In this work, we investigate the potential of highly sulfated synthetic glycomimetics to act as inhibitors of viral binding/infection. Our results indicate that both long-chain glycopolymers and short-chain glycooligomers are capable of preventing viral infection. Notably, glycopolymers efficiently inhibit Human Papillomavirus (HPV16) infection in vitro and maintain their antiviral activity in vivo, while the glycooligomers exert their inhibitory function post attachment of viruses to cells. Moreover, when we tested the potential for broader activity against several other human pathogenic viruses, we observed broad-spectrum antiviral activity of these compounds beyond our initial assumptions. While the compounds tested displayed a range of antiviral efficacies, viruses with rather diverse glycan specificities such as Herpes Simplex Virus (HSV), Influenza A Virus (IAV), and Merkel Cell Polyomavirus (MCPyV) could be targeted. This opens new opportunities to develop broadly active glycomimetic inhibitors of viral entry and infection.
The purpose of this prospective study was to assess whether outcome of speech and language in children 5-10 years after corrective surgery for tetralogy of Fallot (TOF) or ventricular septal defect (VSD) in infancy was influenced by the preoperative condition of hypoxemia or cardiac insufficiency and whether it was associated with perioperative risk factors and neurodevelopmental outcome.A total of 35 unselected children, 19 with TOF and hypoxemia and 16 with VSD and cardiac insufficiency, operated with combined deep hypothermic circulatory arrest and low-flow cardiopulmonary bypass at mean age 0.7 ± 0.3 (mean ± standard deviation) years, underwent, at mean age 7.4 ± 1.6 years, standardized evaluation of speech and language functions. Results were compared between subgroups and related to perioperative factors, sociodemographic and neurodevelopmental status.Age at testing, socioeconomic status and history of speech and language development were not different between the subgroups. In contrast, total scores on oral and speech motor control functions (TFS) as well as on oral and speech apraxia (Mayo Test) were significantly reduced (p<0.02 to <0.05), and scores on anatomical oral structures tended to be lower (p<0.09) in the TOF group as compared to the VSD group. No differences were found for auditory word recognition and phonological awareness as assessed by the Auditory Closure subtest of the Illinois Test of Psycholinguistic Abilities and the test of auditory analysis skills, respectively. In all children, higher age at testing and better socioeconomic status were associated with better results in all domains of assessment (p<0.001 to <0.04). Consistent impairments of all oral and speech motor control functions (TFS and Mayo Test) were present in 29% of all children with a mean age of 6.5 years in contrast to 43% with normal performance and a mean age of 8.3 years. On the receptive speech tasks, only 6% scored below the normal range of their age group. TFS subscores were significantly correlated with age, bypass duration and motor function, but not correlated with socioeconomic status, duration of cardiac arrest, intelligence and academic achievement.Children with preoperative hypoxemia due to cyanotic cardiac defects in infancy are at higher risk for dysfunction in speech and language than those with cardiac insufficiency due to acyanotic heart defects. Age at testing, socioeconomic status, and duration of cardiopulmonary bypass influenced test results. Long-term outcome in speech and language functions can be considered as a sensitive indicator of overall child development after cardiac surgery.Keywords : Speech and language development ; Tetralogy of Fallot ; Ventricular septal defect ; Cardiac surgery Abbreviations : AC, auditory closure subtest of ITPA ; CPB, cardiopulmonary bypass ; DHCA, deep hypothermic cardiocirculatory arrest ; FISH, fluorescence in situ hybridization ; IQ, intelligence quotient ; ITPA, Illinois test of psycholinguistic abilities ; K-ABC, Kaufman assessment battery for childr...
Despite the critical feature of heparin-induced thrombocytopenia (HIT) for patients on mechanical circulatory support, reports on its incidence and outcome are still scarce. Thus, we report on clinical features of HIT in patients under Impella 5.0 or 5.5 (Abiomed Inc., Danvers, MA, USA) (Impella 5+) support for acute cardiogenic shock (CS) by focusing on observed thrombotic events. Between November 2018 and December 2020, a total of 56 consecutive patients were enrolled in a single-center retrospective study. A total of 21 patients (37.5%) were tested for HIT, and 6 (10.7%) proved positive for HIT at 10.5 ± 2.89 days after the first heparin administration during current admission. Interestingly, thrombocyte counts dropped under Impella support in all groups (all cases, no HIT test, and HIT negative group: p < 0.001, HIT-positive group: p = 0.001). All HIT-positive patients were switched from heparin to argatroban. HIT-associated thrombotic events were observed in two cases resulting in Impella dysfunction due to pump thrombosis (n = 1) and left ventricular (LV) thrombus formation (n = 1). Under large Impella support, the prevalence of HIT was relatively high. Further, thrombocytopenia does not deliver a high specificity in the setting of Impella 5+ support. Considering HIT manifestation, a routine HIT test may be considered to avoid critical thrombotic adverse events.
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