Validation of Geant4 nuclear reaction models for hadrontherapy and preliminary results with SMF and BLOB

Reliable nuclear fragmentation models are of utmost importance in hadrontherapy, where Monte Carlo (MC) simulations are used to compute the input parameters of the treatment planning software, to validate the deposited dose calculation, to evaluate the biological effectiveness of the radiation, to correlate the bþ emitters production in the patient body with the delivered dose, and to allow a non- invasive treatment verification. Despite of its large use, the models implemented in Geant4 have shown severe limitations in reproducing the measured secondaries yields in ions interaction below 100 MeV/A, in term of production rates, angular and energy distributions [1–3]. We will present a benchmark of the Geant4 models with double-differential cross sec- tion and angular distributions of the secondary fragments produced in the 12C fragmentation at 62 MeV/A on thin carbon target, such a benchmark includes the recently implemented model INCL++ [4,5]. Moreover, we will present the preliminary results, obtained in simulating the same interaction, with SMF [6] and BLOB [7]. Both, SMF and BLOB are semiclassical one-body approaches to solve the Boltzmann-Langevin equation. They include an identical treatment of the mean-field propagation, on the basis of the same effective interaction, but they differ in the way fluctuations are included. In particular, while SMF employs a Uehling-Uhlenbeck collision term and introduces fluctuations as projected on the density space, BLOB introduces fluctuations in full phase space through a modified collision term where nucleon-nucleon correlations are explicitly involved. Both of them, SMF and BLOB, have been developed to sim- ulate the heavy ion interactions in the Fermi-energy regime. We will show their capabilities in describing 12C fragmentation foreseen their implementation in Geant4

A computational tool for evaluating HIFU safety

Background. High Intensity Focused Ultrasound (HIFU) is a noninvasive treatment for therapeutic applications, in particular the treatment of either benign or malignant tumor lesions. HIFU treatment is based on the power of a focused ultrasound beam to locally heat biological tissues over a necrotic level with minimal impact on the surrounding tissues. Therapies based on HIFU are becoming widely spread in the panorama of options offered by the Health Care System. Consequently, there is an ever increasing need to standardise quality assurance protocols and to develop computational tools to evaluate the output of clinical HIFU devices and ensuring safe delivery of HIFU treatment.Aims. Goal of this study is the development of a computational tool for HIFU ablation therapy to assure safety of the patient and effectiveness of the treatment. Results. The simulated results provide information about the behaviour of the focalized ultrasound in their interaction with different biological tissues.Conclusions. Numerical simulation represents a useful approach to predict the heath deposition and, consequently, to assess the safety and effectiveness of HIFU devices

A 10-year follow-up of yearly indoor radon measurements in homes, review of other studies and implications on lung cancer risk estimates

Uncertainty on long-term average radon concentration has a large impact on lung cancer risk assessment in epidemiological studies. The uncertainty can be estimated by year-to-year radon concentration variability, however few data are available. In Italy a study has been planned and conducted to evaluate year-to-year radon variability over several years in normally inhabited dwellings, mainly located in Rome. This is the longest study of this kind in Europe; repeat radon measurements are carried out for 10 years using LR-115 radon detectors in the same home in consecutive years. The study includes 84 dwellings with long-term average radon concentration ranging from 28 to 636 Bq/m3. The result shows that year-to-year variability of repeated measurements made in the same home in different years is low, with an overall coefficient of variation of 17%. This is smaller than most of those observed in studies from other European countries and USA, ranging from 15% to 62%. Influencing factors that may explain the differences between this study and other studies have been discussed. Due to the low yearly variability estimated in the present 10-year study, a negligible impact on lung cancer risk estimate for the Italian epidemiologica

Cholesterol-loaded nanoparticles ameliorate synaptic and cognitive function in Huntington's disease mice

Brain cholesterol biosynthesis and cholesterol levels are reduced in mouse models of Huntington's disease (HD), suggesting that locally synthesized, newly formed cholesterol is less available to neurons. This may be detrimental for neuronal function, especially given that locally synthesized cholesterol is implicated in synapse integrity and remodeling. Here, we used biodegradable and biocompatible polymeric nanoparticles (NPs) modified with glycopeptides (g7) and loaded with cholesterol (g7-NPs-Chol), which per se is not blood-brain barrier (BBB) permeable, to obtain high-rate cholesterol delivery into the brain after intraperitoneal injection in HD mice. We report that g7-NPs, in contrast to unmodified NPs, efficiently crossed the BBB and localized in glial and neuronal cells in different brain regions. We also found that repeated systemic delivery of g7-NPs-Chol rescued synaptic and cognitive dysfunction and partially improved global activity in HD mice. These results demonstrate that cholesterol supplementation to the HD brain reverses functional alterations associated with HD and highlight the potential of this new drug-administration route to the diseased brain

Soft Robotics: A Route to Equality, Diversity, and Inclusivity in Robotics

: Robotics is entering our daily lives. The discipline is increasingly crucial in fields such as agriculture, medicine, and rescue operations, impacting our food, health, and planet. At the same time, it is becoming evident that robotic research must embrace and reflect the diversity of human society to address these broad challenges effectively. In recent years, gender inclusivity has received increasing attention, but it still remains a distant goal. In addition, awareness is rising around other dimensions of diversity, including nationality, religion, and politics. Unfortunately, despite the efforts, empirical evidence shows that the field has still a long way to go before achieving a sufficient level of equality, diversity, and inclusion across these spectra. This study focuses on the soft robotics community-a growing and relatively recent subfield-and it outlines the present state of equality and diversity panorama in this discipline. The article argues that its high interdisciplinary and accessibility make it a particularly welcoming branch of robotics. We discuss the elements that make this subdiscipline an example for the broader robotic field. At the same time, we recognize that the field should still improve in several ways and become more inclusive and diverse. We propose concrete actions that we believe will contribute to achieving this goal, and provide metrics to monitor its evolution

