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At least 505 records · Page 28

Oxidative Stress and Neuroconsequences of the Spaceflight Environment –A 5-ion GCRsim Dose-response Study

The overall scope of this project is to test the hypothesis that Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure/function, and neurobehavioral/cognitive performance. Specific Aims for this project are to: (1) Determine dose-response curves for acute ‘Five-Ion GCR Simulation’ exposure for immune, brain and performance responses in crew age-matched adult male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune, brain and performance responses in crew age-matched male and female mice mimicking deep space missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. Here we exposed mature (23-24-week-old) male and female mice to simulated 5-Ion GCR (either 0, 5, 15, or 50cGy) at the NASA Space Radiation Laboratory (NSRL). Across ‘Acute’ (IR+72hrs and IR+14 days) and ‘Delayed’ (IR+28 to IR+124 days) phases of the 6-month-long study, we assessed immune, neural, and functional (sensorimotor/behavioral/cognitive) responses anticipated during a transit to Mars. This presentation will report on dose-response curves for 5-ion GCRsim related to potential biomarkers; structural/functional changes in the immune and nervous systems; and behavioral/cognitive performance deficits. This project addresses NASA’s efforts to characterize risks and identify appropriate countermeasures in anticipation of future deep space missions. Ensuring crew health and performance during extended transits necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes.

deep space↗

Sex differences and deep space stressors: effects of 5-ion gcrsim, simulated microgravityand social isolation on immune function, brain, and behavior in mice

This project is testing the hypothesis that Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure/function, and neurobehavioral/cognitive performance. Specific Aims for this project are to: (1) Determine dose-response curves for acute ‘Five-Ion GCR Simulation’ exposure for immune, brain and performance responses in crew age-matched adult male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune, brain and performance responses in crew age-matched male and female mice mimicking deep space missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. Here we report findings from our studies of mature (24-week-old) male and female mice exposed to simulated 5-Ion GCRsim (0, 5, 15, or 50cGy) at the NASA Space Radiation Laboratory (NSRL) followed by combinatorial exposures to 15cGy, simulated microgravity via head-down tilt (hindlimb unloading) and social isolation. Immune, brain and behavioral (sensorimotor, risk-taking & cognitive) measures were acquired at ‘Acute’ (IR+24hrs, IR+72hrs), ‘Intermediate’ (IR+14 days) and ‘Delayed’ (IR+28 to IR+124 days) to inform biological responses anticipated during a transit to Mars. This project addresses NASA’s efforts to characterize risks and identify appropriate countermeasures in both women and men in anticipation of future deep space missions. Ensuring crew health and performance during extended transits necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes. Supported by the NASA Human Research Program (HRP) Human Factors Behavioral Performance Element Grant 18 18FLAG 2 0028.

behavioral sciences↗

The Effects of Spaceflight and Microgravity Exposure on Female Astronaut Health and Performance

Over the past half century, our understanding of the physiological effects of space exploration and microgravity exposure have improved immensely. Microgravity causes incredible changes to the human body that increase risk of injury upon return to Earth and lunar/planetary egress scenarios. This is due to deconditioning of the cardiovascular and skeletal muscle systems that reduce aerobic capacity and muscular strength. With upcoming exploration class missions, such as NASA’s Artemis lunar exploration program which aims to send the first female astronaut to the lunar surface by 2030, as well as a long-term goal of Martian exploration, maintaining astronaut health during extended-duration space flight is critical for achieving mission objectives. However, our understanding of these physiological implications due to microgravity are based primarily on flight studies of male astronauts and 1g bedrest analog study participants, with few investigations focusing specifically on females. Innate physiologic differences in endocrine signaling and reproductive function impact sex-dependent responses to various health conditions, treatments, and environmental factors in nearly every system in the body. Therefore, to assume comparable alterations in females in response to microgravity exposure may be inappropriate and consequentially, could lead to lasting impacts on female astronaut health and impact mission success. Moreover, differences in sex hormones may also influence the regulation of cardiovascular control during egress activity after space flight-induced deconditioning and blood volume loss (i.e., risk for orthostatic intolerance). Other potential physiological systems and factors related to musculoskeletal health and aerobic capacity that warrant investigation with respect to microgravity include endocrine/reproductive function, vascular control, bone mineral density/microarchitecture, and soft-tissue health. The purpose of this investigation is two-fold: 1) to summarize the data available from space flight and simulated bedrest analog exposures to begin addressing these gaps in knowledge regarding impacts to female astronaut health, and 2) to describe differences in demographic health characteristics, injury prevalence, and aerobic capacity and muscular strength in NASA female and male astronauts. Female astronauts make up 50% of Artemis-specific astronaut corps and the extent to which microgravity exposure impacts female cardiovascular and musculoskeletal health, and whether these alterations are consistent with their male counterparts, is inconclusive. With the growing inclusion of female astronauts in the NASA space program and the increased duration of missions beyond low Earth orbit, a greater understanding of the sex-specific adaptation to space travel will help determine the development of appropriate countermeasures for minimizing risk and maintaining health of all astronauts.

