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[PMID]: 25549194
[Au] Autor:Swanson KI; Clark PA; Zhang RR; Kandela IK; Farhoud M; Weichert JP; Kuo JS
[Ad] Address:*Department of Neurological Surgery, ‡Cellular and Molecular Biology Training Program, ¶Department of Radiology, ‖Department Medical Physics, and #Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; §Cellectar Biosciences, Inc, Madison, Wisconsin; **Department of Surgery, National University of Singapore, Singapore.
[Ti] Title:Fluorescent cancer-selective alkylphosphocholine analogs for intraoperative glioma detection.
[So] Source:Neurosurgery;76(2):115-24, 2015 Feb.
[Is] ISSN:1524-4040
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: 5-Aminolevulinic acid (5-ALA)-induced tumor fluorescence aids brain tumor resections but is not approved for routine use in the United States. We developed and describe testing of 2 novel fluorescent, cancer-selective alkylphosphocholine analogs, CLR1501 (green) and CLR1502 (near infrared), in a proof-of-principle study for fluorescence-guided glioma surgery. OBJECTIVE: To demonstrate that CLR1501 and CLR1502 are cancer cell-selective fluorescence agents in glioblastoma models and to compare tumor-to-normal brain (T:N) fluorescence ratios with 5-ALA. METHODS: CLR1501, CLR1502, and 5-ALA were administered to mice with magnetic resonance imaging-verified orthotopic U251 glioblastoma multiforme- and glioblastoma stem cell-derived xenografts. Harvested brains were imaged with confocal microscopy (CLR1501), the IVIS Spectrum imaging system (CLR1501, CLR1502, and 5-ALA), or the Fluobeam near-infrared fluorescence imaging system (CLR1502). Imaging and quantitative analysis of T:N fluorescence ratios were performed. RESULTS: Excitation/emission peaks are 500/517 nm for CLR1501 and 760/778 nm for CLR1502. The observed T:N ratio for CLR1502 (9.28 ± 1.08) was significantly higher (P < .01) than for CLR1501 (3.51 ± 0.44 on confocal imaging; 7.23 ± 1.63 on IVIS imaging) and 5-ALA (4.81 ± 0.92). Near-infrared Fluobeam CLR1502 imaging in a mouse xenograft model demonstrated high- contrast tumor visualization compatible with surgical applications. CONCLUSION: CLR1501 (green) and CLR1502 (near infrared) are novel tumor-selective fluorescent agents for discriminating tumor from normal brain. CLR1501 exhibits a tumor-to-brain fluorescence ratio similar to that of 5-ALA, whereas CLR1502 has a superior tumor-to-brain fluorescence ratio. This study demonstrates the potential use of CLR1501 and CLR1502 in fluorescence-guided tumor surgery. ABBREVIATIONS: APC, alkylphosphocholine5-ALA, 5-aminolevulinic acidGBM, glioblastoma multiformeGSC, glioblastoma stem cellGTR, gross total resectionHGG, high-grade gliomaPBS, phosphate-buffered solutionPpIX, protoporphyrin IXT:N, tumor to normal brain.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1501
[Cu] Class update date: 150117
[Lr] Last revision date:150117
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1227/NEU.0000000000000622

