Safety of Rotavirus Vaccination in Preterm Infants Admitted in Neonatal Intensive Care Units in Sicily, Italy: A Multicenter Observational Study

Rotavirus (RV) is among the most common vaccine-preventable diseases in children under five years of age. Despite the severity of rotavirus pathology in early childhood, rotavirus vaccination for children admitted to the neonatal intensive care unit (NICU), who are often born preterm and with various previous illnesses, is not performed. This multicenter, 3-year project aims to evaluate the safety of RV vaccine administration within the six main neonatal intensive care units of the Sicilian Region to preterm infants. Methods: Monovalent live attenuated anti-RV vaccination (RV1) was administered from April 2018 to December 2019 to preterm infants with gestational age ≥ 28 weeks. Vaccine administrations were performed in both inpatient and outpatient hospital settings as a post discharge follow-up (NICU setting) starting at 6 weeks of age according to the official immunization schedule. Any adverse events (expected, unexpected, and serious) were monitored from vaccine administration up to 14 days (first assessment) and 28 days (second assessment) after each of the two scheduled vaccine doses. Results: At the end of December 2019, 449 preterm infants were vaccinated with both doses of rotavirus vaccine within the six participating Sicilian NICUs. Mean gestational age in weeks was 33.1 (±3.8 SD) and the first dose of RV vaccine was administered at 55 days (±12.9 SD) on average. The mean weight at the first dose was 3388 (SD ± 903) grams. Only 0.6% and 0.2% of infants reported abdominal colic and fever above 38.5 ◦C in the 14 days after the first dose, respectively. Overall, 1.9% EAEs were observed at 14 days and 0.4% at 28 days after the first/second dose administration. Conclusions: Data obtained from this study confirm the safety of the monovalent rotavirus vaccine even in preterm infants with gestational age ≥ 28 weeks, presenting an opportunity to improve the vaccination offer both in Sicily and in Italy by protecting the most fragile infants who are more at risk of contracting severe rotavirus gastroenteritis and nosocomial RV infection

Cell‐penetrating peptides: Achievements and challenges in application for cancer treatment

One of the major hurdles to cure cancer lies in the low potency of currently available drugs, which could eventually be solved by using more potent therapeutic macromolecules, such as proteins or genes. However, although these macromolecules possess greater potency inside the cancer cells, the barely permeable cell membrane remains a formidable barrier to exert their efficacy. A widely used strategy is to use cell penetrating peptides (CPPs) to improve their intracellular uptake. Since the discovery of the first CPP, numerous CPPs have been derived from natural or synthesized products. Both in vitro and in vivo studies have demonstrated that those CPPs are highly efficient in transducing cargoes into almost all cell types. Therefore, to date, CPPs have been widely used for intracellular delivery of various cargoes, including peptides, proteins, genes, and even nanoparticles. In addition, recently, based on the successes of CPPs in cellular studies, their applications in vivo have been actively pursued. This review will focus on the advanced applications of CPP‐based in vivo delivery of therapeutics (e.g., small molecule drugs, proteins, and genes). In addition, we will highlight certain updated applications of CPPs for intracellular delivery of nanoparticulate drug carriers, as well as several “smart” strategies for tumor targeted delivery of CPP‐cargoes. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 575–587, 2014.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102051/1/jbma34859.pd

Emerging techniques in the isolation and characterization of extracellular vesicles and their roles in cancer diagnostics and prognostics

Extracellular vesicles (EVs) are cell-derived nanovesicles, present in almost all types of body fluids, which play an important role in intercellular communication and are involved in the transport of biological signals for regulating diverse cellular functions. Due to the increasing clinical interest in the role of EVs in tumor promotion, various techniques for their isolation, detection, and characterization are being developed. In this review, we present an overview of the current EV isolation and characterization methods in addition to their applications and limitations. Furthermore, EVs as the potential emerging biomarkers in cancer management and their clinical implementation are briefly discussed.clos

Recent Developments in Peptide-Based Nucleic Acid Delivery

Despite the fact that non-viral nucleic acid delivery systems are generally considered to be less efficient than viral vectors, they have gained much interest in recent years due to their superior safety profile compared to their viral counterpart. Among these synthetic vectors are cationic polymers, branched dendrimers, cationic liposomes and cell-penetrating peptides (CPPs). The latter represent an assortment of fairly unrelated sequences essentially characterised by a high content of basic amino acids and a length of 10–30 residues. CPPs are capable of mediating the cellular uptake of hydrophilic macromolecules like peptides and nucleic acids (e.g. siRNAs, aptamers and antisense-oligonucleotides), which are internalised by cells at a very low rate when applied alone. Up to now, numerous sequences have been reported to show cell-penetrating properties and many of them have been used to successfully transport a variety of different cargos into mammalian cells. In recent years, it has become apparent that endocytosis is a major route of internalisation even though the mechanisms underlying the cellular translocation of CPPs are poorly understood and still subject to controversial discussions. In this review, we will summarise the latest developments in peptide-based cellular delivery of nucleic acid cargos. We will discuss different mechanisms of entry, the intracellular fate of the cargo, correlation studies of uptake versus biological activity of the cargo as well as technical problems and pitfalls

Choose your cell model wisely: The in vitro nanoneurotoxicity of differentially coated iron oxide nanoparticles for neural cell labeling

Currently, there is a large interest in the labeling of neural stem cells (NSCs) with iron oxide nanoparticles (IONPs) to allow MRI-guided detection after transplantation in regenerative medicine. For such biomedical applications, excluding nanotoxicity is key. Nanosafety is primarily evaluated in vitro where an immortalized or cancer cell line of murine origin is often applied, which is not necessarily an ideal cell model. Previous work revealed clear neurotoxic effects of PMA-coated IONPs in distinct cell types that could potentially be applied for nanosafety studies regarding neural cell labeling. Here, we aimed to assess if DMSA-coated IONPs could be regarded as a safer alternative for this purpose and how the cell model impacted our nanosafety optimization study. Hereto, we evaluated cytotoxicity, ROS production, calcium levels, mitochondrial homeostasis and cell morphology in six related neural cell types, namely neural stem cells, an immortalized cell line and a cancer cell line from human and murine origin. The cell lines mostly showed similar responses to both IONPs, which were frequently more pronounced for the PMA-IONPs. Of note, ROS and calcium levels showed opposite trends in the human and murine NSCs, indicating the importance of the species. Indeed, the human cell models were overall more sensitive than their murine counterpart. Despite the clear cell type-specific nanotoxicity profiles, our multiparametric approach revealed that the DMSA-IONPs outperformed the PMA-IONPs in terms of biocompatibility in each cell type. However, major cell type-dependent variations in the observed effects additionally warrant the use of relevant human cell models.status: publishe