A Rare Case of Stroke in a 76-Year-Old Woman: Left Atrial Papillary Fibroelastoma as the Culprit.

BACKGROUND Papillary fibroelastoma is the most common type of benign primary cardiac tumor and is usually asymptomatic. However, tumor fragments or surface thrombus can embolize and cause transient ischemic attacks, strokes, or myocardial infarction. This report describes a 76-year-old woman who presented with dysarthria and right-sided weakness due to a stroke associated with a left atrial papillary fibroelastoma. CASE REPORT A 76-year-old woman visited the Emergency Department because she had right-sided weakness and dysarthria from 12 h ago. Brain magnetic resonance image was done at the Emergency Department, showing multiple small embolic, acute infarction in left basal ganglia and fronto-temporo-parietal lobes. Transthoracic and transesophageal echocardiogram showed a hypermobile echogenic mass (0.8×1.5 cm) with villous surface on the orifice of left atrial appendage. Twenty-four-hour Holter monitoring was performed to evaluate the cause of cerebral infarction, and there was no paroxysmal atrial fibrillation. Thoracic computed tomography angiography also showed a sea anemone-shaped mass around the left atrial appendage. Cardiac tumor excision was done via a lower partial sternotomy. Histopathologic analysis showed multiple delicate fronds, and the avascular fibroelastic cores were lined by a single layer of CD31-positive endothelial cells. Histopathologic findings were consistent with papillary fibroelastoma. The patient was discharged without any other complications on day 30 of hospitalization. CONCLUSIONS This case highlights the importance of cardiac imaging in patients with acute stroke, including transthoracic and transesophageal echocardiography, which can show the typical imaging features of papillary fibroelastoma and other intracardiac sources of embolus.

Association Between Ambulance Station Case Volume and Clinical Outcomes in Moderate to Severe Trauma.

OBJECTIVES: The effect of the case volume of emergency medical services (EMS) on the clinical outcomes of trauma is uncertain. The purpose of this study was to evaluate the association between the case volume of an ambulance station and clinical outcomes in moderate to severe trauma patients. METHODS: Adult trauma patients with injury severity scores greater than 8 who were transported by the EMS between 2018 and 2019 were analyzed. The main exposure was the annual case volume of moderate to severe trauma at the ambulance station where the patient-transporting ambulance was based: low-volume (less than 60 cases), intermediate-volume (between 60 and 89 cases), and high-volume (equal or greater than 90 cases). The primary outcome was in-hospital mortality. Multilevel multivariable logistic regression analysis was conducted to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs), with the high-volume group used as the reference. RESULTS: In total, 21,498 trauma patients were analyzed. The high-volume group exhibited lower in-hospital mortality, 447 (9.0%), compared to 867 (14.1%) in the intermediate-volume group and 1,458 (14.1%) in the low-volume group. There were a significantly higher odds of in-hospital mortality: the low-volume group (AOR 95% CI: 1.20 (0.95-1.51)) and intermediate-volume group (AOR 95% CI: 1.29 (1.02-1.64)) when compared to the high-volume group. CONCLUSIONS: The case volume at an ambulance station is associated with in-hospital mortality in patients with moderate to severe trauma. These results should be considered when constructing an EMS system and education program for prehospital trauma care.

Disparity in guideline adherence for prehospital care according to patient age in emergency medical service transport for moderate to severe trauma.

