Association between migraine and the risk of vascular dementia: A nationwide longitudinal study in South Korea.

OBJECTIVE: We aimed to examine the potential association between migraine and vascular dementia (VaD) using a nationwide population database. BACKGROUND: Migraine and VaD showed similar structural and functional changes in pathophysiology process and shared common risk factors, However, whether migraine prevalence increases VaD incidence remains controversial. METHODS: This retrospective population-based cohort study used the medical records from the Korean National Health Insurance System database. Migraine (G43) was defined by using the Tenth Revision of the International Classification of Diseases code. More than two migraine diagnoses at least 3 months apart were defined as "chronic migraine". Cox proportional hazards model estimated hazard ratios (HRs) of VaD for group comparisons. RESULTS: We included 212,836 patients with migraine and 5,863,348 individuals without migraine. During 10 years of follow-up, 3,914 (1.8%) and 60,258 (1.0%) patients with and without migraine, respectively, were newly diagnosed with VaD. After adjustment, patients with migraine showed a 1.21-fold higher risk of VaD than those without migraine (HR = 1.21; 95% confidence interval (CI): 1.17-1.25). Patients with chronic migraine showed a higher cumulative incidence of VaD than those with episodic migraine. The adjusted HR for the VaD incidence with migraine was higher in: (1) patients aged <65 years; (2) women; (3) patients without hypertension, diabetes, or atrial fibrillation; and (4) non-smokers. CONCLUSION: Migraine is associated with an increased risk of VaD, particularly in chronic migraine patients. Incidence of VaD in the setting of migraine may have distinct pathophysiology from that of VaD with traditional cardiovascular risks.

In vivo effects of cell seeding technique in an ex vivo regional gene therapy model for bone regeneration.

When delivering cells on a scaffold to treat a bone defect, the cell seeding technique determines the number and distribution of cells within a scaffold, however the optimal technique has not been established. This study investigated if human adipose-derived stem cells (ASCs) transduced with a lentiviral vector to overexpress bone morphogenetic protein 2 (BMP-2) and loaded on a scaffold using dynamic orbital shaker could reduce the total cell dose required to heal a critical sized bone defect when compared with static seeding. Human ASCs were loaded onto a collagen/biphasic ceramic scaffold using static loading and dynamic orbital shaker techniques, compared with our labs standard loading technique, and implanted into femoral defects of nude rats. Both a low dose and standard dose of transduced cells were evaluated. Outcomes investigated included BMP-2 production, radiographic healing, micro-computerized tomography, histologic assessment, and biomechanical torsional testing. BMP-2 production was higher in the orbital shaker cohort compared with the static seeding cohort. No statistically significant differences were noted in radiographic, histomorphometric, and biomechanical outcomes between the low-dose static and dynamic seeding groups, however the standard-dose static seeding cohort had superior biomechanical properties. The standard-dose 5 million cell dose standard loading cohort had superior maximum torque and torsional stiffness on biomechanical testing. The use of orbital shaker technique was labor intensive and did not provide equivalent biomechanical results with the use of fewer cells.

Challenges in capacity building of national immunization programs and emergency or pandemic vaccination responses in the Global Health Security Agenda member countries.

The Immunization Action Package aims to increase the vaccination rate for vaccine-preventable diseases to save lives. To achieve this, member countries of the Global Health Security Agenda (GHSA) must have the capacity to implement sustainable national immunization programs (NIPs) and to respond to emergency vaccination scenarios. This article focuses on 4 major areas of NIP capacity, including in emergency situations: infrastructure capacity, sustainable financing capacity, vaccine access and equity, and vaccination hesitancy. Countries require resilient infrastructure to achieve high vaccination rates and develop preparedness for public health emergencies. Financial sustainability is crucial in achieving high vaccination coverage to best implement initiatives and national programs. Furthermore, challenges to NIPs include vaccine access and equity, as inequitable distribution and access to vaccines for coronavirus disease 2019 accelerated the impact of the pandemic. Lastly, the correlation between low acceptance and successful implementation of national initiatives suggests that vaccination hesitancy is another challenge to NIPs. In an attempt to overcome these challenges, the Expert Forum of the GHSA Seventh Ministerial Meeting was held to provide sessions allowing countries to share their national case studies and discuss strategies for capacity building of country-level NIPs, including for emergency responses.

