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Objective The aim was to determine the proportion of patients with inflammatory arthritis who have a flare of their rheumatological disease within 4 weeks of receiving a coronavirus disease 2019 (COVID-19) vaccine, using CRP as a surrogate marker. Methods A retrospective review was conducted of notes for patients with inflammatory arthritis within 30 days of their COVID-19 vaccine. An electronic database (DAWN) was used to identify all patients who were currently on a DMARD or biologic therapy. This was then correlated with vaccine data from the National Immunisation and Vaccination System (NIVS) and CRP within 30 days of their vaccination. Results From the DAWN database, 1620 adults were identified (mean age 61 years, 64% female). Three types of vaccinations were administered: AstraZeneca (AZ), BioNTech-Pfizer or Moderna. Vaccine uptake was 1542 of 1620 (95.2% for the first dose), 1550 of 1620 (95.7% for the second dose) and 1437 of 1620 (88.7% for the third dose). One hundred and ninety-two of 1542 patients (12.5%) had a CRP rise of >10 mg/l within 30 days of their vaccine, which was higher than the baseline flare rate of 8.6% (P = 0.0004). Conclusion Patients with inflammatory arthritis and on DMARDs have a high uptake of COVID-19 vaccine (95%), which is greater than the national average. A CRP rise >10 mg/l within 30 days of vaccination was observed in ∼1 in 10 patients in our study population after all three doses. There might be a slight increase in disease flare in patients with inflammatory arthritis after COVID-19 vaccinations, and additional research is required to assess this association further.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.

Background/Aims With widespread implementation of COVID-19 vaccine, there has been concern that it would trigger an immune activation due to its immunogenic properties. There is low-level evidence that patients with rheumatological diagnosis often have a disease flare following COVID-19 vaccination which not only has personal health implications but also wider socioeconomic implications. Inflammatory arthritis patients are classified as vulnerable patients requiring booster vaccinations. Therefore, there is a need to ascertain whether there is a risk of disease flare in this group of patients so as to counsel them appropriately in order to ensure flares are managed in timely manner. This study aims to determine the proportion of patients with inflammatory arthritis who have a flare of their rheumatological disease within 30 days of receiving a COVID-19 vaccine using CRP as a surrogate marker. Methods A retrospective notes review was conducted of patients with inflammatory arthritis within 30 days of their COVID-19 vaccine. An electronic database (DAWN) was used to identify all patients that were currently on a disease-modifying anti-rheumatic drug (DMARD) or biologic therapy. This was then correlated with vaccine data from the National Immunisation and Vaccination system (NIVS) and C-reactive protein (CRP) within 30 days of their vaccination. Results 1620 adults were identified from DAWN databases (mean age 61 years, 64% female). Three types of vaccination were used: AstraZeneca (AZ), BioNTech-Pfizer or Moderna. Vaccine uptake was 1542/1620 (95.2% 1st dose), 1550/1620 (95.7% 2nd dose) and 1437/1620 (88.7% 3rd dose). 192/1542 patients (12.5%) had a CRP rise of greater than 10mg/L within 30 days of their vaccine, which was higher than baseline flare rate of 8.6% (p = 0.0004). Conclusion Patients with inflammatory arthritis and on DMARDS have high uptake of COVID-19 vaccine (95%) which is greater than the national average. A CRP rise greater than 10mg/L within 30 days of vaccination was observed in roughly 1 in 10 patients in our study population on all three doses which is consistent with other studies in the literature. Our results show statistically significant increase in the rate of disease flare (12.5% compared with baseline rate of 8.6%). However, SARS-CoV-2 infection has been shown many times to be an independent risk factor for rheumatic disease flare ranging from 20-40%. Therefore, patients with inflammatory arthritis should still be encouraged to receive COVID-19 vaccination. To maintain high levels of vaccine uptake, it is important to ensure that patients are aware of the risks of vaccinations and sufficiently safety netted so flares are managed early. As on-going booster vaccinations are planned for rheumatology patients, we recommend further research to better inform and counsel our patients. Furthermore, this study calls for diligence in monitoring patients with inflammatory arthritis for disease flare and for swift intervention to prevent losing disease control. Disclosure S. Kim: None. S. Gor: None. K. Yein: None. J. Michael: None. E. Price: None.

