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https://www.readbyqxmd.com/read/28732062/a-drosophila-model-for-toxicogenomics-genetic-variation-in-susceptibility-to-heavy-metal-exposure
#1
Shanshan Zhou, Sarah E Luoma, Genevieve E St Armour, Esha Thakkar, Trudy F C Mackay, Robert R H Anholt
The genetic factors that give rise to variation in susceptibility to environmental toxins remain largely unexplored. Studies on genetic variation in susceptibility to environmental toxins are challenging in human populations, due to the variety of clinical symptoms and difficulty in determining which symptoms causally result from toxic exposure; uncontrolled environments, often with exposure to multiple toxicants; and difficulty in relating phenotypic effect size to toxic dose, especially when symptoms become manifest with a substantial time lag...
July 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28731927/injectate-spread-following-anterior-sub-costal-and-posterior-approaches-to-the-quadratus-lumborum-block-a-comparative-cadaveric-study
#2
Hesham Elsharkawy, Kariem El-Boghdadly, Sree Kolli, Wael A S Esa, Sean DeGrande, Loran M Soliman, Richard L Drake
BACKGROUND: The dermatomal level of analgesia achieved with quadratus lumborum blocks varies according to the location of injection. The most commonly used approaches are either at the postero-lateral aspect or anterior to the quadratus lumborum muscle. The aim of the study was to determine whether the site of injection of contrast dye around the quadratus lumborum muscle of cadavers affects the extent and mechanism of dye spread. METHODS: Six fresh human cadavers received either a posterior quadratus lumborum block or an anterior sub-costal quadratus lumborum block on each side...
July 20, 2017: European Journal of Anaesthesiology
https://www.readbyqxmd.com/read/28731408/defining-the-biological-basis-of-radiomic-phenotypes-in-lung-cancer
#3
Patrick Grossmann, Olya Stringfield, Nehme El-Hachem, Marilyn M Bui, Emmanuel Rios Velazquez, Chintan Parmar, Ralph Th Leijenaar, Benjamin Haibe-Kains, Philippe Lambin, Robert Gillies, Hugo Jwl Aerts
Medical imaging can visualize characteristics of human cancer noninvasively. Radiomics is an emerging field that translates these medical images into quantitative data to enable phenotypic profiling of tumors. While radiomics has been associated with several clinical endpoints, the complex relationships of radiomics, clinical factors, and tumor biology are largely unknown. To this end, we analyzed two independent cohorts of respectively 262 North American and 89 European patients with lung cancer, and consistently identified previously undescribed associations between radiomic imaging features, molecular pathways, and clinical factors...
July 21, 2017: ELife
https://www.readbyqxmd.com/read/28731336/triple-reuptake-inhibitors-as-potential-therapeutics-for-depression-and-other-disorders-design-paradigm-and-developmental-challenges
#4
Murugaiah A M Subbaiah
Although first-line antidepressants offer therapeutic benefit, about 35% of depressed patients are not adequately treated, creating a large unmet medical need. These medicines mostly enhance the synaptic levels of serotonin and/or norepinephrine. Evidence from preclinical and clinical studies implicate dopamine hypofunction in the pathophysiology of depression. Triple reuptake inhibitors (TRIs), which elevate dopamine in addition to serotonin and norepinephrine, may demonstrate greater efficacy, with the reversal of anhedonia and improved tolerability...
July 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28730950/statistical-analysis-plan-for-the-head-position-in-stroke-trial-headpost-an-international-cluster-cross-over-randomized-trial
#5
Laurent Billot, Mark Woodward, Hisatomi Arima, Maree L Hackett, Paula Muñoz Venturelli, Pablo M Lavados, Alejandro Brunser, Bin Peng, Liying Cui, Lily Song, Stephane Heritier, Stephen Jan, Sandy Middleton, Verónica V Olavarría, Joyce Lim, Thompson Robinson, Octavio Pontes-Neto, Caroline Watkins, Craig S Anderson
Background There is evidence to indicate that the lying flat head position increases cerebral blood flow and oxygenation in patients with acute ischemic stroke, but how these physiological effects translate into clinical outcomes is uncertain. The Head Position in Stroke Trial aims to determine the comparative effectiveness of lying flat (0°) compared to sitting up (≥30°) head positioning, initiated within 24 h of hospital admission for patients with acute stroke. Design An international, pragmatic, cluster-randomized, crossover, open, blinded outcome assessed clinical trial...