Chronic cholesterol administration to the brain supports complete and long-lasting cognitive and motor amelioration in Huntington's disease

: Evidence that Huntington's disease (HD) is characterized by impaired cholesterol biosynthesis in the brain has led to strategies to increase its level in the brain of the rapidly progressing R6/2 mouse model, with a positive therapeutic outcome. Here we tested the long-term efficacy of chronic administration of cholesterol to the brain of the slowly progressing zQ175DN knock-in HD mice in preventing ("early treatment") or reversing ("late treatment") HD symptoms. To do this we used the most advanced formulation of cholesterol loaded brain-permeable nanoparticles (NPs), termed hybrid-g7-NPs-chol, which were injected intraperitoneally. We show that one cycle of treatment with hybrid-g7-NPs-chol, administered in the presymptomatic ("early treatment") or symptomatic ("late treatment") stages is sufficient to normalize cognitive defects up to 5 months, as well as to improve other behavioral and neuropathological parameters. A multiple cycle treatment combining both early and late treatments ("2 cycle treatment") lasting 6 months generates therapeutic effects for more than 11 months, without severe adverse reactions. Sustained cholesterol delivery to the brain of zQ175DN mice also reduces mutant Huntingtin aggregates in both the striatum and cortex and completely normalizes synaptic communication in the striatal medium spiny neurons compared to saline-treated HD mice. Furthermore, through a meta-analysis of published and current data, we demonstrated the power of hybrid-g7-NPs-chol and other strategies able to increase brain cholesterol biosynthesis, to reverse cognitive decline and counteract the formation of mutant Huntingtin aggregates. These results demonstrate that cholesterol delivery via brain-permeable NPs is a therapeutic option to sustainably reverse HD-related behavioral decline and neuropathological signs over time, highlighting the therapeutic potential of cholesterol-based strategies in HD patients. DATA AVAILABILITY: This study does not include data deposited in public repositories. Data are available on request to the corresponding authors

A morphological and functional characterization of Bombyx mori larval midgut cells in culture

Recent studies have shown that Bombyx mori larval midgut can transport proteins unaltered following the transcellular pathway by transcytosis. The numerous steps involved in this complex process are still unknown in the insect midgut, and a promising tool to elucidate this aspect is the availability of single midgut cells in culture suitable for transport experiments. Mature midgut cells in culture were obtained from stem cells isolated from B. mori larvae cultured in Grace’s medium supplemented with 20-hydroxyecdysone (20-HE) and α-arylphorin. After three weeks, up to 60 % of the cultured cells were differentiated into columnar and goblet cells, the two predominant cell types in the midgut epithelium. These cells presented in vitro the same shape, morphology and polarity recorded in vivo, even if their dimensions were slightly reduced. Columnar cells displayed a well developed cytoskeletal arrangement, with actin filaments highly organized within the thick brush border and distributed in faint filaments in the cell cytoplasm. Microtubules formed a substantial net just beneath the brush border and ran longitudinally from the apical to the basal pole of the cell. Cultured cells homogenates displayed aminopeptidase N and alkaline phosphatase activity, proving that these two enzymes, involved in vivo in the intermediate and final digestion, are expressed also in vitro. The columnar cells differentiated in culture were able to internalize two model proteins with quite different transport rate

Functional characterization of sugar transport in the intestinal epithelium of an insect (Aphidius ervi, Hymenoptera)

Aphidius ervi is an entomophagous wasp, widely used in biological control because adult females lay the eggs in the haemocoel of several aphid species. After hatching, A. ervi larvae develop in the living host feeding on its haemolymph and, just before metamorphosis, kill the host by devouring its internal tissues and pupating inside the body wall, from which the adult will finally emerge. Like many other parasitoids, A. ervi finely redirects host metabolism in order to optimize haemolymph nutrient contents to support larval specific needs. In aphid haemolymph, sugar titre is extremely high, reaching a concentration of 129 and 60 mM for fructose and glucose respectively. The peculiar sugar-rich environment in which A. ervi larvae develop, suggestive of a critical role of these nutrients for the insect survival, stimulated us to identify the transporters involved in glucose and fructose intestinal absorption, especially considering that information on sugar transport in insect midgut is scanty. The study performed in larval A. ervi intestine, isolated and incubated in vitro, allowed us to detect, with functional, immunohistochemical and immunoblotting approaches, the transport proteins responsible for glucose and fructose uptake and to characterise their basic properties. The results unequivocally show that the cellular model for sugar transport in the larval stage of this insect is surprisingly similar to that conventionally described for mammals (i.e. SGLT1-like and GLUT5-like transporters on the apical membrane of the intestinal epithelial cell, and GLUT2-like transporters on the basolateral one), with the expression, apparently constitutive, of GLUT2 transporters also in the apical membrane, in agreement with the model for the transcellular absorption of hexoses recently proposed (Kellett, J. Physiol. 531, 585, 2001)