OBJECTIVES: The aim of this study was to investigate the association between patient age and guideline adherence for prehospital care in emergency medical services (EMS) for moderate to severe trauma. METHODS: This was a retrospective observational study that used a nationwide EMS-based trauma database from 2016 to 2019. Adult trauma patients whose injury severity score was greater than or equal to nine were screened, and those with cardiac arrest or without outcome data were excluded. The enrolled patients were categorized into four groups according to patient age: young (<45 years), middle-aged (45-64 years), old (65-84 years), and very old (>84 years). The primary outcome was guideline adherence, which was defined as following all prehospital care components: airway management for level of consciousness below verbal response, oxygen supply for pulse oximetry under 94 %, intravenous fluid administration for systolic blood pressure under 90 mmHg, scene resuscitation time within 10 min, and transport to the trauma center or level 1 emergency department. Multivariable logistic regression was conducted to calculate the adjusted odds ratios (aORs) and 95 % confidence intervals (95 % CIs). RESULTS: Among the 430,365 EMS-treated trauma patients, 38,580 patients were analyzed-9,573 (24.8 %) in the young group, 15,296 (39.7 %) in the middle-aged group, 9,562 (24.8 %) in the old group, and 4,149 (10.8 %) in the very old group. The main analysis revealed a lower probability of guideline adherence in the old group (aOR 95 % CI = 0.84 (0.76-0.94)) and very old group (aOR 95 % CI = 0.68 (0.58-0.81)) than in the young group. CONCLUSION: We found disparities in guideline adherence for prehospital care according to patient age at the time of EMS assessment of moderate to severe trauma. Considering this disparity, the prehospital trauma triage and management for older patients needs to be improved and educated to EMS providers.

Development of Prediction Model for Intensive Care Unit Admission Based on Heart Rate Variability: A Case-Control Matched Analysis.

This study aimed to develop a predictive model for intensive care unit (ICU) admission by using heart rate variability (HRV) data. This retrospective case-control study used two datasets (emergency department [ED] patients admitted to the ICU, and patients in the operating room without ICU admission) from a single academic tertiary hospital. HRV metrics were measured every 5 min using R-peak-to-R-peak (R-R) intervals. We developed a generalized linear mixed model to predict ICU admission and assessed the area under the receiver operating characteristic curve (AUC). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated from the coefficients. We analyzed 610 (ICU: 122; non-ICU: 488) patients, and the factors influencing the odds of ICU admission included a history of diabetes mellitus (OR [95% CI]: 3.33 [1.71-6.48]); a higher heart rate (OR [95% CI]: 3.40 [2.97-3.90] per 10-unit increase); a higher root mean square of successive R-R interval differences (RMSSD; OR [95% CI]: 1.36 [1.22-1.51] per 10-unit increase); and a lower standard deviation of R-R intervals (SDRR; OR [95% CI], 0.68 [0.60-0.78] per 10-unit increase). The final model achieved an AUC of 0.947 (95% CI: 0.906-0.987). The developed model effectively predicted ICU admission among a mixed population from the ED and operating room.

Early identification of suspected serious infection among patients afebrile at initial presentation using neural network models and natural language processing: A development and external validation study in the emergency department.

OBJECTIVE: To develop and externally validate models based on neural networks and natural language processing (NLP) to identify suspected serious infections in emergency department (ED) patients afebrile at initial presentation. METHODS: This retrospective study included adults who visited the ED afebrile at initial presentation. We developed four models based on artificial neural networks to identify suspected serious infection. Patient demographics, vital signs, laboratory test results and information extracted from initial ED physician notes using term frequency-inverse document frequency were used as model variables. Models were trained and internally validated with data from one hospital and externally validated using data from a different hospital. Model discrimination was evaluated using area under the receiver operating characteristic curve (AUC) and 95% confidence intervals (CIs). RESULTS: The training, internal validation, and external validation datasets comprised 150,699, 37,675, and 85,098 patients, respectively. The AUCs (95% CIs) for Models 1 (demographics + vital signs), 2 (demographics + vital signs + initial ED physician note), 3 (demographics + vital signs + laboratory tests), and 4 (demographics + vital signs + laboratory tests + initial ED physician note) in the internal validation dataset were 0.789 (0.782-0.796), 0.867 (0.862-0.872), 0.881 (0.876-0.887), and 0.911 (0.906-0.915), respectively. In the external validation dataset, the AUCs (95% CIs) of Models 1, 2, 3, and 4 were 0.824 (0.817-0.830), 0.895 (0.890-0.899), 0.879 (0.873-0.884), and 0.913 (0.909-0.917), respectively. Model 1 can be utilized immediately after ED triage, Model 2 can be utilized after the initial physician notes are recorded (median time from ED triage: 28 min), and Models 3 and 4 can be utilized after the initial laboratory tests are reported (median time from ED triage: 68 min). CONCLUSIONS: We developed and validated models to identify suspected serious infection in the ED. Extracted information from initial ED physician notes using NLP contributed to increased model performance, permitting identification of suspected serious infection at early stages of ED visits.

