Simple and sensitive galactose monitoring based on capillary SERS sensor.

Galactosemia, a severe genetic metabolic disorder, results from the absence of galactose-degrading enzymes, leading to harmful galactose accumulation. In this study, we introduce a novel capillary-based surface-enhanced Raman spectroscopy (SERS) sensor for convenient and sensitive galactose detection. The developed sensor enhances SERS signals by introducing gold nanoparticles (Au NPs) onto the surface of silver nanoshells (Ag NSs) within a capillary, creating Ag NSs with Au NPs as satellites. Utilizing 4-mercaptophenylboronic acid (4-MPBA) as a Raman reporter molecule, the detection method relies on the conversion of 4-MPBA to 4-mercaptophenol (4-MPhOH) driven by hydrogen peroxide (H2O2) generated during galactose oxidation by galactose oxidase (GOx). A new SERS signal was observed, which was generated by H2O2 produced when galactose and GOx reacted. Our strategy yielded a quantitative change in the SERS signal, specifically in the band intensity ratio of 998 to 1076 cm-1 (I998/I1076) as the galactose concentration increased. Our capillary-based SERS biosensor provides a promising platform for early galactosemia diagnosis.

Combined effect of changes in NO2, O3, PM2.5, SO2 and CO concentrations on small airway dysfunction.

BACKGROUND AND OBJECTIVE: When multiple complex air pollutants are combined in real-world settings, the reliability of estimating the effect of a single pollutant is questionable. This study aimed to investigate the combined effects of changes in air pollutants on small airway dysfunction (SAD). METHODS: We analysed Korea National Health and Nutrition Examination Survey (KNHANES) V-VIII database from 2010 to 2018 to elucidate the associations between annual changes in air pollutants over a previous 5-year period and small airway function. We estimated the annual concentrations of five air pollutants: NO2, O3, PM2.5, SO2 and CO. Forced expiratory flow between 25% and 75% of vital capacity (FEF25%-75%) <65% was defined as SAD. Using the quantile generalized-Computation (g-Computation) model, the combined effect of the annual changes in different air pollutants was estimated. RESULTS: A total of 29,115 individuals were included. We found significant associations between SAD and the quartiles of annual changes in NO2 (OR = 1.10, 95% CI = 1.08-1.12), O3 (OR = 1.03, 95% CI = 1.00-1.05), PM2.5 (OR = 1.03, 95% CI = 1.00-1.05), SO2 (OR = 1.04, 95% CI = 1.02-1.08) and CO (OR = 1.16, 95% CI = 1.12-1.19). The combined effect of the air pollutant changes was significantly associated with SAD independent of smoking (OR = 1.31, 95% CI = 1.26-1.35, p-value <0.001), and this trend was consistently observed across the entire study population and various subgroup populations. As the estimated risk of SAD, determined by individual-specific combined effect models, increased and the log odds for SAD increased linearly. CONCLUSION: The combined effect of annual changes in multiple air pollutant concentrations were associated with an increased risk of SAD.

Clinical outcomes of long-term inhaled combination therapies in patients with bronchiectasis and airflow obstruction.

BACKGROUND AND OBJECTIVES: Few studies have reported which inhaled combination therapy, either bronchodilators and/or inhaled corticosteroids (ICSs), is beneficial in patients with bronchiectasis and airflow obstruction. Our study compared the efficacy and safety among different inhaled combination therapies in patients with bronchiectasis and airflow obstruction. METHODS: Our retrospective study analyzed the patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity < 0.7 and radiologically confirmed bronchiectasis in chest computed tomography between January 2005 and December 2021. The eligible patients underwent baseline and follow-up spirometric assessments. The primary endpoint was the development of a moderate-to-severe exacerbation. The secondary endpoints were the change in the annual FEV1 and the adverse events. Subgroup analyses were performed according to the blood eosinophil count (BEC). RESULTS: Among 179 patients, the ICS/long-acting beta-agonist (LABA)/long-acting muscarinic antagonist (LAMA), ICS/LABA, and LABA/LAMA groups were comprised of 58 (32.4%), 52 (29.1%), and 69 (38.5%) patients, respectively. ICS/LABA/LAMA group had a higher severity of bronchiectasis and airflow obstruction, than other groups. In the subgroup with BEC ≥ 300/uL, the risk of moderate-to-severe exacerbation was lower in the ICS/LABA/LAMA group (adjusted HR = 0.137 [95% CI = 0.034-0.553]) and the ICS/LABA group (adjusted HR = 0.196 [95% CI = 0.045-0.861]) compared with the LABA/LAMA group. The annual FEV1 decline rate was significantly worsened in the ICS/LABA group compared to the LABA/LAMA group (adjusted ß-coefficient=-197 [95% CI=-307--87]) in the subgroup with BEC < 200/uL. CONCLUSION: In patients with bronchiectasis and airflow obstruction, the use of ICS/LABA/LAMA and ICS/LABA demonstrated a reduced risk of exacerbation compared to LABA/LAMA therapy in those with BEC ≥ 300/uL. Conversely, for those with BEC < 200/uL, the use of ICS/LABA was associated with an accelerated decline in FEV1 in comparison to LABA/LAMA therapy. Further assessment of BEC is necessary as a potential biomarker for the use of ICS in patients with bronchiectasis and airflow obstruction.

