Association of Body Composition Changes with the Development of Diabetes Mellitus: A Nation-Wide Population Study.

Background: We investigated the association between body composition changes and new-onset diabetes mellitus (DM) development according to the body mass index (BMI) in a longitudinal setting in the general Korean population. Methods: From 2010 to 2011 (1st) and 2012 to 2013 (2nd), we included 1,607,508 stratified random sample participants without DM from the National Health Insurance Service-Health Screening dataset of Korean. The predicted appendicular skeletal muscle mass index (pASMMI), body fat mass index (pBFMI), and lean body mass index (pLBMI) were calculated using pre-validated anthropometric prediction equations. A prediction equation was constructed by combining age, weight, height, waist circumference, serum creatinine levels, alcohol consumption status, physical activity, and smoking history as variables affecting body composition. Results: Decreased pASMMI (men: hazard ratio [HR], 0.866; 95% confidence interval [CI], 0.830 to 0.903; P<0.001; women: HR, 0.748; 95% CI, 0.635 to 0.881; P<0.001), decreased pLBMI (men: HR, 0.931; 95% CI, 0.912 to 0.952; P<0.001; women: HR, 0.906; 95% CI, 0.856 to 0.959; P=0.007), and increased pBFMI (men: HR, 1.073; 95% CI, 1.050 to 1.096; P<0.001; women: HR, 1.114; 95% CI, 1.047 to 1.186; P=0.007) correlated with the development of new-onset DM. Notably, only in the overweight and obese BMI categories, decreases in pASMMI and pLBMI and increases in pBFMI associated with new-onset DM, regardless of gender. Conclusion: Decreased pASMMI and pLBMI, and increased pBFMI with excess fat accumulation may enhance the risk of newonset DM. Therefore, appropriate changes in body composition can help prevent new-onset DM.

Regional Disparities in Prehospital Delay of Acute Ischemic Stroke: The Korean Stroke Registry.

BACKGROUND: Late hospital arrival keeps patients with stroke from receiving recanalization therapy and is associated with poor outcomes. This study used a nationwide acute stroke registry to investigate the trends and regional disparities in prehospital delay and analyze the significant factors associated with late arrivals. METHODS: Patients with acute ischemic stroke or transient ischemic attack between January 2012 and December 2021 were included. The prehospital delay was identified, and its regional disparity was evaluated using the Gini coefficient for nine administrative regions. Multivariate models were used to identify factors significantly associated with prehospital delays of >4.5 h. RESULTS: A total of 144,014 patients from 61 hospitals were included. The median prehospital delay was 460 min (interquartile range, 116-1912), and only 36.8% of patients arrived at hospitals within 4.5 h. Long prehospital delays and high regional inequality (Gini coefficient > 0.3) persisted throughout the observation period. After adjusting for confounders, age > 65 years old (adjusted odds ratio [aOR] = 1.23; 95% confidence interval [CI], 1.19-1.27), female sex (aOR = 1.09; 95% CI, 1.05-1.13), hypertension (aOR = 1.12; 95% CI, 1.08-1.16), diabetes mellitus (aOR = 1.38; 95% CI, 1.33-1.43), smoking (aOR = 1.15, 95% CI, 1.11-1.20), premorbid disability (aOR = 1.44; 95% CI, 1.37-1.52), and mild stroke severity (aOR = 1.55; 95% CI, 1.50-1.61) were found to independently predict prehospital delays of >4.5 h. CONCLUSION: Prehospital delays were lengthy and had not improved in Korea, and there was a high regional disparity. To overcome these inequalities, a deeper understanding of regional characteristics and further research is warranted to address the vulnerabilities identified.

Repetitive Transcranial Alternating Current Stimulation to Improve Working Memory: An EEG-fNIRS Study.

