Discovery of a new long COVID mouse model via systemic histopathological comparison of SARS-CoV-2 intranasal and inhalation infection.

Intranasal infection is commonly used to establish a SARS-CoV-2 mouse model due to its non-invasive procedures and a minimal effect from the operation itself. However, mice intranasally infected with SARS-CoV-2 have a high mortality rate, which limits the utility of this model for exploring therapeutic strategies and the sequelae of non-fatal COVID-19 cases. To resolve these limitations, an aerosolised viral administration method has been suggested. However, an in-depth pathological analysis comparing the two models is lacking. Here, we show that inhalation and intranasal SARS-CoV-2 (106 PFU) infection models established in K18-hACE2 mice develop unique pathological features in both the respiratory and central nervous systems, which could be directly attributed to the infection method. While the inhalation-infection model exhibited relatively milder pathological parameters, it closely mimicked the prevalent chest CT pattern observed in COVID-19 patients with focal, peripheral lesions and fibrotic scarring in the recuperating lung. We also found the evidence of direct neuron-invasion from the olfactory receptor neurons to the olfactory bulb in the intranasal model and showed the trigeminal nerve as an alternative route of transmission to the brain in inhalation infected mice. Even after viral clearance confirmed at 14 days post-infection, mild lesions were still found in the brain of inhalation-infected mice. These findings suggest that the inhalation-infection model has advantages over the intranasal-infection model in closely mimicking the pathological features of non-fatal symptoms of COVID-19, demonstrating its potential to study the sequelae and possible interventions for long COVID.

Clinical profile and treatment outcomes of idiopathic intracranial hypertension: a multicenter study from Korea.

BACKGROUND: Currently, there is a relative lack of detailed reports regarding clinical presentation and outcome of idiopathic intracranial hypertension in Asians. This study aims to describe the clinical features and treatment outcomes of Korean patients with idiopathic intracranial hypertension. METHODS: We prospectively recruited patients with idiopathic intracranial hypertension from one hospital and retrospectively analyzed the medical records of 11 hospitals in Korea. We collected data regarding preceding medical conditions or suspected medication exposure, headache phenotypes, other associated symptoms, detailed neuroimaging findings, treatments, and outcomes after 1-2 and 3-6 months of treatment. RESULTS: Fifty-nine (83.1% women) patients were included. The mean body mass index was 29.11 (standard deviation, 5.87) kg/m2; only 27 patients (45.8%) had a body mass index of ≥ 30 kg/m2. Fifty-one (86.4%) patients experienced headaches, patterns of which included chronic migraine (15/51 [29.4%]), episodic migraine (8/51 [15.7%]), probable migraine (4/51 [7.8%]), chronic tension-type headache (3/51 [5.9%]), episodic tension-type headache (2/51 [3.9%]), probable tension-type headache (2/51 [3.9%]), and unclassified (17/51 [33.3%]). Medication overuse headache was diagnosed in 4/51 (7.8%) patients. After 3-6 months of treatment, the intracranial pressure normalized in 8/32 (25.0%), improved in 17/32 (53.1%), no changed in 7/32 (21.9%), and worsened in none. Over the same period, headaches remitted or significantly improved by more than 50% in 24/39 patients (61.5%), improved less than 50% in 9/39 (23.1%), and persisted or worsened in 6/39 (15.4%) patients. CONCLUSION: Our findings suggest that the features of Asian patients with idiopathic intracranial hypertension may be atypical (i.e., less likely obese, less female predominance). A wide spectrum of headache phenotypes was observed. Medical treatment resulted in overall favorable short-term outcomes; however, the headaches did not improve in a small proportion of patients.

Tonic type 2 immunity is a critical tissue checkpoint controlling autoimmunity in the skin.

Immunoregulatory mechanisms established in the lymphoid organs are vital for preventing autoimmunity. However, the presence of similar mechanisms in non-lymphoid tissues remains unclear. Through transcriptomic and lipidomic analyses, we find a negative association between psoriasis and fatty acid metabolism, as well as Th2 signature. Homeostatic expression of liver X receptor (LXR) and peroxisome proliferator-activated receptor gamma (PPARγ) is essential for maintaining fatty acid metabolism and for conferring resistance to psoriasis in mice. Perturbation of signal transducer and activator of transcription 6 (STAT6) diminishes the homeostatic levels of LXR and PPARγ. Furthermore, mice lacking STAT6, interleukin 4 receptor alpha (IL-4Rα), or IL-13, but not IL-4, exhibit increased susceptibility to psoriasis. Under steady state, innate lymphoid cells (ILCs) are the primary producers of IL-13. In human skin, inhibiting tonic type 2 immunity exacerbates psoriasis-like inflammation and IL-17A, while activating LXR or PPARγ inhibits them. Hence, we propose that tonic type 2 immunity, driven by IL-13-producing ILCs, represents a crucial tissue checkpoint that represses autoimmunity and maintains lipid homeostasis in the skin.