Symmetrical Ligand's Fabricated Porous Silicon Surface Based Photoluminescence Sensor for Metal Detection and Entrapment.

This study was based on the development of surface-based photoluminescence sensor for metal detection, quantification, and sample purification employing the solid sensory chip having the capability of metal entrapment. The Co(II), Cu(II) and Hg(II) sensitive fluorescence sensor (TP) was first synthesized and characterized its sensing abilities towards tested metal ions by using fluorescence spectral investigation while the synthesis and complexation of the receptor was confirmed by the chromogenic, optical, spectroscopic and spectrometric analysis. Under optical investigation, the ligand solution exhibited substantial chromogenic changes as well as spectral variations upon reacting with copper, cobalt, and mercuric ions, while these behaviors were not seen for the rest of tested metallic ions i.e., Na+, Ag+, Ni2+, Mn2+, Pd2+, Pb2+, Cd2+, Zn2+, Sn2+, Fe2+, Fe3+, Cr3+, and Al3+. These colorimetric alterations and spectral shifting could potentially be employed to detect and quantify these specific metal ions. After the establishment of the ligand's selective complexation ability towards selected metals, it was fabricated over the substituted porous silicon surface (FPS) keeping in view of the development of surface-based photoluminescence sensor (TP-FPS) for the selected metal sensation and entrapment to purify the sample just be putting off the metal entrapped sensory solid chip. Surface characterization and ligand fabrication was inspected by plan and cross sectional electron microscopic investigations, vibrational and electronic spectral analysis. The sensitivity of the ligand (TP) in the solution phase metal discrimination was determined by employing the fluorescence titration analysis of the ligand solution after progressive induction of Co2+, Cu2+, and Hg2+, which afford the detection limit values of 2.14 × 10- 8, 3.47 × 10- 8 and 3.13 × 10- 3, respectively. Concurrently, photoluminescence titration of the surface fabricated sensor (TP-FPS) revealed detection limit values of 3.14 × 10- 9, 7.43 × 10- 9, and 8.21 × 10- 4, respectively, for the selected metal ions.

Generation of synthetic PET/MR fusion images from MR images using a combination of generative adversarial networks and conditional denoising diffusion probabilistic models based on simultaneous 18F-FDG PET/MR image data of pyogenic spondylodiscitis.

BACKGROUND CONTEXT: Cross-modality image generation from magnetic resonance (MR) to positron emission tomography (PET) using the generative model can be expected to have complementary effects by addressing the limitations and maximizing the advantages inherent in each modality. PURPOSE: This study aims to generate synthetic PET/MR fusion images from MR images using a combination of generative adversarial networks (GANs) and conditional denoising diffusion probabilistic models (cDDPMs) based on simultaneous 18F-fluorodeoxyglucose (18F-FDG) PET/MR image data. STUDY DESIGN: Retrospective study with prospectively collected clinical and radiological data. PATIENT SAMPLE: This study included 94 patients (60 men and 34 women) with thoraco-lumbar pyogenic spondylodiscitis (PSD) from February 2017 to January 2020 in a single tertiary institution. OUTCOME MEASURES: Quantitative and qualitative image similarity were analyzed between the real and synthetic PET/ T2-weighted fat saturation MR (T2FS) fusion images on the test data set. METHODS: We used paired spinal sagittal T2FS and PET/T2FS fusion images of simultaneous 18F-FDG PET/MR imaging examination in patients with PSD, which were employed to generate synthetic PET/T2FS fusion images from T2FS images using a combination of Pix2Pix (U-Net generator + Least Squares GANs discriminator) and cDDPMs algorithms. In the analyses of image similarity between the real and synthetic PET/T2FS fusion images, we adopted the values of mean peak signal to noise ratio (PSNR), mean structural similarity measurement (SSIM), mean absolute error (MAE), and mean squared error (MSE) for quantitative analysis, while the discrimination accuracy by three spine surgeons was applied for qualitative analysis. RESULTS: Total 2082 pairs of T2FS and PET/T2FS fusion images were obtained from 172 examinations on 94 patients, which were randomly assigned to training, validation, and test data sets in 8:1:1 ratio (1664, 209, and 209 pairs). The quantitative analysis revealed PSNR of 30.634 ± 3.437, SSIM of 0.910 ± 0.067, MAE of 0.017 ± 0.008, and MSE of 0.001 ± 0.001, respectively. The values of PSNR, MAE, and MSE significantly decreased as FDG uptake increase in real PET/T2FS fusion image, with no significant correlation on SSIM. In the qualitative analysis, the overall discrimination accuracy between real and synthetic PET/T2FS fusion images was 47.4%. CONCLUSIONS: The combination of Pix2Pix and cDDPMs demonstrated the potential for cross-modal image generation from MR to PET images, with reliable quantitative and qualitative image similarities.

