Immunomodulation in pediatric asthma

Childhood asthma is actually defined as a heterogeneous disease, including different clinical variants and partially sharing similar immune mechanisms. Asthma management is mainly focused on maintaining the control of the disease and reducing the risk of adverse outcomes. Most children achieve good control with standard therapies, such as low doses of inhaled corticosteroids (ICS) and/or one or more controller. These medications are targeted to suppress bronchial inflammation and to restore airway responsiveness. However, they are not disease-modifying and do not specifically target inflammatory pathways of asthma; in addition, they are not significantly effective in patients with severe uncontrolled asthma. The aim of this review is to update knowledge on current and novel therapeutic options targeted to immunomodulate inflammatory pathways underlying pediatric asthma, with particular reference on biologic therapies

Deliveries by caesarean sections on request of women: legal-medical evidence

Introduction: In Italy the use of caesarean delivery has a rising trend moving away from European standards appeared on Euro-Peristat on maternal and child health, presenting the highest percentage of use of this procedure with significant regional differences. This study have analyzed the most recent data of a Sicilian reality about normal delivery and caesarean sections carried out in a hospital situated in Messina (Italy). Materials and methods: A total number of 1,573 medical records from 1st January 2011 to 31st December 2013 were analyzed and data gathered were statistically examined to describe general and specific parameters of the sample making use of Epi Info 7.1.4 software (CDC Atlanta – USA). Chi-square test was used to show any statistic differences among studied population. Results: Overall data showed that were carried out 38.27% of spontaneous deliveries, 7.06% of induced labor, and 54.67% of caesarean deliveries. There were no significant statistical differences between recourse to caesarean section and vaginal delivery in relation to nationality, age, level of education and/or work. The enrolled group, based on the parameters examined, was divided into appropriate caesarean section, in 79.49% of cases, inappropriate in 7.20% (mother’s request) and unjustified in 13.31% (with no indication, incomplete medical record). An examination of the anesthetic medical records showed that the caesarean section was considered to be urgent in 31.74% of the cases; however in 17.92% of these cases there is no information in the medical records justifying the use of emergency procedures. Conclusion: The reported data from the study that we conducted, lead to medical-legal and juridical considerations, especially as regards the use of caesarean delivery on the woman request. The complexity of the phenomenon requires the development of a variety of intervention strategies, not only for issues related to the reduction of health care costs, but also with regard to the clinical risk management and medical legal aspects related to the several profiles of professional responsibility

Food allergies: Current and future treatments

Food allergies are an increasingly public health problem, affecting up to 10% of children and causing a significant burden on affected patients, resulting in dietary restrictions, fear of accidental ingestion and related risk of severe reactions, as well as a reduced quality of life. Currently, there is no specific cure for a food allergy, so the only available management is limited to strict dietary avoidance, education on prompt recognition of symptoms, and emergency treatment of adverse reactions. Several allergen specific-and nonspecific-therapies, aiming to acquire a persistent food tolerance, are under investigation as potential treatments; however, to date, only immunotherapy has been identified as the most promising therapeutic approach for food allergy treatment. The aim of this review is to provide an updated overview on changes in the treatment landscape for food allergies

Evaluation of Proton-Induced Biomolecular Changes in MCF-10A Breast Cells by Means of FT-IR Microspectroscopy

Radiotherapy (RT) with accelerated beams of charged particles (protons and carbon ions), also known as hadrontherapy, is a treatment modality that is increasingly being adopted thanks to the several benefits that it grants compared to conventional radiotherapy (CRT) treatments performed by means of high-energy photons/electrons. Hence, information about the biomolecular effects in exposed cells caused by such particles is needed to better realize the underlying radiobiological mechanisms and to improve this therapeutic strategy. To this end, Fourier transform infrared microspectroscopy (µ-FT-IR) can be usefully employed, in addition to long-established radiobiological techniques, since it is currently considered a helpful tool for examining radiation-induced cellular changes. In the present study, MCF-10A breast cells were chosen to evaluate the effects of proton exposure using µ-FT-IR. They were exposed to different proton doses and fixed at various times after exposure to evaluate direct effects due to proton exposure and the kinetics of DNA damage repair. Irradiated and control cells were examined in transflection mode using low-e substrates that have been recently demonstrated to offer a fast and direct way to examine proton-exposed cells. The acquired spectra were analyzed using a deconvolution procedure and a ratiometric approach, both of which showed the different contributions of DNA, protein, lipid, and carbohydrate cell components. These changes were particularly significant for cells fixed 48 and 72 h after exposure. Lipid changes were related to variations in membrane fluidity, and evidence of DNA damage was highlighted. The analysis of the Amide III band also indicated changes that could be related to different enzyme contributions in DNA repair

