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Importance The development of Parkinson disease (PD) may be promoted by exposure to air pollution. Objective To investigate the potential association between exposure to particulate matters (PM2.5and PM10), nitrogen dioxide (NO2), ozone (O3), sulfur dioxide (SO2), and carbon monoxide (CO) and the risk of incident PD. Design, Setting, and Participants This retrospective cohort study used data from the Korean National Health Insurance Service. Among the 1 021 208 Korean individuals in the database, those who had lived in Seoul from January 2002 to December 2006 (n = 176 875) were screened for eligibility. A total of 78 830 adults older than 40 years without PD and who lived in Seoul between January 2002 and December 2006 were included in this study. Individuals diagnosed with PD before 2006 (n = 159) and individuals 40 years or younger (n = 97 886) were excluded. Each participant was followed up with annually from January 2007 to December 2015, thereby adding up to 757 704 total person-years of follow-up. Data were analyzed from January to September 2020. Exposures Individual exposure levels to PM2.5, PM10, NO2, O3, SO2, and CO were estimated based on the participants’ residential address at the district level. To evaluate long-term exposure to air pollution, time-varying 5-year mean air pollutant exposure was calculated for each participant. Main Outcomes and Measures The outcome measure was the association between air pollution and the risk of incident PD measured as hazard ratios after adjusting for demographic factors, socioeconomic factors, and medical comorbidities. Results At baseline, the mean (SD) age of the 78 830 participants was 54.4 (10.7) years, and 41 070 (52.1%) were female. A total of 338 individuals with newly diagnosed PD were identified during the study period. Exposure to NO2was associated with an increase in risk of PD (hazard ratio for highest vs lowest quartile, 1.41; 95% CI, 1.02-1.95;Pfor trend = .045). No statistically significant associations between exposure to PM2.5,PM10, O3, SO2, or CO and PD incidence were found. Conclusions and Relevance In this large cohort study, a statistically significant association between NO2exposure and PD risk was identified. This finding suggests the role of air pollutants in PD development, advocating for the need to implement a targeted public health policy.

SUMMARY This study examines the audit pricing by the auditor of a parent company (i.e., principal auditor) when other independent auditors that are not affiliated with the principal auditor (i.e., other auditors) are involved in the audit of the group financial statements. Using Korean data, we find that audit fees charged to the parent company by the principal auditor are negatively associated with the proportion of total assets or sales of subsidiaries audited by other auditors in the pre-IFRS period. This finding is consistent with the argument that the principal auditor views subsidiaries audited by other auditors as a business opportunity to attract new clients, and thus offers fee discounts to its client. However, in the post-IFRS period, this negative relation between audit fees and the involvement of other auditors becomes insignificant or positive, suggesting that IFRS adoption restricts auditors' strategic behavior in audit pricing because IFRS adoption increases the audit complexity and risk associated with the involvement of other auditors.

Three rapidly growing mycobacterial strains, QIA-37T, QIA-40 and QIA-41, were isolated from the lymph nodes of three separate Korean native cattle, Hanwoo (Bos taurus coreanae). These strains were previously shown to be phylogenetically distinct but closely related to Mycobacterium chelonae ATCC 35752T by taxonomic approaches targeting three genes (16S rRNA, hsp6 and rpoB) and were further characterized using a polyphasic approach in this study. The 16S rRNA gene sequences of all three strains showed 99.7 % sequence similarity with that of the M. chelonae type strain. A multilocus sequence typing analysis targeting 10 housekeeping genes, including hsp65 and rpoB, revealed a phylogenetic cluster of these strains with M. chelonae . DNA–DNA hybridization values of 78.2 % between QIA-37T and M. chelonae indicated that it belongs to M. chelonae but is a novel subspecies distinct from M. chelonae . Phylogenetic analysis based on whole-genome sequences revealed a 95.44±0.06 % average nucleotide identity (ANI) value with M. chelonae , slightly higher than the 95.0 % ANI criterion for determining a novel species. In addition, distinct phenotypic characteristics such as positive growth at 37 °C, at which temperature M. chelonae does not grow, further support the taxonomic status of these strains as representatives of a novel subspecies of M. chelonae . Therefore, we propose an emended description of Mycobacterium chelonae , and descriptions of M. chelonae subsp. chelonae subsp. nov. and M. chelonae subsp. bovis subsp. nov. are presented; strains ATCC 35752T(=CCUG 47445T=CIP 104535T=DSM 43804T=JCM 6388T=NCTC 946T) and QIA-37T (=KCTC 39630T=JCM 30986T) are the type strains of the two novel subspecies.

We tested the effectiveness of a novel 13-bp hepatitis B virus (HBV)-derived cis -acting element (CAE) (ACCTCGACAAGGC), called the DT2 CAE, in augmenting transgene expression delivered by plasmid vectors in eukaryotic cells. The addition of the DT2 CAE just upstream of the start codon of several different target proteins (luciferase, EGFP, LHB, HBsAg, and MIF) in DNA plasmid constructs enhanced their translation in a posttranscriptional manner, irrespective of cell type (cell lines or primary cells) or promoter (CMV or HBV preS1 promoters), suggesting its feasibility for enhanced protein production in eukaryotic cell systems. In conclusion, a novel HBV-derived DT2 CAE could be used effectively for enhanced protein production in eukaryotic cell culture systems.

Cultivation of the smooth colony Mycobacterium abscessus at the sub-minimum inhibitory concentration (MIC) of amikacin changed its growth pattern including its colony morphology (smooth to rough) and cell arrangement (dispersed to cord formation). In addition, reduced sliding motility and biofilm formation were observed. The amount of glycogpetidolipid (GPL) and mRNA expression of key genes involved in GPL synthesis were decreased in the amikacin-treated M. abscessus strain. An in vitro infection assay revealed that the amikacin-treated smooth M. abscessus strain induced more pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) than that of the smooth strain in murine macrophage cells. These results suggest that long-term exposure to a low concentration of amikacin causes a physical change in the cell wall which may increase its virulence.

Objective Odontoid fracture is common in cervical injury, representing about 20% of total cervical fractures. Classic odontoid fracture classification focused on anatomy of fracture site has no treatment recommendation and a modified treatment-oriented classification of odontoid fracture was suggested in 2005. We reviewed our odontoid fracture patients to assess the feasibility and efficacy of Grauer’s classification. Methods Between October 2000 and September 2015, we collected data from patients who came to our institute for odontoid fracture. Demographic data of patients was reviewed, and neck visual analog scale (VAS) score and fusion rate were assessed by reviewing electronic medical records retrospectively. Results Sixty-nine patients out of a total of eighty two odontoid fracture patients were reviewed according to Grauer’s classification. Neck VAS of all subtypes in odontoid fracture classification were decreased at last follow-up (p=0.001). Overall fusion rate was 88.4% at last follow-up. Concordance rate between Grauer’s recommendation and our treatment was 69.9%, especially in type II with the concordance higher than 80%. Complication was minimal representing 7.2%, only in types I and III. Conclusion In this study, there were statistically significant improvement in all subtypes in terms of neck VAS at the last follow up, especially in types II and III. Grauer’s classification appears to be meaningful to decide treatment plan for odontoid fractures, especially type II odontoid fracture.