Zeolite application mitigates NH3 and N2O emissions from pig slurry-applied field and improves nitrogen use efficiency in Italian ryegrass-maize crop rotation system for forage production.

The present study aimed to assess the efficiency of zeolite in mitigating the nitrogen (N) losses through ammonia (NH3) and nitrous oxide (N2O) emissions from pig slurry (PS) applied to Italian ryegrass (IRG)-maize fields under a crop rotation system and the consequent effect on nitrogen use efficiency (NUE) for forage production. PS was applied at rates of 150 and 200 kg N ha-1 for the IRG and maize growing seasons, respectively, with or without zeolite. Soil mineral N content and NH3 and N2O emissions were measured periodically throughout the year-round cultivation of IRG and maize. Forage yield and nutritional composition were also analyzed at the harvest time of each crop. The PS with/without zeolite application effects were interpreted by comparison with those obtained for the negative control (no-N fertilization). Soil ammonium (NH4+) content in the PS-applied plots sharply increased within the first week, then progressively decreased in both the IRG and maize growing seasons. Soil NH4+ contents in the zeolite-amended plots were higher compared to the treatment without zeolite except for the first 1 or 2 weeks after PS application when soil nitrate (NO3-) contents significantly decreased. The increase in soil NH4+ content as affected by zeolite application was more distinct in the maize growing season than in the IRG growing season. NH3 emission was predominant at the early 2 weeks after PS application. Zeolite application reduced the cumulative emission of NH3 from PS by 16.7% and 24.4% and that of N2O by 15.6% and 31.5% in the IRG growing and maize growing seasons, respectively. NUE for dry matter (DM) and total digestible nutrients (TDN) production significantly improved in annual yield basis of the IRG-maize cropping. Zeolite application in PS-applied field may represent effective management in mitigating N losses through odorous NH3 and greenhouse gas (N2O) emissions, thereby improving NUE forage production.

Federated learning with knowledge distillation for multi-organ segmentation with partially labeled datasets.

The state-of-the-art multi-organ CT segmentation relies on deep learning models, which only generalize when trained on large samples of carefully curated data. However, it is challenging to train a single model that can segment all organs and types of tumors since most large datasets are partially labeled or are acquired across multiple institutes that may differ in their acquisitions. A possible solution is Federated learning, which is often used to train models on multi-institutional datasets where the data is not shared across sites. However, predictions of federated learning can be unreliable after the model is locally updated at sites due to 'catastrophic forgetting'. Here, we address this issue by using knowledge distillation (KD) so that the local training is regularized with the knowledge of a global model and pre-trained organ-specific segmentation models. We implement the models in a multi-head U-Net architecture that learns a shared embedding space for different organ segmentation, thereby obtaining multi-organ predictions without repeated processes. We evaluate the proposed method using 8 publicly available abdominal CT datasets of 7 different organs. Of those datasets, 889 CTs were used for training, 233 for internal testing, and 30 volumes for external testing. Experimental results verified that our proposed method substantially outperforms other state-of-the-art methods in terms of accuracy, inference time, and the number of parameters.

Ratiometric Fluorescence and Chromogenic Probe for Trace Detection of Selected Transition Metals.

