Neuroprotective Effects of Geopung-Chunghyuldan Based on Its Salvianolic Acid B Content Using an In Vivo Stroke Model.

BACKGROUND: Geopung-Chunghyuldan (GCD) has neuroprotective properties. Salviae miltiorrhizae Radix plays an essential role in GCD's effect. The Salviae miltiorrhizae Radix marker compound is salvianolic acid B; however, its content is not uniform among samples. This study aimed to evaluate the neuroprotective effects of GCD based on salvianolic acid B content. METHODS: The neuroprotective effects of GCD based on the salvianolic acid B content were evaluated by measuring infarct volume 24 h after permanent middle cerebral artery occlusion in an in vivo stroke model. For the experimental group, each GCD was administered immediately before surgery. The control groups were administered distilled water and aspirin (30 mg/kg) in the same way. The salvianolic acid B content in five types of Salviae Miltiorrhizae Radix (two Chinese and three Korean regions) based on different cultivation regions was analyzed by high-performance liquid chromatography. RESULTS: Three samples met the Korean and Chinese Pharmacopeia standards for salvianolic acid B. However, two samples did not. GCDs with high salvianolic acid B showed marked neuroprotective effects compared to the control groups, whereas GCDs with low salvianolic acid B did not. CONCLUSIONS: The salvianolic acid B content of Salviae miltiorrhizae Radix affects the neuroprotection effect of GCD. Stable, raw Salviae miltiorrhizae Radix is essential for GCD homogenization.

Treatment evaluation of Kami Guibi-tang on participants with amnestic mild cognitive impairment using magnetic resonance imaging on brain metabolites, gamma-aminobutyric acid, and cerebral blood flow.

PURPOSE: To evaluate the effectiveness of Kami Guibi-tang (KGT) in the treatment of mild cognitive impairment (MCI) using magnetic resonance imaging (MRI) on brain metabolites, neurotransmitter, and cerebral blood flow (CBF). METHODS: We randomly allocated a total of 30 MCI patients to a KGT (N = 16) or a placebo (N = 14) group and performed MRI scans before and after 24 weeks of treatment. The participants underwent brain magnetic resonance spectroscopy and MRI scans to obtain brain metabolites using Point-RESolved Spectroscopy (PRESS) single-voxel spectroscopy, gamma-aminobutyric acid (GABA) neurotransmitter using Mescher-Garwood PRESS, and CBF using pseudocontinuous arterial spin labeling sequences using a 3.0 Tesla MRI system. We analyzed metabolite and neurotransmitter levels and CBF using repeated-measure analysis of variance to evaluate between-subject group effect, within-subject treatment condition effect, and interaction of group by condition (group x condition). RESULTS: The GABA+/creatine (Cr) ratio values were not significantly different between the before and after treatment conditions. The glutamate complex/Cr ratio difference before and after treatment was lower in the KGT group than in the placebo group, but was not statistically significant (p = 0.077). The result of region of interest-based CBF measurement showed that CBF values were significantly lower after treatment at Cluster 2 for the KGT group (p = 0.003) and the placebo group (p = 0.011), at hippocampus for the KGT group (p = 0.004) and the placebo group (p = 0.008), and at the fusiform gyrus for the KGT group (p = 0.002). Furthermore, the absolute CBF difference before and after treatment in the fusiform gyrus was significantly lower in the KGT group than in the placebo group (p = 0.024). CONCLUSIONS: Although a KGT treatment of 24 weeks showed some significant impact on the level of CBF, the Korean version of the mini-mental state examination score was not significantly different between before and after treatment conditions, indicating that there was no memory function improvement after treatment in amnestic MCI patients. Therefore, further studies should be performed with a relatively larger population and extending the duration of the KGT treatment.

Atrial Fibrillation is Strongly Associated With the Neutrophil to Lymphocyte Ratio in Acute Ischemic Stroke Patients: A Retrospective Study.

