DDX41 is a DEAD-box helicase and is conserved across species. Mutations in DDX41 have been associated with myeloid neoplasms, including myelodysplastic syndrome and acute myeloid leukemia. Though its pathogenesis is not completely known, DDX41 has been shown to have many cellular roles, including in pre-mRNA splicing, innate immune sensing, ribosome biogenesis, translational regulation, and R-loop metabolism. In this review, we will summarize the latest understandings regarding the various roles of DDX41, as well as highlight challenges associated with drug development to target DDX41. Overall, understanding the molecular and cellular mechanisms of DDX41 could help develop novel therapeutic options for DDX41 mutation-related hematologic malignancies.
Hematologic Neoplasms , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Humans , DEAD-box RNA Helicases/genetics , DEAD-box RNA Helicases/metabolism , Myelodysplastic Syndromes/genetics , Mutation
To prevent immediate mortality in patients with a tracheostomy tube, it is essential to ensure timely suctioning or replacement of the tube. Breathing sounds at the entrance of tracheostomy tubes were recorded with a microphone and analyzed using a spectrogram to detect airway problems. The sounds were classified into three categories based on the waveform of the spectrogram according to the obstacle status: normal breathing sounds (NS), vibrant breathing sounds (VS) caused by movable obstacles, and sharp breathing sounds (SS) caused by fixed obstacles. A total of 3950 breathing sounds from 23 patients were analyzed. Despite neither the patients nor the medical staff recognizing any airway problems, the number and percentage of NS, VS, and SS were 1449 (36.7%), 1313 (33.2%), and 1188 (30.1%), respectively. Artificial intelligence (AI) was utilized to automatically classify breathing sounds. MobileNet and Inception_v3 exhibited the highest sensitivity and specificity scores of 0.9441 and 0.9414, respectively. When classifying into three categories, ResNet_50 showed the highest accuracy of 0.9027, and AlexNet showed the highest accuracy of 0.9660 in abnormal sounds. Classifying breathing sounds into three categories is very useful in deciding whether to suction or change the tracheostomy tubes, and AI can accomplish this with high accuracy.
Respiratory Sounds , Tracheostomy , Humans , Artificial Intelligence , Respiration , Suction
Although clinical studies have demonstrated that prior use of antiplatelets was associated with decreased blood viscosity (BV) in patients with acute ischemic stroke, the impact of previous anticoagulant use on blood viscosity in cardioembolic stroke with non-valvular AF (NVAF) has not yet been clearly studied. This single-center retrospective observational study aimed to determine the impact of prior antithrombotic (antiplatelet and anticoagulant) use on BV in patients with cardioembolic stroke (CES) due to NVAF. Patients with CES and NVAF were analyzed with the following inclusion criteria: (1) patients over 20 years of age admitted within five days of stroke onset; (2) ischemic stroke presumably due to an NVAF-derived embolus; (3) compatible cortical/subcortical lesion on brain computed tomography or magnetic resonance imaging; (4) hemoglobin level of 10-18 mg/dL; and (5) receiving antiplatelets within five days or anticoagulants within two days if previously medicated. From the screening of 195 patients (22% of the total stroke population during the study period) who had experienced ischemic stroke with AF, 160 were included for the final analysis. Eighty-nine patients (56%) were taking antithrombotics (antiplatelet, 57%; warfarin, 13%; NOACs, 30%) regularly. Compared to patients without previous antithrombotic use, those with previous antithrombotic use (antiplatelets, warfarin, and NOACs) were significantly associated with decreased systolic BV (SBV) and diastolic BV (DBV) (p < 0.036). In multiple linear regression analysis, hematocrit (Hct) level and prior antithrombotic use were significantly associated with decreased SBV and DBV. Hct was positively correlated with increased SBV and DBV. In Hct-adjusted partial correlation analysis, prior uses of any antithrombotic agents were associated with decreased SBV (r < -0.270, p < 0.015) and DBV (r < -0.183, p < 0.044). In conclusion, this study showed that prior antithrombotic use (antiplatelets, VKAs, and NOACs) was associated with decreased SBV and DBV in patients presenting with acute CES secondary to NVAF. Our results indicated that previous use of NOACs may be a useful hemorheological parameter in patients with acute CES due to NVAF. Accumulation of clinical data from a large number of patients with the risk of stroke occurrence, initial stroke severity, and functional outcome is necessary to assess the usefulness of BV.