Evaluating the Nutritional Composition of Unripe Citrus and Its Effect on Inhibiting Adipogenesis and Adipocyte Differentiation.

Citrus fruits offer a range of health benefits due to their rich nutritional profile, including vitamin C, flavonoids, carotenoids, and fiber. It is known that unripe citrus has higher levels of vitamin C, dietary fiber, polyphenols, and flavonoids compared to mature fruits. In this study, we assessed the nutritional components of unripe citrus peel and pressed juices, as well as their anti-obesity potential through the modulation of adipocyte differentiation and the expression of adipogenesis-related genes, specifically PPARγ and C/EBPα, in 3T3-L1 preadipocytes. Our analysis revealed that unripe citrus peel exhibited elevated levels of fiber and protein compared to pressed juice, with markedly low levels of free sugar, particularly sucrose. The content of hesperidin, a representative flavonoid in citrus fruits, was 3,157.6 mg/kg in unripe citrus peel and 455.5 mg/kg in pressed juice, indicating that it was approximately seven times higher in unripe citrus peel compared to pressed juice. Moreover, we observed that the peel had a dose-dependently inhibitory effect on adipocyte differentiation, which was linked to a significant downregulation of adipogenesis-related gene expression. Thus, our findings suggest that unripe citrus possesses anti-obesity effects by impeding adipogenesis and adipocyte differentiation, with the peel demonstrating a more pronounced effect compared to pressed juice.

Persistent Severe Headache After Removal of Fungus Ball From the Sphenoid Sinus: A Case Report.

OBJECTIVE: Granulomatous invasive fungal sinusitis (GIFS) is a rare and life-threatening disease, whereas fungus ball (FB) is the most common form of noninvasive fungal sinusitis. Both GIFS and FB primarily develop in immunocompetent patients, with the former associated with higher mortality and morbidity. METHODS: A chart review and review of the literature. RESULTS: We present the case of a 77-year-old woman with mixed fungal sinusitis who was successfully treated with voriconazole. CONCLUSIONS: GIFS and FB can coexist in extremely rare cases, known as mixed fungal sinusitis; however, the diagnosis and subsequent treatment of mixed fungal sinusitis can be delayed because of a lack of awareness of the underlying concept. Therefore, it is crucial for clinicians to recognize the concept of mixed fungal sinusitis.

Immune Cells Are Differentially Affected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virus-infected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105 PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Anti-Inflammatory Effect of Chamaecyparis obtusa (Siebold & Zucc.) Endl. Leaf Essential Oil.

Chamaecyparis obtusa (Siebold & Zucc.) Endl. (C. obtusa) belongs to the Cupressaceae family and is native to East Asian regions. Essential oils extracted from the leaves, bark, branches, and roots of C. obtusa have both aesthetic and medicinal properties and are thus widely used. However, detailed analyses of the active ingredients of C. obtusa extract are lacking. In this study, the sabinene content in the hydro-distillation of C. obtusa leaf essential oil (COD) was analyzed using GC-MS, and the anti-inflammatory effect of COD was compared with that of pure sabinene. Cell viability was evaluated by MTT assay, and nitric oxide (NO) production was measured using Griess reagent. Relative mRNA and protein levels were analyzed using RT-qPCR and western blot, and secreted cytokines were analyzed using a cytokine array kit. The results showed that both COD and sabinene inhibited the expression of inducible nitric oxide synthase (iNOS) and the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 in lipopolysaccharide (LPS)-induced RAW 264.7 cells. COD and sabinene also reduced the production of pro-inflammatory cytokines interleukin (IL)-1ß, IL-6, IL-27, IL-1 receptor antagonist (IL-1ra), and granulocyte-macrophage colony-stimulating factor (GM-CSF). The anti-inflammatory mechanisms of COD and sabinene partially overlap, as COD was shown to inhibit MAPKs and the JAK/STAT axis, and sabinene inhibited MAPKs, thereby preventing LPS-induced macrophage activation.

