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Abstract Deep neural networks are increasingly used in medical imaging for tasks such as pathological classification, but they face challenges due to the scarcity of high-quality, expert-labeled training data. Recent efforts have utilized pre-trained contrastive image-text models like CLIP, adapting them for medical use by fine-tuning the model with chest X-ray images and corresponding reports for zero-shot pathology classification, thus eliminating the need for pathology-specific annotations. However, most studies continue to use the same contrastive learning objectives as in the general domain, overlooking the multi-labeled nature of medical image-report pairs. In this paper, we propose a new fine-tuning strategy that includes positive-pair loss relaxation and random sentence sampling. We aim to improve the performance of zero-shot pathology classification without relying on external knowledge. Our method can be applied to any pre-trained contrastive image-text encoder and easily transferred to out-of-domain datasets without further training, as it does not use external data. Our approach consistently improves overall zero-shot pathology classification across four chest X-ray datasets and three pre-trained models, with an average macro AUROC increase of 4.3%. Additionally, our method outperforms the state-of-the-art and marginally surpasses board-certified radiologists in zero-shot classification for the five competition pathologies in the CheXpert dataset.

IntroductionThe predominant hybrid pathogenic E. coli, enterohemorrhagic E. coli (EHEC), combines characteristics of Shiga toxin-producing E. coli (STEC) and enteropathogenic E. coli (EPEC), contributing to global outbreaks with severe symptoms including fatal consequences. Since EHEC infection was designated as a notifiable disease in 2000 in South Korea, around 2000 cases have been reported, averaging approximately 90 cases annually.AimIn this work, genome-based characteristic analysis and cell-based assay of hybrid STEC/aEPEC strains isolated from livestock feces, animal source foods, and water in South Korea was performed.MethodsTo identify the virulence and antimicrobial resistance genes, determining the phylogenetic position of hybrid STEC/aEPEC strains isolated in South Korea, a combination of real-time PCR and whole-genome sequencing (WGS) was used. Additionally, to assess the virulence of the hybrid strains and compare them with genomic characterization, we performed a cell cytotoxicity and invasion assays.ResultsThe hybrid STEC/aEPEC strains harbored stx and eae genes, encoding Shiga toxins and E. coli attachment/effacement related protein of STEC and EPEC, respectively. Furthermore, all hybrid strains harbored plasmid-carried enterohemolysin(ehxCABD), a key virulence factor in prevalent pathogenic E. coli infections, such as diarrheal disease and hemolytic-uremic syndrome (HUS). Genome-wide phylogenetic analysis revealed a close association between all hybrid strains and specific EPEC strains, suggesting the potential acquisition of Stx phages during STEC/aEPEC hybrid formation. Some hybrid strains showed cytotoxic activity against HeLa cells and invasive properties against epithelial cells. Notably, all STEC/aEPEC hybrids with sequence type (ST) 1,034 (n = 11) exhibited higher invasiveness than those with E2348/69. This highlights the importance of investigating potential correlations between STs and virulence characteristics of E. coli hybrid strains.ConclusionThrough genome-based characterization, we confirmed that the hybrid STEC/aEPEC strains are likely EPEC strains that have acquired STEC virulence genes via phage. Furthermore, our results emphasize the potential increased danger to humans posed by hybrid STEC/aEPEC strains isolated in South Korea, containing both stx and eaeA, compared to STEC or EPEC alone.

In this study, we have developed an amplifier waveguide module suitable for broadband communication in the sub-THz band. To achieve a waveguide module with excellent gain flatness characteristics, the effects of errors during the packaging procedures of the waveguide module and the space occupied by the bondwire were analyzed through an electromagnetic simulation. Furthermore, a photonics-based sub-THz wireless link with a carrier frequency of 288 GHz was established using a packaged amplifier module. The amplifier module was placed at the output of the sub-THz transmitter based on a uni-traveling-carrier photodiode and at the input of the sub-THz receiver. The maximum gain and 3 dB bandwidth of the amplifier module are 17.3 dB and 39 GHz, respectively. With this setup, we successfully transmitted a 100-Gbps 16-QAM modulated signal, employing a carrier frequency of 288 GHz, across a wireless distance of 100 m.

