Palladium Single-Atom (In)Stability Under Aqueous Reductive Conditions.

Here, we investigate the stability and performance of single-atom Pd on TiO2 for the selective dechlorination of 4-chlorophenol. A challenge inherent to single atoms is their high surface free energy, which results in a tendency for the surface migration and aggregation of metal atoms. This work evaluates various factors affecting the stability of Pd single-atoms, including atomic dispersion, coordination environment, and substrate properties, under reductive aqueous conditions. The transition from single atoms to clusters vastly enhanced dechlorination kinetics without diminishing carbon-chlorine bond selectivity. X-ray absorption spectroscopy analysis using both in situ and ex situ conditions followed the dynamic transformation of single atoms into amorphous clusters, which consist of a unique unsaturated coordination environment and few nanometer diameter. The intricate relationship between stability and performance underscores the vital role of detailed characterization to properly determine the true active species for dehalogenation reactions.

Impact of Renal Function on Short-Term Outcome After Reperfusion Therapy in Patients With Ischemic Stroke.

BACKGROUND: A high and low estimated glomerular filtration rate (eGFR) could affect outcomes after reperfusion therapy for ischemic stroke. This study aimed to determine whether renal function based on eGFR affects mortality risk in patients with ischemic stroke within 6 months following reperfusion therapy. METHODS: This prospective registry-based cohort study included 2266 patients who received reperfusion therapy between January 2000 and September 2019 and were registered in the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) study or the Yonsei Stroke Cohort. A high and low eGFR were based on the Chronic Kidney Disease Epidemiology Collaboration equation and defined, respectively, as the 5th and 95th percentiles of age- and sex-specific eGFR. Occurrence of death within 6 months was compared among the groups according to their eGFR such as low, normal, or high eGFR. RESULTS: Of the 2266 patients, 2051 (90.5%) had a normal eGFR, 110 (4.9%) a low eGFR, and 105 (4.6%) a high eGFR. Patients with high eGFR were younger or less likely to have hypertension, diabetes, or atrial fibrillation than the other groups. Active cancer was more prevalent in the high-eGFR group. During the 6-month follow-up, there were 24 deaths (22.9%) in the high-eGFR group, 37 (33.6%) in the low-eGFR group, and 237 (11.6%) in the normal-eGFR group. After adjusting for variables with P<0.10 in the univariable analysis, 6-month mortality was independently associated with high eGFR (hazard ratio, 2.22 [95% CI, 1.36-3.62]; P=0.001) and low eGFR (HR, 2.29 [95% CI, 1.41-3.72]; P=0.001). These associations persisted regardless of treatment modality or various baseline characteristics. CONCLUSIONS: High eGFR as well as low eGFR were independently associated with 6-month mortality after reperfusion therapy. Kidney function could be considered a prognostic factor in patients with ischemic stroke after reperfusion therapy.

Short-Term Cessation of Dabigatran Causes a Paradoxical Prothrombotic State.

OBJECTIVE: It is unclear if stopping treatment with dabigatran, a new oral anticoagulant (NOAC), induces a paradoxical rebound prothrombotic state. We investigated if short-term (1-3 days) dabigatran cessation is associated with a higher thrombus volume than expected from a simple reversal of the anticoagulant effect. METHODS: Ten-week-old C57Bl/6 mice (n = 338) received one of the following oral treatments: phosphate-buffered saline (PBS), dabigatran for 7 days with or without 1 to 4 day cessation, and aspirin in either a single dose or daily for 7 days. Some of the animals that ceased dabigatran for 1 to 3 days received single-dose aspirin. Thereafter, we induced FeCl3 -mediated carotid thrombosis in 130 mice, after which we performed micro computed tomography thrombus imaging. The other 208 mice underwent coagulation assays or platelet function tests. As an explorative pilot study, we reviewed the medical records of 18 consecutive patients with NOAC cessation-related cerebral infarction in a large acute stroke cohort. RESULTS: We observed a ~ 40% higher volume of carotid thrombus after dabigatran cessation at 1 to 3 days than after vehicle treatment and showed that this effect could be prevented by single-dose aspirin pretreatment. Dabigatran cessation unduly increased platelet aggregability for 2 days after drug cessation, an effect mediated through thrombin or arachidonic acid, which effect was significantly attenuated by single-dose aspirin pretreatment. In patients, short-term (≤ 3 days) cessation of NOAC therapy, compared with longer-term (≥ 5 days) cessation, tended to be associated with relatively high stroke severity. INTERPRETATION: We provide the first preclinical evidence that a rebound prothrombotic state follows short-term cessation of dabigatran therapy. ANN NEUROL 2021;89:444-458.

