Improvement in Delivery of Ischemic Stroke Treatments but Stagnation of Clinical Outcomes in Young Adults in South Korea.

BACKGROUND: There is limited information on the delivery of acute stroke therapies and secondary preventive measures and clinical outcomes over time in young adults with acute ischemic stroke. This study investigated whether advances in these treatments improved outcomes in this population. METHODS: Using a prospective multicenter stroke registry in Korea, young adults (aged 18-50 years) with acute ischemic stroke hospitalized between 2008 and 2019 were identified. The observation period was divided into 4 epochs: 2008 to 2010, 2011 to 2013, 2014 to 2016, and 2017 to 2019. Secular trends for patient characteristics, treatments, and outcomes were analyzed. RESULTS: A total of 7050 eligible patients (mean age, 43.1; men, 71.9%) were registered. The mean age decreased from 43.6 to 42.9 years (Ptrend=0.01). Current smoking decreased, whereas obesity increased. Other risk factors remained unchanged. Intravenous thrombolysis and mechanical thrombectomy rates increased over time from 2008 to 2010 to 2017 to 2019 (9.5%-13.8% and 3.2%-9.2%, respectively; Ptrend<0.01). Door-to-needle time improved (Ptrend <.001), but onset-to-door and door-to-puncture times remained constant. Secondary prevention, including dual antiplatelets for noncardioembolic minor stroke (26.7%-47.0%), direct oral anticoagulants for atrial fibrillation (0.0%-56.2%), and statins for large artery atherosclerosis (76.1%-95.3%) increased (Ptrend<0.01). Outcome data were available from 2011. One-year mortality (2.5% in 2011-2013 and 2.3% in 2017-2019) and 3-month modified Rankin Scale scores 0 to 1 (68.3%-69.1%) and 0 to 2 (87.6%-86.2%) remained unchanged. The 1-year stroke recurrence rate increased (4.1%-5.5%; Ptrend=0.04), although the difference was not significant after adjusting for sex and age. CONCLUSIONS: Improvements in the delivery of acute stroke treatments did not necessarily lead to better outcomes in young adults with acute ischemic stroke over the past decade, indicating a need for further progress.

Interim analysis from a phase 2 randomized trial of EuCorVac-19: a recombinant protein SARS-CoV-2 RBD nanoliposome vaccine.

BACKGROUND: Numerous vaccine strategies are being advanced to control SARS-CoV-2, the cause of the COVID-19 pandemic. EuCorVac-19 (ECV19) is a recombinant protein nanoparticle vaccine that displays the SARS-CoV-2 receptor-binding domain (RBD) on immunogenic nanoliposomes. METHODS: Initial study of a phase 2 randomized, observer-blind, placebo-controlled trial to assess the immunogenicity, safety, and tolerance of ECV19 was carried out between July and October 2021. Two hundred twenty-nine participants were enrolled at 5 hospital sites in South Korea. Healthy adults aged 19-75 without prior known exposure to COVID-19 were vaccinated intramuscularly on day 0 and day 21. Of the participants who received two vaccine doses according to protocol, 100 received high-dose ECV19 (20 µg RBD), 96 received low-dose ECV19 (10 µg RBD), and 27 received placebo. Local and systemic adverse events were monitored. Serum was assessed on days 0, 21, and 42 for immunogenicity analysis by ELISA and neutralizing antibody response by focus reduction neutralization test (FRNT). RESULTS: Low-grade injection site tenderness and pain were observed in most participants. Solicited systemic adverse events were less frequent, and mostly involved low-grade fatigue/malaise, myalgia, and headache. No clinical laboratory abnormalities were observed. Adverse events did not increase with the second injection and no serious adverse events were solicited by ECV19. On day 42, Spike IgG geometric mean ELISA titers were 0.8, 211, and 590 Spike binding antibody units (BAU/mL) for placebo, low-dose and high-dose ECV19, respectively (p < 0.001 between groups). Neutralizing antibodies levels of the low-dose and high-dose ECV19 groups had FRNT50 geometric mean values of 129 and 316, respectively. Boosting responses and dose responses were observed. Antibodies against the RBD correlated with antibodies against the Spike and with virus neutralization. CONCLUSIONS: ECV19 was generally well-tolerated and induced antibodies in a dose-dependent manner that neutralized SARS-CoV-2. The unique liposome display approach of ECV19, which lacks any immunogenic protein components besides the antigen itself, coupled with the lack of increased adverse events during boosting suggest the vaccine platform may be amenable to multiple boosting regimes in the future. Taken together, these findings motivate further investigation of ECV19 in larger scale clinical testing that is underway. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov as # NCT04783311.