Nicole Christine Strock↗

The Effects of Space Flight and Microgravity Exposure on Female Astronaut Health and Performance

Over the past half century, our understanding of the physiological effects of space exploration and microgravity exposure have improved immensely. Microgravity causes incredible changes to the human body that increase risk of injury upon return to Earth and lunar/planetary egress scenarios. This is due to deconditioning of the cardiovascular and skeletal muscle systems that reduce aerobic capacity and muscular strength. With upcoming exploration class missions, such as NASA’s Artemis lunar exploration program which aims to send the first female astronaut to the lunar surface by 2030, as well as a long-term goal of Martian exploration, maintaining astronaut health during extended-duration space flight is critical for achieving mission objectives. However, our understanding of these physiological implications due to microgravity are based primarily on flight studies of male astronauts and 1g bed rest analog study participants, with few investigations focusing specifically on females. Innate physiologic differences in endocrine signaling and reproductive function impact sex-dependent responses to various health conditions, treatments, and environmental factors in nearly every system in the body. Therefore, to assume comparable alterations in females in response to microgravity exposure may be inappropriate and consequentially, could lead to lasting impacts on female astronaut health and impact mission success. Moreover, differences in sex hormones may also influence the regulation of cardiovascular control during egress activity after space flight-induced deconditioning and blood volume loss (i.e., risk for orthostatic intolerance). Other potential physiological systems and factors related to musculoskeletal health and aerobic capacity that warrant investigation with respect to microgravity include endocrine/reproductive function, vascular control, bone mineral density/microarchitecture, and soft-tissue health. The purpose of this investigation is two-fold: 1) to summarize the data available from space flight and simulated bed rest analog exposures to begin addressing these gaps in knowledge regarding impacts to female astronaut health, and 2) to describe differences in demographic health characteristics, injury prevalence, and aerobic capacity and muscular strength in NASA female and male astronauts. Female astronauts make up 50% of Artemis-specific astronaut corps and the extent to which microgravity exposure impacts female cardiovascular and musculoskeletal health, and whether these alterations are consistent with their male counterparts, is inconclusive. With the growing inclusion of female astronauts in the NASA space program and the increased duration of missions beyond low Earth orbit, a greater understanding of the sex-specific adaptation to space travel will help determine the development of appropriate countermeasures for minimizing risk and maintaining health of all astronauts.

Female Astronaut↗

Neuro-behavioral Consequences of Low Dose Radiation Social Isolation and Sex Differences in the Longevity MCAT Mouse Model

The physiological responses to spaceflight elicit wide-ranging consequences and resemble aspects of aging on Earth. Previous studies have shown that oxidative damage via reactive oxygen species (ROS), contributes to aging-related pathologies. Our study uses 1-year old C57BL/6NJ male and female mice (astronaut-relevant age) that underwent exposure to 0.5 gray of gamma radiation together with social isolation and were euthanized 12 weeks after. We used the longevity MCAT mouse model in which human catalase is overexpressed in the mitochondria, for ROS quenching. We aimed to determine whether in older mice quenching ROS, will mitigate the neuro-behavioral consequences of low dose ionizing radiation and/or social isolation and whether the outcomes will differ in males and females. We have performed five mission relevant behavioral tests which focused on performance, memory, physical stance, and stress. We have detected both sex and radiation effects; the older females look physically better are faster and perform better almost in all behavioral tests compared to their male counterparts. On the other hand, they are more sensitive to low dose radiation in many cases, in some cases this effect was indeed mitigated in the MCAT mice, pointing out to the importance of ROS in response to radiation stress and social isolation. We have measured plasma (7- and 90-days post radiation), cytokines, corticosterone and hippocampal cytokine and microglial activation at the end of the experiment. We saw significant changes in the plasma markers due to radiation, sex, and genotype in both short and long post radiation period and detected long term sex and radiation effects in the brain. Our focus is now on applying advanced statistical modeling to corelate the behavioral tests with our recent molecular findings to look for specific biomarkers that could predict behavioral deficits.

