Case report: Therapeutic potential of Flourishing-Life-Of-Wish Virtual Reality Therapy on Relaxation (FLOW-VRT-Relaxation)—a novel personalized relaxation in palliative care

In view of the global aging population and growing need of palliative care, innovative intervention for effective symptom management is of urgent need. Flourishing-Life-Of-Wish Virtual Reality Therapy (FLOW-VRT) is a brief, structured, manualized, and personalized psychological intervention with theoretical foundations based on stress coping theory, self-determination theory, flow theory, and attention restoration theory. With a specific focus on relaxation, FLOW-VRT-Relaxation intends to facilitate adaptive end-of-life coping through delivering personalized relaxation. This paper reports a case study of the application of FLOW-VRT-Relaxation, and discusses its therapeutic potential as a cost-effective method for reducing palliative symptoms by addressing patient's unmet needs. The case study is a 51-year-old Chinese female, diagnosed with advanced cervix cancer, and presented with unmet psychological (i.e., unfulfilled wishes) and physical needs (i.e., pain and fatigue) before FLOW-VRT-Relaxation. To address her unmet needs, FLOW-VRT-Relaxation was delivered by a registered clinical psychologist specialized in palliative care. Need assessment was first conducted, followed by a 10-min VR travel of Japan as her own choice. Relaxation was verbally coached during VR. Right after VR, consolidation with psychological components including psychoeducation, cognitive and emotional processing, and reminiscence intervention were delivered. The patient showed improvement in physical and psychological symptoms, lower sense of loneliness and engulfment, as well as enhanced peace after FLOW-VRT-Relaxation. The current findings provide encouraging initial support for the feasibility, acceptability, and therapeutic potential of using FLOW-VRT-Relaxation as a cost-effective, scalable and personalized VR relaxation for patients under palliative care. It is hoped that with its optimal use, FLOW-VRT-Relaxation can serve as an alternative therapeutic tool that effectively improves the end-on-life care

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Emerging roles of ATF2 and the dynamic AP1 network in cancer

Cooperation among transcription factors is central for their ability to execute specific transcriptional programmes. The AP1 complex exemplifies a network of transcription factors that function in unison under normal circumstances and during the course of tumour development and progression. This Perspective summarizes our current understanding of the changes in members of the AP1 complex and the role of ATF2 as part of this complex in tumorigenesis.Fil: Lopez Bergami, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Lau, Eric . Burnham Institute for Medical Research; Estados UnidosFil: Ronai, Zeev . Burnham Institute for Medical Research; Estados Unido

Impact of inactivity and exercise on the vasculature in humans

The effects of inactivity and exercise training on established and novel cardiovascular risk factors are relatively modest and do not account for the impact of inactivity and exercise on vascular risk. We examine evidence that inactivity and exercise have direct effects on both vasculature function and structure in humans. Physical deconditioning is associated with enhanced vasoconstrictor tone and has profound and rapid effects on arterial remodelling in both large and smaller arteries. Evidence for an effect of deconditioning on vasodilator function is less consistent. Studies of the impact of exercise training suggest that both functional and structural remodelling adaptations occur and that the magnitude and time-course of these changes depends upon training duration and intensity and the vessel beds involved. Inactivity and exercise have direct “vascular deconditioning and conditioning” effects which likely modify cardiovascular risk

New constraints on the mid-IR EBL from the HESS discovery of VHE gamma-rays from 1ES 0229+200

