Dosimetric Evaluation of a New Rotating Gamma System for Stereotactic Radiosurgery

Purpose: A novel rotating gamma stereotactic radiosurgery (SRS) system (Galaxy RTi) with real-time image guidance technology has been developed for high-precision SRS and frameless fractionated stereotactic radiotherapy (SRT). This work investigated the dosimetric quality of Galaxy by comparing both the machine treatment parameters and plan dosimetry parameters with those of the widely used Leksell Gamma Knife (LGK) systems for SRS. Methods: The Galaxy RTi system uses 30 cobalt-60 sources on a rotating gantry to deliver non-coplanar, non-overlapping arcs simultaneously while the LGK 4C uses 201 static cobalt-60 sources to deliver noncoplanar beams. Ten brain cancer patients were unarchived from our clinical database, which were previously treated on the LGK 4C. The lesion volume for these cases varied from 0.1 cm3 to 15.4 cm3. Galaxy plans were generated using the Prowess TPS (Prowess, Concord, CA) with the same dose constraints and optimization parameters. Treatment quality metrics such as target coverage (%volume receiving the prescription dose), conformity index (CI), cone size, shots number, beam-on time were compared together with DVH curves and dose distributions. Results: Superior treatment plans were generated for the Galaxy system that met our clinical acceptance criteria. For the 10 patients investigated, the mean CI and dose coverage for Galaxy was 1.77 and 99.24 compared to 1.94 and 99.19 for LGK, respectively. The beam-on time for Galaxy was 17.42 minutes compared to 21.34 minutes for LGK (both assuming dose rates at the initial installation). The dose fall-off is much faster for Galaxy, compared with LGK. Conclusion: The Galaxy RTi system can provide dose distributions with similar quality to that of LGK with less beam-on time and faster dose fall-off. The system is also capable of real-time image guidance at treatment position to ensure accurate dose delivery for SRS.Comment: 14 pages, 7 figure

On Holographic description of the Kerr-Newman-AdS-dS black holes

In this paper, we study the holographic description of the generic four-dimensional non-extremal Kerr-Newman-AdS-dS black holes. We find that if focusing on the near-horizon region, for the massless scalar scattering in the low-frequency limit, there exists hidden conformal symmetry on the solution space. Similar to the Kerr case, this suggests that the Kerr-Newman-AdS-dS black hole is dual to a two-dimensional CFT with central charges $c_L=c_R=\frac{6a(r_++r_\ast)}{k}$ and temperatures $T_L=\frac{k(r_+^2+r_\ast^2+2a^2)}{4\pi a\Xi(r_++r_\ast)}, T_R=\frac{k(r_+-r_\ast)}{4\pi a\Xi}$. The macroscopic Bekenstein-Hawking entropy could be recovered from the microscopic counting in dual CFT via the Cardy formula. Using the Minkowski prescription, we compute the real-time correlators of the scalar, photon and graviton in near horizon geometry of near extremal Kerr-AdS-dS black hole. In all these cases, the retarded Green's function and the corresponding absorption cross section are in perfect match with CFT prediction. We further discuss the low-frequency scattering of a charged scalar by a Kerr-Newman-AdS-dS black hole and find the dual CFT description.Comment: 22 pages; minor corrections, conlusion unchanged, references added;published versio

Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells

Cell microparticles (MPs) released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5), and serotype 35 (HAdV35), respectively. We found that MPs derived from CHO cells (MP-donor cells) constitutively expressing CAR (MP-CAR) or CD46 (MP-CD46) were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR) were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins

Anti-epileptic effect of Ganoderma lucidum polysaccharides by inhibition of intracellular calcium accumulation and stimulation of expression of CaMKII a in epileptic hippocampal neurons

Purpose: To investigate the mechanism of the anti-epileptic effect of Ganoderma lucidum polysaccharides (GLP), the changes of intracellular calcium and CaMK II a expression in a model of epileptic neurons were investigated. Method: Primary hippocampal neurons were divided into: 1) Control group, neurons were cultured with Neurobasal medium, for 3 hours; 2) Model group I: neurons were incubated with Mg2+ free medium for 3 hours; 3) Model group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with the normal medium for a further 3 hours; 4) GLP group I: neurons were incubated with Mg2+ free medium containing GLP (0.375 mg/ml) for 3 hours; 5) GLP group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with a normal culture medium containing GLP for a further 3 hours. The CaMK II a protein expression was assessed by Western-blot. Ca2+ turnover in neurons was assessed using Fluo-3/AM which was added into the replacement medium and Ca2+ turnover was observed under a laser scanning confocal microscope. Results: The CaMK II a expression in the model groups was less than in the control groups, however, in the GLP groups, it was higher than that observed in the model group. Ca2+ fluorescence intensity in GLP group I was significantly lower than that in model group I after 30 seconds, while in GLP group II, it was reduced significantly compared to model group II after 5 minutes. Conclusion: GLP may inhibit calcium overload and promote CaMK II a expression to protect epileptic neuron

Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.

Abstract Introduction Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Methods Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. Results We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. Conclusions In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship

Surgical treatment of tricuspid regurgitation after mitral valve surgery: a retrospective study in China

<p>Abstract</p> <p>Background</p> <p>Functional tricuspid regurgitation (TR) occurs in patients with rheumatic mitral valve disease even after mitral valve surgery. The aim of this study was to analyze surgical results of TR after previous successful mitral valve surgery.</p> <p>Methods</p> <p>From September 1996 to September 2008, 45 patients with TR after previous mitral valve replacement underwent second operation for TR. In those, 43 patients (95.6%) had right heart failure symptoms (edema of lower extremities, ascites, hepatic congestion, etc.) and 40 patients (88.9%) had atrial fibrillation. Twenty-six patients (57.8%) were in New York Heart Association (NYHA) functional class III, and 19 (42.2%) in class IV. Previous operations included: 41 for mechanical mitral valve replacement (91.1%), 4 for bioprosthetic mitral valve replacement (8.9%), and 7 for tricuspid annuloplasty (15.6%).</p> <p>Results</p> <p>The tricuspid valves were repaired with Kay's (7 cases, 15.6%) or De Vega technique (4 cases, 8.9%). Tricuspid valve replacement was performed in 34 cases (75.6%). One patient (2.2%) died. Postoperative low cardiac output (LCO) occurred in 5 patients and treated successfully. Postoperative echocardiography showed obvious reduction of right atrium and ventricle. The anterioposterior diameter of the right ventricle decreased to 25.5 ± 7.1 mm from 33.7 ± 6.2 mm preoperatively (P < 0. 05).</p> <p>Conclusion</p> <p>TR after mitral valve replacement in rheumatic heart disease is a serious clinical problem. If it occurs or progresses late after mitral valve surgery, tricuspid valve annuloplasty or replacement may be performed with satisfactory results. Due to the serious consequence of untreated TR, aggressive treatment of existing TR during mitral valve surgery is recommended.</p

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies

Structural Diversity in Bacterial Ribosomes: Mycobacterial 70S Ribosome Structure Reveals Novel Features

Here we present analysis of a 3D cryo-EM map of the 70S ribosome from Mycobacterium smegmatis, a saprophytic cousin of the etiological agent of tuberculosis in humans, Mycobacterium tuberculosis. In comparison with the 3D structures of other prokaryotic ribosomes, the density map of the M. smegmatis 70S ribosome reveals unique structural features and their relative orientations in the ribosome. Dramatic changes in the periphery due to additional rRNA segments and extra domains of some of the peripheral ribosomal proteins like S3, S5, S16, L17, L25, are evident. One of the most notable features appears in the large subunit near L1 stalk as a long helical structure next to helix 54 of the 23S rRNA. The sharp upper end of this structure is located in the vicinity of the mRNA exit channel. Although the M. smegmatis 70S ribosome possesses conserved core structure of bacterial ribosome, the new structural features, unveiled in this study, demonstrates diversity in the 3D architecture of bacterial ribosomes. We postulate that the prominent helical structure related to the 23S rRNA actively participates in the mechanisms of translation in mycobacteria