Three-Dimensional Convolutional Neural Network for Prostate MRI Segmentation and Comparison of Prostate Volume Measurements by Use of Artificial Neural Network and Ellipsoid Formula.

OBJECTIVE. The purposes of this study were to assess the performance of a 3D convolutional neural network (CNN) for automatic segmentation of prostates on MR images and to compare the volume estimates from the 3D CNN with those of the ellipsoid formula. MATERIALS AND METHODS. The study included 330 MR image sets that were divided into 260 training sets and 70 test sets for automated segmentation of the entire prostate. Among these, 162 training sets and 50 test sets were used for transition zone segmentation. Assisted by manual segmentation by two radiologists, the following values were obtained: estimates of ground-truth volume (VGT), software-derived volume (VSW), mean of VGT and VSW (VAV), and automatically generated volume from the 3D CNN (VNET). These values were compared with the volume calculated with the ellipsoid formula (VEL). RESULTS. The Dice similarity coefficient for the entire prostate was 87.12% and for the transition zone was 76.48%. There was no significant difference between VNET and VAV (p = 0.689) in the test sets of the entire prostate, whereas a significant difference was found between VEL and VAV (p < 0.001). No significant difference was found among the volume estimates in the test sets of the transition zone. Overall intraclass correlation coefficients between the volume estimates were excellent (0.887-0.995). In the test sets of entire prostate, the mean error between VGT and VNET (2.5) was smaller than that between VGT and VEL (3.3). CONCLUSION. The fully automated network studied provides reliable volume estimates of the entire prostate compared with those obtained with the ellipsoid formula. Fast and accurate volume measurement by use of the 3D CNN may help clinicians evaluate prostate disease.

Detailed visual assessment of striatal dopaminergic depletion in patients with idiopathic normal pressure hydrocephalus: unremarkable or not?

BACKGROUND: Dopamine transporter (DAT) imaging may enable clinicians to discriminate idiopathic normal pressure hydrocephalus (iNPH) from other parkinsonian disorders. However, a specific pattern of dopaminergic loss in DAT imaging of iNPH patients remains to be further elucidated. METHODS: In this preliminary study, 11 patients with iNPH in our hospital between March 2017 and February 2019 were finally enrolled. A diagnosis of iNPH was made according to the two established criteria. For visual analysis of DAT imaging, a striatum was divided into five domains. A semi-quantitative visual assessment was performed with a consensus between a nuclear medicine specialist and an experienced neurologist who were blinded to the clinical diagnosis. RESULTS: Striatal dopaminergic deficits were abnormal in 90.9% (10/11) of patients with iNPH. The degree of dopaminergic reduction was mild and heterogeneous. However, a tendency of preferential striatal DAT loss in the caudate nucleus (90.9%, 10/11) than in the putamen (72.7%, 8/11) was observed, whereas ventral portion (9.1%, 1/11) was relatively preserved. CONCLUSION: Striatal dopaminergic depletion might be mild and heterogeneous in patients with iNPH. These dopaminergic deficits were more common in the caudate nucleus than in the putamen, suggesting a pattern different from other degenerative parkinsonian disorders.