CrAssphages are human gut bacteriophages with potential use as an indicator of human fecal contamination in water and other environmental systems. We determined the prevalence and abundance of crAssphages in water, food, and fecal samples and compared these estimates with the prevalence of norovirus. Samples were tested using two crAssphage-specific qPCR assays (CPQ056 and TN201-203) and for norovirus using TaqMan realtime RT-PCR. CrAssphage was detected in 40% of human fecal specimens, 61% of irrigation water samples, 58.5% of stream water samples, and 68.5% of fresh leafy greens samples. Interestingly, across all sample categories, crAssphage concentrations were 2–3 log10 higher than norovirus concentrations. The correlation of detection of crAssphage and norovirus was significant for the irrigation water samples (r = 0.74, p = 7.4e-06). Sequences obtained from crAssphage positive samples from human fecal and stream water samples phylogenetically clustered with genotype I crAssphages, whereas sequences derived from irrigation water samples clustered differently from other genotypes. Our data show that crAssphages were prevalent in norovirus-positive water samples and in fresh leafy green samples, there was a strong correlation between the presence of crAssphage and norovirus. CrAssphage genomic copies were consistently higher than norovirus copies in all sample types. Overall, our findings suggest that crAssphages could be used as reliable indicators to monitor fecal-borne virus contamination within the food safety chain.

In day-to-day living, individuals are exposed to various environmentally hazardous substances that have been associated with diverse diseases. Exposure to air pollutants can occur during breathing, posing a considerable risk to those with environmental health vulnerabilities. Among vulnerable individuals, maternal exposure can negatively impact the mother and child in utero. The developing fetus is particularly vulnerable to environmentally hazardous substances, with potentially greater implications. Among air pollutants, toluene is neurotoxic, and its effects have been widely explored. However, the impact of low-level toluene exposure in daily life remains unclear. Herein, we evaluated 194 mothers and infants from the Growing children’s health and Evaluation of Environment (GREEN) cohort to determine the possible effects of early-life toluene exposure on the nervous system. Using Omics experiments, the effects of toluene were confirmed based on epigenetic changes and altered mRNA expression. Various epigenetic changes were identified, with upregulated expression potentially contributing to diseases such as glioblastoma and Alzheimer’s, and downregulated expression being associated with structural neuronal abnormalities. These findings were detected in both maternal and infant groups, suggesting that maternal exposure to environmental hazardous substances can negatively impact the fetus. Our findings will facilitate the establishment of environmental health policies, including the management of environmentally hazardous substances for vulnerable groups.

Enteroviruses (EVs), which belong to the Picornaviridae family, infect individuals asymptomatically or cause mild symptoms (fever, runny nose, cough, skin rash, sneezing, mouth blister). Severe cases can cause various diseases, such as acute hemorrhagic conjunctivitis, aseptic meningitis, or myocarditis, especially in infants. These viruses can be transmitted via the fecal-oral route via contaminated water. In this study, we established a polymerase chain reaction (PCR) method for detecting EVs in water sample using Coxsackievirus B5 (CV-B5) and Echovirus 30 (E-30), which belong to species B of the four species of EVs (EV-A to D). Several methods have been investigated and compared for the detection of EVs, including real-time reverse transcription (RT) polymerase chain reaction and conventional RT-PCR. The most sensitive primer sets were selected, and the PCR conditions were modified to increase sensitivity. We also quantified the detection limits of real-time and conventional RT-PCR. The detection limits of conventional RT-PCR were detected in 105–106 copy/mL for CV-B5 and 106–107 copy/mL for E-30, respectively. This optimized method for detecting EVs is expected to contribute substantially to the investigation of EV outbreaks in water samples.

This paper examines the technological structures of the manufacturing and the ICT sectors in Korea to examine the potential shift of dominant technological sectors in the era of the Fourth Industrial Revolution (4IR). By using patent data of Korean firms from 1990 to 2021, we find that the manufacturing sector has been the dominant technological leader in Korea in terms of both the number of patents and the diversity of technologies, even in the era of 4IR. Although the ICT sector has shown an increasing focus on Industry 4.0 (I4) technologies after the 2000s, indicating the potential for a shift in dominance in the future, the gap between the two sectors is still significant. The study also reveals that the manufacturing sector tends to diversify technologies, while the ICT sector specializes in several target technologies. Our analysis also suggests that both sectors exhibit path-dependency, with the ICT sector exhibiting stronger characteristics, and firms in both sectors shows the tendency of intensive and extensive margin in their patenting activities, with the manufacturing sector exhibiting the stronger tendency.

