From DNA Radiation Damage to Cell Death: Theoretical Approaches

Some representative models of radiation-induced cell death, which is a crucial endpoint in radiobiology, were reviewed. The basic assumptions were identified, their consequences on predicted cell survival were analyzed, and the advantages and drawbacks of each approach were outlined. In addition to “historical” approaches such as the Target Theory, the Linear-Quadratic model, the Theory of Dual Radiation Action and Katz' model, the more recent Local Effect Model was discussed, focusing on its application in Carbon-ion hadrontherapy. Furthermore, a mechanistic model developed at the University of Pavia and based on the relationship between cell inactivation and chromosome aberrations was presented, together with recent results; the good agreement between model predictions and literature experimental data on different radiation types (photons, protons, alpha particles, and Carbon ions) supported the idea that asymmetric chromosome aberrations like dicentrics and rings play a fundamental role for cell death. Basing on these results, a reinterpretation of the TDRA was also proposed, identifying the TDRA “sublesions” and “lesions” as clustered DNA double-strand breaks and (lethal) chromosome aberrations, respectively

A Mission to Mars: Prediction of GCR Doses and Comparison with Astronaut Dose Limits

Long-term human space missions such as a future journey to Mars could be characterized by several hazards, among which radiation is one the highest-priority problems for astronaut health. In this work, exploiting a pre-existing interface between the BIANCA biophysical model and the FLUKA Monte Carlo transport code, a study was performed to calculate astronaut absorbed doses and equivalent doses following GCR exposure under different shielding conditions. More specifically, the interface with BIANCA allowed us to calculate both the RBE for cell survival, which is related to non-cancer effects, and that for chromosome aberrations, related to the induction of stochastic effects, including cancer. The results were then compared with cancer and non-cancer astronaut dose limits. Concerning the stochastic effects, the equivalent doses calculated by multiplying the absorbed dose by the RBE for chromosome aberrations (“high-dose method”) were similar to those calculated using the Q-values recommended by ICRP. For a 650-day mission at solar minimum (representative of a possible Mars mission scenario), the obtained values are always lower than the career limit recommended by ICRP (1 Sv), but higher than the limit of 600 mSv recently adopted by NASA. The comparison with the JAXA limits is more complex, since they are age and sex dependent. Concerning the deterministic limits, even for a 650-day mission at solar minimum, the values obtained by multiplying the absorbed dose by the RBE for cell survival are largely below the limits established by the various space agencies. Following this work, BIANCA, interfaced with an MC transport code such as FLUKA, can now predict RBE values for cell death and chromosome aberrations following GCR exposure. More generally, both at solar minimum and at solar maximum, shielding of 10 g/cm$^2$ Al seems to be a better choice than 20 g/cm$^2$ for astronaut protection against GCR

Perinatal outcomes in twin late preterm pregnancies: results from an Italian area-based, prospective cohort study

Background Multiple gestations represent a considerable proportion of pregnancies delivering in the late preterm (LP) period. Only 30% of LP twins are due to spontaneous preterm labor and 70% are medically indicated; among this literature described that 16-50% of indicated LP twin deliveries are non-evidence based. As non-evidence-based delivery indications account for iatrogenic morbidity that could be prevented, the objective of our observational study is to investigate first neonatal outcomes of LP twin pregnancies according to gestational age at delivery, chorionicity and delivery indication, then non evidence-based delivery indications. Methods Prospective cohort study among twins infants born between 34 + 0 and 36 + 6 weeks, in Emilia Romagna, Italy, during 2013-2015. The primary outcome was a composite of adverse perinatal outcomes. Results Among 346 LP twins, 84 (23.4%) were monochorionic and 262 (75.7%) were dichorionic; spontaneous preterm labor accounted for 85 (24.6%) deliveries, preterm prelabor rupture of membranes for 66 (19.1%), evidence based indicated deliveries were 117 (33.8%), while non-evidence-based indications were 78 (22.5%). When compared to spontaneous preterm labor or preterm prelabor rupture of membranes, pregnancies delivered due to maternal and/or fetal indications were associated with higher maternal age (p < 0.01), higher gestational age at delivery (p < 0.01), Caucasian race (p 0.04), ART use (p < 0.01), gestational diabetes (p < 0.01), vaginal bleeding (p < 0.01), antenatal corticosteroids (p < 0.01), diagnosis of fetal growth restriction (FGR) (p < 0.01), and monochorionic (p < 0.01). Two hundred twenty-six pregnancies (65.3%) had at least one fetus experiencing one composite of adverse perinatal outcome. Multivariate analysis confirmed that delivery indication did not affect the composite of adverse perinatal outcomes; the only characteristic that affect the outcome after controlling for confounding was gestational age at delivery (p < 0.01). Moreover, there was at least one adverse neonatal outcome for 94% of babies born at 34 weeks, for 73% of those born at 35 weeks and for 46% of those born at 36 weeks (p < 0.01). Conclusion Our study suggests that the decision to deliver or not twins in LP period should consider gestational age at delivery as the main determinant infants' prognosis. Delivery indications should be accurately considered, to avoid iatrogenic early birth responsible of preventable complications