Background There are several treatment modalities for vertebral dissecting aneurysms. The purpose of this study was to evaluate the efficacy and safety of triple stent therapy for intracranial vertebral dissecting aneurysm (VDA). Methods Eight patients with 9 VDAs underwent multiple stent insertion therapy. Seven patients who presented with progressive ischemic symptoms and showed changes in follow-up images underwent triple stent insertion therapy, and 1 patient who presented with subarachnoid hemorrhage underwent double stent therapy twice and 1 additional single stent therapy with coil embolization (total 5 stents). Safety, technical feasibility, clinical, and imaging follow-up data for triple stent therapy were retrospectively evaluated. Results Triple stent deployment for VDAs was successfully performed in all 9 VDAs without any procedure-related complication. Among them, 8 unruptured VDAs showed near normalization on follow-up imaging studies within 90 days after the procedure. One case of ruptured VDA showed repeated recurrence without new symptoms and delayed normalization after insertion of 5 stents. Seven patients with long-term follow-up (median clinical follow-up, 22.6 months; median imaging follow-up, 17.1 months) showed clinical and imaging improvement without development of new symptoms. Conclusions Triple stent therapy for VDAs was safe and effective. This technique showed favorable results in clinical and imaging follow-up for unruptured VDAs, although caution is advised for ruptured VDAs.

OBJECTIVE Solid bone fusion is an essential process in spinal stabilization surgery. Recently, as several minimally invasive spinal surgeries have developed, a need of artificial bone substitutes such as demineralized bone matrix (DBM), has arisen. We investigated the in vivo bone growth rate of DBM as a bone void filler compared to a local autologous bone grafts. METHODS From April 2014 to August 2015, 20 patients with a one or two-level spinal stenosis were included. A posterior lumbar interbody fusion using two cages and pedicle screw fixation was performed for every patient, and each cage was packed with autologous local bone and DBM. Clinical outcomes were assessed using the Numeric Rating Scale (NRS) of leg pain and back pain and the Korean Oswestry Disability Index (K-ODI). Clinical outcome parameters and range of motion (ROM) of the operated level were collected preoperatively and at 3 months, 6 months, and 1 year postoperatively. Computed tomography was performed 1 year after fusion surgery and bone growth of the autologous bone grafts and DBM were analyzed by ImageJ software. RESULTS Eighteen patients completed 1 year of follow-up, including 10 men and 8 women, and the mean age was 56.4 (32-71). The operated level ranged from L3/4 to L5/S1. Eleven patients had single level and 7 patients had two-level repairs. The mean back pain NRS improved from 4.61 to 2.78 (p=0.003) and the leg pain NRS improved from 6.89 to 2.39 (p

To evaluate the volume and position of the temporomandibular joint structures, specifically the glenoid fossa and the condylar head, in patients with facial asymmetry.Fifty-six adult patients were divided into two groups-asymmetry group and control group-based on the severity of the mandibular asymmetry, as seen on their orthopantomograms. The volumes and positions of the bilateral temporomandibular joint components were measured by using computed tomography images and a three-dimensional analysis program. Each of the variables was compared between and within the groups.The volumes of the condyle and the glenoid fossa on the side of the smaller condyle were significantly smaller in the asymmetry group (P .05) than in the control group. The volumetric ratios of the glenoid fossa and the joint space to the condyle were also significantly higher on that side (P .001). The distance of the uppermost point of the glenoid fossa from the midaxial plane in the smaller condyle was significantly shorter (P .05) only in the asymmetry group.When evaluating mandibular asymmetry, the volume of the glenoid fossa and the volume and vertical position of the condylar head need to be considered in addition to length or width of the condylar head.

Background: Genetic variants may play a role in determining the location of cerebral atherosclerosis. We aimed to investigate the association between RNF213, MMP2, and genetic polymorphisms linked to vascular tortuosity with the location of cerebral arterial atherosclerosis. Methods: A prospective case-control study was conducted on patients with ischemic stroke and age- and sex-matched stroke-free controls. The stroke patients were categorized into those with intracranial artery atherosclerosis (ICAS), extracranial artery atherosclerosis (ECAS), and small vessel occlusion (SVO). Six single nucleotide polymorphisms (SNPs) including rs2118181 (FBN1), rs2179357 (SLC2A10), rs1036095 (TGFBR2), rs243865 (MMP2), rs1800470 (TGFB1), and rs112735431 (RNF213) were analyzed with the TaqMan Genotyping Assay, and the distribution of genotypes across groups was compared. Results: None of the 6 SNPs were associated with stroke on comparing the 449 stroke patients (71 with ECAS, 169 with ICAS, and 209 with SVO) to the 447 controls. In the subgroup analysis, the adjusted odds ratios (aORs) for age and sex indicated a significant association between rs112735431 and ICAS in the allele comparison analysis and in the additive and dominant model analyses. rs112735431 was associated with anterior circulation involvement and increased burden of cerebral atherosclerosis. rs2179357 was significantly associated with ICAS in the recessive model analysis, and rs1800470 was significantly associated with ECAS in the recessive model analysis when compared to controls. Conclusion: rs112735431 was associated with ICAS and increased atherosclerosis burden in Korean stroke patients. Further studies are needed to elucidate the role of rs112735431 and to confirm the association of rs2179357 and rs1800470 with cerebral atherosclerosis.

Influenza is an epidemical acute respiratory disease caused by viral infection. Several complications in the respiratory tract, such as pneumonia can occur. However, rare but serious neurological complications are also observed. Here, we described the prevalence, characteristics and suggestive pathomechanism of syncope after influenza infection season. Of 2.2% of patients diagnosed as influenza experienced syncope. None of the patients had severe cough, low blood pressure (BP) or dehydration. Patients suffered with frequent dizziness before syncope. Patient with long duration of loss of consciousness was more observed in those with high fever or positive orthostatic BP drop., Graphical Abstract

Background: Though several neuroprotective agents have been evaluated as potential treatments for acute ischemic stroke, none have demonstrated a definitive treatment efficacy, which remains elusive. HT047 is an herbal extract of Scutellaria baicalensis and Pueraria lobata, both of which have been widely used to treat ischemic stroke in traditional Korean medicine. The aims of this trial are to investigate whether HT047 can improve neurologic status, particularly motor function, in acute ischemic stroke patients, and to determine the safety of HT047. Methods: A multicenter, double-blind, randomized, placebo-controlled, 3-arm parallel group, phase II trial will be conducted in patients who have had an acute ischemic stroke within the past 14 days. The participating patients must have a Fugl-Meyer assessment (FMA) motor score ≤55, with arm or leg weakness, and Korean version of the National Institutes of Health Stroke scale (K-NIHSS) score of ≥4 and ≤15. Seventy-eight participants will be randomized in a 1:1:1 ratio and given high-dose HT047 (750 mg 3 times a day), low-dose HT047 (500 mg 3 times a day), or a placebo for 12 weeks. The primary endpoint is the change in FMA motor score between baseline and week 12. Secondary endpoints are as follows: the change in FMA motor score at weeks 4 and 8 from baseline; the change in FMA motor score at weeks 4, 8, and 12 from baseline according to the timing of treatment initiation (either within 1 week, or 1–2 weeks), or according to the presence of prognostic risk factors (hypertension, diabetes, dyslipidemia, etc); the change in K-NIHSS and Korean versions of the modified Rankin scale (K-mRS) and the modified Barthel index at weeks 4 and 12 from baseline; and the proportion of subjects at week 12 with a K-NIHSS score of 0 to 2, or with K-mRS scores of 0, ≤1, and ≤2. Discussion: This study is a 1st-in-human trial of HT047 to explore the efficacy and safety in acute ischemic stroke patients. The results will provide the appropriate dosage and evidence of therapeutic benefit of HT047 for stroke recovery. Trial registration: ClinicalTrials.gov (NCT02828540) Registered July 11, 2016.

