A Pilot Prospective Study Evaluating the Effect of Curcuma-Based Herbal Food Supplement on the Outcome of In Vitro Fertilization in Patients Testing Positive for Four Immunological Biomarkers

Background and Objectives: Inflammation and oxidative stress have been described to reduce the chance for pregnancy instauration and maintenance. NOFLAMOX, a recently developed herbal preparation with recognized antioxidant and anti-inflammatory properties, can represent an interesting treatment to increase the chance of pregnancy, both physiological or after in vitro fertilization (IVF). The aim of this study was to assess NOFLAMOX’s effect; a population with unexplained infertility was screened for the recently described IMMUNOX panel based on four immunological biomarkers with a prospective study approach. Materials and Methods: Patients with unexplained infertility and positive for at least one of the biomarkers of the IMMUNOX panel were included in this study and treated with NOFLAMOX for three months prior to an IVF cycle. Results: Eighty-six patients (n = 86) were screened with the IMMUNOX panel and the forty-seven (54.5%) found positive were included in this study. In more detail, 11 were positive for TNFα (23.4%), 18 (38.3%) for glycodelin (GLY), 29 (61.7%) for Total Oxidative Status (TOS), and 32 (68.1%) for Complement Activity Toxic Factor (CATF). After three months of treatment, a significant reduction in the number of IMMUNOX-positive patients was observable, with 26 patients who turned IMMUNOX-negative displaying a quantitative statistically significant variation of 100% (11/11), 38.9% (7/18), 65.5% (18/29), and 75% (24/32), for TNFα, glycodelin, TOS, and CATF, respectively. Followed in the subsequent IVF cycle, this NOFLAMOX-treated population showed a pregnancy rate of 42.3% compared to the 4.7% of the IMMUNOX-positive group of patients. Conclusions: Taken together, the results of this study suggest that NOFLAMOX could represent an interesting option for those patients with unexplained infertility of inflammatory/oxidative origin. Further studies are needed to confirm these results and explore possible strategies to restore fertility in women with immune-mediated sterility

225Ac-DOTA-Substance P as a potential radiopharmaceutical for targeted alpha therapy of glioblastoma multiforme

Gliomas, particularly WHO grade IV glioblastoma multiforme (GBM) are one of the most common and aggressive primary types of the cancer of the central nervous system and are composed of morphologically diverse population of cells in the tumour mass. Despite all current forms of treatment such as advanced surgery techniques, radiation therapy and chemotherapy, the life expectancy of patients diagnosed with GBM is 12 to 15 months displaying the worst median overall survival among all human neoplasms. Targeted alpha therapy has been shown to overcome chemo- and radioresistance in vitro and thus presents a promising new approach for therapy of GBM. The findings that high affinity Substance P receptor NK1 is high consistently expressed in primary malignant gliomas and in the intratumoral and peritumoral vasculature makes this receptor a very attractive target for glioma cancer therapy.JRC.G.I.5-Advanced Nuclear Knowledg

In vitro evaluation of 225Ac-DOTA-Substance P for targeted alpha therapy of glioblastoma multiforme

Glioblastoma multiforme (GBM) is the most malignant form of brain tumors with dismal prognosis despite treatment by surgery combined with radiotherapy and chemotherapy. The neuropeptide Substance P (SP) is the physiological ligand of the neurokinin‐1 receptor, which is highly expressed in glioblastoma cells. Thus, SP represents a potential ligand for targeted alpha therapy. In this study, a protocol for the synthesis of SP labeled with the alpha emitter 225Ac was developed and binding affinity properties were determined. The effects of 225Ac‐DOTA‐SP were investigated on human glioblastoma cell lines (T98G, U87MG, U138MG) as well as GBM stem cells. A significant dose‐dependent reduction in cell viability was detected up to 6 days after treatment. Also, colony‐forming capacity was inhibited at the lower doses tested. In comparison, treatment with the conventional agent temozolomide showed higher cell viability and colony‐forming capacity. 225Ac‐DOTA‐SP treatment caused induction of late apoptosis pathways. Cells were arrested to G2/M‐phase upon treatment. Increasing doses and treatment time caused additional S‐phase arrest. Similar results were obtained using human glioblastoma stem cells, known to show radioresistance. Our data suggest that 225Ac‐DOTA‐SP is a promising compound for treatment of GBM.JRC.G.I.5-Advanced Nuclear Knowledg

Improvement rate of patients with severe brain injury during post-acute intensive rehabilitation