Anti-obesity activity of human gut microbiota Bacteroides stercoris KGMB02265.

Obesity is a global health threat that causes various complications such as type 2 diabetes and nonalcoholic fatty liver disease. Gut microbiota is closely related to obesity. In particular, a higher Firmicutes to Bacteroidetes ratio has been reported as a biomarker of obesity, suggesting that the phylum Bacteroidetes may play a role in inhibiting obesity. Indeed, the genus Bacteroides was enriched in the healthy subjects based on metagenome analysis. In this study, we determined the effects of Bacteroides stercoris KGMB02265, a species belonging to the phylum Bacteroidetes, on obesity both in vitro and in vivo. The cell-free supernatant of B. stercoris KGMB02265 inhibited lipid accumulation in 3T3-L1 preadipocytes, in which the expression of adipogenic marker genes was repressed. In vivo study showed that the oral administration of B. stercoris KGMB02265 substantially reduced body weight and fat weight in high-fat diet induced obesity in mice. Furthermore, obese mice orally administered with B. stercoris KGMB02265 restored glucose sensitivity and reduced leptin and triglyceride levels. Taken together, our study reveals that B. stercoris KGMB02265 has anti-obesity activity and suggests that it may be a promising candidate for treating obesity.

Changes in abdominal fat depots after bariatric surgery are associated with improved metabolic profile.

BACKGROUND AND AIMS: Obesity associated with a change in the quantity and quality of fat depots. Using computed tomography (CT), we analyzed abdominal fat depots in patients with obesity after bariatric surgery according to their metabolic health status. METHODS AND RESULTS: We recruited 79 individuals with metabolically unhealthy obesity before bariatric surgery and compared them with age-sex matched healthy controls. The volume and fat attenuation index (FAI) of fat depots were measured using CT scans that were conducted prior to and a year after bariatric surgery. 'Metabolically healthy' was defined as having no hypertension, normal fasting glucose and a waist-to-hip ratio of <1.05 for men and <0.95 for women. Individuals who achieved a metabolic health status conversion (MHC) (n = 29, 37%)-from unhealthy to healthy-were younger (p < 0.001) as compared to individuals without MHC. Pre-surgery BMI and reduction of BMI did not differ between the two groups (p = 0.099, p = 0.5730). Bariatric surgery reduced the volume and increased the FAI of fat depots. Baseline lower abdominal periaortic adipose tissue (AT) volume (p = 0.014) and great percent reduction in renal sinus AT volume after surgery (p = 0.019) were associated with MHC after surgery. Increased intraperitoneal AT FAI (p = 0.031) was also associated with MHC. CONCLUSION: MHC was not associated with improvement in general obesity, based on indicators such as reduction of BMI after surgery. Weight reduction induced specific abdominal fat depot changes measured by CT are positively associated with MHC.

Rapid FEV1/FVC Decline Is Related With Incidence of Obstructive Lung Disease and Mortality in General Population.