Background and Purpose— We performed a systematic review and meta-analysis to explore the efficacy and safety of cilostazol as a mono or combination (plus aspirin or clopidogrel) treatments compared to conventional single antiplatelet therapy (SAPT, mainly aspirin) for secondary stroke prevention. Methods— Randomized controlled trial studies were searched across multiple comprehensive databases (MEDLINE, EMBASE, and Cochrane) for review. The primary outcome was recurrent stroke comprising ischemic and hemorrhagic stroke. Secondary outcomes included ischemic stroke, hemorrhagic stroke, myocardial infarction, and composite outcomes. We performed an updated systematic review and meta-analysis of the identified reports, including 2 recently published randomized controlled trials. In addition, network meta-analysis was performed to compare the relative effects of mono versus combination cilostazol treatments. Results— Ten studies were included in this review, 5 of which were assigned to the cilostazol mono group (n=5429) and the other 5 to the combination group (n=2456). The relative risks of recurrent stroke, ischemic stroke, and composite outcomes with cilostazol mono as well as combination treatments were significantly lower than with SAPT without any significant heterogeneity. An indirect comparison of these 3 outcomes revealed the cilostazol combination approach to be superior. The cilostazol mono treatment diminished hemorrhagic stroke more significantly than SAPT and the cilostazol combination did not increase hemorrhagic stroke compared to SAPT. The outcomes from the 2 cilostazol regimens were comparable to SAPT in the case of myocardial infarction. Conclusions— Cilostazol is a more effective and safer treatment option than SAPT approaches using mainly aspirin. Cilostazol regimens can also be modified to clinical situations as this drug reduces recurrent and ischemic stroke more efficiently as a combination therapy but is more beneficial for hemorrhagic stroke as a monotherapy.

A therapeutic strategy capable of skewing toward a Th1-type immune response is crucial for cancer treatment. Recently, we reported Mycobacterium paragordonae (Mpg) as a potential live vaccine for mycobacterium infections. In this study, we explored the immunotherapeutic potential of heat-killed Mpg (HK-Mpg) in a mouse tumor xenograft model and elucidated its underlying antitumor mechanisms. MC38 cells derived from murine colon adenocarcinoma were implanted by subcutaneously injecting mice. The anticancer effects of HK-Mpg therapy were compared with HK-M. bovis BCG, an effective adjuvant for cancer immunotherapy. HK-Mpg treatment enhanced tumor reduction and mouse survival. Furthermore, HK-Mpg treatment synergistically enhanced the anticancer therapeutic effect of cisplatin. In addition, HK-Mpg enhanced inflammatory cytokine production and recruitment of immune cell into tumor-infiltrating sites and splenocytes in vaccinated mice. Our mechanistic study demonstrates that HK-Mpg therapy elicits a strong antitumor immune response in mice, mainly through natural killer cell-mediated oncolytic activity via the activation of dendritic cells (DCs) and by enhancing inflammatory cytokines production such as IL-12 from DC. Hence, HK-Mpg can be a potential immunotherapy adjuvant, enhancing the effect of cancer chemotherapy.

Background: We investigated the effect of D-dimer levels and efficacy of different antithrombotic therapies according to the baseline D-dimer levels on recurrent stroke in patients with atrial fibrillation (AF)-related stroke and atherosclerosis. Methods: We enrolled 1441 patients with AF-related stroke and atherosclerosis in this nationwide multicenter study. The primary outcome measure was the occurrence of recurrent ischemic stroke over a 3-year period. Results: High D-dimer levels (&ge, 2 &mu, g/mL) were significantly associated with higher risk of recurrent ischemic stroke (adjusted hazard ratio (HR), 1.80, 95% confidence interval (CI), 1.13&ndash, 2.84, p = 0.012). The risk of recurrent stroke was similar between the anticoagulant and the antiplatelet groups in all subjects (adjusted HR, 0.78, 95% CI, 0.46&ndash, 1.32, p = 0.369). However, in patients with high D-dimer levels (&ge, g/mL), risk of recurrent stroke was significantly lower in the anticoagulant group than in the antiplatelet group (adjusted HR, 0.40, 95% CI, 0.18&ndash, 0.87, p = 0.022). Conclusion: Our findings suggested that baseline D-dimer levels could be used as a risk assessment biomarker of recurrent stroke in patients with AF-related stroke and atherosclerosis. High D-dimer levels would facilitate the identification of patients who are more likely to benefit from anticoagulants to ensure secondary prevention of stroke.

Background and Purpose The outcome of endovascular treatment (EVT) may differ depending on the etiology of arterial occlusion. This study aimed to assess the differences in EVT outcomes in patients with intracranial arterial steno-occlusion (ICAS-O), artery-to-artery embolism (AT-O), and cardiac embolism (CA-O).Methods We retrospectively analyzed 330 patients with ischemic stroke who underwent EVT between January 2012 and August 2017. Patients were classified according to the etiology. The clinical data, EVT-related factors, and clinical outcomes were compared. The modified Rankin Scale (mRS) score at 3 months, determined using ordinal logistic regression (shift analysis), was the primary outcome.Results CA-O (n=149) was the most common etiology, followed by ICAS-O (n=63) and AT-O (n=49). Age, initial National Institutes of Health Stroke Scale (NIHSS) score, and rate of hemorrhagic transformation were significantly higher in patients with CA-O compared to AT-O and ICAS-O. The time from onset-to-recanalization was the shortest in the CA-O (356.0 minutes) groups, followed by the AT-O (847.0 minutes) and ICAS-O (944.0 minutes) groups. The rates of successful recanalization, mRS distribution, and favorable outcomes at 3 months (mRS 0–2; CA-O, 36.9%, AT-O, 53.1%; and ICAS-O, 41.3%) did not differ among the three groups. Baseline NIHSS score (odds ratio, 0.87; 95% confidence interval, 0.83 to 0.91) could independently predict a favorable shift in mRS distribution.Conclusions The functional outcomes of ICAS-O and AT-O were similar to those of CA-O, despite the delay in symptom onset-to-recanalization, suggesting that the therapeutic time window may be extended in these patients.

Background and purpose We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial fibrillation. Methods The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K-ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence. Results Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance [103 episodes (31.3%)] followed by extracranial bleeding [96 episodes (29.2%)]. Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2 DS2 -VASc score were not significantly different between patients with and without recurrent stroke. Conclusions A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.