Electrical circuits require ideal switches with low power consumption for future electronic applications. However, transistors, the most developed electrical switches available currently, have certain fundamental limitations such as increased leakage current and limited subthreshold swing. To overcome these limitations, micromechanical switches have been extensively studied; however, it is challenging to develop micromechanical switches with high endurance and low contact resistance. This study demonstrates highly reliable microelectromechanical switches using nanocomposites. Nanocomposites consisting of gold nanoparticles (Au NPs) and carbon nanotubes (CNTs) are coated on contact electrodes as contact surfaces through a scalable and solution-based fabrication process. While deformable CNTs in the nanocomposite increase the effective contact area under mechanical loads, highly conductive Au NPs provide current paths with low contact resistance between CNTs. Given these advantages, the switches exhibit robust switching operations over 5 × 106 cycles under hot-switching conditions in air. The switches also show low contact resistance without subthreshold region, an extremely small leakage current, and a high on/off ratio.
Although statins are established therapy for the secondary prevention of ischemic stroke, factors associated with adherence to statin treatment following ischemic stroke are not well known. To address this, we assessed the 6-month statin adherence using 8-item Morisky Medication Adherence Scale-8 in patients with acute ischemic stroke. Of 991 patients, 65.6% were adherent to statin at 6-month after discharge. Multiple logistic regression analysis showed that patients' awareness of hyperlipidemia (OR 1.62; 95% CI 1.07-2.43), large artery stroke subtype (versus non-large artery stroke, OR 1.79; 95% CI 1.19-2.68), and alcohol drinking habits (OR 1.64; 95% CI 1.06-2.53) were positively associated, while high statin dose (versus low dose, OR 0.6; 95% CI 0.40-0.90) and higher daily number of medication pills (OR 0.93; 95% CI 0.88-0.97) were found to have a negative association with self-reported good adherence to statin medication after acute ischemic stroke. However, stroke severity and diagnosis of hyperlipidemia were not associated with adherence. These results suggest that educational and motivational interventions may enhance statin adherence because modifiable factors were associated with statin adherence.
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Medication Adherence/statistics & numerical data , Secondary Prevention/methods , Stroke/prevention & control , Aged , Female , Humans , Hyperlipidemias/complications , Hyperlipidemias/drug therapy , Male , Middle Aged
Statins mediate vascular protection and reduce the prevalence of cardiovascular diseases. Recent work indicates that statins have anticonvulsive effects in the brain; however, little is known about the precise mechanism for its protective effect in kainic acid (KA)-induced seizures. Here, we investigated the protective effects of atorvastatin pretreatment on KA-induced neuroinflammation and hippocampal cell death. Mice were treated via intragastric administration of atorvastatin for 7 days, injected with KA, and then sacrificed after 24 h. We observed that atorvastatin pretreatment reduced KA-induced seizure activity, hippocampal cell death, and neuroinflammation. Atorvastatin pretreatment also inhibited KA-induced lipocalin-2 expression in the hippocampus and attenuated KA-induced hippocampal cyclooxygenase-2 expression and glial activation. Moreover, AKT phosphorylation in KA-treated hippocampus was inhibited by atorvastatin pretreatment. These findings suggest that atorvastatin pretreatment may protect hippocampal neurons during seizures by controlling lipocalin-2-associated neuroinflammation.
