Publications by authors named "Min Jae Kim"

219 Publications

Fluorination-Induced Charge Trapping and Operational Instability in Conjugated-Polymer Field-Effect Transistors.

ACS Appl Mater Interfaces 2022 Aug 16. Epub 2022 Aug 16.

Department of Chemical Engineering, Pohang University of Science and Technology, Pohang 37673, Korea.

Fluorination of a conjugated polymer backbone is an effective strategy to control the microstructure and electronic structure of a conjugated polymer. Although fluorination has been widely reported to increase charge carrier mobility, its effect on the operational stability of electronic devices has not been extensively investigated. Here, the effect of fluorination of a conjugated polymer backbone on charge trapping and the operational stability of organic field-effect transistors is investigated. The results show that the device based on a fluorinated conjugated polymer exhibits relatively poor operational stability despite its greater charge carrier mobility compared with that in the device based on its nonfluorinated polymer counterpart. Experimental results reveal that the low stability originates from the greater degree of shallow trapping of charge carriers within the fluorinated polymer thin film and that the shallow trapping is closely related to the presence of minority charge carriers. A mechanism of charge trapping is proposed.
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http://dx.doi.org/10.1021/acsami.2c04643DOI Listing
August 2022

Dynamic regulation of lipid metabolism in the placenta of in vitro and in vivo models of Gestational Diabetes Mellitus.

Biol Reprod 2022 Aug 6. Epub 2022 Aug 6.

Department of Biomaterials Science (BK21 Four Program), College of Natural Resources & Life Science, Pusan National University, Miryang 50463, Republic of Korea.

The purpose of this study was to investigate lipid metabolism in the placenta of Gestational diabetes mellitus (GDM) individuals and to evaluate its effect on the fetus. We examined the expression of lipogenesis- and lipolysis-related proteins in the in vitro and in vivo GDM placenta models. The levels of sterol regulatory element binding protein-1c (SREBP-1c) were increased, and fat accumulated more during early hyperglycemia, indicating that lipogenesis was stimulated. When hyperglycemia was further extended, lipolysis was activated due to the phosphorylation of hormone-sensitive lipase (HSL) and expression of adipose triglyceride lipase (ATGL). In the animal model of GDM and in the placenta of GDM patients during the extended stage of GDM, the expression of SREBP-1c decreased and the deposition of fat increased. Similar to the results obtained in the in vitro study, lipolysis was enhanced in the animal and human placenta of extended GDM. These results suggest that fat synthesis may be stimulated by lipogenesis in the placenta when the blood glucose level is high. Subsequently, the accumulated fat can be degraded by lipolysis and more fat and its metabolites can be delivered to the fetus when the GDM condition is extended at the late stage of gestation. Imbalanced fat metabolism in the placenta and fetus of GDM patients can cause metabolic complications in the fetus, including fetal macrosomia, obesity, and type 2 diabetes mellitus.
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http://dx.doi.org/10.1093/biolre/ioac156DOI Listing
August 2022

Heat-shock triggers inverted induction of hypo-S-nitrosylation and hyper-O-GlcNAcylation.

Protein Pept Lett 2022 Aug 5. Epub 2022 Aug 5.

Department of Life Science Laboratory of Functional Glycomics, Ajou University, San 5, Wonchon-dong, Suwon 443-749, Korea.

Introduction: Protein S-nitrosylation (SNO) and O-GlcNAcylation are important posttranslational modifications. Biological connection between SNO and O-GlcNAcylation is not clear.

Objective: We aim to identify the crosstalk between SNO and O-GlcNAcylation during heat-shock.

Methods: Ex vivo heat-shock on mouse tissues together with in vitro heat-shock on culture cells was performed and global levels of SNO and O-GlcNAcylation were analyzed with Biotin-switch assay (BSA) and RL2 immunoblots.

Results And Discussion: Heat-shock induces hypo-SNO in parallel with hyper-O-GlcNAcylation. Inverted induction of hypo-SNO and hyper-O-GlcNAcylation is globally progressed in a time-dependent manner. Moreover, heat-shock ubiquitously facilitates S-denitrosylation (SdeNO) of endogenous SNO-proteins including SNO-OGT, SNO-Hsp70, SNO-Hsp90, SNO-Akt, and SNO-actin. Particularly, SdeNO of SNO-OGT leads to enhanced OGT activity.

Conclusion: These findings provide mechanistic evidence that heat-shock triggers SdeNO of SNO-OGT by which OGT activity is up-regulated, resulting in hyper-O-GlcNAcylation.
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http://dx.doi.org/10.2174/0929866529666220805151725DOI Listing
August 2022

Localization-adjusted diagnostic performance and assistance effect of a computer-aided detection system for pneumothorax and consolidation.

NPJ Digit Med 2022 Jul 30;5(1):107. Epub 2022 Jul 30.

Department of Medical Artificial Intelligence, Deepnoid, Inc., Seoul, Republic of Korea.

While many deep-learning-based computer-aided detection systems (CAD) have been developed and commercialized for abnormality detection in chest radiographs (CXR), their ability to localize a target abnormality is rarely reported. Localization accuracy is important in terms of model interpretability, which is crucial in clinical settings. Moreover, diagnostic performances are likely to vary depending on thresholds which define an accurate localization. In a multi-center, stand-alone clinical trial using temporal and external validation datasets of 1,050 CXRs, we evaluated localization accuracy, localization-adjusted discrimination, and calibration of a commercially available deep-learning-based CAD for detecting consolidation and pneumothorax. The CAD achieved image-level AUROC (95% CI) of 0.960 (0.945, 0.975), sensitivity of 0.933 (0.899, 0.959), specificity of 0.948 (0.930, 0.963), dice of 0.691 (0.664, 0.718), moderate calibration for consolidation, and image-level AUROC of 0.978 (0.965, 0.991), sensitivity of 0.956 (0.923, 0.978), specificity of 0.996 (0.989, 0.999), dice of 0.798 (0.770, 0.826), moderate calibration for pneumothorax. Diagnostic performances varied substantially when localization accuracy was accounted for but remained high at the minimum threshold of clinical relevance. In a separate trial for diagnostic impact using 461 CXRs, the causal effect of the CAD assistance on clinicians' diagnostic performances was estimated. After adjusting for age, sex, dataset, and abnormality type, the CAD improved clinicians' diagnostic performances on average (OR [95% CI] = 1.73 [1.30, 2.32]; p < 0.001), although the effects varied substantially by clinical backgrounds. The CAD was found to have high stand-alone diagnostic performances and may beneficially impact clinicians' diagnostic performances when used in clinical settings.
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http://dx.doi.org/10.1038/s41746-022-00658-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339006PMC
July 2022

