DIFFERENTIAL PROFILES OF CHOLINESTERASE INHIBITION AND NEUROBEHAVIORAL EFFECTS IN RATS EXPOSED TO FENAMIPHOS AND PROFENOPHOS.

EPA Science Inventory

The relationship between cholinesterase (ChE) inhibition and neurobehavioral changes was examined using two ChE-inhibiting organophosphorus pesticides, fenamiphos and profenophos. Both pesticides inhibit blood ChE, yet brain ChE is relatively spared (little to no inhibition up t...

Image-guided total marrow and total lymphatic irradiation using helical tomotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultheiss, Timothy E.; Wong, Jeffrey; Liu, An

2007-03-15

Purpose: To develop a treatment technique to spare normal tissue and allow dose escalation in total body irradiation (TBI). We have developed intensity-modulated radiotherapy techniques for the total marrow irradiation (TMI), total lymphatic irradiation, or total bone marrow plus lymphatic irradiation using helical tomotherapy. Methods and Materials: For TBI, we typically use 12 Gy in 10 fractions delivered at an extended source-to-surface distance (SSD). Using helical tomotherapy, it is possible to deliver equally effective doses to the bone marrow and lymphatics while sparing normal organs to a significant degree. In the TMI patients, whole body skeletal bone, including the ribsmore » and sternum, comprise the treatment target. In the total lymphatic irradiation, the target is expanded to include the spleen and major lymph node areas. Sanctuary sites for disease (brain and testes) are included when clinically indicated. Spared organs include the lungs, esophagus, parotid glands, eyes, oral cavity, liver, kidneys, stomach, small and large intestine, bladder, and ovaries. Results: With TBI, all normal organs received the TBI dose; with TMI, total lymphatic irradiation, and total bone marrow plus lymphatic irradiation, the visceral organs are spared. For the first 6 patients treated with TMI, the median dose to organs at risk averaged 51% lower than would be achieved with TBI. By putting greater weight on the avoidance of specific organs, greater sparing was possible. Conclusion: Sparing of normal tissues and dose escalation is possible using helical tomotherapy. Late effects such as radiation pneumonitis, veno-occlusive disease, cataracts, neurocognitive effects, and the development of second tumors should be diminished in severity and frequency according to the dose reduction realized for the organs at risk.« less

Acute hepatic encephalopathy presenting as cortical laminar necrosis: case report.

PubMed

Choi, Jong Mun; Kim, Yoon Hee; Roh, Sook Young

2013-01-01

We report on a 55-year-old man with alcoholic liver cirrhosis who presented with status epilepticus. Laboratory analysis showed markedly elevated blood ammonia. Brain magnetic resonance imaging (MRI) showed widespread cortical signal changes with restricted diffusion, involving both temporo-fronto-parietal cortex, while the perirolandic regions and occipital cortex were uniquely spared. A follow-up brain MRI demonstrated diffuse cortical atrophy with increased signals on T1-weighted images in both the basal ganglia and temporal lobe cortex, representing cortical laminar necrosis. We suggest that the brain lesions, in our case, represent a consequence of toxic effect of ammonia.

SU-E-T-587: Optimal Volumetric Modulated Arc Radiotherapy Treatment Planning Technique for Multiple Brain Metastases with Increasing Number of Arcs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keeling, V; Hossain, S; Hildebrand, K

Purpose: To show improvements in dose conformity and normal brain tissue sparing using an optimal planning technique (OPT) against clinically acceptable planning technique (CAP) in the treatment of multiple brain metastases. Methods: A standardized international benchmark case with12 intracranial tumors was planned using two different VMAT optimization methods. Plans were split into four groups with 3, 6, 9, and 12 targets each planned with 3, 5, and 7 arcs using Eclipse TPS. The beam geometries were 1 full coplanar and half non-coplanar arcs. A prescription dose of 20Gy was used for all targets. The following optimization criteria was used (OPTmore » vs. CAP): (No upper limit vs.108% upper limit for target volume), (priority 140–150 vs. 75–85 for normal-brain-tissue), and (selection of automatic sparing Normal-Tissue-Objective (NTO) vs. Manual NTO). Both had priority 50 to critical structures such as brainstem and optic-chiasm, and both had an NTO priority 150. Normal-brain-tissue doses along with Paddick Conformity Index (PCI) were evaluated. Results: In all cases PCI was higher for OPT plans. The average PCI (OPT,CAP) for all targets was (0.81,0.64), (0.81,0.63), (0.79,0.57), and (0.72,0.55) for 3, 6, 9, and 12 target plans respectively. The percent decrease in normal brain tissue volume (OPT/CAP*100) achieved by OPT plans was (reported as follows: V4, V8, V12, V16, V20) (184, 343, 350, 294, 371%), (192, 417, 380, 299, 360%), and (235, 390, 299, 281, 502%) for the 3, 5, 7 arc 12 target plans, respectively. The maximum brainstem dose decreased for the OPT plan by 4.93, 4.89, and 5.30 Gy for 3, 5, 7 arc 12 target plans, respectively. Conclusion: Substantial increases in PCI, critical structure sparing, and decreases in normal brain tissue dose were achieved by eliminating upper limits from optimization, using automatic sparing of normal tissue function with high priority, and a high priority to normal brain tissue.« less

Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Katrina, E-mail: Trinabena23@gmail.com; Lenards, Nishele; Holson, Janice

The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient's neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to themore » hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient's data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain.« less

Enriched environment improves motor function and increases neurotrophins in hemicerebellar lesioned rats.

PubMed

Gelfo, Francesca; Cutuli, Debora; Foti, Francesca; Laricchiuta, Daniela; De Bartolo, Paola; Caltagirone, Carlo; Petrosini, Laura; Angelucci, Francesco

2011-01-01

Environmental enrichment (EE) defined as "a combination of complex inanimate and social stimulation" influences brain function and anatomy by enhancing sensory, cognitive, motor, and social stimulation. The beneficial effects of EE in the presence of brain damage have been partially attributed to upregulation of neurotrophins, proteins involved in neuronal survival and in activity-dependent plasticity. The authors tested the hypothesis that EE may have advantageous effects on recovery of motor function after cerebellar damage, associated with changes in local neurotrophin production. They performed a hemicerebellectomy in rats previously exposed to EE or reared in standard conditions. The time course of compensation of motor symptoms was analyzed in both lesioned groups. Then, the local production of the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the spared hemicerebellum and other extracerebellar regions was evaluated. Long-term exposure to EE accelerated the motor recovery in hemicerebellectomized rats and elicited an increase in NGF levels in the spared hemicerebellum, as compared with nonenriched lesioned and control rats. BDNF levels were higher in hemicerebellectomized rats but not influenced by EE. In the frontal cortex, both NGF and BDNF levels were upregulated in hemicerebellectomized enriched rats as compared with hemicerebellectomized nonenriched and control rats. This study suggests that the beneficial effects of EE on motor symptoms after cerebellar damage may be, at least partly, because of modulation of neurotrophic proteins involved in the regeneration processes.

Biology of Bilirubin Photoisomers.

PubMed

Hansen, Thor Willy Ruud

2016-06-01

Phototherapy is the main treatment for neonatal hyperbilirubinemia. In acute treatment of extreme hyperbilirubinemia, intensive phototherapy may have a role in 'detoxifying' the bilirubin molecule to more polar photoisomers, which should be less prone to crossing the blood-brain barrier, providing a 'brain-sparing' effect. This article reviews the biology of bilirubin isomers. Although there is evidence supporting the lower toxicity of bilirubin photoisomers, there are studies showing the opposite. There are methodologic weaknesses in most studies and better-designed experiments are needed. In an infant acutely threatened by bilirubin-induced brain damage, intensified phototherapy should be used expediently and aggressively. Copyright © 2016 Elsevier Inc. All rights reserved.

Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study.

PubMed

Lee, Katrina; Lenards, Nishele; Holson, Janice

2016-01-01

The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient׳s neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient׳s data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

SU-E-T-340: Use of Intensity Modulated Proton Therapy (IMPT) for Reducing the Dose to Cochlea in Craniospinal Irradiation (CSI) of Pediatric Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dormer, J; Kassaee, A; Lin, H

2014-06-01

Purpose: To evaluate use of intensity modulated proton therapy (IMPT) and number of beams for sparing cochlea in treatment of whole brain for pediatric medulloblastoma patients. Methods: In our institution, craniospinal irradiation patients are treated in supine position on our proton gantries using pencil beam scanning with each beam uniformly covering the target volume (SFUD). Each treatment plan consists of two opposed lateral whole brain fields and one or two spinal fields. For sparing the cochlea for the whole brain treatment, we created three different plans using IMPT for five pediatric patients. The first plan consisted of two lateral fields,more » the second two lateral fields and a superior-inferior field, and the third two lateral fields and two superior oblique fields. Optimization was performed with heavy weights applied to the eye, lens and cochlea while maintaining a dose prescription of 36 Gy to the whole brain. Results: IMPT plans reduce the dose to the cochlea. Increasing the number of treatment fields was found to lower the average dose to the cochlea: 15.0, 14.5 and 12.5 Gy for the two-field, three-field, and four-field plans respectively. The D95 for the two-field plan was 98.2%, compared to 100.0% for both the three-field and four-field plan. Coverage in the mid-brain was noticeably better in the three- and four-field plans, with more dose conformality surrounding the cochlea. Conclusion: IMPT plans for CSI and the whole brain irradiations are capable of sparing cochlea and reduce the dose considerably without compromising treating brain tissues. The reduction in average dose increases with three and four field plans as compared to traditional two lateral beam plans.« less

Corticosteroids in brain cancer patients: benefits and pitfalls

PubMed Central

Dietrich, Jörg; Rao, Krithika; Pastorino, Sandra; Kesari, Santosh

2011-01-01

Glucocorticoids have been used for decades in the treatment of brain tumor patients and belong to the most powerful class of agents in reducing tumor-associated edema and minimizing side effects and the risk of encephalopathy in patients undergoing radiation therapy. Unfortunately, corticosteroids are associated with numerous and well-characterized adverse effects, constituting a major challenge in patients requiring long-term application of corticosteroids. Novel anti-angiogenic agents, such as bevacizumab (Avastin®), which have been increasingly used in cancer patients, are associated with significant steroid-sparing effects, allowing neuro-oncologists to reduce the overall use of corticosteroids in patients with progressive malignant brain tumors. Recent experimental studies have revealed novel insights into the mechanisms and effects of corticosteroids in cancer patients, including modulation of tumor biology, angiogenesis and steroid-associated neurotoxicity. This article summarizes current concepts of using corticosteroids in brain cancer patients and highlights potential pitfalls in their effects on both tumor and neural progenitor cells. PMID:21666852

EEG Correlates of Preparatory Orienting, Contextual Updating, and Inhibition of Sensory Processing in Left Spatial Neglect.

PubMed

Lasaponara, Stefano; D'Onofrio, Marianna; Pinto, Mario; Dragone, Alessio; Menicagli, Dario; Bueti, Domenica; De Lucia, Marzia; Tomaiuolo, Francesco; Doricchi, Fabrizio

2018-04-11

Studies with event-related potentials have highlighted deficits in the early phases of orienting to left visual targets in right-brain-damaged patients with left spatial neglect (N+). However, brain responses associated with preparatory orienting of attention, with target novelty and with the detection of a match/mismatch between expected and actual targets (contextual updating), have not been explored in N+. Here in a study in healthy humans and brain-damaged patients of both sexes we demonstrate that frontal activity that reflects supramodal mechanisms of attentional orienting (Anterior Directing Attention Negativity, ADAN) is entirely spared in N+. In contrast, posterior responses that mark the early phases of cued orienting (Early Directing Attention Negativity, EDAN) and the setting up of sensory facilitation over the visual cortex (Late Directing Attention Positivity, LDAP) are suppressed in N+. This uncoupling is associated with damage of parietal-frontal white matter. N+ also exhibit exaggerated novelty reaction to targets in the right side of space and reduced novelty reaction for those in the left side (P3a) together with impaired contextual updating (P3b) in the left space. Finally, we highlight a drop in the amplitude and latency of the P1 that over the left hemisphere signals the early blocking of sensory processing in the right space when targets occur in the left one: this identifies a new electrophysiological marker of the rightward attentional bias in N+. The heterogeneous effects and spatial biases produced by localized brain damage on the different phases of attentional processing indicate relevant functional independence among their underlying neural mechanisms and improve the understanding of the spatial neglect syndrome. SIGNIFICANCE STATEMENT Our investigation answers important questions: are the different components of preparatory orienting (EDAN, ADAN, LDAP) functionally independent in the healthy brain? Is preparatory orienting of attention spared in left spatial neglect? Does the sparing of preparatory orienting have an impact on deficits in reflexive orienting and in the assignment of behavioral relevance to the left space? We show that supramodal preparatory orienting in frontal areas is entirely spared in neglect patients though this does not counterbalance deficits in preparatory parietal-occipital activity, reflexive orienting, and contextual updating. This points at relevant functional dissociations among different components of attention and suggests that improving voluntary attention in N+ might be behaviorally ineffective unless associated with stimulations boosting the response of posterior parietal-occipital areas. Copyright © 2018 the authors 0270-6474/18/383792-17$15.00/0.

Reduction in cardiolipin decreases mitochondrial spare respiratory capacity and increases glucose transport into and across human brain cerebral microvascular endothelial cells.

PubMed

Nguyen, Hieu M; Mejia, Edgard M; Chang, Wenguang; Wang, Ying; Watson, Emily; On, Ngoc; Miller, Donald W; Hatch, Grant M

2016-10-01

Microvessel endothelial cells form part of the blood-brain barrier, a restrictively permeable interface that allows transport of only specific compounds into the brain. Cardiolipin is a mitochondrial phospholipid required for function of the electron transport chain and ATP generation. We examined the role of cardiolipin in maintaining mitochondrial function necessary to support barrier properties of brain microvessel endothelial cells. Knockdown of the terminal enzyme of cardiolipin synthesis, cardiolipin synthase, in hCMEC/D3 cells resulted in decreased cellular cardiolipin levels compared to controls. The reduction in cardiolipin resulted in decreased mitochondrial spare respiratory capacity, increased pyruvate kinase activity, and increased 2-deoxy-[(3) H]glucose uptake and glucose transporter-1 expression and localization to membranes in hCMEC/D3 cells compared to controls. The mechanism for the increase in glucose uptake was an increase in adenosine-5'-monophosphate kinase and protein kinase B activity and decreased glycogen synthase kinase 3 beta activity. Knockdown of cardiolipin synthase did not affect permeability of fluorescent dextran across confluent hCMEC/D3 monolayers grown on Transwell(®) inserts. In contrast, knockdown of cardiolipin synthase resulted in an increase in 2-deoxy-[(3) H]glucose transport across these monolayers compared to controls. The data indicate that in hCMEC/D3 cells, spare respiratory capacity is dependent on cardiolipin. In addition, reduction in cardiolipin in these cells alters their cellular energy status and this results in increased glucose transport into and across hCMEC/D3 monolayers. Microvessel endothelial cells form part of the blood-brain barrier, a restrictively permeable interface that allows transport of only specific compounds into the brain. In human adult brain endothelial cell hCMEC/D3 monolayers cultured on Transwell(®) plates, knockdown of cardiolipin synthase results in decrease in mitochondrial cardiolipin and decreased mitochondrial spare respiratory capacity. The reduced cardiolipin results in an increased activity of adenosine monophosphate kinase (pAMPK) and protein kinase B (pAKT) and decreased activity of glycogen synthase kinase 3 beta (pGSK3β) which results in elevated glucose transporter-1 (GLUT-1) expression and association with membranes. This in turn increases 2-dexoyglucose uptake from the apical medium into the cells with a resultant 2-deoxyglucose movement into the basolateral medium. © 2016 International Society for Neurochemistry.

Theoretical Benefits of Dynamic Collimation in Pencil Beam Scanning Proton Therapy for Brain Tumors: Dosimetric and Radiobiological Metrics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moignier, Alexandra, E-mail: alexandra-moignier@uiowa.edu; Gelover, Edgar; Wang, Dongxu

Purpose: To quantify the dosimetric benefit of using a dynamic collimation system (DCS) for penumbra reduction during the treatment of brain tumors by pencil beam scanning proton therapy (PBS PT). Methods and Materials: Collimated and uncollimated brain treatment plans were created for 5 patients previously treated with PBS PT and retrospectively enrolled in an institutional review board–approved study. The in-house treatment planning system, RDX, was used to generate the plans because it is capable of modeling both collimated and uncollimated beamlets. The clinically delivered plans were reproduced with uncollimated plans in terms of target coverage and organ at risk (OAR) sparingmore » to ensure a clinically relevant starting point, and collimated plans were generated to improve the OAR sparing while maintaining target coverage. Physical and biological comparison metrics, such as dose distribution conformity, mean and maximum doses, normal tissue complication probability, and risk of secondary brain cancer, were used to evaluate the plans. Results: The DCS systematically improved the dose distribution conformity while preserving the target coverage. The average reduction of the mean dose to the 10-mm ring surrounding the target and the healthy brain were 13.7% (95% confidence interval [CI] 11.6%-15.7%; P<.0001) and 25.1% (95% CI 16.8%-33.4%; P<.001), respectively. This yielded an average reduction of 24.8% (95% CI 0.8%-48.8%; P<.05) for the brain necrosis normal tissue complication probability using the Flickinger model, and 25.1% (95% CI 16.8%-33.4%; P<.001) for the risk of secondary brain cancer. A general improvement of the OAR sparing was also observed. Conclusion: The lateral penumbra reduction afforded by the DCS increases the normal tissue sparing capabilities of PBS PT for brain cancer treatment while preserving target coverage.« less

Advanced brain aging: relationship with epidemiologic and genetic risk factors, and overlap with Alzheimer disease atrophy patterns.

PubMed

Habes, M; Janowitz, D; Erus, G; Toledo, J B; Resnick, S M; Doshi, J; Van der Auwera, S; Wittfeld, K; Hegenscheid, K; Hosten, N; Biffar, R; Homuth, G; Völzke, H; Grabe, H J; Hoffmann, W; Davatzikos, C

2016-04-05

We systematically compared structural imaging patterns of advanced brain aging (ABA) in the general-population, herein defined as significant deviation from typical BA to those found in Alzheimer disease (AD). The hypothesis that ABA would show different patterns of structural change compared with those found in AD was tested via advanced pattern analysis methods. In particular, magnetic resonance images of 2705 participants from the Study of Health in Pomerania (aged 20-90 years) were analyzed using an index that captures aging atrophy patterns (Spatial Pattern of Atrophy for Recognition of BA (SPARE-BA)), and an index previously shown to capture atrophy patterns found in clinical AD (Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease (SPARE-AD)). We studied the association between these indices and risk factors, including an AD polygenic risk score. Finally, we compared the ABA-associated atrophy with typical AD-like patterns. We observed that SPARE-BA had significant association with: smoking (P<0.05), anti-hypertensive (P<0.05), anti-diabetic drug use (men P<0.05, women P=0.06) and waist circumference for the male cohort (P<0.05), after adjusting for age. Subjects with ABA had spatially extensive gray matter loss in the frontal, parietal and temporal lobes (false-discovery-rate-corrected q<0.001). ABA patterns of atrophy were partially overlapping with, but notably deviating from those typically found in AD. Subjects with ABA had higher SPARE-AD values; largely due to the partial spatial overlap of associated patterns in temporal regions. The AD polygenic risk score was significantly associated with SPARE-AD but not with SPARE-BA. Our findings suggest that ABA is likely characterized by pathophysiologic mechanisms that are distinct from, or only partially overlapping with those of AD.

Effect of the Maximum Dose on White Matter Fiber Bundles Using Longitudinal Diffusion Tensor Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Tong; Chapman, Christopher H.; Tsien, Christina

2016-11-01

Purpose: Previous efforts to decrease neurocognitive effects of radiation focused on sparing isolated cortical structures. We hypothesize that understanding temporal, spatial, and dosimetric patterns of radiation damage to whole-brain white matter (WM) after partial-brain irradiation might also be important. Therefore, we carried out a study to develop the methodology to assess radiation therapy (RT)–induced damage to whole-brain WM bundles. Methods and Materials: An atlas-based, automated WM tractography analysis was implemented to quantify longitudinal changes in indices of diffusion tensor imaging (DTI) of 22 major WM fibers in 33 patients with predominantly low-grade or benign brain tumors treated by RT. Sixmore » DTI scans per patient were performed from before RT to 18 months after RT. The DTI indices and planned doses (maximum and mean doses) were mapped onto profiles of each of 22 WM bundles. A multivariate linear regression was performed to determine the main dose effect as well as the influence of other clinical factors on longitudinal percentage changes in axial diffusivity (AD) and radial diffusivity (RD) from before RT. Results: Among 22 fiber bundles, AD or RD changes in 12 bundles were affected significantly by doses (P<.05), as the effect was progressive over time. In 9 elongated tracts, decreased AD or RD was significantly related to maximum doses received, consistent with a serial structure. In individual bundles, AD changes were up to 11.5% at the maximum dose locations 18 months after RT. The dose effect on WM was greater in older female patients than younger male patients. Conclusions: Our study demonstrates for the first time that the maximum dose to the elongated WM bundles causes post-RT damage in WM. Validation and correlative studies are necessary to determine the ability and impact of sparing these bundles on preserving neurocognitive function after RT.« less

[Clinical feature of ALS with communication disturbance; the possibility to communicate in TLS].

PubMed

Nagao, Masahiro

2013-01-01

In the subsets of amyotrohic lateral sclerosis (ALS), totally-locked in state (TLS) is shown as the result of marked progression of motor neuron degeneration. In TLS, patients are impossible to move any voluntary muscles. As the result, patients with TLS cannot communicate with any augmentative and alternative communication devices(AACD) at present. To find the AACD that enables for TLS to communicate, we examined the clinical character, brain MRI, SPECT and evoked potentials in TLS. Brain MRI showed marked brain atrophy including the brainstem, but the occipital lobe was spared. SPECT and visual evoked potentials (VEP) showed preserved physiological function of the occipital lobe in TLS. The results suggest that neuronal degeneration in TLS is not restricted to motor system, but that the visual pathways are spared. Patients with TLS may be possible to use AACD that utilize the visual pathway.

Sparing of the Neural Stem Cell Compartment During Whole-Brain Radiation Therapy: A Dosimetric Study Using Helical Tomotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marsh, James C., E-mail: james_marsh@rush.ed; Godbole, Rohit H.; Herskovic, Arnold M.

2010-11-01

Purpose: To assess the feasibility of dosimetrically sparing the hippocampus and neural stem cell (NSC) compartment during whole-brain radiotherapy (WBRT) and prophylactic cranial irradiation (PCI). Methods and Materials: We contoured the brain/brainstem on fused magnetic resonance /computed tomography images as the planning target volume (PTV) in 10 patients, excluding the hippocampus and NSC compartment as organs at risk. PCI and WBRT helical tomotherapy plans were prepared for each patient, with 1.0-cm field width, a pitch of 0.285, and a modulation factor of 2.5. We attempted to maximally spare the hippocampus and NSC compartment while treating the rest of the brainmore » to 30 Gy in 15 fractions (PCI) or 35 Gy in 14 fractions (WBRT) with a V{sub 100} of {>=}95%. Plan quality was assessed by calculating mean dose, equivalent uniform dose (EUD), and biologically equivalent dose (BED) for organs at risk and the percent volume of the PTV receiving the prescribed dose of V{sub 100}. Results: In the PCI plans, mean doses/EUD/BED for the hippocampus and NSC compartment were 11.5 Gy/13.1 Gy/15.7 Gy{sub 2} (BED assuming alpha/beta ratio of 2Gy) and 11.5 Gy/13.1 Gy/12.3 Gy{sub 10} (BED assuming alpha/beta ratio of 10Gy), respectively. In the WBRT plans, mean doses/EUD/BED for the hippocampus and NSC compartment were 11.8 Gy/14.8 Gy/16.8 Gy{sub 2} and 11.8 Gy/14.8 Gy/12.8 Gy{sub 10}, respectively. The mean V{sub 95} for the rest of the brain (PTV) was 96.9% for both the PCI and WBRT plans. Mean PCI and WBRT treatment times were 15.93 min (range, 14.28 min-17.50 min) and 20.18 min (range, 18.43 min-22.32 min), respectively. Conclusions: It is dosimetrically feasible to spare the hippocampus and NSC compartment using helical tomotherapy during the administration of whole-brain irradiation.« less

Discovery of a brain-penetrant S1P₃-sparing direct agonist of the S1P₁ and S1P₅ receptors efficacious at low oral dose.

PubMed

Demont, Emmanuel H; Arpino, Sandra; Bit, Rino A; Campbell, Colin A; Deeks, Nigel; Desai, Sapna; Dowell, Simon J; Gaskin, Pam; Gray, James R J; Harrison, Lee A; Haynes, Andrea; Heightman, Tom D; Holmes, Duncan S; Humphreys, Philip G; Kumar, Umesh; Morse, Mary A; Osborne, Greg J; Panchal, Terry; Philpott, Karen L; Taylor, Simon; Watson, Robert; Willis, Robert; Witherington, Jason

2011-10-13

2-Amino-2-(4-octylphenethyl)propane-1,3-diol 1 (fingolimod, FTY720) has been recently marketed in the United States for the treatment of patients with remitting relapsing multiple sclerosis (RRMS). Its efficacy has been primarily linked to the agonism on T cells of S1P(1), one of the five sphingosine 1-phosphate (S1P) G-protein-coupled receptors, while its cardiovascular side effects have been associated with activity at S1P(3). Emerging data suggest that the ability of this molecule to cross the blood-brain barrier and to interact with both S1P(1) and S1P(5) in the central nervous system (CNS) may contribute to its efficacy in treating patients with RRMS. We have recently disclosed the structure of an advanced, first generation S1P(3)-sparing S1P(1) agonist, a zwitterion with limited CNS exposure. In this Article, we highlight our strategy toward the identification of CNS-penetrant S1P(3)-sparing S1P(1) and S1P(5) agonists resulting in the discovery of 5-(3-{2-[2-hydroxy-1-(hydroxymethyl)ethyl]-5-methyl-1,2,3,4-tetrahydro-6-isoquinolinyl}-1,2,4-oxadiazol-5-yl)-2-[(1-methylethyl)oxy]benzonitrile 15. Its exceptional in vivo potency and good pharmacokinetic properties translate into a very low predicted therapeutic dose in human (<1 mg p.o. once daily).

Doppler velocimetry of ductus venous in preterm fetuses with brain sparing effect: neonatal outcome

PubMed Central

Cosmo, Ynesmara Coelho; Júnior, Edward Araujo; de Sá, Renato Augusto Moreira; de Carvalho, Paulo Roberto Nassar; Mattar, Rosiane; Lopes, Laudelino Marques; Nardozza, Luciano Marcondes Machado; de Souza, Eduardo; Moron, Antonio Fernandes

2012-01-01

Summary Objective to evaluate the relationship between ductus venous (DV) and Doppler velocimetry in neonatal outcome in severe compromised preterm fetuses. Methods the study was designed as an observational and cross-sectional study with 52 premature neonates with brain sparing effect. The criteria of neonatal severe morbidity were: severe intraventricular hemorrhage (grades 3 or 4), retinopathy of prematurity (grade 3 or 4), cystic periventricular leukomalatia, bronchopneumo dysplasia and neonatal mortality. The fetuses were divided in two groups: group 0 - all the fetuses with ventricular systole/atrial contraction (S/A) in DV ratio values less them 3.4; group 1 - fetuses with values of S/A ratio greater than 3.4. Results 42% of fetuses showed abnormal S/A ratio in DV and 48% showed birth weight below percentile 3 for gestational age. There was no statistical significance comparing the 02 groups according to bronchopneumo dysplasia, retinopathy of prematurity (grade 3 or 4) and intraventricular hemorrhage (grade 3 or 4). Only one fetus presented cystic periventricular leukomalatia. We found statistically significant association between abnormal DV S/A ratio and neonatal mortality (CI 95%, 1.28 –38.22, p< 0.002). Conclusions our results suggest that abnormal DV blood flow detected by Doppler examination isn’t associated with severe neonatal morbidity but with neonatal mortality. PMID:23181172

Music as a memory enhancer in patients with Alzheimer's disease.

PubMed

Simmons-Stern, Nicholas R; Budson, Andrew E; Ally, Brandon A

2010-08-01

Musical mnemonics have a long and diverse history of popular use. In addition, music processing in general is often considered spared by the neurodegenerative effects of Alzheimer's disease (AD). Research examining these two phenomena is limited, and no work to our knowledge has explored the effectiveness of musical mnemonics in AD. The present study sought to investigate the effect of music at encoding on the subsequent recognition of associated verbal information. Lyrics of unfamiliar children's songs were presented bimodally at encoding, and visual stimuli were accompanied by either a sung or a spoken recording. Patients with AD demonstrated better recognition accuracy for the sung lyrics than the spoken lyrics, while healthy older adults showed no significant difference between the two conditions. We propose two possible explanations for these findings: first, that the brain areas subserving music processing may be preferentially spared by AD, allowing a more holistic encoding that facilitates recognition, and second, that music heightens arousal in patients with AD, allowing better attention and improved memory. Published by Elsevier Ltd.

Profiles of Impaired, Spared, and Recovered Neuropsychological Processes in Alcoholism

PubMed Central

Oscar-Berman, Marlene; Valmas, Mary M.; Sawyer, Kayle S.; Ruiz, Susan Mosher; Luhar, Riya B.; Gravitz, Zoe R.

2015-01-01

Long-term chronic alcoholism is associated with disparate and widespread residual consequences for brain functioning and behavior, and alcoholics suffer a variety of cognitive deficiencies and emotional abnormalities. Alcoholism has heterogeneous origins and outcomes, depending upon factors such as family history, age, gender, and mental or physical health. Consequently, the neuropsychological profiles associated with alcoholism are not uniform among individuals. Moreover, within and across research studies, variability among participants is substantial and contributes to characteristics associated with differential treatment outcomes after detoxification. In order to refine our understanding of alcoholism-related impaired, spared, and recovered abilities, we focus on five specific functional domains: (1) memory, (2) executive functions, (3) emotion and psychosocial skills, (4) visuospatial cognition, and (5) psychomotor abilities. The brain systems that are most vulnerable to alcoholism are the frontocerebellar and mesocorticolimbic circuitries. Over time, with abstinence from alcohol, the brain appears to become reorganized to provide compensation for structural and behavioral deficits. By relying on a combination of clinical and scientific approaches, future research will help to refine the compensatory roles of healthy brain systems, the degree to which abstinence and treatment facilitate the reversal of brain atrophy and dysfunction, and the importance of individual differences to outcome. PMID:25307576

A Computational Analysis of Mental Image Generation: Evidence from Functional Dissociations in Split-Brain Patients.

DTIC Science & Technology

1984-08-20

neuropsychological data on the apraxias and the visual agnosias imply that motor and visual memories can be separately spared or destroyed after brain...agraphia Imagery dissociations 53 and (vice versa), and visual object agnosia without apraxia (and vice versa). We next asked him to *draw the letters in

Skull Base Tumors

NASA Astrophysics Data System (ADS)

Schulz-Ertner, Daniela

In skull base tumors associated with a low radiosensitivity for conventional radiotherapy (RT), irradiation with proton or carbon ion beams facilitates a safe and accurate application of high tumor doses due to the favorable beam localization properties of these particle beams. Cranial nerves, the brain stem and normal brain tissue can at the same time be optimally spared.

Profiles of impaired, spared, and recovered neuropsychologic processes in alcoholism.

PubMed

Oscar-Berman, Marlene; Valmas, Mary M; Sawyer, Kayle S; Ruiz, Susan Mosher; Luhar, Riya B; Gravitz, Zoe R

2014-01-01

Long-term chronic alcoholism is associated with disparate and widespread residual consequences for brain functioning and behavior, and alcoholics suffer a variety of cognitive deficiencies and emotional abnormalities. Alcoholism has heterogeneous origins and outcomes, depending upon factors such as family history, age, gender, and mental or physical health. Consequently, the neuropsychologic profiles associated with alcoholism are not uniform among individuals. Moreover, within and across research studies, variability among subjects is substantial and contributes to characteristics associated with differential treatment outcomes after detoxification. In order to refine our understanding of alcoholism-related impaired, spared, and recovered abilities, we focus on five specific functional domains: (1) memory; (2) executive functions; (3) emotion and psychosocial skills; (4) visuospatial cognition; and (5) psychomotor abilities. Although the entire brain might be vulnerable in uncomplicated alcoholism, the brain systems that are considered to be most at risk are the frontocerebellar and mesocorticolimbic circuitries. Over time, with abstinence from alcohol, the brain appears to become reorganized to provide compensation for structural and behavioral deficits. By relying on a combination of clinical and scientific approaches, future research will help to refine the compensatory roles of healthy brain systems, the degree to which abstinence and treatment facilitate the reversal of brain atrophy and dysfunction, and the importance of individual differences to outcome. © 2014 Elsevier B.V. All rights reserved.

Increasing the efficacy of antitumor glioma vaccines by photodynamic therapy and local injection of allogeneic glioma cells

NASA Astrophysics Data System (ADS)

Christie, Catherine E.; Peng, Qian; Madsen, Steen J.; Uzal, Francisco A.; Hirschberg, Henry

2016-03-01

Immunotherapy of brain tumors involves the stimulation of an antitumor immune response. This type of therapy can be targeted specifically to tumor cells thus sparing surrounding normal brain. Due to the presence of the blood-brain barrier, the brain is relatively isolated from the systemic circulation and, as such, the initiation of significant immune responses is more limited than other types of cancers. The purpose of this study was to show that the efficacy of tumor primed antigen presenting macrophage vaccines could be increased by: (1) PDT of the priming tumor cells, and (2) injection of allogeneic glioma cells directly into brain tumors. Experiments were conducted in an in vivo brain tumor model using Fisher rats and BT4C (allogeneic) and F98 (syngeneic) glioma cells. Preliminary results showed that vaccination alone had significantly less inhibitory effect on F98 tumor growth compared to the combination of vaccination and allogeneic cell (BT4C) injection.

Whole-brain radiotherapy and stereotactic radiosurgery in brain metastases: what is the evidence?

PubMed

Mehta, Minesh P; Ahluwalia, Manmeet S

2015-01-01

The overall local treatment paradigm of brain metastases, which includes whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS), continues to evolve. Local therapies play an important role in the management of brain metastases. The choice of local therapy depends on factors that involve the patient (performance status, expected survival, and age), the prior treatment history, and the tumor (type and subtype, number, size, location of metastases, and extracranial disease status). Multidisciplinary collaboration is required to facilitate an individualized plan to improve the outcome of disease in patients with this life-limiting complication. There has been concern about the neurocognitive effects of WBRT. A number of approaches that mitigate cognitive dysfunction, such as pharmacologic intervention (memantine) or a hippocampal-sparing strategy, have been studied in a prospective manner with WBRT. Although there has been an increase in the use of SRS in the management of brain metastases in recent years, WBRT retains an important therapeutic role.

Treatment planning and 3D dose verification of whole brain radiation therapy with hippocampal avoidance in rats

NASA Astrophysics Data System (ADS)

Yoon, S. W.; Miles, D.; Cramer, C.; Reinsvold, M.; Kirsch, D.; Oldham, M.

2017-05-01

Despite increasing use of stereotactic radiosurgery, whole brain radiotherapy (WBRT) continues to have a therapeutic role in a selected subset of patients. Selectively avoiding the hippocampus during such treatment (HA-WBRT) emerged as a strategy to reduce the cognitive morbidity associated with WBRT and gave rise to a recently published the phase II trial (RTOG 0933) and now multiple ongoing clinical trials. While conceptually hippocampal avoidance is supported by pre-clinical evidence showing that the hippocampus plays a vital role in memory, there is minimal pre-clinic data showing that selectively avoiding the hippocampus will reduce radiation-induced cognitive decline. Largely the lack of pre-clinical evidence can be attributed to the technical hurdles associated with delivering precise conformal treatment the rat brain. In this work we develop a novel conformal HA-WBRT technique for Wistar rats, utilizing a 225kVp micro-irradiator with precise 3D-printed radiation blocks designed to spare hippocampus while delivering whole brain dose. The technique was verified on rodent-morphic Presage® 3D dosimeters created from micro-CT scans of Wistar rats with Duke Large Field-of-View Optical Scanner (DLOS) at 1mm isotropic voxel resolution. A 4-field box with parallel opposed AP-PA and two lateral opposed fields was explored with conformal hippocampal sparing aided by 3D-printed radiation blocks. The measured DVH aligned reasonably well with that calculated from SmART Plan Monte Carlo simulations with simulated blocks for 4-field HA-WBRT with both demonstrating hippocampal sparing of 20% volume receiving less than 30% the prescription dose.

SU-E-T-449: Hippocampal Sparing Radiotherapy Using Intensity Modulated Radiotherapy and Volumetric Modulated Arc Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moon, S; Kyung Hee University Hospital at Gangdong, Gangdong-gu; Kim, D

2015-06-15

Purpose: The hippocampus sparing during the cranial irradiation has become interesting because it may mitigate radiation-induced neurocognitive toxicity. Herein we report our preliminary study for sparing the hippocampus with and without tilling condition for patient with brain metastases. Methods: Ten patients previously treated with whole brain were reviewed. Five patients tilted the head to around 30 degrees and others were treated without tilting. Treatment plans of linear accelerator (Linac)-based volumetric modulated arc therapy (VMAT) and intensity modulated radiotherapy (IMRT) were generated for prescription dose of 30 Gy in 15 fractions. Hippocampal avoidance regions were created with 5-mm volumetric expansion aroundmore » the hippocampus. Whole brain, hippocampus and hippocampal avoidance volume were 1372cm3, 6cm3 and 30cm3 and hippocampal avoidance volume was 2.2% of the whole brain planned target volume in average. Organs at risk (OARs) are hippocampus, eyes, lens, and cochleae. Coverage index (CVI), conformity index (CI), homogeneity index (HI) and mean dose to OARs were used to compare dose characteristic of tilted and non-tilted cases. Results: In IMRT, when CI, CVI and HI of whole brain were 0.88, 0.09 and 0.98 in both tilted and non-tilted cases, absorbed dose of hippocampal avoidance volume in tilted cases were 10% lower than non-tilted cases. Doses in other OARs such as eyes, lens, and cochleae were also decreased about 20% when tilting the head. When CI, HI and CVI in VMAT were 0.9, 0.08 and 0.99, the dose-decreased ratio of OARs in both with and without tilting cases were almost the same with IMRT. But absolute dose of hippocampal avoidance volume in VMAT was 30% lower than IMRT. Conclusion: This study confirms that dose to hippocampus decreases if patients tilt the head. When treating the whole brain with head tilted, patients can acquire the same successful treatment Result and also preserve their valuable memory.« less

Dose specification for hippocampal sparing whole brain radiotherapy (HS WBRT): considerations from the UK HIPPO trial QA programme.

PubMed

Megias, Daniel; Phillips, Mark; Clifton-Hadley, Laura; Harron, Elizabeth; Eaton, David J; Sanghera, Paul; Whitfield, Gillian

2017-03-01

The HIPPO trial is a UK randomized Phase II trial of hippocampal sparing (HS) vs conventional whole-brain radiotherapy after surgical resection or radiosurgery in patients with favourable prognosis with 1-4 brain metastases. Each participating centre completed a planning benchmark case as part of the dedicated radiotherapy trials quality assurance programme (RTQA), promoting the safe and effective delivery of HS intensity-modulated radiotherapy (IMRT) in a multicentre trial setting. Submitted planning benchmark cases were reviewed using visualization for radiotherapy software (VODCA) evaluating plan quality and compliance in relation to the HIPPO radiotherapy planning and delivery guidelines. Comparison of the planning benchmark data highlighted a plan specified using dose to medium as an outlier by comparison with those specified using dose to water. Further evaluation identified that the reported plan statistics for dose to medium were lower as a result of the dose calculated at regions of PTV inclusive of bony cranium being lower relative to brain. Specification of dose to water or medium remains a source of potential ambiguity and it is essential that as part of a multicentre trial, consideration is given to reported differences, particularly in the presence of bone. Evaluation of planning benchmark data as part of an RTQA programme has highlighted an important feature of HS IMRT dosimetry dependent on dose being specified to water or medium, informing the development and undertaking of HS IMRT as part of the HIPPO trial. Advances in knowledge: The potential clinical impact of differences between dose to medium and dose to water are demonstrated for the first time, in the setting of HS whole-brain radiotherapy.

SU-E-T-56: Brain Metastasis Treatment Plans for Contrast-Enhanced Synchrotron Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Obeid, L; Adam, J; Tessier, A

2014-06-01

Purpose: Iodine-enhanced radiotherapy is an innovative treatment combining the selective accumulation of an iodinated contrast agent in brain tumors with irradiations using monochromatic medium energy x-rays. The aim of this study is to compare dynamic stereotactic arc-therapy and iodineenhanced SSRT. Methods: Five patients bearing brain metastasis received a standard helical 3D-scan without iodine. A second scan was acquired 13 min after an 80 g iodine infusion. Two SSRT treatment plans (with/without iodine) were performed for each patient using a dedicated Monte Carlo (MC) treatment planning system (TPS) based on the ISOgray TPS. Ten coplanar beams (6×6 cm2, shaped with collimator)more » were simulated. MC statistical error objective was less than 5% in the 50% isodose. The dynamic arc-therapy plan was achieved on the Iplan Brainlab TPS. The treatment plan validation criteria were fixed such that 100% of the prescribed dose is delivered at the beam isocentre and the 70% isodose contains the whole target volume. The comparison elements were the 70% isodose volume, the average and maximum doses delivered to organs at risk (OAR): brainstem, optical nerves, chiasma, eyes, skull bone and healthy brain parenchyma. Results: The stereotactic dynamic arc-therapy remains the best technique in terms of dose conformation. Iodine-enhanced SSRT presents similar performances to dynamic arc-therapy with increased brainstem and brain parenchyma sparing. One disadvantage of SSRT is the high dose to the skull bone. Iodine accumulation in metastasis may increase the dose by 20–30%, allowing a normal tissue sparing effect at constant prescribed dose. Treatment without any iodine enhancement (medium-energy stereotactic radiotherapy) is not relevant with degraded HDVs (brain, parenchyma and skull bone) comparing to stereotactic dynamic arc-therapy. Conclusion: Iodine-enhanced SSRT exhibits a good potential for brain metastasis treatment regarding the dose distribution and OAR criteria.« less

Improved plan quality with automated radiotherapy planning for whole brain with hippocampus sparing: a comparison to the RTOG 0933 trial.

PubMed

Krayenbuehl, J; Di Martino, M; Guckenberger, M; Andratschke, N

2017-10-02

Whole-brain radiation therapy (WBRT) with hippocampus sparing (HS) has been investigated by the radiation oncology working group (RTOG) 0933 trial for patients with multiple brain metastases. They showed a decrease of adverse neurocognitive effects with HS WBRT compared to WBRT alone. With the development of automated treatment planning system (aTPS) in the last years, a standardization of the plan quality at a high level was achieved. The goal of this study was to evaluate the feasibility of using an aTPS for the treatment of HS WBRT and see if the RTOG 0933 dose constraints could be achieved and improved. Ten consecutive patients treated with HS WBRT were enrolled in this study. 10 × 3 Gy was prescribed according to the RTOG 0933 protocol to 92% of the target volume (whole-brain excluding the hippocampus expanded by 5 mm in 3-dimensions). In contrast to RTOG 0933, the maximum allowed point dose to normal brain was significantly lowered and restricted to 36.5 Gy. All patients were planned with volumetric modulated arc therapy (VMAT) technique using four arcs. Plans were optimized using Auto-Planning (AP) (Philips Radiation Oncology Systems) with one single AP template and optimization. All the constraints from the RTOG 0933 trial were achieved. A significant improvement for the maximal dose to 2% of the brain with a reduction of 4 Gy was achieved (33.5 Gy vs. RTOG 37.5 Gy) and the minimum hippocampus dose was reduced by 10% (8.1 Gy vs. RTOG 9 Gy). A steep dose gradient around the hippocampus was achieved with a mean dose of 27.3 Gy at a distance between 0.5 cm and 1 cm from the hippocampus. The effective working time to optimize a plan was kept below 6'. Automated treatment planning for HS WBRT was able to fulfil all the recommendations from the RTOG 0933 study while significantly improving dose homogeneity and decreasing unnecessary hot spot in the normal brain. With this approach, a standardization of plan quality was achieved and the effective time required for plan optimization was minimized.

Mechanism of impaired consciousness in absence seizures: a cross-sectional study

PubMed Central

Guo, Jennifer N.; Kim, Robert; Chen, Yu; Negishi, Michiro; Jhun, Stephen; Weiss, Sarah; Ryu, Jun Hwan; Bai, Xiaoxiao; Xiao, Wendy; Feeney, Erin; Rodriguez-Fernandez, Jorge; Mistry, Hetal; Crunelli, Vincenzo; Crowley, Michael J.; Mayes, Linda C.; Todd Constable, R.; Blumenfeld, Hal

2017-01-01

Background Absence seizures are brief episodes of impaired consciousness characterized by staring and behavioral arrest. The neural underpinnings of impaired consciousness and of the variable severity of behavioral impairment observed from one absence seizure to the next are not well understood. We therefore compared fMRI and EEG changes in absence seizures with impaired task performance to seizures in which performance was spared. Methods Patients were recruited from 59 pediatric neurology practices including hospitals and neurology outpatient offices throughout the United States. We performed simultaneous electroencephalography (EEG), fMRI, and behavioral testing in children and adolescents aged 6 to 19 years with typical absence epilepsy. fMRI and EEG were analyzed using data-driven approaches without prior assumptions about signal time courses or spatial distributions. The main outcomes were fMRI and EEG amplitudes in seizures with impaired versus spared behavioral responses analysed by t-test. We also examined the timing of fMRI and EEG changes in seizures with impaired behavioral responses compared to seizures with spared responses. Findings 93 patients were enrolled between September 1, 2005 and January 1, 2013, and we captured a total of 1032 seizures in 39 patients. fMRI changes during seizures occurred sequentially in three functional brain networks previously well-validated in studies of normal subjects. Seizures associated with more impaired behavior showed higher fMRI amplitude in all three networks compared to seizures with spared performance. In the default-mode network fMRI, amplitude was 0·57 ± 0·26% for seizures with impaired and 0·40 ± 0·16% for seizures with spared behavioral responses (mean difference 017%; 95% CI: 0·11 to 0·23%; p < 0.0001). In the task-positive network, fMRI amplitude was 0·53 ± 0·29% for impaired and 0·39 ± 0·15% for spared seizures (mean difference 0·14%; 95% CI: 008 to 0·21%; p < 0.0001). In the sensorimotor-thalamic network, fMRI amplitude was 0·41 ± 0·25% for impaired and 0·34 ± 014% for spared seizures (mean difference 0 07%; 95% CI: 001 to 0·13%; p = 0.02). Seizures with impaired behavior also showed greater EEG power in widespread brain regions compared to seizures with spared behavior. Mean fractional EEG power in the frontal leads was 50·4 ± 15·2 for seizures with impaired and 24·8 ± 6·5 for seizures with spared behavior (mean difference 25·6; 95% CI: 210 to 30·3); middle leads 35·4 ± 6·5 for impaired, 13 3 ± 34 for spared seizures (mean difference 22·1; 95% CI: 20.0 to 24·1); posterior leads 41·6 ± 5·3 for impaired, 24·6 ± 86 for spared seizures (mean difference 170; 95% CI: 14·4 to 19·7); p < 00001 for all comparisons. Average seizure duration was longer for seizures with impaired behavior at 79 ± 66 s, compared to 3·8 ± 3.0 s for seizures with spared behavior (mean difference 4.1 s; 95% CI 3.0 to 5.3 s, p < 00001). However, larger amplitude fMRI and EEG signals occurred at the outset or even preceding seizures with impairment. Interpretation Impaired consciousness in absence seizures is related to the intensity of physiological changes in established networks affecting widespread regions of the brain. Increased EEG and fMRI amplitude occurs at the onset of seizures associated with behavioral impairment. These findings suggest that a vulnerable state may exist at the initiation of some seizures leading to greater physiological changes and altered consciousness. PMID:27839650

Neuroplastic Changes Following Brain Ischemia and their Contribution to Stroke Recovery: Novel Approaches in Neurorehabilitation

PubMed Central

Alia, Claudia; Spalletti, Cristina; Lai, Stefano; Panarese, Alessandro; Lamola, Giuseppe; Bertolucci, Federica; Vallone, Fabio; Di Garbo, Angelo; Chisari, Carmelo; Micera, Silvestro; Caleo, Matteo

2017-01-01

Ischemic damage to the brain triggers substantial reorganization of spared areas and pathways, which is associated with limited, spontaneous restoration of function. A better understanding of this plastic remodeling is crucial to develop more effective strategies for stroke rehabilitation. In this review article, we discuss advances in the comprehension of post-stroke network reorganization in patients and animal models. We first focus on rodent studies that have shed light on the mechanisms underlying neuronal remodeling in the perilesional area and contralesional hemisphere after motor cortex infarcts. Analysis of electrophysiological data has demonstrated brain-wide alterations in functional connectivity in both hemispheres, well beyond the infarcted area. We then illustrate the potential use of non-invasive brain stimulation (NIBS) techniques to boost recovery. We finally discuss rehabilitative protocols based on robotic devices as a tool to promote endogenous plasticity and functional restoration. PMID:28360842

The consequences of fetal growth restriction on brain structure and neurodevelopmental outcome.

PubMed

Miller, Suzanne L; Huppi, Petra S; Mallard, Carina

2016-02-15

Fetal growth restriction (FGR) is a significant complication of pregnancy describing a fetus that does not grow to full potential due to pathological compromise. FGR affects 3-9% of pregnancies in high-income countries, and is a leading cause of perinatal mortality and morbidity. Placental insufficiency is the principal cause of FGR, resulting in chronic fetal hypoxia. This hypoxia induces a fetal adaptive response of cardiac output redistribution to favour vital organs, including the brain, and is in consequence called brain sparing. Despite this, it is now apparent that brain sparing does not ensure normal brain development in growth-restricted fetuses. In this review we have brought together available evidence from human and experimental animal studies to describe the complex changes in brain structure and function that occur as a consequence of FGR. In both humans and animals, neurodevelopmental outcomes are influenced by the timing of the onset of FGR, the severity of FGR, and gestational age at delivery. FGR is broadly associated with reduced total brain volume and altered cortical volume and structure, decreased total number of cells and myelination deficits. Brain connectivity is also impaired, evidenced by neuronal migration deficits, reduced dendritic processes, and less efficient networks with decreased long-range connections. Subsequent to these structural alterations, short- and long-term functional consequences have been described in school children who had FGR, most commonly including problems in motor skills, cognition, memory and neuropsychological dysfunctions. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Object recognition with severe spatial deficits in Williams syndrome: sparing and breakdown.

PubMed

Landau, Barbara; Hoffman, James E; Kurz, Nicole

2006-07-01

Williams syndrome (WS) is a rare genetic disorder that results in severe visual-spatial cognitive deficits coupled with relative sparing in language, face recognition, and certain aspects of motion processing. Here, we look for evidence for sparing or impairment in another cognitive system-object recognition. Children with WS, normal mental-age (MA) and chronological age-matched (CA) children, and normal adults viewed pictures of a large range of objects briefly presented under various conditions of degradation, including canonical and unusual orientations, and clear or blurred contours. Objects were shown as either full-color views (Experiment 1) or line drawings (Experiment 2). Across both experiments, WS and MA children performed similarly in all conditions while CA children performed better than both WS group and MA groups with unusual views. This advantage, however, was eliminated when images were also blurred. The error types and relative difficulty of different objects were similar across all participant groups. The results indicate selective sparing of basic mechanisms of object recognition in WS, together with developmental delay or arrest in recognition of objects from unusual viewpoints. These findings are consistent with the growing literature on brain abnormalities in WS which points to selective impairment in the parietal areas of the brain. As a whole, the results lend further support to the growing literature on the functional separability of object recognition mechanisms from other spatial functions, and raise intriguing questions about the link between genetic deficits and cognition.

Central-Variant Posterior Reversible Encephalopathy Syndrome with Albuminocytologic Dissociation.

PubMed

Lee, Sang-Woo; Lee, Seung-Jae

2018-01-01

Posterior reversible encephalopathy syndrome (PRES) is a disorder of reversible vasogenic brain edema which mainly involves the parieto-occipital lobes in various clinical settings. The main mechanism is known to be cerebral autoregulation failure and endothelial dysfunction leading to the disruption of the blood-brain barrier. We report the case of a 47-year-old woman with PRES which involved the brain stem and thalami, sparing the cerebral hemispheres. She was admitted to the emergency room because of acute-onset confusion. Her initial blood pressure was 270/220 mm Hg. Routine blood lab tests showed pleocytosis, hyperglycemia, and azotemia. Brain magnetic resonance imaging (MRI) showed a lesion of vasogenic edema involving nearly the whole area of pons, the left side of the midbrain, and the bilateral medial thalami. Cerebrospinal fluid (CSF) examination revealed an increased level of protein with normal white blood cell count. With conservative care, the patient markedly recovered 3 days after symptom onset, and a follow-up MRI confirmed complete resolution of the vasogenic edema. This case suggests that PRES can rarely involve the "central zone" only, sparing the cerebral hemispheres, which may be confused with other neurological diseases. Besides, the CSF albuminocytologic dissociation may suggest the disruption of the blood-brain barrier in patients with PRES.

SU-F-T-339: Comparison Between Coplanar and Non-Coplanar RapidArc Approach of Hippocampal-Sparing Whole Brain Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, B; Kim, J

Purpose: To compare the dosimetry of coplanar and non-coplanar RapidArc whole brain plans for hippocampal sparing Methods: We studied the RapidArc plans of patient with brain metastases, with the prescription of 3750 cGy in 15 fractions. The coplanar approach used a full clockwise (CW) arc and a full counterclockwise (CCW) arc, with the couch angle to be 0°. The non-coplanar approach used a full arc with a couch angle of 0°, and a partial arc with a couch angle of 90°. Treatment planning system is Eclipse Ver. 11. Constraints for eyes, lens, brainstem, optical nerves and chiasm are employed inmore » the optimization so that these OARs’ dose are below tolerance. Constraints for hippocampus are employed so that they receive dose as low as possible while maintain good coverage to whole brain. The beam delivery machine is Varian 21 IX. T1-weighted MRI images were used for hippocampus contouring. Results: The target coverage index for coplanar and non-coplanar RapidArc plans are 94.9% and 95.4%, respectively, with homogeneity index of 0.223 vs 0.226, which is defined as (D2% – D98%)/Dmean of target volume. V95 and V100 are 99.0% and 94.8% for coplanar plan, vs 99.1% and 95.4% for non-coplanar plan, while the mean dose of hippocampus are 1244.5 cGy for coplanar plan vs 1212.3 cGy for non-coplanar plan. Dose for eyes, lens, optical nerves, optical chiasm and brainstem are all below tolerance. Conclusion: Coplanar RapidArc plan provides good target coverage while achieves good hippocampal sparing, and there is no benefit to use non-coplanar approach.« less

Neurocognitive sparing of desktop microbeam irradiation.

PubMed

Bazyar, Soha; Inscoe, Christina R; Benefield, Thad; Zhang, Lei; Lu, Jianping; Zhou, Otto; Lee, Yueh Z

2017-08-11

Normal tissue toxicity is the dose-limiting side effect of radiotherapy. Spatial fractionation irradiation techniques, like microbeam radiotherapy (MRT), have shown promising results in sparing the normal brain tissue. Most MRT studies have been conducted at synchrotron facilities. With the aim to make this promising treatment more available, we have built the first desktop image-guided MRT device based on carbon nanotube x-ray technology. In the current study, our purpose was to evaluate the effects of MRT on the rodent normal brain tissue using our device and compare it with the effect of the integrated equivalent homogenous dose. Twenty-four, 8-week-old male C57BL/6 J mice were randomly assigned to three groups: MRT, broad-beam (BB) and sham. The hippocampal region was irradiated with two parallel microbeams in the MRT group (beam width = 300 μm, center-to-center = 900 μm, 160 kVp). The BB group received the equivalent integral dose in the same area of their brain. Rotarod, marble burying and open-field activity tests were done pre- and every month post-irradiation up until 8 months to evaluate the cognitive changes and potential irradiation side effects on normal brain tissue. The open-field activity test was substituted by Barnes maze test at 8th month. A multilevel model, random coefficients approach was used to evaluate the longitudinal and temporal differences among treatment groups. We found significant differences between BB group as compared to the microbeam-treated and sham mice in the number of buried marble and duration of the locomotion around the open-field arena than shams. Barnes maze revealed that BB mice had a lower capacity for spatial learning than MRT and shams. Mice in the BB group tend to gain weight at the slower pace than shams. No meaningful differences were found between MRT and sham up until 8-month follow-up using our measurements. Applying MRT with our newly developed prototype compact CNT-based image-guided MRT system utilizing the current irradiation protocol can better preserve the integrity of normal brain tissue. Consequently, it enables applying higher irradiation dose that promises better tumor control. Further studies are required to evaluate the full extent effects of this novel modality.

Poster — Thur Eve — 64: Preliminary investigation of arc configurations for optimal sparing of normal tissue in hypofractionated stereotactic radiotherapy (HF-SRT) of multiple brain metastases using a 5mm interdigitating micro-multileaf collimator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leavens, C; Wronski, M; Lee, YK

2014-08-15

Purpose: To evaluate normal tissue sparing in intra-cranial HF-SRT, comparing various arc configurations with the Synergy Beam Modulator (SynBM) and Agility linacs, the latter incorporating leaf interdigitation and backup jaws. Methods: Five patients with multiple brain metastases (BMs), (5 BMs (n=2), 3 BMs (n=3)) treated with HF-SRT using 25 Gy (n=2) or 30 Gy (n=3) in 5 fractions, were investigated. Clinical treatment plans used the SynBM. Each patient was retrospectively re-planned on Agility, employing three planning strategies: (A) one isocenter and dedicated arc for each BM; (B) a single isocenter, centrally placed with respect to BMs; (C) the isocenter andmore » arc configuration used in the SynBM plan, where closely spaced (<5cm) BMs used a dedicated isocenter and arcs. Agility plans were normalized for PTV coverage and heterogeneity. Results and Conclusion: Strategy A obtained the greatest improvements over the SynBM plan, where the maximum OAR dose, and mean dose to normal brain (averaged for all patients) were reduced by 55cGy and 25cGy, respectively. Strategy B was limited by having a single isocenter, hence less jaw shielding and increased MLC leakage. The maximum OAR dose was reduced by 13cGy, however mean dose to normal brain increased by 84cGy. Strategy C reduced the maximum OAR dose and mean dose to normal brain by 32cGy and 9cGy, respectively. The results from this study indicate that, for intra-cranial HF-SRT of multiple BMs, Agility plans are equal or better than SynBM plans. Further planning is needed to investigate dose sparing using Strategy A and the SynBM.« less

Minibeam therapy with protons and light ions: physical feasibility and potential to reduce radiation side effects and to facilitate hypofractionation.

PubMed

Dilmanian, F Avraham; Eley, John G; Krishnan, Sunil

2015-06-01

Despite several advantages of proton therapy over megavoltage x-ray therapy, its lack of proximal tissue sparing is a concern. The method presented here adds proximal tissue sparing to protons and light ions by turning their uniform incident beams into arrays of parallel, small, or thin (0.3-mm) pencil or planar minibeams, which are known to spare tissues. As these minibeams penetrate the tissues, they gradually broaden and merge with each other to produce a solid beam. Broadening of 0.3-mm-diameter, 109-MeV proton pencil minibeams was measured using a stack of radiochromic films with plastic spacers. Monte Carlo simulations were used to evaluate the broadening in water of minibeams of protons and several light ions and the dose from neutron generated by collimator. A central parameter was tissue depth, where the beam full width at half maximum (FWHM) reached 0.7 mm, beyond which tissue sparing decreases. This depth was 22 mm for 109-MeV protons in a film stack. It was also found by simulations in water to be 23.5 mm for 109 MeV proton pencil minibeams and 26 mm for 116 MeV proton planar minibeams. For light ions, all with 10 cm range in water, that depth increased with particle size; specifically it was 51 mm for Li-7 ions. The ∼2.7% photon equivalent neutron skin dose from the collimator was reduced 7-fold by introducing a gap between the collimator and the skin. Proton minibeams can be implemented at existing particle therapy centers. Because they spare the shallow tissues, they could augment the efficacy of proton therapy and light particle therapy, particularly in treating tumors that benefit from sparing of proximal tissues such as pediatric brain tumors. They should also allow hypofractionated treatment of all tumors by allowing the use of higher incident doses with less concern about proximal tissue damage. Copyright © 2015 Elsevier Inc. All rights reserved.

TU-EF-304-11: Therapeutic Benefits of Collimation in Spot Scanning Proton Therapy in the Treatment of Brain Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moignier, A; Gelover, E; Wang, D

Purpose: A dynamic collimation system (DCS) based on two orthogonal pairs of mobile trimmer blades has recently been proposed to reduce the lateral penumbra in spot scanning proton therapy (SSPT). The purpose of this work is to quantify the therapeutic benefit of using the DCS for SSPT of brain cancer by comparing un-collimated and collimated treatment plans. Methods: Un-collimated and collimated brain treatment plans were created for five patients, previously treated with SSPT, using an in-house treatment planning system capable of modeling collimated and un-collimated beamlets. Un-collimated plans reproduced the clinically delivered plans in terms of target coverage and organ-at-riskmore » (OAR) sparing, whereas collimated plans were re-optimized to improve the organ-at-risk sparing while maintaining target coverage. Physical and biological comparison metrics such as dose distribution conformity, mean and maximum doses, normal tissue complication probability (NTCP) and risk of secondary brain cancer were used to evaluate the plans. Results: The DCS systematically improved the dose distribution conformity while preserving the target coverage. The average reduction of the mean dose to the 10-mm ring surrounding the target and the healthy brain were 7.1% (95% CI: 4.2%–9.9%; p<0.01) and 14.3% (95% CI: 7.8%–20.8%; p<0.01), respectively. This yielded an average reduction of 12.0% (95% CI: 8.2%–15.7%; p<0.01) for the brain necrosis NTCP using the Flickinger model, and 14.2% (95% CI: 7.7%–20.8%; p<0.01) for the risk of secondary brain cancer. The average maximum dose reductions for the brainstem, chiasm, optic nerves, cochleae and pituitary gland when comparing un-collimated and collimated plans were 14.3%, 10.4%, 11.2%, 13.0%, 12.9% and 3.4%, respectively. Evaluating individual plans using the Lyman-Kutcher-Burman NTCP model also yielded improvements. Conclusion: The lateral penumbra reduction performed by the DCS increases the normal tissue sparing capabilities of SSPT for brain tumor treatment while preserving the target coverage. This research was financially supported by Ion Beam Applications S.A. (IBA, Louvain-La-Neuve, Belgium)« less

Collision avoidance in persons with homonymous visual field defects under virtual reality conditions.

PubMed

Papageorgiou, Eleni; Hardiess, Gregor; Ackermann, Hermann; Wiethoelter, Horst; Dietz, Klaus; Mallot, Hanspeter A; Schiefer, Ulrich

2012-01-01

The aim of the present study was to examine the effect of homonymous visual field defects (HVFDs) on collision avoidance of dynamic obstacles at an intersection under virtual reality (VR) conditions. Overall performance was quantitatively assessed as the number of collisions at a virtual intersection at two difficulty levels. HVFDs were assessed by binocular semi-automated kinetic perimetry within the 90° visual field, stimulus III4e and the area of sparing within the affected hemifield (A-SPAR in deg(2)) was calculated. The effect of A-SPAR, age, gender, side of brain lesion, time since brain lesion and presence of macular sparing on the number of collisions, as well as performance over time were investigated. Thirty patients (10 female, 20 male, age range: 19-71 years) with HVFDs due to unilateral vascular brain lesions and 30 group-age-matched subjects with normal visual fields were examined. The mean number of collisions was higher for patients and in the more difficult level they experienced more collisions with vehicles approaching from the blind side than the seeing side. Lower A-SPAR and increasing age were associated with decreasing performance. However, in agreement with previous studies, wide variability in performance among patients with identical visual field defects was observed and performance of some patients was similar to that of normal subjects. Both patients and healthy subjects displayed equal improvement of performance over time in the more difficult level. In conclusion, our results suggest that visual-field related parameters per se are inadequate in predicting successful collision avoidance. Individualized approaches which also consider compensatory strategies by means of eye and head movements should be introduced. Copyright © 2011 Elsevier Ltd. All rights reserved.

Equivalence in Dose Fall-Off for Isocentric and Nonisocentric Intracranial Treatment Modalities and Its Impact on Dose Fractionation Schemes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma Lijun, E-mail: lijunma@radonc.ucsf.ed; Sahgal, Arjun; Descovich, Martina

2010-03-01

Purpose: To investigate whether dose fall-off characteristics would be significantly different among intracranial radiosurgery modalities and the influence of these characteristics on fractionation schemes in terms of normal tissue sparing. Methods and Materials: An analytic model was developed to measure dose fall-off characteristics near the target independent of treatment modalities. Variations in the peripheral dose fall-off characteristics were then examined and compared for intracranial tumors treated with Gamma Knife, Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective dose (EUBED) for the normal brain tissue was calculated. Functional dependence of the normal brain EUBED on varying numbers of fractions (1more » to 30) was studied for the three modalities. Results: The derived model fitted remarkably well for all the cases (R{sup 2} > 0.99). No statistically significant differences in the dose fall-off relationships were found between the three modalities. Based on the extent of variations in the dose fall-off curves, normal brain EUBED was found to decrease with increasing number of fractions for the targets, with alpha/beta ranging from 10 to 20. This decrease was most pronounced for hypofractionated treatments with fewer than 10 fractions. Additionally, EUBED was found to increase slightly with increasing number of fractions for targets with alpha/beta ranging from 2 to 5. Conclusion: Nearly identical dose fall-off characteristics were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED calculations, normal brain sparing was found to favor hypofractionated treatments for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2.« less

Hippocampal dosimetry correlates with the change in neurocognitive function after hippocampal sparing during whole brain radiotherapy: a prospective study.

PubMed

Tsai, Ping-Fang; Yang, Chi-Cheng; Chuang, Chi-Cheng; Huang, Ting-Yi; Wu, Yi-Ming; Pai, Ping-Ching; Tseng, Chen-Kan; Wu, Tung-Ho; Shen, Yi-Liang; Lin, Shinn-Yn

2015-12-10

Whole brain radiotherapy (WBRT) has been the treatment of choice for patients with brain metastases. However, change/decline of neurocognitive functions (NCFs) resulting from impaired hippocampal neurogenesis might occur after WBRT. It is reported that conformal hippocampal sparing would provide the preservation of NCFs. Our study aims to investigate the hippocampal dosimetry and to demonstrate the correlation between hippocampal dosimetry and neurocognitive outcomes in patients receiving hippocampal sparing during WBRT (HS-WBRT). Forty prospectively recruited cancer patients underwent HS-WBRT for therapeutic or prophylactic purposes. Before receiving HS-WBRT, all participants received a battery of baseline neurocognitive assessment, including memory, executive functions and psychomotor speed. The follow-up neurocognitive assessment at 4 months after HS-WBRT was also performed. For the delivery of HS-WBRT, Volumetric Modulated Arc Therapy (VMAT) with two full arcs and two non-coplanar partial arcs was employed. For each treatment planning, dose volume histograms were generated for left hippocampus, right hippocampus, and the composite hippocampal structure respectively. Biologically equivalent doses in 2-Gy fractions (EQD2) assuming an alpha/beta ratio of 2 Gy were computed. To perform analyses addressing the correlation between hippocampal dosimetry and the change in scores of NCFs, pre- and post-HS-WBRT neurocognitive assessments were available in 24 patients in this study. Scores of NCFs were quite stable before and after HS-WBRT in terms of hippocampus-dependent memory. Regarding verbal memory, the corresponding EQD2 values of 0, 10, 50, 80 % irradiating the composite hippocampal structure with <12.60 Gy, <8.81, <7.45 Gy and <5.83 Gy respectively were significantly associated with neurocognitive preservation indicated by the immediate recall of Word List Test of Wechsler Memory Scale-III. According to logistic regression analyses, it was noted that dosimetric parameters specific to left sided hippocampus exerted an influence on immediate recall of verbal memory (adjusted odds ratio, 4.08; p-value, 0.042, predicting patients' neurocognitive decline after receiving HS-WBRT). Functional preservation by hippocampal sparing during WBRT is indeed achieved in our study. Providing that modern VMAT techniques can reduce the dose irradiating bilateral hippocampi below dosimetric threshold, patients should be recruited in prospective trials of hippocampal sparing during cranial irradiation to accomplish neurocognitive preservation while maintaining intracranial control. Current Controlled Trials NCT02504788.

Object memory effects on figure assignment: conscious object recognition is not necessary or sufficient.

PubMed

Peterson, M A; de Gelder, B; Rapcsak, S Z; Gerhardstein, P C; Bachoud-Lévi, A

2000-01-01

In three experiments we investigated whether conscious object recognition is necessary or sufficient for effects of object memories on figure assignment. In experiment 1, we examined a brain-damaged participant, AD, whose conscious object recognition is severely impaired. AD's responses about figure assignment do reveal effects from memories of object structure, indicating that conscious object recognition is not necessary for these effects, and identifying the figure-ground test employed here as a new implicit test of access to memories of object structure. In experiments 2 and 3, we tested a second brain-damaged participant, WG, for whom conscious object recognition was relatively spared. Nevertheless, effects from memories of object structure on figure assignment were not evident in WG's responses about figure assignment in experiment 2, indicating that conscious object recognition is not sufficient for effects of object memories on figure assignment. WG's performance sheds light on AD's performance, and has implications for the theoretical understanding of object memory effects on figure assignment.

Leucoencephalopathy following abuse of sniffed heroin.

PubMed

Lefaucheur, Romain; Lebas, Axel; Gérardin, Emmanuel; Grangeon, Lou; Ozkul-Wermester, Ozlem; Aubier-Girard, Carole; Martinaud, Olivier; Maltête, David

2017-01-01

A 29-year-old man was admitted for acute cognitive impairment. Three weeks earlier, he had been admitted for coma due to sniffed heroin abuse responsive to naloxone infusion. At admission, the patient presented with apraxia, severe memory impairment and anosognosia. Brain MRI revealed symmetric hyperintensities of supratentorial white matter, sparing brainstem and cerebellum, on FLAIR and B1000 sequences. Four months later, repeated neuropsychological assessment revealed dramatic improvement of global cognitive functions. Toxic leucoencephalopathy excluding the cerebellum and brainstem is a rare complication of heroin abuse, and seems to concern especially patients that use heroin by sniff or injection. In these patients, cognitive troubles are predominant, prognosis seems better and infratentorial brain structures can be spared. In conclusion, our observation emphasizes that heroin-induced encephalopathy can have a favourable outcome and that imaging and clinical patterns can indicate the mode of drug administration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Left hippocampus sparing whole brain radiotherapy (WBRT): A planning study.

PubMed

Kazda, Tomas; Vrzal, Miroslav; Prochazka, Tomas; Dvoracek, Petr; Burkon, Petr; Pospisil, Petr; Dziacky, Adam; Nikl, Tomas; Jancalek, Radim; Slampa, Pavel; Lakomy, Radek

2017-12-01

Unilateral sparing of the dominant (left) hippocampus during whole brain radiotherapy (WBRT) could mitigate cognitive decline, especially verbal memory, similar to the widely investigated bilateral hippocampus avoidance (HA-WBRT). The aim of this planning study is dosimetrical comparison of HA-WBRT with only left hippocampus sparing (LHA-WBRT) plans. HA-WBRT plans for 10 patients were prepared in accordance with RTOG 0933 trial and served as baseline for comparisons with several LHA-WBRT plans prepared with an effort: 1) to maintain the same left hippocampus dosimetry ("BEST PTV") and 2) to maintain same dosimetry in planning target volume as in HA-WBRT ("BEST LH"). All HA-WBRT plans met RTOG 0933 protocol criteria with a mean Conformity index 1.09 and mean Homogeneity index (HI) 0.21. Mean right and left hippocampal D100% was 7.8 Gy and 8.5 Gy and mean Dmax 14.0 Gy and 13.8 Gy, respectively. "BEST PTV" plans reduced HI by 31.2% (P=0.005) which is mirrored by lower PTV_D2% (-0.8 Gy, P=0.005) and higher PTV_D98% (+1.3 Gy, P=0.005) as well as decreased optic pathway's Dmax by 1 Gy. In "BEST LH", mean D100% and Dmax for the left hippocampus were significantly reduced by 11.2% (P=0.005) and 10.9% (P=0.005) respectively. LHA-WBRT could improve target coverage and/or further decrease in dose to spared hippocampus. Future clinical trials must confirm whether statistically significant reduction in left hippocampal dose is also clinically significant.

Cognitive Spare Capacity as an Index of Listening Effort.

PubMed

Rudner, Mary

2016-01-01

Everyday listening may be experienced as effortful, especially by individuals with hearing loss. This may be due to internal factors, such as cognitive load, and external factors, such as noise. Even when speech is audible, internal and external factors may combine to reduce cognitive spare capacity, or the ability to engage in cognitive processing of spoken information. A better understanding of cognitive spare capacity and how it can be optimally allocated may guide new approaches to rehabilitation and ultimately improve outcomes. This article presents results of three tests of cognitive spare capacity:1. Sentence-final Word Identification and Recall (SWIR) test2. Cognitive Spare Capacity Test (CSCT)3. Auditory Inference Span Test (AIST)Results show that noise reduces cognitive spare capacity even when speech intelligibility is retained. In addition, SWIR results show that hearing aid signal processing can increase cognitive spare capacity, and CSCT and AIST results show that increasing load reduces cognitive spare capacity. Correlational evidence suggests that while the effect of noise on cognitive spare capacity is related to working memory capacity, the effect of load is related to executive function. Future studies should continue to investigate how hearing aid signal processing can mitigate the effect of load on cognitive spare capacity, and whether such effects can be enhanced by developing executive skills through training. The mechanisms modulating cognitive spare capacity should be investigated by studying their neural correlates, and tests of cognitive spare capacity should be developed for clinical use in conjunction with developing new approaches to rehabilitation.

Descending brain neurons in larval lamprey: Spinal projection patterns and initiation of locomotion

PubMed Central

Shaw, Albert C.; Jackson, Adam W.; Holmes, Tamra; Thurman, Suzie; Davis, G.R.; McClellan, Andrew D.

2010-01-01

In larval lamprey, partial lesions were made in the rostral spinal cord to determine which spinal tracts are important for descending activation of locomotion and to identify descending brain neurons that project in these tracts. In whole animals and in vitro brain/spinal cord preparations, brain-initiated spinal locomotor activity was present when the lateral or intermediate spinal tracts were spared but usually was abolished when the medial tracts were spared. We previously showed that descending brain neurons are located in eleven cell groups, including reticulospinal (RS) neurons in the mesenecephalic reticular nucleus (MRN) as well as the anterior (ARRN), middle (MRRN), and posterior (PRRN) rhombencephalic reticular nuclei. Other descending brain neurons are located in the diencephalic (Di) as well as the anterolateral (ALV), dorsolateral (DLV), and posterolateral (PLV) vagal groups. In the present study, the Mauthner and auxillary Mauthner cells, most neurons in the Di, ALV, DLV, and PLV cell groups, and some neurons in the ARRN and PRRN had crossed descending axons. The majority of neurons projecting in medial spinal tracts included large identified Müller cells and neurons in the Di, MRN, ALV, and DLV. Axons of individual descending brain neurons usually did not switch spinal tracts, have branches in multiple tracts, or cross the midline within the rostral cord. Most neurons that projected in the lateral/intermediate spinal tracts were in the ARRN, MRRN, and PRRN. Thus, output neurons of the locomotor command system are distributed in several reticular nuclei, whose neurons project in relatively wide areas of the cord. PMID:20510243

Reducing late effects of radiotherapy in average risk medulloblastoma.

PubMed

Ibrahim, Noha Yehia; Abdel Aal, Hisham H; Abdel Kader, Mohamed S; Makaar, Wael S; Shaaban, Ahmed H

2014-03-01

To assess the efficacy and safety in average-risk pediatric medulloblastoma (MB) receiving tumor bed boost irradiation compared to a posterior fossa (PF) boost. Thirty patients were enrolled in the study and divided evenly into two treatment arms of 15. Both arms received 23.4 Gy craniospinal irradiation (CS) and a 32.4 Gy boost. Patients in arm 1 were given PF boosts, and those in arm 2 were given boosts to the gross target volume (GTV). Weekly oncovin was given throughout all radiotherapy (RT). Eight cycles of adjuvant chemotherapy of CCNU, oncovin and platinol were given to all patients after RT. MRI, pure tone audiogram (PTA) and intelligence quotient (IQ) tests were performed before and after RT and every three months thereafter. There were significant differences in the sparing dose to the cochlea and brain stem as well as the volume of the normal brain receiving a 100% dose. There was a significant initial improvement of hearing function in patients given the target volume boost after RT, which was lost after chemotherapy. With a median follow up of 23 months, there was no difference in progression free survival or overall survival between the two arms. Irradiation of the tumor bed after 23.4 Gy craniospinal irradiation for average-risk MB results in similar disease control as a PF boost. Dosimetric sparing for the cochleae and normal tissue is evident in patients receiving tumor bed boosts. The hearing improvement and cognitive function preservation effects of the treatment need more follow up.

Genetics and mathematics: evidence from Prader-Willi syndrome.

PubMed

Semenza, Carlo; Pignatti, Riccardo; Bertella, Laura; Ceriani, Francesca; Mori, Ileana; Molinari, Enrico; Giardino, Daniela; Malvestiti, Francesca; Grugni, Graziano

2008-01-15

Mathematical abilities were tested in people with Prader-Willi syndrome (PWS), using a series of basic mathematical tasks for which normative data are available. The difference between the deletion and the disomy variants of this condition was explored. While a wide phenotypic variation was found, some basic findings emerge clearly. As expected from previous literature, deletion and disomy participants were found to differ in their degree of impairment, with disomy being overall the most spared condition. However, the tasks selectively spared in the disomy condition are not necessarily the easiest ones and those that discriminate less the PWS group from controls. It rather seems that disomy patients are spared, with respect to deletion, in tasks entailing transcoding and comparison of numbers in the Arabic code. Overall a particular difficulty was detected in reliably performing parity judgments. This task has been shown to be very frequently spared after a brain injury, even in severe aphasic conditions. The most interesting result is the sparing in analog number scale, whereby PWS seem, overall, to outperform controls. This finding may help in understanding previously reported, surprising results about cognitive skills in PWS. Elevated performances in PWS may result from life-long hyper-reliance on one visuo-spatial system in presence of underdevelopment of the other.

Microdialysate concentration changes do not provide sufficient information to evaluate metabolic effects of lactate supplementation in brain-injured patients

PubMed Central

Rothman, Douglas L; Nordström, Carl-Henrik

2016-01-01

Cerebral microdialysis is a widely used clinical tool for monitoring extracellular concentrations of selected metabolites after brain injury and to guide neurocritical care. Extracellular glucose levels and lactate/pyruvate ratios have high diagnostic value because they can detect hypoglycemia and deficits in oxidative metabolism, respectively. In addition, patterns of metabolite concentrations can distinguish between ischemia and mitochondrial dysfunction, and are helpful to choose and evaluate therapy. Increased intracranial pressure can be life-threatening after brain injury, and hypertonic solutions are commonly used for pressure reduction. Recent reports have advocated use of hypertonic sodium lactate, based on claims that it is glucose sparing and provides an oxidative fuel for injured brain. However, changes in extracellular concentrations in microdialysate are not evidence that a rise in extracellular glucose level is beneficial or that lactate is metabolized and improves neuroenergetics. The increase in glucose concentration may reflect inhibition of glycolysis, glycogenolysis, and pentose phosphate shunt pathway fluxes by lactate flooding in patients with mitochondrial dysfunction. In such cases, lactate will not be metabolizable and lactate flooding may be harmful. More rigorous approaches are required to evaluate metabolic and physiological effects of administration of hypertonic sodium lactate to brain-injured patients. PMID:27604313

Minibeam Therapy With Protons and Light Ions: Physical Feasibility and Potential to Reduce Radiation Side Effects and to Facilitate Hypofractionation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dilmanian, F. Avraham, E-mail: avraham.dilmanian@stonybrook.edu; Eley, John G.; Krishnan, Sunil

2015-06-01

Purpose: Despite several advantages of proton therapy over megavoltage x-ray therapy, its lack of proximal tissue sparing is a concern. The method presented here adds proximal tissue sparing to protons and light ions by turning their uniform incident beams into arrays of parallel, small, or thin (0.3-mm) pencil or planar minibeams, which are known to spare tissues. As these minibeams penetrate the tissues, they gradually broaden and merge with each other to produce a solid beam. Methods and Materials: Broadening of 0.3-mm-diameter, 109-MeV proton pencil minibeams was measured using a stack of radiochromic films with plastic spacers. Monte Carlo simulationsmore » were used to evaluate the broadening in water of minibeams of protons and several light ions and the dose from neutron generated by collimator. Results: A central parameter was tissue depth, where the beam full width at half maximum (FWHM) reached 0.7 mm, beyond which tissue sparing decreases. This depth was 22 mm for 109-MeV protons in a film stack. It was also found by simulations in water to be 23.5 mm for 109 MeV proton pencil minibeams and 26 mm for 116 MeV proton planar minibeams. For light ions, all with 10 cm range in water, that depth increased with particle size; specifically it was 51 mm for Li-7 ions. The ∼2.7% photon equivalent neutron skin dose from the collimator was reduced 7-fold by introducing a gap between the collimator and the skin. Conclusions: Proton minibeams can be implemented at existing particle therapy centers. Because they spare the shallow tissues, they could augment the efficacy of proton therapy and light particle therapy, particularly in treating tumors that benefit from sparing of proximal tissues such as pediatric brain tumors. They should also allow hypofractionated treatment of all tumors by allowing the use of higher incident doses with less concern about proximal tissue damage.« less

Evaluating the impact of hippocampal sparing during whole brain radiotherapy on neurocognitive functions: A preliminary report of a prospective phase II study.

PubMed

Lin, Shinn-Yn; Yang, Chi-Cheng; Wu, Yi-Ming; Tseng, Chen-Kan; Wei, Kuo-Chen; Chu, Yi-Chuan; Hsieh, Hsiang-Yao; Wu, Tung-Ho; Pai, Ping-Ching; Hsu, Peng-Wei; Chuang, Chi-Cheng

2015-01-01

Whole brain radiotherapy (WBRT) is the treatment of choice for patients with brain metastases. However, neurocognitive functions (NCFs) decline due to impaired hippocampal neurogenesis might occur thereafter. It is hypothesized that conformal hippocampal avoidance during the course of WBRT (HA-WBRT) might provide meaningful NCF preservation. Our study aims to demonstrate the impact of delivering HA-WBRT on NCF changes in patients receiving WBRT. Twenty-five patients who were referred for prophylactic cranial irradiation (PCI) or treating oligometastatic brain disease were enrolled in the study. Before the HA-WBRT course, all participants should receive baseline neurocognitive assessment, including memory, executive functions, and psychomotor speed. The primary endpoint was delayed recall, as determined by the change/decline in verbal memory [Wechsler Memory Scale - 3rd edition (WMS III)- Word List score] from the baseline assessment to 4 months after the start of HA-WBRT. Only three patients belonged to the clinical setting of PCI; the remaining 22 patients had oligometastatic brain disease. Regarding neurocognitive outcomes, no statistically significant differences were found between various NCF scores obtained at baseline and at post-radiotherapy intervals, in immediate verbal memory and non-verbal memory, except for delayed recall memory on Word List (F = 5.727, p = 0.048). Functional preservation by hippocampal sparing during WBRT could largely be achieved in this study, which also suggests that HA-WBRT should be a feasible technique preserving neurocognitive functions while maintaining intracranial control.

Late-stage optimization of a tercyclic class of S1P3-sparing, S1P1 receptor agonists.

PubMed

Horan, Joshua C; Kuzmich, Daniel; Liu, Pingrong; DiSalvo, Darren; Lord, John; Mao, Can; Hopkins, Tamara D; Yu, Hui; Harcken, Christian; Betageri, Raj; Hill-Drzewi, Melissa; Patenaude, Lori; Patel, Monica; Fletcher, Kimberly; Terenzzio, Donna; Linehan, Brian; Xia, Heather; Patel, Mita; Studwell, Debbie; Miller, Craig; Hickey, Eugene; Levin, Jeremy I; Smith, Dustin; Kemper, Raymond A; Modis, Louise K; Bannen, Lynne C; Chan, Diva S; Mac, Morrison B; Ng, Stephanie; Wang, Yong; Xu, Wei; Lemieux, René M

2016-01-15

Poor solubility and cationic amphiphilic drug-likeness were liabilities identified for a lead series of S1P3-sparing, S1P1 agonists originally developed from a high-throughput screening campaign. This work describes the subsequent optimization of these leads by balancing potency, selectivity, solubility and overall molecular charge. Focused SAR studies revealed favorable structural modifications that, when combined, produced compounds with overall balanced profiles. The low brain exposure observed in rat suggests that these compounds would be best suited for the potential treatment of peripheral autoimmune disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cost-effectiveness analysis of neurocognitive-sparing treatments for brain metastases.