Retinal vascular occlusions are a common cause of visual loss. The association between oral health and the risk of retinal vascular occlusions remains unknown. We investigated whether oral health was associated with the risk of retinal vascular occlusions. We conducted a retrospective cohort study including 138,484 participants who completed a national health screening program with an oral health examination from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) 2002–2015. Oral health markers, such as the presence of periodontitis, tooth loss, and dental caries, and the frequency of daily tooth brushing, were evaluated. The primary outcome was the occurrence of retinal vascular occlusions up to December 2015. In total, 2533 participants developed retinal vascular occlusions (215 with retinal artery occlusion, 1686 with retinal vein occlusion, 632 with unspecified retinal vascular occlusion). In the multivariable Cox regression analysis, periodontitis was an independent risk factor for retinal vascular occlusions (adjusted hazard ratio: 1.18; 95% confidence interval: 1.02–1.36; p = 0.024). Frequent tooth brushing was negatively associated with the risk of retinal vascular occlusions (adjusted hazard ratio: 0.89; 95% confidence interval: 0.80–0.98; p = 0.022). Improving oral hygiene may contribute to the attenuation of the risk of retinal vascular occlusions.

A 29-year-old patient with diplopia showed a unilateral fourth nerve palsy combined with a Horner syndrome on the opposite side. Magnetic resonance images disclosed a focal hemorrhage in the left dorsal midbrain, affecting the nucleus of the fourth nerve and adjacent oculosympathetic fibers. Further evaluations including a bone marrow biopsy confirmed acute lymphoblastic leukemia. The combination of ocular motor and oculosympathetic palsy has a distinct localizing value. Fourth nerve palsy ipsilateral to Horner syndrome locates lesion in the cavernous sinus, while contralateral fourth nerve palsy locates the lesion in the midbrain.

Paraneoplastic cerebellar degeneration is a rare neurological manifestation of nonmetastatic malignancy. Its usual manifestation is subacute to chronic dizziness, gait ataxia, and dysarthria. There have been only a few cases of paraneoplastic cerebellar degeneration with acute presentation. This study describes a patient with paraneoplastic cerebellar degeneration, who presented acute vestibular syndrome and then episodically developed horizontal gaze-evoked nystagmus and gait ataxia.

Background Costal cartilage is commonly employed as a dorsal implant in Asian rhinoplasty. To achieve better outcomes, it is important to know which types of costal cartilage are most appropriate for dorsal augmentation. Objectives The authors investigated how various forms of costal cartilage affect the surrounding tissues and their resorption over time, as well as their clinical appearance, using histomorphological analysis. Methods Cartilage samples were collected from the anterior chest wall of 10 rabbits. Four forms of cartilage—2-mm solid block, 1-mm solid block, diced, and crushed—were prepared and inserted into the subcutaneous tissue pockets of the nasal dorsum of each rabbit. The animals were killed 3 and 6 months later, and graft specimens were examined. Results Histomorphological analysis revealed important findings of the cartilage and surrounding tissues. The thickness of thick cartilage significantly decreased over time, but the thickness of thin cartilage did not significantly change (P = 0.038). Additionally, the thick cartilages showed a lower degree of vascularization than the thin cartilages (P < 0.001). A comparison of the cartilage forms revealed that the diced cartilages had better chondrocyte survival than the solid block cartilages (P < 0.001). Fat tissues were prominently observed surrounding the diced cartilages at 3 months (P = 0.01), and fibrosis was more prominently observed in the crushed cartilage than in the other types of cartilages (P = 0.04 and P = 0.005 at 3 and 6 months, respectively). Conclusions This study revealed differences in resorption depending on the thickness of the costal cartilage in rabbits. Among the various forms of costal cartilages, diced and thin solid-block cartilage were the best option for dorsal augmentation when considering long-term graft survival.