BACKGROUND: Forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) naturally decreases with age; however, an excessive decline may be related with increased morbidity and mortality. This study aimed to evaluate the FEV1/FVC decline rate in the Korean general population and to identify whether rapid FEV1/FVC decline is a risk factor for obstructive lung disease (OLD) and all-cause and respiratory mortality. METHODS: We evaluated individuals aged 40-69 years who underwent baseline and biannual follow-up spirometric assessments for up to 18 years, excluding those with airflow limitations at baseline. Based on the quartiles of the annual FEV1/FVC decline rate, the most negative FEV1/FVC change (1st quartile of annual FEV1/FVC decline rate) was classified as rapid FEV1/FVC decline. We investigated the risk of progression to OLD and all-cause and respiratory mortality in individuals with rapid FEV1/FVC decline. RESULTS: The annual FEV1/FVC decline rate in the eligible 7,768 patients was 0.32 percentage point/year. The incidence rate of OLD was significantly higher in patients with rapid FEV1/FVC decline than in those with non-rapid FEV1/FVC decline (adjusted incidence rate, 2.119; 95% confidence interval [CI], 1.932-2.324). Rapid FEV1/FVC decline was an independent risk factor for all-cause mortality (adjusted hazard [HR], 1.374; 95% CI, 1.105-1.709) and respiratory mortality (adjusted HR, 1.353; 95% CI, 1.089-1.680). CONCLUSION: The annual FEV1/FVC decline rate was 0.32%p in the general population in Korea. The incidence rate of OLD and the hazards of all-cause and respiratory mortality were increased in rapid FEV1/FVC decliners.

Association between oxygen saturation level during bronchoscopy and post-bronchoscopy adverse events: a retrospective cohort study.

BACKGROUND: Flexible bronchoscopy is widely used to diagnose and treat various respiratory diseases. However, caution is warranted for post-bronchoscopy adverse events. Although desaturation frequently occurs during bronchoscopy, its clinical impact and the optimal oxygen saturation level during the procedure remain unclear. This study aimed to investigate whether the percutaneous oxygen saturation (SpO2) level during bronchoscopy is associated with the development of post-bronchoscopy respiratory adverse events. METHODS: In this single-center retrospective cohort study conducted from March 2020 to February 2021, 569 patients were classified into high or low oxygen saturation groups based on the SpO2 level during bronchoscopy. The primary outcome was post-bronchoscopy respiratory adverse events, and secondary outcomes were other post-bronchoscopy adverse events and clinical outcomes. RESULTS: Among 569 patients, 458 and 111 patients were classified into the high oxygen saturation (SpO2 > 96%) and low oxygen saturation (SpO2 ≤ 94%) groups, respectively. After propensity score matching, the low oxygen saturation group had more post-bronchoscopy respiratory and febrile adverse events than the high oxygen saturation group. In the multivariable regression analysis, low SpO2 level during bronchoscopy was an independent risk factor for post-bronchoscopy respiratory adverse events (odds ratio = 3.16 [95% confidence interval 1.37-7.30]). In the low oxygen saturation group, the high-risk subgroups for post-bronchoscopy respiratory adverse events were the elderly, women, current smokers, and patients with chronic obstructive pulmonary disease or acute decompensated heart failure before bronchoscopy. There was no significant difference in the length of hospital stay, intensive care unit admission, or mortality between the high and low oxygen saturation groups. CONCLUSIONS: Close monitoring is recommended for patients with SpO2 ≤ 94% during bronchoscopy due to the increased risk of respiratory adverse events after the procedure.

Clinical characteristics and the diagnostic role of molecular tests in musculoskeletal infections caused by nontuberculous Mycobacterium: a single-center experience.

PURPOSE: We retrospectively investigated NTM musculoskeletal infections to understand the clinical characteristics as well as the diagnostic performance of molecular tests as a useful supplementary test. METHODS: A retrospective cohort study was conducted from January 2016 to December 2019. Intraoperative specimens for culture and pathological analysis were obtained during surgery under sterile conditions. AdvanSure TB/NTM real-time PCR (LG Life Sciences, Seoul, Korea) and PCR-reverse blot hybridization assay (REBA, REBA Myco-ID; YD Diagnostics, Yongin, Republic of Korea) was performed directly from tissue specimens for the rapid and accurate identification of 20 mycobacterial species. RESULTS: A series of 24 patients was identified during the study period. Agricultural/aquatic exposure were predisposing factors in 9 patients, trauma in 4 patients, but no predisposing host factor was identified for 11 patients. Twenty-two patients presented with tenosynovitis and two with arthritis with substantial delays between initial presentation of symptoms and microbiologic diagnosis, with a median of 147 days (range 5-396 days). Pathologic tissue examination of musculoskeletal NTM infections was positive for chronic granulomatous inflammation in 18 cases. Fifteen were positive in the culture study, and nine were positive only in the molecular study using tissue specimens. All 6 M. ulcerans/M. marinum isolates were identified only by PCR. CONCLUSIONS: This study is an important reminder that NTM infections should be a part of the differential diagnosis in patients with chronic musculoskeletal infections refractory to regular treatment. Although molecular test cannot replace the conventional smear and culture methods, it can be used as a useful supplementary test especially in diagnosing M. marinum infection.