Clinical characteristics of persistent postural-perceptual dizziness and its visual subtype in Korean patients: A multicenter cross-sectional study.

OBJECTIVES: Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder for which the Bárány Society has established diagnostic criteria. This nationwide multicenter study aims to investigate the clinical features of individuals with definite PPPD and clinical variant PPPD who do not fully meet the diagnostic criteria, with a particular focus on visual exaggeration. METHODS: Between September 2020 and September 2021, a total of 76 individuals with definite PPPD and 109 individuals with clinical variant PPPD who did not meet all three exacerbating factors outlined in Criterion B were recruited from 18 medical centers in South Korea. The study gathered information on demographic factors, clinical manifestations, balance scales, and personality assessments. RESULTS: Comparative analysis between groups with definite PPPD and clinical variant with visual exacerbation revealed no significant differences in sociodemographic characteristics, clinical course, dizziness impact, and specific precipitants. Only disease duration was significantly longer in definite PPPD compared with variant with visual exacerbation. However, the variant without visual exacerbation displayed significantly reduced rates of panic disorder, diminished space-motion discomfort, lesser impact of dizziness, and decreased prevalence of depression when compared with the definitive PPPD. CONCLUSION: This is the first comprehensive nationwide study examining clinical features of both definite PPPD patients and its clinical variants, considering visual exacerbating factors. Differences in dizziness and personality traits emerged between definite PPPD and its potential variant without visual issues. Our results highlight the possibility of a distinct clinical variant of PPPD influenced by visual dependency.

The Modernization of Oriental Music Therapy: Five-Element Music Therapy Combined with Artificial Intelligence.

In recent years, music has been regarded as a promising non-pharmacological intervention for a number of physical and mental conditions. Five-elements music therapy-based on the five-element theory-is a unique non-pharmacological therapy of East Asian traditional medicine. It has the potential to effectively provide individualized music therapy to individuals with illness. However, one limitation of this music therapy is that the classification of the five elements and its application is mainly based on subjective judgment. The development of artificial intelligence (AI) has enabled the acoustic analysis of multi-factor sound sources. This can develop five-element music therapy. Here, we discussed the challenges proposed by the future combination of five-element music therapy and AI. Further, we hypothesized that AI may promote its use in the medical field.

Changes in depression trends during and after the COVID-19 pandemic among older adults in Korea.

This study aimed to complement the previous studies conducted within a short period of time by examining the long-term trends in depression levels of older adults through a longitudinal study that includes the period following the onset of COVID-19. For analysis, this study used the data from the 12th (2017) through 16th (2021) Korea Welfare Panel Study, and 2,716 data of older adults 65 years and older were included. Variables included gender, age, equalized annual income (USD $), education background, residential area, living alone and disability status. As a result, two types of changes in depression were identified: the 'rapidly rising' type and the 'steadily increasing'. We found that the lower the equalized annual income, women, the lower the education, living in urban and living alone showed a higher likelihood of belonging to the 'rapidly rising' type. The result suggests that those at risk of depression are at much higher risk during and after the COVID-19 pandemic. It is also necessary to provide timely and effective guidelines to prevent depression in older adults when implementing policies in response to an outbreak of infectious diseases, such as COVID-19.

Statistical considerations for some issues in clinical bridging studies evaluating companion diagnostic devices.

An in vitro diagnostic device (IVD) that is essential for the safe and effective use of a corresponding therapeutic product is commonly referred to as companion diagnostic device. Clinical trials using companion diagnostic devices (tests) together with therapies can yield the information necessary to address whether both products are safe and effective. A clinical trial ideally assesses safety and effectiveness of a therapy, where the clinical trial enrolls subjects based on the final market ready companion diagnostic test (CDx). However, such a requirement may be difficult to accomplish or impractical to achieve at the time of the clinical trial enrollment, due to unavailability of the CDx. Instead, clinical trial assay(s) (CTA), which are not the final marketable product, are often used in enrollment of patients in a clinical trial. When CTA is used for subject enrollment, a clinical bridging study provides a mechanism to bridge the clinical efficacy of the therapeutic product from CTA to CDx. This manuscript reviews some issues and challenges commonly associated with clinical bridging studies, including missing data, use of local tests for enrollment, prescreening before enrollment, and evaluation of CDx for low positive rate biomarkers, with particular focus on clinical trials using a binary endpoint and provide alternative statistical methodologies to assess effectiveness of CDx.