  2 / 1257092 MEDLINE  
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[PMID]: 25255260
[Au] Autor:Chohan MO; Bragina O; Kazim SF; Statom G; Baazaoui N; Bragin D; Iqbal K; Nemoto E; Yonas H
[Ad] Address:*Department of Neurosurgery, University of New Mexico Hospital, Albuquerque, New Mexico; ‡Department of Neurochemistry, Inge Grundke-Iqbal Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York; §Neural and Behavioral Science Graduate Program, State University of New York (SUNY) Downstate Medical Center, Brooklyn, New York.
[Ti] Title:Enhancement of neurogenesis and memory by a neurotrophic Peptide in mild to moderate traumatic brain injury.
[So] Source:Neurosurgery;76(2):201-15, 2015 Feb.
[Is] ISSN:1524-4040
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Traumatic brain injury (TBI) is a risk factor for Alzheimer disease (AD), a neurocognitive disorder with similar cellular abnormalities. We recently discovered a small molecule (Peptide 6) corresponding to an active region of human ciliary neurotrophic factor, with neurogenic and neurotrophic properties in mouse models of AD and Down syndrome. OBJECTIVE: To describe hippocampal abnormalities in a mouse model of mild to moderate TBI and their reversal by Peptide 6. METHODS: TBI was induced in adult C57Bl6 mice using controlled cortical impact with 1.5 mm of cortical penetration. The animals were treated with 50 nmol/d of Peptide 6 or saline solution for 30 days. Dentate gyrus neurogenesis, dendritic and synaptic density, and AD biomarkers were quantitatively analyzed, and behavioral tests were performed. RESULTS: Ipsilateral neuronal loss in CA1 and the parietal cortex and increase in Alzheimer-type hyperphosphorylated tau and A-ß were seen in TBI mice. Compared with saline solution, Peptide 6 treatment increased the number of newborn neurons, but not uncommitted progenitor cells, in dentate gyrus by 80%. Peptide 6 treatment also reversed TBI-induced dendritic and synaptic density loss while increasing activity in tri-synaptic hippocampal circuitry, ultimately leading to improvement in memory recall on behavioral testing. CONCLUSION: Long-term treatment with Peptide 6 enhances the pool of newborn neurons in the dentate gyrus, prevents neuronal loss in CA1 and parietal cortex, preserves the dendritic and synaptic architecture in the hippocampus, and improves performance on a hippocampus-dependent memory task in TBI mice. These findings necessitate further inquiry into the therapeutic potential of small molecules based on neurotrophic factors. ABBREVIATIONS: AD, Alzheimer diseaseBrdU, bromodeoxyuridineBrdU-IR, bromodeoxyuridine immunoreactiveBrdU-NeuN-IR, BrdU-NeuN immunoreactive cellsCCI, controlled cortical impactCNTF, ciliary neurotrophic factorDG, dentate gyrusGCL, granular cell layerLIF, leukemia inhibitory factorMAP2, microtubule-associated protein 2MWM, Morris water mazeSEM, standard error of the meanTBI, traumatic brain injury.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1501
[Cu] Class update date: 150117
[Lr] Last revision date:150117
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1227/NEU.0000000000000577

  3 / 1257092 MEDLINE  
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[PMID]: 25514108
[Au] Autor:FitzGerald TH; Schwartenbeck P; Moutoussis M; Dolan RJ; Friston K
[Ad] Address:Wellcome Trust Centre for Neuroimaging, UCL, London, WC1N 3BG, U.K. thomas.fitzgerald@ucl.ac.uk.
[Ti] Title:Active inference, evidence accumulation, and the urn task.
[So] Source:Neural Comput;27(2):306-28, 2015 Feb.
[Is] ISSN:1530-888X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Deciding how much evidence to accumulate before making a decision is a problem we and other animals often face, but one that is not completely understood. This issue is particularly important because a tendency to sample less information (often known as reflection impulsivity) is a feature in several psychopathologies, such as psychosis. A formal understanding of information sampling may therefore clarify the computational anatomy of psychopathology. In this theoretical letter, we consider evidence accumulation in terms of active (Bayesian) inference using a generic model of Markov decision processes. Here, agents are equipped with beliefs about their own behavior-in this case, that they will make informed decisions. Normative decision making is then modeled using variational Bayes to minimize surprise about choice outcomes. Under this scheme, different facets of belief updating map naturally onto the functional anatomy of the brain (at least at a heuristic level). Of particular interest is the key role played by the expected precision of beliefs about control, which we have previously suggested may be encoded by dopaminergic neurons in the midbrain. We show that manipulating expected precision strongly affects how much information an agent characteristically samples, and thus provides a possible link between impulsivity and dopaminergic dysfunction. Our study therefore represents a step toward understanding evidence accumulation in terms of neurobiologically plausible Bayesian inference and may cast light on why this process is disordered in psychopathology.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1501
[Cu] Class update date: 150117
[Lr] Last revision date:150117
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1162/NECO_a_00699