This research identifies factors that affect the technological transition of firms toward industry 4.0 (IT) technologies focusing on capabilities and policy impacts using relatedness and complexity measures. For the analysis, a unique dataset was used of Korean manufacturing firms’ patents and their financial and market information. Following the Principle of Relatedness, which is a recently shaped empirical principle in the field of economic complexity, economic geography, and regional studies, a technology space is built, and each firm’s footprint in the space is traced. Using the firms’ technology space can identify those firms that successfully develop new I4 technologies and can examine whether their accumulated capabilities in their previous technology domains positively affect their technological diversification and which factors play a critical role in their transition towards I4. In addition, combining data on whether the firms received government support for R&D activities can help further analyze the role of government policy in supporting firms’ knowledge activities in new I4 technologies. Firms with higher related technologies and more government support are more likely to engage in new I4 technologies. This research is expected to inform policymakers who intend to diversify firms’ technological capabilities towards I4 technologies.

Abstract Salmonella infections represent an important public health problem. In 2018, a multistate outbreak of S. enterica subsp. enterica serovar Thompson infection associated with contaminated chocolate cakes in schools was reported in South Korea. In this study, we sequenced the 37 S. Thompson strains isolated from chocolate cakes, egg whites, preserves, and cookware associated with the outbreak. In addition, we analyze the genomic sequences of 61 S. Thompson strains (37 chocolate cake-related outbreak strains, 4 strains isolated from outbreaks in South Korea and 20 strains available in the National Center for Biotechnology Information) to assess the genomic characteristics of outbreak-related strains by comparative genomics and phylogenetic analysis. The results showed that identically classified clusters divided strains into two clusters, sub-clusters A & I (with strains from 2018 in South Korea) and sub-clusters B & II (with strains from 2014 to 2015 in South Korea). S. Thompson isolated from South Korea were accurately distinguished from publicly-available strains. Unlike other S. Thompson genomes, those of chocolate cake outbreak-related strains had three Salmonella phages (SEN8, vB SosS Oslo, and SI7) integrated into their chromosome. Comparative genomics revealed several genes responsible for the specific genomic features of chocolate cake outbreak-related strains and three bacteriophages that may contribute to the pathogenicity of other S. Thompson strains.

Anthracnose disease is a serious threat to red pepper crops in Korea and many other countries, resulting in considerable yield losses. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. This study aims to investigate the biological activity of Trichoderma isolates in controlling red pepper anthracnose caused by Colletotrichum acutatum in vitro and in the field. Out of 11 Trichoderma isolates screened for biocontrol agents against three fungal pathogens, including C. acutatum; two effective Trichoderma isolates, T. atroviride ATR697 (ATR697) and T. longibrachiatum LON701 (LON701) were selected for further investigation. Using the overlapping plates experiment, it was discovered that the volatile organic compounds (VOCs) produced by ATR697 strongly inhibited C. acutatum mycelial growth to a larger extent than the isolate LON701. A cellophane membrane experiment has shown that mycelial growth of C. acutatum was inhibited by 36% and 27% when treated with ATR697 and LON701, respectively. Culture filtrates (CFs) of two Trichoderma isolates inhibited the mycelial growth of C. acutatum in vitro. When red peppers were treated with spore suspensions of LON701 and ATR697, the disease severity (%) was 44.1% and 55.8%, respectively, in a curative method; while the disease severity (%) was 5% and 11.6%, in LON701- and ATR697-treated red peppers, respectively, in a preventive method. These results showed the suppression of disease severity (%) was relatively higher in the preventive method than in the curative method. Furthermore, Trichoderma isolates ATR697 and LON701 were resistant to commercial chemical fungicides in vitro, indicating these strains may also be used synergistically with a chemical fungicide (pyraclostrobin) against the growth of C. acutatum. There was no difference in the inhibition rate (%) of the pathogen between the treatment with LON701 alone and LON701+pyraclostrobin. Based on in vitro findings, ATR697 and LON701 played a role in effectively controlling red pepper anthracnose in field conditions, with LON701 treatment resulting in a disease rate of 14% when compared to ATR697, chemical, and non-treated controls. Overall, our study showed the ability of Trichoderma isolates to control red pepper anthracnose and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