Clinical impact of and microbiological risk factors for qacA/B positivity in ICU-acquired ST5-methicillin-resistant SCCmec type II Staphylococcus aureus bacteremia.

Sci Rep 2022 Jul 6;12(1):11413. Epub 2022 Jul 6.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro-43-gil, Songpa-gu, Seoul, 05505, South Korea.

Concern about resistance to chlorhexidine has increased due to the wide use of the latter. The impact of the qacA/B and smr chlorhexidine tolerance genes on the outcome of methicillin-resistant Staphylococcus aureus (MRSA) infections is unclear. We evaluated the prevalence and clinical impact of, and microbiological risk factors for, qacA/B tolerance in MRSA bacteremia. MRSA bacteremia that occurred more than two days after intensive care unit admission between January 2009 and December 2018 was identified from a prospective cohort of S. aureus bacteremia in a tertiary-care hospital from South Korea. A total of 183 MRSA blood isolates was identified, and the major genotype found was ST5-MRSA-II (87.4%). The prevalences of qacA/B and smr were 67.2% and 3.8%, respectively. qacA/B-positive isolates were predominantly ST5-MRSA-II (96.7% [119/123]), the dominant hospital clone. In a homogenous ST5-MRSA-II background, qacA/B positivity was independently associated with septic shock (aOR, 4.85), gentamicin resistance (aOR, 74.43), and non-t002 spa type (aOR, 74.12). qacA/B positivity was found to have decreased significantly in ST5-MRSA-II in association with a decline in qacA/B-positive t2460, despite the increasing use of chlorhexidine since 2010 (P < 0.001 for trend). Continuous surveillance of the qac genes, and molecular characterization of their plasmids, are needed to understand their role in MRSA epidemiology.
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http://dx.doi.org/10.1038/s41598-022-15546-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259651PMC
July 2022

Risk Factors of Recurrent Infection in Patients with Staphylococcus aureus Bacteremia: a Competing Risk Analysis.

Antimicrob Agents Chemother 2022 07 28;66(7):e0012622. Epub 2022 Jun 28.

Division of Infectious Diseases, Department of Internal Medicine, Asan Medical Centergrid.413967.e, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Although several clinical variables have been reported as risk factors for recurrence of Staphylococcus aureus infection, most studies have not considered competing risk events that may overestimate the risk. In this study, we performed competing risk analysis to identify risk factors related to 90-day recurrence in patients with S. aureus bacteremia (SAB) using a large cohort data from a single tertiary hospital in South Korea. All adults who experienced SAB during admission were prospectively enrolled from August 2008 to December 2019. After the day of the first positive blood culture, recurrence and all-cause mortality were assessed for 90 days. Recurrence was defined as a development of symptoms or signs of infection with or without repeated bacteremia after >7 days of negative blood culture and clinically apparent improvement. Subdistribution hazard ratios (sHR) for recurrence and all-cause mortality were estimated using Fine and Gray models. Of 1,725 SAB patients, including 885 cases (51.3%) of methicillin-resistant S. aureus (MRSA) bacteremia, 85 (5.0%) experienced recurrence during the study period. In a multivariate Fine and Gray regression model, the presence of a vascular graft (subdistribution HR [sHR], 3.48; 95% confidence interval [CI], 1.90-6.40), nasal MRSA carriage (sHR, 2.10; 95% CI, 1.28-3.44), methicillin resistance (sHR, 1.69; 95% CI, 1.00-2.84), and rifampicin resistance (sHR, 2.20; 95% CI, 1.12-4.33) were significantly associated with 90-day recurrence. In a large cohort of SAB patients with a high prevalence of MRSA, indwelling vascular graft, nasal MRSA carriage, methicillin resistance, and rifampicin resistance were potential risk factors for recurrence of S. aureus infection.
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http://dx.doi.org/10.1128/aac.00126-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295554PMC
July 2022

Geographical distribution and genetic diversity of Plasmodium vivax reticulocyte binding protein 1a correlates with patient antigenicity.

PLoS Negl Trop Dis 2022 06 23;16(6):e0010492. Epub 2022 Jun 23.

Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea.

Plasmodium vivax is the most widespread cause of human malaria. Recent reports of drug resistant vivax malaria and the challenge of eradicating the dormant liver forms increase the importance of vaccine development against this relapsing disease. P. vivax reticulocyte binding protein 1a (PvRBP1a) is a potential vaccine candidate, which is involved in red cell tropism, a crucial step in the merozoite invasion of host reticulocytes. As part of the initial evaluation of the PvRBP1a vaccine candidate, we investigated its genetic diversity and antigenicity using geographically diverse clinical isolates. We analysed pvrbp1a genetic polymorphisms using 202 vivax clinical isolates from six countries. Pvrbp1a was separated into six regions based on specific domain features, sequence conserved/polymorphic regions, and the reticulocyte binding like (RBL) domains. In the fragmented gene sequence analysis, PvRBP1a region II (RII) and RIII (head and tail structure homolog, 152-625 aa.) showed extensive polymorphism caused by random point mutations. The haplotype network of these polymorphic regions was classified into three clusters that converged to independent populations. Antigenicity screening was performed using recombinant proteins PvRBP1a-N (157-560 aa.) and PvRBP1a-C (606-962 aa.), which contained head and tail structure region and sequence conserved region, respectively. Sensitivity against PvRBP1a-N (46.7%) was higher than PvRBP1a-C (17.8%). PvRBP1a-N was reported as a reticulocyte binding domain and this study identified a linear epitope with moderate antigenicity, thus an attractive domain for merozoite invasion-blocking vaccine development. However, our study highlights that a global PvRBP1a-based vaccine design needs to overcome several difficulties due to three distinct genotypes and low antigenicity levels.
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http://dx.doi.org/10.1371/journal.pntd.0010492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258880PMC
June 2022

Application of iron flocculation to concentrate white spot syndrome virus in seawater.