  4 / 1257092 MEDLINE  
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[PMID]: 25360773
[Au] Autor:Dileep Kumar JS; Mann JJ
[Ti] Title:PET Tracers for Serotonin Receptors and Their Applications.
[So] Source:Cent Nerv Syst Agents Med Chem;14(2):96-112, 2014.
[Is] ISSN:1875-6166
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Serotonin receptors (5-HTRs) are implicated in the pathophysiology of a variety of neuropsychiatric and neurodegenerative disorders and are also targets for drug therapy. In the CNS, most of these receptors are expressed in high abundance in specific brain regions reflecting their role in brain functions. Quantifying binding to 5-HTRs in vivo may permit assessment of physiologic and pathologic conditions, and monitoring disease progression, evaluating treatment response, and for investigating new treatment modalities. Positron emission tomography (PET) molecular imaging has the sensitivity to quantify binding of 5-HTRs in CNS disorders and to measure drug occupancy as part of a process of new drug development. Although research on PET imaging of 5-HTRs have been performed more than two decades, the successful radiotracers so far developed for human studies are limited to 5-HT1AR, 5-HT1BR, 5-HT2AR, 5-HT4R and 5-HT6R. Herein we review the development and application of radioligands for PET imaging of 5-HTRs in living brain.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1501
[Cu] Class update date: 150117
[Lr] Last revision date:150117
[Js] Journal subset:IM
[St] Status:In-Data-Review

  5 / 1257092 MEDLINE  
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[PMID]: 25592457
[Au] Autor:Church CC; Labuda C; Nightingale K
[Ad] Address:National Center for Physical Acoustics and Department of Physics and Astronomy, University of Mississippi, University, Mississippi, USA. Electronic address: cchurch@olemiss.edu.
[Ti] Title:A theoretical study of inertial cavitation from acoustic radiation force impulse imaging and implications for the mechanical index.
[So] Source:Ultrasound Med Biol;41(2):472-85, 2015 Feb.
[Is] ISSN:1879-291X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The mechanical index (MI) attempts to quantify the likelihood that exposure to diagnostic ultrasound will produce an adverse biological effect by a non-thermal mechanism. The current formulation of the MI implicitly assumes that the acoustic field is generated using the short pulse durations appropriate to B-mode imaging. However, acoustic radiation force impulse (ARFI) imaging employs high-intensity pulses up to several hundred acoustic periods long. The effect of increased pulse durations on the thresholds for inertial cavitation was studied computationally in water, urine, blood, cardiac and skeletal muscle, brain, kidney, liver and skin. The results indicate that, although the effect of pulse duration on cavitation thresholds in the three liquids can be considerable, reducing them by, for example, 6%-24% at 1 MHz, the effect on tissue is minor. More importantly, the frequency dependence of the MI appears to be unnecessarily conservative; that is, the magnitude of the exponent on frequency could be increased to 0.75. Comparison of these theoretical results with experimental measurements suggests that some tissues do not contain the pre-existing, optimally sized bubbles assumed for the MI. This means that in these tissues, the MI is not necessarily a strong predictor of the probability of an adverse biological effect.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1501
[Cu] Class update date: 150117
[Lr] Last revision date:150117
[Js] Journal subset:IM
[St] Status:In-Data-Review

