Radioprotection for Astronauts' Missions: Numerical Results on the Nomex Shielding Effectiveness.

Space missions with humans expose the crews to ionizing radiation, mainly due to the galactic cosmic radiation (GCR). All radiation protection programs in space aim to minimize crews' exposure to radiation. The radiation protection of astronauts can be achieved through the use of shields. The shields could serve as a suit to reduce GCR exposure and, in an emergency, as a radiation shelter to perform necessary interventions outside the space habitat in case of a solar proton event (SPE). A space radiation shielding that is suitable for exploration during space missions requires particular features and a proper knowledge of the radiation type. This study shows the results of numerical simulations performed with the Geant4 toolkit-based code DOSE. Calculations to evaluate the performance of Nomex, an aramidic fiber with high mechanical resistance, in terms of dose reduction to crews, were performed considering the interaction between protons with an energy spectrum ranging from 50 to 1100 MeV and a target slab of 20 g/cm2. This paper shows the properties of secondary products obtained as a result of the interaction between space radiation and a Nomex target and the properties of the secondary particles that come out the shield. The results of this study show that Nomex can be considered a good shield candidate material in terms of dose reductions. We also note that the secondary particles that provide the greatest contribution to the dose are protons, neutrons and, in a very small percentage, α-particles and Li ions.

Initial Testing of an Approximated, Fast Calculation Procedure for Personalized Dosimetry in Radionuclide Therapy Based on Planar Whole-Body Scan and Monte-Carlo Specific Dose Rates from the OpenDose Project.

Individualized dosimetry in nuclear medicine is currently at least advisable in order to obtain the best risk-benefit balance in terms of the maximal dose to lesions and under-threshold doses to radiosensitive organs. This article aims to propose a procedure for fast dosimetric calculations based on planar whole-body scintigraphy (WBS) images and developed to be employed in everyday clinical practice. METHODS: For simplicity and legacy reasons, the method is based on planar imaging dosimetry, complemented with some assumptions on the radiopharmaceutical kinetics empirically derived from single-photon emission tomography/computed tomography (SPECT/CT) image analysis. The idea is to exploit a rough estimate of the time-integrated activity as has been suggested for SPECT/CT dosimetry but using planar images. The resulting further reduction in dose estimation accuracy is moderated by the use of a high-precision Monte-Carlo S-factor, such as those available within the OpenDose project. RESULTS: We moved the problem of individualized dosimetry to a transformed space where comparing doses was imparted to the ICRP Average Male/Female computational phantom, resulting from an activity distribution related to patient's pharmaceutical uptake. This is a fast method for the personalized dosimetric evaluation of radionuclide therapy, bearing in mind that the resulting doses are meaningful in comparison with thresholds calculated in the same framework. CONCLUSION: The simplified scheme proposed here can help the community, or even the single physician, establish a quantitative guide-for-the-eye approach to individualized dosimetry.

SBRT for Localized Prostate Cancer: CyberKnife vs. VMAT-FFF, a Dosimetric Study.

In recent years, stereotactic body radiation therapy (SBRT) has gained popularity among clinical methods for the treatment of medium and low risk prostate cancer (PCa), mainly as an alternative to surgery. The hypo-fractionated regimen allows the administration of high doses of radiation in a small number of fractions; such a fractionation is possible by exploiting the different intrinsic prostate radiosensitivity compared with the surrounding healthy tissues. In addition, SBRT treatment guaranteed a better quality of life compared with surgery, avoiding risks, aftermaths, and possible complications. At present, most stereotactic prostate treatments are performed with the CyberKnife (CK) system, which is an accelerator exclusively dedicated for stereotaxis and it is not widely spread in every radiotherapy centre like a classic linear accelerator (LINAC). To be fair, a stereotactic treatment is achievable also by using a LINAC through Volumetric Modulated Arc Therapy (VMAT), but some precautions must be taken. The aim of this work is to carry out a dosimetric comparison between these two methodologies. In order to pursue such a goal, two groups of patients were selected at Instituto Nazionale Tumori-IRCCS Fondazione G. Pascale: the first group consisting of ten patients previously treated with a SBRT performed with CK; the second one was composed of ten patients who received a hypo-fractionated VMAT treatment and replanned in VMAT-SBRT flattening filter free mode (FFF). The two SBRT techniques were rescaled at the same target coverage and compared by normal tissue sparing, dose distribution parameters and delivery time. All organs at risk (OAR) constraints were achieved by both platforms. CK exhibits higher performances in terms of dose delivery; nevertheless, the general satisfying dosimetric results and the significantly shorter delivery time make VMAT-FFF an attractive and reasonable alternative SBRT technique for the treatment of localized prostate cancer.