Transcranial electrical stimulation has demonstrated the potential to enhance cognitive functions such as working memory, learning capacity, and attentional allocation. Recently, it was shown that periodic stimulation within a specific duration could augment the human brain's neuroplasticity. This study investigates the effects of repetitive transcranial alternating current stimulation (tACS; 1 mA, 5 Hz, 2 min duration) on cognitive function, functional connectivity, and topographic changes using both electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). Fifteen healthy subjects were recruited to measure brain activity in the pre-, during-, and post-stimulation sessions under tACS and sham stimulation conditions. Fourteen trials of working memory tasks and eight repetitions of tACS/sham stimulation with a 1-minute intersession interval were applied to the frontal cortex of the participants. The working memory score, EEG band-wise powers, EEG topography, concentration changes of oxygenated hemoglobin, and functional connectivity (FC) were individually analyzed to quantify the behavioral and neurophysiological effects of tACS. Our results indicate that tACS increases: i) behavioral scores (i.e., 15.08, ) and EEG band-wise powers (i.e., theta and beta bands) compared to the sham stimulation condition, ii) FC of both EEG-fNIRS signals, especially in the large-scale brain network communication and interhemispheric connections, and iii) the hemodynamic response in comparison to the pre-stimulation session and the sham condition. Conclusively, the repetitive theta-band tACS stimulation improves the working memory capacity regarding behavioral and neuroplasticity perspectives. Additionally, the proposed fNIRS biomarkers (mean, slope), EEG band-wise powers, and FC can be used as neuro-feedback indices for closed-loop brain stimulation.

Resolved Proteinuria May Attenuate the Risk of Heart Failure: A Nationwide Population-Based Cohort Study.

Although proteinuria is a risk factor for heart failure (HF), proteinuria can be reversible or persistent. Our objective was to explore the link between changes in the proteinuria status and the risk of HF. We included participants from a Korean national health screening cohort who underwent health examinations in 2003-2004 and 2005-2006 and had no history of HF. Participants were categorized into four groups: proteinuria-free, proteinuria-resolved, proteinuria-developed, and proteinuria-persistent. The outcome of interest was the occurrence of HF. The study included 1,703,651 participants, among whom 17,543 (1.03%) were in the proteinuria-resolved group and 4585 (0.27%) were in the proteinuria-persistent group. After a median follow-up period of 14.04 years (interquartile range 14.19-15.07), HF occurred in 75,064 (4.41%) participants. A multivariable Cox proportional hazards regression analysis indicated that the proteinuria-persistent group had a higher risk of HF compared with the proteinuria-free group (hazard ratio (HR): 2.19, 95% confidence interval (CI): 2.03-2.36, p < 0.001). In a further pairwise comparison analysis, participants in the proteinuria-resolved group had a relatively low risk of HF compared with those in the proteinuria-persistent group (HR: 0.64, 95% CI: 0.58-0.70, p < 0.001). In conclusion, the risk of HF can change with alterations in the proteinuria status.

Association of high-estimated glomerular filtration rate with the severity of ischemic stroke during non-vitamin K antagonist oral anticoagulants therapy: a nationwide cohort study.

Aim: While the relationship between impaired kidney function and non-vitamin K antagonist oral anticoagulants (NOACs) is well established, there is limited research exploring the association between an elevated estimated glomerular filtration rate (eGFR) and the efficacy of NOACs, especially concerning the outcomes of acute ischemic stroke (AIS). This study aimed to examine the association between higher-than-normal eGFR and the severity of AIS during the use of NOACs using a nationwide multicenter stroke registry in Korea. Material and methods: This study utilized data from the Korean Stroke Registry (KSR) database, examining information from 2,379 patients with AIS, who had atrial fibrillation (AF) and a history of utilizing NOACs prior to hospitalization due to incident stroke occurring between 2016 and 2021. Patients with a history involving two or more types of anticoagulants or one or more forms of antiplatelet agents were excluded. Baseline characteristics, medical history, medication usage, CHADS2-VASc score, and the anticoagulation and risk factors in atrial fibrillation (ATRIA) score were evaluated. Renal function was assessed using eGFR levels and calculated with the Cockcroft-Gault equation. The severity of stroke was measured by the National Institutes of Health Stroke Scale as an outcome. For sensitivity analysis, further evaluation was performed using eGFR levels according to the modification of diet in renal disease (MDRD) study equation. Results: The mean age of subjects was 76.1 ± 8.9 years. The moderate-to-severe stroke severity group exhibited an elevation in creatinine levels. The eGFR of 60 to 89 mL/min/1.73 m2 group was associated with a decreased risk of moderate-to-severe stroke severity [hazard ratio (HR)] (0.77, 95% confidence interval (CI) [0.61, 0.98], p = 0.031) compared to the eGFR≥90 mL/min/1.73 m2 group. An increment of 10 units in eGFR was marginally associated with an increased risk of moderate-to-severe stroke severity (HR: 1.03, 95% CI [1.00, 1.07], p = 0.054). Conclusion: The study revealed that individuals with eGFR ≥ 90 mL/min/1.73 m2 had an association linked to an increased risk of moderate-to-severe stroke severity. Our study suggests that patients taking NOACs with higher-than-normal eGFR levels may have an increased severity of AIS.