Detecting and identifying the origins of foodborne pathogen outbreaks is a challenging. The Next-Generation Sequencing (NGS) panel method offers a potential solution by enabling efficient screening and identification of various bacteria in one reaction. In this study, new NGS panel primer sets that target 18 specific virulence factor genes from six target pathogens (Bacillus cereus, Yersinia enterocolitica, Staphylococcus aureus, Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus) were developed and optimized. The primer sets were validated for specificity and selectivity through singleplex PCR, confirming the expected amplicon size. Crosscheck and multiplex PCR showed no interference in the primer set or pathogenic DNA mixture. The NGS panel analysis of spiked water samples detected all 18 target genes in a single reaction, with pathogen concentrations ranging from 108 to 105 colony-forming units (CFUs) per target pathogen. Notably, the total sequence read counts from the virulence factor genes showed a positive association with the CFUs per target pathogen. However, the method exhibited relatively low sensitivity and occasional false positive results at low pathogen concentrations of 105 CFUs. To validate the detection and identification results, two sets of quantitative real-time PCR (qPCR) analyses were independently performed on the same spiked water samples, yielding almost the same efficiency and specificity compared to the NGS panel analysis. Comparative statistical analysis and Spearman correlation analysis further supported the similarity of the results by showing a negative association between the NGS panel sequence read counts and qPCR cycle threshold (Ct) values. To enhance NGS panel analysis for better detection, optimization of primer sets and real-time NGS sequencing technology are essential. Nonetheless, this study provides valuable insights into applying NGS panel analysis for multiple foodborne pathogen detection, emphasizing its potential in ensuring food safety.

Bisphenol is a chemical substance widely used in plastic products and food containers. In this study, we observed a relationship between DNA methylation and atopic dermatitis (AD) in the peripheral blood mononuclear cells (PBMCs) of pregnant women exposed to bisphenol A (BPA) and its alternatives, bisphenol S (BPS) and bisphenol F (BPF). DNA methylation is an epigenetic mechanism that regulates gene expression, which can be altered by environmental factors, and affects the onset and progression of diseases. We found that genes belonging to the JAK-STAT and PI3K-AKT signaling pathways were hypomethylated in the blood of pregnant women exposed to bisphenols. These genes play important roles in skin barrier function and immune responses, and may influence AD. Therefore, we suggest that not only BPA, but also BPS and BPF, which are used as alternatives, can have a negative impact on AD through epigenetic mechanisms.

Hybrid strains Escherichia coli acquires genetic characteristics from multiple pathotypes and is speculated to be more virulent; however, understanding their pathogenicity is elusive. Here, we performed genome-based characterization of the hybrid of enteropathogenic (EPEC) and enterotoxigenic E. coli (ETEC), the strains that cause diarrhea and mortality in children. The virulence genes in the strains isolated from different sources in the South Korea were identified, and their phylogenetic positions were analyzed. The EPEC/ETEC hybrid strains harbored eae and est encoding E. coli attaching and effacing lesions and heat-stable enterotoxins of EPEC and ETEC, respectively. Genome-wide phylogeny revealed that all hybrids (n = 6) were closely related to EPEC strains, implying the potential acquisition of ETEC virulence genes during ETEC/EPEC hybrid emergence. The hybrids represented diverse serotypes (O153:H19 (n = 3), O49:H10 (n = 2), and O71:H19 (n = 1)) and sequence types (ST546, n = 4; ST785, n = 2). Furthermore, heat-stable toxin-encoding plasmids possessing estA and various other virulence genes and transporters, including nleH2, hlyA, hlyB, hlyC, hlyD, espC, espP, phage endopeptidase Rz, and phage holin, were identified. These findings provide insights into understanding the pathogenicity of EPEC/ETEC hybrid strains and may aid in comparative studies, virulence characterization, and understanding evolutionary biology.