Background Both human and mouse allergic contact dermatitis (ACD) frequently demonstrates a combined type 1 and type 2 immune response. However, the relative importance of type 2 immunity in this setting has been incompletely understood yet. Objective To explore an effector function of type 2 immunity in ACD with mixed type 1/type 2 immune response. Methods Gene expression characteristics of contact hypersensitivity (CHS) model was examined by quantitative polymerase chain reaction. Cytokine profile of T cells was analyzed by flow cytometry. The involvement of type 2 immunity was assessed by antibody-mediated cytokine neutralization and cell depletion. The role of specific subset of cutaneous dendritic cells was evaluated using diphtheria toxin-induced cell-depleting mouse strains. Results Oxazolone-induced CHS revealed a combination of type 1/type 2 gene expression. The severity of oxazolone-induced CHS was ameliorated by neutralization of IL-4 but not of IFN-γ, indicating that type 2 immunity plays a dominant effector function in this mixed type 1/type 2 model. Mechanistically, type 2 effector immunity was mounted by CD301b+Langeirn− dermal dendritic cells in part through thymic stromal lymphopoietin-interleukin 7 receptor alpha signaling-dependent manner. Conclusion Our findings suggest the clinical rationale for targeting type 2 immunity as a relevant therapeutic strategy for the mixed immune phenotype of ACD.

Owing to stringent international environmental and fuel efficiency requirements for lightweight automotive systems, polymer composites have attracted widespread attention. Polypropylene (PP) is a widely employed commercial polymer because of its lightweight and low cost. In this study, PP nanocomposites were fabricated to reduce the moisture absorption of PP composites in automotive headlamp housings. Alkylated chemically modified graphene (CMG-R) was synthesized to reduce the surface hydrophilicity of graphene and increase compatibility with the PP matrix. Fourier transform-infrared spectroscopy and scanning electron microscopy were performed to analyze the nanofillers. X-ray diffraction was performed to determine the interlayer spacing of the nanofiller resulting from surface treatment. Differential scanning calorimetry was used to analyze the crystallinity of the nanocomposites. The results indicated that the improved hydrophobicity of the nanofiller due to alkylation reduced the maximum moisture absorption of the PP nanocomposites by 15% compared to PP composites. The findings of this study are useful for reducing fogging in automotive headlamps.

Electrochemical redox supercapcitor is one of promising rechargeable power sources for portable electronic, display or telecommunication devices since it has a large energy density, very fast charge/discharge time and long life cycle. In this study, poly(3,4-ethylene dioxythiophene) (PEDOT) thin film as the electrode of electrochemical supercapacitor was deposited on a metal current collector by in-situ polymerization method. Symmetrical electrochemical capacitor was then assembled using PEDOT films as working and counter electrodes, where 0.1 M lithium perchlorate (LiClO4) solution in acetonitrile was used as the electrolyte solution. Typical specific discharge capacitance of the capacitor was about 70 F/g and showed little decrease after 1,000 charge/discharge cycles. We also found that UV irradiation improved the electrochemical properties of redox capacitor by formation of hydrophilic polar groups on PEDOT film surface. After UV irradiation on the surface of PEDOT film for 2 hours with the intensity of 30 mW/cm2, the specific discharge capacitance increased by about 10% compared to capacitance of pristine PEDOT film.

ObjectiveGastric cancer (GC) is a leading cause of cancer-related mortality. Although microbes besides Helicobacter pylori may also contribute to gastric carcinogenesis, wild-type germ-free (GF) mouse models investigating the role of human gastric microbiota in the process are not yet available. We aimed to evaluate the histopathological features of GF mouse stomachs transplanted with gastric microbiota from patients with different gastric disease states and their relationships with the microbiota.DesignMicrobiota profiles in corpus and antrum tissues and gastric fluid from 12 patients with gastric dysplasia or GC were analysed. Thereafter, biopsied corpus and antrum tissues and gastric fluid from patients (n=15 and n=12, respectively) with chronic superficial gastritis, intestinal metaplasia or GC were inoculated into 42 GF C57BL/6 mice. The gastric microbiota was analysed by amplicon sequencing. Histopathological features of mouse stomachs were analysed immunohistochemically at 1 month after inoculation. An independent set of an additional 15 GF mice was also analysed at 1 year.ResultsThe microbial community structures of patients with dysplasia or GC in the corpus and antrum were similar. The gastric microbiota from patients with intestinal metaplasia or GC selectively colonised the mouse stomachs and induced premalignant lesions: loss of parietal cells and increases in inflammation foci, in F4/80 and Ki-67 expression, and in CD44v9/GSII lectin expression. Marked dysplastic changes were noted at 1 year post inoculation.ConclusionMajor histopathological features of premalignant changes are reproducible in GF mice transplanted with gastric microbiota from patients with intestinal metaplasia or GC. Our results suggest that GF mice are useful for analysing the causality of associations reported in human gastric microbiome studies.

