Adenosine evokes potassium currents by protein kinase C activated via a novel signaling pathway in superior colliculus neurons

AbstractAdenosine evoked whole-cell potassium currents and enhanced intracellular free Ca2+ concentration ([Ca2+]i) in superior colliculus neurons through a P2Y purinoceptor linked to a pertussis toxin-insensitive G-protein, possibly Gq-protein, which is involved in a protein kinase C(PKC) activation pathway. The [Ca2+]i increase was inhibited by a phospholipase C(PLC) inhibitor, whereas the evoked currents were not affected by a PLC inhibitor or a phospholipase A2(PLA2) inhibitor. Adenosine elicited single channel currents via PKC activation in cell-attached patches and furthermore, those currents with conductances of the same slope were induced even in excised patches, suggesting that PKC can be activated only by cell membrane factors without intracellular components. These results thus indicate that the P2Y purinoceptor-coupled potassium channel is regulated via a novel PKC activation pathway independent of PLC or PLA2

Predictive Model for Adverse Events and Immune Response Based on the Production of Antibodies After the Second-Dose of the BNT162b2 mRNA Vaccine

Background: The BNT162b mRNA vaccine for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mimics the immune response to natural infection. Few studies have predicted the adverse effects (AEs) after the second-dose vaccination. We present a predictive model for AEs and immune response after the second-dose of the BNT162b mRNA vaccine. Methods: To predict AEs, 282 healthcare workers (HCWs) were enrolled in this prospective observational study. The classification and regression tree (CART) model was established, and its predictive efficacy was assessed. To predict immune response, 282 HCWs were included in the analysis. Moreover, the factors affected by anti-SARS-CoV-2 spike protein RBD antibody (s-IgG) were evaluated using serum samples collected 2 months after the second-dose vaccination. The s-IgG level was assessed using Lumipulse G1200. Multiple regression analyses were conducted to evaluate variables associated with anti-s-IgG titer levels. Results: The most common AEs after the second-dose vaccination were pain (87.6%), redness (17.0%) at the injection site, fatigue (68.8%), headache (53.5%), and fever (37.5%). Based on the CART model, headache after the first-dose vaccination and age < 30 years were identified as the first and second discriminators for predicting the headache after the second-dose vaccination, respectively. In the multiple linear regression model, anti-s-IgG titer levels were associated with age, female sex, and AEs including headache and induration at the injection site after the second-dose vaccination. Conclusion: Headache after the first-dose vaccination can be a predictor of headache after the second-dose vaccination, and AEs are indicators of immune response

Physical Characteristics of Injection Site Pain After COVID-19 mRNA BNT162b2 Vaccination

Background: BNT162b2, an mRNA COVID-19 vaccine, was launched in many countries as an intramuscular vaccination for COVID-19 infection. Few studies have assessed the physical indications of pain at the immunization site. This study aimed to characterize pain at the injection site and investigate morphological attributes using ultrasound. Methods: Forty-three of 211 healthcare workers who received a second dose of BNT162b2 between February 2021 and March 2021 were enrolled in the study. The mean age of the subjects was 40 years. We evaluated patients’ pain at the injection site using the Numerical Rating Pain Scale (NRPS). We also assessed the thickness of the deltoid muscle fascia at the injection site by ultrasound. Bayesian robust correlation was employed to explore the relationship between the pain intensity scores and ultrasound measurements. Results: All eligible subjects complained of pain at the injection site. A median pain onset of 8 hours post-vaccination and a median peak intensity score of 4 were reported. Onset of relief occurred after 2 days. Ultrasound images demonstrated a 2.5-fold increase in fascia thickness at the injection site without intramuscular echogenicity change in all subjects. A correlation was established between the NRPS score and the non-injection-to-injection-side ratio of fascia thickness at the injection site (rho = 0.66). Conclusion: A sore arm was the most prevalent side effect of BNT162b2 vaccination and could be attributed to temporal fasciitis

Clinical characteristics for distinguishing between acute cardiogenic pulmonary edema and community-acquired pneumonia in elderly patients: a prospective observational study

Heart failure and pneumonia are highly prevalent in elderly patients. We conducted a study to evaluate the differences in the patterns of symptoms, laboratory findings, and computed tomography (CT) results in elderly patients with acute cardiogenic pulmonary edema (ACPE) and community-acquired pneumonia (CAP). From January 1, 2015 to December 31, 2017, we studied 140 patients aged >75 years who were diagnosed with ACPE and CAP. Symptoms, laboratory findings, mean ostial pulmonary vein (PV) diameter and patterns on CT images were assessed. The primary measures of diagnostic accuracy were assessed using the positive likelihood ratio (LR+). The cutoff value of ostial PVs for differentiating patients with ACPE from CAP was evaluated using the receiver operating characteristic (ROC) analysis. Ninety-three patients with ACPE, 36 with CAP, and 11 with complicated ACPE/CAP were included. In patients with ACPE, edema (LR+ 5.4) was a moderate factor for rule-in, and a high brain natriuretic peptide level (LR+ 4.2) was weak. In patients with CAP, cough (LR+ 5.7) and leukocytosis (LR+ 5.2) were moderate factors for rule-in, while fever (LR+ 3.8) and a high C-reactive protein level (LR+ 4.8) were weak factors. The mean diameter of ostial PVs in patients with ACPE was significantly larger than that of patients with CAP (15.8± 1.8 mm vs 9.6±1.5 mm, p< 0.01). ROC analysis revealed that an ostial PV diameter cutoff of 12.5 mm was strong evidence for distinguishing ACPE from CAP with an area under the ROC curve of 0.99 and LR+ 36.0. In conclusion, as ACPE and CAP have similar symptoms and laboratory findings, dilated ostial PVs were useful in characterizing CT images to distinguish ACPE from CAP

Early Intervention of Pulmonary Rehabilitation for Fibrotic Interstitial Lung Disease Is a Favorable Factor for Short-Term Improvement in Health-Related Quality of Life

Patients with fibrosing interstitial lung disease (FILD) have poor health-related quality of life (HRQOL). We analyzed predictors of short-term improvement of HRQOL after starting pulmonary rehabilitation (PR) in moderate to severe FILD patients. This study involved 28 consecutive patients with FILD (20 males, median age of 77.5 years), who participated in PR program of our hospital for &gt;6 weeks. The St. George’s Respiratory Questionnaire (SGRQ) score and the 6-min walk distance (6MWD) were evaluated before and after PR, and the predictors of efficacy of PR were analyzed. The duration from diagnosis of FILD to start of PR showed a positive correlation with the increase in the SGRQ score, and the baseline SGRQ score showed a negative correlation with increase in the 6MWD. The FILD subtype, modified Medical Research Council score, and treatment history were not associated with the endpoints. According to the receiver operating characteristic curve (ROC) analyses, starting PR within 514 days after diagnosis of FILD was a significant favorable predictor of improvement in the SGRQ total score more than a minimal clinically important difference of 4. In this study, early intervention of PR and lower SGRQ score were associated with the favorable response to PR. PR for FILD should be initiated early before the disease becomes severe