Prevalence and clinical characterization of BRCA1 and BRCA2 mutations in Korean patients with epithelial ovarian cancer.

This study was performed to investigate the prevalence, clinical characteristics, and treatment response according to BRCA1 and BRCA2 (BRCA) mutations in Korean patients with epithelial ovarian cancer (EOC). Two-hundred and ninety-eight Korean women diagnosed with high-grade serous and/or endometrioid EOC from 2010 to 2015 were tested for germline and 86 specimens for somatic BRCA mutations, regardless of the family history. Clinical characteristics including survival outcomes were compared in patients with and without BRCA mutations (NCT02963688). A total of 43 different germline BRCA mutations were identified in 78 patients among 298 patients (26.2%). Somatic BRCA mutations were identified in 11 (12.8%) patients among patients without germline BRCA mutations. Haplotype analysis demonstrated no founder mutations in our Korean patient cohort. Insignificant differences in age at diagnosis, primary site, and residual disease after surgery were observed between patients with and without BRCA mutations. In multivariate analysis for overall survival (OS), the presence of BRCA mutation was significantly associated with OS (P = .049) in addition to platinum sensitivity (P < .001), indicating it is an independent prognostic factor for survival regardless of platinum sensitivity to first-line chemotherapy. In addition, a higher response rate to subsequent chemotherapy after recurrence was observed in EOC patients with BRCA mutations resulting in better OS. In the current study, the prevalence of BRCA mutations in Korean patients with EOC was higher than previously reported in other ethnic groups. We demonstrated characteristics and treatment response in Korean EOC patients with BRCA mutations. These findings may provide valuable information to be considered in future clinical trials including Asian patients.

Genome-wide association study of non-tuberculous mycobacterial pulmonary disease.

BACKGROUND: The prevalence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing in South Korea and many parts of the world. However, the genetic factors underlying susceptibility to this disease remain elusive. METHODS: To identify genetic variants in patients with NTM-PD, we performed a genome-wide association study with 403 Korean patients with NTM-PD and 306 healthy controls from the Healthy Twin Study, Korea cohort. Candidate variants from the discovery cohort were subsequently validated in an independent cohort. The Genotype-Tissue Expression (GTEx) database was used to identify expression quantitative trait loci (eQTL) and to conduct Mendelian randomisation (MR). RESULTS: We identified a putatively significant locus on chromosome 7p13, rs849177 (OR, 2.34; 95% CI, 1.71 to 3.21; p=1.36×10-7), as the candidate genetic variant associated with NTM-PD susceptibility. Its association was subsequently replicated and the combined p value was 4.92×10-8. The eQTL analysis showed that a risk allele at rs849177 was associated with lower expression levels of STK17A, a proapoptotic gene. In the MR analysis, a causal effect of STK17A on NTM-PD development was identified (ß, -4.627; 95% CI, -8.768 to -0.486; p=0.029). CONCLUSIONS: The 7p13 genetic variant might be associated with susceptibility to NTM-PD in the Korean population by altering the expression level of STK17A.

Synthesis of novel 1H-Pyrazolo[3,4-b]pyridine derivatives as DYRK 1A/1B inhibitors.