Hepatitis B virus infection is a serious global health problem and causes life-threatening liver disease. In particular, genotype C shows high prevalence and severe liver disease compared with other genotypes. However, the underlying mechanisms regarding virological traits still remain unclear. This study investigated the clinical factors and capacity to modulate Type I interferon (IFN-I) between two HBV polymerase polymorphisms rt269L and rt269I in genotype C. This report compared clinical factors between rt269L and rt269I in 220 Korean chronic patients with genotype C infections. The prevalence of preC mutations between rt269L and rt269I was compared using this study's cohort and the GenBank database. For in vitro and in vivo experiments, transient transfection using HBV genome plasmid and HBV virion infection using HepG2-hNTCP-C4 and HepaRG systems and hydrodynamic injection of HBV genome into mice tails were conducted, respectively. This report's clinical data indicated that rt269I vs. rt269L was more significantly related to HBV e antigen (HBeAg) negative serostatus, lower levels of HBV DNA and HBsAg, and disease progression. Our epidemiological study showed HBeAg negative infections of rt269I infections were attributed to a higher frequency of preC mutations at 1896 (G to A). Our in vitro and in vivo studies also found that rt269I could lead to mitochondrial stress mediated STING dependent IFN-I production, resulting in decreasing HBV replication via the induction of heme-oxygenase-1. In addition, we also found that rt269I could lead to enhanced iNOS mediated NO production in an IFN-I dependent manner. These data demonstrated that rt269I can contribute to HBeAg negative infections and liver disease progression in chronic patients with genotype C infections via mitochondrial stress mediated IFN-I production.

Mycobacterium paragordonae (Mpg) is a temperature-sensitive Mycobacterium species that can grow at permissive temperatures but fails to grow above 37°C. Due to this unique growth trait, Mpg has recently been proposed as a novel live vaccine candidate for the prevention of mycobacterial infections. Furthermore, the increasing frequency of the isolation of Mpg from water supply systems led us to hypothesize that the free-living amoeba system is the natural reservoir of Mpg. In this study, we report the complete 6.7-Mb genome sequence of Mpg and show that this genome comprises four different plasmids with lengths of 305 kb (pMpg-1), 144 kb (pMpg-2), 26 kb (pMpg-3), and 17 kb (pMpg-4). The first two plasmids, pMpg-1 and -2, encode distinct Type VII secretion systems (T7SS), ESX-P5 and ESX-2, respectively. Genome-based phylogeny indicated that Mpg is the closest relative to M. gordonae, which has a 7.7-Mb genome; phylogenetic analysis revealed an average of 86.68% nucleotide identity between these two species. The most important feature of Mpg genome is the acquisition of massive genes related to T7SS, which may have had effect on adaptation to their intracellular lifestyle within free-living environmental predators, such as amoeba. Comparisons of the resistance to bacterial killing within amoeba indicated that Mpg exhibited stronger resistance to amoeba killing compared to M. gordonae and M. marinum, further supporting our genome-based findings indicating the special adaptation of Mpg to free-living amoeba. We also determined that, among the strains studied, there were more shared CDS between M. tuberculosis and Mpg. In addition, the presence of diverse T7SSs in the Mpg genome, including an intact ESX-1, may suggest the feasibility of Mpg as a novel tuberculosis vaccine. Our data highlight a significant role of lateral gene transfer in the evolution of mycobacteria for niche diversification and for increasing the intracellular survival capacity.

Background Although vascular abnormality is an uncommon comorbidity of neurofibromatosis type 1 (NF1), it is potentially fatal. We present spontaneous hemothorax caused by rupture of a vertebral artery (VA) aneurysm in a patient with NF1. Case Description A 36-year-old man with a history of NF1 was transferred to the emergency department with dyspnea. Chest computed tomography scan revealed hemothorax in the left lung field with mediastinal shifting and aneurysmal dilatation of the left VA at the C6 vertebra level. Immediate drainage of the hematoma by chest tube insertion was performed. Diagnostic angiogram showed a 3- to 4-cm fusiform aneurysm of the VA. After the angiogram, cardiopulmonary arrest occurred after a rebleed of the VA aneurysm. The aneurysmal segment of the VA was urgently occluded with detachable coils. Postoperatively, the patient was in intensive care for 1 month because of fulminant pneumonia. After the patient regained consciousness, he was found to have right hemiparesis from a small infarction at the pons. The patient's function improved to near normal after 1 year of recovery. Conclusions Hemothorax caused by VA rupture in a patient with NF1 is an extremely rare condition that can be fatal. Careful examination with suspicion for early detection and treatment is required for this urgent condition. Endovascular coiling was safe even for an unstable patient with massive bleeding.

Aim: Development of atherosclerotic plaques is affected by vascular geometry and hemodynamics. Hemodynamics in the basilar artery (BA) is unique as the flow converges from vertebral arteries (VAs). Here, we investigated the characteristics of BA plaque based on VA and BA geometry. Methods: Consecutive patients evaluated using high-resolution magnetic resonance imaging (MRI) at a general health center were screened. Geometric characteristics of VA (VA dominancy and VA-BA angles) and BA (BA convexity and BA angles) were assessed. The burden of BA plaques was investigated in each wall (anterior, posterior, left, and right lateral). The characteristics of BA plaques were compared according to VA dominancy (right vs. left), BA angle of lateral view (lateral mid-BA angle; dichotomized), and total plaque burden (divided by tertiles). Results: Of the 1029 subjects, BA plaques were observed in 98 (9.5%) patients, and were more frequently located at the anterior wall (32.4%) and posterior wall (35.0%) than the right wall (15.3%) and left lateral wall (17.6%). Right and left lateral plaques were more frequent in the left and right convex BA, respectively (p = 0.009 and p = 0.024, respectively). Anterior plaques were more frequently observed in low lateral mid-BA angle (p = 0.043). BA plaques were predominant in anterior and posterior walls in patients with lower plaque burden, whereas they were predominant in right and left lateral walls in patients with higher plaque burden (p = 0.001 and p = 0.025, respectively). Conclusions: Asymptomatic BA plaque location was associated with BA convexity and lateral mid-BA angle. The anteriorly and posteriorly located BA plaques may extend to the lateral walls as the plaque burden increases.

Acupuncture is widely used in Asian countries. A 27-year-old man visited our center with a newly developed orthostatic headache. A few weeks previously, he had undergone multiple and repetitive acupunctures at the low back (L3-S1) to relieve pain, which remained after laminectomy and interbody fusion (L4-S1) for the last few years. CSF drops were observed from the skin at the left low back (figure 1). Brain MRI was normal. CSF leakage with fistula formation was confirmed by magnetic resonance myelography (figure 2).1 Duroplasty (L4-5) with primary suture of the fistula was performed and the headache improved.