Eliciting unnatural immune responses by activating cryptic epitopes in viral antigens.

Antigenic variation in viral surface antigens is a strategy for escaping the host's adaptive immunity, whereas regions with pivotal functions for infection are less subject to antigenic variability. We hypothesized that genetically invariable and immunologically dormant regions of a viral surface antigen could be exposed to the host immune system and activated by rendering them susceptible to antigen-processing machinery in professional antigen-presenting cells (APCs). Considering the frequent antigen drift and shift in influenza viruses, we identified and used structural modeling to evaluate the conserved regions on the influenza hemagglutinin (HA) surface as potential epitopes. Mutant viruses containing the cleavage motifs of cathepsin S within HA were generated. Immunization of mice showed that the mutant, but not the wild-type virus, elicited specific antibodies against the cryptic epitope. Those antibodies were purified, and specific binding to HA was confirmed. These results suggest that an unnatural immune response can be elicited through the processing of target antigens in APCs, followed by presentation via the major histocompatibility complex, if not subjected to regulatory pathways. By harnessing the antigen-processing machinery, our study shows a proof-of-principle for designer vaccines with increased efficacy and safety by either activating cryptic, or inactivating naturally occurring, epitopes of viral antigens.-Lee, Y. J., Yu, J. E., Kim, P., Lee, J.-Y., Cheong, Y. C., Lee, Y. J., Chang, J., Seong, B. L. Eliciting unnatural immune responses by activating cryptic epitopes in viral antigens.

Lack of association between dopamine transporter loss and non-motor symptoms in patients with Parkinson's disease: a detailed PET analysis of 12 striatal subregions.

INTRODUCTION: Patients with Parkinson's disease (PD) present a variety of non-motor symptoms. However, it remains unclear whether dopamine depletion is related to non-motor symptoms, and which non-motor symptoms are significantly dependent on dopaminergic deficit. METHODS: Forty-one patients with PD who underwent positron emission tomography imaging of dopamine transporters (DATs) were recruited for this study. The striatum was divided into 12 subregions, and DAT activity, as striatal dopaminergic concentration, was calculated in each subregion. In addition to measuring motor symptoms using the Unified Parkinson's Disease Rating Scale-part III (UPDRS-III), various non-motor symptoms were assessed using the Montreal cognitive assessment, frontal assessment battery, Beck depression inventory (BDI), Beck anxiety inventory, PD sleep scale (PDSS), PD fatigue scale, and non-motor symptoms scale (NMSS) for PD. RESULTS: For simple linear regression analyses, dopaminergic depletion in all striatal subregions was negatively correlated with the UPDRS-III score. The most relevant non-motor symptom assessment related to dopaminergic loss in the 12 subregions was NMSS, followed by BDI and PDSS. However, following multiple linear regression analyses, dopaminergic depletion in the 12 striatal subregions was not related with any of the non-motor symptoms. Conversely, dopaminergic deficit in the right anterior and posterior putamen was associated with the UPDRS-III score. CONCLUSIONS: Striatal dopaminergic depletion was not significantly correlated with any of the various non-motor symptoms in PD. Our findings suggest that non-dopaminergic systems are significantly implicated in the pathogenesis of non-motor symptoms in patients with PD.

Chemical Vapor Deposition Carbon Film as a Capping Layer in 4H-SiC Based MOSFETs.

Radio-frequency plasma enhanced CVD (RF-PECVD) carbon films were grown directly on 4-inch 4H-SiC substrates as a capping layer for MOSFET device applications. An approximately 50-nm-thick CVD carbon capping layer was found to reduce the surface roughness, as determined by atomic force microscopy (AFM). The secondary ion mass spectroscopy (SIMS) depth profile results revealed that carbon capping layer can suppress the dopant out-diffusion on the implanted surface after annealing even at high temperature (1700 °C) for 30 min. The calculated subthreshold swing (S) values of devices with CVD carbon capping layer and photo-resist process (base) measured at room temperature were 460 ± 50 (mV/dec) and 770 ± 70 (mV/dec), respectively. The lower value of 'S' for the device with carbon capping layer was related to the very low density of interface traps at the SiC-SiO2 interface. These results show the potential of CVD carbon as a capping layer for SiC MOSFET device applications.