SPADA: A project to study the effectiveness of shielding materials in space

The SPADA (SPAce Dosimetry for Astronauts) project is a part of an extensive teamwork that aims to optimize shielding solutions against space radiation. Shielding is indeed an irreplaceable tool to reduce exposure of crews of future Moon and Mars missions. We concentrated our studies on two flexible materials, Kevlar R� and Nextel R,� because of their ability to protect human space infrastructures from micrometeoroids. We measured radiation hardness of these shielding materials and compared to polyethylene, generally acknowledged as the most effective space radiation shield with practical applications in spacecraft. Both flight test (on the International Space Station and on the Russian FOTON M3 rocket), with passive dosimeters and accelerator-based experiments have been performed. Accelerator tests using high-energy Fe ions have demonstrated that Kevlar is almost as effective as polyethylene in shielding heavy ions, while Nextel is a poor shield against high-charge and -energy particles. Preliminary results from spaceflight, however, show that for the radiation environment in low-Earth orbit, dominated by trapped protons, thin shields of Kevlar and Nextel provide limited reduction

Biologic drugs in chronic spontaneous urticaria

Chronic spontaneous urticaria (CSU) is a condition defined by the presence of recurrent urticaria, angioedema, or both, which persist for more than six weeks in duration and occurs in the absence of an identifiable trigger. Both children and adults can develop CSU, although it is more common in adults and in women than in men, with a peak occurrence in the third to fifth decades of life. It imposes a significant burden on patients, families and healthcare systems. The goal of therapy in patients with CSU is to achieve a level of symptom control and improvement in quality of life that is acceptable to the patient, while minimizing therapy-related side effects. The recent introduction of biologic drugs has changed the management of the disease. This work aims to provide a narrative review of the current state of biological therapy and the promising drugs under development for CSU

Radiobiological outcomes, microdosimetric evaluations and monte carlo predictions in eye proton therapy

CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) was the first Italian protontherapy facility dedicated to the treatment of ocular neoplastic pathologies. It is in operation at the LNS Laboratories of the Italian Institute for Nuclear Physics (INFN-LNS) and to date, 500 patients have been successfully treated. Even though proton therapy has demonstrated success in clinical settings, there is still a need for more accurate models because they are crucial for the estimation of clinically relevant RBE values. Since RBE can vary depending on several physical and biological parameters, there is a clear need for more experimental data to generate predictions. Establishing a database of cell survival experiments is therefore useful to accurately predict the effects of irradiations on both cancerous and normal tissue. The main aim of this work was to compare RBE values obtained from in-vitro experimental data with predictions made by the LEM II (Local Effect Model), Monte Carlo approaches, and semi-empirical models based on LET experimental measurements. For this purpose, the 92.1 uveal melanoma and ARPE-19 cells derived from normal retinal pigmented epithelium were selected and irradiated in the middle of clinical SOBP of the CATANA proton therapy facility. The remarkable results show the potentiality of using microdosimetric spectrum, Monte Carlo simulations and LEM model to predict not only the RBE but also the survival curves

The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives

Protontherapy is a rapidly expanding radiotherapy modality where accelerated proton beams are used to precisely deliver the dose to the tumor target but is generally considered ineffective against radioresistant tumors. Proton-Boron Capture Therapy (PBCT) is a novel approach aimed at enhancing proton biological effectiveness. PBCT exploits a nuclear fusion reaction between low-energy protons and 11B atoms, i.e. p+11B→ 3α (p-B), which is supposed to produce highly-DNA damaging α-particles exclusively across the tumor-conformed Spread-Out Bragg Peak (SOBP), without harming healthy tissues in the beam entrance channel. To confirm previous work on PBCT, here we report new in-vitro data obtained at the 62-MeV ocular melanoma-dedicated proton beamline of the INFN-Laboratori Nazionali del Sud (LNS), Catania, Italy. For the first time, we also tested PBCT at the 250-MeV proton beamline used for deep-seated cancers at the Centro Nazionale di Adroterapia Oncologica (CNAO), Pavia, Italy. We used Sodium Mercaptododecaborate (BSH) as 11B carrier, DU145 prostate cancer cells to assess cell killing and non-cancer epithelial breast MCF-10A cells for quantifying chromosome aberrations (CAs) by FISH painting and DNA repair pathway protein expression by western blotting. Cells were exposed at various depths along the two clinical SOBPs. Compared to exposure in the absence of boron, proton irradiation in the presence of BSH significantly reduced DU145 clonogenic survival and increased both frequency and complexity of CAs in MCF-10A cells at the mid- and distal SOBP positions, but not at the beam entrance. BSH-mediated enhancement of DNA damage response was also found at mid-SOBP. These results corroborate PBCT as a strategy to render protontherapy amenable towards radiotherapy-resilient tumor. If coupled with emerging proton FLASH radiotherapy modalities, PBCT could thus widen the protontherapy therapeutic index