BACKGROUND High blood pressure variability (BPV) is associated with recurrent stroke. We investigated the association between BPV, new ischemic lesions (NILs), and white matter lesion (WML) growth in patients with ischemic stroke due to intracranial atherosclerosis (ICAS). METHODS This study was performed as a post-hoc analysis of the STABLE-ICAS trial, which enrolled subacute ischemic stroke patients with symptomatic ICAS (>50% stenosis) and hypertension. BPV was measured at the office (visit by visit) and at home (day by day). Patients were divided into 3 groups (tertiles) according to their home BPV. WML growth and the occurrence of NILs were compared among the 3 groups. Multivariable analyses were performed to identify the independent risk factors of WML growth and NILs. RESULTS Of the 111 enrolled patients, 69 patients (67.6%) demonstrated WML growth and 15 patients (13.7%) had NILs. Patients with higher BPV demonstrated a more WML growth (50% vs. 61.8% vs. 83.8; P = 0.02, by tertiles) and more NILs (5.4% vs. 5.4% vs. 29.7%; P = 0.002, by tertiles). In multivariable analyses, old age [odds ratio (OR) = 1.052 (95% confidence interval (CI) = 1.005–1.101); P = 0.03] and home BPV [OR = 1.149 (95% CI = 1.013–1.304); P = 0.02] were independently associated with WML growth. Low mean diastolic blood pressure [OR = 0.913 (95% CI = 0.874–0.984); P = 0.02] and high home BPV [OR = 1.287 (95% CI = 1.086–1.526); P = 0.004] were independently associated with NILs at follow-up. CONCLUSIONS High BPV is associated with WML growth and NIL in ischemic stroke patients with symptomatic ICAS. BPV monitoring at home may be helpful.

Background: While transthoracic echocardiography (TTE) is performed to find out potential embolic sources and certain cardiac abnormalities as a routine workup of stroke, clinical implication of echocardiographic findings for long-term outcomes in atrial fibrillation (AF)-related stroke patients has been unknown. Methods: This was a sub-study of K-ATTENTION (Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts), a multicenter-based cohort composed of prospective stroke registries from 11 tertiary centers. All stroke survivals enrolled in this study underwent TTE during hospitalization. Echocardiographic findings included left atrial (LA) diameter, left ventricular ejection fraction (LVEF), LV end-diastolic dimension (LVEDV), stenosis and regurgitation of mitral and aortic valves, and peak trans-mitral filling velocity/mean mitral annular velocity during early diastole (E/e’ ratio). Indexed-LA size was acquired as dividing LA size by body surface area. LV systolic function was grouped into normal (LVEF≥55%), mild (55%>LVEF>40%), and severe (LVEF≤40%). Level of E/e’ ratio associated with LV filling pressure was divided into normal ( Results: A total of 1952 patients were finally included. Over a mean follow-up of 1.72±1.31 years, 140 patients had recurrent stroke, 36 had coronary artery disease, and of 236 fatalities, 33 died of a vascular cause. Multivariable analyses demonstrated that severe LV systolic dysfunction was associated with a higher risk of coronary artery disease (hazard ratio [HR] 3.80, 95% confidence interval [CI] 1.53-9.41), vascular death (HR 3.59, 95% CI 1.42-9.10) and all-cause death (HR 2.29, 95% CI 1.47-3.56). Conclusions: LV ejection fraction could be important predictor for long-term outcomes in AF-related stroke.

Background: The importance of antiplatelet failure due to antiplatelet resistance may differ between those receiving mono antiplatelet and dual antiplatelet treatment (DAPT). Smoking is a well-known factor which influences the resistance of clopidogrel. Here, we compared antiplatelet resistance between those who receive mono and dual antiplatelet treatment and between smokers and non-smokers Methods: We have consecutively enrolled patients who experienced ischemic stroke under antiplatelet treatment. First, patients were divided in to three groups according to the antiplatelet treatment at the time of stroke; aspirin, clopidogrel and DAPT. Demographics, conventional risk factor and aspirin (ARU) and P2Y12 reaction unit (PRU) measured by VerifyNow was compared between the three groups. Among those who received DAPT, patients were dichotomized to smokers and non-smokers. ARU and PRU were compared between the two groups. Results: Among 783 patients, 485 patients were under aspirin, 133 patients under clopidogrel and 165 patients under DAPT. There was no significant difference in demographics and risk factor among three groups. However, ARU was higher in those under aspirin than DAPT (482.00±73.12 vs. 453.02±82.94; p=0.001), and PRU was higher in those under clopidogrel than DAPT (257.79±92.82 vs. 225.71±87.71; p=0.013). Among those under DAPT, 88 patients were non-smokers and 76 patients were smokers. Smokers were younger, more male, but had less hypertension. The ARU was similar between the two groups, PRU was significantly lower in the smoker group (195.95±80.66 vs. 245.98±85.31, p=0.004). Conclusion: Antiplatelet resistance may be more important in those receiving mono antiplatelet than in those receiving DAPT. Therefore, selecting antiplatelet agent may be more critical in those receiving mono antiplatelet. Smoking paradox was also confirmed in stroke population and can be considered in determining antiplatelet treatment strategy.

Background: White matter lesion (WML) is associated with future stroke risk and cognitive decline. Though antiplatelet treatment strategy is important in the prevention of secondary stroke, the effect on WML volume change is not clarified yet. Methods: This study was performed by a post-hoc analysis of PICASSO study which compared the efficacy and safety of cilostazol versus aspirin in patients with small vessel disease. Among those who have a follow-up imaging data, change of WML volume was measured quantitatively and automatically. Segmented lesion maps of different time points were compared using the longitudinal pipeline. The absolute difference was compared between aspirin and cilostazol. Factors associated with the change of WML volume were analyzed. Result: Among those enrolled in PICASSO trial, 505 patients (254 in aspirin group and 251 in cilostazol group) was measured. WML volume decreased 0.5±11.6cc at follow-up. There was no difference in WML change between cilostazol and aspirin (-0.7±12.5cc vs. -0.2±10.6; p=0.60). Old age (r=0.12, p=0.006), diabetes (p=0.03) and longer follow-up period (r=0.11; p=0.012) was associated with increase of WML. Interestingly, the presence of diabetes was associated with increased WML in aspirin group (2.4±10.3cc vs. -1.5±10.6cc; p=0.006), but not in cilostazol group (-0.3±15.0cc vs, -0.9±11.4cc; p=0.7; p for interaction=0.15). Furthermore, WML increased in aspirin group significantly with low initial systolic blood pressure (r=0.20, p=0.02), but not in cilostazol group (p=0.75; p for interaction=0.01). Conclusion: Though there is no significant difference in WML change between cilostazol and aspirin treatment, factors associated with WML change may differ according to antiplatelet treatment.