radiation↗

The Effects of Space Flight and Microgravity Exposure on Female Astronaut Health and Performance

Over the past half century, our understanding of the physiological effects of space exploration and microgravity exposure have improved immensely. Microgravity causes incredible changes to the human body that increase risk of injury upon return to Earth and lunar/planetary egress scenarios. This is due to deconditioning of the cardiovascular and skeletal muscle systems that reduce aerobic capacity and muscular strength. With upcoming exploration class missions, such as NASA’s Artemis lunar exploration program which aims to send the first female astronaut to the lunar surface by 2030, as well as a long-term goal of Martian exploration, maintaining astronaut health during extended-duration space flight is critical for achieving mission objectives. However, our understanding of these physiological implications due to microgravity are based primarily on flight studies of male astronauts and 1g bed rest analog study participants, with few investigations focusing specifically on females. Innate physiologic differences in endocrine signaling and reproductive function impact sex-dependent responses to various health conditions, treatments, and environmental factors in nearly every system in the body. Therefore, to assume comparable alterations in females in response to microgravity exposure may be inappropriate and consequentially, could lead to lasting impacts on female astronaut health and impact mission success. Moreover, differences in sex hormones may also influence the regulation of cardiovascular control during egress activity after space flight-induced deconditioning and blood volume loss (i.e., risk for orthostatic intolerance). Other potential physiological systems and factors related to musculoskeletal health and aerobic capacity that warrant investigation with respect to microgravity include endocrine/reproductive function, vascular control, bone mineral density/microarchitecture, and soft-tissue health. The purpose of this investigation is two-fold: 1) to summarize the data available from space flight and simulated bed rest analog exposures to begin addressing these gaps in knowledge regarding impacts to female astronaut health, and 2) to describe differences in demographic health characteristics, injury prevalence, and aerobic capacity and muscular strength in NASA female and male astronauts. Female astronauts make up 50% of Artemis-specific astronaut corps and the extent to which microgravity exposure impacts female cardiovascular and musculoskeletal health, and whether these alterations are consistent with their male counterparts, is inconclusive. With the growing inclusion of female astronauts in the NASA space program and the increased duration of missions beyond low Earth orbit, a greater understanding of the sex-specific adaptation to space travel will help determine the development of appropriate countermeasures for minimizing risk and maintaining health of all astronauts.

Female Astronaut↗

Case Study: Polycystic Livers in a Transgenic Mouse Line

Three mice (2 male, 1 female; age, 5 to 16 mo) from a mouse line transgenic for keratin 14 (K14)-driven LacZ expression and on an outbred Crl:CD1(ICR) background, were identified as having distended abdomens and livers that were diffusely enlarged by numerous cysts (diameter, 0.1 to 2.0 cm). Histopathology revealed hepatic cysts lined by biliary type epithelium and mild chronic inflammation, and confirmed the absence of parasites. Among 21 related mice, 5 additional affected mice were identified via laparotomy. Breeding of these 5 mice (after 5 mo of age) did not result in any offspring; the K14 mice with olycystic livers failed to reproduce. Affected male mice had degenerative testicular lesions, and their sperm was immotile. Nonpolycystic K14 control male mice bred well, had no testicular lesions, and had appropriate sperm motility. Genetic analysis did not identify an association of this phenotype with the transgene or insertion site.

Lovaglio, Jamie A.↗

Frequency and Temporal Analysis of Cicada Brood X Sounds

Cicadas are insects that belong to the order Hemiptera (i.e., true bugs). They feed on plant fluids above and below ground. Cicada species fall into two categories: periodical and annual. Seven species of periodical cicadas have been identified, emerging in 13-, 17-, and 21-year cycles [1]. The largest brood (i.e., periodical cicadas of the same cycle) of 17-year cicadas is Brood X, examples of which are shown in Fig. 1. Male cicadas produce the loudest sounds of the insect world. A single male can produce a clicking sound that exceeds 100 dB sound pressure level. This male cicada sound emanates from an organ called the tympanic membrane, which is located on both sides of the body near the base of the wing [2]. The vibrations from this organ generate the sound. Female cicadas make a similar— although less loud—clicking sound with their wings. Figure 2 shows the locations of active cicadas within the United States.