Association between White Matter Lesions and Non-Motor Symptoms in Parkinson Disease.

BACKGROUND: There are only few studies exploring the relationship between white matter lesions (WMLs) and non-motor symptoms in Parkinson disease (PD). This study aimed to investigate the association between WMLs and the severity of non-motor symptoms in PD. METHODS: The severity of motor dysfunction, cognitive impairment, and non-motor symptoms was assessed by various scales in 105 PD patients. We used a visual semiquantitative rating scale and divided the subjects into four groups: no, mild, moderate, and severe WMLs. We compared the means of all scores between the four groups and analyzed the association between the severity of WMLs and the specific domain of non-motor symptoms. RESULTS: The non-motor symptoms as assessed by the Non-Motor Symptoms Scale, Parkinson's Disease Questionnaire (PDQ-39), Parkinson's Disease Sleep Scale, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Neuropsychiatric Inventory (NPI), and Parkinson Fatigue Scale (PFS) were significantly worse in the patients with moderate and severe WMLs than in those without WMLs. Compared with the no WML group, the scores for motor dysfunction were significantly higher in the mild, moderate, and severe WML groups. The scores for cognitive dysfunction were significantly higher in the patients with severe WMLs than in those without WMLs. The severity of WMLs showed linear associations with PFS, BDI, BAI, NPI, and PDQ-39 scores. The severity of WMLs also correlated linearly with scores for motor and cognitive dysfunction. CONCLUSIONS: Among the non-motor symptoms, fatigue, depression, anxiety, and quality of life were significantly affected by WMLs in PD. Confirmation of the possible role of WMLs in non-motor symptoms associated with PD in a prospective manner may be crucial not only for understanding non-motor symptoms but also for the development of treatment strategies.

Role of MyD88 in adenovirus keratitis.

Pattern recognition receptors (PRRs) are critical to the early detection and innate immune responses to pathogens. In particular, the toll-like receptor (TLR) system and its associated adaptor proteins have essential roles in early host responses to infection. Epidemic keratoconjunctivitis, caused by the human adenovirus, is a severe ocular surface infection associated with corneal inflammation (stromal keratitis). We previously showed that adenovirus capsid was a key molecular pattern in adenovirus keratitis, with viral DNA having a lesser role. We have now investigated the role of the adaptor molecule MyD88 in a mouse model of adenovirus keratitis in which there is no viral replication. In MyD88-/- mice infected with human adenovirus type 37, clinical keratitis was markedly reduced, along with infiltration of CD45+ cells, and expression of inflammatory cytokines. Reduction of inflammatory cytokines was also observed in infected primary human corneal fibroblasts pretreated with a MyD88 inhibitory peptide. Keratitis similar to wild type mice was observed in TLR2, TLR9 and IL-1R knockout mice, but was reduced in TLR2/9 double knockout mice, consistent with synergy of TLR2 and TLR9 in the response to adenovirus infection. MyD88 co-immunoprecipitated with Src kinase in mice corneas and in human corneal fibroblasts infected with adenovirus, and MyD88 inhibitory peptide reduced Src phosphorylation, linking MyD88 activation to inflammatory gene expression through a signaling cascade previously shown to be directed by Src. Our findings reveal a critical role for the PRRs TLR2 and 9, and their adaptor protein MyD88, in corneal inflammation upon adenovirus infection.

Recently Uncontrolled Glycemia in Diabetic Patients Is Associated with the Severity of Intracranial Atherosclerosis.