PubMed

Savitz, Samuel T; Chen, Ronald C; Sher, David J

2015-12-01

Decisions regarding how to treat patients who have 1 to 3 brain metastases require important tradeoffs between controlling recurrences, side effects, and costs. In this analysis, the authors compared novel treatments versus usual care to determine the incremental cost-effectiveness ratio from a payer's (Medicare) perspective. Cost-effectiveness was evaluated using a microsimulation of a Markov model for 60 one-month cycles. The model used 4 simulated cohorts of patients aged 65 years with 1 to 3 brain metastases. The 4 cohorts had a median survival of 3, 6, 12, and 24 months to test the sensitivity of the model to different prognoses. The treatment alternatives evaluated included stereotactic radiosurgery (SRS) with 3 variants of salvage after recurrence (whole-brain radiotherapy [WBRT], hippocampal avoidance WBRT [HA-WBRT], SRS plus WBRT, and SRS plus HA-WBRT). The findings were tested for robustness using probabilistic and deterministic sensitivity analyses. Traditional radiation therapies remained cost-effective for patients in the 3-month and 6-month cohorts. In the cohorts with longer median survival, HA-WBRT and SRS plus HA-WBRT became cost-effective relative to traditional treatments. When the treatments that involved HA-WBRT were excluded, either SRS alone or SRS plus WBRT was cost-effective relative to WBRT alone. The deterministic and probabilistic sensitivity analyses confirmed the robustness of these results. HA-WBRT and SRS plus HA-WBRT were cost-effective for 2 of the 4 cohorts, demonstrating the value of controlling late brain toxicity with this novel therapy. Cost-effectiveness depended on patient life expectancy. SRS was cost-effective in the cohorts with short prognoses (3 and 6 months), whereas HA-WBRT and SRS plus HA-WBRT were cost-effective in the cohorts with longer prognoses (12 and 24 months). © 2015 American Cancer Society.

Treatment planning strategy for whole-brain radiotherapy with hippocampal sparing and simultaneous integrated boost for multiple brain metastases using intensity-modulated arc therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, Damodar, E-mail: dpokhrel@kumc.edu; Sood, Sumit; McClinton, Christopher

Purpose: To retrospectively evaluate the accuracy, plan quality and efficiency of intensity-modulated arc therapy (IMAT) for hippocampal sparing whole-brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in patients with multiple brain metastases (m-BM). Materials and methods: A total of 5 patients with m-BM were retrospectively replanned for HS-WBRT with SIB using IMAT treatment planning. The hippocampus was contoured on diagnostic T1-weighted magnetic resonance imaging (MRI) which had been fused with the planning CT image set. The hippocampal avoidance zone (HAZ) was generated using a 5-mm uniform margin around the paired hippocampi. The m-BM planning target volumes (PTVs) were contoured onmore » T1/T2-weighted MRI registered with the 3D planning computed tomography (CT). The whole-brain planning target volume (WB-PTV) was defined as the whole-brain tissue volume minus HAZ and m-BM PTVs. Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis-TX linear accelerator consisting of high-definition multileaf collimators (HD-MLCs: 2.5-mm leaf width at isocenter) and 6-MV beam. Prescription dose was 30 Gy for WB-PTV and 45 Gy for each m-BM in 10 fractions. Three full coplanar arcs with orbit avoidance sectors were used. Treatment plans were evaluated using homogeneity (HI) and conformity indices (CI) for target coverage and dose to organs at risk (OAR). Dose delivery efficiency and accuracy of each IMAT plan was assessed via quality assurance (QA) with a MapCHECK device. Actual beam-on time was recorded and a gamma index was used to compare dose agreement between the planned and measured doses. Results: All 5 HS-WBRT with SIB plans met WB-PTV D{sub 2%}, D{sub 98%}, and V{sub 30} {sub Gy} NRG-CC001 requirements. The plans demonstrated highly conformal and homogenous coverage of the WB-PTV with mean HI and CI values of 0.33 ± 0.04 (range: 0.27 to 0.36), and 0.96 ± 0.01 (range: 0.95 to 0.97), respectively. All 5 hippocampal sparing patients met protocol guidelines with maximum dose and dose to 100% of hippocampus (D{sub 100%}) less than 16 and 9 Gy, respectively. The dose to the optic apparatus was kept below protocol guidelines for all 5 patients. Highly conformal and homogenous radiosurgical dose distributions were achieved for all 5 patients with a total of 33 brain metastases. The m-BM PTVs had a mean HI = 0.09 ± 0.02 (range: 0.07 to 0.19) and a mean CI = 1.02 ± 0.06 (range: 0.93 to 1.2). The total number of monitor units (MU) was, on average, 1677 ± 166. The average beam-on time was 4.1 ± 0.4 minute . The IMAT plans demonstrated accurate dose delivery of 95.2 ± 0.6%, on average, for clinical gamma passing rate with 2%/2-mm criteria and 98.5 ± 0.9%, on average, with 3%/3-mm criteria. Conclusions: All hippocampal sparing plans were considered clinically acceptable per NRG-CC001 dosimetric compliance criteria. IMAT planning provided highly conformal and homogenous dose distributions for the WB-PTV and m-BM PTVs with lower doses to OAR such as the hippocampus. These results suggest that HS-WBRT with SIB is a clinically feasible, fast, and effective treatment option for patients with a relatively large numbers of m-BM lesions.« less

Irradiation of intracerebral 9L gliosarcoma by a single array of microplanar x-ray beams from a synchrotron: balance between curing and sparing

NASA Astrophysics Data System (ADS)

Regnard, Pierrick; LeDuc, Géraldine; Bräuer-Krisch, Elke; Troprès, Irène; Siegbahn, Erik Albert; Kusak, Audrey; Clair, Charlotte; Bernard, Hélène; Dallery, Dominique; Laissue, Jean A.; Bravin, Alberto

2008-02-01

The purpose of this work was the understanding of microbeam radiation therapy at the ESRF in order to find the best compromise between curing of tumors and sparing of normal tissues, to obtain a better understanding of survival curves and to report its efficiency. This method uses synchrotron-generated x-ray microbeams. Rats were implanted with 9L gliosarcomas and the tumors were diagnosed by MRI. They were irradiated 14 days after implantation by arrays of 25 µm wide microbeams in unidirectional mode, with a skin entrance dose of 625 Gy. The effect of using 200 or 100 µm center-to-center spacing between the microbeams was compared. The median survival time (post-implantation) was 40 and 67 days at 200 and 100 µm spacing, respectively. However, 72% of rats irradiated at 100 µm spacing showed abnormal clinical signs and weight patterns, whereas only 12% of rats were affected at 200 µm spacing. In parallel, histological lesions of the normal brain were found in the 100 µm series only. Although the increase in lifespan was equal to 273% and 102% for the 100 and 200 µm series, respectively, the 200 µm spacing protocol provides a better sparing of healthy tissue and may prove useful in combination with other radiation modalities or additional drugs.

Dietary Docosahexaenoic Acid Improves Cognitive Function, Tissue Sparing, and Magnetic Resonance Imaging Indices of Edema and White Matter Injury in the Immature Rat after Traumatic Brain Injury.

PubMed

Schober, Michelle E; Requena, Daniela F; Abdullah, Osama M; Casper, T Charles; Beachy, Joanna; Malleske, Daniel; Pauly, James R

2016-02-15

Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. Specific therapies to treat acute TBI are lacking. Cognitive impairment from TBI may be blunted by decreasing inflammation and oxidative damage after injury. Docosahexaenoic acid (DHA) decreases cognitive impairment, oxidative stress, and white matter injury in adult rats after TBI. Effects of DHA on cognitive outcome, oxidative stress, and white matter injury in the developing rat after experimental TBI are unknown. We hypothesized that DHA would decrease early inflammatory markers and oxidative stress, and improve cognitive, imaging and histologic outcomes in rat pups after controlled cortical impact (CCI). CCI or sham surgery was delivered to 17 d old male rat pups exposed to DHA or standard diet for the duration of the experiments. DHA was introduced into the dam diet the day before CCI to allow timely DHA delivery to the pre-weanling pups. Inflammatory cytokines and nitrates/nitrites were measured in the injured brains at post-injury Day (PID) 1 and PID2. Morris water maze (MWM) testing was performed at PID41-PID47. T2-weighted and diffusion tensor imaging studies were obtained at PID12 and PID28. Tissue sparing was calculated histologically at PID3 and PID50. DHA did not adversely affect rat survival or weight gain. DHA acutely decreased oxidative stress and increased anti-inflammatory interleukin 10 in CCI brains. DHA improved MWM performance and lesion volume late after injury. At PID12, DHA decreased T2-imaging measures of cerebral edema and decreased radial diffusivity, an index of white matter injury. DHA improved short- and long-term neurologic outcomes after CCI in the rat pup. Given its favorable safety profile, DHA is a promising candidate therapy for pediatric TBI. Further studies are needed to explore neuroprotective mechanisms of DHA after developmental TBI.

Dietary Docosahexaenoic Acid Improves Cognitive Function, Tissue Sparing, and Magnetic Resonance Imaging Indices of Edema and White Matter Injury in the Immature Rat after Traumatic Brain Injury

PubMed Central

Requena, Daniela F.; Abdullah, Osama M.; Casper, T. Charles; Beachy, Joanna; Malleske, Daniel; Pauly, James R.

2016-01-01

Abstract Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. Specific therapies to treat acute TBI are lacking. Cognitive impairment from TBI may be blunted by decreasing inflammation and oxidative damage after injury. Docosahexaenoic acid (DHA) decreases cognitive impairment, oxidative stress, and white matter injury in adult rats after TBI. Effects of DHA on cognitive outcome, oxidative stress, and white matter injury in the developing rat after experimental TBI are unknown. We hypothesized that DHA would decrease early inflammatory markers and oxidative stress, and improve cognitive, imaging and histologic outcomes in rat pups after controlled cortical impact (CCI). CCI or sham surgery was delivered to 17 d old male rat pups exposed to DHA or standard diet for the duration of the experiments. DHA was introduced into the dam diet the day before CCI to allow timely DHA delivery to the pre-weanling pups. Inflammatory cytokines and nitrates/nitrites were measured in the injured brains at post-injury Day (PID) 1 and PID2. Morris water maze (MWM) testing was performed at PID41-PID47. T2-weighted and diffusion tensor imaging studies were obtained at PID12 and PID28. Tissue sparing was calculated histologically at PID3 and PID50. DHA did not adversely affect rat survival or weight gain. DHA acutely decreased oxidative stress and increased anti-inflammatory interleukin 10 in CCI brains. DHA improved MWM performance and lesion volume late after injury. At PID12, DHA decreased T2-imaging measures of cerebral edema and decreased radial diffusivity, an index of white matter injury. DHA improved short- and long-term neurologic outcomes after CCI in the rat pup. Given its favorable safety profile, DHA is a promising candidate therapy for pediatric TBI. Further studies are needed to explore neuroprotective mechanisms of DHA after developmental TBI. PMID:26247583

Emerging Trends in the Management of Brain Metastases from Non-small Cell Lung Cancer.

PubMed

Churilla, Thomas M; Weiss, Stephanie E

2018-05-07

To summarize current approaches in the management of brain metastases from non-small cell lung cancer (NSCLC). Local treatment has evolved from whole-brain radiotherapy (WBRT) to increasing use of stereotactic radiosurgery (SRS) alone for patients with limited (1-4) brain metastases. Trials have established post-operative SRS as an alternative to adjuvant WBRT following resection of brain metastases. Second-generation TKIs for ALK rearranged NSCLC have demonstrated improved CNS penetration and activity. Current brain metastasis trials are focused on reducing cognitive toxicity: hippocampal sparing WBRT, SRS for 5-15 metastases, pre-operative SRS, and use of systemic targeted agents or immunotherapy. The role for radiotherapy in the management of brain metastases is becoming better defined with local treatment shifting from WBRT to SRS alone for limited brain metastases and post-operative SRS for resected metastases. Further trials are warranted to define the optimal integration of newer systemic agents with local therapies.

Getting signals into the brain: visual prosthetics through thalamic microstimulation.

PubMed

Pezaris, John S; Eskandar, Emad N

2009-07-01

Common causes of blindness are diseases that affect the ocular structures, such as glaucoma, retinitis pigmentosa, and macular degeneration, rendering the eyes no longer sensitive to light. The visual pathway, however, as a predominantly central structure, is largely spared in these cases. It is thus widely thought that a device-based prosthetic approach to restoration of visual function will be effective and will enjoy similar success as cochlear implants have for restoration of auditory function. In this article the authors review the potential locations for stimulation electrode placement for visual prostheses, assessing the anatomical and functional advantages and disadvantages of each. Of particular interest to the neurosurgical community is placement of deep brain stimulating electrodes in thalamic structures that has shown substantial promise in an animal model. The theory of operation of visual prostheses is discussed, along with a review of the current state of knowledge. Finally, the visual prosthesis is proposed as a model for a general high-fidelity machine-brain interface.

Nutrition, somatomedins, and the brain.

PubMed

Phillips, L S

1986-01-01

Conditions of decreased nutrient supply (malnutrition) and/or decreased nutrient utilization (diabetes) are attended by impairment of growth despite an increase in circulating levels of growth hormone (GH). Growth involves the actions of somatomedins, circulating insulinlike polypeptides with anabolic effects on cartilage, fat, and muscle. In malnutrition and diabetes, mechanisms of growth impairment appear to include a decrease in GH-induced generation of somatomedins, together with an increase in somatomedin inhibitors, factors which antagonize somatomedin action. Brain mediation of these alterations involves a rise in GH secretion due to decreased negative feedback from somatomedins, perhaps accentuated by blunting of feedback via actions of somatomedin inhibitors. In combination these processes lead to shunting of metabolic fuels toward vital processes and away from growth (via decreased somatomedin action) and to protein-sparing and increase in alternate metabolic fuels (via direct GH actions on muscle and fat). Further study of involved hypothalamic and pituitary mechanisms should yield additional insights into the role of the brain in metabolic homeostasis.

REPEATED MATERNAL SEPARATION IN THE NEONATAL RAT: CELLULAR MECHANISMS CONTRIBUTING TO BRAIN GROWTH SPARING

EPA Science Inventory

Separation of rat neonates from their dam has been shown to evoke acutely a variety of biochemical and physiological responses. n the current study, we examined whether these responses were extended to pups who were subject to daily episodes of maternal deprivation, and whether t...

Treatment Planning and Delivery of Whole Brain Irradiation with Hippocampal Avoidance in Rats.

PubMed

Cramer, C K; Yoon, S W; Reinsvold, M; Joo, K M; Norris, H; Hood, R C; Adamson, J D; Klein, R C; Kirsch, D G; Oldham, M

2015-01-01

Despite the clinical benefit of whole brain radiotherapy (WBRT), patients and physicians are concerned by the long-term impact on cognitive functioning. Many studies investigating the molecular and cellular impact of WBRT have used rodent models. However, there has not been a rodent protocol comparable to the recently reported Radiation Therapy Oncology Group (RTOG) protocol for WBRT with hippocampal avoidance (HA) which is intended to spare cognitive function. The aim of this study was to develop a hippocampal-sparing WBRT protocol in Wistar rats. The technical and clinical challenges encountered in hippocampal sparing during rat WBRT are substantial. Three key challenges were identified: hippocampal localization, treatment planning, and treatment localization. Hippocampal localization was achieved with sophisticated imaging techniques requiring deformable registration of a rat MRI atlas with a high resolution MRI followed by fusion via rigid registration to a CBCT. Treatment planning employed a Monte Carlo dose calculation in SmART-Plan and creation of 0.5 cm thick lead blocks custom-shaped to match DRR projections. Treatment localization necessitated the on-board image-guidance capability of the XRAD C225Cx micro-CT/micro-irradiator (Precision X-Ray). Treatment was accomplished with opposed lateral fields with 225 KVp X-rays at a current of 13 mA filtered through 0.3 mm of copper using a 40x40 mm square collimator and the lead blocks. A single fraction of 4 Gy was delivered (2 Gy per lateral field) with a 41 second beam on time per field at a dose rate of 304.5 cGy/min. Dosimetric verification of hippocampal sparing was performed using radiochromic film. In vivo verification of HA was performed after delivery of a single 4 Gy fraction either with or without HA using γ-H2Ax staining of tissue sections from the brain to quantify the amount of DNA damage in rats treated with HA, WBRT, or sham-irradiated (negative controls). The mean dose delivered to radiochromic film beneath the hippocampal block was 0.52 Gy compared to 3.93 Gy without the block, indicating an 87% reduction in the dose delivered to the hippocampus. This difference was consistent with doses predicted by Monte Carlo dose calculation. The Dose Volume Histogram (DVH) generated via Monte Carlo simulation showed an underdose of the target volume (brain minus hippocampus) with 50% of the target volume receiving 100% of the prescription isodose as a result of the lateral blocking techniques sparing some midline thalamic and subcortical tissue. Staining of brain sections with anti-phospho-Histone H2A.X (reflecting double-strand DNA breaks) demonstrated that this treatment protocol limited radiation dose to the hippocampus in vivo. The mean signal intensity from γ-H2Ax staining in the cortex was not significantly different from the signal intensity in the cortex of rats treated with WBRT (5.40 v. 5.75, P = 0.32). In contrast, the signal intensity in the hippocampus of rats treated with HA was significantly lower than rats treated with WBRT (4.55 v. 6.93, P = 0.012). Despite the challenges of planning conformal treatments for small volumes in rodents, our dosimetric and in vivo data show that WBRT with HA is feasible in rats. This study provides a useful platform for further application and refinement of the technique.

Limiting glioma development by photodynamic therapy-generated macrophage vaccine and allo-stimulation: an in vivo histological study in rats

NASA Astrophysics Data System (ADS)

Madsen, Steen J.; Christie, Catherine; Huynh, Khoi; Peng, Qian; Uzal, Francisco A.; Krasieva, Tatiana B.; Hirschberg, Henry

2018-02-01

Immunotherapy of brain tumors involves the stimulation of an antitumor immune response. This type of therapy can be targeted specifically to tumor cells thus sparing surrounding normal brain. Due to the presence of the blood-brain barrier, the brain is relatively isolated from the systemic circulation and, as such, the initiation of significant immune responses is more limited than other types of cancers. The purpose of this study was to show that the efficacy of tumor primed antigen presenting macrophage (MaF98) vaccines can be increased by: (1) photodynamic therapy (PDT) of the priming tumor cells and (2) intracranial injection of allogeneic glioma cells directly into the tumor site. Experiments were conducted in an in vivo brain tumor development model using Fischer rats and F98 (syngeneic) and BT4C (allogeneic) glioma cells. The results showed that immunization with Ma (acting as antigen-presenting cells), primed with PDT-treated tumor cells (MaF98), significantly slowed but did not prevent the growth of F98-induced tumors in the brain. Complete suppression of tumor development was obtained via MaF98 inoculation combined with direct intracranial injection of allogeneic glioma cells. No deleterious effects were noted in any of the animals during the 14-day observation period.

Air pollution and your brain: what do you need to know right now.

PubMed

Calderón-Garcidueñas, Lilian; Calderón-Garcidueñas, Ana; Torres-Jardón, Ricardo; Avila-Ramírez, José; Kulesza, Randy J; Angiulli, Amedeo D

2015-07-01

Research links air pollution mostly to respiratory and cardiovascular disease. The effects of air pollution on the central nervous system (CNS) are not broadly recognized. Urban outdoor pollution is a global public health problem particularly severe in megacities and in underdeveloped countries, but large and small cities in the United States and the United Kingom are not spared. Fine and ultrafine particulate matter (UFPM) defined by aerodynamic diameter (<2.5-μm fine particles, PM2.5, and <100-nm UFPM) pose a special interest for the brain effects given the capability of very small particles to reach the brain. In adults, ambient pollution is associated to stroke and depression, whereas the emerging picture in children show significant systemic inflammation, immunodysregulation at systemic, intratechal and brain levels, neuroinflammation and brain oxidative stress, along with the main hallmarks of Alzheimer and Parkinson's diseases: hyperphosphorilated tau, amyloid plaques and misfolded α-synuclein. Animal models exposed to particulate matter components show markers of both neuroinflammation and neurodegeneration. Epidemiological, cognitive, behavioral and mechanistic studies into the association between air pollution exposures and the development of CNS damage particularly in children are of pressing importance for public health and quality of life. Primary health providers have to include a complete prenatal and postnatal environmental and occupational history to indoor and outdoor toxic hazards and measures should be taken to prevent or reduce further exposures.

Interpreting and Utilising Intersubject Variability in Brain Function.

PubMed

Seghier, Mohamed L; Price, Cathy J

2018-06-01

We consider between-subject variance in brain function as data rather than noise. We describe variability as a natural output of a noisy plastic system (the brain) where each subject embodies a particular parameterisation of that system. In this context, variability becomes an opportunity to: (i) better characterise typical versus atypical brain functions; (ii) reveal the different cognitive strategies and processing networks that can sustain similar tasks; and (iii) predict recovery capacity after brain damage by taking into account both damaged and spared processing pathways. This has many ramifications for understanding individual learning preferences and explaining the wide differences in human abilities and disabilities. Understanding variability boosts the translational potential of neuroimaging findings, in particular in clinical and educational neuroscience. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Resection of a Pediatric Thalamic Juvenile Pilocytic Astrocytoma with Whole Brain Tractography

PubMed Central

Weiner, Howard L

2017-01-01

The resection of deep-seated brain tumors has been associated with morbidity due to injury to critical neural structures during the approach. Recent technological advancements in navigation and stereotaxy, surgical planning, brain tractography and minimal-access brain ports present the opportunity to overcome such limitations. Here, we present the case of a pediatric patient with a left thalamic/midbrain juvenile pilocytic astrocytoma (JPA). The tumor displaced the corticospinal fibers posteriorly and resulted in hemiparesis. Using whole brain tractography to plan a corridor for the approach, neuronavigation, a tubular retractor and an exoscope for visualization, we obtained gross total resection of the tumor, while minimizing injury to white matter bundles, including the corticospinal fibers. We propose that surgical planning with whole brain tractography is essential for reducing morbidity while accessing deep-lying brain lesions via retractor tubes, by means of sparing critical fiber tracts. PMID:29234572

Evidence for widespread, severe brain copper deficiency in Alzheimer's dementia.

PubMed

Xu, Jingshu; Church, Stephanie J; Patassini, Stefano; Begley, Paul; Waldvogel, Henry J; Curtis, Maurice A; Faull, Richard L M; Unwin, Richard D; Cooper, Garth J S

2017-08-16

Datasets comprising simultaneous measurements of many essential metals in Alzheimer's disease (AD) brain are sparse, and available studies are not entirely in agreement. To further elucidate this matter, we employed inductively-coupled-plasma mass spectrometry to measure post-mortem levels of 8 essential metals and selenium, in 7 brain regions from 9 cases with AD (neuropathological severity Braak IV-VI), and 13 controls who had normal ante-mortem mental function and no evidence of brain disease. Of the regions studied, three undergo severe neuronal damage in AD (hippocampus, entorhinal cortex and middle-temporal gyrus); three are less-severely affected (sensory cortex, motor cortex and cingulate gyrus); and one (cerebellum) is relatively spared. Metal concentrations in the controls differed among brain regions, and AD-associated perturbations in most metals occurred in only a few: regions more severely affected by neurodegeneration generally showed alterations in more metals, and cerebellum displayed a distinctive pattern. By contrast, copper levels were substantively decreased in all AD-brain regions, to 52.8-70.2% of corresponding control values, consistent with pan-cerebral copper deficiency. This copper deficiency could be pathogenic in AD, since levels are lowered to values approximating those in Menkes' disease, an X-linked recessive disorder where brain-copper deficiency is the accepted cause of severe brain damage. Our study reinforces others reporting deficient brain copper in AD, and indicates that interventions aimed at safely and effectively elevating brain copper could provide a new experimental-therapeutic approach.

Cysteine-sparing CADASIL mutations in NOTCH3 show proaggregatory properties in vitro.

PubMed

Wollenweber, Frank Arne; Hanecker, Patrizia; Bayer-Karpinska, Anna; Malik, Rainer; Bäzner, Hansjörg; Moreton, Fiona; Muir, Keith W; Müller, Susanna; Giese, Armin; Opherk, Christian; Dichgans, Martin; Haffner, Christof; Duering, Marco

2015-03-01

Mutations in NOTCH3 cause cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common monogenic cause of stroke and vascular dementia. Misfolding and aggregation of NOTCH3 proteins triggered by cysteine-affecting mutations are considered to be the key disease mechanisms. However, the significance of cysteine-sparing mutations is still debated. We studied a family with inherited small vessel disease by standardized medical history, clinical examination, MRI, ultrastructural analysis of skin biopsies, and Sanger sequencing of all NOTCH3 exons. In addition, we performed in vitro characterization of NOTCH3 variants using recombinant protein fragments and a single-particle aggregation assay. We identified a novel cysteine-sparing NOTCH3 mutation (D80G) in 4 family members, which was absent in a healthy sibling. All mutation carriers exhibited a CADASIL typical brain imaging and clinical phenotype, whereas skin biopsy showed inconsistent results. In vitro aggregation behavior of the D80G mutant was similar compared with cysteine-affecting mutations. This was reproduced with cysteine-sparing mutations from previously reported families having a phenotype consistent with CADASIL. Our findings support the view that cysteine-sparing mutations, such as D80G, might cause CADASIL with a phenotype largely indistinguishable from cysteine mutations. The in vitro aggregation analysis of atypical NOTCH3 mutations offers novel insights into pathomechanisms and might represent a tool for estimating their clinical significance. © 2015 American Heart Association, Inc.

Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium-chain triglyceride ketogenic diet.

PubMed

Khabbush, Aziza; Orford, Michael; Tsai, Yi-Chen; Rutherford, Tricia; O'Donnell, Maura; Eaton, Simon; Heales, Simon J R

2017-08-01

The medium-chain triglyceride (MCT) ketogenic diet contains both octanoic (C8) and decanoic (C10) acids. The diet is an effective treatment for pharmacoresistant epilepsy. Although the exact mechanism for its efficacy is not known, it is emerging that C10, but not C8, interacts with targets that can explain antiseizure effects, for example, peroxisome proliferator-activated receptor-γ (eliciting mitochondrial biogenesis and increased antioxidant status) and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. For such effects to occur, significant concentrations of C10 are likely to be required in the brain. To investigate how this might occur, we measured the β-oxidation rate of 13 C-labeled C8 and C10 in neuronal SH-SY5Y cells using isotope-ratio mass spectrometry. The effects of carnitine palmitoyltransferase I (CPT1) inhibition, with the CPT1 inhibitor etomoxir, on C8 and C10 β-oxidation were also investigated. Both fatty acids were catabolized, as judged by 13 CO 2 release. However, C10 was β-oxidized at a significantly lower rate, 20% that of C8. This difference was explained by a clear dependence of C10 on CPT1 activity, which is low in neurons, whereas 66% of C8 β-oxidation was independent of CPT1. In addition, C10 β-oxidation was decreased further in the presence of C8. It is concluded that, because CPT1 is poorly expressed in the brain, C10 is relatively spared from β-oxidation and can accumulate. This is further facilitated by the presence of C8 in the MCT ketogenic diet, which has a sparing effect upon C10 β-oxidation. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

The endocannabinoid hydrolysis inhibitor SA-57: Intrinsic antinociceptive effects, augmented morphine-induced antinociception, and attenuated heroin seeking behavior in mice.

PubMed

Wilkerson, Jenny L; Ghosh, Sudeshna; Mustafa, Mohammed; Abdullah, Rehab A; Niphakis, Micah J; Cabrera, Roberto; Maldonado, Rafael L; Cravatt, Benjamin F; Lichtman, Aron H

2017-03-01

Although opioids are highly efficacious analgesics, their abuse potential and other untoward side effects diminish their therapeutic utility. The addition of non-opioid analgesics offers a promising strategy to reduce required antinociceptive opioid doses that concomitantly reduce opioid-related side effects. Inhibitors of the primary endocannabinoid catabolic enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) show opioid-sparing effects in preclinical models of pain. As simultaneous inhibition of these enzymes elicits enhanced antinociceptive effects compared with single enzyme inhibition, the present study tested whether the dual FAAH-MAGL inhibitor SA-57 [4-[2-(4-chlorophenyl)ethyl]-1-piperidinecarboxylic acid 2-(methylamino)-2-oxoethyl ester] produces morphine-sparing antinociceptive effects, without major side effects associated with either drug class. SA-57 dose-dependently reversed mechanical allodynia in the constriction injury (CCI) of the sciatic nerve model of neuropathic pain and carrageenan inflammatory pain model. As previously reported, SA-57 was considerably more potent in elevating anandamide (AEA) than 2-arachidonyl glycerol (2-AG) in brain. Its anti-allodynic effects required cannabinoid (CB) 1 and CB 2 receptors; however, only CB 2 receptors were necessary for the anti-edematous effects in the carrageenan assay. Although high doses of SA-57 alone were required to produce antinociception, low doses of this compound, which elevated AEA and did not affect 2-AG brain levels, augmented the antinociceptive effects of morphine, but lacked cannabimimetic side effects. Because of the high abuse liability of opioids and implication of the endocannabinoid system in the reinforcing effects of opioids, the final experiment tested whether SA-57 would alter heroin seeking behavior. Strikingly, SA-57 reduced heroin-reinforced nose poke behavior and the progressive ratio break point for heroin. In conclusion, the results of the present study suggest that inhibition of endocannabinoid degradative enzymes represents a promising therapeutic approach to decrease effective doses of opioids needed for clinical pain control, and may also possess therapeutic potential to reduce opioid abuse. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Endocannabinoid Hydrolysis Inhibitor SA-57: Intrinsic Antinociceptive Effects, Augmented Morphine-induced Antinociception, and Attenuated Heroin Seeking Behavior in Mice

PubMed Central

Wilkerson, Jenny L.; Ghosh, Sudeshna; Mustafa, Mohammed; Abdullah, Rehab A.; Niphakis, Micah J.; Cabrera, Roberto; Maldonado, Rafael L.; Cravatt, Benjamin F.; Lichtman, Aron H.

2017-01-01

Although opioids are highly efficacious analgesics, their abuse potential and other untoward side effects diminish their therapeutic utility. The addition of non-opioid analgesics offers a promising strategy to reduce required antinociceptive opioid doses that concomitantly reduce opioid-related side effects. Inhibitors of the primary endocannabinoid catabolic enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) show opioid-sparing effects in preclinical models of pain. As simultaneous inhibition of these enzymes elicits enhanced antinociceptive effects compared with single enzyme inhibition, the present study tested whether the dual FAAH-MAGL inhibitor SA-57 [4-[2-(4-chlorophenyl)ethyl]-1-piperidinecarboxylic acid 2-(methylamino)-2-oxoethyl ester] produces morphine-sparing antinociceptive effects, without major side effects associated with either drug class. SA-57 dose-dependently reversed mechanical allodynia in the constriction injury (CCI) of the sciatic nerve model of neuropathic pain and carrageenan inflammatory pain model. As previously reported, SA-57 was considerably more potent in elevating anandamide (AEA) than 2-arachidonyl glycerol (2-AG) in brain. Its anti-allodynic effects required cannabinoid (CB)1 and CB2 receptors; however, only CB2 receptors were necessary for the anti-edematous effects in the carrageenan assay. Although high doses of SA-57 alone were required to produce antinociception, low doses of this compound, which elevated AEA and did not affect 2-AG brain levels, augmented the antinociceptive effects of morphine, but lacked cannabimimetic side effects. Because of the high abuse liability of opioids and implication of the endocannabinoid system in the reinforcing effects of opioids, the final experiment tested whether SA-57 would alter heroin seeking behavior. Strikingly, SA-57 reduced heroin-reinforced nose poke behavior and the progressive ratio break point for heroin. In conclusion, the results of the present study suggest that inhibition of endocannabinoid degradative enzymes represents a promising therapeutic approach to decrease effective doses of opioids needed for clinical pain control, and may also possess therapeutic potential to reduce opioid abuse. PMID:27890602

Lifelong Brain Health is a Lifelong Challenge: From Evolutionary Principles to Empirical Evidence

PubMed Central

Mattson, Mark P.

2015-01-01

Although the human brain is exceptional in size and information processing capabilities, it is similar to other mammals with regards to the factors that promote its optimal performance. Three such factors are the challenges of physical exercise, food deprivation/fasting, and social/intellectual engagement. Because it evolved, in part, for success in seeking and acquiring food, the brain functions best when the individual is hungry and physically active, as typified by the hungry lion stalking and chasing its prey. Indeed, studies of animal models and human subjects demonstrate robust beneficial effects of regular exercise and intermittent energy restriction/fasting on cognitive function and mood, particularly in the contexts of aging and associated neurodegenerative disorders. Unfortunately, the agricultural revolution and the invention of effort-sparing technologies have resulted in a dramatic reduction or elimination of vigorous exercise and fasting, leaving only intellectual challenges to bolster brain function. In addition to disengaging beneficial adaptive responses in the brain, sedentary overindulgent lifestyles promote obesity, diabetes and cardiovascular disease, all of which may increase the risk of cognitive impairment and Alzheimer’s disease. It is therefore important to embrace the reality of the requirements for exercise, intermittent fasting and critical thinking for optimal brain health throughout life, and to recognize the dire consequences for our aging population of failing to implement such brain-healthy lifestyles. PMID:25576651

Lifelong brain health is a lifelong challenge: from evolutionary principles to empirical evidence.

PubMed

Mattson, Mark P

2015-03-01

Although the human brain is exceptional in size and information processing capabilities, it is similar to other mammals with regard to the factors that promote its optimal performance. Three such factors are the challenges of physical exercise, food deprivation/fasting, and social/intellectual engagement. Because it evolved, in part, for success in seeking and acquiring food, the brain functions best when the individual is hungry and physically active, as typified by the hungry lion stalking and chasing its prey. Indeed, studies of animal models and human subjects demonstrate robust beneficial effects of regular exercise and intermittent energy restriction/fasting on cognitive function and mood, particularly in the contexts of aging and associated neurodegenerative disorders. Unfortunately, the agricultural revolution and the invention of effort-sparing technologies have resulted in a dramatic reduction or elimination of vigorous exercise and fasting, leaving only intellectual challenges to bolster brain function. In addition to disengaging beneficial adaptive responses in the brain, sedentary overindulgent lifestyles promote obesity, diabetes and cardiovascular disease, all of which may increase the risk of cognitive impairment and Alzheimer's disease. It is therefore important to embrace the reality of the requirements for exercise, intermittent fasting and critical thinking for optimal brain health throughout life, and to recognize the dire consequences for our aging population of failing to implement such brain-healthy lifestyles. Published by Elsevier B.V.

Anomalous brain functional connectivity contributing to poor adaptive behavior in Down syndrome.

PubMed

Pujol, Jesus; del Hoyo, Laura; Blanco-Hinojo, Laura; de Sola, Susana; Macià, Dídac; Martínez-Vilavella, Gerard; Amor, Marta; Deus, Joan; Rodríguez, Joan; Farré, Magí; Dierssen, Mara; de la Torre, Rafael

2015-03-01

Research in Down syndrome has substantially progressed in the understanding of the effect of gene overexpression at the molecular level, but there is a paucity of information on the ultimate consequences on overall brain functional organization. We have assessed the brain functional status in Down syndrome using functional connectivity MRI. Resting-state whole-brain connectivity degree maps were generated in 20 Down syndrome individuals and 20 control subjects to identify sites showing anomalous synchrony with other areas. A subsequent region-of-interest mapping served to detail the anomalies and to assess their potential contribution to poor adaptive behavior. Down syndrome individuals showed higher regional connectivity in a ventral brain system involving the amygdala/anterior temporal region and the ventral aspect of both the anterior cingulate and frontal cortices. By contrast, lower functional connectivity was identified in dorsal executive networks involving dorsal prefrontal and anterior cingulate cortices and posterior insula. Both functional connectivity increases and decreases contributed to account for patient scoring on adaptive behavior related to communication skills. The data overall suggest a distinctive functional organization with system-specific anomalies associated with reduced adaptive efficiency. Opposite effects were identified on distinct frontal and anterior temporal structures and relative sparing of posterior brain areas, which is generally consistent with Down syndrome cognitive profile. Relevantly, measurable connectivity changes, as a marker of the brain functional anomaly, could have a role in the development of therapeutic strategies addressed to improve the quality of life in Down syndrome individuals. Copyright © 2014 Elsevier Ltd. All rights reserved.

TH-EF-BRB-01: BEST IN PHYSICS (THERAPY): Dosimetric Comparison of 4π and Clinical IMRT for Cortex-Sparing High-Grade Glioma Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woods, K; Tran, A; Yu, V

Purpose: Thinning of the cerebral cortex has been observed in patients treated with fractionated partial brain radiation therapy and may contribute to cognitive decline following treatment. The extent of this thinning is dose-dependent, and was shown comparable to that of neurodegenerative diseases such as Alzheimer’s disease at one year post-therapy. This study investigates whether 4π radiotherapy can enable better sparing of the cortex and other critical structures when compared to conventional clinical IMRT plans. Methods: Clinical cortex-sparing IMRT plans for 15 high-grade glioma patients were included in this study. 4π radiotherapy plans were created for each patient with 20 intensity-modulatedmore » non-coplanar fields selected with a greedy column-generation optimization. All plans were normalized to deliver 100% of the prescribed dose to 95% of the planning target volume (PTV). The mean and maximum dose to the cerebral cortex and other organs at risk (OARs) were compared for the two plan types, as well as the conformity index (CI), homogeneity index (HI), and 50% dose spillage volume (R50). Results: The 4π plans significantly reduced the mean cortex dose by an average of 16% (range 6% to 27%) compared to the clinical plans. The mean dose to every other OAR compared was also reduced by 15% to 43%, with statistically significant reductions to the brainstem, chiasm, eyes, optic nerves, subcortical whit, and hippocampus. The average maximum doses were also reduced for 10/12 OARs. The R50 was significantly reduced with the 4π plans (>14%) and the homogeneity index was significantly improved. Conclusion: 4π enables significant sparing of the cerebral cortex when treating high-grade gliomas with fractionated partial brain radiation therapy, potentially reducing the risk of harmful dose-dependent cortical thinning. NIH R43CA183390, NIH R01CA188300, Varian Medical Systems.« less

What Aspects of Face Processing Are Impaired in Developmental Prosopagnosia?

ERIC Educational Resources Information Center

Le Grand, Richard; Cooper, Philip A.; Mondloch, Catherine J.; Lewis, Terri L.; Sagiv, Noam; de Gelder, Beatrice; Maurer, Daphne

2006-01-01

Developmental prosopagnosia (DP) is a severe impairment in identifying faces that is present from early in life and that occurs despite no apparent brain damage and intact visual and intellectual function. Here, we investigated what aspects of face processing are impaired/spared in developmental prosopagnosia by examining a relatively large group…

Modulation of brain plasticity in stroke: a novel model for neurorehabilitation.

PubMed

Di Pino, Giovanni; Pellegrino, Giovanni; Assenza, Giovanni; Capone, Fioravante; Ferreri, Florinda; Formica, Domenico; Ranieri, Federico; Tombini, Mario; Ziemann, Ulf; Rothwell, John C; Di Lazzaro, Vincenzo

2014-10-01

Noninvasive brain stimulation (NIBS) techniques can be used to monitor and modulate the excitability of intracortical neuronal circuits. Long periods of cortical stimulation can produce lasting effects on brain function, paving the way for therapeutic applications of NIBS in chronic neurological disease. The potential of NIBS in stroke rehabilitation has been of particular interest, because stroke is the main cause of permanent disability in industrial nations, and treatment outcomes often fail to meet the expectations of patients. Despite promising reports from many clinical trials on NIBS for stroke recovery, the number of studies reporting a null effect remains a concern. One possible explanation is that the interhemispheric competition model--which posits that suppressing the excitability of the hemisphere not affected by stroke will enhance recovery by reducing interhemispheric inhibition of the stroke hemisphere, and forms the rationale for many studies--is oversimplified or even incorrect. Here, we critically review the proposed mechanisms of synaptic and functional reorganization after stroke, and suggest a bimodal balance-recovery model that links interhemispheric balancing and functional recovery to the structural reserve spared by the lesion. The proposed model could enable NIBS to be tailored to the needs of individual patients.

Tangential symbols: using visual symbolization to teach pharmacological principles of drug addiction to international audiences.

PubMed

Giannini, A J

1993-12-01

Visual art was used to teach the biopsychiatric model of addiction to audiences in the Caribbean, Europe and Mideast. Art slides were tangentially linked to slides of pharmacological data. Stylistically dense art was processed by the intuitive right brain while spare notational pharmacological data was processed by the intellectual (rationalistic) left brain. Simultaneous presentation of these data enhanced attention and retention. This teaching paradigm was based on the nonliterate methods developed by Medieval architects and refined by Italian Renaissance philosopher, Marsilio Ficino.

How Does the Air Force Create Effective Accountability for Initial Spares?

DTIC Science & Technology

1990-05-01

effective accountability for initial spares? AUTHOR: Pamela J. Henson, Civilian, USAF The accountability for acquisition cost , schedule, and...in place to allow the Program Manager to effectively manage this cost element. Initial spares have traditionally been managed in Air Force Logistics...at Maxwell Air Force Base. Pamela became the Chief, Cost Analysis Division at HQ Air Force Logistics Command in 1987, where she received the Civilian

The incidence rate and mortality of malignant brain tumors after 10 years of intensive cell phone use in Taiwan.

PubMed

Hsu, Min-Huei; Syed-Abdul, Shabbir; Scholl, Jeremiah; Jian, Wen-Shan; Lee, Peisan; Iqbal, Usman; Li, Yu-Chuan

2013-11-01

The issue of whether cell phone usage can contribute toward the development of brain tumors has recently been reignited with the International Agency for Research on Cancer classifying radiofrequency electromagnetic fields as 'possibly' carcinogenic to humans in a WHO report. To our knowledge, this is the largest study reporting on the incidence and mortality of malignant brain tumors after long-term use of the cell phone by more than 23 million users. A population-based study was carried out the numbers of cell phone users were collected from the official statistics provided by the National Communication Commission. According to National Cancer Registry, there were 4 incidences and 4 deaths due to malignant neoplasms in Taiwan during the period 2000-2009. The 10 years of observational data show that the intensive user rate of cell phones has had no significant effect on the incidence rate or on the mortality of malignant brain tumors in Taiwan. In conclusion, we do not detect any correlation between the morbidity/mortality of malignant brain tumors and cell phone use in Taiwan. We thus urge international agencies to publish only confirmatory reports with more applicable conclusions in public. This will help spare the public from unnecessary worries.

[The neurotrophic effect of endogenous NT-3 from adult cat spared dorsal root ganglion on ganglionic neurons].

PubMed

Zhang, Wei; Zhou, Xue; Wang, Ting-hua; Wang, Te-wei; Liu, Su; Chen, Si-xiu; Ou, Ke-qun

2004-01-01

To investigate the neurotrophic effect of endogenous NT-3 from adult cat dorsal root ganglion (DRG) on ganglionic neurons. Rhizotomy of bilateral L1, L3, L5 and L7 dorsal roots of cats was performed, leaving L2, L4 and L6 DRG as spared DRGs. The separate neurons of normal (control) DRG, spared DRG and anti-NT-3 antibody blocking DRG were cultured in vitro respectively. The number of survival neurons and the length of neurites were measured and used for comparison in the control, spared DRG, and block groups. There were survival neurons and cell clusters in every group. The number of survival neurons and cell clusters of spared DRG group were much larger than those of the control and block groups. The neurite length of neurons, the neurite number and the length of cell clusters of spared DRG group were much greater than those of control and block groups. Endogenous NT-3 from spared DRG may act on ganglionic neurons to maintain survival of neuron and stimulate growth of neurite.

Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions

PubMed Central

Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

2017-01-01

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping. PMID:28700619

Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions.

PubMed

Gonen, Tal; Gazit, Tomer; Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

2017-01-01

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping.

Impaired consciousness in patients with absence seizures investigated by functional MRI, EEG, and behavioural measures: a cross-sectional study.

PubMed

Guo, Jennifer N; Kim, Robert; Chen, Yu; Negishi, Michiro; Jhun, Stephen; Weiss, Sarah; Ryu, Jun Hwan; Bai, Xiaoxiao; Xiao, Wendy; Feeney, Erin; Rodriguez-Fernandez, Jorge; Mistry, Hetal; Crunelli, Vincenzo; Crowley, Michael J; Mayes, Linda C; Constable, R Todd; Blumenfeld, Hal

2016-12-01

The neural underpinnings of impaired consciousness and of the variable severity of behavioural deficits from one absence seizure to the next are not well understood. We aimed to measure functional MRI (fMRI) and electroencephalography (EEG) changes in absence seizures with impaired task performance compared with seizures in which performance was spared. In this cross-sectional study done at the Yale School of Medicine, CT, USA, we recruited patients from 59 paediatric neurology practices in the USA. We did simultaneous EEG, fMRI, and behavioural testing in patients aged 6-19 years with childhood or juvenile absence epilepsy, and with an EEG with typical 3-4 Hz bilateral spike-wave discharges and normal background. The main outcomes were fMRI and EEG amplitudes in seizures with impaired versus spared behavioural responses analysed by t test. We also examined the timing of fMRI and EEG changes in seizures with impaired behavioural responses compared with seizures with spared responses. 93 patients were enrolled between Jan 1, 2005, and Sept 1, 2013; we recorded 1032 seizures in 39 patients. fMRI changes during seizures occurred sequentially in three functional brain networks. In the default mode network, fMRI amplitude was 0·57% (SD 0·26) for seizures with impaired and 0·40% (0·16) for seizures with spared behavioural responses (mean difference 0·17%, 95% CI 0·11-0·23; p<0·0001). In the task-positive network, fMRI amplitude was 0·53% (SD 0·29) for seizures with impaired and 0·39% (0·15) for seizures with spared behavioral responses (mean difference 0·14%, 95% CI 0·08-0·21; p<0·0001). In the sensorimotor-thalamic network, fMRI amplitude was 0·41% (0·25) for seizures with impaired and 0·34% (0·14) for seizures with spared behavioural responses (mean difference 0·07%, 95% CI 0·01-0·13; p=0·02). Mean fractional EEG power in the frontal leads was 50·4 (SD 15·2) for seizures with impaired and 24·8 (6·5) for seizures with spared behavioural responses (mean difference 25·6, 95% CI 21·0-30·3); middle leads 35·4 (6·5) for seizures with impaired, 13·3 (3·4) for seizures with spared behavioural responses (mean difference 22·1, 95% CI 20·0-24·1); posterior leads 41·6 (5·3) for seizures with impaired, 24·6 (8·6) for seizures with spared behavioural responses (mean difference 17·0, 95% CI 14·4-19·7); p<0·0001 for all comparisons. Mean seizure duration was longer for seizures with impaired behaviour at 7·9 s (SD 6·6), compared with 3·8 s (3·0) for seizures with spared behaviour (mean difference 4·1 s, 95% CI 3·0-5·3; p<0·0001). However, larger amplitude fMRI and EEG signals occurred at the outset or even preceding seizures with behavioural impairment. Impaired consciousness in absence seizures is related to the intensity of physiological changes in established networks affecting widespread regions of the brain. Increased EEG and fMRI amplitude occurs at the onset of seizures associated with behavioural impairment. These finding suggest that a vulnerable state might exist at the initiation of some absence seizures leading them to have more severe physiological changes and altered consciousness than other absence seizures. National Institutes of Health, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Science, the Loughridge Williams Foundation, and the Betsy and Jonathan Blattmachr Family. Copyright © 2016 Elsevier Ltd. All rights reserved.

Origins of the brain networks for advanced mathematics in expert mathematicians

PubMed Central

Amalric, Marie; Dehaene, Stanislas

2016-01-01

The origins of human abilities for mathematics are debated: Some theories suggest that they are founded upon evolutionarily ancient brain circuits for number and space and others that they are grounded in language competence. To evaluate what brain systems underlie higher mathematics, we scanned professional mathematicians and mathematically naive subjects of equal academic standing as they evaluated the truth of advanced mathematical and nonmathematical statements. In professional mathematicians only, mathematical statements, whether in algebra, analysis, topology or geometry, activated a reproducible set of bilateral frontal, Intraparietal, and ventrolateral temporal regions. Crucially, these activations spared areas related to language and to general-knowledge semantics. Rather, mathematical judgments were related to an amplification of brain activity at sites that are activated by numbers and formulas in nonmathematicians, with a corresponding reduction in nearby face responses. The evidence suggests that high-level mathematical expertise and basic number sense share common roots in a nonlinguistic brain circuit. PMID:27071124

Origins of the brain networks for advanced mathematics in expert mathematicians.

PubMed

Amalric, Marie; Dehaene, Stanislas

2016-05-03

The origins of human abilities for mathematics are debated: Some theories suggest that they are founded upon evolutionarily ancient brain circuits for number and space and others that they are grounded in language competence. To evaluate what brain systems underlie higher mathematics, we scanned professional mathematicians and mathematically naive subjects of equal academic standing as they evaluated the truth of advanced mathematical and nonmathematical statements. In professional mathematicians only, mathematical statements, whether in algebra, analysis, topology or geometry, activated a reproducible set of bilateral frontal, Intraparietal, and ventrolateral temporal regions. Crucially, these activations spared areas related to language and to general-knowledge semantics. Rather, mathematical judgments were related to an amplification of brain activity at sites that are activated by numbers and formulas in nonmathematicians, with a corresponding reduction in nearby face responses. The evidence suggests that high-level mathematical expertise and basic number sense share common roots in a nonlinguistic brain circuit.

Patterns of Invasive Growth in Malignant Gliomas-The Hippocampus Emerges as an Invasion-Spared Brain Region.

PubMed

Mughal, Awais A; Zhang, Lili; Fayzullin, Artem; Server, Andres; Li, Yuping; Wu, Yingxi; Glass, Rainer; Meling, Torstein; Langmoen, Iver A; Leergaard, Trygve B; Vik-Mo, Einar O

2018-05-21

Widespread infiltration of tumor cells into surrounding brain parenchyma is a hallmark of malignant gliomas, but little data exist on the overall invasion pattern of tumor cells throughout the brain. We have studied the invasive phenotype of malignant gliomas in two invasive mouse models and patients. Tumor invasion patterns were characterized in a patient-derived xenograft mouse model using brain-wide histological analysis and magnetic resonance (MR) imaging. Findings were histologically validated in a cdkn2a-/- PDGF-β lentivirus-induced mouse glioblastoma model. Clinical verification of the results was obtained by analysis of MR images of malignant gliomas. Histological analysis using human-specific cellular markers revealed invasive tumors with a non-radial invasion pattern. Tumors cells accumulated in structures located far from the transplant site, such as the optic white matter and pons, whereas certain adjacent regions were spared. As such, the hippocampus was remarkably free of infiltrating tumor cells despite the extensive invasion of surrounding regions. Similarly, MR images of xenografted mouse brains displayed tumors with bihemispheric pathology, while the hippocampi appeared relatively normal. In patients, most malignant temporal lobe gliomas were located lateral to the collateral sulcus. Despite widespread pathological fluid-attenuated inversion recovery signal in the temporal lobe, 74% of the "lateral tumors" did not show signs of involvement of the amygdalo-hippocampal complex. Our data provide clear evidence for a compartmental pattern of invasive growth in malignant gliomas. The observed invasion patterns suggest the presence of preferred migratory paths, as well as intra-parenchymal boundaries that may be difficult for glioma cells to traverse supporting the notion of compartmental growth. In both mice and human patients, the hippocampus appears to be a brain region that is less prone to tumor invasion. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Developmental changes in metabolism and transport properties of capillaries isolated from rat brain.

PubMed

Betz, A L; Goldstein, G W

1981-03-01

1. Capillaries were isolated from the brains of 1- to 45-day-old rats in order to study the development of metabolic and transport aspects of the blood-brain barrier. 2. The hydroxyproline content of capillary hydrolysates increased nearly threefold between 5 and 45 days of age. This finding is consistent with histological studies showing thickening of capillary basement membrane during development. 3. The activities of L-DOPA decarboxylase and monoamine oxidase were greatest in capillaries from 10-day-old rat brain. Thus, the metabolic blood-brain barrier for amine precursors is present during early development. 4. Capillaries from all ages were able to metabolize glucose, beta-hydroxybutyrate and palmitate. The rate of glucose oxidation more than doubled between 21 and 30 days of age but subsequently decreased. In contrast, beta-hydroxybutyrate and palmitate oxidation increased throughout development. These data suggest a sparing effect by alternate fuels on glucose metabolism. 5. Capillary glucose uptake was similar at 10 and 30 days of age and activity of the ouabain-sensitive K+ pump (measured using 86Rb+) was relatively constant at all ages. In contrast, Na+-dependent neutral amino acid transport was not present until after 21 days of age. Since this transport system may be responsible for the active efflux of neutral amino acids from brain to blood, it is likely that this process does not occur at the immature blood-brain barrier. 6. We conclude that various aspects of brain capillary functions show distinct developmental patterns which may be related to changes in blood-brain barrier permeability during development.

A brain leptin-renin angiotensin system interaction in the regulation of sympathetic nerve activity

PubMed Central

Hilzendeger, Aline M.; Morgan, Donald A.; Brooks, Leonard; Dellsperger, David; Liu, Xuebo; Grobe, Justin L.; Rahmouni, Kamal; Sigmund, Curt D.

2012-01-01

The sympathetic nervous system, leptin, and renin-angiotensin system (RAS) have been implicated in obesity-associated hypertension. There is increasing evidence for the presence of both leptin and angiotensin II receptors in several key brain cardiovascular and metabolic control regions. We tested the hypothesis that the brain RAS plays a facilitatory role in the sympathetic nerve responses to leptin. In rats, intracerebroventricular (ICV) administration of losartan (5 μg) selectively inhibited increases in renal and brown adipose tissue (BAT) sympathetic nerve activity (SNA) produced by leptin (10 μg ICV) but did not reduce the SNA responses to corticotrophin-releasing factor (CRF) or the melanocortin receptor agonist MTII. In mice with deletion of angiotensin II type-1a receptors (AT1aR−/−), increases in renal and BAT SNA induced by leptin (2 μg ICV) were impaired whereas SNA responses to MTII were preserved. Decreases in food intake and body weight with ICV leptin did not differ in AT1aR−/− vs. AT1aR+/+ mice. ICV leptin in rats increased AT1aR and angiotensin-converting enzyme (ACE) mRNA in the subfornical organ and AT1aR mRNA in the arcuate nucleus, suggesting leptin-induced upregulation of the brain RAS in specific brain regions. To evaluate the role of de novo production of brain angiotensin II in SNA responses to leptin, we treated rats with captopril (12.5 μg ICV). Captopril attenuated leptin effects on renal and BAT SNA. In conclusion, these studies provide evidence that the brain RAS selectively facilitates renal and BAT sympathetic nerve responses to leptin while sparing effects on food intake. PMID:22610169

A brain leptin-renin angiotensin system interaction in the regulation of sympathetic nerve activity.

PubMed

Hilzendeger, Aline M; Morgan, Donald A; Brooks, Leonard; Dellsperger, David; Liu, Xuebo; Grobe, Justin L; Rahmouni, Kamal; Sigmund, Curt D; Mark, Allyn L

2012-07-15

The sympathetic nervous system, leptin, and renin-angiotensin system (RAS) have been implicated in obesity-associated hypertension. There is increasing evidence for the presence of both leptin and angiotensin II receptors in several key brain cardiovascular and metabolic control regions. We tested the hypothesis that the brain RAS plays a facilitatory role in the sympathetic nerve responses to leptin. In rats, intracerebroventricular (ICV) administration of losartan (5 μg) selectively inhibited increases in renal and brown adipose tissue (BAT) sympathetic nerve activity (SNA) produced by leptin (10 μg ICV) but did not reduce the SNA responses to corticotrophin-releasing factor (CRF) or the melanocortin receptor agonist MTII. In mice with deletion of angiotensin II type-1a receptors (AT(1a)R(-/-)), increases in renal and BAT SNA induced by leptin (2 μg ICV) were impaired whereas SNA responses to MTII were preserved. Decreases in food intake and body weight with ICV leptin did not differ in AT(1a)R(-/-) vs. AT(1a)R(+/+) mice. ICV leptin in rats increased AT(1a)R and angiotensin-converting enzyme (ACE) mRNA in the subfornical organ and AT(1a)R mRNA in the arcuate nucleus, suggesting leptin-induced upregulation of the brain RAS in specific brain regions. To evaluate the role of de novo production of brain angiotensin II in SNA responses to leptin, we treated rats with captopril (12.5 μg ICV). Captopril attenuated leptin effects on renal and BAT SNA. In conclusion, these studies provide evidence that the brain RAS selectively facilitates renal and BAT sympathetic nerve responses to leptin while sparing effects on food intake.

Effects of Inter-Alpha Inhibitor Proteins on Neonatal Brain Injury: Age, Task and Treatment Dependent Neurobehavioral Outcomes

PubMed Central

Threlkeld, Steven W.; Gaudet, Cynthia M.; La Rue, Molly E.; Dugas, Ethan; Hill, Courtney A.; Lim, Yow-Pin; Stonestreet, Barbara S.

2014-01-01

Hypoxic-ischemic (HI) brain injury is frequently associated with premature and/or full term birth related complications. HI injury often results in learning and processing deficits that reflect widespread damage to an extensive range of cortical and sub-cortical brain structures. Further, inflammation has been implicated in the long-term progression and severity of HI injury. Recently, Inter-alpha Inhibitor Proteins (IAIPs) have been shown to attenuate inflammation in models of systemic infection. Importantly, preclinical studies of neonatal HI injury and neuroprotection often focus on single time windows of assessment or single behavioral domains. This approach limits translational validity, given evidence for a diverse spectrum of neurobehavioral deficits that may change across developmental windows following neonatal brain injury. Therefore, the aims of this research were to assess the effects of human IAIPs on early neocortical cell death (72 hours post insult), adult regional brain volume measurements (cerebral cortex, hippocampus, striatum, corpus callosum) and long-term behavioral outcomes in juvenile (P38-50) and adult (P80+) periods across two independent learning domains (spatial and non-spatial learning), after postnatal day 7 HI injury in rats. Here, for the first time, we show that IAIPs reduce acute neocortical neuronal cell death and improve brain weight outcome 72 hours following HI injury in the neonatal rat. Further, these longitudinal studies are the first to show age, task and treatment dependent improvements in behavioral outcome for both spatial and non-spatial learning following systemic administration of IAIPs in neonatal HI injured rats. Finally, results also show sparing of brain regions critical for spatial and non-spatial learning in adult animals treated with IAIPs at the time of injury onset. These data support the proposal that Inter-alpha Inhibitor Proteins may serve as novel therapeutics for brain injury associated with premature birth and/or neonatal brain injury and highlight the importance of assessing multiple ages, brain regions and behavioral domains when investigating experimental treatment efficacy. PMID:25084519

Comparison of proton therapy techniques for treatment of the whole brain as a component of craniospinal radiation.

PubMed

Dinh, Jeffrey; Stoker, Joshua; Georges, Rola H; Sahoo, Narayan; Zhu, X Ronald; Rath, Smruti; Mahajan, Anita; Grosshans, David R

2013-12-17

For treatment of the entire cranium using passive scattering proton therapy (PSPT) compensators are often employed in order to reduce lens and cochlear exposure. We sought to assess the advantages and consequences of utilizing compensators for the treatment of the whole brain as a component of craniospinal radiation (CSI) with PSPT. Moreover, we evaluated the potential benefits of spot scanning beam delivery in comparison to PSPT. Planning computed tomography scans for 50 consecutive CSI patients were utilized to generate passive scattering proton therapy treatment plans with and without Lucite compensators (PSW and PSWO respectively). A subset of 10 patients was randomly chosen to generate scanning beam treatment plans for comparison. All plans were generated using an Eclipse treatment planning system and were prescribed to a dose of 36 Gy(RBE), delivered in 20 fractions, to the whole brain PTV. Plans were normalized to ensure equal whole brain target coverage. Dosimetric data was compiled and statistical analyses performed using a two-tailed Student's t-test with Bonferroni corrections to account for multiple comparisons. Whole brain target coverage was comparable between all methods. However, cribriform plate coverage was superior in PSWO plans in comparison to PSW (V95%; 92.9 ± 14 vs. 97.4 ± 5, p < 0.05). As predicted, PSWO plans had significantly higher lens exposure in comparison to PSW plans (max lens dose Gy(RBE): left; 24.8 ± 0.8 vs. 22.2 ± 0.7, p < 0.05, right; 25.2 ± 0.8 vs. 22.8 ± 0.7, p < 0.05). However, PSW plans demonstrated no significant cochlear sparing vs. PSWO (mean cochlea dose Gy(RBE): 36.4 ± 0.2 vs. 36.7 ± 0.1, p = NS). Moreover, dose homogeneity was inferior in PSW plans in comparison to PSWO plans as reflected by significant alterations in both whole brain and brainstem homogeneity index (HI) and inhomogeneity coefficient (IC). In comparison to both PSPT techniques, multi-field optimized intensity modulated (MFO-IMPT) spot scanning treatment plans displayed superior sparing of both lens and cochlea (max lens: 12.5 ± 0.6 and 12.9 ± 0.7 right and left respectively; mean cochlea 28.6 ± 0.5 and 27.4 ± 0.2), although heterogeneity within target volumes was comparable to PSW plans. For PSPT treatments, the addition of a compensator imparts little clinical advantage. In contrast, the incorporation of spot scanning technology as a component of CSI treatments, offers additional normal tissue sparing which is likely of clinical significance.

[Neuropsychopharmacology of delta-9-tetrahydrocannabinol].

PubMed

Costentin, J

2008-08-01

Today, the main route of introduction of tetrahydrocannabinol (THC), the main active substance of cannabis, into the human body is via the lungs, from smokes produced by combustion of a haschich-tobacco mixture. The use of a water pipe (nargileh-like) intensifies its fast supply to the body. THC reaches the brain easily where it stimulates CB1 receptors; their ubiquity underlies a wide variety of effects. THC disappears from extracellular spaces by dissolving in lipid rich membranes, and not by excretion from the body. This is followed by a slow release, leading to long lasting effects originating from brain areas containing a large proportion of spare receptors ("reserve receptors"). Far from mimicking the effects of endocannabinoids, THC caricatures and disturbs them. It induces both psychical and physical dependencies, but the perception of withdrawal is weak on account of its very slow elimination. THC disturbs cognition. Acutely, it develops anxiolytic- and antidepressant-like effects, which causes a lot of users to abuse THC, thus leading to a tolerance (desensitization of CB1 receptors) making anxiety and depression to reappear more intensely than originally. THC has close relationships with schizophrenia. It incites to tobacco, alcohol and heroine abuses.

Energy Sparing Orexigenic Inflammation of Obesity.

PubMed

Lee, Aileen; Dixit, Vishwa Deep

2017-07-05

The neuro-immune interactions that integrate host metabolism in health and disease are unclear. A new study by Valdearcos et al. (2017) describes how sensing of high-fat diet by microglia, brain's resident innate immune cells, recruits additional bone-marrow-derived myeloid cells into the hypothalamus to produce inflammation and cause weight gain. Copyright © 2017 Elsevier Inc. All rights reserved.

SU-E-T-589: Optimization of Patient Head Angle Position to Spare Hippocampus During the Brain Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheon, G; Kang, Y; Kang, S

Purpose: Hippocampus is one of the important organs which controls emotions, behaviors, movements the memorizing and learning ability. In the conventional head & neck therapy position, it is difficult to perform the hippocampal-sparing brain radiation therapy. The purpose of this study is to investigate optimal head angle which can save the hippocampal-sparing and organ at risk (OAR) in conformal radiation therapy (CRT), Intensity modulation radiation therapy (IMRT) and helical tomotherapy (HT). Methods: Three types of radiation treatment plans, CRT, IMRT and Tomotherapy plans, were performed for 10 brain tumor patients. The image fusion between CT and MRI data were usedmore » in the contour due to the limited delineation of the target and OAR in the CT scan. The optimal condition plan was determined by comparing the dosimetric performance of the each plan with the use of various parameters which include three different techniques (CRT, IMRT, HT) and 4 angle (0, 15, 30, 40 degree). The each treatment plans of three different techniques were compared with the following parameters: conformity index (CI), homogeneity index (HI), target coverage, dose in the OARs, monitor units (MU), beam on time and the normal tissue complication probability (NTCP). Results: HI, CI and target coverage was most excellent in head angle 30 degree among all angle. When compared by modality, target coverage and CI showed good results in IMRT and TOMO than compared to the CRT. HI at the head angle 0 degrees is 1.137±0.17 (CRT), 1.085±0.09 (IMRT) and 1.077±0.06 (HT). HI at the head angle 30 degrees is 1.056±0.08 (CRT), 1.020±0.05 (IMRT) and 1.022±0.07 (HT). Conclusion: The results of our study show that when head angle tilted at 30 degree, target coverage, HI, CI were improved, and the dose delivered to OAR was reduced compared with conventional supine position in brain radiation therapy. This work was supported by the Radiation Technology R&D program (No. 2013M2A2A7043498) and the Mid-career Researcher Program (2014R1A2A1A10050270) through the National Research Foundation of Korea funded by the Ministry of Science, ICT&Future Planning.« less

Comparative survival study of glial cells and cells composing walls of blood vessels in crustacean ventral nerve cord after photodynamic treatment

NASA Astrophysics Data System (ADS)

Kolosov, Mikhail S.; Shubina, Elena

2015-03-01

Photodynamic therapy is a prospective treatment modality of brain cancers. It is of importance to have information about relative survival rate of different cell types in nerve tissue during photodynamic treatment. Particularly, for development of sparing strategy of the photodynamic therapy of brain tumors, which pursuits both total elimination of malignant cells, which are usually of glial origin, and, at the same time, preservation of normal blood circulation as well as normal glial cells in the brain. The aim of this work was to carry out comparative survival study of glial cells and cells composing walls of blood vessels after photodynamic treatment, using simple model object - ventral nerve cord of crustacean.

Evaluation of Larynx-Sparing Techniques With IMRT When Treating the Head and Neck

DOE Office of Scientific and Technical Information (OSTI.GOV)

Webster, Gareth J.; Rowbottom, Carl G.; Ho, Kean F.

2008-10-01

Purpose: Concern exists that widespread implementation of whole-field intensity-modulated radiotherapy (IMRT) for the treatment of head-and-neck cancer has resulted in increased levels of dysphagia relative to those seen with conventional planning. Other investigators have suggested an alternative junctioned-IMRT (J-IMRT) method, which matches an IMRT plan to a centrally blocked neck field to restrict the laryngeal dose and reduce dysphagia. The effect on target coverage and sparing of organs at risk, including laryngeal sparing, in the optimization was evaluated and compared with that achieved using a J-IMRT technique. Methods and Materials: A total of 13 oropharyngeal cancer whole-field IMRT plans weremore » planned with and without including laryngeal sparing in the optimization. A comparison of the target coverage and sparing of organs at risk was made using the resulting dose-volume histograms and dose distribution. The nine plans with disease located superior to the level of the larynx were replanned using a series of J-IMRT techniques to compare the two laryngeal-sparing techniques. Results: An average mean larynx dose of 29.1 Gy was achieved if disease did not extend to the level of the larynx, with 38.8 Gy for disease extending inferiorly and close to the larynx (reduced from 46.2 and 47.7 Gy, respectively, without laryngeal sparing). Additional laryngeal sparing could be achieved with J-IMRT (mean dose 24.4 Gy), although often at the expense of significantly reduced coverage of the target volume and with no improvement to other areas of the IMRT plan. Conclusion: The benefits of J-IMRT can be achieved with whole-field IMRT if laryngeal sparing is incorporated into the class solution. Inclusion of laryngeal sparing had no effect on other parameters in the plan.« less

An acidosis-sparing ketogenic (ASK) diet to improve efficacy and reduce adverse effects in the treatment of refractory epilepsy.

PubMed

Yuen, Alan W C; Walcutt, Isabel A; Sander, Josemir W

2017-09-01

Diets that increase production of ketone bodies to provide alternative fuel for the brain are evolving from the classic ketogenic diet for epilepsy devised nearly a century ago. The classic ketogenic diet and its more recent variants all appear to have similar efficacy with approximately 50% of users showing a greater than 50% seizure reduction. They all require significant medical and dietetic support, and there are tolerability issues. A review suggests that low-grade chronic metabolic acidosis associated with ketosis is likely to be an important contributor to the short term and long term adverse effects of ketogenic diets. Recent studies, particularly with the characterization of the acid sensing ion channels, suggest that chronic metabolic acidosis may increase the propensity for seizures. It is also known that low-grade chronic metabolic acidosis has a broad range of negative health effects and an increased risk of early mortality in the general population. The modified ketogenic dietary treatment we propose is formulated to limit acidosis by measures that include monitoring protein intake and maximizing consumption of alkaline mineral-rich, low carbohydrate green vegetables. We hypothesize that this acidosis-sparing ketogenic diet is expected to be associated with less adverse effects and improved efficacy. A case history of life-long intractable epilepsy shows this diet to be a successful long-term strategy but, clearly, clinical studies are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Cerebral Blood Flow and Glucose Metabolism in Appetite-Related Brain Regions in Type 1 Diabetic Patients After Treatment With Insulin Detemir and NPH Insulin

PubMed Central

van Golen, Larissa W.; IJzerman, Richard G.; Huisman, Marc C.; Hensbergen, Jolanda F.; Hoogma, Roel P.; Drent, Madeleine L.; Lammertsma, Adriaan A.; Diamant, Michaela

2013-01-01

OBJECTIVE To test the hypothesis that insulin detemir, which is associated with less weight gain than other basal insulin formulations, exerts its weight-modulating effects by acting on brain regions involved in appetite regulation, as represented by altered cerebral blood flow (CBF) or cerebral glucose metabolism (CMRglu). RESEARCH DESIGN AND METHODS Twenty-eight male type 1 diabetic patients (age 36.9 ± 9.7 years, BMI 24.9 ± 2.7 kg/m2, A1C 7.5 ± 0.6%) successfully completed a randomized crossover study, consisting of two periods of 12-week treatment with either insulin detemir or NPH insulin, both in combination with prandial insulin aspart. After each treatment period, patients underwent positron emission tomography scans to measure regional CBF and CMRglu. RESULTS After 12 weeks, A1C, daily insulin doses, fasting insulin, and blood glucose levels were similar between treatments. Insulin detemir resulted in body weight loss, whereas NPH insulin induced weight gain (between-treatment difference 1.3 kg; P = 0.02). After treatment with insulin detemir relative to NPH insulin, CBF was higher in brain regions involved in appetite regulation, whereas no significant difference in CMRglu was observed. CONCLUSIONS Treatment with insulin detemir versus NPH insulin resulted in weight loss, paralleled by increased CBF in appetite-related brain regions in the resting state, in men with well-controlled type 1 diabetes. These findings lend support to the hypothesis that a differential effect on the brain may contribute to the consistently observed weight-sparing effect of insulin detemir. PMID:24130356

Longitudinal Structural and Functional Brain Network Alterations in a Mouse Model of Neuropathic Pain.

PubMed

Bilbao, Ainhoa; Falfán-Melgoza, Claudia; Leixner, Sarah; Becker, Robert; Singaravelu, Sathish Kumar; Sack, Markus; Sartorius, Alexander; Spanagel, Rainer; Weber-Fahr, Wolfgang

2018-04-22

Neuropathic pain affects multiple brain functions, including motivational processing. However, little is known about the structural and functional brain changes involved in the transition from an acute to a chronic pain state. Here we combined behavioral phenotyping of pain thresholds with multimodal neuroimaging to longitudinally monitor changes in brain metabolism, structure and connectivity using the spared nerve injury (SNI) mouse model of chronic neuropathic pain. We investigated stimulus-evoked pain responses prior to SNI surgery, and one and twelve weeks following surgery. A progressive development and potentiation of stimulus-evoked pain responses (cold and mechanical allodynia) were detected during the course of pain chronification. Voxel-based morphometry demonstrated striking decreases in volume following pain induction in all brain sites assessed - an effect that reversed over time. Similarly, all global and local network changes that occurred following pain induction disappeared over time, with two notable exceptions: the nucleus accumbens, which played a more dominant role in the global network in a chronic pain state and the prefrontal cortex and hippocampus, which showed lower connectivity. These changes in connectivity were accompanied by enhanced glutamate levels in the hippocampus, but not in the prefrontal cortex. We suggest that hippocampal hyperexcitability may contribute to alterations in synaptic plasticity within the nucleus accumbens, and to pain chronification. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Influence of different treatment techniques on radiation dose to the LAD coronary artery

PubMed Central

Nieder, Carsten; Schill, Sabine; Kneschaurek, Peter; Molls, Michael

2007-01-01

Background The purpose of this proof-of-principle study was to test the ability of an intensity-modulated radiotherapy (IMRT) technique to reduce the radiation dose to the heart plus the left ventricle and a coronary artery. Radiation-induced heart disease might be a serious complication in long-term cancer survivors. Methods Planning CT scans from 6 female patients were available. They were part of a previous study of mediastinal IMRT for target volumes used in lymphoma treatment that included 8 patients and represent all cases where the left anterior descending coronary artery (LAD) could be contoured. We compared 6 MV AP/PA opposed fields to a 3D conformal 4-field technique and an optimised 7-field step-and-shoot IMRT technique and evaluated DVH's for several structures. The planning system was BrainSCAN 5.21 (BrainLAB, Heimstetten, Germany). Results IMRT maintained target volume coverage but resulted in better dose reduction to the heart, left ventricle and LAD than the other techniques. Selective dose reduction could be accomplished, although not to the degree initially attempted. The median LAD dose was approximately 50% lower with IMRT. In 5 out of 6 patients, IMRT was the best technique with regard to heart sparing. Conclusion IMRT techniques are able to reduce the radiation dose to the heart. In addition to dose reduction to whole heart, individualised dose distributions can be created, which spare, e.g., one ventricle plus one of the coronary arteries. Certain patients with well-defined vessel pathology might profit from an approach of general heart sparing with further selective dose reduction, accounting for the individual aspects of pre-existing damage. PMID:17547777

Foveal-Sparing Scotomas in Advanced Dry Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Sunness, Janet S.; Rubin, Gary S.; Zuckerbrod, Abraham; Applegate, Carol A.

2008-01-01

Foveal-sparing scotomas are common in advanced dry macular degeneration (geographic atrophy). Foveal preservation may be present for a number of years. Despite good visual acuity, these patients have reduced reading rates. Magnification may not be effective if the text becomes too large to "fit" within the central spared area. (Contains 2 tables…

S. aureus-dependent microglial activation is selectively attenuated by the cyclopentenone prostaglandin 15-deoxy-Delta12,14- prostaglandin J2 (15d-PGJ2).

PubMed

Kielian, Tammy; McMahon, Meredith; Bearden, Edward D; Baldwin, Aaron C; Drew, Paul D; Esen, Nilufer

2004-09-01

Microglial activation is a hallmark of brain abscess. The continual release of proinflammatory mediators by microglia following bacterial challenge may contribute, in part, to the destruction of surrounding normal tissue characteristic of brain abscess. Therefore, attenuating chronic microglial activation during the course of CNS bacterial infections may have therapeutic benefits. The purpose of this study was to evaluate the ability of the natural peroxisome proliferator-activated receptor (PPAR)-gamma agonist 15-deoxy-Delta12,14- prostaglandin J2 (15d-PGJ2) to modulate microglial activation in response to Staphylococcus aureus, one of the main etiologic agents of brain abscess in humans. 15d-PGJ2 was a potent inhibitor of proinflammatory cytokine (IL-1beta, TNF-alpha, IL-12 p40) and CC chemokine (MIP-1beta, MCP-1) production in primary microglia, but had no effect upon the expression of select CXC chemokines (MIP-2, KC). 15d-PGJ2 also selectively inhibited the S. aureus-dependent increase in microglial TLR2, CD14, MHC class II, and CD40 expression, whereas it had no effect on the co-stimulatory molecules CD80 and CD86. Microarray analysis revealed additional inflammatory mediators modulated by 15d-PGJ2 in primary microglia following S. aureus exposure, the majority of which were chemokines. These results suggest that suppressing microglial activation through the use of 15d-PGJ2 may lead to the sparing of damage to normal brain parenchyma that often results from brain abscess. Copyright 2004 International Society for Neurochemistry

Increased CD127+ and decreased CD57+ T cell expression levels in HIV-infected patients on NRTI-sparing regimens.

PubMed

Gonzalez-Serna, A; Ferrando-Martinez, S; Tarancon-Diez, L; De Pablo-Bernal, R S; Dominguez-Molina, B; Jiménez, J L; Muñoz-Fernández, M Á; Leal, M; Ruiz-Mateos, E

2017-12-20

NRTIs-sparing regimens exert favourable profiles on T-cell homeostasis associated parameters. Our aim was to analyze the effect of NRTIs sparing regimen (NRTI-sparing-cART) vs NRTIs-containing regimen (NRTI-cART), on T-cell homeostasis associated parameters in naive HIV-infected patients. Biomarkers of cell survival (CD127) and replicative senescence (CD57), were measured by multiparametric flow cytometry for T-cell phenotyping on peripheral blood mononuclear cells (PBMCs) samples just before (baseline) and after 48 weeks of undetectable viral load in patients on NRTI-sparing-cART (N = 13) and NRTI-cART (N = 14). After 48 weeks a subgroup of patients (n = 5) on NRTI-cART switched to NRTI-sparing-cART for another additional 48 weeks. In vitro assays were performed on PBMCs from HIV-uninfected healthy donors exposed or not to HIV. To analyze the independent factors associated with type of cART bivariate and stepwise multivariate analysis were performed after adjusting for basal CD4+, CD8+ and nadir CD4+ T-cell counts. After 48 weeks of a NRTI-sparing-cART vs NRTI-cART patients have higher effector memory (EM) CD4+ CD127+ T-cell levels, lower EM CD4+ CD57+ T-cell levels, higher CD8+ CD127+ T-cell levels, lower CD8+ CD57+ T-cell levels and higher memory CD8+ T-cell levels. This effect was confirmed in the subgroup of patients who switched to NRTI-sparing-cART. In vitro assays confirmed that the deleterious effect of a NRTIs-containing regimen was due to NRTIs. The implementation of NRTI-sparing regimens, with a favourable profile in CD127 and CD57 T-cell expression, could benefit cART-patients. These results could have potential implications in a decrease in the number of Non-AIDS events.

Energy modulated electron therapy using a few leaf electron collimator in combination with IMRT and 3D-CRT: Monte Carlo-based planning and dosimetric evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Yahya, Khalid; Schwartz, Matthew; Shenouda, George

2005-09-15

Energy modulated electron therapy (EMET) based on Monte Carlo dose calculation is a promising technique that enhances the treatment planning and delivery of superficially located tumors. This study investigated the application of EMET using a novel few-leaf electron collimator (FLEC) in head and neck and breast sites in comparison with three-dimensional conventional radiation therapy (3D-CRT) and intensity modulated radiation therapy (IMRT) techniques. Treatment planning was performed for two parotid cases and one breast case. Four plans were compared for each case: 3D-CRT, IMRT, 3D-CRT in conjunction with EMET (EMET-CRT), and IMRT in conjunction with EMET (EMET-IMRT), all of which weremore » performed and calculated with Monte Carlo techniques. For all patients, dose volume histograms (DVHs) were obtained for all organs of interest and the DVHs were used as a means of comparing the plans. Homogeneity and conformity of dose distributions were calculated, as well as a sparing index that compares the effect of the low isodose lines. In addition, the whole-body dose equivalent (WBDE) was estimated for each plan. Adding EMET delivered with the FLEC to 3D-CRT improves sparing of normal tissues. For the two head and neck cases, the mean dose to the contralateral parotid and brain stem was reduced relative to IMRT by 43% and 84%, and by 57% and 71%, respectively. Improved normal tissue sparing was quantified as an increase in sparing index of 47% and 30% for the head and neck and the breast cases, respectively. Adding EMET to either 3D-CRT or IMRT results in preservation of target conformity and dose homogeneity. When adding EMET to the treatment plan, the WBDE was reduced by between 6% and 19% for 3D-CRT and by between 21% and 33% for IMRT, while WBDE for EMET-CRT was reduced by up to 72% when compared with IMRT. FLEC offers a practical means of delivering modulated electron therapy. Although adding EMET delivered using the FLEC results in perturbation of target conformity when compared to IMRT, it significantly improves normal tissue sparing while offering enhanced target conformity to the 3D-CRT planning. The addition of EMET systematically leads to a reduction in WBDE especially when compared with IMRT.« less

Brain’s DNA Repair Response to Neurotoxicants

DTIC Science & Technology

2005-07-01

it is possible that OTA exposure may impact on this ability of this structure to maintain its functional integrity over time. Indeed it is known...Gordon et al., 2004). In light of the critical role played by hippocampus in cognitive function, and the importance of neurogenesis in this structure ...uncompetitive inhibitorof both succinate-cytochrome c reductase and succinate dehydrogenase while sparing cytochrome oxidase and NADH dehydrogenase

Dissociating basal forebrain and medial temporal amnesic syndromes: insights from classical conditioning.

PubMed

Myer, Catherine E; Bryant, Deborah; DeLuca, John; Gluck, Mark A

2002-01-01

In humans, anterograde amnesia can result from damage to the medial temporal (MT) lobes (including hippocampus), as well as to other brain areas such as basal forebrain. Results from animal classical conditioning studies suggest that there may be qualitative differences in the memory impairment following MT vs. basal forebrain damage. Specifically, delay eyeblink conditioning is spared after MT damage in animals and humans, but impaired in animals with basal forebrain damage. Recently, we have likewise shown delay eyeblink conditioning impairment in humans with amnesia following anterior communicating artery (ACoA) aneurysm rupture, which damages the basal forebrain. Another associative learning task, a computer-based concurrent visual discrimination, also appears to be spared in MT amnesia while ACoA amnesics are slower to learn the discriminations. Conversely, animal and computational models suggest that, even though MT amnesics may learn quickly, they may learn qualitatively differently from controls, and these differences may result in impaired transfer when familiar information is presented in novel combinations. Our initial data suggests such a two-phase learning and transfer task may provide a double dissociation between MT amnesics (spared initial learning but impaired transfer) and ACoA amnesics (slow initial learning but spared transfer). Together, these emerging data suggest that there are subtle but dissociable differences in the amnesic syndrome following damage to the MT lobes vs. basal forebrain, and that these differences may be most visible in non-declarative tasks such as eyeblink classical conditioning and simple associative learning.

Intracavitary moderator balloon combined with (252)Cf brachytherapy and boron neutron capture therapy, improving dosimetry in brain tumour and infiltrations.

PubMed

Brandão, S F; Campos, T P R

2015-07-01

This article proposes a combination of californium-252 ((252)Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Dosimetric evaluations were performed on three protocol set-ups: (252)Cf brachytherapy combined with BNCT (Cf-BNCT); Cf-BNCT with a balloon catheter filled with light water (LWB) and the same set-up with heavy water (HWB). Cf-BNCT-HWB has presented dosimetric advantages to Cf-BNCT-LWB and Cf-BNCT in infiltrations at 2.0-5.0 cm from the balloon surface. However, Cf-BNCT-LWB has shown superior dosimetry up to 2.0 cm from the balloon surface. Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the (252)Cf source, sparing the normal brain tissue. Malignant brain tumours grow rapidly and often spread to adjacent brain tissues, leading to death. Improvements in brain radiation protocols have been continuously achieved; however, brain tumour recurrence is observed in most cases. Cf-BNCT-LWB and Cf-BNCT-HWB represent new modalities for selectively combating brain tumour infiltrations and metastasis.

A critical spare part inventory control based on hazard function approach: A case study in a garment company

NASA Astrophysics Data System (ADS)

Melinda, Intan Dewi; Jauhari, Wakhid Ahmad

2018-02-01

Spare part procurement is a complex issue and requires an accurate analysis. Stock outs of spare part can leads a great impact on production. Therefore, it is necessary to design the inventory control of spare parts that guarantee the availability of spare parts needed for supporting the maintenance activity. This paper studies the inventory policy for sewing machine spare part using hazard function to approximate the demand. Hazard function is the indicator of the effect of ageing on the reliability of the system. It quantifies the risk of failure as the age of the system increases. We use a continuous review policy based on Hadley Within Approach to calculate the optimum inventory level for critical spare parts. There are four spare parts categorized as critical spare parts, which are needle plate, feed dog, rotary and binder attachment. The optimal ordering quantity for needle plate, feed, rotary and binder attachment are 5 units, 17 units, 5 units, and 9 units, respectively and the reorder point are 2 units, 1 unit, 2 units and 1 unit, respectively. Finally, the service level achieved by the proposed policy is in a range of 95.91%-97.93%, which indicates that the inventory level of spare parts can be used to support the required parts in the maintenance activity.

Potential for reduced radiation‐induced toxicity using intensity‐modulated arc therapy for whole‐brain radiotherapy with hippocampal sparing

PubMed Central

Sood, Sumit; Lominska, Christopher; Kumar, Parvesh; Badkul, Rajeev; Jiang, Hongyu; Wang, Fen

2015-01-01

The purpose of this study was to retrospectively investigate the accuracy, plan quality, and efficiency of using intensity‐modulated arc therapy (IMAT) for whole brain radiotherapy (WBRT) patients with sparing not only the hippocampus (following RTOG 0933 compliance criteria) but also other organs at risk (OARs). A total of 10 patients previously treated with nonconformal opposed laterals whole‐brain radiotherapy (NC‐WBRT) were retrospectively replanned for hippocampal sparing using IMAT treatment planning. The hippocampus was volumetrically contoured on fused diagnostic T1‐weighted MRI with planning CT images and hippocampus avoidance zone (HAZ) was generated using a 5 mm uniform margin around the hippocampus. Both hippocampi were defined as one paired organ. Whole brain tissue minus HAZ was defined as the whole‐brain planning target volume (WB‐PTV). Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis TX linear accelerator consisting of high‐definition multileaf collimators (HD‐MLCs: 2.5 mm leaf width at isocenter) and 6 MV beam for a prescription dose of 30 Gy in 10 fractions following RTOG 0933 dosimetric criteria. Two full coplanar arcs with orbits avoidance sectors were used. In addition to RTOG criteria, doses to other organs at risk (OARs), such as parotid glands, cochlea, external/middle ear canals, skin, scalp, optic pathways, brainstem, and eyes/lens, were also evaluated. Subsequently, dose delivery efficiency and accuracy of each IMAT plan was assessed by delivering quality assurance (QA) plans with a MapCHECK device, recording actual beam‐on time and measuring planed vs. measured dose agreement using a gamma index. On IMAT plans, following RTOG 0933 dosimetric criteria, the maximum dose to WB‐PTV, mean WB‐PTV D2%, and mean WB‐PTV D98% were 34.9±0.3 Gy,33.2±0.4 Gy, and 26.0±0.4 Gy, respectively. Accordingly, WB‐PTV received the prescription dose of 30 Gy and mean V30 was 90.5%±0.5%. The D100%, and mean and maximum doses to hippocampus were 8.4±0.3 Gy,11.2±0.3 Gy, and 15.6±0.4 Gy, on average, respectively. The mean values of homogeneity index (HI) and conformity index (CI) were 0.23×0.02 and 0.96×0.02, respectively. The maximum point dose to WB‐PTV was 35.3 Gy, well below the optic pathway tolerance of 37.5 Gy. In addition, compared to NC‐WBRT, dose reduction of mean and maximum of parotid glands from IMAT were 65% and 50%, respectively. Ear canals mean and maximum doses were reduced by 26% and 12%, and mean and maximum scalp doses were reduced by 9 Gy (32%) and 2 Gy (6%), on average, respectively. The mean dose to skin was 9.7 Gy with IMAT plans compared to 16 Gy with conventional NC‐WBRT, demonstrating that absolute reduction of skin dose by a factor of 2. The mean values of the total number of monitor units (MUs) and actual beam on time were 719×44 and 2.34×0.14 min, respectively. The accuracy of IMAT QA plan delivery was (98.1±0.8) %, on average, with a 3%/3 mm gamma index passing rate criteria. All of these plans were considered clinically acceptable per RTOG 0933 criteria. IMAT planning provided highly conformal and homogenous plan with a fast and effective treatment option for WBRT patients, sparing not only hippocampi but also other OARs, which could potentially result in an additional improvement of the quality life (QoL). In the future, we plan to evaluate the clinical potential of IMAT planning and treatment option with hippocampal and other OARs avoidance in our patient's cohort and asses the QoL of the WBRT patients, as well as simultaneous integrated boost (SIB) for the brain metastases diseases. PACS number: 87 PMID:26699321

Consolidation Needed for Procurements of DoD H-60 Helicopter Spare Parts (REDACTED)

DTIC Science & Technology

2016-10-12

Information Act. Report No. DODIG-2017-002 O C T O B E R 1 2 , 2 0 1 6 Consolidation Needed for Procurements of DoD H -60 Helicopter Spare Parts I N T E G R...Brief Consolidation Needed for Procurements of DoD H -60 Helicopter Spare Parts October 12, 2016 Visit us at www.dodig.mil Objective We determined...whether DoD was effectively managing the procurement of H -60 helicopter ( H -60) spare parts. The Army, Navy, Air Force, and U.S. Special Operations

Transient global amnesia: implicit/explicit memory dissociation and PET assessment of brain perfusion and oxygen metabolism in the acute stage.

