Single-session and multisession CyberKnife radiosurgery for spine metastases-University of Pittsburgh and Georgetown University experience.

Object: The authors compared the effectiveness of single-session (SS) and multisession (MS) stereotactic radiosurgery (SRS) for the treatment of spinal metastases.

Methods: The authors conducted a retrospective review of the clinical outcomes of 348 lesions in 228 patients treated with the CyberKnife radiosurgery at the University of Pittsburgh Cancer Institute and Georgetown University Medical Center. One hundred ninety-five lesions were treated using an SS treatment regimen (mean 16.

A retrospective, deformable registration analysis of the impact of PET-CT planning on patterns of failure in stereotactic body radiation therapy for recurrent head and neck cancer.

Background: Stereotactic body radiation therapy (SBRT) has seen increasing use as a salvage strategy for selected patients with recurrent, previously-irradiated squamous cell carcinoma of the head and neck (rSCCHN). PET-CT may be advantageous for tumor delineation and evaluation of treatment failures in SBRT. We analyzed the patterns of failure following SBRT for rSCCHN and assessed the impact of PET-CT treatment planning on these patterns of failure.

Differences in the in vitro and in vivo pharmacokinetic profiles of once-daily modified-release methylphenidate formulations in Canada: examination of current bioequivalence criteria.

Background: Current Canadian bioequivalence criteria rely on rate and extent of drug exposure, that is, C(max) and AUC. In the case of complex modified-release formulations, these criteria may not address pharmacokinetic differences with potential therapeutic and tolerability implications.

Objective: This study was performed to characterize in vitro dissolution and in vivo pharmacokinetic profiles of three modified-release formulations of methylphenidate (MPH) marketed in Canada, two of which meet the criteria for assuming bioequivalence as defined by Health Canada: MPH extended-release (ER-C) and osmotic controlled-release oral-delivery-system (OROS-MPH).

Insights into the pathophysiology of the antiphospholipid syndrome provided by atomic force microscopy.

The antiphospholipid syndrome (APS) is an enigmatic autoimmune disorder in which patients present with thrombosis and/or recurrent pregnancy losses together with laboratory evidence for the presence of autoantibodies in the blood that recognize proteins that bind to anionic phospholipids - the most important of which is β(2)-glycoprotein I (β(2)GPI). Earlier, we hypothesized that the clinical manifestations arise from antibody-induced disruption of a two-dimensional anticoagulant crystal shield, composed of annexin A5, present on placental trophoblast plasma membranes. Accordingly, we reasoned that a high resolution imaging technology, such as atomic force microscopy could be used to investigate such molecular interactions at high resolution in a non-fixed hydrated environment.

Mechanical constraint and release generates long, ordered horizontal pores in anodic alumina templates.

We describe the formation of long, highly ordered arrays of planar oriented anodic aluminum oxide (AAO) pores during plane parallel anodization of thin aluminum 'finger' microstructures fabricated on thermally oxidized silicon substrates and capped with a silicon oxide layer. The pore morphology was found to be strongly influenced by mechanical constraint imposed by the oxide layers surrounding the Al fingers. Tractions induced by the SiO(2) substrate and capping layer led to frustrated volume expansion and restricted oxide flow along the interface, with extrusion of oxide into the primary pore volume, leading to the formation of dendritic pore structures and meandering pore growth.

SCD1 inhibition causes cancer cell death by depleting mono-unsaturated fatty acids.

Increased metabolism is a requirement for tumor cell proliferation. To understand the dependence of tumor cells on fatty acid metabolism, we evaluated various nodes of the fatty acid synthesis pathway. Using RNAi we have demonstrated that depletion of fatty-acid synthesis pathway enzymes SCD1, FASN, or ACC1 in HCT116 colon cancer cells results in cytotoxicity that is reversible by addition of exogenous fatty acids.

Scanning the potential energy surface for synthesis of dendrimer-wrapped gold clusters: design rules for true single-molecule nanostructures.

The formation of true single-molecule complexes between organic ligands and nanoparticles is challenging and requires careful design of molecules with size, shape, and chemical properties tailored for the specific nanoparticle. Here we use computer simulations to describe the atomic-scale structure, dynamics, and energetics of ligand-mediated synthesis and interlinking of 1 nm gold clusters. The models help explain recent experimental results and provide insight into how multidentate thioether dendrimers can be employed for synthesis of true single-ligand-nanoparticle complexes and also nanoparticle-molecule-nanoparticle "dumbbell" nanostructures.