As DYRK1A and 1B inhibitors, 1H-pyrazolo[3,4-b]pyridine derivatives were synthesized. Mostly, 3-aryl-5-arylamino compounds (6) and 3,5-diaryl compounds (8 and 9) were prepared and especially, 3,5-diaryl compound 8 and 9 showed excellent DYRK1B inhibitory enzymatic activities with IC50 Values of 3-287 nM. Among them, 3-(4-hydroxyphenyl), 5-(3,4-dihydroxyphenyl)-1H-pyrazolo[3,4-b]pyridine (8h) exhibited the highest inhibitory enzymatic activity (IC50 = 3 nM) and cell proliferation inhibitory activity (IC50 = 1.6 µM) towards HCT116 colon cancer cells. Also compound 8h has excellent inhibitory activities in patient-derived colon cancer organoids model as well as in 3D spheroid assay model of SW480 and SW620. The docking study supported that we confirmed that compound 8h binds to DYRK1B through various hydrogen bonding interactions and hydrophobic interactions.

Comparison of QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In-Tube tests for patients with active and latent tuberculosis: A prospective cohort study.

INTRODUCTION: We aimed to determine the diagnostic performance and clinical value of the QuantiFERON-TB Gold In-Tube (QFT-GIT) and QuantiFERON-TB Gold Plus (QFT-Plus) tests in patients with active tuberculosis (TB) or latent TB infection (LTBI). METHODS: We prospectively enrolled 140 patients, including 63 with active TB and 77 with LTBI, between March 2017 and October 2018. QFT-GIT and QFT-Plus were performed simultaneously in all subjects. RESULTS: QFT-Plus and QFT-GIT test results showed significant agreement, in both active TB and LTBI patients, in terms of the interferon-γ concentration and interpretation result. QFT-Plus had higher sensitivity than QFT-GIT for predicting active TB (82.5% vs. 77.8%) and showed fewer false-negative and indeterminate results in both active TB and LTBI patients due to its "TB2 tube". The QFT-Plus TB2-TB1 value was higher in the active TB group than in the LTBI group. The QFT-Plus TB1-Nil and TB2-Nil values were useful in predicting remote LTBI, rather than recent LTBI. CONCLUSIONS: QFT-Plus showed good agreement with QFT-GIT in both active TB and LTBI patients, and higher sensitivity for predicting active TB than QFT-GIT. The QFT-Plus TB2 tube results, which reflect CD8+ T cell immunity, may improve predictive accuracy and detection of the immune response associated with active TB and LTBI.

The Impact of Erosive Reflux Esophagitis on the Decline of Lung Function in the General Population.

BACKGROUND: The impact of reflux esophagitis on the decline of lung function has been rarely reported. This study was performed to evaluate the association between erosive reflux esophagitis and lung function changes. METHODS: We included patients with normal lung function who underwent esophagogastroduodenoscopy for health screening from a health screening center. Patients with persistent erosive reflux esophagitis on two discrete endoscopic examinations were designated as the erosive reflux esophagitis group. We also selected patients without erosive reflux esophagitis and matched them 1:4 with patients from the erosive reflux esophagitis group. We estimated annual forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) changes from baseline and compared these estimates by the linear mixed regression model. We also estimated the biannual incidence of chronic obstructive pulmonary disease (COPD). RESULTS: In total, 1,050 patients (210 patients with erosive reflux esophagitis, and 840 matched controls) were included. The median follow-up duration for spirometry was six years. In patients with erosive reflux esophagitis, mild reflux esophagitis (A grade) was most common (165 patients, 78.6%). The adjusted annual FEV1 change in patients with erosive reflux esophagitis was -51.8 mL/yr, while it decreased by 46.8 mL/yr in controls (P = 0.270). The adjusted annual FVC decline was similar between the two groups (-55.8 vs. -50.5 mL/yr, P = 0.215). The estimated COPD incidence during the follow-up period was not different between the erosive reflux esophagitis and control groups. CONCLUSION: In patients with normal lung function, the presence of erosive reflux esophagitis did not affect the annual declines in FEV1 or FVC.

Clinical and Virologic Effectiveness of Remdesivir Treatment for Severe Coronavirus Disease 2019 (COVID-19) in Korea: a Nationwide Multicenter Retrospective Cohort Study.

BACKGROUND: Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain. METHODS: A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values. RESULTS: A total of 86 severe COVID-19 patients were evaluated including 48 remdesivir-treated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, P = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; P = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1-5 to 11-15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; P = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; P = 0.007). CONCLUSION: The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.

Dosimetric comparison of VitalBeam® and HalcyonTM 2.0 for hypofractionated VMAT with simultaneous integrated boost treatment of early-stage left-sided breast cancer.

