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https://www.readbyqxmd.com/read/28721015/cell-and-small-animal-models-for-phenotypic-drug-discovery
#1
REVIEW
Mihaly Szabo, Sara Svensson Akusjärvi, Ankur Saxena, Jianping Liu, Gayathri Chandrasekar, Satish S Kitambi
The phenotype-based drug discovery (PDD) approach is re-emerging as an alternative platform for drug discovery. This review provides an overview of the various model systems and technical advances in imaging and image analyses that strengthen the PDD platform. In PDD screens, compounds of therapeutic value are identified based on the phenotypic perturbations produced irrespective of target(s) or mechanism of action. In this article, examples of phenotypic changes that can be detected and quantified with relative ease in a cell-based setup are discussed...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28711480/commissioning-of-small-field-size-radiosurgery-cones-in-a-6-mv-flattening-filter-free-beam
#2
Juan Diego Azcona, Benigno Barbés, Verónica Morán, Javier Burguete
This study aimed to describe the commissioning of small field size radiosurgery cones in a 6-MV flattening filter free (FFF) beam and report our measured values. Four radiosurgery cones of diameters 5, 10, 12.5, and 15 mm supplied by Elekta Medical were commissioned in a 6-MV FFF beam from an Elekta Versa linear accelerator. The extraction of a reference signal for measuring small fields in scanning mode is challenging. A transmission chamber was attached to the lower part of the collimators and used for percentage depth dose (PDD) and profile measurements in scanning mode with a stereotactic diode...
July 12, 2017: Medical Dosimetry: Official Journal of the American Association of Medical Dosimetrists
https://www.readbyqxmd.com/read/28705553/long-term-outcomes-after-pancreaticoduodenectomy-using-pair-watch-suturing-technique-different-roles-of-pancreatic-duct-dilatation-and-remnant-pancreatic-volume-for-the-development-of-pancreatic-endocrine-and-exocrine-dysfunction
#3
Yusuke Iizawa, Hiroyuki Kato, Masashi Kishiwada, Aoi Hayasaki, Akihiro Tanemura, Yasuhiro Murata, Yoshinori Azumi, Naohisa Kuriyama, Shugo Mizuno, Masanobu Usui, Hiroyuki Sakurai, Shuji Isaji
BACKGROUND: We evaluated long-term outcomes including endo- and exocrine functions after pancreaticoduodenectomy (PD) with standardized pancreaticojejunostomy, paying attention to postoperative pancreatic duct dilatation (PDD) and remnant pancreatic volume (RPV), and examined whether postoperative pancreatic fistula (POPF) influenced the configuration of remnant pancreas. METHODS: We analyzed the records of 187 patients with PD who could have RPV measured by CT volumetry at 1 month after operation and had been followed for more than 6 months...
June 23, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28696500/development-of-a-silicon-diode-detector-for-skin-dosimetry-in-radiotherapy
#4
Nikolina Vicoroski, Anthony Espinoza, Mitchell Duncan, Bradley Michael Oborn, Martin Carolan, Peter Metcalfe, David Menichelli, Vladimir L Perevertaylo, Michael L F Lerch, Anatoly B Rosenfeld, Marco Petasecca
PURPOSE: The aim of in-vivo skin dosimetry is to measure the absorbed dose to the skin during radiotherapy, when treatment planning calculations cannot be relied on. It is of particularly importance in hypo-fractionated stereotactic modalities, where excessive dose can lead to severe skin toxicity. Currently commercial diodes for such applications are with water equivalent depths ranging from 0.5 to 0.8 mm. In this study, we investigate a new detector for skin dosimetry based on a silicon epitaxial diode, referred to as the skin diode...
July 11, 2017: Medical Physics
https://www.readbyqxmd.com/read/28685762/opportunities-and-challenges-in-phenotypic-drug-discovery-an-industry-perspective
#5
REVIEW
John G Moffat, Fabien Vincent, Jonathan A Lee, Jörg Eder, Marco Prunotto
Phenotypic drug discovery (PDD) approaches do not rely on knowledge of the identity of a specific drug target or a hypothesis about its role in disease, in contrast to the target-based strategies that have been widely used in the pharmaceutical industry in the past three decades. However, in recent years, there has been a resurgence in interest in PDD approaches based on their potential to address the incompletely understood complexity of diseases and their promise of delivering first-in-class drugs, as well as major advances in the tools for cell-based phenotypic screening...