59 BASIC BIOLOGICAL SCIENCES↗

Effects of pre- and postnatal exposure to the UV-filter Octyl Methoxycinnamate (OMC) on the reproductive, auditory and neurological development of rat offspring

Octyl Methoxycinnamate (OMC) is a frequently used UV-filter in sunscreens and other cosmetics. The aim of the present study was to address the potential endocrine disrupting properties of OMC, and to investigate how OMC induced changes in thyroid hormone levels would be related to the neurological development of treated offspring. Groups of 14-18 pregnant Wistar rats were dosed with 0, 500, 750 or 1000 mg OMC/kg bw/day during gestation and lactation. Serum thyroxine (T{sub 4}), testosterone, estradiol and progesterone levels were measured in dams and offspring. Anogenital distance, nipple retention, postnatal growth and timing of sexual maturation were assessed. On postnatal day 16, gene expression in prostate and testes, and weight and histopathology of the thyroid gland, liver, adrenals, prostate, testes, epididymis and ovaries were measured. After weaning, offspring were evaluated in a battery of behavioral and neurophysiological tests, including tests of activity, startle response, cognitive and auditory function. In adult animals, reproductive organ weights and semen quality were investigated. Thyroxine (T{sub 4}) levels showed a very marked decrease during the dosing period in all dosed dams, but were less severely affected in the offspring. On postnatal day 16, high dose male offspring showed reduced relative prostate and testis weights, and a dose-dependent decrease in testosterone levels. In OMC exposed female offspring, motor activity levels were decreased, while low and high dose males showed improved spatial learning abilities. The observed behavioral changes were probably not mediated solely by early T{sub 4} deficiencies, as the observed effects differed from those seen in other studies of developmental hypothyroxinemia. At eight months of age, sperm counts were reduced in all three OMC-dosed groups, and prostate weights were reduced in the highest dose group. Taken together, these results indicate that perinatal OMC-exposure can affect both the reproductive and neurological development of rat offspring, which may be a cause of concern, as humans are systematically exposed to the compound through usage of sunscreens and other cosmetics.

60 APPLIED LIFE SCIENCES↗

Factors affecting breeding season survival of Red-Headed Woodpeckers in South Carolina.

Red-headed woodpecker (Melanerpes erythrocephalus) populations have declined in the United States and Canada over the past 40 years. However, few demographic studies have been published on the species and none have addressed adult survival. During 2006-2007, we estimated survival probabilities of 80 radio-tagged red-headed woodpeckers during the breeding season in mature loblolly pine (Pinus taeda) forests in South Carolina. We used known-fate models in Program MARK to estimate survival within and between years and to evaluate the effects of foliar cover (number of available cover patches), snag density treatment (high density vs. low density), and sex and age of woodpeckers. Weekly survival probabilities followed a quadratic time trend, being lowest during mid-summer, which coincided with the late nestling and fledgling period. Avian predation, particularly by Cooper's (Accipiter cooperii) and sharp-shinned hawks (A. striatus), accounted for 85% of all mortalities. Our best-supported model estimated an 18-week breeding season survival probability of 0.72 (95% CI = 0.54-0.85) and indicated that the number of cover patches interacted with sex of woodpeckers to affect survival; females with few available cover patches had a lower probability of survival than either males or females with more cover patches. At the median number of cover patches available (n = 6), breeding season survival of females was 0.82 (95% CI = 0.54-0.94) and of males was 0.60 (95% CI = 0.42-0.76). The number of cover patches available to woodpeckers appeared in all 3 of our top models predicting weekly survival, providing further evidence that woodpecker survival was positively associated with availability of cover. Woodpecker survival was not associated with snag density. Our results suggest that protection of {ge}0.7 cover patches per ha during vegetation control activities in mature pine forests will benefit survival of this Partners In Flight Watch List species.

