Search

Background: A proportion of the convalescent SARS‐CoV‐2 pediatric population presents nonspecific symptoms, mental health problems, and a reduction in quality of life similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID‐19 symptomatic. However, data regarding its clinical manifestation and immune mechanisms are currently scarce. Methods: In this study, we perform a comprehensive clinical and immunological profiling of 17 convalescent COVID‐19 children with post‐acute COVID‐19 sequelae (PASC) manifestation and 13 convalescent children without PASC manifestation. A detailed medical history, blood and instrumental tests, and physical examination were obtained from all patients. SARS‐CoV‐2 reactive T‐cell response was analyzed via multiparametric flow cytometry and the humoral immunity was addressed via pseudovirus neutralization and ELISA assay. Results: The most common PASC symptoms were shortness of breath/exercise intolerance, paresthesia, smell/taste disturbance, chest pain, dyspnea, headache, and lack of concentration. Blood count and clinical chemistry showed no statistical differences among the study groups. We detected higher frequencies of spike (S) reactive CD4+ and CD8+ T cells among the PASC study group, characterized by TNFα and IFNγ production and low functional avidity. CRP levels are positively correlated with IFNγ producing reactive CD8+ T cells. Conclusions: Our data might indicate a possible involvement of a persistent cellular inflammatory response triggered by SARS‐CoV‐2 in the development of the observed sequelae in pediatric PASC. These results may have implications on future therapeutic and prevention strategies. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background In pediatric patients, invasive procedures such as the insertion of a central venous catheter or gastroscopy require deep sedation. It is unknown whether listening to parental voice during deep sedation in children can reduce sedative doses. Aim The aim of this prospective study was to determine the effect of listening to a parent's voice during deep sedation on consumption of sedatives in children. Methods Fifty children aged 2-14 years undergoing central line placement or gastroscopy under deep sedation with propofol were randomly assigned to two groups: (A) listening or (B) not listening their parents' recorded voice reading a standardized text by the use of earphones. Depth of sedation was monitored by Comfort Score and by Bispectral Index. Results Mean sedative dose of propofol in both groups was equal (A 0.25 mg·kg−1·min−1; B 0.28 mg·kg−1·min−1; Δ −0.03 mg·kg−1·min−1 ( CI 95% −0.08 to 0.01); P = 0.089). Furthermore, complication rate ( P = 1.0) and recovery time (A 14.5 min; B 16.1 min; Δ = −1.6 min ( CI 95% −6.98 to 3.81); P = 0.60) did not differ between the intervention and the control group. Conclusion Listening to parental voice during deep sedation does not result in a reduction of sedative dose in children undergoing short medical procedures. [ABSTRACT FROM AUTHOR]

Perinatal infections have a negative impact on brain development. However, the underlying mechanisms leading to neurological impairment are not completely understood and reliable models of inflammation are urgently needed. Using phorbol-myristate-acetate as an activator of inflammation, we investigated the effect on the developing rodent brain. Neonatal rats and mice deficient in IL-18 or IRAK-4 were exposed to PMA. Brains were assessed for regulation of pro- and anti-inflammatory cytokines and cell death 24 hrs, 7 and 14 days after treatment. PMA induced an inflammatory response and caused widespread neurodegeneration in the brains of 3- and 7-day-old rats. In contrast, 14-day-old rats were resistant to the neurotoxic effect of PMA. Histological evaluation at the age of 14 and 21 days revealed a destruction of the cortical microstructure with decreased numerical density of neuronal cells. Mice deficient in IL-18 or IRAK-4 were protected against PMA induced brain injury. PMA treatment during a vulnerable period can alter brain development. IL-18 and IRAK-4 appear to be important for the development of PMA induced injury. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed. [ABSTRACT FROM AUTHOR]

Background and aim: Preterm birth is the major cause of infant mortality and morbidity in both developed and developing countries. In Europe, the prevalence rate of premature birth ranges from 5.5 to 11.4% - an average of 7.1% of all live births. In this report, we aim to compare the current health and social policies, as well as practices in 13 EU member states. Materials and methods: Using desk research, relevant information was gathered from each of the 13 European countries with regard to the prevalence of preterm birth, the cost of preterm birth to healthcare budgets, and the relevant policies, guidelines and practices in place at the national and, in some cases, regional level. The information comes from a range of sources, including government and parent association websites, published scientific literature and media reports. Results: Despite the growing prevalence and increasing costs, neonatal and preterm infant health rank low on the policy agendas of EU member states. Conclusion: Based on the findings, there are a number of recommendations that should be considered. The European Union should (i) recognize the growing challenge of prematurity in Europe and its significant impact on infant morbidity and mortality, (ii) improve neonatal health through the development and implementation of coordinated EU health and social policies, (iii) address the lack of comparable European data on prematurity, including prevalence, mortality, acute morbidity and long-term impairment, (iv) also increase the standard of neonatal care across Europe by supporting the development and implementation of European medical guidelines and quality standards, (v) support the development of European postgraduate training programmes in Peri- and Neonatology in order to increase the quality and availability of trained healthcare professionals. [ABSTRACT FROM AUTHOR]

