (43.2%) had pneumonia after chemotherapy, but the occurrence of pneumonia did not differ according to the colonization. There were no patients for whom the initial isolated organism was a causative microbe for the development of pneumonia after or during chemotherapy. The pneumonia group had poorer prognosis than the non-pneumonia group (378 705 days, P=0.0004).

Conclusions: Microbial colonization in bronchoscopy specimens was not associated with pneumonia development or mortality after chemotherapy for lung cancer. This finding suggests that testing surveillance culture may not be helpful for predicting pneumonia or improving survival in lung cancer patients with chemotherapy.
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http://dx.doi.org/10.21037/jtd-20-2722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024789PMC
March 2021

Comparison of the Ulnar Nerve Blockade between Intertruncal and Corner Pocket Approaches for Supraclavicular Block: A Randomized Controlled Trial.

Korean J Anesthesiol 2021 Apr 12. Epub 2021 Apr 12.

Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital.

Background: The corner pocket (CP) approach for supraclavicular block (SCB) prevents ulnar nerve (UN) sparing due to needle proximity of lower trunk. Improved ultrasound resolution has suggested that the intertruncal (IT) approach is a suitable alternative method. However, the comparative efficiency of these two approaches on UN block has not been evaluated.

Methods: Sixty patients were randomized to undergo SCB using the ultrasound-guided CP or IT approach. For lower trunk blockade, 10 mL of local anesthetic agents (1:1 mixture of 0.75% ropivacaine and 1% lidocaine) were injected in the CP (CP approach) or between the lower and middle trunk (IT approach). Additional 15mL was injected identically to block the middle and upper trunks in both groups. Sensory and motor blockade was evaluated after intervention.

Results: Complete sensory blockade (75.9% [22/29] vs 43.3% [13/30], P = 0.023) and complete motor blockade (82.8% [24/29] vs 50.0% [15/30], P = 0.017) of the UN at 15 min after SCB were significantly more frequent in the IT than in the CP group. Sensory block onset time of UN was significantly shorter in the IT compared to the CP group (15.0 [10.0; 15.0] min vs 20.0 [15.0; 20.0] min; P = 0.011).

Conclusions: The IT approach provided a more rapid onset of sensory and motor block of the UN than the CP approach. These results suggest that the IT approach is a suitable alternative to the CP approach and can provide faster surgical readiness.
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http://dx.doi.org/10.4097/kja.21028DOI Listing
April 2021

Effect of microbial community structure in inoculum on the stimulation of direct interspecies electron transfer for methanogenesis.

Bioresour Technol 2021 Apr 5;332:125100. Epub 2021 Apr 5.

School of Civil, Environmental and Architectural Engineering, Korea University, Seoul 02841, South Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, South Korea. Electronic address:

To investigate how the seed microbial community structure affects the improvement of methanogenesis efficiency through direct interspecies electron transfer (DIET), a biomethane potential (BMP) test was conducted using sludge collected from a total of six anaerobic digesters. DIET-stimulating microbial populations were investigated by 16S rRNA gene sequence analysis. Correlations between microbial community composition and methane production performance by DIET were analyzed. The methane production rate increased under all conditions when granular activated carbon (GAC) was injected regardless of the inoculum type. However, redundancy analysis indicated a significant correlation between the inoculum microbial community and lag time. In a network analysis, Methanolinea species distributed in the inocula formed a single modularity with lag time, suggesting that the methanogens in the inocula might reduce the lag time of methanogenesis through DIET. Overall, this study revealed that the inoculum microbial community composition is an important factor affecting methane production efficiency by DIET.
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http://dx.doi.org/10.1016/j.biortech.2021.125100DOI Listing
April 2021

Outcomes of multidrug-resistant tuberculosis treated with bedaquiline or delamanid.

Clin Infect Dis 2021 Apr 10. Epub 2021 Apr 10.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.

Background: Since September 1, 2016, bedaquiline and delamanid have been administered for treatment of patients with multidrug-resistant/rifampicin-resistant tuberculosis after the official approval in South Korea. This study aimed to assess and compare the final treatment outcomes of patients who received bedaquiline with those of patients who received delamanid.

Methods: This is a nationwide cohort study of patients with multidrug-resistant/rifampicin-resistant tuberculosis in whom bedaquiline or delamanid was administered from September 1, 2016, to February 28, 2018, after receiving the official approval in South Korea. Patients were classified into the bedaquiline and delamanid group according to the first used drug. We evaluated and compared the final treatment outcomes between the groups.