J Virol Methods 2022 Aug 24;306:114554. Epub 2022 May 24.

Department of Aquatic Life Medicine, Pukyong National University, Busan 48513, the Republic of Korea. Electronic address:

The iron flocculation method, which comprises the Fe-virus flocculate formation-filtration-resuspension steps, is extensively used to concentrate and precipitate viruses distributed in water. To apply this method to concentrate white spot syndrome virus (WSSV) in seawater, viral genomic and infective recovery yields were compared between polyethylene sulfone (PES) and polycarbonate (PC) membrane filters and two types of resuspension buffers (oxalate and ascorbate). Viral genome quantitation was determined above a 95 % limit of detection (11.48 viral DNA copies/μL) using quantitative real-time PCR. From WSSV-spiked seawater (10-10 viral DNA copies/mL), the viral genomic recovery yields of the PES-Oxalate, PC-Oxalate, PES-Ascorbate, and PC-Ascorbate conditions were 78.67 % ± 12.90 %, 84.53 % ± 24.30 %, 85.59 % ± 16.98 %, and 93.74 % ± 7.44 %, respectively. The detectable Fe-virus flocculates collected by the PC membrane were approximately 10 WSSV DNA copies/mL of seawater, a value more than 10-fold higher than that compared to the PES membrane filter (10 WSSV DNA copies/mL), regardless of the resuspension buffer types. WSSV resuspended with oxalate buffer caused mass mortality among whiteleg shrimp (Litopenaeus vannamei), inducing the expression of the virus envelope protein, VP28, similar to that of a native virus, suggesting stable viral activity during the resuspension process. Based on the PES-Ascorbate, WSSV particles could be successfully concentrated in seawater from shrimp farms with white spot disease outbreaks (approximately 10 WSSV DNA copies/mL). Collectively, these findings indicate that the simple and efficient method of iron flocculation is sufficient to concentrate WSSV in seawater and could be used as a non-invasive approach and one of the reasonable diagnostic processes for white spot disease surveillance.
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http://dx.doi.org/10.1016/j.jviromet.2022.114554DOI Listing
August 2022

Piriform Cortex Ablation Volume Is Associated With Seizure Outcome in Mesial Temporal Lobe Epilepsy.

Neurosurgery 2022 09 24;91(3):414-421. Epub 2022 May 24.

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Background: Growing evidence suggests that piriform cortex resection during anterior temporal lobectomy is important for achieving good seizure outcome in mesial temporal lobe epilepsy (mTLE). However, the relationship between seizure outcome and piriform cortex ablation during MR-guided laser interstitial thermal therapy (MRgLITT) remains unclear.

Objective: To determine whether ablation of piriform cortex was associated with seizure outcome in patients with mTLE undergoing MRgLITT.

Methods: We performed preablation and postablation volumetric analyses of hippocampus, amygdala, piriform cortex, and ablation volumes in patients with mTLE who underwent MRgLITT at our institution from 2014 to 2019.

Results: Thirty nine patients with mTLE were analyzed. In univariate logistic regression, percent piriform cortex ablation was associated with International League Against Epilepsy (ILAE) class 1 at 6 months (odds ratio [OR] 1.051, 95% CI [1.001-1.117], P = .045), whereas ablation volume, percent amygdala ablation, and percent hippocampus ablation were not ( P > .05). At 1 year, ablation volume was associated with ILAE class 1 (OR 1.608, 95% CI [1.071-2.571], P = .021) while percent piriform cortex ablation became a trend (OR 1.050, 95% CI [0.994-1.109], P = .054), and both percent hippocampus ablation and percent amygdala ablation were not significantly associated with ILAE class 1 ( P > .05). In multivariable logistic regression, only percent piriform cortex ablation was a significant predictor of seizure freedom at 6 months (OR 1.085, 95% CI [1.012-1.193], P = .019) and at 1 year (OR 1.074, 95% CI [1.003-1.178], P = .041).

Conclusion: Piriform cortex ablation volume is associated with seizure outcome in patients with mTLE undergoing MRgLITT. The piriform cortex should be considered a high yield ablation target to achieve good seizure outcome.
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http://dx.doi.org/10.1227/neu.0000000000002041DOI Listing
September 2022

Apparent diffusion coefficient of piriform cortex and seizure outcome in mesial temporal lobe epilepsy after MR-guided laser interstitial thermal therapy: a single-institution experience.

J Neurosurg 2022 Apr 29:1-9. Epub 2022 Apr 29.

1Department of Neurosurgery, Johns Hopkins School of Medicine.

Objective: Piriform cortex (PC) is one of the critical structures in the epileptogenesis of mesial temporal lobe epilepsy (mTLE), but its role is poorly understood. The authors examined the utility of apparent diffusion coefficient (ADC; an MR-based marker of tissue pathology) of the PC as a predictor of seizure outcome in patients with mTLE undergoing MR-guided laser interstitial thermal therapy (MRgLITT).