Inhibition of Glial Activation and Subsequent Reduction in White Matter Damage through Supplementation with a Combined Extract of Wheat Bran, Citrus Peel, and Jujube in a Rat Model of Vascular Dementia.

Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease. In our previous studies, we showed that wheat bran extract (WBE) reduced white matter damage in a rat VaD model and improved memory in a human clinical trial. However, starch gelatinization made the large-scale preparation of WBE difficult. To simplify the manufacturing process and increase efficacy, we attempted to find a decoction containing an optimum ratio of wheat bran, sliced citrus peel, and sliced jujube (WCJ). To find an optimal ratio, the cell survival of C6 (rat glioma) cultured under hypoxic conditions (1% O2) was measured, and apoptosis was assessed. To confirm the efficacies of the optimized WCJ for VaD, pupillary light reflex, white matter damage, and the activation of astrocytes and microglia were assessed in a rat model of bilateral common carotid artery occlusion (BCCAO) causing chronic hypoperfusion. Using a combination of both searching the literature and cell survival experiments, we chose 6:2:1 as the optimal ratio of wheat bran to sliced citrus peel to sliced jujube to prepare WCJ. We showed that phytic acid contained only in wheat bran can be used as an indicator component for the quality control of WCJ. We observed in vitro that the WCJ treatment improved cell survival by reducing apoptosis through an increase in the Bcl-2/Bax ratio. In the BCCAO experiments, the WCJ-supplemented diet prevented astrocytic and microglial activation, mitigated myelin damage in the corpus callosum and optic tract, and, consequently, improved pupillary light reflex at dosages over 100 mg/kg/day. The results suggest that the consumption of WCJ can prevent VaD by reducing white matter damage, and WCJ can be developed as a safe, herbal medicine to prevent VaD.

Effect of first epinephrine administration time on cerebral perfusion pressure and cortical cerebral blood flow in a porcine cardiac arrest model.

OBJECTIVE: The optimal time for epinephrine administration and its effects on cerebral blood flow (CBF) and microcirculation remain controversial. This study aimed to assess the effect of the first administration of epinephrine on cerebral perfusion pressure (CePP) and cortical CBF in porcine cardiac arrest model. METHODS: After 4 min of untreated ventricular fibrillation, eight of 24 swine were randomly assigned to the early, intermediate, and late groups. In each group, epinephrine was administered intravenously at 5, 10, and 15 min after cardiac arrest induction. CePP was calculated as the difference between the mean arterial pressure and intracranial pressure. Cortical CBF was measured using a laser Doppler flow probe. The outcomes were CePP and cortical CBF measured continuously during cardiopulmonary resuscitation (CPR). Mean CePP and cortical CBF were compared using analysis of variance and a linear mixed model. RESULTS: The mean CePP was significantly different between the groups at 6-11 min after cardiac arrest induction. The mean CePP in the early group was significantly higher than that in the intermediate group at 8-10 min and that in the late group at 6-9 min and 10-11 min. The mean cortical CBF was significantly different between the groups at 9-11 min. The mean cortical CBF was significantly higher in the early group than in the intermediate and late group at 9-10 min. CONCLUSION: Early administration of epinephrine was associated with improved CePP and cortical CBF compared to intermediate or late administration during the early period of CPR.

Effect of no-flow period on the vasopressor effect of initial epinephrine administration in cardiac arrest.

