Adverse Events in Healthcare Workers after the First Dose of ChAdOx1 nCoV-19 or BNT162b2 mRNA COVID-19 Vaccination: a Single Center Experience

Coronavirus disease 2019 vaccinations for healthcare workers (HCWs) have begun in South Korea. To investigate adverse events (AEs) of the first dose of each vaccine, any symptom was collected daily for seven days after vaccination in a tertiary hospital. We found that 1,301 of 1,403 ChAdOx1 nCoV-19 recipients and 38 of 80 BNT162b2 recipients reported AEs respectively (90.9% vs. 52.5%): injection-site pain (77.7% vs. 51.2%), myalgia (60.5% vs.11.2%), fatigue (50.7% vs. 7.5%), headache (47.4% vs. 7.5%), and fever (36.1% vs. 5%; P < 0.001 for all). Young HCWs reported more AEs with ChAdOx1 nCoV-19 than with BNT162b2.No incidences of anaphylaxis were observed. Only one serious AE required hospitalization for serious vomiting, and completely recovered. In conclusion, reported AEs were more common in recipients with ChAdOx1 nCoV-19 than in those with BNT162b2. However, most of the reported AEs were mild to moderate in severity. Sufficient explanation and preparation for expected AEs required to promote widespread vaccination.

Adverse Events in Healthcare Workers after the First Dose of ChAdOx1 nCoV-19 or BNT162b2 mRNA COVID-19 Vaccination: a Single Center Experience

Coronavirus disease 2019 vaccinations for healthcare workers (HCWs) have begun in South Korea. To investigate adverse events (AEs) of the first dose of each vaccine, any symptom was collected daily for seven days after vaccination in a tertiary hospital. We found that 1,301 of 1,403 ChAdOx1 nCoV-19 recipients and 38 of 80 BNT162b2 recipients reported AEs respectively (90.9% vs. 52.5%): injection-site pain (77.7% vs. 51.2%), myalgia (60.5% vs.11.2%), fatigue (50.7% vs. 7.5%), headache (47.4% vs. 7.5%), and fever (36.1% vs. 5%; P < 0.001 for all). Young HCWs reported more AEs with ChAdOx1 nCoV-19 than with BNT162b2.No incidences of anaphylaxis were observed. Only one serious AE required hospitalization for serious vomiting, and completely recovered. In conclusion, reported AEs were more common in recipients with ChAdOx1 nCoV-19 than in those with BNT162b2. However, most of the reported AEs were mild to moderate in severity. Sufficient explanation and preparation for expected AEs required to promote widespread vaccination.

A focus on extracellular Ca²⁺ entry into skeletal muscle

The main task of skeletal muscle is contraction and relaxation for body movement and posture maintenance. During contraction and relaxation, Ca²⁺ in the cytosol has a critical role in activating and deactivating a series of contractile proteins. In skeletal muscle, the cytosolic Ca²⁺ level is mainly determined by Ca²⁺ movements between the cytosol and the sarcoplasmic reticulum. The importance of Ca²⁺ entry from extracellular spaces to the cytosol has gained significant attention over the past decade. Store-operated Ca²⁺ entry with a low amplitude and relatively slow kinetics is a main extracellular Ca²⁺ entryway into skeletal muscle. Herein, recent studies on extracellular Ca²⁺ entry into skeletal muscle are reviewed along with descriptions of the proteins that are related to extracellular Ca²⁺ entry and their influences on skeletal muscle function and disease.

The maintenance ability and Ca²⁺ availability of skeletal muscle are enhanced by sildenafil

Sildenafil relaxes vascular smooth muscle cells and is used to treat pulmonary artery hypertension as well as erectile dysfunction. However, the effectiveness of sildenafil on skeletal muscle and the benefit of its clinical use have been controversial, and most studies focus primarily on tissues and organs from disease models without cellular examination. Here, the effects of sildenafil on skeletal muscle at the cellular level were examined using mouse primary skeletal myoblasts (the proliferative form of skeletal muscle stem cells) and myotubes, along with single-cell Ca2+ imaging experiments and cellular and biochemical studies. The proliferation of skeletal myoblasts was enhanced by sildenafil in a dose-independent manner. In skeletal myotubes, sildenafil enhanced the activity of ryanodine receptor 1, an internal Ca2+ channel, and Ca2+ movement that promotes skeletal muscle contraction, possibly due to an increase in the resting cytosolic Ca2+ level and a unique microscopic shape in the myotube membranes. Therefore, these results suggest that the maintenance ability of skeletal muscle mass and the contractility of skeletal muscle could be improved by sildenafil by enhancing the proliferation of skeletal myoblasts and increasing the Ca2+ availability of skeletal myotubes, respectively.

