Impact of COVID-19 Infection and Its Association With Previous Vaccination in Patients With Myasthenia Gravis in Korea: A Multicenter Retrospective Study.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. METHODS: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. RESULTS: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. CONCLUSION: This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.

Convergence Gas Sensors with One-Dimensional Nanotubes and Pt Nanoparticles Based on Ultraviolet Photonic Energy for Room-Temperature NO2 Gas Sensing.

Zinc oxide (ZnO) is a promising material for nitrogen dioxide (NO2) gas sensors because of its nontoxicity, low cost, and small size. We fabricated one-dimensional (1D) and zero-dimensional (0D) convergence gas sensors activated via ultraviolet (UV) photonic energy to sense NO2 gas at room temperature. One-dimensional ZnO nanorod (ZNR)-based and ZnO nanotube (ZNT)-based gas sensors were synthesized using a simple hydrothermal method. All the sensors were tested under UV irradiation (365 nm) so that they could be operated at room temperature rather than a high temperature. In addition, we decorated 0D Pt nanoparticles (NPs) on the gas sensors to further improve their sensing responsivity. The NO2-sensing response of the ZNT/Pt NP convergence gas sensor was 2.93 times higher than that of the ZNR gas sensor. We demonstrated the complex effects of UV radiation on 1D ZnO nanostructures and 0D metal nanostructures in NO2 gas sensing.

QUANTIFIED ANASTOMOTIC AREAS OF NEOVASCULARIZATION AS FACTORS ASSOCIATED WITH FREQUENT RECURRENCE IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate the quantitative characteristics of anastomoses of macular neovascularization (MNV) in neovascular age-related macular degeneration using optical coherence tomography angiography according to the frequency of intravitreal injections. METHODS: Eighty-six eyes of 86 patients treated for neovascular age-related macular degeneration were classified into two groups based on the number of intravitreal injections administered over 12 months: stable (<3) and unstable (≥3). Anastomotic areas were defined as areas surrounded by neighboring vessels in the MNV; their total number, mean area, maximal and minimal diameters (i.e., maximal and minimum Feret diameters), and ratio (Feret aspect ratio) were analyzed in the inner and outer areas of the MNV. RESULTS: Forty-four and 42 eyes were classified into the stable and unstable groups, respectively. The eyes in the unstable group had larger anastomotic areas with longer minimum Feret diameters and longer perimeters in the outer MNV. In the logistic regression analysis, instability was associated with a larger anastomotic area and a longer minimum Feret diameter in the outer MNV. Multivariate analysis revealed that a longer minimum Feret diameter in the outer MNV was the most significant factor ( P = 0.03). CONCLUSION: The quantitative characteristics of the anastomotic areas in the MNV might indicate the need for intravitreal injections in patients with neovascular age-related macular degeneration.

Changes of Optical Coherence Tomography Parameters after Cataract Surgery in Primary Open-Angle Glaucoma Eyes.

PURPOSE: To investigate the impact of uncomplicated cataract surgery on the measurement of Bruch's membrane opening-minimum rim width (BMO-MRW) and retinal nerve fiber layer thickness (RNFLT) using spectral domain optical coherence tomography (SD-OCT) in primary open-angle glaucoma (POAG) patients. METHODS: This retrospective study included 63 eyes of 63 patients, including 32 POAG eyes and 31 normal eyes who underwent uneventful cataract surgery and follow-up for at least 6 months. Using SD-OCT, BMO-MRW and RNFLT were measured preoperatively and postoperatively at 6 months. Paired t-test was used to compare intraocular pressure (IOP), BMO-MRW, RNFLT, and image quality before and after surgery. These parameters and their changes were compared between POAG and normal groups. Univariate and multivariate linear regression analyses were performed to determine the factors associated with the postoperative change (Δ) in RNFLT and BMO-MRW. RESULTS: BMO-MRW and RNFLT were significantly increased and IOP was decreased after phacoemulsification in both groups (p < 0.001, respectively). The ΔRNFLT was significantly greater in POAG eyes compared with the normal eyes (p < 0.001). The ΔRNFLT was associated with the postoperative IOP reduction and glaucoma diagnosis (p < 0.001 and p = 0.001, respectively). In the normal group, only the ΔIOP had a significant influence on the ΔRNFLT (p = 0.003), but in the POAG group, not only the ΔIOP (p = 0.044) but also preoperative visual field mean deviation (p = 0.029) showed a significant influence. The ΔBMO-MRW showed no difference between POAG and normal eyes. CONCLUSIONS: The postoperative increase of RNFLT was significantly greater in the POAG group, and the postoperative increase of RNFLT was associated with the preoperative visual field mean deviation and ΔIOP in POAG eyes and with the ΔIOP in normal eyes. Our results imply that RNFLT is more affected than BMO-MRW in POAG eyes compared to normal eyes by cataract surgery.