BACKGROUND: No study has investigated the relationship between hospital-admission neutrophil and lymphocyte ratio (NLR) and various stroke risk factors. We sought to determine which stroke risk factor could be the most appropriate predictor of NLR in acute ischemic stroke. METHODS: We collected data on various stroke risk factors and National Institutes of Health Stroke Scale (NIHSS) score in 1,053 acute ischemic stroke patients. The regression analysis was adjusted for confounding factors such as stroke risk factors. RESULTS: There was a trend of increased NLR with a rise in alcohol consumption, the prevalence of hypertension, cardioembolism (CE) etiology, the NIHSS scores in men and the prevalence of atrial fibrillation, other heart diseases, CE and small vessel occlusion etiology and the NIHSS scores in women. Multiple linear regression analyses, adjusted for confounding factors, showed that the atrial fibrillation and NIHSS scores in men and atrial fibrillation, diabetes mellitus as well as NIHSS scores in women had a significant positive association with NLR. However, a negative association was showed for body mass index (BMI). CONCLUSION: We confirmed that the atrial fibrillation can be a predictor of high NLR in acute stroke patients, and diabetes mellitus as well as low BMI could be a predictor of high NLR in female acute ischemic stroke patients.

Design and validation of a wearable dynamometry system for knee extension-flexion torque measurement.

Muscle strength assessments are vital in rehabilitation, orthopedics, and sports medicine. However, current methods used in clinical settings, such as manual muscle testing and hand-held dynamometers, often lack reliability, and isokinetic dynamometers (IKD), while reliable, are not easily portable. The aim of this study was to design and validate a wearable dynamometry system with high accessibility, accuracy, and reliability, and to validate the device. Therefore, we designed a wearable dynamometry system (WDS) equipped with knee joint torque sensors. To validate this WDS, we measured knee extension and flexion strength in 39 healthy adults using both the IKD and WDS. Comparing maximal isometric torque measurements, WDS and IKD showed strong correlation and good reliability for extension (Pearson's r: 0.900; intraclass correlation coefficient [ICC]: 0.893; standard error of measurement [SEM]: 9.85%; minimal detectable change [MDC]: 27.31%) and flexion (Pearson's r: 0.870; ICC: 0.857; SEM: 11.93%; MDC: 33.07%). WDS demonstrated excellent inter-rater (Pearson's r: 0.990; ICC: 0.993; SEM: 4.05%) and test-retest (Pearson's r: 0.970; ICC: 0.984; SEM: 6.15%) reliability during extension/flexion. User feedback from 35 participants, including healthcare professionals, underscores WDS's positive user experience and clinical potential. The proposed WDS is a suitable alternative to IKD, providing high accuracy, reliability, and potentially greater accessibility.

The effectiveness of Kami Guibi-tang for cognitive impairment patients: A retrospective chart review.

Background: and Purpose: The number of patients with cognitive impairment is increasing worldwide. Therapeutic drugs that slow disease progression are being developed; however, further research is required. This study investigated the effects of Kami Guibi-tang on patients with various types of cognitive decline. Methods: This study was a single-center, retrospective chart review of patients who visited KyungHee University Hospital at Gangdong from January 2015 to March 2022. The study included participants who took Kami Guibi-tang for more than 90 days and were assessed on the Korean version Mini-Mental State Examination (MMSE-K) scores before and after treatment. Participants who received other liquid herbal medicines during the treatment were excluded. The outcome of interest was changed scores in MMSE-K and Short form of Geriatric Depression Scale (S-GDS). Results: A total of 31 participants were included. The total MMSE-K score significantly increased with time and showed a significant increase at 3 and 9 months compared with baseline. Among the MMSE-K subscores, the orientation subscore showed a significant increase at three months compared with baseline, and the attention and calculation subscore showed a significant increase with time. In addition, four participants with vascular dementia showed a significant increase in the total MMSE-K score over time and a significant increase after 9 months compared with baseline. The S-GDS score in 31 participants showed a significant decrease with time and at all time points compared with baseline. Conclusions: Kami Guibi-tang may improve cognitive function in patients with cognitive decline.