PubMed

Eustache, F; Desgranges, B; Petit-Taboué, M C; de la Sayette, V; Piot, V; Sablé, C; Marchal, G; Baron, J C

1997-09-01

To assess explicit memory and two components of implicit memory--that is, perceptual-verbal skill learning and lexical-semantic priming effects--as well as resting cerebral blood flow (CBF) and oxygen metabolism (CMRO2) during the acute phase of transient global amnesia. In a 59 year old woman, whose amnestic episode fulfilled all current criteria for transient global amnesia, a neuropsychological protocol was administered, including word learning, story recall, categorical fluency, mirror reading, and word stem completion tasks. PET was performed using the (15)O steady state inhalation method, while the patient still exhibited severe anterograde amnesia and was interleaved with the cognitive tests. There was a clear cut dissociation between impaired long term episodic memory and preserved implicit memory for its two components. Categorical fluency was significantly altered, suggesting word retrieval strategy--rather than semantic memory--impairment. The PET study disclosed a reduced CMRO2 with relatively or fully preserved CBF in the left prefrontotemporal cortex and lentiform nucleus, and the reverse pattern over the left occipital cortex. The PET alterations with patchy CBF-CMRO2 uncoupling would be compatible with a migraine-like phenomenon and indicate that the isolated assessment of perfusion in transient global amnesia may be misleading. The pattern of metabolic depression, with sparing of the hippocampal area, is one among the distinct patterns of brain dysfunction that underlie the (apparently) uniform clinical presentation of transient global amnesia. The finding of a left prefrontal hypometabolism in the face of impaired episodic memory and altered verbal fluency would fit present day concepts from PET activation studies about the role of this area in episodic and semantic memory encoding/retrieval. Likewise, the changes affecting the lenticular nucleus but sparing the caudate would be consistent with the normal performance in perceptual-verbal skill learning. Finally, unaltered lexical-semantic priming effects, despite left temporal cortex hypometabolism, suggest that these processes are subserved by a more distributed neocortical network.

Effects of Insulin Detemir and NPH Insulin on Body Weight and Appetite-Regulating Brain Regions in Human Type 1 Diabetes: A Randomized Controlled Trial

PubMed Central

van Golen, Larissa W.; Veltman, Dick J.; IJzerman, Richard G.; Deijen, Jan Berend; Heijboer, Annemieke C.; Barkhof, Frederik; Drent, Madeleine L.; Diamant, Michaela

2014-01-01

Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli. Trial Registration ClinicalTrials.gov NCT00626080. PMID:24739875

Effects of insulin detemir and NPH insulin on body weight and appetite-regulating brain regions in human type 1 diabetes: a randomized controlled trial.

PubMed

van Golen, Larissa W; Veltman, Dick J; IJzerman, Richard G; Deijen, Jan Berend; Heijboer, Annemieke C; Barkhof, Frederik; Drent, Madeleine L; Diamant, Michaela

2014-01-01

Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli. ClinicalTrials.gov NCT00626080.

Sparing functional anatomical structures during intensity-modulated radiotherapy: an old problem, a new solution.

PubMed

Tan, Wenyong; Han, Guang; Wei, Shaozhong; Hu, Desheng

2014-08-01

During intensity-modulated radiotherapy, an organ is usually assumed to be functionally homogeneous and, generally, its anatomical and spatial heterogeneity with respect to radiation response are not taken into consideration. However, advances in imaging and radiation techniques as well as an improved understanding of the radiobiological response of organs have raised the possibility of sparing the critical functional structures within various organs at risk during intensity-modulated radiotherapy. Here, we discuss these structures, which include the critical brain structure, or neural nuclei, and the nerve fiber tracts in the CNS, head and neck structures related to radiation-induced salivary and swallowing dysfunction, and functional structures in the heart and lung. We suggest that these structures can be used as potential surrogate organs at risk in order to minimize their radiation dose and/or irradiated volume without compromising the dose coverage of the target volume during radiation treatment.

Impaired consciousness in partial seizures is bimodally distributed

PubMed Central

Cunningham, Courtney; Chen, William C.; Shorten, Andrew; McClurkin, Michael; Choezom, Tenzin; Schmidt, Christian P.; Chu, Victoria; Bozik, Anne; Best, Cameron; Chapman, Melissa; Furman, Moran; Detyniecki, Kamil; Giacino, Joseph T.

2014-01-01

Objective: To investigate whether impaired consciousness in partial seizures can usually be attributed to specific deficits in the content of consciousness or to a more general decrease in the overall level of consciousness. Methods: Prospective testing during partial seizures was performed in patients with epilepsy using the Responsiveness in Epilepsy Scale (n = 83 partial seizures, 30 patients). Results were compared with responsiveness scores in a cohort of patients with severe traumatic brain injury evaluated with the JFK Coma Recovery Scale–Revised (n = 552 test administrations, 184 patients). Results: Standardized testing during partial seizures reveals a bimodal scoring distribution, such that most patients were either fully impaired or relatively spared in their ability to respond on multiple cognitive tests. Seizures with impaired performance on initial test items remained consistently impaired on subsequent items, while other seizures showed spared performance throughout. In the comparison group, we found that scores of patients with brain injury were more evenly distributed across the full range in severity of impairment. Conclusions: Partial seizures can often be cleanly separated into those with vs without overall impaired responsiveness. Results from similar testing in a comparison group of patients with brain injury suggest that the bimodal nature of Responsiveness in Epilepsy Scale scores is not a result of scale bias but may be a finding unique to partial seizures. These findings support a model in which seizures either propagate or do not propagate to key structures that regulate overall arousal and thalamocortical function. Future investigations are needed to relate these behavioral findings to the physiology underlying impaired consciousness in partial seizures. PMID:24727311

Impaired consciousness in partial seizures is bimodally distributed.

PubMed

Cunningham, Courtney; Chen, William C; Shorten, Andrew; McClurkin, Michael; Choezom, Tenzin; Schmidt, Christian P; Chu, Victoria; Bozik, Anne; Best, Cameron; Chapman, Melissa; Furman, Moran; Detyniecki, Kamil; Giacino, Joseph T; Blumenfeld, Hal

2014-05-13

To investigate whether impaired consciousness in partial seizures can usually be attributed to specific deficits in the content of consciousness or to a more general decrease in the overall level of consciousness. Prospective testing during partial seizures was performed in patients with epilepsy using the Responsiveness in Epilepsy Scale (n = 83 partial seizures, 30 patients). Results were compared with responsiveness scores in a cohort of patients with severe traumatic brain injury evaluated with the JFK Coma Recovery Scale-Revised (n = 552 test administrations, 184 patients). Standardized testing during partial seizures reveals a bimodal scoring distribution, such that most patients were either fully impaired or relatively spared in their ability to respond on multiple cognitive tests. Seizures with impaired performance on initial test items remained consistently impaired on subsequent items, while other seizures showed spared performance throughout. In the comparison group, we found that scores of patients with brain injury were more evenly distributed across the full range in severity of impairment. Partial seizures can often be cleanly separated into those with vs without overall impaired responsiveness. Results from similar testing in a comparison group of patients with brain injury suggest that the bimodal nature of Responsiveness in Epilepsy Scale scores is not a result of scale bias but may be a finding unique to partial seizures. These findings support a model in which seizures either propagate or do not propagate to key structures that regulate overall arousal and thalamocortical function. Future investigations are needed to relate these behavioral findings to the physiology underlying impaired consciousness in partial seizures.

Non-uniform dose distributions in cranial radiation therapy

NASA Astrophysics Data System (ADS)

Bender, Edward T.

Radiation treatments are often delivered to patients with brain metastases. For those patients who receive radiation to the entire brain, there is a risk of long-term neuro-cognitive side effects, which may be due to damage to the hippocampus. In clinical MRI and CT scans it can be difficult to identify the hippocampus, but once identified it can be partially spared from radiation dose. Using deformable image registration we demonstrate a semi-automatic technique for obtaining an estimated location of this structure in a clinical MRI or CT scan. Deformable image registration is a useful tool in other areas such as adaptive radiotherapy, where the radiation oncology team monitors patients during the course of treatment and adjusts the radiation treatments if necessary when the patient anatomy changes. Deformable image registration is used in this setting, but there is a considerable level of uncertainty. This work represents one of many possible approaches at investigating the nature of these uncertainties utilizing consistency metrics. We will show that metrics such as the inverse consistency error correlate with actual registration uncertainties. Specifically relating to brain metastases, this work investigates where in the brain metastases are likely to form, and how the primary cancer site is related. We will show that the cerebellum is at high risk for metastases and that non-uniform dose distributions may be advantageous when delivering prophylactic cranial irradiation for patients with small cell lung cancer in complete remission.

Evaluation of normalization of cerebro-placental ratio as a potential predictor for adverse outcome in SGA fetuses.

PubMed

Monteith, Cathy; Flood, Karen; Mullers, Sieglinde; Unterscheider, Julia; Breathnach, Fionnuala; Daly, Sean; Geary, Michael P; Kennelly, Mairead M; McAuliffe, Fionnuala M; O'Donoghue, Keelin; Hunter, Alison; Morrison, John J; Burke, Gerald; Dicker, Patrick; Tully, Elizabeth C; Malone, Fergal D

2017-03-01

Intrauterine growth restriction accounts for a significant proportion of perinatal morbidity and mortality currently encountered in obstetric practice. The primary goal of antenatal care is the early recognition of such conditions to allow treatment and optimization of both maternal and fetal outcomes. Management of pregnancies complicated by intrauterine growth restriction remains one of the greatest challenges in obstetrics. Frequently, however, clinical evidence of underlying uteroplacental dysfunction may only emerge at a late stage in the disease process. With advanced disease the only therapeutic intervention is delivery of the fetus and placenta. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the at-risk fetus in both intrauterine growth restriction and the appropriate-for-gestational-age setting. The cerebroplacental ratio quantifies the redistribution of the cardiac output resulting in a brain-sparing effect. The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect is significantly associated with an adverse perinatal outcome in the intrauterine growth restriction cohort. The aim of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction study was to evaluate the optimal management of fetuses with an estimated fetal weight <10th centile. The objective of this secondary analysis was to evaluate if normalizing cerebroplacental ratio predicts adverse perinatal outcome. In all, 1116 consecutive singleton pregnancies with intrauterine growth restriction completed the study protocol over 2 years at 7 centers, undergoing serial sonographic evaluation and multivessel Doppler measurement. Cerebroplacental ratio was calculated using the pulsatility and resistance indices of the middle cerebral and umbilical artery. Abnormal cerebroplacental ratio was defined as <1.0. Adverse perinatal outcome was defined as a composite of intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, and death. Data for cerebroplacental ratio calculation were available in 881 cases, with a mean gestational age of 33 (interquartile range, 28.7-35.9) weeks. Of the 87 cases of abnormal serial cerebroplacental ratio with an initial value <1.0, 52% (n = 45) of cases remained abnormal and 22% of these (n = 10) had an adverse perinatal outcome. The remaining 48% (n = 42) demonstrated normalizing cerebroplacental ratio on serial sonography, and 5% of these (n = 2) had an adverse perinatal outcome. Mean gestation at delivery was 33.4 weeks (n = 45) in the continuing abnormal cerebroplacental ratio group and 36.5 weeks (n = 42) in the normalizing cerebroplacental ratio group (P value <.001). The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect was significantly associated with an adverse perinatal outcome in our intrauterine growth restriction cohort. It was hypothesized that a normalizing cerebroplacental ratio would be a further predictor of an adverse outcome due to the loss of this compensatory mechanism. However, in this subanalysis we did not demonstrate an additional poor prognostic effect when the cerebroplacental ratio value returned to a value >1.0. Overall, this secondary analysis demonstrated the importance of a serial abnormal cerebroplacental ratio value of <1 within the <34 weeks' gestation population. Contrary to our proposed hypothesis, we recognize that reversion of an abnormal cerebroplacental ratio to a normal ratio is not associated with a heightened degree of adverse perinatal outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

Allocation of systemic glucose output to cerebral utilization as a function of fetal canine growth.

PubMed

Huang, M M; Kliegman, R M; Trindade, C; Kall, D; Voelker, K

1988-05-01

To determine whether the neonatal canine brain consumes a major proportion of the systemic glucose production, we investigated the cerebral glucose requirement and hepatic glucose production in beagle pups. Sixteen pups received D-[6-3H]-glucose to determine systemic glucose production. Cerebral blood flow was measured by [N-methyl-14C]antipyrine, and the brain uptake index (BUI) of glucose was determined using 2-[14C]deoxy-D-glucose. Glucose production was 49.6 +/- 11.0 mumol.kg-1.min-1. Cerebral blood flow was 0.83 ml.g-1.min-1; cerebral uptake of glucose was 0.60 +/- 0.15 mumol.g-1.min-1. Of the total glucose production 36.6 +/- 7.9% was accounted for by the cerebral uptake of glucose. Brain-to-body weight and brain-to-liver weight ratios were the greatest in the smallest pups, suggesting brain sparing. The effect of growth status on cerebral substrate availability could not be correlated with cerebral uptake of glucose or oxygen or with systemic glucose production. However, the percentage of systemic glucose production allotted to the cerebral cortex increased with increasing body weight (r = 0.50, P less than 0.05). Cerebral glucose entry measured by BUI was demonstrated to be 0.108 +/- 0.014; BUI inversely correlated with canine birth weight (r = -0.832, P less than 0.001). We conclude that the percentage of glucose production utilized by the neonatal canine brain is not proportionately larger in the smaller pups despite a proportionately larger brain. Because the absolute cerebral glucose utilization may be static, we speculate that BUI (glucose entry) may be less of a rate-limiting factor for cerebral glucose entry in the smallest pups.

Intracavitary moderator balloon combined with 252Cf brachytherapy and boron neutron capture therapy, improving dosimetry in brain tumour and infiltrations

PubMed Central

Brandão, S F

2015-01-01

Objective: This article proposes a combination of californium-252 (252Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Methods: Dosimetric evaluations were performed on three protocol set-ups: 252Cf brachytherapy combined with BNCT (Cf-BNCT); Cf-BNCT with a balloon catheter filled with light water (LWB) and the same set-up with heavy water (HWB). Results: Cf-BNCT-HWB has presented dosimetric advantages to Cf-BNCT-LWB and Cf-BNCT in infiltrations at 2.0–5.0 cm from the balloon surface. However, Cf-BNCT-LWB has shown superior dosimetry up to 2.0 cm from the balloon surface. Conclusion: Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the 252Cf source, sparing the normal brain tissue. Advances in knowledge: Malignant brain tumours grow rapidly and often spread to adjacent brain tissues, leading to death. Improvements in brain radiation protocols have been continuously achieved; however, brain tumour recurrence is observed in most cases. Cf-BNCT-LWB and Cf-BNCT-HWB represent new modalities for selectively combating brain tumour infiltrations and metastasis. PMID:25927876

MO-F-CAMPUS-T-02: Optimizing Orientations of Hundreds of Intensity-Modulated Beams to Treat Multiple Brain Targets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, L; Dong, P; Larson, D

Purpose: To investigate a new modulated beam orientation optimization (MBOO) approach maximizing treatment planning quality for the state-of-the-art flattening filter free (FFF) beam that has enabled rapid treatments of multiple brain targets. Methods: MBOO selects and optimizes a large number of intensity-modulated beams (400 or more) from all accessible beam angles surrounding a patient’s skull. The optimization algorithm was implemented on a standalone system that interfaced with the 3D Dicom images and structure sets. A standard published data set that consisted of 1 to 12 metastatic brain tumor combinations was selected for MBOO planning. The planning results from various coplanarmore » and non-coplanar configurations via MBOO were then compared with the results obtained from a clinical volume modulated arc therapy (VMAT) delivery system (Truebeam RapidArc, Varian Oncology). Results: When planning a few number of targets (n<4), MBOO produced results equivalent to non-coplanar multi-arc VMAT planning in terms of target volume coverage and normal tissue sparing. For example, the 12-Gy and 4-Gy normal brain volumes for the 3-target plans differed by less than 1 mL ( 3.0 mLvs 3.8 mL; and 35.2 mL vs 36.3 mL, respectively) for MBOO versus VMAT. However, when planning a larger number of targets (n≥4), MBOO significantly reduced the dose to the normal brain as compared to VMAT, though the target volume coverage was equivalent. For example, the 12-Gy and 4-Gy normal brain volumes for the 12-target plans were 10.8 mL vs. 18.0 mL and 217.9 mL vs. 390.0 mL, respectively for the non-coplanar MBOO versus the non-coplanar VMAT treatment plans, yielding a reduction in volume of more than 60% for the case. Conclusion: MBOO is a unique approach for maximizing normal tissue sparing when treating a large number (n≥4) of brain tumors with FFF linear accelerators. Dr Ma and Dr Sahgal are currently on the board of international society of stereotactic radiosurgery. Dr Sahgal has received support for educational presentations from Elekta company.« less

AMPAkines Target the Nucleus Accumbens to Relieve Postoperative Pain.

PubMed

Su, Chen; Lin, Hau Yeuh; Yang, Runtao; Xu, Duo; Lee, Michelle; Pawlak, Natalie; Norcini, Monica; Sideris, Alexandra; Recio-Pinto, Esperanza; Huang, Dong; Wang, Jing

2016-11-01

AMPAkines augment the function of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the brain to increase excitatory outputs. These drugs are known to relieve persistent pain. However, their role in acute pain is unknown. Furthermore, a specific molecular and anatomic target for these novel analgesics remains elusive. The authors studied the analgesic role of an AMPAkine, CX546, in a rat paw incision (PI) model of acute postoperative pain. The authors measured the effect of AMPAkines on sensory and depressive symptoms of pain using mechanical hypersensitivity and forced swim tests. The authors asked whether AMPA receptors in the nucleus accumbens (NAc), a key node in the brain's reward and pain circuitry, can be a target for AMPAkine analgesia. Systemic administration of CX546 (n = 13), compared with control (n = 13), reduced mechanical hypersensitivity (50% withdrawal threshold of 6.05 ± 1.30 g [mean ± SEM] vs. 0.62 ± 0.13 g), and it reduced depressive features of pain by decreasing immobility on the forced swim test in PI-treated rats (89.0 ± 15.5 vs. 156.7 ± 18.5 s). Meanwhile, CX546 delivered locally into the NAc provided pain-relieving effects in both PI (50% withdrawal threshold of 6.81 ± 1.91 vs. 0.50 ± 0.03 g; control, n = 6; CX546, n = 8) and persistent postoperative pain (spared nerve injury) models (50% withdrawal threshold of 3.85 ± 1.23 vs. 0.45 ± 0.00 g; control, n = 7; CX546, n = 11). Blocking AMPA receptors in the NAc with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione inhibited these pain-relieving effects (50% withdrawal threshold of 7.18 ± 1.52 vs. 1.59 ± 0.66 g; n = 8 for PI groups; 10.70 ± 3.45 vs. 1.39 ± 0.88 g; n = 4 for spared nerve injury groups). AMPAkines relieve postoperative pain by acting through AMPA receptors in the NAc.

An Analysis of Causes of Contract Price Change for Competitive Procurements of Replenishment Spare Parts.

DTIC Science & Technology

1984-09-01

Research Study Number Three. In 1982, Mr. Edward Brost , then a graduate student at AFIT, completed a thesis which further analyzed the effects of sole...task, Brost formulated three research questions. They are as follows: 1. Is there a reduction in replenishment spare parts prices when competition is...analysis, Brost made three significant conclusions. They are: 1. The introduction of competition into the replenishment spare parts acquisition process

Vamorolone, a dissociative steroidal compound, reduces pro-inflammatory cytokine expression in glioma cells and increases activity and survival in a murine model of cortical tumor.

PubMed

Wells, Elizabeth; Kambhampati, Madhuri; Damsker, Jesse M; Gordish-Dressman, Heather; Yadavilli, Sridevi; Becher, Oren J; Gittens, Jamila; Stampar, Mojca; Packer, Roger J; Nazarian, Javad

2017-02-07

Corticosteroids, such as dexamethasone, are routinely used as palliative care in neuro-oncology for their anti-inflammatory benefits, however many patients experience dose limiting side effects caused by glucocorticoid response element (GRE)-mediated transcription. The purpose of this study was to use a murine model to investigate a new steroid alternative, vamorolone, which promises to reduce side effects through dissociating GRE-mediated transcription and NF-κB -mediated anti-inflammatory actions. To compare vamorolone to dexamethasone in reducing pro-inflammatory signals in vitro, murine glioma cells were treated with dexamethasone, vamorolone or vehicle control. Changes in mRNA expression were assessed using the nanostring inflammatory platform. Furthermore, drug efficacy, post-treatment behavioral activity and side effects were assessed by treating two cohorts of brain tumor bearing mice with dexamethasone, vamorolone, or vehicle control. Our investigation showed that treatment with vamorolone resulted in a reduction of pro-inflammatory signals in tumor cells in vitro similar to treatment with dexamethasone. Treatment with vamorolone resulted in a better safety profile in comparison to dexamethasone treatment. Vamorolone- treated mice showed similar or better activity and survival when compared to dexamethasone-treated mice. Our data indicate vamorolone is a potential steroid-sparing alternative for treating patients with brain tumors.

Brain areas impaired in oral and verbal apraxic patients

PubMed Central

Yadegari, Fariba; Azimian, Mojtaba; Rahgozar, Mahdi; Shekarchi, Babak

2014-01-01

Background: As both oral and verbal apraxia are related to vocal orofacial musculature, this study aimed at identifying brain regions impaired in cases with oral and verbal apraxia. Methods: In this non-experimental study, 46 left brain damaged subjects (17 females) aged 23–84 years, were examined by oral and verbal apraxia tasks. Impaired and spared Broca’s area, insula, and middle frontal gyrus in the left hemisphere were checked from magnetic resonance imaging and computed tomography scans utilizing Talairach Atlas. Data were analyzed using chi-square test. Results: Insula was significantly impaired in both forms of oral and verbal apraxia and different severities and prominent forms of both apraxias (P < 0.05). Broca’s area was slightly less involved than insula in two forms of apraxia. Conclusion: As the damage of insula was more prominent in both forms of apraxias, it seems that oral and verbal apraxia may have commonalities regarding their underlying brain lesions. PMID:25295150

TARGETED DELETION OF INDUCIBLE HEAT SHOCK PROTEIN 70 ABROGATES THE LATE INFARCT-SPARING EFFECT OF MYOCARDIAL ISCHEMIC PRECONDITIONING

EPA Science Inventory

Abstract submitted for 82nd annual meeting of the American Association for Thoracic Surgery, May 4-8, 2002 in Washington D.C.

Targeted Deletion of Inducible Heat Shock Protein 70 Abrogates the Late Infarct-Sparing Effect of Myocardial Ischemic Preconditioning

Craig...

Intensity-Modulated and 3D-Conformal Radiotherapy for Whole-Ventricular Irradiation as Compared With Conventional Whole-Brain Irradiation in the Management of Localized Central Nervous System Germ Cell Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Michael Jenwei, E-mail: michaelchen@einstein.b; Silva Santos, Adriana da; Sakuraba, Roberto Kenji

Purpose: To compare the sparing potential of cerebral hemispheres with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for whole-ventricular irradiation (WVI) and conventional whole-brain irradiation (WBI) in the management of localized central nervous system germ cell tumors (CNSGCTs). Methods and Materials: Ten cases of patients with localized CNSGCTs and submitted to WVI by use of IMRT with or without a 'boost' to the primary lesion were selected. For comparison purposes, similar treatment plans were produced by use of 3D-CRT (WVI with or without boost) and WBI (opposed lateral fields with or without boost), and cerebral hemisphere sparing was evaluatedmore » at dose levels ranging from 2 Gy to 40 Gy. Results: The median prescription dose for WVI was 30.6 Gy (range, 25.2-37.5 Gy), and that for the boost was 16.5 Gy (range, 0-23.4 Gy). Mean irradiated cerebral hemisphere volumes were lower for WVI with IMRT than for 3D-CRT and were lower for WVI with 3D-CRT than for WBI. Intensity-modulated radiotherapy was associated with the lowest irradiated volumes, with reductions of 7.5%, 12.2%, and 9.0% at dose levels of 20, 30, and 40 Gy, respectively, compared with 3D-CRT. Intensity-modulated radiotherapy provided statistically significant reductions of median irradiated volumes at all dose levels (p = 0.002 or less). However, estimated radiation doses to peripheral areas of the body were 1.9 times higher with IMRT than with 3D-CRT. Conclusions: Although IMRT is associated with increased radiation doses to peripheral areas of the body, its use can spare a significant amount of normal central nervous system tissue compared with 3D-CRT or WBI in the setting of CNSGCT treatment.« less

Comparing the quality of passively-scattered proton and photon tomotherapy plans for brain and head and neck disease sites.

PubMed

Kainz, Kristofer; Firat, Selim; Wilson, J Frank; Schultz, Christopher; Siker, Malika; Wang, Andrew; Olson, Dan; Li, X Allen

2015-03-21

We compare the quality of photon IMRT (helical tomotherapy) with classic proton plans for brain, head and neck tumors, in terms of target dose uniformity and conformity along with organ-at-risk (OAR) sparing. Plans were created for twelve target volumes among eight cases. All patients were originally planned and treated using helical tomotherapy. Proton plans were generated using a passively-scattered beam model with a maximum range of 32 g cm(-2) (225 MeV), range modulation in 0.5 g cm(-2) increments and range compensators with 4.8 mm milling tool diameters. All proton plans were limited to two to four beams. Plan quality was compared using uniformity index (UI), conformation number (CN) and a EUD-based plan quality index (fEUD). For 11 of the 12 targets, UI was improved for the proton plan; on average, UI was 1.05 for protons versus 1.08 for tomotherapy. For 7 of the 12 targets, the tomotherapy plan exhibited more favorable CN. For proximal OARs, the improved dose conformity to the target volume from tomotherapy led to a lower maximum dose. For distal OARs, the maximum dose was much lower for proton plans. For 6 of the 8 cases, near-total avoidance for distal OARs provided by protons leads to improved fEUD. However, if distal OARs are excluded in the fEUD calculation, the proton plans exhibit better fEUD in only 3 of the 8 cases. The distal OAR sparing and target dose uniformity are generally better with passive-scatter proton planning than with photon tomotherapy; proton therapy may be preferred if the clinician deems those attributes critical. However, tomotherapy may serve equally as well as protons for cases where superior target dose conformity from tomotherapy leads to plan quality nearly identical to or better than protons and for cases where distal OAR sparing is not concerning.

SU-F-T-618: Evaluation of a Mono-Isocentric Treatment Planning Software for Stereotactic Radiosurgery of Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sham, E; Sattarivand, M; Mulroy, L

Purpose: To evaluate planning performance of an automated treatment planning software (BrainLAB; Elements) for stereotactic radiosurgery (SRS) of multiple brain metastases. Methods: Brainlab’s Multiple Metastases Elements (MME) uses single isocentric technique to treat up to 10 cranial planning target volumes (PTVs). The planning algorithm of the MME accounts for multiple PTVs overlapping with one another on the beam eyes view (BEV) and automatically selects a subset of all overlapping PTVs on each arc for sparing normal tissues in the brain. The algorithm also optimizes collimator angles, margins between multi-leaf collimators (MLCs) and PTVs, as well as monitor units (MUs) usingmore » minimization of conformity index (CI) for all targets. Planning performance was evaluated by comparing the MME-calculated treatment plan parameters with the same parameters calculated with the Volumetric Modulated Arc Therapy (VMAT) optimization on Varian’s Eclipse platform. Results: Figures 1 to 3 compare several treatment plan outcomes calculated between the MME and VMAT for 5 clinical multi-targets SRS patient plans. Prescribed target dose was volume-dependent and defined based on the RTOG recommendation. For a total number of 18 PTV’s, mean values for the CI, PITV, and GI were comparable between the MME and VMAT within one standard deviation (σ). However, MME-calculated MDPD was larger than the same VMAT-calculated parameter. While both techniques delivered similar maximum point doses to the critical cranial structures and total MU’s for the 5 patient plans, the MME required less treatment planning time by an order of magnitude compared to VMAT. Conclusion: The MME and VMAT produce similar plan qualities in terms of MUs, target dose conformation, and OAR dose sparing. While the selective use of PTVs for arc-optimization with the MME reduces significantly the total planning time in comparison to VMAT, the target dose homogeneity was also compromised due to its simplified inverse planning algorithm used.« less

Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain

PubMed Central

Liang, Winnie S.; Dunckley, Travis; Beach, Thomas G.; Grover, Andrew; Mastroeni, Diego; Walker, Douglas G.; Caselli, Richard J.; Kukull, Walter A.; McKeel, Daniel; Morris, John C.; Hulette, Christine; Schmechel, Donald; Alexander, Gene E.; Reiman, Eric M.; Rogers, Joseph; Stephan, Dietrich A.

2008-01-01

In this article, we have characterized and compared gene expression profiles from laser capture microdissected neurons in six functionally and anatomically distinct regions from clinically and histopathologically normal aged human brains. These regions, which are also known to be differentially vulnerable to the histopathological and metabolic features of Alzheimer’s disease (AD), include the entorhinal cortex and hippocampus (limbic and paralimbic areas vulnerable to early neurofibrillary tangle pathology in AD), posterior cingulate cortex (a paralimbic area vulnerable to early metabolic abnormalities in AD), temporal and prefrontal cortex (unimodal and heteromodal sensory association areas vulnerable to early neuritic plaque pathology in AD), and primary visual cortex (a primary sensory area relatively spared in early AD). These neuronal profiles will provide valuable reference information for future studies of the brain, in normal aging, AD and other neurological and psychiatric disorders. PMID:17077275

Chronic In Vivo Imaging Shows No Evidence of Dendritic Plasticity or Functional Remapping in the Contralesional Cortex after Stroke

PubMed Central

Johnston, David G.; Denizet, Marie; Mostany, Ricardo

2013-01-01

Most stroke survivors exhibit a partial recovery from their deficits. This presumably occurs because of remapping of lost capabilities to functionally related brain areas. Functional brain imaging studies suggest that remapping in the contralateral uninjured cortex might represent a transient stage of compensatory plasticity. Some postmortem studies have also shown that cortical lesions, including stroke, can trigger dendritic plasticity in the contralateral hemisphere, but the data are controversial. We used longitudinal in vivo two-photon microscopy in the contralateral homotopic cortex to record changes in dendritic spines of layer 5 pyramidal neurons in green fluorescent protein mice. We could not detect de novo growth of dendrites or changes in the density or turnover of spines for up to 4 weeks after stroke. We also used intrinsic optical signal imaging to investigate whether the forepaw (FP) sensory representation is remapped to the spared homotopic cortex after stroke. Stimulation of the contralateral FP reliably produced strong intrinsic signals in the spared hemisphere, but we could never detect a signal with ipsilateral FP stimulation after stroke. This lack of contralateral plasticity at the level of apical dendrites of layer 5 pyramidal neurons and FP sensory maps suggests that the contralesional cortex may not contribute to functional recovery after stroke and that, at least in mice, the peri-infarct cortex plays the dominant role in postischemic plasticity. PMID:22499800

Chronic in vivo imaging shows no evidence of dendritic plasticity or functional remapping in the contralesional cortex after stroke.

PubMed

Johnston, David G; Denizet, Marie; Mostany, Ricardo; Portera-Cailliau, Carlos

2013-04-01

Most stroke survivors exhibit a partial recovery from their deficits. This presumably occurs because of remapping of lost capabilities to functionally related brain areas. Functional brain imaging studies suggest that remapping in the contralateral uninjured cortex might represent a transient stage of compensatory plasticity. Some postmortem studies have also shown that cortical lesions, including stroke, can trigger dendritic plasticity in the contralateral hemisphere, but the data are controversial. We used longitudinal in vivo two-photon microscopy in the contralateral homotopic cortex to record changes in dendritic spines of layer 5 pyramidal neurons in green fluorescent protein mice. We could not detect de novo growth of dendrites or changes in the density or turnover of spines for up to 4 weeks after stroke. We also used intrinsic optical signal imaging to investigate whether the forepaw (FP) sensory representation is remapped to the spared homotopic cortex after stroke. Stimulation of the contralateral FP reliably produced strong intrinsic signals in the spared hemisphere, but we could never detect a signal with ipsilateral FP stimulation after stroke. This lack of contralateral plasticity at the level of apical dendrites of layer 5 pyramidal neurons and FP sensory maps suggests that the contralesional cortex may not contribute to functional recovery after stroke and that, at least in mice, the peri-infarct cortex plays the dominant role in postischemic plasticity.

Urea cycle disorders: brain MRI and neurological outcome.

PubMed

Bireley, William R; Van Hove, Johan L K; Gallagher, Renata C; Fenton, Laura Z

2012-04-01

Urea cycle disorders encompass several enzyme deficiencies that can result in cerebral damage, with a wide clinical spectrum from asymptomatic to severe. The goal of this study was to correlate brain MRI abnormalities in urea cycle disorders with clinical neurological sequelae to evaluate whether MRI abnormalities can assist in guiding difficult treatment decisions. We performed a retrospective chart review of patients with urea cycle disorders and symptomatic hyperammonemia. Brain MRI images were reviewed for abnormalities that correlated with severity of clinical neurological sequelae. Our case series comprises six urea cycle disorder patients, five with ornithine transcarbamylase deficiency and one with citrullinemia type 1. The observed trend in distribution of brain MRI abnormalities as the severity of neurological sequelae increased was the peri-insular region first, extending into the frontal, parietal, temporal and, finally, the occipital lobes. There was thalamic restricted diffusion in three children with prolonged hyperammonemia. Prior to death, this site is typically reported to be spared in urea cycle disorders. The pattern and extent of brain MRI abnormalities correlate with clinical neurological outcome in our case series. This suggests that brain MRI abnormalities may assist in determining prognosis and helping clinicians with subsequent treatment decisions.

Clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma.

PubMed

Hu, Jun; Zhu, Li-rong; Liang, Zhi-qing; Meng, Yuan-guang; Guo, Hong-yan; Qu, Peng-peng; Ma, Cai-ling; Xu, Cong-jian; Yuan, Bi-bo

2011-10-01

To assess the clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma (EOC). A retrospective study of young EOC inpatients (≤40 years old) was performed during January 1994 and December 2010 in eight institutions. Data were analyzed from 94 patients treated with fertility-sparing surgery with a median follow-up time of 58.7 months. As histologic grade increased, overall survival (OS) and disease-free survival (DFS) of patients receiving fertility-sparing surgery declined. Neither staging surgery nor laparoscopy of early stage EOC with conservative surgery had a significant effect on OS or DFS. Normal menstruation recommenced after chemotherapy in 89% of the fertility-sparing group. Seventeen pregnancies among twelve patients were achieved by the end of the follow-ups. Fertility-sparing treatment for patients with EOC Stage I Grade 1 could be cautiously considered for young patients. The surgical procedure and surgical route might not significantly influence the prognosis. Standard chemotherapy is not likely to have an evident impact on ovarian function or fertility in young patients.

Hair sparing does not compromise real-time magnetic resonance imaging guided stereotactic laser fiber placement for temporal lobe epilepsy.

PubMed

Singh, Shikha; Kumar, Kevin K; Rabon, Matthew J; Dolce, Dana; Halpern, Casey H

2018-06-01

Pre-operative scalp shaving is conventionally thought to simplify postoperative cranial wound care, lower the rate of wound infections, and ease optimal incision localization. Over the past few decades, some neurosurgeons have refrained from scalp shaving in order to improve patient satisfaction with brain surgery. However, this hair-sparing approach has not yet been explored in the growing field of magnetic resonance-guided laser interstitial thermal therapy (MRgLITT). This study investigated the initial impact of a no-shave technique on post-operative wound infection rate as well as on entry and target accuracy in MRgLITT for mesial temporal epilepsy. Eighteen patients selected by the Stanford Comprehensive Epilepsy Program between November 2015 and August 2017 were included in the study. All patients underwent functional selective amygdalohippocampotomies using MRgLITT entirely within a diagnostic MRI suite. No hair was removed and no additional precautions were taken for hair or scalp care. Otherwise, routine protocols for surgical preparations and wound closure were followed. The study was performed under approval from Stanford University's Internal Review Board (IRB-37830). No post-operative wound infections or erosions occurred for any patient. The mean entry point error was 2.87 ± 1.3 mm and the mean target error was 1.0 ± 0.9 mm. There have been no other complications associated with this hair-sparing approach. The study's results suggest that hair sparing in MRgLITT surgery for temporal epilepsy does not increase the risk of wound complications or compromise accuracy. This preferred cosmetic approach may thus appeal to epilepsy patients considering such interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Upregulation of neuronal kynurenine 3-monooxygenase mediates depression-like behavior in a mouse model of neuropathic pain.

PubMed

Laumet, Geoffroy; Zhou, Wenjun; Dantzer, Robert; Edralin, Jules D; Huo, XiaoJiao; Budac, David P; O'Connor, Jason C; Lee, Anna W; Heijnen, Cobi J; Kavelaars, Annemieke

2017-11-01

Pain and depression often co-occur, but the underlying mechanisms have not been elucidated. Here, we used the spared nerve injury (SNI) model in mice to induce both neuropathic pain and depression-like behavior. We investigated whether brain interleukin (IL)-1 signaling and activity of kynurenine 3-monoxygenase (KMO), a key enzyme for metabolism of kynurenine into the neurotoxic NMDA receptor agonist quinolinic acid, are necessary for comorbid neuropathic pain and depression-like behavior. SNI mice showed increased expression levels of Il1b and Kmo mRNA in the contralateral side of the brain. The SNI-induced increase of Kmo mRNA was associated with increased KMO protein and elevated quinolinic acid and reduced kynurenic acid in the contralateral hippocampus. The increase in KMO-protein in response to SNI mostly took place in hippocampal NeuN-positive neurons rather than microglia. Inhibition of brain IL-1 signaling by intracerebroventricular administration of IL-1 receptor antagonist after SNI prevented the increase in Kmo mRNA and depression-like behavior measured by forced swim test. However, inhibition of brain IL-1 signaling has no effect on mechanical allodynia. In addition, intracerebroventricular administration of the KMO inhibitor Ro 61-8048 abrogated depression-like behavior without affecting mechanical allodynia after SNI. We show for the first time that the development of depression-like behavior in the SNI model requires brain IL-1 signaling and activation of neuronal KMO, while pain is independent of this pathway. Inhibition of KMO may represent a promising target for treating depression. Copyright © 2017 Elsevier Inc. All rights reserved.

Modeling Brain Dynamics in Brain Tumor Patients Using the Virtual Brain.

PubMed

Aerts, Hannelore; Schirner, Michael; Jeurissen, Ben; Van Roost, Dirk; Achten, Eric; Ritter, Petra; Marinazzo, Daniele

2018-01-01

Presurgical planning for brain tumor resection aims at delineating eloquent tissue in the vicinity of the lesion to spare during surgery. To this end, noninvasive neuroimaging techniques such as functional MRI and diffusion-weighted imaging fiber tracking are currently employed. However, taking into account this information is often still insufficient, as the complex nonlinear dynamics of the brain impede straightforward prediction of functional outcome after surgical intervention. Large-scale brain network modeling carries the potential to bridge this gap by integrating neuroimaging data with biophysically based models to predict collective brain dynamics. As a first step in this direction, an appropriate computational model has to be selected, after which suitable model parameter values have to be determined. To this end, we simulated large-scale brain dynamics in 25 human brain tumor patients and 11 human control participants using The Virtual Brain, an open-source neuroinformatics platform. Local and global model parameters of the Reduced Wong-Wang model were individually optimized and compared between brain tumor patients and control subjects. In addition, the relationship between model parameters and structural network topology and cognitive performance was assessed. Results showed (1) significantly improved prediction accuracy of individual functional connectivity when using individually optimized model parameters; (2) local model parameters that can differentiate between regions directly affected by a tumor, regions distant from a tumor, and regions in a healthy brain; and (3) interesting associations between individually optimized model parameters and structural network topology and cognitive performance.

Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis.

PubMed

Nielsen, Suzanne; Sabioni, Pamela; Trigo, Jose M; Ware, Mark A; Betz-Stablein, Brigid D; Murnion, Bridin; Lintzeris, Nicholas; Khor, Kok Eng; Farrell, Michael; Smith, Andrew; Le Foll, Bernard

2017-08-01

Cannabinoids, when co-administered with opioids, may enable reduced opioid doses without loss of analgesic efficacy (ie, an opioid-sparing effect). The aim of this study was to conduct a systematic review to determine the opioid-sparing potential of cannabinoids. Eligible studies included pre-clinical and clinical studies for which the outcome was either analgesia or opioid dose requirements. Clinical studies included controlled studies and case series. We searched Scopus, Cochrane Database of Systematic Reviews, Medline, and Embase. Nineteen pre-clinical and nine clinical studies met the search criteria. Seventeen of the 19 pre-clinical studies provided evidence of synergistic effects from opioid and cannabinoid co-administration. Our meta-analysis of pre-clinical studies indicated that the median effective dose (ED 50 ) of morphine administered in combination with delta-9-tetrahydrocannabinol (delta-9-THC) is 3.6 times lower (95% confidence interval (CI) 1.95, 6.76; n=6) than the ED 50 of morphine alone. In addition, the ED 50 for codeine administered in combination with delta-9-THC was 9.5 times lower (95% CI 1.6, 57.5, n=2) than the ED 50 of codeine alone. One case series (n=3) provided very-low-quality evidence of a reduction in opioid requirements with cannabinoid co-administration. Larger controlled clinical studies showed some clinical benefits of cannabinoids; however, opioid dose changes were rarely reported and mixed findings were observed for analgesia. In summary, pre-clinical studies provide robust evidence of the opioid-sparing effect of cannabinoids, whereas one of the nine clinical studies identified provided very-low-quality evidence of such an effect. Prospective high-quality-controlled clinical trials are required to determine the opioid-sparing effect of cannabinoids.

Blindness, dancing extremities, and corpus callosum and brain stem involvement: an unusual presentation of fulminant subacute sclerosing panencephalitis.

PubMed

Singhi, Pratibha; Saini, Arushi Gahlot; Sankhyan, Naveen; Gupta, Pankaj; Vyas, Sameer

2015-01-01

A 4-year-old girl presented with acute visual loss followed 2 weeks later with loss of speech and audition, fulminant neuroregression, and choreo-athetoid movements of extremities. Fundus showed bilateral chorioretinitis. Electroencephalography showed periodic complexes. Measles antibody titers were elevated in both serum and cerebrospinal fluid, consistent with subacute sclerosing panencephalitis. Neuroimaging showed discontiguous involvement of splenium of the corpus callosum and ventral pons with sparing of cortical white matter. Our case highlights the atypical clinical and radiologic presentations of subacute sclerosing panencephalitis. Pediatricians need to be aware that necrotizing chorioretinitis in a child and/or atypical brain stem changes could be the heralding feature of this condition in endemic countries. © The Author(s) 2014.

Selective Androgen Receptor Modulator RAD140 Is Neuroprotective in Cultured Neurons and Kainate-Lesioned Male Rats

PubMed Central

Jayaraman, Anusha; Christensen, Amy; Moser, V. Alexandra; Vest, Rebekah S.; Miller, Chris P.; Hattersley, Gary

2014-01-01

The decline in testosterone levels in men during normal aging increases risks of dysfunction and disease in androgen-responsive tissues, including brain. The use of testosterone therapy has the potential to increase the risks for developing prostate cancer and or accelerating its progression. To overcome this limitation, novel compounds termed “selective androgen receptor modulators” (SARMs) have been developed that lack significant androgen action in prostate but exert agonist effects in select androgen-responsive tissues. The efficacy of SARMs in brain is largely unknown. In this study, we investigate the SARM RAD140 in cultured rat neurons and male rat brain for its ability to provide neuroprotection, an important neural action of endogenous androgens that is relevant to neural health and resilience to neurodegenerative diseases. In cultured hippocampal neurons, RAD140 was as effective as testosterone in reducing cell death induced by apoptotic insults. Mechanistically, RAD140 neuroprotection was dependent upon MAPK signaling, as evidenced by elevation of ERK phosphorylation and inhibition of protection by the MAPK kinase inhibitor U0126. Importantly, RAD140 was also neuroprotective in vivo using the rat kainate lesion model. In experiments with gonadectomized, adult male rats, RAD140 was shown to exhibit peripheral tissue-specific androgen action that largely spared prostate, neural efficacy as demonstrated by activation of androgenic gene regulation effects, and neuroprotection of hippocampal neurons against cell death caused by systemic administration of the excitotoxin kainate. These novel findings demonstrate initial preclinical efficacy of a SARM in neuroprotective actions relevant to Alzheimer's disease and related neurodegenerative diseases. PMID:24428527

Neural correlates of motor recovery after stroke: a longitudinal fMRI study

PubMed Central

Ward, N. S.; Brown, M. M.; Thompson, A. J.; Frackowiak, R. S. J.

2013-01-01

Summary Recovery of motor function after stroke may occur over weeks or months and is often attributed to cerebral reorganization. We have investigated the longitudinal relationship between recovery after stroke and task-related brain activation during a motor task as measured using functional MRI (fMRI). Eight first-ever stroke patients presenting with hemiparesis resulting from cerebral infarction sparing the primary motor cortex, and four control subjects were recruited. Subjects were scanned on a number of occasions whilst performing an isometric dynamic visually paced hand grip task. Recovery in the patient group was assessed using a battery of outcome measures at each time point. Task-related brain activations decreased over sessions as a function of recovery in a number of primary and non-primary motor regions in all patients, but no session effects were seen in the controls. Furthermore, consistent decreases across sessions correlating with recovery were seen across the whole patient group independent of rate of recovery or initial severity, in primary motor cortex, premotor and prefrontal cortex, supplementary motor areas, cingulate sulcus, temporal lobe, striate cortex, cerebellum, thalamus and basal ganglia. Although recovery-related increases were seen in different brain regions in four patients, there were no consistent effects across the group. These results further our understanding of the recovery process by demonstrating for the first time a clear temporal relationship between recovery and task-related activation of the motor system after stroke. PMID:12937084

Lomustine Nanoparticles Enable Both Bone Marrow Sparing and High Brain Drug Levels - A Strategy for Brain Cancer Treatments.

PubMed

Fisusi, Funmilola A; Siew, Adeline; Chooi, Kar Wai; Okubanjo, Omotunde; Garrett, Natalie; Lalatsa, Katerina; Serrano, Dolores; Summers, Ian; Moger, Julian; Stapleton, Paul; Satchi-Fainaro, Ronit; Schätzlein, Andreas G; Uchegbu, Ijeoma F

2016-05-01

The blood brain barrier compromises glioblastoma chemotherapy. However high blood concentrations of lipophilic, alkylating drugs result in brain uptake, but cause myelosuppression. We hypothesised that nanoparticles could achieve therapeutic brain concentrations without dose-limiting myelosuppression. Mice were dosed with either intravenous lomustine Molecular Envelope Technology (MET) nanoparticles (13 mg kg(-1)) or ethanolic lomustine (6.5 mg kg(-1)) and tissues analysed. Efficacy was assessed in an orthotopic U-87 MG glioblastoma model, following intravenous MET lomustine (daily 13 mg kg(-1)) or ethanolic lomustine (daily 1.2 mg kg(-1) - the highest repeated dose possible). Myelosuppression and MET particle macrophage uptake were also investigated. The MET formulation resulted in modest brain targeting (brain/ bone AUC0-4h ratios for MET and ethanolic lomustine = 0.90 and 0.53 respectively and brain/ liver AUC0-4h ratios for MET and ethanolic lomustine = 0.24 and 0.15 respectively). The MET formulation significantly increased mice (U-87 MG tumours) survival times; with MET lomustine, ethanolic lomustine and untreated mean survival times of 33.2, 22.5 and 21.3 days respectively and there were no material treatment-related differences in blood and femoral cell counts. Macrophage uptake is slower for MET nanoparticles than for liposomes. Particulate drug formulations improved brain tumour therapy without major bone marrow toxicity.

Photodynamic therapy in the treatment of brain tumours. A feasibility study.

PubMed

Vanaclocha, Vicente; Sureda, Manuel; Azinovic, Ignacio; Rebollo, Joseba; Cañón, Rosa; Sapena, Nieves Saiz; Cases, Francisco García; Brugarolas, Antonio

2015-09-01

Photodynamic therapy (PDT) constitutes a treatment modality that combines a photosensitizing agent with exposure to laser light in order to elicit phototoxic reactions that selectively destroy tumor cells and spare normal cells. PDT is a local treatment modality without long-term systemic effects. Its application can be repeated more than once to the same area without accumulative effects. Patients diagnosed with primary brain tumors were treated with PDT. Treatment consisted in administration of the photosensitizer followed by craniotomy, surgical resection and laser illumination of the surgical bed. Primary brain tumors received also temozolomide-based chemotherapy and radiotherapy (RT). From May 2000 to December 2010, 41 patients (27 male, 14 female) with a median age of 49 years (range 13-70) diagnosed of primary brain tumors were included in the study. In 7 patients PDT was repeated at the time of the relapse. In 22 episodes PDT was part of the initial treatment of primary brain tumors and in 26 episodes was part of the treatment at relapse. Median PFS observed was 10 months for GBM (95% confidence interval 5.7-14.3), 26 months for AA (95% CI 4.5-47.5), and 43 months for OD (95% CI 4.5-47.5). Median OS was 9 months for GBM (95% CI 2.3-15.7), 20 months for AA (95% CI 0.0-59) and 50 months for OD (95% CI 32.5-67.5). The apparent discrepancy between PFS and OS data is due to patients not censored for PFS because they die from causes other than tumor progression. Median OS since first diagnosis was 17 months for GBM (95% CI 15.2-17.8), 66 months for AA (95% CI 2.9-129.1) and 122 months for OD (95% CI 116.1-127.8). Side effects were mild and manageable. This study confirms that PDT can be considered as an adjunctive to surgery and/or RT and chemotherapy in the treatment of brain tumors, excluding those patients with thalamic or brain stem locations. It adds therapeutic effect without adding significant toxicity. In order to improve its contribution, it is essential to find new drugs with more penetration in order to destroy tumor cells more deeply at resection margins. Copyright © 2015 Elsevier B.V. All rights reserved.

Brain lactate metabolism: the discoveries and the controversies

PubMed Central

Dienel, Gerald A

2012-01-01

Potential roles for lactate in the energetics of brain activation have changed radically during the past three decades, shifting from waste product to supplemental fuel and signaling molecule. Current models for lactate transport and metabolism involving cellular responses to excitatory neurotransmission are highly debated, owing, in part, to discordant results obtained in different experimental systems and conditions. Major conclusions drawn from tabular data summarizing results obtained in many laboratories are as follows: Glutamate-stimulated glycolysis is not an inherent property of all astrocyte cultures. Synaptosomes from the adult brain and many preparations of cultured neurons have high capacities to increase glucose transport, glycolysis, and glucose-supported respiration, and pathway rates are stimulated by glutamate and compounds that enhance metabolic demand. Lactate accumulation in activated tissue is a minor fraction of glucose metabolized and does not reflect pathway fluxes. Brain activation in subjects with low plasma lactate causes outward, brain-to-blood lactate gradients, and lactate is quickly released in substantial amounts. Lactate utilization by the adult brain increases during lactate infusions and strenuous exercise that markedly increase blood lactate levels. Lactate can be an ‘opportunistic', glucose-sparing substrate when present in high amounts, but most evidence supports glucose as the major fuel for normal, activated brain. PMID:22186669

Assessing the clinical effect of residual cortical disconnection after ischemic strokes.

PubMed

Bonilha, Leonardo; Rorden, Chris; Fridriksson, Julius

2014-04-01

Studies assessing the relationship between chronic poststroke language impairment (aphasia) and ischemic brain damage usually rely on measuring the extent of brain necrosis observed on MRI. Nonetheless, clinical observation suggests that patients can exhibit deficits that are more severe than what would be expected based on lesion location and size. This phenomenon is commonly explained as being the result of cortical disconnection. To understand whether disconnection contributes to clinical symptoms, we assessed the relationship between language impairments and structural brain connectivity (the connectome) in patients with chronic aphasia after a stroke. Thirty-nine patients with chronic aphasia underwent language assessment and MRI scanning. Relying on MRI data, we reconstructed the individual connectome from T1-weighted and diffusion tensor imaging. Deterministic fiber tractography was used to assess connectivity between each possible pair of cortical Brodmann areas. Multiple linear regression analyses were performed to evaluate the relationship between language performance and cortical necrosis and cortical disconnection. We observed that structural disconnection of Brodmann area 45 (spared by the necrotic tissue) was independently associated with naming performance, controlling for the extent of Brodmann area 45 necrosis (F=4.62; P<0.01; necrosis: β=0.43; P=0.03; disconnection β=1.21; P<0.001). We suggest that cortical disconnection, as measured by the structural connectome, is an independent predictor of naming impairment in patients with chronic aphasia. The full extent of clinically relevant brain damage after an ischemic stroke may be underappreciated by visual inspection of cortical necrosis alone.

Supine craniospinal irradiation in pediatric patients by proton pencil beam scanning.

PubMed

Farace, Paolo; Bizzocchi, Nicola; Righetto, Roberto; Fellin, Francesco; Fracchiolla, Francesco; Lorentini, Stefano; Widesott, Lamberto; Algranati, Carlo; Rombi, Barbara; Vennarini, Sabina; Amichetti, Maurizio; Schwarz, Marco

2017-04-01

Proton therapy is the emerging treatment modality for craniospinal irradiation (CSI) in pediatric patients. Herein, special methods adopted for CSI at proton Therapy Center of Trento by pencil beam scanning (PBS) are comprehensively described. Twelve pediatric patients were treated by proton PBS using two/three isocenters. Special methods refer to: (i) patient positioning in supine position on immobilization devices crossed by the beams; (ii) planning field-junctions via the ancillary-beam technique; (iii) achieving lens-sparing by three-beams whole-brain-irradiation; (iv) applying a movable-snout and beam-splitting technique to reduce the lateral penumbra. Patient-specific quality assurance (QA) program was performed using two-dimensional ion chamber array and γ-analysis. Daily kilovoltage alignment was performed. PBS allowed to obtain optimal target coverage (mean D98%>98%) with reduced dose to organs-at-risk. Lens sparing was obtained (mean D1∼730cGyE). Reducing lateral penumbra decreased the dose to the kidneys (mean Dmean<600cGyE). After kilovoltage alignment, potential dose deviations in the upper and lower junctions were small (average 0.8% and 1.2% respectively). Due to imperfect modeling of range shifter, QA showed better agreements between measurements and calculations at depths >4cm (mean γ>95%) than at depths<4cm. The reported methods allowed to effectively perform proton PBS CSI. Copyright © 2017 Elsevier B.V. All rights reserved.

[The left central gyral lesion and pure anarthria].

PubMed

Tabuchi, M; Odashima, K; Fujii, T; Suzuki, K; Saitou, J; Yamadori, A

2000-05-01

We report a very rare case of pure anarthria with lesion analysis. A 44-year-old right-handed man suffered from a cerebral infarction with a mild right hemiparesis and speech disturbance. An MRI of the brain 1.5 months post onset revealed a lesion confined to the left central gyrus. One month after the onset, his spontaneous speech was dysprosodic and laborious. It was contaminated with dysarthria and phonological paraphasias. However, language comprehension, repetition and naming abilities were normal. Most remarkably he showed no impairment in writing with his left hand. Over the following months, his difficulties in verbal output showed general amelioration, but the isolated impairment in the domain of articulation characterized by dysprosody, dysarthria, and phonological paraphasia persisted. As for the symptomatology of pure anarthria resulting from precentral gyral lesions, there have been controversies about its pureness. Some argue that the so called pure anarthria always shows some degree of writing disturbances, albeit mild in degree. Others maintain there certainly exists the pure type without any signs of agraphia. In the present case lesions were limited to the central gyrus but spared the lowest opercular portion. The previous reports of pure anarthria that had mild agraphia all had lesions involving the opercular portion. We conclude the sparing of this area is most likely related with sparing of writing capacity in pure anarthria.

Evolution in Monitoring of Free Flap Autologous Breast Reconstruction after Nipple-Sparing Mastectomy: Is There a Best Way?

PubMed

Frey, Jordan D; Stranix, John T; Chiodo, Michael V; Alperovich, Michael; Ahn, Christina Y; Allen, Robert J; Choi, Mihye; Karp, Nolan S; Levine, Jamie P

2018-05-01

Free flap monitoring in autologous reconstruction after nipple-sparing mastectomy remains controversial. The authors therefore examined outcomes in nipple-sparing mastectomy with buried free flap reconstruction versus free flap reconstruction incorporating a monitoring skin paddle. Autologous free flap reconstructions with nipple-sparing mastectomy performed from 2006 to 2015 were identified. Demographics and operative results were analyzed and compared between buried flaps and those with a skin paddle for monitoring. Two hundred twenty-one free flaps for nipple-sparing mastectomy reconstruction were identified: 50 buried flaps and 171 flaps incorporating a skin paddle. The most common flaps used were deep inferior epigastric perforator (64 percent), profunda artery perforator (12.1 percent), and muscle-sparing transverse rectus abdominis myocutaneous flaps (10.4 percent). Patients undergoing autologous reconstructions with a skin paddle had a significantly greater body mass index (p = 0.006). Mastectomy weight (p = 0.017) and flap weight (p < 0.0001) were significantly greater in flaps incorporating a skin paddle. Comparing outcomes, there were no significant differences in flap failure (2.0 percent versus 2.3 percent; p = 1.000) or percentage of flaps requiring return to the operating room (6.0 percent versus 4.7 percent; p = 0.715) between groups. Buried flaps had an absolute greater mean number of revision procedures per nipple-sparing mastectomy (0.82) compared with the skin paddle group (0.44); however, rates of revision procedures per nipple-sparing mastectomy were statistically equivalent between the groups (p = 0.296). Although buried free flap reconstruction in nipple-sparing mastectomy has been shown to be safe and effective, the authors' technique has evolved to favor incorporating a skin paddle, which allows for clinical monitoring and can be removed at the time of secondary revision. Therapeutic, III.

Dexamethasone Attenuates the Enhanced Rewarding Effects of Cocaine Following Experimental Traumatic Brain Injury.

PubMed

Merkel, Steven F; Andrews, Allison M; Lutton, Evan M; Razmpour, Roshanak; Cannella, Lee Anne; Ramirez, Servio H

2017-07-01

Clinical studies have identified traumatic brain injury (TBI) as a risk factor for the development of cocaine dependence. This claim is supported by our recent preclinical studies showing enhancement of the rewarding effects of cocaine in mice sustaining moderate controlled cortical impact (CCI) injury during adolescence. Here we test the efficacy of dexamethasone, an anti-inflammatory corticosteroid, to attenuate augmentation of the behavioral response to cocaine observed in CCI-TBI animals using the conditioned place preference (CPP) assay. These studies were performed in order to determine whether proinflammatory activity in the nucleus accumbens (NAc), a key brain nucleus in the reward pathway, mediates enhanced cocaine-induced CPP in adolescent animals sustaining moderate CCI-TBI. Our data reveal robust glial activation in the NAc following CCI-TBI and a significant increase in the cocaine-induced CPP of untreated CCI-TBI mice. Furthermore, our results show that dexamethasone treatment following CCI-TBI can attenuate the cocaine place preference of injured animals without producing aversion in the CPP assay. Our studies also found that dexamethasone treatment significantly reduced the expression of select immune response genes including Monocyte chemoattractant protein-1 (MCP-1/CCL2) and intercellular adhesion molecule-1 ( ICAM-1), returning their expression to control levels, which prompted an investigation of peripheral blood monocytes in dexamethasone-treated animals. Experimental findings showed that no craniectomy/dexamethasone mice had a significant increase, while CCI-TBI/dexamethasone animals had a significant decrease in the percentage of circulating nonclassical patrolling monocytes. These results suggest that a portion of these monocytes may migrate to the brain in response to CCI-TBI, potentially sparing the development of chronic neuroinflammation in regions associated with the reward circuitry such as the NAc. Overall, our findings indicate that anti-inflammatory agents, such as dexamethasone, may be effective in normalizing the rewarding effects of cocaine following CCI-TBI.

Mere exposure effect can be elicited in transient global amnesia.

PubMed

Marin-Garcia, Eugenia; Ruiz-Vargas, Jose M; Kapur, Narinder

2013-01-01

Transient global amnesia (TGA) is one of the most severe forms of anterograde amnesia seen in clinical practice, yet patients may show evidence of spared learning during the amnesic episode. The scope of spared learning in such a severe form of amnesia remains uncertain, and it is also unclear whether findings from single-case studies hold up in group studies of TGA patients. In this group study, we found evidence that extended the domain of spared learning in TGA to include the mere exposure effect, whereby enhanced preference is primed by prior exposure to stimuli. We demonstrate this effect during an acute episode in a group of TGA patients, where they showed enhanced preference for previously exposed faces, despite markedly impaired performance on standard anterograde memory tests.

MRI findings in eastern equine encephalitis: the "parenthesis" sign.

PubMed

Nickerson, Joshua P; Kannabiran, Suma; Burbank, Heather N

2016-01-01

Two patients with eastern equine encephalitis (EEE) presented to a tertiary referral center. Both subjects' brain magnetic resonance imaging showed T2/FLAIR (fluid-attenuated inversion recovery) hyperintensities including linear areas of hyperintensity in the external and internal capsules with sparing of the lentiform nuclei. Single case reports of imaging findings in EEE exist with nonspecific patterns of abnormality. We propose that this "( ) parentheses sign" on T2 or FLAIR imaging may distinguish EEE from other processes. Copyright © 2015 Elsevier Inc. All rights reserved.

Fluorodeoxyglucose /sup 18/F scan in Alzheimer's disease and multi-infarct dementia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benson, D.F.; Kuhl, D.E.; Hawkins, R.A.

1983-11-01

Patients with Alzheimer's disease and multi-infarct dementia were studied with scans using fluorodeoxyglucose tagged with fluorine 18. The rates of glucose metabolism were calculated. Patients with Alzheimer's dementia showed decreased metabolism in all areas of the brain but with preferential sparing of the primary motor and sensory cortex. Patients with multi-infarct dementia also had global reductions in glucose metabolic rates when compared with normal control subjects, but the areas of hypometabolism were focal and asymmetric.

Comparison of WBRT alone, SRS alone, and their combination in the treatment of one or more brain metastases: Review and meta-analysis.

PubMed

Khan, Muhammad; Lin, Jie; Liao, Guixiang; Li, Rong; Wang, Baiyao; Xie, Guozhu; Zheng, Jieling; Yuan, Yawei

2017-07-01

Whole brain radiotherapy has been a standard treatment of brain metastases. Stereotactic radiosurgery provides more focal and aggressive radiation and normal tissue sparing but worse local and distant control. This meta-analysis was performed to assess and compare the effectiveness of whole brain radiotherapy alone, stereotactic radiosurgery alone, and their combination in the treatment of brain metastases based on randomized controlled trial studies. Electronic databases (PubMed, MEDLINE, Embase, and Cochrane Library) were searched to identify randomized controlled trial studies that compared treatment outcome of whole brain radiotherapy and stereotactic radiosurgery. This meta-analysis was performed using the Review Manager (RevMan) software (version 5.2) that is provided by the Cochrane Collaboration. The data used were hazard ratios with 95% confidence intervals calculated for time-to-event data extracted from survival curves and local tumor control rate curves. Odds ratio with 95% confidence intervals were calculated for dichotomous data, while mean differences with 95% confidence intervals were calculated for continuous data. Fixed-effects or random-effects models were adopted according to heterogeneity. Five studies (n = 763) were included in this meta-analysis meeting the inclusion criteria. All the included studies were randomized controlled trials. The sample size ranged from 27 to 331. In total 202 (26%) patients with whole brain radiotherapy alone, 196 (26%) patients receiving stereotactic radiosurgery alone, and 365 (48%) patients were in whole brain radiotherapy plus stereotactic radiosurgery group. No significant survival benefit was observed for any treatment approach; hazard ratio was 1.19 (95% confidence interval: 0.96-1.43, p = 0.12) based on three randomized controlled trials for whole brain radiotherapy only compared to whole brain radiotherapy plus stereotactic radiosurgery and hazard ratio was 1.03 (95% confidence interval: 0.82-1.29, p = 0.81) for stereotactic radiosurgery only compared to combined approach. Local control was best achieved when whole brain radiotherapy was combined with stereotactic radiosurgery. Hazard ratio 2.05 (95% confidence interval: 1.36-3.09, p = 0.0006) and hazard ratio 1.84 (95% confidence interval: 1.26-2.70, p = 0.002) were obtained from comparing whole brain radiotherapy only and stereotactic radiosurgery only to whole brain radiotherapy + stereotactic radiosurgery, respectively. No difference in adverse events for treatment difference; odds ratio 1.16 (95% confidence interval: 0.77-1.76, p = 0.48) and odds ratio 0.92 (95% confidence interval: 0.59-1.42, p = 71) for whole brain radiotherapy + stereotactic radiosurgery versus whole brain radiotherapy only and whole brain radiotherapy + stereotactic radiosurgery versus stereotactic radiosurgery only, respectively. Adding stereotactic radiosurgery to whole brain radiotherapy provides better local control as compared to whole brain radiotherapy only and stereotactic radiosurgery only with no difference in radiation related toxicities.

Effect of two different doses of intravitreal bevacizumab with temporal retina-sparing laser photocoagulation for retinopathy of prematurity.

PubMed

Choi, A Young; Cho, Hochan; Kim, Yu Cheol

2018-01-01

This study aims to compare the efficacy and safety between two different doses of intravitreal bevacizumab (IVB) injection with temporal retina-sparing laser (TRSL) photocoagulation for retinopathy of prematurity (ROP). We retrospectively evaluated 22 eyes of ROP infants who underwent IVB combined with partial TRSL for stage 3+ zone I or posterior zone II ROP. Laser photocoagulation was applied on the avascular retina, sparing two-disc-diameter width temporal avascular area anterior to ridge. A half dose (0.625 mg) or minimal dose (0.25 mg) of IVB was conducted. Four eyes in minimal dose group were retreated with IVB and laser photocoagulation on the spared retina. Of those 4 retreated eyes, three developed preretinal hemorrhage around the ridge after the first treatment, resulting in fibrotic macular dragging. A half dose of IVB may be more effective than a minimal dose with partial TRSL for ROP. Preretinal hemorrhage may be a harbinger of poor prognosis.

SU-E-T-615: Plan Comparison Between Photon IMRT and Proton Plans Incorporating Uncertainty Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, C; Wessels, B; Jesseph, F

2015-06-15

Purpose: In this study, we investigate the effect of setup uncertainty on DVH calculations which may impact plan comparison. Methods: Treatment plans (6 MV VMAT calculated on Pinnacle TPS) were chosen for different disease sites: brain, prostate, H&N and spine in this retrospective study. A proton plan (PP) using double scattering beams was generated for each selected VMAT plan subject to the same set of dose-volume constraints as in VMAT. An uncertainty analysis was incorporated on the DVH calculations in which isocenter shifts from 1 to 5 mm in each of the ±x, ±y and ±z directions were used tomore » simulate the setup uncertainty and residual positioning errors. A total of 40 different combinations of isocenter shifts were used in the re-calculation of DVH of the PTV and the various OARs for both the VMAT and the corresponding PT. Results: For the brain case, both VMAT and PP are comparable in PTV coverage and OAR sparing, and VMAT is a clear choice for treatment due to its ease of delivery. However, when incorporating isoshifts in DVH calculations, a significant change in dose-volume relationship emerges. For example, both VMAT and PT provide adequate coverage, even with ±3mm isoshift. However, +3mm isoshift results in increase of V40(Lcochlea, VMAT) from 7.2% in the original plan to 45% and V40(R cochlea, VMAT) from 75% to 92%. For protons, V40(Lcochlea, PT) increases from 62% in the initial plan to 75%, while V40(Rcochea, PT) increases from 7% to 26%. Conclusion: DVH alone may not be sufficient to allow an unequivocal decision in plan comparison, especially when two rival plans are very similar in both PTV coverage and OAR sparing. It is a good practice to incorporate uncertainty analysis on photon and proton plan comparison studies to test the plan robustness in plan evaluation.« less

Characterization and quantification of cerebral edema induced by synchrotron x-ray microbeam radiation therapy

NASA Astrophysics Data System (ADS)

Serduc, Raphaël; van de Looij, Yohan; Francony, Gilles; Verdonck, Olivier; van der Sanden, Boudewijn; Laissue, Jean; Farion, Régine; Bräuer-Krisch, Elke; Siegbahn, Erik Albert; Bravin, Alberto; Prezado, Yolanda; Segebarth, Christoph; Rémy, Chantal; Lahrech, Hana

2008-03-01

Cerebral edema is one of the main acute complications arising after irradiation of brain tumors. Microbeam radiation therapy (MRT), an innovative experimental radiotherapy technique using spatially fractionated synchrotron x-rays, has been shown to spare radiosensitive tissues such as mammal brains. The aim of this study was to determine if cerebral edema occurs after MRT using diffusion-weighted MRI and microgravimetry. Prone Swiss nude mice's heads were positioned horizontally in the synchrotron x-ray beam and the upper part of the left hemisphere was irradiated in the antero-posterior direction by an array of 18 planar microbeams (25 mm wide, on-center spacing 211 mm, height 4 mm, entrance dose 312 Gy or 1000 Gy). An apparent diffusion coefficient (ADC) was measured at 7 T 1, 7, 14, 21 and 28 days after irradiation. Eventually, the cerebral water content (CWC) was determined by microgravimetry. The ADC and CWC in the irradiated (312 Gy or 1000 Gy) and in the contralateral non-irradiated hemispheres were not significantly different at all measurement times, with two exceptions: (1) a 9% ADC decrease (p < 0.05) was observed in the irradiated cortex 1 day after exposure to 312 Gy, (2) a 0.7% increase (p < 0.05) in the CWC was measured in the irradiated hemispheres 1 day after exposure to 1000 Gy. The results demonstrate the presence of a minor and transient cellular edema (ADC decrease) at 1 day after a 312 Gy exposure, without a significant CWC increase. One day after a 1000 Gy exposure, the CWC increased, while the ADC remained unchanged and may reflect the simultaneous presence of cellular and vasogenic edema. Both types of edema disappear within a week after microbeam exposure which may confirm the normal tissue sparing effect of MRT. For more information on this article, see medicalphysicsweb.org

Optimization of Craniospinal Irradiation for Pediatric Medulloblastoma Using VMAT and IMRT.

PubMed

Al-Wassia, Rolina K; Ghassal, Noor M; Naga, Adly; Awad, Nesreen A; Bahadur, Yasir A; Constantinescu, Camelia

2015-10-01

Intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) provide highly conformal target radiation doses, but also expose large volumes of healthy tissue to low-dose radiation. With improving survival, more children with medulloblastoma (MB) are at risk of late adverse effects of radiotherapy, including secondary cancers. We evaluated the characteristics of IMRT and VMAT craniospinal irradiation treatment plans in children with standard-risk MB to compare radiation dose delivery to target organs and organs at risk (OAR). Each of 10 children with standard-risk MB underwent both IMRT and VMAT treatment planning. Dose calculations used inverse planning optimization with a craniospinal dose of 23.4 Gy followed by a posterior fossa boost to 55.8 Gy. Clinical and planning target volumes were demarcated on axial computed tomography images. Dose distributions to target organs and OAR for each planning technique were measured and compared with published dose-volume toxicity data for pediatric patients. All patients completed treatment planning for both techniques. Analyses and comparisons of dose distributions and dose-volume histograms for the planned target volumes, and dose delivery to the OAR for each technique demonstrated the following: (1) VMAT had a modest, but significantly better, planning target volume-dose coverage and homogeneity compared with IMRT; (2) there were different OAR dose-sparing profiles for IMRT versus VMAT; and (3) neither IMRT nor VMAT demonstrated dose reductions to the published pediatric dose limits for the eyes, the lens, the cochlea, the pituitary, and the brain. The use of both IMRT and VMAT provides good target tissue coverage and sparing of the adjacent tissue for MB. Both techniques resulted in OAR dose delivery within published pediatric dose guidelines, except those mentioned above. Pediatric patients with standard-risk MB remain at risk for late endocrinologic, sensory (auditory and visual), and brain functional impairments.

Brain effect of insulin and clonazepam in diabetic rats under depressive-like behavior.

PubMed

Wayhs, Carlos Alberto Yasin; Mescka, Caroline Paula; Vanzin, Camila Simioni; Ribas, Graziela Schmitt; Guerreiro, Gilian; Nin, Maurício Schüler; Manfredini, Vanusa; Barros, Helena Maria Tannhauser; Vargas, Carmen Regla

2013-12-01

Diabetes mellitus is characterized by hyperglycemia resulting from defects on insulin secretion, insulin action, or both. It has recently become clear that the central nervous system is not spared from the deleterious effects of diabetes, since diabetic encephalopathy was recognized as a complication of this heterogeneous metabolic disorder. There is a well recognized association between depression and diabetes, once prevalence of depression in diabetic patients is higher than in general population, and clonazepam is being used to treat this complication. Oxidative stress is widely accepted as playing a key mediatory role in the development and progression of diabetes and its complications. In this work we analyzed DNA damage by comet assay and lipid damage in prefrontal cortex, hippocampus and striatum of streptozotocin-induced diabetic rats submitted to the forced swimming test. It was verified that the diabetic group presented DNA and lipid damage in the brain areas evaluated, when compared to the control groups. Additionally, a significant reduction of the DNA and lipid damage in animals treated with insulin and/or clonazepam was observed. These data suggest that the association of these two drugs could protect against DNA and lipid damage in diabetic rats submitted to the forced swimming test, an animal model of depression.

SU-E-T-13: A Comparative Dosimetric Study On Radio-Dynamic Therapy for Pelvic Cancer Treatment: Strategies for Bone Marrow Dose and Volume Reduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, C; Renmin Hospital of Wuhan University, Wuhan, Hubei Province; Wang, B

Purpose: Radio-dynamic therapy (RDT) is a potentially effective modality for local and systemic cancer treatment. Using RDT, the administration of a radio-sensitizer enhances the biological effect of high-energy photons. Although the sensitizer uptake ratio of tumor to normal tissue is normally high, one cannot simply neglect its effect on critical structures. In this study, we aim to explore planning strategies to improve bone marrow sparing without compromising the plan quality for RDT treatment of pelvic cancers. Methods: Ten cervical and ten prostate cancer patients who previously received radiotherapy at our institution were selected for this study. For each patient, ninemore » plans were created using the Varian Eclipse treatmentplanning-system (TPS) with 3D-CRT, IMRT, and VMAT delivery techniques containing various gantry angle combinations and optimization parameters (dose constraints to the bone marrow). To evaluate the plans for bone marrow sparing, the dose-volume parameters V5, V10, V15, V20, V30, and V40 for bone marrow were examined. Effective doseenhancement factors for the sensitizer were used to weigh the dose-volume histograms for various tissues from individual fractions. Results: The planning strategies had different impacts on bone marrow sparing for the cervical and prostate cases. For the cervical cases, provided the bone marrow constraints were properly set during optimization, the dose to bone marrow sparing was found to be comparable between different IMRT and VMAT plans regardless of the gantry angle selection. For the prostate cases, however, careful selection of gantry angles could dramatically improve the bone marrow sparing, although the dose distribution in bone marrow was clinically acceptable for all prostate plans that we created. Conclusion: For intensity-modulated RDT planning for cervical cancer, planners should set bone marrow constraints properly to avoid any adverse damage, while for prostate cancer one can carefully select gantry angles to improve bone marrow sparing when necessary.« less

Impact of Salivary Gland Dosimetry on Post-IMRT Recovery of Saliva Output and Xerostomia Grade for Head-and-Neck Cancer Patients Treated With or Without Contralateral Submandibular Gland Sparing: A Longitudinal Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Zhonghe; Yan Chao; Zhang Zhiyuan

Purpose: To observe the recovery of saliva output and effect on xerostomia grade after intensity-modulated radiotherapy (IMRT) with or without contralateral submandibular gland (cSMG) sparing and to assess the impact of salivary gland dosimetry on this recovery among patients with head-and-neck cancer. Methods and Materials: Between May 2007 and May 2008, 52 patients with head-and-neck cancer received definitive (n = 5 patients) and postoperative (n = 47 patients) IMRT at our institution, with at least one parotid gland spared. Of these patients, 26 patients with a low risk of recurrence in the cSMG region underwent IMRT and had their cSMGsmore » spared (cSMG-sparing group). The remaining 26 high-risk patients had no cSMGs spared (cSMG-unspared group). Xerostomia grades and salivary flow rates were monitored at five time points (before IMRT and at 2, 6, 12, and 18 months after IMRT). Results: Average mean doses and mean volumes receiving 30 Gy (V30) of the cSMGs were lower in the cSMG-sparing group than in the cSMG-unspared group (mean dose, 20.4 Gy vs. 57.4 Gy; mean V30, 14.7% vs. 99.8%, respectively). Xerostomia grades at 2 and 6 months post-IMRT were also significantly lower among patients in the cSMG-sparing group than in the cSMG-unspared group, but differences were not significant at 12 and 18 months after IMRT. Patients in the cSMG-sparing group had significantly better mean unstimulated salivary flow rates at each time point post- IMRT as well as better mean stimulated salivary flow rates at 2 months post-IMRT. Conclusions: Recovery of saliva output and grade of xerostomia post-IMRT in patients whose cSMGs were spared were much better than in patients whose cSMGs were not spared. The influence of the mean doses to the cSMG and parotid gland on the recovery of saliva output was equivalent to that of the mean V30 to the glands.« less

BDNF levels are increased by aminoindan and rasagiline in a double lesion model of Parkinson׳s disease.

PubMed

Ledreux, Aurélie; Boger, Heather A; Hinson, Vanessa K; Cantwell, Kelsey; Granholm, Ann-Charlotte

2016-01-15

The anti-Parkinsonian drug rasagiline is a selective, irreversible inhibitor of monoamine oxidase and is used in the treatment of Parkinson׳s disease (PD). Its postulated neuroprotective effects may be attributed to MAO inhibition, or to its propargylamine moiety. The major metabolite of rasagiline, aminoindan, has shown promising neuroprotective properties in vitro but there is a paucity of studies investigating in vivo effects of this compound. Therefore, we examined neuroprotective effects of rasagiline and its metabolite aminoindan in a double lesion model of PD. Male Fisher 344 rats received i.p. injections of the noradrenergic neurotoxin DSP-4 and intra-striatal stereotaxic microinjections of the dopamine neurotoxin 6-OHDA. Saline, rasagiline or aminoindan (3mg/kg/day s.c.) were delivered via Alzet minipumps for 4 weeks. Rats were then tested for spontaneous locomotion and a novel object recognition task. Following behavioral testing, brain tissue was processed for ELISA measurements of growth factors and immunohistochemistry. Double-lesioned rats treated with rasagiline or aminoindan had reduced behavioral deficits, both in motor and cognitive tasks compared to saline-treated double-lesioned rats. BDNF levels were significantly increased in the hippocampus and striatum of the rasagiline- and aminoindan-lesioned groups compared to the saline-treated lesioned group. Double-lesioned rats treated with rasagiline or aminoindan exhibited a sparing in the mitochondrial marker Hsp60, suggesting mitochondrial involvement in neuroprotection. Tyrosine hydroxylase (TH) immunohistochemistry revealed a sparing of TH-immunoreactive terminals in double-lesioned rats treated with rasagiline or aminoindan in the striatum, hippocampus, and substantia nigra. These data provide evidence of neuroprotection by aminoindan and rasagiline via their ability to enhance BDNF levels. Published by Elsevier B.V.

Comprehension of Idioms in Turkish Aphasic Participants.

PubMed

Aydin, Burcu; Barin, Muzaffer; Yagiz, Oktay

2017-12-01

Brain damaged participants offer an opportunity to evaluate the cognitive and linguistic processes and make assumptions about how the brain works. Cognitive linguists have been investigating the underlying mechanisms of idiom comprehension to unravel the ongoing debate on hemispheric specialization in figurative language comprehension. The aim of this study is to evaluate and compare the comprehension of idiomatic expressions in left brain damaged (LBD) aphasic, right brain damaged (RBD) and healthy control participants. Idiom comprehension in eleven LBD aphasic participants, ten RBD participants and eleven healthy control participants were assessed with three tasks: String to Picture Matching Task, Literal Sentence Comprehension Task and Oral Idiom Definition Task. The results of the tasks showed that in overall idiom comprehension category, the left brain-damaged aphasic participants interpret idioms more literally compared to right brain-damaged participants. What is more, there is a significant difference in opaque idiom comprehension implying that left brain-damaged aphasic participants perform worse compared to right brain-damaged participants. On the other hand, there is no statistically significant difference in scores of transparent idiom comprehension between the left brain-damaged aphasic and right brain-damaged participants. This result also contribute to the idea that while figurative processing system is damaged in LBD aphasics, the literal comprehension mechanism is spared to some extent. The results of this study support the view that idiom comprehension sites are mainly left lateralized. Furthermore, the results of this study are in consistence with the Giora's Graded Salience Hypothesis.

Cortical circuits for mathematical knowledge: evidence for a major subdivision within the brain's semantic networks.

PubMed

Amalric, Marie; Dehaene, Stanislas

2017-02-19

Is mathematical language similar to natural language? Are language areas used by mathematicians when they do mathematics? And does the brain comprise a generic semantic system that stores mathematical knowledge alongside knowledge of history, geography or famous people? Here, we refute those views by reviewing three functional MRI studies of the representation and manipulation of high-level mathematical knowledge in professional mathematicians. The results reveal that brain activity during professional mathematical reflection spares perisylvian language-related brain regions as well as temporal lobe areas classically involved in general semantic knowledge. Instead, mathematical reflection recycles bilateral intraparietal and ventral temporal regions involved in elementary number sense. Even simple fact retrieval, such as remembering that 'the sine function is periodical' or that 'London buses are red', activates dissociated areas for math versus non-math knowledge. Together with other fMRI and recent intracranial studies, our results indicated a major separation between two brain networks for mathematical and non-mathematical semantics, which goes a long way to explain a variety of facts in neuroimaging, neuropsychology and developmental disorders.This article is part of a discussion meeting issue 'The origins of numerical abilities'. © 2017 The Author(s).

Atrophy of spared gray matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke.

PubMed

Gauthier, Lynne V; Taub, Edward; Mark, Victor W; Barghi, Ameen; Uswatte, Gitendra

2012-02-01

Although the motor deficit after stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to constraint-induced movement therapy in patients with chronic stroke may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. Voxel-based morphometry analysis was performed on MRI scans from 80 patients with chronic stroke to investigate whether variations in gray matter density were correlated with extent of residual motor impairment or with constraint-induced movement therapy-induced motor recovery. Decreased gray matter density in noninfarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced gray matter density in multiple remote brain regions predicted a lesser extent of motor improvement from constraint-induced movement therapy. Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke.

Atrophy of spared grey matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke

PubMed Central

Gauthier, Lynne V.; Taub, Edward; Mark, Victor W.; Barghi, Ameen; Uswatte, Gitendra

2011-01-01

Background and Purpose Although the motor deficit following stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to Constraint-Induced Movement therapy (CI therapy) in chronic stroke patients may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. Methods Voxel-based morphometry (VBM) analysis was performed on MRI scans from 80 chronic stroke patients to investigate whether variations in grey matter density were correlated with extent of residual motor impairment or with CI therapy-induced motor recovery. Results Decreased grey matter density in non-infarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced grey matter density in multiple remote brain regions predicted a lesser extent of motor improvement from CI therapy. Conclusions Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke. PMID:22096036

The Influence of Exercise on Cognitive Abilities

PubMed Central

Gomez-Pinilla, Fernando; Hillman, Charles

2013-01-01

Scientific evidence based on neuroimaging approaches over the last decade has demonstrated the efficacy of physical activity improving cognitive health across the human lifespan. Aerobic fitness spares age-related loss of brain tissue during aging, and enhances functional aspects of higher order regions involved in the control of cognition. More active or higher fit individuals are capable of allocating greater attentional resources toward the environment and are able to process information more quickly. These data are suggestive that aerobic fitness enhances cognitive strategies enabling to respond effectively to an imposed challenge with a better yield in task performance. In turn, animal studies have shown that exercise has a benevolent action on health and plasticity of the nervous system. New evidence indicates that exercise exerts its effects on cognition by affecting molecular events related to the management of energy metabolism and synaptic plasticity. An important instigator in the molecular machinery stimulated by exercise is brain-derived neurotrophic factor, which acts at the interface of metabolism and plasticity. Recent studies show that exercise collaborates with other aspects of lifestyle to influence the molecular substrates of cognition. In particular, select dietary factors share similar mechanisms with exercise, and in some cases they can complement the action of exercise. Therefore, exercise and dietary management appear as a noninvasive and effective strategy to counteract neurological and cognitive disorders. PMID:23720292

Low GDP Solution and Glucose-Sparing Strategies for Peritoneal Dialysis.

PubMed

Szeto, Cheuk Chun; Johnson, David W

2017-01-01

Long-term exposure to a high glucose concentration in conventional peritoneal dialysis (PD) solution has a number of direct and indirect (via glucose degradation products [GDP]) detrimental effects on the peritoneal membrane, as well as systemic metabolism. Glucose- or GDP-sparing strategies often are hypothesized to confer clinical benefits to PD patients. Icodextrin (glucose polymer) solution improves peritoneal ultrafiltration and reduces the risk of fluid overload, but these beneficial effects are probably the result of better fluid removal rather than being glucose sparing. Although frequently used for glucose sparing, the role of amino acid-based solution in this regard has not been tested thoroughly. When glucose-free solutions are used in a combination regimen, published studies showed that glycemic control was improved significantly in diabetic PD patients, and there probably are beneficial effects on peritoneal function. However, the long-term effects of glucose-free solutions, used either alone or as a combination regimen, require further studies. On the other hand, neutral pH-low GDP fluids have been shown convincingly to preserve residual renal function and urine volume. The cost effectiveness of these solutions supports the regular use of neutral pH-low GDP solutions. Nevertheless, further studies are required to determine whether neutral pH-low GDP solutions exert beneficial effects on patient-level outcomes, such as peritonitis, technique survival, and patient survival. Copyright © 2017 Elsevier Inc. All rights reserved.

Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetry

NASA Astrophysics Data System (ADS)

Ateca-Cabarga, Juan C.; Cosa, Alejandro; Pallarés, Vicente; López-Atalaya, José P.; Barco, Ángel; Canals, Santiago; Moratal, David

2015-11-01

The Rubinstein-Taybi Syndrome (RSTS) is a congenital disease that affects brain development causing severe cognitive deficits. In most cases the disease is associated with dominant mutations in the gene encoding the CREB binding protein (CBP). In this work, we present the first quantitative analysis of brain abnormalities in a mouse model of RSTS using magnetic resonance imaging (MRI) and two novel self-developed automated algorithms for image volumetric analysis. Our results quantitatively confirm key syndromic features observed in RSTS patients, such as reductions in brain size (-16.31%, p < 0.05), white matter volume (-16.00%, p < 0.05), and corpus callosum (-12.40%, p < 0.05). Furthermore, they provide new insight into the developmental origin of the disease. By comparing brain tissues in a region by region basis between cbp+/- and cbp+/+ littermates, we found that cbp haploinsufficiency is specifically associated with significant reductions in prosencephalic tissue, such us in the olfactory bulb and neocortex, whereas regions evolved from the embryonic rhombencephalon were spared. Despite the large volume reductions, the proportion between gray-, white-matter and cerebrospinal fluid were conserved, suggesting a role of CBP in brain size regulation. The commonalities with holoprosencephaly and arhinencephaly conditions suggest the inclusion of RSTS in the family of neuronal migration disorders.

Magnetic resonance guided high-intensity focused ultrasound ablation of musculoskeletal tumors

PubMed Central

Avedian, Raffi S.; Gold, Garry; Ghanouni, Pejman; Pauly, Kim Butts

2015-01-01

This article reviews the fundamental principles and clinical experimental uses of magnetic resonance guided high-intensity focused ultrasound (MRgHIFU) ablation of musculoskeletal tumors. MRgHIFU is a noninvasive treatment modality that takes advantage of the ability of magnetic resonance to measure tissue temperature and uses this technology to guide high-intensity focused ultrasound waves to a specific focus within the human body that results in heat generation and complete thermal necrosis of the targeted tissue. Adjacent normal tissues are spared because of the accurate delivery of thermal energy, as well as, local blood perfusion that provides a cooling effect. MRgHIFU is approved by the Food and Drug Administration for the treatment of uterine fibroids and is used on an experimental basis to treat breast, prostate, liver, bone, and brain tumors. PMID:26120376

SU-E-T-558: Assessing the Effect of Inter-Fractional Motion in Esophageal Sparing Plans.

PubMed

Williamson, R; Bluett, J; Niedzielski, J; Liao, Z; Gomez, D; Court, L

2012-06-01

To compare esophageal dose distributions in esophageal sparing IMRT plans with predicted dose distributions which include the effect of inter-fraction motion. Seven lung cancer patients were used, each with a standard and an esophageal sparing plan (74Gy, 2Gy fractions). The average max dose to esophagus was 8351cGy and 7758cGy for the standard and sparing plans, respectively. The average length of esophagus for which the total circumference was treated above 60Gy (LETT60) was 9.4cm in the standard plans and 5.8cm in the sparing plans. In order to simulate inter-fractional motion, a three-dimensional rigid shift was applied to the calculated dose field. A simulated course of treatment consisted of a single systematic shift applied throughout the treatment as well a random shift for each of the 37 fractions. Both systematic and random shifts were generated from Gaussian distributions of 3mm and 5mm standard deviation. Each treatment course was simulated 1000 times to obtain an expected distribution of the delivered dose. Simulated treatment dose received by the esophagus was less than dose seen in the treatment plan. The average reduction in maximum esophageal dose for the standard plans was 234cGy and 386cGY for the 3mm and 5mm Gaussian distributions, respectively. The average reduction in LETT60 was 0.6cm and 1.7cm, for the 3mm and 5mm distributions respectively. For the esophageal sparing plans, the average reduction in maximum esophageal dose was 94cGy and 202cGy for 3mm and 5mm Gaussian distributions, respectively. The average change in LETT60 for the esophageal sparing plans was smaller, at 0.1cm (increase) and 0.6cm (reduction), for the 3mm and 5mm distributions, respectively. Interfraction motion consistently reduced the maximum doses to the esophagus for both standard and esophageal sparing plans. © 2012 American Association of Physicists in Medicine.

Nicotinamide nucleotide transhydrogenase (Nnt) links the substrate requirement in brain mitochondria for hydrogen peroxide removal to the thioredoxin/peroxiredoxin (Trx/Prx) system.

PubMed

Lopert, Pamela; Patel, Manisha

2014-05-30

Mitochondrial reactive oxygen species are implicated in the etiology of multiple neurodegenerative diseases, including Parkinson disease. Mitochondria are known to be net producers of ROS, but recently we have shown that brain mitochondria can consume mitochondrial hydrogen peroxide (H2O2) in a respiration-dependent manner predominantly by the thioredoxin/peroxiredoxin system. Here, we sought to determine the mechanism linking mitochondrial respiration with H2O2 catabolism in brain mitochondria and dopaminergic cells. We hypothesized that nicotinamide nucleotide transhydrogenase (Nnt), which utilizes the proton gradient to generate NADPH from NADH and NADP(+), provides the link between mitochondrial respiration and H2O2 detoxification through the thioredoxin/peroxiredoxin system. Pharmacological inhibition of Nnt in isolated brain mitochondria significantly decreased their ability to consume H2O2 in the presence, but not absence, of respiration substrates. Nnt inhibition in liver mitochondria, which do not require substrates to detoxify H2O2, had no effect. Pharmacological inhibition or lentiviral knockdown of Nnt in N27 dopaminergic cells (a) decreased H2O2 catabolism, (b) decreased NADPH and increased NADP(+) levels, and (c) decreased basal, spare, and maximal mitochondrial oxygen consumption rates. Nnt-deficient cells possessed higher levels of oxidized mitochondrial Prx, which rendered them more susceptible to steady-state increases in H2O2 and cell death following exposure to subtoxic levels of paraquat. These data implicate Nnt as the critical link between the metabolic and H2O2 antioxidant function in brain mitochondria and suggests Nnt as a potential therapeutic target to improve the redox balance in conditions of oxidative stress associated with neurodegenerative diseases. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

EGFRvIII-specific chimeric antigen receptor T cells migrate to and kill tumor deposits infiltrating the brain parenchyma in an invasive xenograft model of glioblastoma.

PubMed

Miao, Hongsheng; Choi, Bryan D; Suryadevara, Carter M; Sanchez-Perez, Luis; Yang, Shicheng; De Leon, Gabriel; Sayour, Elias J; McLendon, Roger; Herndon, James E; Healy, Patrick; Archer, Gary E; Bigner, Darell D; Johnson, Laura A; Sampson, John H

2014-01-01

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and is uniformly lethal. T-cell-based immunotherapy offers a promising platform for treatment given its potential to specifically target tumor tissue while sparing the normal brain. However, the diffuse and infiltrative nature of these tumors in the brain parenchyma may pose an exceptional hurdle to successful immunotherapy in patients. Areas of invasive tumor are thought to reside behind an intact blood brain barrier, isolating them from effective immunosurveillance and thereby predisposing the development of "immunologically silent" tumor peninsulas. Therefore, it remains unclear if adoptively transferred T cells can migrate to and mediate regression in areas of invasive GBM. One barrier has been the lack of a preclinical mouse model that accurately recapitulates the growth patterns of human GBM in vivo. Here, we demonstrate that D-270 MG xenografts exhibit the classical features of GBM and produce the diffuse and invasive tumors seen in patients. Using this model, we designed experiments to assess whether T cells expressing third-generation chimeric antigen receptors (CARs) targeting the tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, would localize to and treat invasive intracerebral GBM. EGFRvIII-targeted CAR (EGFRvIII+ CAR) T cells demonstrated in vitro EGFRvIII antigen-specific recognition and reactivity to the D-270 MG cell line, which naturally expresses EGFRvIII. Moreover, when administered systemically, EGFRvIII+ CAR T cells localized to areas of invasive tumor, suppressed tumor growth, and enhanced survival of mice with established intracranial D-270 MG tumors. Together, these data demonstrate that systemically administered T cells are capable of migrating to the invasive edges of GBM to mediate antitumor efficacy and tumor regression.

Helical tomotherapy with dynamic running-start-stop delivery compared to conventional tomotherapy delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rong, Yi, E-mail: yi.rong@osumc.edu; Chen, Yu; Lu, Weiguo

Purpose: Despite superior target dose uniformity, helical tomotherapy{sup ®} (HT) may involve a trade-off between longitudinal dose conformity and beam-on time (BOT), due to the limitation of only three available jaw sizes with the conventional HT (1.0, 2.5, and 5.0 cm). The recently introduced dynamic running-start-stop (RSS) delivery allows smaller jaw opening at the superior and inferior ends of the target when a sharp penumbra is needed. This study compared the dosimetric performance of RSS delivery with the fixed jaw HT delivery. Methods: Twenty patient cases were selected and deidentified prior to treatment planning, including 16 common clinical cases (brain,more » head and neck (HN), lung, and prostate) and four special cases of whole brain with hippocampus avoidance (WBHA) that require a high degree of dose modulation. HT plans were generated for common clinical cases using the fixed 2.5 cm jaw width (HT2.5) and WBHA cases using 1.0 cm (HT1.0). The jaw widths for RSS were preset with a larger size (RSS5.0 vs HT2.5 and RSS2.5 vs HT1.0). Both delivery techniques were planned based on identical contours, prescriptions, and planning objectives. Dose indices for targets and critical organs were compared using dose-volume histograms, BOT, and monitor units. Results: The average BOT was reduced from 4.8 min with HT2.5 to 2.5 min with RSS5.0. Target dose homogeneity with RSS5.0 was shown comparable to HT2.5 for common clinical sites. Superior normal tissue sparing was observed in RSS5.0 for optic nerves and optic chiasm in brain and HN cases. RSS5.0 demonstrated improved dose sparing for cord and esophagus in lung cases, as well as penile bulb in prostate cases. The mean body dose was comparable for both techniques. For the WBHA cases, the target homogeneity was significantly degraded in RSS2.5 without distinct dose sparing for hippocampus, compared to HT1.0. Conclusions: Compared to the fixed jaw HT delivery, RSS combined with a larger jaw width provides faster treatment delivery and improved cranial-caudal target dose conformity. The target coverage achieved by RSS with a large jaw width is comparable to the fixed jaw HT delivery for common cancer sites, but may deteriorate for cases where complex geometry is present in the middle part of the target.« less

Performance Assessment of the Spare Parts for the Activation of Relocated Systems (SPARES) Forecasting Model

DTIC Science & Technology

1991-09-01

constant data into the gaining base’s computer records. Among the data elements to be loaded, the 1XT434 image contains the level detail effective date...the mission support effective date, and the PBR override (19:19-203). In conjunction with the 1XT434, the Mission Change Parameter Image (Constant...the gaining base (19:19-208). The level detail effective date establishes the date the MCDDFR and MCDDR "are considered by the requirements computation

p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development.

PubMed

Contreras, Esteban G; Sierralta, Jimena; Glavic, Alvaro

2018-01-01

Animal growth is influenced by the genetic background and the environmental circumstances. How genes promote growth and coordinate adaptation to nutrient availability is still an open question. p53 is a transcription factor that commands the cellular response to different types of stresses. In adult Drosophila melanogaster, p53 regulates the metabolic adaptation to nutrient restriction that supports fly viability. Furthermore, the larval brain is protected from nutrient restriction in a phenomenon called 'brain sparing'. Therefore, we hypothesised that p53 may regulate brain growth and show a protective role over brain development under nutrient restriction. Here, we studied the function of p53 during brain growth in normal conditions and in animals subjected to developmental nutrient restriction. We showed that p53 loss of function reduced animal growth and larval brain size. Endogenous p53 was expressed in larval neural stem cells, but its levels and activity were not affected by nutritional stress. Interestingly, p53 knockdown only in neural stem cells was sufficient to decrease larval brain growth. Finally, we showed that in p53 mutant larvae under nutrient restriction, the energy storage levels were not altered, and these larvae generated adults with brains of similar size than wild-type animals. Using genetic approaches, we demonstrate that p53 is required for proper growth of the larval brain. This developmental role of p53 does not have an impact on animal resistance to nutritional stress since brain growth in p53 mutants under nutrient restriction is similar to control animals.

Nonsteroidal anti-inflammatory drugs (NSAID) sparing effects of glucosamine hydrochloride through N-glycosylation inhibition; strategy to rescue stomach from NSAID damage.

PubMed

Park, S H; Hong, H; Han, Y M; Kangwan, N; Kim, S J; Kim, E H; Hahm, K B

2013-04-01

Gastrointestinal or cardiovascular complications limit nonsteroidal anti-inflammatory drugs (NSAID) prescription. Glucosamine hydrochloride (GS-HCl) alternatively chosen, but debates still exist in its clinical efficiency. COX-2 instability through inhibiting COX-2 N-glycosylation of GS-HCl raised the possibility of NSAID sparing effect. Study was done to determine whether combination treatment of glucosamine and NSAID contributes to gastric safety through NSAID sparing effect. IEC-6 cells were stimulated with TNF-α and compared the expressions of inflammatory mediators after indomethacin alone or combination of indomethacin and GS-HCl by Western blotting and RT-PCR. C57BL/6 mice injected with type II collagen to induce arthritis were treated with indomethacin alone or combination of reduced dose of indomethacin and GS-HCl after 3 weeks. TNF-α increased the expression of COX-2, iNOS and inflammatory cytokines, but GS-HCl significantly attenuated TNF-α-induced COX-2 expression. Decreased COX-2 after GS-HCl was caused by N-glycosylation inhibition as much as tunicamycin. Combination of reduced dose of indomethacin and GS-HCl significantly reduced the expressions of ICAM-1, VCAM-1, IL-8, IL-1β, MMP-2, MMP-7, MMP-9, and MMP-11 mRNA as well as NF-κB activation better than high dose indomethacin alone. These NSAID sparing effect of GS-HCl was further proven in collagen-induced arthritis model. Combination of GS-HCl and 2.5 mg/kg indomethacin showed significant protection from gastric damages as well as efficacious anti-arthritic effect. Taken together, COX-2 N-glycosylation inhibition by GS-HCl led to indomethacin sparing effects, based on which combination of GS-HCl and reduced dose of NSAID can provide the strategy to secure stomach from NSAID-induced gastric damage as well as excellent anti-arthritic effects.

Comparison of the extent of hippocampal sparing according to the tilt of a patient's head during WBRT using linear accelerator-based IMRT and VMAT.

PubMed

Moon, Sun Young; Yoon, Myonggeun; Chung, Mijoo; Chung, Weon Kuu; Kim, Dong Wook

2016-05-01

In this paper, we report the results of our investigation into whole brain radiotherapy (WBRT) using linear accelerator-based intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in lung cancer patients with a high risk of metastasis to the brain. Specifically, we assessed the absorbed dose and the rate of adverse effects for several organs at risk (OAR), including the hippocampus, according to the tilt of a patient's head. We arbitrarily selected five cases where measurements were made with the patients' heads tilted forward and five cases without such tilt. We set the entire brain as the planning target volume (PTV), and the hippocampi, the lenses, the eyes, and the cochleae as the main OAR, and formulated new plans for IMRT (coplanar, non-coplanar) and VMAT (coplanar, non-coplanar). Using the dose-volume histogram (DVH), we calculated and compared the effective uniform dose (EUD), normal tissue complication probability (NTCP) of the OAR and the mean and the maximum doses of hippocampus. As a result, if the patient tilted the head forward when receiving the Linac-based treatment, for the same treatment effect in the PTV, we confirmed that a lower dose entered the OAR, such as the hippocampus, eye, lens, and cochlea. Moreover, the damage to the hippocampus was expected to be the least when receiving coplanar VMAT with the head tilted forward. Accordingly, if patients tilt their heads forward when undergoing Linac-based WBRT, we anticipate that a smaller dose would be transmitted to the OAR, resulting in better quality of life following treatment. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Laryngeal Muscles Are Spared in the Dystrophin Deficient "mdx" Mouse

ERIC Educational Resources Information Center

Thomas, Lisa B.; Joseph, Gayle L.; Adkins, Tracey D.; Andrade, Francisco H.; Stemple, Joseph C.

2008-01-01

Purpose: "Duchenne muscular dystrophy (DMD)" is caused by the loss of the cytoskeletal protein, dystrophin. The disease leads to severe and progressive skeletal muscle wasting. Interestingly, the disease spares some muscles. The purpose of the study was to determine the effects of dystrophin deficiency on 2 intrinsic laryngeal muscles, the…

Opioid-sparing effects of the thoracic interfascial plane blocks: A meta-analysis of randomized controlled trials.

PubMed

Singh, Preet Mohinder; Borle, Anuradha; Kaur, Manpreet; Trikha, Anjan; Sinha, Ashish

2018-01-01

Thoracic interfascial plane blocks and modification (PECS) have recently gained popularity for analgesic potential during breast surgery. We evaluate/consolidate the evidence on opioid-sparing effect of PECS blocks in comparison with conventional intravenous analgesia (IVA) and paravertebral block (PVB). Prospective, randomized controlled trials comparing PECS block to conventional IVA or PVB in patients undergoing breast surgery published till June 2017 were searched in the medical database. Comparisons were made for 24-h postoperative morphine consumption and intraoperative fentanyl-equivalent consumption. Final analysis included nine trials (PECS vs. IVA 4 trials and PECS vs. PVB 5 trials). PECS block showed a decreased intraoperative fentanyl consumption over IVA by 49.20 mcg (95% confidence interval [CI] =42.67-55.74) ( I 2 = 98.47%, P < 0.001) and PVB by 15.88 mcg (95% CI = 12.95-18.81) ( I 2 = 95.51%, P < 0.001). Postoperative, 24-h morphine consumption with PECS block was lower than IVA by 7.66 mg (95% CI being 6.23-9.10) ( I 2 = 63.15, P < 0.001) but was higher than PVB group by 1.26 mg (95% CI being 0.91-1.62) ( I 2 = 99.53%, P < 0.001). Two cases of pneumothorax were reported with PVB, and no complication was reported in any other group. Use of PECS block and its modifications with general anesthesia for breast surgery has significant opioid-sparing effect intraoperatively and during the first 24 h after surgery. It also has higher intraoperative opioid-sparing effect when compared to PVB. During the 1 st postoperative day, PVB has slightly more morphine sparing potential that may however be associated with higher complication rates. The present PECS block techniques show marked interstudy variations and need standardization.

Understanding 'not': neuropsychological dissociations between hand and head markers of negation in BSL.

PubMed

Atkinson, Jo; Campbell, Ruth; Marshall, Jane; Thacker, Alice; Woll, Bencie

2004-01-01

Simple negation in natural languages represents a complex interrelationship of syntax, prosody, semantics and pragmatics, and may be realised in various ways: lexically, morphologically and prosodically. In almost all spoken languages, the first two of these are the primary realisations of syntactic negation. In contrast, in many signed languages negation can occur without lexical or morphological marking. Thus, in British Sign Language (BSL), negation is obligatorily expressed using face-head actions alone (facial negation) with the option of articulating a manual form alongside the required face-head actions (lexical negation). What are the processes underlying facial negation? Here, we explore this question neuropsychologically. If facial negation reflects lexico-syntactic processing in BSL, it may be relatively spared in people with unilateral right hemisphere (RH) lesions, as has been suggested for other 'grammatical facial actions' [Language and Speech 42 (1999) 307; Emmorey, K. (2002). Language, cognition and the brain: Insights from sign language research. Mahwah, NJ: Erlbaum (Lawrence)]. Three BSL users with RH lesions were specifically impaired in perceiving facial compared with manual (lexical and morphological) negation. This dissociation was absent in three users of BSL with left hemisphere lesions and different degrees of language disorder, who also showed relative sparing of negation comprehension. We conclude that, in contrast to some analyses [Applied Psycholinguistics 18 (1997) 411; Emmorey, K. (2002). Language, cognition and the brain: Insights from sign language research. Mahwah, NJ: Erlbaum (Lawrence); Archives of Neurology 36 (1979) 837], non-manual negation in sign may not be a direct surface realisation of syntax [Language and Speech 42 (1999) 143; Language and Speech 42 (1999) 127]. Difficulties with facial negation in the RH-lesion group were associated with specific impairments in processing facial images, including facial expressions. However, they did not reflect generalised 'face-blindness', since the reading of (English) speech patterns from faces was spared in this group. We propose that some aspects of the linguistic analysis of sign language are achieved by prosodic analysis systems (analysis of face and head gestures), which are lateralised to the minor hemisphere.

Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.

2012-07-15

Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation ofmore » the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients should be enrolled in ongoing prospective trials of hippocampal sparing during cranial irradiation to confirm these preliminary results.« less

Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.

2013-02-01

Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation ofmore » the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients should be enrolled in ongoing prospective trials of hippocampal sparing during cranial irradiation to confirm these preliminary results.« less

Exploring Opioid-Sparing Multimodal Analgesia Options in Trauma: A Nursing Perspective

PubMed Central

Lyons, Mary; Montgomery, Robert; Quinlan-Colwell, Ann

2016-01-01

Challenges with opioids (e.g., adverse events, misuse and abuse with long-term administration) have led to a renewed emphasis on opioid-sparing multimodal management of trauma pain. To assess the extent to which currently available evidence supports the efficacy and safety of various nonopioid analgesics and techniques to manage trauma pain, a literature search of recently published references was performed. Additional citations were included on the basis of authors' knowledge of the literature. Effective options for opioid-sparing analgesics include oral and intravenous (IV) acetaminophen; nonsteroidal anti-inflammatory drugs available via multiple routes; and anticonvulsants, which are especially effective for neuropathic pain associated with trauma. Intravenous routes (e.g., IV acetaminophen, IV ketorolac) may be associated with a faster onset of action than oral routes. Additional adjuvants for the treatment of trauma pain are muscle relaxants and alpha-2 adrenergic agonists. Ketamine and regional techniques play an important role in multimodal therapy but require medical and nursing support. Nonpharmacologic treatments (e.g., cryotherapy, distraction techniques, breathing and relaxation, acupuncture) supplement pharmacologic analgesics and can be safe and easy to implement. In conclusion, opioid-sparing multimodal analgesia addresses concerns associated with high doses of opioids, and many pharmacologic and nonpharmacologic options are available to implement this strategy. Nurses play key roles in comprehensive patient assessment; administration of patient-focused, opioid-sparing, multimodal analgesia in trauma; and monitoring for safety concerns. PMID:27828892

Exploring Opioid-Sparing Multimodal Analgesia Options in Trauma: A Nursing Perspective.

PubMed

Sullivan, Denise; Lyons, Mary; Montgomery, Robert; Quinlan-Colwell, Ann

Challenges with opioids (e.g., adverse events, misuse and abuse with long-term administration) have led to a renewed emphasis on opioid-sparing multimodal management of trauma pain. To assess the extent to which currently available evidence supports the efficacy and safety of various nonopioid analgesics and techniques to manage trauma pain, a literature search of recently published references was performed. Additional citations were included on the basis of authors' knowledge of the literature. Effective options for opioid-sparing analgesics include oral and intravenous (IV) acetaminophen; nonsteroidal anti-inflammatory drugs available via multiple routes; and anticonvulsants, which are especially effective for neuropathic pain associated with trauma. Intravenous routes (e.g., IV acetaminophen, IV ketorolac) may be associated with a faster onset of action than oral routes. Additional adjuvants for the treatment of trauma pain are muscle relaxants and alpha-2 adrenergic agonists. Ketamine and regional techniques play an important role in multimodal therapy but require medical and nursing support. Nonpharmacologic treatments (e.g., cryotherapy, distraction techniques, breathing and relaxation, acupuncture) supplement pharmacologic analgesics and can be safe and easy to implement. In conclusion, opioid-sparing multimodal analgesia addresses concerns associated with high doses of opioids, and many pharmacologic and nonpharmacologic options are available to implement this strategy. Nurses play key roles in comprehensive patient assessment; administration of patient-focused, opioid-sparing, multimodal analgesia in trauma; and monitoring for safety concerns.

Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases.

PubMed

Tsao, May N; Xu, Wei; Wong, Rebecca Ks; Lloyd, Nancy; Laperriere, Normand; Sahgal, Arjun; Rakovitch, Eileen; Chow, Edward

2018-01-25

This is an update to the review published in the Cochrane Library (2012, Issue 4).It is estimated that 20% to 40% of people with cancer will develop brain metastases during the course of their illness. The burden of brain metastases impacts quality and length of survival. To assess the effectiveness and adverse effects of whole brain radiotherapy (WBRT) given alone or in combination with other therapies to adults with newly diagnosed multiple brain metastases. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase to May 2017 and the National Cancer Institute Physicians Data Query for ongoing trials. We included phase III randomised controlled trials (RCTs) comparing WBRT versus other treatments for adults with newly diagnosed multiple brain metastases. Two review authors independently assessed trial quality and abstracted information in accordance with Cochrane methods. We added 10 RCTs to this updated review. The review now includes 54 published trials (45 fully published reports, four abstracts, and five subsets of data from previously published RCTs) involving 11,898 participants.Lower biological WBRT doses versus controlThe hazard ratio (HR) for overall survival (OS) with lower biological WBRT doses as compared with control (3000 cGy in 10 daily fractions) was 1.21 (95% confidence interval (CI) 1.04 to 1.40; P = 0.01; moderate-certainty evidence) in favour of control. The HR for neurological function improvement (NFI) was 1.74 (95% CI 1.06 to 2.84; P = 0.03; moderate-certainty evidence) in favour of control fractionation.Higher biological WBRT doses versus controlThe HR for OS with higher biological WBRT doses as compared with control (3000 cGy in 10 daily fractions) was 0.97 (95% CI 0.83 to 1.12; P = 0.65; moderate-certainty evidence). The HR for NFI was 1.14 (95% CI 0.92 to 1.42; P = 0.23; moderate-certainty evidence).WBRT and radiosensitisersThe addition of radiosensitisers to WBRT did not confer additional benefit for OS (HR 1.05, 95% CI 0.99 to 1.12; P = 0.12; moderate-certainty evidence) or for brain tumour response rates (odds ratio (OR) 0.84, 95% CI 0.63 to 1.11; P = 0.22; high-certainty evidence).Radiosurgery and WBRT versus WBRT aloneThe HR for OS with use of WBRT and radiosurgery boost as compared with WBRT alone for selected participants was 0.61 (95% CI 0.27 to 1.39; P = 0.24; moderate-certainty evidence). For overall brain control at one year, the HR was 0.39 (95% CI 0.25 to 0.60; P < 0.0001; high-certainty evidence) favouring the WBRT and radiosurgery boost group.Radiosurgery alone versus radiosurgery and WBRTThe HR for local brain control was 2.73 (95% CI 1.87 to 3.99; P < 0.00001; high-certainty evidence)favouring the addition of WBRT to radiosurgery. The HR for distant brain control was 2.34 (95% CI 1.73 to 3.18; P < 0.00001; high-certainty evidence) favouring WBRT and radiosurgery. The HR for OS was 1.00 (95% CI 0.80 to 1.25; P = 0.99; moderate-certainty evidence). Two trials reported worse neurocognitive outcomes and one trial reported worse quality of life outcomes when WBRT was added to radiosurgery.We could not pool data from trials related to chemotherapy, optimal supportive care (OSC), molecular targeted agents, neurocognitive protective agents, and hippocampal sparing WBRT. However, one trial reported no differences in quality-adjusted life-years for selected participants with brain metastases from non-small-cell lung cancer randomised to OSC and WBRT versus OSC alone. None of the trials with altered higher biological WBRT dose-fractionation schemes reported benefit for OS, NFI, or symptom control compared with standard care. However, OS and NFI were worse for lower biological WBRT dose-fractionation schemes than for standard dose schedules.The addition of WBRT to radiosurgery improved local and distant brain control in selected people with brain metastases, but data show worse neurocognitive outcomes and no differences in OS.Selected people with multiple brain metastases from non-small-cell lung cancer may show no difference in OS when OSC is given and WBRT is omitted.Use of radiosensitisers, chemotherapy, or molecular targeted agents in conjunction with WBRT remains experimental.Further trials are needed to evaluate the use of neurocognitive protective agents and hippocampal sparing with WBRT. As well, future trials should examine homogeneous participants with brain metastases with focus on prognostic features and molecular markers.

SU-E-T-331: Dosimetric Impact of Multileaf Collimator Leaf Width On Stereotactic Radiosurgery (SRS) RapidArc Treatment Plans for Single and Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, S; Keeling, V; Ahmad, S

Purpose: To determine the effects of multileaf collimator (MLC) leaf width on normal-brain-tissue doses and dose conformity of SRS RapidArc treatment plans for brain tumors. Methods: Ten patients with 24 intracranial tumors (seven with 1–2 and three with 4–6 lesions) were planned using RapidArc for both Varian Millennium 120 MLC (5 mm leaf width) and high definition (HD) MLC (2.5 mm leaf width). Between 2 and 8 arcs were used with two full coplanar arcs and the rest non-coplanar half arcs. 6 MV beams were used and plans were optimized with a high priority to the Normal Tissue Objective (tomore » achieve dose conformity and sharp dose fall-off) and normal brain tissue. Calculation was done using AAA on a 1 mm grid size. The prescription dose ranged from 14–22 Gy. Plans were normalized such that 99% of the target received the prescription dose. Identical beam geometries, optimizations, calculations, and normalizations were used for both plans. Paddick Conformity Index (PCI), V4, V8 and V12 Gy for normal brain tissue and Integral Dose were used for analysis. Results: In all cases, HD MLC plans performed better in sparing normal brain tissue, achieving a higher PCI with a lower Integral Dose. The average PCI for all 24 targets was 0.75±0.23 and 0.70±0.23 (p ≤0.0015) for HD MLC and Millennium MLC plans, respectively. The average ratio of normal brain doses for Millennium MLC to HD MLC plans was 1.30±0.16, 1.27±0.15, and 1.31±0.18 for the V4, V8, and V12, respectively. The differences in normal brain dose for all criteria were statistically significant with p-value < 0.02. On average Millennium MLC plans had a 16% higher integral dose than HD MLC plans. Conclusion: Significantly better dose conformity with reduced volume of normal brain tissue and integral dose was achieved with HD MLC plans compared to Millennium MLC plans.« less

Radiation Dose–Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seibert, Tyler M.; Karunamuni, Roshan; Bartsch, Hauke

Purpose: After radiation therapy (RT) to the brain, patients often experience memory impairment, which may be partially mediated by damage to the hippocampus. Hippocampal sparing in RT planning is the subject of recent and ongoing clinical trials. Calculating appropriate hippocampal dose constraints would be improved by efficient in vivo measurements of hippocampal damage. In this study we sought to determine whether brain RT was associated with dose-dependent hippocampal atrophy. Methods and Materials: Hippocampal volume was measured with magnetic resonance imaging (MRI) in 52 patients who underwent fractionated, partial brain RT for primary brain tumors. Study patients had high-resolution, 3-dimensional volumetric MRI beforemore » and 1 year after RT. Images were processed using software with clearance from the US Food and Drug Administration and Conformité Européene marking for automated measurement of hippocampal volume. Automated results were inspected visually for accuracy. Tumor and surgical changes were censored. Mean hippocampal dose was tested for correlation with hippocampal atrophy 1 year after RT. Average hippocampal volume change was also calculated for hippocampi receiving high (>40 Gy) or low (<10 Gy) mean RT dose. A multivariate analysis was conducted with linear mixed-effects modeling to evaluate other potential predictors of hippocampal volume change, including patient (random effect), age, hemisphere, sex, seizure history, and baseline volume. Statistical significance was evaluated at α = 0.05. Results: Mean hippocampal dose was significantly correlated with hippocampal volume loss (r=−0.24, P=.03). Mean hippocampal volume was significantly reduced 1 year after high-dose RT (mean −6%, P=.009) but not after low-dose RT. In multivariate analysis, both RT dose and patient age were significant predictors of hippocampal atrophy (P<.01). Conclusions: The hippocampus demonstrates radiation dose–dependent atrophy after treatment for brain tumors. Quantitative MRI is a noninvasive imaging technique capable of measuring radiation effects on intracranial structures. This technique could be investigated as a potential biomarker for development of reliable dose constraints for improved cognitive outcomes.« less

Nanotechnology-based cancer therapeutics--promise and challenge--lessons learned through the NCI Alliance for Nanotechnology in Cancer.

PubMed

Farrell, Dorothy; Ptak, Krzysztof; Panaro, Nicholas J; Grodzinski, Piotr

2011-02-01

The new generation of nanotechnology-based drug formulations is challenging the accepted ways of cancer treatment. Multi-functional nanomaterial constructs have the capability to be delivered directly to the tumor site and eradicate cancer cells selectively, while sparing healthy cells. Tailoring of the nano-construct design can result in enhanced drug efficacy at lower doses as compared to free drug treatment, wider therapeutic window, and lower side effects. Nanoparticle carriers can also address several drug delivery problems which could not be effectively solved in the past and include reduction of multi-drug resistance effects, delivery of siRNA, and penetration of the blood-brain-barrier. Although challenges in understanding toxicity, biodistribution, and paving an effective regulatory path must be met, nanoscale devices carry a formidable promise to change ways cancer is diagnosed and treated. This article summarizes current developments in nanotechnology-based drug delivery and discusses path forward in this field. The discussion is done in context of research and development occurring within the NCI Alliance for Nanotechnology in Cancer program.

Xerostomia and its predictors following parotid-sparing irradiation of head-and-neck cancer.

PubMed

Eisbruch, A; Kim, H M; Terrell, J E; Marsh, L H; Dawson, L A; Ship, J A

2001-07-01

To assess long-term xerostomia in patients receiving parotid-sparing radiation therapy (RT) for head-and-neck cancer, and to find the patient and therapy-related factors that affect its severity. From March 1994 through January 2000, 84 patients received comprehensive bilateral neck RT using conformal and multisegmental intensity-modulated RT (IMRT) aiming to spare the major salivary glands. Before RT and periodically through 2 years after the completion of RT, salivary flow rates from each of the major salivary glands were selectively measured. At the same time intervals, each patient completed an 8-item self-reported xerostomia-specific questionnaire (XQ). To gain a relative measure of the effect of RT on the minor salivary glands, whose output could not be measured, the surfaces of the oral cavity (extending to include the surface of the base of tongue) were outlined in the planning CT scans. The mean doses to the new organ ("oral cavity") were recorded. Forty-eight patients receiving unilateral neck RT were similarly studied and served as a benchmark for comparison. Factors predicting the XQ scores were analyzed using a random-effects model. The XQ was found to be reliable and valid in measuring patient-reported xerostomia. The spared salivary glands which had received moderate doses in the bilateral RT group recovered to their baseline salivary flow rates during the second year after RT, and the spared glands in the unilateral RT group, which had received very low doses, demonstrated increased salivary production beyond their pre-RT levels. The increase in the salivary flow rates during the second year after RT paralleled an improvement in xerostomia in both patient groups. The improvement in xerostomia was faster in the unilateral compared with the bilateral RT group, but the difference narrowed at 2 years. The major salivary gland flow rates had only a weak correlation with the xerostomia scores. Factors found to be independently associated with the xerostomia scores were the pre-RT baseline scores, the time since RT, and the mean doses to the major salivary glands (notably to the submandibular glands) and to the oral cavity. An improvement over time in xerostomia, occurring in tandem with rising salivary production from the spared major salivary glands, suggests a long-term clinical benefit from their sparing. The oral cavity mean dose, representing RT effect on the minor salivary glands, was found to be a significant, independent predictor of xerostomia. Thus, in addition to the major salivary glands, sparing the uninvolved oral cavity should be considered as a planning objective to further reduce xerostomia.

[The effect of acupuncture and endogenous c-Fos, c-Jun on regeneration of neuronal dendrite of spared DRG in vitro following partial ganglionectomy].

PubMed

Wang, Te-wei; Wang, Ting-hua; Zhou, Xue; Zhang, Lian-shuang; Xu, Xin-yun

2007-09-01

To explore the effect of acupuncture, endogenous c-Fos and c-Jun on the regeneration of neuronal dendrite of spared dorsal root ganglion (DRG) in vitro following partial ganglionectomy. Five adult male cats were used in this experiment. Their bilateral L1-L5, L7-S2 DRG were removed, and L6 DRG were spared. Then unilaterally, two sets of acupoints (Zusanli(St. 36) and Xuanzhong(G. B. 39); Futu (St. 32) and Sanyinjiao (Sp. 6) located in the distribution area of spinal nerve L6) were electro-stimulated alternately 30 min everyday by electro-needling. Seven days after operation, bilateral L6 DRGs were taken out and were cultured respectively in vitro. Some cultured mediums of the acupuncture lateral wells were totally replaced by each corresponding antibody-cultured medium including respectively 100 ng/mL anti-c-Fos and anti-c-Jun antibody at the 24th hour and terminated after 7 days. The length of the neurite was measured by upside-down light microscopy. Then, cultured cells were stained by the immunohistochemistry ABC method. Data were analyzed by One-way ANOVA and q test. Immunocytochemical staining revealed that over 95% cells were NSE positive cells which were the typical neuron of DRG in vitro. On the 7th day, the average neurite length of the spared DRG group, the anti-c-Fos antibody and the anti-c-Jun antibody group were shorter than that of the acupuncture group (P < 0.05); the average neurite length of the two antibody groups were longer than that of the spared DRG group (P < 0.05). These results indicate that acupuncture, endogenous c-Fos and c-Jun probably promote regeneration of neuronal dendrite of spared DRG in vitro.

Age Disparities in the Use of Steroid-sparing Therapy for Inflammatory Bowel Disease.

PubMed

Govani, Shail M; Wiitala, Wyndy L; Stidham, Ryan W; Saini, Sameer D; Hou, Jason K; Feagins, Linda A; Sussman, Jeremy B; Higgins, Peter D R; Waljee, Akbar K

2016-08-01

Corticosteroids are effective rescue therapies for patients with inflammatory bowel disease (IBD), but have significant side effects, which may be amplified in the growing population of elderly patients with IBD. We aimed to compare the use of steroids and steroid-sparing therapies (immunomodulators and biologics) and rates of complications among elderly (≥65) and younger patients in a national cohort of veterans with IBD. We used national Veterans Health Administrative data to conduct a retrospective study of veterans with IBD between 2002 and 2010. Medications and the incidence of complications were obtained from the Veterans Health Administrative Decision Support Systems. Multivariate logistic regression accounting for facility-level clustering was used to identify predictors of use of steroid-sparing medications. We identified 30,456 veterans with IBD. Of these, 94% were men and 40% were more than 65, and 32% were given steroids. Elderly veterans were less likely to receive steroids (23.8% versus 38.3%, P < 0.001) and were less likely to be prescribed steroid-sparing medications (25.5% versus 46.9%, respectively, P < 0.001). In multivariate analysis controlling for sex, age <65 (odds ratio, 2.19; 95% CI, 1.54-3.11) and gastroenterology care (odds ratio, 8.42; 95% CI, 6.18-11.47) were associated with initiation of steroid-sparing medications. After starting steroids, fracture rates increased in the elderly patients with IBD, whereas increases in venous thromboembolism and infections after starting steroids affected both age groups. Elderly veterans are less likely to receive steroids and steroid-sparing medications than younger veterans; elderly patients exposed to steroids were more likely to have fractures than the younger population.

The efficacy and utilisation of preoperative multiparametric magnetic resonance imaging in robot-assisted radical prostatectomy: does it change the surgical dissection plan?

PubMed

Tavukçu, Hasan Hüseyin; Aytaç, Ömer; Balcı, Numan Cem; Kulaksızoğlu, Haluk; Atuğ, Fatih

2017-12-01

We investigated the effect of the use of multiparametric prostate magnetic resonance imaging (mp-MRI) on the dissection plan of the neurovascular bundle and the oncological results of our patients who underwent robot-assisted radical prostatectomy. We prospectively evaluated 60 consecutive patients, including 30 patients who had (Group 1), and 30 patients who had not (Group 2) mp-MRI before robot-assisted radical prostatectomy. Based on the findings of mp-MRI, the dissection plan was changed as intrafascial, interfascial, and extrafascial in the mp-MRI group. Two groups were compared in terms of age, prostate-specific antigen (PSA), Gleason sum scores and surgical margin positivity. There was no statistically significant difference between the two groups in terms of age, PSA, biopsy Gleason score, final pathological Gleason score and surgical margin positivity. mp-MRI changed the initial surgical plan in 18 of 30 patients (60%) in Group 1. In seventeen of these patients (56%) surgical plan was changed from non-nerve sparing to interfascial nerve sparing plan. In one patient dissection plan was changed to non-nerve sparing technique which had extraprostatic extension on final pathology. Surgical margin positivity was similar in Groups 1, and 2 (16% and 13%, respectively) although, Group 1 had higher number of high- risk patients. mp-MRI confirmed the primary tumour localisation in the final pathology in 27 of of 30 patients (90%). Preoperative mp-MRI effected the decision to perform a nerve-sparing technique in 56% of the patients in our study; moreover, changing the dissection plan from non-nerve-sparing technique to a nerve sparing technique did not increase the rate of surgical margin positivity.

SU-F-T-198: Dosimetric Comparison of Carbon and Proton Radiotherapy for Recurrent Nasopharynx Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheng, Y; Zhao, J; Wang, W

2016-06-15

Purpose: Various radiotherapy planning methods for locally recurrent nasopharynx carcinoma (R-NPC) have been proposed. The purpose of this study was to compare carbon and proton therapy for the treatment of R-NPC in terms of dose coverage for target volume and sparing for organs at risk (OARs). Methods: Six patients who were suffering from R-NPC and treated using carbon therapy were selected for this study. Treatment plans with a total dose of 57.5Gy (RBE) in 23 fractions were made using SIEMENS Syngo V11. An intensity-modulated radiotherapy optimization method was chosen for carbon plans (IMCT) while for proton plans both intensity-modulated radiotherapymore » (IMPT) and single beam optimization (proton-SBO) methods were chosen. Dose distributions, dose volume parameters, and selected dosimetric indices for target volumes and OARs were compared for all treatment plans. Results: All plans provided comparable PTV coverage. The volume covered by 95% of the prescribed dose was comparable for all three plans. The average values were 96.11%, 96.24% and 96.11% for IMCT, IMPT, and proton-SBO respectively. A significant reduction of the 80% and 50% dose volumes were observed for the IMCT plans compared to the IMPT and proton-SBO plans. Critical organs lateral to the target such as brain stem and spinal cord were better spared by IMPT than by proton-SBO, while IMCT spared those organs best. For organs in the beam path, such as parotid glands, the mean dose results were similar for all three plans. Conclusion: Carbon plans yielded better dose conformity than proton plans. They provided similar or better target coverage while significantly lowering the dose for normal tissues. Dose sparing for critical organs in IMPT plans was better than proton-SBO, however, IMPT is known to be more sensitive to range uncertainties. For proton plans it is essential to find a balance between the two optimization methods.« less

Temporal Aspects of Life Satisfaction

ERIC Educational Resources Information Center

Eriksson, Lina; Rice, James Mahmud; Goodin, Robert E.

2007-01-01

Time pressure is a familiar phenomenon. The quantity of spare time people have clearly effects their satisfaction with their leisure and with their life as a whole. But so too, we show, does how much control people have over how much spare time they have. We measure this through an indicator of "discretionary time", which proves to be equally or…

Earth Observing System (EOS) Advanced Microwave Sounding Unit-A (AMSU-A) Spares Program Plan

NASA Technical Reports Server (NTRS)

Chapman, Weldon

1994-01-01

This plan specifies the spare components to be provided for the EOS/AMSU-A instrument and the general spares philosophy for their procurement. It also address key components not recommended for spares, as well as the schedule and method for obtaining the spares. The selected spares list was generated based on component criticality, reliability, repairability, and availability. An alternative spares list is also proposed based on more stringent fiscal constraints.

Episodic memory, semantic memory, and amnesia.

PubMed

Squire, L R; Zola, S M

1998-01-01

Episodic memory and semantic memory are two types of declarative memory. There have been two principal views about how this distinction might be reflected in the organization of memory functions in the brain. One view, that episodic memory and semantic memory are both dependent on the integrity of medial temporal lobe and midline diencephalic structures, predicts that amnesic patients with medial temporal lobe/diencephalic damage should be proportionately impaired in both episodic and semantic memory. An alternative view is that the capacity for semantic memory is spared, or partially spared, in amnesia relative to episodic memory ability. This article reviews two kinds of relevant data: 1) case studies where amnesia has occurred early in childhood, before much of an individual's semantic knowledge has been acquired, and 2) experimental studies with amnesic patients of fact and event learning, remembering and knowing, and remote memory. The data provide no compelling support for the view that episodic and semantic memory are affected differently in medial temporal lobe/diencephalic amnesia. However, episodic and semantic memory may be dissociable in those amnesic patients who additionally have severe frontal lobe damage.

Volumetric-modulated arc therapy (VMAT) for whole brain radiotherapy: not only for hippocampal sparing, but also for reduction of dose to organs at risk.

PubMed

Sood, Sumit; Pokhrel, Damodar; McClinton, Christopher; Lominska, Christopher; Badkul, Rajeev; Jiang, Hongyu; Wang, Fen

2017-01-01

A prospective clinical trial, Radiation Therapy Oncology Group (RTOG) 0933, has demonstrated that whole brain radiotherapy (WBRT) using conformal radiation delivery technique with hippocampal avoidance is associated with less memory complications. Further sparing of other organs at risk (OARs) including the scalp, ear canals, cochleae, and parotid glands could be associated with reductions in additional toxicities for patients treated with WBRT. We investigated the feasibility of WBRT using volumetric-modulated arc therapy (VMAT) to spare the hippocampi and the aforementioned OARs. Ten patients previously treated with nonconformal WBRT (NC-WBRT) using opposed lateral beams were retrospectively re-planned using VMAT with hippocampal sparing according to the RTOG 0933 protocol. The OARs (scalp, auditory canals, cochleae, and parotid glands) were considered as dose-constrained structures. VMAT plans were generated for a prescription dose of 30 Gy in 10 fractions. Comparison of the dosimetric parameters achieved by VMAT and NC-WBRT plans was performed using paired t-tests using upper bound p-value of < 0.001. Average beam on time and monitor units (MUs) delivered to the patients on VMAT were compared with those obtained with NC-WBRT. All VMAT plans met RTOG 0933 dosimetric criteria including the dose to hippocampi of 100% of the volume (D 100% ) of 8.4 ± 0.3 Gy and maximum dose of 15.6 ± 0.4 Gy, respectively. A statistically significant dose reduction (p < 0.001) to all OARs was achieved. The mean and maximum scalp doses were reduced by an average of 9 Gy (32%) and 2 Gy (6%), respectively. The mean and maximum doses to the auditory canals were reduced from 29.5 ± 0.5 Gy and 31.0 ± 0.4 Gy with NC-WBRT, to 21.8 ± 1.6 Gy (26%) and 27.4 ± 1.4 Gy (12%) with VMAT. VMAT also reduced mean and maximum doses to the cochlea by an average of 4 Gy (13%) and 2 Gy (6%), respectively. The parotid glands mean and maximum doses with VMAT were 4.4 ± 1.9 Gy and 15.7 ± 5.0 Gy, compared to 12.8 ± 4.9 Gy and 30.6 ± 0.5 Gy with NC-WBRT, respectively. The average dose reduction of mean and maximum of parotid glands from VMAT were 65% and 50%, respectively. The average beam on time and MUs were 2.3minutes and 719 on VMAT, and 0.7 minutes and 350 on NC-WBRT. This study demonstrated the feasibility of WBRT using VMAT to not only spare the hippocampi, but also significantly reduce dose to OARs. These advantages of VMAT could potentially decrease the toxicities associated with NC-WBRT and improve patients' quality of life, especially for patients with favorable prognosis receiving WBRT or patients receiving prophylactic cranial irradiation (PCI). Published by Elsevier Inc.

Pubertal development, spare time activities, and adolescent delinquency: testing the contextual amplification hypothesis.

PubMed

Kretschmer, Tina; Oliver, Bonamy R; Maughan, Barbara

2014-08-01

Extensive evidence supports associations between early pubertal timing and adolescent externalizing behavior, but how and under which conditions they are linked is not fully understood. In addition, pubertal development is also characterized by variations in the relative speed at which individuals mature, but studies linking pubertal 'tempo' and outcomes are scarce. This study examined the mediating and moderating roles of spare time activities in associations between pubertal development and later delinquency, using data from a large (4,327 girls, 4,250 boys) longitudinal UK cohort (Avon Longitudinal Study of Parents and Children). Self-reports of Tanner stage were available from ages 9 to 14, spare time activities at age 12 and delinquency at age 15. Pubertal development was examined using latent growth models. Spare time activities were categorized using factor analyses, yielding four types (hanging out at home, hanging out outside, consumerist behavior, and sports/games), which were examined as mediators and moderators. Earlier and faster maturation predicted delinquency in boys and girls. Spare time activities partially mediated these links such that early maturing girls more often engaged in hanging out outside, which placed them at greater risk for delinquency. In addition, compared to their later and slower maturing counterparts, boys who matured earlier and faster were less likely to engage in sports/games, a spare time activity type that is linked to lower delinquency risk. No moderation effects were found. The findings extend previous research on outcomes of early maturation and show how spare time activities act as proxies between pubertal development and delinquency.

Impact of penile rehabilitation with low-dose vardenafil on recovery of erectile function in Japanese men following nerve-sparing radical prostatectomy

PubMed Central

Nakano, Yuzo; Miyake, Hideaki; Chiba, Koji; Fujisawa, Masato

2014-01-01

Erectile dysfunction (ED) is a major complication after radical prostatectomy (RP); however, debate continues regarding the efficacy of penile rehabilitation in the recovery of the postoperative erectile function (EF). This study included a total of 103 consecutive sexually active Japanese men with localized prostate cancer undergoing nerve-sparing RP, and analyzed the postoperative EF, focusing on the significance of penile rehabilitation. In this series, 24 and 79 patients underwent bilateral and unilateral nerve-sparing RPs, respectively, and 10 or 20 mg of vardenafil was administered to 35 patients at least once weekly, who agreed to undergo penile rehabilitation. Twelve months after RP, 48 (46.6%) of the 103 patients were judged to have recovered EF sufficient for sexual intercourse without any assistance. The proportion of patients who recovered EF in those undergoing penile rehabilitation (60.0%) was significantly greater than that in those without penile rehabilitation (38.2%). Of several parameters examined, the preoperative International Index of Erectile Function-5 (IIEF-5) score and nerve-sparing procedure were significantly associated with the postoperative EF recovery rates in patients with and without management by penile rehabilitation, respectively. Furthermore, univariate analysis identified the preoperative IIEF-5 score, nerve-sparing procedure and penile rehabilitation as significant predictors of EF recovery, among which the preoperative IIEF-5 score and nerve-sparing procedure appeared to be independently associated with EF recovery. Considering these findings, despite the lack of independent significance, penile rehabilitation with low-dose vardenafil could exert a beneficial effect on EF recovery in Japanese men following nerve-sparing RP. PMID:24994781

Comparing proton treatment plans of pediatric brain tumors in two pencil beam scanning nozzles with different spot sizes

PubMed Central

Kralik, John C.; Xi, Liwen; Solberg, Timothy D.; Simone, Charles B.

2015-01-01

Target coverage and organ‐at‐risk sparing were compared for 22 pediatric patients with primary brain tumors treated using two distinct nozzles in pencil beam scanning (PBS) proton therapy. Consecutive patients treated at our institution using a PBS‐dedicated nozzle (DN) were replanned using a universal nozzle (UN) beam model and the original DN plan objectives. Various cranial sites were treated among the patients to prescription doses ranging from 45 to 54 Gy. Organs at risk (OARs) evaluated were patient‐dependent; 15 unique OARs were analyzed, all of which were assessed in at least 10 patients. Clinical target volume (CTV) coverage and organ sparing were compared for the two nozzles using dose‐volume histogram data. Statistical analysis using a confidence‐interval approach demonstrates that CTV coverage is equivalent for UN and DN plans within ±5% equivalence bounds. In contrast, average mean and maximum doses are significantly higher for nearly all 15 OARs in the UN plans. The average median increase over all OARs and patients is approximately 1.7 Gy, with an increase in the 25%–75% of 1.0–2.3 Gy; the median increase to the pituitary gland, temporal lobes, eyes and cochleas are 1.8, 1.7, 0.7, and 2.7 Gy, respectively. The CTV dose distributions fall off slower for UN than for the DN plans; hence, normal tissue structures in close proximity to CTVs receive higher doses in UN plans than in DN plans. The higher OAR doses in the UN plans are likely due to the larger spot profile in plans created with UN beams. In light of the high rates of toxicities in pediatric patients receiving cranial irradiation and in light of selected brain tumor types having high cure rates, this study suggests the smaller DN beam profile is preferable for the advantage of reducing dose to OARs. PACS number: 87.55.D‐ PMID:26699553

Functional recovery after cerebellar damage is related to GAP-43-mediated reactive responses of pre-cerebellar and deep cerebellar nuclei.

PubMed

Burello, Lorena; De Bartolo, Paola; Gelfo, Francesca; Foti, Francesca; Angelucci, Francesco; Petrosini, Laura

2012-01-01

Since brain injuries in adulthood are a leading cause of long-term disabilities, the development of rehabilitative strategies able to impact on functional outcomes requires detailing adaptive neurobiological responses. Functional recovery following brain insult is mainly ascribed to brain neuroplastic properties although the close linkage between neuronal plasticity and functional recovery is not yet fully clarified. The present study analyzed the reactive responses of pre-cerebellar (inferior olive, lateral reticular nucleus and pontine nuclei) and deep cerebellar nuclei after a hemicerebellectomy, considering the great plastic potential of the cerebellar system in physiological and pathological conditions. The time course of the plastic reorganization following cerebellar lesion was investigated by monitoring the Growth Associated Protein-43 (GAP-43) immunoreactivity. The time course of recovery from cerebellar symptoms was also assessed to parallel behavioral and neurobiological parameters. A key role of GAP-43 in neuronal reactive responses was evidenced. Neurons that underwent an axotomy as consequence of the right hemicerebellectomy (neurons of left inferior olive, right lateral reticular nucleus and left pontine nuclei) exhibited enhanced GAP-43 immunoreactivity and cell death. As for the not-axotomized neurons, we found enhanced GAP-43 immunoreactivity only in right pontine nuclei projecting to the spared (left) hemicerebellum. GAP-43 levels augmented also in the three deep cerebellar nuclei of the spared hemicerebellum, indicating the ponto-cerebellar circuit as crucially involved in functional recovery. Interestingly, each nucleus showed a distinct time course in GAP-43 immunoreactivity. GAP-43 levels peaked during the first post-operative week in the fastigial and interposed nuclei and after one month in the dentate nucleus. These results suggest that the earlier plastic events of the fastigial and interposed nuclei were driving compensation of the elementary features of posture and locomotion, while the later plastic events of the dentate nucleus were mediating the recovered ability to flexibly adjust the locomotor plan. Copyright © 2011. Published by Elsevier Inc.

Increased permeability-glycoprotein inhibition at the human blood-brain barrier can be safely achieved by performing PET during peak plasma concentrations of tariquidar.

PubMed

Kreisl, William C; Bhatia, Ritwik; Morse, Cheryl L; Woock, Alicia E; Zoghbi, Sami S; Shetty, H Umesha; Pike, Victor W; Innis, Robert B

2015-01-01

The permeability-glycoprotein (P-gp) efflux transporter is densely expressed at the blood-brain barrier, and its resultant spare capacity requires substantial blockade to increase the uptake of avid substrates, blunting the ability of investigators to measure clinically meaningful alterations in P-gp function. This study, conducted in humans, examined 2 P-gp inhibitors (tariquidar, a known inhibitor, and disulfiram, a putative inhibitor) and 2 routes of administration (intravenous and oral) to maximally increase brain uptake of the avid and selective P-gp substrate (11)C-N-desmethyl-loperamide (dLop) while avoiding side effects associated with high doses of tariquidar. Forty-two (11)C-dLop PET scans were obtained from 37 healthy volunteers. PET was performed with (11)C-dLop under the following 5 conditions: injected under baseline conditions without P-gp inhibition, injected 1 h after intravenous tariquidar infusion, injected during intravenous tariquidar infusion, injected after oral tariquidar, and injected after disulfiram. (11)C-dLop uptake was quantified with kinetic modeling using metabolite-corrected arterial input function or by measuring the area under the time-activity curve in the brain from 10 to 30 min. Neither oral tariquidar nor oral disulfiram increased brain uptake of (11)C-dLop. Injecting (11)C-dLop during tariquidar infusion, when plasma tariquidar concentrations reach their peak, resulted in a brain uptake of the radioligand approximately 5-fold greater than baseline. Brain uptake was similar with 2 and 4 mg of intravenous tariquidar per kilogram; however, the lower dose was better tolerated. Injecting (11)C-dLop after tariquidar infusion also increased brain uptake, though higher doses (up to 6 mg/kg) were required. Brain uptake of (11)C-dLop increased fairly linearly with increasing plasma tariquidar concentrations, but we are uncertain whether maximal uptake was achieved. We sought to increase the dynamic range of P-gp function measured after blockade. Performing (11)C-dLop PET during peak plasma concentrations of tariquidar, achieved with concurrent administration of intravenous tariquidar, resulted in greater P-gp inhibition at the human blood-brain barrier than delayed administration and allowed the use of a lower, more tolerable dose of tariquidar. On the basis of prior monkey studies, we suspect that plasma concentrations of tariquidar did not fully block P-gp; however, higher doses of tariquidar would likely be associated with unacceptable side effects. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

A causal relationship between face-patch activity and face-detection behavior.

PubMed

Sadagopan, Srivatsun; Zarco, Wilbert; Freiwald, Winrich A

2017-04-04

The primate brain contains distinct areas densely populated by face-selective neurons. One of these, face-patch ML, contains neurons selective for contrast relationships between face parts. Such contrast-relationships can serve as powerful heuristics for face detection. However, it is unknown whether neurons with such selectivity actually support face-detection behavior. Here, we devised a naturalistic face-detection task and combined it with fMRI-guided pharmacological inactivation of ML to test whether ML is of critical importance for real-world face detection. We found that inactivation of ML impairs face detection. The effect was anatomically specific, as inactivation of areas outside ML did not affect face detection, and it was categorically specific, as inactivation of ML impaired face detection while sparing body and object detection. These results establish that ML function is crucial for detection of faces in natural scenes, performing a critical first step on which other face processing operations can build.

Managing the urinary tract in spinal cord injury

PubMed Central

Harrison, Simon C. W.

2010-01-01

This review sets out to provide an overview of the author’s approach to the management of the urinary tract in the patient who has suffered from an injury to their spinal cord. Emphasis is given to the need to understand the fundamental pathophysiological patterns that are seen with injuries that involve the sacral segments of the cord (the conus) and those that spare the conus but interrupt communication between the sacral parasympathetic and somatic centers and the brain (supraconal lesions). The importance of patient participation in management decisions is highlighted by considering the different ways in which the urinary tract can be managed and how the clinician needs to try to meet patient expectations and requirements while establishing safe urological management. Finally, consideration is given to the importance of establishing an appropriate follow up regime and managing urinary tract complications effectively. PMID:20877604

ExAblate magnetic resonance-guided focused ultrasound system in multiple body applications.

PubMed

Dick, E A; Gedroyc, W M W

2010-09-01

Focused ultrasound surgery (FUS) is a completely noninvasive method of thermally destroying a target tissue while sparing adjacent tissues and organs. Treatment is relatively painless and can be carried out under conscious sedation on an out-patient basis. The combination of magnetic resonance guidance with FUS (MRgFUS) provides the ability to plan and monitor treatments in near real-time, further increasing the safety profile of MRgFUS. This technology provides a very personalized treatment, adjusted to the individual patient anatomy, pathology and treatment response, hence it meets the needs of patients, as well as of physicians. MRgFUS has been used extensively in the successful treatment of uterine fibroids, and has been shown to be an effective treatment in the breast and in bone metastases in smaller scale studies. It shows great potential in the treatment of prostate and liver tumors, as well as in the brain and facet joints.

COMPLEXITY AND HETEROGENEITY: WHAT DRIVES THE EVER-CHANGING BRAIN IN HUNTINGTONS DISEASE?

PubMed Central

Rosas, H. Diana; Salat, David H; Lee, Stephanie Y; Zaleta, Alexandra K; Hevelone, Nathanael; Hersch, Steven M.

2008-01-01

Significant advances are being made in our understanding of basic pathophyiological and biochemical mechanisms that cause HuntingtonÕs disease (HD). There is increasing reason to believe that pathologic alterations occur in the brain for years before symptoms manifest. The “classic” hallmark of neuropathology in HD is selective neurodegeneration in which vulnerable populations of neurons degenerate while less vulnerable populations are spared. While, the earliest and most striking neuropathologic changes have been found in the neostriatum, neuronal loss has been identified in many other regions of the brain. We report topologically selective, early, and progressive changes in the cortex, striatum, extra-striatal brain structures and white matter throughout the spectrum of disease. Our growing understanding of HD underscores the reality that points to the complexity of HD. A single, well-defined genetic mutation causes a cascade of events whose final result is an aggregate insult of the homeostatic process. We explore possible explanations for the selective vulnerability of the brain in HD. The ultimate goal in HD is to develop disease-modifying therapies that will prevent the onset of clinical symptoms in those individuals who are at risk and slow the progression of symptoms in those individuals already affected with symptoms. Understanding changes in brain morphometry and their relationship to clinical symptoms may provide important new and important insights into basic pathophysiological mechanisms at play in the disease. PMID:19076442

Expression of Tau Pathology-Related Proteins in Different Brain Regions: A Molecular Basis of Tau Pathogenesis.

PubMed

Hu, Wen; Wu, Feng; Zhang, Yanchong; Gong, Cheng-Xin; Iqbal, Khalid; Liu, Fei

2017-01-01

Microtubule-associated protein tau is hyperphosphorylated and aggregated in affected neurons in Alzheimer disease (AD) brains. The tau pathology starts from the entorhinal cortex (EC), spreads to the hippocampus and frontal and temporal cortices, and finally to all isocortex areas, but the cerebellum is spared from tau lesions. The molecular basis of differential vulnerability of different brain regions to tau pathology is not understood. In the present study, we analyzed brain regional expressions of tau and tau pathology-related proteins. We found that tau was hyperphosphorylated at multiple sites in the frontal cortex (FC), but not in the cerebellum, from AD brain. The level of tau expression in the cerebellum was about 1/4 of that seen in the frontal and temporal cortices in human brain. In the rat brain, the expression level of tau with three microtubule-binding repeats (3R-tau) was comparable in the hippocampus, EC, FC, parietal-temporal cortex (PTC), occipital-temporal cortex (OTC), striatum, thalamus, olfactory bulb (OB) and cerebellum. However, the expression level of 4R-tau was the highest in the EC and the lowest in the cerebellum. Tau phosphatases, kinases, microtubule-related proteins and other tau pathology-related proteins were also expressed in a region-specific manner in the rat brain. These results suggest that higher levels of tau and tau kinases in the EC and low levels of these proteins in the cerebellum may accounts for the vulnerability and resistance of these representative brain regions to the development of tau pathology, respectively. The present study provides the regional expression profiles of tau and tau pathology-related proteins in the brain, which may help understand the brain regional vulnerability to tau pathology in neurodegenerative tauopathies.

Preliminary dosimetric study on feasibility of multi-beam boron neutron capture therapy in patients with diffuse intrinsic pontine glioma without craniotomy.

PubMed

Lee, Jia-Cheng; Chuang, Keh-Shih; Chen, Yi-Wei; Hsu, Fang-Yuh; Chou, Fong-In; Yen, Sang-Hue; Wu, Yuan-Hung

2017-01-01

Diffuse intrinsic pontine glioma is a very frustrating disease. Since the tumor infiltrates the brain stem, surgical removal is often impossible. For conventional radiotherapy, the dose constraint of the brain stem impedes attempts at further dose escalation. Boron neutron capture therapy (BNCT), a targeted radiotherapy, carries the potential to selectively irradiate tumors with an adequate dose while sparing adjacent normal tissue. In this study, 12 consecutive patients treated with conventional radiotherapy in our institute were reviewed to evaluate the feasibility of BNCT. NCTPlan Ver. 1.1.44 was used for dose calculations. Compared with two and three fields, the average maximal dose to the normal brain may be lowered to 7.35 ± 0.72 Gy-Eq by four-field irradiation. The mean ratio of minimal dose to clinical target volume and maximal dose to normal tissue was 2.41 ± 0.26 by four-field irradiation. A therapeutic benefit may be expected with multi-field boron neutron capture therapy to treat diffuse intrinsic pontine glioma without craniotomy, while the maximal dose to the normal brain would be minimized by using the four-field setting.

Preliminary dosimetric study on feasibility of multi-beam boron neutron capture therapy in patients with diffuse intrinsic pontine glioma without craniotomy

PubMed Central

Lee, Jia-Cheng; Chuang, Keh-Shih; Chen, Yi-Wei; Hsu, Fang-Yuh; Chou, Fong-In; Yen, Sang-Hue

2017-01-01

Diffuse intrinsic pontine glioma is a very frustrating disease. Since the tumor infiltrates the brain stem, surgical removal is often impossible. For conventional radiotherapy, the dose constraint of the brain stem impedes attempts at further dose escalation. Boron neutron capture therapy (BNCT), a targeted radiotherapy, carries the potential to selectively irradiate tumors with an adequate dose while sparing adjacent normal tissue. In this study, 12 consecutive patients treated with conventional radiotherapy in our institute were reviewed to evaluate the feasibility of BNCT. NCTPlan Ver. 1.1.44 was used for dose calculations. Compared with two and three fields, the average maximal dose to the normal brain may be lowered to 7.35 ± 0.72 Gy-Eq by four-field irradiation. The mean ratio of minimal dose to clinical target volume and maximal dose to normal tissue was 2.41 ± 0.26 by four-field irradiation. A therapeutic benefit may be expected with multi-field boron neutron capture therapy to treat diffuse intrinsic pontine glioma without craniotomy, while the maximal dose to the normal brain would be minimized by using the four-field setting. PMID:28662135

Brain cortex mitochondrial bioenergetics in synaptosomes and non-synaptic mitochondria during aging.

PubMed

Lores-Arnaiz, Silvia; Lombardi, Paulina; Karadayian, Analía G; Orgambide, Federico; Cicerchia, Daniela; Bustamante, Juanita

2016-02-01

Alterations in mitochondrial bioenergetics have been associated with brain aging. In order to evaluate the susceptibility of brain cortex synaptosomes and non-synaptic mitochondria to aging-dependent dysfunction, male Swiss mice of 3 or 17 months old were used. Mitochondrial function was evaluated by oxygen consumption, mitochondrial membrane potential and respiratory complexes activity, together with UCP-2 protein expression. Basal respiration and respiration driving proton leak were decreased by 26 and 33 % in synaptosomes from 17-months old mice, but spare respiratory capacity was not modified by aging. Succinate supported state 3 respiratory rate was decreased by 45 % in brain cortex non-synaptic mitochondria from 17-month-old mice, as compared with young animals, but respiratory control was not affected. Synaptosomal mitochondria would be susceptible to undergo calcium-induced depolarization in 17 months-old mice, while non-synaptic mitochondria would not be affected by calcium overload. UCP-2 was significantly up-regulated in both synaptosomal and submitochondrial membranes from 17-months old mice, compared to young animals. UCP-2 upregulation seems to be a possible mechanism by which mitochondria would be resistant to suffer oxidative damage during aging.

Right medial thalamic lesion causes isolated retrograde amnesia.

PubMed

Miller, L A; Caine, D; Harding, A; Thompson, E J; Large, M; Watson, J D

2001-01-01

Pervasive retrograde amnesia without anterograde memory impairment has rarely been described as a consequence of circumscribed brain damage. We report this phenomenon in a 33 yr-old, right-handed man (JG) in association with the extension in the right thalamus of a previously small, bilateral thalamic lesion. JG presented with a dense amnesia for autobiographical material more than a few years old, with some sparing of recent memories. Furthermore, he was completely unable to recognise famous people or world events. Many other aspects of semantic knowledge were intact and there was no evidence of general intellectual impairment, executive dysfunction or loss of visual imagery. Magnetic resonance imaging revealed an acute lesion in the right thalamus and two small, symmetrical, bilateral non-acute thalamic lesions. Follow-up neuropsychological assessment indicated a stable pattern of impaired retrograde and spared anterograde memory over 18 months and psychiatric assessments yielded no evidence of confabulation, malingering or other symptoms to suggest psychogenic amnesia. JG's profile indicates that the division of declarative memory into just two categories - episodic and semantic - is inadequate. Rather, his case adds to the growing body evidence to suggest that world knowledge pertaining to people and events is stored or accessed similarly to autobiographical information and differently from other types of more general factual knowledge. We hypothesize that the right mediodorsal thalamic nucleus and immediately surrounding regions comprise the central processing mechanism referred to by McClelland (Revue Neurologique, 150 (1994) 570) and Markowitsch (Brain Research Review, 21 (1995) 117) as responsible for inducing and co-ordinating the recall of these sorts of cortically stored memory engrams.

Equivalent survival after nipple-sparing compared to non-nipple-sparing mastectomy: data from California, 1988-2013.

PubMed

Kurian, Allison W; Canchola, Alison J; Gomez, Scarlett L; Clarke, Christina A

2016-11-01

Nipple-sparing mastectomy, which may improve cosmesis, body image, and sexual function in comparison to non-nipple-sparing mastectomy, is increasingly used to treat early-stage breast cancer; however, long-term survival data are lacking. We evaluated survival after nipple-sparing mastectomy versus non-nipple-sparing mastectomy in a population-based cancer registry. We conducted an observational study using the California Cancer Registry, considering all stage 0-III breast cancers diagnosed in California from 1988 to 2013. We compared breast cancer-specific and overall survival time after nipple-sparing versus non-nipple-sparing mastectomy, using multivariable analysis. Among 157,592 stage 0-III female breast cancer patients treated with unilateral mastectomy from 1988-2013, 993 (0.6 %) were reported as having nipple-sparing and 156,599 (99.4 %) non-nipple-sparing mastectomies; median follow-up was 7.9 years. The proportion of mastectomies that were nipple-sparing increased over time (1988, 0.2 %; 2013, 5.1 %) and with neighborhood socioeconomic status, and decreased with age and stage. On multivariable analysis, nipple-sparing mastectomy was associated with a lower risk of breast cancer-specific mortality compared to non-nipple-sparing mastectomy [hazard ratio (HR) 0.71, 95 % confidence interval (CI) 0.51-0.98]. However, when restricting to diagnoses 1996 or later and adjusting for a larger set of covariates, risk was attenuated (HR 0.86, 95 % CI 0.52-1.42). Among California breast cancer patients diagnosed from 1988-2013, nipple-sparing mastectomy was not associated with worse survival than non-nipple-sparing mastectomy. These results may inform the decisions of patients and doctors deliberating between these surgical approaches for breast cancer treatment.

Alternative Lipid Emulsions in the Critically Ill: A Systematic Review of the Evidence

PubMed Central

Manzanares, William; Dhaliwal, Rupinder; Jurewitsch, Brian; Stapleton, Renee D.; Jeejeebhoy, Khursheed N.; Heyland, Daren K.

2015-01-01

Introduction Parenteral lipid emulsions (LEs) are commonly rich in long-chain triglycerides (LCT) derived from soybean oil (SO). SO containing emulsions may promote systemic inflammation and therefore may adversely affect clinical outcomes. We hypothesized that alternative oil-based LEs (SO-sparing strategies) may improve clinical outcomes in critically ill adult patients compared to SO emulsion only products. The purpose of this systematic review was to evaluate the effect of parenteral SO-sparing strategies on clinical outcomes in intensive care unit (ICU) patients. Methods We searched computerized databases from 1980 to 2013. We included randomized controlled trials (RCTs) conducted in critically ill adult patients that evaluated SO-sparing strategies versus SO-based LEs in the context of parenteral nutrition (PN). Results A total of 12 RCTs met inclusion criteria. When the results of these RCTs that were statistically aggregated, SO-sparing strategies were associated with clinically important reductions in mortality (risk ratio RR= 0.83, 95% confidence intervals CI 0.62, 1.11, P = 0.20), in duration of ventilation (weighted mean difference, WMD −2.57, 95% CI −5.51, 0.37, P= 0.09), and in ICU length of stay (WMD −2.31, 95% CI −5.28, 0.66, P= 0.13) but none of these differences were statistically significant. SO-sparing strategies had no effect on infectious complications (RR=1.13, 95% CI 0.87, 1.46, P=0.35). Conclusion Alternative oil-based LEs may be associated with clinically important reductions in mortality, duration of ventilation, and ICU LOS but lack of statistical precision precludes any clinical recommendations at this time. Further research is warranted to confirm these potential positive treatment effects. PMID:23812404

Alternative lipid emulsions in the critically ill: a systematic review of the evidence.

PubMed

Manzanares, William; Dhaliwal, Rupinder; Jurewitsch, Brian; Stapleton, Renee D; Jeejeebhoy, Khursheed N; Heyland, Daren K

2013-10-01

Parenteral lipid emulsions (LEs) are commonly rich in long-chain triglycerides derived from soybean oil (SO). SO-containing emulsions may promote systemic inflammation and therefore may adversely affect clinical outcomes. We hypothesized that alternative oil-based LEs (SO-sparing strategies) may improve clinical outcomes in critically ill adult patients compared to products containing SO emulsion only. The purpose of this systematic review was to evaluate the effect of parenteral SO-sparing strategies on clinical outcomes in intensive care unit (ICU) patients. We searched computerized databases from 1980 to 2013. We included randomized controlled trials (RCTs) conducted in critically ill adult patients that evaluated SO-sparing strategies versus SO-based LEs in the context of parenteral nutrition. A total of 12 RCTs met the inclusion criteria. When the results of these RCTs were statistically aggregated, SO-sparing strategies were associated with clinically important reductions in mortality (risk ratio, RR 0.83; 95 % confidence intervals, CI 0.62, 1.11; P = 0.20), in duration of ventilation (weighted mean difference, WMD -2.57; 95 % CI -5.51, 0.37; P = 0.09), and in ICU length of stay (LOS) (WMD -2.31; 95 % CI -5.28, 0.66; P = 0.13) but none of these differences were statistically significant. SO-sparing strategies had no effect on infectious complications (RR 1.13; 95 % CI 0.87, 1.46; P = 0.35). Alternative oil-based LEs may be associated with clinically important reductions in mortality, duration of ventilation, and ICU LOS but lack of statistical precision precludes any clinical recommendations at this time. Further research is warranted to confirm these potential positive treatment effects.

47 CFR 80.866 - Spare antenna.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Spare antenna. 80.866 Section 80.866... Spare antenna. A spare transmitting antenna completely assembled for immediate erection must be provided. If the installed transmitting antenna is suspended between supports, this spare antenna must be a...

47 CFR 80.866 - Spare antenna.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Spare antenna. 80.866 Section 80.866... Spare antenna. A spare transmitting antenna completely assembled for immediate erection must be provided. If the installed transmitting antenna is suspended between supports, this spare antenna must be a...

47 CFR 80.866 - Spare antenna.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false Spare antenna. 80.866 Section 80.866... Spare antenna. A spare transmitting antenna completely assembled for immediate erection must be provided. If the installed transmitting antenna is suspended between supports, this spare antenna must be a...

47 CFR 80.866 - Spare antenna.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Spare antenna. 80.866 Section 80.866... Spare antenna. A spare transmitting antenna completely assembled for immediate erection must be provided. If the installed transmitting antenna is suspended between supports, this spare antenna must be a...

47 CFR 80.866 - Spare antenna.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Spare antenna. 80.866 Section 80.866... Spare antenna. A spare transmitting antenna completely assembled for immediate erection must be provided. If the installed transmitting antenna is suspended between supports, this spare antenna must be a...

Cerebral localization, then and now.

PubMed

Marshall, John C; Fink, Gereon R

2003-11-01

We review some of the progress made in understanding the nature of functional specialization in the human brain, beginning with the anatomical claim that all mental faculties have their own distinct material substrate in different regions of the brain and the psychological claim that each mental faculty is characterized by the content domain with which it deals. This conceptual framework led behavioral neurologists to show how discrete brain lesions provoked different types of language, praxic, gnostic, spatial, and memory disorders. The simplest way of interpreting these anatomoclinical associations was to conjecture that the normal function (now impaired by brain damage) was localized within that lesioned region. It was also realized that cognitive impairments could arise from lesions that spared the functional centers themselves but disconnected them from other centers. Nonetheless, many neuroscientists remained skeptical of the entire paradigm. Accordingly, in the late 19th century functional localization began to be studied in the intact human brain by such techniques as measuring the temperature of different brain regions when different cognitive tasks were performed. During the 20th century these crude techniques gave way to positron emission tomography, functional magnetic resonance imaging, and magnetoencephalography. The relatively precise spatial and temporal resolution of modern methods now raises a crucial question: Do the functional localizations obtained by the anatomoclinical method converge with those implied by the functional neuroimaging of cognition in healthy volunteers? We then conclude with some recent suggestions that functional specialization is not such a fixed property of brain regions as previously supposed.

Postoperative Radiation Therapy after Nipple-Sparing or Skin-Sparing Mastectomy: A Survey of European, North American, and South American Practices.

PubMed

Marta, Gustavo Nader; Poortmans, Philip M; Buchholz, Thomas A; Hijal, Tarek

2017-01-01

Skin sparing mastectomy, a surgical procedure sparing a large portion of the overlying skin of the breast, and nipple-sparing mastectomy, sparing the whole nipple-areolar complex, are increasingly used, although their oncologic efficacy remains unclear. The aim of this study was to assess the radiation oncologists' opinions regarding the indications of radiation therapy (RT) after skin-sparing mastectomy and nipple-sparing mastectomy. Radiation oncology members of four national and international societies were invited to complete a questionnaire comprising of 22 questions to assess their opinions regarding RT indications in the context of skin-sparing and nipple-sparing mastectomy. A total of 298 radiation oncologists answered the questionnaire. 90.9% of respondents affirmed that breast cancer is one of their specializations. The majority declared that post-mastectomy RT is indicated for early-stage (stages I and II) breast cancer patients who present with risk factors for recurrence after skin-sparing or nipple-sparing mastectomy (87.2% and 80.2%, respectively). All suggested risk factors (tumor size, lymph node involvement, extracapsular extension, lymphovascular space invasion, positive surgical margins, triple negative tumor, multicentric tumor, and age) were considered as major elements (important or very important). There is no consensus regarding the necessity of evaluating residual breast tissue or the definition of residual breast tissue after mastectomy. All classic factors were considered as major elements, potentially influencing the decision to advice or not postoperative RT. Many uncertainties remain about the indications for RT after skin-sparing mastectomy or nipple-sparing mastectomy. © 2016 Wiley Periodicals, Inc.

Interleukin-1β overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents.

PubMed

Gui, Wen-Shan; Wei, Xiao; Mai, Chun-Lin; Murugan, Madhuvika; Wu, Long-Jun; Xin, Wen-Jun; Zhou, Li-Jun; Liu, Xian-Guo

2016-01-01

Chronic pain is often accompanied by short-term memory deficit and depression. Currently, it is believed that short-term memory deficit and depression are consequences of chronic pain. Here, we test the hypothesis that the symptoms might be caused by overproduction of interleukin-1beta (IL-1β) in the injured nerve independent of neuropathic pain following spared nerve injury in rats and mice. Mechanical allodynia, a behavioral sign of neuropathic pain, was not correlated with short-term memory deficit and depressive behavior in spared nerve injury rats. Spared nerve injury upregulated IL-1β in the injured sciatic nerve, plasma, and the regions in central nervous system closely associated with pain, memory and emotion, including spinal dorsal horn, hippocampus, prefrontal cortex, nucleus accumbens, and amygdala. Importantly, the spared nerve injury-induced memory deficits, depressive, and pain behaviors were substantially prevented by peri-sciatic administration of IL-1β neutralizing antibody in rats or deletion of IL-1 receptor type 1 in mice. Furthermore, the behavioral abnormalities induced by spared nerve injury were mimicked in naïve rats by repetitive intravenous injection of re combinant rat IL-1β (rrIL-1β) at a pathological concentration as determined from spared nerve injury rats. In addition, microglia were activated by both spared nerve injury and intravenous injection of rrIL-1β and the effect of spared nerve injury was substantially reversed by peri-sciatic administration of anti-IL-1β. Neuropathic pain was not necessary for the development of cognitive and emotional disorders, while the overproduction of IL-1β in the injured sciatic nerve following peripheral nerve injury may be a common mechanism underlying the generation of neuropathic pain, memory deficit, and depression. © The Author(s) 2016.

Incorporating single-side sparing in models for predicting parotid dose sparing in head and neck IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuan, Lulin, E-mail: lulin.yuan@duke.edu; Wu, Q. Jackie; Yin, Fang-Fang

2014-02-15

Purpose: Sparing of single-side parotid gland is a common practice in head-and-neck (HN) intensity modulated radiation therapy (IMRT) planning. It is a special case of dose sparing tradeoff between different organs-at-risk. The authors describe an improved mathematical model for predicting achievable dose sparing in parotid glands in HN IMRT planning that incorporates single-side sparing considerations based on patient anatomy and learning from prior plan data. Methods: Among 68 HN cases analyzed retrospectively, 35 cases had physician prescribed single-side parotid sparing preferences. The single-side sparing model was trained with cases which had single-side sparing preferences, while the standard model was trainedmore » with the remainder of cases. A receiver operating characteristics (ROC) analysis was performed to determine the best criterion that separates the two case groups using the physician's single-side sparing prescription as ground truth. The final predictive model (combined model) takes into account the single-side sparing by switching between the standard and single-side sparing models according to the single-side sparing criterion. The models were tested with 20 additional cases. The significance of the improvement of prediction accuracy by the combined model over the standard model was evaluated using the Wilcoxon rank-sum test. Results: Using the ROC analysis, the best single-side sparing criterion is (1) the predicted median dose of one parotid is higher than 24 Gy; and (2) that of the other is higher than 7 Gy. This criterion gives a true positive rate of 0.82 and a false positive rate of 0.19, respectively. For the bilateral sparing cases, the combined and the standard models performed equally well, with the median of the prediction errors for parotid median dose being 0.34 Gy by both models (p = 0.81). For the single-side sparing cases, the standard model overestimates the median dose by 7.8 Gy on average, while the predictions by the combined model differ from actual values by only 2.2 Gy (p = 0.005). Similarly, the sum of residues between the modeled and the actual plan DVHs is the same for the bilateral sparing cases by both models (p = 0.67), while the standard model predicts significantly higher DVHs than the combined model for the single-side sparing cases (p = 0.01). Conclusions: The combined model for predicting parotid sparing that takes into account single-side sparing improves the prediction accuracy over the previous model.« less

Incorporating single-side sparing in models for predicting parotid dose sparing in head and neck IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuan, Lulin, E-mail: lulin.yuan@duke.edu; Wu, Q. Jackie; Yin, Fang-Fang

Purpose: Sparing of single-side parotid gland is a common practice in head-and-neck (HN) intensity modulated radiation therapy (IMRT) planning. It is a special case of dose sparing tradeoff between different organs-at-risk. The authors describe an improved mathematical model for predicting achievable dose sparing in parotid glands in HN IMRT planning that incorporates single-side sparing considerations based on patient anatomy and learning from prior plan data. Methods: Among 68 HN cases analyzed retrospectively, 35 cases had physician prescribed single-side parotid sparing preferences. The single-side sparing model was trained with cases which had single-side sparing preferences, while the standard model was trainedmore » with the remainder of cases. A receiver operating characteristics (ROC) analysis was performed to determine the best criterion that separates the two case groups using the physician's single-side sparing prescription as ground truth. The final predictive model (combined model) takes into account the single-side sparing by switching between the standard and single-side sparing models according to the single-side sparing criterion. The models were tested with 20 additional cases. The significance of the improvement of prediction accuracy by the combined model over the standard model was evaluated using the Wilcoxon rank-sum test. Results: Using the ROC analysis, the best single-side sparing criterion is (1) the predicted median dose of one parotid is higher than 24 Gy; and (2) that of the other is higher than 7 Gy. This criterion gives a true positive rate of 0.82 and a false positive rate of 0.19, respectively. For the bilateral sparing cases, the combined and the standard models performed equally well, with the median of the prediction errors for parotid median dose being 0.34 Gy by both models (p = 0.81). For the single-side sparing cases, the standard model overestimates the median dose by 7.8 Gy on average, while the predictions by the combined model differ from actual values by only 2.2 Gy (p = 0.005). Similarly, the sum of residues between the modeled and the actual plan DVHs is the same for the bilateral sparing cases by both models (p = 0.67), while the standard model predicts significantly higher DVHs than the combined model for the single-side sparing cases (p = 0.01). Conclusions: The combined model for predicting parotid sparing that takes into account single-side sparing improves the prediction accuracy over the previous model.« less

Comparative dosimetry of volumetric modulated arc therapy and limited-angle static intensity-modulated radiation therapy for early-stage larynx cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riegel, Adam C.; Antone, Jeffrey; Schwartz, David L., E-mail: dschwartz3@nshs.edu

2013-04-01

To compare relative carotid and normal tissue sparing using volumetric-modulated arc therapy (VMAT) or intensity-modulated radiation therapy (IMRT) for early-stage larynx cancer. Seven treatment plans were retrospectively created on 2 commercial treatment planning systems for 11 consecutive patients with T1-2N0 larynx cancer. Conventional plans consisted of opposed-wedged fields. IMRT planning used an anterior 3-field beam arrangement. Two VMAT plans were created, a full 360° arc and an anterior 180° arc. Given planning target volume (PTV) coverage of 95% total volume at 95% of 6300 cGy and maximum spinal cord dose below 2500 cGy, mean carotid artery dose was pushed asmore » low as possible for each plan. Deliverability was assessed by comparing measured and planned planar dose with the gamma (γ) index. Full-arc planning provided the most effective carotid sparing but yielded the highest mean normal tissue dose (where normal tissue was defined as all soft tissue minus PTV). Static IMRT produced next-best carotid sparing with lower normal tissue dose. The anterior half-arc produced the highest carotid artery dose, in some cases comparable with conventional opposed fields. On the whole, carotid sparing was inversely related to normal tissue dose sparing. Mean γ indexes were much less than 1, consistent with accurate delivery of planned treatment. Full-arc VMAT yields greater carotid sparing than half-arc VMAT. Limited-angle IMRT remains a reasonable alternative to full-arc VMAT, given its ability to mediate the competing demands of carotid and normal tissue dose constraints. The respective clinical significance of carotid and normal tissue sparing will require prospective evaluation.« less

Inventory-transportation integrated optimization for maintenance spare parts of high-speed trains

PubMed Central

Wang, Jiaxi; Wang, Huasheng; Wang, Zhongkai; Li, Jian; Lin, Ruixi; Xiao, Jie; Wu, Jianping

2017-01-01

This paper presents a 0–1 programming model aimed at obtaining the optimal inventory policy and transportation mode for maintenance spare parts of high-speed trains. To obtain the model parameters for occasionally-replaced spare parts, a demand estimation method based on the maintenance strategies of China’s high-speed railway system is proposed. In addition, we analyse the shortage time using PERT, and then calculate the unit time shortage cost from the viewpoint of train operation revenue. Finally, a real-world case study from Shanghai Depot is conducted to demonstrate our method. Computational results offer an effective and efficient decision support for inventory managers. PMID:28472097

Proton Radiotherapy for Childhood Ependymoma: Initial Clinical Outcomes and Dose Comparisons

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacDonald, Shannon M.; Safai, Sairos; Trofimov, Alexei

2008-07-15

Purpose: To report preliminary clinical outcomes for pediatric patients treated with proton beam radiation for intracranial ependymoma and compare the dose distributions of intensity-modulated radiation therapy with photons (IMRT), three-dimensional conformal proton radiation, and intensity-modulated proton radiation therapy (IMPT) for representative patients. Methods and Materials: All children with intracranial ependymoma confined to the supratentorial or infratentorial brain treated at the Francis H. Burr Proton Facility and Harvard Cyclotron between November 2000 and March 2006 were included in this study. Seventeen patients were treated with protons. Proton, IMRT, and IMPT plans were generated with similar clinical constraints for representative infratentorial andmore » supratentorial ependymoma cases. Tumor and normal tissue dose-volume histograms were calculated and compared. Results: At a median follow-up of 26 months from the start date of radiation therapy, local control, progression-free survival, and overall survival rates were 86%, 80%, and 89%, respectively. Subtotal resection was significantly associated with decreased local control (p = 0.016). Similar tumor volume coverage was achieved with IMPT, proton therapy, and IMRT. Substantial normal tissue sparing was seen with proton therapy compared with IMRT. Use of IMPT will allow for additional sparing of some critical structures. Conclusions: Preliminary disease control with proton therapy compares favorably with the literature. Dosimetric comparisons show the advantage of proton radiation compared with IMRT in the treatment of ependymoma. Further sparing of normal structures appears possible with IMPT. Superior dose distributions were accomplished with fewer beam angles with the use of protons and IMPT.« less

Exercise-induced rescue of tongue function without striatal dopamine sparing in a rat neurotoxin model of Parkinson disease.

PubMed

Ciucci, Michelle R; Schaser, Allison J; Russell, John A

2013-09-01

Unilateral lesions to the medial forebrain bundle with 6-hydroxydopamine (6-OHDA) lead to force and timing deficits during a complex licking task. We hypothesized that training targeting tongue force generation during licking would improve timing and force measures and also lead to striatal dopamine sparing. Nine month-old male Fisher344/Brown Norway rats were used in this experiment. Sixteen rats were in the control condition and received tongue exercise (n=8) or no exercise (n=8). Fourteen rats were in the 6-OHDA lesion condition and underwent tongue exercise (n=7) and or no exercise (n=7). Following 4 weeks of training and post-training measures, all animals underwent bilateral stimulation of the hypoglossal nerves to measure muscle contractile properties and were then transcardially perfused and brain tissues collected for immunohistochemistry to examine striatal dopamine content. Results demonstrated that exercise animals performed better for maximal force, average force, and press rate than their no-exercise counterparts, and the 6-OHDA animals that underwent exercise performed as well as the Control No Exercise group. Interestingly, there were no group differences for tetanic muscle force, despite behavioral recovery of forces. Additionally, behavioral and neurochemical analyses indicate that there were no differences in striatal dopamine. Thus, targeted exercise can improve tongue force and timing deficits related to 6-OHDA lesions and this exercise likely has a central, versus peripheral (muscle strength) mechanism. However, this mechanism is not related to sparing of striatal dopamine content. Copyright © 2013 Elsevier B.V. All rights reserved.

Innate immunity and protective neuroinflammation: new emphasis on the role of neuroimmune regulatory proteins.

PubMed

Griffiths, M; Neal, J W; Gasque, P

2007-01-01

Brain inflammation due to infection, hemorrhage, and aging is associated with activation of the local innate immune system as expressed by infiltrating cells, resident glial cells, and neurons. The innate immune response relies on the detection of "nonself" and "danger-self" ligands behaving as "eat me signals" by a plethora of pattern recognition receptors (PRRs) expressed by professional and amateur phagocytes to promote the clearance of pathogens, toxic cell debris (amyloid fibrils, aggregated synucleins, prions), and apoptotic cells accumulating within the brain parenchyma and the cerebrospinal fluid (CSF). These PRRs (e.g., complement, TLR, CD14, scavenger receptors) are highly conserved between vertebrates and invertebrates and may represent the most ancestral innate scavenging system involved in tissue homeostasis. However, in some diseases, these protective mechanisms lead to neurodegeneration on the ground that several innate immune molecules have neurocytotoxic activities. The response is a "double-edged sword" representing a fine balance between protective and detrimental effects. Several key regulatory mechanisms have now been evidenced in the control of CNS innate immunity, and these could be harnessed to explore novel therapeutic avenues. We will herein provide new emphasis on the role of neuroimmune regulatory proteins (NIRegs), such as CD95L, TNF, CD200, CD47, sialic acids, CD55, CD46, fH, C3a, HMGB1, which are involved in silencing innate immunity at the cellular and molecular levels and suppression of inflammation. For instance, NIRegs may play an important role in controlling lymphocyte/macrophage/microglia hyperinflammatory responses, while sparing host defense and repair mechanisms. Moreover, NIRegs have direct beneficial effects on neurogenesis and contributing to brain tissue remodeling.

The effects of a high-energy diet on hippocampal function and blood-brain barrier integrity in the rat.

PubMed

Kanoski, Scott E; Zhang, Yanshu; Zheng, Wei; Davidson, Terry L

2010-01-01

Cognitive impairment and Alzheimer's disease are linked with intake of a Western diet, characterized by high levels of saturated fats and simple carbohydrates. In rats, these dietary components have been shown to disrupt hippocampal-dependent learning and memory processes, particularly those involving spatial memory. Using a rat model, the present research assessed the degree to which consumption of a high-energy (HE) diet, similar to those found in modern Western cultures, produces a selective impairment in hippocampal function as opposed to a more global cognitive disruption. Learning and memory performance was examined following 90-day consumption of an HE-diet in three nonspatial discrimination learning problems that differed with respect to their dependence on the integrity of the hippocampus. The results showed that consumption of the HE-diet impaired performance in a hippocampal-dependent feature negative discrimination problem relative to chow-fed controls, whereas performance was spared on two discrimination problems that do not rely on the hippocampus. To explore the mechanism whereby consuming HE-diets impairs cognitive function, we investigated the effect of HE-diets on the integrity of the blood-brain barrier (BBB). We found that HE-diet consumption produced a decrease in mRNA expression of tight junction proteins, particularly Claudin-5 and -12, in the choroid plexus and the BBB. Consequently, an increased blood-to-brain permeability of sodium fluorescein was observed in the hippocampus, but not in the striatum and prefrontal cortex following HE-diet access. These results indicate that hippocampal function may be particularly vulnerable to disruption by HE-diets, and this disruption may be related to impaired BBB integrity.

Dexmedetomidine in Attenuation of Haemodynamic Response and Dose Sparing Effect on Opioid and Anaesthetic Agents in Patients undergoing Laparoscopic Cholecystectomy- A Randomized Study

PubMed Central

Bhagat, Nandlal; Karim, Habib Md Reazaul; Hajong, Ranendra; Bhattacharyya, Prithwis; Singh, Manorama

2016-01-01

Introduction Perioperative procedures are stressful and lead to haemodynamic instability with potentially devastating consequences. Dexmedetomidine is found to have many of the desired characteristics that are required in perioperative period. Aim To evaluate the ability of pre and intraoperative dexmedetomidine to attenuate stress induced haemodynamic responses, quantifying the anaesthetic agents sparing as well as its cost-effectiveness in patients undergoing laparoscopic cholecystectomy. Materials and Methods The present single blind randomized study was conducted with 120 ASA I and II consented patients who underwent laparoscopic cholecystectomy. Patients were randomly divided into 2 groups (i.e., group D and group N). Prior to induction, group D received 1 μg/kg of Dexmedetomidine and group N received Normal saline infusion over 20 minutes. Group D also received maintenance Dexmedetomidine intraoperatively. Bispectral index and minimum alveolar concentration monitoring was done in both the groups. Haemodynamic parameters were noted till 100 minutes post laryngoscopy. Opioid and anaesthetic agent consumptions were also noted and cost analysis was done. Medcalc–Version 12.5.0.0 software was used for statistics and p <0.05 was considered significant. Results Dexmedetomidine attenuated the stress induced haemodynamics responses and produced stable, relatively non fluctuating haemodynamics throughout. The Minimum Alveolar Concentration (MAC) requirement and the consumptions of Fentanyl and Isoflurane were significantly less in the Dexmedetomidine group (p<0.0001). However, despite anaesthetic dose sparing effect the anaesthetic technique was not cost-effective. Conclusion Dexmedetomidine is effective in attenuating haemodynamic responses in laparoscopic surgery and having dose sparing effect on Fentanyl, Propofol and Isoflurane. However, overall this technique is not cost-effective. PMID:28050479

Opioid-sparing effects of the thoracic interfascial plane blocks: A meta-analysis of randomized controlled trials

PubMed Central

Singh, Preet Mohinder; Borle, Anuradha; Kaur, Manpreet; Trikha, Anjan; Sinha, Ashish

2018-01-01

Background: Thoracic interfascial plane blocks and modification (PECS) have recently gained popularity for analgesic potential during breast surgery. We evaluate/consolidate the evidence on opioid-sparing effect of PECS blocks in comparison with conventional intravenous analgesia (IVA) and paravertebral block (PVB). Materials and Methods: Prospective, randomized controlled trials comparing PECS block to conventional IVA or PVB in patients undergoing breast surgery published till June 2017 were searched in the medical database. Comparisons were made for 24-h postoperative morphine consumption and intraoperative fentanyl-equivalent consumption. Results: Final analysis included nine trials (PECS vs. IVA 4 trials and PECS vs. PVB 5 trials). PECS block showed a decreased intraoperative fentanyl consumption over IVA by 49.20 mcg (95% confidence interval [CI] =42.67–55.74) (I2 = 98.47%, P < 0.001) and PVB by 15.88 mcg (95% CI = 12.95–18.81) (I2 = 95.51%, P < 0.001). Postoperative, 24-h morphine consumption with PECS block was lower than IVA by 7.66 mg (95% CI being 6.23–9.10) (I2 = 63.15, P < 0.001) but was higher than PVB group by 1.26 mg (95% CI being 0.91–1.62) (I2 = 99.53%, P < 0.001). Two cases of pneumothorax were reported with PVB, and no complication was reported in any other group. Conclusions: Use of PECS block and its modifications with general anesthesia for breast surgery has significant opioid-sparing effect intraoperatively and during the first 24 h after surgery. It also has higher intraoperative opioid-sparing effect when compared to PVB. During the 1st postoperative day, PVB has slightly more morphine sparing potential that may however be associated with higher complication rates. The present PECS block techniques show marked interstudy variations and need standardization. PMID:29416465

Stereotactic Radiosurgery in the Management of Patients With Brain Metastases of Non-Small Cell Lung Cancer: Indications, Decision Tools and Future Directions

PubMed Central

Hartgerink, Dianne; van der Heijden, Britt; De Ruysscher, Dirk; Postma, Alida; Ackermans, Linda; Hoeben, Ann; Anten, Monique; Lambin, Philippe; Terhaag, Karin; Jochems, Arthur; Dekker, Andre; Schoenmaekers, Janna; Hendriks, Lizza; Zindler, Jaap

2018-01-01

Brain metastases (BM) frequently occur in non-small cell lung cancer (NSCLC) patients. Most patients with BM have a limited life expectancy, measured in months. Selected patients may experience a very long progression-free survival, for example, patients with a targetable driver mutation. Traditionally, whole-brain radiotherapy (WBRT) has been the cornerstone of the treatment, but its indication is a matter of debate. A randomized trial has shown that for patients with a poor prognosis, WBRT does not add quality of life (QoL) nor survival over the best supportive care. In recent decades, stereotactic radiosurgery (SRS) has become an attractive non-invasive treatment for patients with BM. Only the BM is irradiated to an ablative dose, sparing healthy brain tissue. Intracranial recurrence rates decrease when WBRT is administered following SRS or resection but does not improve overall survival and comes at the expense of neurocognitive function and QoL. The downside of SRS compared with WBRT is a risk of radionecrosis (RN) and a higher risk of developing new BM during follow-up. Currently, SRS is an established treatment for patients with a maximum of four BM. Several promising strategies are currently being investigated to further improve the indication and outcome of SRS for patients with BM: the effectivity and safety of SRS in patients with more than four BM, combining SRS with systemic therapy such as targeted agents or immunotherapy, shared decision-making with SRS as a treatment option, and individualized isotoxic dose prescription to mitigate the risk of RN and further enhance local control probability of SRS. This review discusses the current indications of SRS and future directions of treatment for patients with BM of NSCLC with focus on the value of SRS.

Evaluation of porphyrin C analogues for photodynamic therapy of cerebral glioma.

PubMed

Karagianis, G; Hill, J S; Stylli, S S; Kaye, A H; Varadaxis, N J; Reiss, J A; Phillips, D R

1996-02-01

A series of monomeric porphyrins (2-8) based on porphyrin C (1) have been tested as sensitisers for photodynamic therapy (PDT) of cerebral glioma using the in vitro/in vivo C6 intracerebral animal tumour model. The in vivo screening, consisting of cytotoxicity, phototoxicity (red light) and subcellular localisation studies, revealed two sensitisers (porphyrin 7, molecular weight 863 Da and porphyrin 8, molecular weight 889 Da), which had greater photoactivity than porphyrin C and similar photoactivity to haematoporphyrin derivative (HpD) although at a 5-fold higher dose than HpD. Both sensitisers showed intracellular localisation to discrete organelle sites and exhibited considerably less 'dark' cytotoxicity than HpD. The kinetics of uptake of porphyrins 7 and 8 was studied in the mouse C6 glioma model as well as in biopsy samples from normal brain, liver, spleen and blood. Maximal drug uptake levels in tumour occurred 9 and 6 h after intraperitoneal injection for 7 and 8 respectively, at which time the tumour to normal brain ratios were 15:1 and 13:1 respectively. The effect of PDT using porphyrin 7 activated by the gold metal vapour laser tuned to 627.8 nm was studied in Wistar rats bearing intracerebral C6 glioma. At a drug dose of 10 mg porphyrin 7 kg-1 body weight and laser doses of up to 400 J cm-2 light, selective tumour kill with sparing of normal brain was achieved, with a maximal depth of tumour kill of 1.77+/-0.40. mm. Irradiation following a higher drug dose of 75 mg porphyrin 7 kg-1 body weight resulted in a greater depth of tumour kill, but also significantly increased the likelihood and extent of necrosis in normal brain.

Land-Sparing Agriculture Best Protects Avian Phylogenetic Diversity.

PubMed

Edwards, David P; Gilroy, James J; Thomas, Gavin H; Uribe, Claudia A Medina; Haugaasen, Torbjørn

2015-09-21

The conversion of natural habitats to farmland is a major driver of the global extinction crisis. Two strategies are promoted to mitigate the impacts of agricultural expansion on biodiversity: land sharing integrates wildlife-friendly habitats within farmland landscapes, and land sparing intensifies farming to allow the offset of natural reserves. A key question is which strategy would protect the most phylogenetic diversity--the total evolutionary history shared across all species within a community. Conserving phylogenetic diversity decreases the chance of losing unique phenotypic and ecological traits and provides benefits for ecosystem function and stability. Focusing on birds in the threatened Chocó-Andes hotspot of endemism, we tested the relative benefits of each strategy for retaining phylogenetic diversity in tropical cloud forest landscapes threatened by cattle pastures. Using landscape simulations, we find that land sharing would protect lower community-level phylogenetic diversity than land sparing and that with increasing distance from forest (from 500 to >1,500 m), land sharing is increasingly inferior to land sparing. Isolation from forest also leads to the loss of more evolutionarily distinct species from communities within land-sharing landscapes, which can be avoided with effective land sparing. Land-sharing policies that promote the integration of small-scale wildlife-friendly habitats might be of limited benefit without the simultaneous protection of larger blocks of natural habitat, which is most likely to be achieved via land-sparing measures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Emotional power of music in patients with memory disorders: clinical implications of cognitive neuroscience.

PubMed

Samson, Séverine; Dellacherie, Delphine; Platel, Hervé

2009-07-01

By adapting methods of cognitive psychology to neuropsychology, we examined memory and familiarity abilities in music in relation to emotion. First we present data illustrating how the emotional content of stimuli influences memory for music. Second, we discuss recent findings obtained in patients with two different brain disorders (medically intractable epilepsy and Alzheimer's disease) that show relatively spared memory performance for music, despite severe verbal memory disorders. Studies on musical memory and its relation to emotion open up paths for new strategies in cognitive rehabilitation and reinstate the importance of examining interactions between cognitive and clinical neurosciences.

White Matter Abnormalities in Autism and Unaffected Siblings.

PubMed

Jou, Roger J; Reed, Hannah E; Kaiser, Martha D; Voos, Avery C; Volkmar, Fred R; Pelphrey, Kevin A

2016-01-01

This study was conducted to identify a potential neuroendophenotype for autism using diffusion tensor imaging. Whole-brain, voxel-based analysis of fractional anisotropy was conducted in 50 children: 19 with autism, 20 unaffected siblings, and 11 controls. Relative to controls, participants with autism exhibited bilateral reductions in fractional anisotropy across association, commissure, and projection fibers. The most severely affected tracts included the uncinate fasciculus, forceps minor, and inferior fronto-occipital fasciculus. Unaffected siblings also exhibited reductions in fractional anisotropy, albeit less severe with fewer affected tracts, sparing the uncinate fasciculus and forceps minor. These results suggest the presence of a neuroendophenotype for autism.

Ischemic stroke of the pyramidal decussation causing quadriplegia and anarthria.

PubMed

Wilkins, Emilia G; Kamel, Hooman; Johnson, Eric C B; Shalev, Sarah M; Josephson, S Andrew

2012-10-01

A 52-year-old man with a history of hypertension and previously irradiated head and neck cancer presented with quadriplegia and anarthria sparing the face and sensory functions. Brain magnetic resonance imaging (MRI) demonstrated acute infarction of the pyramidal decussation. We describe the clinical and radiological characteristics of infarction at the pyramidal decussation and review the arterial supply to this region in the lower brainstem. Although rare, infarction of the pyramidal decussation should be considered in the differential diagnosis when patients present with atraumatic pure motor quadriplegia. Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Cerebral Proliferative Angiopathy (CPA): Imaging Findings and Response to Therapy.

PubMed

Lopci, Egesta; Olivari, Laura; Bello, Lorenzo; Navarria, Pierina; Chiti, Arturo

2016-12-01

We report the case of a 55-year-old woman with cerebral proliferative angiopathy (CPA). Her medical history included brain surgery for small vascular lesions and suspicion of cerebral malignancy. C methionine PET (C-METH PET) demonstrated a diffusely increased uptake on the right hemisphere. Contrast-enhanced MRI documented a massive lesion with a diffuse "nidus" appearance, involving the right cerebral hemisphere (sparing the inferior frontal gyrus and the anterior frontal lobe), the brainstem, and the middle cerebellar peduncle. Pathology confirmed the diagnosis of CPA and, after radiation treatment, the patient presented with clinical and radiological response.

The influence of sociocultural factors on organ donation and transplantation in Korea: findings from key informant interviews.

PubMed

Kim, Jung Ran; Elliott, Doug; Hyde, Cheryl

2004-04-01

Although brain death was formally recognized in Korea in 2000 for the purpose of organ donation, traditional Confucian-based thought still prevails. The aim of this study was to explore sociocultural perspectives that influence health professionals' attitudes and perceptions regarding organ donation. Semistructured interviews were conducted with nine key informants from three major hospitals providing transplant services in South Korea. Several themes were identified as barriers to organ donation: Confucianism, misunderstandings and myths, organs as spare for selling, lack of clarity in the definition of death in the new legislation, and limited medical insurance coverage. It remains difficult for brain death to be accepted as true death, and there is currently a poor rate of organ procurement. Findings of the study will help identify socioculturally appropriate strategies to promote acceptance and accessibility of organ transplantation among South Koreans.

A Probabilistic Tool that Aids Logistics Engineers in the Establishment of High Confidence Repair Need-Dates at the NASA Shuttle Logistics Depot

NASA Technical Reports Server (NTRS)

Bullington, J. V.; Winkler, J. C.; Linton, D. G.; Khajenoori, S.

1995-01-01

The NASA Shuttle Logistics Depot (NSLD) is tasked with the responsibility for repair and manufacture of Line Replaceable Unit (LRU) hardware and components to support the Space Shuttle Orbiter. Due to shrinking budgets, cost effective repair of LRU's becomes a primary objective. To achieve this objective, is imperative that resources be assigned to those LRU's which have the greatest expectation of being needed as a spare. Forecasting the times at which spares are needed requires consideration of many significant factors including: failure rate, flight rate, spares availability, and desired level of support, among others. This paper summarizes the results of the research and development work that has been accomplished in producing an automated tool that assists in the assignment of effective repair start-times for LRU's at the NSLD. This system, called the Repair Start-time Assessment System (RSAS), uses probabilistic modeling technology to calculate a need date for a repair that considers the current repair pipeline status, as well as, serviceable spares and projections of future demands. The output from the system is a date for beginning the repair that has significantly greater confidence (in the sense that a desired probability of support is ensured) than times produced using other techniques. Since an important output of RSAS is the longest repair turn-around time that will ensure a desired probability of support, RSAS has the potential for being applied to operations at any repair depot where spares are on-hand and repair start-times are of interest. In addition, RSAS incorporates tenants of Just-in-Time (JIT) techniques in that the latest repair start-time (i.e., the latest time at which repair resources must be committed) may be calculated for every failed unit This could reduce the spares inventory for certain items, without significantly increasing the risk of unsatisfied demand.

A Neuroprotective Sericin Hydrogel As an Effective Neuronal Cell Carrier for the Repair of Ischemic Stroke.

PubMed

Wang, Zheng; Wang, Jian; Jin, Yang; Luo, Zhen; Yang, Wen; Xie, Hongjian; Huang, Kai; Wang, Lin

2015-11-11

Ischemic stroke causes extensive cellular loss that impairs brain functions, resulting in severe disabilities. No effective treatments are currently available for brain tissue regeneration. The need to develop effective therapeutic approaches for treating stroke is compelling. A tissue engineering approach employing a hydrogel carrying both cells and neurotrophic cytokines to damaged regions is an encouraging alternative for neuronal repair. However, this approach is often challenged by low in vivo cell survival rate, and low encapsulation efficiency and loss of cytokines. To address these limitations, we propose to develop a biomaterial that can form a matrix capable of improving in vivo survival of transplanted cells and reducing in vivo loss of cytokines. Here, we report that using sericin, a natural protein from silk, we have fabricated a genipin-cross-linked sericin hydrogel (GSH) with porous structure and mild swelling ratio. The GSH supports the effective attachment and growth of neurons in vitro. Strikingly, our data reveal that sericin protein is intrinsically neurotrophic and neuroprotective, promoting axon extension and branching as well as preventing primary neurons from hypoxia-induced cell death. Notably, these functions are inherited by the GSH's degradation products, which might spare a need of incorporating costly cytokines. We further demonstrate that this neurotrophic effect is dependent on the Lkb1-Nuak1 pathway, while the neuroprotective effect is realized through regulating the Bcl-2/Bax protein ratio. Importantly, when transplanted in vivo, the GSH gives a high cell survival rate and allows the cells to continuously proliferate. Together, this work unmasks the neurotrophic and neuroprotective functions for sericin and provides strong evidence justifying the GSH's suitability as a potential neuronal cell delivery vehicle for ischemic stroke repair.

Complete spinal cord injury (SCI) transforms how brain derived neurotrophic factor (BDNF) affects nociceptive sensitization.

PubMed

Huang, Yung-Jen; Lee, Kuan H; Grau, James W

2017-02-01

Noxious stimulation can induce a lasting increase in neural excitability within the spinal cord (central sensitization) that can promote pain and disrupt adaptive function (maladaptive plasticity). Brain-derived neurotrophic factor (BDNF) is known to regulate the development of plasticity and has been shown to impact the development of spinally-mediated central sensitization. The latter effect has been linked to an alteration in GABA-dependent inhibition. Prior studies have shown that, in spinally transected rats, exposure to regular (fixed spaced) stimulation can counter the development of maladaptive plasticity and have linked this effect to an up-regulation of BDNF. Here it is shown that application of the irritant capsaicin to one hind paw induces enhanced mechanical reactivity (EMR) after spinal cord injury (SCI) and that the induction of this effect is blocked by pretreatment with fixed spaced shock. This protective effect was eliminated if rats were pretreated with the BDNF sequestering antibody TrkB-IgG. Intrathecal (i.t.) application of BDNF prevented, but did not reverse, capsaicin-induced EMR. BDNF also attenuated cellular indices (ERK and pERK expression) of central sensitization after SCI. In uninjured rats, i.t. BDNF enhanced, rather than attenuated, capsaicin-induced EMR and ERK/pERK expression. These opposing effects were related to a transformation in GABA function. In uninjured rats, BDNF reduced membrane-bound KCC2 and the inhibitory effect of the GABA A agonist muscimol. After SCI, BDNF increased KCC2 expression, which would help restore GABAergic inhibition. The results suggest that SCI transforms how BDNF affects GABA function and imply that the clinical usefulness of BDNF will depend upon the extent of fiber sparing. Copyright © 2016 Elsevier Inc. All rights reserved.

Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study.

PubMed

Yuan, Hong; Zhang, Lei; Frank, Jonathan E; Inscoe, Christina R; Burk, Laurel M; Hadsell, Mike; Lee, Yueh Z; Lu, Jianping; Chang, Sha; Zhou, Otto

2015-09-01

Microbeam radiation treatment (MRT) using synchrotron radiation has shown great promise in the treatment of brain tumors, with a demonstrated ability to eradicate the tumor while sparing normal tissue in small animal models. With the goal of expediting the advancement of MRT research beyond the limited number of synchrotron facilities in the world, we recently developed a compact laboratory-scale microbeam irradiator using carbon nanotube (CNT) field emission-based X-ray source array technology. The focus of this study is to evaluate the effects of the microbeam radiation generated by this compact irradiator in terms of tumor control and normal tissue damage in a mouse brain tumor model. Mice with U87MG human glioblastoma were treated with sham irradiation, low-dose MRT, high-dose MRT or 10 Gy broad-beam radiation treatment (BRT). The microbeams were 280 μm wide and spaced at 900 μm center-to-center with peak dose at either 48 Gy (low-dose MRT) or 72 Gy (high-dose MRT). Survival studies showed that the mice treated with both MRT protocols had a significantly extended life span compared to the untreated control group (31.4 and 48.5% of life extension for low- and high-dose MRT, respectively) and had similar survival to the BRT group. Immunostaining on MRT mice demonstrated much higher DNA damage and apoptosis level in tumor tissue compared to the normal brain tissue. Apoptosis in normal tissue was significantly lower in the low-dose MRT group compared to that in the BRT group at 48 h postirradiation. Interestingly, there was a significantly higher level of cell proliferation in the MRT-treated normal tissue compared to that in the BRT-treated mice, indicating rapid normal tissue repairing process after MRT. Microbeam radiation exposure on normal brain tissue causes little apoptosis and no macrophage infiltration at 30 days after exposure. This study is the first biological assessment on MRT effects using the compact CNT-based irradiator. It provides an alternative technology that can enable widespread MRT research on mechanistic studies using a preclinical model, as well as further translational research towards clinical applications.

Muscarinic receptors in amygdala control trace fear conditioning.

PubMed

Baysinger, Amber N; Kent, Brianne A; Brown, Thomas H

2012-01-01

Intelligent behavior requires transient memory, which entails the ability to retain information over short time periods. A newly-emerging hypothesis posits that endogenous persistent firing (EPF) is the neurophysiological foundation for aspects or types of transient memory. EPF is enabled by the activation of muscarinic acetylcholine receptors (mAChRs) and is triggered by suprathreshold stimulation. EPF occurs in several brain regions, including the lateral amygdala (LA). The present study examined the role of amygdalar mAChRs in trace fear conditioning, a paradigm that requires transient memory. If mAChR-dependent EPF selectively supports transient memory, then blocking amygdalar mAChRs should impair trace conditioning, while sparing delay and context conditioning, which presumably do not rely upon transient memory. To test the EPF hypothesis, LA was bilaterally infused, prior to trace or delay conditioning, with either a mAChR antagonist (scopolamine) or saline. Computerized video analysis quantified the amount of freezing elicited by the cue and by the training context. Scopolamine infusion profoundly reduced freezing in the trace conditioning group but had no significant effect on delay or context conditioning. This pattern of results was uniquely anticipated by the EPF hypothesis. The present findings are discussed in terms of a systems-level theory of how EPF in LA and several other brain regions might help support trace fear conditioning.

Long-term paired associative stimulation can restore voluntary control over paralyzed muscles in incomplete chronic spinal cord injury patients

PubMed Central

Shulga, Anastasia; Lioumis, Pantelis; Zubareva, Aleksandra; Brandstack, Nina; Kuusela, Linda; Kirveskari, Erika; Savolainen, Sarianna; Ylinen, Aarne; Mäkelä, Jyrki P

2016-01-01

Emerging therapeutic strategies for spinal cord injury aim at sparing or restoring at least part of the corticospinal tract at the acute stage. Hence, approaches that strengthen the weak connections that are spared or restored are crucial. Transient plastic changes in the human corticospinal tract can be induced through paired associative stimulation, a noninvasive technique in which transcranial magnetic brain stimulation is synchronized with electrical peripheral nerve stimulation. A single paired associative stimulation session can induce transient plasticity in spinal cord injury patients. It is not known whether paired associative stimulation can strengthen neuronal connections persistently and have therapeutic effects that are clinically relevant. We recruited two patients with motor-incomplete chronic (one para- and one tetraplegic) spinal cord injuries. The patients received paired associative stimulation for 20–24 weeks. The paraplegic patient, previously paralyzed below the knee level, regained plantarflexion and dorsiflexion of the ankles of both legs. The tetraplegic patient regained grasping ability. The newly acquired voluntary movements could be performed by the patients in the absence of stimulation and for at least 1 month after the last stimulation session. In this unblinded proof-of-principle demonstration in two subjects, long-term paired associative stimulation induced persistent and clinically relevant strengthening of neural connections and restored voluntary movement in previously paralyzed muscles. Further study is needed to confirm whether long-term paired associative stimulation can be used in rehabilitation after spinal cord injury by itself and, possibly, in combination with other therapeutic strategies. PMID:28053760

Methotrexate therapy for chronic noninfectious uveitis: analysis of a case series of 160 patients.

PubMed

Samson, C M; Waheed, N; Baltatzis, S; Foster, C S

2001-06-01

To evaluate the outcomes of patients with chronic noninfectious uveitis unresponsive to conventional antiinflammatory therapy who were treated with methotrexate. Retrospective noncomparative interventional case series. All patients with chronic noninfectious uveitis treated with methotrexate at a single institution from 1985 to 1999. Charts of patients seen on the Ocular Immunology & Uveitis Service at the Massachusetts Eye & Ear Infirmary were reviewed. Patients with chronic uveitis of noninfectious origin treated with methotrexate were included in the study. Control of inflammation, steroid-sparing effect, visual acuity, adverse reactions. A total of 160 patients met the inclusion criteria. Control of inflammation was achieved in 76.2% of patients. Steroid-sparing effect was achieved in 56% of patients. Visual acuity was maintained or improved in 90% of patients. Side effects requiring discontinuation of medication occurred in 18% of patients. Potentially serious adverse reactions occurred in only 8.1% of patients. There was neither long-term morbidity nor mortality caused by methotrexate. Methotrexate is effective in the treatment of chronic noninfectious uveitis that fails to respond to conventional steroid treatment. It is an effective steroid-sparing immunomodulator, is a safe medication, and is well tolerated.

A reconfigurable common spare for co-located direct television broadcasting satellites

NASA Astrophysics Data System (ADS)

Roederer, A.; Fromm, H.-H.; Berretta, G.

1984-10-01

Spare spacecraft are needed to assure continuous operation in broadcasting services provided with the aid of satellites. The present investigation is concerned with the employment of a common spare approach in which two or three countries share one or several spare spacecraft that can support or temporarily replace any of the prime satellites. Such common spares would have to be reconfigurable to adapt their antenna coverage and polarization, as well as their operating frequencies and possibly their RF output power, to the corresponding parameters assigned to the country to be served. The considered concept is discussed, taking into account questions related to system and transponder, a repointable antenna with a few feed horns, a fixed antenna (apart from fine pointing) with more feeds, and a reconfigurable broadcast payload for a common spare. A common spare for France, Germany, and Italy is considered along with a common spare for the United Kingdom and Spain.

Residual neurological function after sacral root resection during en-bloc sacrectomy: a systematic review.

PubMed

Zoccali, Carmine; Skoch, Jesse; Patel, Apar S; Walter, Christina M; Maykowski, Philip; Baaj, Ali A

2016-12-01

Sacrectomy is a highly demanding surgery representing the main treatment for primary tumors arising in the sacrum and pelvis. Unfortunately, it is correlated with loss of important function depending on the resection level and nerve roots sacrificed. The current literature regarding residual function after sacral resection comes from several small case series. The goal of this review is to appraise residual motor function and gait, sensitivity, bladder, bowel, and sexual function after sacrectomies, with consideration to the specific roots sacrificed. An exhaustive literature search was conducted. All manuscripts published before May 2015 regarding residual function after sacrectomy were considered; if a clear correlation between root level and functioning was not present, the paper was excluded. The review identified 15 retrospective case series, totaling 244 patients; 42 patients underwent sacrectomies sparing L4/L4, L4/L5 and L5/L5; 45 sparing both L5 and one or both S1 roots; 8 sparing both S1 and one S2; 48 sparing both S2; 11 sparing both S2 and one S3, 54 sparing both S3, 9 sparing both S3 and one or both S4, and 27 underwent unilateral variable resection. Patients who underwent a sacrectomy maintained functionally normal ambulation in 56.2 % of cases when both S2 roots were spared, 94.1 % when both S3 were spared, and in 100 % of more distal resections. Normal bladder and bowel function were not present when both S2 were cut. When one S2 root was spared, normal bladder function was present in 25 % of cases; when both S2 were spared, 39.9 %; when one S3 was spared, 72.7 %; and when both S3 were spared, 83.3 %. Abnormal bowel function was present in 12.5 % of cases when both S1 and one S2 were spared; in 50.0 % of cases when both S2 were spared; and in 70 % of cases when one S3 was spared; if both S3 were spared, bowel function was normal in 94 % of cases. When even one S4 root was spared, normal bladder and bowel function were present in 100 % of cases. Unilateral sacral nerve root resection preserved normal bladder function in 75 % of cases and normal bowel function in 82.6 % of cases. Motor function depended on S1 root involvement. Total sacrectomy is associated with compromising important motor, bladder, bowel, sensitivity, and sexual function. Residual motor function is dependent on sparing L5 and S1 nerve roots. Bladder and bowel function is consistently compromised in higher sacrectomies; nevertheless, the probability of maintaining sufficient function increases progressively with the roots spared, especially when S3 nerve roots are spared. Unilateral resection is usually associated with more normal function. To the best of our knowledge, this is the first comprehensive literature review to analyze published reports of residual sacral nerve root function after sacrectomy.

Volumetric neuroimaging in Usher syndrome: evidence of global involvement.

PubMed

Schaefer, G B; Bodensteiner, J B; Thompson, J N; Kimberling, W J; Craft, J M

1998-08-27

Usher syndrome is a group of genetic disorders consisting of congenital sensorineural hearing loss and retinitis pigmentosa of variable onset and severity depending on the genetic type. It was suggested that the psychosis of Usher syndrome might be secondary to a metabolic degeneration involving the brain more diffusely. There have been reports of focal and diffuse atrophic changes in the supratentorial brain as well as atrophy of some of the structures of the posterior fossa. We previously performed quantitative analysis of magnetic resonance imaging studies of 19 Usher syndrome patients (12 with type I and 7 with type II) looking at the cerebellum and various cerebellar components. We found atrophy of the cerebellum in both types and sparing of cerebellar vermis lobules I-V in type II Usher syndrome patients only. We now have studied another group of 19 patients (with some overlap in the patients studied from the previous report) with Usher syndrome (8 with type I, 11 with type II). We performed quantitative volumetric measurements of various brain structures compared to age- and sex-matched controls. We found a significant decrease in intracranial volume and in size of the brain and cerebellum with a trend toward an increase in the size of the subarachnoid spaces. These data suggest that the disease process in Usher syndrome involves the entire brain and is not limited to the posterior fossa or auditory and visual systems.

Whole-brain analytic measures of network communication reveal increased structure-function correlation in right temporal lobe epilepsy.

PubMed

Wirsich, Jonathan; Perry, Alistair; Ridley, Ben; Proix, Timothée; Golos, Mathieu; Bénar, Christian; Ranjeva, Jean-Philippe; Bartolomei, Fabrice; Breakspear, Michael; Jirsa, Viktor; Guye, Maxime

2016-01-01

The in vivo structure-function relationship is key to understanding brain network reorganization due to pathologies. This relationship is likely to be particularly complex in brain network diseases such as temporal lobe epilepsy, in which disturbed large-scale systems are involved in both transient electrical events and long-lasting functional and structural impairments. Herein, we estimated this relationship by analyzing the correlation between structural connectivity and functional connectivity in terms of analytical network communication parameters. As such, we targeted the gradual topological structure-function reorganization caused by the pathology not only at the whole brain scale but also both in core and peripheral regions of the brain. We acquired diffusion (dMRI) and resting-state fMRI (rsfMRI) data in seven right-lateralized TLE (rTLE) patients and fourteen healthy controls and analyzed the structure-function relationship by using analytical network communication metrics derived from the structural connectome. In rTLE patients, we found a widespread hypercorrelated functional network. Network communication analysis revealed greater unspecific branching of the shortest path (search information) in the structural connectome and a higher global correlation between the structural and functional connectivity for the patient group. We also found evidence for a preserved structural rich-club in the patient group. In sum, global augmentation of structure-function correlation might be linked to a smaller functional repertoire in rTLE patients, while sparing the central core of the brain which may represent a pathway that facilitates the spread of seizures.

Memory-guided saccade processing in visual form agnosia (patient DF).

PubMed

Rossit, Stéphanie; Szymanek, Larissa; Butler, Stephen H; Harvey, Monika

2010-01-01

According to Milner and Goodale's model (The visual brain in action, Oxford University Press, Oxford, 2006) areas in the ventral visual stream mediate visual perception and oV-line actions, whilst regions in the dorsal visual stream mediate the on-line visual control of action. Strong evidence for this model comes from a patient (DF), who suffers from visual form agnosia after bilateral damage to the ventro-lateral occipital region, sparing V1. It has been reported that she is normal in immediate reaching and grasping, yet severely impaired when asked to perform delayed actions. Here we investigated whether this dissociation would extend to saccade execution. Neurophysiological studies and TMS work in humans have shown that the posterior parietal cortex (PPC), on the right in particular (supposedly spared in DF), is involved in the control of memory-guided saccades. Surprisingly though, we found that, just as reported for reaching and grasping, DF's saccadic accuracy was much reduced in the memory compared to the stimulus-guided condition. These data support the idea of a tight coupling of eye and hand movements and further suggest that dorsal stream structures may not be sufficient to drive memory-guided saccadic performance.

Improved normal tissue sparing in head and neck radiotherapy using biological cost function based-IMRT.

PubMed

Anderson, N; Lawford, C; Khoo, V; Rolfo, M; Joon, D L; Wada, M

2011-12-01

Intensity-modulated radiotherapy (IMRT) has reduced the impact of acute and late toxicities associated with head and neck radiotherapy. Treatment planning system (TPS) advances in biological cost function based optimization (BBO) and improved segmentation techniques have increased organ at risk (OAR) sparing compared to conventional dose-based optimization (DBO). A planning study was undertaken to compare OAR avoidance in DBO and BBO treatment planning. Simultaneous integrated boost treatment plans were produced for 10 head and neck patients using both planning systems. Plans were compared for tar get coverage and OAR avoidance. Comparisons were made using the BBO TPS Monte Carlo dose engine to eliminate differences due to inherent algorithms. Target coverage (V95%) was maintained for both solutions. BBO produced lower OAR doses, with statistically significant improvement to left (12.3%, p = 0.005) and right parotid mean dose (16.9%, p = 0.004), larynx V50_Gy (71.0%, p = 0.005), spinal cord (21.9%, p < 0.001) and brain stem dose maximums (31.5%, p = 0.002). This study observed improved OAR avoidance with BBO planning. Further investigations will be undertaken to review any clinical benefit of this improved planned dosimetry.

Improved Normal Tissue Sparing in Head and Neck Radiotherapy Using Biological Cost Function Based-IMRT

PubMed Central

Anderson, N.; Lawford, C.; Khoo, V.; Rolfo, M.; Joon, D. Lim; Wada, M.

2011-01-01

Intensity-modulated radiotherapy (IMRT) has reduced the impact of acute and late toxicities associated with head and neck radiotherapy. Treatment planning system (TPS) advances in biological cost function based optimization (BBO) and improved segmentation techniques have increased organ at risk (OAR) sparing compared to conventional dose-based optimization (DBO). A planning study was undertaken to compare OAR avoidance in DBO and BBO treatment planning. Simultaneous integrated boost treatment plans were produced for 10 head and neck patients using both planning systems. Plans were compared for tar get coverage and OAR avoidance. Comparisons were made using the BBO TPS Monte Carlo dose engine to eliminate differences due to inherent algorithms. Target coverage (V95%) was maintained for both solutions. BBO produced lower OAR doses, with statistically significant improvement to left (12.3%, p = 0.005) and right parotid mean dose (16.9%, p = 0.004), larynx V50 Gy (71.0%, p = 0.005), spinal cord (21.9%, p < 0.001) and brain stem dose maximums (31.5%, p = 0.002). This study observed improved OAR avoidance with BBO planning. Further investigations will be undertaken to review any clinical benefit of this improved planned dosimetry. PMID:22066597

Pilot study assessing the feasibility of applying bilateral subthalamic nucleus deep brain stimulation in very early stage Parkinson's disease: study design and rationale.

PubMed

Charles, David; Tolleson, Christopher; Davis, Thomas L; Gill, Chandler E; Molinari, Anna L; Bliton, Mark J; Tramontana, Michael G; Salomon, Ronald M; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T; Neimat, Joseph S; Konrad, Peter E

2012-01-01

Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease.

Pilot Study Assessing the Feasibility of Applying Bilateral Subthalamic Nucleus Deep Brain Stimulation in Very Early Stage Parkinson's Disease: Study design and rationale

PubMed Central

Charles, David; Tolleson, Christopher; Davis, Thomas L.; Gill, Chandler E.; Molinari, Anna L.; Bliton, Mark J.; Tramontana, Michael G.; Salomon, Ronald M.; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T.; Neimat, Joseph S.; Konrad, Peter E.

2014-01-01

Background Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. Objective We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. Methods We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Results Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. Conclusions This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease. PMID:23938229

Using normalization 3D model for automatic clinical brain quantative analysis and evaluation

NASA Astrophysics Data System (ADS)

Lin, Hong-Dun; Yao, Wei-Jen; Hwang, Wen-Ju; Chung, Being-Tau; Lin, Kang-Ping

2003-05-01

Functional medical imaging, such as PET or SPECT, is capable of revealing physiological functions of the brain, and has been broadly used in diagnosing brain disorders by clinically quantitative analysis for many years. In routine procedures, physicians manually select desired ROIs from structural MR images and then obtain physiological information from correspondent functional PET or SPECT images. The accuracy of quantitative analysis thus relies on that of the subjectively selected ROIs. Therefore, standardizing the analysis procedure is fundamental and important in improving the analysis outcome. In this paper, we propose and evaluate a normalization procedure with a standard 3D-brain model to achieve precise quantitative analysis. In the normalization process, the mutual information registration technique was applied for realigning functional medical images to standard structural medical images. Then, the standard 3D-brain model that shows well-defined brain regions was used, replacing the manual ROIs in the objective clinical analysis. To validate the performance, twenty cases of I-123 IBZM SPECT images were used in practical clinical evaluation. The results show that the quantitative analysis outcomes obtained from this automated method are in agreement with the clinical diagnosis evaluation score with less than 3% error in average. To sum up, the method takes advantage of obtaining precise VOIs, information automatically by well-defined standard 3-D brain model, sparing manually drawn ROIs slice by slice from structural medical images in traditional procedure. That is, the method not only can provide precise analysis results, but also improve the process rate for mass medical images in clinical.

SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, S; Hildebrand, K; Ahmad, S

Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targetsmore » were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery.« less

Examining the impact of grape consumption on brain metabolism and cognitive function in patients with mild decline in cognition: A double-blinded placebo controlled pilot study.

PubMed

Lee, Jooyeon; Torosyan, Nare; Silverman, Daniel H

2017-01-01

Natural compounds in grapes such as resveratrol are known for their antioxidant and anti-inflammatory properties. Some studies have shown a potential role for grapes or wine in slowing cognitive decline and other effects of aging. However, well-controlled experimental data obtained in human subjects are still in need of further development. Here we aimed to systematically assess effects of grapes on regional cerebral metabolism. Ten subjects with mild decline in cognition (mean, 72.2±4.7years; 50% female) were included in this analysis. Participants were randomized into an active grape formulation arm or a placebo arm which consumed a formulation free of polyphenols for six months. Cognitive performance was measured through neuropsychological assessments performed at baseline and 6months after initiation of therapy. Changes in brain metabolism occurring with each therapy regimen were assessed by brain PET scans with the radiotracer [F-18] fluorodeoxyglucose (FDG), obtained during initial evaluation and 6months later. Standardized volumes of interest (sVOI) and statistical parametric mapping (SPM) methods were applied to FDG-PET scans to identify significant regional cerebral metabolic changes. In contrast to participants taking the active grape formulation, who displayed no significant decline in metabolism, the placebo arm underwent significant metabolic decline in sVOI's of the right posterior cingulate cortex (p=0.01), and left superior posterolateral temporal cortex (p=0.04). SPM analyses also found significant declines in the placebo group, particularly in left prefrontal, cingulate, and left superior posterolateral temporal cortex (p<0.01) with stable brain metabolism in the active formulation arm. No significant differences were seen in scores on the neuropsychological battery of tests between the two groups. However, metabolism in right superior parietal cortex and left inferior anterior temporal cortex was correlated with improvements in attention/working memory, as measured with WAIS-III Digital Span within the active formulation group (r=-0.69, p=0.04). The placebo arm had declines in regions of the brain known to be significantly affected in the early stages of Alzheimer's disease, while the active formulation group was spared such decline. This suggests a protective effect of grapes against early pathologic metabolic decline. Copyright © 2016 Elsevier Inc. All rights reserved.

FANCD2 re-expression is associated with glioma grade and chemical inhibition of the Fanconi Anaemia pathway sensitises gliomas to chemotherapeutic agents.

PubMed

Patil, Abhijit A; Sayal, Parag; Depondt, Marie-Lise; Beveridge, Ryan D; Roylance, Anthony; Kriplani, Deepti H; Myers, Katie N; Cox, Angela; Jellinek, David; Fernando, Malee; Carroll, Thomas A; Collis, Spencer J

2014-08-15

Brain tumours kill more children and adults under 40 than any other cancer. Around half of primary brain tumours are glioblastoma multiforme (GBMs) where treatment remains a significant challenge, where survival rates have improved little over the last 40 years, thus highlighting an unmet need for the identification/development of novel therapeutic targets and agents to improve GBM treatment. Using archived and fresh glioma tissue, we show that in contrast to normal brain or benign schwannomas GBMs exhibit re-expression of FANCD2, a key protein of the Fanconi Anaemia (FA) DNA repair pathway, and possess an active FA pathway. Importantly, FANCD2 expression levels are strongly associated with tumour grade, revealing a potential exploitable therapeutic window to allow inhibition of the FA pathway in tumour cells, whilst sparing normal brain tissue. Using several small molecule inhibitors of the FA pathway in combination with isogenic FA-proficient/deficient glioma cell lines as well as primary GBM cultures, we demonstrate that inhibition of the FA pathway sensitises gliomas to the chemotherapeutic agents Temozolomide and Carmustine. Our findings therefore provide a strong rationale for the development of novel and potent inhibitors of the FA pathway to improve the treatment of GBMs, which may ultimately impact on patient outcome.

Brain dynamics in ASD during movie-watching show idiosyncratic functional integration and segregation.

PubMed

Bolton, Thomas A W; Jochaut, Delphine; Giraud, Anne-Lise; Van De Ville, Dimitri

2018-06-01

To refine our understanding of autism spectrum disorders (ASD), studies of the brain in dynamic, multimodal and ecological experimental settings are required. One way to achieve this is to compare the neural responses of ASD and typically developing (TD) individuals when viewing a naturalistic movie, but the temporal complexity of the stimulus hampers this task, and the presence of intrinsic functional connectivity (FC) may overshadow movie-driven fluctuations. Here, we detected inter-subject functional correlation (ISFC) transients to disentangle movie-induced functional changes from underlying resting-state activity while probing FC dynamically. When considering the number of significant ISFC excursions triggered by the movie across the brain, connections between remote functional modules were more heterogeneously engaged in the ASD population. Dynamically tracking the temporal profiles of those ISFC changes and tying them to specific movie subparts, this idiosyncrasy in ASD responses was then shown to involve functional integration and segregation mechanisms such as response inhibition, background suppression, or multisensory integration, while low-level visual processing was spared. Through the application of a new framework for the study of dynamic experimental paradigms, our results reveal a temporally localized idiosyncrasy in ASD responses, specific to short-lived episodes of long-range functional interplays. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

FANCD2 re-expression is associated with glioma grade and chemical inhibition of the Fanconi Anaemia pathway sensitises gliomas to chemotherapeutic agents

PubMed Central

Patil, Abhijit A.; Sayal, Parag; Depondt, Marie-Lise; Beveridge, Ryan D.; Roylance, Anthony; Kriplani, Deepti H.; Myers, Katie N.; Cox, Angela; Jellinek, David; Fernando, Malee; Carroll, Thomas A.; Collis, Spencer J.

2014-01-01

Brain tumours kill more children and adults under 40 than any other cancer. Around half of primary brain tumours are glioblastoma multiforme (GBMs) where treatment remains a significant challenge. GBM survival rates have improved little over the last 40 years, thus highlighting an unmet need for the identification/development of novel therapeutic targets and agents to improve GBM treatment. Using archived and fresh glioma tissue, we show that in contrast to normal brain or benign schwannomas GBMs exhibit re-expression of FANCD2, a key protein of the Fanconi Anaemia (FA) DNA repair pathway, and possess an active FA pathway. Importantly, FANCD2 expression levels are strongly associated with tumour grade, revealing a potential exploitable therapeutic window to allow inhibition of the FA pathway in tumour cells, whilst sparing normal brain tissue. Using several small molecule inhibitors of the FA pathway in combination with isogenic FA-proficient/deficient glioma cell lines as well as primary GBM cultures, we demonstrate that inhibition of the FA pathway sensitises gliomas to the chemotherapeutic agents Temozolomide and Carmustine. Our findings therefore provide a strong rationale for the development of novel and potent inhibitors of the FA pathway to improve the treatment of GBMs, which may ultimately impact on patient outcome. PMID:25071006

Diuretics in the treatment of hypertension. Part 2: loop diuretics and potassium-sparing agents.

PubMed

Tamargo, Juan; Segura, Julian; Ruilope, Luis M

2014-04-01

Diuretics enhance the renal excretion of Na(+) and water due to a direct action at different tubular sites of the nephron where solute re-absorption occurs. This paper focuses on the mechanism of action, pharmacodynamics, antihypertensive effects, adverse effects, interactions and contraindications of loop diuretics and potassium-sparing agents (including mineralocorticoid receptor antagonists (MRAs) and epithelial Na(+) channel blockers). Loop diuretics are less effective than thiazide diuretics in lowering blood pressure, so that their major use is in edematous patients with congestive heart failure (HF), cirrhosis with ascites and nephritic edema. MRAs represent a major advance in the treatment of resistant hypertension, primary and secondary hyperaldosteronism and in patients with systolic HF to reduce the risks of hospitalization and of premature death. Potassium-sparing diuretics when coadministered with diuretics (thiazides and loop diuretics) working at more proximal nephron locations reduce the risk of hypokalemia and hypomagnesemia and the risk of cardiac arrhythmias. At the end of the article, the basis for the combination of diuretics with other antihypertensive drugs to achieve blood pressure targets is presented.

An Assessment of the Dyna-Metric Inventory Model during Initial Provisioning.

DTIC Science & Technology

1986-09-01

model for computing initial spares levels. Currently, Air Force 3 policy for the provisioning of initial spares and repair parts requires that "all...Force inventory. The key to an effective inventory policy , and a credible defense posture in times of a constrained budget, is to maximize the repair... policy and procedures for deciding which items qualify for stockage, and for computing new requirements for all types of initially provisioned items

Temporally graded semantic memory loss in amnesia and semantic dementia: Further evidence for opposite gradients.

PubMed

Estmacott, Robyn W; Moscovitch, Morris

2002-03-01

The consolidation theory of long-term memory (e.g., Squire, 1992) predicts that damage to the medial temporal lobes will result in temporally graded retrograde memory loss, with a disproportionate impairment of recent relative to remote knowledge; in contrast, severe atrophy of the temporal neocortex is predicted to result in the reverse temporally graded pattern, with a selective sparing of recent memory (K.S. Graham & Hodges, 1997). Previously, we reported evidence that autobiographical episodic memory does not follow this temporal pattern (Westmacott, Leach, Freedman, & Moscovitch, 2001). In the present study, we found evidence suggesting that semantic memory loss does follow the predicted temporal pattern. We used a set of tasks that tap implicit and explicit memory for famous names and English vocabulary terms from across the 20th century. KC, a person with medial temporal amnesia, consistently demonstrated across tasks a selective deficit for famous names and vocabulary terms from the 5-year period just prior to injury; this deficit was particularly profound for elaborated semantic knowledge (e.g., word definitions, occupation of famous person). However, when asked to guess on unfamiliar items, KC's performance for names and words from this 5-year time period increased substantially, suggesting that he retains some of this knowledge at an implicit or rudimentary level. Conversely, EL, a semantic dementia patient with temporal neocortical atrophy and relative sparing of the medial temporal lobe, demonstrated a selective sparing of names and words from the most recent time period. However, this selective sparing of recent semantic memory was demonstrated in the implicit tasks only; performance on explicit tasks suggested an equally severe impairment of semantics across all time periods. Unlike the data from our previous study of autobiographical episodic memory, these findings are consistent with the predictions both of consolidation theory (Hodges & Graham, 1998; Squire, 1992) and multiple trace theory (Nadel & Moscovitch, 1999) that the hippocampus plays a timelimited role in the acquisition and representation of long-term semantic memories. Moreover, our findings suggest that tasks requiring minimal verbal production and explicit recall may provide a more sensitive and comprehensive assessment of intact memory capacity in brain-damaged individuals.

Hypofractionated conformal irradiation of patients with malignant glioma.

PubMed

Aboziada, Mohamed A; Abo-Kresha, Ahmed E

2012-09-01

The aim of the study is to evaluate the effect of a conformal irradiation in short fractionation scheme of 49.5Gy in 15 fractions in an overall time of 3 weeks, in terms of overall survival (OAS) and progression free survival (PFS) rates in brain glioma patients. A prospective study was conducted on 54 brain glioma patients and was carried out in the Radiation Oncology Department, South Egypt Cancer Institute, Assiut University during the period from April 2006 till June 2009. Patients were treated by hypofractionated conformal irradiation (49.5 Gy/15 fractions/3 weeks). The median follow up was 23 months (range: 9-39 months). Two-year OAS and PFS rates were 68% and 60%, respectively. In univariate analysis, age >50 years, poor performance status [Karnofasky score of ≥40-≤70%], poor neuroperformance status of score III, high-grade tumor [glioblastoma multiforme], and biopsy were all associated with statistically significant reduction in OAS and PFS rates. Multivariate analysis, showed that age >50 years and glioblastoma pathology were the only independent prognostic factors that were associated with poor OAS (p=0.003 and p=0.004, respectively), and PFS (p=0.027 and p=0.011, respectively). Hypofractionated conformal radiotherapy was as effective as the conventional radiotherapy, with time sparing for patients, and for radiation oncology centers. Hypofractionated radiotherapy may be considered the radiotherapy regimen of choice in clinical practice for patients with gliomas. Copyright © 2012. Published by Elsevier B.V.

Developmental amnesia: effect of age at injury.

PubMed

Vargha-Khadem, F; Salmond, C H; Watkins, K E; Friston, K J; Gadian, D G; Mishkin, M

2003-08-19

Hypoxic-ischemic events sustained within the first year of life can result in developmental amnesia, a disorder characterized by markedly impaired episodic memory and relatively preserved semantic memory, in association with medial temporal pathology that appears to be restricted to the hippocampus. Here we compared children who had hypoxic-ischemic events before 1 year of age (early group, n = 6) with others who showed memory problems after suffering hypoxic-ischemic events between the ages of 6 and 14 years (late group, n = 5). Morphometric analyses of the whole brain revealed that, compared with age-matched controls, both groups had bilateral abnormalities in the hippocampus, putamen, and posterior thalamus, as well as in the right retrosplenial cortex. The two groups also showed similar reductions (approximately 40%) in hippocampal volumes. Neuropsychologically, the only significant differences between the two were on a few tests of immediate memory, where the early group surpassed the late group. The latter measures provided the only clear indication that very early injury can lead to greater functional sparing than injury acquired later in childhood, due perhaps to the greater plasticity of the infant brain. On measures of long-term memory, by contrast, the two groups had highly similar profiles, both showing roughly equivalent preservation of semantic memory combined with marked impairment in episodic memory. It thus appears that, if this selective memory disorder is a special syndrome related to the early occurrence of hypoxia-induced damage, then the effective age at injury for this syndrome extends from birth to puberty.

Global brain ischemia and reperfusion.

PubMed

White, B C; Grossman, L I; O'Neil, B J; DeGracia, D J; Neumar, R W; Rafols, J A; Krause, G S

1996-05-01

Brain damage accompanying cardiac arrest and resuscitation is frequent and devastating. Neurons in the hippocampus CA1 and CA4 zones and cortical layers III and V are selectively vulnerable to death after injury by ischemia and reperfusion. Ultrastructural evidence indicates that most of the structural damage is associated with reperfusion, during which the vulnerable neurons develop disaggregation of polyribosomes, peroxidative damage to unsaturated fatty acids in the plasma membrane, and prominent alterations in the structure of the Golgi apparatus that is responsible for membrane assembly. Reperfusion is also associated with vulnerable neurons with prominent production of messenger RNAs for stress proteins and for the proteins of the activator protein-1 complex, but these vulnerable neurons fail to efficiently translate these messages into the proteins. The inhibition of protein synthesis during reperfusion involves alteration of translation initiation factors, specifically serine phosphorylation of the alpha-subunit of eukaryotic initiation factor-2 (elF-2 alpha). Growth factors--in particular, insulin--have the potential to reverse phosphorylation of elF-2 alpha, promote effective translation of the mRNA transcripts generated in response to ischemia and reperfusion, enhance neuronal defenses against radicals, and stimulate lipid synthesis and membrane repair. There is now substantial evidence that the insulin-class growth factors have neuron-sparing effects against damage by radicals and ischemia and reperfusion. This new knowledge may provide a fundamental basis for a rational approach to "cerebral resuscitation" that will allow substantial amelioration of the often dismal neurologic outcome now associated with resuscitation from cardiac arrest.

Endocannabinoids in brain plasticity: Cortical maturation, HPA axis function and behavior.

PubMed

Dow-Edwards, Diana; Silva, Lindsay

2017-01-01

Marijuana use during adolescence has reached virtually every strata of society. The general population has the perception that marijuana use is safe for mature people and therefore is also safe for developing adolescents. However, both clinical and preclinical research shows that marijuana use, particularly prior to age 16, could have long-term effects on cognition, anxiety and stress-related behaviors, mood disorders and substance abuse. These effects derive from the role of the endocannabinoid system, the endogenous cannabinoid system, in the development of cortex, amygdala, hippocampus and hypothalamus during adolescence. Endocannabinoids are necessary for normal neuronal excitation and inhibition through actions at glutamate and GABA terminals. Synaptic pruning at excitatory synapses and sparing of inhibitory synapses likely results in changes in the balance of excitation/inhibition in individual neurons and within networks; processes which are necessary for normal cortical development. The interaction between prefrontal cortex (PFC), amygdala and hippocampus is responsible for emotional memory, anxiety-related behaviors and drug abuse and all utilize the endogenous cannabinoid system to maintain homeostasis. Also, endocannabinoids are required for fast and slow feedback in the normal stress response, processes which mature during adolescence. Therefore, exogenous cannabinoids, such as marijuana, have the potential to alter the course of development of each of these major systems (limbic, hypothalamic-pituitary-adrenal (HPA) axis and neocortex) if used during the critical period of brain development, adolescence. This article is part of a Special Issue entitled SI: Adolescent plasticity. Copyright © 2016 Elsevier B.V. All rights reserved.

Active patient decision making regarding nerve sparing during radical prostatectomy: a novel approach.

PubMed

Lavery, Hugh J; Prall, David N; Abaza, Ronney

2011-08-01

The motivation to preserve sexual function can vary widely among patients before prostatectomy. Increasing patient involvement may allow a more personalized experience and may improve satisfaction. We assessed a strategy of surgeon deference to patient choice in regard to nerve sparing to determine to what degree patients are rational actors and capable of active decision making. A total of 150 patients treated with prostatectomy participated in a standardized preoperative discussion regarding the concept of nerve sparing, extracapsular extension and the potential need for adjuvant radiation in the event of local recurrence. Each patient was given his nomogram predicted risk of extracapsular extension and then elected nerve sparing or nonnerve sparing. The corresponding procedure was performed unless grossly invasive disease was encountered. Of the 150 patients 109 chose nerve sparing (73%) and 41 chose nonnerve sparing (27%). In patients with a nomogram predicted risk of extracapsular extension less than 20%, 20% to 50% and greater than 50%, nerve sparing was elected by 88%, 41% and 25%, respectively. Patients with lower risks of extracapsular extension electing nonnerve sparing were older and had higher rates of erectile dysfunction. Empowering patients to decide on their nerve sparing status is a reasonable strategy that did not lead to a high rate of patients with a high risk of extracapsular extension electing nerve sparing. With proper counseling informed patients made reasonable decisions, and appeared to be conservative, prioritizing cancer control in the majority of instances where extracapsular extension risk was high. In addition, they may have been overly conservative in electing nonnerve sparing when the risk was low. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

In the Age of Breast Augmentation, Breast Reconstruction Provides an Opportunity to Augment the Breast.

PubMed

Zimmerman, Amanda L; Tugertimur, Bugra; Smith, Paul D; Kumar, Ambuj; Dayicioglu, Deniz

2017-01-01

Augmentation mammoplasty remains the most common cosmetic surgery procedure performed. The objective of this article is to evaluate the impact of augmented volume of the reconstructed breast in patients that undergo nipple-sparing mastectomy and patients previously augmented who undergo mastectomy with tissue expander/implant-based reconstruction. Patients undergoing skin-sparing mastectomy, nipple-sparing mastectomy, and mastectomy after previous augmentation followed by tissue expander/implant-based reconstruction between June 2011 and April 2015 by 2 surgeons at the same institution were included. Retrospective chart review of the patients identified using these criteria was performed to record patient characteristics, complications, breast volume, implant volume, and percentage change in volume at the time of reconstruction. Percentage change of breast volume was calculated using the formula (implant breast weight)/(breast weight) for skin-sparing and nipple-sparing mastectomy patients and (final breast implant weight - [breast weight + augmentation breast implant weight])/([breast weight + augmentation breast implant]) for patients undergoing mastectomy following previous augmentation. A total of 293 patients were included in the study with 63 patients who underwent nipple-sparing mastectomy, 166 patients who underwent skin-sparing mastectomy, and 64 patients who underwent previous augmentation with subsequent mastectomy. Mean percentage change in breast volume was 66% in the nipple-sparing mastectomy group, 15% for the right breast and 18% for the left breast in the skin-sparing mastectomy group, and 81% for the right breast and 72% for the left breast in the mastectomy following previous augmentation group. Complication rate for nipple-sparing mastectomy was 27%, mastectomy following previous augmentation was 20.3%, and skin-sparing mastectomy group was 18.7%. Patients who undergo nipple-sparing mastectomy or mastectomy following previous augmentation have the ability to achieve greater volume in their reconstructed breast via tissue expander/implant-based reconstruction.

Prenatal Dexamethasone, as Used in Preterm Labor, Worsens the Impact of Postnatal Chlorpyrifos Exposure on Serotonergic Pathways

PubMed Central

Slotkin, Theodore A.; Card, Jennifer; Seidler, Frederic J.

2014-01-01

This study explores how glucocorticoids sensitize the developing brain to the organophosphate pesticide, chlorpyrifos. Pregnant rats received a standard therapeutic dose (0.2 mg/kg) of dexamethasone on gestational days 17–19; pups were given subtoxic doses of chlorpyrifos on postnatal days 1–4, (1 mg/kg, <10% cholinesterase inhibition). We evaluated serotonin (5HT) synaptic function from postnatal day 30 to day 150, assessing the expression of 5HT receptors and the 5HT transporter, along with 5HT turnover (index of presynaptic impulse activity) in brain regions encompassing all the 5HT projections and cell bodies. These parameters are known targets for neurodevelopmental effects of dexamethasone and chlorpyrifos individually. In males, chlorpyrifos evoked overall elevations in the expression of 5HT synaptic proteins, with a progressive increase from adolescence to adulthood; this effect was attenuated by prenatal dexamethasone treatment. The chlorpyrifos-induced upregulation was preceded by deficits in 5HT turnover, indicating that the receptor upregulation was an adaptive response to deficient presynaptic activity. Turnover deficiencies were magnified by dexamethasone pretreatment, worsening the functional impairment caused by chlorpyrifos. In females, chlorpyrifos-induced receptor changes reflected relative sparing of adverse effects compared to males. Nevertheless, prenatal dexamethasone still worsened the 5HT turnover deficits and reduced 5HT receptor expression in females, demonstrating the same adverse interaction. Glucocorticoids are used in 10% of U.S. pregnancies, and are also elevated in maternal stress; accordingly, our results indicate that this group represents a large subpopulation that may have heightened vulnerability to developmental neurotoxicants such as the organophosphates. PMID:24280657

Prenatal Dexamethasone Augments the Sex-Selective Developmental Neurotoxicity of Chlorpyrifos: Implications for Vulnerability after Pharmacotherapy for Preterm Labor

PubMed Central

Slotkin, Theodore A.; Card, Jennifer; Infante, Alice; Seidler, Frederic J.

2013-01-01

Glucocorticoids are routinely given in preterm labor and are also elevated by maternal stress; organophosphate exposures are virtually ubiquitous, so coexposures to these two agents are pervasive. We administered dexamethasone to pregnant rats on gestational days 17–19 at a standard therapeutic dose (0.2 mg/kg); offspring were then given chlorpyrifos on postnatal days 1–4, at a dose (1 mg/kg) that produces barely-detectable (<10%) inhibition of brain cholinesterase activity. We evaluated indices for acetylcholine (ACh) synaptic function throughout adolescence, young adulthood and later adulthood, in brain regions possessing the majority of ACh projections and cell bodies; we measured nicotinic ACh receptor binding, hemicholinium-3 binding to the presynaptic choline transporter and choline acetyltransferase activity, all known targets for the adverse developmental effects of dexamethasone and chlorpyrifos given individually. Dexamethasone did not enhance the systemic toxicity of chlorpyrifos, as evidenced by weight gain and measurements of cholinesterase inhibition during chlorpyrifos treatment. Nevertheless, it enhanced the loss of presynaptic ACh function selectively in females, who ordinarily show sparing of organophosphate developmental neurotoxicity relative to males. Females receiving the combined treatment showed decrements in choline transporter binding and choline acetyltransferase activity that were unique (not found with either treatment alone), as well as additive decrements in nicotinic receptor binding. On the other hand, males given dexamethasone showed no augmentation of the effects of chlorpyrifos. Our findings indicate that prior dexamethasone exposure could create a subpopulation that is especially vulnerable to the adverse effects of organophosphates or other developmental neurotoxicants. PMID:23416428

[Effect of partial ganglionectomy and acupuncture on culturing spared DRG in vitro].

PubMed

Wang, Te-Wei; Wang, Ting-Hua; Zhou, Xue; Zhang, Lian-Shuang; Xu, Xin-Yun

2005-09-01

To explore the effect of partial dorsal root rhizotomy and Acup on culturing dorsal root ganglion(DRG) in vitro. Ten adult cats were divided into 2 groups: normal control group; Acup spared DRG 7 d group, in which bilateral L1-L5, L7-S2 DRG were removed; and L6DRG were spared; then unilaterally two sets of acupoints [Zusanlily (St. 36) and Xuanzhong (G. B. 39): Futu (St. 32) and Sanyinjiao (Sp. 6) located in the distribution area of spinal nerve L6] were electro-stimulated alternatively 30 min everyday by electro-needling. Five cats were used in every group. Bilateral L6 DRGs of every group were taken out on the condition of asepsis and were cultured respectively in vitro. Cultures were terminated after day 7. Then the cultured cells were stained under the same condition using specific NSE (1 : 200) antibody, a neuron-specific marker, by the immunohistochemistry ABC method. The neurite length was measured by micro-measured ruler in upside-down light microscope on the 1st, 3rd, 5th, 7th day. Immunocytochemical staining revealed that over 95% cells were NSE positive cells which were the typical neuron of DRG in vitro; on the 1st, 3rd, 5th, 7th day, the average neurite length of the normal group was shorter than that of the spared DRG group(P < 0. 05), and the spared DRG group's was shorter than the Acup group's at each time stage (P < 0.05). These results indicated that DRG had plasticity and acupuncture probably promoted the plasticity, which were probably in close relation with the spinal plasticity.

Mission Reliability Estimation for Repairable Robot Teams

NASA Technical Reports Server (NTRS)

Trebi-Ollennu, Ashitey; Dolan, John; Stancliff, Stephen

2010-01-01

A mission reliability estimation method has been designed to translate mission requirements into choices of robot modules in order to configure a multi-robot team to have high reliability at minimal cost. In order to build cost-effective robot teams for long-term missions, one must be able to compare alternative design paradigms in a principled way by comparing the reliability of different robot models and robot team configurations. Core modules have been created including: a probabilistic module with reliability-cost characteristics, a method for combining the characteristics of multiple modules to determine an overall reliability-cost characteristic, and a method for the generation of legitimate module combinations based on mission specifications and the selection of the best of the resulting combinations from a cost-reliability standpoint. The developed methodology can be used to predict the probability of a mission being completed, given information about the components used to build the robots, as well as information about the mission tasks. In the research for this innovation, sample robot missions were examined and compared to the performance of robot teams with different numbers of robots and different numbers of spare components. Data that a mission designer would need was factored in, such as whether it would be better to have a spare robot versus an equivalent number of spare parts, or if mission cost can be reduced while maintaining reliability using spares. This analytical model was applied to an example robot mission, examining the cost-reliability tradeoffs among different team configurations. Particularly scrutinized were teams using either redundancy (spare robots) or repairability (spare components). Using conservative estimates of the cost-reliability relationship, results show that it is possible to significantly reduce the cost of a robotic mission by using cheaper, lower-reliability components and providing spares. This suggests that the current design paradigm of building a minimal number of highly robust robots may not be the best way to design robots for extended missions.

Increases in cytoplasmic dopamine compromise the normal resistance of the nucleus accumbens to methamphetamine neurotoxicity

PubMed Central

Thomas, David M.; Francescutti-Verbeem, Dina M.; Kuhnt, Donald M.

2016-01-01

Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the caudate–putamen (CPu) where long-term DA depletion and microglial activation are most evident. Even damage within the CPu is remarkably heterogenous with lateral and ventral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared of the damage that accompanies binge METH intoxication. Increases in cytoplasmic DA produced by reserpine, L-DOPA or clorgyline prior to METH uncover damage in the NAc as evidenced by microglial activation and depletion of DA, tyrosine hydroxylase (TH), and the DA transporter. These effects do not occur in the NAc after treatment with METH alone. In contrast to the CPu where DA, TH, and DA transporter levels remain depleted chronically, DA nerve ending alterations in the NAc show a partial recovery over time. None of the treatments that enhance METH toxicity in the NAc and CPu lead to losses of TH protein or DA cell bodies in the substantia nigra or the ventral tegmentum. These data show that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of METH to include brain structures not normally targeted for damage by METH alone. The resistance of the NAc to METH-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of METH neurotoxicity by alterations in DA homeostasis is significant in light of the important roles played by this brain structure. PMID:19457119

Increases in cytoplasmic dopamine compromise the normal resistance of the nucleus accumbens to methamphetamine neurotoxicity.

PubMed

Thomas, David M; Francescutti-Verbeem, Dina M; Kuhn, Donald M

2009-06-01

Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the caudate-putamen (CPu) where long-term DA depletion and microglial activation are most evident. Even damage within the CPu is remarkably heterogenous with lateral and ventral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared of the damage that accompanies binge METH intoxication. Increases in cytoplasmic DA produced by reserpine, L-DOPA or clorgyline prior to METH uncover damage in the NAc as evidenced by microglial activation and depletion of DA, tyrosine hydroxylase (TH), and the DA transporter. These effects do not occur in the NAc after treatment with METH alone. In contrast to the CPu where DA, TH, and DA transporter levels remain depleted chronically, DA nerve ending alterations in the NAc show a partial recovery over time. None of the treatments that enhance METH toxicity in the NAc and CPu lead to losses of TH protein or DA cell bodies in the substantia nigra or the ventral tegmentum. These data show that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of METH to include brain structures not normally targeted for damage by METH alone. The resistance of the NAc to METH-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of METH neurotoxicity by alterations in DA homeostasis is significant in light of the important roles played by this brain structure.

Paediatric brain tumours: A review of radiotherapy, state of the art and challenges for the future regarding protontherapy and carbontherapy.

PubMed

Laprie, A; Hu, Y; Alapetite, C; Carrie, C; Habrand, J-L; Bolle, S; Bondiau, P-Y; Ducassou, A; Huchet, A; Bertozzi, A-I; Perel, Y; Moyal, É; Balosso, J

2015-12-01

Brain tumours are the most frequent solid tumours in children and the most frequent radiotherapy indications in paediatrics, with frequent late effects: cognitive, osseous, visual, auditory and hormonal. A better protection of healthy tissues by improved beam ballistics, with particle therapy, is expected to decrease significantly late effects without decreasing local control and survival. This article reviews the scientific literature to advocate indications of protontherapy and carbon ion therapy for childhood central nervous system cancer, and estimate the expected therapeutic benefits. A systematic review was performed on paediatric brain tumour treatments using Medline (from 1966 to March of 2014). To be included, clinical trials had to meet the following criteria: age of patients 18 years or younger, treated with radiation, and report of survival. Studies were also selected according to the evidence level. A secondary search of cited references found other studies about cognitive functions, quality of life, the comparison of photon and proton dosimetry showing potential dose escalation and/or sparing of organs at risk with protontherapy; and studies on dosimetric and technical issues related to protontherapy. A total of 7051 primary references published were retrieved, among which 40 clinical studies and 60 papers about quality of life, dose distribution and dosimetry were analysed, as well as the ongoing clinical trials. These papers have been summarized and reported in a specific document made available to the participants of a final 1-day workshop. Tumours of the meningeal envelop and bony cranial structures were excluded from the analysis. Protontherapy allows outstanding ballistics to target the tumour area, while substantially decreasing radiation dose to the normal tissues. There are many indications of protontherapy for paediatric brain tumours in curative intent, either for localized treatment of ependymomas, germ-cell tumours, craniopharyngiomas, low-grade gliomas; or panventricular irradiation of pure non-secreting germinoma; or craniospinal irradiation of medulloblastomas and metastatic pure germinomas. Carbon ion therapy is just emerging and may be studied for highly aggressive and radioresistant tumours, as an initial treatment for diffuse brainstem gliomas, and for relapse of high-grade gliomas. Both protontherapy and carbon ion therapy are promising for paediatric brain tumours. The benefit of decreasing late effects without altering survival has been described for most paediatric brain tumours with protontherapy and is currently assessed in ongoing clinical trials with up-to-date proton devices. Unfortunately, in 2015, only a minority of paediatric patients in France can receive protontherapy due to the lack of equipment. Copyright © 2015. Published by Elsevier SAS.

SU-E-T-326: Dosimetric Impact of Beam Energies and Jaw Tracking On Intracranial Tumors Using RapidArc

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, S; Keeling, V; Ali, I

2015-06-15

Purpose: To determine the dosimetric impact of jaw tracking and beam energies on dose conformity and normal-brain-tissue doses for intracranial tumors using VMAT (RapidArc). Methods: Seven patients with 1–2 and three patients with 4–6 intracranial tumors were planned using RapidArc for Varian TrueBeam STx machine with beam energies 6MV-FFF (Flattening-Filter-Free), 8MV, 10MV, and 10MV-FFF. The prescription dose ranged from 14–23Gy. Between 2 and 8 arcs were used with the following geometries: 2 full coplanar arcs and the non-coplanar half arcs. Plans were optimized (jaw tracking ON) with a high priority to Normal-Tissue-Objective and normal-brain-tissue. Plans were calculated on 1mm gridmore » size using AAA algorithm and then normalized so that 99% of each target volume received the prescription dose. Plans for the 6MV-FFF were also optimized without jaw tracking (No-JT) for comparison. Plan quality was assessed by target coverage using Paddick Conformity Index (PCI), sparing of normal-brain-tissue through analysis of V4Gy, V8Gy and V12Gy, and integral dose. Results: The average PCI ± standard deviation was 0.76±0.21 and 0.76±0.22 for 6MV-FFF and 10 MV-FFF, respectively. The average ratio in normal brain tissue volume (reported as follows V4,V8,V12) were (1.12±0.07,1.12±0.07,1.14±0.04), (1.12±0.08,1.12±0.09,1.13±0.06), (1.19±0.10,1.18±0.10,1.20±0.04), and (1.04±0.03,1.03±0.03,1.03±0.04) for 8MV/6MV-FFF, 10MV-FFF/6MV-FFF, 10MV/6MV-FFF, 6MV-FFF No-JT/6MV-FFF, respectively. Statistically significant differences in normal-brain-tissue for V4, V8, and V12 were observed in all cases for the different energies (p-values <0.05). V4 data shows significant differences in JT vs. No-JT (p=0.04), however no difference was found for V8 and V12. Brain tissue sparing from best to worst occurred in this order 6MV-FFF, 6MV-FFF no-JT, 10MV-FFF, 8MV, and 10MV. The average ratio of integral brain dose was 1.05±0.04 (p=0.21), 1.04±0.05 (p=0.33), 1.09±0.06 (p=0.04), and 1.02±0.06 (p=0.61) for 8MV/6MV-FFF, 10MV-FFF/6MV-FFF, 10MV/6MV-FFF, and 6MV-FFF No-JT/6MV-FFF, respectively. Conclusion: Normal brain tissue and integral dose improved using the lower energy and FFF beams, though plan conformity showed energy independence.« less

Submandibular gland-sparing radiation therapy for locally advanced oropharyngeal squamous cell carcinoma: patterns of failure and xerostomia outcomes.

PubMed

Gensheimer, Michael F; Liao, Jay J; Garden, Adam S; Laramore, George E; Parvathaneni, Upendra

2014-11-26

Saliva from submandibular glands (SMG) is necessary to minimize xerostomia. It is unclear whether SMG can be safely spared in patients undergoing bilateral neck radiotherapy for locally advanced oropharyngeal cancer without increasing the risk of marginal recurrence. We evaluated the outcomes of contralateral submandibular gland (cSMG) sparing intensity-modulated radiation therapy (IMRT). All patients with stage III/IV oropharyngeal squamous cell carcinoma treated with bilateral neck IMRT from 2006-2012 at our institution were included. Appropriately selected patients with favorable primary tumor characteristics and no definite contralateral neck disease were treated with cSMG-sparing IMRT. Patterns of failure and xerostomia outcomes were retrospectively analyzed. 114 patients were treated. 89% had stage IV disease and 89% received definitive radiation therapy. 76 patients (67%) received cSMG sparing IMRT. With a median follow-up of 30 months, there were 10 local, 9 regional, and 10 distant recurrences. 2-year overall survival was 86% and 2-year loco-regional control was 87%. In cSMG spared patients, the mean cSMG dose was 30.7 Gy. Late grade 2+ xerostomia was significantly reduced in the cSMG spared group compared to those without SMG sparing (6 months: 23% vs. 72%, 12 months: 6% vs. 41%, 24 months: 3% vs. 36%, all p < 0.0007). There were no peri-SMG marginal recurrences in the cSMG-spared cohort. cSMG sparing IMRT did not increase marginal failures in this series of locally advanced oropharyngeal SCC patients. Xerostomia was significantly reduced in cSMG spared patients.

Cattle ranching intensification in Brazil can reduce global greenhouse gas emissions by sparing land from deforestation

PubMed Central

Cohn, Avery S.; Mosnier, Aline; Havlík, Petr; Valin, Hugo; Herrero, Mario; Schmid, Erwin; O’Hare, Michael; Obersteiner, Michael

2014-01-01

This study examines whether policies to encourage cattle ranching intensification in Brazil can abate global greenhouse gas (GHG) emissions by sparing land from deforestation. We use an economic model of global land use to investigate, from 2010 to 2030, the global agricultural outcomes, land use changes, and GHG abatement resulting from two potential Brazilian policies: a tax on cattle from conventional pasture and a subsidy for cattle from semi-intensive pasture. We find that under either policy, Brazil could achieve considerable sparing of forests and abatement of GHGs, in line with its national policy targets. The land spared, particularly under the tax, is far less than proportional to the productivity increased. However, the tax, despite prompting less adoption of semi-intensive ranching, delivers slightly more forest sparing and GHG abatement than the subsidy. This difference is explained by increased deforestation associated with increased beef consumption under the subsidy and reduced deforestation associated with reduced beef consumption under the tax. Complementary policies to directly limit deforestation could help limit these effects. GHG abatement from either the tax or subsidy appears inexpensive but, over time, the tax would become cheaper than the subsidy. A revenue-neutral combination of the policies could be an element of a sustainable development strategy for Brazil and other emerging economies seeking to balance agricultural development and forest protection. PMID:24778243

Cattle ranching intensification in Brazil can reduce global greenhouse gas emissions by sparing land from deforestation.

PubMed

Cohn, Avery S; Mosnier, Aline; Havlík, Petr; Valin, Hugo; Herrero, Mario; Schmid, Erwin; O'Hare, Michael; Obersteiner, Michael

2014-05-20

This study examines whether policies to encourage cattle ranching intensification in Brazil can abate global greenhouse gas (GHG) emissions by sparing land from deforestation. We use an economic model of global land use to investigate, from 2010 to 2030, the global agricultural outcomes, land use changes, and GHG abatement resulting from two potential Brazilian policies: a tax on cattle from conventional pasture and a subsidy for cattle from semi-intensive pasture. We find that under either policy, Brazil could achieve considerable sparing of forests and abatement of GHGs, in line with its national policy targets. The land spared, particularly under the tax, is far less than proportional to the productivity increased. However, the tax, despite prompting less adoption of semi-intensive ranching, delivers slightly more forest sparing and GHG abatement than the subsidy. This difference is explained by increased deforestation associated with increased beef consumption under the subsidy and reduced deforestation associated with reduced beef consumption under the tax. Complementary policies to directly limit deforestation could help limit these effects. GHG abatement from either the tax or subsidy appears inexpensive but, over time, the tax would become cheaper than the subsidy. A revenue-neutral combination of the policies could be an element of a sustainable development strategy for Brazil and other emerging economies seeking to balance agricultural development and forest protection.