Background and Purpose: Little is known about the different effect of outcomes and factors associated with vascular outcomes in stroke patients with atrial fibrillation in real world practice setting especially in Korea. In this study, we investigated the effect of each oral anticoagulants on vascular outcomes using K-ATTENTION (Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts) study. Methods: Consecutive data of acute stroke patients with atrial fibrillation were collected from 11 centers in Korea from January 2013 to December 2015. Eligibility of inclusion was acute stroke within 7 days from the onset of stroke and diagnosis of non-valvular or valvular atrial fibrillation. Vascular outcomes included ischemic stroke, hemorrhagic stroke, death of any cause, and major adverse cerebro/cardiovascular events (MACE). To describe the effect of each oral anticoagulants on vascular outcomes, we performed time-dependent Cox’s regression analyses with the class of oral anticoagulant as a time dependent covariate. For stroke, hemorrhagic stroke, and any stroke, death was considered as competing risk. Results: Among 3213 stroke patients included in K-ATTENTION study, a total 3033 stroke patients (mean age 73.45 ± 9.93 years old, female 48.5%) were included. Mean CHA2DS2-VASc score was 4.89 ± 1.37. During the study period, a total of 161 ischemic strokes, 46 hemorrhagic strokes, 199 any strokes, 556 death and 720 MACE were captured. Time-dependent Cox’s regression analysis revealed that use of oral anticoagulants [vitamin K antagonist (VKA), dabigatran, rivaroxaban, or apixaban] was associated with significantly lower risk of death and MACE compared with no oral anticoagulants use. Although, there was no difference among oral anticoagulants for ischemic stroke, hemorrhagic stroke, or any stroke when compared with no oral anticoagulants, dabigatran showed a trend of reduced risk of any stroke (HR 0.48, 95%CI 0.23 - 1.01, p = 0.0545). Conclusion: This real-world data revealed that the use of oral anticoagulants was associated with the reduced risk of MACE and death. However, for ischemic stroke and hemorrhagic stroke, the results were not conclusive. Dabigatran showed a trend of reduced risk of any stroke.

Background: Clinical and radiological characteristics of middle cerebral artery (MCA) infarction may differ according to the location of occlusion. Objectives: We investigated the difference between proximal and distal symptomatic MCA occlusion (MCAO) in patients with ischemic stroke. The factors associated with the imaging characteristics were also analyzed. Methods: Patients with ischemic stroke due to MCAO were consecutively enrolled. The location of MCAO was determined by the ratio of the length of the ipsilesional MCA to that of the contralateral MCA and dichotomized to proximal and distal MCAO. Clinical and radiological characteristics were compared between patients with proximal and distal MCAO. Factors associated with the basal ganglia (BG) involvement, hemorrhagic transformation (HT), and neurological change during admission were investigated. Results: Among 181 included patients, MCAO location showed a bimodal peak (at the proximal [n = 99] and distal MCA [n = 82]). Proximal MCAO was more frequently associated with hyperlipidemia and large artery atherosclerosis, whereas distal MCAO was more frequently associated with hypertension, atrial fibrillation, and cardioembolic stroke. BG involvement was similar between the 2 groups (48 vs. 39%; p = 0.21), whereas HT was more frequent in distal MCAO (10 vs. 23%; p = 0.02). Among patients with proximal MCAO, hyperintense vessel sign was less frequently observed in those with a BG involvement than those without (38 vs. 60%; p = 0.03). Among those without BG involvement, the presence of HT was very low and similar between patients with proximal and distal MCAOs (1.9 vs. 2.0%). However, in patients with BG involvement, HT was more frequently observed in those with distal MCAO than in those with proximal MCAO (54.8 vs. 15.7%; p < 0.001). The presence of hyperintense vessel sign (OR 0.172, 95% CI 0.051–0.586; p = 0.005) and distal MCAO (OR 0.200, 95% CI 0.059–0.683; p = 0.011) was independently associated with improvement during admission. Conclusion: Proximal MCAO is more frequently associated with atherosclerosis, whereas distal MCAO is more frequently associated with cardioembolism. In proximal MCAO, the status of collateral flow presented by hyperintense vessel sign may affect the involvement of BG. In distal MCAO, distal migration of the embolus, which first impacted at the proximal MCA causing BG ischemia, may explain the high rate of HT by reperfusion injury. Hyperintense vessel sign and distal MCAO were independently associated with neurological improvement during admission.

Hepatitis B virus (HBV) infection is a global health problem that causes a wide range of pathological outcomes, including cirrhosis and hepatocellular carcinoma (HCC). Endoplasmic reticulum (ER) stress induction by HBV infection has been implicated in liver carcinogenesis and disease progression with chronic inflammation via enhanced inflammation, oxidative stress-mediated DNA damage, and hepatocyte proliferation. In the natural course of HBV infection, the accumulation of naturally occurring mutations in the HBV genome can generate several mutant types of HBV-encoded proteins, including three different proteins in the S ORF (SHBs, MHBs, and LHBs) and HBcAg in the C ORF, which could contribute to enhanced ER stress in infected hepatocytes mainly via increased ER accumulation of mutant proteins. However, it seems that there may be distinct capacity and pathway in ER stress-induction and distinct resulting clinical outcomes between HBV variants. In addition, the role of HBxAg mutations in ER stress remains unknown. However, it has been reported that HBxAg itself could exert ER stress in infected cells, resulting in HCC generation in chronic HBV patients. To date, review papers regarding ER stress-mediated HBV mutation have been limited into a specific mutation type: preS2 deletion. So, in this review, we will discuss details about various mutation types in all four regions of the HBV genome (preS1, preS2, S, and C) related to ER stress and their distinct ER stress mechanisms and clinical outcomes in terms of mutation types.

Mycobacterium abscessus complex (MAB) is a rapidly growing mycobacterium(RGM) whose clinical significance as an emerging human pathogen has been increasing worldwide. It has two types of colony morphology, a smooth (S) type, producing high glycopeptidolipid (GPL) content, and a rough (R) type, which produces low levels of GPLs and is associated with increased virulence. However, the mechanism responsible for their difference in virulence is poorly known. By ultrastructural examination of murine macrophages infected, we found that MAB-R strains could replicate more actively in the macrophage phagosome than the S variants and that they could escape into cytosol via phagosomal rupture. The cytosolic access of MAB-R strains via phagosomal rupture led to enhanced Type I interferon (IFN) production and cell death, which resulted in their cell-to-cell spreading. This behavior can provide an additional niche for the survival of MAB-R strains. In addition, we found that their enhancement of cell death mediated cell spreading are dependent on Type I IFN signaling via comparison of wild-type and IFNAR1 knockout mice. In conclusion, our data indicated that a transition of MAB-S strains into MAB-R variants increased their virulence via enhanced Type I IFN production, which led to enhanced survival in infected macrophage via cell death mediated cell-to-cell spreading. This result provides not only a novel insight into the difference in virulence between MAB-R and -S variants but also hints to their treatment strategy.

Rationale: With the development of multi-slice computed tomography (CT) technology, perfusion CT angiography (p-CTA) is now widely used for the diagnosis of acute cerebral infarction. Although p-CTA has the advantage of distinguishing between an ischemic penumbra and an infarct core, more research is needed with respect to its clinical use. Patient concerns: A healthy 36-year-old man experienced sudden dizziness while swimming. His dizziness persisted irrespective of the change in position, and then improved during transport. He had no neurological abnormality when he arrived at the emergency room. Diagnoses: CT perfusion findings suggested left cerebellar infarction. P-CTA revealed a markedly delayed mean transit time, delayed time to peak, and increased cerebral blood volume in the left posterior inferior cerebellar artery territory at admission. However, the diffusion-weighted image (DWI) taken a few hours later revealed a large right cerebellar infarction. Interventions: Because of the time window, thrombolysis could not be performed and anti-platelet therapy was started. Outcomes: Dysarthria and right-sided limb ataxia were newly developed before DWI (after p-CTA). Persistent foramen ovale was detected through transesophageal echography and identified as the cause of the stroke. Lessons: This case report suggests that dynamic image changes can occur within a short period of time depending on the vascular status and hemodynamic changes of the patients.