Anti-titin antibodies are associated with myocarditis in patients with myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) can affect cardiac muscles with variable presentations. Myocarditis is a rare but potentially serious cardiac manifestation of MG. Although thymomas and anti-titin antibodies have been suggested as risk factors for myocarditis in patients with MG, their independent influence on myocarditis has rarely been assessed. METHODS: A retrospective chart review was conducted on 247 patients diagnosed with MG who were tested for anti-titin antibodies. Myocarditis was diagnosed on the basis of the European Society of Cardiology 2013 Task Force criteria for clinically suspected myocarditis. Patients were classified into myocarditis-positive and myocarditis-negative groups. Multivariate analysis was performed to analyze the risk factors for myocarditis. RESULTS: Of the 247 patients, 25 (10.1%) were myocarditis-positive and 222 (89.9%) were myocarditis-negative. Anti-titin antibody positivity was higher in the myocarditis-positive group than in the myocarditis-negative group (68.0% vs. 28.4%, p < 0.001). A history of MG crisis was more frequent in the myocarditis-positive group than in the myocarditis-negative group (64.0% vs. 10.4%, p < 0.001). The presence of anti-titin antibodies (odds ratio [OR] 7.906; confidence interval [CI] 2.460-25.401) and MG crisis (OR 24.807; CI 7.476-82.311) was significantly associated with myocarditis. The Cox regression model showed that the anti-titin antibody levels (hazard ratio [HR] 3.639; 95% CI 1.557-8.505) and MG crisis (HR 6.137; 95% CI 2.639-14.272) were significant risk factors for the development of myocarditis. CONCLUSION: The presence of anti-titin antibody was associated with myocarditis in patients with MG, whereas thymoma was not. Although rare, early suspicion of myocarditis could be required, especially in patients with MG having anti-titin antibodies.

Old age and multiple comorbidity are associated with delayed diagnosis of Guillain-Barre syndrome.

To assess whether older age and presence of comorbidities were associated with a delayed diagnosis of Guillain-Barré syndrome (GBS). The medical records of 140 patients diagnosed with GBS at Severance Hospital from March 2011 to December 2020 were retrospectively reviewed. Comorbidity profiles were assessed using the Charlson comorbidity index (CCI). The age-adjusted CCI (ACCI) score was calculated, which further incorporated the effect of age. Patients were classified into the early diagnosis group (diagnosis duration ≤ 14 days) and late diagnosis group (diagnosis duration > 14 days). Clinical features and comorbidity profiles were compared between the two groups. The cumulative incidence of diagnosis was compared between the low and high ACCI groups. Age was significantly higher in the late diagnosis group (61.8 ± 15.0 years) than in the early diagnosis group (49.1 ± 18.4, p = 0.001). The CCI score was higher in the late diagnosis group (≥ 3 in 26.1%) than in the early diagnosis group (≥ 3 in 5.1%, p = 0.01). The ACCI score demonstrated a positive correlation with the diagnosis duration (ß = 1.636, p < 0.001), indicating that the diagnosis was delayed in patients with a higher ACCI score. The duration from onset to diagnosis was longer in the high ACCI group than in the low ACCI group (log-rank test, p < 0.001). The diagnosis duration was significantly longer, especially in patients with malignancy and cardiovascular diseases. Delayed diagnosis of GBS is associated with older age and multiple comorbidities. Diagnostic delay was significant in patients with malignancies and cardiovascular diseases. Early suspicion of GBS is required in these patients.

Morphology of en face Haller vessel and macular neovascularization at baseline and 3 months as predictive factors in age-related macular degeneration.