OBJECTIVES: Whether a longer no-flow (NF) interval affects the magnitude of response to epinephrine in the resuscitation has not been well studied. Therefore, this study aimed to evaluate the effect of NF interval on the vasopressor effect of initial epinephrine administration in a porcine model. METHODS: We enrolled 20 pigs from two randomized porcine experimental studies using a ventricular fibrillation (VF) cardiac arrest model. The first experiment subjects were resuscitated after 4 min of NF (Short NF group), followed by three cycles (6 min) of chest compression using a mechanical cardiopulmonary resuscitation device before epinephrine administration. Second experiment subjects received 6 min of NF (Long NF group), two cycles (4 min) of chest compressions, and administration of epinephrine. Defibrillation for VF was delivered 8 and 10 min after VF induction in the Short NF and Long NF groups, respectively. The mean arterial pressure (MAP) and cerebral perfusion pressure (CePP) in the 2-min resuscitation period after epinephrine administration were compared between the study groups using the Wilcoxon rank-sum test. The mean differences in the parameters between phases were also compared. RESULTS: Seven pigs in the Short NF group and 13 pigs in the Long NF group were included in the analysis. All 2-min resuscitation phases from 6 to 16 min after VF induction were compared between the study groups. The Short NF group showed higher MAP and CePP in all phases (p < 0.01). Change of mean MAP after the epinephrine administration was significantly different between the study groups: mean difference (95% confidence interval) of 16.6 (15.8-17.4) mmHg in the Short NF group and 4.2 (3.9-4.5) mmHg in the Long NF group. CONCLUSION: In the porcine VF cardiac arrest model, 6 min of NF before resuscitation may affect the vasopressor effect of the initial epinephrine administered compared to 4 min of NF. A short NF may play a role in maximizing the effect of epinephrine in advanced cardiovascular life support.

Update of Rehabilitation in Huntington's Disease: Narrative Review.

Huntington's disease (HD) is a neurodegenerative disease that has motor dysfunction, predominantly chorea, cognitive impairment, and psychiatric disturbances as symptoms. Treatment is directed to reduce the severity of symptoms, although there are few studies and no clinical guidelines for rehabilitation in HD. Therefore, this review aimed to establish an effective rehabilitation approach for HD according to the stage of the disease. In the early stage of HD, the motor symptoms are mild, and psychological symptoms occur. Treatment in this period should focus on aerobic and resistance exercises, task-specific training, secondary prevention education, cognitive training, and psychological management. In the middle stage of HD, the motor symptoms are more severe. Task-specific rehabilitation approaches, education for the patient and caregiver, functional respiratory exercises, activities of daily living training, multidisciplinary and multimodal daycare rehabilitation are helpful to patients in this stage. At the late stage of HD, most patients need complete support for activity of daily living. Mobility and balance evaluation and prevention strategies should be focused on for safety, and respiratory exercises and physical exercise to prevent complications in patients with severely impaired mobility should be considered based on the patient's condition. Programmed rehabilitation management based on the stage of the disease is effective for patients with HD.

A new genotype of decapod hepanhamaparvovirus 1 (DHPV) from cultured Penaeus vannamei in South Korea.

Decapod hepanhamaparvovirus 1 (DHPV), also known as hepatopancreatic parvovirus (HPV), has caused death in larvae or stunted growth in juveniles of cultured shrimp. To date, 4 genotypes (genotype I, II, III, and IV) have been reported from various shrimp species and various geographical regions. In the present study, we isolated 2 types of DHPV (GHPV-Goseong and DHPV-Geoje) from cultured Penaeus vannamei in Korea. Based on the capsid protein (VP) amino acid sequences, DHPV-Goseong was highly identical to previously reported DHPV genotype IV in Taiwan and Korea. Different from DHPV-Goseong, DHPV-Geoje showed approximately 63% similarity with DHPV genotype I, II, III and 84% similarity with DHPV genotype IV, suggesting an independent new genotype of DHPV (genotype V). Further research is needed to elucidate the origin and biological meanings of the present new genotype.

Generation of Recombinant Snakehead Rhabdovirus (SHRV) Expressing Artificial MicroRNA Targeting Spring Viremia of Carp Virus (SVCV) P Gene and In Vivo Therapeutic Use Against SVCV Infection.