A longitudinal molecular and cellular lung atlas of lethal SARS-CoV-2 infection in K18-hACE2 transgenic mice.

BACKGROUND: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to approximately 500 million cases and 6 million deaths worldwide. Previous investigations into the pathophysiology of SARS-CoV-2 primarily focused on peripheral blood mononuclear cells from patients, lacking detailed mechanistic insights into the virus's impact on inflamed tissue. Existing animal models, such as hamster and ferret, do not faithfully replicate the severe SARS-CoV-2 infection seen in patients, underscoring the need for more relevant animal system-based research. METHODS: In this study, we employed single-cell RNA sequencing (scRNA-seq) with lung tissues from K18-hACE2 transgenic (TG) mice during SARS-CoV-2 infection. This approach allowed for a comprehensive examination of the molecular and cellular responses to the virus in lung tissue. FINDINGS: Upon SARS-CoV-2 infection, K18-hACE2 TG mice exhibited severe lung pathologies, including acute pneumonia, alveolar collapse, and immune cell infiltration. Through scRNA-seq, we identified 36 different types of cells dynamically orchestrating SARS-CoV-2-induced pathologies. Notably, SPP1+ macrophages in the myeloid compartment emerged as key drivers of severe lung inflammation and fibrosis in K18-hACE2 TG mice. Dynamic receptor-ligand interactions, involving various cell types such as immunological and bronchial cells, defined an enhanced TGFß signaling pathway linked to delayed tissue regeneration, severe lung injury, and fibrotic processes. INTERPRETATION: Our study provides a comprehensive understanding of SARS-CoV-2 pathogenesis in lung tissue, surpassing previous limitations in investigating inflamed tissues. The identified SPP1+ macrophages and the dysregulated TGFß signaling pathway offer potential targets for therapeutic intervention. Insights from this research may contribute to the development of innovative diagnostics and therapies for COVID-19. FUNDING: This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2020M3A9I2109027, 2021R1A2C2004501).

A bivalent form of a RBD-specific synthetic antibody effectively neutralizes SARS-CoV-2 variants.

Coronavirus Disease 2019 (COVID-19) pandemic is severely impacting the world, and tremendous efforts have been made to deal with it. Despite many advances in vaccines and therapeutics, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remains an intractable challenge. We present a bivalent Receptor Binding Domain (RBD)-specific synthetic antibody, specific for the RBD of wild-type (lineage A), developed from a non-antibody protein scaffold composed of LRR (Leucine-rich repeat) modules through phage display. We further reinforced the unique feature of the synthetic antibody by constructing a tandem dimeric form. The resulting bivalent form showed a broader neutralizing activity against the variants. The in vivo neutralizing efficacy of the bivalent synthetic antibody was confirmed using a human ACE2-expressing mouse model that significantly alleviated viral titer and lung infection. The present approach can be used to develop a synthetic antibody showing a broader neutralizing activity against a multitude of SARS-CoV-2 variants.

Cdon ablation in motor neurons causes age-related motor neuron degeneration and impaired sciatic nerve repair.

