Multisystem Inflammatory Syndrome after Breakthrough SARS-CoV-2 Infection in 2 Immunized Adolescents,United States

Eight weeks after having laboratory-confirmed SARS-CoV-2 breakthrough infections, 2 otherwise healthy, fully immunized adolescent patients in the United States who were experiencing related signs and symptoms were diagnosed with multisystem inflammatory syndrome in children. Our findings indicate that COVID-19 vaccination does not completely protect adolescents against multisystem inflammatory syndrome.     

功能性便秘与情感障碍相关性分析

功能性便秘是一种常见的功能性肠病,焦虑抑郁等情感障碍与功能性便秘是相互影响的。该文从三个方面阐述功能性便秘与焦虑抑郁等情感障碍的相关性。     

De novo discovery of serotonin N-acetyltransferase inhibitors

Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) is a member of the GCN5 N-acetyltransferase (GNAT) superfamily and catalyzes the penultimate step in the biosynthesis of melatonin; a large daily rhythm in AANAT activity drives the daily rhythm in circulating melatonin. We have used a structure-based computational approach to identify the first druglike and selective inhibitors of AANAT. Approximately 1.2 million compounds were virtually screened by 3D high-throughput docking into the active site of X-ray structures for AANAT, and in total 241 compounds were tested as inhibitors. One compound class, containing a rhodanine scaffold, exhibited low micromolar competitive inhibition against acetyl-CoA (AcCoA) and proved to be effective in blocking melatonin production in pineal cells. Compounds from this class are predicted to bind as bisubstrate inhibitors through interactions with the AcCoA and serotonin binding sites. Overall, this study demonstrates the feasibility of using virtual screening to identify small molecules that are selective inhibitors of AANAT.     

Dose-dependent impairment in the performance of a go-no go successive discrimination by chlordiazepoxide

After learning a light-cued, go-no go successive discrimination to criterion, male Sprague-Dawley rats received 0, 5, or 10 mg/kg chlordiazepoxide on six performance sessions, followed by two drug-recovery (saline) sessions. Chlordiazepoxide impaired discrimination performance in a dose-dependent manner, with animals in the 5 mg/kg dose condition demonstrating tolerance to the drug after two performance sessions. The degree of discrimination impairment in both drug dose conditions paralleled an increase in responding during no-go phases of the performance task. These findings are consistent with a disinhibitory hypothesis of performance impairment and suggest that CDP-drugged animals have difficulty in withholding incorrect responses.These data were presented at the Annual Meeting of the Psychonomic Society, San Antonio, Texas, 1984     

Ia antigens in serum during different murine infections.

Cholera toxin has been shown to modulate immune responses, generally producing enhancement when administered simultaneously with antigen and suppression when administered a day or more earlier. In a previous study using chronically isolated ileal loops in rabbits, we found that two subcutaneous (s.c.) "priming" and "boosting" doses of biologically active cholera toxin suppressed the local intestinal immunoglobulin A response to intraloop doses of cholera toxin. In the study reported here, two different biologically inactive but antigenically intact cholera toxoids, glutaraldehyde toxoid and choleragenoid, where administered s.c. by the same immunization schedule as for toxin in the earlier experiment. Suppression of local immune response to intraloop cholera toxin as compared with animals receiving no s.c. inoculations was again found. The results suggest that in this model suppression was immunological (mediated by an immunological mechanism) rather than toxigenic (mediated by biological activity of cholera toxin). In addition, the occurrence of suppression of local intestinal immune response after systemic immunization suggests that suboptimal protection against enteric infections could occur after s.c. vaccination.