Spring viremia of carp virus (SVCV) is a highly lethal virus in common carp (Cyprinus carpio) and other cyprinid fish species. The aim of the present study was to develop an in vivo therapeutic measure against SVCV using artificial microRNA (AmiRNA) targeting the SVCV P gene transcript. Three candidates of AmiRNAs (AmiR-P1, -P2, and -P3) were selected, and their ability to downregulate SVCV P gene transcript was analyzed by both synthesized AmiRNA mimics and AmiRNA-expressing vector system, in which AmiR-P3 showed the strongest inhibitory activity among the three candidates. To overcome in vivo limitation of miRNA mimics or plasmid-based miRNA expression systems, we rescued recombinant snakehead rhabdoviruses (SHRVs) expressing SVCV P gene-targeting AmiRNA (rSHRV-AmiR-P3) or control AmiRNA (rSHRV-AmiR-C) using reverse genetic technology. The successful expression of AmiR-P3 and AmiR-C in cells infected with the rescued viruses was verified by quantitative PCR. To evaluate the availability of rSHRV-AmiR-P3 for in vivo control of SVCV, zebrafish (Danio rerio) were (i) infected with either rSHRV-AmiR-C or rSHRV-AmiR-P3 followed by SVCV infection or (ii) infected with SVCV followed by either rSHRV-AmiR-C or rSHRV-AmiR-P3 infection. Fish infected with rSHRVs before and after SVCV infection showed significantly higher survival rates than fish infected with SVCV alone. There was no significant difference in survival rates between groups of fish infected with rSHRV-AmiR-C and rSHRV-AmiR-P3 before SVCV infection; however, fish infected with SVCV followed by infection with rSHRV-AmiR-P3 showed significantly higher survival rates than fish infected with rSHRV-AmiR-C. These results suggest that rSHRV-AmiR-P3 has therapeutic potential against SVCV in fish when administered after SVCV infection, and rSHRVs expressing artificial microRNAs targeting SVCV transcripts could be used as a tool to control SVCV infection in fish for a therapeutic purpose.

Fact Sheet on Cardiac Rehabilitation for Cardiovascular Disease in South Korea.

Cardiovascular disease (CVD) poses a significant health challenge globally, including in Korea, due to its status as a leading cause of death and its impact on cardiopulmonary function. Cardiac rehabilitation (CR) is a well-established program that not only aids in restoring cardiopulmonary function, but also improves physical and social conditions. The benefits of CR are widely recognized, and it is implemented globally. While the effectiveness of CR has been proven in Korea, it is underutilized. This fact sheet summarizes the current status of CR in Korea, including the prevalence of CVD, the clinical practice guidelines for CR programs, and the challenges of implementing CR in Korea.

Measurement of level of consciousness by AVPU scale assessment system based on automated video and speech recognition technology.

OBJECTIVE: To develop an alert/verbal/painful/unresponsive (AVPU) scale assessment system based on automated video and speech recognition technology (AVPU-AVSR) that can automatically assess a patient's level of consciousness and evaluate its performance through clinical simulation. METHODS: We developed an AVPU-AVSR system with a whole-body camera, face camera, and microphone. The AVPU-AVSR system automatically extracted essential audiovisual features to assess the AVPU score from the recorded video files. Arm movement, pain stimulus, and eyes-open state were extracted using a rule-based approach using landmarks estimated from pre-trained pose and face estimation models. Verbal stimuli were extracted using a pre-trained speech-recognition model. Simulations of a physician examining the consciousness of 12 simulated patients for 16 simulation scenarios (4 for each of "Alert", "Verbal", "Painful", and "Unresponsive") were conducted under the AVPU-AVSR system. The accuracy, sensitivity, and specificity of the AVPU-AVSR system were assessed. RESULTS: A total of 192 cases with 12 simulated patients were assessed using the AVPU-AVSR system with a multi-class accuracy of 0.95 (95% confidence interval [CI] (0.92-0.98). The sensitivity and specificity (95% CIs) for detecting impaired consciousness were 1.00 (0.97-1.00) and 0.88 (0.75-0.95), respectively. The sensitivity and specificity of each extracted feature ranged from 0.88 to 1.00 and 0.98 to 1.00. CONCLUSIONS: The AVPU-AVSR system showed good accuracy in assessing consciousness levels in a clinical simulation and has the potential to be implemented in clinical practice to automatically assess mental status.

