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ying disease recurrence in patients. Accurate assessment of primary responses to radiation may provide potential targets that can be manipulated for therapeutic benefit to sensitize cancer cells to radiotherapy, while sparing normal tissue.Human induced pluripotent stem cells (iPSCs) can generate virtually any cell type and therefore are applied to studies of organ development, disease modeling, drug screening and cell replacement therapy. Under proper culture conditions in vitro induced pluripotent stem cells (iPSCs) can be differentiated to form organ-like tissues, also known as "organoids", which resemble organs more closely than cells, in vivo. We hypothesized that human brain organoids can be used as an experimental model to study mechanisms underlying DNA repair in human neurons and their progenitors after radiation-induced DNA double-strand breaks (DSBs), the most severe form of DNA damage. To this end, we customized a protocol for brain organoid generation that is time efficient. These organoids recapitulate key features of human cortical neuron development, including a subventricular zone containing neural progenitors that mature to postmitotic cortical neurons. Using immunofluorescence to measure DNA DSB markers, such as γ-H2AX and 53BP1, we quantified the kinetics of DSB repair in neural progenitors within the subventricular zone for up to 24 h after a single 2 Gy dose of ionizing radiation. Our data on DNA repair in progenitor versus mature neurons indicate a similar timeline both repair DNA DSBs which is mostly resolved by 18 h postirradiation. However, repair kinetics are more acute in progenitors than mature neurons in the mature organoid. Overall, this study supports the use of 3D organoid culture technology as a novel platform to study DNA damage responses in developing or mature neurons, which has been previously difficult to study.An important hallmark of the field of radiation oncology has traditionally been multidisciplinary collaboration among its clinicians and scientists. Increased specialization, resulting from increased complexity, threatens to diminish this important characteristic. This article evaluates the success of a short-term educational environment developed specifically to enhance multidisciplinary collaboration. This NIH-funded educational course, named "Integration of Biology and Physics into Radiation Oncology (IBPRO)," was developed at Wayne State University, and designed to facilitate engagement among radiation oncologists, medical physicists and radiobiologists in activities that foster collaborative investigation. The question we address here is, "Did it work?" The 240 clinicians and researchers participating in IBPRO over the five years of the course were surveyed to quantify its effectiveness. In total, 95 respondents identified 45 institutional protocols, 52 research grant applications (19 of which have been rse continue to actively drive research productivity. Additionally, one of the many enduring legacies of this course is the creation of a new debate series in a professional journal. IBPRO serves as a model for our ability to leverage collaborative learning in an educational intervention to foster multidisciplinary clinical and research collaboration. It has already had a profound impact on the profession of radiation oncology, and this impact can be anticipated to increase in the future.The clinical superiority of proton therapy over photon therapy has recently gained recognition; however, the biological effects of proton therapy remain poorly understood. The lack of in vivo evidence is especially important. Therefore, the goal of this study was to validate the usefulness of Drosophila melanogaster as an alternative tool in proton radiobiology. To determine whether the comparative biological effects of protons and X rays are detectable in Drosophila, we assessed their influence on survival and mRNA expression. Postirradiation observation revealed that protons inhibited their development and reduced the overall survival rates more effectively than X rays. The relative biological effectiveness of the proton beams compared to the X rays estimated from the 50% lethal doses was 1.31. At 2 or 24 h postirradiation, mRNA expression analysis demonstrated that the expression patterns of several genes (such as DNA-repair-, apoptosis- and angiogenesis-related genes) followed different time courses depending on radiation type. Moreover, our trials suggested that the knockdown of individual genes by the GAL4/UAS system changes the radiosensitivity in a radiation type-specific manner. We confirmed this Drosophila model to be considerably useful to evaluate the findings from in vitro studies in an in vivo system. Furthermore, this model has a potential to elucidate more complex biological mechanisms underlying proton irradiation.Astronauts on deep space missions will be required to work autonomously and thus their ability to perform executive functions could be critical to mission success. Ground-based rodent experiments have shown that low ( less then 25 cGy) doses of several space radiation (SR) ions impair various aspects of executive function. Translating ground-based rodent studies into tangible risk estimates for astronauts remains an enormous challenge, but should similar neurocognitive impairments occur in astronauts exposed to low-SR doses, a Numbers-Needed-to-Harm analysis (of the rodent data) predicts that approximately 30% of the astronauts could develop severe cognitive flexibility decrements. In addition to the health risks associated with SR exposure, astronauts have to contend with other stressors, of which inadequate sleep quantity and quality are considered to be major concerns. We have shown that a single session of fragmented sleep uncovered latent attentional set-shifting (ATSET) performance deficits in rats expoonality of the brain regions that regulate performance in the IDR, EDS and EDR stages of ATSET. The uncovering of these latent SR-induced ATSET performance deficits in both