The global emergence of hybrid diarrheagenic E. coli strains incorporating genetic markers from different pathotypes is a public health concern. Hybrids of Shiga toxin-producing and enterotoxigenic E. coli (STEC/ETEC) are associated with diarrhea and hemolytic uremic syndrome (HUS) in humans. In this study, we identified and characterized STEC/ETEC hybrid strains isolated from livestock feces (cattle and pigs) and animal food sources (beef, pork, and meat patties) in South Korea between 2016 and 2020. The strains were positive for genes from STEC and ETEC, such as stx (encodes Shiga toxins, Stxs) and est (encodes heat-stable enterotoxins, ST), respectively. The strains belong to diverse serogroups (O100, O168, O8, O155, O2, O141, O148, and O174) and sequence types (ST446, ST1021, ST21, ST74, ST785, ST670, ST1780, ST1782, ST10, and ST726). Genome-wide phylogenetic analysis revealed that these hybrids were closely related to certain ETEC and STEC strains, implying the potential acquisition of Stx-phage and/or ETEC virulence genes during the emergence of STEC/ETEC hybrids. Particularly, STEC/ETEC strains isolated from livestock feces and animal source foods mostly exhibited close relatedness with ETEC strains. These findings allow further exploration of the pathogenicity and virulence of STEC/ETEC hybrid strains and may serve as a data source for future comparative studies in evolutionary biology.

Gynostemma (G.) pentaphyllum (Cucurbitaceae) contains various bioactive gypenosides. Ethanol extract from G. pentaphyllum (GP-EX) has been shown to have ameliorative effects on the death of dopaminergic neurons in animal models of Parkinson’s disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- and 6-hydroxydopamine. PD patients exhibit multiple symptoms, so PD-related research should combine neurotoxin models with genetic models. In the present study, we investigated the ameliorative effects of GP-EX, including gypenosides, on the cell death of dopaminergic neurons in the midbrain of A53T α-synuclein transgenic mouse models of PD (A53T). Both GP-EX and gypenosides at 50 mg/kg per day were orally administered to the A53T mice for 20 weeks. α-Synuclein-immunopositive cells and α-synuclein phosphorylation were increased in the midbrain of A53T mice, which was reduced following treatment with GP-EX. Treatment with GP-EX modulated the reduced phosphorylation of tyrosine hydroxylase, extracellular signal-regulated kinase (ERK1/2), Bcl-2-associated death promoter (Bad) at Ser112, and c-Jun N-terminal kinase (JNK1/2) due to α-synuclein overexpression. In the A53T group, GP-EX treatment prolonged the latency of the step-through passive avoidance test and shortened the transfer latency of the elevated plus maze test. Gypenosides treatment exhibited the effects and efficacy similar to those of GP-EX. Taken together, GP-EX, including gypenosides, has ameliorative effects on dopaminergic neuronal cell death due to the overexpression of α-synuclein by modulating ERK1/2, Bad at Ser112, and JNK1/2 signaling in the midbrain of A53T mouse model of PD. Further studies are needed to investigate GP-EX as a treatment for neurodegenerative synucleinopathies, including PD. This study was approved by the Animal Ethics Committee of Chungbuk National University (approval No. CBNUA-956-16-01) on September 21, 2016.

The incidence of renal cell carcinoma (RCC) is high, and its outcomes remain poor. Mortality is attributable largely to metastatic disease and a dearth of effective therapeutic interventions. The lungs are the most common metastatic site. To elucidate the biological mechanisms underlying pulmonary metastasis and identify superior therapeutic strategies, we developed a novel and clinically relevant murine RCC model exhibiting enhanced pulmonary metastasis. Mice underwent intrarenal implantation using luciferase-expressing Renca, a murine renal adenocarcinoma cell line. Primary renal tumor progression and development of metastatic lung lesions were monitored in live mice using bioluminescent imaging, followed by post-mortem organ assessment. Cells were isolated from pulmonary metastases for reimplantation, followed by repeat monitoring and assessment. This process was repeated once more for a total of two in vivo passages to select for pulmonary metastatic Renca cell subpopulations. However, a single round of in vivo selection was sufficient to produce a near-maximally metastatic subpopulation. Relative to Renca cell-implanted mice, subpopulation-implanted mice exhibited shorter implantation-metastasis intervals (5 days), shorter implantation-moribundity intervals (sacrificed at 18.6±2.9 versus 22.3±1.1 days), a higher number of metastatic lung lesions at 23 days (183.9±39.0 versus 172.6±38.2) and poorer survival. Implantation of cells derived from the second round of in vivo selection produced no further significant differences in the above metrics. This model consistently and efficiently recapitulates RCC pulmonary metastasis while allowing in vivo monitoring of tumor progression, thereby facilitating elucidation of the molecular mechanisms underlying pulmonary metastasis and evaluation of therapeutic modalities.

