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

A small solitary non-parasitic hepatic cyst causing an intra-hepatic bile duct stricture: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report an unusual presentation of a small hepatic cyst causing cholangitis.</p> <p>Case presentation</p> <p>A 70-year-old Asian man was hospitalized for aggravated chronic pain in the right upper portion of his abdomen. Fever developed after admission. Laboratory tests revealed elevated hepatobiliary enzymes, inflammatory markers and carbohydrate antigen 19-9 without hyperbilirubinemia. Ultrasound and computed tomography demonstrated dilatation of the left intra-hepatic bile ducts. Endoscopic retrograde cholangiopancreatography showed that the right intra-hepatic bile ducts were normally filled with contrast medium, but the left intra-hepatic bile ducts were not seen in the confluence. A left hepatectomy was performed because a hidden malignancy could not be excluded. The surgical findings showed no tumor around the bile duct but rather a 2 cm cyst in segment four of Couinaud's category of the liver around the hilum. The pathology report was a solitary non-parasitic hepatic cyst compressing the bile duct.</p> <p>Conclusion</p> <p>A very small solitary hepatic cyst might cause hepatic duct stricture if it is located near the hepatic hilum, and should be considered in the differential diagnosis of a hepatic duct stricture.</p

Half-Metallic Graphene Nanoribbons

Electrical current can be completely spin polarized in a class of materials known as half-metals, as a result of the coexistence of metallic nature for electrons with one spin orientation and insulating for electrons with the other. Such asymmetric electronic states for the different spins have been predicted for some ferromagnetic metals - for example, the Heusler compounds- and were first observed in a manganese perovskite. In view of the potential for use of this property in realizing spin-based electronics, substantial efforts have been made to search for half-metallic materials. However, organic materials have hardly been investigated in this context even though carbon-based nanostructures hold significant promise for future electronic device. Here we predict half-metallicity in nanometre-scale graphene ribbons by using first-principles calculations. We show that this phenomenon is realizable if in-plane homogeneous electric fields are applied across the zigzag-shaped edges of the graphene nanoribbons, and that their magnetic property can be controlled by the external electric fields. The results are not only of scientific interests in the interplay between electric fields and electronic spin degree of freedom in solids but may also open a new path to explore spintronics at nanometre scale, based on graphene

Task-Dependent Inhomogeneous Muscle Activities within the Bi-Articular Human Rectus Femoris Muscle

The motor nerve of the bi-articular rectus femoris muscle is generally split from the femoral nerve trunk into two sub-branches just before it reaches the distal and proximal regions of the muscle. In this study, we examined whether the regional difference in muscle activities exists within the human rectus femoris muscle during maximal voluntary isometric contractions of knee extension and hip flexion. Surface electromyographic signals were recorded from the distal, middle, and proximal regions. In addition, twitch responses were evoked by stimulating the femoral nerve with supramaximal intensity. The root mean square value of electromyographic amplitude during each voluntary task was normalized to the maximal compound muscle action potential amplitude (M-wave) for each region. The electromyographic amplitudes were significantly smaller during hip flexion than during knee extension task for all regions. There was no significant difference in the normalized electromyographic amplitude during knee extension among regions within the rectus femoris muscle, whereas those were significantly smaller in the distal than in the middle and proximal regions during hip flexion task. These results indicate that the bi-articular rectus femoris muscle is differentially controlled along the longitudinal direction and that in particular the distal region of the muscle cannot be fully activated during hip flexion

Carbon ion therapy for ameloblastic carcinoma

Ameloblastic carcinomas are rare odontogenic tumors. Treatment usually consists of surgical resection and sometimes adjuvant radiation. We report the case of a 71 year-old male patient undergoing carbon ion therapy for extensive local relapse of ameloblastic carcinoma. Treatment outcome was favourable with a complete remission at 6 weeks post completion of radiotherapy while RT-treatment itself was tolerated well with only mild side effects. High dose radiation hence is a potential alternative for patients unfit or unwilling to undergo extensive surgery or in cases when only a subtotal resection is planned or the resection is mutilating

WNT signalling in prostate cancer

Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer

Is TEA an inhibitor for human Aquaporin-1?