Si- and neutron-irradiated rats suggests that the true impact of SR-induced cognitive impairment may not be fully evident in normally rested rats, and thus cognitive testing needs to be conducted under both rested wakefulness and sleep fragmentation conditions.Cataract is one of the major morbidities in the U.S. population and it has long been appreciated that high and acutely delivered radiation doses of 1 Gy or more can induce cataract. Some more recent studies, in particular those of the U.S. Radiologic Technologists, have suggested that cataract may be induced by much lower, chronically delivered doses of ionizing radiation. It is well recognized that dosimetric measurement error can substantially alter the shape of the radiation dose-response relationship and thus, the derived study risk estimates, and can also inflate the variance of the estimates. In the current study, we evaluate the impact of uncertainties in eye-lens absorbed doses on the estimated risk of cataract in the U.S. Radiologic Technologists' Monte Carlo Dosimetry System, using both absolute and relative risk models. Among 11,345 cases we show that the inflation in the standard error for the excess relative risk (ERR) is generally modest, at most approximately 20% of the unadjusted standard error, depending on the model used for the baseline risk. The largest adjustment results from use of relative risk models, so that the ERR/Gy and its 95% confidence intervals change from 1.085 (0.645, 1.525) to 1.085 (0.558, 1.612) after adjustment. However, the inflation in the standard error of the excess absolute risk (EAR) coefficient is generally minimal, at most approximately 0.04% of the standard error.The findings from previously published studies have suggested that radiation exposure is associated with increased mortality and incidence of gastric cancer. However, few cohort studies have incorporated risk factors such as Helicobacter pylori (H. pylori) infection or chronic atrophic gastritis (CAG). The current study is aimed at evaluating the modifying effect of CAG on radiation risk of noncardia gastric cancer by histological type, by reanalyzing data from a nested case-control study conducted within the longitudinal clinical cohort of atomic bomb survivors. click here The analysis was restricted to 297 intestinal- or diffuse-type noncardia cases and 873 controls rematched to the cases on gender, age, city, and time and type of serum storage, and countermatched on radiation dose. Multivariable-adjusted relative risks [95% confidence interval (CI)] of noncardia gastric cancer were 3.9 (2.1-7.2) for H. pylori IgG seropositivity with cytotoxin-associated gene A (CagA) IgG low titer, 2.6 (1.9-3.6) for CAG, 1.9 (1.3-2.8) for current smoking, and 1.4 (1.1-1.9) for 1 Gy irradiation. Among subjects without CAG, the relative risk (95% CI) of noncardia gastric cancer at 1 Gy was 2.3 (1.4-3.7), whereas relative risk (95% CI) at 1 Gy was 1.1 (0.8-1.5) among subjects with CAG (for the overall interaction, P = 0.012). By histological type, the risk at 1 Gy was high for diffuse type without CAG, with adjusted relative risk (95% CI) of 3.8 (2.0-7.6), but was not high for diffuse type with CAG or for intestinal-type irrespective of CAG status. The results indicate that radiation exposure is associated with increased risk of diffuse-type noncardia gastric cancer without CAG, and this association exists despite adjustment for H. pylori infection and smoking habit.In this work, we developed a DNA dosimeter, consisting of 4-kb DNA strands attached to magnetic streptavidin beads and labeled with fluorescein, to detect double-strand breaks (DSBs). The purpose here was to evaluate whether the DNA dosimeter readings reflect the relative biological effects of 160 kVp and 6 MV X rays. AVarian 600 C/D linac (6 MV) and a Faxitron cabinet X-ray system (160 kVp), both calibrated using traceable methods, were used to deliver high- and low-energy photons, respectively, to DNA dosimeters and multiple cell lines (mNs-5, HT-22 and Daoy). The responses were fit versus dose, and were used to quantify the dose of low-energy photons that produced the same response as that of the high-energy photons, at doses of 3, 6 and 9 Gy. The equivalent doses were utilized to calculate the relative biological effectiveness (RBEDSB and RBEcell survival). Additionally, a neutral comet assay was performed to measure the amount of intracellular DNA DSB, and ultimately the RBEcomet assay. The results of this work showed 160-kVp photon RBE values and 95% confidence intervals of 1.12 ± 0.04 (mNS-5), 1.16 ± 0.06 (HT-22), 1.25 ± 0.09 (Daoy) and 1.21 ± 0.24 (DNA dosimeter) at 9 Gy and 1.32 ± 0.16 (comet assay) at 3 Gy. Within the current error, the DNA dosimeter measured RBEDSB values in agreement with the RBEcell survival and assay from the cell survival and comet assay RBEcomet measurements. These results suggest that the DNA dosimeter can measure the changes in the radiobiological effects from different energy photons.Thrombocytopenia (TCP) may cause severe and life-threatening bleeding. While this may be prevented by platelet transfusions, transfusions are associated with potential complications, do not always work (platelet refractory) and are not always available. There is an urgent need for a synthetic alternative. We evaluated the ability of fibrinogen-coated nanospheres (FCNs) to prevent TCP-related bleeding. FCNs are made of human albumin polymerized into a 100-nm sphere and coated with fibrinogen. We hypothesized that FCNs would bind to platelets through fibrinogen-GPIIb/IIIa interactions, contributing to hemostasis in the setting of TCP. We used two murine models to test these effects in the first model, BALB/c mice received 7.25 Gy total-body irradiation (TBI); in the second model, lower dose TBI (7.0 Gy) was combined with an anti-platelet antibody (anti-CD41) to induce severe TCP. Deaths in both models were due to gastrointestinal or intracranial bleeding. Addition of antiplatelet antibody to 7.0 Gy TBI significantly worsened TCP and increased mortality compared to 7.