Perspectives on the discovery of small-molecule modulators for epigenetic processes.

Epigenetic gene regulation is a critical process controlling differentiation and development, the malfunction of which may underpin a variety of diseases. In this article, we review the current landscape of small-molecule epigenetic modulators including drugs on the market, key compounds in clinical trials, and chemical probes being used in epigenetic mechanistic studies. Hit identification strategies for the discovery of small-molecule epigenetic modulators are summarized with respect to writers, erasers, and readers of histone marks.

Lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage: a prospective, randomized, controlled trial (LUMAS).

Background And Purpose: A single-center prospective randomized controlled trial has been conducted to determine if lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage reduces the prevalence of delayed ischemic neurological deficit and improves clinical outcome.

Methods: Patients with World Federation of Neurological Surgeons Grade 1 to 3 aneurysmal subarachnoid hemorrhage and modified Fisher Grades 2, 3, 4, and 3+4 were randomized to either the study group of standard therapy plus insertion of a lumbar drain or the control group of standard therapy alone. The primary outcome measure was the prevalence of delayed ischemic neurological deficit.

Enzyme activity evaluation of organic solvent-treated phenylalanine ammonia lyase.

The direct one-step synthesis of L-phenylalanine methyl ester in an organic-aqueous biphasic system using phenylalanine ammonia lyase (E.C.4.

Controllable selective exfoliation of high-quality graphene nanosheets and nanodots by ionic liquid assisted grinding.

Bulk quantities of graphene nanosheets and nanodots have been selectively fabricated by mechanical grinding exfoliation of natural graphite in a small quantity of ionic liquids. The resulting graphene sheets and dots are solvent free with low levels of naturally absorbed oxygen, inherited from the starting graphite. The sheets are only two to five layers thick.

InterPro in 2011: new developments in the family and domain prediction database.

InterPro (http://www.ebi.ac.

Stereotactic body radiation therapy for locally recurrent, previously irradiated nonsquamous cell cancers of the head and neck.

Background: Stereotactic body radiotherapy (SBRT) has emerged as a promising salvage strategy for patients with recurrent, previously irradiated head and neck cancer; however, data are limited predominantly to squamous cell carcinomas. Herein, we report the efficacy of SBRT in recurrent, nonsquamous cell cancers of the head and neck (NSCHNs).

Methods: In all, 34 patients with pathologically proven NSCHN were re-irradiated with SBRT to a median dose of 40 Gy in 5 fractions (interquartile range, 30-44 Gy).

Megavoltage cone beam CT near surface dose measurements: potential implications for breast radiotherapy.

Purpose: Cone beam computed tomography (CBCT) is fast becoming standard on modern linear accelerators. CBCT increases the dose to regions within and outside the treatment field, potentially increasing secondary cancer induction and toxicity. This study quantified megavoltage (MV) CBCT skin dose and compared it to skin dose delivered during standard tangential breast radiotherapy.

Methods for Activity Analysis of the Proteins that Regulate Histone Methylation.

The enzymes that regulate histone methylation states and the protein domains that recognize methylated histone residues have been implicated in a number of human diseases, including cancer, as a result of their ability to affect transcriptional changes by altering chromatin structure. These proteins are recognized as potential therapeutic targets for the treatment of diseases associated with epigenetic disruption; however, few inhibitors of their activity have been identified. The majority of histone demethylase and methyltransferase enzyme inhibitors have been discovered on the basis of their structural similarity to substrates or known inhibitors of enzymes with analogous mechanisms.

A novel aza-anthrapyrazole blocks the progression of experimental autoimmune encephalomyelitis after the priming of autoimmunity.

Mitoxantrone is one of the few FDA-approved drugs available to treat rapidly progressing forms of multiple sclerosis; however, its utilization is compromised by a cardiotoxic potential and the risk of mitoxantrone-induced leukemia. BBR3378, a novel aza-anthrapyrazole, is structurally similar to mitoxantrone, but lacks the ring hydroxyls that may contribute to cardiotoxicity. Here, we investigated the therapeutic activity of BBR3378 in a C57BL/6 mouse model of multiple sclerosis.

