Galactic cosmic ray simulation at the NASA space radiation laboratory - Progress, challenges and recommendations on mixed-field effects.

For missions beyond low Earth orbit to the moon or Mars, space explorers will encounter a complex radiation field composed of various ion species with a broad range of energies. Such missions pose significant radiation protection challenges that need to be solved in order to minimize exposures and associated health risks. An innovative galactic cosmic ray simulator (GCRsim) was recently developed at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL). The GCRsim technology is intended to represent major components of the space radiation environment in a ground analog laboratory setting where it can be used to improve understanding of biological risks and serve as a testbed for countermeasure development and validation. The current GCRsim consists of 33 energetic ion beams that collectively simulate the primary and secondary GCR field encountered by humans in space over the broad range of particle types, energies, and linear energy transfer (LET) of interest to health effects. A virtual workshop was held in December 2020 to assess the status of the NASA baseline GCRsim. Workshop attendees examined various aspects of simulator design, with a particular emphasis on beam selection strategies. Experimental results, modeling approaches, areas of consensus, and questions of concern were also discussed in detail. This report includes a summary of the GCRsim workshop and a description of the current status of the GCRsim. This information is important for future advancements and applications in space radiobiology.

Ionizing radiation, cerebrovascular disease, and consequent dementia: A review and proposed framework relevant to space radiation exposure.

Space exploration requires the characterization and management or mitigation of a variety of human health risks. Exposure to space radiation is one of the main health concerns because it has the potential to increase the risk of cancer, cardiovascular disease, and both acute and late neurodegeneration. Space radiation-induced decrements to the vascular system may impact the risk for cerebrovascular disease and consequent dementia. These risks may be independent or synergistic with direct damage to central nervous system tissues. The purpose of this work is to review epidemiological and experimental data regarding the impact of low-to-moderate dose ionizing radiation on the central nervous system and the cerebrovascular system. A proposed framework outlines how space radiation-induced effects on the vasculature may increase risk for both cerebrovascular dysfunction and neural and cognitive adverse outcomes. The results of this work suggest that there are multiple processes by which ionizing radiation exposure may impact cerebrovascular function including increases in oxidative stress, neuroinflammation, endothelial cell dysfunction, arterial stiffening, atherosclerosis, and cerebral amyloid angiopathy. Cerebrovascular adverse outcomes may also promote neural and cognitive adverse outcomes. However, there are many gaps in both the human and preclinical evidence base regarding the long-term impact of ionizing radiation exposure on brain health due to heterogeneity in both exposures and outcomes. The unique composition of the space radiation environment makes the translation of the evidence base from terrestrial exposures to space exposures difficult. Additional investigation and understanding of the impact of low-to-moderate doses of ionizing radiation including high (H) atomic number (Z) and energy (E) (HZE) ions on the cerebrovascular system is needed. Furthermore, investigation of how decrements in vascular systems may contribute to development of neurodegenerative diseases in independent or synergistic pathways is important for protecting the long-term health of astronauts.

Geometrical Properties of the Nucleus and Chromosome Intermingling Are Possible Major Parameters of Chromosome Aberration Formation.

Ionizing radiation causes chromosome aberrations, which are possible biomarkers to assess space radiation cancer risks. Using the Monte Carlo codes Relativistic Ion Tracks (RITRACKS) and Radiation-Induced Tracks, Chromosome Aberrations, Repair and Damage (RITCARD), we investigated how geometrical properties of the cell nucleus, irradiated with ion beams of linear energy transfer (LET) ranging from 0.22 keV/µm to 195 keV/µm, influence the yield of simple and complex exchanges. We focused on the effect of (1) nuclear volume by considering spherical nuclei of varying radii; (2) nuclear shape by considering ellipsoidal nuclei of varying thicknesses; (3) beam orientation; and (4) chromosome intermingling by constraining or not constraining chromosomes in non-overlapping domains. In general, small nuclear volumes yield a higher number of complex exchanges, as compared to larger nuclear volumes, and a higher number of simple exchanges for LET < 40 keV/µm. Nuclear flattening reduces complex exchanges for high-LET beams when irradiated along the flattened axis. The beam orientation also affects yields for ellipsoidal nuclei. Reducing chromosome intermingling decreases both simple and complex exchanges. Our results suggest that the beam orientation, the geometry of the cell nucleus, and the organization of the chromosomes within are important parameters for the formation of aberrations that must be considered to model and translate in vitro results to in vivo risks.