Results: During the study period, 284 patients with multidrug-resistant/rifampicin-resistant tuberculosis were approved to use bedaquiline or delamanid and 260 were included in the final analysis; 119 (45.8%) and 141 patients (54.2%) were classified into bedaquiline and delamanid groups, respectively. Among them, 30 patients (11.5%) exhibited additional resistance to second-line injectable drugs, 94 patients (36.2%) had additional resistance to fluoroquinolones, and 37 patients (14.2%) had resistance to both drugs. The overall treatment success rate was 79.2%. Initiation of bedaquiline rather than delamanid was not associated with treatment success (adjusted odds ratio = 0.671, 95% confidence interval = 0.350-1.285). Frequencies of adverse events were not significantly different between the two groups.

Conclusions: Initial choice of bedaquiline or delamanid did not make any significant difference in the final treatment outcome or the frequencies of adverse events among patients with multidrug-resistant/rifampicin-resistant tuberculosis.
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http://dx.doi.org/10.1093/cid/ciab304DOI Listing
April 2021

A staggered 3-layer DOI PET detector using BaSOreflector for enhanced crystal identification and inter-crystal scattering event discrimination capability.

Biomed Phys Eng Express 2021 Apr 9. Epub 2021 Apr 9.

National Institute of Radiological Sciences, 4-9-1 Anagawa, Chiba, 263-8555, JAPAN.

The spatial resolution of small animal positron emission tomography (PET) scanners can be improved by the use of crystals with fine pitch and rejection of inter-crystal scattering (ICS) events, which leads to a better quantification of radiopharmaceuticals. On the other hand, depth-of-interaction (DOI) information is essential to preserve the spatial resolution at the PET field-of-view (FOV) periphery while keeping the sensitivity. In this study we proposed a novel staggered 3-layer DOI detector using BaSO4 reflector material for an enhanced crystal identification performance as well as ICS event rejection capability over those of ESR reflector based DOI detectors. The proposed staggered 3-layer DOI detector had 3-layer staggered LYSO crystal arrays (crystal pitch = 1 mm), an acrylic light guide, and a 4×4 SiPM array. The 16 SiPM anode signals were read out by using a resistive network to encode the crystal position and energy information while the timing signal was extracted from the common cathode. The crystal map quality was substantially enhanced by using the BaSO4 reflector material as compared to that of the ESR reflector due to the low optical crosstalk between the LYSO crystals. The ICS events can be rejected with BaSO4 by using simple pulse height discrimination thanks to the light collection efficiency difference that depends on the crystal layers. As a result, the total number of events was decreased around 26% with BaSO4 as compared to that of ESR. The overall energy resolution and coincidence timing resolution with BaSO4 were 19.7±5.6% and 591±160 ps, respectively which were significantly worse than 10.9±2.2% and 308±23 ps values of ESR because of the relatively low light collection efficiency with BaSO4 (1057±308 ADC) compared to that of ESR (1808±118 ADC). In conclusion, we found the proposed staggered 3-layer DOI detector using the BaSO4 reflector material with ICS event rejection-capability-can-be-a-cost-effective-solution-for-realizing-high-resolution-and-highly-sensitive-small-animal-PET-scanners-while-minimizing-the-complexity-of-the-SiPM-readout-circuit.
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http://dx.doi.org/10.1088/2057-1976/abf6a8DOI Listing
April 2021

Virtual noncontrast images derived from dual-energy CT for assessment of hepatic steatosis in living liver donors.

Eur J Radiol 2021 Mar 27;139:109687. Epub 2021 Mar 27.

Department of Radiology, Seoul National University Hospital, Seoul, South Korea; Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea; Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, South Korea.

Purpose: This study aimed to investigate the correlation of attenuation between virtual noncontrast (VNC) and true noncontrast (TNC) CT images and compare the diagnostic performance for hepatic steatosis using MR spectroscopy (MRS) as the reference standard.

Methods: A total of 131 consecutive hepatic donor candidates who underwent dual-source dual-energy CT and MRS within one month from January 2018 to April 2019 were included. An MRS value > 5.8 % was regarded as substantial hepatic steatosis. The correlation of attenuation between TNC and VNC in the liver and spleen, and liver attenuation index (LAI), defined as hepatic minus splenic attenuation, was evaluated using Spearman's rank correlation. The diagnostic performance of the LAI for hepatic steatosis was compared using receiver operating characteristic analyses.