Objective Prematurely born infants are at risk for development of neurocognitive impairment in later life. Oxygen treatment has been recently identified as a trigger of neuronal and oligodendrocyte apoptosis in the developing rodent brain. We investigated the role of the Fas death receptor pathway in oxygen-triggered developmental brain injury. Methods Six-day-old Wistar rats were exposed to 80% oxygen for various periods (2, 6, 12, 24, 48, and 72 hours), and mice deficient in either Fas (B6.MRL- Tnfrsf6 lpr) or Fas ligand (B6Smn.C3- Fasl gld) and control mice (C57BL/6J) were exposed to 80% oxygen for 24 hours. Polymerase chain reaction, Western blotting, and caspase activity assays of thalamus and cortex tissue were performed. Results Fas and Fas ligand messenger RNA and protein were upregulated. Furthermore, hyperoxia resulted in induction of downstream signaling events of Fas, such as Fas-associated death domain (FADD), the long and short form of FADD-like interleukin-1β-converting enzyme (FLICE) inhibitory protein (FLIP-L, FLIP-S), and cleavage of caspase-8 and caspase-3. Injection of a selective caspase-8 inhibitor (TRP801, 1mg/kg) at the beginning of hyperoxia blocked subsequent caspase-3 cleavage in this model. B6.MRL- Tnfrsf6 lpr mice were protected against oxygen-mediated injury, confirming Fas involvement in hyperoxia-induced cell death. Mice deficient in Fas ligand did not differ from control animals in the amount of cell death. Interpretation We conclude that neonatal hyperoxia triggers Fas receptor and its downstream signaling events in a Fas ligand-independent fashion. Lack of functional Fas receptors and selective pharmacological inhibition of caspase-8 prevents activation of caspase-3 and provides significant neuroprotection. Ann Neurol 2008;64:664-673 [ABSTRACT FROM AUTHOR]

Objective Oxygen toxicity has been identified as a risk factor for adverse neurological outcome in survivors of preterm birth. In infant rodent brains, hyperoxia induces disseminated apoptotic neurodegeneration. Because a tissue-protective effect has been observed for recombinant erythropoietin (rEpo), widely used in neonatal medicine for its hematopoietic effect, we examined the effect of rEpo on hyperoxia-induced brain damage. Methods Six-day-old C57Bl/6 mice or Wistar rats were exposed to hyperoxia (80% O2) or normoxia for 24 hours and received rEpo or normal saline injections intraperitoneally. The amount of degenerating cells in their brains was determined by DeOlmos cupric silver staining. Changes of their brain proteome were determined through two-dimensional electrophoresis and mass spectrometry. Western blot, enzyme activity assays and real-time polymerase chain reaction were performed for further analysis of candidate proteins. Results Systemic treatment with 20,000 IE/kg rEpo significantly reduced hyperoxia-induced apoptosis and caspase-2, -3, and -8 activity in the brains of infant rodents. In parallel, rEpo inhibited most brain proteome changes observed in infant mice when hyperoxia was applied exclusively. Furthermore, brain proteome changes after a single systemic rEpo treatment point toward a number of mechanisms through which rEpo may generate its protective effect against oxygen toxicity. These include reduction of oxidative stress and restoration of hyperoxia-induced increased levels of proapoptotic factors, as well as decreased levels of neurotrophins. Interpretation These findings are highly relevant from a clinical perspective because oxygen administration to neonates is often inevitable, and rEpo may serve as an adjunctive neuroprotective therapy. Ann Neurol 2008;64:523-534 [ABSTRACT FROM AUTHOR]

The article focuses on the use of erythropoietin (Epo) and recombinant human Epo (rhEpo) for treatment and prevention of anemia in various patients, including preterm newborn infants. from neuronal cell culture to in vivo brain injury. The study suggests that Epo may protect cells against damage caused by such diverse pathological conditions as stroke, cortical trauma, inflammation, demyelinating conditions, radiation, cytostatic agents, toxin-induced epileptic seizures, and retinal ischemia. Epo has been identified as a neuroprotective agent in a wide variety of experimental models, from neuronal cell vivo brain injury.

A subset of patients with type 2 Gaucher disease is characterized by intrauterine onset of rapidly progressive neuropathic disease, arthrogryposis, hydrops fetalis and in some cases restrictive dermopathy. beta-Glucocerebrosidase (beta-glucosidase) activity is usually low or undetectable. In most cases death ensues either in-utero or within hours or days after birth. We report on an infant born to non-consanguineous parents of Caucasian origin presenting at birth with hydrops, arthrogryposis, severe respiratory distress, hepatosplenomegaly, and liver failure. Death occurred within several hours after delivery and autopsy revealed typical Gaucher cells in multiple organs in combination with severe apoptotic neurodegeneration throughout the brain. beta-Glucocerebrosidase activity was 1% of the norm in fibroblasts and a novel heterozygous insertion c.1515_1516insAGTGAGGGCAAT was identified by genomic sequencing and an insertion-specific seminested PCR. In addition, molecular studies revealed a previously described in type 1 Gaucher disease missense mutation c.476G --> A which results in a heterozygous substitution of R120Q. Our observations confirm considerable genotypic heterogeneity in patients with type 2 Gaucher disease. The transheterozygous combination of a mutation, previously described in type 1 Gaucher disease, together with a newly identified insertion may result in this severe phenotype., (Copyright 2004 Wiley-Liss, Inc.)