Association between changes in predicted body composition and occurrence of heart failure: a nationwide population study.

Background: Large population-based studies on the association between changes in body composition and the occurrence of heart failure (HF) are rare. We aimed to determine the association between changes in body composition, including the predicted body fat mass index (pBFMI), predicted appendicular skeletal muscle mass index (pASMI), and predicted lean body mass index (pLBMI), and the occurrence of HF. Methods: For present study, 2,036,940 people who consecutively underwent national health examinations from 2010~2011 (baseline period) to 2012~2013 (follow-up period) were included. The pBFMI, pASMI, and pLBMI were indirectly investigated using validated anthropometric prediction equations from the Korean National Health and Nutrition Examination Survey cohort. The outcome was defined as at least two or more claims of HF. Results: During a median of 7.59 years of follow-up, 22,172 participants (event rate, 1.09%) with HF were observed. Decreased changes in the pASMI and pLBMI were associated with the occurrence of HF among males (hazard ratio [HR] 0.966, 95% confidence interval (CI) [0.944-0.988]; HR 0.939, 95%CI [0.923-0.955], respectively) and females (HR 0.924, 95%CI [0.900-0.947]; HR 0.951, 95%CI [0.939-0.963], respectively). An increased change in the pBFMI was associated with the occurrence of HF in males (HR 1.017, 95%CI [1.001-1.034]). However, paradoxically, a change in the pBFMI was associated with the occurrence of HF in females (HR 0.925, 95%CI [0.909-0.942]). Conclusion: Decreased skeletal muscle mass was related to the occurrence of HF. However, the relationship between a change in fat mass and the occurrence of HF was different and even paradoxical depending on sex.

Association of predicted body composition with occurrence of atrial fibrillation.

Background: Body mass index (BMI) is insufficient evidence as a risk factor for numerous health disorders. Body composition may be more appropriate for confirming the association with cardiovascular diseases, including atrial fibrillation (AF). This study aimed to examine the association between body composition and the occurrence of AF. Methods: A total of 2,673,108 participants (48.6% women) without AF at baseline from the Korean national health insurance data were included. Body composition including appendicular skeletal muscle mass, body fat mass, and lean body mass were indirectly measured through validated anthropometric prediction equations. The diagnosis of AF and comorbidities were defined. Results: With a median of 9.5 (interquartile range 9.2-10.1) years' follow-up, 25,841 (0.96%) cases of incident AF were included. In multivariable analysis, higher appendicular skeletal muscle was related to low risk of AF [hazard ratio (HR) 0.829, 95% confidence interval (CI) 0.753-0.912 for men (fifth quintile) and HR 0.888, 95% CI 0.792-0.995 for women (fifth quintile)]. In contrast, a higher body fat mass [HR 1.345, 95% CI 1.221-1.483 for men (fifth quintile) and HR 1.420, 95% CI 1.274-1.591 for women (fifth quintile)] and lean body mass [HR 2.241, 95% CI 2.182-2.303 for men (fifth quintile) and HR 1.516, 95% CI 1.368-1.667 for women (fifth quintile)] were associated with the occurrence of AF. Conclusions: In this study, body composition parameters were associated with the occurrence of AF. It should be noted that when appendicular skeletal muscle mass decreases and body fat mass and lean body mass increase, the risk of AF may be increased in general population except underweighted BMI group.