Methods: A total of 33 patients diagnosed with mTLE who underwent MRgLITT at the authors' institution were included in the study. The 6-month postoperative seizure outcomes were classified using the International League Against Epilepsy (ILAE) system as good (complete seizure freedom, ILAE class I) and poor (seizure present, ILAE classes II-VI). The PC and ablation volumes were manually segmented from both the preoperative and intraoperative MRI sequences, respectively. The mean ADC intensities of 1) preablation PC; 2) total ablation volume; 3) ablated portion of PC; and 4) postablation residual PC were calculated and compared between good and poor outcome groups. Additionally, the preoperative PC volumes and proportion of PC volume ablated were examined and compared between the subjects in the two outcome groups.

Results: The mean age at surgery was 36.5 ± 3.0 years, and the mean follow-up duration was 1.9 ± 0.2 years. Thirteen patients (39.4%) had a good outcome. The proportion of PC ablated was significantly associated with seizure outcome (10.16 vs 3.30, p < 0.05). After accounting for the variability in diffusion tensor imaging acquisition parameters, patients with good outcome had a significantly higher mean ADC of the preablation PC (0.3770 vs -0.0108, p < 0.05) and the postoperative residual PC (0.4197 vs 0.0309, p < 0.05) regions compared to those with poor outcomes. No significant differences in ADC of the ablated portion of PC were observed (0.2758 vs -0.4628, p = 0.12) after performing multivariate analysis.

Conclusions: A higher proportion of PC ablated was associated with complete seizure freedom. Preoperative and postoperative residual ADC measures of PC were significantly higher in the good seizure outcome group in patients with mTLE who underwent MRgLITT, suggesting that ADC analysis can assist with postablation outcome prediction and patient stratification.
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http://dx.doi.org/10.3171/2022.3.JNS212490DOI Listing
April 2022

DNA Shuffling of Genes to Increase Fibrinolytic Activity and Thermostability.

J Microbiol Biotechnol 2022 Jun 25;32(6):800-807. Epub 2022 Apr 25.

Division of Applied Life Science (BK21 4), Graduate School, Gyeongsang National University, Jinju 52828, Republic of Korea.

Four genes encoding alkaline serine proteases from strains were used as template genes for family gene shuffling. Shuffled genes obtained by DNase I digestion followed by consecutive primerless and regular PCR reactions were ligated with pHY300PLK, an shuttle vector. The ligation mixture was introduced into WB600 and one transformant (FSM4) showed higher fibrinolytic activity. DNA sequencing confirmed that the shuffled gene () consisted of DNA mostly originated from either or in addition to some DNA from either or . Mature AprEFSM4 (275 amino acids) was different from mature AprEJS2 in 4 amino acids and mature AprE176 in 2 amino acids. was overexpressed in BL21 (DE3) by using pET26b(+) and recombinant AprEFSM4 was purified. The optimal temperature and pH of AprEFSM4 were similar to those of parental enzymes. However, AprEFM4 showed better thermostability and fibrinogen hydrolytic activity than the parental enzymes. The results indicated that DNA shuffling could be used to improve fibrinolytic enzymes from sp. for industrial applications.
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http://dx.doi.org/10.4014/jmb.2202.02017DOI Listing
June 2022

Membrane-Free Stem Cell Extract Enhances Blood-Brain Barrier Integrity by Suppressing NF-κB-Mediated Activation of NLRP3 Inflammasome in Mice with Ischemic Stroke.

Life (Basel) 2022 Mar 29;12(4). Epub 2022 Mar 29.

Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Gyeongnam, Korea.

Membrane-free stem cell extract (MFSCE) of human adipose tissues possesses various biological activities. However, the effects of MFSCE on blood-brain barrier dysfunction and brain damage are unknown. In this study, we determined the role of MFSCE in an ischemic stroke mouse model. Mice were treated with MFSCE once daily for 4 days and 1 h before ischemic damage. Experimental ischemia was induced by photothrombosis. Pretreatment with MFSCE reduced infarct volume and edema and improved neurological, as well as motor functions. Evans blue leakage and water content in the brain tissue were reduced by MFSCE pretreatment relative to those in the vehicle group. MFSCE increased the expression of the tight junction proteins zonula occludens 1 and claudin-5, as well as vascular endothelial-cadherin, but decreased that of matrix metalloproteinase 9. Notably, MFSCE treatment decreased cell death and the level of NOD-like receptor protein 3 inflammasome, consistent with the downregulated expression of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 in the ischemic brain. These effects might have occurred via the suppression of the expression of Toll-like receptor 4 and activation of nuclear factor-κB. The results highlighted the potential of MFSCE treatment as a novel and preventive strategy for patients at a high risk of ischemic stroke.
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http://dx.doi.org/10.3390/life12040503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032759PMC
March 2022

Comparison of isolated respiratory and extrarespiratory mucormycosis: a 21-year observational study of 44 cases.

Infection 2022 Apr 21. Epub 2022 Apr 21.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Objectives: This study aimed to compare the clinical characteristics and outcomes of patients with isolated respiratory and extrarespiratory mucormycosis.

Methods: Adult patients diagnosed with proven or probable invasive mucormycosis in a tertiary hospital in South Korea, between 1999 and 2020 were retrospectively reviewed. We compared the clinical, mycological characteristics, and outcomes of patients with isolated respiratory mucormycosis (IRM) and those with extrarespiratory mucormycosis (ERM).

Results: A total of 44 patients including 32 (72%) with IRM, and 12 (27%) with ERM were enrolled. Of these, 38 (86%) were classified as proven and 6 (14%) as probable invasive mucormycosis according to the EORTC/MSG criteria. Univariate analysis exhibited that old age, surgery, and intensive care unit were associated with ERM, and multivariable analysis revealed that variable associated with ERM was intensive care unit (aOR 9.80; 95% CI 2.07-46.35; P = 0.004). There were no significant differences in 90-day mortality between patients with IRM and ERM (38% vs 50%, P = 0.45). In multivariable analysis, neutropenia (aOR 6.88; 95% CI 1.67-28.27; P = 0.01) was an independent risk factor for 90-day mortality.

