From the clinic to the lab (and back) : a call for laboratory research to optimize cognitive-behaviour treatment of pain

Cognitive behavioural therapy (CBT) is the dominant psychological treatment for chronic pain. CBT covers a mixture of aims and a broad range of techniques, including attentional control, modification of maladaptive beliefs and coping strategies and flexible goal setting and acceptance. Patients are exposed to varying selections of these strategies, and a major challenge for clinical practice is to determine what works for whom in which context. We propose that incorporating laboratory research into translational behaviour medicine is a critical developmental step that will help optimizing CBT and provide examples of representative experimental research programs

The impact of species and cell type on the nanosafety profile of iron oxide nanoparticles in neural cells

Background: While nanotechnology is advancing rapidly, nanosafety tends to lag behind since general mechanistic insights into cell-nanoparticle (NP) interactions remain rare. To tackle this issue, standardization of nanosafety assessment is imperative. In this regard, we believe that the cell type selection should not be overlooked since the applicability of cell lines could be questioned given their altered phenotype. Hence, we evaluated the impact of the cell type on in vitro nanosafety evaluations in a human and murine neuroblastoma cell line, neural progenitor cell line and in neural stem cells. Acute toxicity was evaluated for gold, silver and iron oxide (IO) NPs, and the latter were additionally subjected to a multiparametric analysis to assess sublethal effects. Results: The stem cells and murine neuroblastoma cell line respectively showed most and least acute cytotoxicity. Using high content imaging, we observed cell type-and species-specific responses to the IONPs on the level of reactive oxygen species production, calcium homeostasis, mitochondrial integrity and cell morphology, indicating that cellular homeostasis is impaired in distinct ways. Conclusions: Our data reveal cell type-specific toxicity profiles and demonstrate that a single cell line or toxicity end point will not provide sufficient information on in vitro nanosafety. We propose to identify a set of standard cell lines for screening purposes and to select cell types for detailed nanosafety studies based on the intended application and/or expected exposure

The cellular interactions of PEGylated gold nanoparticles : effect of PEGylation on cellular uptake and cytotoxicity

Poly(ethylene glycol) (PEG) is frequently used to coat various medical nanoparticles (NPs). As PEG is known to minimize NP interactions with biological specimens, the question remains whether PEGylated NPs are intrinsically less toxic or whether this is caused by reduced NP uptake. In the present work, the effect of gold NP PEGylation on uptake by three cell types is compared and evaluated the effect on cell viability, oxidative stress, cell morphology, and functionality using a multiparametric methodology. The data reveal that PEGylation affects cellular NP uptake in a cell-type-dependent manner and influences toxicity by different mechanisms. At similar intracellular NP numbers, PEGylated NPs are found to yield higher levels of cell death, mostly by induction of oxidative stress. These findings reveal that PEGylation significantly reduces NP uptake, but that at similar functional (= cell-associated) NP levels, non-PEGylated NPs are better tolerated by the cells

Toxocariasis Presenting as Encephalomyelitis

We describe a farmer who presented with a clinical picture of a transverse thoracic myelitis. MRI showed inflammatory lesions in brain and thoracic spinal cord. Toxocariasis was suspected because of eosinophilia in blood and cerebrospinal fluid, and this diagnosis was confirmed immunologically. He was successfully treated with antihelminthics in combination with corticosteroids. Neurotoxocariasis is rare and diagnosis can be difficult because of the different and atypical clinical manifestations. It should be considered in every case of central neurological syndrome associated with eosinophilia

Introduction: responsibility for action and belief

This paper is a presentation of a special issue of Philosophical Explorations, whose origin is a meeting held in Valencia in 2008. The issue includes contributions by David Widerker, Derk Pereboom, Timothy O'Connor, Thomas Pink, Dana Nelkin, Helen Steward, Maria Alvarez, Christopher Hookway, and Pascal Engel. The paper contains a map of the main positions in the debate about free action, free will, and moral responsibility, as well as a reference to some central issues in this traditional and yet lively debate. The discussion about responsibility and related notions, such as agency and freedom, has recently been extended from decisions and actions to beliefs, to give rise to new research perspectives, both in epistemology and in the metaphysics of freedom and responsibility for actions. The papers included in this special issue are valuable contributions to the research about freedom and responsibility in both action and belief

Evaluation of resistive-plate-chamber-based TOF-PET applied to in-beam particle therapy monitoring

Particle therapy is a highly conformal radiotherapy technique which reduces the dose deposited to the surrounding normal tissues. In order to fully exploit its advantages, treatment monitoring is necessary to minimize uncertainties related to the dose delivery. Up to now, the only clinically feasible technique for the monitoring of therapeutic irradiation with particle beams is Positron Emission Tomography (PET). In this work we have compared a Resistive Plate Chamber (RPC)-based PET scanner with a scintillation-crystal-based PET scanner for this application. In general, the main advantages of the RPC-PET system are its excellent timing resolution, low cost, and the possibility of building large area systems. We simulated a partial-ring scannerbeam monitoring, which has an intrinsically low positron yield compared to diagnostic PET. In addition, for in-beam PET there is a further data loss due to the partial ring configuration. In order to improve the performance of the RPC-based scanner, an improved version of the RPC detector (modifying the thickness of the gas and glass layers), providing a larger sensitivity, has been simulated and compared with an axially extended version of the crystal-based device. The improved version of the RPC shows better performance than the prototype, but the extended version of the crystal-based PET outperforms all other options. based on an RPC prototype under construction within the Fondazione per Adroterapia Oncologica (TERA). For comparison with the crystal-based PET scanner we have chosen the geometry of a commercially available PET scanner, the Philips Gemini TF. The coincidence time resolution used in the simulations takes into account the current achievable values as well as expected improvements of both technologies. Several scenarios (including patient data) have been simulated to evaluate the performance of different scanners. Initial results have shown that the low sensitivity of the RPC hampers its application to hadro

On over-reflection and generation of Gravito-Alfven waves in solar-type stars

The dynamics of linear perturbations is studied in magnetized plasma shear flows with a constant shearing rate and with gravity-induced stratification. The general set of linearized equations is derived and the two-dimensional case is considered in detail. The Boussinesq approximation is used in order to examine relatively small-scale perturbations of low-frequency modes: Gravito-Alfven waves (GAW) and Entropy Mode (EM) perturbations. It is shown that for flows with arbitrary shearing rate there exists a finite time interval of non-adiabatic evolution of the perturbations. The non-adiabatic behavior manifests itself in a twofold way, viz. by the over-reflection of the GAWs and by the generation of GAWs from EM perturbations. It is shown that these phenomena act as efficient transformers of the equilibrium flow energy into the energy of the perturbations for moderate and high shearing rate solar plasma flows. Efficient generation of GAW by EM takes place for shearing rates about an order of magnitude smaller than necessary for development of a shear instability. The latter fact could have important consequences for the problem of angular momentum redistribution within the Sun and solar-type stars.Comment: 20 pages (preprint format), 4 figures; to appear in The Astrophysical Journal (August 1, 2007, v664, N2 issue