60 APPLIED LIFE SCIENCES↗

Alternative Techniques for Treatment of Complex Below-the Knee Arterial Occlusions in Diabetic Patients With Critical Limb Ischemia

The purpose of this study was to describe alternative endovascular (EV) techniques and assess their feasibility and efficacy in minimizing failure rates in limb salvage for the treatment of complex below-the knee (BTK) occlusions that could not be crossed with a conventional antegrade access. Between December 2007 and November 2010, 1,035 patients (557 male) underwent EV treatment for critical limb ischemia in our institution. In 124 (12% [83 male], mean age 68.2 {+-} 0.5 years) patients, transfemoral antegrade revascularization attempt failed, and an alternative approach was used. Follow-up was performed at 1 and 6 months. Results were compared with 56 patients treated between November 2002 and November 2007, in whom conventional technique was unsuccessful and unconventional techniques were not adopted. Technical success was achieved in 119 (96%) patients. The limb-salvage rates were 96.8% and 83% at 1- and 6-month follow-up, respectively. Sixteen (12.9%) and 33 (26.6%) patients underwent reintervention at 1- and 6-month follow-up, respectively. Transcutaneous oxygen tension increased at 1 month (44.7 {+-} 1.1 vs. 15.7 {+-} 0.8 mmHg; p < 0.001) and remained stable at follow-up. Twenty (16.1%) patients required major amputation. Thirteen (10.4%) patients died during follow-up. In our previous experience, percutaneous transluminal angioplasty failure, amputation, and death rates were 10.9, 39.2, and 23.2%, respectively. Alternative techniques allowed a significant decrease of major amputation and death rates (p = 0.0001 and p = 0.02, respectively). The use of alternative techniques seems feasible in case of a failed antegrade BTK revascularization attempt and could minimize failure rates in the treatment of complex occlusions while providing satisfying clinical success rates at 6 months.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A New Occlusion Device: Application of the ArtVentive Endoluminal Occlusion System (EOS)—First in Human Clinical Trial

Purpose: The purpose of this study was to determine the safety and efficacy of a new endoluminal occlusion device, ArtVentive endoluminal occlusion system (EOS), to occlude the spermatic vein in symptomatic males with varicoceles. Methods: The ArtVentive EOS device has been developed for percutaneous, peripheral occlusion of the peripheral arterial and venous vasculature. The system is comprised of an implantable occlusion device and a delivery catheter. At present, there are two device sizes: (a) size 1 for target vessels ranging between 3.5 and 5.5 mm in diameter, and (b) size 2 for target vessels 5.5–8.5 mm in diameter. The treatment group included six adult males, ages 22–34 years. Nine target vessels were occluded. A total of 20 devices were implanted in six subjects. Results: The acute occlusion rate at the end of the procedure was 100 % occurring in nine of nine vessels. The spermatic veins of all patients remained occluded on venography at 30 days follow-up. Pain scores related to varicoceles decreased in five of six patients. Conclusions: Although we recognize this study is limited, initial experience indicates that the ArtVentive EOS is a safe and effective new device for occlusion of vessels (varicoceles). The device has potential applications in other clinical conditions requiring occlusion of veins or arteries.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

The impact of heatwaves on workers' health and safety in Adelaide, South Australia

This study aims to investigate the impact of heatwaves on worker's health and safety; to identify workers at higher risk of prevalent illnesses and injuries due to heatwaves; and to provide evidence for policy-makers and service providers. South Australian workers' compensation claims data for 2001–2010 were transformed into time series format, merged with meteorological data and analysed using generalized estimating equation (GEE) models. For total injury claims there was no significant difference detected between heatwave and non-heatwave periods. However, for outdoor industries, daily claims increased significantly by 6.2% during heatwaves. Over-represented in hot weather were male labourers and tradespersons aged ≥55 years, and those employed in ‘agriculture, forestry and fishing’ and ‘electricity, gas and water’. Occupational burns, wounds, lacerations, and amputations as well as heat illnesses were significantly associated with heatwaves. Similarly, moving objects, contact with chemicals, and injuries related to environmental factors increased significantly during heatwaves, especially among middle-aged and older male workers. With the predicted increase of extremely hot weather, there is a need for relevant adaptation and prevention measures at both practice and policy levels for vulnerable work groups. - Highlights: • We investigate the impacts of heatwaves on workers' health and safety. • We identify workers at higher risk of illnesses and injuries during heatwaves. • The differences between two heatwave definitions on effect estimates are compared. • Daily injury claims for outdoor industries increased by 6.2% during heatwaves. • Relevant heat prevention measures are required for vulnerable workers.

