Considering clonal hematopoiesis of indeterminate potential in space radiation risk analysis for hematologic cancers and cardiovascular disease.

Background: Expanding human presence in space through long-duration exploration missions and commercial space operations warrants improvements in approaches for quantifying crew space radiation health risks. Currently, risk assessment models for radiogenic cancer and cardiovascular disease consider age, sex, and tobacco use, but do not incorporate other modifiable (e.g.

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).

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Label-free protein and pathogen detection using the atomic force microscope.

The atomic force microscope (AFM) uses a sharp micron-scale tip to scan and amplify surface features, providing exceptionally detailed topographical information with magnification on the order of x10(6). This instrument is used extensively for quality control in the computer and semiconductor industries and is becoming a progressively more important tool in the biological sciences. Advantages of the AFM for biological application include the ability to obtain information in a direct, label-free manner and the ability to image in solution, providing real-time data acquisition under physiologically relevant conditions.

Microfabricated quill-type surface patterning tools for the creation of biological micro/nano arrays.

Novel quill-type cantilever-based surface patterning tools (SPTs) were designed and constructed for use in controlled placement of femtoliter volumes of biological molecules on surfaces for biological applications. These tools were fabricated from silicon dioxide using microelectromechanical systems (MEMS) techniques. They featured a 1 microm split gap, fluidic transport microchannels and self-replenishing reservoirs.

Perillyl Alcohol Inhibits Breast Cell Migration without Affecting Cell Adhesion.

The monoterpene d-limonene exhibits chemotherapeutic and chemopreventive potential in breast cancer patients. D-limonene and its related compounds, perillyl alcohol and perillyl aldehyde, were chosen as candidate drugs for application in a screen for nontoxic inhibitors of cell migration. Using the nontumorigenic human breast cell line MCF-10A, we delineated the toxicity as greatest for the perillyl aldehyde, intermediate for perillyl alcohol, and least for limonene.

Drosophila windpipe codes for a leucine-rich repeat protein expressed in the developing trachea.

The embryonic tracheal system of Drosophila provides an important model for understanding the process of epithelial branching morphogenesis. Here we report the sequence and expression analysis of a novel tracheal gene, named windpipe (wdp). wdp is identical to the predicted gene CG3413 and encodes a transmembrane, leucine-rich repeat family member.