Towards optimal design of patient isolation units in emergency rooms to prevent airborne virus transmission: From computational fluid dynamics to data-driven modeling.

BACKGROUND: Patient isolation units (PIUs) can be an effective method for effective infection control. Computational fluid dynamics (CFD) is commonly used for PIU design; however, optimizing this design requires extensive computational resources. Our study aims to provide data-driven models to determine the PIU settings, thereby promoting a more rapid design process. METHOD: Using CFD simulations, we evaluated various PIU parameters and room conditions to assess the impact of PIU installation on ventilation and isolation. We investigated particle dispersion from coughing subjects and airflow patterns. Machine-learning models were trained using CFD simulation data to estimate the performance and identify significant parameters. RESULTS: Physical isolation alone was insufficient to prevent the dispersion of smaller particles. However, a properly installed fan filter unit (FFU) generally enhanced the effectiveness of physical isolation. Ventilation and isolation performance under various conditions were predicted with a mean absolute percentage error of within 13%. The position of the FFU was found to be the most important factor affecting the PIU performance. CONCLUSION: Data-driven modeling based on CFD simulations can expedite the PIU design process by offering predictive capabilities and clarifying important performance factors. Reducing the time required to design a PIU is critical when a rapid response is required.

Prevention of inflammation-mediated neurotoxicity by butylidenephthalide and its role in microglial activation.

Microglial cells are the prime effectors in immune and inflammatory responses of the central nervous system (CNS). During pathological conditions, the activation of these cells helps restore CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various proinflammatory molecules and neurotoxins. Thus, negative regulators of microglial activation have been considered as potential therapeutic candidates to target neurodegeneration, such as that in Alzheimer's and Parkinson's diseases. The rhizome of Ligusticum chuanxiong Hort. (Ligusticum wallichii Franch) has been widely used for the treatment of vascular diseases in traditional oriental medicine. Butylidenephthalide (BP), a major bioactive component from L. chuanxiong, has been reported to have a variety of pharmacological activities, including vasorelaxant, anti-anginal, anti-platelet and anti-cancer effects. The aim of this study was to examine whether BP represses microglial activation. In rat brain microglia, BP significantly inhibited the lipopolysaccharide (LPS)-induced production of nitric oxide (NO), tumour necrosis factor-α and interleukin-1ß. In organotypic hippocampal slice cultures, BP clearly blocked the effect of LPS on hippocampal cell death and inhibited LPS-induced NO production in culture medium. These results newly suggest that BP provide neuroprotection by reducing the release of various proinflammatory molecules from activated microglia.

A portable articulated dynamometer for ankle dorsiflexion and plantar flexion strength measurement: a design, validation, and user experience study.

Monitoring ankle strength is crucial for assessing daily activities, functional ability, and preventing lower extremity injuries. However, the current methods for measuring ankle strength are often unreliable or not easily portable to be used in clinical settings. Therefore, this study proposes a portable dynamometer with high reliability capable of measuring ankle dorsiflexion and plantar flexion. The proposed portable dynamometer comprised plates made of aluminum alloy 6061 and a miniature tension-compression load cell. A total of 41 healthy adult participants applied maximal isometric dorsiflexor and plantar flexor forces on a Lafayette Handheld Dynamometer (HHD) and the portable dynamometer. The results were cross-validated, using change in mean, and two independent examiners evaluated the inter-rater and test-retest reliabilities in separate sessions using intraclass correlation coefficients, standard error of measurement, and minimal detectable change. Both dorsiflexion and plantar flexion measurements demonstrated a strong correlation with the HHD (r = 0.827; r = 0.973) and showed high inter-rater and test-retest reliabilities. Additionally, the participant responses to the user experience questionnaire survey indicated vastly superior positive experiences with the portable dynamometer. The study findings suggest that the designed portable dynamometer can provide accurate and reliable measurements of ankle strengths, making it a potential alternative to current methods in clinical settings.