Cardiovascular Disease Risk Modeling for Astronauts: Making the Leap From Earth to Space.

NASA has recently completed several long-duration missions to the International Space Station and is solidifying plans to return to the Moon, with an eye toward Mars and beyond. As NASA pushes the boundaries of human space exploration, the hazards of spaceflight, including space radiation, levy an increasing burden on astronaut health and performance. The cardiovascular system may be especially vulnerable due to the combined impacts of space radiation exposure, lack of gravity, and other spaceflight hazards. On Earth, the risk for cardiovascular disease (CVD) following moderate to high radiation doses is well-established from clinical, environmental, and occupational exposures (largely from gamma- and x-rays). Less is known about CVD risks associated with high-energy charged ions found in space and increasingly used in radiotherapy applications on Earth, making this a critical area of investigation for occupational radiation protection. Assessing CVD risk is complicated by its multifactorial nature, where an individual's risk is strongly influenced by factors such as family history, blood pressure, and lipid profiles. These known risk factors provide the basis for development of a variety of clinical risk prediction models (CPMs) that inform the likelihood of medical outcomes over a defined period. These tools improve clinical decision-making, personalize care, and support primary prevention of CVD. They may also be useful for individualizing risk estimates for CVD following radiation exposure both in the clinic and in space. In this review, we summarize unique aspects of radiation risk assessment for astronauts, and we evaluate the most widely used CVD CPMs for their use in NASA radiation risk assessment applications. We describe a comprehensive dual-use risk assessment framework that supports both clinical care and operational management of space radiation health risks using quantitative metrics. This approach is a first step in using personalized medicine for radiation risk assessment to support safe and productive spaceflight and long-term quality of life for NASA astronauts.

Medical Countermeasure Requirements to Meet NASA's Space Radiation Permissible Exposure Limits for a Mars Mission Scenario.

ABSTRACT: The space radiation environment consists of a complex mixture of ionizing particles that pose significant health risks to crew members. NASA currently requires that an astronaut's career Risk of Exposure Induced Death (REID) for cancer mortality should not exceed 3% at the upper 95% confidence level. This career radiation limit is likely to be exceeded for even the shortest round-trip mission scenario to Mars. As such, NASA has begun to pursue more vigorously approaches to directly reduce radiation risks, despite the large uncertainties associated with such projections. A recent study considered cohort studies of aspirin and warfarin as possible medical countermeasures (MCMs) acting to reduce background cancer mortality rates used in astronaut risk projections. It was shown that such MCMs can reduce the REID for specific tissues in restricted time intervals over which the drugs were administered; however, the cumulative effect on total lifetime REID was minimal. As an extension, the present work addresses more general MCM requirements that would be needed to meet current NASA radiation limits for a Mars mission scenario. A sensitivity analysis is performed within the major components of the NASA cancer risk model that would likely be modified by MCM interventions. This includes the background cancer incidence and mortality rates, epidemiologically based hazard rates derived from acute terrestrial exposures, and radiation quality factors used to translate terrestrial exposures to space radiation. Relationships between possible MCMs and each of these components are discussed. Results from this study provide important information regarding MCM requirements needed to meet NASA limits for planned Mars missions. Insight into the types of countermeasures expected to yield greatest reductions in crew risk is also gained.

Expert consultation is vital for adverse outcome pathway development: a case example of cardiovascular effects of ionizing radiation.