July 7, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28667807/improved-algorithm-for-ostium-size-assessment-in-watchman-left-atrial-appendage-occlusion-using-three-dimensional-echocardiography
#6
Maximilian Schmidt-Salzmann, Felix Meincke, Felix Kreidel, Tobias Spangenberg, Alexander Ghanem, Karl-Heinz Kuck, Martin W Bergmann
AIMS: Correct sizing of the ostium is a crucial step in left atrial appendage (LAA) occlusion procedures. However, unfavorable anatomy of the ostium often complicates the assessment of the true ostium diameter. We hypothesized that area-derived diameter (ADD) and perimeter-derived diameter (PDD) from three-dimensional transesophageal echocardiogram (3D-TEE) can facilitate this step of the procedure as compared with two-dimensional (2D) measurements. METHODS AND RESULTS: For 55 patients within the ALSTER-LAA registry, retrospective analysis of PDD and ADD was correlated with 2D measurements used during the procedure to ascertain correct size of the Watchman device (Boston Scientific)...
July 2017: Journal of Invasive Cardiology
https://www.readbyqxmd.com/read/28663290/draft-genome-sequence-of-pseudomonas-graminis-pdd-13b-3-a-model-strain-isolated-from-cloud-water
#7
L Besaury, P Amato, N Wirgot, M Sancelme, A M Delort
The whole genome of Pseudomonas graminis PDD-13b-3, a strain of bacteria isolated from cloud water, was sequenced. This showed that this microorganism is equipped with genes that could potentially be involved in its survival in the atmosphere and clouds: those for oxidative stress and carbon starvation responses, DNA repair, and iron uptake.
June 29, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28655442/effects-of-common-functional-mmp12-gene-polymorphisms-on-pd-in-a-polish-population
#8
Monika Białecka, Mateusz Kurzawski, Tatyana Vlaykova, Tanya Tacheva, Violetta Dziedziejko, Anna Pierzchlińska, Marek Droździk
The present study investigated associations of two functional MMP12 polymorphisms with PD risk and cognitive impairment in PD. A total of 478 study subjects (241 PD and 237 age and sex matched controls) were included in the study. UPDRS score, Hoehn-Yahr staging and Schwab-England scale were used to assess motor abilities and activity during daily life. All patients were classified into groups with dementia (PDD, n=72) and without dementia (nPDD, n=159) based on the neuropsychological assessment. The two most common functional single nucleotide polymorphisms (SNPs) in MMP12 gene were determined using TaqMan real-time PCR assays...
June 16, 2017: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/28641204/towards-dosimetry-for-photodynamic-diagnosis-with-the-low-level-dose-of-photosensitizer
#9
Igor Buzalewicz, Iwona Hołowacz, Agnieszka Ulatowska-Jarża, Halina Podbielska
BACKGROUND: Contemporary medicine does not concern the issue of dosimetry in photodynamic diagnosis (PDD) but follows the photosensitizer (PS) producers recommendation. Most preclinical and clinical PDD studies indicate a considerable variation in the possibility of visualization and treatment, as e.g. in case of cervix lesions. Although some of these variations can be caused by the different histological subtypes or various tumor geometries, the issue of varying PS concentration in the tumor tissue volume is definitely an important factor...