The design and development of a fluorescence sensor aimed at detecting and quantifying trace amounts of toxic transition metal ions within environmental, biological, and aquatic samples has garnered significant attention from diagnostic and testing laboratories, driven by the imperative to mitigate the health risks associated with these contaminants. In this context, we present the utilization of a heterocyclic symmetrical Schiff Base derivative for the purpose of fluorogenic and chromogenic detection of Co2+, Cu2+ and Hg2+ ions. The characterization of the ligand involved a comprehensive array of techniques, including physical assessments, optical analyses, NMR, FT-IR, and mass spectrometric examinations. The mechanism of ligand-metal complexation was elucidated through the utilization of photophysical parameters and FT-IR spectroscopic analysis, both before and after the interaction between the ligand and the metal salt solution. The pronounced alterations observed in absorption and fluorescence spectra, along with the distinctive chromogenic changes, following treatment with Co2+, Cu2+ and Hg2+, affirm the successful formation of complexes between the ligands and the treated metal ions. Notably, the receptor's complexation response exhibited selectivity towards Co(II), Cu(II), and Hg(II), with no observed chromogenic changes, spectral variations, or band shifts for the various tested metal ions, including Na+, Ag+, Ni2+, Mn2+, Pd2+, Pb2+, Cd2+, Zn2+, Sn2+, Fe2+, Fe3+, Cr3+ and Al3+. This absence of interaction between these metal ions and the ligand could be attributed to their compact or inadequately conducive conduction bands for complexation with the ligand's structural composition. To quantify the sensor's efficacy, fluorescence titration spectra were employed to determine the detection limits for Co2+, Cu2+ and Hg2+, yielding values of 2.92 × 10-8, 8.91 × 10-8, and 4.39 × 10-3 M, respectively. The Benesi-Hildebrand plots provided association constant values for the ligand-cobalt, ligand-copper, and ligand-mercury complexes as 0.74, 2.52, and 13.89 M-1, respectively.

Determination of Optimal Antigen Yield and Virus Inactivation Conditions for the Production of the Candidate Foot-and-Mouth Disease Recombinant Vaccine Strain Asia1 Shamir-R in a Bioreactor.

Since the foot-and-mouth disease (FMD) outbreak in South Korea in 2010-2011, vaccination policies utilizing inactivated FMD vaccines composed of types O and A have been implemented nationwide. However, because type Asia1 occurred in North Korea in 2007 and intermittently in neighboring countries, the risk of type Asia1 introduction cannot be ruled out. This study evaluated the antigen yield and viral inactivation kinetics of the recombinant Asia1 Shamir vaccine strain (Asia1 Shamir-R). When Asia1 Shamir-R was proliferated in shaking flasks (1 L), a 2 L bioreactor (1 L), and a wave bioreactor (25 L), the antigen yields were 7.5 µg/mL, 5.2 µg/mL, and 3.8 µg/mL, respectively. The optimal FMDV inactivation conditions were 2 mM BEI at 26 °C and 1.0 mM BEI at 37 °C. There was no antigen loss due to BEI treatment, and only a decrease in antigen levels was observed during storage. The sera from pigs immunized with antigen derived from a bioreactor exhibited a neutralizing antibody titer of approximately 1/1000 against Asia1 Shamir and Asia1/MOG/05 viruses; therefore, Asia1 Shamir-R is expected to provide sufficient protection against both viruses. If an FMD vaccine production facility is established, this Asia1 Shamir-R can be employed for domestic antigen banks in South Korea.

Enhanced Nuclei Segmentation and Classification via Category Descriptors in the SAM Model.

Segmenting and classifying nuclei in H&E histopathology images is often limited by the long-tailed distribution of nuclei types. However, the strong generalization ability of image segmentation foundation models like the Segment Anything Model (SAM) can help improve the detection quality of rare types of nuclei. In this work, we introduce category descriptors to perform nuclei segmentation and classification by prompting the SAM model. We close the domain gap between histopathology and natural scene images by aligning features in low-level space while preserving the high-level representations of SAM. We performed extensive experiments on the Lizard dataset, validating the ability of our model to perform automatic nuclei segmentation and classification, especially for rare nuclei types, where achieved a significant detection improvement in the F1 score of up to 12%. Our model also maintains compatibility with manual point prompts for interactive refinement during inference without requiring any additional training.

Exosome Secretion and Cellular Signaling Change in a Fabry Disease Cell Model Induced by Gene-silencing.