Immediate and Long-Term Outcomes of Reperfusion Therapy in Patients With Cancer.

Background and Purpose: Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients. The purpose of this study was to evaluate the association between cancer and the outcomes of reperfusion therapy in patients with stroke. Methods: We compared treatment outcomes in patients who underwent reperfusion therapy, using a nationwide reperfusion therapy registry. We divided the patients into 3 groups according to cancer activity: active cancer, nonactive cancer, and without a history of cancer. We investigated reperfusion processes, 24-hour neurological improvement, adverse events, 3-month functional outcome, and 6-month survival and related factors after reperfusion therapy. Results: Among 1338 patients who underwent reperfusion therapy, 62 patients (4.6%) had active cancer, 78 patients (5.8%) had nonactive cancer, and 1198 patients (89.5%) had no history of cancer. Of the enrolled patients, 969 patients received intravenous thrombolysis and 685 patients underwent endovascular treatment (316 patients received combined therapy). Patients with active cancer had more comorbidities and experienced more severe strokes; however, they showed similar 24-hour neurological improvement and adverse events, including cerebral hemorrhage, compared with the other groups. Although the functional outcome at 3 months was poorer than the other groups, 36.4% of patients with active cancer showed functional independence. Additionally, 52.9% of the patients with determined stroke etiology showed functional independence despite active cancer. During the 6-month follow-up, 46.6% of patients with active cancer died, and active cancer was independently associated with poor survival (hazard ratio, 3.973 [95% CI, 2.528­6.245]). Conclusions: In patients with active cancer, reperfusion therapy showed similar adverse events and short-term outcomes to that of other groups. While long-term prognosis was worse in the active cancer group than the nonactive cancer groups, not negligible number of patients had good functional outcomes, especially those with determined stroke mechanisms.

Assessment of respiratory and systemic toxicity of Benzalkonium chloride following a 14-day inhalation study in rats.

BACKGROUND: Although biocides at low concentrations have been used to control pests, they can be more harmful than industrial chemicals as humans are directly and frequently exposed to such biocides. Benzalkonium chloride (BAC or BKC) is a non-toxic substance used to control pests. Recently, BAC has been increasingly used as a component in humidifier disinfectants in Korea, raising a serious health concern. Moreover, it poses significant health hazards to workers handling the chemical because of direct exposure. In the present study, we aimed to evaluate the respiratory toxicity of BAC due to its inhalation at exposure concentrations of 0.8 (T1 group), 4 (T2 group) and 20 (T3 group) mg/m3. RESULTS: In our previous study on the acute inhalational toxicity of BAC, bleeding from the nasal cavity was observed in all the rats after exposure to 50 mg/m3 BAC. Therefore, in this study, 20 mg/m3 was set as the highest exposure concentration, followed by 4 and 0.8 mg/m3 as the medium and low concentrations for 6 h/day and 14 days, respectively. After exposure, recovery periods of 2 and 4 weeks were provided. Additionally, alveolar lavage fluid was analyzed in males of the BAC-exposed groups at the end of exposure and 2 weeks after exposure to evaluate oxidative damage. In the T3 group exposed to BAC, deep breathing, hoarseness, and nasal discharge were observed along with a decline in feed intake and body weight, and nasal discharge was also observed in the T1 and T2 groups. ROS/RNS, IL-1ß, IL-6, and MIP-2 levels decreased in a concentration-dependent manner in the bronchoalveolar lavage fluid. Histopathological examination showed cellular changes in the nasal cavity and the lungs of the TI, T2, and T3 groups. CONCLUSIONS: As a result, it was confirmed that the target organs in the respiratory system were the nasal cavity and the lungs. The adverse effects were evaluated as reversible responses to oxidative damage. Furthermore, the no observed adverse effect level was found to be less than 0.8 mg/m3 and the lowest benchmark dose was 0.0031 mg/m3. Accordingly, the derived no-effect level of BAC was calculated as 0.000062 mg/m3.

Distal versus Proximal Middle Cerebral Artery Occlusion: Different Mechanisms.

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.

Thrombus Volume as a Predictor of Nonrecanalization After Intravenous Thrombolysis in Acute Stroke.