BACKGROUND: The functional deterioration and loss of motor neurons are tightly associated with degenerative motor neuron diseases and aging-related muscle wasting. Motor neuron diseases or aging-related muscle wasting in turn contribute to increased risk of adverse health outcomes in the elderly. Cdon (cell adhesion molecule-downregulated oncogene) belongs to the immunoglobulin superfamily of cell adhesion molecule and plays essential roles in multiple signalling pathways, including sonic hedgehog (Shh), netrin, and cadherin-mediated signalling. Cdon as a Shh coreceptor plays a critical role in motor neuron specification during embryonic development. However, its role in adult motor neuron function is unknown. METHODS: Hb9-Cre recombinase-driven motor neuron-specific Cdon deficient mice (mnKO) and a compound mutant mice (mnKO::SOD1G93A ) were generated to investigate the role of Cdon in motor neuron degeneration. Motor neuron regeneration was examined by using a sciatic nerve crush injury model. To investigate the phenotype, physical activity, compound muscle action potential, immunostaining, and transmission electron microscopy were carried out. In the mechanism study, RNA sequencing and RNA/protein analyses were employed. RESULTS: Mice lacking Cdon in motor neurons exhibited middle age onset lethality and aging-related decline in motor function. In the sciatic nerve crush injury model, mnKO mice exhibited an impairment in motor function recovery evident by prolonged compound muscle action potential duration (4.63 ± 0.35 vs. 3.93 ± 0.22 s for f/f, P < 0.01) and physical activity. Consistently, neuromuscular junctions of mnKO muscles were incompletely occupied (49.79 ± 5.74 vs. 79.39 ± 3.77% fully occupied neuromuscular junctions for f/f, P < 0.0001), suggesting an impaired reinnervation. The transmission electron microscopy analysis revealed that mnKO sciatic nerves had smaller axon diameter (0.88 ± 0.13 vs. 1.43 ± 0.48 µm for f/f, P < 0.0001) and myelination defects. RNA sequencing of mnKO lumbar spinal cords showed alteration in genes related to neurogenesis, inflammation and cell death. Among the altered genes, ErbB4 and FgfR expressions were significantly altered in mnKO as well as in Cdon-depleted NSC34 motor neuron cells. Consistently, Cdon-depleted NSC34 cells exhibited elevated levels of cleaved Caspase3 and γH2AX proteins, as well as Bax transcription. Cdon-depleted NSC34 cells also exhibited impaired activation of Akt in response to neuregulin-1 (NRG1) treatment. CONCLUSIONS: Our current data demonstrate the functional importance of Cdon in motor neuron function and nerve repair. Cdon ablation causes alterations in neurotrophin signalling that leads to motor neuron degeneration.

Role of Nox4 in Mitigating Inflammation and Fibrosis in Dextran Sulfate Sodium-Induced Colitis.

BACKGROUND & AIMS: Fibrosis development in ulcerative colitis is associated directly with the severity of mucosal inflammation, which increases the risk of colorectal cancer. The transforming growth factor-ß (TGF-ß) signaling pathway is an important source of tissue fibrogenesis, which is stimulated directly by reactive oxygen species produced from nicotinamide adenine dinucleotide phosphate oxidases (NOX). Among members of the NOX family, NOX4 expression is up-regulated in patients with fibrostenotic Crohn's disease (CD) and in dextran sulfate sodium (DSS)-induced murine colitis. The aim of this study was to determine whether NOX4 plays a role in fibrogenesis during inflammation in the colon using a mouse model. METHODS: Acute and recovery models of colonic inflammation were performed by DSS administration to newly generated Nox4-/- mice. Pathologic analysis of colon tissues was performed, including detection of immune cells, proliferation, and fibrotic and inflammatory markers. RNA sequencing was performed to detect differentially expressed genes between Nox4-/- and wild-type mice in both the untreated and DSS-treated conditions, followed by functional enrichment analysis to explore the molecular mechanisms contributing to pathologic differences during DSS-induced colitis and after recovery. RESULTS: Nox4-/- mice showed increased endogenous TGF-ß signaling in the colon, increased reactive oxygen species levels, intensive inflammation, and an increased fibrotic region after DSS treatment compared with wild-type mice. Bulk RNA sequencing confirmed involvement of canonical TGF-ß signaling in fibrogenesis of the DSS-induced colitis model. Up-regulation of TGF-ß signaling affects collagen activation and T-cell lineage commitment, increasing the susceptibility for inflammation. CONCLUSIONS: Nox4 protects against injury and plays a crucial role in fibrogenesis in DSS-induced colitis through canonical TGF-ß signaling regulation, highlighting a new treatment target.

The relationship between psychological distress, depressive symptoms, emotional eating behaviors and the health-related quality of life of middle-aged korean females: a serial mediation model.