BACKGROUND/AIM: Fabry disease (FD) is caused by α-galactosidase A (AGA) deficiency, which ultimately leads to the intracellular accumulation of globotriaosylceramide (Gb3). Exosomes play a role in maintaining cellular homeostasis by clearing damaged or toxic materials, including proteins. In the process of excessive accumulation of intracellular Gb3 in Fabry disease, it may be suggested that exosomal secretion of Gb3 increases to preserve cell homeostasis. This study sought to determine how exosomal secretion and cell signaling change in an FD cell model produced by gene silencing. MATERIALS AND METHODS: HEK293T cells were transfected with plasmids carrying shRNA against the GLA gene to produce the FD cell model. A recombinant AGA, agalsidase-beta, was used to evaluate the effect of enzyme replacement therapy (ERT) on exosomal secretion and cell signaling. RESULTS: Exosome secretion was significantly increased in the Fabry disease cell model compared to the control vector cell model, and significantly decreased after agalsidase-beta treatment. The FD cell model showed higher reactive oxygen species (ROS) production and p53 protein expression compared to the control vector cell model. CONCLUSION: Increased exosomal secretion in Fabry disease may be a cellular mechanism to avoid excessive and cytotoxic accumulation of Gb3 in lysosomes through intracellular signaling, including increased p53 expression.

Evaluation of Foot-and-Mouth Disease (FMD) Virus Asia1 Genotype-V as an FMD Vaccine Candidate: Study on Vaccine Antigen Production Yield and Inactivation Kinetics.

South Korea has experienced outbreaks of foot-and-mouth disease (FMD) of serotypes O and A, leading to nationwide vaccination with a bivalent vaccine. Since the FMD virus (FMDV) Asia1 group-V genotype occurred in North Korea in 2007, an Asia1/MOG/05 vaccine strain belonging to the Asia1 group-V genotype was developed using a genetic recombination method (Asia1/MOG/05-R). This study aimed to evaluate the antigen productivity and viral inactivation kinetics of Asia1/MOG/05-R to assess its commercial viability. The antigen yield of Asia1/MOG/05-R produced in flasks and bioreactors was approximately 4.0 µg/mL. Binary ethylenimine (BEI) inactivation kinetics of Asia1/MOG/05-R showed that 2 mM and 1.0 mM BEI treatment at 26 °C and 37 °C, respectively, resulted in a virus titer <10-7 TCID50/mL within 24 h, meeting the inactivation kinetics criteria. During incubation at 26 °C and 37 °C, 10% antigen loss occurred, but not due to BEI treatment. When pigs were inoculated twice with the Asia1/MOG/05-R antigen, the virus neutralization titer increased to approximately 1:1000; therefore, it can sufficiently protect against Asia1/MOG/05-R and Asia1 Shamir viruses. The Asia1/MOG/05-R will be useful as a vaccine strain for domestic antigen banks.

Glucose control and outcomes in diabetic and nondiabetic patients treated with targeted temperature management after cardiac arrest.

Hyperglycemia is commonly observed in critically ill patients and postcardiac arrest patients, with higher glucose levels and variability associated with poorer outcomes. In this study, we aim to compare glucose control in diabetic and nondiabetic patients using glycated hemoglobin (HbA1c) levels, providing insights for better glucose management strategies. This retrospective observational study was conducted at Seoul St. Mary's Hospital from February 2009 to May 2022. Blood glucose levels were measured hourly for 48 h after return of spontaneous circulation (ROSC), and a glucose management protocol was followed to maintain arterial blood glucose levels between 140 and 180 mg/dL using short-acting insulin infusion. Patients were categorized into four groups based on diabetes status and glycemic control. The primary outcomes assessed were neurological outcome and mortality at 6 months after cardiac arrest. Among the 332 included patients, 83 (25.0%) had a previous diabetes diagnosis, and 114 (34.3%) had an HbA1c of 6.0% or higher. At least one hyperglycemic episode was observed in 314 patients (94.6%) and hypoglycemia was found in 63 patients (19.0%) during 48 h. After the categorization, unrecognized diabetes was noticed in 51 patients with median HbA1c of 6.3% (interquartile range [IQR] 6.1-6.6). Patients with inadequate diabetes control had the highest initial HbA1c level (7.0%, IQR 6.5-7.8) and admission glucose (314 mg/dL, IQR 257-424). Median time to target glucose in controlled diabetes was significantly shorter with the slowest glucose reducing rate. The total insulin dose required to reach the target glucose level and cumulative insulin requirement during 48 h were different among the categories (p <0.001). Poor neurological outcomes and mortality were more frequently observed in patients with diagnosed diabetes. Occurrence of a hypoglycemic episode during the 48 h after ROSC was independently associated with poor neurologic outcomes (odds ratio [OR] 3.505; 95% confidence interval [CI], 2.382-9.663). Surviving patients following cardiac arrest exhibited variations in glucose hemodynamics and outcomes according to the categories based on their preexisting diabetes status and glycemic condition. Specifically, even experiencing a single episode of hypoglycemia during the acute phase could have an influence on unfavorable neurological outcomes. While the classification did not directly affect neurological outcomes, the present results indicate the need for a customized approach to glucose control based on these categories.