Dose-Tracking Software: A Retrospective Analysis of Dosimetric Data in CT Procedures.

ABSTRACT: The increasing use of ionizing radiation in healthcare is causing growing alarm about radiation protection of patients and the doses they receive during procedures. Radiation dose assessment for patients in radiodiagnostic procedures is the subject of interest in view of the recent Italian D.Lgs 31 July 2020, n. 101 (Decreto Legislativo 31 luglio 2020, n. 101) and one of its most important focuses is the prescription to provide patient exposure information as an integral part of the examination report. Dose monitoring systems are therefore essential for the collection of the dosimetric data. In order to analyse potential and critical issues of these software, different systems, adopted at the Antonio Cardarelli Hospital in Naples, were employed. Data extracted from the DoseWatch software (GE Healthcare) and Gray Detector (EL.CO. S.r.l. Healthcare Solutions, Italy) and relating to several protocols adopted for computed tomography (CT), were retrospectively analysed for the purpose of identifying critical issues in the data acquisition and recording phase, comparing with Italian nationwide diagnostic reference levels (DRLs), as provided for in regulatory provisions for radiation safety. Multiphase examinations were also included in this study. Once the distributions of volumetric CT Dose Index (CTDIvol) and dose-length product (DLP) were determined for each acquisition phase and total DLP (DLPtot) for each examination, the 25th, 50th and 75th percentiles were calculated for each distribution and then compared with the relevant Italian nationwide DRLs. In addition, to improve protocol optimization and dose reduction the magnitude of the CT acquisition settings chosen in each procedure was evaluated. In conclusion, these systems allow accurate analysis of radiation dose according to equipment and protocol over time. For the application of optimization measures, a constant use of the dose tracking software is required, which can be translated into actions on scan parameters and prospective data analysis.

Indoor Radon Concentration and Risk Assessment in 27 Districts of a Public Healthcare Company in Naples, South Italy.

Radon is a major source of ionizing radiation exposure for the general population. It is known that exposure to radon is a risk factor for the onset of lung cancer. In this study, the results of a radon survey conducted in all districts of a Public Healthcare in Italy, are reported. Measurements of indoor radon were performed using nuclear track detectors, CR-39. The entire survey was conducted according to a well-established quality assurance program. The annual effective dose and excess lifetime cancer risk were also calculated. Results show that the radon concentrations varied from 7 ± 1 Bq/m3 and 5148 ± 772 Bq/m3, with a geometric mean of 67 Bq/m3 and geometric standard deviation of 2.5. The annual effective dose to workers was found to be 1.6 mSv/y and comparable with the worldwide average. In Italy, following the transposition of the European Directive 59/2013, great attention was paid to the radon risk in workplaces. The interest of the workers of the monitored sites was very high and this, certainly contributed to the high return rate of the detectors after exposure and therefore, to the presence of few missing data. Although it was not possible to study the factors affecting radon concentrations, certainly the main advantage of this study is that it was the first in which an entire public health company was monitored in regards to all the premises on the underground and ground floor.

Dosimetric comparison among cyberknife, helical tomotherapy and VMAT for hypofractionated treatment in localized prostate cancer.