Conclusions: More than a quarter of patients with mucormycosis had extrarespiratory manifestations, especially in patients who were admitted to intensive care unit. The mortality of the patients with ERM was comparable to that of the patients with IRM, although the patients with ERM received ICU care more frequently.
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http://dx.doi.org/10.1007/s15010-022-01831-wDOI Listing
April 2022

Fluvoxamine Treatment of Patients with Symptomatic COVID-19 in a Community Treatment Center: A Preliminary Result of Randomized Controlled Trial.

Infect Chemother 2022 Mar;54(1):102-113

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

Background: This study aimed to evaluate whether fluvoxamine reduces clinical deterioration in adult patients with mild to moderate coronavirus disease 2019 (COVID-19), and to identify risk factors for clinical deterioration in patients admitted to a community treatment center (CTC).

Materials And Methods: A randomized, placebo-controlled trial was conducted in a CTC, in Seoul, Korea from January 15, 2021, to February 19, 2021. Symptomatic adult patients with positive results of severe acute respiratory syndrome coronavirus 2 real time-polymerase chain reaction within 3 days of randomization were assigned at random to receive 100 mg of fluvoxamine or placebo twice daily for 10 days. The primary outcome was clinical deterioration defined by any of the following criteria: oxygen requirement to keep oxygen saturation over 94.0%, aggravation of pneumonia with dyspnea, or World Health Organization clinical progression scale 4 or greater.

Results: Of 52 randomized participants [median (interquartile range) age, 53.5 (43.3 - 60.0) years; 31 (60.0%) men], 44 (85.0%) completed the trial. Clinical deterioration occurred in 2 of 26 patients in each group ( >0.99). There were no serious adverse events in either group. Clinical deterioration occurred in 15 (6.0%) of 271 patients admitted to the CTC, and all of them were transferred to a hospital. In multivariate analysis, age between 55 and 64, fever and pneumonia at admission were independent risk factors for clinical deterioration.

Conclusion: In this study of adult patients with symptomatic COVID-19 who were admitted to the CTC, there was no significant differences in clinical deterioration between patients treated with fluvoxamine and placebo (ClinicalTrials.gov Identifier: NCT04711863).
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http://dx.doi.org/10.3947/ic.2021.0142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8987178PMC
March 2022

Clinical and virological characteristics of SARS-CoV-2 B.1.617.2 (Delta) variant: a prospective cohort study.

Clin Infect Dis 2022 Apr 1. Epub 2022 Apr 1.

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

Background: Data on the clinical and virological characteristics of the delta variant of SARS-CoV-2 are limited. This prospective cohort study compared the characteristics of the delta variant to other variants.

Methods: Adult patients with mild COVID-19 who agreed to daily saliva sampling at a community isolation facility in South Korea between July and August 2021 were enrolled. Scores of 28 COVID-19-related symptoms were recorded daily. The genomic RNA and subgenomic RNA from saliva samples were measured by real-time reverse-transcriptase-PCR. Cell cultures were performed on saliva samples with positive genomic RNA results.

Results: A total of 141 patients (delta group, n = 108 [77%]; non-delta group, n = 33 [23%]) were enrolled. Myalgia was more common in the delta group than in the non-delta group (52% vs. 27%, P = .03). Total symptom scores were significantly higher in the delta group between days 3 to 10 after symptom onset. Initial genomic RNA titers were similar between the two groups; however, during the late course of disease, genomic RNA titers were higher in the delta group. Negative conversion of subgenomic RNA was slower in the delta group (median 9 vs. 5 days; P < .001). The duration of viral shedding in terms of positive viral culture was also longer in the delta group (median 5 vs. 3 days; P = .002).

Conclusions: COVID-19 patients infected with the delta variant exhibited prolonged viable viral shedding with more severe symptoms than those infected with non-delta variants.
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http://dx.doi.org/10.1093/cid/ciac239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047158PMC
April 2022

Anaerobe coverage is important for the prognosis of pyogenic liver abscess: A population-based study in Korea.

J Infect Public Health 2022 Apr 15;15(4):425-432. Epub 2022 Mar 15.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Gram-negative bacteria such as Klebsiella pneumoniae and Escherichia coli are the most common cause of pyogenic liver abscess (PLA). We investigated whether the use of anaerobic-covering antibiotics is essential for the treatment of pyogenic liver abscess.

Methods: We analyzed the Health Insurance Review and Assessment Service data in Korea between 2007 and 2017. We classified PLA into two groups: a group using antibiotics that inhibited only aerobic strains (anaerobe (-) group) and a group using antibiotics that inhibited both aerobic and anaerobic strains (anaerobe (+) group). The primary outcome was the difference in in-hospital mortality between the two groups.

Results: During this period, a total of 30,690 PLA patients were obtained. There were 6733 patients in the anaerobe (-) group and 23,957 patients in the anaerobe (+) group. In-hospital mortality was significantly lower in the anaerobe (+) group than the anaerobe (-) group (7.9% vs. 15.6%, p < 0.001). In multivariate analysis, the use of anaerobic antibiotics reduced the in-hospital mortality by 42% (odds ratio 0.42, 95% confidence interval 0.38-0.46, p < 0.001) after adjusting for age and comorbidities. Furthermore, the improvement of in-hospital mortality was present regardless of the presence of cancer or diabetes.

Conclusion: The use of broad-spectrum empirical antibiotics covering anaerobic strains is important for the treatment of pyogenic liver abscess.
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http://dx.doi.org/10.1016/j.jiph.2022.03.003DOI Listing
April 2022

Four Times of Relapse of Plasmodium vivax Malaria Despite Primaquine Treatment in a Patient with Impaired Cytochrome P450 2D6 Function.

Korean J Parasitol 2022 Feb 23;60(1):39-43. Epub 2022 Feb 23.