Patients with severe acquired brain injury (SABI) may evolve towards different outcomes. The primary aim was to evaluate the clinical evolution of a large population of patients with SABI admitted to post-acute rehabilitation from 2001 to 2016, diagnosed with severe brain injury (GCS ≤ 8) in the acute phase and a coma duration of at least 24 h. The possible changes between the admission time to a post-acute rehabilitation hospital and the discharge time were measured by means of Glasgow Outcome Scale (GOS), Level of Cognitive Functioning (LCF), and Disability Rating Scale (DRS). We also correlated the improvement rate with some sociodemographic and clinical features of the individuals with SABI enrolled. Data of 890 patients were analyzed (54% TBI, length of stay = 162 ± 186 days, GCS = 7.46 ± 1.28); time interval from the SABI (OR = 0.246, CI 95% = 0.181 – 0.333), scores at admission of LCF (OR = 2.243, CI 95% = 1.492 – 3.73), GOS (OR = 0.138, CI 95% = 0.071 – 0.266), DRS (OR = 0.457, CI 95% = 0.330 – 0.632), and etiology (OR = 2.273, CI 95% = 1.676 – 3.084) played a significant role (p < 0.001, explained variance 69.9%) for improving GOS score. Time interval from the SABI to admission in our post-acute rehabilitation ward (OR = 0.300, CI 95% = 0.179 – 0.501, p < 0.001), length of rehabilitation stay (OR = 2.808, CI 95% = 1.694 – 4.653, p < 0.001), and etiology (OR = 1.769, CI 95% = 1.095 – 2.857, p = 0.020) led to a statistically significant improvement in DRS (explained variance 91%). The most significant predictive factors for the outcome of patients with SABI were etiology, time interval from SABI to admission in rehabilitation, and length of rehabilitation stay

The Drift Chamber detector of the FOOT experiment: Performance analysis and external calibration

The study that we present is part of the preparation work for the setup of the FOOT (FragmentatiOn Of Target) experiment whose main goal is the measurement of the double differential cross sections of fragments produced in nuclear interactions of particles with energies relevant for particle therapy. The present work is focused on the characterization of the gas-filled drift chamber detector composed of 36 sensitive cells, distributed over two perpendicular views. Each view consists of six consecutive and staggered layers with three cells per layer. We investigated the detector efficiency and we performed an external calibration of the space–time relations at the level of single cells. This information was then used to evaluate the drift chamber resolution. An external tracking system realized with microstrip silicon detectors was adopted to have a track measurement independent on the drift chamber. The characterization was performed with a proton beam at the energies of 228 and 80 MeV. The overall hit detection efficiency of the drift chamber has been found to be 0.929±0.008 , independent on the proton beam energy. The spatial resolution in the central part of the cell is about 150±10 μ m and 300±10 μ m and the corresponding detector angular resolution has been measured to be 1.62±0.16 mrad and 2.1±0.4 mrad for the higher and lower beam energies, respectively. In addition, the best value on the intrinsic drift chamber resolution has been evaluated to be in the range 60−100 μ m. In the framework of the FOOT experiment, the drift chamber will be adopted in the pre-target region, and will be exploited to measure the projectile direction and position, as well as for the identification of pre-target fragmentation events

Characterization of 150 μm\mu m thick silicon microstrip prototype for the FOOT experiment

International audienceThe goals of the FOOT (FragmentatiOn Of Target) experiment are to measure the proton double differential fragmentation cross-section on H, C, O targets at beam energies of interest for hadrontherapy (50–250 MeV for protons and 50–400 MeV/u for carbon ions), and also at higher energy, up to 1 GeV/u for radioprotection in space. Given the short range of the fragments, an inverse kinematic approach has been chosen, requiring precise tracking capabilities for charged particles. One of the subsystems designed for the experiment will be the MSD (Microstrip Silicon Detector), consisting of three x-y measurement planes, each one made by two single sided silicon microstrip sensors. In this document, we will present a detailed description of the first MSD prototype assembly, developed by INFN Perugia group and the subsequent characterization of the detector performance. The prototype is a wide area(∼ 100 cm$^{2}$) single sensor, 150 μm thick to reduce material budget and fragmentation probability along the beam path, with 50 μm strip pitch and 2 floating strip readout approach. The pitch adapter to connect strips with the readout channels of the ASIC has been implemented directly on the silicon surface. Beside the interest for the FOOT experiment, the results in terms of cluster signal, signal-to-noise ratio, dynamic range of the readout chips, as well as long-term stability studies in terms of noise, are relevant also for other experiments where the use of thin sensors is crucial

Characterization of 150 μm thick silicon microstrip prototype for the FOOT experiment

International audienceThe goals of the FOOT (FragmentatiOn Of Target) experiment are to measure the proton double differential fragmentation cross-section on H, C, O targets at beam energies of interest for hadrontherapy (50–250 MeV for protons and 50–400 MeV/u for carbon ions), and also at higher energy, up to 1 GeV/u for radioprotection in space. Given the short range of the fragments, an inverse kinematic approach has been chosen, requiring precise tracking capabilities for charged particles. One of the subsystems designed for the experiment will be the MSD (Microstrip Silicon Detector), consisting of three x-y measurement planes, each one made by two single sided silicon microstrip sensors. In this document, we will present a detailed description of the first MSD prototype assembly, developed by INFN Perugia group and the subsequent characterization of the detector performance. The prototype is a wide area(∼ 100 cm$^{2}$) single sensor, 150 μm thick to reduce material budget and fragmentation probability along the beam path, with 50 μm strip pitch and 2 floating strip readout approach. The pitch adapter to connect strips with the readout channels of the ASIC has been implemented directly on the silicon surface. Beside the interest for the FOOT experiment, the results in terms of cluster signal, signal-to-noise ratio, dynamic range of the readout chips, as well as long-term stability studies in terms of noise, are relevant also for other experiments where the use of thin sensors is crucial