BACKGROUND: The circulatory system distributes nutrients, signaling molecules, and immune cells to vital organs and soft tissues. Epidemiological, animal, and in vitro cellular mechanistic studies have highlighted that exposure to ionizing radiation (IR) can induce molecular changes in cellular and subcellular milieus leading to long-term health impacts, particularly on the circulatory system. Although the mechanisms for the pathologies are not fully elucidated, endothelial dysfunction is proven to be a critical event via radiation-induced oxidative stress mediators. To delineate connectivities of events specifically to cardiovascular disease (CVD) initiation and progression, the adverse outcome pathway (AOP) approach was used with consultation from field experts. AOPs are a means to organize information around a disease of interest to a regulatory question. An AOP begins with a molecular initiating event and ends in an adverse outcome via sequential linkages of key event relationships that are supported by evidence in the form of the modified Bradford-Hill criteria. Detailed guidelines on building AOPs are provided by the Organisation for Economic Cooperation and Development (OECD) AOP program. Here, we report on the questions and discussions needed to develop an AOP for CVD resulting from IR exposure. A recent workshop jointly organized by the MELODI (Multidisciplinary European Low Dose Initiative) and the ALLIANCE (European Radioecology Alliance) associations brought together experts from the OECD to present the AOP approach and tools with examples from the toxicology field. As part of this workshop, four working groups were formed to discuss the identification of adverse outcomes relevant to radiation exposures and development of potential AOPs, one of which was focused on IR-induced cardiovascular effects. Each working group comprised subject matter experts and radiation researchers interested in the specific disease area and included an AOP coach. CONCLUSION: The CVD working group identified the critical questions of interest for AOP development, including the exposure scenario that would inform the evidence, the mechanisms of toxicity, the initiating event, intermediate key events/relationships, and the type of data currently available. This commentary describes the four-day discussion of the CVD working group, its outcomes, and demonstrates how collaboration and expert consultation is vital to informing AOP construction.

Cancer incidence and mortality in the USA Astronaut Corps, 1959-2017.

OBJECTIVES: Cancer incidence and mortality are important outcomes in the surveillance of long-term astronaut health. We compare cancer incidence rates, cancer-specific mortality rates, and cancer case-fatality ratios in US astronauts with those in the US general population. METHODS: We use standardised incidence ratios (SIRs) and standardised mortality ratios (SMRs) to index the incidence and mortality of various cancers against rates in the US general population, from the US astronaut cohort inception in April 1959 through 31 December 2017. We compare the lethality of these cancers using the relative case-fatality ratio. RESULTS: Overall cancer incidence and mortality were slightly lower than expected from national rates with SIR 82 (95% CI 63 to 104) and SMR 72 (95% CI 44 to 111) with a modest 14% reduction in case-fatality ratio. Prostate cancer and melanoma skin cancer had significant increases in incidence, with SIR of 162 (95% CI 109 to 232) and 252 (95% CI 126 to 452), respectively, though only melanoma had a significant increase in mortality, with SMR 508 (95% CI 105 to 1485). Lung cancer had a significant deficit of both cases and deaths, while colon cancer had sizeable (but not significant) reductions in incidence and mortality. CONCLUSIONS: The increase in incidence of melanoma is consistent with that observed in aircraft pilots, suggesting this may be associated with ultraviolet radiation or lifestyle factors rather than any astronaut-specific exposure. Reductions in lung cancer incidence and mortality, and trends towards such reductions in colon cancer, may be explained in part by healthy lifestyle, as well as differential screening among astronauts.

Earth-Based Research Analogs to Investigate Space-Based Health Risks.

During spaceflight, astronauts are exposed to a variety of unique hazards, including altered gravity fields, long periods of isolation and confinement, living in a closed environment at increasing distances from Earth, and exposure to higher levels of hazardous ionizing radiation. Preserving human health and performance in the face of these relentless hazards becomes progressively more difficult as missions increase in length and extend beyond low Earth orbit. Finding solutions is a significant challenge that is further complicated by logistical issues associated with studying these unique hazards. Although research studies using space-based platforms are the gold standard, these are not without limitations. Factors such as the small sample size of the available astronaut crew, high expense, and time constraints all add to the logistical challenge. To overcome these limitations, a wide variety of Earth-based analogs, from polar research outposts to an undersea laboratory, are available to augment space-based studies. Each analog simulates unique physiological and behavioral effects associated with spaceflight and, therefore, for any given study, the choice of an appropriate platform is closely linked to the phenomena under investigation as well as the characteristics of the analog. There are pros and cons to each type of analog and each actual facility, but overall they provide a reasonable means to overcome the barriers associated with conducting experimental research in space. Analogs, by definition, will never be perfect, but they are a useful component of an integrated effort to understand the human risks of living and working in space. They are a necessary resource for pushing the frontier of human spaceflight, both for astronauts and for commercial space activities. In this review, we describe the use of analogs here on Earth to replicate specific aspects of the spaceflight environment and highlight how analog studies support future human endeavors in space.