Results: Twenty-three candidates (17.6 %) had substantial hepatic steatosis. The median liver attenuation (66.7 [IQR, 63.5-70.9] vs. 63.5 [IQR, 60.3-66.9], p < .001) and LAI (12.9 [9.3-16.7] vs. 7.4 [3.9-11.9], p < .001) in the VNC were higher than those in the TNC. Hepatic attenuation (r = 0.93, p < .001), splenic attenuation (r = 0.55, p < .001), and LAI (r = 0.87, p < .001) were significantly correlated between TNC and VNC. Area under the curve of LAI in TNC and VNC were 0.88 (cutoff, LAI < 3.1) and 0.84 (cutoff, LAI < 10.1), respectively, indicating no statistically significant difference (p = 0.11).

Conclusion: The LAI of VNC is significantly correlated with that of TNC and might be feasible for diagnosing substantial hepatic steatosis in living liver donor candidates using different cutoff values of LAI.
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http://dx.doi.org/10.1016/j.ejrad.2021.109687DOI Listing
March 2021

Phenotypic and transcriptomic responses of the rotifer Brachionus koreanus by single and combined exposures to nano-sized microplastics and water-accommodated fractions of crude oil.

J Hazard Mater 2021 Mar 26;416:125703. Epub 2021 Mar 26.

Department of Biological Sciences, College of Science, Sungkyunkwan University, Suwon 16419, South Korea. Electronic address:

Sorption of organic pollutants on microplastics can be an alternative uptake route for organic pollutants in aquatic organisms. To assess the combined effects of microplastics and organic pollutants, we employed phenotypic and transcriptomic analyses to the responses of the marine rotifer Brachionus koreanus to environmentally relevant concentrations of nano-sized microplastic (0.05 µm), water-accommodated fractions of crude oil, and binary mixtures thereof. Our multigenerational in vivo experiments revealed more than additive effects on population growth of B. koreanus in response to combined exposure, while a single exposure to nano-sized microplastic did not induce observable adverse effects. Synergistic transcriptome deregulation was consistently associated with dramatically higher numbers of differentially expressed genes, and increased gene expression was associated with combined exposure. The majority of synergistic transcriptional alteration was related to metabolism and transcription, with impaired reproduction resulting from energetic reallocation toward adaptation. As further supported by chemistry analysis for polycyclic aromatic hydrocarbons sorption on microplastic, our findings imply that nano-sized microplastics can synergistically mediate the effects of organic pollutants in aquatic organisms.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125703DOI Listing
March 2021

Extracellular superoxide dismutase prevents skin aging by promoting collagen production via activation of AMPK and Nrf2/HO-1 cascades.

J Invest Dermatol 2021 Apr 6. Epub 2021 Apr 6.

Laboratory of Dermato-Immunology, College of Medicine, The Catholic University of Korea, 06591, Seoul, Republic of Korea. Electronic address:

With aging, the skin becomes thin and drastically losses collagen. Extracellular (EC) Superoxide dismutase (SOD), also known as SOD3 is the major SOD in the extracellular matrix of the tissues, and is well known to maintain the redox homeostasis and matrix components of such tissues. However, the role of EC-SOD in aging-associated reductions of skin thickness and collagen production is not well studied. In this study, we compared the histological differences in the dorsal skin of EC-SOD overexpressing transgenic mice (SOD3) of different age-group with wild-type (WT) mice, and also determined the underlying signaling mechanism. Our data showed that the skin thickness in SOD3 mice significantly increased with age compared to WT male mice. Further, SOD3 promoted collagen production via activation of AMPK and Nrf2/HO-1 in aged mice. Interestingly, subcutaneous injection of adeno-associated virus overexpressing EC-SOD exhibited increased skin thickness and collagen expression. Furthermore, combined recombinant EC-SOD and dihydrotestosterone (DHT) treatment synergistically elevated collagen production via activation of TGF-β in human dermal fibroblasts. Altogether, these results demonstrated that EC-SOD prevents skin aging by promoting collagen production in vivo and in vitro. Therefore, we propose that EC-SOD may be a potential therapeutic target for anti-aging in the skin.
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http://dx.doi.org/10.1016/j.jid.2021.02.757DOI Listing
April 2021

Clinical Features and Treatment Outcomes of Seronegative Pediatric Autoimmune Encephalitis.