The effect of a manual instrumentation technique on five types of premolar root canal geometry assessed by microcomputed tomography and three-dimensional reconstruction

<p>Abstract</p> <p>Background</p> <p>Together with diagnosis and treatment planning, a good knowledge of the root canal system and its frequent variations is a necessity for successful root canal therapy. The selection of instrumentation techniques for variants in internal anatomy of teeth has significant effects on the shaping ability and cleaning effectiveness. The aim of this study was to reveal the differences made by including variations in the internal anatomy of premolars into the study protocol for investigation of a single instrumentation technique (hand ProTaper instruments) assessed by microcomputed tomography and three-dimensional reconstruction.</p> <p>Methods</p> <p>Five single-root premolars, whose root canal systems were classified into one of five types, were scanned with micro-CT before and after preparation with a hand ProTaper instrument. Instrumentation characteristics were measured quantitatively in 3-D using a customized application framework based on MeVisLab. Numeric values were obtained for canal surface area, volume, volume changes, percentage of untouched surface, dentin wall thickness, and the thickness of dentin removed. Preparation errors were also evaluated using a color-coded reconstruction.</p> <p>Results</p> <p>Canal volumes and surface areas were increased after instrumentation. Prepared canals of all five types were straightened, with transportation toward the inner aspects of S-shaped or multiple curves. However, a ledge was formed at the apical third curve of the type II canal system and a wide range in the percentage of unchanged canal surfaces (27.4-83.0%) was recorded. The dentin walls were more than 0.3 mm thick except in a 1 mm zone from the apical surface and the hazardous area of the type II canal system after preparation with an F3 instrument.</p> <p>Conclusions</p> <p>The 3-D color-coded images showed different morphological changes in the five types of root canal systems shaped with the same hand instrumentation technique. Premolars are among the most complex teeth for root canal treatment and instrumentation techniques for the root canal systems of premolars should be selected individually depending on the 3-D canal configuration of each tooth. Further study is needed to demonstrate the differences made by including variations in the internal anatomy of teeth into the study protocol of clinical RCT for identifying the best preparation technique.</p

Expression of Dickkopf-1 and Beta-Catenin Related to the Prognosis of Breast Cancer Patients with Triple Negative Phenotype

BACKGROUND AND AIM: We investigated the prognostic importance of dickkopf-1(DKK1) and beta-catenin expression in triple negative breast cancers. METHODS: The expression of DKK1 and beta-catenin was evaluated in breast cell lines using RT-PCR and western blot. Immunohistochemistry was used to characterize the expression pattern of DKK1 and beta-catenin in 85 triple negative breast cancers and prognostic significance was assessed by Kaplan-Meier analysis and Cox proportional hazards regression modeling. RESULTS: The expression of DKK1 was confirmed in hormone-resistant breast cell lines MDA-MB-231, MDA-MB-231-HM and MDA-MB-435. Expression of DKK1 in triple negative breast cancers correlated with cytoplasmic/nuclear beta-catenin (p = 0.000). Elevated expression of DKK1 and cytoplasmic/nuclear beta-catenin in triple negative cancers indicate poor outcome of patients. DKK1 was also a prognostic factor for patients with earlier stage or no lymph node metastasis. CONCLUSION: DKK1 together with beta-catenin might be important prognostic factors in triple negative breast carcinoma. DKK1 might be a valuable biomarker in predicting the prognosis of patients with earlier stage or no lymph node metastasis. It is possible that through further understanding of the role of Wnt/beta-catenin pathway activation, beta-catenin would be a potential therapeutic target for the triple negative breast cancer