Red risks for a journey to the red planet: The highest priority human health risks for a mission to Mars.

NASA's plans for space exploration include a return to the Moon to stay-boots back on the lunar surface with an orbital outpost. This station will be a launch point for voyages to destinations further away in our solar system, including journeys to the red planet Mars. To ensure success of these missions, health and performance risks associated with the unique hazards of spaceflight must be adequately controlled. These hazards-space radiation, altered gravity fields, isolation and confinement, closed environments, and distance from Earth-are linked with over 30 human health risks as documented by NASA's Human Research Program. The programmatic goal is to develop the tools and technologies to adequately mitigate, control, or accept these risks. The risks ranked as "red" have the highest priority based on both the likelihood of occurrence and the severity of their impact on human health, performance in mission, and long-term quality of life. These include: (1) space radiation health effects of cancer, cardiovascular disease, and cognitive decrements (2) Spaceflight-Associated Neuro-ocular Syndrome (3) behavioral health and performance decrements, and (4) inadequate food and nutrition. Evaluation of the hazards and risks in terms of the space exposome-the total sum of spaceflight and lifetime exposures and how they relate to genetics and determine the whole-body outcome-will provide a comprehensive picture of risk profiles for individual astronauts. In this review, we provide a primer on these "red" risks for the research community. The aim is to inform the development of studies and projects with high potential for generating both new knowledge and technologies to assist with mitigating multisystem risks to crew health during exploratory missions.

Coronary Artery Dose-Volume Parameters Predict Risk of Calcification After Radiation Therapy.

BACKGROUND: Radiation exposure increases the risk of coronary artery disease (CAD). We explored the association of CAD with coronary artery dose-volume parameters in patients treated with 3D-planned radiation therapy (RT). METHODS: Patients who received thoracic RT and were evaluated by cardiac computed tomography ≥ 1 year later were included. Demographic data and cardiac risk factors were retrospectively collected. Dosimetric data (mean heart dose, dmax, dmean, V50 - V5) were collected for the whole heart and for each coronary artery. A coronary artery calcium (CAC) Agatston score was calculated on a per-coronary basis and as a total score. Multivariable generalized linear mixed models were generated. The predicted probabilities were used for receiver operating characteristic analyses. RESULTS: Twenty patients with a median age of 53 years at the time of RT were included. Nine patients (45%) had ≥ 3/6 conventional cardiac risk factors. Patients received RT for breast cancer (10, 50%), lung cancer (6, 30%), or lymphoma/myeloma (4, 20%) with a median dose of 60 Gy. CAC scans were performed a median of 32 months after RT. CAC score was significantly associated with radiation dose and presence of diabetes. In a multivariable model adjusted for diabetes, segmental coronary artery dosimetric parameters (dmax, dmean, V50, V40 V30, V20, V10, and V5) were significantly associated with CAC score > 0. V50 had the highest area under the ROC curve (0.89, 95% confidence interval, 0.80-0.97). CONCLUSIONS: Coronary artery radiation exposure is strongly correlated with subsequent segmental CAC score. Coronary calcification may occur soon after RT and in individuals with conventional cardiac risk factors.

Radiation Exposure and Mortality from Cardiovascular Disease and Cancer in Early NASA Astronauts.