J Clin Neurol 2021 Apr;17(2):300-306

Division of Pediatric Neurology, Epilepsy Research Institute, Severance Children's Hospital, Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.

Background And Purpose: New diagnostic criteria for pediatric autoimmune encephalitis (AIE) have been introduced recently. A substantial proportion of cases of pediatric AIE are diagnosed as seronegative based on these criteria, and so the clinical characteristics of this group remain to be investigated.

Methods: This study included 46 pediatric patients younger than 18 years with suspected AIE. Clinical features, laboratory or radiological findings, and treatment outcomes were compared between seronegative and seropositive patients.

Results: Nine (19.6%) of the 46 patients were diagnosed as seropositive AIE. All of the patients with seropositive AIE had anti-N-methyl-D-aspartate receptor antibodies. Commonly identified neuropsychiatric symptoms were altered mental status, cognitive dysfunction, seizure, speech dysfunction, and psychotic disorder in both the seronegative and seropositive groups. Immunotherapy produced favorable treatment outcomes in both the seropositive (=7, 77.8%) and seronegative (=35, 94.6%) AIE patients. Treatment outcomes for first-line immunotherapy were better in seronegative AIE than seropositive AIE patients (=0.003), and hence a smaller proportion of seronegative patients required second-line treatment (=0.015).

Conclusions: Pediatric seronegative AIE patients showed clinical presentations similar to those of seropositive AIE patients, with favorable treatment outcomes after immunotherapy.
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http://dx.doi.org/10.3988/jcn.2021.17.2.300DOI Listing
April 2021

Epidemiological Features and Economic Burden of Guillain-Barré Syndrome in South Korea: A Nationwide Population-Based Study.

J Clin Neurol 2021 Apr;17(2):257-264

College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Korea.

Background And Purpose: Guillain-Barré syndrome (GBS) is rare, but its symptoms are severe and they occasionally lead to long-term disability. Country-specific epidemiological evidence is useful for detecting potential problems at the population level. This study investigated the epidemiological and economic characteristics of GBS in South Korea.

Methods: The Korean National Health Insurance Service claims data from 2010 to 2016 were used to identify incident cases as newly hospitalized patients with a primary diagnosis of GBS (the 10th revision of the International Classification Disease code of G61.0). New cases were defined as patients not having claim records for GBS within one year prior to the hospital admission for GBS.

Results: The incidence rate increased by 45.6% between 2010 and 2016, from 1.28 to 1.82 per 100,000 population. All age groups other than <20 years showed increasing trends. The incidence rate was highest in those aged 65 years to 74 years. Approximately 72% of the incident GBS cases had antecedent infection within 42 days before GBS was diagnosed. Children younger than 10 years constituted the highest proportion of antecedent infections (93.7%). The average length of stay per GBS hospitalization was 33.5 days. Patients had an average of 7.48 outpatient visits for GBS treatment per year. The economic burden from a societal perspective of treating GBS during the first year was USD 16,428.

Conclusions: The increasing incidence trend and substantial economic burden of GBS strongly advocate the development of effective strategies for preventing and managing GBS.
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http://dx.doi.org/10.3988/jcn.2021.17.2.257DOI Listing
April 2021

Urinary microRNA-1913 to microRNA-3659 expression ratio as a non-invasive diagnostic biomarker for prostate cancer.

Investig Clin Urol 2021 Mar 16. Epub 2021 Mar 16.

Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.

Purpose: MicroRNAs (miRNAs) are small non-coding RNAs and are involved in the development, proliferation, and pathogenesis of prostate cancer (PCa). Urinary miRNAs are promising non-invasive biomarkers for PCa diagnosis because of their stability in urine. Here, we evaluated the diagnostic value of urinary miR-1913 to miR-3659 ratio in PCa patients and benign prostate hyperplasia (BPH) controls.

Materials And Methods: Candidate miRNAs were identified from urinary microarray data and tested by real-time PCR. The urinary miR-1913 to miR-3659 expression ratio was selected and tested in 83 urine samples (44 PCa and 39 BPH) to confirm its validity as a non-invasive diagnostic biomarker for PCa.