Atypical necrotizing encephalitis associated with systemic canine distemper virus infection in pups

PubMed Central

Amude, Alexandre Mendes; Alfieri, Amauri Alcindo; Beloni, Suely Nunes Esteves; Alfieri, Alice Fernandes

2011-01-01

This report describes the naturally occurring atypical neuropathological manifestation of systemic canine distemper virus (CDV) infection in two 16-day-old Pit Bull pups. CDV-induced changes affected the gray and white matter of the forebrain while sparing the hindbrain. Histologically, there was necrosis with destruction of the nervous parenchyma due to an influx of inflammatory and reactive cells associated with eosinophilic intranuclear inclusion bodies within glial cells. Positive immunoreactivity against CDV antigens was predominantly observed within astrocytes and neurons. RT-PCR was used to amplify CDV-specific amplicons from brain fragments. These findings suggest the participation of CDV in the etiopathogenesis of these lesions. PMID:22122909

Diffusion Tensor Imaging Tractography Detecting Isolated Oculomotor Nerve Damage After Traumatic Brain Injury.

PubMed

Jacquesson, Timothée; Frindel, Carole; Cotton, Francois

2017-04-01

A 24-year-old woman was hit by a bus and suffered an isolated complete oculomotor nerve palsy. Computed tomography scan did not show a skull base fracture. T2*-weighted magnetic resonance imaging revealed petechial cerebral hemorrhages sparing the brainstem. T2 constructive interference in steady state suggested a partial sectioning of the left oculomotor nerve just before entering the superior orbital fissure. Diffusion tensor imaging fiber tractography confirmed a sharp arrest of the left oculomotor nerve. This recent imaging technique could be of interest to assess white fiber damage and help make a diagnosis or prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

The modality-specific organization of grammatical categories: evidence from impaired spoken and written sentence production.

PubMed

Rapp, B; Caramazza, A

1997-02-01

We describe the case of a brain-damaged individual whose speech is characterized by difficulty with practically all words except for elements of the closed class vocabulary. In contrast, his written sentence production exhibits a complementary impairment involving the omission of closed class vocabulary items and the relative sparing of nouns. On the basis of these differences we argue: (1) that grammatical categories constitute an organizing parameter of representation and/or processing for each of the independent, modality-specific lexicons, and (2) that these observations contribute to the growing evidence that access to the orthographic and phonological forms of words can occur independently.

Logistics and Operational Effectiveness of the P-3 Aircraft.

DTIC Science & Technology

1977-03-01

Memory Module Tester for the AIMD at HAS Jacksonville Module Caddy utilization for the Position Indicator Failure rate and spares availability of the...into the P—3 aircraft • Investigated TRIAC failures in the AN/AQA-7(V) Sonar Computer Recorder Group • Identified and investigated incorrect use of...Magnetic Tape Transport: Replacement vacuum blower motors Piece parts for A7A1 circuit board • Investigated the availability of spare HI/LO Backward Wave

Differential effects of natural rewards and pain on vesicular glutamate transporter expression in the nucleus accumbens.

PubMed

Tukey, David S; Lee, Michelle; Xu, Duo; Eberle, Sarah E; Goffer, Yossef; Manders, Toby R; Ziff, Edward B; Wang, Jing

2013-07-09

Pain and natural rewards such as food elicit different behavioral effects. Both pain and rewards, however, have been shown to alter synaptic activities in the nucleus accumbens (NAc), a key component of the brain reward system. Mechanisms by which external stimuli regulate plasticity at NAc synapses are largely unexplored. Medium spiny neurons (MSNs) from the NAc receive excitatory glutamatergic inputs and modulatory dopaminergic and cholinergic inputs from a variety of cortical and subcortical structures. Glutamate inputs to the NAc arise primarily from prefrontal cortex, thalamus, amygdala, and hippocampus, and different glutamate projections provide distinct synaptic and ultimately behavioral functions. The family of vesicular glutamate transporters (VGLUTs 1-3) plays a key role in the uploading of glutamate into synaptic vesicles. VGLUT1-3 isoforms have distinct expression patterns in the brain, but the effects of external stimuli on their expression patterns have not been studied. In this study, we use a sucrose self-administration paradigm for natural rewards, and spared nerve injury (SNI) model for chronic pain. We examine the levels of VGLUTs (1-3) in synaptoneurosomes of the NAc in these two behavioral models. We find that chronic pain leads to a decrease of VGLUT1, likely reflecting decreased projections from the cortex. Pain also decreases VGLUT3 levels, likely representing a decrease in projections from GABAergic, serotonergic, and/or cholinergic interneurons. In contrast, chronic consumption of sucrose increases VGLUT3 in the NAc, possibly reflecting an increase from these interneuron projections. Our study shows that natural rewards and pain have distinct effects on the VGLUT expression pattern in the NAc, indicating that glutamate inputs to the NAc are differentially modulated by rewards and pain.

Dilantin therapy in an experimental model of traumatic brain injury: effects of limited versus daily treatment on neurological and behavioral recovery.

PubMed

Darrah, Shaun D; Darrah, Shaun H; Chuang, Jerry; Mohler, Laura M; Chen, Xiangbai; Cummings, Erin E; Burnett, Tiffany; Reyes-Littaua, M Christina; Galang, Gary N; Wagner, Amy K

2011-01-01

The mechanisms by which Dilantin confers anticonvulsant benefits may also be neuroprotective by attenuating the acute excitatory insult in cortical and subcortical structures when the drug is given in the acute phase after traumatic brain injury (TBI). However, when Dilantin is used for prolonged periods, we hypothesized that it may impede recovery, synaptic plasticity may be impaired, and neuroprotective benefits may be lost. As such, we assessed the effect of daily chronic administration (75 mg/kg day 0 followed by 50 mg/kg daily i.p.) and acute administration (75 mg/kg day 0 followed by 50 mg/kg i.p. day 1) of Dilantin in young adult male rats on motor performance, y-maze exploration, Morris Water Maze (MWM), hippocampal (HC) cell survival, contusion size, and regional expression of neuroplasticity markers after controlled cortical impact (CCI) injury. Chronic daily Dilantin administration resulted in beam walking impairments on day 6, whereas acute Dilantin administration resulted in beam walking impairments on days 3 and 4. Chronic Dilantin administration also resulted in worse MWM performance, more HC cell loss and no increases in neuroplasticity markers compared to rats with CCI receiving chronic vehicle. Conversely, rats receiving acute Dilantin administration exhibited more novel arm exploration in the y-maze, greater HC cell sparing, and greater growth-associated protein 43 (GAP-43) expression in the HC ipsilateral to the CCI, compared to injured rats receiving vehicle. MWM was not influenced by acute Dilantin administration. These results suggest that there are beneficial effects of limited acute Dilantin therapy after TBI, and that extended daily Dilantin therapy has deleterious effects on neural recovery. These findings support clinical guidelines for limited use of Dilantin in seizure prophylaxis after TBI.

Proton Radiotherapy for Solid Tumors of Childhood

PubMed Central

Cotter, Shane E.; McBride, Sean M.; Yock, Torunn I.

2012-01-01

The increasing efficacy of pediatric cancer therapy over the past four decades has produced many long-term survivors that now struggle with serious treatment related morbidities affecting their quality of life. Radiation therapy is responsible for a significant proportion of these late effects, but a relatively new and emerging modality, proton radiotherapy hold great promise to drastically reduce these treatment related late effects in long term survivors by sparing dose to normal tissues. Dosimetric studies of proton radiotherapy compared with best available photon based treatment show significant dose sparing to developing normal tissues. Furthermore, clinical data are now emerging that begin to quantify the benefit in decreased late treatment effects while maintaining excellent cancer control rates. PMID:22417062

Monoamine oxidase-B inhibitors in the treatment of Parkinson's disease: clinical-pharmacological aspects.

PubMed

Riederer, Peter; Müller, Thomas

2018-03-22

This invited narrative review emphasizes the role of MAO-B inhibition in the drug portfolio for dopamine substitution in patients with Parkinson's disease. Neuronal and glial MAO-B inhibition contributes to more stable levels of dopamine and other biogenic amines in the synaptic cleft. Accordingly, symptomatic effects of MAO-B inhibition for a limited amelioration of impaired motor behaviour and wearing-off phenomena in patients with Parkinson's disease are well proven, even when MAO-B inhibitors are only applied together with dopamine agonists. Delay of disease progression by MAO-B inhibition is under debate despite positive experimental findings. This discussion does not consider, that levodopa, respectively, dopamine agonists, are substrates, respectively, inhibitors of the ABCB1 (P-gp, MDR1, and CD243) transporter system. It supports toxin efflux over the blood-brain barrier. ABCB1 transporters have a limited capacity. MAO-B inhibitors do not weaken it. Treatment with MAO-B inhibitors is advantageous as it enables sparing of dopamine agonist and levodopa dosing.

Stimulation of the Rat Subthalamic Nucleus is Neuroprotective Following Significant Nigral Dopamine Neuron Loss

PubMed Central

Spieles-Engemann, A. L.; Behbehani, M. M.; Collier, T. J.; Wohlgenant, S. L.; Steece-Collier, K.; Paumier, K.; Daley, B. F.; Gombash, S.; Madhavan, L.; Mandybur, G. T.; Lipton, J.W.; Terpstra, B.T.; Sortwell, C.E.

2010-01-01

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is efficacious in treating the motor symptoms of Parkinson’s disease (PD). However, the impact of STN-DBS on the progression of PD is unknown. Previous preclinical studies have demonstrated that STN-DBS can attenuate the degeneration of a relatively intact nigrostriatal system from dopamine (DA)-depleting neurotoxins. The present study examined whether STN-DBS can provide neuroprotection in the face of prior significant nigral DA neuron loss similar to PD patients at the time of diagnosis. STN-DBS between two and four weeks after intrastriatal 6-hydroxydopamine (6-OHDA) provided significant sparing of DA neurons in the SN of rats. This effect was not due to inadvertent lesioning of the STN and was dependent upon proper electrode placement. Since STN-DBS appears to have significant neuroprotective properties, initiation of STN-DBS earlier in the course of PD may provide added neuroprotective benefits in addition to its ability to provide symptomatic relief. PMID:20307668

Frontal Lobe Contusion in Mice Chronically Impairs Prefrontal-Dependent Behavior

PubMed Central

Rosi, Susanna

2016-01-01

Traumatic brain injury (TBI) is a major cause of chronic disability in the world. Moderate to severe TBI often results in damage to the frontal lobe region and leads to cognitive, emotional, and social behavioral sequelae that negatively affect quality of life. More specifically, TBI patients often develop persistent deficits in social behavior, anxiety, and executive functions such as attention, mental flexibility, and task switching. These deficits are intrinsically associated with prefrontal cortex (PFC) functionality. Currently, there is a lack of analogous, behaviorally characterized TBI models for investigating frontal lobe injuries despite the prevalence of focal contusions to the frontal lobe in TBI patients. We used the controlled cortical impact (CCI) model in mice to generate a frontal lobe contusion and studied behavioral changes associated with PFC function. We found that unilateral frontal lobe contusion in mice produced long-term impairments to social recognition and reversal learning while having only a minor effect on anxiety and completely sparing rule shifting and hippocampal-dependent behavior. PMID:26964036

19 CFR 10.537 - Accessories, spare parts, or tools.

Code of Federal Regulations, 2010 CFR

2010-04-01

... parts, or tools will be taken into account as originating or non-originating materials, as the case may... 19 Customs Duties 1 2010-04-01 2010-04-01 false Accessories, spare parts, or tools. 10.537 Section... Free Trade Agreement Rules of Origin § 10.537 Accessories, spare parts, or tools. Accessories, spare...

46 CFR 34.50-15 - Spare charges-TB/ALL.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 1 2012-10-01 2012-10-01 false Spare charges-TB/ALL. 34.50-15 Section 34.50-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS FIREFIGHTING EQUIPMENT Portable and Semiportable Extinguishers § 34.50-15 Spare charges—TB/ALL. (a) Spare charges shall be carried on all vessels...

46 CFR 34.50-15 - Spare charges-TB/ALL.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Spare charges-TB/ALL. 34.50-15 Section 34.50-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS FIREFIGHTING EQUIPMENT Portable and Semiportable Extinguishers § 34.50-15 Spare charges—TB/ALL. (a) Spare charges shall be carried on all vessels...

46 CFR 34.50-15 - Spare charges-TB/ALL.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Spare charges-TB/ALL. 34.50-15 Section 34.50-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS FIREFIGHTING EQUIPMENT Portable and Semiportable Extinguishers § 34.50-15 Spare charges—TB/ALL. (a) Spare charges shall be carried on all vessels...

46 CFR 34.50-15 - Spare charges-TB/ALL.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Spare charges-TB/ALL. 34.50-15 Section 34.50-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS FIREFIGHTING EQUIPMENT Portable and Semiportable Extinguishers § 34.50-15 Spare charges—TB/ALL. (a) Spare charges shall be carried on all vessels...

46 CFR 34.50-15 - Spare charges-TB/ALL.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Spare charges-TB/ALL. 34.50-15 Section 34.50-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS FIREFIGHTING EQUIPMENT Portable and Semiportable Extinguishers § 34.50-15 Spare charges—TB/ALL. (a) Spare charges shall be carried on all vessels...

Can sparing of the superficial contralateral parotid lobe reduce xerostomia following radiotherapy for head and neck cancer?

PubMed

Nevens, Daan; Nuyts, Sandra

2017-12-01

The purpose of this study is to see whether sparing the superficial contralateral parotid lobe can help limiting xerostomia following radiotherapy for head and neck cancer. 88 patients that were included in two prospective randomized studies were analysed in the current study. Using the dosimetry of both the parotid glands, we divided our patients in four groups. Group 1 includes patients where we were able to reduce the radiation dose below the threshold in order to spare both the ipsilateral and contralateral parotid glands, Group 2 consists of patients where only the contralateral parotid gland could be spared. Group 3 consists of patients where only the contralateral superficial parotid lobe could be spared, while in Group 4 not even the contralateral superficial lobe could be spared. When we compared Group 1 and Group 2, we did not observe a significant difference between both groups in terms of xerostomia scores at 6 or 12 months. When we compared these groups with Group 3, we observed significant differences with more xerostomia in Group 3 where only the contralateral superficial lobe was spared. A significant difference was also observed between Group 3 and Group 4 with more xerostomia in Group 4. Sparing of just one superficial parotid lobe results in less xerostomia when compared to not sparing any lobe of both parotid glands. Advances in knowledge: When sparing of the whole contralateral parotid gland is not possible, delineating both the superficial parotid glands and trying to spare at least one of them can mean a way forward in limiting xerostomia in head and neck cancer patients treated with radiotherapy.

Contributions of glycogen to astrocytic energetics during brain activation.

PubMed

Dienel, Gerald A; Cruz, Nancy F

2015-02-01

Glycogen is the major store of glucose in brain and is mainly in astrocytes. Brain glycogen levels in unstimulated, carefully-handled rats are 10-12 μmol/g, and assuming that astrocytes account for half the brain mass, astrocytic glycogen content is twice as high. Glycogen turnover is slow under basal conditions, but it is mobilized during activation. There is no net increase in incorporation of label from glucose during activation, whereas label release from pre-labeled glycogen exceeds net glycogen consumption, which increases during stronger stimuli. Because glycogen level is restored by non-oxidative metabolism, astrocytes can influence the global ratio of oxygen to glucose utilization. Compensatory increases in utilization of blood glucose during inhibition of glycogen phosphorylase are large and approximate glycogenolysis rates during sensory stimulation. In contrast, glycogenolysis rates during hypoglycemia are low due to continued glucose delivery and oxidation of endogenous substrates; rates that preserve neuronal function in the absence of glucose are also low, probably due to metabolite oxidation. Modeling studies predict that glycogenolysis maintains a high level of glucose-6-phosphate in astrocytes to maintain feedback inhibition of hexokinase, thereby diverting glucose for use by neurons. The fate of glycogen carbon in vivo is not known, but lactate efflux from brain best accounts for the major metabolic characteristics during activation of living brain. Substantial shuttling coupled with oxidation of glycogen-derived lactate is inconsistent with available evidence. Glycogen has important roles in astrocytic energetics, including glucose sparing, control of extracellular K(+) level, oxidative stress management, and memory consolidation; it is a multi-functional compound.

Contributions of Glycogen to Astrocytic Energetics during Brain Activation

PubMed Central

Dienel, Gerald A.; Cruz, Nancy F.

2014-01-01

Glycogen is the major store of glucose in brain and is mainly in astrocytes. Brain glycogen levels in unstimulated, carefully-handled rats are 10-12 mol/g, and assuming that astrocytes account for half the brain mass, astrocytic glycogen content is twice as high. Glycogen turnover is slow under basal conditions, but it is mobilized during activation. There is no net increase in incorporation of label from glucose during activation, whereas label release from pre-labeled glycogen exceeds net glycogen consumption, which increases during stronger stimuli. Because glycogen level is restored by non-oxidative metabolism, astrocytes can influence the global ratio of oxygen to glucose utilization. Compensatory increases in utilization of blood glucose during inhibition of glycogen phosphorylase are large and approximate glycogenolysis rates during sensory stimulation. In contrast, glycogenolysis rates during hypoglycemia are low due to continued glucose delivery and oxidation of endogenous substrates; rates that preserve neuronal function in the absence of glucose are also low, probably due to metabolite oxidation. Modeling studies predict that glycogenolysis maintains a high level of glucose-6-phosphate in astrocytes to maintain feedback inhibition of hexokinase, thereby diverting glucose for use by neurons. The fate of glycogen carbon in vivo is not known, but lactate efflux from brain best accounts for the major metabolic characteristics during activation of living brain. Substantial shuttling coupled with oxidation of glycogen-derived lactate is inconsistent with available evidence. Glycogen has important roles in astrocytic energetics, including glucose sparing, control of extracellular K+ level, oxidative stress management, and memory consolidation; it is a multi-functional compound. PMID:24515302

Numeracy Skills in Patients With Degenerative Disorders and Focal Brain Lesions

PubMed Central

Cappelletti, Marinella; Butterworth, Brian; Kopelman, Michael

2012-01-01

Objective: To characterize the numerical profile of patients with acquired brain disorders. Method: We investigated numeracy skills in 76 participants—40 healthy controls and 36 patients with neurodegenerative disorders (Alzheimer dementia, frontotemporal dementia, semantic dementia, progressive aphasia) and with focal brain lesions affecting parietal, frontal, and temporal areas as in herpes simplex encephalitis (HSE). All patients were tested with the same comprehensive battery of paper-and-pencil and computerized tasks assessing numerical abilities and calculation. Degenerative and HSE patients also performed nonnumerical semantic tasks. Results: Our results, based on nonparametric group statistics as well as on the analysis of individual patients, and all highly significant, show that: (a) all patients, including those with parietal lesions—a key brain area for numeracy processing—had intact processing of number quantity; (b) patients with impaired semantic knowledge had much better preserved numerical knowledge; and (c) most patients showed impaired calculation skills, with the exception of most semantic dementia and HSE patients. Conclusion: Our results allow us, for the first time, to characterize the numeracy skills in patients with a variety of neurological conditions and to suggest that the pattern of numerical performance can vary considerably across different neurological populations. Moreover, the selective sparing of calculation skills in most semantic dementia and HSE suggest that numerical abilities are an independent component of the semantic system. Finally, our data suggest that, besides the parietal areas, other brain regions might be critical to the understanding and processing of numerical concepts. PMID:22122516

Cognitive and subjective acute dose effects of intramuscular ketamine in healthy adults.

PubMed

Lofwall, Michelle R; Griffiths, Roland R; Mintzer, Miriam Z

2006-11-01

Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) antagonist. Given the purported role of the NMDA receptor in long-term potentiation, the primary purpose of the present study was to further understand the dose-related effects of ketamine on memory. The study was also designed to provide information about the relative effects of ketamine on memory versus nonmemory effects and to more fully characterize ketamine's overall pattern and time course of effects. Single intramuscular injections of ketamine (0.2 mg/kg, 0.4 mg/kg) were administered to 18 healthy adult volunteers using a double-blind, placebo-controlled, crossover design. Word lists were used to evaluate episodic memory (free recall, recognition memory, source memory) and metamemory. Working memory, time estimation, psychomotor performance, and subjective effects were assessed repeatedly for 5 hours after drug administration. Ketamine selectively impaired encoding (as measured by free recall) while sparing retrieval, working memory while sparing attention, and digit symbol substitution task speed while sparing accuracy. Ketamine did not significantly impair recognition or source memory, metamemory, or time estimation. There were no hallucinations or increases in mystical experiences with ketamine. Memory measures were less sensitive to ketamine effects than subjective or psychomotor measures. Subjective effects lasted longer than memory and most psychomotor impairments. Ketamine produces selective, transient, dose- and time-related effects. In conjunction with previous studies of drugs with different mechanisms of actions, the observed selectivity of effects enhances the understanding of the pharmacological mechanisms underlying memory, attention, psychomotor performance, and subjective experience.

[Recurrent urological cancer--diagnose and treatment].

PubMed

Takeshima, H; Akaza, H

1998-02-01

Clinical efforts to spare bladder function even in the case of muscle invasive recurrent bladder cancer is taking. Early detection of recurrence is essential for bladder sparing, and both urinary NMP22 and BTA are thought to have potency to detect recurrence of bladder cancer earlier than urinary cytology. Intravesical administration of BCG for superficial bladder cancer and intraarterial injection of chemoagents (Methotrexate and Cisplatin) with radiation for muscle invasive bladder cancer are thought to play important roles in sparing the bladder. Early detection of recurrent prostate cancer is becoming easier by ultrasensitive PSA assay. Though the value of early detection of recurrence is not proven since the benefits of early hormonal treatment have not yet been established, that should be a good indicator to evaluate new and coming treatments and play a important role to develop an effective treatment for recurrent prostate cancer.

Electrophysiology of glioma: a Rho GTPase-activating protein reduces tumor growth and spares neuron structure and function.

PubMed

Vannini, Eleonora; Olimpico, Francesco; Middei, Silvia; Ammassari-Teule, Martine; de Graaf, Erik L; McDonnell, Liam; Schmidt, Gudula; Fabbri, Alessia; Fiorentini, Carla; Baroncelli, Laura; Costa, Mario; Caleo, Matteo

2016-12-01

Glioblastomas are the most aggressive type of brain tumor. A successful treatment should aim at halting tumor growth and protecting neuronal cells to prevent functional deficits and cognitive deterioration. Here, we exploited a Rho GTPase-activating bacterial protein toxin, cytotoxic necrotizing factor 1 (CNF1), to interfere with glioma cell growth in vitro and vivo. We also investigated whether this toxin spares neuron structure and function in peritumoral areas. We performed a microarray transcriptomic and in-depth proteomic analysis to characterize the molecular changes triggered by CNF1 in glioma cells. We also examined tumor cell senescence and growth in vehicle- and CNF1-treated glioma-bearing mice. Electrophysiological and morphological techniques were used to investigate neuronal alterations in peritumoral cortical areas. Administration of CNF1 triggered molecular and morphological hallmarks of senescence in mouse and human glioma cells in vitro. CNF1 treatment in vivo induced glioma cell senescence and potently reduced tumor volumes. In peritumoral areas of glioma-bearing mice, neurons showed a shrunken dendritic arbor and severe functional alterations such as increased spontaneous activity and reduced visual responsiveness. CNF1 treatment enhanced dendritic length and improved several physiological properties of pyramidal neurons, demonstrating functional preservation of the cortical network. Our findings demonstrate that CNF1 reduces glioma volume while at the same time maintaining the physiological and structural properties of peritumoral neurons. These data indicate a promising strategy for the development of more effective antiglioma therapies. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Influence of acupunction on NT-4 expression in spared root ganglion and spinal cord].

PubMed

Long, Shuang-Lian; Liu, Fen; Wang, Ting-Hua; Wang, Te-Wei; Ke, Qing; Yuan, Yuan

2005-09-01

To explore the changes of the expression of NT-4 in spared dorsal root ganglia (DRG,L6) on both the operation/Acup side and the nonoperation/non-Acup side as well as in the spinal lamina II (L3, L5, L6) and Clarke' nucleus (L3) of the normal adult cats, partial dorsal rhizotomy cats, and Acup spared DRG cats so as to disclose the relation between NT-4 and the plasticity of spinal cord as well as the Acup promoting spinal cord plasticity. Twenty-five adult cats were divided into 5 groups; normal control group; unilateral partial root rhizotomy 7 d and 14 d groups (unilateral L1-L5, L7-S2 DRG were transected, but L6 DRG was spared); Acup spared DRG 7 d and 14 d groups (electro-needle stimulation was performed following unilateral partial root rhizotomy). The cats survived for 7 or 14 days after operation respectively. Bilateral L6 dorsal root ganglia and L3, L5, L6 spinal cord of every group were made into 20 microm frozen sections. Then, sections were stained under the same condition using specific NT-4 (1 : 200) antibody by the immunohistochemistry ABC method. The distribution and the number of NT-4 immunoreactive neurons in bilateral spared DRG (L6) on the operation/Acup side and the nonoperation/Acup side as well as in the, spinal lamina II (L3, L5, L6) and Clarke' nucleus (L3) of each cat were oberserved and counted. All data were analyzed by one-way ANOVA, SNK-q test and paired-t test. Partial dorsal root rhizotomy led to continuous declination of total NT-4 immunoreactive neurons in spared ganglia, till the 14 d, while Acup reversed this tendency and made NT-4 immunoreactive neurons decrease firstly and then approach to normal level till the 14 d after Acup. In addition, Acup increased NT-4 expression in L5, L6 spinal lamina II. The above finding indicate that NT-4 plays an important role in the mechanism by which Acup promotes spinal cord plasticity. Partial dorsal root rhizotomy and Acup spared DRG may exert effects on the expression of NT-4 in the/non-operrtion non-Acup side of DRG.

Longitudinal Investigation of Adaptive Functioning following Conformal Irradiation for Pediatric Craniopharyngioma and Low-Grade Glioma

PubMed Central

Netson, Kelli L.; Conklin, Heather M.; Wu, Shengjie; Xiong, Xiaoping; Merchant, Thomas E.

2013-01-01

Purpose Children treated for brain tumors with conformal radiation therapy experience preserved cognitive outcomes. Early evidence suggests that adaptive functions or independent living skills may be spared. This longitudinal investigation prospectively examined intellectual and adaptive functioning during the first 5 years following irradiation for childhood craniopharyngioma and low-grade glioma (LGG). The effect of visual impairment on adaptive outcomes was investigated. Methods and Materials Children with craniopharyngioma (n=62) and LGG (n=77) were treated using conformal or intensity-modulated radiation therapy. The median age was 8.05 years (3.21 years –17.64 years) and 8.09 years (2.20 years–19.27 years), respectively. Serial cognitive evaluations including measures of intelligence quotient (IQ) and the Vineland Adaptive Behavior Scales (VABS) were conducted at pre-irradiation baseline, 6 months after treatment, and annually through 5 years. A total of 588 evaluations were completed during the follow-up period. Results Baseline assessment revealed no deficits in IQ and VABS indices for children with craniopharyngioma, with significant (p < .05) longitudinal decline in VABS Communication and Socialization indices. Clinical factors associated with more rapid decline included females and pre-irradiation chemotherapy (interferon). The only change in VABS Daily Living Skills correlated with IQ change (r = .34; p = .01) in children with craniopharyngioma. Children with LGG performed below population norms (p < .05) at baseline on VABS Communication, Daily Living Indices, and the Adaptive Behavior Composite, with significant (p < .05) longitudinal decline limited to VABS Communication. Older age at irradiation was a protective factor against longitudinal decline. Severe visual impairment did not independently correlate with poorer adaptive outcomes for either tumor group. Conclusions There was relative sparing of post-irradiation functional outcomes over time in this sample. Baseline differences in functional abilities prior to the initiation of irradiation suggested that other factors influence functional outcomes above and beyond the effects of irradiation. PMID:23245284

Longitudinal Investigation of Adaptive Functioning Following Conformal Irradiation for Pediatric Craniopharyngioma and Low-Grade Glioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Netson, Kelli L.; Conklin, Heather M.; Wu, Shengjie

2013-04-01

Purpose: Children treated for brain tumors with conformal radiation therapy experience preserved cognitive outcomes. Early evidence suggests that adaptive functions or independent-living skills may be spared. This longitudinal investigation prospectively examined intellectual and adaptive functioning during the first 5 years following irradiation for childhood craniopharyngioma and low-grade glioma (LGG). The effect of visual impairment on adaptive outcomes was investigated. Methods and Materials: Children with craniopharyngioma (n=62) and LGG (n=77) were treated using conformal or intensity modulated radiation therapy. The median age was 8.05 years (3.21-17.64 years) and 8.09 years (2.20-19.27 years), respectively. Serial cognitive evaluations including measures of intelligence quotientmore » (IQ) and the Vineland Adaptive Behavior Scales (VABS) were conducted at preirradiation baseline, 6 months after treatment, and annually through 5 years. Five hundred eighty-eight evaluations were completed during the follow-up period. Results: Baseline assessment revealed no deficits in IQ and VABS indices for children with craniopharyngioma, with significant (P<.05) longitudinal decline in VABS Communication and Socialization indices. Clinical factors associated with more rapid decline included females and preirradiation chemotherapy (interferon). The only change in VABS Daily Living Skills correlated with IQ change (r=0.34; P=.01) in children with craniopharyngioma. Children with LGG performed below population norms (P<.05) at baseline on VABS Communication, Daily Living Indices, and the Adaptive Behavior Composite, with significant (P<.05) longitudinal decline limited to VABS Communication. Older age at irradiation was a protective factor against longitudinal decline. Severe visual impairment did not independently correlate with poorer adaptive outcomes for either tumor group. Conclusions: There was relative sparing of postirradiation functional outcomes over time in this sample. Baseline differences in functional abilities before the initiation of irradiation suggested that other factors influence functional outcomes above and beyond the effects of irradiation.« less

Cost analysis of medical device spare parts

PubMed Central

Bektemur, Guven; Muzoglu, Nedim; Arici, Mehmet Ali; Karaaslan, Melike Kaya

2018-01-01

Objective: To establish estimation method on budget management of medical device spare parts and to evaluate the cost of medical device spare parts in affiliated hospitals of Istanbul Public Hospital Unions (PHUs). Methods: While this evaluation was performed, the relationship between paid cost for spare parts according to technological development level of device groups and total inventory value was used. Spare part cost analysis was carried out by using the normalized weighted arithmetic average method. Cost analysis of medical equipment spare parts of Istanbul PHUs was performed by using the data retrieved from Ministry of Health Business Intelligence Decision Support System for spending of spare parts in 2015. Results: The medical device spare part groups were categorized based on technological development. Among 1 to 6 PHUs, the cost ratios were acquired for high, middle, low and simple technology group as 17.31 – 40.08%, 29.14 – 43.36%, 22.62 – 27.44% and 8.16 – 11.89%, respectively. The ratio between the spare part and total inventory costs for 1-6 PHUs were calculated as 1.66%, 2.87%, 3.03%, 3.31%, 2.57% and 4.69% respectively. Expected rates based on normalized weighted method were obtained as follows; 5.76%, 4.67%, 5.31%, 4.87%, 4.34% and 4.27%. Conclusion: The expenditure analysis and budget planning for medical device spare parts in PHU could be predicted more accurately by taking into consideration the expected rate calculated by the normal weight method. In additon, the importance of Clinical Engineering Service Units in management of medical devices has been determined. PMID:29805429

Testing the domain-specificity of a theory of mind deficit in brain-injured patients: evidence for consistent performance on non-verbal, "reality-unknown" false belief and false photograph tasks.

PubMed

Apperly, Ian A; Samson, Dana; Chiavarino, Claudia; Bickerton, Wai-Ling; Humphreys, Glyn W

2007-05-01

To test the domain-specificity of "theory of mind" abilities we compared the performance of a case-series of 11 brain-lesioned patients on a recently developed test of false belief reasoning () and on a matched false photograph task, which did not require belief reasoning and which addressed problems with existing false photograph methods. A strikingly similar pattern of performance was shown across the false belief and false photograph tests. Patients who were selectively impaired on false belief tasks were also impaired on false photograph tasks; patients spared on false belief tasks also showed preserved performance with false photographs. In some cases the impairment on false belief and false photograph tasks coincided with good performance on control tasks matched for executive demands. We discuss whether the patients have a domain-specific deficit in reasoning about representations common to both false belief and false photograph tasks.

Converging models of schizophrenia - Network alterations of prefrontal cortex underlying cognitive impairments

PubMed Central

Sakurai, Takeshi; Gamo, Nao J; Hikida, Takatoshi; Kim, Sun-Hong; Murai, Toshiya; Tomoda, Toshifumi; Sawa, Akira

2015-01-01

The prefrontal cortex (PFC) and its connections with other brain areas are crucial for cognitive function. Cognitive impairments are one of the core symptoms associated with schizophrenia, and manifest even before the onset of the disorder. Altered neural networks involving PFC contribute to cognitive impairments in schizophrenia. Both genetic and environmental risk factors affect the development of the local circuitry within PFC as well as development of broader brain networks, and make the system vulnerable to further insults during adolescence, leading to the onset of the disorder in young adulthood. Since spared cognitive functions correlate with functional outcome and prognosis, a better understanding of the mechanisms underlying cognitive impairments will have important implications for novel therapeutics for schizophrenia focusing on cognitive functions. Multidisciplinary approaches, from basic neuroscience to clinical studies, are required to link molecules, circuitry, networks, and behavioral phenotypes. Close interactions among such fields by sharing a common language on connectomes, behavioral readouts, and other concepts are crucial for this goal. PMID:26408506

Language Learning Variability within the Dorsal and Ventral Streams as a Cue for Compensatory Mechanisms in Aphasia Recovery

PubMed Central

López-Barroso, Diana; de Diego-Balaguer, Ruth

2017-01-01

Dorsal and ventral pathways connecting perisylvian language areas have been shown to be functionally and anatomically segregated. Whereas the dorsal pathway integrates the sensory-motor information required for verbal repetition, the ventral pathway has classically been associated with semantic processes. The great individual differences characterizing language learning through life partly correlate with brain structure and function within these dorsal and ventral language networks. Variability and plasticity within these networks also underlie inter-individual differences in the recovery of linguistic abilities in aphasia. Despite the division of labor of the dorsal and ventral streams, studies in healthy individuals have shown how the interaction of them and the redundancy in the areas they connect allow for compensatory strategies in functions that are usually segregated. In this mini-review we highlight the need to examine compensatory mechanisms between streams in healthy individuals as a helpful guide to choosing the most appropriate rehabilitation strategies, using spared functions and targeting preserved compensatory networks for brain plasticity. PMID:29021751

Molecular Pathways Bridging Frontotemporal Lobar Degeneration and Psychiatric Disorders

PubMed Central

Zanardini, Roberta; Ciani, Miriam; Benussi, Luisa; Ghidoni, Roberta

2016-01-01

The overlap of symptoms between neurodegenerative and psychiatric diseases has been reported. Neuropsychiatric alterations are commonly observed in dementia, especially in the behavioral variant of frontotemporal dementia (bvFTD), which is the most common clinical FTD subtype. At the same time, psychiatric disorders, like schizophrenia (SCZ), can display symptoms of dementia, including features of frontal dysfunction with relative sparing of memory. In the present review, we discuss common molecular features in these pathologies with a special focus on FTD. Molecules like Brain Derived Neurotrophic Factor (BDNF) and progranulin are linked to the pathophysiology of both neurodegenerative and psychiatric diseases. In these brain-associated illnesses, the presence of disease-associated variants in BDNF and progranulin (GRN) genes cause a reduction of circulating proteins levels, through alterations in proteins expression or secretion. For these reasons, we believe that prevention and therapy of psychiatric and neurological disorders could be achieved enhancing both BDNF and progranulin levels thanks to drug discovery efforts. PMID:26869919

Reversal of pathological pain through specific spinal GABAA receptor subtypes.

PubMed

Knabl, Julia; Witschi, Robert; Hösl, Katharina; Reinold, Heiko; Zeilhofer, Ulrike B; Ahmadi, Seifollah; Brockhaus, Johannes; Sergejeva, Marina; Hess, Andreas; Brune, Kay; Fritschy, Jean-Marc; Rudolph, Uwe; Möhler, Hanns; Zeilhofer, Hanns Ulrich

2008-01-17

Inflammatory diseases and neuropathic insults are frequently accompanied by severe and debilitating pain, which can become chronic and often unresponsive to conventional analgesic treatment. A loss of synaptic inhibition in the spinal dorsal horn is considered to contribute significantly to this pain pathology. Facilitation of spinal gamma-aminobutyric acid (GABA)ergic neurotransmission through modulation of GABA(A) receptors should be able to compensate for this loss. With the use of GABA(A)-receptor point-mutated knock-in mice in which specific GABA(A) receptor subtypes have been selectively rendered insensitive to benzodiazepine-site ligands, we show here that pronounced analgesia can be achieved by specifically targeting spinal GABA(A) receptors containing the alpha2 and/or alpha3 subunits. We show that their selective activation by the non-sedative ('alpha1-sparing') benzodiazepine-site ligand L-838,417 (ref. 13) is highly effective against inflammatory and neuropathic pain yet devoid of unwanted sedation, motor impairment and tolerance development. L-838,417 not only diminished the nociceptive input to the brain but also reduced the activity of brain areas related to the associative-emotional components of pain, as shown by functional magnetic resonance imaging in rats. These results provide a rational basis for the development of subtype-selective GABAergic drugs for the treatment of chronic pain, which is often refractory to classical analgesics.

Can Plasticity Transform Functions in Neurodegeneration in Children as Well as Adults? An Observational Study

PubMed Central

Chandra, Sadanandavalli Retnaswami; Ahamed, Safwan; Vidhya Annapoorni, Chandra Sasitharan

2018-01-01

Introduction: Creativity is a physiological need based biological function very essential for survival. However, generally in disorders of progressive cognitive dysfunction creative skills are lost. However there are situations where these potentials are temporarily enhanced. Patients and Methods: We did an observational study of children and adults, 5 adults and 2 childrens, who showed extraordinary creativity evaluated based on evidence shown by patient, peers and re produced in test situation. Discussion: Our observational study reveals spontaneous interest in new and useful creative activity in our patients with various disorders causing progressive cognitive dysfunction. This observation reveals creative gain of function does take place in the face of progressive cognitive dysfunction in the setting of several diseases and it serves as a treatment option in behaviour management. Whether it is due to disinhibition of creative areas in the brain or facilitated function in regenerating data linking circuits needs further study. Conclusion: Set goals which are survival instinct based activities are probably removed by neurodegeneration and thereby the innate creativity gets disinhibited and expressed in wonderful forms of creativity. Whether special creative circuits in the brain, which causes this extraordinary creativity also needs to be studied. These creative skills in some of our patients served as effective pharmaco sparing agents during periods of aggression and agitation by engaging them in those activities, utility of which can be considered as a therapeutic option. PMID:29403132

Fetal Sex Modulates Developmental Response to Maternal Malnutrition

PubMed Central

Gonzalez-Bulnes, Antonio; Torres-Rovira, Laura; Astiz, Susana; Ovilo, Cristina; Sanchez-Sanchez, Raul; Gomez-Fidalgo, Ernesto; Perez-Solana, Mariluz; Martin-Lluch, Mercedes; Garcia-Contreras, Consuelo; Vazquez-Gomez, Marta

2015-01-01

The incidence of obesity and metabolic diseases is dramatically high in rapidly developing countries. Causes have been related to intrinsic ethnic features with development of a thrifty genotype for adapting to food scarcity, prenatal programming by undernutrition, and postnatal exposure to obesogenic lifestyle. Observational studies in humans and experimental studies in animal models evidence that the adaptive responses of the offspring may be modulated by their sex. In the contemporary context of world globalization, the new question arising is the existence and extent of sex-related differences in developmental and metabolic traits in case of mixed-race. Hence, in the current study, using a swine model, we compared male and female fetuses that were crossbred from mothers with thrifty genotype and fathers without thrifty genotype. Female conceptuses evidence stronger protective strategies for their adequate growth and postnatal survival. In brief, both male and female fetuses developed a brain-sparing effect but female fetuses were still able to maintain the development of other viscerae than the brain (mainly liver, intestine and kidneys) at the expense of carcass development. Furthermore, these morphometric differences were reinforced by differences in nutrient availability (glucose and cholesterol) favoring female fetuses with severe developmental predicament. These findings set the basis for further studies aiming to increase the knowledge on the interaction between genetic and environmental factors in the determination of adult phenotype PMID:26544862

Model of delivery consolidation of critical spare part : case study of an oil and gas company

NASA Astrophysics Data System (ADS)

Hartanto, D.; Agustinita, A.

2018-04-01

The availability of spare parts in oil and gas industry is very important to prevent the occurrence of very high opportunity cost, that is the loss caused by exploitation equipment which must stop because of unavailability of the spare part. This is done by providing safety stock with a very high service level that leads to high inventory costs. If the company wants to lower inventory costs, the choices are not to lower the service level but to lower the ordering cost. One of the components of ordering cost is the delivery cost. Exploitation facilities are usually located in remote areas so that the cost of delivery is high. In addition, many spare parts are supplied by the same supplier. Therefore, there is an opportunity to lower the cost of delivery of spare parts by consolidation. In this paper,mixed integer linear programming (MILP) model is developed to plan the procurement of spare parts so that inventory costs which include holding and ordering cost for spare parts can be minimized. The model has been verified and validated. Using this model the company can lower inventory costs of the spare part by 32%.

The role of annular dimension and annuloplasty in tricuspid aortic valve repair.

PubMed

de Kerchove, Laurent; Mastrobuoni, Stefano; Boodhwani, Munir; Astarci, Parla; Rubay, Jean; Poncelet, Alain; Vanoverschelde, Jean-Louis; Noirhomme, Philippe; El Khoury, Gebrine

2016-02-01

Valve sparing reimplantation can improve the durability of bicuspid aortic valve repair compared with subcommissural annuloplasty, especially in patients with a large basal ring. This study analyses the effect of basal ring size and annuloplasty on valve repair in the setting of a tricuspid aortic valve. From 1995 to 2013, 382 patients underwent elective tricuspid aortic valve repair. We included only those undergoing subcommissural annuloplasty, valve sparing reimplantation or no annuloplasty and in whom intraoperative transoesophageal echocardiography images were available for retrospective pre- and post-repair basal ring measurements (n = 323, subcommissural annuloplasty: 146, valve sparing reimplantation: 154, no annuloplasty: 23). In a subgroup of patients with available echocardiographic images, basal ring was retrospectively measured at the latest follow-up or prior to reoperation. subcommissural annuloplasty and valve sparing reimplantation were compared after matching for degree of aortic regurgitation and root size. All three groups differed significantly for most of preoperative characteristics. Hospital mortality was 0.9%. The median follow-up was 4.7 years. At 8 years, overall survival was 80 ± 5%. Freedom from reoperation and freedom from aortic regurgitation >1+ were 92 ± 5% and 71 ± 8%, respectively. In multivariate analysis, predictors of aortic regurgitation >1+ were left ventricular end-diastolic diameter (P = 0.003), cusp repair (P = 0.006), body surface area (P = 0.01) and subcommissural annuloplasty (P = 0.05). In subcommissural annuloplasty, freedom from aortic regurgitation >1+ was lower for patients with basal ring ≥28 mm compared with patients with basal ring <28 mm (P = 0.0001). In valve sparing reimplantation, freedom from aortic regurgitation >1+ was independent of basal ring size (P = 0.38). In matched comparison between subcommissural annuloplasty and valve sparing reimplantation, freedom from aortic regurgitation >1+ was not significantly different (P = 0.06), but in patients with basal ring ≥28 mm, valve sparing reimplantation was superior to subcommissural annuloplasty (P = 0.04). Despite similar intraoperative reduction in basal ring size in subcommissural annuloplasty and valve sparing reimplantation, patients with subcommissural annuloplasty exhibited greater increase in basal ring size during the follow-up compared with the valve sparing reimplantation group (P < 0.001). As with a bicuspid aortic valve, a large basal ring predicts recurrence of aortic regurgitation in patients with tricuspid aortic valve undergoing repair with the subcommissural annuloplasty technique. This recurrence is caused by basal ring dilatation over time after subcommissural annuloplasty. With the valve sparing reimplantation technique, large basal ring did not predict aortic regurgitation recurrence, as prosthetic-based circumferential annuloplasty displayed better stability over time. Stable circumferential annuloplasty is recommended in tricuspid aortic valve repair whenever the basal ring size is ≥28 mm. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Assessment of lexical semantic judgment abilities in alcohol-dependent subjects: an fMRI study.

PubMed

Bagga, D; Singh, N; Modi, S; Kumar, P; Bhattacharya, D; Garg, M L; Khushu, S

2013-12-01

Neuropsychological studies have shown that alcohol dependence is associated with neurocognitive deficits in tasks requiring memory, perceptual motor skills, abstraction and problem solving, whereas language skills are relatively spared in alcoholics despite structural abnormalities in the language-related brain regions. To investigate the preserved mechanisms of language processing in alcohol-dependents, functional brain imaging was undertaken in healthy controls (n=18) and alcohol-dependents (n=16) while completing a lexical semantic judgment task in a 3 T MR scanner. Behavioural data indicated that alcohol-dependents took more time than controls for performing the task but there was no significant difference in their response accuracy. fMRI data analysis revealed that while performing the task, the alcoholics showed enhanced activations in left supramarginal gyrus, precuneus bilaterally, left angular gyrus, and left middle temporal gyrus as compared to control subjects. The extensive activations observed in alcoholics as compared to controls suggest that alcoholics recruit additional brain areas to meet the behavioural demands for equivalent task performance. The results are consistent with previous fMRI studies suggesting compensatory mechanisms for the execution of task for showing an equivalent performance or decreased neural efficiency of relevant brain networks. However, on direct comparison of the two groups, the results did not survive correction for multiple comparisons; therefore, the present findings need further exploration.

Ketamine differentially restores diverse alterations of neuroligins in brain regions in a rat model of neuropathic pain-induced depression.

PubMed

Pan, Wei; Zhang, Guang-Fen; Li, Hui-Hui; Ji, Mu-Huo; Zhou, Zhi-Qiang; Li, Kuan-Yu; Yang, Jian-Jun

2018-07-04

Depression is present in a large proportion of patients suffering from chronic pain, and yet the underlying mechanisms remain to be elucidated. Neuroligins (NLs), as a family of cell-adhesion proteins, are involved in synaptic formation and have been linked to various neuropsychiatric disorders. Here, we studied the alterations in NL1 and NL2 in the medial prefrontal cortex (mPFC), the anterior cingulate cortex (ACC), and the hippocampus in a rat model of neuropathic pain-induced depression, and whether ketamine, a rapid and robust antidepressant, could restore these abnormalities. In the present study, we found that spared nerve injury induced significant mechanical allodynia and subsequent depressive-like symptoms, along with decreased NL1 and increased NL2 in the mPFC, decreased NL1 in the ACC, and decreased NL2 in the hippocampus. In addition, brain-derived neurotrophic factor (BDNF) was reduced in these brain regions. It is noteworthy that ketamine (10 mg/kg) relieved neuropathic pain-induced depressive behaviors and restored alterations of BDNF and NLs in the mPFC and the hippocampus at 24 h and 72 h after the administration of ketamine, but only restored BDNF in the ACC. In conclusion, NLs showed diverse changes in different brain regions in the rat model of neuropathic pain-induced depression, which could be reversed differentially by the administration of ketamine.

Cost Allocation and Overpricing of Spare Parts.

DTIC Science & Technology

1986-09-01

5 defense contractors are presently treating spare parts as cost objectives and using a type of spare parts accounting system as described in the...survey instrument. The other 7 contractor respondents who do not treat spare parts as cost objectives were not favor- able to this accounting treatment...company accounting systems or lised to resolve specific contract or formula pricing cost allocation issues, contribute signi- ficantly to overpricing

Analysis of a Proposal to Implement the Readiness Based Sparing Process in the Brazilian Navy

DTIC Science & Technology

2017-06-01

determine inventory levels. This research investigates whether implementing the U.S. DOD readiness-based sparing (RBS) methodology could provide the...suggested by applying the methodology first for determining reparable spares initial provisioning. 14. SUBJECT TERMS reparable, system-approach...This research investigates whether implementing the U.S. DOD readiness-based sparing (RBS) methodology could provide the Brazilian Navy with greater

Increasing Competition for Spares within AFLC (Air Force Logistics Center). Revision.

DTIC Science & Technology

1982-11-30

Managers 45 On Competing the Production of Weapon Systems 46 Sole Source and Competitive Price Trends in Spare Parts Acquisition 47 Controlled...future directions in research and policy . 3- TOPIC: Acquisition TYPE: AFIT Thesis TITLE: Spares Acquisition Integrated with Production and Its...evaluate Air Force management policies , procedures, practices, and controls over the acquisition and pricing of spare parts. Specific objectives

SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou, P; Park, P; Li, H

Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated withmore » PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.« less

Heart-sparing radiotherapy in patients with breast cancer: What are the techniques used in the clinical routine?: A pattern of practice survey in the German-speaking countries.

PubMed

Duma, Marciana-Nona; Münch, Stefan; Oechsner, Markus; Combs, Stephanie E

2017-01-01

The aim of this study was to understand the practice of care in German-speaking countries with regard to heart-sparing radiotherapy techniques. Between August 2015 and September 2015, an e-mail/fax-based survey was sent to radiation oncology departments in Germany, Austria, and the German-speaking Switzerland. The questionnaire was divided into 3 chapters: a general chapter on the department, a chapter specific for heart-sparing techniques in patients with breast cancer, and a third chapter on personal beliefs on the topic of heart sparing in patients with breast cancer. A total of 82 radiation oncology departments answered the questionnaire: 16 university clinics and 66 other departments. In general, heart-sparing techniques are being offered by 90.2% of departments for radiation oncology in the German-speaking countries. However, in the clinical routine, 87.7% of institutions use heart-sparing techniques in less than 50% of patients with breast cancer. Heart-sparing techniques are especially provided for patients with left-sided breast cancer (80%), patients after mastectomy (52.5%), and when the mammaria interna lymph drainage vessels are irradiated (41.3%). In 46.3% of departments, there are written internal guidelines for heart sparing in patients with breast cancer. Breathing-adapted radiotherapy is used as the most frequent heart-sparing technique in 64.7% of the institutions, followed by intensity-modulated radiation therapy, which is most frequently used by 22.1%. The only significant difference between university hospitals and other departments was seen for the offering of partial breast irradiation. The most commonly used heart-sparing technique is breathing-adapted radiotherapy, but there is no coherent approach for heart sparing in patients with breast cancer in the German-speaking countries. Overall, all options for cardiac protection/cardiac avoidance have their advantages and disadvantages, with deep inspiration breath-hold radiotherapyhaving the most clear data, which should be the preferred choice when using heart-sparing techniques. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

The "Skull Flap" a new conceived device for decompressive craniectomy experimental study on dogs to evaluate the safety and efficacy in reducing intracranial pressure and subsequent impact on brain perfusion.

PubMed

Salvatore, Chibbaro; Fabrice, Vallee; Marco, Marsella; Leonardo, Tigan; Thomas, Lilin; Benoit, Lecuelle; Bernard, George; Pierre, Kehrli; Eric, Vicaut; Paolo, Diemidio

2013-10-01

Decompressive craniectomy (DC) is a procedure performed increasingly often in current neurosurgical practice. Significant perioperative morbidity may be associated to this procedure because of the large skull defect; also, later closure of the skull defect (cranioplasty) may be associated to post-operative morbidity as much as any other reconstructive operation. The authors present a newly conceived/developed device: The "Skull Flap" (SF). This system, placed at the time of the craniectomy, offers the possibility to provide cranial reconstruction sparing patients a second operation. In other words, DC and cranioplasty essentially take place at the same time and in addition, patients retain their own bone flap. The current study conducted on animal models, represents the logical continuation of a prior recent study, realized on cadaver specimens, to assess the efficacy and safety of this recently developed device. This is an experimental pilot study on dogs to assess both safety and efficacy of the SF device. Two groups of experimental raised intracranial pressure animal models underwent DC; in the first group of dogs, the bone flap was left in raised position above the skull defect using the SF device; on the second group the flap was discarded. All dogs underwent transcranial Doppler (TCD) to assess brain perfusion. Head computed tomography (CT) scan to determine flap position was also obtained in the group in which the SF device was placed. SF has proved to be a strong fixation device that allows satisfactory brain decompression by keeping the bone flap elevated from the swollen brain; later on, the SF allows cranial reconstruction in a simple way without requiring a second staged operation. In addition, it is relevant to note that brain perfusion was measured and found to be better in the group receiving the SF (while the flap being in a raised as well as in its natural position) comparing to the other group. The SF device has proved to be very easy to place, well-adaptable to a different type of flaps and ultimately very effective in maintaining satisfactory brain decompression and later on, making easy bone flap repositioning after brain swelling has subsided.

Supportability Issues and Approaches for Exploration Missions

NASA Technical Reports Server (NTRS)

Watson, J. K.; Ivins, M. S.; Cunningham, R. A.

2006-01-01

Maintaining and repairing spacecraft systems hardware to achieve required levels of operational availability during long-duration exploration missions will be challenged by limited resupply opportunities, constraints on the mass and volume available for spares and other maintenance-related provisions, and extended communications times. These factors will force the adoption of new approaches to the integrated logistics support of spacecraft systems hardware. For missions beyond the Moon, all spares, equipment, and supplies must either be prepositioned prior to departure from Earth of human crews or carried with the crews. The mass and volume of spares must be minimized by enabling repair at the lowest hardware levels, imposing commonality and standardization across all mission elements at all hardware levels, and providing the capability to fabricate structural and mechanical spares as required. Long round-trip communications times will require increasing levels of autonomy by the crews for most operations including spacecraft maintenance. Effective implementation of these approaches will only be possible when their need is recognized at the earliest stages of the program, when they are incorporated in operational concepts and programmatic requirements, and when diligence is applied in enforcing these requirements throughout system design in an integrated way across all contractors and suppliers. These approaches will be essential for the success of missions to Mars. Although limited duration lunar missions may be successfully accomplished with more traditional approaches to supportability, those missions will offer an opportunity to refine these concepts, associated technologies, and programmatic implementation methodologies so that they can be most effectively applied to later missions.

ADAPTIVE OPTICS IMAGING OF FOVEAL SPARING IN GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PubMed

Querques, Giuseppe; Kamami-Levy, Cynthia; Georges, Anouk; Pedinielli, Alexandre; Capuano, Vittorio; Blanco-Garavito, Rocio; Poulon, Fanny; Souied, Eric H

2016-02-01

To describe adaptive optics (AO) imaging of foveal sparing in geographic atrophy (GA) secondary to age-related macular degeneration. Flood-illumination AO infrared (IR) fundus images were obtained in four consecutive patients with GA using an AO retinal camera (rtx1; Imagine Eyes). Adaptive optics IR images were overlaid with confocal scanning laser ophthalmoscope near-IR autofluorescence images to allow direct correlation of en face AO features with areas of foveal sparing. Adaptive optics appearance of GA and foveal sparing, preservation of functional photoreceptors, and cone densities in areas of foveal sparing were investigated. In 5 eyes of 4 patients (all female; mean age 74.2 ± 11.9 years), a total of 5 images, sized 4° × 4°, of foveal sparing visualized on confocal scanning laser ophthalmoscope near-IR autofluorescence were investigated by AO imaging. En face AO images revealed GA as regions of inhomogeneous hyperreflectivity with irregularly dispersed hyporeflective clumps. By direct comparison with adjacent regions of GA, foveal sparing appeared as well-demarcated areas of reduced reflectivity with less hyporeflective clumps (mean 14.2 vs. 3.2; P = 0.03). Of note, in these areas, en face AO IR images revealed cone photoreceptors as hyperreflective dots over the background reflectivity (mean cone density 3,271 ± 1,109 cones per square millimeter). Microperimetry demonstrated residual function in areas of foveal sparing detected by confocal scanning laser ophthalmoscope near-IR autofluorescence. Adaptive optics allows the appreciation of differences in reflectivity between regions of GA and foveal sparing. Preservation of functional cone photoreceptors was demonstrated on en face AO IR images in areas of foveal sparing detected by confocal scanning laser ophthalmoscope near-IR autofluorescence.

Nonthermal ablation with microbubble-enhanced focused ultrasound close to the optic tract without affecting nerve function.

PubMed

McDannold, Nathan; Zhang, Yong-Zhi; Power, Chanikarn; Jolesz, Ferenc; Vykhodtseva, Natalia

2013-11-01

Tumors at the skull base are challenging for both resection and radiosurgery given the presence of critical adjacent structures, such as cranial nerves, blood vessels, and brainstem. Magnetic resonance imaging-guided thermal ablation via laser or other methods has been evaluated as a minimally invasive alternative to these techniques in the brain. Focused ultrasound (FUS) offers a noninvasive method of thermal ablation; however, skull heating limits currently available technology to ablation at regions distant from the skull bone. Here, the authors evaluated a method that circumvents this problem by combining the FUS exposures with injected microbubble-based ultrasound contrast agent. These microbubbles concentrate the ultrasound-induced effects on the vasculature, enabling an ablation method that does not cause significant heating of the brain or skull. In 29 rats, a 525-kHz FUS transducer was used to ablate tissue structures at the skull base that were centered on or adjacent to the optic tract or chiasm. Low-intensity, low-duty-cycle ultrasound exposures (sonications) were applied for 5 minutes after intravenous injection of an ultrasound contrast agent (Definity, Lantheus Medical Imaging Inc.). Using histological analysis and visual evoked potential (VEP) measurements, the authors determined whether structural or functional damage was induced in the optic tract or chiasm. Overall, while the sonications produced a well-defined lesion in the gray matter targets, the adjacent tract and chiasm had comparatively little or no damage. No significant changes (p > 0.05) were found in the magnitude or latency of the VEP recordings, either immediately after sonication or at later times up to 4 weeks after sonication, and no delayed effects were evident in the histological features of the optic nerve and retina. This technique, which selectively targets the intravascular microbubbles, appears to be a promising method of noninvasively producing sharply demarcated lesions in deep brain structures while preserving function in adjacent nerves. Because of low vascularity--and thus a low microbubble concentration--some large white matter tracts appear to have some natural resistance to this type of ablation compared with gray matter. While future work is needed to develop methods of monitoring the procedure and establishing its safety at deep brain targets, the technique does appear to be a potential solution that allows FUS ablation of deep brain targets while sparing adjacent nerve structures.

Nonthermal ablation with microbubble-enhanced focused ultrasound close to the optic tract without affecting nerve function

PubMed Central

McDannold, Nathan; Zhang, Yong-Zhi; Power, Chanikarn; Jolesz, Ferenc; Vykhodtseva, Natalia

2014-01-01

Object Tumors at the skull base are challenging for both resection and radiosurgery given the presence of critical adjacent structures, such as cranial nerves, blood vessels, and brainstem. Magnetic resonance imaging–guided thermal ablation via laser or other methods has been evaluated as a minimally invasive alternative to these techniques in the brain. Focused ultrasound (FUS) offers a noninvasive method of thermal ablation; however, skull heating limits currently available technology to ablation at regions distant from the skull bone. Here, the authors evaluated a method that circumvents this problem by combining the FUS exposures with injected microbubble-based ultrasound contrast agent. These microbubbles concentrate the ultrasound-induced effects on the vasculature, enabling an ablation method that does not cause significant heating of the brain or skull. Methods In 29 rats, a 525-kHz FUS transducer was used to ablate tissue structures at the skull base that were centered on or adjacent to the optic tract or chiasm. Low-intensity, low-duty-cycle ultrasound exposures (sonications) were applied for 5 minutes after intravenous injection of an ultrasound contrast agent (Definity, Lantheus Medical Imaging Inc.). Using histological analysis and visual evoked potential (VEP) measurements, the authors determined whether structural or functional damage was induced in the optic tract or chiasm. Results Overall, while the sonications produced a well-defined lesion in the gray matter targets, the adjacent tract and chiasm had comparatively little or no damage. No significant changes (p > 0.05) were found in the magnitude or latency of the VEP recordings, either immediately after sonication or at later times up to 4 weeks after sonication, and no delayed effects were evident in the histological features of the optic nerve and retina. Conclusions This technique, which selectively targets the intravascular microbubbles, appears to be a promising method of noninvasively producing sharply demarcated lesions in deep brain structures while preserving function in adjacent nerves. Because of low vascularity—and thus a low microbubble concentration—some large white matter tracts appear to have some natural resistance to this type of ablation compared with gray matter. While future work is needed to develop methods of monitoring the procedure and establishing its safety at deep brain targets, the technique does appear to be a potential solution that allows FUS ablation of deep brain targets while sparing adjacent nerve structures. PMID:24010975

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL): assessment of the involved white matter tracts by MRI.

PubMed

Kassem, Hassan; Wafaie, Ahmed; Abdelfattah, Sherif; Farid, Tarek

2014-01-01

Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is a recently identified autosomal recessive disorder with early onset of symptoms and slowly progressive pyramidal, cerebellar and dorsal column dysfunction. LBSL is characterized by distinct white matter abnormalities and selective involvement of brainstem and spinal cord tracts. The purpose of this study is to assess the imaging features of the involved white matter tracts in cases of LBSL by MRI. We retrospectively reviewed the imaging features of the selectively involved white matter tracts in sixteen genetically proven cases of leukoencephalopathy with brainstem and spinal cord involvement and elevated brain lactate (LBSL). All patients presented with slowly progressive cerebellar sensory ataxia with spasticity and dorsal column dysfunction. MRI of the brain and spine using 1.5 T machine and proton magnetic resonance spectroscopy (1H MRS) on the abnormal white matter were done to all patients. The MRI and MRS data sets were analyzed according to lesion location, extent, distribution and signal pattern as well as metabolite values and ratios in MRS. Laboratory examinations ruled out classic leukodystrophies. In all cases, MRI showed high signal intensity in T2-weighted and FLAIR images within the cerebral subcortical, periventricular and deep white matter, posterior limbs of internal capsules, centrum semiovale, medulla oblongata, intraparenchymal trajectory of trigeminal nerves and deep cerebellar white matter. In the spine, the signal intensity of the dorsal column and lateral cortico-spinal tracts were altered in all patients. The subcortical U fibers, globi pallidi, thalami, midbrain and transverse pontine fibers were spared in all cases. In 11 cases (68.8%), the signal changes were inhomogeneous and confluent whereas in 5 patients (31.2%), the signal abnormalities were spotty. MRI also showed variable signal abnormalities in the sensory and pyramidal tracts in addition to the brainstem and cerebellar connections. Proton MRS showed consistent elevation of the lactate within the abnormal white matter. Distinct MRI findings in the form of selective affection of subcortical and deep white matter tracts of the brain (involving the posterior limb of internal capsules and sparing the subcortical U fibers), dorsal column and lateral cortico-spinal tracts of the spinal cord should lead to the diagnosis of LBSL supported by the presence of lactate peak in 1H MRS. The disease can be confirmed by the analysis of the disease gene DARS2.

Greater intake of vitamins B6 and B12 spares gray matter in healthy elderly: a voxel-based morphometry study

PubMed Central

Erickson, Kirk I.; Suever, Barbara L.; Shaurya Prakash, Ruchika; Colcombe, Stanley J.; McAuley, Edward; Kramer, Arthur F.

2008-01-01

Previous studies have reported that high concentrations of homocysteine and lower concentrations of vitamin B6, B12, and folate increase the risk for cognitive decline and pathology in aging populations. In this cross-sectional study, high-resolution magnetic resonance imaging (MRI) scans and a 3-day food diary were collected on 32 community-dwelling adults between the ages of 59 and 79. We examined the relation between vitamin B6, B12, and folate intake on cortical volume using an optimized voxel-based morphometry (VBM) method and global gray and white matter volume after correcting for age, sex, body mass index, calorie intake, and education. All participants met or surpassed the recommended daily intake for these vitamins. In the VBM analysis, we found that adults with greater vitamin B6 intake had greater gray matter volume along the medial wall, anterior cingulate cortex, medial parietal cortex, middle temporal gyrus, and superior frontal gyrus, whereas people with greater B12 intake had greater volume in the left and right superior parietal sulcus. These effects were driven by vitamin supplementation and were negated when only examining vitamin intake from diet. Folate had no effect on brain volume. Furthermore, there was no relationship between vitamin B6, B12, or folate intake on global brain volume measures, indicating that VBM methods are more sensitive for detecting localized differences in gray matter volume than global measures. These results are discussed in relation to a growing literature on vitamin intake on age-related neurocognitive deterioration. PMID:18281020

Radiotherapy Dose-Volume Effects on Salivary Gland Function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deasy, Joseph O., E-mail: jdeasy@radonc.wustl.ed; Moiseenko, Vitali; Marks, Lawrence

2010-03-01

Publications relating parotid dose-volume characteristics to radiotherapy-induced salivary toxicity were reviewed. Late salivary dysfunction has been correlated to the mean parotid gland dose, with recovery occurring with time. Severe xerostomia (defined as long-term salivary function of <25% of baseline) is usually avoided if at least one parotid gland is spared to a mean dose of less than {approx}20 Gy or if both glands are spared to less than {approx}25 Gy (mean dose). For complex, partial-volume RT patterns (e.g., intensity-modulated radiotherapy), each parotid mean dose should be kept as low as possible, consistent with the desired clinical target volume coverage. Amore » lower parotid mean dose usually results in better function. Submandibular gland sparing also significantly decreases the risk of xerostomia. The currently available predictive models are imprecise, and additional study is required to identify more accurate models of xerostomia risk.« less

Protein-sparing effect of carbohydrate in diets for juvenile turbot Scophthalmus maximus reared at different salinities

NASA Astrophysics Data System (ADS)

Zeng, Lin; Lei, Jilin; Ai, Chunxiang; Hong, Wanshu; Liu, Bin

2015-01-01

The aim of the present study was to investigate the protein-sparing effect of carbohydrate in diets for juvenile turbot ( Scophthalmus maximus) reared at five salinities (12, 18, 24, 30, and 36). The fish were fed three isocaloric and isolipidic diets for 60 days. The results show that specific growth rate (SGR) and feed conversion efficiency (FCE) were higher in fish reared at salinities of 18 and 36, but lower at 12. Fish fed with diet C25P40 (25% carbohydrate and 40% protein) had lower SGR and FCE values compared with those fed with the C5P52 (5% carbohydrate and 52% protein) and C15P46 (15% carbohydrate and 46% protein) diets; however, there was no statistical difference between diet C5P52 and C15P46. SGR and FCE values were unaffected by diet composition in fish reared at salinity 36. Hepatic lipogenic enzyme activities were higher in fish reared at 18 and 36, but lower at 12, while glucokinase (GK) activity was higher in fish reared at 12, and lower at 18 and 36. Dietary starch enhanced GK activity while depressing lipogenic enzyme activity. However, lipogenic enzyme activity increased with increasing dietary starch in fish reared at 36. It is recommended that salinity should be maintained >12 in the farming of juvenile turbot. In addition, an increase in gelatinized starch from 5% to 15% could spare 6% dietary protein in fish reared at salinities of 18-30, while higher salinity (36) could improve dietary carbohydrate use and enhance the protein-sparing effect, which is linked with the induction of lipogenic capacities.

Quantitative Magnetic Resonance Diffusion-Weighted Imaging Evaluation of the Supratentorial Brain Regions in Patients Diagnosed with Brainstem Variant of Posterior Reversible Encephalopathy Syndrome: A Preliminary Study.

PubMed

Chen, Tai-Yuan; Wu, Te-Chang; Ko, Ching-Chung; Feng, I-Jung; Tsui, Yu-Kun; Lin, Chien-Jen; Chen, Jeon-Hor; Lin, Ching-Po

2017-07-01

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic entity with several causes, characterized by rapid onset of symptoms and typical neuroimaging features, which usually resolve if promptly recognized and treated. Brainstem variant of PRES presents with vasogenic edema in brainstem regions on magnetic resonance (MR) images and there is sparing of the supratentorial regions. Because PRES is usually caused by a hypertensive crisis, which would likely have a systemic effect and global manifestations on the brain tissue, we thus proposed that some microscopic abnormalities of the supratentorial regions could be detected with diffusion-weighted imaging (DWI) using apparent diffusion coefficient (ADC) analysis in brainstem variant of PRES and hypothesized that "normal-looking" supratentorial regions will increase water diffusion. We retrospectively identified patients with PRES who underwent brain magnetic resonance imaging studies. We identified 11 brainstem variants of PRES patients, who formed the study cohort, and 11 typical PRES patients and 20 normal control subjects as the comparison cohorts for this study. Nineteen regions of interest were drawn and systematically placed. The mean ADC values were measured and compared among these 3 groups. ADC values of the typical PRES group were consistently elevated compared with those in normal control subjects. ADC values of the brainstem variant group were consistently elevated compared with those in normal control subjects. ADC values of the typical PRES group and brainstem variant group did not differ significantly, except for the pons area. Quantitative MR DWI may aid in the evaluation of supratentorial microscopic abnormalities in brainstem variant of PRES patients. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Targeted Deletion of Sox10 by Wnt1-cre Defects Neuronal Migration and Projection in the Mouse Inner Ear

PubMed Central

Mao, YanYan; Reiprich, Simone; Wegner, Michael; Fritzsch, Bernd

2014-01-01

Sensory nerves of the brainstem are mostly composed of placode-derived neurons, neural crest-derived neurons and neural crest-derived Schwann cells. This mixed origin of cells has made it difficult to dissect interdependence for fiber guidance. Inner ear-derived neurons are known to connect to the brain after delayed loss of Schwann cells in ErbB2 mutants. However, the ErbB2 mutant related alterations in the ear and the brain compound interpretation of the data. We present here a new model to evaluate exclusively the effect of Schwann cell loss on inner ear innervation. Conditional deletion of the neural crest specific transcription factor, Sox10, using the rhombic lip/neural crest specific Wnt1-cre driver spares Sox10 expression in the ear. We confirm that neural crest-derived cells provide a stop signal for migrating spiral ganglion neurons. In the absence of Schwann cells, spiral ganglion neurons migrate into the center of the cochlea and even out of the ear toward the brain. Spiral ganglion neuron afferent processes reach the organ of Corti, but many afferent fibers bypass the organ of Corti to enter the lateral wall of the cochlea. In contrast to this peripheral disorganization, the central projection to cochlear nuclei is normal. Compared to ErbB2 mutants, conditional Sox10 mutants have limited cell death in spiral ganglion neurons, indicating that the absence of Schwann cells alone contributes little to the embryonic survival of neurons. These data suggest that neural crest-derived cells are dispensable for all central and some peripheral targeting of inner ear neurons. However, Schwann cells provide a stop signal for migratory spiral ganglion neurons and facilitate proper targeting of the organ of Corti by spiral ganglion afferents. PMID:24718611

Spatial patterns of atrophy, hypometabolism, and amyloid deposition in Alzheimer's disease correspond to dissociable functional brain networks.

PubMed

Grothe, Michel J; Teipel, Stefan J

2016-01-01

Recent neuroimaging studies of Alzheimer's disease (AD) have emphasized topographical similarities between AD-related brain changes and a prominent cortical association network called the default-mode network (DMN). However, the specificity of distinct imaging abnormalities for the DMN compared to other intrinsic connectivity networks (ICNs) of the limbic and heteromodal association cortex has not yet been examined systematically. We assessed regional amyloid load using AV45-PET, neuronal metabolism using FDG-PET, and gray matter volume using structural MRI in 473 participants from the Alzheimer's Disease Neuroimaging Initiative, including preclinical, predementia, and clinically manifest AD stages. Complementary region-of-interest and voxel-based analyses were used to assess disease stage- and modality-specific changes within seven principle ICNs of the human brain as defined by a standardized functional connectivity atlas. Amyloid deposition in AD dementia showed a preference for the DMN, but high effect sizes were also observed for other neocortical ICNs, most notably the frontoparietal-control network. Atrophic changes were most specific for an anterior limbic network, followed by the DMN, whereas other neocortical networks were relatively spared. Hypometabolism appeared to be a mixture of both amyloid- and atrophy-related profiles. Similar patterns of modality-dependent network specificity were also observed in the predementia and, for amyloid deposition, in the preclinical stage. These quantitative data confirm a high vulnerability of the DMN for multimodal imaging abnormalities in AD. However, rather than being selective for the DMN, imaging abnormalities more generally affect higher order cognitive networks and, importantly, the vulnerability profiles of these networks markedly differ for distinct aspects of AD pathology. © 2015 Wiley Periodicals, Inc.

Remodelling of supraspinal neuroglial network in neuropathic pain is featured by a reactive gliosis of the nociceptive amygdala.

PubMed

Marcello, L; Cavaliere, C; Colangelo, A M; Bianco, M R; Cirillo, G; Alberghina, L; Papa, M

2013-07-01

Many brain areas participate to supraspinal control of nociception. In these regions, few studies have investigated the role of glial cells in supraspinal plasticity and the effect of 7-day intrathecal nerve growth factor-like (BB14®, Blueprint Biotech, Milano, Italy) treatment. In male Sprague-Dawley rats, we evaluated by immunohistochemistry the morphological and molecular rearrangement of neuroglial network occurring in several supraspinal brain regions involved in pain processing following spared nerve injury (SNI) of the sciatic nerve. In particular, the medial prefrontal cortex, the amygdala (Amy), the nucleus accumbens (Acb), the thalamus and the periaqueductal gray were analysed. Despite the modifications occurring in the dorsal horn of spinal cord following SNI, no significant changes in the Iba1 and glial fibrillary acidic protein (GFAP) expression were detected in all the analysed supraspinal regions, except for the Amy, showing a remarkable GFAP increase. Interestingly, neuropathic rats also displayed a significant increase of glial transporters (GTs) in all the supraspinal regions. Finally, the analysis of vesicular glutamate transporter 1 (vGLUT1) and vesicular gamma-aminobutyric acid (GABA) transporter (vGAT) expression revealed a significant enhancement of glutamatergic/GABAergic ratio in all selected brain regions of SNI animals, except for Acb. Both glial activation in the Amy and alteration of GTs and vGLUT/vGAT levels observed in neuropathic animals were largely reversed by BB14® treatment. All together, these data strengthen the role of supraspinal neuroglial network plasticity in the establishment of neuropathic pain syndrome. The hallmark is represented by the divergence between glial reaction confined to Amy and the widespread changes in the GT distribution and glutamate/GABA ratio detected in the other supraspinal region. © 2012 European Federation of International Association for the Study of Pain Chapters.

Intensity Modulated Radiotherapy (IMRT) in head and neck cancers - an overview.

PubMed

Nutting, C M

2012-07-01

Radiotherapy (RT) is effective in head and neck cancers. Following RT, dryness and dysphagia are the 2 major sequelae which alter the quality of life (QOL) significantly in these patients. There is randomized evidence that Intensity Modulated Radiotherapy (IMRT) effectively spares the parotid glands. IMRT has been attempted in all head and neck subsites with encouraging results (discussed below). Role of IMRT in swallowing structure (constrictor muscles) sparing is less clear.Further improvement in results may be possible by using functional imaging at the time of RT planning and by image guidance/verification at the time of treatment delivery. The following text discusses these issues in detail. Head and neck cancer, IMRT.

Current and emerging pharmacological treatments for sarcoidosis: a review

PubMed Central

Beegle, Scott H; Barba, Kerry; Gobunsuy, Romel; Judson, Marc A

2013-01-01

The treatment of sarcoidosis is not standardized. Because sarcoidosis may never cause significant symptoms or organ dysfunction, treatment is not mandatory. When treatment is indicated, oral corticosteroids are usually recommended because they are highly likely to be effective in a relative short period of time. However, because sarcoidosis is often a chronic condition, long-term treatment with corticosteroids may cause significant toxicity. Therefore, corticosteroid sparing agents are often indicated in patients requiring chronic therapy. This review outlines the indications for treatment, corticosteroid treatment, and corticosteroid sparing treatments for sarcoidosis. PMID:23596348

Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson's disease (PD MED): a large, open-label, pragmatic randomised trial.

PubMed

Gray, Richard; Ives, Natalie; Rick, Caroline; Patel, Smitaa; Gray, Alastair; Jenkinson, Crispin; McIntosh, Emma; Wheatley, Keith; Williams, Adrian; Clarke, Carl E

2014-09-27

Whether initial treatment for Parkinson's disease should consist of levodopa, dopamine agonists, or monoamine oxidase type B inhibitors (MAOBI) is uncertain. We aimed to establish which of these three classes of drug, as initial treatment, provides the most effective long-term control of symptoms and best quality of life for people with early Parkinson's disease. In this pragmatic, open-label randomised trial, patients newly diagnosed with Parkinson's disease were randomly assigned (by telephone call to a central office; 1:1:1) between levodopa-sparing therapy (dopamine agonists or MAOBI) and levodopa alone. Patients and investigators were not masked to group assignment. Primary outcomes were the mobility dimension on the 39-item patient-rated Parkinson's disease questionnaire (PDQ-39) quality-of-life scale (range 0-100 with six points defined as the minimally important difference) and cost-effectiveness. Analysis was intention to treat. This trial is registered, number ISRCTN69812316. Between Nov 9, 2000, and Dec 22, 2009, 1620 patients were assigned to study groups (528 to levodopa, 632 to dopamine agonist, 460 to MAOBI). With 3-year median follow-up, PDQ-39 mobility scores averaged 1·8 points (95% CI 0·5-3·0, p=0·005) better in patients randomly assigned to levodopa than those assigned to levodopa-sparing therapy, with no increase or attrition of benefit during 7 years' observation. PDQ-39 mobility scores were 1·4 points (95% CI 0·0-2·9, p=0·05) better in patients allocated MAOBI than in those allocated dopamine agonists. EQ-5D utility scores averaged 0·03 (95% CI 0·01-0·05; p=0·0002) better with levodopa than with levodopa-sparing therapy; rates of dementia (hazard ratio [HR] 0·81, 95% CI 0·61-1·08, p=0·14), admissions to institutions (0·86, 0·63-1·18; p=0·4), and death (0·85, 0·69-1·06, p=0·17) were not significantly different, but the upper CIs precluded any substantial increase with levodopa compared with levodopa-sparing therapy. 179 (28%) of 632 patients allocated dopamine agonists and 104 (23%) of 460 patients allocated MAOBI discontinued allocated treatment because of side-effects compared with 11 (2%) of 528 patients allocated levodopa (p<0·0001). Very small but persistent benefits are shown for patient-rated mobility scores when treatment is initiated with levodopa compared with levodopa-sparing therapy. MAOBI as initial levodopa-sparing therapy was at least as effective as dopamine agonists. UK National Institute for Health Research Health Technology Assessment Programme and UK Department of Health. Copyright © 2014 Elsevier Ltd. All rights reserved.

Who is who: areas of the brain associated with recognizing and naming famous faces.

PubMed

Giussani, Carlo; Roux, Franck-Emmanuel; Bello, Lorenzo; Lauwers-Cances, Valérie; Papagno, Costanza; Gaini, Sergio M; Puel, Michelle; Démonet, Jean-François

2009-02-01

It has been hypothesized that specific brain regions involved in face naming may exist in the brain. To spare these areas and to gain a better understanding of their organization, the authors studied patients who underwent surgery by using direct electrical stimulation mapping for brain tumors, and they compared an object-naming task to a famous face-naming task. Fifty-six patients with brain tumors (39 and 17 in the left and right hemispheres, respectively) and with no significant preoperative overall language deficit were prospectively studied over a 2-year period. Four patients who had a partially selective famous face anomia and 2 with prosopagnosia were not included in the final analysis. Face-naming interferences were exclusively localized in small cortical areas (< 1 cm2). Among 35 patients whose dominant left hemisphere was studied, 26 face-naming specific areas (that is, sites of interference in face naming only and not in object naming) were found. These face naming-specific sites were significantly detected in 2 regions: in the left frontal areas of the superior, middle, and inferior frontal gyri (p < 0.001) and in the anterior part of the superior and middle temporal gyri (p < 0.01). Variable patterns of interference were observed (speech arrest, anomia, phonemic, or semantic paraphasia) probably related to the different stages in famous face processing. Only 4 famous face-naming interferences were found in the right hemisphere. Relative anatomical segregation of naming categories within language areas was detected. This study showed that famous face naming was preferentially processed in the left frontal and anterior temporal gyri. The authors think it is necessary to adapt naming tasks in neurosurgical patients to the brain region studied.

Lung Size and the Risk of Radiation Pneumonitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Briere, Tina Marie, E-mail: tmbriere@mdanderson.org; Krafft, Shane; Liao, Zhongxing

2016-02-01

Purpose: The purpose of this study was to identify patient populations treated for non-small cell lung cancer (NSCLC) who may be more at risk of radiation pneumonitis. Methods and Materials: A total of 579 patients receiving fractionated 3D conformal or intensity modulated radiation therapy (IMRT) for NSCLC were included in the study. Statistical analysis was performed to search for cohorts of patients with higher incidences of radiation pneumonitis. In addition to conventional risk factors, total and spared lung volumes were analyzed. The Lyman-Kutcher-Burman (LKB) and cure models were then used to fit the incidence of radiation pneumonitis as a functionmore » of lung dose and other factors. Results: Total lung volumes with a sparing of less than 1854 cc at 40 Gy were associated with a significantly higher incidence of radiation pneumonitis at 6 months (38% vs 12% for patients with larger volumes, P<.001). This patient cohort was overwhelmingly female and represented 22% of the total female population of patients and nearly 30% of the cases of radiation pneumonitis. An LKB fit to normal tissue complication probability (NTCP) including volume as a dose modifying factor resulted in a dose that results in a 50% probability of complication for the smaller spared volume cohort that was 9 Gy lower than the fit to all mean lung dose data and improved the ability to predict radiation pneumonitis (P<.001). Using an effective dose parameter of n=0.42 instead of mean lung dose further improved the LKB fit. Fits to the data using the cure model produced similar results. Conclusions: Spared lung volume should be considered when treating NSCLC patients. Separate dose constraints based on smaller spared lung volume should be considered. Smaller spared lung volume patients should be followed closely for signs of radiation pneumonitis.« less

Analgesic and anti-inflammatory effects of honey: the involvement of autonomic receptors.

PubMed

Owoyele, Bamidele Victor; Oladejo, Rasheed Olajiire; Ajomale, Kayode; Ahmed, Rasheedat Omotayo; Mustapha, Abdulrasheed

2014-03-01

The use of honey for therapeutic purposes is on the increase and many studies have shown that honey has the ability to influence biological systems including pain transmission. Therefore, this study was designed to investigate the analgesic and anti-inflammatory effects of honey and the effects of concurrent administration of autonomic nervous system blocking drugs. Studies on analgesic activities was carried out using hotplate and formalin-induced paw licking models while the anti-inflammatory activity was by the carrageenan paw oedema method. Animals were distributed into six groups consisting of five animals each. They were administered saline, honey (600 mg/kg), indomethacin (5 mg/kg), autonomic blockers (3 μg/kg of tamsulosin, 20 mg/kg (intraperitoneally) of propranolol, 2 ml/kg of atropine or 10 mg/kg (intra muscularly) of hexamethonium) or honey (200 and 600 mg/kg) with one of the blockers. The results showed that honey reduced pain perception especially inflammatory pain and the administration of tamsulosin and propranolol spared the effect of honey. Hexamethonium also spared the effects of honey at the early and late phases of the test while atropine only inhibited the early phase of the test. However, atropine and hexamethonium spared the anti-inflammatory effects of honey but tamsulosin abolished the effects while propranolol only abolished the anti-inflammatory effects at the peak of the inflammation. The results suggest the involvement of autonomic receptors in the anti-nociceptive and anti-inflammatory effects of honey although the level of involvement depends on the different types of the receptors.

Rehabilitation of pure alexia: A review

PubMed Central

Starrfelt, Randi; Ólafsdóttir, Rannveig Rós; Arendt, Ida-Marie

2013-01-01

Acquired reading problems caused by brain injury (alexia) are common, either as a part of an aphasic syndrome, or as an isolated symptom. In pure alexia, reading is impaired while other language functions, including writing, are spared. Being in many ways a simple syndrome, one would think that pure alexia was an easy target for rehabilitation efforts. We review the literature on rehabilitation of pure alexia from 1990 to the present, and find that patients differ widely on several dimensions, such as alexia severity and associated deficits. Many patients reported to have pure alexia in the reviewed studies, have associated deficits such as agraphia or aphasia and thus do not strictly conform to the diagnosis. Few studies report clear and generalisable effects of training, none report control data, and in many cases the reported findings are not supported by statistics. We can, however, tentatively conclude that Multiple Oral Re-reading techniques may have some effect in mild pure alexia where diminished reading speed is the main problem, while Tacile-Kinesthetic training may improve letter identification in more severe cases of alexia. There is, however, still a great need for well-designed and controlled studies of rehabilitation of pure alexia. PMID:23808895

C-peptide and Central Nervous System Complications in Diabetes

PubMed Central

Li, Zhen-guo

2004-01-01

Substantial evidence collected from clinical data and experimental studies has indicated that CNS is not spared from diabetes complications. Impairments in CNS function are well documented in both type 1 and type 2 diabetic patients as well as in various animal models of diabetes, in terms of alterations in cognition, neuropsychology, neurobehavior, electrophysiology, structure, neurochemistry and apoptotic activities. These data suggest that primary diabetic encephalopathy exists as a definable diabetic complication. The mechanisms underlying this CNS complication are not clear. Experimental studies have suggested that neuronal apoptosis may play an important role in neuronal loss and impaired cognitive function. In diabetes multiple factors are responsible for neuronal apoptosis, such as a perturbed IGF system, hyperglycemia and the aging process itself. Recent data suggest that insulin/C-peptide deficiency may exert an eminent role. Administration of C-peptide partially corrects the perturbed IGF system in the brain and prevents neuronal apoptosis in hippocampus of type 1 diabetes. In neuroblastoma SH-SY5Y cells C-peptide provides a dose-dependent stimulation on cell proliferation and an anti-apoptotic effect as well. These studies provide a basis for administration of C-peptide as a potentially effective therapy for type 1 diabetes. PMID:15198373

The safety of istradefylline for the treatment of Parkinson's disease.

PubMed

Müller, Thomas

2015-05-01

Antagonism of the A2A receptor improves motor behavior in patients with Parkinson's disease (PD), according to results of clinical studies which confirm findings of previous experimental research. The xanthine derivative, istradefylline , has the longest half-life out of the available A2A receptor antagonists. Istradefylline easily crosses the blood-brain barrier and shows a high affinity to the human A2A receptor. This narrative review aims to discuss the safety and tolerability of istradefylline against the background of the currently available drug portfolio for the treatment of PD patients. Istradefylline was safe and well tolerated in clinical trials, which have focused on l-DOPA-treated PD patients. The future of istradefylline as a complementary drug for modulation of the dopaminergic neurotransmission also relies on its potential to act like an l-DOPA plus dopamine agonist sparing future treatment alternative and to reduce the risk of predominant l-DOPA-related onset of motor complications in addition to its direct ameliorating effect on motor symptoms. Dopamine-substituting drugs may dose-dependently produce systemic side effects, particularly onset of hypotension and nausea by peripheral dopamine receptor stimulation. Istradefylline does not interfere with these peripheral receptors and therefore shows a good safety and tolerability profile.

Vascular risk factors, cerebrovascular reactivity, and the default-mode brain network.

PubMed

Haight, Thaddeus J; Bryan, R Nick; Erus, Guray; Davatzikos, Christos; Jacobs, David R; D'Esposito, Mark; Lewis, Cora E; Launer, Lenore J

2015-07-15

Cumulating evidence from epidemiologic studies implicates cardiovascular health and cerebrovascular function in several brain diseases in late life. We examined vascular risk factors with respect to a cerebrovascular measure of brain functioning in subjects in mid-life, which could represent a marker of brain changes in later life. Breath-hold functional MRI (fMRI) was performed in 541 women and men (mean age 50.4 years) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Cerebrovascular reactivity (CVR) was quantified as percentage change in blood-oxygen level dependent (BOLD) signal in activated voxels, which was mapped to a common brain template and log-transformed. Mean CVR was calculated for anatomic regions underlying the default-mode network (DMN) - a network implicated in AD and other brain disorders - in addition to areas considered to be relatively spared in the disease (e.g. occipital lobe), which were utilized as reference regions. Mean CVR was significantly reduced in the posterior cingulate/precuneus (β=-0.063, 95% CI: -0.106, -0.020), anterior cingulate (β=-0.055, 95% CI: -0.101, -0.010), and medial frontal lobe (β=-0.050, 95% CI: -0.092, -0.008) relative to mean CVR in the occipital lobe, after adjustment for age, sex, race, education, and smoking status, in subjects with pre-hypertension/hypertension compared to normotensive subjects. By contrast, mean CVR was lower, but not significantly, in the inferior parietal lobe (β=-0.024, 95% CI: -0.062, 0.014) and the hippocampus (β=-0.006, 95% CI: -0.062, 0.050) relative to mean CVR in the occipital lobe. Similar results were observed in subjects with diabetes and dyslipidemia compared to those without these conditions, though the differences were non-significant. Reduced CVR may represent diminished vascular functionality for the DMN for individuals with prehypertension/hypertension in mid-life, and may serve as a preclinical marker for brain dysfunction in later life. Copyright © 2015 Elsevier Inc. All rights reserved.

A Review of Selected International Aircraft Spares Pooling Programs: Lessons Learned for F-35 Spares Pooling

DTIC Science & Technology

2016-01-01

fund its share of program costs , and how the program will manage divergence from a common configuration baseline. In the formal agreement establishing...total spare parts than if all the participants operated on a purely national basis because of differentials in demand, particularly for high- cost parts...by the House of Commons Committee of Public Accounts , whose findings were published in 2011, the international spares pooling contracts did not work

All-Cause Mortality After Fertility-Sparing Surgery for Stage I Epithelial Ovarian Cancer.

PubMed

Melamed, Alexander; Rizzo, Anthony E; Nitecki, Roni; Gockley, Allison A; Bregar, Amy J; Schorge, John O; Del Carmen, Marcela G; Rauh-Hain, J Alejandro

2017-07-01

To compare all-cause mortality between women who underwent fertility-sparing surgery with those who underwent conventional surgery for stage I ovarian cancer. In a cohort study using the National Cancer Database, we identified women younger than 40 years diagnosed with stage IA and unilateral IC epithelial ovarian cancer between 2004 and 2012. Fertility-sparing surgery was defined as conservation of one ovary and the uterus. The primary outcome was time from diagnosis to death. We used propensity score methods to assemble a cohort of women who underwent fertility-sparing or conventional surgery but were otherwise similar on observed covariates and conducted survival analyses using the Kaplan-Meier method and Cox proportional hazard models. We identified 1,726 women with stage IA and unilateral IC epithelial ovarian cancer of whom 825 (47.8%) underwent fertility-sparing surgery. Fertility-sparing surgery was associated with younger age, residence in the northeastern and western United States, and serous or mucinous histology (P<.05 for all). Propensity score matching yielded a cohort of 904 women who were balanced on observed covariates. We observed 30 deaths among women who underwent fertility-sparing surgery and 37 deaths among propensity-matched women who underwent conventional surgery after a median follow-up of 63 months. Fertility-sparing surgery was not associated with hazard of death (hazard ratio 0.80, 95% confidence interval [CI] 0.49-1.29, P=.36). The probability of survival 10 years after diagnosis was 88.5% (95% CI 82.4-92.6) in the fertility-sparing group and 88.9% (95% CI 84.9-92.0) in the conventional surgery group. In patients with high-risk features such as clear cell histology, grade 3, or stage IC, 10-year survival was 80.5% (95% CI 68.5-88.3) among women who underwent fertility-sparing surgery and 83.4% (95% 76.0-88.7) among those who had conventional surgery (hazard ratio 0.86, 95% CI 0.49-1.53, P=.61). Compared with conventional surgery, fertility-sparing surgery was not associated with increased risk of death in young women with stage I epithelial ovarian cancer.

Simultaneous infield boost with helical tomotherapy for patients with 1 to 3 brain metastases.

PubMed

Bauman, Glenn; Yartsev, Slav; Fisher, Barb; Kron, Tomas; Laperriere, Normand; Heydarian, Mostafa; VanDyk, Jake

2007-02-01

We sought to model the feasibility of a simultaneous in field boost (SIB) to individual brain metastases during a course of whole brain radiotherapy (WBXRT) using helical tomotherapy (HT) intensity-modulated radiation therapy. Planning computed tomography data from 14 patients with 1 to 3 brain metastases were used to model an intralesional SIB delivery that yielded a total intralesional dose of 60 Gy with a surrounding whole brain dose of 30 Gy (designed to be isoeffective to WBXRT of 30 Gy with an 18 Gy in 1 fraction radiosurgery boost). Accuracy of treatment of a phantom on the HT unit was measured. Comparisons of HT delivery versus a conventional stereotactic radiotherapy technique for a particularly challenging simulated anatomy were made. In all cases, SIB to 60 Gy with WBXRT to 30 Gy was possible while maintaining critical structures below assigned dose limits. Estimated radiation delivery time for the SIB treatment was approximately 10 minutes per fraction. Planning and treatment of the head phantom was associated with an overall accuracy of 2 mm. Comparison to conventional noncoplanar arc fractionated stereotactic radiotherapy plan demonstrated similar target coverage and improved critical tissue sparing even for a challenging anatomy with multiple lesions in the same plane as the optic apparatus. Based on this study, use of an image guided SIB using HT seemed feasible and a phase I trial initiated at our institution is described. Potential advantages of this approach include frameless stereotaxis through daily megavoltage computed tomography localization, more efficient use of resources and exploitation of radiobiologic advantages of fractionation.

Whole-brain diffusion tensor imaging in correlation to visual-evoked potentials in multiple sclerosis: a tract-based spatial statistics analysis.

PubMed

Lobsien, D; Ettrich, B; Sotiriou, K; Classen, J; Then Bergh, F; Hoffmann, K-T

2014-01-01

Functional correlates of microstructural damage of the brain affected by MS are incompletely understood. The purpose of this study was to evaluate correlations of visual-evoked potentials with microstructural brain changes as determined by DTI in patients with demyelinating central nervous disease. Sixty-one patients with clinically isolated syndrome or MS were prospectively recruited. The mean P100 visual-evoked potential latencies of the right and left eyes of each patient were calculated and used for the analysis. For DTI acquisition, a single-shot echo-planar imaging pulse sequence with 80 diffusion directions was performed at 3T. Fractional anisotropy, radial diffusivity, and axial diffusivity were calculated and correlated with mean P100 visual-evoked potentials by tract-based spatial statistics. Significant negative correlations between mean P100 visual-evoked potentials and fractional anisotropy and significant positive correlations between mean P100 visual-evoked potentials and radial diffusivity were found widespread over the whole brain. The highest significance was found in the optic radiation, frontoparietal white matter, and corpus callosum. Significant positive correlations between mean P100 visual-evoked potentials and axial diffusivity were less widespread, notably sparing the optic radiation. Microstructural changes of the whole brain correlated significantly with mean P100 visual-evoked potentials. The distribution of the correlations showed clear differences among axial diffusivity, fractional anisotropy, and radial diffusivity, notably in the optic radiation. This finding suggests a stronger correlation of mean P100 visual-evoked potentials to demyelination than to axonal damage. © 2014 by American Journal of Neuroradiology.

Poster - 31: Predicting IQ and hearing loss following radiotherapy in pediatric brain tumors: proton vs photon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fortin, Dominique; Ng, Angela; Tsang, Derek

Purpose: The increased sparing of normal tissues in intensity modulated proton therapy (IMPT) in pediatric brain tumor treatments should translate into improved neurocognitive outcomes. Models were used to estimate the intelligence quotient (IQ) and the risk of hearing loss 5 years post radiotherapy and to compare outcomes of proton against photon in pediatric brain tumors. Methods: Patients who had received intensity modulated radiotherapy (IMRT) were randomly selected from our retrospective database. The existing planning CT and contours were used to generate IMPT plans. The RBE-corrected dose was calculated for both IMPT and IMRT. For each patient, the IQ was estimatedmore » via a Monte Carlo technique, whereas the reported incidence of hearing loss as a function of cochlear dose was used to estimate the probability of occurrence. Results: The integrated brain dose was reduced in all IMPT plans, translating into a gain of 2 IQ points on average for protons for the whole cohort at 5 years post-treatment. In terms of specific diseases, the gains in IQ ranged from 0.8 points for medulloblastoma, to 2.7 points for craniopharyngioma. Hearing loss probability was evaluated on a per-ear-basis and was found to be systematically less for proton versus photon: overall 2.9% versus 7.2%. Conclusions: A method was developed to predict IQ and hearing outcomes in pediatric brain tumor patients on a case-by-case basis. A modest gain was systematically observed for proton in all patients. Given the uncertainties within the model used and our reinterpretation, these gains may be underestimated.« less

Review of the poster "Dosimetric comparison of gamma knife radiosurgery vs. 125I plaque brachytherapy in a cohort of choroidal melanomas".

PubMed

Odell, Kelly R

2009-01-01

Historically, treatment for choroidal melanomas was surgical enucleation. Currently, treatment methods such as stereotactic radiosurgery and brachytherapy are being used to spare the eye. The poster "Dosimetric Comparison of Gamma Knife Radiosurgery vs. I-125 Plaque Brachytherapy in a Cohort of Choroidal Melanomas" presented at ASTRO 2007 by Anderson et al. provides a comparison of these methods. The dose to disk, fovea and lens in 29 patients from a simulated I-125 treatment and a delivered Gamma Knife radiosurgery was compared. Thirty Gy was prescribed to the 50% Isodose line in the radiosurgery and 85 Gy was prescribed to the apex of the tumor in the I-125 simulation. It was found that the Gamma Knife spares the disk better in 59% of the tumors, including those >or=6.5 mm in height; spares the fovea better in 69% of the tumors, including those >or=5.5 mm; and spares lens better in only 30% of the tumors, with no distinction in size. Tumor location was not taken into account for this study, which could explain the variations in smaller tumors. For larger tumors, gamma knife will protect most organs at risk more effectively. This study shows how a tumor's parameters can be used in selecting treatment modality.

Safety of long-term subcutaneous free flap skin banking after skin-sparing mastectomy

PubMed Central

Verstappen, Ralph; Djedovic, Gabriel; Morandi, Evi Maria; Heiser, Dietmar; Rieger, Ulrich Michael; Bauer, Thomas

2018-01-01

Background A persistent problem in autologous breast reconstruction in skin-sparing mastectomies is skin restoration after skin necrosis or secondary oncological resection. As a solution to facilitate reconstruction, skin banking of free-flap skin has been proposed in cases where the overlying skin envelope must be resected, as this technique spares the patient an additional donor site. Herein, we present the largest series to date in which this method was used. We investigated its safety and the possibility of skin banking for prolonged periods of time. Methods All skin-sparing mastectomies and immediate autologous breast reconstructions from December 2009 until June 2013 at our institution were analysed. Results We identified 31 patients who underwent 33 free flap reconstructions in which skin banking was performed. Our median skin banking period was 7 days, with a maximum duration of 171 days. In 22.5% of cases, the banked skin was used to reconstruct overlying skin defects, and in 9.6% of cases to reconstruct the nipple-areolar complex. Microbiological and histological investigations of the banked skin revealed neither clinical infections nor malignancies. Conclusions In situ skin banking, even for prolonged periods of time, is a safe and cost-effective method to ensure that skin defects due to necrosis or secondary oncological resection can be easily reconstructed. PMID:29506331

Safety of long-term subcutaneous free flap skin banking after skin-sparing mastectomy.

PubMed

Verstappen, Ralph; Djedovic, Gabriel; Morandi, Evi Maria; Heiser, Dietmar; Rieger, Ulrich Michael; Bauer, Thomas

2018-03-01

A persistent problem in autologous breast reconstruction in skin-sparing mastectomies is skin restoration after skin necrosis or secondary oncological resection. As a solution to facilitate reconstruction, skin banking of free-flap skin has been proposed in cases where the overlying skin envelope must be resected, as this technique spares the patient an additional donor site. Herein, we present the largest series to date in which this method was used. We investigated its safety and the possibility of skin banking for prolonged periods of time. All skin-sparing mastectomies and immediate autologous breast reconstructions from December 2009 until June 2013 at our institution were analysed. We identified 31 patients who underwent 33 free flap reconstructions in which skin banking was performed. Our median skin banking period was 7 days, with a maximum duration of 171 days. In 22.5% of cases, the banked skin was used to reconstruct overlying skin defects, and in 9.6% of cases to reconstruct the nipple-areolar complex. Microbiological and histological investigations of the banked skin revealed neither clinical infections nor malignancies. In situ skin banking, even for prolonged periods of time, is a safe and cost-effective method to ensure that skin defects due to necrosis or secondary oncological resection can be easily reconstructed.

Factors affecting return of continence 3 months after robot-assisted radical prostatectomy: analysis from a large, prospective data by a single surgeon.

PubMed

Ko, Young Hwii; Coelho, Rafael F; Chauhan, Sanket; Sivaraman, Ananthakrishnan; Schatloff, Oscar; Cheon, Jun; Patel, Vipul R

2012-01-01

In this study we identified preoperative or intraoperative factors responsible for the early return of continence after robot-assisted radical prostatectomy using data from a high volume center. Data from 1,299 patients who underwent robot-assisted radical prostatectomy performed by a single surgeon from January 2008 to June 2010 were collected prospectively and analyzed retrospectively. Patients were categorized according to whether they regained continence (no pad and no urinary leakage) within 3 months and variables were then compared. A self-administered validated questionnaire (Expanded Prostate Cancer Index Composite) was used for assessment of continence status and time to recovery. Within 3 months after surgery 86.3% of patients (1,121/1,299) had recovered continence. Multivariable Cox regression analysis revealed that only age (p <0.001, hazard ratio 0.98, 95% CI 0.97-0.99) and performance of a nerve sparing procedure were independent predictors. After adjusting for age, the hazard ratio was 1.61 (95% CI 1.25-2.07, p <0.001) for partial nerve sparing and 1.44 (1.13-1.83, p = 0.003) for bilateral nerve sparing compared to the nonnerve sparing group. Median time (95% CI) to the recovery of continence was prolonged in the nonnerve sparing group compared to nerve sparing counterparts at 6 (5.12-6.88), 4 (3.60-4.40) and 5 weeks (4.70-5.30) in the nonnerve sparing, partial nerve sparing and bilateral nerve sparing groups, respectively, with log rank p <0.01. Findings from our analysis indicate that the likelihood of postoperative urinary control was significantly higher in younger patients and when a nerve sparing procedure was performed. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Sparing bilateral neck level IB in oropharyngeal carcinoma and xerostomia outcomes.

PubMed

Tam, Moses; Riaz, Nadeem; Kannarunimit, Danita; Peña, Angela P; Schupak, Karen D; Gelblum, Daphna Y; Wolden, Suzanne L; Rao, Shyam; Lee, Nancy Y

2015-08-01

To assess whether sparing neck-level IB in target delineation of node-positive (N+) oropharyngeal carcinoma (OPC) can improve xerostomia outcomes without compromising locoregional control (LRC). A total of 125 N+ OPC patients with a median age of 57 years underwent chemoradiation between May 2010 and December 2011. A total of 74% of patients had T1-T2 disease, 26% T3-T4, 16% N1, 8% N2A, 48% N2B, 28% N2C; 53% base of tongue, 41% tonsil, and 6% other. Patients were divided into those who had target delineation sparing of bilateral level IB (the spared cohort) versus no sparing (the treated cohort). Sparing of contralateral high-level II nodes was also performed more consistently in the spared cohort. A prospective xerostomia questionnaire (patient reported) was given at each patient follow-up visit to this cohort of patients to assess late xerostomia. Clinical assessment (observer rated) at each patient follow-up visit was also recorded. The 2-year LRC for the spared and treated cohorts was 97.5% and 93.8%, respectively (median follow-up, 23.2 mo). No locoregional failures occurred outside of treatment fields. The spared cohort experienced significant benefits in patient-reported xerostomia summary scores (P=0.021) and observer-rated xerostomia scores (P=0.006). In addition, there were significant reductions in mean doses to the ipsilateral submandibular gland (63.9 vs. 70.5 Gy; P<0.001), contralateral submandibular gland (45.0 vs. 56.2 Gy; P<0.001), oral cavity (35.9 vs. 45.2 Gy; P<0.001), and contralateral parotid gland (20.0 vs. 24.4 Gy; P<0.001). Target delineation sparing of bilateral level IB nodes in N+ OPC reduced mean doses to salivary organs without compromising LRC. Patients with reduced target volumes had better patient-reported xerostomia outcomes.

Sparing Bilateral Neck Level IB in Oropharyngeal Carcinoma and Xerostomia Outcomes

PubMed Central

Tam, Moses; Riaz, Nadeem; Kannarunimit, Danita; Peña, Angela P.; Schupak, Karen D.; Gelblum, Daphna Y.; Wolden, Suzanne L.; Rao, Shyam; Lee, Nancy Y.

2017-01-01

Objectives To assess whether sparing neck level IB in target delineation of node positive (N+) oropharyngeal carcinoma (OPC) can improve xerostomia outcomes without compromising local-regional control (LRC). Methods 125 N+ OPC patients with a median age of 57 years underwent chemoradiation between 5/10 and 12/11. 74% of patients had T1-2 disease, 26% T3-4, 16% N1, 8% N2A, 48% N2B, 28% N2C; 53% base of tongue, 41% tonsil, and 6% other. Patients were divided into those who had target delineation sparing of bilateral level IB (the spared cohort) vs. no sparing (the treated cohort). Sparing of contralateral high level II nodes was also performed more consistently in the spared cohort. A prospective xerostomia questionnaire (patient reported) was given at each patient follow-up visit to this cohort of patients to assess late xerostomia. Clinical assessment (observer rated) at each patient follow-up visit was also recorded. Results The 2-year LRC for the spared and treated cohorts was 97.5% and 93.8%, respectively (median follow-up, 23.2 months). No local-regional failures occurred outside of treatment fields. The spared cohort experienced significant benefits in patient-reported xerostomia summary scores (P = 0.021) and observer-rated xerostomia scores (P = 0.006). In addition, there were significant reductions in mean doses to the ipsilateral submandibular gland (SMG; 63.9 Gy vs. 70.5 Gy; P < 0.001), contralateral SMG (45.0 Gy vs. 56.2 Gy; P < 0.001), oral cavity (35.9 Gy vs. 45.2 Gy; P < 0.001), and contralateral parotid gland (20.0 Gy vs. 24.4 Gy; P < 0.001). Conclusions Target delineation sparing of bilateral level IB nodes in N+ OPC reduced mean doses to salivary organs without compromising LRC. Patients with reduced target volumes had better patient-reported xerostomia outcomes. PMID:26208401

The Impact of Agency Audits on the Buy Our Spares Smart (BOSS) Program

DTIC Science & Technology

1988-06-01

MULTILOCATION DOD-WODE FOLLOW- UP AUDIT OF SPARE’ PARTS PROCUREMENT NAVY T 48185 13 53 TABLE III (PAGE 2 OF 3) AUDITS AND RECOMMENDATIONS CLASSIFICATION S... Audit agency/number: GAO/NSIAD 85-119 111 7. Multilocation DOD-wide Follow-up Audit of Spare Parts Procurement. Date completed: 19 November 1985 Audit ...SFILE NAVAL POSTGRADUATE SCHOOL 0_ Monterey, California DTIC AUG 3 0 1988 DCO THESIS UIMPA T OF AGMY AUDITS BJY OUR SPARES S6AR (BOSS) PRGRAM by

Anesthetics act in quantum channels in brain microtubules to prevent consciousness.

PubMed

Craddock, Travis J A; Hameroff, Stuart R; Ayoub, Ahmed T; Klobukowski, Mariusz; Tuszynski, Jack A

2015-01-01

The mechanism by which anesthetic gases selectively prevent consciousness and memory (sparing non-conscious brain functions) remains unknown. At the turn of the 20(th) century Meyer and Overton showed that potency of structurally dissimilar anesthetic gas molecules correlated precisely over many orders of magnitude with one factor, solubility in a non-polar, 'hydrophobic' medium akin to olive oil. In the 1980s Franks and Lieb showed anesthetics acted in such a medium within proteins, suggesting post-synaptic membrane receptors. But anesthetic studies on such proteins yielded only confusing results. In recent years Eckenhoff and colleagues have found anesthetic action in microtubules, cytoskeletal polymers of the protein tubulin inside brain neurons. 'Quantum mobility' in microtubules has been proposed to mediate consciousness. Through molecular modeling we have previously shown: (1) olive oil-like non-polar, hydrophobic quantum mobility pathways ('quantum channels') of tryptophan rings in tubulin, (2) binding of anesthetic gas molecules in these channels, and (3) capabilities for π-electron resonant energy transfer, or exciton hopping, among tryptophan aromatic rings in quantum channels, similar to photosynthesis protein quantum coherence. Here, we show anesthetic molecules can impair π-resonance energy transfer and exciton hopping in tubulin quantum channels, and thus account for selective action of anesthetics on consciousness and memory.

Ketosis proportionately spares glucose utilization in brain.

PubMed

Zhang, Yifan; Kuang, Youzhi; Xu, Kui; Harris, Donald; Lee, Zhenghong; LaManna, Joseph; Puchowicz, Michelle A

2013-08-01

The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as β-hydroxybutyrate and acetoacetate, as occurs with fasting, starvation, or chronic feeding of a ketogenic diet. The relationship between changes in cerebral metabolic rates of glucose (CMRglc) and degree or duration of ketosis remains uncertain. To investigate if CMRglc decreases with chronic ketosis, 2-[(18)F]fluoro-2-deoxy-D-glucose in combination with positron emission tomography, was applied in anesthetized young adult rats fed 3 weeks of either standard or ketogenic diets. Cerebral metabolic rates of glucose (μmol/min per 100 g) was determined in the cerebral cortex and cerebellum using Gjedde-Patlak analysis. The average CMRglc significantly decreased in the cerebral cortex (23.0±4.9 versus 32.9±4.7) and cerebellum (29.3±8.6 versus 41.2±6.4) with increased plasma ketone bodies in the ketotic rats compared with standard diet group. The reduction of CMRglc in both brain regions correlates linearly by ∼9% for each 1 mmol/L increase of total plasma ketone bodies (0.3 to 6.3 mmol/L). Together with our meta-analysis, these data revealed that the degree and duration of ketosis has a major role in determining the corresponding change in CMRglc with ketosis.

Parenchymal-sparing hepatectomy for deep-placed colorectal liver metastases.

PubMed

Matsuki, Ryota; Mise, Yoshihiro; Saiura, Akio; Inoue, Yosuke; Ishizawa, Takeaki; Takahashi, Yu

2016-11-01

The feasibility of parenchymal-sparing hepatectomy has yet to be assessed based on the tumor location, which affects the choice of treatment in patients with colorectal liver metastases. Sixty-three patients underwent first curative hepatectomy for deep-placed colorectal liver metastases whose center was located >30 mm from the liver surface. Operative outcomes were compared among patients who underwent parenchymal-sparing hepatectomy or major hepatectomy (≥3 segments). Parenchymal-sparing hepatectomy and major hepatectomy were performed for deep-placed colorectal liver metastases in 40 (63%) and 23 (37%) patients, respectively. Resection time was longer in the parenchymal-sparing hepatectomy than in the major hepatectomy group (57 vs 39 minutes) (P = .02) and cut-surface area was wider (120 vs 86 cm 2 ) (P < .01). Resected volume was smaller in the parenchymal-sparing hepatectomy than in the major hepatectomy group (251 vs 560 g) (P < .01). No differences were found between the 2 groups for total operation time (306 vs 328 minutes), amount of blood loss (516 vs 400 mL), rate of major complications (10% vs 13%), and positive operative margins (5% vs 4%). Overall, recurrence-free, and liver recurrence-free survivals did not differ between the 2 groups. Direct major hepatectomy without portal venous embolization could not have been performed in 40% of the parenchymal-sparing hepatectomy group (16/40) because of the small liver remnant volume. Parenchymal-sparing hepatectomy for deep-placed colorectal liver metastases was performed safely without compromising oncologic radicality. Parenchymal-sparing hepatectomy can increase the number of patients eligible for an operation by halving the resection volume and by increasing the chance of direct operative treatment in patients with ill-located colorectal liver metastases. Copyright © 2016 Elsevier Inc. All rights reserved.

Borderline ovarian tumors, fertility-sparing surgery and pregnancy outcome.

PubMed

Frega, A; Coluccia, A C; Di Martino, G; Catalano, A; Milazzo, G N; Assorgi, C; Manzara, F; Romeo, G D; Gentile, M; Marziani, R; Moscarini, M

2014-01-01

Borderline ovarian tumors (BOTs) represent a type of epithelial tumors having a biologic intermediate behavior between clearly malignant and straight benign tumors. Most of BOTs interest women during fertile age, for which it is necessary to consider a fertility sparing surgery. To evaluate the clinical aspects and pregnancy rate of women affected by borderline ovarian tumors who have undergone fertility sparing surgery. A study of 22 patients affected by BOTs who have been treated with a fertility sparing surgery was conducted between January 2005 and October 2011 at Sant'Andrea Hospital, "Sapienza" University of Rome. The patients' characteristics analyzed were: age, histological type, tumor size, adnexal surgery, pre-operative serum CA-125, diagnostic circumstances, number of patients who became pregnant and number of overall pregnancies. Among the 22 patients treated with a fertility sparing surgery, only sixteen wanted to get pregnant. Eleven patents out of 16 accomplished it. The pregnancy rate was 68.7%. Fertility sparing surgery can be considered a safe procedure for young women affected by borderline ovarian tumors.

Levamisole in steroid-sensitive nephrotic syndrome of childhood: the lost paradise?

PubMed

Davin, J C; Merkus, M P

2005-01-01

Among the different drugs used for sparing steroids in steroid-sensitive nephrotic syndrome (SSNS) with frequent relapses and steroid dependency, levamisole is the least toxic and the least expensive. However, it is neither approved for this indication nor widely used in Europe. This may be explained by the difficulty in obtaining levamisole in some countries and the lack of good quality evidence for its effectiveness. Evidence is limited to three clinical trials that all suffered from methodological limitations. Statistical synthesis of these trials showed that levamisole reduces the risk of a relapse during treatment (relative risk 0.60, 95% confidence interval 0.45-0.79). From the available information, no conclusions can be drawn on the steroid-sparing effect, the long-term efficacy, and safety, as well as possible differences in efficacy in different subgroups of SSNS patients. The confirmation of a favorable effect of levamisole on the reduction of the frequency of relapses and on sparing steroids in an adequately powered, double-blind, placebo-controlled, randomized, multi-center clinical trial will promote consensus on the place of levamisole in the treatment of SSNS of childhood. Follow-up should be at least 1 year to evaluate long-term efficacy and side effects. If the results of such a clinical trial confirm the beneficial effects of levamisole in nephrotic syndrome, this may allow registration for this indication and interest companies other than Jansen-Cilag, which only recently has decided to stop its production.

SU-F-T-392: Superior Brainstem and Cochlea Sparing with VMAT for Glioblastoma Multiforme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Briere, TM; McAleer, MF; Levy, LB

Purpose: Volumetric arc therapy (VMAT) can provide similar target coverage and normal tissue sparing as IMRT but with shorter treatment times. At our institution VMAT was adopted for the treatment glioblastoma multiforme (GBM) after a small number of test plans demonstrated its non-inferiority. In this study, we compare actual clinical treatment plans for a larger cohort of patients treated with either VMAT or IMRT. Methods: 90 GBM patients were included in this study, 45 treated with IMRT and 45 with VMAT. All planning target volumes (PTVs) were prescribed a dose of 50 Gy, with a simultaneous integrated boost to 60more » Gy. Most IMRT plans used 5 non-coplanar beams, while most VMAT plans used 2 coplanar beams. Statistical analysis was performed using Fisher’s exact test or the Wilcoxon-Mann-Whitney rank sum test. Included in the analysis were patient and treatment characteristics as well as the doses to the target volumes and organs at risk. Results: Treatment times for the VMAT plans were reduced by 5 minutes compared with IMRT. The PTV coverage was similar, with at least 95% covered for all plans, while the median boost PTV dose differed by 0.1 Gy between the IMRT and VMAT cohorts. The doses to the brain, optic chiasm, optic nerves and eyes were not significantly different. The mean dose to the brainstem, however, was 9.4 Gy less with VMAT (p<0.001). The dose to the ipsilateral and contralateral cochleae were respectively 19.7 and 9.5 Gy less (p<0.001). Conclusion: Comparison of clinical treatment plans for separate IMRT and VMAT cohorts demonstrates that VMAT can save substantial treatment time while providing similar target coverage and superior sparing of the brainstem and cochleae. To our knowledge this is the first study to demonstrate this benefit of VMAT in the management of GBM.« less

Bowel sparing in pediatric cranio-spinal radiotherapy: a comparison of combined electron and photon and helical TomoTherapy techniques to a standard photon method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harron, Elizabeth, E-mail: elizabeth.harron@nuh.nhs.uk; Lewis, Joanne

2012-07-01

The aim of this study was to compare the dose to organs at risk (OARs) from different craniospinal radiotherapy treatment approaches available at the Northern Centre for Cancer Care (NCCC), with a particular emphasis on sparing the bowel. Method: Treatment plans were produced for a pediatric medulloblastoma patient with inflammatory bowel disease using 3D conformal 6-MV photons (3DCP), combined 3D 6-MV photons and 18-MeV electrons (3DPE), and helical photon TomoTherapy (HT). The 3DPE plan was a modification of the standard 3DCP technique, using electrons to treat the spine inferior to the level of the diaphragm. The plans were compared inmore » terms of the dose-volume data to OARs and the nontumor integral dose. Results: The 3DPE plan was found to give the lowest dose to the bowel and the lowest nontumor integral dose of the 3 techniques. However, the coverage of the spine planning target volume (PTV) was least homogeneous using this technique, with only 74.6% of the PTV covered by 95% of the prescribed dose. HT was able to achieve the best coverage of the PTVs (99.0% of the whole-brain PTV and 93.1% of the spine PTV received 95% of the prescribed dose), but delivered a significantly higher integral dose. HT was able to spare the heart, thyroid, and eyes better than the linac-based techniques, but other OARs received a higher dose. Conclusions: Use of electrons was the best method for reducing the dose to the bowel and the integral dose, at the expense of compromised spine PTV coverage. For some patients, HT may be a viable method of improving dose homogeneity and reducing selected OAR doses.« less

Modeling Combined Immunosuppressive and Anti-inflammatory Effects of Dexamethasone and Naproxen in Rats Predicts the Steroid-Sparing Potential of Naproxen.

PubMed

Li, Xiaonan; DuBois, Debra C; Song, Dawei; Almon, Richard R; Jusko, William J; Chen, Xijing

2017-07-01

Dexamethasone (DEX), a widely prescribed corticosteroid, has long been the cornerstone of the treatment of inflammation and immunologic dysfunctions in rheumatoid arthritis. Corticosteroids are frequently used in combination with other antirheumatic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs to mitigate disease symptoms and minimize unwanted effects. We explored the steroid dose-sparing potential of the NSAID naproxen (NPX) with in vitro and in vivo studies. The single and joint suppressive effects of DEX and NPX on the in vitro mitogen-induced proliferation of T lymphocytes in blood and their anti-inflammatory actions on paw edema were investigated in female and male Lewis rats with collagen-induced arthritis (CIA). As expected, DEX was far more potent than NPX in these systems. Mathematical models incorporating an interaction term ψ were applied to quantitatively assess the nature and intensity of pharmacodynamic interactions between DEX and NPX. Modest synergistic effects of the two drugs were found in suppressing the mitogenic response of T lymphocytes. A pharmacokinetic/pharmacodynamic/disease progression model integrating dual drug inhibition quantitatively described the pharmacokinetics, time-course of single and joint anti-inflammatory effects (paw edema), and sex differences in CIA rats, and indicated additive effects of DEX and NPX. Further model simulations demonstrated the promising steroid-sparing potential of NPX in CIA rats, with the beneficial effects of the combination therapy more likely in males than females. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

46 CFR 195.35-20 - Spare charges.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Spare charges. 195.35-20 Section 195.35-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS VESSEL CONTROL... recharge shall be carried for each self-contained breathing apparatus, and a complete set of spare...

14 CFR 49.53 - Eligibility for recording: general requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Aircraft Engines, Propellers, Appliances, and Spare Parts § 49.53 Eligibility for recording: general... engine, propeller, appliance, or spare part, maintained by or on behalf of an air carrier certificated... need only describe generally, by type, the engines, propellers, appliances, or spare parts covered by...

14 CFR 49.53 - Eligibility for recording: general requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Aircraft Engines, Propellers, Appliances, and Spare Parts § 49.53 Eligibility for recording: general... engine, propeller, appliance, or spare part, maintained by or on behalf of an air carrier certificated... need only describe generally, by type, the engines, propellers, appliances, or spare parts covered by...

14 CFR 49.53 - Eligibility for recording: general requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Aircraft Engines, Propellers, Appliances, and Spare Parts § 49.53 Eligibility for recording: general... engine, propeller, appliance, or spare part, maintained by or on behalf of an air carrier certificated... need only describe generally, by type, the engines, propellers, appliances, or spare parts covered by...

14 CFR 49.53 - Eligibility for recording: general requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Aircraft Engines, Propellers, Appliances, and Spare Parts § 49.53 Eligibility for recording: general... engine, propeller, appliance, or spare part, maintained by or on behalf of an air carrier certificated... need only describe generally, by type, the engines, propellers, appliances, or spare parts covered by...

14 CFR 49.53 - Eligibility for recording: general requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Aircraft Engines, Propellers, Appliances, and Spare Parts § 49.53 Eligibility for recording: general... engine, propeller, appliance, or spare part, maintained by or on behalf of an air carrier certificated... need only describe generally, by type, the engines, propellers, appliances, or spare parts covered by...

Probability and Confidence Trade-Space (PACT) Evaluation: Accounting for Uncertainty in Sparing Assessments

NASA Technical Reports Server (NTRS)

Anderson, Leif; Box, Neil; Carter-Journet, Katrina; DiFilippo, Denise; Harrington, Sean; Jackson, David; Lutomski, Michael

2012-01-01

Purpose of presentation: (1) Status update on the developing methodology to revise sub-system sparing targets. (2) To describe how to incorporate uncertainty into spare assessments and why it is important to do so (3) Demonstrate hardware risk postures through PACT evaluation

Primary central nervous system lymphoma in immunocompetent patients: spectrum of findings and differential characteristics.

PubMed

Gómez Roselló, E; Quiles Granado, A M; Laguillo Sala, G; Pedraza Gutiérrez, S

2018-02-23

Primary central nervous system (CNS) lymphomas are uncommon and their management differs significantly from that of other malignant tumors involving the CNS. This article explains how the imaging findings often suggest the diagnosis early. The typical findings in immunocompetent patients consist of a supratentorial intraaxial mass that enhances homogeneously. Other findings to evaluate include multifocality and incomplete ring enhancement. The differential diagnosis of primary CNS lymphomas should consider mainly other malignant tumors of the CNS such as glioblastomas or metastases. Primary CNS lymphomas tend to have less edema and less mass effect; they also tend to spare the adjacent cortex. Necrosis, hemorrhage, and calcification are uncommon in primary CNS lymphomas. Although the findings in morphologic sequences are characteristic, they are not completely specific and atypical types are sometimes encountered. Advanced imaging techniques such as diffusion or especially perfusion provide qualitative and quantitative data that play an important role in differentiating primary CNS lymphomas from other brain tumors. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

A treatment program for individuals with deficient evaluative processing and consequent impaired social and risk judgement.

PubMed

Park, Norman W; Conrod, Brian; Hussain, Zahra; Murphy, Kelly J; Rewilak, Dmytro; Black, Sandra E

2003-01-01

The current study evaluated the effectiveness of a rehabilitation program developed to assist individuals such as AM who have impaired social and risk judgement. AM's difficulties developed after a severe traumatic brain injury that resulted in bilateral frontal and temporal lobe damage including damage to the amygdala. Previous work (Park et al., 2001) established that AM had impaired automatic processing of negative, but not positive evaluative information, and relatively spared processing of both types of evaluative information when using controlled or strategic processing. In the Strategic Evaluation of Alternatives (SEA) treatment program, AM was trained to compensate for his impairments by explicitly retrieving positive and negative attributes associated with potential actions prior to performing them. The SEA treatment focused specifically on improving AM's ability to obtain financial compensation for his work-related activities. Results showed improved performance on work-related activities and evidence of generalization. Analyses suggested that the process underlying improved performance was compensatory rather than restorative in nature. We discuss the implications of these results for the development of rehabilitation treatment for patients with impaired social and risk judgement.

Baroreflex failure in a patient with central nervous system lesions involving the nucleus tractus solitarii

NASA Technical Reports Server (NTRS)

Biaggioni, I.; Whetsell, W. O.; Jobe, J.; Nadeau, J. H.

1994-01-01

Animal studies have shown the importance of the nucleus tractus solitarii, a collection of neurons in the brain stem, in the acute regulation of blood pressure. Impulses arising from the carotid and aortic baroreceptors converge in this center, where the first synapse of the baroreflex is located. Stimulation of the nucleus tractus solitarii provides an inhibitory signal to other brain stem structures, particularly the rostral ventrolateral medulla, resulting in a reduction in sympathetic outflow and a decrease in blood pressure. Conversely, experimental lesions of the nucleus tractus solitarii lead to loss of baroreflex control of blood pressure, sympathetic activation, and severe hypertension in animals. In humans, baroreflex failure due to deafferentation of baroreceptors has been previously reported and is characterized by episodes of severe hypertension and tachycardia. We present a patient with an undetermined process of the central nervous system characterized pathologically by ubiquitous infarctions that were particularly prominent in the nucleus tractus solitarii bilaterally but spared the rostral ventrolateral medulla. Absence of a functioning baroreflex was evidenced by the lack of reflex tachycardia to the hypotensive effects of sodium nitroprusside, exaggerated pressor responses to handgrip and cold pressor test, and exaggerated depressor responses to meals and centrally acting alpha 2-agonists. This clinicopathological correlate suggests that the patient's baroreflex failure can be explained by the unique combination of the destruction of sympathetic inhibitory centers (ie, the nucleus tractus solitarii) and preservation of centers that exert a positive modulation on sympathetic tone (ie, the rostral ventrolateral medulla).

Trial-unique, delayed nonmatching-to-location (TUNL) touchscreen testing for mice: sensitivity to dorsal hippocampal dysfunction.

PubMed

Kim, Chi Hun; Romberg, Carola; Hvoslef-Eide, Martha; Oomen, Charlotte A; Mar, Adam C; Heath, Christopher J; Berthiaume, Andrée-Anne; Bussey, Timothy J; Saksida, Lisa M

2015-11-01

The hippocampus is implicated in many of the cognitive impairments observed in conditions such as Alzheimer's disease (AD) and schizophrenia (SCZ). Often, mice are the species of choice for models of these diseases and the study of the relationship between brain and behaviour more generally. Thus, automated and efficient hippocampal-sensitive cognitive tests for the mouse are important for developing therapeutic targets for these diseases, and understanding brain-behaviour relationships. One promising option is to adapt the touchscreen-based trial-unique nonmatching-to-location (TUNL) task that has been shown to be sensitive to hippocampal dysfunction in the rat. This study aims to adapt the TUNL task for use in mice and to test for hippocampus-dependency of the task. TUNL training protocols were altered such that C57BL/6 mice were able to acquire the task. Following acquisition, dysfunction of the dorsal hippocampus (dHp) was induced using a fibre-sparing excitotoxin, and the effects of manipulation of several task parameters were examined. Mice could acquire the TUNL task using training optimised for the mouse (experiments 1). TUNL was found to be sensitive to dHp dysfunction in the mouse (experiments 2, 3 and 4). In addition, we observed that performance of dHp dysfunction group was somewhat consistently lower when sample locations were presented in the centre of the screen. This study opens up the possibility of testing both mouse and rat models on this flexible and hippocampus-sensitive touchscreen task.

Role of testis sparing surgery in the conservative management of small testicular masses: oncological and functional perspectives.

PubMed

Borghesi, M; Brunocilla, E; Schiavina, R; Gentile, G; Dababneh, H; Della Mora, L; del Prete, C; Franceschelli, A; Colombo, F; Martorana, G

2015-01-01

Radical orchiectomy (RO) is still considered the standard of care for malignant germ cell tumours, which represent the vast majority of the palpable testicular masses. In those patients diagnosed with small testicular masses (STMs), testis-sparing surgery (TSS) could be an alternative treatment to RO. The aim of this updated review is to evaluate the current indications for TSS, and discuss the oncological and functional results of patients who had undergone organ-sparing surgery for STMs. A non-systematic review of the Literature using the Medline database has been performed, including a free-text protocol using the terms "testis-sparing surgery", "testicular sparing surgery", "partial orchiectomy", "testis tumour", "sex cord tumour", and "testis function". Other significant studies cited in the reference lists of the selected papers were also evaluated. No randomized controlled trials comparing TSS with radical orchiectomy have been reported yet. In those patients with normal contra-lateral testis, the use of TSS is still controversial. In selected cases of gonadal masses < 2 cm, TSS seems to be a safe and feasible treatment option. Frozen section examination allows us to discriminate between benign and malignant neoplasms during TSS. Intermediate and long-term follow-up results showed no significant risk of local and distant recurrences in the main series reported in the literature. TSS is an effective treatment for STMs in selected patients, limiting the unnecessary surgical over-treatments, without compromising the oncological and functional outcomes. Further studies are needed in order to confirm the oncological safety. Copyright © 2013 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Conversations for Providers Caring for Rectal Cancer Patients: Comparison of Long-Term Patient-Centered Outcomes for Low Rectal Cancer Patients Facing Ostomy or Sphincter-Sparing Surgery

PubMed Central

Herrinton, Lisa J.; Altschuler, Andrea; McMullen, Carmit K.; Bulkley, Joanna E.; Hornbrook, Mark C.; Sun, Virginia; Wendel, Christopher S.; Grant, Marcia; Baldwin, Carol M.; Demark-Wahnefried, Wendy; Temple, Larissa K.F.; Krouse, Robert S.

2017-01-01

For some low rectal cancer patients, ostomy (with elimination into a pouch) may be the only realistic surgical option. However, some patients have a choice between ostomy and sphincter-sparing surgery. Sphincter-sparing surgery has been preferred over ostomy because it offers preservation of normal bowel function. However, this surgery can cause incontinence and bowel dysfunction. Increasingly, it has become evident that certain patients eligible for sphincter-sparing surgery may not be well served by the surgery and construction of an ostomy may be better. No validated assessment tool or decision aid has been published to help newly diagnosed patients decide between the two surgeries, or to help physicians elicit long-term surgical outcomes. Furthermore, comparison of long-term outcomes and late effects following the two surgeries has not been synthesized. We therefore conducted a systematic review to examine this ? This systematic review summarizes controlled studies that compared long-term survivorship outcomes between these two surgical groups. Our goals are: 1) improve understanding and shared decision-making among surgeons, oncologists, primary care providers, patients, and caregivers; 2) increase the patient’s participation in the decision; (3) alert the primary care provider to patient challenges that could be addressed by provider attention and intervention; and 4) ultimately, improve patients’ long-term quality of life. This report includes discussion points for health care providers to use with their patients during initial discussions of ostomy and sphincter-sparing surgery, as well as questions to ask during follow-up examinations to ascertain any long-term challenges facing the patient. PMID:26999757

Conversations for providers caring for patients with rectal cancer: Comparison of long-term patient-centered outcomes for patients with low rectal cancer facing ostomy or sphincter-sparing surgery.

PubMed

Herrinton, Lisa J; Altschuler, Andrea; McMullen, Carmit K; Bulkley, Joanna E; Hornbrook, Mark C; Sun, Virginia; Wendel, Christopher S; Grant, Marcia; Baldwin, Carol M; Demark-Wahnefried, Wendy; Temple, Larissa K F; Krouse, Robert S

2016-09-01

For some patients with low rectal cancer, ostomy (with elimination into a pouch) may be the only realistic surgical option. However, some patients have a choice between ostomy and sphincter-sparing surgery. Sphincter-sparing surgery has been preferred over ostomy because it offers preservation of normal bowel function. However, this surgery can cause incontinence and bowel dysfunction. Increasingly, it has become evident that certain patients who are eligible for sphincter-sparing surgery may not be well served by the surgery, and construction of an ostomy may be better. No validated assessment tool or decision aid has been published to help newly diagnosed patients decide between the two surgeries or to help physicians elicit long-term surgical outcomes. Furthermore, comparison of long-term outcomes and late effects after the two surgeries has not been synthesized. Therefore, this systematic review summarizes controlled studies that compared long-term survivorship outcomes between these two surgical groups. The goals are: 1) to improve understanding and shared decision-making among surgeons, oncologists, primary care providers, patients, and caregivers; 2) to increase the patient's participation in the decision; 3) to alert the primary care provider to patient challenges that could be addressed by provider attention and intervention; and 4) ultimately, to improve patients' long-term quality of life. This report includes discussion points for health care providers to use with their patients during initial discussions of ostomy and sphincter-sparing surgery as well as questions to ask during follow-up examinations to ascertain any long-term challenges facing the patient. CA Cancer J Clin 2016;66:387-397. © 2016 American Cancer Society. © 2016 American Cancer Society.

Monitoring foveal sparing in geographic atrophy with fluorescence lifetime imaging ophthalmoscopy - a novel approach.

PubMed

Sauer, Lydia; Klemm, Matthias; Peters, Sven; Schweitzer, Dietrich; Schmidt, Johanna; Kreilkamp, Lukas; Ramm, Lisa; Meller, Daniel; Hammer, Martin

2018-05-01

To investigate fundus autofluorescence (FAF) lifetimes in geographic atrophy (GA) with a focus on macular pigment (MP) and foveal sparing. The study included 35 eyes from 28 patients (mean age 79.2 ± 8.0 years) with GA. A 30° retinal field, centred at the macula, was investigated using fluorescence lifetime imaging ophthalmoscopy (FLIO). The FLIO technology is based on a Heidelberg Engineering Spectralis system. Decays of FAF were detected in a short (498-560 nm, SSC) and long (560-720 nm, LSC) spectral channel. The mean fluorescence lifetime, τ m , was calculated from a three-exponential approximation of the FAF decays. Macular optical coherence tomography (OCT) scans as well as fundus photography were recorded. Review of FLIO data reveals specific patterns of significantly prolonged τ m in regions of GA (SSC 616 ± 343 ps, LSC 615 ± 154 ps) as compared to non-atrophic regions. Large τ m differences between the fovea and atrophic areas correlate with better visual acuity (VA). Shorter τ m at the fovea than within other non-atrophic regions indicates sparing, which was identified in 16 eyes. Seventy per cent of patients treated with lutein supplementation showed foveal sparing, whereas the rate among non-supplemented patients was 22%. Using FLIO, we present a novel way to detect foveal sparing, investigate MP, and analyse variability of τ m in different foveal regions (including the prognostic valuable border region) in GA. These findings support the potential utility of FLIO in monitoring disease progression. The findings also highlight the possibly protective effect of lutein supplementation, with implication in recording the presence and distributional pattern of MP. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

46 CFR 96.35-20 - Spare charges.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Spare charges. 96.35-20 Section 96.35-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS VESSEL CONTROL AND... carried for each self-contained breathing apparatus, and a complete set of spare batteries shall be...

46 CFR 77.35-20 - Spare charges.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 3 2010-10-01 2010-10-01 false Spare charges. 77.35-20 Section 77.35-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS VESSEL CONTROL AND MISCELLANEOUS... for each self-contained breathing apparatus, and a complete set of spare batteries shall be carried...

46 CFR 77.30-15 - Spare charges.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 3 2010-10-01 2010-10-01 false Spare charges. 77.30-15 Section 77.30-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS VESSEL CONTROL AND MISCELLANEOUS... carried for each gas mask and self-contained breathing apparatus. The spare charge shall be stowed in the...

46 CFR 77.35-20 - Spare charges.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 3 2011-10-01 2011-10-01 false Spare charges. 77.35-20 Section 77.35-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS VESSEL CONTROL AND MISCELLANEOUS... for each self-contained breathing apparatus, and a complete set of spare batteries shall be carried...

46 CFR 77.30-15 - Spare charges.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 3 2011-10-01 2011-10-01 false Spare charges. 77.30-15 Section 77.30-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS VESSEL CONTROL AND MISCELLANEOUS... carried for each gas mask and self-contained breathing apparatus. The spare charge shall be stowed in the...

Illustrating the Concept of Sparingly Soluble Salts Using Various Copper Compounds: A Classroom Demonstration

ERIC Educational Resources Information Center

O'Sullivan, Daniel W.; Crouch, Collier C.

2009-01-01

Many students in general and advanced chemistry courses have difficulty understanding differences in solubility by inspecting changing values of the solubility product constants for sparingly soluble salts. In this demonstration, the concepts involved in understanding the solubility of sparingly soluble salts are illustrated visually. Utilizing…

19 CFR 10.2020 - Accessories, spare parts, or tools.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 1 2014-04-01 2014-04-01 false Accessories, spare parts, or tools. 10.2020 Section 10.2020 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... Trade Promotion Agreement Rules of Origin § 10.2020 Accessories, spare parts, or tools. (a) General...

19 CFR 10.600 - Accessories, spare parts, or tools.

Code of Federal Regulations, 2010 CFR

2010-04-01

...-Central America-United States Free Trade Agreement Rules of Origin § 10.600 Accessories, spare parts, or... 10.600 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... of the good's standard accessories, spare parts, or tools will be treated as originating goods if the...

Successful treatment of facial systemic lupus erythematosus lesions with Dr Michaels® (Soratinex®) product family. A case report.

PubMed

Tirant, M; Bayer, P; Hercogovấ, J; Fioranelli, M; Gianfaldoni, S; Chokoeva, A A; Tchernev, G; Wollina, U; Novotny, F; Roccia, M G; Maximov, G K; França, K; Lotti, T

2016-01-01

Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which the body’s immune system mistakenly attacks healthy tissue. It can affect the skin, joints, kidneys, brain and other organs. We report the case of a 7-year-old female patient with facial lesions of SLE since the age of 5. There was no significant family history and patient had been a healthy child from birth. The child presented with a malar rash, also known as a butterfly rash, with distribution over the cheeks but sparing the nasal bridge. This case represents the efficacy of the Dr. Michaels® (Soratinex®) product family in the successful resolution of facial lesions of SLE.

A systematic review of cognitive performance in patients with childhood craniopharyngioma.

PubMed

Özyurt, Jale; Müller, Hermann L; Thiel, Christiane M

2015-10-01

Craniopharyngiomas are rare brain tumors of the sellar/suprasellar region, often adversely affecting patients' physical and psychosocial functioning. Until a few years ago, knowledge on cognitive deficits in craniopharyngioma patients was based on little valid evidence, with considerable inconsistencies across studies. Findings from recent research, with partly larger sample sizes, add to existing evidence to provide a more clear and reliable picture. The current review aims to summarize and systemize current findings on cognitive deficits in childhood craniopharyngioma, taking account of patient- and treatment-related variables where possible. Those studies were included that reported results of childhood craniopharyngioma patients tested with formalized neuropsychological tests (irrespective of their age at study, group size ≥10). A systematic assignment of test results to subcomponents of broader cognitive domains (e.g. to specific memory systems and processes) allows for a first comprehensive overview of patterns of spared and impaired cognitive functions. We show that episodic memory recall in particular is impaired, largely sparing other memory components. In accordance with recent knowledge on mammillary function, patients with hypothalamic involvement appear to be at particular risk. Deficits in higher cognitive processes, relying on the integrity of the prefrontal cortex and its subcortical pathways, may also occur, but results are still inconsistent. To gain deeper insight into the pattern of deficits and their association with patient- and treatment-related variables, further multi-site research with larger cohorts is needed.

Heterogeneous patterns of brain atrophy in Alzheimer's disease.

PubMed

Poulakis, Konstantinos; Pereira, Joana B; Mecocci, Patrizia; Vellas, Bruno; Tsolaki, Magda; Kłoszewska, Iwona; Soininen, Hilkka; Lovestone, Simon; Simmons, Andrew; Wahlund, Lars-Olof; Westman, Eric

2018-05-01

There is increasing evidence showing that brain atrophy varies between patients with Alzheimer's disease (AD), suggesting that different anatomical patterns might exist within the same disorder. We investigated AD heterogeneity based on cortical and subcortical atrophy patterns in 299 AD subjects from 2 multicenter cohorts. Clusters of patients and important discriminative features were determined using random forest pairwise similarity, multidimensional scaling, and distance-based hierarchical clustering. We discovered 2 typical (72.2%) and 3 atypical (28.8%) subtypes with significantly different demographic, clinical, and cognitive characteristics, and different rates of cognitive decline. In contrast to previous studies, our unsupervised random forest approach based on cortical and subcortical volume measures and their linear and nonlinear interactions revealed more typical AD subtypes with important anatomically discriminative features, while the prevalence of atypical cases was lower. The hippocampal-sparing and typical AD subtypes exhibited worse clinical progression in visuospatial, memory, and executive cognitive functions. Our findings suggest there is substantial heterogeneity in AD that has an impact on how patients function and progress over time. Copyright © 2018 Elsevier Inc. All rights reserved.

Fertility sparing surgery in early stage epithelial ovarian cancer

PubMed Central

Martinelli, Fabio; Lorusso, Domenica; Haeusler, Edward; Carcangiu, Marialuisa; Raspagliesi, Francesco

2014-01-01

Objective Fertility sparing surgery (FSS) is a strategy often considered in young patients with early epithelial ovarian cancer. We investigated the role and the outcomes of FSS in eEOC patients who underwent comprehensive surgery. Methods From January 2003 to January 2011, 24 patients underwent fertility sparing surgery. Eighteen were one-to-one matched and balanced for stage, histologic type and grading with a group of patients who underwent radical comprehensive staging (n=18). Demographics, surgical procedures, morbidities, pathologic findings, recurrence-rate, pregnancy-rate and correlations with disease-free survival were assessed. Results A total of 36 patients had a complete surgical staging including lymphadenectomy and were therefore analyzed. Seven patients experienced a recurrence: four (22%) in the fertility sparing surgery group and three (16%) in the control group (p=not significant). Sites of recurrence were: residual ovary (two), abdominal wall and peritoneal carcinomatosis in the fertility sparing surgery group; pelvic (two) and abdominal wall in the control group. Recurrences in the fertility sparing surgery group appeared earlier (mean, 10.3 months) than in radical comprehensive staging group (mean, 53.3 months) p<0.001. Disease-free survival were comparable between the two groups (p=0.422). No deaths were reported. All the patients in fertility sparing surgery group recovered a regular period. Thirteen out of 18 (72.2%) attempted to have a pregnancy. Five (38%) achieved a spontaneous pregnancy with a full term delivery. Conclusion Fertility sparing surgery in early epithelial ovarian cancer submitted to a comprehensive surgical staging could be considered safe with oncological results comparable to radical surgery group. PMID:25142621

Oncologic results of nephron sparing endoscopic approach for upper tract low grade transitional cell carcinoma in comparison to nephroureterectomy - a case control study.

PubMed

Hoffman, Azik; Yossepowitch, Ofer; Erlich, Yaron; Holland, Ronen; Lifshitz, David

2014-12-02

There is paucity of data as to the results of the endoscopic approach in comparison to the golden standard of nephro-ureterectomy in elective, low grade TCC, patients. Our purpose is to report our results of a nephron sparing approach compared to nephro-ureterectomy in those patients. From a retrospective data base we identified 25 patients and 23 patients who underwent a nephron sparing ureterosocpic resection and nephro-reterectomy for low grade UT-TCC, respectively. The endoscopic technique included endoscopic tumor biopsy followed by primary resection and/or fulguration. The nephron sparing group was followed by bi-annual ureteroscopy and upper tract imaging, timely cystoscopy and urine cytology collection. Data for overall and disease related mortality, bladder and ureteral TCC recurrence and renal function are reported in both groups. Median follow - up time was 26 months. 11 (44%) patients developed bladder recurrence at a median period of 9 months after initial ureteroscopy, compared to 9 (39%) in the NUx group (P < 0.05). Recurrent ureteral low grade TCC was observed in 9 patients (median: 9 months). All were treated endoscopicaly successfully. Renal function remained stable in the nephron sparing group. No disease related mortality was recorded in the nephron-sparing group while one patient died of his disease following NUx. Disease related mortality following a nephron sparing endoscopic approach or nephroureterectomy for low grade upper tract TCC is excellent. However, the nephron sparing approach is associated with a relatively high rate of ureteral and bladder recurrence. Therefore, a stringent follow-up protocol is required.

Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo.

PubMed

Itoh, Yoshiaki; Esaki, Takanori; Shimoji, Kazuaki; Cook, Michelle; Law, Mona J; Kaufman, Elaine; Sokoloff, Louis

2003-04-15

Neuronal cultures in vitro readily oxidized both D-[(14)C]glucose and l-[(14)C]lactate to (14)CO(2), whereas astroglial cultures oxidized both substrates sparingly and metabolized glucose predominantly to lactate and released it into the medium. [(14)C]Glucose oxidation to (14)CO(2) varied inversely with unlabeled lactate concentration in the medium, particularly in neurons, and increased progressively with decreasing lactate concentration. Adding unlabeled glucose to the medium inhibited [(14)C]lactate oxidation to (14)CO(2) only in astroglia but not in neurons, indicating a kinetic preference in neurons for oxidation of extracellular lactate over intracellular pyruvatelactate produced by glycolysis. Protein kinase-catalyzed phosphorylation inactivates pyruvate dehydrogenase (PDH), which regulates pyruvate entry into the tricarboxylic acid cycle. Dichloroacetate inhibits this kinase, thus enhancing PDH activity. In vitro dichloroacetate stimulated glucose and lactate oxidation to CO(2) and reduced lactate release mainly in astroglia, indicating that limitations in glucose and lactate oxidation by astroglia may be due to a greater balance of PDH toward the inactive form. To assess the significance of astroglial export of lactate to neurons in vivo, we attempted to diminish this traffic in rats by administering dichloroacetate (50 mgkg) intravenously to stimulate astroglial lactate oxidation and then examined the effects on baseline and functionally activated local cerebral glucose utilization (lCMR(glc)). Dichloroacetate raised baseline lCMR(glc) throughout the brain and decreased the percent increases in lCMR(glc) evoked by functional activation. These studies provide evidence in support of the compartmentalization of glucose metabolism between astroglia and neurons but indicate that the compartmentalization may be neither complete nor entirely obligatory.

A small-scale land-sparing approach to conserving biological diversity in tropical agricultural landscapes

Treesearch

Richard B. Chandler; David I. King; Raul Raudales; Richard Trubey; Carlin Chandler; Víctor Julio Arce Chávez

2013-01-01

Two contrasting strategies have been proposed for conserving biological diversity while meeting the increasing demand for agricultural products: land sparing and land sharing production systems. Land sparing involves increasing yield to reduce the amount of land needed for agriculture, whereas land-sharing agricultural practices incorporate elements of native...

Anal wall sparing effect of an endorectal balloon in 3D conformal and intensity-modulated prostate radiotherapy.

PubMed

Smeenk, Robert Jan; van Lin, Emile N J Th; van Kollenburg, Peter; Kunze-Busch, Martina; Kaanders, Johannes H A M

2009-10-01

To investigate the anal wall (Awall) sparing effect of an endorectal balloon (ERB) in 3D conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for prostate cancer. In 24 patients with localized prostate carcinoma, two planning CT-scans were performed: with and without ERB. A prostate planning target volume (PTV) was defined, and the Awall was delineated, using two different methods. Three-field and 4-field 3D-CRT plans, and IMRT plans were generated with a prescription dose of 78Gy. In 144 treatment plans, the minimum dose (D(min)), maximum dose (D(max)), and mean dose (D(mean)) to the Awall were calculated, as well as the Awall volumes exposed to doses ranging from >or=20Gy to >or=70Gy (V(20)-V(70), respectively). In the 3D-CRT plans, an ERB significantly reduced D(mean), D(max), and V(30)-V(70). For IMRT all investigated dose parameters were significantly reduced by the ERB. The absolute reduction of D(mean) was 12Gy in 3D-CRT and was 7.5Gy in IMRT for both methods of Awall delineation. Application of an ERB showed a significant Awall sparing effect in both 3D-CRT and IMRT. This may lead to reduced late anal toxicity in prostate radiotherapy.

[Impact of acupuncture to IGF-I expression in spared dorsal root ganglion of cats].

PubMed

Liu, Fen; Wang, Ting-Hua; Zhang, Yi; Hong, Sun-quan; Song, Xin-bo

2006-05-01

To explore the relationship between Insulin-like growth factor-I (IGF-I) and acupuncture promoting the spinal cord plasticity, the changes of IGF- I expressing in spared dorsal root ganglia (DRG,L6) after operation and acupuncture were investigated. 25 adult cats were divided into 5 groups: normal control group; 7th day and 14th day group after unilateral partial rhizotomy (unilateral L1-L5,L7-S2 DRG Were transected, but L6 DRG was spared); 7th day and 14th day group of acupuncture stimulating the spared DRG (electro-needle stimulation was performed by following unilateral partial root rhizotomy). Animals survived for 7 or 14 days after operation respectively. Unilateral L6 dorsal root ganglia of each group were made into 20 microm frozen sections. By immunohistochemistry ABC method, the sections were stained with specific IGF-I (1:200) antibody. The distribution and the number of IGF-I positive neurons in spared DRG (L6) that located the operated/acupuncture side of each animal were observed and counted. For 7th day group after acupuncture stiumlation, the number of IGF-I positive neurons of spared DRG of acupuncture side showed significantly more than that of 7th day operation group (P<0.05), but still less than that of normal group (P < 0.05); In 14th day group, IGF- I expression in neuron of L6 DRG also increased apparently more than that of 14th day operation group, with coming back to normal level. After acupuncture stimulating the spared DRG for 14 days, the numbers of IGF- I positive neurons in spared DRG increased significantly more than that of 7th day group after acupuncture (P<0.05). Acupuncture can significantly increase the number of IGF- I positive neurons. Our results indicate that the expression changes of IGF-I in spared DRG associate with acupuncture promoting the spinal cord plasticity.

Critical dose and toxicity index of organs at risk in radiotherapy: Analyzing the calculated effects of modified dose fractionation in non–small cell lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pedicini, Piernicola, E-mail: ppiern@libero.it; Strigari, Lidia; Benassi, Marcello

2014-04-01

To increase the efficacy of radiotherapy for non–small cell lung cancer (NSCLC), many schemes of dose fractionation were assessed by a new “toxicity index” (I), which allows one to choose the fractionation schedules that produce less toxic treatments. Thirty-two patients affected by non resectable NSCLC were treated by standard 3-dimensional conformal radiotherapy (3DCRT) with a strategy of limited treated volume. Computed tomography datasets were employed to re plan by simultaneous integrated boost intensity-modulated radiotherapy (IMRT). The dose distributions from plans were used to test various schemes of dose fractionation, in 3DCRT as well as in IMRT, by transforming the dose-volumemore » histogram (DVH) into a biological equivalent DVH (BDVH) and by varying the overall treatment time. The BDVHs were obtained through the toxicity index, which was defined for each of the organs at risk (OAR) by a linear quadratic model keeping an equivalent radiobiological effect on the target volume. The less toxic fractionation consisted in a severe/moderate hyper fractionation for the volume including the primary tumor and lymph nodes, followed by a hypofractionation for the reduced volume of the primary tumor. The 3DCRT and IMRT resulted, respectively, in 4.7% and 4.3% of dose sparing for the spinal cord, without significant changes for the combined-lungs toxicity (p < 0.001). Schedules with reduced overall treatment time (accelerated fractionations) led to a 12.5% dose sparing for the spinal cord (7.5% in IMRT), 8.3% dose sparing for V{sub 20} in the combined lungs (5.5% in IMRT), and also significant dose sparing for all the other OARs (p < 0.001). The toxicity index allows to choose fractionation schedules with reduced toxicity for all the OARs and equivalent radiobiological effect for the tumor in 3DCRT, as well as in IMRT, treatments of NSCLC.« less

[Umbilical cord collision in the first trimester in a monoamniotic twin pregnancy--does it really matter?].

PubMed

Ropacka-Lesiak, Mariola; Lebioda, Anna; Breborowicz, Grzegorz

2012-09-01

A case of an umbilical cord collision diagnosed in the first trimester of a monochorionic monoamniotic twin pregnancy is presented. An intensive surveillance included ultrasound monitoring with color and spectral Doppler and fetal echocardiography. The first signs of fetal distress were observed at 31 weeks of gestation. The brain sparing effect as well as a periodic appearance of the "notch" in the wave forms obtained from the umbilical artery from the collision region were observed. In the first ultrasound scan there were no abnormalities in twin I. In contrast, in twin II a vascular resistance in the umbilical artery was at the upper limit for the gestational age. Five days later, decreased vascular resistance in the middle cerebral artery, which fluctuated at the lower limit, was noticed in twin II. After the next four days, PI in the middle cerebral artery decreased below the lower limit and tricuspid regurgitation appeared. In twin I the vascular resistance in the umbilical artery increased and remained at the upper limit of the reference ranges. Cardiotocographic records did not reveal signs of fetal distress. After a week the signs of brain sparing effect were visible in both fetuses. However, twin II showed features of umbilical cord clamping in the form of abnormal blood flow waveforms in the umbilical artery ("notch"). Therefore, despite the absence of signs of fetal distress in CTG in monochorionic monoamniotic twins with growth discordance of 20% and exponents of periodical clamping of the umbilical cord in twin II at 34 weeks, the decision to perform a caesarean section was made. The patient gave birth to two daughters (twin I: weight 1780g, Ap 10, pH 7.39, 7.40, BE -3.0, -2.6, and twin II: weight 1860g, Ap 10, pH 7.29, 7.35, BE -1.4, -2.4). During the delivery the umbilical cords collision was found at the region close to the body of twins. This case presents the possibility of using ultrasound and Doppler in the early diagnosis, monitoring and surveillance of pregnancies complicated by umbilical cords collision in monochorionic monoamniotic twins from the first trimester. Application of these methods allowed a safe monitoring of the fetuses and the identification of the onset of the cords collision. This in turn allowed the achievement of fetal maturity at 34 weeks, when both the risk of death and neonatal morbidity are significantly minimized. The use of Doppler blood flow velocimetry allowed the diagnosis of umbilical cords tightening before there were any signs of cardiac dysfunction in the CTG. This enabled to determine the most favorable, earlier time for delivery. The paper presents diagnostic management and surveillance in monochorionic monoamniotic pregnancy complicated by umbilical cord collision since the early pregnancy.

Reconfigurable tree architectures using subtree oriented fault tolerance

NASA Technical Reports Server (NTRS)

Lowrie, Matthew B.

1987-01-01

An approach to the design of reconfigurable tree architecture is presented in which spare processors are allocated at the leaves. The approach is unique in that spares are associated with subtrees and sharing of spares between these subtrees can occur. The Subtree Oriented Fault Tolerance (SOFT) approach is more reliable than previous approaches capable of tolerating link and switch failures for both single chip and multichip tree implementations while reducing redundancy in terms of both spare processors and links. VLSI layout is 0(n) for binary trees and is directly extensible to N-ary trees and fault tolerance through performance degradation.

Utility of the General Ability Index (GAI) and Cognitive Proficiency Index (CPI) with Survivors of Pediatric Brain Tumors: Comparison to Full Scale IQ and Premorbid IQ Estimates

PubMed Central

Kahalley, Lisa S.; Winter-Greenberg, Amanda; Stancel, Heather; Ris, M. Douglas; Gragert, Marsha

2016-01-01

Introduction Pediatric brain tumor survivors are at risk for working memory and processing speed impairment. The General Ability Index (GAI) provides an estimate of intellectual functioning that is less influenced by working memory and processing speed than a Full Scale IQ (FSIQ). The Cognitive Proficiency Index (CPI) provides a measure of efficient information processing derived from working memory and processing speed tasks. We examined the utility of the GAI and CPI to quantify neurocognitive outcomes in a sample of pediatric brain tumor survivors. Methods GAI, CPI, and FSIQ scores from the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) were examined for 57 pediatric brain tumor survivors (ages 6–16) treated with cranial radiation therapy (RT). Results GAI scores were higher than FSIQ and CPI scores, both p < .001. Lower CPI scores were associated with history of craniospinal irradiation and time since RT. Lower FSIQ and GAI scores were associated with higher RT dose and time since RT. The rate of clinically significant GAI-FSIQ discrepancies in our sample was greater than observed in the WISC-IV standardization sample, p < .001. Estimated premorbid IQ scores were higher than GAI, p < .01, and FSIQ scores, p < .001. Conclusions Pediatric brain tumor survivors exhibit weaker cognitive proficiency than expected for age, while general reasoning ability remains relatively spared. The GAI may be useful to quantify the intellectual potential of a survivor when appropriate accommodations are in place for relative cognitive proficiency weaknesses. The CPI may be a particularly sensitive outcome measure of treatment-related cognitive change in this population. PMID:27295192

Nipple- and areola-sparing mastectomy for the treatment of breast cancer.

PubMed

Mota, Bruna S; Riera, Rachel; Ricci, Marcos Desidério; Barrett, Jessica; de Castria, Tiago B; Atallah, Álvaro N; Bevilacqua, Jose Luiz B

2016-11-29

The efficacy and safety of nipple-sparing mastectomy and areola-sparing mastectomy for the treatment of breast cancer are still questionable. It is estimated that the local recurrence rates following nipple-sparing mastectomy are very similar to breast-conserving surgery followed by radiotherapy. To assess the efficacy and safety of nipple-sparing mastectomy and areola-sparing mastectomy for the treatment of ductal carcinoma in situ and invasive breast cancer in women. We searched the Cochrane Breast Cancer Group's Specialized Register, the Cochrane Center Register of Controlled Trials (CENTRAL), MEDLINE (via PubMed), Embase (via OVID) and LILACS (via Biblioteca Virtual em Saúde [BVS]) using the search terms "nipple sparing mastectomy" and "areola-sparing mastectomy". Also, we searched the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov. All searches were conducted on 30th September 2014 and we did not apply any language restrictions. Randomised controlled trials (RCTs) however if there were no RCTs, we expanded our criteria to include non-randomised comparative studies (cohort and case-control studies). Studies evaluated nipple-sparing and areola-sparing mastectomy compared to modified radical mastectomy or skin-sparing mastectomy for the treatment of ductal carcinoma in situ or invasive breast cancer. Two review authors (BS and RR) performed data extraction and resolved disagreements. We performed descriptive analyses and meta-analyses of the data using Review Manager software. We used Cochrane's risk of bias tool to assess studies, and adapted it for non-randomised studies, and we evaluated the quality of the evidence using GRADE criteria. We included 11 cohort studies, evaluating a total of 6502 participants undergoing 7018 procedures: 2529 underwent a nipple-sparing mastectomy (NSM), 818 underwent skin-sparing mastectomy (SSM) and 3671 underwent traditional mastectomy, also known as modified radical mastectomy (MRM). No participants underwent areola-sparing mastectomy. There was a high risk of confounding for all reported outcomes. For overall survival, the hazard ratio (HR) for NSM compared to SSM was 0.70 (95% CI 0.28 to 1.73; 2 studies; 781 participants) and the HR for NSM compared to MRM was 0.72 (95% CI 0.46 to 1.13; 2 studies, 1202 participants). Local recurrence was evaluated in two studies, the HR for NSM compared to MRM was 0.28 (95% CI 0.12 to 0.68; 2 studies, 1303 participants). The overall risk of complications was different in NSM when compared to other types of mastectomy in general (RR 0.10, 95% CI 0.01 to 0.82, 2 studies, P = 0.03; 1067 participants). With respect to skin necrosis, there was no evidence of a difference with NSM compared to other types of mastectomy, but the confidence interval was wide (RR 4.22, 95% CI 0.59 to 30.03, P = 0.15; 4 studies, 1948 participants). We observed no difference among the three types of mastectomy with respect to the risk of local infection (RR 0.95, 95% CI 0.44 to 2.09, P = 0.91, 2 studies; 496 participants). Meta-analysis was not possible when assessing cosmetic outcomes and quality of life, but in general the NSM studies reported a favourable aesthetic result and a gain in quality of life compared with the other types of mastectomy. The quality of evidence was considered very low for all outcomes due to the high risk of selection bias and wide confidence intervals. The findings from these observational studies of very low-quality evidence were inconclusive for all outcomes due to the high risk of selection bias.

Fractionation Spares Mice From Radiation-Induced Reductions in Weight Gain But Does Not Prevent Late Oligodendrocyte Lineage Side Effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Begolly, Sage; Shrager, Peter G.; Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, New York

Purpose: To determine the late effects of fractionated versus single-dose cranial radiation on murine white matter. Methods and Materials: Mice were exposed to 0 Gy, 6 × 6 Gy, or 1 × 20 Gy cranial irradiation at 10 to 12 weeks of age. Endpoints were assessed through 18 months from exposure using immunohistochemistry, electron microscopy, and electrophysiology. Results: Weight gain was temporarily reduced after irradiation; greater loss was seen after single versus fractionated doses. Oligodendrocyte progenitor cells were reduced early and late after both single and fractionated irradiation. Both protocols also increased myelin g-ratio, reduced the number of nodes of Ranvier, and promoted a shift in the proportion of small, unmyelinatedmore » versus large, myelinated axon fibers. Conclusions: Fractionation does not adequately spare normal white matter from late radiation side effects.« less

Functional outcome in amputation versus limb sparing of patients with lower extremity sarcoma: a matched case-control study.

PubMed

Davis, A M; Devlin, M; Griffin, A M; Wunder, J S; Bell, R S

1999-06-01

To quantify the differences in physical disability and handicap experienced by patients with lower extremity sarcoma who required amputation for their primary tumor as compared with those treated by limb-sparing surgery. Matched case-control study. Twelve patients with amputation were matched with 24 patients treated by limb-sparing surgery on the following variables: age, gender, length of follow-up, bone versus soft-tissue tumor, anatomic site, and treatment with adjuvant chemotherapy. Patients who underwent above-knee amputation (AKA) or below-knee amputation (BKA) for primary soft-tissue or bone sarcoma, who had not developed local or systemic recurrence, and who had been followed up for at least 1 year since surgery. The Toronto Extremity Salvage Score (TESS), a measure of physical disability; the Shortform-36 (SF-36), a generic health status measure; and the Reintegration to Normal Living (RNL), a measure of handicap. Mean TESS score for the patients with amputations was 74.5 versus 85.1 for the limb-sparing patients. (p = .15). Only the physical function subscale of the SF-36 showed statistically significant differences, with means of 45 and 71.1 for the amputation versus limb-sparing groups, respectively (p = .03). The RNL for the amputation group was 84.4 versus 97 for the limb-sparing group (p = .05). Seven of the 12 patients with amputations experienced ongoing difficulty with the soft tissues overlying their stumps. There was a trend toward increased disability for those in the amputation group versus those in the limb-sparing group, with the amputation group showing significantly higher levels of handicap. These data suggest that the differences in disability between amputation and limb-sparing patients are smaller than anticipated. The differences may be more notable in measuring handicap.

Limiting the risk of cardiac toxicity with esophageal-sparing intensity modulated radiotherapy for locally advanced lung cancers.

PubMed

Woodford, Katrina; Panettieri, Vanessa; Ruben, Jeremy D; Senthi, Sashendra

2016-05-01

Intensity modulated radiotherapy (IMRT) is routinely utilized in the treatment of locally advanced non-small cell lung cancer (NSCLC). RTOG 0617 found that overall survival was impacted by increased low (5 Gy) and intermediate (30 Gy) cardiac doses. We evaluated the impact of esophageal-sparing IMRT on cardiac doses with and without the heart considered in the planning process and predicted toxicity compared to 3D-conventional radiotherapy (3DCRT). Ten consecutive patients with N2 Stage III NSCLC treated to 60 Gy in 30 fractions, between February 2012 and September 2014, were evaluated. For each patient, 3DCRT and esophageal-sparing IMRT plans were generated. IMRT plans were then created with and without the heart considered in the optimization process. To compare plans, the dose delivered to 95% and 99% of the target (D95% and D99%), and doses to the esophagus, lung and heart were compared by determining the volume receiving X dose (VXGy) and the normal tissue complication probability (NTCP) calculated. IMRT reduced maximum esophagus dose to below 60 Gy in all patients and produced significant reductions to V50Gy, V40Gy and esophageal NTCP. The cost of this reduction was a non-statistically, non-clinically significant increase in low dose (5 Gy) lung exposure that did not worsen lung NTCP. IMRT plans produced significant cardiac sparing, with the amount of improvement correlating to the amount of heart overlapping with the target. When included in plan optimization, for selected patients further sparing of the heart and improvement in heart NTCP was possible. Esophageal-sparing IMRT can significantly spare the heart even if it is not considered in the optimization process. Further sparing can be achieved if plan optimization constrains low and intermediate heart doses, without compromising lung doses.

The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy.

PubMed

McGeer, Patrick L; McGeer, Edith G

2013-10-01

The amyloid cascade hypothesis is widely accepted as the centerpiece of Alzheimer disease (AD) pathogenesis. It proposes that abnormal production of beta amyloid protein (Abeta) is the cause of AD and that the neurotoxicity is due to Abeta itself or its oligomeric forms. We suggest that this, in itself, cannot be the cause of AD because demonstrating such toxicity requires micromolar concentrations of these Abeta forms, while their levels in brain are a million times lower in the picomolar range. AD probably results from the inflammatory response induced by extracellular Abeta deposits, which later become enhanced by aggregates of tau. The inflammatory response, which is driven by activated microglia, increases over time as the disease progresses. Disease-modifying therapeutic attempts to date have failed and may continue to do so as long as the central role of inflammation is not taken into account. Multiple epidemiological and animal model studies show that NSAIDs, the most widely used antiinflammatory agents, have a substantial sparing effect on AD. These studies provide a proof of concept regarding the anti-inflammatory approach to disease modification. Biomarker studies have indicated that early intervention may be necessary. They have established that disease onset occurs more than a decade before it becomes clinically evident. By combining biomarker and pathological data, it is possible to define six phases of disease development, each separated by about 5 years. Phase one can be identified by decreases in Abeta in the CSF, phase 2 by increases of tau in the CSF plus clear evidence of Abeta brain deposits by PET scanning, phase 3 by slight decreases in brain metabolic rate by PET-FDG scanning, phase 4 by slight decreases in brain volume by MRI scanning plus minimal cognitive impairment, phase 5 by increased scanning abnormalities plus clinical diagnosis of AD, and phase 6 by advanced AD requiring institutional care. Utilization of antiinflammatory agents early in the disease process remains an overlooked therapeutic opportunity. Such agents, while not preventative, have the advantage of being able to inhibit the consequences of both Abeta and tau aggregation. Since there is more than a decade between disease onset and cognitive decline, a window of opportunity exists to introduce truly effective disease-modifying regimens. Taking advantage of this opportunity is the challenge for the future.

Measuring the effectiveness of the episodic control program Spare the Air in the San Francisco Bay Area

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, T.G.; Hinman, T.T.

1997-12-31

Episodic control programs that ask the public to voluntarily reduce activities that pollute on days when ozone excesses are predicted are now operating in many parts of the country. The activities include driving, using consumer products that contain reactive organic compounds and lawn and garden equipment with small gasoline engines like lawn mowers and leaf blowers. The effectiveness of these programs as public education tools, their impact in changing behavior and their potential as control tools needs to be assessed. In the nine-county San Francisco Bay Area the Spare the Air program has been operating for five years. The programmore » has a strong employer component as well as a program directed at the general public. During the 1996 ozone season, the Bay Area AQMD, in cooperation with the business community, used several methods to assess awareness and behavior change on Spare the Air days. This included telephone public opinion surveys, a pilot program that offered free transit for employees at 8 companies with measurement feedback from the companies, a telecommuting web page that measured participation, a special carpool matching program and a broad based Capture the Credit initiative by business. This paper describes these initiatives, their results and the next steps anticipated for the 1997 program.« less

Comparison of two fertility-sparing approaches for bilateral borderline ovarian tumours: a randomized controlled study.

PubMed

Palomba, S; Zupi, E; Russo, T; Falbo, A; Del Negro, S; Manguso, F; Marconi, D; Tolino, A; Zullo, F

2007-02-01

During the childbearing years, the standard fertility-sparing treatment for bilateral borderline ovarian tumours (BOTs) is the unilateral oophorectomy plus controlateral cystectomy. The aim of the present study was to compare the effects of two laparoscopic fertility-sparing surgical procedures for the treatment of bilateral BOTs on recurrence and fertility in young women who desire to conceive as soon as possible. Thirty-two women affected by bilateral early-stage BOTs who desired to conceive were randomized to receive bilateral cystectomy (experimental group, n=15) or oophorectomy plus controlateral cystectomy (control group, n=17). At the first recurrence after childbearing completion, each patient was treated with non-conservative standard treatment. Recurrences and reproductive events were recorded. After a follow-up period of 81 months (19 inter-quartile; 60-96 range), the cumulative pregnancy rate (CPR) (14/15 versus 9/17; P=0.003) and the cumulative probability of first pregnancy (P= 0.011) were significantly higher in the experimental than in control group. No significant (P=0.358) difference between groups was detected in cumulative probability of first recurrence. The laparoscopic bilateral cystectomy followed by non-conservative treatment performed at the first recurrence after the childbearing completion is an effective surgical strategy for patients with bilateral early-stage BOTs who desire to conceive as soon as possible.

Intradermal Inactivated Poliovirus Vaccine: A Preclinical Dose-Finding Study

PubMed Central

Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin

2015-01-01

Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial vaccine doses induced antibodies at titers comparable to those after immunization with full human dose delivered intramuscularly. The results suggest that intradermal delivery of IPV may lead to dose-sparing effect and reduction of the vaccination cost. PMID:25391313

Neonatal Perirhinal Lesions in Rhesus Macaques Alter Performance on Working Memory Tasks with High Proactive Interference.

PubMed

Weiss, Alison R; Nadji, Ryhan; Bachevalier, Jocelyne

2015-01-01

The lateral prefrontal cortex is known for its contribution to working memory (WM) processes in both humans and animals. Yet, recent studies indicate that the prefrontal cortex is part of a broader network of interconnected brain areas involved in WM. Within the medial temporal lobe (MTL) structures, the perirhinal cortex, which has extensive direct interactions with the lateral and orbital prefrontal cortex, is required to form active/flexible representations of familiar objects. However, its participation in WM processes has not be fully explored. The goal of this study was to assess the effects of neonatal perirhinal lesions on maintenance and monitoring WM processes. As adults, animals with neonatal perirhinal lesions and their matched controls were tested in three object-based (non-spatial) WM tasks that tapped different WM processing domains, e.g., maintenance only (Session-unique Delayed-nonmatching-to Sample, SU-DNMS), and maintenance and monitoring (Object-Self-Order, OBJ-SO; Serial Order Memory Task, SOMT). Neonatal perirhinal lesions transiently impaired the acquisition of SU-DNMS at a short (5 s) delay, but not when re-tested with a longer delay (30 s). The same neonatal lesions severely impacted acquisition of OBJ-SO task, and the impairment was characterized by a sharp increase in perseverative errors. By contrast, neonatal perirhinal lesion spared the ability to monitor the temporal order of items in WM as measured by the SOMT. Contrary to the SU-DNMS and OBJ-SO, which re-use the same stimuli across trials and thus produce proactive interference, the SOMT uses novel objects on each trial and is devoid of interference. Therefore, the impairment of monkeys with neonatal perirhinal lesions on SU-DNMS and OBJ-SO tasks is likely to be caused by an inability to solve working memory tasks with high proactive interference. The sparing of performance on the SOMT demonstrates that neonatal perirhinal lesions do not alter working memory processes per se but rather impact processes modulating impulse control and/or behavioral flexibility.

Fincke holds up a spare RPCM in the A/L during Expedition 9

NASA Image and Video Library

2004-06-04

ISS009-E-10554 (4 June 2004) --- Astronaut Edward M. (Mike) Fincke, Expedition 9 NASA ISS science officer and flight engineer, holds the spare Remote Power Controller Module (RPCM) in the Quest airlock of the International Space Station (ISS). The spare is scheduled to replace the failed RPCM on the S0 (S-Zero) Truss.

7 CFR 1755.522 - RUS general specification for digital, stored program controlled central office equipment.

Code of Federal Regulations, 2011 CFR

2011-01-01

... (Hz) High Group Frequencies (Hz) 1209 1336 1477 1633 697 1 2 3 Spare 770 4 5 6 Spare 852 7 8 9 Spare..._regulations/ibr_locations.html. (5) Bell Communications Research (Bellcore) document SR-TSV-002275, BOC Notes... Extender Voice Frequency Repeater Combinations, December 1973, is incorporated by reference by RUS. This...

7 CFR 1755.522 - RUS general specification for digital, stored program controlled central office equipment.

Code of Federal Regulations, 2014 CFR

2014-01-01

... (Hz) High Group Frequencies (Hz) 1209 1336 1477 1633 697 1 2 3 Spare 770 4 5 6 Spare 852 7 8 9 Spare..._regulations/ibr_locations.html. (5) Bell Communications Research (Bellcore) document SR-TSV-002275, BOC Notes... Extender Voice Frequency Repeater Combinations, December 1973, is incorporated by reference by RUS. This...

7 CFR 1755.522 - RUS general specification for digital, stored program controlled central office equipment.

Code of Federal Regulations, 2013 CFR

2013-01-01

... (Hz) High Group Frequencies (Hz) 1209 1336 1477 1633 697 1 2 3 Spare 770 4 5 6 Spare 852 7 8 9 Spare..._regulations/ibr_locations.html. (5) Bell Communications Research (Bellcore) document SR-TSV-002275, BOC Notes... Extender Voice Frequency Repeater Combinations, December 1973, is incorporated by reference by RUS. This...

7 CFR 1755.522 - RUS general specification for digital, stored program controlled central office equipment.

Code of Federal Regulations, 2012 CFR

2012-01-01

... (Hz) High Group Frequencies (Hz) 1209 1336 1477 1633 697 1 2 3 Spare 770 4 5 6 Spare 852 7 8 9 Spare..._regulations/ibr_locations.html. (5) Bell Communications Research (Bellcore) document SR-TSV-002275, BOC Notes... Extender Voice Frequency Repeater Combinations, December 1973, is incorporated by reference by RUS. This...

Penile sparing surgical approaches for primary penile tumors: preserving function and appearance

PubMed Central

Baumgarten, Adam S.; Fisher, John S.; Lawindy, Samuel M.; Pavlinec, Jonathan G.; Carrion, Rafael E.

2017-01-01

Penile cancer is a rare and potentially disfiguring disease. There are multiple treatment options for primary penile lesions. Penile sparing approaches offer an attractive option as they can provide several quality of life benefits without detrimental oncologic outcomes. With appropriate diagnostic evaluation and staging, penile sparing techniques provide proper cancer control with improved cosmetic and functional results. Regardless of the chosen treatment modality, a commitment to close follow-up remains a critical component of all treatment considerations. The goal of this review is to provide an overview of the multiple treatment strategies for primary penile tumors with a focus on penile sparing surgical approaches. PMID:29184777

Methotrexate for ocular inflammatory diseases.

PubMed

Gangaputra, Sapna; Newcomb, Craig W; Liesegang, Teresa L; Kaçmaz, R Oktay; Jabs, Douglas A; Levy-Clarke, Grace A; Nussenblatt, Robert B; Rosenbaum, James T; Suhler, Eric B; Thorne, Jennifer E; Foster, C Stephen; Kempen, John H

2009-11-01

To evaluate the outcome of treatment with methotrexate for noninfectious ocular inflammation. Retrospective cohort study. Patients with noninfectious ocular inflammation managed at 4 tertiary ocular inflammation clinics in the United States observed to add methotrexate as a single, noncorticosteroid immunosuppressive agent to their treatment regimen, between 1979 and 2007, inclusive. Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage, route of administration of methotrexate, and main outcome measures, were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers. Control of inflammation, corticosteroid-sparing effects, and incidence of and reason for discontinuation of therapy. Among 384 patients (639 eyes) observed from the point of addition of methotrexate to an anti-inflammatory regimen, 32.8%, 9.9%, 21.4%, 14.6%, 15.1%, and 6.3%, respectively, had anterior uveitis, intermediate uveitis, posterior or panuveitis, scleritis, ocular mucous membrane pemphigoid, and other forms of ocular inflammation. In these groups, complete suppression of inflammation sustained for >or=28 days was achieved within 6 months in 55.6%, 47.4%, 38.6%, 56.4%, 39.5%, and 76.7%, respectively. Corticosteroid-sparing success (sustained suppression of inflammation with prednisone

Functional Neuroimaging of Spike-Wave Seizures

PubMed Central

Motelow, Joshua E.; Blumenfeld, Hal

2013-01-01

Generalized spike-wave seizures are typically brief events associated with dynamic changes in brain physiology, metabolism, and behavior. Functional magnetic resonance imaging (fMRI) provides a relatively high spatio-temporal resolution method for imaging cortical-subcortical network activity during spike-wave seizures. Patients with spike-wave seizures often have episodes of staring and unresponsiveness which interfere with normal behavior. Results from human fMRI studies suggest that spike-wave seizures disrupt specific networks in the thalamus and fronto-parietal association cortex which are critical for normal attentive consciousness. However, the neuronal activity underlying imaging changes seen during fMRI is not well understood, particularly in abnormal conditions such as seizures. Animal models have begun to provide important fundamental insights into the neuronal basis for fMRI changes during spike-wave activity. Work from these models including both fMRI and direct neuronal recordings suggest that, like in humans, specific cortical-subcortical networks are involved in spike-wave, while other regions are spared. Regions showing fMRI increases demonstrate correlated increases in neuronal activity in animal models. The mechanisms of fMRI decreases in spike-wave will require further investigation. A better understanding of the specific brain regions involved in generating spike-wave seizures may help guide efforts to develop targeted therapies aimed at preventing or reversing abnormal excitability in these brain regions, ultimately leading to a cure for this disorder. PMID:18839093

Ketosis proportionately spares glucose utilization in brain

PubMed Central

Zhang, Yifan; Kuang, Youzhi; Xu, Kui; Harris, Donald; Lee, Zhenghong; LaManna, Joseph; Puchowicz, Michelle A

2013-01-01

The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as β-hydroxybutyrate and acetoacetate, as occurs with fasting, starvation, or chronic feeding of a ketogenic diet. The relationship between changes in cerebral metabolic rates of glucose (CMRglc) and degree or duration of ketosis remains uncertain. To investigate if CMRglc decreases with chronic ketosis, 2-[18F]fluoro-2-deoxy-D-glucose in combination with positron emission tomography, was applied in anesthetized young adult rats fed 3 weeks of either standard or ketogenic diets. Cerebral metabolic rates of glucose (μmol/min per 100 g) was determined in the cerebral cortex and cerebellum using Gjedde–Patlak analysis. The average CMRglc significantly decreased in the cerebral cortex (23.0±4.9 versus 32.9±4.7) and cerebellum (29.3±8.6 versus 41.2±6.4) with increased plasma ketone bodies in the ketotic rats compared with standard diet group. The reduction of CMRglc in both brain regions correlates linearly by ∼9% for each 1 mmol/L increase of total plasma ketone bodies (0.3 to 6.3 mmol/L). Together with our meta-analysis, these data revealed that the degree and duration of ketosis has a major role in determining the corresponding change in CMRglc with ketosis. PMID:23736643

Outcomes of fertility-sparing surgery among young women with FIGO stage I clear cell carcinoma of the ovary.

PubMed

Park, Jeong-Yeol; Suh, Dae-Shik; Kim, Jong-Hyeok; Kim, Yong-Man; Kim, Young-Tak; Nam, Joo-Hyun

2016-07-01

To evaluate the outcome of fertility-sparing surgery among young women with early-stage clear cell carcinoma of the ovary. In a retrospective study, data were reviewed for patients aged 45years or younger who had FIGO stage I clear cell carcinoma of the ovary and had attended one institution in South Korea between December 1999 and December 2009. Outcomes were compared between women undergoing fertility-sparing surgery, defined as preservation of the uterus and at least one adnexa, and those undergoing radical surgery. Overall, 47 patients were included (22 underwent fertility-sparing surgery, 25 radical surgery). After a median follow-up of 72months (range 8-175), 5 (23%) patients who underwent fertility-sparing surgery and 5 (20%) in the radical surgery group had recurrent disease (P=0.820). The mean time to recurrence was 19months after fertility-sparing surgery versus 20months after radical surgery (P=0.935). The anatomical location of recurrence did not differ. There was no difference in 5-year disease-free survival (77% vs 84%; P=0.849) or 5-year overall survival (91% vs 88%; P=0.480). Fertility-sparing surgery was found to be a safe alternative for young women with FIGO stage I clear cell carcinoma of the ovary who wish to preserve fertility. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Dosimetric effect on pediatric conformal treatment plans using dynamic jaw with Tomotherapy HDA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Eun Young, E-mail: eyhan@uams.edu; Kim, Dong-Wook; Zhang, Xin

It is important to minimize the radiation dose delivered to healthy tissues in pediatric cancer treatment because of the risk of secondary malignancies. Tomotherapy HDA provides a dynamic jaw (DJ) delivery mode that creates a sharper penumbra at the craniocaudal ends of a target in addition to a fixed jaw (FJ) delivery mode. The purpose of this study was to evaluate its dosimetric effect on the pediatric cancer cases. We included 6 pediatric cases in this study. The dose profiles and plan statistics—target dose conformity, uniformity, organ-at-risk (OAR) mean dose, beam-on time, and integral dose—were compared for each case. Consequently,more » the target dose coverage and uniformity were similar for different jaw settings. The OAR dose sparing depended on its relative location to the target and disease sites. For example, in the head and neck cancer cases, the brain stem dose using DJ 2.5 was reduced by more than two-fold (2.4 Gy vs. 6.3 Gy) than that obtained with FJ 2.5. The integral dose with DJ 2.5 decreased by more than 9% compared with that with FJ 2.5. Thus, using dynamic jaw in pediatric cases could be critical to reduce a probability of a secondary malignancy.« less

Executive dysfunction, brain aging, and political leadership.

PubMed

Fisher, Mark; Franklin, David L; Post, Jerrold M

2014-01-01

Decision-making is an essential component of executive function, and a critical skill of political leadership. Neuroanatomic localization studies have established the prefrontal cortex as the critical brain site for executive function. In addition to the prefrontal cortex, white matter tracts as well as subcortical brain structures are crucial for optimal executive function. Executive function shows a significant decline beginning at age 60, and this is associated with age-related atrophy of prefrontal cortex, cerebral white matter disease, and cerebral microbleeds. Notably, age-related decline in executive function appears to be a relatively selective cognitive deterioration, generally sparing language and memory function. While an individual may appear to be functioning normally with regard to relatively obvious cognitive functions such as language and memory, that same individual may lack the capacity to integrate these cognitive functions to achieve normal decision-making. From a historical perspective, global decline in cognitive function of political leaders has been alternatively described as a catastrophic event, a slowly progressive deterioration, or a relatively episodic phenomenon. Selective loss of executive function in political leaders is less appreciated, but increased utilization of highly sensitive brain imaging techniques will likely bring greater appreciation to this phenomenon. Former Israeli Prime Minister Ariel Sharon was an example of a political leader with a well-described neurodegenerative condition (cerebral amyloid angiopathy) that creates a neuropathological substrate for executive dysfunction. Based on the known neuroanatomical and neuropathological changes that occur with aging, we should probably assume that a significant proportion of political leaders over the age of 65 have impairment of executive function.

Image-guided microbeam irradiation to brain tumour bearing mice using a carbon nanotube x-ray source array

NASA Astrophysics Data System (ADS)

Zhang, Lei; Yuan, Hong; Burk, Laurel M.; Inscoe, Christy R.; Hadsell, Michael J.; Chtcheprov, Pavel; Lee, Yueh Z.; Lu, Jianping; Chang, Sha; Zhou, Otto

2014-03-01

Microbeam radiation therapy (MRT) is a promising experimental and preclinical radiotherapy method for cancer treatment. Synchrotron based MRT experiments have shown that spatially fractionated microbeam radiation has the unique capability of preferentially eradicating tumour cells while sparing normal tissue in brain tumour bearing animal models. We recently demonstrated the feasibility of generating orthovoltage microbeam radiation with an adjustable microbeam width using a carbon nanotube based x-ray source array. Here we report the preliminary results from our efforts in developing an image guidance procedure for the targeted delivery of the narrow microbeams to the small tumour region in the mouse brain. Magnetic resonance imaging was used for tumour identification, and on-board x-ray radiography was used for imaging of landmarks without contrast agents. The two images were aligned using 2D rigid body image registration to determine the relative position of the tumour with respect to a landmark. The targeting accuracy and consistency were evaluated by first irradiating a group of mice inoculated with U87 human glioma brain tumours using the present protocol and then determining the locations of the microbeam radiation tracks using γ-H2AX immunofluorescence staining. The histology results showed that among 14 mice irradiated, 11 received the prescribed number of microbeams on the targeted tumour, with an average localization accuracy of 454 µm measured directly from the histology (537 µm if measured from the registered histological images). Two mice received one of the three prescribed microbeams on the tumour site. One mouse was excluded from the analysis due to tissue staining errors.

Mechanism of Hyperphagia Contributing to Obesity in Brain-Derived Neurotrophic Factor Knockout Mice

PubMed Central

Fox, Edward A.; Biddinger, Jessica E.; Jones, Kevin R.; McAdams, Jennifer; Worman, Amber

2012-01-01

Global-heterozygous and brain-specific homozygous knockouts (KO's) of brain-derived neurotrophic factor (BDNF) cause late- and early-onset obesity, respectively, both involving hyperphagia. Little is known about the mechanism underlying this hyperphagia or whether BDNF loss from peripheral tissues could contribute to overeating. Since global-homozygous BDNF-KO is perinatal lethal, a BDNF-KO that spared sufficient brainstem BDNF to support normal health was utilized to begin to address these issues. Meal pattern and microstructure analyses suggested overeating of BDNF-KO mice was mediated by deficits in both satiation and satiety that resulted in increased meal size and frequency and implicated a reduction of vagal signaling from gut-to-brain. Meal-induced c-Fos activation in the nucleus of the solitary tract, a more direct measure of vagal afferent signaling, however, was not decreased in BDNF-KO mice, and thus was not consistent with a vagal afferent role. Interestingly though, meal-induced c-Fos activation was increased in the dorsal vagal motor nucleus (DMV) of BDNF-KO mice. This could imply that augmentation of vago-vagal digestive reflexes occurred (e.g., accommodation), which would support increased meal size and possibly increased meal number by reducing the increase in intragastric pressure produced by a given amount of ingesta. Additionally, vagal sensory neuron number in BDNF-KO mice was altered in a manner consistent with the increased meal-induced activation of the DMV. These results suggest reduced BDNF causes satiety and satiation deficits that support hyperphagia, possibly involving augmentation of vago-vagal reflexes mediated by central pathways or vagal afferents regulated by BDNF levels. PMID:23069761

ON THE BENEFITS AND RISKS OF PROTON THERAPY IN PEDIATRIC CRANIOPHARYNGIOMA

PubMed Central

Beltran, Chris; Roca, Monica; Merchant, Thomas E.

2013-01-01

Purpose Craniopharyngioma is a pediatric brain tumor whose volume is prone to change during radiation therapy. We compared photon- and proton-based irradiation methods to determine the effect of tumor volume change on target coverage and normal tissue irradiation in these patients. Methods and Materials For this retrospective study, we acquired imaging and treatment-planning data from 14 children with craniopharyngioma (mean age, 5.1 years) irradiated with photons (54 Gy) and monitored by weekly magnetic resonance imaging (MRI) examinations during radiation therapy. Photon intensity-modulated radiation therapy (IMRT), double-scatter proton (DSP) therapy, and intensity-modulated proton therapy (IMPT) plans were created for each patient based on his or her pre-irradiation MRI. Target volumes were contoured on each weekly MRI scan for adaptive modeling. The measured differences in conformity index (CI) and normal tissue doses, including functional sub-volumes of the brain, were compared across the planning methods, as was target coverage based on changes in target volumes during treatment. Results CI and normal tissue dose values of IMPT plans were significantly better than those of the IMRT and DSP plans (p < 0.01). Although IMRT plans had a higher CI and lower optic nerve doses (p < 0.01) than did DSP plans, DSP plans had lower cochlear, optic chiasm, brain, and scanned body doses (p < 0.01). The mean planning target volume (PTV) at baseline was 54.8 cm3, and the mean increase in PTV was 11.3% over the course of treatment. The dose to 95% of the PTV was correlated with a change in the PTV; the R2 values for all models, 0.73 (IMRT), 0.38 (DSP), and 0.62 (IMPT), were significant (p < 0.01). Conclusions Compared with photon IMRT, proton therapy has the potential to significantly reduce whole-brain and -body irradiation in pediatric patients with craniopharyngioma. IMPT is the most conformal method and spares the most normal tissue; however, it is highly sensitive to target volume changes, whereas the DSP method is not. PMID:21570209

Automatic planning on hippocampal avoidance whole-brain radiotherapy.

PubMed

Wang, Shuo; Zheng, Dandan; Zhang, Chi; Ma, Rongtao; Bennion, Nathan R; Lei, Yu; Zhu, Xiaofeng; Enke, Charles A; Zhou, Sumin

2017-01-01

Mounting evidence suggests that radiation-induced damage to the hippocampus plays a role in neurocognitive decline for patients receiving whole-brain radiotherapy (WBRT). Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) has been proposed to reduce the putative neurocognitive deficits by limiting the dose to the hippocampus. However, urgency of palliation for patients as well as the complexities of the treatment planning may be barriers to protocol enrollment to accumulate further clinical evidence. This warrants expedited quality planning of HA-WBRT. Pinnacle 3 Automatic treatment planning was designed to increase planning efficiency while maintaining or improving plan quality and consistency. The aim of the present study is to evaluate the performance of the Pinnacle 3 Auto-Planning on HA-WBRT treatment planning. Ten patients previously treated for brain metastases were selected. Hippocampal volumes were contoured on T1 magnetic resonance (MR) images, and planning target volumes (PTVs) were generated based on RTOG0933. The following 2 types of plans were generated by Pinnacle 3 Auto-Planning: the one with 2 coplanar volumetric modulated arc therapy (VMAT) arcs and the other with 9-field noncoplanar intensity-modulated radiation therapy (IMRT). D 2% and D 98% of PTV were used to calculate homogeneity index (HI). HI and Paddick Conformity index (CI) of PTV as well as D 100% and D max of the hippocampus were used to evaluate the plan quality. All the auto-plans met the dose coverage and constraint objectives based on RTOG0933. The auto-plans eliminated the necessity of generating pseudostructures by the planners, and it required little manual intervention which expedited the planning process. IMRT quality assurance (QA) results also suggest that all the auto-plans are practically acceptable on delivery. Pinnacle 3 Auto-Planning generates acceptable plans by RTOG0933 criteria without time-consuming planning process. The expedited quality planning achieved by Auto-Planning (AP) may facilitate protocol enrollment of patients to further investigate the hippocampal-sparing effect and be used to ensure timely start of palliative treatment in future clinical practice. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

SU-E-T-216: Comparison of Volumetrically Modulated Arc Therapy Treatment Using Flattening Filter Free Beams Vs. Flattened Beams for Partial Brain Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, S; Roa, D; Hanna, N

2015-06-15

Purpose: Flattening Filter Free (FFF) beams offer the potential for higher dose rates, short treatment time, and lower out of field dose. Therefore, the aim of this study was to investigate the dosimetric effects and out of field dose of Volumetric Modulated Arc Therapy (VMAT) plans using FFF vs Flattening Filtering (FF) beams for partial brain irradiation. Methods: Ten brain patients treated with a 6FF beam from a Truebeam STX were analyzed retrospectively for this study. These plans (46Gy at 2 Gy per fraction) were re-optimized for 6FFF beams using the same dose constraints as the original plans. PTV coverage,more » PTV Dmax, total MUs, and mean dose to organs-at-risk (OAR) were evaluated. In addition, the out-of-field dose for 6FF and 6FFF plans for one patient was measured on an anthropomorphic phantom. TLDs were placed inside (central axis) and outside (surface) the phantom at distances ranging from 0.5 cm to 17 cm from the field edge. Paired T-test was used for statistical analysis. Results: PTV coverage and PTV Dmax were comparable for the FF and FFF plans with 95.9% versus 95.6% and 111.2% versus 111.9%, respectively. Mean dose to the OARs were 3.7% less for FFF than FF plans (p<0.0001). Total MUs were, on average, 12.5% greater for FFF than FF plans with 481±55 MU (FFF) versus 429±50 MU (FF), p=0.0003. On average, the measured out of field dose was 24% less for FFF compared to FF, p<0.0001. A similar beam-on time was observed for the FFF and FF treatment. Conclusion: It is beneficial to use 6FFF beams for regular fractionated brain VMAT treatments. VMAT treatment plans using FFF beams can achieve comparable PTV coverage but with more OAR sparing. The out of field dose is significant less with mean reduction of 24%.« less

Automatic planning on hippocampal avoidance whole-brain radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Shuo, E-mail: shuo0220@gmail.com; Zheng, Dandan; Zhang, Chi

Mounting evidence suggests that radiation-induced damage to the hippocampus plays a role in neurocognitive decline for patients receiving whole-brain radiotherapy (WBRT). Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) has been proposed to reduce the putative neurocognitive deficits by limiting the dose to the hippocampus. However, urgency of palliation for patients as well as the complexities of the treatment planning may be barriers to protocol enrollment to accumulate further clinical evidence. This warrants expedited quality planning of HA-WBRT. Pinnacle{sup 3} Automatic treatment planning was designed to increase planning efficiency while maintaining or improving plan quality and consistency. The aim of the present studymore » is to evaluate the performance of the Pinnacle{sup 3} Auto-Planning on HA-WBRT treatment planning. Ten patients previously treated for brain metastases were selected. Hippocampal volumes were contoured on T1 magnetic resonance (MR) images, and planning target volumes (PTVs) were generated based on RTOG0933. The following 2 types of plans were generated by Pinnacle{sup 3} Auto-Planning: the one with 2 coplanar volumetric modulated arc therapy (VMAT) arcs and the other with 9-field noncoplanar intensity-modulated radiation therapy (IMRT). D{sub 2%} and D{sub 98%} of PTV were used to calculate homogeneity index (HI). HI and Paddick Conformity index (CI) of PTV as well as D{sub 100%} and D{sub max} of the hippocampus were used to evaluate the plan quality. All the auto-plans met the dose coverage and constraint objectives based on RTOG0933. The auto-plans eliminated the necessity of generating pseudostructures by the planners, and it required little manual intervention which expedited the planning process. IMRT quality assurance (QA) results also suggest that all the auto-plans are practically acceptable on delivery. Pinnacle{sup 3} Auto-Planning generates acceptable plans by RTOG0933 criteria without time-consuming planning process. The expedited quality planning achieved by Auto-Planning (AP) may facilitate protocol enrollment of patients to further investigate the hippocampal-sparing effect and be used to ensure timely start of palliative treatment in future clinical practice.« less

Optimized Determination of Deployable Consumable Spares Packages

DTIC Science & Technology

2007-06-01

also called deployable bench stock) • CRSP = Consumable Readiness Spares Package • COLT = Customer -Oriented Leveling Technique • ASM = Aircraft...changed please list both.) Original title on 712 A/B: Optimized Determination of Deployable Consumable Spares Packages If the title was revised...number. 1. REPORT DATE 01 JUN 2007 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Optimized Determination of Deployable Consumable

Integration of land-sharing and land-sparing conservation strategies through regional networking: the Mesoamerican Biological Corridor as a lifeline for carnivores in El Salvador.

PubMed

Crespin, Silvio J; García-Villalta, Jorge E

2014-10-01

Nations with little remaining natural habitat and small extent are challenged when trying to achieve biodiversity targets. We show that the Central American nation of El Salvador cannot viably sustain populations of 87 % of its extant carnivores, especially in the case of large-bodied species with low population densities. Current land-sparing strategies will not suffice; therefore we propose that land-sharing strategies be implemented in tandem with protected areas to expand current conservation efforts via new regional networks. In Central America such a network can be established by linking international protected area systems in a way that implements the existing vision for the Mesoamerican Biological Corridor. Specifically, we propose a re-envisioning of the Mesoamerican Biological Corridor in which land-sharing practices are adopted throughout the agricultural matrix while ensuring formal protection of the remaining natural habitat. Such an integration of land-sparing and land-sharing could result in the creation of an effective network of protected areas, thereby increasing the probability of safeguarding species with populations that overlap national borders.

Nutrient-driven O-GlcNAc in proteostasis and neurodegeneration.

PubMed

Akan, Ilhan; Olivier-Van Stichelen, Stephanie; Bond, Michelle R; Hanover, John A

2018-01-01

Proteostasis is essential in the mammalian brain where post-mitotic cells must function for decades to maintain synaptic contacts and memory. The brain is dependent on glucose and other metabolites for proper function and is spared from metabolic deficits even during starvation. In this review, we outline how the nutrient-sensitive nucleocytoplasmic post-translational modification O-linked N-acetylglucosamine (O-GlcNAc) regulates protein homeostasis. The O-GlcNAc modification is highly abundant in the mammalian brain and has been linked to proteopathies, including neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's. C. elegans, Drosophila, and mouse models harboring O-GlcNAc transferase- and O-GlcNAcase-knockout alleles have helped define the role O-GlcNAc plays in development as well as age-associated neurodegenerative disease. These enzymes add and remove the single monosaccharide from protein serine and threonine residues, respectively. Blocking O-GlcNAc cycling is detrimental to mammalian brain development and interferes with neurogenesis, neural migration, and proteostasis. Findings in C. elegans and Drosophila model systems indicate that the dynamic turnover of O-GlcNAc is critical for maintaining levels of key transcriptional regulators responsible for neurodevelopment cell fate decisions. In addition, pathways of autophagy and proteasomal degradation depend on a transcriptional network that is also reliant on O-GlcNAc cycling. Like the quality control system in the endoplasmic reticulum which uses a 'mannose timer' to monitor protein folding, we propose that cytoplasmic proteostasis relies on an 'O-GlcNAc timer' to help regulate the lifetime and fate of nuclear and cytoplasmic proteins. O-GlcNAc-dependent developmental alterations impact metabolism and growth of the developing mouse embryo and persist into adulthood. Brain-selective knockout mouse models will be an important tool for understanding the role of O-GlcNAc in the physiology of the brain and its susceptibility to neurodegenerative injury. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howard, Michelle, E-mail: howard.michelle1@mayo.edu; Beltran, Chris; Mayo, Charles S.

Purpose: To investigate the influence of the minimum monitor unit (MU) on the quality of clinical treatment plans for scanned proton therapy. Methods: Delivery system characteristics limit the minimum number of protons that can be delivered per spot, resulting in a min-MU limit. Plan quality can be impacted by the min-MU limit. Two sites were used to investigate the impact of min-MU on treatment plans: pediatric brain tumor at a depth of 5–10 cm; a head and neck tumor at a depth of 1–20 cm. Three-field, intensity modulated spot scanning proton plans were created for each site with the followingmore » parameter variations: min-MU limit range of 0.0000–0.0060; and spot spacing range of 2–8 mm. Comparisons were based on target homogeneity and normal tissue sparing. For the pediatric brain, two versions of the treatment planning system were also compared to judge the effects of the min-MU limit based on when it is accounted for in the optimization process (Eclipse v.10 and v.13, Varian Medical Systems, Palo Alto, CA). Results: The increase of the min-MU limit with a fixed spot spacing decreases plan quality both in homogeneous target coverage and in the avoidance of critical structures. Both head and neck and pediatric brain plans show a 20% increase in relative dose for the hot spot in the CTV and 10% increase in key critical structures when comparing min-MU limits of 0.0000 and 0.0060 with a fixed spot spacing of 4 mm. The DVHs of CTVs show min-MU limits of 0.0000 and 0.0010 produce similar plan quality and quality decreases as the min-MU limit increases beyond 0.0020. As spot spacing approaches 8 mm, degradation in plan quality is observed when no min-MU limit is imposed. Conclusions: Given a fixed spot spacing of ≤4 mm, plan quality decreases as min-MU increased beyond 0.0020. The effect of min-MU needs to be taken into consideration while planning proton therapy treatments.« less

Proposal to Reduce Sports Scholarships Assailed as Unfair.

ERIC Educational Resources Information Center

Lederman, Douglas

1987-01-01

The National Collegiate Athletic Association's proposed reductions in scholarships, affecting most non-revenue sports but sparing big-time football, are widely criticized for their disproportionate effects on women and minority groups. (MSE)

Beam-specific planning volumes for scattered-proton lung radiotherapy

NASA Astrophysics Data System (ADS)

Flampouri, S.; Hoppe, B. S.; Slopsema, R. L.; Li, Z.

2014-08-01

This work describes the clinical implementation of a beam-specific planning treatment volume (bsPTV) calculation for lung cancer proton therapy and its integration into the treatment planning process. Uncertainties incorporated in the calculation of the bsPTV included setup errors, machine delivery variability, breathing effects, inherent proton range uncertainties and combinations of the above. Margins were added for translational and rotational setup errors and breathing motion variability during the course of treatment as well as for their effect on proton range of each treatment field. The effect of breathing motion and deformation on the proton range was calculated from 4D computed tomography data. Range uncertainties were considered taking into account the individual voxel HU uncertainty along each proton beamlet. Beam-specific treatment volumes generated for 12 patients were used: a) as planning targets, b) for routine plan evaluation, c) to aid beam angle selection and d) to create beam-specific margins for organs at risk to insure sparing. The alternative planning technique based on the bsPTVs produced similar target coverage as the conventional proton plans while better sparing the surrounding tissues. Conventional proton plans were evaluated by comparing the dose distributions per beam with the corresponding bsPTV. The bsPTV volume as a function of beam angle revealed some unexpected sources of uncertainty and could help the planner choose more robust beams. Beam-specific planning volume for the spinal cord was used for dose distribution shaping to ensure organ sparing laterally and distally to the beam.

The cheating liver: imaging of focal steatosis and fatty sparing.

PubMed

Dioguardi Burgio, Marco; Bruno, Onorina; Agnello, Francesco; Torrisi, Chiara; Vernuccio, Federica; Cabibbo, Giuseppe; Soresi, Maurizio; Petta, Salvatore; Calamia, Mauro; Papia, Giovanni; Gambino, Angelo; Ricceri, Viola; Midiri, Massimo; Lagalla, Roberto; Brancatelli, Giuseppe

2016-06-01

Focal steatosis and fatty sparing are a frequent finding in liver imaging, and can mimic solid lesions. Liver regional variations in the degree of fat accumulation can be related to vascular anomalies, metabolic disorders, use of certain drugs or coexistence of hepatic masses. CT and MRI are the modalities of choice for the noninvasive diagnosis of hepatic steatosis. Knowledge of CT and MRI appearance of focal steatosis and fatty sparing is crucial for an accurate diagnosis, and to rule-out other pathologic processes. This paper will review the CT and MRI techniques for the diagnosis of hepatic steatosis and the CT and MRI features of common and uncommon causes of focal steatosis and fatty sparing.

SNS Central Helium Liquefier spare Carbon Bed installation and commissioning

NASA Astrophysics Data System (ADS)

DeGraff, B.; Howell, M.; Kim, S.; Neustadt, T.

2017-12-01

The Spallation Neutron Source (SNS) Central Helium Liquefier (CHL) at Oak Ridge National Laboratory (ORNL) has been without major operations downtime since operations were started back in 2006. This system utilizes a vessel filled with activated carbon as the final major component to remove oil vapor from the compressed helium circuit prior to insertion into the system’s cryogenic cold box. The need for a spare carbon bed at SNS due to the variability of carbon media lifetime calculation to adsorption efficiency will be discussed. The fabrication, installation and commissioning of this spare carbon vessel will be presented. The novel plan for connecting the spare carbon vessel piping to the existing infrastructure will be presented.

Effects of the dimeric PSD-95 inhibitor UCCB01-144 in mouse models of pain, cognition and motor function.

PubMed

Andreasen, Jesper T; Nasser, Arafat; Caballero-Puntiverio, Maitane; Sahlholt, Maj; Bach, Anders; Gynther, Mikko; Strømgaard, Kristian; Pickering, Darryl S

2016-06-05

NMDAR antagonism shows analgesic action in humans and animal pain models, but disrupts cognitive and motor functions. NMDAR-dependent NO production requires tethering of the NMDAR to neuronal NO synthase (nNOS) by the postsynaptic density protein-95 (PSD-95). Perturbing the NMDAR/PSD-95/nNOS interaction has therefore been proposed as an alternative analgesic mechanism. We recently reported that UCCB01-125, a dimeric PSD-95 inhibitor with limited blood-brain-barrier permeability, reduced mechanical hypersensitivity in the complete Freund's adjuvant (CFA) inflammatory pain model, without disrupting cognitive or motor functions. Here, we investigated the analgesic efficacy in the CFA model of UCCB01-144, a PSD-95 inhibitor with improved blood-brain-barrier permeability. To extend the comparison of UCCB01-125 and UCCB01-144, we also tested both compounds in the spared nerve injury (SNI) model of neuropathic pain. Potential cognitive effects of UCCB01-144 were examined using the social transmission of food preference (STFP) test and the V-maze test, and motor coordination was assessed with the rotarod test. UCCB01-144 (10mg/kg) reversed CFA-induced mechanical hypersensitivity after 1h, and completely normalised sensitivity after 24h. In the SNI model, UCCB01-144 (30mg/kg) partially reversed hypersensitivity after 1h, but no effect was observed after 24h. UCCB01-125 did not affect SNI-induced hypersensitivity. Rotarod performance was unaffected by UCCB01-144, but 30mg/kg UCCB01-144 impaired performance in the STFP test. Collectively, UCCB01-144 reversed both CFA and SNI-induced hypersensitivity, but the efficacy in the SNI model was only transient. This suggests that enhanced BBB permeability of PSD-95 inhibitors improves the analgesic action in neuropathic pain states. Copyright © 2016 Elsevier B.V. All rights reserved.

Spinal versus brain microglial and macrophage activation traits determine the differential neuroinflammatory responses and analgesic effect of minocycline in chronic neuropathic pain.

PubMed

Li, Zhilin; Wei, Hong; Piirainen, Sami; Chen, Zuyue; Kalso, Eija; Pertovaara, Antti; Tian, Li

2016-11-01

Substantial evidence indicates involvement of microglia/macrophages in chronic neuropathic pain. However, the temporal-spatial features of microglial/macrophage activation and their pain-bound roles remain elusive. Here, we evaluated microglia/macrophages and the subtypes in the lumbar spinal cord (SC) and prefrontal cortex (PFC), and analgesic-anxiolytic effect of minocycline at different stages following spared nerve injury (SNI) in rats. While SNI enhanced the number of spinal microglia/macrophages since post-operative day (POD)3, pro-inflammatory MHCII + spinal microglia/macrophages were unexpectedly less abundant in SNI rats than shams on POD21. By contrast, less abundant anti-inflammatory CD172a (SIRPα) + microglia/macrophages were found in the PFC of SNI rats. Interestingly in naïve rats, microglial/macrophage expression of CD11b/c, MHCII and MHCII + /CD172a + ratio were higher in the SC than the cortex. Consistently, multiple immune genes involved in anti-inflammation, phagocytosis, complement activation and M2 microglial/macrophage polarization were upregulated in the spinal dorsal horn and dorsal root ganglia but downregulated in the PFC of SNI rats. Furthermore, daily intrathecal minocycline treatment starting from POD0 for two weeks alleviated mechanical allodynia most robustly before POD3 and attenuated anxiety on POD9. Although minocycline dampened spinal MHCII + microglia/macrophages until POD13, it failed to do so on cortical microglia/macrophages, indicating that dampening only spinal inflammation may not be enough to alleviate centralized pain at the chronic stage. Taken together, our data provide the first evidence that basal microglial/macrophage traits underlie differential region-specific responses to SNI and minocycline treatment, and suggest that drug treatment efficiently targeting not only spinal but also brain inflammation may be more effective in treating chronic neuropathic pain. Copyright © 2016 Elsevier Inc. All rights reserved.

The potential for land sparing to offset greenhouse gas emissions from agriculture

NASA Astrophysics Data System (ADS)

Lamb, Anthony; Green, Rhys; Bateman, Ian; Broadmeadow, Mark; Bruce, Toby; Burney, Jennifer; Carey, Pete; Chadwick, David; Crane, Ellie; Field, Rob; Goulding, Keith; Griffiths, Howard; Hastings, Astley; Kasoar, Tim; Kindred, Daniel; Phalan, Ben; Pickett, John; Smith, Pete; Wall, Eileen; Zu Ermgassen, Erasmus K. H. J.; Balmford, Andrew

2016-05-01

Greenhouse gas emissions from global agriculture are increasing at around 1% per annum, yet substantial cuts in emissions are needed across all sectors. The challenge of reducing agricultural emissions is particularly acute, because the reductions achievable by changing farming practices are limited and are hampered by rapidly rising food demand. Here we assess the technical mitigation potential offered by land sparing--increasing agricultural yields, reducing farmland area and actively restoring natural habitats on the land spared. Restored habitats can sequester carbon and can offset emissions from agriculture. Using the UK as an example, we estimate net emissions in 2050 under a range of future agricultural scenarios. We find that a land-sparing strategy has the technical potential to achieve significant reductions in net emissions from agriculture and land-use change. Coupling land sparing with demand-side strategies to reduce meat consumption and food waste can further increase the technical mitigation potential--however, economic and implementation considerations might limit the degree to which this technical potential could be realized in practice.

Oncolytic herpes simplex virus-based strategies: toward a breakthrough in glioblastoma therapy

PubMed Central

Ning, Jianfang; Wakimoto, Hiroaki

2014-01-01

Oncolytic viruses (OV) are a class of antitumor agents that selectively kill tumor cells while sparing normal cells. Oncolytic herpes simplex virus (oHSV) has been investigated in clinical trials for patients with the malignant brain tumor glioblastoma for more than a decade. These clinical studies have shown the safety of oHSV administration to the human brain, however, therapeutic efficacy of oHSV as a single treatment remains unsatisfactory. Factors that could hamper the anti-glioblastoma efficacy of oHSV include: attenuated potency of oHSV due to deletion or mutation of viral genes involved in virulence, restricting viral replication and spread within the tumor; suboptimal oHSV delivery associated with intratumoral injection; virus infection-induced inflammatory and cellular immune responses which could inhibit oHSV replication and promote its clearance; lack of effective incorporation of oHSV into standard-of-care, and poor knowledge about the ability of oHSV to target glioblastoma stem cells (GSCs). In an attempt to address these issues, recent research efforts have been directed at: (1) design of new engineered viruses to enhance potency, (2) better understanding of the role of the cellular immunity elicited by oHSV infection of tumors, (3) combinatorial strategies with different antitumor agents with a mechanistic rationale, (4) “armed” viruses expressing therapeutic transgenes, (5) use of GSC-derived models in oHSV evaluation, and (6) combinations of these. In this review, we will describe the current status of oHSV clinical trials for glioblastoma, and discuss recent research advances and future directions toward successful oHSV-based therapy of glioblastoma. PMID:24999342

Right parietal cortex and calculation processing: intraoperative functional mapping of multiplication and addition in patients affected by a brain tumor.

PubMed

Della Puppa, Alessandro; De Pellegrin, Serena; d'Avella, Elena; Gioffrè, Giorgio; Munari, Marina; Saladini, Marina; Salillas, Elena; Scienza, Renato; Semenza, Carlo

2013-11-01

The role of parietal areas in number processing is well known. The significance of intraoperative functional mapping of these areas has been only partially explored, however, and only a few discordant data are available in the surgical literature with regard to the right parietal lobe. The purpose of this study was to evaluate the clinical impact of simple calculation in cortical electrostimulation of right-handed patients affected by a right parietal brain tumor. Calculation mapping in awake surgery was performed in 3 right-handed patients affected by high-grade gliomas located in the right parietal lobe. Preoperatively, none of the patients presented with calculation deficits. In all 3 cases, after sensorimotor and language mapping, cortical and intraparietal sulcus areas involved in single-digit multiplication and addition calculations were mapped using bipolar electrostimulation. In all patients, different sites of the right parietal cortex, mainly in the inferior lobule, were detected as being specifically related to calculation (multiplication or addition). In 2 patients the intraparietal sulcus was functionally specific for multiplication. No functional sites for language were detected. All sites functional for calculation were spared during tumor resection, which was complete in all cases without postoperative neurological deficits. These findings provide intraoperative data in support of an anatomofunctional organization for multiplication and addition within the right parietal area. Furthermore, the study shows the potential clinical relevance of intraoperative mapping of calculation in patients undergoing surgery in the right parietal area. Further and larger studies are needed to confirm these data and assess whether mapped areas are effectively essential for function.

A Principled Relation between Reading and Naming in Acquired and Developmental Anomia: Surface Dyslexia Following Impairment in the Phonological Output Lexicon

PubMed Central

Gvion, Aviah; Friedmann, Naama

2016-01-01

Lexical retrieval and reading aloud are often viewed as two separate processes. However, they are not completely separate—they share components. This study assessed the effect of an impairment in a shared component, the phonological output lexicon, on lexical retrieval and on reading aloud. Because the phonological output lexicon is part of the lexical route for reading, individuals with an impairment in this lexicon may be forced to read aloud via the sublexical route and therefore show a reading pattern that is typical of surface dyslexia. To examine the effect of phonological output lexicon deficit on reading, we tested the reading of 16 Hebrew-speaking individuals with phonological output lexicon anomia, eight with acquired anomia following brain damage and eight with developmental anomia. We established that they had a phonological output lexicon deficit according to the types of errors and the effects on their naming in a picture naming task, and excluded other deficit loci in the lexical retrieval process according to a line of tests assessing their picture and word comprehension, word and non-word repetition, and phonological working memory. After we have established that the participants have a phonological output lexicon deficit, we tested their reading. To assess their reading and type of reading impairment, we tested their reading aloud, lexical decision, and written word comprehension. We found that all of the participants with phonological output lexicon impairment showed, in addition to anomia, also the typical surface dyslexia errors in reading aloud of irregular words, words with ambiguous conversion to phonemes, and potentiophones (words like “now” that, when read via the sublexical route, can be sounded out as another word, “know”). Importantly, the participants performed normally on pseudohomophone lexical decision and on homophone/potentiophone reading comprehension, indicating spared orthographic input lexicon and spared access to it and from it to lexical semantics. This pattern was shown both by the adults with acquired anomia and by the participants with developmental anomia. These results thus suggest a principled relation between anomia and dyslexia, and point to a distinct type of surface dyslexia. They further show the possibility of good comprehension of written words when the phonological output stages are impaired. PMID:27065897

Role of spared pathways in locomotor recovery after body-weight-supported treadmill training in contused rats.

PubMed

Singh, Anita; Balasubramanian, Sriram; Murray, Marion; Lemay, Michel; Houle, John

2011-12-01

Body-weight-supported treadmill training (BWSTT)-related locomotor recovery has been shown in spinalized animals. Only a few animal studies have demonstrated locomotor recovery after BWSTT in an incomplete spinal cord injury (SCI) model, such as contusion injury. The contribution of spared descending pathways after BWSTT to behavioral recovery is unclear. Our goal was to evaluate locomotor recovery in contused rats after BWSTT, and to study the role of spared pathways in spinal plasticity after BWSTT. Forty-eight rats received a contusion, a transection, or a contusion followed at 9 weeks by a second transection injury. Half of the animals in the three injury groups were given BWSTT for up to 8 weeks. Kinematics and the Basso-Beattie-Bresnahan (BBB) test assessed behavioral improvements. Changes in Hoffmann-reflex (H-reflex) rate depression property, soleus muscle mass, and sprouting of primary afferent fibers were also evaluated. BWSTT-contused animals showed accelerated locomotor recovery, improved H-reflex properties, reduced muscle atrophy, and decreased sprouting of small caliber afferent fibers. BBB scores were not improved by BWSTT. Untrained contused rats that received a transection exhibited a decrease in kinematic parameters immediately after the transection; in contrast, trained contused rats did not show an immediate decrease in kinematic parameters after transection. This suggests that BWSTT with spared descending pathways leads to neuroplasticity at the lumbar spinal level that is capable of maintaining locomotor activity. Discontinuing training after the transection in the trained contused rats abolished the improved kinematics within 2 weeks and led to a reversal of the improved H-reflex response, increased muscle atrophy, and an increase in primary afferent fiber sprouting. Thus continued training may be required for maintenance of the recovery. Transected animals had no effect of BWSTT, indicating that in the absence of spared pathways this training paradigm did not improve function.

Interaction between maropitant and carprofen on sparing of the minimum alveolar concentration for blunting adrenergic response (MAC-BAR) of sevoflurane in dogs

PubMed Central

FUKUI, Sho; OOYAMA, Norihiko; TAMURA, Jun; UMAR, Mohammed Ahmed; ISHIZUKA, Tomohito; ITAMI, Takaharu; MIYOSHI, Kenjiro; SANO, Tadashi; YAMASHITA, Kazuto

2017-01-01

Maropitant, a neurokinin-1 receptor antagonist, may provide analgesic effects by blocking pharmacological action of substance P. Carprofen is a non-steroidal anti-inflammatory drug commonly used for pain control in dogs. The purpose of this study was to evaluate the effect of a combination of maropitant and carprofen on the minimum alveolar concentration for blunting adrenergic response (MAC-BAR) of sevoflurane in dogs. Six healthy adult beagle dogs were anesthetized with sevoflurane four times with a minimum of 7-day washout period. On each occasion, maropitant (1 mg/kg) alone, carprofen (4 mg/kg) alone, a combination of maropitant (1 mg/kg) and carprofen (4 mg/kg), or saline (0.1 ml/kg) was subcutaneously administered at 1 hr prior to the first electrical stimulation for the sevoflurane MAC-BAR determination. The sevoflurane MAC-BAR was significantly reduced by maropitant alone (2.88 ± 0.73%, P=0.010), carprofen alone (2.96 ± 0.38%, P=0.016) and the combination (2.81 ± 0.51%, P=0.0003), compared with saline (3.37 ± 0.56%). There was no significant difference in the percentage of MAC-BAR reductions between maropitant alone, carprofen alone and the combination. The administration of maropitant alone and carprofen alone produced clinically significant sparing effects on the sevoflurane MAC-BAR in dogs. However, the combination of maropitant and carprofen did not produce any additive effect on the sevoflurane MAC-BAR reduction. Anesthetic premedication with a combination of maropitant and carprofen may not provide any further sparing effect on anesthetic requirement in dogs. PMID:28111373

Interaction between maropitant and carprofen on sparing of the minimum alveolar concentration for blunting adrenergic response (MAC-BAR) of sevoflurane in dogs.

PubMed

Fukui, Sho; Ooyama, Norihiko; Tamura, Jun; Umar, Mohammed Ahmed; Ishizuka, Tomohito; Itami, Takaharu; Miyoshi, Kenjiro; Sano, Tadashi; Yamashita, Kazuto

2017-03-18

Maropitant, a neurokinin-1 receptor antagonist, may provide analgesic effects by blocking pharmacological action of substance P. Carprofen is a non-steroidal anti-inflammatory drug commonly used for pain control in dogs. The purpose of this study was to evaluate the effect of a combination of maropitant and carprofen on the minimum alveolar concentration for blunting adrenergic response (MAC-BAR) of sevoflurane in dogs. Six healthy adult beagle dogs were anesthetized with sevoflurane four times with a minimum of 7-day washout period. On each occasion, maropitant (1 mg/kg) alone, carprofen (4 mg/kg) alone, a combination of maropitant (1 mg/kg) and carprofen (4 mg/kg), or saline (0.1 ml/kg) was subcutaneously administered at 1 hr prior to the first electrical stimulation for the sevoflurane MAC-BAR determination. The sevoflurane MAC-BAR was significantly reduced by maropitant alone (2.88 ± 0.73%, P=0.010), carprofen alone (2.96 ± 0.38%, P=0.016) and the combination (2.81 ± 0.51%, P=0.0003), compared with saline (3.37 ± 0.56%). There was no significant difference in the percentage of MAC-BAR reductions between maropitant alone, carprofen alone and the combination. The administration of maropitant alone and carprofen alone produced clinically significant sparing effects on the sevoflurane MAC-BAR in dogs. However, the combination of maropitant and carprofen did not produce any additive effect on the sevoflurane MAC-BAR reduction. Anesthetic premedication with a combination of maropitant and carprofen may not provide any further sparing effect on anesthetic requirement in dogs.

The effect of anti-tumor necrosis factor alpha agents on the outcome in pediatric uveitis of diverse etiologies.

PubMed

Deitch, Iris; Amer, Radgonde; Tomkins-Netzer, Oren; Habot-Wilner, Zohar; Friling, Ronit; Neumann, Ron; Kramer, Michal

2018-04-01

This study aimed to report the clinical outcome of children with uveitis treated with anti-tumor necrosis factor alpha (TNF-α) agents. This included a retrospective cohort study. Children with uveitis treated with infliximab or adalimumab in 2008-2014 at five dedicated uveitis clinics were identified by database search. Their medical records were reviewed for demographic data, clinical presentation, ocular complications, and visual outcome. Systemic side effects and the steroid-sparing effect of treatment were documented. The cohort included 24 patients (43 eyes) of whom 14 received infliximab and 10 received adalimumab after failing conventional immunosuppression therapy. Mean age was 9.3 ± 4.0 years. The most common diagnosis was juvenile idiopathic arthritis-related uveitis (n = 10), followed by Behçet's disease (n = 4), sarcoidosis (n = 1), and ankylosing spondylitis (n = 1); eight had idiopathic uveitis. Ocular manifestations included panuveitis in 20 eyes (46.5%), chronic anterior uveitis in 19 (44.2%), and intermediate uveitis in 4 (9.3%). The duration of biologic treatment ranged from 6 to 72 months. During the 12 months prior to biologic treatment, while on conventional immunosuppressive therapy, mean visual acuity deteriorated from 0.22 to 0.45 logMAR, with a trend of recovery to 0.25 at 3 months after initiation of biologic treatment, remaining stable thereafter. A full corticosteroid-sparing effect was demonstrated in 16 of the 19 patients (84.2%) for whom data were available. Treatment was well tolerated. Treatment of pediatric uveitis with anti-TNF-α agents may improve outcome while providing steroid-sparing effect, when conventional immunosuppression fails. The role of anti-TNF-α agents as first-line treatment should be further investigated in controlled prospective clinical trials.

Management Sciences Division Annual Report (10th)

DTIC Science & Technology

1993-01-01

of the Weapon System Management Information System (WSMIS). TheI Aircraft Sustainability Model ( ASM ) is the computational technique employed by...provisioning. We enhanced the capabilities of RBIRD by using the Aircraft Sustainability Model ( ASM ) for the spares calculation. ASM offers many... ASM for several years to 3 compute spares for war. It is also fully compatible with the Air Force’s peacetime spares computation system (D041). This

Defense Logistics Agency Can Improve Its Product Quality Deficiency Report Processing

DTIC Science & Technology

2015-07-01

Contracts for M2 Machine Gun Spare Parts in Support of Operations in Southwest Asia,” January 11, 2010 Appendixes DODIG-2015-140 │ 29 Appendix B...personnel are adequately processing product quality deficiency reports and identifying the root cause for defective spare parts . This is the first...quality deficiency report program and prevents meaningful analysis of the primary causes of spare- part quality deficiencies. In addition, the

Near-Earth Phase Risk Comparison of Human Mars Campaign Architectures

NASA Technical Reports Server (NTRS)

Manning, Ted A.; Nejad, Hamed S.; Mattenberger, Chris

2013-01-01

A risk analysis of the launch, orbital assembly, and Earth-departure phases of human Mars exploration campaign architectures was completed as an extension of a probabilistic risk assessment (PRA) originally carried out under the NASA Constellation Program Ares V Project. The objective of the updated analysis was to study the sensitivity of loss-of-campaign risk to such architectural factors as composition of the propellant delivery portion of the launch vehicle fleet (Ares V heavy-lift launch vehicle vs. smaller/cheaper commercial launchers) and the degree of launcher or Mars-bound spacecraft element sparing. Both a static PRA analysis and a dynamic, event-based Monte Carlo simulation were developed and used to evaluate the probability of loss of campaign under different sparing options. Results showed that with no sparing, loss-of-campaign risk is strongly driven by launcher count and on-orbit loiter duration, favoring an all-Ares V launch approach. Further, the reliability of the all-Ares V architecture showed significant improvement with the addition of a single spare launcher/payload. Among architectures utilizing a mix of Ares V and commercial launchers, those that minimized the on-orbit loiter duration of Mars-bound elements were found to exceed the reliability of no spare all-Ares V campaign if unlimited commercial vehicle sparing was assumed

A Computational Model of the Fetal Circulation to Quantify Blood Redistribution in Intrauterine Growth Restriction

PubMed Central

Garcia-Canadilla, Patricia; Rudenick, Paula A.; Crispi, Fatima; Cruz-Lemini, Monica; Palau, Georgina; Camara, Oscar; Gratacos, Eduard; Bijens, Bart H.

2014-01-01

Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this brain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental understanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has been limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since they allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be directly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed, including the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow personalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to understand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery (MCA) flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this affects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the proposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The results support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance between increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying the balance between cerebral and peripheral-placental remodeling, thus providing potentially novel information to aid clinical follow up. PMID:24921933

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deman, Pierre; Universite Joseph Fourier, Institut des Neurosciences, Grenoble; European Synchrotron Radiation Facility, Grenoble

Purpose: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. Methods and Materials: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 Multiplication-Sign 5 Multiplication-Sign 4.8 mm{sup 3} volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability mapsmore » were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 Multiplication-Sign 8 Multiplication-Sign 7.8 mm{sup 3} volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired. Results: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 {+-} 12.5 days versus 23.3 {+-} 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation. Conclusions: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy.« less

Clinical applications of image guided-intensity modulated radiation therapy (IG-IMRT) for conformal avoidance of normal tissue

NASA Astrophysics Data System (ADS)

Gutierrez, Alonso Navar

2007-12-01

Recent improvements in imaging technology and radiation delivery have led to the development of advanced treatment techniques in radiotherapy which have opened the door for novel therapeutic approaches to improve the efficacy of radiation cancer treatments. Among these advances is image-guided, intensity modulated radiation therapy (IG-IMRT), in which imaging is incorporated to aid in inter-/intra-fractional target localization and to ensure accurate delivery of precise and highly conformal dose distributions. In principle, clinical implementation of IG-IMRT should improve normal tissue sparing and permit effective biological dose escalation thus widening the radiation therapeutic window and lead to increases in survival through improved local control of primary neoplastic diseases. Details of the development of three clinical applications made possible solely with IG-IMRT radiation delivery techniques are presented: (1) Laparoscopically implanted tissue expander radiotherapy (LITE-RT) has been developed to enhance conformal avoidance of normal tissue during the treatment of intra-abdominopelvic cancers. LITE-RT functions by geometrically displacing surrounding normal tissue and isolating the target volume through the interfractional inflation of a custom-shaped tissue expander throughout the course of treatment. (2) The unique delivery geometry of helical tomotherapy, a novel form of IG-IMRT, enables the delivery of composite treatment plan m which whole brain radiotherapy (WBRT) with hippocampal avoidance, hypothesized to reduce the risk of memory function decline and improve the patient's quality of life, and simultaneously integrated boost to multiple brain metastases to improve intracranial tumor control is achieved. (3) Escalation of biological dose to targets through integrated, selective subvolume boosts have been shown to efficiently increase tumor dose without significantly increasing normal tissue dose. Helical tomotherapy was used to investigate the feasibility of delivering a simultaneously integrated subvolume boost to canine nasal tumors and was found to dramatically increase estimated 1-year tumor control probability (TCP) without increasing the dose to the eyes, so as to preserve vision, and to the brain, so as to prevent neuropathy.

Significance of a Pronator Quadratus–Sparing Approach for Volar Locking Plate Fixation of Comminuted Intra-articular Fractures of the Distal Radius

PubMed Central

Itoh, Soichiro; Yumoto, Myu; Kanai, Misa; Yoshida, Wataru; Yoshioka, Taro

2016-01-01

Background: The preservation of the integrity of the pronator quadratus (PQ) muscle is expected to have many benefits, particularly in cases of highly comminuted intra-articular fractures of the distal radius. Therefore, we examined the significance of a PQ muscle–sparing approach for volar locking plate (VLP) fixation of these types of fractures. Methods: Sixty-five patients who sustained AO Foundation and Orthopaedic Trauma Association (AO/OTA) type C2 and C3 distal radius fractures were treated with VLP fixation using either a PQ muscle release and repair (PQ-releasing group, n = 30) or a PQ muscle–sparing approach (PQ-sparing group, n = 35). Radiographic parameters, active range of motion (ROM), percentage of the grip power of the injured hand compared with that of the opposite hand, wrist pain visual analog scale (VAS) score, and Quick Disability of the Arm, Shoulder, and Hand (DASH) score (disability/symptom) were evaluated monthly up to 12 months after surgery. Results: The mean VAS score was significantly lower in the PQ-sparing group at 2, 3, and 4 months postoperatively than in the PQ-releasing group. Furthermore, the mean Quick DASH score in the PQ-sparing group was significantly lower than that in the PQ-releasing group at 1 and 2 months postoperatively. There were no significant differences, however, in the other functional parameters in the groups through the observation period. Conclusions: The PQ muscle–sparing approach appears to achieve satisfactory results in patients undergoing VLP fixation of comminuted intra-articular fractures of the distal radius. PMID:27418895

Valve-sparing options in tetralogy of Fallot surgery.

PubMed

Bacha, Emile

2012-01-01

Given late outcomes of patients with tetralogy of Fallot repaired in the 1970s and 1980s, as well as a better understanding of the late deleterious effects of pulmonary regurgitation, there is a tendency toward preservation of the pulmonary valve function during primary repair of tetralogy of Fallot. The bar keeps moving downward, to include smaller and more dysmorphic pulmonary valves. This article reviews some useful indications and techniques for valve-sparing options, including intraoperative balloon dilation and cusp reconstruction using a patch. Just like other valve repair techniques, no one technique can be applied uniformly, and surgeons must master a wide armamentarium of techniques. Copyright © 2012 Elsevier Inc. All rights reserved.

Clinical evaluation of intensity-modulated radiotherapy for head and neck cancers

PubMed Central

Bhide, S A; Newbold, K L; Harrington, K J; Nutting, C M

2012-01-01

Radiotherapy and surgery are the principal curative modalities in treatment of head and neck cancer. Conventional two-dimensional and three-dimensional conformal radiotherapy result in significant side effects and altered quality of life. Intensity-modulated radiotherapy (IMRT) can spare the normal tissues, while delivering a curative dose to the tumour-bearing tissues. This article reviews the current role of IMRT in head and neck cancer from the point of view of normal tissue sparing, and also reviews the current published literature by individual head and neck cancer subsites. In addition, we briefly discuss the role of image guidance in head and neck IMRT, and future directions in this area. PMID:22556403

Comparison of organ-at-risk sparing and plan robustness for spot-scanning proton therapy and volumetric modulated arc photon therapy in head-and-neck cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barten, Danique L. J., E-mail: d.barten@vumc.nl; Tol, Jim P.; Dahele, Max

Purpose: Proton radiotherapy for head-and-neck cancer (HNC) aims to improve organ-at-risk (OAR) sparing over photon radiotherapy. However, it may be less robust for setup and range uncertainties. The authors investigated OAR sparing and plan robustness for spot-scanning proton planning techniques and compared these with volumetric modulated arc therapy (VMAT) photon plans. Methods: Ten HNC patients were replanned using two arc VMAT (RapidArc) and spot-scanning proton techniques. OARs to be spared included the contra- and ipsilateral parotid and submandibular glands and individual swallowing muscles. Proton plans were made using Multifield Optimization (MFO, using three, five, and seven fields) and Single-field Optimizationmore » (SFO, using three fields). OAR sparing was evaluated using mean dose to composite salivary glands (Comp{sub Sal}) and composite swallowing muscles (Comp{sub Swal}). Plan robustness was determined for setup and range uncertainties (±3 mm for setup, ±3% HU) evaluating V95% and V107% for clinical target volumes. Results: Averaged over all patients Comp{sub Sal}/Comp{sub Swal} mean doses were lower for the three-field MFO plans (14.6/16.4 Gy) compared to the three-field SFO plans (20.0/23.7 Gy) and VMAT plans (23.0/25.3 Gy). Using more than three fields resulted in differences in OAR sparing of less than 1.5 Gy between plans. SFO plans were significantly more robust than MFO plans. VMAT plans were the most robust. Conclusions: MFO plans had improved OAR sparing but were less robust than SFO and VMAT plans, while SFO plans were more robust than MFO plans but resulted in less OAR sparing. Robustness of the MFO plans did not increase with more fields.« less

Prospective study of functional bone marrow-sparing intensity modulated radiation therapy with concurrent chemotherapy for pelvic malignancies.

PubMed

Liang, Yun; Bydder, Mark; Yashar, Catheryn M; Rose, Brent S; Cornell, Mariel; Hoh, Carl K; Lawson, Joshua D; Einck, John; Saenz, Cheryl; Fanta, Paul; Mundt, Arno J; Bydder, Graeme M; Mell, Loren K

2013-02-01

To test the hypothesis that intensity modulated radiation therapy (IMRT) can reduce radiation dose to functional bone marrow (BM) in patients with pelvic malignancies (phase IA) and estimate the clinical feasibility and acute toxicity associated with this technique (phase IB). We enrolled 31 subjects (19 with gynecologic cancer and 12 with anal cancer) in an institutional review board-approved prospective trial (6 in the pilot study, 10 in phase IA, and 15 in phase IB). The mean age was 52 years; 8 of 31 patients (26%) were men. Twenty-one subjects completed (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) simulation and magnetic resonance imaging by use of quantitative IDEAL (IDEAL IQ; GE Healthcare, Waukesha, WI). The PET/CT and IDEAL IQ were registered, and BM subvolumes were segmented above the mean standardized uptake value and below the mean fat fraction within the pelvis and lumbar spine; their intersection was designated as functional BM for IMRT planning. Functional BM-sparing vs total BM-sparing IMRT plans were compared in 12 subjects; 10 were treated with functional BM-sparing pelvic IMRT per protocol. In gynecologic cancer patients, the mean functional BM V(10) (volume receiving ≥10 Gy) and V(20) (volume receiving ≥20 Gy) were 85% vs 94% (P<.0001) and 70% vs 82% (P<.0001), respectively, for functional BM-sparing IMRT vs total BM-sparing IMRT. In anal cancer patients, the corresponding values were 75% vs 77% (P=.06) and 62% vs 67% (P=.002), respectively. Of 10 subjects treated with functional BM-sparing pelvic IMRT, 3 (30%) had acute grade 3 hematologic toxicity or greater. IMRT can reduce dose to BM subregions identified by (18)F-fluorodeoxyglucose-PET/CT and IDEAL IQ. The efficacy of BM-sparing IMRT is being tested in a phase II trial. Copyright © 2013 Elsevier Inc. All rights reserved.

Prospective Study of Functional Bone Marrow-Sparing Intensity Modulated Radiation Therapy With Concurrent Chemotherapy for Pelvic Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang Yun; Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, California; Bydder, Mark

2013-02-01

Purpose: To test the hypothesis that intensity modulated radiation therapy (IMRT) can reduce radiation dose to functional bone marrow (BM) in patients with pelvic malignancies (phase IA) and estimate the clinical feasibility and acute toxicity associated with this technique (phase IB). Methods and Materials: We enrolled 31 subjects (19 with gynecologic cancer and 12 with anal cancer) in an institutional review board-approved prospective trial (6 in the pilot study, 10 in phase IA, and 15 in phase IB). The mean age was 52 years; 8 of 31 patients (26%) were men. Twenty-one subjects completed {sup 18}F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computedmore » tomography (CT) simulation and magnetic resonance imaging by use of quantitative IDEAL (IDEAL IQ; GE Healthcare, Waukesha, WI). The PET/CT and IDEAL IQ were registered, and BM subvolumes were segmented above the mean standardized uptake value and below the mean fat fraction within the pelvis and lumbar spine; their intersection was designated as functional BM for IMRT planning. Functional BM-sparing vs total BM-sparing IMRT plans were compared in 12 subjects; 10 were treated with functional BM-sparing pelvic IMRT per protocol. Results: In gynecologic cancer patients, the mean functional BM V{sub 10} (volume receiving {>=}10 Gy) and V{sub 20} (volume receiving {>=}20 Gy) were 85% vs 94% (P<.0001) and 70% vs 82% (P<.0001), respectively, for functional BM-sparing IMRT vs total BM-sparing IMRT. In anal cancer patients, the corresponding values were 75% vs 77% (P=.06) and 62% vs 67% (P=.002), respectively. Of 10 subjects treated with functional BM-sparing pelvic IMRT, 3 (30%) had acute grade 3 hematologic toxicity or greater. Conclusions: IMRT can reduce dose to BM subregions identified by {sup 18}F-fluorodeoxyglucose-PET/CT and IDEAL IQ. The efficacy of BM-sparing IMRT is being tested in a phase II trial.« less

Esophagus and Contralateral Lung-Sparing IMRT for Locally Advanced Lung Cancer in the Community Hospital Setting.

PubMed

Kao, Johnny; Pettit, Jeffrey; Zahid, Soombal; Gold, Kenneth D; Palatt, Terry

2015-01-01

The optimal technique for performing lung IMRT remains poorly defined. We hypothesize that improved dose distributions associated with normal tissue-sparing IMRT can allow safe dose escalation resulting in decreased acute and late toxicity. We performed a retrospective analysis of 82 consecutive lung cancer patients treated with curative intent from 1/10 to 9/14. From 1/10 to 4/12, 44 patients were treated with the community standard of three-dimensional conformal radiotherapy or IMRT without specific esophagus or contralateral lung constraints (standard RT). From 5/12 to 9/14, 38 patients were treated with normal tissue-sparing IMRT with selective sparing of contralateral lung and esophagus. The study endpoints were dosimetry, toxicity, and overall survival. Despite higher mean prescribed radiation doses in the normal tissue-sparing IMRT cohort (64.5 vs. 60.8 Gy, p = 0.04), patients treated with normal tissue-sparing IMRT had significantly lower lung V20, V10, V5, mean lung, esophageal V60, and mean esophagus doses compared to patients treated with standard RT (p ≤ 0.001). Patients in the normal tissue-sparing IMRT group had reduced acute grade ≥3 esophagitis (0 vs. 11%, p < 0.001), acute grade ≥2 weight loss (2 vs. 16%, p = 0.04), and late grade ≥2 pneumonitis (7 vs. 21%, p = 0.02). The 2-year overall survival was 52% with normal tissue-sparing IMRT arm compared to 28% for standard RT (p = 0.015). These data provide proof of principle that suboptimal radiation dose distributions are associated with significant acute and late lung and esophageal toxicity that may result in hospitalization or even premature mortality. Strict attention to contralateral lung and esophageal dose-volume constraints are feasible in the community hospital setting without sacrificing disease control.

TH-CD-209-05: Impact of Spot Size and Spacing On the Quality of Robustly-Optimized Intensity-Modulated Proton Therapy Plans for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, W; Ding, X; Hu, Y

Purpose: To investigate how spot size and spacing affect plan quality, especially, plan robustness and the impact of interplay effect, of robustly-optimized intensity-modulated proton therapy (IMPT) plans for lung cancer. Methods: Two robustly-optimized IMPT plans were created for 10 lung cancer patients: (1) one for a proton beam with in-air energy dependent large spot size at isocenter (σ: 5–15 mm) and spacing (1.53σ); (2) the other for a proton beam with small spot size (σ: 2–6 mm) and spacing (5 mm). Both plans were generated on the average CTs with internal-gross-tumor-volume density overridden to irradiate internal target volume (ITV). Themore » root-mean-square-dose volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under RVH curves were used to evaluate plan robustness. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Patient anatomy voxels were mapped from phase to phase via deformable image registration to score doses. Dose-volume-histogram indices including ITV coverage, homogeneity, and organs-at-risk (OAR) sparing were compared using Student-t test. Results: Compared to large spots, small spots resulted in significantly better OAR sparing with comparable ITV coverage and homogeneity in the nominal plan. Plan robustness was comparable for ITV and most OARs. With interplay effect considered, significantly better OAR sparing with comparable ITV coverage and homogeneity is observed using smaller spots. Conclusion: Robust optimization with smaller spots significantly improves OAR sparing with comparable plan robustness and similar impact of interplay effect compare to larger spots. Small spot size requires the use of larger number of spots, which gives optimizer more freedom to render a plan more robust. The ratio between spot size and spacing was found to be more relevant to determine plan robustness and the impact of interplay effect than spot size alone. This research was supported by the National Cancer Institute Career Developmental Award K25CA168984, by the Fraternal Order of Eagles Cancer Research Fund Career Development Award, by The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, by Mayo Arizona State University Seed Grant, and by The Kemper Marley Foundation.« less

Biofuels on the landscape: Is "land sharing" preferable to "land sparing"?

NASA Astrophysics Data System (ADS)

DeLucia, E. H.; Anderson-Teixeira, K. J.; Duval, B. D.; Long, S. P.

2012-12-01

Widespread land use changes—and ensuing effects on biodiversity and ecosystem services—are expected as a result of expanding bioenergy production. Although almost all US production of ethanol today is from corn, it is envisaged that future ethanol production will also draw from cellulosic sources such as perennial grasses. In selecting optimal bioenergy crops, there is debate as to whether it is preferable from an environmental standpoint to cultivate bioenergy crops with high ecosystem services (a "land sharing" strategy) or to grow crops with lower ecosystem services but higher yield, thereby requiring less land to meet bioenergy demand (a "land sparing" strategy). Here, we develop a simple model to address this question. Assuming that bioenergy crops are competing with uncultivated land, our model calculates land requirements to meet a given bioenergy demand intensity based upon the yields of bioenergy crops and combines fractional land cover of each ecosystem type with its associated ecosystem services to determine whether land sharing or land sparing strategies maximize ecosystem services at the landscape level. We apply this model to a case in which climate protection through GHG regulation—an ecosystem's greenhouse gas value (GHGV)—is the ecosystem service of interest. We consider five bioenergy crops competing for land area with five unfarmed ecosystem types in the central and eastern US. Our results show that the relative advantages of land sparing and land sharing depend upon the type of ecosystem with which the bioenergy crop is competing for land; as the GHGV value of the unfarmed land increases, the preferable strategy shifts from land sharing to land sparing. This implies that, while it may be preferable to replace ecologically degraded land with high-GHGV, lower yielding bioenergy crops, average landscape GHGV will most often be maximized through high yielding bioenergy crops that leave more land for uncultivated, high-GHGV ecosystems. While our case study focuses on GHGV, the same principles will be generally applicable to any ecosystem service whose value does not depend upon the spatial configuration of the landscape. Whenever bioenergy crops have substantially lower ecosystem services than the ecosystems with which they are competing for land, the most effective strategy for meeting bioenergy demand while maximizing ecosystem services on a landscape level is one of land sparing—that is, focusing simultaneously on maximizing the yield of bioenergy crops while preserving or restoring natural ecosystems.

Nipple- and areola-sparing mastectomy for the treatment of breast cancer

PubMed Central

Mota, Bruna S; Riera, Rachel; Desidério Ricci, Marcos; Barrett, Jessica; de Castria, Tiago B; Atallah, Álvaro N; Bevilacqua, Jose Luiz B

2018-01-01

Background The efficacy and safety of nipple-sparing mastectomy and areola-sparing mastectomy for the treatment of breast cancer are still questionable. It is estimated that the local recurrence rates following nipple-sparing mastectomy are very similar to breast-conserving surgery followed by radiotherapy. Objectives To assess the efficacy and safety of nipple-sparing mastectomy and areola-sparing mastectomy for the treatment of ductal carcinoma in situ and invasive breast cancer in women. Search methods We searched the Cochrane Breast Cancer Group’s Specialized Register, the Cochrane Center Register of Controlled Trials (CENTRAL), MEDLINE (via PubMed), Embase (via OVID) and LILACS (via Biblioteca Virtual em Saúde [BVS]) using the search terms “nipple sparing mastectomy” and “areola-sparing mastectomy”. Also, we searched the World Health Organization’s International Clinical Trials Registry Platform and ClinicalTrials.gov. All searches were conducted on 30th September 2014 and we did not apply any language restrictions. Selection criteria Randomised controlled trials (RCTs) however if there were no RCTs, we expanded our criteria to include non-randomised comparative studies (cohort and case-control studies). Studies evaluated nipple-sparing and areola-sparing mastectomy compared to modified radical mastectomy or skin-sparing mastectomy for the treatment of ductal carcinoma in situ or invasive breast cancer. Data collection and analysis Two review authors (BS and RR) performed data extraction and resolved disagreements. We performed descriptive analyses and meta-analyses of the data using Review Manager software. We used Cochrane’s risk of bias tool to assess studies, and adapted it for non-randomised studies, and we evaluated the quality of the evidence using GRADE criteria. Main results We included 11 cohort studies, evaluating a total of 6502 participants undergoing 7018 procedures: 2529 underwent a nipple-sparing mastectomy (NSM), 818 underwent skin-sparing mastectomy (SSM) and 3671 underwent traditional mastectomy, also known as modified radical mastectomy (MRM). No participants underwent areola-sparing mastectomy. There was a high risk of confounding for all reported outcomes. For overall survival, the hazard ratio (HR) for NSM compared to SSM was 0.70 (95% CI 0.28 to 1.73; 2 studies; 781 participants) and the HR for NSM compared to MRM was 0.72 (95% CI 0.46 to 1.13; 2 studies, 1202 participants). Local recurrence was evaluated in two studies, the HR for NSM compared to MRM was 0.28 (95% CI 0.12 to 0.68; 2 studies, 1303 participants). The overall risk of complications was different in NSM when compared to other types of mastectomy in general (RR 0.10, 95% CI 0.01 to 0.82, 2 studies, P = 0.03; 1067 participants). With respect to skin necrosis, there was no evidence of a difference with NSM compared to other types of mastectomy, but the confidence interval was wide (RR 4.22, 95% CI 0.59 to 30.03, P = 0.15; 4 studies, 1948 participants). We observed no difference among the three types of mastectomy with respect to the risk of local infection (RR 0.95, 95% CI 0.44 to 2.09, P = 0.91, 2 studies; 496 participants). Meta-analysis was not possible when assessing cosmetic outcomes and quality of life, but in general the NSM studies reported a favourable aesthetic result and a gain in quality of life compared with the other types of mastectomy. The quality of evidence was considered very low for all outcomes due to the high risk of selection bias and wide confidence intervals. Authors’ conclusions The findings from these observational studies of very low-quality evidence were inconclusive for all outcomes due to the high risk of selection bias. PMID:27898991

[Nerve-sparing radical prostatectomy--effect and risks].

PubMed

Borre, Michael

2008-08-18

The purpose of nerve-sparing technique performing radical prostatectomy (NSRP) is to attempt to preserve the neurovascular bundle which is located posterolaterally on both sides of the prostate. The nerve-sparing technique presupposes the pre- and per operative tumour stage as well as preoperative erectile function--so as not to unnecessarily risk compromising the radicalism of the surgery. In the period 2003-2006 242 patients were radical prostatectomized (RP) at the Dept. of Urology, Aarhus University Hospital, Skejby. A total of 84 of these were offered NSRP. Data concerning erectile function preoperatively and 12 months postoperatively were compared. Likewise the postoperative tumour control following NSRP was investigated. There was a statistically significant association between NSRP and preserved potency 12 months postoperatively compared to the non-NSRP patient group. Moreover, no association between risks of positive surgical margins in patients treated with or without NSRP technique was observed. During follow up (median 39 months) the rate of biochemical recurrence was 40. Among these 8, 13 and 20% of the patients were respectively treated with bilateral-, unilateral- and non-NSRP. NSRP seems to be both a safe and effective procedure in carefully selected patients. Furthermore, the results suggest that if preoperatively potent, low- to middle-risk group patients (cT1-2a/b, Gleason score < 7 and PSA < 10 ng/mL) are potential candidates for at least unilateral NSRP.

The contribution of LM to the neuroscience of movement vision

PubMed Central

Zihl, Josef; Heywood, Charles A.

2015-01-01

The significance of early and sporadic reports in the 19th century of impairments of motion vision following brain damage was largely unrecognized. In the absence of satisfactory post-mortem evidence, impairments were interpreted as the consequence of a more general disturbance resulting from brain damage, the location and extent of which was unknown. Moreover, evidence that movement constituted a special visual perception and may be selectively spared was similarly dismissed. Such skepticism derived from a reluctance to acknowledge that the neural substrates of visual perception may not be confined to primary visual cortex. This view did not persist. First, it was realized that visual movement perception does not depend simply on the analysis of spatial displacements and temporal intervals, but represents a specific visual movement sensation. Second persuasive evidence for functional specialization in extrastriate cortex, and notably the discovery of cortical area V5/MT, suggested a separate region specialized for motion processing. Shortly thereafter the remarkable case of patient LM was published, providing compelling evidence for a selective and specific loss of movement vision. The case is reviewed here, along with an assessment of its contribution to visual neuroscience. PMID:25741251

Congenital amusias.

PubMed

Tillmann, B; Albouy, P; Caclin, A

2015-01-01

In contrast to the sophisticated music processing reported in the general population, individuals with congenital amusia show deficits in music perception and production. Congenital amusia occurs without brain damage, sensory or cognitive deficits, and has been suggested as a lifelong deficit with genetic origin. Even though recognized for a long time, this disorder has been systematically studied only relatively recently for its behavioral and neural correlates. The currently most investigated hypothesis about the underlying deficits concerns the pitch dimension, notably with impaired pitch discrimination and memory. Anatomic and functional investigations of pitch processing revealed that the amusic brain presents abnormalities in the auditory and inferior frontal cortices, associated with decreased connectivity between these structures. The deficit also impairs processing of pitch in speech material and processing of the time dimension in music for some of the amusic individuals, but does not seem to affect spatial processing. Some studies suggest at least partial dissociation in the disorder between perception and production. Recent studies revealed spared implicit pitch perception in congenital amusia, supporting the power of implicit cognition in the music domain. Current challenges consist in defining different subtypes of congenital amusia as well as developing rehabilitation programs for this "musical handicap." © 2015 Elsevier B.V. All rights reserved.

[CADASIL with cysteine-sparing NOTCH3 mutation manifesting as dissociated progression between cognitive impairment and brain image findings in 3 years: A case report].

PubMed

Tachiyama, Keisuke; Shiga, Yuji; Shimoe, Yutaka; Mizuta, Ikuko; Mizuno, Toshiki; Kuriyama, Masaru

2018-04-25

A 55-year-old man with no history of stroke or migraine presented to the clinic with cognitive impairment and depression that had been experiencing for two years. Neurological examination showed bilateral pyramidal signs, and impairments in cognition and attention. Brain MRI revealed multiple lacunar lesions and microbleeds in the deep cerebral white matter, subcortical regions, and brainstem, as well as diffuse white matter hyperintensities without anterior temporal pole involvement. Cerebral single-photon emission computed tomography (SPECT) revealed bilateral hypoperfusion in the basal ganglia. Gene analysis revealed an arginine-to-proline missense mutation in the NOTCH3 gene at codon 75. The patient was administered lomerizine (10 mg/day), but the patient's cognitive impairment and cerebral atrophy continued to worsen. Follow-up testing with MRI three years after his initial diagnosis revealed similar lacunar infarctions, cerebral microbleeds, and diffuse white matter hyperintensities to those observed three years earlier. However, MRI scans revealed signs of increased cerebral blood flow. Together, these findings suggest that the patient's cognitive impairments may have been caused by pathogenesis in the cerebral cortex.

Impact of parental acquired brain injury on children: Review of the literature and conceptual model.

PubMed

Tiar, Anna Maria Vitale; Dumas, Jean E

2015-01-01

Data on children's adjustment following parental acquired brain injury (ABI) are disparate and spare, and appear inconclusive. Nonetheless, they suggest that children's well-being is at risk, but often neglected. Indeed, lack of a unifying conceptual model makes it difficult to integrate available evidence, in order to circumscribe relevant factors and understand how these may influence children's outcomes in more or less favourable ways. The present review proposes the coping competence model as a theoretical framework apt to clarify these issues and organize the available evidence. In brief, the model states that impact of parental ABI on children reflects the extent of the challenges children face and their preponderant ways of coping with them, i.e. pro-socially, anti-socially or asocially. Evidence shows that children deal with some common socioaffective as well as achievement challenges. Further, it is consistent with the three main coping modalities supported by the model. Overall, children's outcomes appear variable, but clearly at risk and in need of special attention. This review summarizes these outcomes, raises conceptual as well as methodological questions to be addressed in future research and eventually presents relevant issues for support and clinical services.

Current Status of Nephron-Sparing Surgery (NSS) in the Management of Renal Tumours.

PubMed

Venkatramani, Vivek; Swain, Sanjaya; Satyanarayana, Ramgopal; Parekh, Dipen J

2017-06-01

Nephron-sparing surgery has emerged as the surgical treatment of choice for small renal masses over the past two decades, replacing the traditional teaching of radical nephrectomy for renal cell carcinoma. With time, there has been an evolution in the techniques and indications for partial nephrectomy. This review summarizes the current status of nephron-sparing surgery for renal carcinoma and also deals with the future of this procedure.

Cost Comparison of B-1B Non-Mission-Capable Drivers Using Finite Source Queueing with Spares

DTIC Science & Technology

2012-09-06

COMPARISON OF B-1B NON-MISSION-CAPABLE DRIVERS USING FINITE SOURCE QUEUEING WITH SPARES GRADUATE RESEARCH PAPER Presented to the Faculty...step into the lineup making large-number approximations unusable. Instead, a finite source queueing model including spares is incorporated...were reported as flying time accrued since last occurrence. Service time was given in both start-stop format and MX man-hours utilized. Service time was

Planning for Follow-On Spare Part Support by the Naval Electronic Systems Command.

DTIC Science & Technology

1984-06-01

System Replenishment Spare Parts", by Edward J. Brost , Air Force Institute of Technology [17]_ The objective of this study was to determine the...Competition in the Acquisition of Replenishment Spare Parts, M.S. Thesis, Air Force Institute of Technology, WPAFB, Ohio, September 1983. 17. Brost ...Instruction 4000.6D, Integrated Logistic Support (ILS); policy and responsibilities. 21 July 1983. 20. Mr. George Hughes, NAVELEX Code 81234

SNS Central Helium Liquefier spare Carbon Bed installation and commissioning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Degraff, Brian D.; Howell, Matthew P.; Kim, Sang-Ho

The Spallation Neutron Source (SNS) Central Helium Liquefier (CHL) at Oak Ridge National Laboratory (ORNL) has been without major operations downtime since operations were started back in 2006. This system utilizes a vessel filled with activated carbon as the final major component to remove oil vapor from the compressed helium circuit prior to insertion into the system's cryogenic cold box. The need for a spare carbon bed at SNS due to the variability of carbon media lifetime calculation to adsorption efficiency will be discussed. The fabrication, installation and commissioning of this spare carbon vessel will be presented. The novel planmore » for connecting the spare carbon vessel piping to the existing infrastructure will be presented.« less

Graft-Sparing Strategy for Thoracic Prosthetic Graft Infection.

PubMed

Uchino, Gaku; Yoshida, Takeshi; Kakii, Bunpachi; Furui, Masato

2018-04-01

 Thoracic prosthetic graft infection is a rare but serious complication with no standard management. We reported our surgical experience on graft-sparing strategy for thoracic prosthetic graft infection.  This study included patients who underwent graft-sparing surgery for thoracic prosthetic graft infection at Matsubara Tokushukai Hospital in Japan from January 2000 to October 2017.  There were 17 patients included in the analyses, with a mean age at surgery of 71.0 ± 10.5 years; 11 were men. In-hospital mortality was observed in five patients (29.4%).  Graft-sparing surgery for thoracic prosthetic graft infection is an alternative option particularly for early graft infection after hemiarch replacement. Georg Thieme Verlag KG Stuttgart · New York.

SU-F-T-335: Piecewise Uniform Dose Prescription and Optimization Based On PET/CT Images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, G; Liu, J

Purpose: In intensity modulated radiation therapy (IMRT), the tumor target volume is given a uniform dose prescription, which does not consider the heterogeneous characteristics of tumor such as hypoxia, clonogen density, radiosensitivity, tumor proliferation rate and so on. Our goal is to develop a nonuniform target dose prescription method which can spare organs at risk (OARs) better and does not decrease the tumor control probability (TCP). Methods: We propose a piecewise uniform dose prescription (PUDP) based on PET/CT images of tumor. First, we propose to delineate biological target volumes (BTV) and sub-biological target volumes (sub-BTVs) by our Hierarchical Mumford-Shah Vectormore » Model based on PET/CT images of tumor. Then, in order to spare OARs better, we make the BTV mean dose minimized while restrict the TCP to a constant. So, we can get a general formula for determining an optimal dose prescription based on a linearquadratic model (LQ). However, this dose prescription is high heterogeneous, it is very difficult to deliver by IMRT. Therefore we propose to use the equivalent uniform dose (EUD) in each sub-BTV as its final dose prescription, which makes a PUDP for the BTV. Results: We have evaluated the IMRT planning of a patient with nasopharyngeal carcinoma respectively using PUDP and UDP. The results show that the highest and mean doses inside brain stem are 48.425Gy and 19.151Gy respectively when the PUDP is used for IMRT planning, while they are 52.975Gy and 20.0776Gy respectively when the UDP is used. Both of the resulting TCPs(0.9245, 0.9674) are higher than the theoretical TCP(0.8739), when 70Gy is delivered to the BTV. Conclusion: Comparing with the UDP, the PUDP can spare the OARs better while the resulting TCP by PUDP is not significantly lower than by UDP. This work was supported in part by National Natural Science Foundation of China undergrant no.61271382 and by the foundation for construction of scientific project platform forthe cancer hospital of Hunan province.« less