Screening for EGFR and KRAS mutations in endobronchial ultrasound derived transbronchial needle aspirates in non-small cell lung cancer using COLD-PCR.

EGFR mutations correlate with improved clinical outcome whereas KRAS mutations are associated with lack of response to tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC). Endobronchial ultrasound (EBUS)-transbronchial needle aspiration (TBNA) is being increasingly used in the management of NSCLC. Co-amplification at lower denaturation temperature (COLD)-polymerase chain reaction (PCR) (COLD-PCR) is a sensitive assay for the detection of genetic mutations in solid tumours.

Specificity of human aldo-keto reductases, NAD(P)H:quinone oxidoreductase, and carbonyl reductases to redox-cycle polycyclic aromatic hydrocarbon diones and 4-hydroxyequilenin-o-quinone.

Polycyclic aromatic hydrocarbons (PAHs) are suspect human lung carcinogens and can be metabolically activated to remote quinones, for example, benzo[a]pyrene-1,6-dione (B[a]P-1,6-dione) and B[a]P-3,6-dione by the action of either P450 monooxygenase or peroxidases, and to non-K region o-quinones, for example B[a]P-7,8-dione, by the action of aldo keto reductases (AKRs). B[a]P-7,8-dione also structurally resembles 4-hydroxyequilenin o-quinone. These three classes of quinones can redox cycle, generate reactive oxygen species (ROS), and produce the mutagenic lesion 8-oxo-dGuo and may contribute to PAH- and estrogen-induced carcinogenesis.

Roundtable on Urban Living Environment Research (RULER).

For 18 months in 2009-2010, the Rockefeller Foundation provided support to establish the Roundtable on Urban Living Environment Research (RULER). Composed of leading experts in population health measurement from a variety of disciplines, sectors, and continents, RULER met for the purpose of reviewing existing methods of measurement for urban health in the context of recent reports from UN agencies on health inequities in urban settings. The audience for this report was identified as international, national, and local governing bodies; civil society; and donor agencies.

Single nanoskived nanowires for electrochemical applications.

In this work, we fabricate gold nanowires with well controlled critical dimensions using a recently demonstrated facile approach termed nanoskiving. Nanowires are fabricated with lengths of several hundreds of micrometers and are easily electrically contacted using overlay electrodes. Following fabrication, nanowire device performance is assessed using both electrical and electrochemical characterization techniques.

IL-13Rα1 expression on β-cell-specific T cells in NOD mice.

Objective: Immunotherapy using peptides from the β-cell antigen GAD65 can preserve glucose homeostasis in diabetes-prone NOD mice; however, the precise mechanisms that arrest islet-reactive T cells remain unresolved. Our previous work revealed that a dominant GAD65 epitope contained two overlapping I-A(g7)-restricted determinants, 524-538 and 530-543, with the former associated with amelioration of hyperglycemia. Here, we sought to discover whether p524-538-specific T cells could directly regulate islet-reactive T cells.

Psychometric evaluation of the functional walking test for children with cerebral palsy.

Purpose: This study examined the psychometric properties of the functional walking test (FWT).

Method: Fifty-six subjects with cerebral palsy (CP) (21 females and 35 males, mean age 9 years 6 months, SD 3 years 9 months, range 4-17 years) were assessed on two occasions, 6 months apart, using both the FWT and the gross motor function measure (GMFM).

Results: Generalisability correlation coefficients (GCC) for all 11 items were high (0.

Quality of life in thyroid eye disease: impact of quality of care.

Thyroid eye disease (TED) is a chronic debilitating condition causing physical discomfort, facial disfigurement and impaired visual function. The physical consequences of TED could have a negative and lasting impact on patients' employment, hobbies and psychosocial function. In this review, we assess the evidence of the impact of TED on patients' quality of life (QOL) and also explore the effects of suboptimal quality of care on QOL of patients with this disease.

Surface dosimetry for breast radiotherapy in the presence of immobilization cast material.

Curative breast radiotherapy typically leaves patients with varying degrees of cosmetic damage. One problem interfering with cosmetically acceptable breast radiotherapy is the external contour for large pendulous breasts which often results in high doses to skin folds. Thermoplastic casts are often employed to secure the breasts to maintain setup reproducibility and limit the presence of skin folds.