Hypofractionation for localized prostate cancer treatment is rapidly spreading in the medical community and it is supported by radiobiological evidences (lower α/ß ratio compared with surrounding tissues). Stereotactic body radiation therapy (SBRT) is a technique to administer high doses with great precision, which is commonly performed with CyberKnife (CK) in prostate cancer treatment. Since the CyberKnife (CK) is not available at all radiotherapy center, alternative SBRT techniques are available such as Volumetric Modulated Arc Therapy (VMAT) and Helical Tomotherapy (HT). The aim of the present study was to compare the dosimetric differences between the CK, VMAT, and HT plans for localized prostate cancer treatment.Seventeenpatients have been recruited and replanned using VMAT and HT to this purpose: they received the treatment using the CK with a prescription of 36.25 Gy in 5 fractions; bladder, rectum and penis bulb were considered as organs at risk (OAR). In order to compare the techniques, we considered DVHs, PTV coverage, Conformity Index and new Conformity Index, Homogeneity Index, beam-on time and OARs received dose.The 3 treatments methods showed a comparable coverage of the lesion (PTV 95%: 99.8 ± 0.4% CK; 98.5 ± 0.8% VMAT; 99.4 ±â€Š0.5% HT. P < .05) and good sparing of OARs. Nevertheless, the beam-on time showed a significant difference (37 ±â€Š9 m CK; 7.1 ±â€Š0.3 m VMAT; 17 ±â€Š2 m HT. P < .05).Our results showed that, although CK is the best SBRT technique for prostate cancer treatment, in case this technology is not available, it can be replaced by a similar treatment delivered by VMAT technique. VMAT can be administrated only if it has an appropriate Image Guided Radiation Therapy (IGRT) tracking system.

CHARACTERIZATION OF A SMALL FOV PORTABLE GC: MediPROBE.

In this work, we evaluated the performance of the prototype SFOV MediPROBE developed at the University of Naples Federico II through the protocol proposed by (Bhatia B.S., Bugby S.L., Lees J.E., Perkins A.C. A scheme for assessing the performance characteristics of a small field of-view gamma cameras. Physica. Medica., 31 (1), pp. 98-103. (2015) doi: 10.1016/j.ejmp.2014.08.004). We extensively investigated a new device configuration where the pinhole collimator was placed outside the housing of the probe, in order to increase the system spatial resolution, and the pixel size was doubled, in order to reduce the charge sharing effect. The experimental measurements show that the spatial resolution is enhanced by only about 10%, but the sensitivity decreases strongly. Therefore, the trade-off between these two features does not seem to be advantageous. In addition, our experiments suggest that the charge sharing effect is not completely canceled. Despite these results, the features of this device appear suitable for intraoperative surgical survey. We aim to use this device in the clinical practice for the intraoperative imaging of lymph nodes, breast, thyroid and parathyroid tumors.

Evaluation of Dose Homogeneity in Cone-Beam Breast Computed Tomography.

The aim of this study is to determine, via measurements on phantoms and Monte Carlo (MC) simulations, the dose distribution of absorbed dose in a cone-beam breast computed tomography scan. The absorbed dose volume distribution was measured inside a polyethylene cylindrical phantom, simulating adipose breast tissue, using LiF:Mg,Ti thermoluminescence dosimeters. A reasonable agreement (between 2 and 8%) between the simulated and measured data was observed. The 3D distribution of absorbed dose was evaluated at 40, 60 and 80 kV in a phantom simulating a pendant breast. MC simulations indicate a significantly lower spread of volume dose than in mammography. The dose variation along the radial distance in the simulated phantoms was in the range of 4‒14%. These findings might be useful when devising models for breast imaging dose assessment that take into account the uneven distribution of the glandular mass in the breast volume.

X-rays effects on cytoskeleton mechanics of healthy and tumor cells.

Alterations in the cytoskeleton structure are frequently found in several diseases and particularly in cancer cells. It is also through the alterations of the cytoskeleton structure that cancer cells acquire most of their common features such as uncontrolled cell proliferation, cell death evasion, and the gaining of migratory and invasive characteristics. Although radiation therapies currently represent one of the most effective treatments for patients, the effects of X-irradiation on the cytoskeleton architecture are still poorly understood. In this case we investigated the effects, over time of two different doses of X-ray irradiation, on cell cytoskeletons of BALB/c3T3 and Sv40-transformed BALB/c 3T3 cells (SVT2). Biophysical parameters - focal adhesion size, actin bundles organization, and cell mechanical properties - were measured before and after irradiations (1 and 2 Gy) at 24 and 72 h, comparing the cytoskeleton properties of normal and transformed cells. The differences, before and after X-irradiation, were revealed in terms of cell morphology and deformability. Finally, such parameters were correlated to the alterations of cytoskeleton dynamics by evaluating cell adhesion at the level of focal adhesion and cytoskeleton mechanics. X-irradiation modifies the structure and the activity of cell cytoskeleton in a dose-dependent manner. For transformed cells, radiation sensitively increased cell adhesion, as indicated by paxillin-rich focal adhesion, flat morphology, a well-organized actin cytoskeleton, and intracellular mechanics. On the other hand, for normal fibroblasts IR had negligible effects on cytoskeletal and adhesive protein organization. © 2016 Wiley Periodicals, Inc.