Results: The expression ratio of urinary miR-1913 to miR-3659 was significantly higher in PCa than in BPH (p=0.002) and showed a higher area under the receiver operating characteristic curve than prostate-specific antigen (PSA; 0.821 vs. 0.518) in patients within the PSA gray zone (tPSA: 3-10 ng/mL), with sensitivity of 75.0% and specificity of 78.6% (p=0.003).

Conclusions: The urinary miR-1913 to miR-3659 expression ratio was increased in PCa and may serve as a useful supplemental biomarker to PSA for the diagnosis of PCa, particularly in patients within the PSA gray zone.
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http://dx.doi.org/10.4111/icu.20200488DOI Listing
March 2021

Crosstalk between WNT and STAT3 is mediated by galectin-3 in tumor progression.

Gastric Cancer 2021 Apr 8. Epub 2021 Apr 8.

Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Background: Aberrant activation of the WNT/β-catenin and STAT3 signaling pathways plays a critical role in cancer progression. However, direct targeting of these pathways as an anti-cancer therapeutic approach needs to be reconsidered due to its serious side effects. Here, we demonstrate that overexpression of WNT induces STAT3 activation in a galectin-3-dependent manner.

Methods: We investigated how galectin-3 mediates the crosstalk between WNT/β-catenin and STAT3 signaling and whether inhibition of galectin-3 can reduce gastric cancer. The molecular mechanisms were analyzed by biochemical assays using cultured gastric cancer cells, patient tissues, and genetically engineered mice. Moreover, we confirm of therapeutic effects of GB1107, a cell-penetrating galectin-3 specific inhibitor, using orthotopic gastric cancer-bearing mice RESULTS: Increased levels of galectin-3 and STAT3 phosphorylation were detected in the stomach tissues of WNT1-overexpressing mouse models. Also, high expression levels and co-localization of β-catenin, pSTAT3, and galectin-3 in patients with advanced gastric cancer were correlated with a poorer prognosis. Galectin-3 depletion significantly decreased STAT3 Tyr705 phosphorylation, which regulates its nuclear localization and transcriptional activation. A peptide of galectin-3 (Y45-Q48) directly bound to the STAT3 SH2 domain and enhanced its phosphorylation. GB1107, a specific membrane-penetrating inhibitor of galectin-3, significantly reduced the activation of both STAT3 and β-catenin and inhibited tumor growth in orthotopic gastric cancer-bearing mice.

Conclusions: We propose that galectin-3 mediates the crosstalk between the WNT and STAT3 signaling pathways. Therefore GB1107, a galectin-3-specific inhibitor, maybe a potent agent with anti-gastric cancer activity. Further studies are needed for its clinical application in gastric cancer therapy.
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http://dx.doi.org/10.1007/s10120-021-01186-5DOI Listing
April 2021

Optical characteristics of type-II hexagonal-shaped GaSb quantum dots on GaAs synthesized using nanowire self-growth mechanism from Ga metal droplet.

Sci Rep 2021 Apr 8;11(1):7699. Epub 2021 Apr 8.

Center of Opto-Electronic Convergence Systems, Korea Institute of Science and Technology, Seoul, 02792, Korea.

We report the growth mechanism and optical characteristics of type-II band-aligned GaSb quantum dots (QDs) grown on GaAs using a droplet epitaxy-driven nanowire formation mechanism with molecular beam epitaxy. Using transmission electron microscopy and scanning electron microscopy images, we confirmed that the QDs, which comprised zinc-blende crystal structures with hexagonal shapes, were successfully grown through the formation of a nanowire from a Ga droplet, with reduced strain between GaAs and GaSb. Photoluminescence (PL) peaks of GaSb capped by a GaAs layer were observed at 1.11 eV, 1.26 eV, and 1.47 eV, assigned to the QDs, a wetting-like layer (WLL), and bulk GaAs, respectively, at the measurement temperature of 14 K and excitation laser power of 30 mW. The integrated PL intensity of the QDs was significantly stronger than that of the WLL, which indicated well-grown GaSb QDs on GaAs and the generation of an interlayer exciton, as shown in the power- and temperature-dependent PL spectra, respectively. In addition, time-resolved PL data showed that the GaSb QD and GaAs layers formed a self-aligned type-II band alignment; the temperature-dependent PL data exhibited a high equivalent internal quantum efficiency of 15 ± 0.2%.
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http://dx.doi.org/10.1038/s41598-021-87321-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032789PMC
April 2021

Identification of novel 1,3-diaryl-1,2,4-triazole-capped histone deacetylase 6 inhibitors with potential anti-gastric cancer activity.

