Studies and initiatives such as the “Choosing wisely” (CW) campaign emphasise evidence-based investigations and treatment to avoid overdiagnosis and overtreatment. The perception of the extent of medical overactivity among professionals and drivers behind are not well studied in the paediatric field.Aim: We aimed to investigate the physicians‘ opinion and clarify the main drivers regarding medical overactivity in member countries of the European Academy of Paediatrics (EAP).Methods: In this study, paediatricians, paediatric residents, primary care paediatricians, and family doctors treating children were surveyed in Norway, Lithuania, Ukraine, Italy, and Switzerland. Over-investigation was defined as “diagnostic work-up or referral that is unlikely to provide information which is relevant for a patient” and overtreatment was defined as “treatment that does not benefit or can harm more than benefit the patient.” The original questionnaire was developed in 2018 by a working group from the Norwegian Paediatric Association.Results: Overall, 1,416 medical doctors participated in the survey, ranging from 144 in Lithuania to 337 in Switzerland. 83% stated that they experienced over-investigation/overtreatment, and 81% perceived this as a problem. The majority (83%) perceived expectations from family and patients as the most important driver for overtreatment in their country. Other drivers for overuse were use of national guidelines/recommendations, worry for reactions, and reduction of uncertainty.Conclusion: This is the first study investigating knowledge and attitude toward medical overactivity in European countries. Despite different cultural and economic environments, the patterns and drivers of increased investigations and medicalisation are similar.

From the start of pandemics, children were described as the ones who were less affected by SARS-Cov-2 or COVID-19, which was mild in most of the cases. However, with the growing vaccination rate of the adult population, children became more exposed to the virus and more cases of severe SARS-CoV-2-induced ARDS are being diagnosed with the disabling consequences or lethal outcomes associated with the cytokine storm. Thus, we do hypothesize that some of the children could benefit from nervus vagus stimulation during COVID-19 ARDS through the inhibition of HMGB1 release and interaction with the receptor, resulting in decreased neutrophil accumulation, oxidative stress, and coagulopathy as well as lung vascular permeability. Moreover, stimulation through alpha-7 nicotinic acetylcholine receptors could boost macrophage phagocytosis and increase the clearance of DAMPs and PAMPs. Further rise of FGF10 could contribute to lung stem cell proliferation and potential regeneration of the injured lung. However, this stimulation should be very specific, timely, and of proper duration, as it could lead to such adverse effects as increased viral spread and systemic infection, especially in small children or infants due to specific pediatric immunity state and anatomical features of the respiratory system.

Polycaprolactone (PCL) is a non-cytotoxic, completely biodegradable biomaterial, ideal for cartilage tissue engineering. Despite drawbacks such as low hydrophilicity and lack of functional groups necessary for incorporating growth factors, it provides a proper environment for different cells, including stem cells. In our study, we aimed to improve properties of scaffolds for better cell adherence and cartilage regeneration. Thus, electrospun PCL–scaffolds were functionalized with ozone and loaded with TGF-β3. Together, human-muscle-derived stem cells (hMDSCs) were isolated and assessed for their phenotype and potential to differentiate into specific lineages. Then, hMDSCs were seeded on ozonated (O) and non-ozonated (“naïve” (NO)) scaffolds with or without protein and submitted for in vitro and in vivo experiments. In vitro studies showed that hMDSC and control cells (human chondrocyte) could be tracked for at least 14 days. We observed better proliferation of hMDSCs in O scaffolds compared to NO scaffolds from day 7 to day 28. Protein analysis revealed slightly higher expression of type II collagen (Coll2) on O scaffolds compared to NO on days 21 and 28. We detected more pronounced formation of glycosaminoglycans in the O scaffolds containing TGF-β3 and hMDSC compared to NO and scaffolds without TGF-β3 in in vivo animal experiments. Coll2-positive extracellular matrix was observed within O and NO scaffolds containing TGF-β3 and hMDSC for up to 8 weeks after implantation. These findings suggest that ozone-treated, TGF-β3-loaded scaffold with hMDSC is a promising tool in neocartilage formation.

Since early 2020, SARS-CoV-2-induced infection resulted in global pandemics with high morbidity, especially in the adult population. COVID-19 is a highly prothrombotic condition associated with subsequent multiorgan failure and lethal outcomes. The exact mechanism of the prothrombotic state is not well understood and might be multifactorial. Nevertheless, platelets are attributed to play a crucial role in COVID-19-associated thrombosis. To date, platelets' role was defined primarily in thrombosis and homeostasis. Currently, more focus has been set on their part in inflammation and immunity. Moreover, their ability to release various soluble factors under activation as well as internalize and degrade specific pathogens has been highly addressed in viral research. This review article will discuss platelet role in COVID-19-associated thrombosis and their role in the cholinergic anti-inflammatory pathway. Multiple studies confirmed that platelets display a hyperactivated phenotype in COVID-19 patients. Critically ill patients demonstrate increased platelet activation markers such as P-selectin, PF4, or serotonin. In addition, platelets contain acetylcholine and express α7 nicotinic acetylcholine receptors (α7nAchR). Thus, acetylcholine can be released under activation, and α7nAchR can be stimulated in an autocrine manner and support platelet function. α7 receptor is one of the most important mediators of the anti-inflammatory properties as it is associated with humoral and intrinsic immunity and was demonstrated to contribute to better outcomes in COVID-19 patients when under stimulation. Hematopoietic α7nAchR deficiency increases platelet activation and, in experimental studies, α7nAchR stimulation can diminish the pro-inflammatory state and modulate platelet reactiveness via increased levels of NO. NO has been described to inhibit platelet adhesion, activation, and aggregation. In addition, acetylcholine has been demonstrated to decrease platelet aggregation possibly by blocking the e p-38 pathway. SARS-CoV-2 proteins have been found to be similar to neurotoxins which can bind to nAChR and prevent the action of acetylcholine. Concluding, the platelet role in COVID-19 thrombotic events could be explained by their active function in the cholinergic anti-inflammatory pathway.

Viral infections induce extracellular vesicles (EVs) containing viral material and inflammatory factors. Exosomes can easily cross the blood-brain barrier during respiratory tract infection and transmit the inflammatory signal to the brain; however, such a hypothesis has no experimental evidence. The study investigated whether exosome-like vesicles (ELVs) from virus mimetic poly (I:C)-primed airway cells enter the brain and interact with brain immune cells microglia. Airway cells were isolated from Wistar rats and BALB/c mice; microglial cell cultures—from Wistar rats. ELVs from poly (I:C)-stimulated airway cell culture medium were isolated by precipitation, visualised by transmission electron microscopy, and evaluated by nanoparticle analyser; exosomal markers CD81 and CD9 were determined by ELISA. For in vitro and in vivo tracking, particles were loaded with Alexa Fluor 555-labelled RNA. Intracellular reactive oxygen species (ROS) were evaluated by DCFDA fluorescence and mitochondrial superoxide—by MitoSOX. ELVs from poly (I:C)-primed airway cells entered the brain within an hour after intranasal introduction, were internalised by microglia and induced intracellular and intramitochondrial ROS production. There was no ROS increase in microglial cells was after treatment with ELVs from airway cells untreated with poly (I:C). In addition, poly (I:C)-primed airway cells induced inflammatory cytokine expression in the brain. The data indicate that ELVs secreted by virus-primed airway cells might enter the brain, cause the activation of microglial cells and neuroinflammation.