The Impact of Social and Cultural Engagement and Dieting on Well-Being and Resilience in a Group of Residents in the Metropolitan Area of Naples.

Social isolation and exclusion are associated with poor health status and premature death. A number of related isolation factors, inadequate transportation system and restrictions in individuals' life space, have been associated with malnutrition in older adults. Since eating is a social event, isolation can have a negative effect on nutrition. Cultural involvement and participation in interactive activities are essential tools to fight social isolation, and they can counteract the detrimental effects of social isolation on health. To provide data supporting the hypothesis that encouraging participation might represent an innovative preventive and health promoting strategy for healthy living and aging, we developed an ad hoc questionnaire to investigate the relationship between cultural participation, well-being, and resilience in a sample of residents in the metropolitan area of Naples. The questionnaire includes a question on adherence to diet or to a special nutritional regimen; in addition, the participants are asked to mention their height and weight. We investigated the relationship between BMI, adherence to diet, and perceived well-being (PWB) and resilience in a sample of 571 subjects over 60 years of age. Here, we present evidence that engagement into social and cultural activities is associated with higher well-being and resilience, in particular in females over 60 years of age.

Indoor radon activity concentration measurements in the great historical museums of University of Naples, Italy.

Indoor radon activity concentrations were measured in seven Museums of University of Naples, very old buildings of great historical value. The measurements were performed using a time-integrated technique based on LR-115 solid-state nuclear track detectors. The annual average concentrations were found to range from 40 up to 1935 Bq m(-3) and in 26 % of measurement sites, the values were higher than 500 Bq m(-3) which is the limit value of Italian legislation for workplace. Moreover, we analysed the seasonal variations of radon concentrations observing the highest average in cold weather than in warm.

Radon Exposure Assessment and Relative Effective Dose Estimation to Inhabitants of Puglia Region, South Italy.

Indoor radon concentrations were measured in dwellings of the Puglia region in Southern Italy using LR-115 passive detectors. The results show that the radon concentrations varied from 15 ± 2 to 2166 ± 133 Bq/m³ with a geometric mean of 114 Bq/m³ and a geometric standard deviation of 2.3. An analysis on the factors affecting radon concentration such as age of the dwellings, floors, and stories, was performed. The mean effective dose to inhabitants has been calculated and found to be 8.2 mSv/y. Finally, for estimation of cancer risks, the lifetime risk and lung cancer cases per years per million have been calculated.

Indoor radon concentration measurements in some dwellings of the Penisola Sorrentina, South Italy.

In this study, the indoor radon concentrations have been measured in 93 dwellings of the Penisola Sorrentina, using LR115 detectors. The detectors were placed in the bedrooms and living rooms for two consecutive semesters starting from December 2010 to December 2011. The annual average indoor radon concentrations vary from 25 to 722 Bq m(-3), with a mean value of 132 ± 114 Bq m(-3). Correlation between indoor radon measurements and same building characteristics was also studied. Based on the obtained results, the mean annual effective dose of 2.4 mSv y(-1) received by inhabitants was estimated.

The occurrence of genetic polymorphism and related non-allelic proteins increases the compositional complexity of goat α((s1)) -CN.

A genetic survey on three autochthonous goat breeds reared in Italy was carried out by a proteomic approach. This methodology, further to providing the phenotypic frequency of identified α(s1) genetic variants, allowed to determine (i) the additional constitutive presence of a non-allelic 'α(s1) -casein (CN) F like' protein in goat 'strong' α(s1) variants; (ii) an α(s1) -CN B(2) like protein, expressed at very low quantitative level, in goat 'weak' α(s1) -CN variants, and, as main focus; (iii) the occurrence of a new α(s1) -CN D(1) variant characterised by the lack of α(s1) (f59-69) sequence otherwise encoded by exon 9 in goat α(s1) B(2) reference. The same exon skipping event had been identified since 1990, as responsible of the 'weak quantitative class' of α(s1) -CN D variant (0.6 g/L), while the new α(s1) -CN D(1,) has been 'quantitatively' classified as an 'intermediate' variant, since 1.8 g/L per allele was assessed in the milk.