Background and Purpose- We investigated whether measuring the volume and density of a thrombus could predict nonrecanalization after intravenous thrombolysis. Methods- This study included a retrospective cohort to develop a computed tomography marker of thrombus for predicting nonrecanalization after intravenous thrombolysis and a prospective multicenter cohort for validation of this marker. The volume and density of thrombus were measured semiautomatically using 3-dimensional software on a baseline thin-section noncontrast computed tomography (1 or 1.25 mm). Recanalization was assessed on computed tomography angiography or magnetic resonance angiography immediately after intravenous thrombolysis or conventional angiography in patients who underwent further intra-arterial treatment. Nonrecanalization was defined as a modified Thrombolysis in Cerebral Infarction grade 0, 1, 2a. Results- In the retrospective cohort, 162 of 214 patients (76.7%) failed to achieve recanalization. The thrombus volume was significantly larger in patients with nonrecanalization than in those with successful recanalization (149.5±127.6 versus 65.3±58.3 mm3; P<0.001). In the multivariate analysis, thrombus volume was independently associated with nonrecanalization ( P<0.001). The cutoff for predicting nonrecanalization was calculated as 200 mm3. In the prospective multicenter validation study, none of the patients with a thrombus volume ≥200 mm3 among 78 enrolled patients achieved successful recanalization. The positive and negative predictive values were 95.5 and 29.4 in the retrospective cohort 100 and 23.3 in the prospective validation cohort, respectively. The thrombus density was not associated with nonrecanalization. Conclusions- Thrombus volume was predictive of nonrecanalization after intravenous thrombolysis. Measurement of thrombus volume may help in determining the recanalization strategy and perhaps identify patients suitable for direct endovascular thrombectomy.

Etiology of aseptic meningitis and clinical characteristics in immune-competent adults.

Viral meningitis is the most common cause of aseptic meningitis. Use of the polymerase chain reaction (PCR) has increased the ability to determine the etiology of viral meningitis. This study used PCR analysis to evaluate the etiology of aseptic meningitis in 177 previously healthy adults over a 5-year period, as well as analyzing the clinical characteristics, cerebrospinal fluid (CSF) findings, and prognosis according to each etiology. The most frequent cause of aseptic meningitis was enterovirus (EV), followed by varicella zoster virus (VZV). Patients with EV meningitis were significantly younger than those with VZV meningitis. The percentage of lymphocytes in white blood cell counts and protein concentrations in the CSF differed significantly among patients with EV, VZV and meningitis of undetermined etiology. Younger age and lower percentage of lymphocyte and protein level in CSF analysis may be suggestive of EV meningitis. Further prospective studies are warranted to identify the correlations between the clinical characteristics and the etiologies of meningitis.

The Ischemic Stroke Predictive Risk Score Predicts Early Neurological Deterioration.

BACKGROUND: Although early neurological deterioration (END) during the acute stroke period is known to be directly associated with poor short- and long-term outcomes, few studies have investigated the ability to predict END. The aim of this study was to investigate whether there are differences in the occurrence of END according to the ischemic stroke predictive risk score (iScore), which was developed to predict short- and long-term mortality. METHODS: We collected data from 2150 consecutive ischemic stroke patients who were admitted to 3 study hospitals between January 2012 and June 2014. END was defined as an increase (≥4) in the National Institutes of Health Stroke Scale score within the first 72 hours of stroke onset. We calculated the 30-day iScore for each patient to determine the relationship between the iScore and occurrence of END. RESULTS: Among 2150 patients, END was observed in 146 patients (6.8%). There was a positive correlation between the iScore and occurrence of END. After adjusting for potential confounders, the iScore was independently associated with END (odds ratio: 1.217 per 20-point increase in iScore, 95% confidence interval: 1.121-1.321, P < .001). There was good correlation between observed and expected outcomes predicted by the iScore (Pearson correlation coefficient: r = .950, P < .001). CONCLUSIONS: The iScore can predict the risk of END development within the acute stroke stage.

Predictors of Hemorrhage Volume after Intravenous Thrombolysis.

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.

Production of 10-hydroxy-12,15(Z,Z)-octadecadienoic acid from α-linolenic acid by permeabilized Stenotrophomonas nitritireducens cells.