Association between Proteinuria Status and Risk of Hypertension: A Nationwide Population-Based Cohort Study.

Proteinuria is associated with cardiovascular disease. However, the relationship between changes in proteinuria status and hypertension remains unclear. This study aimed to explore the association between changes in proteinuria status and the risk of developing hypertension with the data from the Korean National Health Insurance Database. We included participants without prior hypertension history who underwent their first health examination in 2003-2004 and a second examination in 2005-2006. Based on their proteinuria status during these two examinations, participants were classified into four groups: the proteinuria-free, proteinuria-resolved, proteinuria-developed, and chronic proteinuria groups. The study outcome was the incidence of hypertension. The study included 935,723 participants followed for a median of 14.2 years (mean age: 40.96 ± 11.01, 62.5% male participants). During this period, 346,686 (37.1%) cases of hypertension were reported. The chronic proteinuria group had the highest hypertension risk, followed by the proteinuria-developed, proteinuria-resolved, and proteinuria-free groups (p < 0.001). Those who recovered from proteinuria had a lower risk of developing hypertension than those with chronic proteinuria (hazard ratio: 0.58; 95% confidence interval: 0.53-0.63, p < 0.001). In contrast, individuals who developed proteinuria had a higher risk of hypertension than proteinuria-free individuals (hazard ratio: 1.31; 95% confidence interval: 1.26-1.35, p < 0.001). Our findings suggest a significant association between proteinuria status changes and hypertension. Effective management of proteinuria may potentially decrease the risk of developing hypertension.

Association of high estimated glomerular filtration rate with risk of atrial fibrillation: a nationwide cohort study.

Aim: While the relationship between impaired kidney function and atrial fibrillation (AF) is well established, there is limited research exploring the association between elevated estimated glomerular filtration rate (eGFR) and AF development. This study aimed to examine the association between higher-than-normal eGFR and AF risk using a nationwide longitudinal study of the general population in Korea. Materials and methods: This study utilized the National Health Insurance Service cohort database of Korea, analyzing data from 2,645,042 participants aged 20-79 years who underwent health examinations between 2010 and 2011. Participants with a history of end-stage renal disease, renal transplantation, and AF prior to the index date were excluded. Renal function was assessed using eGFR levels, calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Baseline characteristics were gathered through questionnaires, while comorbidities and AF occurrence outcomes were identified and validated using diagnostic codes and medication histories. The study employed Kaplan-Meier survival curves and Cox proportional hazard models to evaluate the association between eGFR and AF occurrence. Results: The mean age of subjects was 48.82 ± 10.08 years. Over a median follow-up of 9.58 years, 27,469 (1.04%) AF cases were identified. The risk for AF increased in the higher-than-normal decile, as demonstrated by Kaplan-Meier survival curves (p < 0.001). The eGFR <30 mL/min/1.73 m2 group was associated with an increased risk of AF [hazard ratio (HR): 1.22, 95% confidence interval (CI) (1.01, 1.46), p = 0.039], while the eGFR >120 mL/min/1.73 m2 group was associated with a decreased risk of AF [HR: 0.88, 95% CI (0.78, 0.98), p = 0.045]. Compared to the 5th decile, the 1st [HR: 1.08, 95% CI (1.03, 1.13), p = 0.010] eGFR decile was significantly associated with an increased risk of AF, while the 10th [HR: 0.77, 95% CI (0.70, 0.85), p < 0.001] eGFR decile was significantly associated with a reduced risk of AF. Conclusion: The study revealed that individuals with eGFR>120 mL/min/1.73 m2 or those falling within eGFR 10th decile (>113.41 mL/min/1.73 m2) demonstrated an inverse association linked to a reduced risk of AF. Our study suggests that general population with higher-than-normal eGFR levels may have a lower risk of developing AF.

Assessment of nematicidal and plant growth-promoting effects of Burkholderia sp. JB-2 in root-knot nematode-infested soil.

Root-knot nematodes (RKN), Meloidogyne spp., are plant-parasitic nematodes that are responsible for considerable economic losses worldwide, because of the damage they cause to numerous plant species and the inadequate biological agents available to combat them. Therefore, developing novel and eco-friendly nematicides is necessary. In the present study, Burkholderia sp. JB-2, isolated from RKN-infested rhizosphere soil in South Korea, was evaluated to determine its nematicidal and plant growth-promoting effects under in vitro and in vivo conditions. Cell-free filtrates of the JB-2 strain showed high levels of nematicidal activity against second-stage juveniles (J2) of M. incognita, with 87.5% mortality following two days of treatment. In addition, the assessment of the activity against other six plant parasitic nematodes (M. javanica, M. hapla, M. arenaria, Ditylenchus destructor, Aphelenchoides subtenuis, and Heterodera trifolii) showed that the cell-free filtrates have a broad nematicidal spectrum. The three defense-responsive (MiMIF-2, MiDaf16-like1, and MiSkn1-like1) genes were activated, while Mi-cm-3 was downregulated when treated with cell-free filtrates of JB-2 cultures on J2. The greenhouse experiments suggested that the cell-free filtrates of the JB-2 strain efficiently controlled the nematode population in soil and egg mass formations of M. incognita in tomato (Solanum lycopersicum L., cv. Rutgers). An improvement in the host plant growth was observed, in which the shoot length and fresh weights of shoots and roots increased. The treatment with 10% of JB-2 cell-free filtrates significantly upregulated the expression levels of plant defenses (SlPR1, SlPR5, and SlPAL) and growth-promoting (ACO1, Exp18, and SlIAA1) genes compared with the corresponding parameters of the control group. Therefore, JB-2 could be a promising candidate for the sustainable management of RKN.

Use of proton pump inhibitor may be associated with progression of cerebral small vessel disease.

Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases. However, recent studies have shown that chronic PPI use is associated with the progression of endothelial senescence and cerebrovascular diseases. We hypothesized that PPI users might be vulnerable to fast progression of cerebral small vessel disease (SVD) with cumulative effects. Four hundred and eleven patients, who underwent brain magnetic resonance imaging, more than twice between January 2010 and December 2016 were screened. Patients aged < 50 years, and those who had concomitant diseases that might affect the progression of cerebral SVD were excluded. Baseline characteristics were collected. We evaluated the severity of SVD using the Fazekas score, the number of cerebral microbleeds (CMBs), and assessed the progression of SVD or CMBs based on the cumulative dose of PPIs. Among the included patients (N = 137), 39 were PPI ever-users. Univariate Cox regression analysis showed that PPI use was independently associated with the progression of Fazekas score only in the deep white matter hyperintensities (WMH) (hazard ratio [HR] 2.891, 95% confidence interval [CI] 1.210-6.906, P = 0.017). In multivariate Cox regression analysis, long-term PPI use was associated with a progression of Fazekas score in the deep WMH (HR 3.453, 95% CI 1.027-9.475, P = 0.045). However, PPI use was not associated with the progression of CMB. The present study results suggest that long-term use of PPIs is associated with the progression of deep cerebral WMH. Further research is needed using a large number of patients to validate this relationship.

Developing methylotrophic microbial platforms for a methanol-based bioindustry.

Methanol, a relatively cheap and renewable single-carbon feedstock, has gained considerable attention as a substrate for the bio-production of commodity chemicals. Conventionally produced from syngas, along with emerging possibilities of generation from methane and CO2, this C1 substrate can serve as a pool for sequestering greenhouse gases while supporting a sustainable bio-economy. Methylotrophic organisms, with the inherent ability to use methanol as the sole carbon and energy source, are competent candidates as platform organisms. Accordingly, methanol bioconversion pathways have been an attractive target for biotechnological and bioengineering interventions in developing microbial cell factories. This review summarizes the recent advances in methanol-based production of various bulk and value-added chemicals exploiting the native and synthetic methylotrophic organisms. Finally, the current challenges and prospects of streamlining these methylotrophic platforms are discussed.