Immunophenotyping analysis in invasive micropapillary carcinoma of the breast: role of CD24 and CD44 isoforms expression.

We analyzed immunohistochemically the expression of CD24 and spliced variants of CD44v5 and v9 in invasive micropapillary carcinoma (IMPC) of the breast that is a rather aggressive tumor characterized by alteration of cells adhesion molecules, early lymph node metastases and poor prognosis. We analyzed 31 high-grade IMPCs and compared their expression to 22 high grade (G3) invasive ductal carcinomas of the breast (IDCs). We found a higher expression of CD24 in high-grade IMPCs with a peculiar inverted apical localization, compared to IDCs, showing a strong cytoplasmic staining; normal breast tissue resulted completely negative. IMPCs showed reduced expression of CD44v5 and CD44v9 compared with IDCs, but without a statistical significant difference. This study demonstrated that IMPC represents a distinct entity of breast carcinoma with high expression of CD24 with a typical inverted apical membrane pattern and reduction of CD44 isoforms v5 and v9, compared to IDCs. These features could explain the high lymph-vascular invasion propensity and higher metastatic capability of these tumors and could be a useful tool for a future targeted therapy.

PTPD1 supports receptor stability and mitogenic signaling in bladder cancer cells.

PTPD1, a cytosolic non-receptor protein-tyrosine phosphatase, stimulates the Src-EGF transduction pathway. Localization of PTPD1 at actin cytoskeleton and adhesion sites is required for cell scattering and migration. Here, we show that during EGF stimulation, PTPD1 is rapidly recruited to endocytic vesicles containing the EGF receptor. Endosomal localization of PTPD1 is mediated by interaction with KIF16B, an endosomal kinesin that modulates receptor recycling at the plasma membrane. Silencing of PTPD1 promotes degradation of EGF receptor and inhibits downstream ERK signaling. We also found that PTPD1 is markedly increased in bladder cancer tissue samples. PTPD1 levels positively correlated with the grading and invasiveness potential of these tumors. Transgenic expression of an inactive PTPD1 mutant or genetic knockdown of the endogenous PTPD1 severely inhibited both growth and motility of human bladder cancer cells. These findings identify PTPD1 as a novel component of the endocytic machinery that impacts on EGF receptor stability and on growth and motility of bladder cancer cells.

In vivo tumor detection in small animals by hematoporphyrin-mediated fluorescence imaging.

OBJECTIVE: Noninvasive in vivo imaging of human tumors implanted in mice provides a reliable and economic tool for the investigation of tumor progression and metastasis and of the effectiveness of the antiblastic drugs on them. The purpose of this study is to report on the performance achievable by the well-known and extensively investigated HP-FRI (HematoPorphyrin (HP)-mediated Fluorescence Reflectance Imaging) when a high-quality image-acquisition device is used. BACKGROUND DATA: Previous articles of ours showed that HP-FRI still represents a useful, simple and reliable optical imaging technique to detect surface tumors. Therefore, it is particularly suitable to be used in combination with other imaging modalities in a multimodal imaging system endowed with diagnostic capabilities much better than each separate modality. MATERIALS AND METHODS: Six-week-old Crl:CD-1 nude mice were subcutaneously inoculated with tumor cells. Tumor-bearing mice were irradiated in vivo by a frequency-doubled pulsed Nd:YAG laser (lambda = 532 nm). A cooled CCD digital camera recorded fluorescence light emitted by HP injected in mice through a cut-on long-wavelength pass filter. RESULTS: The system we developed allows in vivo imaging of surface tumors on small animals with a large field of view, high photometric sensitivity, adequate space resolution, and short measurement time. The estimated spatial resolution is 730 microm for a fluorescence source placed about 0.5 mm under the mouse skin. The first exploration of the capabilities of this HP-FRI setup on few mice shows that it allows the detection of (a) both types of investigated tumors, (b) early stage and late stage but visually unrecognizable tumors, (c) the gross structure of tumors, and (d) the discrimination of necrotic and nonnecrotic tumor regions.