BACKGROUND AND PURPOSE: Diabetes mellitus is a specific risk factor for intracranial atherosclerosis (ICAS) regardless of race. However, it is largely unknown whether poor glycemic control is associated with the severity of ICAS in diabetic patients. METHODS: We selected diabetic patients with acute ischemic stroke who were prospectively registered between March 2005 and December 2015. The patients who had a high-risk source of cardiogenic embolism were excluded. ICAS was graded from 0 to 3 by the number of significant (≥50%) stenoses on intracranial magnetic resonance angiography, and was divided into 4 types: unilateral anterior, bilateral anterior, posterior, and anterior plus posterior. Ordinal and multinomial regression tests were applied for the factors influencing the number and types of ICAS. RESULTS: A total of 774 patients with noncardioembolic acute ischemic stroke with diabetes were enrolled. The multiplicity of ICAS was independently associated with age (odds ratio [OR], 1.035 per 1 year, 1.018-1.052; P < .001), hypertension (OR, 1.992, 1.336-2.965; P = .001), and glycated hemoglobin (HbA1c; OR, 1.207 per 1%, 1.089-1.338; P < .001) in the ordinal regression model. In multinomial regression, bilateral anterior stenosis tended to be correlated with age (OR, 1.042, 1.008-1.077; P = .016) and HbA1c (OR, 1.201 per 1%, .991-1.520; P = .057). Both anterior and posterior stenoses were significantly associated with age (OR, 1.056, 1.029-1.084; P < .001), hypertension (OR, 2.584, 1.404-4.762; P = .002), and HbA1c (OR, 1.272, 1.070-1.511; P = .006). CONCLUSIONS: Age, concomitant hypertension, and HbA1c were factors associated with multiple intracranial stenoses. Further study is warranted to elucidate whether poor glycemic control facilitates ICAS in diabetic patients.

Protein Kinase C Signaling in Adenoviral Infection.

Activation of protein kinase C (PKC), a serine/threonine protein kinase, ubiquitously influences cellular signal transduction and has been shown to play a role in viral entry. In this study, we explored a role for PKC in human adenovirus type 37 infection of primary human corneal fibroblasts, a major target cell for infection. We sought evidence for an interaction between PKC activation and two potential downstream targets: cSrc kinase, shown previously to play a critical role in adenovirus signaling in these cells, and caveolin-1, reported earlier to be important to entry of adenovirus type 37. Infection of fibroblasts increased PKCα phosphorylation and translocation of PKCα from the cytosol to caveolin-1 containing vesicles. Virus-induced phosphorylation of both cSrc and AKT was abolished in cell lysates pretreated with calphostin C, a chemical inhibitor of PKC. Inhibition of PKC also reduced virus associated phosphorylation of caveolin-1, while inhibition of cSrc by the chemical inhibitor PP2 reduced only caveolin-1 phosphorylation, but not PKCα phosphorylation, in lipid rafts. These results suggest a role for PKCα upstream to both cSrc and caveolin-1. Phosphorylated PKCα was found in the same endosomal fractions as phosphorylated cSrc, and PKCα was present to a greater degree in caveolin-1 pull downs from virus infected than mock infected cell lysates. Calphostin C also reduced early viral gene expression, indicating that PKCα activity may be required for viral entry. PKCα plays a central role in adenovirus infection of corneal fibroblasts and regulation of downstream molecules, including the important lipid raft component caveolin-1.

Optimal Schedules in Multitask Motor Learning.