The clinical implication of en face imaging of Haller vessels and macular neovascularization (MNV) in neovascular age-related macular degeneration (nAMD) is not well established. The purpose of this study is to investigate whether the early-phase morphology of en face Haller vessel and MNV is related to the injection frequency and visual outcome in treatment-naïve nAMD. En face images of Haller vessel and MNV were acquired from 52 eyes at baseline, after three loading doses and at 12 months later using optical coherence tomography (OCT) and OCT angiography. Vessel area, diameter, length, intersection number, fractal dimension, and lacunarity were calculated. Patients were classified according to the injection frequency (< 5 as the infrequent group) and visual gain (≥ 0.3 logMAR) over 12 months. The infrequent group was associated with a longer Haller vessel length after loading doses (OR 3.05, P = 0.01), while visual gain was associated with a smaller maximal MNV diameter after loading doses (OR 0.22, P = 0.03). A predictive model for frequent injection based on the Haller vessel length demonstrated an AUC of 0.71. In conclusion, the en face Haller vessel and MNV morphology after loading doses can be used as biomarkers for the injection frequency and visual gain during the first year in treatment-naïve nAMD patients.

Technical note: Polyvinylpyrrolidone (PVP) and proteinase-K improve the efficiency of DNA extraction from Japanese larch wood and PCR success rate.

Illegal distribution of timber disrupts the timber market and depletes forest resources. DNA markers are used to verify the legal distribution of wood. However, it is difficult to obtain the quantity and quality of DNA suitable for genetic analysis because of the physicochemical properties of wood; therefore, an efficient wood DNA extraction method is required. In this study, to prepare an efficient DNA extraction method from Japanese larch (Larix kaempferi) wood, we investigated the ability of polyvinylpyrrolidone (PVP) and proteinase-K to improve DNA extraction efficiency and PCR success rate. It was found that the addition of PVP resulted in a significant increase in the DNA concentration of the treatment group compared to that of the control group, while the purity (A260/A280) showed no difference. Moreover, the addition of proteinase-K significantly increased both the DNA concentration and purity of the treatment group compared to those of the control group. Further analysis showed that the PCR success rate of psbC (approximately 350 bp) was higher than 90% in the control, PVP treatment, and proteinase-K treatment groups. However, in the PCR success rate of rbcL (approximately 1.3 kb) was higher in the proteinase-K and PVP treatment groups than in the control group. The addition of PVP and proteinase-K increased the success rate of PCR amplification for long regions by preventing DNA damage caused by phenolic compounds and proteins in the wood. The results of this study can thus develop DNA extraction methods to identify the species and origin of woods.

Selenocysteine mimics the effect of dietary restriction on lifespan via SKN­1 and retards age­associated pathophysiological changes in Caenorhabditis elegans.

Selenocysteine, a sulfur­containing amino acid, can modulate cellular oxidative stress defense systems by incorporating into anti­oxidant enzymes such as glutathione peroxidase and thioredoxin reductase. Selenocysteine can also prevent cancer, neurodegenerative diseases and cardiovascular diseases. A recent study revealed that dietary supplementation with selenocysteine can increase the resistance of Caenorhabditis elegans to environmental stressors and its lifespan. The objective of the present study was to identify the underlying mechanism involved in the lifespan­extending effect of selenocysteine and the effect of selenocysteine on age­associated pathophysiological changes. Lifespan assays with known long­lived mutants of age­1 (the ortholog of the phosphoinositide 3-kinase), clk­1 (the ortholog of demethoxyubiquinone hydroxylase) and eat­2 (a ligand-gated ion channel subunit) revealed that the effect of selenocysteine on lifespan specifically overlapped with that of the eat­2 mutation, a genetic model of dietary restriction (DR). Selenocysteine mimicked the effect of DR on the bacterial dilution method. It required SKN-1 (the ortholog of mammalian nuclear factor-erythroid-related factor) for lifespan extension. In addition, selenocysteine significantly delayed the paralysis induced by human amyloid­ß gene, positively correlated with the incidence of Alzheimer's disease. The effect of selenocysteine on amyloid­ß­induced toxicity was dependent on the nuclear localization of DAF­16. Reduced survival caused by high­glucose­diet was recovered by selenocysteine. Selenocysteine also reduced the cellular level of reactive oxygen species known to be increased by high­glucose­diet. The results of the present study suggested that selenocysteine can mimic the effect of DR on lifespan and age­associated pathophysiological alterations, providing scientific evidence for the development of DR mimetics using selenocysteine.