Proteomic characterization of donkey milk "caseome".

At present, compared with bovine milk, the characterization of donkey milk caseins is at a relatively early stage progress, and only limited data are related to its genetic polymorphism. In this work, the heterogeneity of donkey caseome was investigated using a proteomic approach, based on one- (PAGE, UTLIEF) and two-dimensional (PAGE-->UTLIEF) electrophoresis, stained with either Coomassie Brilliant Blue or specific polyclonal antibodies, and structural MS analysis. These combined methodologies allowed the contemporary identification of donkey alpha(s1), alpha(s2), beta and kappa-CN with their related heterogeneity due to phosphorylation (alpha(s1), alpha(s2) and beta-CN), glycosylation (kappa-CN) and incorrect splicing of RNA in mRNA (deleted forms of alpha(s1)-CN and beta-CN). The results achieved showed 11 components for kappa-CN, six phosphorylated components for beta and alpha(s1)-CN and three main phosphorylated components for alpha(s2)-CN, each accounting for 10, 11 and 12 P/mole. At this regard, for the first time, the primary structure of the expressed protein corresponding to the only available donkey alpha(s2)-CN cDNA sequence was determined. Furthermore beta-CN was found in homozygous and heterozygous state for the occurrence of a genetic beta-CN variant having a MW value 28 mass units higher than the common beta-CN phenotype.

Impact of chronic aspirin and statin therapy on presentation of patients with acute myocardial infarction and impaired renal function.

Chronic use of aspirin and statins has been associated with reduced risk of subsequent myocardial infarction (MI). However, in patients with chronic kidney disease (CKD), the cardioprotective role of aspirin and statins seems to be reduced. To evaluate the impact of chronic aspirin and statin use on clinical presentation of acute MI according to renal function, the authors retrospectively analyzed 595 consecutive patients admitted to our hospital for acute MI. Renal function was normal in 404 patients and impaired in 191. Patients on therapy (113 patients) were less likely to have ST-segment elevation MI (STEMI) compared with patients not treated (36% vs 53%, respectively, P=.0002). These results have been confirmed in the population of patients with CKD (48% of STEMI in patients receiving chronic therapy and 67% in patients without therapy,P=.01). Multivariate analysis in the group of patients with CKD showed that use of aspirin or statins was an independent predictor of a decreased probability of STEMI (odds ratio, 0.5; 95% confidence interval, 0.2-1.0,P=.05). The authors' results suggest that in a community-based sample of patients with acute MI, chronic aspirin and statin therapy has a cardioprotective role that is evident also in patients with CKD.

Elevated expression of the tyrosine phosphatase SHP-1 defines a subset of high-grade breast tumors.

OBJECTIVES: Protein tyrosine phosphatases are key regulators of intracellular signaling that contribute to determining cancer cell growth, which thus makes them attractive targets for therapeutic and diagnostic agents. SHP-1 phosphotyrosine phosphatase is rarely expressed in epithelial tumor cells, but expression has been found in several breast cancer cell lines and tumors. To determine the potential significance of SHP-1 as a prognostic marker in the clinical setting, we examined SHP-1 protein expression in breast tumors. METHODS: We analyzed SHP-1 expression by immunohistochemistry in a breast tissue microarray composed of 2,081 cores, either alone or in combination with known prognostic markers. RESULTS: Our data showed that SHP-1 expression was confined to a well-defined subset of high-grade tumors characterized by unique biological parameters. SHP-1 expression correlated directly with expression of the tyrosine kinase receptor HER-2 and inversely with expression of the estrogen receptor, while it was weakly associated with Bcl-2 expression. CONCLUSIONS: Levels of SHP-1 were correlated with conventional pathologic parameters of tumor aggressiveness and were associated with reduced patient survival, suggesting that elevated expression of SHP-1 is a common molecular abnormality in a defined subset of breast tumors and might be used in routine diagnosis to identify patients with high-risk tumors.