  6 / 1257092 MEDLINE  
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[PMID]: 25376607
[Au] Autor:Meisen WH; Dubin S; Sizemore ST; Mathsyaraja H; Thies K; Lehman NL; Boyer P; Jaime-Ramirez AC; Elder JB; Powell K; Chakravarti A; Ostrowski MC; Kaur B
[Ad] Address:Department of Neurological Surgery, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio....
[Ti] Title:Changes in BAI1 and Nestin Expression Are Prognostic Indicators for Survival and Metastases in Breast Cancer and Provide Opportunities for Dual Targeted Therapies.
[So] Source:Mol Cancer Ther;14(1):307-14, 2015 Jan.
[Is] ISSN:1538-8514
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The 2-year survival rate of patients with breast cancer brain metastases is less than 2%. Treatment options for breast cancer brain metastases are limited, and there is an unmet need to identify novel therapies for this disease. Brain angiogenesis inhibitor 1 (BAI1) is a GPCR involved in tumor angiogenesis, invasion, phagocytosis, and synaptogenesis. For the first time, we identify that BAI1 expression is significantly reduced in breast cancer and higher expression is associated with better patient survival. Nestin is an intermediate filament whose expression is upregulated in several cancers. We found that higher Nestin expression significantly correlated with breast cancer lung and brain metastases, suggesting both BAI1 and Nestin can be therapeutic targets for this disease. Here, we demonstrate the ability of an oncolytic virus, 34.5ENVE, to target and kill high Nestin-expressing cells and deliver Vstat120 (extracellular fragment of BAI1). Finally, we created two orthotopic immune-competent murine models of breast cancer brain metastases and demonstrated 34.5ENVE extended the survival of immune-competent mice bearing intracranial breast cancer tumors. Mol Cancer Ther; 14(1); 307-14. ©2014 AACR.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1501
[Cu] Class update date: 150117
[Lr] Last revision date:150117
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1158/1535-7163.MCT-14-0659

  7 / 1257092 MEDLINE  
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[PMID]: 25589983
[Au] Autor:Xiong F; Wang S; Kai J
[Ad] Address:Department of Thoracic Surgery, Hubei Cancer Hospital, Wuhan 430000, China.
[Ti] Title:Video-assisted thoracic surgery right sleeve lobectomy.
[So] Source:J Thorac Dis;6(12):1831-3, 2014 Dec.
[Is] ISSN:2072-1439
[Cp] Country of publication:China
[La] Language:eng
[Ab] Abstract:A 50-year-old active male with a smoking history of 30 years (20 cigarettes per day) was admitted to hospital because of more than one month's cough without sputum. No comorbidity was present. The preoperative examination showed: blood test normal, ECG normal, cardio-pulmonary function normal, chest computed tomography (CT) display right upper lobe (RUL) mass of 5 cm diameter. Bronchoscopy examination and biopsy indicated large cell neuroendocrine carcinoma (LCNEC) in the take-off of RUL bronchus. No metastatic focus was found after emission computed tomography (ECT) scan of whole body bone, abdominal US scanning and brain MR. After initial evaluation, the clinical stage before operation was cT2bN0M0 (IIA stage). A selective video-assisted thoracic surgery (VATS) operation was arranged after 9 days of smoking cessation. Lateral position, one 10 mm trocar for camera in the 7th intercostals space in the mid-auxiliary line, 4 cm trocar for operation in the 4th intercostal space in the anterior axillary line, 15 mm trocar for auxiliary operation in the 8th intercostal space in the scapula line, the patient received VATS RUL lobectomy, plus systemic mediastinal lymph nodes dissection. The procedure of 200 minutes operation was smooth with blood loss of about 150 mL. Chest tube was removed 6 days after operation, and the patient discharged 11 days after the operation; The post-operation pathological examination showed RUL LCNEC, and the pathological stage was pT2bN0M0R0 (IIA stage). The patient has received four cycles of EP adjuvant chemotherapy per 21 days and is still alive without disease recurrence and metastasis after re-examination.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1501
[Cu] Class update date: 150117
[Lr] Last revision date:150117
[Da] Date of entry for processing:150115
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.3978/j.issn.2072-1439.2014.12.03

  8 / 1257092 MEDLINE  
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[PMID]: 25589537
[Au] Autor:Tailor J; Jaunmuktane Z; Brandner S; Sethi H
[Ad] Address:Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, London, UK jignesh.tailor@nhs.net....
[Ti] Title:Supratentorial ependymoma presenting as a cortical cyst with a mural nodule in an adult.
[So] Source:J Surg Case Rep;2015(1), 2015.
[Is] ISSN:2042-8812
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Supratentorial ependymoma is a rare tumour in the adult central nervous system. We present an unusual case of supratentorial ependymoma in a young adult that presented as a pure cortical cyst with a mural nodule and discuss the differential diagnosis of such lesions in the brain.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1501
[Cu] Class update date: 150117
[Lr] Last revision date:150117
[Da] Date of entry for processing:150115
[St] Status:PubMed-not-MEDLINE