The hot mix asphalt (HMA) dynamic modulus (∣E*∣), or stress/strain response measurement under dynamic loading, is considered the primary mechanical property input for flexible pavement in the Mechanistic-Empirical Pavement Design Guide (MEPDG). The current MEPDG software, AASHTOWare Pavement ME Design (PMED) Version 2.5, employs the Witczak equation for ∣E*∣ estimation when laboratory-measured ∣E*∣ data is unavailable. This study investigates the feasibility of developing alternative ∣E*∣ prediction models with modern machine learning techniques based on an established data library of Georgia HMA mixtures involving varying binder sources, binder grades, and nominal maximum aggregate sizes. Specifically, tree-based ensemble methods, including bagging, random forest, and gradient boosting, were applied considering their superior performance, and balanced versatility and interpretability. The results revealed that the gradient boosting model produced the most accurate predictions with an R2 coefficient of determination of 0.982 as compared to the nationally calibrated Witczak model, which has an R2 of 0.392, using the same test data set. The stark discrepancy in the ∣E*∣ predictions emphasizes the need of local calibration for the MEPDG models and the high potential for developing greatly improved models using modern machine learning techniques with the local data sources. Ultimately, this study provides an excellent example for other state highway agencies to follow to facilitate their MEPDG implementation.

Lactic acid bacteria (LAB) have been widely studied as mucosal vaccine delivery carriers against many infectious diseases for heterologous expression of protein antigens. There are three antigen expression strategies for LAB: cytoplasmic expression (CE), cell surface display (SD), and extracellular secretion (ES). Despite the generally higher protein expression level and many observations of antigen-specific immunogenicity in CE, its application as a mucosal vaccine has been overlooked relative to SD and ES because of the antigens enclosed by the LAB cell wall. We hypothesized that the antigens in CE could be released from the LAB into the intestinal lumen before host bacterial access to gut-associated lymphoid tissue (GALT), which could contribute to antigen-specific immune responses after oral administration. To elucidate this hypothesis, three recombinant Lactobacillus plantarum (LP) strains were constructed to produce a model antigen, BmpB, with or without an M cell-targeting moiety, and their immunogenicities were analyzed comparatively as oral vaccines in mouse model. The data indicated that the recombinant LPs producing BmpBs with different conformations could induce mucosal immunity differentially. This suggests that the cytoplasmic antigens in LAB could be released into the intestinal lumen, subsequently translocated through M cells, and stimulate the GALT to generate antigen-specific immune responses. Therefore, the CE strategy has great potential, especially in the application of oral LAB vaccines as well as SD and ES strategies. This research provides a better understanding of the mechanism for recombinant oral LAB vaccines and gives insight to the future design of LAB vaccines and oral delivery applications for useful therapeutic proteins.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been a global health concern since 2019. The viral spike protein infects the host by binding to angiotensin-converting enzyme 2 (ACE2) expressed on the cell surface, which is then processed by type II transmembrane serine protease. However, ACE2 does not react to SARS-CoV-2 in inbred wild-type mice, which poses a challenge for preclinical research with animal models, necessitating a human ACE2 (hACE2)-expressing transgenic mouse model. Cytokeratin 18 (K18) promoter-derived hACE2 transgenic mice [B6.Cg-Tg(K18-ACE2)2Prlmn/J] are widely used for research on SARS-CoV-1, MERS-CoV, and SARS-CoV-2. However, SARS-CoV-2 infection is lethal at ≥105 PFU and SARS-CoV-2 target cells are limited to type-1 alveolar pneumocytes in K18-hACE2 mice, making this model incompatible with infections in the human lung. Hence, we developed lung-specific SARS-CoV-2 infection mouse models with surfactant protein B (SFTPB) and secretoglobin family 1a member 1 (Scgb1a1) promoters. After