54 ENVIRONMENTAL SCIENCES↗

Twenty-Five-Year Experience With Radical Chemoradiation for Anal Cancer

Purpose: To evaluate the prognostic factors, patterns of failure, and late toxicity in patients treated with chemoradiation (CRT) for anal cancer. Methods and Materials: Consecutive patients with nonmetastatic squamous cell carcinoma of the anus treated by CRT with curative intent between February 1983 and March 2008 were identified through the institutional database. Chart review and telephone follow-up were undertaken to collect demographic data and outcome. Results: Two hundred eighty-four patients (34% male; median age 62 years) were identified. The stages at diagnosis were 23% Stage I, 48% Stage II, 10% Stage IIIA, and 18% Stage IIIB. The median radiotherapy dose to the primary site was 54 Gy. A complete clinical response to CRT was achieved in 89% of patients. With a median follow-up time of 5.3 years, the 5-year rates of locoregional control, distant control, colostomy-free survival, and overall survival were 83% (95% confidence interval [CI] 78-88), 92% (95% CI, 89-96), 73% (95% CI, 68-79), and 82% (95% CI, 77-87), respectively. Higher T stage and male sex predicted for locoregional failure, and higher N stage predicted for distant metastases. Locoregional failure occurred most commonly at the primary site. Omission of elective inguinal irradiation resulted in inguinal failure rates of 1.9% and 12.5% in T1N0 and T2N0 patients, respectively. Pelvic nodal failures were very uncommon. Late vaginal and bone toxicity was observed in addition to gastrointestinal toxicity. Conclusions: CRT is a highly effective approach in anal cancer. However, subgroups of patients fare relatively poorly, and novel approaches are needed. Elective inguinal irradiation can be safely omitted only in patients with Stage I disease. Vaginal toxicity and insufficiency fractures of the hip and pelvis are important late effects that require prospective evaluation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Spot Scanning-Based Proton Therapy for Intracranial Meningioma: Long-Term Results From the Paul Scherrer Institute

Background: To assess the long-term clinical results of spot scanning proton therapy (PT) in the treatment of intracranial meningiomas. Patients and Methods: Thirty-nine patients with meningioma (histologically proven 34/39) were treated with PT between July 1997 and January 2010. Thirty-two (82.1%) patients were treated as primary treatment (exclusive PT, n = 8; postoperative PT, n = 24). Mean age was 48.3 {+-} 17.9 years and 32 (82.1%) patients had skull base lesions. For patients undergoing surgery, 24 patients had a diagnosis of World Health Organization (WHO) Grade I and 10 of a WHO Grade II/III meningioma, respectively. The female-to-male ratio was 3.3. The median administered dose was 56.0 Gy (relative biologic effectiveness [RBE]) (range, 52.2-66.6) at 1.8-2.0 Gy (RBE) per fraction. Gross tumor volume (GTV) ranged from 0.76 to 546.5 cm{sup 3} (median, 21.5). Late toxicity was assessed according to Common Terminology Criteria for Adverse Events version 3.0. Mean follow-up time was 62.0 months and all patients were followed for >6 months. Results: Six patients presented with tumor recurrence and 6 patients died during follow-up, of which 4 of tumor progression. Five-year actuarial local control and overall survival rates were 84.8% and 81.8%, respectively, for the entire cohort and 100% for benign histology. Cumulative 5-year Grade {>=}3 late toxicity-free survival was 84.5%. On univariate analysis, LC was negatively influenced by WHO grade (p = 0.001), GTV (p = 0.013), and male gender (p = 0.058). Conclusions: PT is a safe and effective treatment for patients with untreated, recurrent, or incompletely resected intracranial meningiomas. WHO grade and tumor volume was an adverse prognostic factor for local control.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Effects of Voice Rehabilitation After Radiation Therapy for Laryngeal Cancer: A Randomized Controlled Study