Volumetric changes in gray matter after radiotherapy detected with longitudinal magnetic resonance imaging in glioma patients.

BACKGROUND AND PURPOSE: We evaluated volumetric changes in the gray matter (GM) after radiotherapy (RT) and identified factors that were strongly associated with GM volume reduction. MATERIALS AND METHODS: A total of 461 magnetic resonance imagings (MRI) from 105 glioma patients treated with postoperative RT was retrospectively analyzed. Study patients' MRIs were collected at five time points: before RT and 1 month, 6 months, 1 year, and 2 years after RT. Using the 'FastSurfer' platform, a deep learning-based neuroimaging pipeline, 73 regions were automatically segmented from longitudinal MRIs and their volumetric changes were calculated. Regions were grouped into 10 functional fields. A multivariable linear mixed-effects model was established to identify the potential predictors of significant volume reduction. RESULTS: The median age was 50 years (range, 16-86 years). Forty-seven (44.8 %) patients were female and 68 (64.8 %) had glioblastoma. Postoperative RT was delivered at 54-60 Gy with or without concurrent chemotherapy. At 2 years after RT, the median volumetric changes in the overall, ipsilateral, and contralateral GM were -3.5%, -4.5%, and -2.4%, respectively. The functional fields of cognition and execution of movement showed the greatest volume reductions. In the multivariable linear mixed model, female sex (normalized coefficient = -0.14, P < 0.001) and the interaction between age at RT and days after RT (normalized coefficient = -6.48e-6, P < 0.001) were significantly associated with GM reduction. The older patients received RT, the greater volume reduction was seen over time. However, in patients with relatively younger age (e.g., 45, 50, and 60 years for hippocampus, Broca area, and Wernicke area, respectively), the volume was not significantly reduced. CONCLUSIONS: GM volume reduction was identified after RT that could lead to long-term treatment sequelae. Particularly for susceptible patients, individualized treatment and prevention strategies are needed.

Whole-genome sequencing and analysis of Streptomyces strains producing multiple antinematode drugs.

BACKGROUND: Nematodes are parasitic animals that cause over 100 billion US dollars loss in agricultural business. The whole-genomes of two Streptomyces strains, Streptomyces spectabilis KCTC9218T and Streptomyces sp. AN091965, were sequenced. Both strains produce spectinabilin, an antinematode drug. Its secondary metabolism was examined to aid the development of an efficient nematicidal drug-producing host strain. RESULTS: The whole-genome sequences of S. spectabilis KCTC9218T and Streptomyces sp. AN091965 were analyzed using PacBio and Illumina sequencing platforms, and assembled using hybrid methodology. The total contig lengths for KCTC9218T and AN091965 were 9.97 Mb and 9.84 Mb, respectively. A total of 8,374 and 8,054 protein-coding genes, as well as 39 and 45 secondary metabolite biosynthetic gene clusters were identified in KCTC9218T and AN091965, respectively. 18.4 ± 6.45 mg/L and 213.89 ± 21.30 mg/L of spectinabilin were produced by S. spectabilis KCTC9218T and Streptomyces sp. AN091965, respectively. Pine wilt disease caused by nematode was successfully prevented by lower concentration of spectinabilin injection than that of abamectin recommended by its manufacturer. Production of multiple antinematode drugs, including spectinabilin, streptorubin B, and undecylprodigiosin was observed in both strains using high-resolution liquid chromatography mass spectrometry (LC-MS) analysis. CONCLUSIONS: Whole-genome sequencing of spectinabilin-producing strains, coupled with bioinformatics and mass spectrometry analyses, revealed the production of multiple nematicidal drugs in the KCTC9218T and AN091965 strains. Especially, Streptomyces sp. AN091965 showed high production level of spectinabilin, and this study provides crucial information for the development of potential nematicidal drug producers.