OBJECTIVE: To improve the production of 10-hydroxy-12,15(Z,Z)-octadecadienoic acid (HODA) from α-linolenic acid in Stenotrophomonas nitritireducens. RESULTS: Cells of the bacterium were permeabilized with 1.25% (v/v) methanol. The optimal conditions for HODA production by permeabilized cells were pH 7, 35 °C, 5% (v/v) DMSO, 50 g cells l(-1), and 22.5 g α-linolenic acid l(-1). Under these conditions, permeabilized cells produced 16.4 g HODA l(-1) after 2 h, with a conversion yield of 73 % (w/w) and a volumetric productivity of 8.2 g l(-1) h(-1). These values were 153 and 230 % of the values for non-permeabilized cells CONCLUSIONS: This is the highest concentration and volumetric and specific productivities of HODA reported thus far.

Recurrent oculomotor neuritis related to autoimmune hypothyroidism. Case Report.

Ophthalmopathy related to thyroid disease is due mainly to diffuse periorbital or eye muscle inflammation. It is more common in Grave's hyperthyroidism and rare in Hashimoto's hypothyroidism. Here we report a case of recurrent oculomotor nerve palsy associated with autoimmune hypothyroidism. Brain MRI revealed enhancement of the oculomotor nerves. Despite thyroid hormone replacement therapy, oculomotor nerve palsy recurred at the side contralateral to the initially involved nerve and the autoimmune antibody titer remained high. The symptom was responsive to high-dose steroid therapy.

A phase III, randomized, double-blind, matched-pairs, active-controlled clinical trial and preclinical animal study to compare the durability, efficacy and safety between polynucleotide filler and hyaluronic acid filler in the correction of crow's feet: a new concept of regenerative filler.

The Rejuran® is a new filler product made from purified polynucleotides. Here we present data from an animal study and a clinical trial to examine the durability, efficacy and safety of the Rejuran® on crow's feet. For the animal study, 25 mice were divided into three groups: Group 1 received phosphate buffered saline (PBS); Group 2 were treated with Yvoire®; and Group 3 were treated with Rejuran®. The durability and efficacy of each treatment were assessed by microscopy and staining. In the clinical trial, 72 patients were randomized to receive Rejuran® treatment for crow's feet on one side and Yvoire-Hydro® on the contralateral side, at a ratio of 1:1. Repeated treatments were performed every two weeks for a total of three times, over a total of 12 weeks' observation. All injections and observations of efficacy and safety were performed by the same two investigators. In the animal study, the Rejuran® group showed similar durability and inflammatory response to the Yvoire® group. Upon efficacy assessment, the Rejuran® group showed the greatest elasticity and collagen composition, and a significant difference in skin surface roughness and wrinkle depth. In the clinical trial, the primary and secondary objective efficacy outcome measure showed no statistical significance between the two groups, and in safety outcomes there were no unexpected adverse effects. Our data suggest that the Rejuran®, as a new regenerative filler, can be useful to reduce wrinkles, by showing evidence for its efficacy and safety.

Effectiveness of endovascular treatment for in-hospital stroke vs. community-onset stroke: a propensity score-matched analysis.

BACKGROUND: The effectiveness of endovascular treatment for in-hospital stroke remains debatable. We aimed to compare the outcomes between patients with in-hospital stroke and community-onset stroke who received endovascular treatment. METHODS: This prospective registry-based cohort study included consecutive patients who underwent endovascular treatment from January 2013 to December 2022 and were registered in the Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy study and Yonsei Stroke Cohort. Functional outcomes at day 90, radiological outcomes, and safety outcomes were compared between the in-hospital and community-onset groups using logistic regression and propensity score-matched analysis. RESULTS: Of 1,219 patients who underwent endovascular treatment, 117 (9.6%) had in-hospital stroke. Patients with in-hospital onset were more likely to have a pre-stroke disability and active cancer than those with community-onset. The interval from the last known well to puncture was shorter in the in-hospital group than in the community-onset group (155 vs. 355 min, p<0.001). No significant differences in successful recanalization or safety outcomes were observed between the groups; however, the in-hospital group exhibited worse functional outcomes and higher mortality at day 90 than the community-onset group (all p<0.05). After propensity score matching including baseline characteristics, functional outcomes after endovascular treatment did not differ between the groups (OR: 1.19, 95% CI 0.78-1.83, p=0.4). Safety outcomes did not significantly differ between the groups. CONCLUSION: Endovascular treatment is a safe and effective treatment for eligible patients with in-hospital stroke. Our results will help physicians in making decisions when planning treatment and counseling caregivers or patients.

Visualizing indoor ozone exposures via o-dianisidine based colorimetric passive sampler.