Understanding space radiation health effects is critical due to potential increased morbidity and mortality following spaceflight. We evaluated whether there is evidence for excess cardiovascular disease or cancer mortality in early NASA astronauts and if a correlation exists between space radiation exposure and mortality. Astronauts selected from 1959-1969 were included and followed until death or February 2017, with 39 of 73 individuals still alive at that time. Calculated standardized mortality rates for tested outcomes were significantly below U.S. white male population rates, including all-cardiovascular disease (n = 7, SMR = 33; 95% CI, 14-65) and all-cancer (n = 7, SMR = 43; 95% CI, 18-83), as anticipated in a healthy worker population. Space radiation doses for cohort members ranged from 0-78 mGy. No significant associations between space radiation dose and mortality were found using logistic regression with an internal reference group, adjusting for medical radiation. Statistical power of the logistic regression was <6%, remaining <12% even when expected risk level or observed deaths were assumed to be 10 times higher than currently reported. While no excess radiation-associated cardiovascular or cancer mortality risk was observed, findings must be tempered by the statistical limitations of this cohort; notwithstanding, this small unique cohort provides a foundation for assessment of astronaut health.

Galactic cosmic ray simulation at the NASA Space Radiation Laboratory.

Most accelerator-based space radiation experiments have been performed with single ion beams at fixed energies. However, the space radiation environment consists of a wide variety of ion species with a continuous range of energies. Due to recent developments in beam switching technology implemented at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), it is now possible to rapidly switch ion species and energies, allowing for the possibility to more realistically simulate the actual radiation environment found in space. The present paper discusses a variety of issues related to implementation of galactic cosmic ray (GCR) simulation at NSRL, especially for experiments in radiobiology. Advantages and disadvantages of different approaches to developing a GCR simulator are presented. In addition, issues common to both GCR simulation and single beam experiments are compared to issues unique to GCR simulation studies. A set of conclusions is presented as well as a discussion of the technical implementation of GCR simulation.

Effects of sex and gender on adaptation to space: immune system.

This review is focused on sex and gender effects on immunological alterations occurring during space flight. Sex differences in immune function and the outcome of inflammatory, infectious, and autoimmune diseases are well documented. The work of the Immunology Workgroup identified numerous reasons why there could be sex and/or gender differences observed during and after spaceflight, but thus far, there has been very little investigation in this area of research. In most cases, this is due to either a low total number of subjects or the minimal number of female flight crew members available for these studies. Thus, the availability of a sufficient number of female subjects to enable statistical analysis of the data has been a limiting factor. As the inclusion of female crew members has increased in the recent past, such studies should be possible in the future. It is very difficult to obtain immunologic and infectious data in small animals that can be usefully extrapolated to humans undergoing spaceflight. Thus, it is recommended by the Immunology Workgroup that a greater emphasis be placed on studying astronauts themselves, with a focus on long-term evaluations of specific, known infectious risks.

How safe is safe enough? Radiation risk for a human mission to Mars.

Astronauts on a mission to Mars would be exposed for up to 3 years to galactic cosmic rays (GCR)--made up of high-energy protons and high charge (Z) and energy (E) (HZE) nuclei. GCR exposure rate increases about three times as spacecraft venture out of Earth orbit into deep space where protection of the Earth's magnetosphere and solid body are lost. NASA's radiation standard limits astronaut exposures to a 3% risk of exposure induced death (REID) at the upper 95% confidence interval (CI) of the risk estimate. Fatal cancer risk has been considered the dominant risk for GCR, however recent epidemiological analysis of radiation risks for circulatory diseases allow for predictions of REID for circulatory diseases to be included with cancer risk predictions for space missions. Using NASA's models of risks and uncertainties, we predicted that central estimates for radiation induced mortality and morbidity could exceed 5% and 10% with upper 95% CI near 10% and 20%, respectively for a Mars mission. Additional risks to the central nervous system (CNS) and qualitative differences in the biological effects of GCR compared to terrestrial radiation may significantly increase these estimates, and will require new knowledge to evaluate.

Heavy ions can enhance TGFß mediated epithelial to mesenchymal transition.