August 2017: International Journal of Stroke: Official Journal of the International Stroke Society
https://www.readbyqxmd.com/read/28730491/development-of-selected-reaction-monitoring-methods-to-systematically-quantify-kinase-abundance-and-phosphorylation-stoichiometry-in-human-samples
#6
Kirsten Beck, Nathan Camp, Michael Bereman, James Bollinger, Jarrett Egertson, Michael MacCoss, Alejandro Wolf-Yadlin
Protein phosphorylation, one of the most common types of post-translational modifications, is the central regulatory mechanism of cellular signaling networks. In human cells, thousands of proteins are continuously and dynamically phosphorylated and dephosphorylated at specific sites and times in response to external and internal stimuli. Reversible phosphorylation is facilitated by the action of two protein superfamilies: kinases and phosphatases. Kinases play an essential role in almost every relevant physiological process in human cells and their deregulation is linked to pathologies ranging from cancer to autoimmune diseases...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730480/identification-and-validation-of-driver-kinases-from-next-generation-sequencing-data
#7
Andri Leonidou, Barrie Peck, Rachael Natrajan
It is well appreciated that activating mutations in kinase genes result in kinome reprogramming that leads to altered downstream signaling networks that drive tumor progression. Indeed small-molecule inhibition of activated kinases has heralded the wave of precision medicine in the past decade. The advent of next-generation sequencing has identified a plethora of potentially activating mutations and fusion genes in previously unreported kinase genes that can potentially be developed as targeted therapies. However, the bottleneck in the translation of these alterations into clinically useful therapies lies in their functional validation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730442/chitosan-nanoparticles-for-mirna-delivery
#8
Merve Denizli, Burcu Aslan, Lingegowda S Mangala, Dahai Jiang, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Anil K Sood
RNA interference techniques represent a promising strategy for therapeutic applications. In addition to small interfering RNA-based approaches, which have been widely studied and translated into clinical investigations, microRNA-based approaches are attractive owing to their "one hit, multiple targets" concept. To overcome challenges with in vivo delivery of microRNAs related to stability, cellular uptake, and specific delivery, our group has developed and characterized chitosan nanoparticles for nucleotide delivery...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730348/-pharyngoesophageal-diverticulum
#9
C A Gutschow, P Bauerfeind
Over the last 20-30 years, treatment of pharyngoesophageal diverticula was subject to a number of fundamental changes. Considering the classical open transcervical approaches, the necessity for myotomy of the upper esophageal sphincter with the goal of interrupting the pathogenesis of the disease has become a standard component of the operation. On the other hand, with the growing popularity of rigid and flexible endoscopic techniques, pharyngoesophageal diverticula are increasingly being treated by gastroenterologists and otorhinolaryngologists, often with the argument of a technically easier and less invasive procedure; however, it remains unclear whether this shift towards endoscopic techniques truly translates into better outcome quality...
July 20, 2017: Der Chirurg; Zeitschrift Für Alle Gebiete der Operativen Medizen
https://www.readbyqxmd.com/read/28729965/fluid-overload-as-a-major-target-in-management-of-cardiorenal-syndrome-implications-for-the-practice-of-peritoneal-dialysis
#10
REVIEW
Amir Kazory
Congestion is an integral component of cardiorenal syndrome and portends an adverse impact on the outcomes. Recent studies suggest that congestion has the ability of modulating the interactions between the kidney and the heart in this setting. Peritoneal dialysis (PD) is a home-based therapeutic modality that is not only offered to patients with end-stage renal disease to provide solute clearance and ultrafiltration, but it has also been used in patients with refractory heart failure and fluid overload to help optimize volume status...