inoculation of 105 PFU of SARS-CoV-2 to the K18-hACE2, SFTPB-hACE2, and SCGB1A1-hACE2 models, the peak viral titer was detected at 2 days post-infection and then gradually decreased. In K18-hACE2 mice, the body temperature decreased by approximately 10°C, body weight decreased by over 20%, and the survival rate was reduced. However, SFTPB-hACE2 and SCGB1A1-hACE2 mice showed minimal clinical signs after infection. The virus targeted type I pneumocytes in K18-hACE2 mice; type II pneumocytes in SFTPB-hACE2 mice; and club, goblet, and ciliated cells in SCGB1A1-hACE2 mice. A time-dependent increase in severe lung lesions was detected in K18-hACE2 mice, whereas mild lesions developed in SFTPB-hACE2 and SCGB1A1-hACE2 mice. Spleen, small intestine, and brain lesions developed in K18-hACE2 mice but not in SFTPB-hACE2 and SCGB1A1-hACE2 mice. These newly developed SFTPB-hACE2 and SCGB1A1-hACE2 mice should prove useful to expand research on hACE2-mediated respiratory viruses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, causes life-threatening disease. This novel coronavirus enters host cells via the respiratory tract, promoting the formation of severe pulmonary lesions and systemic disease. Few animal models can simulate the clinical signs and pathology of COVID-19 patients. Diverse preclinical studies using K18-hACE2 mice and Syrian golden hamsters, which are highly permissive to SARS-CoV-2 in the respiratory tract, are emerging; however, the systemic pathogenesis and cellular tropism of these models remain obscure. We intranasally infected K18-hACE2 mice and Syrian golden hamsters with SARS-CoV-2, and compared the clinical features, pathogenesis, cellular tropism and infiltrated immune-cell subsets. In K18-hACE2 mice, SARS-CoV-2 persistently replicated in alveolar cells and caused pulmonary and extrapulmonary disease, resulting in fatal outcomes. Conversely, in Syrian golden hamsters, transient SARS-CoV-2 infection in bronchial cells caused reversible pulmonary disease, without mortality. Our findings provide comprehensive insights into the pathogenic spectrum of COVID-19 using preclinical models.

Electroencephalography (EEG) is used for the diagnosis of epilepsy and testing the brain function. Clinical technologists are responsible for recording EEG without artifacts in accordance with the international 10∼20 electrode system. Training on these techniques requires practical education. In the case of EEG, however, it is difficult for trainees to find the correct location of the electrode. Therefore, this study compared the time spent to locate the electrode attachment between traditional tape and the newly developed band. The time spent for sitting position patients using the band (196.7±61.8s) was 1084.3 s faster than the tape (1,281.0±457.4s) (P＜0.001). Furthermore, the spend time spent for lying position patients using the band (200.2±49.3s) was 1217.7s faster than the tape (1417.9±482.3s) (P＜0.001). Measurements using the band showed fewer differences due to various factors, such as position, practical experience, and gender. The newly developed band can locate the correct electrode attachment position quickly and efficiently, which has been a difficult problem in EEG practical education. In addition, this band is expected to be applied widely by new clinical technologists in the clinical field. Nevertheless, more study will be required to verify the accuracy of the location of the attaching electrode.

Aortic dissection refers to the separation of the aorta into a true and false lumen as the medial membrane of the aorta is torn along the long axis due to a high aortic pressure when a minute rupture occurs in the aortic lining. The mortality rate is very high, and aortic dissection occurs 2∼5 times more in men than women. The prevalent age range is 50∼70 years old. In this case, the authors experienced a diagnosis of aortic dissection that occurred in a young woman in her 30s, which does not occur frequently. In the process of tracking severe aortic regurgitation, aortic valve prolapse was initially suspected. We report this case because aortic dissection could be diagnosed by observing the intimal flap of the ascending aorta in the process of confirming this suspected part.

Background As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.