Prader–Willi syndrome is a genetic disorder that is characterized by obesity, characteristic facial features, hypotonia, and sleep apnea. These abnormalities mean that airway management is difficult in such patients. Several previous reports suggest that neuromuscular blocking agents should not be used to reduce airway and respiratory complications in these patients. However, this is not always possible. Here, we report the case of a patient with Prader–Willi syndrome in whom anesthesia for ophthalmic surgery was managed successfully using sugammadex after administration of rocuronium.

Environmental exposure is known to have toxic effects. Maternal environmental exposure not only affects mothers but also their fetuses in utero, which may interrupt their early development. Preterm birth, one of the outcomes of prenatal exposure, is a significant factor in lifelong health risks. To understand the effects of prenatal exposome on preterm birth, we studied the association between maternal and prenatal heavy metal exposure and gestational age, using resources from the MOthers’ and Children’s Environmental Health (MOCEH) study in South Korea. Additionally, a methylation assay was performed to analyze epigenetic mediation using genomic DNA derived from the cord blood of 384 participants in the MOCEH study. The results suggest that maternal cadmium exposure is associated with a decrease in gestational age through an alteration in DNA methylation at a specific CpG site, cg21010642. The CpG site was annotated to a gene involved in early embryonic development. Therefore, irregular methylation patterns at this site may contribute to premature birth by mediating irregular biological mechanisms.

Background and Objective: Procedural thromboembolism after a mechanical thrombectomy (MT) for an acute ischemic stroke (AIS) has rarely been studied. It may occur from the artery-to-artery embolization of atherosclerotic plaque in the aortic arch. We investigated the relationship between aortic arch calcification (AoAC) on a chest X-ray and procedural thromboembolism on diffusion-weighted imaging (DWI) after an MT. Materials and Methods: From January 2017 to December 2020, 131 patients underwent DWI within two days following an MT for an AIS. Procedural thromboembolism was defined as new DWI-positive lesions in other territories from the occluded artery on DWI within two days after MT. Results: Procedural thromboembolism was observed in 30 (22.9%) patients. Procedural thromboembolism was associated with old age (72.3 ± 9.44 vs. 65.7 ± 12.8 years, p = 0.003), a longer procedural time (77.6 ± 37.6 vs. 60.1 ± 29.7 min, p = 0.024), and AoAC (calcification (73.3%) vs. no calcification (29.7%), p < 0.001). Multivariable logistic regression analysis showed that procedural thromboembolism was independently associated with AoAC (adjusted odds ratio (OR): 6.107, adjusted 95% confidence interval (CI): 2.374–15.705, p < 0.001) and a longer procedural time (adjusted OR: 1.015, adjusted 95% CI: 1.001–1.030, p = 0.031). Conclusions: Procedural thromboembolism after an MT for an AIS was related to AoAC on a chest X-ray and a longer procedural time. Our results suggest that although rapid recanalization is the most crucial goal of an MT for an AIS, the importance of the careful advance of the guiding catheter through the aortic arch should not be underestimated to reduce the risk of procedural thromboembolism, especially in patients with AoAC on a chest X-ray.