TRPC3 cation channel plays an important role in proliferation and differentiation of skeletal muscle myoblasts

During membrane depolarization associated with skeletal excitation-contraction (EC) coupling, dihydropyridine receptor [DHPR, a L-type Ca2+ channel in the transverse (t)-tubule membrane] undergoes conformational changes that are transmitted to ryanodine receptor 1 [RyR1, an internal Ca2+-release channel in the sarcoplasmic reticulum (SR) membrane] causing Ca2+ release from the SR. Canonical-type transient receptor potential cation channel 3 (TRPC3), an extracellular Ca2+-entry channel in the t-tubule and plasma membrane, is required for full-gain of skeletal EC coupling. To examine additional role(s) for TRPC3 in skeletal muscle other than mediation of EC coupling, in the present study, we created a stable myoblast line with reduced TRPC3 expression and without alpha1SDHPR (MDG/TRPC3 KD myoblast) by knock-down of TRPC3 in alpha1SDHPR-null muscular dysgenic (MDG) myoblasts using retrovirus-delivered small interference RNAs in order to eliminate any DHPR-associated EC coupling-related events. Unlike wild-type or alpha1SDHPR-null MDG myoblasts, MDG/TRPC3 KD myoblasts exhibited dramatic changes in cellular morphology (e.g., unusual expansion of both cell volume and the plasma membrane, and multi-nuclei) and failed to differentiate into myotubes possibly due to increased Ca2+ content in the SR. These results suggest that TRPC3 plays an important role in the maintenance of skeletal muscle myoblasts and myotubes.

The Effect of Acetylcholine Esterase Inhibitor on Cerebrospinal Fluid beta-Amyloid 1-42 and Phosphorylated Tau Protein in Korean Alzheimer's Disease Patients: Preliminary Study

BACKGROUND: Alzheimer's disease (AD) is characterized by the pathology of amyloid plaques and tau-associated neurofibrillary tangles. Acetylcholine esterase (AChE) transforms the beta-amyloid monomer into an oligomer, and increases beta-amyloid aggregation in the brain. Increased beta-amyloid breaks the cytoskeleton of the brain by hyperphosphorylation of the tau protein. Previous studies support that AChE inhibitor has an inhibitory effect on toxicity of the beta-amyloid and phophorylated tau protein. The purpose of this study was to analyze the CSF beta-amyloid 1-42 (A beta 1-42) and phosphorylated tau protein in AD and determine their difference depending on whether AChE inhibitor was taken or not. METHODS: Subjects included 16 AD, 14 normal controls, and 15 disease controls. Nine of AD group had taken an AChE inhibitor while the remainder had not. The CSF A beta 1-42 and phosphorylated tau were measured by ELISA. RESULTS: The CSF A beta 1-42 levels were lower in AD patients than in other groups (p<0.01). We also found increased CSF A beta 1-42 levels in the AChE inhibitor users, compared with non-users. CONCLUSIONS: The level of CSF A beta 1-42 may have a diagnostic value in the patients with cognitive impairments. Also, we may expect the effect of AChE inhibitor on Alzheimer's pathology by measuring CSF A beta 1-42 levels. Therefore, the level of CSF A beta 1-42 may serve as a biological surrogate marker for AD treatment.

Homo-dimerization of RyR1 C-terminus via charged residues in random coils or in an alpha-helix

To investigate the mechanism by which the C-terminus (4,938-5,037) of the ryanodine receptor 1 (RyR1) homo-tetramerizes, forming a functional Ca2+ -release channel, the structural requirements for the tetramerization were studied using site-directed mutagenesis. Alanine-substitutions at five charged residues, E4976, H5003, D5026, E5033 and D5034, significantly decreased the formation of homo-dimers (reduced by > 50%). Interaction between the C-terminus and cytoplasmic loop I (4,821-4,835) required two positively charged residues, H4832 and K4835. Based on the predicted protein secondary structures, all seven charged residues are located in random coils. Paired alanine-substitutions at six negatively charged residues (E4942A/D4953A, D4945A/E4952A and E4948A/ E4955A) of the alpha-helix (4,940-4,956) in the C-terminus increased homo-dimerization. Therefore, the homo-tetramerization of RyR1 may be mediated by intra- and/or inter-monomer electrostatic interactions among the C-terminal charged residues in random coils or in an alpha-helix.

Factors influencing quality of life of cervical cancer patients in Korea / 대한산부인과학회지

OBJECTIVE: To assess the quality of life (QOL) of uterine cervical cancer patients after treatment in Korea and to demonstrate influencing factors. METHODS: 127 uterine cancer survivors, 107 controls of benign gynecologic surgery patients were interviewed with study questionnaire by research assistant. RESULTS: Participants were with the mean age of 54 years (cancer patients) and 43 years (controls). Physical component score of General QOL was statistically significant in uterine cervical cancer group compared with control group (p=0.049). Parts of MCS, CS-QOL, Emotional support, Coping efforts didn't show differences between two groups. In patients' characteristics, high economic status and advanced stage influenced patient's adaptation to treatment. When evaluating QOL including sexual function, most parts were statistically significantly worsen in uterine cancer patients, ie, sexual dysfunction (p=0.004), sexual discomfort (p=0.070), sexual pleasure (p=0.011), gynecological symptom (p=0.001). Most factors except age didn't influence sexual function deterioration between cancer group and control group. Common presenting concerns of cancer patients before treatment was health (51%), children (23%), economic problem (16%) but after treatment health (92%). The most helpful people were family members in 84% and physicians in 9%. CONCLUSION: Uterine cervical cancer survivors in Korea appear to experience greater distress on sexual function especially in young age. Therefore it is important for health care professionals to recognize that aspects of cancer survivorship continue to require education and adequate follow-up program.