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

Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.
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http://dx.doi.org/10.3347/kjp.2022.60.1.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8898651PMC
February 2022

Kinetics of Glycoprotein-Specific Antibody Response in Patients with Severe Fever with Thrombocytopenia Syndrome.

Viruses 2022 01 27;14(2). Epub 2022 Jan 27.

Division of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tickborne disease in East Asia that is causing high mortality. The Gn glycoprotein of the SFTS virus (SFTSV) has been considered to be an essential target for virus neutralization. However, data on anti-Gn glycoprotein antibody kinetics are limited. Therefore, we investigated the kinetics of Gn-specific antibodies compared to those of nucleocapsid protein (NP)-specific antibodies. A multicenter prospective study was performed in South Korea from January 2018 to September 2021. Adult patients with SFTS were enrolled. Anti-Gn-specific IgM and IgG were measured using an enzyme-linked immunosorbent assay. A total of 111 samples from 34 patients with confirmed SFTS were analyzed. Anti-Gn-specific IgM was detected at days 5-9 and peaked at day 15-19 from symptom onset, whereas the anti-NP-specific IgM titers peaked at days 5-9. Median seroconversion times of both anti-Gn- and NP-specific IgG were 7.0 days. High anti-Gn-specific IgG titers were maintained until 35-39 months after symptom onset. Only one patient lost their anti-Gn-specific antibodies at 41 days after symptom onset. Our data suggested that the anti-Gn-specific IgM titer peaked later than anti-NP-specific IgM, and that anti-Gn-specific IgG remain for at least 3 years from symptom onset.
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http://dx.doi.org/10.3390/v14020256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880780PMC
January 2022

Minoxidil-loaded hyaluronic acid dissolving microneedles to alleviate hair loss in an alopecia animal model.

Acta Biomater 2022 04 21;143:189-202. Epub 2022 Feb 21.

Department of Biomaterials Science (BK21 Program), Life and Industry Convergence Institute, Pusan National University, Miryang 50463, Republic of Korea. Electronic address:

Alopecia is defined as hair loss in a part of the head due to various causes, such as drugs, stress and autoimmune disorders. Various therapeutic agents have been suggested depending on the cause of the condition and patient sex, and age. Minoxidil (MXD) is commonly used topically to treat alopecia, but its low absorption rate limits widespread use. To overcome the low absorption, we suggest microneedles (MNs) as controlled drug delivery systems that release MXD. We used hyaluronic acid (HA) to construct MN, as it is biocompatible and safe. We examined the effect of HA on the hair dermal papilla (HDP) cells that control the development of hair follicles. HA enhanced proliferation, migration, and aggregation of HDP cell by increasing cell-cell adhesion and decreasing cell substratum. These effects were mediated by the cluster of differentiation (CD)-44 and phosphorylation of serine‑threonine kinase (Akt). In chemotherapy-induced alopecia mice, topical application of HA tended to decrease chemotherapy-induced hair loss. Although the amount of MXD administered by HA-MNs was 10% of topical treatment, the MXD-containing HA-MNs (MXD-HA-MNs) showed better effects on the growth of hair than topical application of MXD. In summary, our results demonstrated that HA reduces hair loss in alopecia mice, and that delivery of MXD and HA using MXD-HA-MNs maximizes therapeutic effects and minimize the side effects of MXD for the treatment of alopecia. STATEMENT OF SIGNIFICANCE: (1) Significance, This work reports a new approach for treatment of alopecia using a dissolving microneedle (MN) prepared with hyaluronic acid (HA). The HA provided a better environment for cellular functions in the hair dermal papilla cells. The HA-MNs containing minoxidil (MXD) exhibited a significant reduction of hair loss, although amount of MXD contained in them was only 10% of topically applied MXD., (2) Scientific impact, This is the first report demonstrating the direct anti-alopecia effects of HA administrated in a transdermal route and the feasibility of novel therapeutics using MXD-containing HA-MNs. We believe that our work will excite interdisciplinary readers of Acta Biomaterialia, those who are interested in the natural polymers, drug delivery, and alopecia.
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http://dx.doi.org/10.1016/j.actbio.2022.02.011DOI Listing
April 2022

A dentate gyrus-CA3 inhibitory circuit promotes evolution of hippocampal-cortical ensembles during memory consolidation.

Elife 2022 02 22;11. Epub 2022 Feb 22.

Center for Regenerative Medicine, Massachusetts General Hospital, Boston, United States.

Memories encoded in the dentate gyrus (DG) ‒ CA3 circuit of the hippocampus are routed from CA1 to anterior cingulate cortex (ACC) for consolidation. Although CA1 parvalbumin inhibitory neurons (PV INs) orchestrate hippocampal-cortical communication, we know less about CA3 PV INs or DG ‒ CA3 principal neuron ‒ IN circuit mechanisms that contribute to evolution of hippocampal-cortical ensembles during memory consolidation. Using viral genetics to selectively mimic and boost an endogenous learning-dependent circuit mechanism, DG cell recruitment of CA3 PV INs and feed-forward inhibition (FFI) in CA3, in combination with longitudinal calcium imaging, we demonstrate that FFI facilitates formation and maintenance of context-associated neuronal ensembles in CA1. Increasing FFI in DG ‒ CA3 promoted context specificity of neuronal ensembles in ACC over time and enhanced long-term contextual fear memory. LFP recordings in mice with increased FFI in DG ‒ CA3 identified enhanced CA1 sharp-wave ripple ‒ ACC spindle coupling as a potential network mechanism facilitating memory consolidation. Our findings illuminate how FFI in DG ‒ CA3 dictates evolution of ensemble properties in CA1 and ACC during memory consolidation and suggest a teacher-like function for hippocampal CA1 in stabilization and re-organization of cortical representations.
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http://dx.doi.org/10.7554/eLife.70586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903830PMC
February 2022

Inhibitory effects and underlying mechanisms of essential oil on melanogenesis in the B16F10 cell line.