BACKGROUND: The gradually increasing demand for coffee worldwide has prompted increased interest in the relationship between coffee and health issues as well as a need for research on metabolic syndrome in adults. METHODS: Data from 3,321 subjects (1,268 men and 2,053 women) enrolled in the 2013-2014 Korean National Health and Nutrition Examination Survey were analyzed. The subjects were divided into three groups according to their daily coffee consumption. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for metabolic syndrome in the coffee-drinking groups were calculated using multiple logistic regression analysis by adjusting for confounding variables. RESULTS: The prevalence of metabolic syndrome was 15.5%, 10.7%, and 9.7% in men and 3.0%, 7.1%, and 6.5% in women according to their coffee consumption (less than one, one or two, or more than three cups of coffee per day), respectively. Compared with the non-coffee consumption group, the ORs (95% CIs) for metabolic syndrome in the group that consumed more than three cups of coffee was 0.638 (0.328-1.244) for men and 1.344 (0.627-2.881) for women after adjusting for age, body mass index, household income, education, smoking, alcohol, regular exercise, and daily caloric intake. CONCLUSION: The OR of metabolic syndrome was not statistically significant in both men and women.
BACKGROUND: Metabolic syndrome is associated with cardiovascular diseases and is characterized by insulin resistance. Recent studies suggest that the triglyceride/high-density lipoprotein cholesterol (TG/HDLC) ratio predicts insulin resistance better than individual lipid levels, including TG, total cholesterol, low-density lipoprotein cholesterol (LDLC), or HDLC. We aimed to elucidate the relationship between the TG/HDLC ratio and metabolic syndrome in the general Korean population. METHODS: We evaluated the data of adults ≥20 years old who were enrolled in the Korean National Health and Nutrition Examination Survey in 2013 and 2014. Subjects with angina pectoris, myocardial infarction, stroke, or cancer were excluded. Metabolic syndrome was defined by the harmonized definition. We examined the odds ratios (ORs) of metabolic syndrome according to TG/HDLC ratio quartiles using logistic regression analysis (SAS ver. 9.4; SAS Institute Inc., Cary, NC, USA). Weighted complex sample analysis was also conducted. RESULTS: We found a significant association between the TG/HDLC ratio and metabolic syndrome. The cutoff value of the TG/HDLC ratio for the fourth quartile was ≥3.52. After adjustment, the OR for metabolic syndrome in the fourth quartile compared with that of the first quartile was 29.65 in men and 20.60 in women (P<0.001). CONCLUSION: The TG/HDLC ratio is significantly associated with metabolic syndrome.
BACKGROUND: Stroke may occur during hospital admission (in-hospital stroke). Although patients with in-hospital stroke are potentially good candidates for reperfusion therapy, they often do not receive treatment as rapidly as expected. AIMS: We investigated the effect of a code stroke program for in-hospital stroke, which included the use of computerized physician order entry, specific evaluation and treatment protocols for in-hospital stroke patients, and regular education of medical staffs. METHODS: We implemented the program in the cardiology and cardiovascular surgery departments/wards (target-ward group) in November 2008. We compared time intervals from symptom onset to evaluation and reperfusion treatment before and after program implementation between the target-ward and other departments/wards (other-ward group). RESULTS: Among 70 consecutive in-hospital stroke patients who received reperfusion therapy between July 2002 and February 2015, 28 and 42 were treated before and after program implementation, respectively. After program implementation, time intervals from symptom onset to neurology notification (50 min vs. 28 min; P = 0.033), symptom onset to brain imaging (91 min vs. 41 min; P < 0.001), and symptom recognition to notification (22 min vs. 9 min; P = 0.011) were reduced in the target-ward group. Finally, times from symptom onset to intravenous tissue plasminogen activator administration and to arterial puncture were reduced by 55 min (120 min vs. 65 min; P < 0.001) and 130 min (295 min vs. 165 min; P < 0.001), respectively. However, time reductions in the other-ward group were not significant. CONCLUSIONS: The comprehensive program for in-hospital stroke that included the use of computerized physician order entry was effective in reducing time intervals to evaluation and reperfusion therapy.
Hospitalization , Reperfusion , Stroke/classification , Stroke/therapy , Administration, Intravesical , Aged , Female , Fibrinolytic Agents/therapeutic use , Humans , Inpatients , Male , Middle Aged , Stroke/diagnostic imaging , Time Factors , Time-to-Treatment , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome
