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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 721 records · Page 40
All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

Endovascular Repair of Abdominal Aortic Aneurysms in the Presence of a Transplanted Kidney

PurposeTo present our experience performing endovascular repair of abdominal aortic aneurysms in kidney transplanted patients.MethodsA retrospective review of all patients who underwent endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAA) performed at our institution from 2007 to 2014. We identified all patients who had previously undergone a kidney transplant. Data collected included: comorbidities, preoperative imaging modalities, indication for surgery, stent graft configurations, pre- and postoperative renal function, perioperative complications, and survival rates.ResultsA total of 267 EVARs were performed. Six (2 %) had a transplanted kidney. Mean age was 74 (range, 64–82) years; five were males. Mean time from transplantation to EVAR was 7.5 (range, 2–12) years. Five underwent preoperative planning with noncontrast modalities only. Devices used included bifurcated (n = 3), aortouniiliac (n = 2), and tube (n = 1) stent grafts. Technical success was achieved in all patients. None experienced deterioration in renal function. Median follow-up was 39 (range, 6–51) months. Four patients were alive at the time of the study. Two patients expired during the period of follow-up from unrelated causes.ConclusionsEVAR is an effective modality for the management of AAAs in the coexistence of a transplanted kidney. It can be performed with minimal morbidity and mortality without harming the transplanted kidney. Special consideration should be given to device configuration to minimize damage to the renal graft.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Use of the Amplatzer Type 2 Plug for Flow Redirection in Failing Autogenous Hemodialysis Fistulae

PurposeTo present our experience with redirecting the outflow of mature arteriovenous fistulae (AVFs) in patients with cannulation and/or suboptimal flow problems by percutaneous intervention using the Amplatzer Vascular Plug II (AVP II).MethodsWe retrospectively reviewed patients who presented with difficulty in cannulation and/or suboptimal flow in the puncture zone of the AVF and who underwent intervention using the AVP II to redirect the outflow through a better cannulation zone from March 2009 to November 2012. The mean survival rate of all AVFs was estimated, and the effects of patient age, sex, and AVF age on the AVF survival time were determined.ResultsIn total, 31 patients (17 male and 14 female) with a mean age of 57.8 years (range, 20–79 years) were included. In 2 patients, the AVF failed within the first 15 days because of rapid thrombosis. In 9 patients, the new AVF route was working effectively until unsalvageable thrombosis developed. One of the 31 patients died 9 months before the last radiologic evaluation. The new AVF route was still being used for dialysis in the remaining 19 patients. The mean AVF survival rate was 1,061.4 ± 139.4 days (range, 788–1,334 days). Patient age, sex, and AVF age did not affect the survival time.ConclusionWe suggest that the AVP II is useful for redirecting the outflow of AVFs with cannulation problems and suboptimal flow. Patency of existing AVFs may be extended, thereby extending surgery-free or catheter intervention-free survival period.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Cone-Beam Computed Tomography (CBCT) Versus CT in Lung Ablation Procedure: Which is Faster?

AimTo compare cone-beam CT (CBCT) versus computed tomography (CT) guidance in terms of time needed to target and place the radiofrequency ablation (RFA) electrode on lung tumours.Materials and MethodsPatients at our institution who received CBCT- or CT-guided RFA for primary or metastatic lung tumours were retrospectively included. Time required to target and place the RFA electrode within the lesion was registered and compared across the two groups. Lesions were stratified into three groups according to their size (<10, 10–20, >20 mm). Occurrences of electrode repositioning, repositioning time, RFA complications, and local recurrence after RFA were also reported.ResultsForty tumours (22 under CT, 18 under CBCT guidance) were treated in 27 patients (19 male, 8 female, median age 67.25 ± 9.13 years). Thirty RFA sessions (16 under CBCT and 14 under CT guidance) were performed. Multivariable linear regression analysis showed that CBCT was faster than CT to target and place the electrode within the tumour independently from its size (β = −9.45, t = −3.09, p = 0.004). Electrode repositioning was required in 10/22 (45.4 %) tumours under CT guidance and 5/18 (27.8 %) tumours under CBCT guidance. Pneumothoraces occurred in 6/14 (42.8 %) sessions under CT guidance and in 6/16 (37.5 %) sessions under CBCT guidance. Two recurrences were noted for tumours receiving CBCT-guided RFA (2/17, 11.7 %) and three after CT-guided RFA (3/19, 15.8 %).ConclusionCBCT with live 3D needle guidance is a useful technique for percutaneous lung ablation. Despite lesion size, CBCT allows faster lung RFA than CT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Pelvic Arterial Anatomy Relevant to Prostatic Artery Embolisation and Proposal for Angiographic Classification

PurposeTo describe and categorize the angiographic findings regarding prostatic vascularization, propose an anatomic classification, and discuss its implications for the PAE procedure.MethodsAngiographic findings from 143 PAE procedures were reviewed retrospectively, and the origin of the inferior vesical artery (IVA) was classified into five subtypes as follows: type I: IVA originating from the anterior division of the internal iliac artery (IIA), from a common trunk with the superior vesical artery (SVA); type II: IVA originating from the anterior division of the IIA, inferior to the SVA origin; type III: IVA originating from the obturator artery; type IV: IVA originating from the internal pudendal artery; and type V: less common origins of the IVA. Incidences were calculated by percentage.ResultsTwo hundred eighty-six pelvic sides (n = 286) were analyzed, and 267 (93.3 %) were classified into I–IV types. Among them, the most common origin was type IV (n = 89, 31.1 %), followed by type I (n = 82, 28.7 %), type III (n = 54, 18.9 %), and type II (n = 42, 14.7 %). Type V anatomy was seen in 16 cases (5.6 %). Double vascularization, defined as two independent prostatic branches in one pelvic side, was seen in 23 cases (8.0 %).ConclusionsDespite the large number of possible anatomical variations of male pelvis, four main patterns corresponded to almost 95 % of the cases. Evaluation of anatomy in a systematic fashion, following a standard classification, will make PAE a faster, safer, and more effective procedure.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Pneumothorax Complicating Coaxial and Non-coaxial CT-Guided Lung Biopsy: Comparative Analysis of Determining Risk Factors and Management of Pneumothorax in a Retrospective Review of 650 Patients

PurposeTo assess the scope and determining risk factors related to the development of pneumothorax throughout CT-guided biopsy of pulmonary lesions in coaxial and non-coaxial techniques and the outcome of its management.Materials and MethodsThe study included CT-guided percutaneous lung biopsies in 650 consecutive patients (407 males, 243 females; mean age 54.6 years, SD 5.2) from November 2008 to June 2013 in a retrospective design. Patients were classified according to lung biopsy technique into coaxial group (318 lesions) and non-coaxial group (332 lesions). Exclusion criteria for biopsy were lesions <5 mm in diameter, uncorrectable coagulopathy, positive-pressure ventilation, severe respiratory compromise, pulmonary arterial hypertension, or refusal of the procedure. Risk factors related to the occurrence of pneumothorax were classified into: (a) Technical risk factors, (b) patient-related risk factors, and (c) lesion-associated risk factors. Radiological assessments were performed by two radiologists in consensus. Mann–Whitney U test and Fisher’s exact tests were used for statistical analysis. p values <0.05 were considered statistically significant.ResultsThe incidence of pneumothorax complicating CT-guided lung biopsy was less in the non-coaxial group (23.2 %, 77 out of 332) than the coaxial group (27 %, 86 out of 318). However, the difference in incidence between both groups was statistically insignificant (p = 0.14). Significant risk factors for the development of pneumothorax in both groups were emphysema (p < 0.001 in both groups), traversing a fissure with the biopsy needle (p value 0.005 in non-coaxial group and 0.001 in coaxial group), small lesion, less than 2 cm in diameter (p value of 0.02 in both groups), location of the lesion in the basal or mid sections of the lung (p = 0.003 and <0.001 in non-coaxial and coaxial groups, respectively), and increased needle track path within the lung tissue of more than 2.5 cm (p = 0.01 in both groups). The incidence of pneumothorax in the non-coaxial group was significantly correlated to the number of specimens obtained (p = 0.006). This factor was statistically insignificant in the coaxial group (p = 0.45). The biopsy yield was more diagnostic and conclusive in the coaxial group in comparison to the non-coaxial group (p = 0.008). Simultaneous incidence of pneumothorax and pulmonary hemorrhage was 27.3 % (21/77) in non-coaxial group and in 30.2 % (26/86) in coaxial group. Conservative management was sufficient for treatment of 91 out of 101 patients of pneumothorax in both groups (90.1 %). Manual evacuation of pneumothorax was efficient in 44/51 patients (86.3 %) in both groups and intercostal chest tube was applied after failure of manual evacuation (7 patients: 13.7 %), from which one patient developed a persistent air leakage necessitating pleurodesis.ConclusionPneumothorax complicating CT-guided core biopsy of pulmonary lesions, showed the insignificant difference between coaxial and non-coaxial techniques. However, both techniques have the same significant risk factors including small and basal lesions, increased lesion’s depth from pleural surface, and increased length of aerated lung parenchyma crossed by biopsy needle and passing through pulmonary fissures in the needle tract.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Patient Satisfaction After Femoral Arterial Access Site Closure Using the ExoSeal{sup ®} Vascular Closure Device Compared to Manual Compression: A Prospective Intra-individual Comparative Study

PurposeTo intra-individually compare discomfort levels and patient satisfaction after arterial access closure using the ExoSeal{sup ®} vascular closure device (VCD) and manual compression (MC) in a prospective study design.MethodsPatients undergoing two planned interventions from 07/2013 to 09/2014 could participate in the study. Access closure was performed with an ExoSeal{sup ®}-VCD in one and MC in the other intervention. Patients were clinically and sonographically examined and were given questionnaires 1 day after intervention [groin- and back-pain during bedrest (100-point visual analog scale; 0: no pain); comfortability of bedrest (10-point Likert scale, 1: comfortable), satisfaction with closure (10-point Likert scale, 1: very satisfied)]. Results were analyzed in a cross-over design.Results48 patients (29 male, median age 62.5 (32–88) years) were included. An ExoSeal{sup ®}-VCD was used first in 25 cases. As four of these subsequently refused MC as second intervention, data from 44 patients could be analyzed. All closures were technically successful (successful device deployment) without major complications. Groin- and back-pain after VCD-use/MC was 0 (0–15) vs. 10 (0–80) and 0 (0–75) vs. 25 (0–90), respectively (p < 0.0001). Bedrest after VCD-use was more comfortable than after MC [1 (range 1–7) vs. 6 (2–10); p < 0.0001]. Satisfaction with the closure procedure and with the intervention in general was higher after VCD-use compared to MC [1 (1–3) vs. 5 (2–10) and 1 (1–2) vs. 2 (1–4), respectively; p < 0.0001].ConclusionIntra-individual comparison showed pain levels and discomfort to be significantly lower after ExoSeal{sup ®} use compared to MC. VCD closure was associated with higher satisfaction both with the closure itself and with the intervention in general.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Abscopal Effects and Yttrium-90 Radioembolization

We present the case of an 80-year-old male with squamous cell carcinoma with bilobar hepatic metastases who underwent targeted Yttrium-90 radioembolization of the right hepatic lobe lesion. Subsequently, there was complete regression of the nontargeted, left hepatic lobe lesion. This may represent the first ever reported abscopal effect in radioembolization. The abscopal effect refers to the phenomenon of tumor response in nontargeted sites after targeted radiotherapy. In this article, we briefly review the immune-mediated mechanisms responsible for the abscopal effect.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

MiR-224 expression increases radiation sensitivity of glioblastoma cells

Highlights: • MiR-224 expression in established glioblastoma cell lines and sporadic tumor tissues is low. • Exogenous miR-224 expression was found to increase radiation sensitivity of glioblastoma cells. • MiR-224 expression brought about 55–60% reduction in API5 expression levels. • Transfection with API5 siRNA increased radiation sensitivity of glioblastoma cells. • Low miR-224 and high API5 expression correlated with worse survival of GBM patients. - Abstract: Glioblastoma (GBM) is the most common and highly aggressive primary malignant brain tumor. The intrinsic resistance of this brain tumor limits the efficacy of administered treatment like radiation therapy. In the present study, effect of miR-224 expression on growth characteristics of established GBM cell lines was analyzed. MiR-224 expression in the cell lines as well as in primary GBM tumor tissues was found to be low. Exogenous transient expression of miR-224 using either synthetic mimics or stable inducible expression using doxycycline inducible lentiviral vector carrying miR-224 gene, was found to bring about 30–55% reduction in clonogenic potential of U87 MG cells. MiR-224 expression reduced clonogenic potential of U87 MG cells by 85–90% on irradiation at a dose of 6 Gy, a dose that brought about 50% reduction in clonogenic potential in the absence of miR-224 expression. MiR-224 expression in glioblastoma cells resulted in 55–65% reduction in the expression levels of API5 gene, a known target of miR-224. Further, siRNA mediated down-regulation of API5 was also found to have radiation sensitizing effect on glioblastoma cell lines. Analysis of the Cancer Genome Atlas data showed lower miR-224 expression levels in male GBM patients to correlate with poorer survival. Higher expression levels of miR-224 target API5 also showed significant correlation with poorer survival of GBM patients. Up-regulation of miR-224 or down-regulation of its target API5 in combination with radiation therapy, therefore appear as promising options for the treatment of glioblastoma, which is refractory to the existing treatment strategies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Mitogen-activated protein kinase kinase 1/2 inhibition and angiotensin II converting inhibition in mice with cardiomyopathy caused by lamin A/C gene mutation

Highlights: • Both ACE and MEK1/2 inhibition are beneficial on cardiac function in Lmna cardiomyopathy. • MEK1/2 inhibitor has beneficial effects beyond ACE inhibition for Lmna cardiomyopathy. • These results provide further preclinical rationale for a clinical trial of a MEK1/2 inhibitor. - Abstract: Background: Mutations in the LMNA gene encoding A-type nuclear lamins can cause dilated cardiomyopathy with or without skeletal muscular dystrophy. Previous studies have shown abnormally increased extracellular signal-regulated kinase 1/2 activity in hearts of Lmna{sup H222P/H222P} mice, a small animal model. Inhibition of this abnormal signaling activity with a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor has beneficial effects on heart function and survival in these mice. However, such treatment has not been examined relative to any standard of care intervention for dilated cardiomyopathy or heart failure. We therefore examined the effects of an angiotensin II converting enzyme (ACE) inhibitor on left ventricular function in Lmna{sup H222P/H222P} mice and assessed if adding a MEK1/2 inhibitor would provide added benefit. Methods: Male Lmna{sup H222P/H222P} mice were treated with the ACE inhibitor benazepril, the MEK1/2 inhibitor selumetinib or both. Transthoracic echocardiography was used to measure left ventricular diameters and fractional shortening was calculated. Results: Treatment of Lmna{sup H222P/H222P} mice with either benazepril or selumetinib started at 8 weeks of age, before the onset of detectable left ventricular dysfunction, lead to statistically significantly increased fractional shortening compared to placebo at 16 weeks of age. There was a trend towards a great value for fractional shortening in the selumetinib-treated mice. When treatment was started at 16 weeks of age, after the onset of left ventricular dysfunction, the addition of selumetinib treatment to benazepril lead to a statistically significant increase in left ventricular fractional shortening at 20 weeks of age. Conclusions: Both ACE inhibition and MEK1/2 inhibition have beneficial effects on left ventricular function in Lmna{sup H222P/H222P} mice and both drugs together have a synergistic benefit when initiated after the onset of left ventricular dysfunction. These results provide further preclinical rationale for a clinical trial of a MEK1/2 inhibitor in addition to standard of care in patients with dilated cardiomyopathy caused by LMNA mutations.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

HL-217, a new topical anti-angiogenic agent, inhibits retinal vascular leakage and pathogenic subretinal neovascularization in Vldlr{sup −/−} mice

Highlights: • HL-217 is a new synthetic topical anti-angiogenic agent. • HL-217 attenuated subretinal neovascularization in Vldlr{sup −/−} mice. • HL-217 blocked the binding of PDGF-BB to PDGFRβ. - Abstract: HL-217 is a new synthetic angiogenesis inhibitor. Platelet derived growth factor (PDGF) is a vasoactive factor and has been implicated in proliferative retinopathies. In this study, we examined the mechanism of action and efficacy of topical application of HL-217 on subretinal neovascularization in very low-density lipoprotein receptor knockout (Vldlr{sup −/−}) mice. In three-week-old male Vldlr{sup −/−} mice, HL-217 (1.5 or 3 mg/ml) was administered twice per day for 4 weeks by topical eye drop instillation. Neovascular areas were then measured. We used a protein array to evaluate the expression levels of angiogenic factors. The inhibitory effect of HL-217 on the PDGF-BB/PDGFRβ interaction was evaluated in vitro. The neovascular area in the Vldlr{sup −/−} mice was significantly reduced by HL-217. Additionally, HL-217 decreased the expression levels of PDGF-BB protein and VEGF mRNA. Moreover, HL-217 dose-dependently inhibited the PDGF-BB/PDGFRβ interaction (IC{sub 50} = 38.9 ± 0.7 μM). These results suggest that HL-217 is a potent inhibitor of PDGF-BB. HL-217, when applied topically, is an effective inhibitor of subretinal neovascularization due to its ability to inhibit the pro-angiogenic effects of PDGF-BB.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

In vitro effects of cannabidiol and its main metabolites in mouse and human Sertoli cells

Cannabidiol (CBD) is a major cannabinoid present in extracts of the plant Cannabis sativa (marijuana). While the therapeutic effects of CBD on epilepsy have been demonstrated, less is understood regarding its potential adverse effects. Recent studies revealed that CBD induced toxicity in the male reproductive system of animal models. In this study, we used TM4, an immortalized mouse Sertoli cell line, and primary human Sertoli cells to evaluate the toxicities of CBD and its main metabolites, 7-carboxy-CBD and 7-hydroxy-CBD. CBD induced concentration- and time-dependent cytotoxicity in mouse and human Sertoli cells, which mainly resulted from the inhibition of the G1/S-phase cell cycle transition. CBD also inhibited DNA synthesis and downregulated key cell cycle proteins. Moreover, CBD reduced the mRNA and protein levels of a functional marker, Wilms’ tumor 1. Similar to CBD, 7-carboxy-CBD and 7-hydroxy-CBD inhibited cellular proliferation and decreased DNA synthesis. 7-Carboxy-CBD was less cytotoxic than CBD, while 7-hydroxy-CBD showed comparable cytotoxicity to CBD in both mouse and human Sertoli cells. Compared to mouse Sertoli cells, CBD, 7-hydroxy-CBD, and 7-carboxy-CBD were more cytotoxic in human Sertoli cells. Finally, our results indicate that CBD and its main metabolites can inhibit cell proliferation in mouse and human Sertoli cells.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Risk of Mortality in Family Members of Men Seeking Fertility Assessment

Objective: To assess mortality in family members of men seeking fertility assessment. Subfertility serves as a biomarker for overall somatic health, and poor semen quality is associated with increased risk of hospitalization and mortality from chronic conditions. However, it is unclear if these risks extend to family members of men with low sperm count. Design: Retrospective cohort study. Subjects: Family members, up to third-degree relatives, of men in the Subfertility, Health and Assisted Reproduction and the Environment cohort who underwent a semen analysis as part of a fertility assessment 1996–2017. Relatives of men with a recorded total sperm count who lived in Utah for ≥1 year 1904–2017 were included in the analysis (N = 22,280 families). Exposure: Individuals were classified by family membership. Families were classified as relatives of azoospermic (0M), oligozoospermic (<39M), or normozoospermic (≥39M) men. The average total sperm count of the proband (male relative) with fertility assessment was also included as a continuous exposure measure. Main Outcome Measures: The main outcomes were all-cause and cause-specific mortality risk by sex, age, and degree of relation: first-, second-, and third-degree. Cox proportional hazard models were used to test the association between fertility classification and mortality, controlling for sex, race/ethnicity, and birth year. Results: A total of 666,437 relatives of men with fertility assessment (N deaths = 183,974) were included in the analysis. Relative to normozoospermia families, all-cause mortality risk increased in oligozoospermia families (hazard ratio [HR] oligozoospermia , 1.03; 95% confidence interval [CI], 1.01–1.05). Close relatives, first- (HR oligozoospermia , 1.17; 95% CI, 1.07–1.28) and second-degree relatives (HR azoospermia , 1.11; 95% CI, 1.04–1.20; HR oligozoospermia , 1.05; 95% CI,1.01–1.09), of azoospermic and oligozoospermic men had the highest all-cause and cause-specific mortality risk, including death attributed to cardiovascular disease or congenital birth conditions. Conclusion: Our results suggest that familial all-cause and cause-specific mortality risk differ by fertility phenotype. Families of azoospermic and oligozoospermic men showed significantly increased risk, particularly for close relatives. This study provides further evidence that shared genetic and/or environmental factors could influence both fertility and somatic health.

Male fertility↗
DOE OSTI2014

Voice Quality After Treatment of Early Vocal Cord Cancer: A Randomized Trial Comparing Laser Surgery With Radiation Therapy

Objective: Early laryngeal cancer is usually treated with either transoral laser surgery or radiation therapy. The quality of voice achieved with these treatments has not been compared in a randomized trial. Methods and Materials: Male patients with carcinoma limited to 1 mobile vocal cord (T1aN0M0) were randomly assigned to receive either laser surgery (n=32) or external beam radiation therapy (n=28). Surgery consisted of tumor excision with a CO{sub 2} laser with the patient under general anaesthesia. External beam radiation therapy to the larynx was delivered to a cumulative dose of 66 Gy in 2-Gy daily fractions over 6.5 weeks. Voice quality was assessed at baseline and 6 and 24 months after treatment. The main outcome measures were expert-rated voice quality on a grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, videolaryngostroboscopic findings, and the patients' self-rated voice quality and its impact on activities of daily living. Results: Overall voice quality between the groups was rated similar, but voice was more breathy and the glottal gap was wider in patients treated with laser surgery than in those who received radiation therapy. Patients treated with radiation therapy reported less hoarseness-related inconvenience in daily living 2 years after treatment. Three patients in each group had local cancer recurrence within 2 years from randomization. Conclusions: Radiation therapy may be the treatment of choice for patients whose requirements for voice quality are demanding. Overall voice quality was similar in both treatment groups, however, indicating a need for careful consideration of patient-related factors in the choice of a treatment option.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Risks of secondary malignancies with heterotopic bone radiation therapy for patients younger than 40 years

Heterotopic ossification (HO) of the bone is defined as a benign condition in which abnormal bone formation occurs in soft tissue. One of the most common prophylactic treatments for HO is radiation therapy (RT). This study retrospectively reviewed 20 patients younger than the age of 40 who received radiation to prevent HO in a single fraction of 7 Gray. The purpose of this study is to assess the risk of a second malignancy in these patients by recreating their treatment fields and contouring organs at risk to estimate the radiation dose absorbed by normal tissues outside the radiation treatment field. Diagnostic computed tomography (CT) scans for each patient were used to recreate treatment fields and to calculate dose to structures of interest. The distance from the field edge to each structure and its depth was recorded. Dose measurements in a water phantom were performed for the range of depths, distances, and field sizes used in the actual treatment plans. Computer-generated doses were compared to estimates based on measurement. The structure dose recorded was the higher dose generated between the 2 methods. Scatter dose was recorded to the rectum, bladder, sigmoid colon, small bowel, ovaries and utero-cervix in female patients, and prostate and gonads in male patients. In some patients, there is considerable dose received by certain organs from scatter because of their proximity to the radiation field. The average dose to the ovarian region was 4.125 Gy with a range of 1.085 to 6.228 Gy. The risk estimate for these patients ranged from 0.16% to 0.93%. The average total lifetime risk estimate for the bladder in all patients is 0.22% and the average total lifetime risk estimate for the remainder organs in all patients is 1.25%. In conclusions, proper shielding created from multileaf collimators (MLCs), blocks, and shields should always be used when possible.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2017

Subungual squamous cell carcinoma: A case study

The purpose of this case study is to describe a dosimetric delivery of radiation to a superficial disease process involving the skin and bone of the distal finger. A 76-year-old male patient presented with a subungual squamous cell carcinoma (SCC) of the left distal index finger with bony involvement. The patient refused conventional surgical treatment but agreed to external beam radiation therapy (EBRT). There is a gap in the current literature describing how to successfully immobilize fingers and which EBRT modality is dosimetrically advantageous in treating them. The construction of a simple immobilization method with the patient in a reproducible position is described. The use of photons and electrons were compared ultimately showing photons to be dosimetrically advantageous. Long-term efficacy of the treatment was not evaluated because of patient noncompliance.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2014

Post-exposure administration of diazepam combined with soluble epoxide hydrolase inhibition stops seizures and modulates neuroinflammation in a murine model of acute TETS intoxication

Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison for which there is currently no approved antidote. The convulsant action of TETS is thought to be mediated by inhibition of type A gamma-aminobutyric acid receptor (GABA{sub A}R) function. We, therefore, investigated the effects of post-exposure administration of diazepam, a GABA{sub A}R positive allosteric modulator, on seizure activity, death and neuroinflammation in adult male Swiss mice injected with a lethal dose of TETS (0.15 mg/kg, ip). Administration of a high dose of diazepam (5 mg/kg, ip) immediately following the second clonic seizure (approximately 20 min post-TETS injection) effectively prevented progression to tonic seizures and death. However, this treatment did not prevent persistent reactive astrogliosis and microglial activation, as determined by GFAP and Iba-1 immunoreactivity and microglial cell morphology. Inhibition of soluble epoxide hydrolase (sEH) has been shown to exert potent anti-inflammatory effects and to increase survival in mice intoxicated with other GABA{sub A}R antagonists. The sEH inhibitor TUPS (1 mg/kg, ip) administered immediately after the second clonic seizure did not protect TETS-intoxicated animals from tonic seizures or death. Combined administration of diazepam (5 mg/kg, ip) and TUPS (1 mg/kg, ip, starting 1 h after diazepam and repeated every 24 h) prevented TETS-induced lethality and influenced signs of neuroinflammation in some brain regions. Significantly decreased microglial activation and enhanced reactive astrogliosis were observed in the hippocampus, with no changes in the cortex. Combining an agent that targets specific anti-inflammatory mechanisms with a traditional antiseizure drug may enhance treatment outcome in TETS intoxication. - Highlights: • Acute TETS intoxication causes delayed and persistent neuroinflammation. • Diazepam given post-TETS prevents lethal tonic seizures but not neuroinflammation. • A soluble epoxide hydrolase inhibitor alters TETS-induced neuroinflammation. • Acute TETS intoxication may be more effectively treated by a combinatorial therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Sulforaphane, a cancer chemopreventive agent, induces pathways associated with membrane biosynthesis in response to tissue damage by aflatoxin B{sub 1}

Aflatoxin B{sub 1} (AFB{sub 1}) is one of the major risk factors for liver cancer globally. A recent study showed that sulforaphane (SF), a potent inducer of phase II enzymes that occurs naturally in widely consumed vegetables, effectively induces hepatic glutathione S-transferases (GSTs) and reduces levels of hepatic AFB{sub 1}-DNA adducts in AFB{sub 1}-exposed Sprague Dawley rats. The present study characterized the effects of SF pre-treatment on global gene expression in the livers of similarly treated male rats. Combined treatment with AFB{sub 1} and SF caused reprogramming of a network of genes involved in signal transduction and transcription. Changes in gene regulation were observable 4 h after AFB{sub 1} administration in SF-pretreated animals and may reflect regeneration of cells in the wake of AFB{sub 1}-induced hepatotoxicity. At 24 h after AFB{sub 1} administration, significant induction of genes that play roles in cellular lipid metabolism and acetyl-CoA biosynthesis was detected in SF-pretreated AFB{sub 1}-dosed rats. Induction of this group of genes may indicate a metabolic shift toward glycolysis and fatty acid synthesis to generate and maintain pools of intermediate molecules required for tissue repair, cell growth and compensatory hepatic cell proliferation. Collectively, gene expression data from this study provide insights into molecular mechanisms underlying the protective effects of SF against AFB{sub 1} hepatotoxicity and hepatocarcinogenicity, in addition to the chemopreventive activity of this compound as a GST inducer. - Highlights: • This study revealed sulforaphane (SF)-deregulated gene sets in aflatoxin B{sub 1} (AFB{sub 1})-treated rat livers. • SF redirects biochemical networks toward lipid biosynthesis in AFB{sub 1}-dosed rats. • SF enhanced gene sets that would be expected to favor cell repair and regeneration.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Use of electroencephalography (EEG) to assess CNS changes produced by pesticides with different modes of action: Effects of permethrin, deltamethrin, fipronil, imidacloprid, carbaryl, and triadimefon

The electroencephalogram (EEG) is an apical measure, capable of detecting changes in brain neuronal activity produced by internal or external stimuli. We assessed whether pesticides with different modes of action produced different changes in the EEG of adult male Long–Evans rats. The EEG was recorded using two montages (visual cortex referenced to the cerebellum and to the frontal cortex) in unrestrained rats at the time of peak behavioral effects. Pesticides included: permethrin and deltamethrin (Type I and Type II pyrethroids; 2 h), fipronil (single and repeated doses; phenylpyrazole; 6 h), imidacloprid (neonicotinoid; 2 h), carbaryl (carbamate; 0.5 h), and triadimefon (triazole; 1 h), using dosages that produced approximately an ED{sub 30} or an ED{sub 50}–ED{sub 80} change in motor activity. Permethrin (43, 100 mg/kg) increased amplitudes or areas (delta, alpha, or gamma bands) in the EEG. Deltamethrin (2.5, 5.5 mg/kg) reduced the amplitudes or areas of the delta, theta, alpha, beta, and gamma bands, but the changes were not dose-related. A single treatment with fipronil (25, 50 mg/kg, but not 5, 10 mg/kg) decreased gamma band area. Additional changes in the delta, theta, and gamma bands were observed when fipronil (5, 10 mg/kg) was administered for 14 days. Imidacloprid (50, 100 mg/kg) did not alter the EEG. Carbaryl (10, 50 mg/kg) decreased theta area, and decreased delta and increased beta frequency. Triadimefon (75, 150 mg/kg) produced minimal changes in the EEG. The results show that the EEG is affected differently by approximately equipotent doses of pesticides with different modes of action. - Highlights: • Pesticides with different modes of action have different effects on in vivo rodent EEG. • The EEG was also changed differently after single vs. repeated treatment with fipronil. • The data suggest that EEG may be used as an apical measure for detecting chemical effects on the central nervous system.

60 APPLIED LIFE SCIENCES↗