Prehospital National Early Warning Score as a predictor of massive transfusion in adult trauma patients.

BACKGROUND: Previous studies have shown that an elevated prehospital National Early Warning Score (preNEWS) is associated with increased levels of adverse outcomes in patients with trauma. However, whether preNEWS is a predictor of massive transfusion (MT) in patients with trauma is currently unknown. This study investigated the accuracy of preNEWS in predicting MT and hospital mortality among trauma patients. METHODS: We analyzed adult trauma patients who were treated and transported by emergency medical services (EMS) between January 2018 and December 2019. The main exposure was the preNEWS calculated for the scene. The primary outcome was the predictive ability for MT, and the secondary outcome was 24 h mortality. We compared the prognostic performance of preNEWS with the shock index, modified shock index, and reverse shock index, and reverse shock index multiplied by Glasgow Coma Scale in the prehospital setting. RESULTS: In total, 41,852 patients were included, and 1456 (3.5%) received MT. preNEWS showed the highest area under the receiver operating characteristic (AUROC) curve for predicting MT (0.8504; 95% confidence interval [CI], 0.840-0.860) and 24 h mortality (AUROC 0.873; 95% CI, 0.863-0.883). The sensitivity of preNEWS for MT was 0.755, and the specificity of preNEWS for MT was 0.793. All indicies had a high negative predictive value and low positive predictive value. CONCLUSION: preNEWS is a useful, rapid predictor for MT and 24 h mortality. Calculation of preNEWS would be helpful for making the decision at the scene such as transfer straightforward to trauma center and advanced treatment.

A simple scoring rule to predict survival to discharge after out of hospital cardiac arrest at the time of ED arrival.

BACKGROUND: It is important to be able to predict the chance of survival to hospital discharge upon ED arrival in order to determine whether to continue or terminate resuscitation efforts after out of hospital cardiac arrest. This study was conducted to develop and validate a simple scoring rule that could predict survival to hospital discharge at the time of ED arrival. METHODS: This was a multicenter retrospective cohort study based on a nationwide registry (Korean Cardiac Arrest Research Consortium) of out of hospital cardiac arrest (OHCA). The study included adult OHCA patients older than 18 years old, who visited one of 33 tertiary hospitals in South Korea from September 1st, 2015 to June 30th, 2020. Among 12,321 screened, 5471 patients were deemed suitable for analysis after exclusion. Pre-hospital ROSC, pre-hospital witness, shockable rhythm, initial pH, and age were selected as the independent variables. The dependent variable was set to be the survival to hospital discharge. Multivariable logistic regression (LR) was performed, and the beta-coefficients were rounded to the nearest integer to formulate the scoring rule. Several machine learning algorithms including the random forest classifier (RF), support vector machine (SVM), and K-nearest neighbor classifier (K-NN) were also trained via 5-fold cross-validation over a pre-specified grid, and validated on the test data. The prediction performances and the calibration curves of each model were obtained. Pre-processing of the registry was done using R, model training & optimization using Python. RESULTS: A total of 5471 patients were included in the analysis. The AUROC of the scoring rule over the test data was 0.7620 (0.7311-0.7929). The AUROCs of the machine learning classifiers (LR, SVM, k-NN, RF) were 0.8126 (0.7748-0.8505), 0.7920 (0.7512-0.8329), 0.6783 (0.6236-0.7329), and 0.7879 (0.7465-0.8294), respectively. CONCLUSION: A simple scoring rule consisting of five, binary variables could aid in the prediction of the survival to hospital discharge at the time of ED arrival, showing comparable results to conventional machine learning classifiers.