Mid- and long-term risk of atrial fibrillation among breast cancer surgery survivors.

BACKGROUND: The risk of incident atrial fibrillation (AF) among breast cancer survivors, especially for younger women, and cancer treatment effects on the association remain unclear. This study aimed to investigate the risk of AF among breast cancer survivors and evaluate the association by age group, length of follow-up, and cancer treatment. METHODS: Using data from the Korean Health Insurance Service database (2010-2017), 113,232 women newly diagnosed with breast cancer (aged ≥ 18 years) without prior AF history who underwent breast cancer surgery were individually matched 1:5 by birth year to a sample female population without cancer (n = 566,160) (mean[SD] follow-up, 5.1[2.1] years). Sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) considering death as a competing risk were estimated, adjusting for sociodemographic factors and cardiovascular/non-cardiovascular comorbidities. RESULTS: BCS had a slightly increased AF risk compared to their cancer-free counterparts (sHR 1.06; 95% CI 1.00-1.13), but the association disappeared over time. Younger BCS (age < 40 years) had more than a 2-fold increase in AF risk (sHR 2.79; 95% CI 1.98-3.94), with the association remaining similar over 5 years of follow-up. The increased risk was not observed among older BCS, especially those aged > 65 years. Use of anthracyclines was associated with increased AF risk among BCS (sHR 1.57; 95% CI 1.28-1.92), which was more robust in younger BCS (sHR 1.94; 95% CI 1.40-2.69 in those aged ≤ 50 years). CONCLUSIONS: Our findings suggest that younger BCS had an elevated risk of incident AF, regardless of the length of follow-up. Use of anthracyclines may be associated with increased mid-to-long-term AF risk among BCS.

The association between migraine and Parkinson's disease: a nationwide cohort study.

OBJECTIVES: Clinical studies have suggested an association between migraine and the occurrence of Parkinson's disease (PD). However, it is unknown whether migraine affects PD risk. We aimed to investigate the incidence of PD in patients with migraine and to determine the risk factors affecting the association between migraine and PD incidence. METHODS: Using the Korean National Health Insurance System database (2002-2019), we enrolled all Koreans aged ≥40 years who participated in the national health screening program in 2009. International Classification of Diseases (10th revision) diagnostic codes and Rare Incurable Diseases System diagnostic codes were used to define patients with migraine (within 12 months of enrollment) and newly diagnosed PD. RESULTS: We included 214,193 patients with migraine and 5,879,711 individuals without migraine. During 9.1 years of follow-up (55,435,626 person-years), 1,973 (0.92%) and 30,664 (0.52%) individuals with and without migraine, respectively, were newly diagnosed with PD. Following covariate adjustment, patients with migraine showed a 1.35-fold higher PD risk than individuals without migraine. The incidence of PD was not significantly different between patients with migraine with aura and those without aura. In males with migraine, underlying dyslipidemia increased the risk of PD (p=0.012). In contrast, among females with migraine, younger age (<65 years) increased the risk of PD (p=0.038). CONCLUSIONS: Patients with migraine were more likely to develop PD than individuals without migraine. Preventive management of underlying comorbidities and chronic migraine may affect the incidence of PD in these patients. Future prospective randomized clinical trials are warranted to clarify this association.

Reduction of Upper Gastrointestinal Bleeding Risk With Proton Pump Inhibitor Therapy in Asian Patients With Atrial Fibrillation Receiving Direct Oral Anticoagulant: A Nationwide Population-based Cohort Study.