Development and validation of a portable articulated dynamometry system to assess knee extensor muscle strength.

Muscle strength assessment is important in predicting clinical and functional outcomes in many disorders. Manual muscle testing, although commonly used, offers suboptimal accuracy and reliability. Isokinetic dynamometers (IKDs) have excellent accuracy and reliability; but are bulky and expensive, offering limited accessibility. This study aimed to design a portable dynamometer that is accessible, accurate and reliable, and to validate the device in a general population. The portable articulated dynamometry system (PADS) is a portable device with an embedded high-precision load cell, designed to measure muscle strength with optimal accuracy. Seventy-two participants underwent maximal isometric and isokinetic knee extensor torque measurement with the PADS and IKD, respectively. The PADS results were cross-validated against IKD results using change in mean (CIM). Interrater and intra-rater reliabilities were assessed using intraclass correlation coefficients, standard error of measurement, and minimal detectable change. The PADS maximal knee extensor strength results were not significantly different from those by IKD (CIM: - 2.13 Nm; 95% CI - 4.74, 0.49 Nm). The PADS showed interrater reliability (Pearson's r: 0.958; ICC: 0.979; SEM: 5.51%) and excellent intra-rater reliability (Pearson's r: 0.912; ICC: 0.954; SEM: 8.38%). The proposed PADS may be an effective alternative to IKD, offering good accuracy, reliability, and potentially better accessibility.

A Systematic Review of In Vivo Studies of the Efficacy of Herbal Medicines for Anti-Aging in the Last Five Years.

BACKGROUND: The world's population is rapidly aging, and attention to and research on the increase in life expectancy and age-related diseases are needed. This study aimed to review the in vivo studies on the anti-aging effects of herbal medicines. METHODS: In vivo studies of single or complex herbal medicines for anti-aging that were published in the last five years were included in this review. The following databases were used: PubMed, Scopus, ScienceDirect, Web of Science and EMBASE. RESULTS: A total of 41 studies were considered eligible for the review. The articles were classified into body organs and functions, experimental country, herbal medicine, extraction method, administration route, dosage, duration, animal model, aging-induced method, sex, number of animals per group, and outcomes and mechanisms A single herbal extract was used in a total of 21 studies including Alpinia oxyphylla Miq., Acanthopanax senticosus and Lyceum barbarum, and a multi-compound herbal prescription was used in a total of 20 studies, including Modified Qiongyu paste, Wuzi Yanzong recipe, etc. Each herbal medicine had anti-aging effects on learning and memory, cognition, emotion, internal organs, gastrointestinal tracts, sexual functions, musculoskeletal function and so on. The common mechanisms of action were antioxidant and anti-inflammatory, and various effects and mechanisms for each organ and function were identified. CONCLUSIONS: Herbal medicine exhibited beneficial effects on anti-aging in various parts of the body and its function. Further investigation of the appropriate herbal medicine prescriptions and their components is recommended.

Efficacy of Artemisia annua Linné in improving cognitive impairment in a chronic cerebral hypoperfusion-induced vascular dementia animal model.