Although scheduling multiple tasks in motor learning to maximize long-term retention of performance is of great practical importance in sports training and motor rehabilitation after brain injury, it is unclear how to do so. We propose here a novel theoretical approach that uses optimal control theory and computational models of motor adaptation to determine schedules that maximize long-term retention predictively. Using Pontryagin's maximum principle, we derived a control law that determines the trial-by-trial task choice that maximizes overall delayed retention for all tasks, as predicted by the state-space model. Simulations of a single session of adaptation with two tasks show that when task interference is high, there exists a threshold in relative task difficulty below which the alternating schedule is optimal. Only for large differences in task difficulties do optimal schedules assign more trials to the harder task. However, over the parameter range tested, alternating schedules yield long-term retention performance that is only slightly inferior to performance given by the true optimal schedules. Our results thus predict that in a large number of learning situations wherein tasks interfere, intermixing tasks with an equal number of trials is an effective strategy in enhancing long-term retention.

Adenoviral Vector System: A Comprehensive Overview of Constructions, Therapeutic Applications and Host Responses.

Adenoviral vectors are crucial for gene therapy and vaccine development, offering a platform for gene delivery into host cells. Since the discovery of adenoviruses, first-generation vectors with limited capacity have evolved to third-generation vectors flacking viral coding sequences, balancing safety and gene-carrying capacity. The applications of adenoviral vectors for gene therapy and anti-viral treatments have expanded through the use of in vitro ligation and homologous recombination, along with gene editing advancements such as CRISPR-Cas9. Current research aims to maintain the efficacy and safety of adenoviral vectors by addressing challenges such as pre-existing immunity against adenoviral vectors and developing new adenoviral vectors from rare adenovirus types and non-human species. In summary, adenoviral vectors have great potential in gene therapy and vaccine development. Through continuous research and technological advancements, these vectors are expected to lead to the development of safer and more effective treatments.

In Silico Intensive Analysis for the E4 Gene Evolution of Human Adenovirus Species D.

Adenovirus (Ad) is a ubiquitous pathogen capable of infecting a wide range of animals and humans. Human Adenovirus (HAdV) can cause severe infection, particularly in individuals with compromised immune systems. To date, over 110 types of HAdV have been classified into seven species from A to G, with the majority belonging to the human adenovirus species D (HAdV-D). In the HAdV-D, the most significant factor for the creation of new adenovirus types is homologous recombination between viral genes involved in determining the virus tropism or evading immune system of host cells. The E4 gene, consisting of seven Open Reading Frames (ORFs), plays a role in both the regulation of host cell metabolism and the replication of viral genes. Despite long-term studies, the function of each ORF remains unclear. Based on our updated information, ORF2, ORF3, and ORF4 have been identified as regions with relatively high mutations compared to other ORFs in the E4 gene, through the use of in silico comparative analysis. Additionally, we managed to visualize high mutation sections, previously undetectable at the DNA level, through a powerful amino acid sequence analysis tool known as proteotyping. Our research has revealed the involvement of the E4 gene in the evolution of human adenovirus, and has established accurate sequence information of the E4 gene, laying the groundwork for further research.

Genomic Evolution and Recombination Dynamics of Human Adenovirus D Species: Insights from Comprehensive Bioinformatic Analysis.

Human adenoviruses (HAdVs) can infect various epithelial mucosal cells, ultimately causing different symptoms in infected organ systems. With more than 110 types classified into seven species (A-G), HAdV-D species possess the highest number of viruses and are the fastest proliferating. The emergence of new adenovirus types and increased diversity are driven by homologous recombination (HR) between viral genes, primarily in structural elements such as the penton base, hexon and fiber proteins, and the E1 and E3 regions. A comprehensive analysis of the HAdV genome provides valuable insights into the evolution of human adenoviruses and identifies genes that display high variation across the entire genome to determine recombination patterns. Hypervariable regions within genetic sequences correlate with functional characteristics, thus allowing for adaptation to new environments and hosts. Proteotyping of newly emerging and already established adenoviruses allows for prediction of the characteristics of novel viruses. HAdV-D species evolved in a direction that increased diversity through gene recombination. Bioinformatics analysis across the genome, particularly in highly variable regions, allows for the verification or re-evaluation of recombination patterns in both newly introduced and pre-existing viruses, ultimately aiding in tracing various biological traits such as virus tropism and pathogenesis. Our research does not only assist in predicting the emergence of new adenoviruses but also offers critical guidance in regard to identifying potential regulatory factors of homologous recombination hotspots.