TGFß is a key modulator of the Epithelial-Mesenchymal Transition (EMT), a process important in cancer progression and metastasis, which leads to the suppression of epithelial genes and expression of mesenchymal proteins. Ionizing radiation was found to specifically induce expression of the TGF-ß1 isoform, which can modulate late post-radiation changes and increase the risk of tumor development and metastasis. Interactions between TGFß induced EMT and DNA damage responses have not been fully elucidated, particularly at low doses and following different radiation quality exposures. Further characterization of the relationship between radiation quality, EMT and cancer development is warranted. We investigated whether space radiation induced TGFß dependent EMT, using hTERT immortalized human esophageal epithelial cells (EPC2-hTERT) and non-transformed mink lung epithelial cells (Mv1Lu). We have observed morphologic and molecular alterations in EPC2 and Mv1Lu cells consistent with EMT after pre-treatment with TGFß1. This effect could be efficiently inhibited in both cell lines by the use of a TGFßRI inhibitor. High-energy silicon or iron nuclei were each able to cause a mild induction of EMT, with the inclusion of TGFß1 inducing a greatly enhanced EMT phenotype even when cells were irradiated with doses as low as 0.1 Gy. A further enhancement of EMT was achieved at a higher dose of 2 Gy. TGFßRI inhibitor was able to reverse the EMT induced by the combination of TGFß1 and radiation. These studies indicate that heavy ions, even at a low dose, may trigger the process of TGFß1-induced EMT, and suggest further studies are needed to determine whether the chronic exposures received in space may potentiate this process in astronauts, leading to an increased risk of cancer.

Ionizing radiation enhances esophageal epithelial cell migration and invasion through a paracrine mechanism involving stromal-derived hepatocyte growth factor.

Esophageal cancer is the sixth leading cause of cancer death worldwide and the seventh leading cause of cancer death in the U.S. male population. Ionizing radiation exposure is a risk factor for development of esophageal squamous cell carcinoma, a histological subtype of esophageal cancer that is highly aggressive and is associated with poor patient prognosis. This study investigated the effects of ionizing radiation on the microenvironment and intercellular communication as it relates to esophageal carcinogenesis. We demonstrate that normal esophageal epithelial cells exhibited increased migration and invasion when cultured in the presence of irradiated stromal fibroblasts or with conditioned medium derived from irradiated stromal fibroblasts. Cytokine antibody arrays and ELISAs were used to identify hepatocyte growth factor (HGF) as an abundant protein that is secreted by esophageal fibroblasts at twofold increased levels in culture medium after γ irradiation. Reverse transcription qPCR analysis confirmed an approximately 50% increase in mRNA levels for HGF at 1 h in irradiated fibroblasts compared to unirradiated controls. Recombinant HGF stimulated increased wound healing, migration and invasion of esophageal epithelial cells, while blocking antibodies against HGF significantly decreased migration and invasion of epithelial cells in coculture with irradiated fibroblasts. Since HGF is known to direct cell migration, invasion and metastasis in a variety of tissues, including the esophagus, its modulation by ionizing radiation may have important implications for nontargeted pathways that influence radiation carcinogenesis in the esophagus.

AT cells are not radiosensitive for simple chromosomal exchanges at low dose.

Cells deficient in ATM (product of the gene that is mutated in ataxia telangiectasia patients) or NBS (product of the gene mutated in the Nijmegen breakage syndrome) show increased yields of both simple and complex chromosomal aberrations after high doses (>0.5Gy) of ionizing radiation (X-rays or γ-rays), however less is known on how these cells respond at low dose. Previously we had shown that the increased chromosome aberrations in ATM and NBS defective lines was due to a significantly larger quadratic dose-response term compared to normal fibroblasts for both simple and complex exchanges. The linear dose-response term for simple exchanges was significantly higher in NBS cells compared to wild type cells, but not for AT cells. However, AT cells have a high background level of exchanges compared to wild type or NBS cells that confounds the understanding of low dose responses. To understand the sensitivity differences for high to low doses, chromosomal aberration analysis was first performed at low dose-rates (0.5Gy/d), and results provided further evidence for the lack of sensitivity for exchanges in AT cells below doses of 1Gy. Normal lung fibroblast cells treated with KU-55933, a specific ATM kinase inhibitor, showed increased numbers of exchanges at a dose of 1Gy and higher, but were similar to wild type cells at 0.5Gy or below. These results were confirmed using siRNA knockdown of ATM. The present study provides evidence that the increased radiation sensitivity of AT cells for chromosomal exchanges found at high dose does not occur at low dose.

Adequacy of wound education in undergraduate nursing curriculum.