BACKGROUND: Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease. Currently, no FDA-approved drugs are available for the treatment of VaD. Artemisia annua Linné (AA) is known to have antioxidant properties, but its effects and mechanisms of action on cognitive impairment are still unknown. PURPOSE: In this study, the improvement in cognitive impairment by AA in terms of protection against oxidative stress, neuroinflammation, and preservation of the integrity of the neurovascular unit (NVU) was assessed in an animal model of VaD with bilateral common carotid artery occlusion (BCCAO). METHODS: Eight-week-old male Wistar rats were allowed to adapt for four weeks, and BCCAO was induced at 12 weeks of age. The rats were randomly assigned into four groups, with seven rats in each group: sham group without BCCAO, VaD group that received oral administration of distilled water after BCCAO surgery, and two AA groups that received oral administration of 150 mg/kg or 750 mg/kg AA after BCCAO surgery for 8 weeks. Nine weeks after BCCAO surgery, the cognitive function of the rats was evaluated and accumulated oxidative stress was assessed by immunohistochemistry, immunofluorescence, and western blotting. Damage to the components of the NVU was evaluated, and sirtuin (Sirt) 1 and 2 expression and nuclear factor-erythrocyte 2-associated factor 2 (Nrf2)/Kelch-like ECH-associated protein1 (Keap1) activation were investigated to assess the reduction in cell signaling and antioxidant pathways. RESULTS: BCCAO-induced cerebral perfusion decreased memory function and induced neuroinflammation and oxidative stress. But AA treatment mitigated cognitive impairment and reduced neuroinflammation and oxidative stress caused by chronic cerebral hypoperfusion. AA extracts activated the Nrf2/Keap1/activating antioxidant response elements pathway and maintained Sirt 1 and 2, subsequently leading to the maintenance of neurons, improved construct of microvessels, increased platelet-derived growth factor receptor beta, and platelet-endothelial cell adhesion molecule-1 associated with the blood-brain barrier integrity. CONCLUSION: AA is effective in alleviating BCCAO-induced cognitive decline and its administration may be a useful therapeutic approach for VaD.

Effectiveness and Therapeutic Mechanism of Pharmacopuncture for Pain in Parkinson's Disease: A Study Protocol for a Pilot Pragmatic Randomized, Assessor-Blinded, Usual Care-Controlled, Three-Arm Parallel Trial.

Pain in Parkinson's disease (PD) represents a complex phenotype known to decrease quality of life. This pragmatic randomized, controlled clinical trial evaluated the efficacy of pharmacopuncture (PA) for improving pain symptoms and investigated the corresponding therapeutic mechanisms in patients with PD. Ninety patients with PD-related pain were randomly allocated to receive either PA, manual acupuncture, or usual care in a 1:1:1 ratio; sixty healthy controls were included for comparative analysis of brain imaging data. Over 12 weeks, study treatment provided 2 days per week for 8 weeks with a follow-up period of 4 weeks. The primary outcome measure was the King's Parkinson's Disease Pain Scale score for assessing improvement in PD-related pain, including a sub-analysis to investigate the pattern of changes in pain according to a PD-related pain mechanism-based classification. Secondary outcome measures included a numerical rating scale-based assessment of the intensity and location of pain and changes in pain-associated symptoms, such as depression, anxiety, and sleep disorders. Exploratory outcome measures included structural and functional brain patterns on magnetic resonance imaging, blood molecular signature changes, gait analysis, facial expression and movement assessment in response to emotional stimuli, and a traditional Korean medicine syndrome differentiation questionnaire. The trial findings provided important clinical evidence for the effectiveness of PA in the management of PD-related pain and its associated symptoms, and helped elucidate the mechanism of its therapeutic effect on PD-related pain.

Efficacy of Kami Guibi-tang as an Add-On Therapy to Acetylcholinesterase Inhibitor for Cognitive Function in Mild Alzheimer's Disease: A Pilot Study.