June 15, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28638598/caregiver-burden-is-increased-in-parkinson-s-disease-with-mild-cognitive-impairment-pd-mci
#10
Ann J Jones, Roeline G Kuijer, Leslie Livingston, Daniel Myall, Kyla Horne, Michael MacAskill, Toni Pitcher, Paul T Barrett, Tim J Anderson, John C Dalrymple-Alford
BACKGROUND: There is limited evidence on caregiver outcomes associated with mild cognitive impairment in patients with Parkinson's disease (PD-MCI) and the coping strategies used by these caregivers. METHODS: To investigate this relationship, we examined levels of burden, depression, anxiety, coping strategies and positive aspects of caregiving in the informal caregivers of 96 PD patients. The PD patients were classified using MDS-Task Force Level II criteria as showing either normal cognition (PD-N; n = 51), PD-MCI (n = 30) or with dementia (PDD; n = 15)...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28630086/psychosocial-therapy-for-parkinson-s-related-dementia-study-protocol-for-the-invest-randomised-controlled-trial
#11
Sheree A McCormick, Kathryn R McDonald, Sabina Vatter, Vasiliki Orgeta, Ellen Poliakoff, Sarah Smith, Monty A Silverdale, Bo Fu, Iracema Leroi
INTRODUCTION: Parkinson's disease (PD) with mild cognitive impairment (MCI-PD) or dementia (PDD) and dementia with Lewy bodies (DLB) are characterised by motor and 'non-motor' symptoms which impact on quality of life. Treatment options are generally limited to pharmacological approaches. We developed a psychosocial intervention to improve cognition, quality of life and companion burden for people with MCI-PD, PDD or DLB. Here, we describe the protocol for a single-blind randomised controlled trial to assess feasibility, acceptability and tolerability of the intervention and to evaluate treatment implementation...
June 19, 2017: BMJ Open
https://www.readbyqxmd.com/read/28626920/experimental-verification-of-egsnrc-monte-carlo-calculated-depth-doses-within-a-realistic-parallel-magnetic-field-in-a-polystyrene-phantom
#12
Andrei Ghila, Stephen Steciw, B Gino Fallone, Satyapal Rathee
PURPOSE: Integrating a linac with a magnetic resonance imager (MRI) will revolutionize the accuracy of external beam radiation treatments. Irradiating in the presence of a strong magnetic field, however, will modify the dose distribution. These dose modifications have been investigated previously, mainly using Monte Carlo simulations. The purpose of this work is to experimentally verify the use of the EGSnrc Monte Carlo (MC) package for calculating percent depth doses (PDDs) in a homogeneous phantom, in the presence of a realistic parallel magnetic field...
June 19, 2017: Medical Physics
https://www.readbyqxmd.com/read/28610688/efficacy-of-patient-specific-bolus-created-using-three-dimensional-printing-technique-in-photon-radiotherapy
#13
Koya Fujimoto, Takehiro Shiinoki, Yuki Yuasa, Hideki Hanazawa, Keiko Shibuya
PURPOSE: A commercially available bolus ("commercial-bolus") does not make complete contact with the irregularly shaped patient skin. This study aims to customise a patient-specific three-dimensional (3D) bolus using a 3D printing technique ("3D-bolus") and to evaluate its clinical feasibility for photon radiotherapy. METHODS: The 3D-bolus was designed using a treatment planning system (TPS) in Digital Imaging and Communications in Medicine-Radiotherapy (DICOM-RT) format, and converted to stereolithographic format for printing...
June 2017: Physica Medica: PM
https://www.readbyqxmd.com/read/28597396/trpv4-activation-contributes-functional-recovery-from-ischemic-stroke-via-angiogenesis-and-neurogenesis
#14
Chun-Kai Chen, Po-Yuan Hsu, Tzu-Ming Wang, Zhi-Feng Miao, Ruey-Tay Lin, Suh-Hang H Juo
The endothelial transient receptor potential cation channel subfamily V member 4 (TRPV4) plays a crucial role in vascular remodeling; however, TRPV4-mediated angiogenesis after ischemic neuronal death as a neurorestorative strategy has not yet been thoroughly examined. In this study, we first tested whether TRPV4 activation can improve functional recovery in rats subjected to transient brain ischemia. The possible mechanisms for TRPV4 activation-promoted functional recovery were explored. A TRPV4 agonist, 4α-phorbol 12,13-didecanoate (4α-PDD), was intravenously injected via the tail vein at 6 h and 1, 2, 3, 4 days after ischemic stroke...