Bloch surface waves-controlled fluorescence emission: coupling into nanometer-sized polymeric waveguides

The lateral confinement of Bloch surface waves on a patterned multilayer is investigated by means of leakage radiation microscopy (LRM). Arrays of nanometric polymeric waveguides are fabricated on a proper silicon-nitride/silicon-oxide multilayer grown on a standard glass coverslip. By exploiting the functional properties of the polymer, fluorescent proteins are grafted onto the waveguides. A fluorescence LRM analysis of both the direct and the Fourier image plane reveals that a substantial amount of emitted radiation couples into a guided mode and then propagates into the nanometric waveguide. The observations of the mode are supported by numerical simulations

Calibrating the Dynamic Energy Simulation Model for an Existing Building: Lessons Learned from a Collective Exercise

Calibration of the existing building simulation model is key to correctly evaluating the energy savings that are achievable through retrofit. However, calibration is a non-standard phase where different approaches can possibly lead to different models. In this study, an existing residential building is simulated in parallel by four research groups with different dynamic simulation tools. Manual/automatic methodologies and basic/detailed measurement data sets are used. The calibration is followed by a validation on two evaluation periods. Monitoring data concerning the windows opening by the occupants are used to analyze the calibration outcomes. It is found that for a good calibration of a model of a well-insulated building, the absence of data regarding the users’ behavior is more critical than uncertainty on the envelope properties. The automatic approach is more effective in managing the model complexity and reaching a better performing calibration, as the RMSE relative to indoor temperature reaches 0.3 C compared to 0.4–0.5 C. Yet, a calibrated model’s performance is often poor outside the calibration period (RMSE increases up to 10.8 times), and thus, the validation is crucial to discriminate among multiple solutions and to refine them, by improving the users’ behavior modeling

Niemann-Pick type C disease mutations of NPC1 gene and evidence of abnormal expression of some mutant alleles in fibroblasts

We analyzed Niemann-Pick type C disease 1 (NP44406) gene in 12 patients with Niemann-Pick type C disease by sequencing both cDNA obtained from fibroblasts and genomic DNA. All the patients were compound heterozygotes. We found 15 mutations, eight of which previously unreported. The comparison of cDNA and genomic DNA revealed discrepancies in some subjects. In two unrelated patients carrying the same mutations (P474L and nt 2972del2) only one mutant allele (P474L), was expressed in fibroblasts. The mRNA corresponding to the other allele was not detected even in cells incubated with cycloheximide. The promoter variants (−1026T/G and −1186T/C or −238 C/G), found to be in linkage with 2972del2 allele do not explain the lack of expression of this allele, as they were also found in control subjects. In another patient, (N1156S/Q922X) the N1156S allele was expressed in fibroblasts while the expression of the other allele was hardly detectable. In a fourth patient cDNA analysis revealed a point mutation in exon 20 (P1007A) and a 56 nt deletion in exon 22 leading to a frameshift and a premature stop codon. The first mutation was confirmed in genomic DNA; the second turned out to be a T→G transversion in exon 22, predicted to cause a missense mutation (V1141G). In fact, this transversion generates a donor splice site in exon 22, which causes an abnormal pre-mRNA splicing leading to a partial deletion of this exon. In some NPC patients, therefore, the comparison between cDNA and genomic DNA may reveal an unexpected expression of some mutant alleles of NPC1 gene