BACKGROUND & AIMS: In patients with atrial fibrillation (AF) receiving direct oral anticoagulant (DOAC), upper gastrointestinal bleeding (UGIB) is a serious complication. There are limited data on the benefit of preventive proton pump inhibitor (PPI) use to reduce the risk of UGIB in DOAC users. METHODS: We included patients with AF receiving DOAC from 2015 to 2020 based on the Korean Health Insurance Review and Assessment database. The propensity score (PS) weighting method was used to compare patients with PPI use and those without PPI use. The primary outcome was hospitalization for UGIB. Weighted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were evaluated using the Cox proportional hazards regression model. RESULTS: A total of 165,624 patients were included (mean age: 72.2 ± 10.8 years; mean CHA2DS2-VASc score: 4.3 ± 1.8; mean HAS-BLED score: 3.3 ± 1.2). Among them, 99,868 and 65,756 were in the non-PPI group and PPI group, respectively. During a median follow-up of 1.5 years, the PPI group was associated with lower risks of hospitalization for UGIB and UGIB requiring red blood cell transfusion than non-PPI group (weighted HR, 0.825; 95% CI, 0.761-0.894 and 0.798; 95% CI, 0.717-0.887, respectively, both P < .001). The benefits of PPI on the risk of hospitalization for UGIB were greater in those with older age (≥75 years), higher HAS-BLED score (≥3), prior GIB history, and concomitant use of antiplatelet agent (all P-for-interaction < .1). Low-dose PPI was consistently associated with a lower risk of significant UGIB by 43.6-49.3% (P < .001). CONCLUSIONS: In this large Asian cohort of patients with AF on DOAC, PPI co-therapy is beneficial for reducing the risk of hospitalization for UGIB, particularly in high-risk patients.

Naturally manufactured biochar materials based sensor electrode for the electrochemical detection of polystyrene microplastics.

In recent times, microplastics have become a disturbance to both aquatic and terrestrial ecosystems and the ingestion of these particles can have severe consequences for wildlife, aquatic organisms, and even humans. In this study, two types of biochars were manufactured through the carbonization of naturally found starfish (SF-1) and aloevera (AL-1). The produced biochars were utilized as sensing electrode materials for the electrochemical detection of ∼100 nm polystyrene microplastics (PS). SF-1 and AL-1 based biochars were thoroughly analyzed in terms of morphology, structure, and composition. The detection of microplastics over biochar based electrodes was carried out by electrochemical studies. From electrochemical results, SF-1 based electrode exhibited the detection efficiency of ∼0.2562 µA/µM∙cm2 with detection limit of ∼0.44 nM whereas, a high detection efficiency of ∼3.263 µA/µM∙cm2 was shown by AL-1 based electrode and detection limit of ∼0.52 nM for PS (100 nm) microplastics. Process contributed to enhancing the sensitivity of AL-1 based electrode might associate to the presence of metal-carbon framework over biochar's surfaces. The AL-1 biochar electrode demonstrated excellent repeatability and detection stability for PS microplastics, suggesting the promising potential of AL-1 biochar for electrochemical microplastics detection.

Association between early lactate-related variables and 6-month neurological outcome in out-of-hospital cardiac arrest patients.

INTRODUCTION: The role of lactate measurement in out-of-hospital cardiac arrest (OHCA) survivors remains controversial. We assessed the association between early lactate-related variables, OHCA characteristics, and long-term neurological outcome. METHODS: In OHCA patients who received targeted temperature management, lactate levels were measured at 0, 12, and 24 h after the return of spontaneous circulation. We calculated lactate clearance and time-weighted cumulative lactate (TWCL), which represent the area under the time-lactate curve. The area under the receiver operating characteristic curve (AUC) and the adjusted odds ratios (AORs) of lactate-related variables for predicting 6-month poor outcome (Cerebral Performance Category 3-5) were evaluated. Interactions between lactate variables and characteristics of OHCA were evaluated by a multivariable logistic model with interaction terms and subgroup analysis. RESULTS: A total of 347 OHCA patients were included. After adjustment, higher lactate levels at the three time points were associated with a poor outcome (AOR 1.10 [95% CI, 1.03-1.18], AOR 1.15 [95% CI, 1.02-1.29], and AOR 1.36 [95% CI, 1.15-1.60], respectively), while TWCL was the only lactate kinetics variable associated with a poor outcome (AOR 1.29 [95% CI, 1.12-1.49]). We identified several interactions between lactate-related variables and OHCA characteristics. In particular, the AUC of TWCL was excellent in cases of noncardiac etiology (AUC 0.92 [95% CI, 0.86-0.96] but only moderate in cardiac etiology (AUC 0.69 [95% CI, 0.62-0.75]). CONCLUSIONS: Early lactate levels, especially at 24 h, and TWCL were independent predictors of neurologic outcome in these patients, whereas lactate clearance was not. The prognostic ability of lactate-related variables varied depending on the OHCA characteristics.