Improvement in Testosterone Production by Acorus gramineus for the Alleviation of Andropause Symptoms.

Acorus gramineus has a number of beneficial effects, including protective effects against age-related disorders. In this study, the effects of A. gramineus on testosterone production and andropause symptoms were evaluated. We first treated TM3 mouse Leydig cells, responsible for testosterone production, with A. gramineus aqueous extract at different concentrations. In TM3 cells, the testosterone concentration increased in a concentration-dependent manner compared with those in the control. In addition, at 400 µg/mL extract, the mRNA expression level of the steroidogenic enzyme CYP11A1 was increased. Subsequently, 23-week-old Sprague-Dawley (SD) rats exhibiting an age-related reduction in serum testosterone (approximately 80% lower than that in 7-week-old SD rats) were administered A. gramineus aqueous extract for 8 weeks. Serum total testosterone and free testosterone levels were higher and serum estradiol, prostate-specific antigen levels, and total cholesterol levels were lower in the AG50 group (A. gramineus aqueous extract 50 mg/kg of body weight/day) than in the OLD (control group). The AG50 group also showed significant elevations in sperm count, grip strength, and mRNA expression of StAR, CYP11A1, 17ß-HSD, and CYP17A1 compared with those in the OLD group. In conclusion, A. gramineus aqueous extract facilitated steroidogenesis in Leydig cells, elevated testosterone levels, lowered serum estradiol and total cholesterol levels, and increased muscle strength and sperm count, thus alleviating the symptoms of andropause. These findings suggest that A. gramineus aqueous extract is a potentially effective therapeutic agent against various symptoms associated with andropause.

Rapid and High-Density Antibody Immobilization Using Electropolymerization of Pyrrole for Highly Sensitive Immunoassay.

Polypyrrole (Ppy) is a biologically compatible polymer that is used as a matrix, in which drugs and enzymes can be incorporated by doping. Here, we suggest an inventive application of Ppy as a biorecognition film encapsulated with an antibody (Ab) as an alternative strategy for the on-site multistep functionalization of thiol-based self-assembled monolayers. The fabrication steps of the recognition films were followed by dropping pyrrole and Ab mixed solutions onto the electrode and obtaining a thin film by direct current electropolymerization. The efficiency of Ab immobilization was studied by using fluorescence microscopy and electrochemical (EC) methods. Finally, the Ab density was increased and immobilized in 1 min, and the sensing performance as an EC immunosensor was demonstrated using α-fetoprotein with a limit of detection of 3.13 pg/mL and sensing range from 1 pg/mL to 100 ng/mL. This study demonstrates the potential for electrochemical functionalization of biomolecules with high affinity and rapidity.

Cutting Balloon Angioplasty for Severe In-Stent Restenosis after Carotid Artery Stenting: Long-Term Outcomes and Review of Literature.

PURPOSE: Cutting balloon-percutaneous transluminal angioplasty (CB-PTA) is a feasible treatment option for in-stent restenosis (ISR) after carotid artery stenting (CAS). However, the longterm durability and safety of CB-PTA for ISR after CAS have not been well established. MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with ISR after CAS who had been treated with CB-PTA from 2012 to 2021 in our center. Detailed information of baseline characteristics, periprocedural and long-term outcomes, and follow-up imaging was collected. RESULTS: During 2012-2021, a total of 301 patients underwent CAS. Of which, CB-PTA was performed on 20 lesions exhibiting severe ISR in 18 patients following CAS. No patient had any history of receiving carotid endarterectomy or radiation therapy. These lesions were located at the cervical segment of the internal carotid artery (n=16), proximal external carotid artery (n=1), and distal common carotid artery (n=1). The median time interval between initial CAS and detection of ISR was 390 days (interquartile range 324-666 days). The follow-up period ranged from 9 months to 9 years with a median value of 21 months. Four patients (22.2%) were symptomatic. The average of stenotic degree before and after the procedure was 79.2% and 34.7%, respectively. Out of the 18 patients receiving CB-PTA, 16 (88.9%) did not require additional stenting, and 16 (88.9%) did not experience recurrent ISR during the follow-up period. Two patients who experienced recurrent ISR were successfully treated with CB-PTA and additional stenting. No periprocedural complication was observed in any case. CONCLUSION: Regarding favorable periprocedural and long-term outcomes in our single-center experience, CB-PTA was a feasible and safe option for the treatment of severe ISR after CAS.