July 6, 2017: World Journal of Nephrology
https://www.readbyqxmd.com/read/28729948/algorithms-for-the-automated-analysis-of-age-related-macular-degeneration-biomarkers-on-optical-coherence-tomography-a-systematic-review
#11
REVIEW
Maximilian W M Wintergerst, Thomas Schultz, Johannes Birtel, Alexander K Schuster, Norbert Pfeiffer, Steffen Schmitz-Valckenberg, Frank G Holz, Robert P Finger
PURPOSE: To assess the quality of optical coherence tomography (OCT) grading algorithms for retinal biomarkers of age-related macular degeneration (AMD). METHODS: Following a systematic review of the literature data on detection and quantification of AMD retinal biomarkers by available algorithms were extracted and descriptively synthesized. Algorithm quality was assessed using a modified version of the Quality Assessment of Diagnostic Accuracy Studies 2 checklist with a focus on accuracy against established reference standards and risk of bias...
July 2017: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/28729824/mouse-models-of-c9orf72-hexanucleotide-repeat-expansion-in-amyotrophic-lateral-sclerosis-frontotemporal-dementia
#12
REVIEW
Ranjan Batra, Chris W Lee
The presence of hexanucleotide repeat expansion (HRE) in the first intron of the human C9orf72 gene is the most common genetic cause underlying both familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Studies aimed at elucidating the pathogenic mechanisms associated of C9orf72 FTD and ALS (C9FTD/ALS) have focused on the hypothesis of RNA and protein toxic gain-of-function models, including formation of nuclear RNA foci containing GGGGCC (G4C2) HRE, inclusions containing dipeptide repeat proteins through a non-canonical repeat associated non-ATG (RAN) translation mechanism, and on loss-of-function of the C9orf72 protein...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28729787/patterns-of-dental-caries-among-school-children-assessed-using-caries-assessment-spectrum-and-treatment-tool
#13
Hisham El Batawi, Kausar Sadia Fakhruddin
OBJECTIVE: The present study aimed to assess and monitor patterns of dental caries among primary and permanent molars using Caries Assessment Spectrum and Treatment (CAST) index and to evaluate integration of CAST tool into patient health information (PHI) system of a Teaching Dental Hospital. MATERIALS AND METHODS: Dental records of n = 348 children, aged 7-9-years, attending University Dental Hospital Sharjah, for routine checkup and treatment as part of School Dental Program were assessed and translated into CAST codes...
April 2017: European Journal of Dentistry
https://www.readbyqxmd.com/read/28729726/heart-regeneration-and-repair-after-myocardial-infarction-translational-opportunities-for-novel-therapeutics
#14
REVIEW
Thomas J Cahill, Robin P Choudhury, Paul R Riley
Current therapies for heart failure after myocardial infarction are limited and non-curative. Although regenerative approaches are receiving significant attention, clinical efforts that involve transplantation of presumed stem and progenitor cells have largely failed to deliver. Recent studies of endogenous heart regeneration in model organisms, such as zebrafish and neonatal mice, are yielding mechanistic insights into the roles of cardiomyocyte proliferation, resident stem cell niches, neovascularization, the immune system and the extracellular matrix...
July 21, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28729428/fluorine-18-labeled-carboplatin-derivative-for-pet-imaging-of-platinum-drug-distribution
#15
Narottam Lamichhane, Gajanan K Dewkar, Sundaresan Gobalakrishnan, Li Wang, Purnima Jose, Muhammad Otabashi, Jean-Luc Morelle, Nicholas Farrell, Jamal Zweit
Increasing evidence indicates that reduced intracellular drug accumulation is the parameter most consistently associated with platinum drug resistance, and emphasizes the need to directly measure intra-tumor drug concentration. In the era of precision medicine and with the advent of powerful imaging and proteomics technologies, there is an opportunity to better understand drug resistance, by exploiting these techniques to provide new knowledge on drug-target interactions. Here, we are contributing to this endeavor by reporting on the development of a fluorine-18 labeled carboplatin derivative ((18)F-FCP) that can be used to potentially image drug uptake and retention, including intra-tumoral distribution, by positron emission tomography (PET)...