SUSTAINABLE MEDICAL PREPAREDNESS AND RESPONSE SYSTEM FOR RADIATION EMERGENCIES IN THE REPUBLIC OF KOREA.

This paper provides information about the medical preparedness and response system for radiation emergencies in Republic of Korea. The National Radiation Emergency Medical Center (NREMC) oversees medical affairs in the Korean radiological disaster prevention system since its establishment in 2002. It has dedicated itself to set up a nationwide radiation emergency medicine network with 24 designated radiation emergency hospitals. NREMC, as one division under the Korea Institute of Radiological And Medical Sciences (KIRAMS), provides efficient medical care to patients suspected with radiation exposure by collaborating with professional medical staffs in Korea Cancer Center Hospital (KCCH). For prompt response to radiation accidents, NREMC has offered specialized trainings for medical staffs and first responders. It has also operated the 24-h on-call system to consult public concerns of radiation exposure, which can be switched into an emergency mode upon receiving accident reports. In addition, NREMC has conducted dose assessments of radiation exposure with high level of accuracy and implemented R&D programs for radiation injury therapeutics and low-dose radiation risks evaluation in daily life. NREMC supports global initiatives for strengthening medical preparedness and response for radiation emergencies with international organizations.

Selenocysteine modulates resistance to environmental stress and confers anti-aging effects in C. elegans

OBJECTIVE: The free radical theory of aging suggests that cellular oxidative damage caused by free radicals is a leading cause of aging. In the present study, we examined the effects of a well-known anti-oxidant amino acid derivative, selenocysteine, in response to environmental stress and aging using Caenorhabditis elegans as a model system. METHOD: The response to oxidative stress induced by H2O2 or ultraviolet irradiation was compared between the untreated control and selenocysteine-treated groups. The effect of selenocysteine on lifespan and fertility was then determined. To examine the effect of selenocysteine on muscle aging, we monitored the change in motility with aging in both the untreated control and selenocysteine-treated groups. RESULTS: Dietary supplementation with selenocysteine significantly increased resistance to oxidative stress. Survival after ultraviolet irradiation was also increased by supplementation with selenocysteine. Treatment with selenocysteine confers a longevity phenotype without an accompanying reduction in fertility, which is frequently observed in lifespan-extending interventions as a trade-off in C. elegans. In addition, the age-related decline in motility was significantly delayed by supplementation of selenocysteine. CONCLUSION: These findings suggest that dietary supplementation of selenocysteine can modulate response to stressors and lead to lifespan extension, thus supporting the free radical theory of aging.

Black Raspberry Extract Increased Circulating Endothelial Progenitor Cells and Improved Arterial Stiffness in Patients with Metabolic Syndrome: A Randomized Controlled Trial.

Administration of black raspberry (Rubus occidentalis) is known to improve vascular endothelial function in patients at a high risk for cardiovascular (CV) disease. We investigated short-term effects of black raspberry on circulating endothelial progenitor cells (EPCs) and arterial stiffness in patients with metabolic syndrome. Patients with metabolic syndrome (n = 51) were prospectively randomized into the black raspberry group (n = 26, 750 mg/day) and placebo group (n = 25) during the 12-week follow-up. Central blood pressure, augmentation index, and EPCs, such as CD34/KDR(+), CD34/CD117(+), and CD34/CD133(+), were measured at baseline and at 12-week follow-up. Radial augmentation indexes were significantly decreased in the black raspberry group compared to the placebo group (-5% ± 10% vs. 3% ± 14%, P < .05). CD34/CD133(+) cells at 12-week follow-up were significantly higher in the black raspberry group compared to the placebo group (19 ± 109/µL vs. -28 ± 57/µL, P < .05). Decreases from the baseline in interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were significantly greater in the black raspberry group compared to the placebo group (-0.5 ± 1.4 pg/mL vs. -0.1 ± 1.1 pg/mL, P < .05 and -5.4 ± 4.5 pg/mL vs. -0.8 ± 4.0 pg/mL, P < .05, respectively). Increases from the baseline in adiponectin levels (2.9 ± 2.1 µg/mL vs. -0.2 ± 2.5 µg/mL, P < .05) were significant in the black raspberry group. The use of black raspberry significantly lowered the augmentation index and increased circulating EPCs, thereby improving CV risks in patients with metabolic syndrome during the 12-week follow-up.