Development of an artificial intelligence bacteremia prediction model and evaluation of its impact on physician predictions focusing on uncertainty.

Prediction of bacteremia is a clinically important but challenging task. An artificial intelligence (AI) model has the potential to facilitate early bacteremia prediction, aiding emergency department (ED) physicians in making timely decisions and reducing unnecessary medical costs. In this study, we developed and externally validated a Bayesian neural network-based AI bacteremia prediction model (AI-BPM). We also evaluated its impact on physician predictive performance considering both AI and physician uncertainties using historical patient data. A retrospective cohort of 15,362 adult patients with blood cultures performed in the ED was used to develop the AI-BPM. The AI-BPM used structured and unstructured text data acquired during the early stage of ED visit, and provided both the point estimate and 95% confidence interval (CI) of its predictions. High AI-BPM uncertainty was defined as when the predetermined bacteremia risk threshold (5%) was included in the 95% CI of the AI-BPM prediction, and low AI-BPM uncertainty was when it was not included. In the temporal validation dataset (N = 8,188), the AI-BPM achieved area under the receiver operating characteristic curve (AUC) of 0.754 (95% CI 0.737-0.771), sensitivity of 0.917 (95% CI 0.897-0.934), and specificity of 0.340 (95% CI 0.330-0.351). In the external validation dataset (N = 7,029), the AI-BPM's AUC was 0.738 (95% CI 0.722-0.755), sensitivity was 0.927 (95% CI 0.909-0.942), and specificity was 0.319 (95% CI 0.307-0.330). The AUC of the post-AI physicians predictions (0.703, 95% CI 0.654-0.753) was significantly improved compared with that of the pre-AI predictions (0.639, 95% CI 0.585-0.693; p-value < 0.001) in the sampled dataset (N = 1,000). The AI-BPM especially improved the predictive performance of physicians in cases with high physician uncertainty (low subjective confidence) and low AI-BPM uncertainty. Our results suggest that the uncertainty of both the AI model and physicians should be considered for successful AI model implementation.

High-Level Expression of Recombinant VHSV Glycoprotein Using Transformed C. vulgaris and Verification of Vaccine Efficacy.

The demand for aquaculture is increasing, but production is declining due to high feed costs and disease outbreaks. Viral hemorrhagic septicemia (VHS) is a viral disease that seriously affects seawater and freshwater fish in aquaculture, including the olive flounder (Paralichthys olivaceus), a major aquaculture fish in Korea. However, very few vaccines are currently available for viral hemorrhagic septicemia virus (VHSV). The nutrient-rich microalga Chlorella vulgaris has been used as a feed additive in aquaculture and as a host for the industrial production of recombinant VHSV glycoprotein as an oral vaccine. In this study, VHSV glycoprotein was cloned with a salt-inducible promoter, and high levels of expression up to 41.1 mg/g wet C. vulgaris, representing 27.4% of total extracted soluble protein, were achieved by growing the transformed C. vulgaris for 5 days in the presence of 250 mM NaCl. The production of a neutralizing antibody was detected in the serum of fish given feed containing 9% VHSV glycoprotein-expressing C. vulgaris. Furthermore, relative survival rates of 100% and 81.9% were achieved following challenges of these fish with VHSV at 106 and 107 pfu/fish, respectively, indicating that C. vulgaris could be used as a platform for the production of recombinant proteins for use as oral vaccines in the control of viral diseases in aquaculture.

Differences between DNA vaccine and single-cycle viral vaccine in the ability of cross-protection against viral hemorrhagic septicemia virus (VHSV) and infectious hematopoietic necrosis virus (IHNV).