Mol Med Rep 2022 Apr 9;25(4). Epub 2022 Feb 9.

Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Gyeongsangnam‑do 50463, Republic of Korea.

The present study investigated the anti‑melanogenic activity of 10 essential oils using the B16F10 cell model. Initially, a wide range of concentrations of these essential oils were screened in order to determine their toxicity levels. The assigned non‑toxic concentrations of the tested essential oils were then used to evaluate their effects on melanogenesis. The effects of the essential oils with potent anti‑melanogenic activity on cell proliferation, protection against HO‑induced cell death and the expression of certain melanogenesis‑related genes, including MITF, tyrosinase, tyrosinase related protein (TRP)‑1 and TRP‑2 were also evaluated. The results revealed that the essential oils extracted from , L., and () inhibited melanogenesis. However, among these four extracts, only extract enhanced cell proliferation, exhibited anti‑HO activities and decreased the expression level of TRP‑1. It was demonstrated that A. capillaris extract inhibited melanin synthesis via the downregulation of the TRP‑1 translational level. These essential oil extracts, particularly that of , may thus be used as natural anti‑melanogenic agents for therapeutic purposes and in the cosmetic industry for skin whitening effects with beneficial proliferative properties. However, further studies using models are required to validate these findings and to examine the effects of these extracts on various molecular pathways.
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http://dx.doi.org/10.3892/mmr.2022.12629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8845066PMC
April 2022

Benefits of a Skull-Interfaced Flexible and Implantable Multilight Emitting Diode Array for Photobiomodulation in Ischemic Stroke.

Adv Sci (Weinh) 2022 04 25;9(11):e2104629. Epub 2022 Jan 25.

Department of Korean Medical Science, Graduate Training Program of Korean Medical Therapeutics for Healthy-Aging, School of Korean Medicine, Pusan National University, Yangsan, 50612, Republic of Korea.

Photobiomodulation (PBM) has received attention due to its potential for improving tissue function and enhancing regeneration in stroke. A lightweight, compact, and simple system of miniaturized electronic devices consisting of packaged light-emitting diodes (LEDs) that incorporates a flexible substrate for in vivo brain PBM in a mouse model is developed. Using this device platform, the preventive and therapeutic effects of PBM affixed to the exposed skull of mice in the photothrombosis and middle cerebral artery occlusion stroke model are evaluated. Among the wavelength range of 630, 850, and 940 nm LED array, the PBM with 630-nm LED array is proved to be the most effective for reducing the infarction volume and neurological impairment after ischemic stroke. Moreover, the PBM with 630 nm LED array remarkably improves the capability of spatial learning and memory in the chronic poststroke phase, attenuates AIM2 inflammasome activation and inflammasome-mediated pyroptosis, and modulates microglial polarization in the hippocampus and cortex 7 days following ischemic stroke. Thus, PBM may prevent tissue and functional damage in acute ischemic injury, thereby attenuating the development of cognitive impairment after stroke.
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http://dx.doi.org/10.1002/advs.202104629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008794PMC
April 2022

Bedside risk prediction for positive follow-up blood culture in Gram-negative bacilli bacteremia: for whom is follow-up blood culture useful?

Infection 2022 Jun 21;50(3):689-697. Epub 2022 Jan 21.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro-43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Purpose: The value of follow-up blood culture (FUBC) in Gram-negative bacteremia (GNB) management is controversial. We evaluated bedside risk predictors and their probabilities of yielding positive FUBCs in GNB.

Methods: All adult patients with GNB in a 2700-bed tertiary center were retrospectively enrolled between January 2019 and December 2019. Only one initial GNB episode was included per patient. Positive FUBC was defined as isolation of the same organism in blood culture 48-72 h after the initial blood culture.

Results: A total of 2216 patients with GNB were identified, of whom 34.4% underwent FUBC. Of the 645 patients with FUBCs analyzed in the study, 89 (13.8%) had positive FUBCs. In multivariate analysis, hemodialysis [adjusted odds ratio (aOR), 2.6], fever on the day of FUBCs (aOR 3.6), intravascular device (aOR 2.4), no use of in vitro active antibiotic within 24 h (aOR 2.5), non-fermenting bacteria (aOR 4.7), and multidrug resistance (aOR 5.4) were independent risk factors for positive FUBCs. If microbiological results were excluded in multivariate analysis, hemodialysis, immunosuppressive treatment, fever on the day of FUBCs, and intravascular device were independent bedside risk predictors for positive FUBCs. The yield of FUBCs increased from 3.0% (95% CI 1.0-7.0) to 63.6% (95% CI 25.6-100) as the number of bedside risk predictors increased from 0 to 4. In addition, positive FUBCs were significantly associated with 30 day mortality.

Conclusions: FUBCs may not need to be routinely used for patients with GNB bacteremia, and bedside risk predictors could be helpful in identifying patients for whom FUBC is likely to be useful.
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http://dx.doi.org/10.1007/s15010-021-01742-2DOI Listing
June 2022

Characterization of a novel glutamate decarboxylase (GAD) from K285 isolated from .

Food Sci Biotechnol 2022 Jan 21;31(1):69-78. Epub 2021 Nov 21.

Division of Applied Life Science (BK21 Four), Graduate School, Gyeongsang National University, Jinju, 52828 Korea.