Reassessing acetyl-CoA supply and NADPH availability for mevalonate biosynthesis from glycerol in Escherichia coli.

Mevalonate is an important platform compound for the biosynthesis of isoprenoids. It can be synthesized from acetyl-CoA in the presence of nicotinamide adenine dinucleotide phosphate (NADPH) by the introduced mvaES operon in Escherichia coli. The influences of E. coli hosts, acetyl-CoA supply, and NADPH availability were assessed and engineered to improve the production titer and yield of mevalonate from glycerol. As a result, E. coli DH5α was found to be the best host with high specific capability and titer of mevalonate from glycerol. Through the engineering of phosphoketolase-phosphotransacetylase (xPK-PTA) bypass and NADPH availability, a final titer of 7.21 g/L with a specific capability of 1.36 g/g dry cell weight was gained in flask culture. Our work could offer new information to metabolically engineer the mevalonate pathway for the efficient production of isoprenoids.

Cardiovascular risk scores in asymptomatic carotid stenosis: A validation study with ultrasonographic parameters.

We evaluated the feasibility of the Framingham stroke risk score (FSRS) and atherosclerotic cardiovascular disease (ASCVD) risk scores for asymptomatic carotid stenosis (ACS). In addition, we developed novel risk prediction models for ischemic stroke and composite outcomes by combining ultrasonographic parameters and conventional cardiovascular risk scores. We retrospectively enrolled 612 patients with ACS greater than 50% over 7 years and evaluated them using transcranial Doppler and carotid duplex ultrasonography. In total, 150 patients were included in the analysis. During the mean 5-year follow-up, 6 ischemic strokes and 25 composite events were detected. Among all ultrasonographic parameters, only a higher peak-systolic velocity/end-diastolic velocity ratio was detected and significantly associated with an increased risk of relevant ischemic stroke (hazard ratio: 1.502, 95% confidence interval: 1.036-1.968). The C-statistics of the FSRS and ASCVD risk scores were 0.646 and 0.649, respectively, for relevant ischemic stroke, and 0.612 and 0.649, respectively, for composite outcomes. C-statistics of the FSRS and ASCVD risk scores combined with ultrasonographic parameters increased to 0.937 and 0.941, respectively, for ischemic stroke, and 0.856 and 0.886, respectively, for composite outcomes. The study suggests that inclusion of ultrasonographic parameters in conventional cardiovascular scores helps identify the risk of further vascular events in ACS patients.

Effect of Structural Fine-Tuning on Chelate Stability and Liver Uptake of Anionic MRI Contrast Agents.

The purpose of this study is to assess the physicochemical properties and MRI diagnostic efficacy of two newly synthesized 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-type Gd chelates, Gd-SucL and Gd-GluL, with an asymmetric α-substituted pendant arm as potential hepatocyte-specific magnetic resonance imaging contrast agents (MRI CAs). Our findings show that fine conformational changes in the chelating arm affect the in vivo pharmacokinetic behavior of the MRI CA, and that a six-membered chelating substituent of Gd-SucL is more advantageous in this system to avoid unwanted interactions with endogenous species. Gd-SucL exhibited a general DOTA-like chelate stability trend, indicating that all chelating arms retain coordination bonding. Finally, the in vivo diagnostic efficacy of highly stable Gd-SucL as a potential hepatocyte-specific MRI CA was evaluated using T1-weighted MR imaging on an orthotopic hepatocarcinoma model.

New discovery on the nematode activity of aureothin and alloaureothin isolated from endophytic bacteria Streptomyces sp. AE170020.