PURPOSE: This study compared the quality of treatment plans for early-stage, left-sided breast cancer, as planned for and delivered by the HalcyonTM and VitalBeam® . MATERIALS AND METHODS: Fifteen patients diagnosed with early-stage left-sided breast cancer, who had received VMAT with hypofractionated SIB, were recruited. All cases were planned using HalcyonTM comprising a dual-layer MLC (DL-MLC) and VitalBeam® with a Millennium 120 MLC (VB-MLC). For the PTVs, the quality of coverage (QC), conformity index (CI), and homogeneity index (HI) were calculated for each plan. The dosimetric differences between the two treatment plans were statistically compared using the Wilcoxon signed-rank test (p < 0.05). To evaluate delivery efficiency, the average delivery time for each patient's treatment plan was recorded and compared. RESULTS: For the PTVs, the two plans (DL-MLC and VB-MLC) were comparable in terms of the QC, CI, and HI. However, V30Gy and Dmean for the heart in the DL-MLC plan were significantly reduced by 0.49% and 14.6%, respectively, compared with those in the VB-MLC plan (p < 0.05). The Dmean value for the ipsilateral lung in the DL-MLC plan significantly decreased by 5.5%, compared with that in the VB-MLC plan (p < 0.05). In addition, the delivery times for the DL-MLC and VB-MLC plans were 79 ± 10 and 101 ± 11 s, respectively. CONCLUSIONS: DL-MLC plans were found to improve OAR sparing. In particular, when treating left-sided breast cancer via DL-MLC plans, the risk of heart toxicity is expected to be reduced.

Template-Assisted Plasmonic Nanogap Shells for Highly Enhanced Detection of Cancer Biomarkers.

We present a template-assisted method for synthesizing nanogap shell structures for biomolecular detections based on surface-enhanced Raman scattering. The interior nanogap-containing a silver shell structure, referred to as a silver nanogap shell (Ag NGS), was fabricated on silver nanoparticles (Ag NPs)-coated silica, by adsorbing small aromatic thiol molecules on the Ag NPs. The Ag NGSs showed a high enhancement factor and good signal uniformity, using 785-nm excitation. We performed in vitro immunoassays using a prostate-specific antigen as a model cancer biomarker with a detection limit of 2 pg/mL. To demonstrate the versatility of Ag NGS nanoprobes, extracellular duplex surface-enhanced Raman scattering (SERS) imaging was also performed to evaluate the co-expression of cancer biomarkers, human epidermal growth factor-2 (HER2) and epidermal growth factor receptor (EGFR), in a non-small cell lung cancer cell line (H522). Developing highly sensitive Ag NGS nanoprobes that enable multiplex biomolecular detection and imaging can open up new possibilities for point-of-care diagnostics and provide appropriate treatment options and prognosis.

Sequential Analysis of Viral Load in a Neonate and Her Mother Infected With Severe Acute Respiratory Syndrome Coronavirus 2.

We report changes in viral load over time in a 27-day-old neonate with coronavirus disease 2019 who presented with fever, cough, and vomiting. Severe acute respiratory syndrome coronavirus 2 RNA was detected in the nasopharynx, oropharynx, stool, saliva, plasma, and urine. The highest viral RNA copies in nasopharynx decreased over time while viral load in stool remained high.

Pulmonary function is associated with fibrosis severity in patients with biopsy-proven nonalcoholic fatty liver disease.