Excessive water uptake through aquaporins can be life threatening, and disregulation of water permeability causes many diseases. Therefore, reversible aquaporin inhibitors are highly desired. In this paper, we identified the binding site for tetraethylammonium (TEA) of the membrane water channel aquaporin-1 by a combined molecular docking and molecular dynamics simulation approach. The binding site identified from docking studies was independently confirmed with an unbiased molecular dynamics simulation of an aquaporin tetramer embedded in a lipid membrane, surrounded by a 100-mM tetraethylammonium solution in water. A third independent assessment of the binding site was obtained by umbrella sampling simulations. These simulations, in addition, revealed a binding affinity of more than 17 kJ/mol, corresponding to an IC50 value of << 3 mM. Finally, we observed in our simulations a 50% reduction of the water flux in the presence of TEA, in agreement with water permeability measurements on aquaporin expressed in oocytes. These results confirm TEA as a putative lead for an aquaporin-1 inhibitor

Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: Marked differences between various antipsychotic drugs

BACKGROUND: The etiology of schizophrenia is unknown, but neurodevelopmental disturbances, myelin- and oligodendrocyte abnormalities and synaptic dysfunction have been suggested as pathophysiological factors in this severe psychiatric disorder. Cholesterol is an essential component of myelin and has proved important for synapse formation. Recently, we demonstrated that the antipsychotic drugs clozapine and haloperidol stimulate lipogenic gene expression in cultured glioma cells through activation of the sterol regulatory element-binding protein (SREBP) transcription factors. We here compare the action of chlorpromazine, haloperidol, clozapine, olanzapine, risperidone and ziprasidone on SREBP activation and SREBP-controlled gene expression (ACAT2, HMGCR, HMGCS1, FDPS, SC5DL, DHCR7, LDLR, FASN and SCD1) in four CNS-relevant human cell lines. RESULTS: There were marked differences in the ability of the antipsychotic drugs to activate the expression of SREBP target genes, with clozapine and chlorpromazine as the most potent stimulators in a context of therapeutically relevant concentrations. Glial-like cells (GaMg glioma and CCF-STTG1 astrocytoma cell lines) displayed more pronounced drug-induced SREBP activation compared to the response in HCN2 human cortical neurons and SH-SY5Y neuroblastoma cells, indicating that antipsychotic-induced activation of lipogenesis is most prominent in glial cells. CONCLUSION: Our present data show a marked variation in the ability of different antipsychotics to induce SREBP-controlled transcriptional activation of lipogenesis in cultured human CNS-relevant cells. We propose that this effect could be relevant for the therapeutic efficacy of some antipsychotic drugs

Correlation between in vitro cytotoxicity and in vivo lethal activity in mice of epsilon toxin mutants from Clostridium perfringens

Epsilon toxin (Etx) from Clostridium perfringens is a pore-forming protein with a lethal effect on livestock, producing severe enterotoxemia characterized by general edema and neurological alterations. Site-specific mutations of the toxin are valuable tools to study the cellular and molecular mechanism of the toxin activity. In particular, mutants with paired cysteine substitutions that affect the membrane insertion domain behaved as dominant-negative inhibitors of toxin activity in MDCK cells. We produced similar mutants, together with a well-known non-toxic mutant (Etx-H106P), as green fluorescent protein (GFP) fusion proteins to perform in vivo studies in an acutely intoxicated mouse model. The mutant (GFP-Etx-I51C/A114C) had a lethal effect with generalized edema, and accumulated in the brain parenchyma due to its ability to cross the blood-brain barrier (BBB). In the renal system, this mutant had a cytotoxic effect on distal tubule epithelial cells. The other mutants studied (GFP-Etx-V56C/F118C and GFP-Etx-H106P) did not have a lethal effect or cross the BBB, and failed to induce a cytotoxic effect on renal epithelial cells. These data suggest a direct correlation between the lethal effect of the toxin, with its cytotoxic effect on the kidney distal tubule cells, and the ability to cross the BBB