Background and objective: Procedural thromboembolisms after mechanical thrombectomy (MT) for acute ischemic stroke has rarely been studied. We retrospectively evaluated factors associated with procedural thromboembolisms after MT using diffusion-weight imaging (DWI) within 2 days of MT. Materials and Methods: From January 2018 to March 2020, 78 patients with acute ischemic stroke who underwent MT were evaluated using DWI. Procedural thromboembolisms were defined as new cerebral infarctions in other territories from the occluded artery on DWI after MT. Results: Procedural thromboembolisms were observed on DWI in 16 patients (20.5%). Procedural thromboembolisms were associated with old age (73.8 ± 8.18 vs. 66.8 ± 11.2 years, p = 0.021), intravenous (IV) thrombolysis (12 out of 16 (75.0%) vs. 25 out of 62 (40.3%), p = 0.023), heparinization (4 out of 16 (25.0%) vs. 37 out of 62 (59.7%), p = 0.023), and longer procedural time (90.9 ± 35.6 vs. 64.4 ± 33.0 min, p = 0.006). Multivariable logistic regression analysis revealed that procedural thromboembolisms were independently associated with procedural time (adjusted odds ratio (OR); 1.020, 95% confidence interval (CI); 1.002–1.039, p = 0.030) and IV thrombolysis (adjusted OR; 4.697, 95% CI; 1.223–18.042, p = 0.024). The cutoff value of procedural time for predicting procedural thromboembolisms was ≥71 min (area under the curve; 0.711, 95% CI; 0.570–0.851, p = 0.010). Conclusions: Procedural thromboembolisms after MT for acute ischemic stroke are significantly associated with longer procedural time and IV thrombolysis. This study suggests that patients with IV thrombolysis and longer procedural time (≥71 min) are at a higher risk of procedural thromboembolisms after MT for acute ischemic stroke.

In this study, the effects of herbal ethanol extracts of Gynostemma pentaphyllum (GP-EX), on chronic electric footshock (EF) stress-induced anxiety disorders were investigated in mice, which were orally treated with GP-EX (30 mg/kg and 50 mg/kg) once a day for 14 days, followed by exposure to EF stress (2 mA, with an interval and duration of 10 s for 3 min). After the final exposure to EF stress, the elevated plus-maze and marble burying tests were performed, and the levels of dopamine and serotonin in the brain, the serum levels of corticosterone, and the expression of c-Fos in the paraventricular nuclei (PVN) were determined. Treatment with GP-EX (30 mg/kg and 50 mg/kg) significantly recovered the number of entries into open arms and time spent on open arms, which was reduced by chronic EF stress. GP-EX (30 mg/kg and 50 mg/kg) also reduced the number of marbles buried, which was increased by chronic EF stress. In addition, electric EF stress significantly decreased the levels of dopamine and serotonin in the brain, which was recovered by treatment with GP-EX (30 mg/kg and 50 mg/kg). The serum levels of corticosterone, which were markedly increased by chronic EF stress, were reduced by treatment with GP-EX (30 mg/kg and 50 mg/kg). Chronic EF stress-induced increases in c-Fos expression were also markedly reduced by GP-EX (30 mg/kg and 50 mg/kg) in the PVN. These results suggest that GP-EX shows anxiolytic functions, determined by the elevated plus-maze and marble burying tests, which are mediated by modulating the activity of dopamine and serotonin neurons as well as the expression of c-Fos in the brain, and the serum levels of corticosterone. Clinical trials of herbal GP-EX and its bioactive components need further investigation.

6-Hydroxydopamine administration for 28 days (8 μg/2 μL) reduced the number of tyrosine hydroxylase (TH)-immunopositive neurons to 40.2% in the substantia nigra compared to the intact contralateral side. Dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid and norepinephrine levels were reduced to 19.1%, 52.3%, 47.1% and 67.4% in the striatum of 6-hydroxydopamine-lesioned rats compared to the control group, respectively. However, an oral administration of herbal ethanol extracts from Gynostemma pentaphyllum (GP-EX) (10 mg/kg and 30 mg/kg) starting on day 3 post-lesion for 28 days markedly ameliorated the reduction of TH-immunopositive neurons induced by 6-hydroxydopamine-lesioned rat brain from 40.2% to 67.4% and 75.8% in the substantia nigra. GP-EX administration (10 and 30 mg/kg) also recovered the levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid and norepinephrine in post-lesion striatum to 64.1% and 65.0%, 77.9% and 89.7%, 82.6% and 90.2%, and 88.1% and 89.2% of the control group. GP-EX at the given doses did not produce any sign of toxicity such as weight loss, diarrhea and vomiting in rats during the 28 day treatment period and four gypenoside derivatives, gynosaponin TN-1, gynosaponin TN-2, gypenoside XLV and gypenoside LXXIV were identified from GP-EX. These results suggest that GP-EX might be helpful in the prevention of Parkinson’s disease.