June 9, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28595550/new-tracers-and-new-perspectives-for-molecular-imaging-in-lewy-body-diseases
#15
Matteo Bauckneht, Dario Arnaldi, Flavio Nobili, Dag Aarsland, Silvia Morbelli
The term Lewy body diseases (LBDs) refers to a subset of neurodegenerative disorders that share the accumulation of the so-called Lewy bodies (LB) including: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and PD later characterized by the occurrence of dementia (PDD). Moreover, multiple system atrophy (MSA) and idiopatic Rem Sleeping behaviour disorders (RBD) complete the group of synucleinopathies and have also common symptoms with respect to LBDs. The clinical diagnosis of LBDs can be challenging for physicians, particularly in the early stages of disease...
June 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28585287/effect-of-vero-pan-tilt-motion-on-the-dose-distribution
#16
Heru Prasetio, Indra Yohannes, Christoph Bert
Tumor tracking is an option for intra-fractional motion management in radiotherapy. The VERO gimbal tracking system creates a unique beam geometry and understanding the effect of the gimbal motion in terms of dose distribution is important to assess the dose deviation from the reference conditions. Beam profiles, output factors (OF) and percentage depth doses (PDD) were measured and evaluated to investigate this effect. In order to find regions affected by the pan-tilt motion, synthesized 2D dose distributions were generated...
June 6, 2017: Journal of Applied Clinical Medical Physics
https://www.readbyqxmd.com/read/28572553/formation-and-distortion-of-iodidoantimonates-iii-the-first-isolated-sbi6-3-octahedron
#17
Maciej Bujak
The ability to intentionally construct, through different types of interactions, inorganic-organic hybrid materials with desired properties is the main goal of inorganic crystal engineering. The primary deformation, related to intrinsic interactions within inorganic substructure, and the secondary deformation, mainly caused by the hydrogen bond interactions, are both responsible for polyhedral distortions of halogenidoantimonates(III) with organic cations. The evolution of structural parameters, in particular the Sb-I secondary- and O/N/C-H...
June 1, 2017: Acta Crystallographica Section B, Structural Science, Crystal Engineering and Materials
https://www.readbyqxmd.com/read/28554411/cerebrospinal-fluid-biomarkers-of-cognitive-decline-in-parkinson-s-disease
#18
Iskandar Johar, Brit Mollenhauer, Dag Aarsland
Among the nonmotor symptoms in Parkinson's disease (PD), cognitive impairment is one of the most common and devastating. Over recent years, mild cognitive impairment (MCI) has become a recognized feature of PD (PD-MCI). The underlying mechanisms which influence onset, rate of decline, and conversion to dementia (PDD) are largely unknown. Adding to this uncertainty is the heterogeneity of cognitive domains affected. Currently there are no disease-modifying treatments that can slow or reverse this process. Identification of biomarkers that can predict rate and risk of cognitive decline is therefore an unmet need...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28550072/plasma-%C3%AE-synuclein-predicts-cognitive-decline-in-parkinson-s-disease
#19
Chin-Hsien Lin, Shieh-Yueh Yang, Herng-Er Horng, Che-Chuan Yang, Jen-Jie Chieh, Hsin-Hsien Chen, Bing-Hsien Liu, Ming-Jang Chiu
OBJECTIVE: α-Synuclein is critical to the pathogenesis of Parkinson's disease (PD). Few studies examined the plasma levels of α-synuclein due to the exceptionally low level of α-synuclein in plasma compared with cerebrospinal fluid. We aimed to investigate plasma α-synuclein in patients with PD of different disease severity. METHODS: There were total 114 participants, including 80 patients with PD and 34 controls, in the study. Participants received a complete evaluation of motor and non-motor symptoms, including cognitive function...
May 26, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28494095/comparison-of-192-ir-169-yb-and-60-co-high-dose-rate-brachytherapy-sources-for-skin-cancer-treatment
#20
Habib Safigholi, Ali S Meigooni, William Y Song
PURPOSE: To evaluate the possibility of utilizing the high-dose rate (HDR) (169) Yb and (60) Co sources, in addition to (192) Ir, for the treatment of skin malignancies with conical applicators. METHODS: Monte Carlo (MC) simulations were used to benchmark the dosimetric parameters of single (169) Yb (4140), (60) Co (Co0.A86), and (192) Ir (mHDR-V2) brachytherapy sources in a water phantom and compared their results against published data. A standard conical tungsten alloy Leipzig-style applicator (Stand...
May 11, 2017: Medical Physics
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