One-year antibody durability induced by EuCorVac-19, a liposome-displayed COVID-19 receptor binding domain subunit vaccine, in healthy Korean subjects.

OBJECTIVE: EuCorVac-19 (ECV-19), an adjuvanted liposome-displayed receptor binding domain (RBD) COVID-19 vaccine, previously reported interim Phase 2 trial results showing induction of neutralizing antibodies 3 weeks after prime-boost immunization. The objective of this study was to determine the longer-term antibody response of the vaccine. METHODS: To assess immunogenicity 6 and 12 months after vaccination, participants in the Phase 2 trial (NCT04783311) were excluded if they: 1) withdrew, 2) reported COVID-19 infection or additional vaccination, or 3) exhibited increasing Spike (S) antibodies (representing possible non-reported infection). Following exclusions, of the 197 initial subjects, anti-S IgG antibodies and neutralizing antibodies were further assessed in 124 subjects at the 6-month timepoint, and 36 subjects at the 12-month timepoint. RESULTS: Median anti-S antibody half-life was 52 days (interquartile range [IQR]:42-70), in the "early" period from 3 weeks to 6 months, and 130 days (IQR:97-169) in the "late" period from 6 to 12 months. There was a negative correlation between initial antibody titer and half-life. Anti-S and neutralizing antibody responses were correlated. Neutralizing antibody responses showed longer half-lives; the early period had a median half-life of 120 days (IQR:81-207), and the late period had a median half-life of 214 days (IQR:140-550). CONCLUSION: These data establish antibody durability of ECV-19, using a framework to analyze COVID-19 vaccine-induced antibodies during periods of high infection.

Effects of ACE and ADD1 gene polymorphisms on blood pressure response to hydrochlorothiazide: a meta-analysis.

Hydrochlorothiazide (HCTZ) is used to treat uncomplicated hypertension. However, many studies have reported the variance of inter-individual response to HCTZ. A meta-analysis of published data was conducted to evaluate the pharmacogenetic associations of ACE I/D and ADD1 Gly460Trp polymorphisms with blood pressure changes during HCTZ therapy. To analyze the influence of ACE I/D polymorphism, 4 studies including 1,439 patients were assessed and the 3 genotypes were compared (II vs. ID, II vs. DD, and ID vs. DD) with respect to blood pressure changes. A significant association between ACE and blood pressure change was observed for the comparison of the II and DD (standard differences in means = 0.256; 95% CI, 0.109 - 0.403). For ADD1 Gly460Trp polymorphism, 4 studies including 1,001 patients were assessed, and GlyGly vs. GlyTrp, GlyGly vs. TrpTrp and GlyTrp vs. TrpTrp genotype comparisons were analyzed. A significant association between ADD1 and blood pressure change was observed for the comparisons of GlyGly vs. GlyTrp (standard differences in means= 2.78; 95% CI, 0.563 - 4.99) and GlyGly vs. TrpTrp (standard differences in means = 1.80; 95% CI, 1.38 - 2.22). This study is the first meta-analysis to evaluate the influences of ACE and ADD1 polymorphisms on blood pressure responses to HCTZ to combine the inconsistent results of previous studies.