Background Evidence suggests that patients with higher blood pressure variability ( BPV ) have a higher risk for stroke, but any link between BPV and stroke recurrence is unknown among those who had a stroke or transient ischemic attack ( TIA ). Methods and Results Data for patients with a history of stroke or TIA at enrollment were extracted from the ASCOT (Anglo Scandinavian Cardiac Outcomes Trial) and the ALLHAT (Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial). BPV was defined as the within‐subject standard deviation or coefficient of variation of systolic blood pressure across visits from 12 weeks poststroke or TIA onward. BPV was significantly higher in patients with a history of stroke or TIA than those without. BPV was a predictor of recurrent stroke in the pooled analysis. In the ASCOT study, 252 patients (12.3%) had a recurrent stroke among 2046 with a history of stroke. Incidence of recurrent stroke was significantly higher in the highest BPV quartile (17.8%) compared with the lowest quartile (10.5%); by treatment arm, this reached significance for the amlodipine‐arm only (high‐ BPV : 18.7% versus low‐ BPV : 12.9%; P =0.029). Of the 2173 patients from the ALLHAT with a history of stroke or TIA , patients with the highest quartile of BPV had a higher incidence of recurrent stroke (9.6%) compared with the lowest quartile BPV (5.5%); by treatment arm, this reached significance for the chlorthalidone‐arm only (high‐ BPV : 12.1% versus low‐ BPV : 5.4%; P =0.007). Conclusions Visit‐to‐visit BPV is a predictor of recurrent stroke in patients with a history of stroke or TIA on antihypertensive treatment. Considering BPV following a stroke may be important to reduce the risk for a recurrent stroke.

Purpose Cigarette smoking (CS) is one of the major risk factors of cerebral atherosclerotic disease, however, its level of contribution to extracranial and intracranial atherosclerotic stenosis (ECAS and ICAS) was not fully revealed yet. The purpose of our study was to assess the association of CS to cerebral atherosclerosis along with other risk factors. Materials and Methods All consecutive patients who were angiographically confirmed with severe symptomatic cerebral atherosclerotic disease between January 2002 and December 2012 were included in this study. Multivariate logistic regression analyses were performed to identify risk factors for ECAS and ICAS. Thereafter, CS group were compared to non-CS group in the entire study population and in a propensity-score matched population with two different age-subgroups. Results Of 1709 enrolled patients, 794 (46.5%) had extracranial (EC) lesions and the other 915 (53.5%) had intracranial (IC) lesions. CS group had more EC lesions (55.8% vs. 35.3%, P

Strategy for secondary prevention of ischemic stroke depends on the mechanism of stroke. The aim of this study was to compare the stroke mechanism according to the location and severity of middle cerebral artery (MCA) disease.We analyzed acute ischemic stroke patients within 7 days of onset with symptomatic MCA disease. The location of MCA disease was classified into proximal MCA M1 (pMCA) and distal MCA M1/proximal M2 (dMCA). The mechanism of stroke was categorized according to the pattern of ischemic lesion: local branch occlusion, artery-to-artery embolism/hemodynamic infarction, in situ-thrombosis, or a combined mechanism. The mechanism and imaging characteristics of stroke were compared according to the location and severity. The factors associated with the stroke mechanism were also investigated.A symptomatic MCA disease was observed in 126 patients (74 pMCA and 52 dMCA). The mechanism of stroke differed according to the location (p 0.001); the combined mechanism was most common in pMCA disease (54.1%), especially in those who presented with MCA occlusion and with a susceptible vessel sign. Artery-to-artery embolism/hemodynamic infarction was most common in dMCA disease (46.2%). A longer length of stenosis was observed in local branch occlusion than in other mechanisms (p = 0.04) and was an independent factor associated with local branch occlusion (OR=1.631, 95% CI=1.161-2.292; p = 0.005).The mechanism of stroke differed according to the location of MCA disease: occlusion caused by plaque rupture with combined mechanism of stroke type was predominant in pMCA. Longer length of stenosis was associated with local branch occlusion.

Recently, we reported a 6-mer hepatitis B virus (HBV)-derived peptide, Poly6, that exerts antiviral effects against human immunodeficiency virus type 1 (HIV-1). Here, we explored the immunotherapeutic potential of Poly6 via its administration into dendritic cells (DCs) in a mouse model. Our data revealed that Poly6 treatment led to enhanced production of tumor necrosis factor alpha (TNF-&alpha, ) and inducible nitric oxide synthase (iNOS)-producing DCs (Tip-DCs) in a type 1 interferon (IFN-I)-dependent manner via the induction of mitochondrial stress. Poly6 treatment in mice implanted with MC38 cells, a murine colon adenocarcinoma line, led to attenuated tumor formation, primarily due to direct cell death induced by Tip-DC mediated nitric oxide (NO) production and indirect killing by Tip-DC mediated cluster of differentiation 8 (CD8) cytotoxic T lymphocyte (CTL) activation via CD40 activation. Moreover, Poly6 treatment demonstrated an enhanced anticancer effect with one of the checkpoint inhibitors, the anti PD-L1 antibody. In conclusion, our data reveal that Poly6 treatment elicits an antitumor immune response in mice, possibly through NO-mediated oncolytic activity via Tip-DC activation and Tip-DC mediated CTL activation. This suggests that Poly6 represents a potential adjuvant for cancer immunotherapy by enhancing the anticancer effects of immune checkpoint inhibitors.

The performance of scoring systems for risk stratification in patients with atrial fibrillation (AF) was not validated well in patients with stroke. The purpose of this study was to evaluate whether the risk scoring systems predict vascular outcomes in stroke patients with AF.Data were obtained from a nationwide multicenter registry for acute stroke with AF from January 1, 2013, to December 31, 2015. We investigated the predictive power of the CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke scores in stroke patients with AF. The subjects were further stratified into groups according to treatment with or without oral anticoagulants (OACs).A total of 3112 stroke with AF subjects were included. The rate of recurrent ischemic stroke and any stroke were not associated with the CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores. The risks of death and major adverse cerebrovascular and cardiovascular events (MACEs) increased sequentially with the increase of each risk score in OAC group. (the range of C-index 0.544-0.558 for recurrent ischemic stroke; 0.523-0.537 for any stroke; 0.580-0.597 for death; 0.564-0.583 for MACEs). However, in the group treated with OACs, all risk scores were significantly associated with the risk of MACEs. The C-statistics of the 4 scoring systems were 0.544 to 0.558, 0.523 to 0.537, 0.580 to 0.597, 0.564 to 0.583, respectively, for recurrent ischemic stroke, any stroke, death, and MACEs.The performance of the CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores for the prediction of recurrent stroke was unsatisfactory in stroke patients with AF whereas the performance for the prediction of recurrent stroke was not MACEs or death was good. A new risk stratification scheme that is specific for secondary stroke prevention in the AF population is needed.

Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway plays critical roles in the development and progression of hepatocellular carcinoma (HCC). Artemisia capillaris (AC) has been widely used to treat various liver diseases including HCC as a herbal medicine. The effects of AC on IL-6/STAT3 signaling axis in HCC cells and subsequent anticancer activity of AC against HCC were analyzed using HCC cell lines and HBV W4P-LHB-expressing NIH3T3 cell line, which has been shown to gain tumorigenicity by activating IL-6/STAT3 signaling in our previous study. AC extract significantly suppressed the growth and colony formation of HCC cells. In addition, it inhibited the activation of STAT3 by IL-6 and subsequent synthesis of downstream molecules in HCC and W4P-NIH3T3 cells. Consequently, migration of cells was significantly suppressed by the AC extract. Collectively, the findings suggest that AC extract is capable of conferring various antitumor effects against HCC through the modulation of the IL-6/STAT3 pathway. The results provide a basis for the therapeutic use of AC in the treatment of HCC. Identification of the compound responsible for the effect may lead to the development of a novel anticancer agent against HCC.

Background and Purpose— Dissection is an increasingly recognized cause of ischemic stroke, which occurs spontaneously or after trauma, in relatively young patients. We hypothesized that there might be a predisposing factor weakening the vascular wall and that arterial tortuosity might be higher in patients with dissection. Methods— We consecutively enrolled cervical artery dissection (CerAD) patients who had undergone magnetic resonance angiography. Age- and sex-matched healthy subjects who underwent magnetic resonance angiography in a routine health examination were used as controls. The tortuosity was measured semiautomatically from the carotid artery and vertebral artery (VA) arteries. Tortuosity index was defined as: [(arc/chord)−1×100] in each arteries. Independent risk factors associated with CerAD were investigated using multivariable analysis. Subgroup analysis according to the dissected artery was performed. Results— There were no differences in vascular risk factors between the 75 CerAD patients and the 75 controls. The tortuosity indexes of the contralesional VA (16.3±6.8 versus 12.1±4.5, respectively; P P =0.01) were higher in patients with CerAD compared with those of control subjects. VA tortuosity (odds ratio, 1.175; P =0.001) was independently associated with the presence of CerAD. In subgroup analysis, VA tortuosity was significantly higher in 57 patients with VA dissection than in controls ( P P =0.05). Conclusions— CerAD is associated with tortuous cervical arteries, which may implicate weakened cervical vascular structure in these patients.

Background Symptomatic intracerebral hemorrhage (sICH) is one of the most feared complications after administration of intravenous recombinant tissue plasminogen activator (IV rtPA). The aim of this study was to determine correlations between hemorrhage volume (HV) after IV rtPA treatment and risk factors for sICH. Methods We analyzed 318 patients from the stroke registries of 4 hospitals in Korea. We confirmed hemorrhage by computed tomography (CT) or magnetic resonance imaging within 36 hours. Patient groups were classified by HV (0, 0-10, 10-25, and greater than 25 mL). Based on the HV, we evaluated the following: (1) predictors for hemorrhage; (2) rates of sICH according to various sICH definitions; and (3) 3-month functional outcomes after IV rtPA treatment. Results Among the 318 patients, hemorrhage occurred in 72 patients. HV was significantly correlated with atrial fibrillation (OR = 3.38, 95% CI = 1.87-6.09), early CT changes (OR = 3.17, 95% CI = 1.69-5.93), and dense artery sign (OR = 1.90, 95% CI = 1.07-3.39). Compared with the groups with HV less than 25 mL, patients with an HV of greater than 25 mL were more likely to have higher mortality rates (33.3% versus 11.8%) and worse outcomes at 3 months (good: 8.3% versus 50.3%; excellent: 0% versus 33.7%). Conclusions HV after IV rtPA is an important predictor of clinical outcomes. Atrial fibrillation, early CT changes, and dense artery sign were significantly associated with large HVs; therefore, these patient factors might be considered before and after thrombolytic treatment.

Background and Purpose The location of cerebral microbleeds (CMBs) may differ according to ischemic stroke subtype, and the underlying pathomechanism may differ by their location. Here, we investigated the characteristics of CMBs according to various ischemic stroke subtypes to verify this issue. Methods Patients with acute ischemic stroke were consecutively included. The presence of CMBs was determined by gradient echo image sequence. The distribution of CMBs was classified as deep, lobar, or diffuse (both deep and lobar). The prevalence, risk factors, and distribution of CMBs were compared among patients with different stroke subtypes. Factors associated with the distribution of CMBs were investigated. Results Among the 1033 patients included in this study, ischemic stroke subtypes were classified as large artery atherosclerosis (LAA; n=432), small vessel occlusion (SVO; n=304), and cardioembolism (CE; n=297). The prevalence of CMBs was highest in patients with SVO (40.5%), followed by CE (33.0%) and LAA (24.8%; P

OBJECTIVE Surgical site infection (SSI) is the one of the most frequent complications in hospitalized patients, and it extends hospital stays and causes extra morbidities. To reduce SSI after spine surgery, we applied the gentamicin-impregnated collagen sponge (Collatamp G) during the operation and analyzed the results retrospectively. METHODS Between October 2012 and December 2015, we collected data who applied the Collatamp G in spine surgery at a single institution. Demographic data of patients and another possible risk factors of SSI were also included, and we assessed the correlation between the risk factors and the developing of SSI by reviewing electronic medical records retrospectively. RESULTS Three percent of all patients (10 of 280) developed the SSI and only 0.8% of patients who applied Collatamp G developed SSI (1 of 119). Otherwise, 5% of patients who did not apply Collatamp G developed SSI (9 of 161) (p=0.034). We also analyzed the correlation between SSI and other potential risk factors but nothings showed statistical correlation with SSI. CONCLUSION In this study, there were statistically significant results that SSI rate was decreased in the group of patients using Collatamp G in spine surgery generally. However, further studies are required to resolve some limitations in the future.

The whitefly Bemisia tabaci is a very destructive pest. B. tabaci is composed of various morphologically undistinguishable biotypes, among which biotypes B and Q, in particular, draw attention because of their wide distribution in Korea and differential potentials for insecticide resistance development. To develop a biotype-specific protein marker that can readily distinguishes biotypes B from other biotypes in the field, we established an ELISA protocol based on carboxylesterase 2 (COE2), which is more abundantly expressed in biotypes B compared with Q. Recombinant COE2 was expressed, purified and used for antibody construction. Polyclonal antibodies specific to B. tabaci COE2 [anti-COE2 pAb and deglycosylated anti-COE2 pAb (DG anti-COE2 pAb)] revealed a 3-9-fold higher reactivity to biotype B COE2 than biotype Q COE2 by Western blot and ELISA analyses. DG anti-COE2 pAb exhibited low non-specific activity, demonstrating its compatibility in diagnosing biotypes. Western blot and ELISA analyses determined that one of the 11 field populations examined was biotype B and the others were biotype Q, suggesting the saturation of biotype Q in Korea. DG anti-COE2 pAb discriminates B. tabaci biotypes B and Q with high specificity and accuracy and could be useful for the development of a B. tabaci biotype diagnosis kit for on-site field applications.