Eur J Med Chem 2021 Mar 31;218:113392. Epub 2021 Mar 31.

Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Technology Drug Preparation (Zhengzhou University), Ministry of Education of China, Key Laboratory of Henan Province for Drug Quality and Evaluation, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China. Electronic address:

Histone deacetylase 6 (HDAC6) has emerged as a critical regulator of many cellular pathways in tumors due to its unique structure basis and abundant substrate types. Over the past few decades, the role played by HDAC6 inhibitors as anticancer agents has sparked great interest of biochemists worldwide. However, they were less reported for gastric cancer therapy. In this paper, with the help of bioisosteric replacement, in-house library screening, and lead optimization strategies, we designed, synthesized and verified a series of 1,3-diaryl-1,2,4-triazole-capped HDAC6 inhibitors with promising anti-gastric cancer activities. Amongst, compound 9r displayed the best inhibitory activity towards HDAC6 (IC = 30.6 nM), with 128-fold selectivity over HDAC1. Further BLI and CETSA assay proved the high affinity of 9r to HDAC6. In addition, 9r could dose-dependently upregulate the levels of acetylated α-tubulin, without significant effect on acetylated histone H3 in MGC803 cells. Besides, 9r exhibited potent antiproliferative effect on MGC803 cells, and promoted apoptosis and suppressed the metastasis without obvious toxicity, suggesting 9r would serve as a potential lead compound for the development of novel therapeutic agents of gastric cancer.
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http://dx.doi.org/10.1016/j.ejmech.2021.113392DOI Listing
March 2021

Microbiome profiling of uncinate tissue and nasal polyps in patients with chronic rhinosinusitis using swab and tissue biopsy.

PLoS One 2021 8;16(4):e0249688. Epub 2021 Apr 8.

Interdisciplinary Program in Precision Public Health, Korea University, Seoul, Republic of Korea.

Chronic rhinosinusitis (CRS) is characterized according to the presence or absence of nasal polyps (NPs) and displays nasal microbiota dysbiosis. However, optimal sampling methods of the nasal microbiome in CRS have not been identified. We aimed to assess the microbial composition in patients with CRS, comparing different sampling methods (swab and tissue biopsy), tissue types (uncinate tissue and NP), and disease subtypes. Samples were obtained by swabbing the middle meatus and taking a biopsy of uncinate tissue (UT) in patients with CRS with (CRSwNP, N = 8) or without NP (CRSsNP, N = 6) and controls (N = 8). NPs were also harvested in CRSwNP. DNAs were extracted from fifty-two samples and analyzed by 16S rRNA gene amplicon sequencing. As a result, a great interpersonal variance was observed in nasal swabs, while UT samples presented distinct microbiome with low inter-personal differences. Moreover, the UT microbiomes were further differentiated into three clusters which are associated with disease status (control, CRSsNP, and CRSwNP). Compared to UT, NP revealed a unique microbiome profile with significantly less bacterial diversity. Prevotella was the genus whose abundance was negatively correlated with disease severity in NP. In conclusion, tissue samples are better specimens than nasal swabs for assessing the microbiomes of CRS patients. Several bacteria in UT and NP tissues revealed an association with clinical severity of CRSwNP.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249688PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8031401PMC
April 2021

Integrated genomic and transcriptomic analysis reveals unique mechanisms for high osmotolerance and halotolerance in Hyphopichia yeast.

Environ Microbiol 2021 Apr 8. Epub 2021 Apr 8.

Molecular Systems Biology Laboratory of Life Science, Chung-Ang University, Seoul, 06974, South Korea.