Aims.To investigate the very high energy (VHE: >100 GeV) γ-ray emission from the high-frequency peaked BL Lac 1ES 0229+200. Methods: Observations of 1ES 0229+200 at energies above 580 GeV were performed with the High Energy Stereoscopic System (HESS) in 2005 and 2006. Results: 1ES 0229+200 is discovered by HESS to be an emitter of VHE photons. A signal is detected at the 6.6σ level in the HESS observations (41.8 h live time). The integral flux above 580 GeV is (9.4±1.5_stat±1.9_syst) × 10-13 cm-2 s-1, corresponding to ~1.8% of the flux observed from the Crab Nebula. The data show no evidence for significant variability on any time scale. The observed spectrum is characterized by a hard power law (Γ = 2.50±0.19_stat±0.10_syst) from 500 GeV to ~15 TeV. Conclusions: The high-energy range and hardness of the observed spectrum, coupled with the object's relatively large redshift (z = 0.1396), enable the strongest constraints so far on the density of the Extragalactic Background Light (EBL) in the mid-infrared band. Assuming that the emitted spectrum is not harder than Γ_int ≈ 1.5, the HESS data support an EBL spectrum ∝λ-1 and density close to the lower limit from source counts measured by Spitzer, confirming the previous indications from the HEGRA data of 1ES 1426+428 (z=0.129). Irrespective of the EBL models used, the intrinsic spectrum of 1ES 0229+200 is hard, thus locating the high-energy peak of its spectral energy distribution above a few TeV.Aharonian, F.; Akhperjanian, A. G.; Barres de Almeida, U.; Bazer-Bachi, A. R.; Behera, B.; Beilicke, M.; Benbow, W.; Bernlöhr, K.; Boisson, C.; Bolz, O.; Borrel, V.; Braun, I.; Brion, E.; Brown, A. M.; Bühler, R.; Bulik, T.; Büsching, I.; Boutelier, T.; Carrigan, S.; Chadwick, P. M.; Chounet, L.-M.; Clapson, A. C.; Coignet, G.; Cornils, R.; Costamante, L.; Dalton, M.; Degrange, B.; Dickinson, H. J.; Djannati-Ataï, A.; Domainko, W.; O'C. Drury, L.; Dubois, F.; Dubus, G.; Dyks, J.; Egberts, K.; Emmanoulopoulos, D.; Espigat, P.; Farnier, C.; Feinstein, F.; Fiasson, A.; Förster, A.; Fontaine, G.; Funk, Seb.; Füßling, M.; Gallant, Y. A.; Giebels, B.; Glicenstein, J. F.; Glück, B.; Goret, P.; Hadjichristidis, C.; Hauser, D.; Hauser, M.; Heinzelmann, G.; Henri, G.; Hermann, G.; Hinton, J. A.; Hoffmann, A.; Hofmann, W.; Holleran, M.; Hoppe, S.; Horns, D.; Jacholkowska, A.; de Jager, O. C.; Jung, I.; Katarzyński, K.; Kendziorra, E.; Kerschhaggl, M.; Khélifi, B.; Keogh, D.; Komin, Nu.; Kosack, K.; Lamanna, G.; Latham, I. J.; Lemière, A.; Lemoine-Goumard, M.; Lenain, J.-P.; Lohse, T.; Martin, J. M.; Martineau-Huynh, O.; Marcowith, A.; Masterson, C.; Maurin, D.; Maurin, G.; McComb, T. J. L.; Moderski, R.; Moulin, E.; de Naurois, M.; Nedbal, D.; Nolan, S. J.; Ohm, S.; Olive, J.-P.; de Oña Wilhelmi, E.; Orford, K. J.; Osborne, J. L.; Ostrowski, M.; Panter, M.; Pedaletti, G.; Pelletier, G.; Petrucci, P.-O.; Pita, S.; Pühlhofer, G.; Punch, M.; Ranchon, S.; Raubenheimer, B. C.; Raue, M.; Rayner, S. M.; Renaud, M.; Ripken, J.; Rob, L.; Rolland, L.; Rosier-Lees, S.; Rowell, G.; Rudak, B.; Ruppel, J.; Sahakian, V.; Santangelo, A.; Schlickeiser, R.; Schöck, F.; Schröder, R.; Schwanke, U.; Schwarzburg, S.; Schwemmer, S.; Shalchi, A.; Sol, H.; Spangler, D.; Stawarz, Ł.; Steenkamp, R.; Stegmann, C.; Superina, G.; Tam, P. H.; Tavernet, J.-P.; Terrier, R.; van Eldik, C.; Vasileiadis, G.; Venter, C.; Vialle, J. P.; Vincent, P.; Vivier, M.; Völk, H. J.; Volpe, F.; Wagner, S. J.; Ward, M.; Zdziarski, A. A.; Zech,

Combined Surface Micropatterning and Reactive Chemistry Maximizes Tissue Adhesion with Minimal Inflammation

The use of tissue adhesives for internal clinical applications is limited due to a lack of materials that balance strong adhesion with biocompatibility. The use of substrate topography is explored to reduce the volume of a highly reactive and toxic glue without compromising adhesive strength. Micro-textured patches coated with a thin layer of cyanoacrylate glue achieve similar adhesion levels to patches employing large amounts of adhesive, and is superior to the level of adhesion achieved when a thin coating is applied to a non-textured patch. In vivo studies demonstrate reduced tissue inflammation and necrosis for patterned patches with a thinly coated layer of reactive glue, thus overcoming a significant challenge with existing tissue adhesives such as cyanoacrylate. Closure of surgical stomach and colon defects in a rat model is achieved without abdominal adhesions. Harnessing the synergy between surface topography and reactive chemistry enables controlled tissue adhesion with an improved biocompatibility profile without requiring changes in the chemical composition of reactive tissue glues. The use of substrate topography is explored to reduce the amount of a highly reactive and toxic tissue glue without compromising adhesive strength. Micro-textured patches coated with a thin layer of cyanoacrylate glue achieve similar adhesion levels as flat patches employing a thick layer of glue. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

An NQO1- and PARP-1-mediated cell death pathway induced in non-small-cell lung cancer cells by β-lapachone

Lung cancer is the number one cause of cancer-related deaths in the world. Patients treated with current chemotherapies for non-small-cell lung cancers (NSCLCs) have a survival rate of ≈15% after 5 years. Novel approaches are needed to treat this disease. We show elevated NAD(P)H:quinone oxidoreductase-1 (NQO1) levels in tumors from NSCLC patients. β-Lapachone, an effective chemotherapeutic and radiosensitizing agent, selectively killed NSCLC cells that expressed high levels of NQO1. Isogenic H596 NSCLC cells that lacked or expressed NQO1 along with A549 NSCLC cells treated with or without dicoumarol, were used to elucidate the mechanism of action and optimal therapeutic window of β-lapachone. NSCLC cells were killed in an NQO1-dependent manner by β-lapachone (LD50, ≈4 μM) with a minimum 2-h exposure. Kinetically, β-lapachone-induced cell death was characterized by the following: (i) dramatic reactive oxygen species (ROS) formation, eliciting extensive DNA damage; (ii) hyperactivation of poly(ADP-ribose)polymerase-1 (PARP-1); (iii) depletion of NAD+/ATP levels; and (iv) proteolytic cleavage of p53/PARP-1, indicating μ-calpain activation and apoptosis. β-Lapachone-induced PARP-1 hyperactivation, nucleotide depletion, and apoptosis were blocked by 3-aminobenzamide, a PARP-1 inhibitor, and 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA-AM), a Ca2+ chelator. NQO1− cells (H596, IMR-90) or dicoumarol-exposed NQO1+ A549 cells were resistant (LD50, >40 μM) to ROS formation and all cytotoxic effects of β-lapachone. Our data indicate that the most efficacious strategy using β-lapachone in chemotherapy was to deliver the drug in short pulses, greatly reducing cytotoxicity to NQO1− “normal” cells. β-Lapachone killed cells in a tumorselective manner and is indicated for use against NQO1+ NSCLC cancers