Dissecting the Impact of Genetic Background on Oncogenic Response to Radiation Exposure in the Mouse Model.

Medulloblastoma (MB) is a common primary brain cancer in children. The sonic hedgehog (SHH) pathway is indispensable for the normal development of the cerebellum, and MB is often caused by persistent SHH activation owing to mutations in pathway components. Patched1 () is the primary receptor for the SHH ligand and a negative regulator of the SHH signal transduction pathway.

The DNA repair protein DNA-PKcs modulates synaptic plasticity via PSD-95 phosphorylation and stability.

The key DNA repair enzyme DNA-PKcs has several and important cellular functions. Loss of DNA-PKcs activity in mice has revealed essential roles in immune and nervous systems. In humans, DNA-PKcs is a critical factor for brain development and function since mutation of the prkdc gene causes severe neurological deficits such as microcephaly and seizures, predicting yet unknown roles of DNA-PKcs in neurons.

Role of Apolipoprotein E in the Hippocampus and Its Impact following Ionizing Radiation Exposure.

Apolipoprotein E (ApoE) is a lipid carrier in both the peripheral and the central nervous systems (CNSs). Lipid-loaded ApoE lipoprotein particles bind to several cell surface receptors to support membrane homeostasis and brain injury repair. In the brain, ApoE is produced predominantly by astrocytes, but it is also abundantly expressed in most neurons of the CNS.

Comparing the effects of irradiation with protons or photons on neonatal mouse brain: Apoptosis, oncogenesis and hippocampal alterations.

Background And Purpose: Medulloblastoma (MB) is a common primary brain cancer in children. Proton therapy in pediatric MB is intensively studied and widely adopted. Compared to photon, proton radiations offer potential for reduced toxicity due to the characteristic Bragg Peak at the end of their path in tissue.

Nanodiamond Effects on Cancer Cell Radiosensitivity: The Interplay between Their Chemical/Physical Characteristics and the Irradiation Energy.

Nanoparticles are being increasingly studied to enhance radiation effects. Among them, nanodiamonds (NDs) are taken into great consideration due to their low toxicity, inertness, chemical stability, and the possibility of surface functionalization. The objective of this study is to explore the influence of the chemical/physical properties of NDs on cellular radiosensitivity to combined treatments with radiation beams of different energies.

Setting up and managing the largest COVID-19 mass vaccination center in Lombardy, Italy.

Background: The rapid global spread of severe acute respiratory syndrome coronavirus (SARS-CoV-2) was met with the rollout of vaccination campaigns at mass vaccination centers. The Palazzo delle Scintille, Milan, was designated by the Lombardy regional administration as a vaccination site with the target of processing about 9,000 users daily.

Methods: For this observational study, we compared data on vaccinations delivered at the Palazzo delle Scintille with coronavirus disease (COVID-19)-related regional data.

Characterization of Early and Late Damage in a Mouse Model of Pelvic Radiation Disease.

Pelvic radiation disease (PRD), a frequent side effect in patients with abdominal/pelvic cancers treated with radiotherapy, remains an unmet medical need. Currently available preclinical models have limited applications for the investigation of PRD pathogenesis and possible therapeutic strategies. In order to select the most effective irradiation protocol for PRD induction in mice, we evaluated the efficacy of three different locally and fractionated X-ray exposures.

In Vivo Radiobiological Investigations with the TOP-IMPLART Proton Beam on a Medulloblastoma Mouse Model.

Protons are now increasingly used to treat pediatric medulloblastoma (MB) patients. We designed and characterized a setup to deliver proton beams for in vivo radiobiology experiments at a TOP-IMPLART facility, a prototype of a proton-therapy linear accelerator developed at the ENEA Frascati Research Center, with the goal of assessing the feasibility of TOP-IMPLART for small animal proton therapy research. Mice bearing Sonic-Hedgehog (Shh)-dependent MB in the flank were irradiated with protons to test whether irradiation could be restricted to a specific depth in the tumor tissue and to compare apoptosis induced by the same dose of protons or photons.

Gut-Brain Axis: Insights from Hippocampal Neurogenesis and Brain Tumor Development in a Mouse Model of Experimental Colitis Induced by Dextran Sodium Sulfate.

Chronic inflammatory bowel disorders (IBD) are idiopathic diseases associated with altered intestinal permeability, which in turn causes an exaggerated immune response to enteric antigens in a genetically susceptible host. A rise in psych cognitive disorders, such as anxiety and depression, has been observed in IBD patients. We here report investigations on a model of chemically induced experimental colitis by oral administration of sodium dextran sulfate (DSS) in C57BL/6 mice.

Out-of-field effects: lessons learned from partial body exposure.

Partial body exposure and inhomogeneous dose delivery are features of the majority of medical and occupational exposure situations. However, mounting evidence indicates that the effects of partial body exposure are not limited to the irradiated area but also have systemic effects that are propagated outside the irradiated field. It was the aim of the "Partial body exposure" session within the MELODI workshop 2020 to discuss recent developments and insights into this field by covering clinical, epidemiological, dosimetric as well as mechanistic aspects.

MiRNA-Mediated Fibrosis in the Out-of-Target Heart following Partial-Body Irradiation.