Background: Kami Guibi-tang (KGT), a traditional Korean herbal medicine is mainly used to treat insomnia and nervousness. Acetylcholinesterase inhibitors (AChEIs) are the main treatments for mild Alzheimer's disease (AD), a degenerative brain disease. However, currently no drug can fundamentally treat AD or reverse the advanced cognitive decline. This clinical study explored the efficacy and safety of adding KGT to AChEI for cognitive function in mild AD. Methods: This was a pilot study for a larger randomized, double-blind, placebo-controlled trial. Participants between 55-90 years diagnosed with mild AD were recruited from Kyung Hee University Hospital at Gangdong, Seoul, Korea. They were randomized to receive either KGT or placebo for 24 weeks, in addition to their regular AChEI. The primary outcome was treatment efficacy, as assessed by the relative amount of change over the study period in total scores on the Dementia version of the Seoul Neuropsychological Screening Battery (SNSB-D). Changes in SNSB subscores were assessed as secondary outcomes. Safety parameters, including adverse events and abnormalities in blood tests, electrocardiograms, and brain magnetic resonance imaging were also monitored. Results: Between March 2018 and November 2020, seven participants each in the KGT group and the placebo group completed the 24-week trial. There were no significant changes in SNSB-D total or subindex scores for either group (p = 0.69 and 0.63, respectively), and no significant differences were observed between them (p=0.71). No adverse events related to KGT were reported. We also compared and analyzed the results of a previous pilot study conducted on amnestic mild cognitive impairment (aMCI) using protocol of this study. The aMCI group showed a significant improvement in the total SNSB-D score, especially in the memory domain, compared to the mild AD group (p = 0.04 and 0.02, respectively). The Korean Mini-Mental State Exam and Korean Instrumental Activities of Daily Living scores also significantly improved in the aMCI group (p = 0.01 and 0.02, respectively). Conclusions: Compared to placebo, adding KGT to AChEI did not significantly improve cognitive function in SNSB in patients with mild AD. We suggest that KGT would have a positive effect on patients with early stages of cognitive impairment such as aMCI. The findings could assist design larger, longer-term clinical trials of KGT use in elderly patients with mild AD. This study was registered in the Korean Clinical Trial Registry on December 26, 2017, with the CRIS approval number KCT0002904.

Effect of Kami Guibi-tang (KGT) in elderly subjects with insomnia: a study protocol from a single center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: The incidence of insomnia increases with age and is related to cognitive function in older adults; therefore, it is important to manage it actively. In this study, we report a protocol for the evaluation of the efficacy and safety of Kami Guibi-tang (KGT), a herbal prescription that has been widely used in East Asia for insomnia, forgetfulness, and depression, in older adults with insomnia. METHODS: In this single-center, double-blind, randomized controlled trial, 60 older adults with insomnia and subjective cognitive decline will be recruited and randomly assigned to the KGT or placebo group. The KGT group will take KGT granules thrice a day for 12 weeks, whereas the control group will take placebo granules in the same manner. Participants will be assessed for sleep, cognitive function, quality of life, and depression using the Pittsburgh Sleep Quality Index-Korean (PSQI-K), Insomnia Severity Index-Korean (ISI-K), Seoul Neuropsychological Screening Battery-Dement (SNSB-D), 36-item MOS Short Form Survey (SF-36) and Short version of the Geriatric Depression Scale (S-GDS) before and at the end of administration of the investigational product. The PSQI-K, ISI-K, and SF-36 will be further assessed 12 weeks after the end of medication to determine whether the effects on sleep and quality of life are sustained. The PSQI-K total score difference between the two groups at 12 and 24 weeks will be the primary outcome; all other endpoints will be secondary. Safety will be assessed by performing blood tests and electrocardiograms before taking the investigational drug, 6 weeks after taking the drug, and 12 weeks after taking the drug; any adverse events will be observed throughout the study. DISCUSSION: The protocol will provide a detailed process for a clinical trial to evaluate the efficacy and safety of KGT in elderly patients with insomnia. We will also investigate if changes in cognitive function correlated with improvements in insomnia. TRIAL REGISTRATION: This trial was registered at CRIS (Clinical Research Information Service) on April 27, 2023 (KCT0008391, version 2.0).  https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24811&search_page=L .

A Comparative Study on the Neuroprotective Effect of Geopung-Chunghyuldan on In Vitro Oxygen-Glucose Deprivation and In Vivo Permanent Middle Cerebral Artery Occlusion Models.