The yeast species Hyphopichia is common in nature and strongly competitive under harsh environmental conditions. Here, we characterized Hyphopichia burtonii KJJ43 and H. pseudoburtonii KJS14, which exhibit strong halotolerance, using genomic and transcriptomic analyses. The genomes of H. burtonii and H. pseudoburtonii comprised eight chromosomes with 85.17% nucleotide identity and significant divergence in synteny. Notably, both Hyphopichia genomes possessed extended gene families of amino acid permeases and ATP-binding cassette (ABC) transporters, whose dynamic expression patterns during osmotic stress were revealed using transcriptome profiling. Intriguingly, we found unique features of the HOG pathway activated by Hog1p even under non-osmotic stress conditions and the upregulation of cytosolic Gpd1p protein during osmotic stress. Associated with hyperfilamentation growth under high osmotic conditions, a set of genes in the FLO family with induced expression in response to NaCl, KCl, and sorbitol supplementation were identified. Moreover, comparative transcriptome analysis reveals the NaCl-specific induction of genes involved in amino acid biosynthesis and metabolism, particularly BAT2. This suggests the potential association between oxoacid reaction involving branched-chain amino acids and osmotolerance. The combined omics analysis of two Hyphopichia species provides insights into the novel mechanisms involved in salt and osmo-stress tolerance exploited by diverse eukaryotic organisms. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/1462-2920.15464DOI Listing
April 2021

Incidence and risk factors of urinary tract infections in hospitalised patients with spinal cord injury.

J Clin Nurs 2021 Apr 7. Epub 2021 Apr 7.

Mo-Im Kim Nursing Research Institute, College of Nursing, Yonsei University, Seoul, South Korea.

Aims And Objectives: To investigate the incidence of urinary tract infection and analyse its risk factors among hospitalised patients with spinal cord injury.

Background: While the incidence of urinary tract infection varies widely according to the healthcare setting and patients' clinical characteristics, formal reports are limited in quantity. There has been no consensus regarding the risk factors for urinary tract infection.

Design: A retrospective descriptive study.

Methods: Electronic medical records of 964 subjects between 2010-2017 were reviewed. Urinary tract infection status was examined to identify newly occurred cases. Data included demographic and clinical characteristics, hydration status and length of hospitalisation. The reporting of the study followed the EQUATOR Network's STROBE checklist.

Results: Of the sample, 31.7% had urinary tract infection (95% confidence interval: 1.288 to 1.347, p < .001). Sex, completeness of injury, type of bladder emptying, detrusor function and urethral pressure were significant factors affecting urinary tract infection. Patients who were male and those with injury classifications A, B and C had higher risk of urinary tract infection. Patients with urinary or suprapubic indwelling catheters, as well as those with areflexic detrusor combined with normotonic urethral pressure or overactive detrusor combined with normotonic urethral pressure, showed higher risk. Length of hospitalisation in patients with urinary tract infection was greater than that in uninfected patients, which implies the importance of prevention of urinary tract infection.

Conclusions: Nurses should carefully assess risk factors to prevent urinary tract infection in patients with spinal cord injury in the acute and sub-acute stages of the disease trajectory and provide individualised nursing care.

Relevance To Clinical Practice: This study contributes evidence for up-to-date clinical nursing practice for the comprehensive management of urinary tract infection. This can lead to improvements in nursing care quality and patient outcomes, including length of hospitalisation.
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http://dx.doi.org/10.1111/jocn.15763DOI Listing
April 2021

Genome-wide enhancer maps link risk variants to disease genes.

Nature 2021 Apr 7. Epub 2021 Apr 7.

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Genome-wide association studies (GWAS) have identified thousands of noncoding loci that are associated with human diseases and complex traits, each of which could reveal insights into the mechanisms of disease. Many of the underlying causal variants may affect enhancers, but we lack accurate maps of enhancers and their target genes to interpret such variants. We recently developed the activity-by-contact (ABC) model to predict which enhancers regulate which genes and validated the model using CRISPR perturbations in several cell types. Here we apply this ABC model to create enhancer-gene maps in 131 human cell types and tissues, and use these maps to interpret the functions of GWAS variants. Across 72 diseases and complex traits, ABC links 5,036 GWAS signals to 2,249 unique genes, including a class of 577 genes that appear to influence multiple phenotypes through variants in enhancers that act in different cell types. In inflammatory bowel disease (IBD), causal variants are enriched in predicted enhancers by more than 20-fold in particular cell types such as dendritic cells, and ABC achieves higher precision than other regulatory methods at connecting noncoding variants to target genes. These variant-to-function maps reveal an enhancer that contains an IBD risk variant and that regulates the expression of PPIF to alter the membrane potential of mitochondria in macrophages. Our study reveals principles of genome regulation, identifies genes that affect IBD and provides a resource and generalizable strategy to connect risk variants of common diseases to their molecular and cellular functions.
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http://dx.doi.org/10.1038/s41586-021-03446-xDOI Listing
April 2021