BACKGROUND: This study aimed to examine the effects of psychological distress, depressive symptoms, and emotional eating behaviors on the health-related quality of life of middle-aged Korean females. This study provides primary data for developing an intervention program to improve the health-related quality of life of middle-aged females. METHODS: Middle-aged females between 35 and 64 years old, from July 22 to August 10, 2021, were included in this study. The mediating effects of depressive symptoms and emotional eating behaviors on the relationship between psychological distress and health-related quality of life were investigated. A cross-sectional survey was conducted on 325 subjects. Researchers conducted questionnaires measuring psychological distress, depressive symptoms, emotional eating behavior, and health-related quality of life. RESULTS: The findings of this study demonstrated a correlation between the severity of a female's depressive symptoms and the degree of their psychological distress, indicating that severe depressive symptoms were associated with negative emotions, which increased emotional eating behaviors. Additionally, more severe depressive symptoms indicated a lower health-related quality of life. Higher psychological distress was associated with increased emotional eating behaviors and lower health-related quality of life. The total and direct effects of psychological distress on the health-related quality of life were statistically significant. CONCLUSIONS: In this study, psychological distress, depressive symptoms, and emotional eating behaviors affected the health-related quality of life of middle-aged Korean females. This study also confirmed that psychological distress had a direct effect on health-related quality of life. These findings serve as primary data for evidence-based intervention programs that alleviate emotional health problems, such as psychological distress and depressive symptoms in middle-aged females. Moreover, nurses can help develop effective treatment strategies to improve health-related quality of life by identifying and assessing potential symptoms of psychological distress, depressive symptoms, and emotional eating behaviors.

C-Reactive protein rise in rheumatology patients following COVID-19 vaccination.

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.

Impact of personal protective equipment attached powered air-purifying respirator on nursing-skill performance and psychosocial stress of intensive care unit COVID-19 nurses: A cross-sectional study.

AIM: To investigate how personal protective equipment with an attached powered air-purifying respirator worn by intensive care unit nurses caring for COVID-19 patients in Korea impacts nursing-skill performance and psychosocial stress. DESIGN: A cross-sectional descriptive study was designed using purposive sampling. REVIEW METHODS: Online data collection was conducted from 3 March 2021-20 March 2021on 181 nurses who had worked for more than 1 month in COVID-19 critical care settings wearing personal protective equipment with a powered air-purifying respirator. A structured questionnaire was used to gather data on sociodemographic characteristics, attitude toward personal protective equipment, nursing-skill performance wearing personal protective equipment and psychosocial stress. DATA SOURCES: Data was sourced from structured questionnaire responses. RESULTS: Nursing skill performance decreased to 63.4%, compared with normal performance. Subjects' perceptions and attitudes related to PPE scored 3.56 out of 5; 44.7% of subjects reported severe psychosocial stress, which was significantly affected by attitude toward personal protective equipment usage, nursing performance, experience caring for COVID-19 patients and length of personal protective equipment usage per shift. CONCLUSION: Greater negative attitude toward usage of personal protective equipment with a powered air-purifying respirator, results in lower nursing-skill performance and higher the psychosocial stress of nurses responding to COVID-19 outbreaks. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: High negative attitude toward PPE and low nursing-skill performance due to PPE with an attached PAPR results in significant and debilitating psychosocial stress in ICU nurses responding to COVID-19 outbreaks. To respond effectively to future infectious disease outbreaks and improve nursing performance, minimising the inconvenience and restrictions experienced by nurses wearing personal protective equipment is critical. REPORTING METHOD: We adhered to relevant EQUATOR guidelines to report. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Oral Health and Risk of Retinal Vascular Occlusions: A Nationwide Cohort Study.

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.

Establishment of multicenter COVID-19 therapeutics preclinical test system in Republic of Korea.

Throughout the recent COVID-19 pandemic, South Korea led national efforts to develop vaccines and therapeutics for SARS-CoV-2. The project proceeded as follows: 1) evaluation system setup (including Animal Biosafety Level 3 (ABSL3) facility alliance, standardized nonclinical evaluation protocol, and laboratory information management system), 2) application (including committee review and selection), and 3) evaluation (including expert judgment and reporting). After receiving 101 applications, the selection committee reviewed pharmacokinetics, toxicity, and efficacy data and selected 32 final candidates. In the nonclinical efficacy test, we used golden Syrian hamsters and human angiotensin-converting enzyme 2 transgenic mice under a cytokeratin 18 promoter to evaluate mortality, clinical signs, body weight, viral titer, neutralizing antibody presence, and histopathology. These data indicated eight new drugs and one repositioned drug having significant efficacy for COVID-19. Three vaccine and four antiviral drugs exerted significant protective activities against SARS-CoV-2 pathogenesis. Additionally, two anti-inflammatory drugs showed therapeutic effects on lung lesions and weight loss through their mechanism of action but did not affect viral replication. Along with systematic verification of COVID-19 animal models through large-scale studies, our findings suggest that ABSL3 multicenter alliance and nonclinical evaluation protocol standardization can promote reliable efficacy testing against COVID-19, thus expediting medical product development.