Background: Patients treated with radiation therapy for laryngeal cancer often experience voice problems. The aim of this randomized controlled trial was to assess the efficacy of voice rehabilitation for laryngeal cancer patients after having undergone radiation therapy and to investigate whether differences between different tumor localizations with regard to rehabilitation outcomes exist. Methods and Materials: Sixty-nine male patients irradiated for laryngeal cancer participated. Voice recordings and self-assessments of communicative dysfunction were performed 1 and 6 months after radiation therapy. Thirty-three patients were randomized to structured voice rehabilitation with a speech-language pathologist and 36 to a control group. Furthermore, comparisons with 23 healthy control individuals were made. Acoustic analyses were performed for all patients, including the healthy control individuals. The Swedish version of the Self Evaluation of Communication Experiences after Laryngeal Cancer and self-ratings of voice function were used to assess vocal and communicative function. Results: The patients who received vocal rehabilitation experienced improved self-rated vocal function after rehabilitation. Patients with supraglottic tumors who received voice rehabilitation had statistically significant improvements in voice quality and self-rated vocal function, whereas the control group did not. Conclusion: Voice rehabilitation for male patients with laryngeal cancer is efficacious regarding patient-reported outcome measurements. The patients experienced better voice function after rehabilitation. Patients with supraglottic tumors also showed an improvement in terms of acoustic voice outcomes. Rehabilitation with a speech-language pathologist is recommended for laryngeal cancer patients after radiation therapy, particularly for patients with supraglottic tumors.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Past, present and emerging toxicity issues for jet fuel

The US Air Force wrote the specification for the first official hydrocarbon-based jet fuel, JP-4, in 1951. This paper will briefly review the toxicity of the current fuel, JP-8, as compared to JP-4. JP-8 has been found to have low acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with slight dermal irritation as the adverse effect. Respiratory tract sensory irritation was greater in JP-8 than in JP-4. Recent data suggest exposure to jet fuel may contribute to hearing loss. Subchronic studies for 90 days with JP-8 and JP-4 showed little toxicity with the primary effect being male rat specific hydrocarbon nephropathy. A 1-year study was conducted for JP-4. The only tumors seen were associated with the male rat specific hydrocarbon nephropathy. A number of immunosuppressive effects have been seen after exposure to JP-8. Limited neurobehavioral effects have been associated with JP-8. JP-8 is not a developmental toxicant and has little reproductive toxicity. JP-4 has not been tested for immune, neurobehavioral or reproductive endpoints. JP-8 and JP-4 were negative in mutagenicity tests but JP-4 showed an increase in unscheduled DNA synthesis. Currently, JP-8 is being used as the standard for comparison of future fuels, including alternative fuels. Emerging issues of concern with jet fuels include naphthalene content, immunotoxicity and inhalation exposure characterization and modeling of complex mixtures such as jet fuels.

60 APPLIED LIFE SCIENCES↗

Prenatal PCBs disrupt early neuroendocrine development of the rat hypothalamus

Neonatal exposure to endocrine disrupting chemicals (EDCs) such as polychlorinated biphenyls (PCBs) can interfere with hormone-sensitive developmental processes, including brain sexual differentiation. We hypothesized that disruption of these processes by gestational PCB exposure would be detectable as early as the day after birth (postnatal day (P) 1) through alterations in hypothalamic gene and protein expression. Pregnant Sprague-Dawley rats were injected twice, once each on gestational days 16 and 18, with one of the following: DMSO vehicle; the industrial PCB mixture Aroclor 1221 (A1221); a reconstituted mixture of the three most prevalent congeners found in humans, PCB138, PCB153, and PCB180; or estradiol benzoate (EB). On P1, litter composition, anogenital distance (AGD), and body weight were assessed. Pups were euthanized for immunohistochemistry of estrogen receptor {alpha} (ER{alpha}) or TUNEL labeling of apoptotic cells or quantitative PCR of 48 selected genes in the preoptic area (POA). We found that treatment with EB or A1221 had a sex-specific effect on developmental apoptosis in the neonatal anteroventral periventricular nucleus (AVPV), a sexually dimorphic hypothalamic region involved in the regulation of reproductive neuroendocrine function. In this region, exposed females had increased numbers of apoptotic nuclei, whereas there was no effect of treatment in males. For ER{alpha}, EB treatment increased immunoreactive cell numbers and density in the medial preoptic nucleus (MPN) of both males and females, while A1221 and the PCB mixture had no effect. PCR analysis of gene expression in the POA identified nine genes that were significantly altered by prenatal EDC exposure, in a manner that varied by sex and treatment. These genes included brain-derived neurotrophic factor, GABA{sub B} receptors-1 and -2, IGF-1, kisspeptin receptor, NMDA receptor subunits NR2b and NR2c, prodynorphin, and TGF{alpha}. Collectively, these results suggest that the disrupted sexual differentiation of the POA by prenatal EDC exposures is already evident as early as the day after birth, effects that may change the trajectory of postnatal development and compromise adult reproductive function.

60 APPLIED LIFE SCIENCES↗