July 20, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28729417/mathematical-modeling-of-tumor-tumor-distant-interactions%C3%A2-supports-a-systemic-control-of-tumor-growth
#16
Sebastien Benzekry, Clare Lamont, Dominique Barbolosi, Lynn Hlatky, Philip Hahnfeldt
Interactions between different tumors within the same organism have major clinical implications, especially in the context of surgery and metastatic disease. Three main explanatory theories (competition, angiogenesis inhibition and proliferation inhibition) have been proposed but precise determinants of the phenomenon remain poorly understood. Here we formalized these theories into mathematical models and performed biological experiments to test them with empirical data. In syngeneic mice bearing two simultaneously implanted tumors, growth of only one of the tumors was significantly suppressed (61% size reduction at day 15, p<0...
July 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28729414/methods-of-academic-course-planning-for-cancer-biology-ph-d-students-to-enhance-knowledge-of-clinical-oncology
#17
Malcolm D Mattes, Elizabeth Swart, Steven M Markwell, Sijin Wen, Linda C Vona-Davis
Little is known about how clinical oncology concepts are taught to Ph.D. students or the most effective methods of doing so. In this study, electronic surveys were sent to faculty and students at Ph.D. training programs, assessing their institution's methods of clinical oncology education and their perspective on optimal approaches to clinical oncology education. Only 40.0% of students reported any clinical oncology component to their institution's training, and only 26.5% had a clinician on their graduate advisory committee...
July 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28729406/tumor-evolution-as-a-therapeutic-target
#18
REVIEW
Nabil Amirouchene-Angelozzi, Charles Swanton, Alberto Bardelli
Recent technological advances in the field of molecular diagnostics (including blood-based tumor genotyping) allow the measurement of clonal evolution in patients with cancer, thus adding a new dimension to precision medicine: time. The translation of this new knowledge into clinical benefit implies rethinking therapeutic strategies. In essence, it means considering as a target not only individual oncogenes but also the evolving nature of human tumors. Here, we analyze the limitations of targeted therapies and propose approaches for treatment within an evolutionary framework...
July 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28728800/-cross-cultural-adaptation-of-the-pedsql-questionnaire-cancer-module-version-3-0-for-use-in-colombia
#19
Luis Fernando Fontibón, Sandra Liliana Ardila, Ricardo Sánchez
INTRODUCTION: Quality of life is an important outcome in paediatric cancer patients. Its evaluation at different times during the clinical course of the disease is essential for clinical practice focused on the needs of the patients. There is not a specific assessment tool for this purpose in Colombia. OBJECTIVE: To perform the cultural adaptation of the quality of life scale PedsQL (Paediatric Quality of Life) Cancer Module, Version 3.0 for use in Colombia. METHODS: Permission for use of the scale was obtained and the algorithm steps of the Mapi Research Trust group were followed: Direct and independent translations of scale by two native Colombian Spanish speaking translators, obtaining a preliminary version from the translations...
July 2017: Revista Colombiana de Psiquiatría
https://www.readbyqxmd.com/read/28728439/translation-of-the-leicester-cough-questionnaire-into-swedish-and-validity-and-reliability-in-chronic-obstructive-pulmonary-disease
#20
Pernilla Sönnerfors, Gun Faager, Ulrika Einarsson
PURPOSE: The purpose of this study was to translate and culturally adapt the Leicester Cough Questionnaire into Swedish and to test the validity and reliability of the Swedish version, in patients with chronic obstructive pulmonary disease. METHODS: The original Leicester Cough Questionnaire was translated into Swedish by a method, which followed an established forward-backward procedure, including cross-cultural adaptation and pretest. To test the validity of the final version of Leicester Cough Questionnaire in Swedish, the St George's Respiratory Questionnaire and the COPD Assessment Test were used (n =112) and to test reliability, the questionnaire was repeated (n = 86)...
July 20, 2017: Disability and Rehabilitation
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