  9 / 1257092 MEDLINE  
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[PMID]: 25227316
[Au] Autor:McClure R; Yanagisawa D; Stec D; Abdollahian D; Koktysh D; Xhillari D; Jaeger R; Stanwood G; Chekmenev E; Tooyama I; Gore JC; Pham W
[Ad] Address:Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA Department of Radiology and Radiological Sciences, Vanderbilt School of Medicine, Nashville, TN, USA Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA....
[Ti] Title:Inhalable curcumin: offering the potential for translation to imaging and treatment of Alzheimer's disease.
[So] Source:J Alzheimers Dis;44(1):283-95, 2015 Jan 1.
[Is] ISSN:1875-8908
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Curcumin is a promising compound that can be used as a theranostic agent to aid research in Alzheimer's disease. Beyond its ability to bind to amyloid plaques, the compound can also cross the blood-brain barrier. Presently, curcumin can be applied only to animal models, as the formulation needed for iv injection renders it unfit for human use. Here, we describe a novel technique to aerosolize a curcumin derivative, FMeC1, and facilitate its safe delivery to the brain. Aside from the translational applicability of this approach, a study in the 5XFAD mouse model suggested that inhalation exposure to an aerosolized FMeC1 modestly improved the distribution of the compound in the brain. Additionally, immunohistochemistry data confirms that following aerosol delivery, FMeC1 binds amyloid plaques expressed in the hippocampal areas and cortex.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1501
[Cu] Class update date: 150117
[Lr] Last revision date:150117
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.3233/JAD-140798

  10 / 1257092 MEDLINE  
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[PMID]: 25213770
[Au] Autor:Riverol M; Becker JT; López OL; Raji CA; Thompson PM; Carmichael OT; Gach HM; Longstreth WT; Fried L; Tracy RP; Kuller LH
[Ad] Address:Department of Neurology, University of Navarra, Pamplona, Spain Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA....
[Ti] Title:Relationship between Systemic and Cerebral Vascular Disease and Brain Structure Integrity in Normal Elderly Individuals.
[So] Source:J Alzheimers Dis;44(1):319-28, 2015 Jan 1.
[Is] ISSN:1875-8908
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Cerebral white matter lesions (WMLs) are considered a reflection of cerebral and systemic small vessel disease (SVD), and are associated with reductions in brain volume. Like the brain, the kidney is also sensitive to factors that affect vasculature. Glomerular dysfunction due to renal vascular damage can be measured with different biochemical parameters, such as creatinine or cystatin C, although cystatin C is considered to be more accurate than creatinine in the elderly. The purpose of the study was to determine whether manifestations of SVD in the kidney can predict SVD-based damage to the brain. We examined the relationship between glomerular dysfunction as a measure of SVD on WMLs, gray matter (GM) volume, and cognition in 735 cognitively normal participants from the Cardiovascular Health Study Cognition Study. The multivariate analyses controlled for demographic characteristics, hypertension, heart disease, diabetes, Apolipoprotein 4 allele, C reactive protein, lipids, physical activity, smoking, and body mass index (BMI). Elevated cystatin C levels were associated with lower neuropsychological test scores, the presence of MRI-identified brain infarcts, the severity of WMLs, and GM atrophy five years later. In adjusted models, GM volume was significantly associated with cystatin-C only until BMI and severity of WMLs were added to the model, meaning that the effect of SVD on GM volume is mediated by these two variables. These findings suggest that age-related SVD is a process that leads to altered brain structure, and creates a vulnerability state for cognitive decline.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1501
[Cu] Class update date: 150117
[Lr] Last revision date:150117
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.3233/JAD-141077


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