In this study, we developed a colorimetric ozone passive sampler (OPS) incorporating o-dianisidine, a redox dye, into a polydimethylsiloxane sheet. The reaction between ozone (O3) and o-dianisidine result in a visible yellowish color change. Unlike previous passive methods that rely on nitrate extraction or the color disappearance of indigotrisulfonate, the OPS offered improved recognition of average O3 exposure. To optimize OPS based on time-weighted average (TWA), we extracted and quantified the amount of reacted o-dianisidine after exposing OPS to O3 by varying concentrations (0-200 ppb) within 8 h. Colorimetric changes of OPS were further analyzed by capturing images, and the effective absorbance of blue scale showed the best fit (EAB, R2 =0.997). OPS validation on visual detection assessed by six parameters: limit of detection, limit of quantification, reproducibility, sampling rate, selectivity to interfering gases, and sensitivity to environmental factors. To enhance visibility, the OPS was assembled with coloration exposure guidelines, and a smartphone app was developed to quantify average O3 exposures. We further conducted field tests that showed the significant disparity between O3 concentrations and personal O3 exposures, which is considered more crucial for assessing health risks. The OPS was optimized to monitor O3 exposure levels and raise awareness among workers and occupants regarding invisible indoor hazards.

Deep learning synthesis of cone-beam computed tomography from zero echo time magnetic resonance imaging.

Cone-beam computed tomography (CBCT) produces high-resolution of hard tissue even in small voxel size, but the process is associated with radiation exposure and poor soft tissue imaging. Thus, we synthesized a CBCT image from the magnetic resonance imaging (MRI), using deep learning and to assess its clinical accuracy. We collected patients who underwent both CBCT and MRI simultaneously in our institution (Seoul). MRI data were registered with CBCT data, and both data were prepared into 512 slices of axial, sagittal, and coronal sections. A deep learning-based synthesis model was trained and the output data were evaluated by comparing the original and synthetic CBCT (syCBCT). According to expert evaluation, syCBCT images showed better performance in terms of artifacts and noise criteria but had poor resolution compared to the original CBCT images. In syCBCT, hard tissue showed better clarity with significantly different MAE and SSIM. This study result would be a basis for replacing CBCT with non-radiation imaging that would be helpful for patients planning to undergo both MRI and CBCT.

Optimal use of antithrombotic agents in ischemic stroke with atrial fibrillation and large artery atherosclerosis.

BACKGROUND: Optimal antithrombotic regimens to prevent recurrent stroke in patients with ischemic stroke due to atrial fibrillation (AF) and atherosclerotic large-vessel stenosis remain unknown. AIMS: This study aimed to evaluate the effect of multiple antithrombotic therapies on outcomes at 1 year after ischemic stroke due to two or more causes. METHODS: We identified 862 patients with ischemic stroke due to AF and large artery atherosclerosis from the linked data. These patients were categorized into three groups according to antithrombotic therapies at discharge: (1) antiplatelets, (2) oral anticoagulants (OAC), and (3) antiplatelets plus OAC. The study outcomes were recurrent ischemic stroke, composite outcomes for cardiovascular events, and major bleeding after 1 year. Inverse probability of treatment weighting (IPTW) was used to balance the three groups using propensity scores. RESULTS: Among 862 patients, 169 (19.6%) were treated with antiplatelets, 405 (47.0%) were treated with OAC, and 288 (33.4%) were treated with antiplatelets and OAC. After applying IPTW, only OAC had a significant beneficial effect on the 1-year composite outcome (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.23-0.60, p < 0.001) and death (HR: 0.35, 95% CI: (0.19-0.63), p < 0.001). The combination of antiplatelet agents and OAC group had an increased risk of major bleeding complications (HR: 5.27, 95% CI: (1.31-21.16), p = 0.019). However, there was no significant difference in 1-year recurrent stroke events among the three groups. CONCLUSION: This study demonstrated that OAC monotherapy was associated with lower risks of composite outcome and death in patients at 1 year after ischemic stroke due to AF and atherosclerotic stenosis. In addition, the combination of an antiplatelet and OAC had a high risk of major bleeding.

Exome sequencing and subsequent association studies identify five amino acid-altering variants influencing human height.