Vaccination procedures can be stressful for fish and can bring severe side effects. Therefore, vaccines that can minimize the number of administrations and maximize cross-protection against multiple serotypes, genotypes, or even different species would be highly advantageous. In the present study, we investigated the cross-protective ability of two types of vaccines - viral hemorrhagic septicemia virus (VHSV) G protein-expressing DNA vaccine and G gene-deleted single-cycle VHSV genotype IVa (rVHSV-ΔG) vaccine - against both VHSV genotype Ia and infectious hematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss). The results showed that rainbow trout immunized with VHSV genotype Ia G gene- or IVa G gene-expressing DNA vaccine were significantly protected against VHSV genotype Ia, but were not protected against IHNV. In contrast to the DNA vaccine, the single-cycle VHSV IVa vaccine induced significant protection against not only VHSV Ia but also IHNV. Considering no significant increase in ELISA titer and serum neutralization activity against IHNV in fish immunized with single-cycle VHSV IVa, the protection might be independent of humoral adaptive immunity. The scarcity of cytotoxic T cell epitopes between VHSV and IHNV suggested that the possibility of involvement of cytotoxic T cell-mediated cellular adaptive immunity would be low. The role of trained immunity (innate immune memory) in cross-protection should be further investigated.

Endoscopic Treatment of Chronic Subdural Hematoma Combined with Inner Subdural Hygroma.

OBJECTIVE: A chronic subdural hematoma (CSDH) is a collection of bloody fluid located in the subdural space and encapsulated by neo-membranes. An inner subdural hygroma (ISH) is observed between the inner membrane of a CSDH and the brain surface. We present six cases of CSDH combined with ISH treated via endoscopy. METHODS: Between 2011 and 2022, among the 107 patients diagnosed with CSDH in our institute, six patients were identified as presenting with CSDH combined with ISH and were included in this study. Preoperative computerized tomography (CT) and magnetic resonance imaging (MRI) were performed simultaneously, and endoscopic surgery for aspiration of the hematoma was performed in all cases of CSDH combined with ISH. RESULTS: The mean age of patients was 71 years (range, 66 to 79). The patients were all male. In two cases, the ISH was not identified on CT, but was clearly seen on MRI in all patients. The inner membrane of the CSDH was tense and bulging after draining of the CSDH in endoscopic view due to the high pressure of the ISH. After fenestration of the inner membrane of the CSDH and aspiration of the ISH, the membrane was sunken down due to the decreasing pressure of the ISH. There was one recurrence in post-operative 2-month follow up. The symptoms improved in all patients after surgery, and there were no surgery-related complications. CONCLUSION: CSDH combined with ISH can be diagnosed on imaging, and endoscopic surgery facilitates safe and effective treatment.

Capacitive Electrode-Based Electric Field Treatments on Redox-Toxic Iron Deposits in Transgenic AD Mouse Models: The Electroceutical Targeting of Alzheimer's Disease Feasibility Study.

Iron accumulation in the brain accelerates Alzheimer's disease progression. To cure iron toxicity, we assessed the therapeutic effects of noncontact transcranial electric field stimulation to the brain on toxic iron deposits in either the Aß fibril structure or the Aß plaque in a mouse model of Alzheimer's disease (AD) as a pilot study. A capacitive electrode-based alternating electric field (AEF) was applied to a suspension of magnetite (Fe3O4) to measure field-sensitized reactive oxygen species (ROS) generation. The increase in ROS generation compared to the untreated control was both exposure-time and AEF-frequency dependent. The frequency-specific exposure of AEF to 0.7-1.4 V/cm on a magnetite-bound Aß-fibril or a transgenic Alzheimer's disease (AD) mouse model revealed the degradation of the Aß fibril or the removal of the Aß-plaque burden and ferrous magnetite compared to the untreated control. The results of the behavioral tests show an improvement in impaired cognitive function following AEF treatment on the AD mouse model. Tissue clearing and 3D-imaging analysis revealed no induced damage to the neuronal structures of normal brain tissue following AEF treatment. In conclusion, our results suggest that the effective degradation of magnetite-bound amyloid fibrils or plaques in the AD brain by the electro-Fenton effect from electric field-sensitized magnetite offers a potential electroceutical treatment option for AD.