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Pediatric stroke is a rare medical condition that often leads to long-lasting motor and cognitive impairments. Although therapies for adults after a stroke are well described, treatments for motor deficits following a pediatric stroke are yet to be investigated. We report a case of pediatric stroke in the chronic phase, in which a combination of novel treatments resulted in a significant improvement in physical function. A seven-year-old girl with a left hemispheric cerebral infarction lost almost all right upper extremity motor function. Following onabotulinumtoxinA treatment, she underwent hand-arm bimanual intensive therapy augmented with a hybrid assistive limb for 90 h over 15 days. Evaluation after the training revealed significant improvements in physical function, daily activities, and occupational performance. This report highlights the importance of innovative combinations of techniques in the treatment of pediatric stroke. [ABSTRACT FROM AUTHOR]

Complex DNA double-strand break (DSB), which is defined as a DSB coupled with additional strand breaks within 10 bp in this study, induced after ionizing radiation or X-rays, is recognized as fatal damage which can induce cell death with a certain probability. In general, a DSB site inside the nucleus of live cells can be experimentally detected using the γ-H2AX focus formation assay. DSB complexity is believed to be detected by analyzing the focus size using such an assay. However, the relationship between focus size and DSB complexity remains uncertain. In this study, using Monte Carlo (MC) track-structure simulation codes, i.e., an in-house WLTrack code and a Particle and Heavy Ion Transport code System (PHITS), we developed an analytical method for qualifying the DSB complexity induced by photon irradiation from the microscopic image of γ-H2AX foci. First, assuming that events (i.e., ionization and excitation) potentially induce DNA strand breaks, we scored the number of events in a water cube (5.03 × 5.03 × 5.03 nm3) along electron tracks. Second, we obtained the relationship between the number of events and the foci size experimentally measured by the γ-H2AX focus formation assay. Third, using this relationship, we evaluated the degree of DSB complexity induced after photon irradiation for various X-ray spectra using the foci size, and the experimental DSB complexity was compared to the results estimated by the well-verified DNA damage estimation model in the PHITS code. The number of events in a water cube was found to be proportional to foci size, suggesting that the number of events intrinsically related to DSB complexity at the DNA scale. The developed method was applicable to focus data measured for various X-ray spectral situations (i.e., diagnostic kV X-rays and therapeutic MV X-rays). This method would contribute to a precise understanding of the early biological impacts of photon irradiation by means of the γ-H2AX focus formation assay. [ABSTRACT FROM AUTHOR]

DNA strand breaks are induced in cells mainly composed of liquid water along ionizing radiation tracks. For estimating DNA strand break yields, track structures for electrons in liquid water in Monte Carlo simulations are of great importance; however, detailed simulations to obtain both energy deposition and free radical reaction to DNA are time-consuming processes. Here, we present a simple model for estimating yields of single- and double-strand breaks (SSB, DSB, and DSB/SSB ratio) based only on spatial patterns of inelastic interactions (i.e., ionization and electronic excitation) generated by electrons, which are evaluated by the track structure mode of Particle and Heavy Ion Transport code System without analyzing the production and diffusion of free radicals. In the present model, the number of events per track and that of a pair composed of two events within 3.4 nm (10 base pairs) were stochastically sampled for calculating SSB and DSB yields. The results calculated by this model agree well with other simulations and experimental data on the DSB yield and the DSB/SSB ratio for monoenergetic electron irradiation. This model also demonstrates the relative biological effectiveness at the DSB endpoint for various photon irradiations, indicating that the spatial pattern composed of ionization and electronic excitation without physicochemical and chemical stages is sufficient to obtain the impact of electrons on the initial DNA strand break induction. [ABSTRACT FROM AUTHOR]

In radiation physics, Monte Carlo radiation transport simulations are powerful tools to evaluate the cellular responses after irradiation. When investigating such radiation-induced biological effects, it is essential to perform track structure simulations by explicitly considering each atomic interaction in liquid water at the sub-cellular and DNA scales. The Particle and Heavy-Ion Transport code System (PHITS) is a Monte Carlo code which enables to calculate track structure at DNA scale by employing the track-structure modes for electrons, protons and carbon ions. In this paper, we review the recent development status and future prospects of the track-structure modes in the PHITS code. To date, the physical features of these modes have been verified using the available experimental data and Monte Carlo simulation results reported in literature. These track-structure modes can be used for calculating microdosimetric distributions to estimate cell survival and for estimating initial DNA damage yields. The use of PHITS track-structure mode is expected not only to clarify the underlying mechanisms of radiation effects but also to predict curative effects in radiation therapy. The results of PHITS simulations coupled with biophysical models will contribute to the radiobiological studies by precisely predicting radiation-induced biological effects based on the Monte Carlo approach. [ABSTRACT FROM AUTHOR]

Complex DNA damage, defined as at least two vicinal lesions within 10–20 base pairs (bp), induced after exposure to ionizing radiation, is recognized as fatal damage to human tissue. Due to the difficulty of directly measuring the aggregation of DNA damage at the nano-meter scale, many cluster analyses of inelastic interactions based on Monte Carlo simulation for radiation track structure in liquid water have been conducted to evaluate DNA damage. Meanwhile, the experimental technique to detect complex DNA damage has evolved in recent decades, so both approaches with simulation and experiment get used for investigating complex DNA damage. During this study, we propose a simplified cluster analysis of ionization and electronic excitation events within 10 bp based on track structure for estimating complex DNA damage yields for electron and X-ray irradiations. We then compare the computational results with the experimental complex DNA damage coupled with base damage (BD) measured by enzymatic cleavage and atomic force microscopy (AFM). The computational results agree well with experimental fractions of complex damage yields, i.e., single and double strand breaks (SSBs, DSBs) and complex BD, when the yield ratio of BD/SSB is assumed to be 1.3. Considering the comparison of complex DSB yields, i.e., DSB + BD and DSB + 2BD, between simulation and experimental data, we find that the aggregation degree of the events along electron tracks reflects the complexity of induced DNA damage, showing 43.5% of DSB induced after 70 kVp X-ray irradiation can be classified as a complex form coupled with BD. The present simulation enables us to quantify the type of complex damage which cannot be measured through in vitro experiments and helps us to interpret the experimental detection efficiency for complex BD measured by AFM. This simple model for estimating complex DNA damage yields contributes to the precise understanding of the DNA damage complexity induced after X-ray and electron irradiations. [ABSTRACT FROM AUTHOR]