Height is a highly heritable trait that involves multiple genetic loci. To identify causal variants that influence stature, we sequenced whole exomes of four children with idiopathic short stature. Ninety-five nonsynonymous single-nucleotide polymorphisms (nsSNPs) were selected as potential candidate variants. We performed association analysis in 740 cohort individuals and identified 11 nsSNPs in 10 loci (DIS3L2, ZBTB38, FAM154A, PTCH1, TSSC4, KIF18A, GPR133, ACAN, FAM59A, and NINL) associated with adult height (P < 0.05), including five novel loci. Of these, two nsSNPs (TSSC4 and KIF18A loci) were significant at P < 0.05 in the replication study (n = 1,000) and five (ZBTB38, FAM154A, TSSC4, KIF18A, and FAM59A loci) were significant at P < 0.01 in the combined analysis (n = 1,740). Together, the five nsSNPs accounted for approximately 2.5% of the height variation. This study demonstrated the utility of next-generation sequencing in identifying genetic variants and loci associated with complex traits.

The frequency and risk of preclinical coronary artery disease detected using multichannel cardiac computed tomography in patients with ischemic stroke.

BACKGROUND: Atherosclerosis is a systemic disease. Many ischemic stroke patients may have concomitant coronary artery disease (CAD). Detection and treatment of preclinical CAD in stroke patients may improve long-term outcome and survival because CAD is a major cause of death during follow-up in stroke patients. However, association between coronary and cerebral artery atherosclerosis in stroke patients has not fully been investigated. This study aimed at examining the frequency and high-risk groups of CAD in ischemic stroke patients. METHODS: Consecutive patients who were admitted due to acute ischemic stroke between July 2006 and June 2010 were prospectively enrolled in this study. A total of 1,304 patients who underwent MSCT coronary angiography and cerebral angiography were included in this study. By using 64-multislice computed tomography coronary angiography, we investigated the frequency of CAD and association between coronary and cerebral artery atherosclerosis in terms of location and burden (severity and extent) in stroke patients. We also sought to identify high-risk groups for CAD among stroke patients. RESULTS: The frequency of significant (≥50%) CAD was 32.3% and the frequency of any degree of CAD was 70.1%. Diabetes mellitus, serum levels of total cholesterol, high-density lipoprotein cholesterol and triglyceride, and significant stenosis of the extracranial carotid, intracranial vertebral and basilar arteries were independently associated with CAD. However, no association was found between CAD and significant stenosis of the anterior, middle and posterior cerebral arteries. The association between CAD and cerebral atherosclerosis was stronger with increased severity and extent of cerebral atherosclerosis. When compared to patients with <2 risk factors and without significant cerebral atherosclerosis, those with multiple (≥2) risk factors and atherosclerosis in both the carotid and the vertebrobasilar arteries had very high risks of CAD [odds ratio (OR) 8.36; 95% confidence interval (CI) 4.15-16.87]. The risk was also high in patients with multiple risk factors and atherosclerosis in either the carotid or the vertebrobasilar artery (OR 4.13; 95% CI 2.62-6.51), and in those with <2 risk factors but atherosclerosis in both the carotid and the vertebrobasilar arteries (OR 3.40; 95% CI 1.22-9.47). CONCLUSIONS: A substantial portion of stroke patients had preclinical CAD, and there was a clear relationship between coronary and cerebral artery atherosclerosis in terms of location and burden. The risk of CAD was particularly high in stroke patients with multiple risk factors and atherosclerosis of the carotid and/or vertebrobasilar arteries.

Back to the Basics: Thorough Vascular Examination Based on Arterial Topography of Acute Ischemic Lesions.

Identification of the precise cause is fundamental to the secondary prevention of acute ischemic stroke. Several uncommon causes of stroke have been identified as a result of the attempts made to identify the cause of a cryptogenic stroke. However, unless proper protocol is followed each time, without missing any steps, it might not be possible to accurately determine the cause of strokes. Herein, we report a case wherein the cause of stroke was not detected in time because a fundamental step was missed while attempting to determine the cause. The 44-year-old male patient in our case developed recurrent ischemic stroke due to vertebral artery dissection. Although vertebral artery dissection is not a rare cause of stroke, it was missed while focusing on the rare embolic condition, Valsalva sinus aneurysm. Although a cardiac embolism is a potential cause of stroke in the present case, it is critical to examine all parts from the ostium to the end of the relevant artery (vertebral arteries) when checking for the possible causes of stroke. The ideal protocol to be followed when determining stroke etiology would be as follows: 1) identifying anatomical location and vascular territory of the lesion, 2) evaluating relevant arterial pathology or testing potential embolic source according to the presence of one relevant artery for ischemic lesion, and 3) performing a detailed evaluation of the rare causes of stroke.