Geopung-Chunghyuldan (GCD), which is a mixture of Chunghyuldan (CD), Radix Salviae Miltiorrhizae, Radix Notoginseng, and Borneolum Syntheticum, is used to treat ischemic stroke in traditional Korean medicine. This study aimed to investigate the effects of GCD and CD on ischemic brain damage using in vitro and in vivo stroke models, as well as to elucidate the synergistic effects of GCD against ischemic insult. To study the effect of GCD in an in vitro ischemia model, SH-SY5Y cells were exposed to oxygen-glucose deprivation (OGD). Cell death after 16 h of OGD exposure was measured using the MTT assay and live/dead cell counting methods. An in vivo ischemia mice model was established through permanent middle cerebral artery occlusion (pMCAO). To determine the neuroprotective effect of GCD, it was orally administered immediately and 2 h after pMCAO. The infarct volume was measured through 2,3,5-triphenyltetrazolium chloride staining at 24 h after pMCAO. Compared with the control group, GCD treatment significantly reduced OGD-induced cell death in SH-SY5Y cells; however, CD treatment did not show a significant protective effect. In the pMCAO model, compared with the control group, treatment with GCD and CD significantly and mildly reduced the infarct volume, respectively. Our findings indicate that compared with CD, GCD may allow a more enhanced neuroprotective effect in acute ischemic stroke, indicating a potential synergistic neuroprotective effect. The possibility of GCD as a novel alternative choice for the prevention and treatment of ischemic stroke is suggested.

Effect of an herbal medicine, Chunghyul-dan, on prevention of recurrence in patients with ischemic stroke: A retrospective cohort study.

Research indicates that Chunghyul-dan (CHD), a herbal medicine, has an inhibitory effect on stroke recurrence in small vessel disease. Recent studies have suggested that CHD might also act on large arteries. This study aimed to verify the preventive effect of CHD on strokes of all the Trial of Org 10172 in Acute Stroke Treatment (TOAST) causative classifications. We retrospectively analyzed 2 years of medical records of patients with ischemic stroke treated with CHD, 600 mg once daily, in combination with antiplatelet or anticoagulant agents. The prevalence of stroke recurrence in 2 years was analyzed. Stroke recurrence was defined as new neurological symptoms with corresponding brain imaging results. Nine of the 202 patients (4.46%) had recurrent ischemic stroke. Four occurred within 180 days, 3 between 180 and 365 days, and 2 between 365 and 730 days. All had only 1 recurrence. The recurrence rates were 1.12%, 5%, and 5.48% for small vessel occlusion, cardioembolism, and large vessel atherosclerosis, respectively. There were no adverse effects. These results suggest that CHD could inhibit ischemic stroke recurrence of all TOAST causative categories. A randomized controlled trial is needed to confirm this hypothesis.

Diagnostic Assessment of Deep Learning Algorithms for Frozen Tissue Section Analysis in Women with Breast Cancer.

PURPOSE: Assessing the metastasis status of the sentinel lymph nodes (SLNs) for hematoxylin and eosin-stained frozen tissue sections by pathologists is an essential but tedious and time-consuming task that contributes to accurate breast cancer staging. This study aimed to review a challenge competition (HeLP 2019) for the development of automated solutions for classifying the metastasis status of breast cancer patients. Materials and Methods: A total of 524 digital slides were obtained from frozen SLN sections: 297 (56.7%) from Asan Medical Center (AMC) and 227 (43.4%) from Seoul National University Bundang Hospital (SNUBH), South Korea. The slides were divided into training, development, and validation sets, where the development set comprised slides from both institutions and training and validation set included slides from only AMC and SNUBH, respectively. The algorithms were assessed for area under the receiver operating characteristic curve (AUC) and measurement of the longest metastatic tumor diameter. The final total scores were calculated as the mean of the two metrics, and the three teams with AUC values greater than 0.500 were selected for review and analysis in this study. RESULTS: The top three teams showed AUC values of 0.891, 0.809, and 0.736 and major axis prediction scores of 0.525, 0.459, and 0.387 for the validation set. The major factor that lowered the diagnostic accuracy was micro-metastasis. CONCLUSION: In this challenge competition, accurate deep learning algorithms were developed that can be helpful for making a diagnosis on intraoperative SLN biopsy. The clinical utility of this approach was evaluated by including an external validation set from SNUBH.