Endophytic bacteria, a rich source of bioactive secondary metabolites, are ideal candidates for environmentally benign agents. In this study, an endophytic strain, Streptomyces sp. AE170020, was isolated and selected for the purification of nematicidal substances based on its high nematicidal activity. Two highly active components, aureothin and alloaureothin, were identified, and their chemical structures were determined using spectroscopic analysis. Both compounds suppressed the growth, reproduction, and behavior of Bursaphelenchus xylophilus. In in vivo experiments, the extracts of strain Streptomyces sp. AE170020 effectively suppressed the development of pine wilt disease in 4-year-old plants of Pinus densiflora. The potency of secondary metabolites isolated from endophytic strains suggests applications in controlling Bursaphelenchus xylophilus and opens an avenue for further research on exploring bioactive substances against the pine wood nematode.

Adverse drug reactions of montelukast and pranlukast: Analysis of the Korea database.

BACKGROUND: Leukotriene receptor antagonists are recommended to treat asthma and allergic rhinitis. Although they had been used for a long time, recent studies have reported neuropsychiatric adverse drug reactions are associated with montelukast. OBJECTIVE: This study analyzed the adverse drug reactions of montelukast and pranlukast, which are the two most frequently prescribed leukotriene receptor antagonists, respectively in Korea. METHODS: This study retrospectively reviewed ADRs of 5,426 montelukast and 1,146 pranlukast reported in the Korea Adverse Event Reporting System between January 2014 and December 2018. RESULTS: When both drugs are classified by system organ class, the most adverse drug reactions were related to the gastro-intestinal system, followed by psychiatric events. The reported adverse drug reactions for both drugs were more common in women, and the ratio of adverse drug reactions to prescriptions was highest in the elderly. Women aged 19 to 64 years reported more than twice as many adverse drug reactions than men of the same age, and more than 5 times in insomnia. CONCLUSIONS: When prescribing montelukast and pranlukast, attention would need to digestive and sleep disorders, especially women aged 19 to 64. After prescribing montelukast, physicians would need to pay more attention to agitation (5/396378 vs 0/82475), bad or vivid dreams (6/396378 vs 0/82475), anxiety (11/396378 vs 0/82475), depression (14/396378 vs 1/82475), tremor (53/396378 vs 7/82475), irritability (5/396378 vs 1/82475), insomnia (159/396378 vs 25/82475), and headache (68/396378 vs 10/82475), compared to when prescribing pranlukast. Further prospective research needs to elucidate the relationship between neuropsychiatric events and montelukast.

Salinarimonas soli sp. nov., isolated from soil.

A light pink coloured bacterium, designated strain BN140002T, was isolated from a soil sample collected in Goesan-gun, Chungcheongbuk-do, Republic of Korea. Cells of strain BN140002T were Gram-stain-negative, aerobic, motile and rod-shaped. Phylogenetic analysis based on 16S rRNA gene sequences showed 94.7, 94.7, 93.9, 93.3, 93.4 and 93.0% similarities to Salinarimonas rosea KCTC 22346T, Salinarimonas ramus DSM 22962T, Saliniramus fredricksonii HL-109T, Microvirga soli R491T, Chelatococcus caeni EBR-4-1T and Chelatococcus composti PC-2T, respectively. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and phosphatidylethanolamine. The major cellular fatty acids were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and summed feature 1 (C12 : 0 aldehyde and/or unknown 10.98) and the predominant ubiquinone was Q-10. The genomic DNA G+C content of strain BN140002T was 70.1 mol%. The genomic orthoANI values between strain BN140002T and Salinarimonas rosea KCTC 22346T and Salinarimonas ramus DSM 22962T were 75.0 and 74.8 %, respectively. Strain BN140002T had a class I-C type CRISPR-Cas system (CRISPR-associated helicase Cas3, CRISPR-associated protein Cas8c, CRISPR-associated protein Cas7, CRISPR-associated RecB family exonuclease Cas4, CRISPR-associated protein 1, 2). Based on phenotypic, chemotaxonomic and phylogenetic data, strain BN140002T should be assigned as a novel species of the genus Salinarimonas, for which the name Salinarimonas soli sp. nov. is proposed. The type strain is BN140002T (=KCTC 42643T=CCTCC AB 2017173T).