BACKGROUND & AIMS: The association between nonalcoholic fatty liver disease (NAFLD) and pulmonary function remains elusive because of the heterogeneous spectrum and inaccurate diagnostic methods of NAFLD, and insufficient pulmonary function data. We conducted this study to identify the association between histological severity of NAFLD and pulmonary function. METHODS: This study included patients ≥18 years old with baseline pulmonary function data between August 2014 and July 2019 within a biopsy-evaluated prospective NAFLD cohort. Cross-sectionally, pre-/post-bronchodilator spirometric data with diffusing capacity (DLCO ) were compared according to histological severity of NAFLD in the various demographic and metabolic subgroups. Multivariable-adjusted analysis revealed specific histological features associated with reduced pulmonary function. RESULTS: In a total of 420 patients with biopsy-proven NAFLD, pre-/post-bronchodilator forced vital capacities (FVCs; a percentage of the predictive value) were inversely correlated with histological severity of NAFLD. Conversely, pre-bronchodilator forced expiratory volume in 1 second (FEV1 )/FVC was positively correlated with NAFLD severity. Post-bronchodilator FVC (%) decreased and DLCO /alveolar volume (VA ) increased linearly with worsening histological severity of NAFLD in multivariable analysis. In particular, fibrosis stage remained a significant independent predictor of decreased post-bronchodilator FVC (%) (ß-coefficient, 4.41; 95% confidence interval [-8.39, -0.43]; P = .031) even after adjusted for clinical variables, exclusively in age <65 years, female, never-smoker and nonchronic obstructive pulmonary disease subgroups. CONCLUSIONS: Pulmonary function deteriorates with worsening histological severity of NAFLD, especially at the fibrosis stage. The common pathogenesis of reduced pulmonary function and NAFLD fibrosis progression should be further explored.

Clinical Characteristics of COVID-19: Clinical Dynamics of Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infection Detected by Early Active Surveillance.

BACKGROUND: There is limited information describing the presenting characteristics and dynamic clinical changes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosed in the early phase of illness. This study is a case series of patients with coronavirus disease 2019 (COVID-19) admitted to 11 hospitals in Korea. METHODS: Patients with confirmed SARS-CoV-2 infection by positive polymerase chain reaction (PCR) testing of respiratory specimens by active surveillance that were finally discharged between February 20 and April 30, 2020 were included. Patients were classified into mild and non-mild groups on initial admission according to oxygen demand and Sequential Organ Failure Assessment score, and the mild group was followed up and subgrouped into non-aggravation and aggravation groups. RESULTS: A total of 161 patients with SARS-CoV2 infection were enrolled. Among the mild group of 136 patients, 11.7% of patients experienced clinical aggravation during hospitalization, but there was no initial clinical parameter on admission predicting their aggravation. Fever (odds ratio [OR], 4.56), thrombocytopenia (OR, 12.87), fever (OR, 27.22) and lactate dehydrogenase (LDH) > 300 U/L (OR, 18.35), and CRP > 1 mg/dL (OR, 11.31) significantly indicated aggravation in the 1st, 2nd, 3rd, and 4th 5-day periods, respectively. PCR positivity lasted for a median of 22 days and 32 days after the onset of illness in the non-aggravation and aggravation groups, respectively. CONCLUSION: Old age was associated with early severe presentation. Clinical aggravation among asymptomatic or mild patients could not be predicted initially but was heralded by fever and several laboratory markers during the clinical course.

Prevalence and Antimicrobial Characteristics of Shiga Toxin-Producing Escherichia coli Isolates from Pork in Korea.

Shiga toxin-producing Escherichia coli (STEC) strains are important food-borne pathogens that can be transmitted through the consumption of food products derived from pigs. Moreover, antimicrobial resistance in STEC has been a matter of increasing concern. The aim of this study was to investigate the prevalence and antimicrobial characteristics of STEC isolates from pork in Korea. We isolated 131 isolates of E. coli from 334 pork samples collected from slaughterhouses and retail markets from 2008 to 2009. Among the 131 isolates, 6 (4.58%) were confirmed to belong to 6 different serotypes of STEC. All six STEC isolates contained stx1 and eaeA virulence genes, and four of them additionally carried the hly gene. The minimum inhibitory concentration (MIC) of 15 antibiotics (amoxicillin/clavulanic acid, ampicillin, cephalothin, cefoxitin, ceftiofur, gentamicin, neomycin, streptomycin, nalidixic acid, ciprofloxacin, colistin, chloramphenicol, florfenicol, tetracycline and sulfamethoxazole/trimethoprim) toward the STEC isolates was determined. As a result, three strains were associated with high MICs for florfenicol and chloramphenicol (64 µg/mL). Furthermore, all three strains were found to contain the florfenicol-resistant gene (floR) but not the chloramphenicol-resistant gene (cat). Sequence alignment and BLAST analysis of the polymerase chain reaction products of the floR gene indicated that they contained sequences with homology to the floR gene of E. coli or Salmonella enterica serovar, Heidelberg. This is the first report on the detection of floR in STEC isolated from pork obtained from retail markets in Korea.