Proof-of-concept for effective antiviral activity of an in silico designed decoy synthetic mRNA against SARS-CoV-2 in the Vero E6 cell-based infection model.

The positive-sense single-stranded (ss) RNA viruses of the Betacoronavirus (beta-CoV) genus can spillover from mammals to humans and are an ongoing threat to global health and commerce, as demonstrated by the current zoonotic pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current anti-viral strategies focus on vaccination or targeting key viral proteins with antibodies and drugs. However, the ongoing evolution of new variants that evade vaccination or may become drug-resistant is a major challenge. Thus, antiviral compounds that circumvent these obstacles are needed. Here we describe an innovative antiviral modality based on in silico designed fully synthetic mRNA that is replication incompetent in uninfected cells (termed herein PSCT: parasitic anti-SARS-CoV-2 transcript). The PSCT sequence was engineered to include key untranslated cis-acting regulatory RNA elements of the SARS-CoV-2 genome, so as to effectively compete for replication and packaging with the standard viral genome. Using the Vero E6 cell-culture based SARS-CoV-2 infection model, we determined that the intracellular delivery of liposome-encapsulated PSCT at 1 hour post infection significantly reduced intercellular SARS-CoV-2 replication and release into the extracellular milieu as compared to mock treatment. In summary, our findings are a proof-of-concept for the therapeutic feasibility of in silico designed mRNA compounds formulated to hinder the replication and packaging of ssRNA viruses sharing a comparable genomic-structure with beta-CoVs.

Impact of Tonsillectomy on the Life Quality of Parents to Children With Obstructive Sleep-Disordered Breathing.

OBJECTIVE: Parents of children with any chronic illness may experience increased anxiety and reduced health-related quality of life (QoL). Our objective was to evaluate the change in parental QoL before vs after tonsillectomy. Our hypothesis was that pediatric tonsil surgery with or without adenoidectomy would improve parental QoL. STUDY DESIGN: A prospective cohort study. SETTING: An otolaryngology department in a tertiary academic center. METHODS: We enrolled parents of 79 children <5 years old. Adenotonsillectomy due to an obstructive airway indication was performed in 45 children. A group of 34 parents to healthy children served as a control group. Initially, we validated a modified version of the PAR-ENT-QoL questionnaire; then, we analyzed QoL parameters among parents of children with obstructive sleep-disordered breathing before and after surgical treatment. RESULTS: We found significant differences between the QoL score before and after surgery (P = .003). The QoL score after surgery significantly improved and was even lower than that of the control group (P < .001). CONCLUSIONS: These results highlight the importance of timely diagnosis and treatment of children with obstructive sleep-disordered breathing, as this condition may affect not only the children themselves but also their caregivers.

Translation and cultural adaptation of the Hebrew version of the Pediatric Sleep Questionnaire: a prospective, non-randomized control trial.

PURPOSE: Left untreated, obstructive sleep-disordered breathing (OSDB) are associated with adverse effects on growth and development. History and physical examination alone are used for diagnosing children with OSDB, as polysomnography is not always feasible. Our objective was to develop and validate a Hebrew version of the Pediatric Sleep Questionnaire (PSQ) to help to diagnose and follow-up children before and after adenotonsillectomy surgery for OSDB. METHODS: We conducted a prospective, nonrandomized, controlled trial in an academic medical center. We enrolled parents of children younger than 5 years of age planned for tonsillectomy with or without adenoidectomy due to obstructive airway indication. The parents completed the validated Hebrew version of PSQ questionnaire before and after surgery. We translated the questionnaire through forward-backward translation method. Our main outcome measures were reliability, validity, and responsiveness of the Hebrew version of PSQ. RESULTS: Overall, 45 parents of children with OSDB and 34 controls filled out the questionnaires. We found significant differences between the PSQ scores before and after surgery (p < 0.001). The Hebrew version of PSQ results after surgery were similar to those of the control group (p = 0.206), as expected. We found high reliability of the Hebrew version of PSQ before surgery (α = 0.931). The translated PSQ had a high specificity (87.9%) and sensitivity (77.3%) to identify children with OSDB. CONCLUSION: The Hebrew version of the validated PSQ for parents to children with OSDB can be used as a reliable screening and diagnostic tool to identify children suffering from OSDB, when polysomnography is not feasible.