Recent reports have shown a link between radiation exposure and non-cancer diseases such as radiation-induced heart disease (RIHD). Radiation exposures are often inhomogeneous, and out-of-target effects have been studied in terms of cancer risk, but very few studies have been carried out for non-cancer diseases. Here, the role of miRNAs in the pathogenesis of RIHD was investigated.

Age effects on radiation response: summary of a recent symposium and future perspectives.

One of the principal uncertainties when estimating population risk of late effects from epidemiological data is that few radiation-exposed cohorts have been followed up to extinction. Therefore, the relative risk model has often been used to estimate radiation-associated risk and to extrapolate risk to the end of life. Epidemiological studies provide evidence that children are generally at higher risk of cancer induction than adults for a given radiation dose.

Long-Term Effects of Ionizing Radiation on the Hippocampus: Linking Effects of the Sonic Hedgehog Pathway Activation with Radiation Response.

Radiation therapy represents one of the primary treatment modalities for primary and metastatic brain tumors. Although recent advances in radiation techniques, that allow the delivery of higher radiation doses to the target volume, reduce the toxicity to normal tissues, long-term neurocognitive decline is still a detrimental factor significantly affecting quality of life, particularly in pediatric patients. This imposes the need for the development of prevention strategies.

Tomato Bushy Stunt Virus Nanoparticles as a Platform for Drug Delivery to Shh-Dependent Medulloblastoma.

Medulloblastoma (MB) is a primary central nervous system tumor affecting mainly young children. New strategies of drug delivery are urgent to treat MB and, in particular, the SHH-dependent subtype-the most common in infants-in whom radiotherapy is precluded due to the severe neurological side effects. Plant virus nanoparticles (NPs) represent an innovative solution for this challenge.

Facing COVID-19 Pandemic in a Tertiary Hospital in Milan: Prevalence of Burnout in Nursing Staff Working in Sub-Intensive Care Units.

In early March 2020, Italy became the epicenter of the Coronavirus Disease 2019 (COVID-19) pandemic in Europe. A different organization of hospital units was required to take care of patients affected by acute respiratory failure caused by COVID-19. This study aimed to evaluate the prevalence of burnout in two sub-intensive care units (SICUs) of the COVID-19 hub center of the Lombardia region in Milan (Italy).

Radiation-Induced Lens Opacity and Cataractogenesis: A Lifetime Study Using Mice of Varying Genetic Backgrounds.

Recent epidemiological findings and reanalysis of historical data suggest lens opacities resulting from ionizing radiation exposures are likely induced at lower doses than previously thought. These observations have led to ICRP recommendations for a reduction in the occupational dose limits for the eye lens, as well as subsequent implementation in EU member states. The EU CONCERT LDLensRad project was initiated to further understand the effects of ionizing radiation on the lens and identify the mechanism(s) involved in radiation-induced cataract, as well as the impact of dose and dose-rate.

Out-of-Field Hippocampus from Partial-Body Irradiated Mice Displays Changes in Multi-Omics Profile and Defects in Neurogenesis.

The brain undergoes ionizing radiation exposure in many clinical situations, particularly during radiotherapy for brain tumors. The critical role of the hippocampus in the pathogenesis of radiation-induced neurocognitive dysfunction is well recognized. The goal of this study is to test the potential contribution of non-targeted effects in the detrimental response of the hippocampus to irradiation and to elucidate the mechanisms involved.

miRNA-Signature of Irradiated Ptch1+/- Mouse Lens is Dependent on Genetic Background.

One harmful long-term effect of ionizing radiation is cataract development. Recent studies have been focused on elucidating the mechanistic pathways involved in this pathogenesis. Since accumulating evidence has established a role of microRNAs in ocular diseases, including cataract, the goal of this work was to determine the microRNA signature of the mouse lens, at short time periods postirradiation, to understand the mechanisms related to radio-induced cataractogenesis.

Contribution of Genetic Background to the Radiation Risk for Cancer and Non-Cancer Diseases in Ptch1+/- Mice.

Experimental mouse studies are important to gain a comprehensive, quantitative and mechanistic understanding of the biological factors that modify individual risk of radiation-induced health effects, including age at exposure, dose, dose rate, organ/tissue specificity and genetic factors. In this study, neonatal Ptch1+/- mice bred on CD1 and C57Bl/6 background received whole-body irradiation at postnatal day 2. This time point represents a critical phase in the development of the eye lens, cerebellum and dentate gyrus (DG), when they are also particularly susceptible to radiation effects.

Radiation-induced DNA Damage and Repair in Lens Epithelial Cells of both Ptch1(+/-) and Ercc2(+/-) Mutated Mice.

Epidemiological studies suggest an increased incidence and risk of cataract after low-dose (<2 Gy) ionizing radiation exposures. However, the biological mechanism(s) of this process are not fully understood. DNA damage and repair are thought to have a contributing role in radiation-induced cataractogenesis.

Cognitive effects of low dose of ionizing radiation - Lessons learned and research gaps from epidemiological and biological studies.

The last decades have seen increased concern about the possible effects of low to moderate doses of ionizing radiation (IR) exposure on cognitive function. An interdisciplinary group of experts (biologists, epidemiologists, dosimetrists and clinicians) in this field gathered together in the framework of the European MELODI workshop on non-cancer effects of IR to summarise the state of knowledge on the topic and elaborate research recommendations for future studies in this area. Overall, there is evidence of cognitive effects from low IR doses both from biology and epidemiology, though a better characterization of effects and understanding of mechanisms is needed.