Novel Broad-Spectrum Antiviral Inhibitors Targeting Host Factors Essential for Replication of Pathogenic RNA Viruses.

Recent RNA virus outbreaks such as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Ebola virus (EBOV) have caused worldwide health emergencies highlighting the urgent need for new antiviral strategies. Targeting host cell pathways supporting viral replication is an attractive approach for development of antiviral compounds, especially with new, unexplored viruses where knowledge of virus biology is limited. Here, we present a strategy to identify host-targeted small molecule inhibitors using an image-based phenotypic antiviral screening assay followed by extensive target identification efforts revealing altered cellular pathways upon antiviral compound treatment.

Prevalence of Sensorineural Hearing Loss in Children with Palliated or Repaired Congenital Heart Disease.

Background Children with congenital heart disease (CHD) are at increased risk of neurodevelopmental deficits, and the presence of sensorineural hearing loss (SNHL) may further lead to poor language skills acquisition and speech delays. Prevalence of SNHL in the general pediatric population is estimated to be 0.2% at birth to 0.

Prenatal and Postnatal PCB-153 and ,'-DDE Exposures and Behavior Scores at 5–9 Years of Age among Children in Greenland and Ukraine.

Background: Studies have reported some evidence of adverse effects of organochlorine exposures on child development, but the results have been inconsistent, and few studies have evaluated associations with child behavior.

Objective: We investigated the association between prenatal and early-life exposures to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and 1,1-dichloro-2,2-bis(-chlorophenyl)-ethylene ('-DDE) and behaviors in children between 5 and 9 y of age.

Methods: In the Biopersistent organochlorines in diet and human fertility: Epidemiologic studies of time to pregnancy and semen quality in Inuit and European populations (INUENDO) cohort, consisting of mother-child pairs from Greenland and Ukraine (=1,018), maternal serum PCB-153 and '-DDE concentrations were measured during pregnancy, and cumulative postnatal exposures during the first 12 months after delivery were estimated using a pharmacokinetic model.

Discovery of β-d-2'-deoxy-2'-dichlorouridine nucleotide prodrugs as potent inhibitors of hepatitis C virus replication.

Discovery of sofosbuvir has radically changed hepatitis C treatment and nucleoside/tide NS5B inhibitors are now viewed as one of the key components in combination therapies with other direct-acting antiviral agents. As part of our program to identify new nucleoside inhibitors of HCV replication, we now wish to report on the discovery of β-d-2'-deoxy-2'-dichlorouridine nucleotide prodrugs as potent inhibitors of HCV replication. Although, cytidine analogues have long been recognized to be metabolized to both cytidine and uridine triphosphates through the action of cytidine deaminase, uridine analogues are generally believed to produce exclusively uridine triphosphate.

Why don't adolescents finish the HPV vaccine series? A qualitative study of parents and providers.

Objective: To describe why adolescent females who initiated HPV vaccination completed or did not complete the series.

Methods: Semi-structured interviews were conducted with parents/guardians of 11-17 year old female adolescents and their pediatric primary care providers in one inner-city public clinic and three private practices to ascertain why girls who initiated HPV vaccination did or did not complete the series. Qualitative analysis was used to identify perceived barriers and facilitators of completion.