Health Impact Assessment Practice and Potential for Integration within Environmental Impact and Strategic Environmental Assessments in Italy

Avoiding or minimizing potential environmental impact is the driving idea behind protecting a population\u27s health via Environmental Impact Assessments (EIAs) and Strategic Environmental Assessments (SEAs). However, both are often carried out without any systematic approach. This paper describes the findings of a review of HIA, EIA and SEA experiences carried out by the authors, who act as institutional competent subjects at the national and regional levels in Italy. The analysis of how health is tackled in EIA and SEA procedures could support the definition of a protocol for the integration of HIA with EIA and SEA. Although EIA and SEA approaches include the aim of protecting health, significant technical and methodological gaps are present when assessing health systematically, and their basic principles regarding assessment are unsatisfactory for promoting and addressing healthcare concepts stated by the WHO. HIA is still poorly integrated into the decision-making process, screening and monitoring phases are only occasionally implemented, and operational details are not well-defined. The collaborative approach of institutions involved in environment and health is a core element in a systematic advancement toward supporting effective decisions and effective protection of the environment and health. At the Italian national level, the definition of guidelines and tools for HIA, also in relation with EIA and SEA, is of great interest

Effects induced by particles derived from two anthropogenic sources on respiratory, cardiovascular and central nervous systems

Air pollution represents a well-known environmental problem related to public health. Particulate matter (PM) is a heterogeneous mixture of chemicals, metals and soils. Its adverse effects have been correlated with particles size, being smaller particles more likely to cause a worst damage, so their study deserves more attention. Ultrafine particles (UFPs, dae < 100 nm) are short-lived particles dispersed in the environment. In Lombardy, diesel combustion and solid biomass burning are the most relevant contributors to primary UFPs emissions (15-30 nm in diameter). Toxicological studies, mainly in vitro, indicate specific effects for particles of different origin but comparative in vivo studies are scarce. PM exposure has been primarily associated to pulmonary and cardiovascular diseases through oxidative stress and inflammatory response, but recently it has been postulated that PM exposure could also be an important risk factor for neurotoxicity and could have a role in neurodegenerative diseases. In this study we analysed in BALB/c mice the effect of single and repeated intratracheal instillation of diesel (DEP) and biomass (BC) particles on respiratory, cardiovascular and central nervous systems, comparing the two different UFPs sources. The study was performed at biochemical and histopathological level. Different pro-inflammatory, cytotoxic, pro-coagulant and oxidative stress markers were measured. For the histopathological evaluation, sections of lung, heart and different parts of the central nervous system (CNS) were examined at light microscope, using standard staining tecniques and immunohistochemical methods. Inflammation was also monitored in living mice following BC or DEP intratracheal repeated administration using the FMT 1500 fluorescence tomography imaging system and the MMPSense 750 Fast probe.  Our results indicate that even a single instillation of both the sources of UFPs induces a wide range of biochemical changes in the respiratory and cardiovascular systems, then confirmed by repeated instillation. In the CNS similar modifications were observed, although these were much more evident after repeated instillations. Histological examination demonstrated the presence of macrophages containing particles in the lungs after UFPs single and, more abundantly, repeated administration. However, significant changes were not observed in sections of heart and CNS. DEP was more effective in inducing oxidative stress and inflammation compared to BC

Bloch surface waves-controlled emission of organic dyes grafted on a one-dimensional photonic crystal

An alternative route to plasmon-controlled fluorescence for improving the detection of fluorescence is proposed. In place of a metallic layer, a suitable silicon-based one-dimensional photonic crystal is used to generate a Bloch surface waves-coupled emission from a thin polymeric layer decorated with a fluorescent dye. Fluorescent radiation coupled to Bloch surface waves is strongly polarized and directional, with an angular divergence of 0.3 corresponding to a spectral bandwidth of 3 nm. Within this range, an overall signal enhancement of a factor larger than 500 is obtained as compared to a conventional glass substrate thanks to an additional enhancement mechanism based on dyes excitation via Bloch surface wave