Sex differences in amygdala subregions: evidence from subregional shape analysis.

Each subregion of the amygdala is characterized by a distinct cytoarchitecture and function. However, most previous studies on sexual dimorphism and aging have assessed differences in the structure of the amygdala at the level of the amygdala in its entirety rather than at the subregional level. Using an amygdala subregional shape analysis, we investigated the effects of sex, age, and the sex × age interaction on the subregion after controlling for intracranial volume. We found the main effect of age in the subregions and the effect of sex in the superficial nucleus, which showed that men had a larger mean radius than women. We also found a sex × age interaction in the centromedial nucleus, in that the radius of the centromedial nucleus showed a steeper decline with age in women compared with men. Regarding the amygdala volume as a whole, we found only an age effect and did not find any other significant difference between genders. The sex difference in the amygdala subregion and its relevance to the circulating gonadal hormone were discussed.

Effects of Hyul-Bu-Chuke-Tang on Erythrocyte Deformability and Cerebrovascular CO(2) Reactivity in Normal Subjects.

Aim. Hyul-bu-chuke-tang (HCEt) is a well-known traditional herbal medicine that is used for the treatment of ischemic cerebrovascular disorders. We investigated the acute effects of HCEt on erythrocyte deformability and cerebrovascular CO(2) reactivity (CVR) in healthy male subjects. Materials and Methods. We examined erythrocyte deformability in an HCEt group (n = 14) and a control group (n = 10). CVR was measured using hyperventilation-induced CO(2) reactivity of the middle cerebral artery and transcranial Doppler (TCD) in the HCEt group (n = 11). A historical control group (n = 10) of CVR measurements was also created from our previous study. All measurements were performed prior to and 1, 2, and 3 hours after HCEt administration. Results. HCEt significantly improved erythrocyte deformability 1 hour after administration compared to the control group (2.9 ± 1.1% versus -0.6 ± 1.0%, P = 0.034). HCEt significantly improved the CVR 2 hours after administration compared to the historical control group (9.1 ± 4.0% versus -8.1 ± 4.1%, P = 0.007). The mean blood pressure and pulse rate did not vary from baseline values in either group. Conclusions. We demonstrated that HCEt improved erythrocyte deformability and CVR. Our findings suggest that an improvement in erythrocyte deformability contributes to HCEt's effect on cerebral microcirculation.

Relationship between Blood Stasis Syndrome Score and Cardioankle Vascular Index in Stroke Patients.

Blood stasis syndrome (BSS) in traditional Asian medicine has been considered to correlate with the extent of atherosclerosis, which can be estimated using the cardioankle vascular index (CAVI). Here, the diagnostic utility of CAVI in predicting BSS was examined. The BSS scores and CAVI were measured in 140 stroke patients and evaluated with respect to stroke risk factors. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic accuracy of CAVI for the diagnosis of BSS. The BSS scores correlated significantly with CAVI, age, and systolic blood pressure (SBP). Multiple logistic regression analysis showed that CAVI was a significant associate factor for BSS (OR 1.55, P = 0.032) after adjusting for the age and SBP. The ROC curve showed that CAVI and age provided moderate diagnostic accuracy for BSS (area under the ROC curve (AUC) for CAVI, 0.703, P < 0.001; AUC for age, 0.692, P = 0.001). The AUC of the "CAVI+Age," which was calculated by combining CAVI with age, showed better accuracy (0.759, P < 0.0001) than those of CAVI or age. The present study suggests that the CAVI combined with age can clinically serve as an objective tool to diagnose BSS in stroke patients.