A lactic acid bacteria (LAB) producing γ-aminobutyric acid (GABA) was isolated from , a Korean vegetable food. The isolate, K285, was identified as (formly ) . The encoding glutamate decarboxylase (GAD) was cloned and an ORF encoding a protein of 451 amino acids was located. K285 GAD was smaller than other LAB GADs, and its amino acid sequence showed less than 80% homology with other LAB GADs, indicating the uniqueness of K285 GAD. The encoding glutamate/GABA antiporter was located 75 bp upstream of , indicating operon structure. The was overexpressed in and recombinant GAD was purified. Optimum pH and temperature of recombinant K285 GAD were pH 5.0 and 50 °C, respectively, and the activity was dependent on pyridoxal 5'-phosphate. The Km and Vmax of GAD were 5.35 ± 0.27 mM and 0.041 ± 0.0008 mM/min, respectively. K285 might be useful for the production of foods enriched with GABA.
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http://dx.doi.org/10.1007/s10068-021-01005-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733076PMC
January 2022

Comparison of the Clinical Outcomes of Patients With Positive Xpert Carba-R Tests for Carbapenemase-Producing Enterobacterales According to Culture Positivity.

Open Forum Infect Dis 2022 Jan 10;9(1):ofab594. Epub 2022 Jan 10.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background: We aimed to compare the clinical outcomes of patients with positive Xpert Carba-R assay results for carbapenemase-producing Enterobacterales (CPE) according to CPE culture positivity.

Methods: We retrospectively collected data for patients with positive CPE (positive Xpert Carba-R or culture) who underwent both tests from August 2018 to March 2021 in a 2700-bed tertiary referral hospital in Seoul, South Korea. We compared the clinical outcomes of patients positive for Xpert Carba-R according to whether they were positive (XPCP) or negative (XPCN) for CPE culture.

Results: Of 322 patients with CPE who underwent both Xpert Carba-R and culture, 313 (97%) were positive for Xpert Carba-R for CPE. Of these, 87 (28%) were XPCN, and 226 (72%) were XPCP. XPCN patients were less likely to have a history of previous antibiotic use (75.9% vs 90.3%;  = .001) and to have carbapenemase (21.8% vs 48.9%;  < .001). None of the XPCN patients developed infection from colonization within 6 months, whereas 13.4% (29/216) of the XPCP patients did ( < .001). XPCN patients had lower transmission rates than XPCP patients (3.0% [9/305] vs 6.3% [37/592];  = .03). There was no significant difference in CPE clearance from positive culture results between XPCN and XPCP patients (40.0% [8/20] vs 26.7% [55/206];  = .21).

Conclusions: Our study suggests that XPCN patients had lower rates of both infection and transmission than XPCP patients. The Xpert Carba-R assay is clinically useful not only for rapid identification of CPE but also for predicting risks of infection and transmission when performed along with culture.
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http://dx.doi.org/10.1093/ofid/ofab594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8754382PMC
January 2022

Optimal duration of antiviral treatment in patients with gastrointestinal cytomegalovirus disease at a low and high risk of relapse.

Medicine (Baltimore) 2022 Jan;101(1):e28359

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Abstract: We evaluated the association between antiviral treatment duration and relapse of gastrointestinal (GI) cytomegalovirus (CMV) disease by analyzing the risk factors for relapse.Patients who were diagnosed with GI CMV disease at a tertiary hospital from January 2008 to April 2019 were retrospectively enrolled. Patients with relapsed disease were those with a recurrence of GI CMV disease at least 4 weeks after the initial antiviral treatment.Of 238 participants, including 145 (51.9%) with upper and 93 (48.1%) with lower GI CMV diseases, 27 (11.3%) had experienced relapses. The difference in antiviral treatment duration between the relapsed and nonrelapsed GI CMV groups was not significant (median days, 21.0 vs 17.0, P = .13). Multivariate analysis revealed that hematologic malignancy (odds ratio, 3.73; P = .026) and ulcerative colitis (odds ratio, 4.61; P = .003) were independent risk factors for relapse. Participants with at least one of these risk factors and those with no independent risk factors were classified under the high- (relapse rate, 25.9%) and low-risk of relapse groups (relapse rate, 6.7%), respectively. Accordingly, we further stratified 180 (75.6%) and 58 (24.4%) participants under the low- and high-risk of relapse groups, respectively. There was no significant difference in relapse rates between the high- and low-risk groups according to antiviral treatment duration.Approximately 10% of the participants experienced relapses after antiviral treatment, with hematologic malignancy and ulcerative colitis featuring as risk factors. Therefore, prolonged antiviral treatment might not be helpful in preventing GI CMV disease relapse.
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http://dx.doi.org/10.1097/MD.0000000000028359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8735784PMC
January 2022

Localization of Ulnar Neuropathy at the Wrist Using Motor and Sensory Ulnar Nerve Segmental Studies.

J Clin Neurol 2022 Jan;18(1):59-64

Department of Physical Medicine and Rehabilitation, Korea University College of Medicine, Seoul, Korea.

Background And Purpose: Diagnosing ulnar neuropathy at the wrist (UNW) is often challenging, and performing several short segmental studies have been suggested for achieving this. We aimed to determine the utility of ulnar nerve segmental studies at the wrist (UNSWs) in patients with suspected UNW.

Methods: Fourteen patients with typical symptoms of unilateral UNW were evaluated using conventional electrophysiological tests, UNSWs, and ultrasonography (US). In UNSWs, the ulnar nerve was stimulated at three sites (3 cm distal, just lateral, and 2 cm proximal to the pisiform), and recordings were made at the first dorsal interosseous (FDI) muscle and the fifth digit. Four types of UNW were identified by conventional ulnar nerve conduction studies based on motor and sensory fiber involvement. UNW was also categorized as either a proximal or distal lesion relative to the pisiform based on the UNSWs. The relationships between the conventional electrophysiological type, UNSW categorization results, and lesion location as verified by US were analyzed.

Results: Proximal UNW lesions were associated with involvement of the entire deep motor and the superficial sensory fibers (type I). Distal lesions were more closely related to deep motor fibers that innervated the FDI (type III). All five proximal and six distal lesions seen in US matched the lesion locations found on UNSWs.

Conclusions: Motor and sensory UNSW are considered useful assistive techniques for diagnosing UNW and localizing its lesion sites.
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http://dx.doi.org/10.3988/jcn.2022.18.1.59DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762509PMC
January 2022
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