PURPOSE: The purpose of this study is to evaluate a 2-hour lecture and laboratory class on wound care by a nurse wound specialist. DESIGN: A quantitative, quasi-experimental nonrandomized design was used to measure undergraduate nursing student's knowledge of wound care, prevention, and documentation. SETTING AND SUBJECTS: Sixty-five undergraduate nursing students in their second year of a 4-year public college participated in the study. Results were compared to 55 undergraduate first year nursing students in a 2-year community college program. Both the intervention and comparison groups received basic instruction on wound care and read a chapter on wound care in a required textbook prior to participating in this study. INSTRUMENTS: A pre- and postintervention questionnaire consisting of 10 multiple choice and true/false questions was used to measure wound care knowledge. METHODS: A comparison cohort study was conducted among 2 groups of nursing students to determine whether students receiving a 2-hour lecture and laboratory class on wound care by a nurse wound specialist retained more knowledge about wound care 2 months following the educational intervention. The intervention was 3-hour lecture and laboratory-based experience delivered by a wound care specialist. The control group completed the questionnaire at the end of the semester and answered questions based on their readings and basic lecture from their nursing program instructors. RESULTS: Intervention group participants had significantly higher scores on 7 of 10 questions as compared to the control group of student nurses. CONCLUSION: A 2-hour lecture or laboratory intervention improved the nursing student's knowledge of basic evidenced wound care; this improvement persisted for a prolonged period of time (2 months).

Dendro[C(60)]fullerene DF-1 provides radioprotection to radiosensitive mammalian cells.

In this study, the ability of the C(60) fullerene derivative DF-1 to protect radiosensitive cells from the effects of high doses of gamma irradiation was examined. Earlier reports of DF-1's lack of toxicity in these cells were confirmed, and DF-1 was also observed to protect both human lymphocytes and rat intestinal crypt cells against radiation-induced cell death. We determined that DF-1 protected both cell types against radiation-induced DNA damage, as measured by inhibition of micronucleus formation. DF-1 also reduced the levels of reactive oxygen species in the crypt cells, a unique capability of fullerenes because of their enhanced reactivity toward electron-rich species. The ability of DF-1 to protect against the cytotoxic effects of radiation was comparable to that of amifostine, another ROS-scavenging radioprotector. Interestingly, localization of fluorescently labeled DF-1 in fibroblast was observed throughout the cell. Taken together, these results suggest that DF-1 provides powerful protection against several deleterious cellular consequences of irradiation in mammalian systems including oxidative stress, DNA damage, and cell death.

The analysis of the densely populated patterns of radiation-induced foci by a stochastic, Monte Carlo model of DNA double-strand breaks induction by heavy ions.

PURPOSE: To resolve the difficulty in counting merged DNA damage foci in high-LET (linear energy transfer) ion-induced patterns. MATERIALS AND METHODS: The analysis of patterns of RIF (radiation-induced foci) produced by high-LET Fe and Ti ions were conducted by using a Monte Carlo model that combines the heavy ion track structure with characteristics of the human genome on the level of chromosomes. The foci patterns were also simulated in the maximum projection plane for flat nuclei. RESULTS: The model predicts the spatial and genomic distributions of DNA DSB (double-strand breaks) in a cell nucleus for a particular dose of radiation. We used the model to do analyses for three irradiation scenarios: (i) The ions were oriented perpendicular to the flattened nuclei in a cell culture monolayer; (ii) the ions were parallel to that plane; and (iii) round nucleus. In the parallel scenario we found that the foci appeared to be merged due to their high density, while, in the perpendicular scenario, the foci appeared as one bright spot per hit. The statistics and spatial distribution of regions of densely arranged foci, termed DNA foci chains, were predicted numerically using this model. Another analysis was done to evaluate the number of ion hits per nucleus, which were visible from streaks of closely located foci. CONCLUSIONS: We showed that DSB clustering needs to be taken into account to determine the true DNA damage foci yield, which helps to determine the DSB yield. Using the model analysis, a researcher can refine the DSB yield per nucleus per particle. We showed that purely geometric artifacts, present in the experimental images, can be analytically resolved with the model, and that the quantisation of track hits and DSB yields can be provided to the experimentalists who use enumeration of radiation-induced foci in immunofluorescence experiment using proteins that detect DNA damage.