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https://www.readbyqxmd.com/read/28429368/-aralar-agc1-deficiency-a-neurodevelopmental-disorder-with-severe-impairment-of-neuronal-mitochondrial-respiration-does-not-produce-a-primary-increase-in-brain-lactate
#1
Inés Juaristi, María L García-Martin, Tiago B Rodrigues, Jorgina Satrústegui, Irene Llorente-Folch, Beatriz Pardo
ARALAR/AGC1 (aspartate-glutamate mitochondrial carrier 1) is an important component of the NADH malate-aspartate shuttle (MAS). AGC1-deficiency is a rare disease causing global cerebral hypomyelination, developmental arrest, hypotonia, and epilepsy (OMIM ID #612949); the aralar-KO mouse recapitulates the major findings in humans. This study was aimed at understanding the impact of ARALAR-deficiency in brain lactate levels as a biomarker. We report that lactate was equally abundant in wild-type and aralar-KO mouse brain in vivo at PND 17...
April 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28428887/differential-intratumoral-distributions-of-cd8-and-cd163-immune-cells-as-prognostic-biomarkers-in-breast-cancer
#2
Sotirios P Fortis, Michael Sofopoulos, Nectaria N Sotiriadou, Christoforos Haritos, Christoforos K Vaxevanis, Eleftheria A Anastasopoulou, Nicole Janssen, Niki Arnogiannaki, Alexandros Ardavanis, Graham Pawelec, Sonia A Perez, Constantin N Baxevanis
BACKGROUND: Tumor immune cell infiltrates are essential in hindering cancer progression and may complement the TNM classification. CD8+ and CD163+ cells have prognostic impact in breast cancer but their spatial heterogeneity has not been extensively explored in this type of cancer. Here, their potential as prognostic biomarkers was evaluated, depending on their combined densities in the tumor center (TC) and the tumor invasive margin (IM). METHODS: CD8+ and CD163+ cells were quantified by immunohistochemistry of formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples from a cohort totaling 162 patients with histologically-confirmed primary invasive non-metastatic ductal breast cancer diagnosed between 2000 and 2015...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428690/implications-of-ace-i-d-gene-variants-to-the-genetic-susceptibility-of-coronary-artery-disease-in-asian-indians
#3
G K Bhatti, J S Bhatti, R Vijayvergiya, B Singh
Angiotensin-1-converting enzyme (ACE) gene has established substantial attention in the recent years as a candidate gene for hypertension, cardiovascular diseases and type 2 diabetes. The aim of the present study was to investigate the association of ACE (I/D) polymorphism with coronary artery disease (CAD) in a north Indian population. A total of 662 subjects (330 CAD patients and 332 healthy controls) were examined for association of ACE gene (I/D) polymorphism and environmental risk factors. The mean age of the CAD patients and control subjects was 60...
June 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28428134/use-of-physiological-biomarkers-in-diagnosis-along-with-field-trials-of-different-trypanisidal-drugs-in-camels-of-cholistan-desert
#4
Aneela Zameer Durrani, Zubair Bashir, Khalid Mehmood, Muhammad Avais, Haroon Akbar, Waqas Ahmad, Muhammad Azeem
The point prevalence of trypanosomiasis with different physiological biomarkers along with evaluation of the most responsive trypanosidal drug against trypanosomiasis under field conditions was studied. For this purpose a total of 300 free range camels were selected at different grazing and watering point in Cholistan desert. The study population of camels included 150 clinically suspected camels for trypanosomiasis and 150 healthy camels with normal temperature, pulse and respiration. For therapeutic trials 36 positively diagnosed animals were randomly divided into three experimental groups for therapeutic trials...
April 17, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28427840/aav-id-a-rapid-and-robust-assay-for-batch-to-batch-consistency-evaluation-of-aav-preparations
#5
Simon Pacouret, Mohammed Bouzelha, Rajani Shelke, Eva Andres-Mateos, Ru Xiao, Anna Maurer, Mathieu Mevel, Heikki Turunen, Trisha Barungi, Magalie Penaud-Budloo, Frédéric Broucque, Véronique Blouin, Philippe Moullier, Eduard Ayuso, Luk H Vandenberghe
Adeno-associated virus (AAV) vectors are promising clinical candidates for therapeutic gene transfer, and a number of AAV-based drugs may emerge on the market over the coming years. To insure the consistency in efficacy and safety of any drug vial that reaches the patient, regulatory agencies require extensive characterization of the final product. Identity is a key characteristic of a therapeutic product, as it ensures its proper labeling and batch-to-batch consistency. Currently, there is no facile, fast, and robust characterization assay enabling to probe the identity of AAV products at the protein level...
April 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28427836/adherence-to-continuous-positive-airway-pressure-in-adults-with-an-intellectual-disability
#6
Kim A Luijks, Nele L Vandenbussche, Dirk Pevernagie, Sebastiaan Overeem, Sigrid Pillen
STUDY OBJECTIVES: This retrospective study evaluated the feasibility of continuous positive airway pressure (CPAP) therapy in adults with intellectual disabilities (ID). METHODS: CPAP therapy of 24 obstructive sleep apnea syndrome (OSA) patients with ID were compared to age- and sex-matched adults with normal cognitive functioning. All ID patients received an intensive in-hospital training protocol to stimulate adherence. Good adherence was defined as a use of >70% of the nights and >4 h/night...
March 30, 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28427813/novel-pyrazoles-and-pyrazolo-1-2-a-pyridazines-as-selective-cox-2-inhibitors-ultrasound-assisted-synthesis-biological-evaluation-and-dft-calculations
#7
Nagat Ghareb, Hosam A Elshihawy, Mohamed M Abdel-Daim, Mohamed A Helal
COX-2 is an inducible enzyme mediating inflammatory responses. Selective targeting of COX-2 is useful for developing anti-inflammatory agents devoid of ulcerogenic activity. Herein, we report the design and synthesis of a series of pyrazoles and pyrazolo[1,2-a]pyridazines with selective COX-2 inhibitory activity and in vivo anti-inflammatory effect. Both series were accessed through acid-catalyzed ultrasound-assisted reactions. The most active compounds in this study are two novel molecules, 11 and 16, showing promising selectivity and decent IC50 of 16...
April 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28426748/tails-of-the-travelling-gaussian-model-and-the-relative-age-effect-tales-of-age-discrimination-and-wasted-talent
#8
John R Doyle, Paul A Bottomley, Rob Angell
The Relative Age Effect (RAE) documents the inherent disadvantages of being younger rather than older in an age-banded cohort, typically a school- or competition-year, to the detriment of career-progression, earnings and wellbeing into adulthood. We develop the Tails of the Travelling Gaussian (TTG) to model the mechanisms behind RAE. TTG has notable advantages over existing approaches, which have been largely descriptive, potentially confounded, and non-comparable across contexts. In Study 1, using data from the UK's Millennium Cohort Study, we investigate the different levels of RAE bias across school-level academic subjects and "personality" traits...
2017: PloS One
https://www.readbyqxmd.com/read/28426136/differentiating-signals-to-make-biological-sense-a-guide-through-databases-for-ms-based-non-targeted-metabolomics
#9
REVIEW
Alberto Gil de la Fuente, Emily Grace Armitage, Abraham Otero, Coral Barbas, Joanna Godzien
Metabolite identification is one of the most challenging steps in metabolomics studies and reflects one of the greatest bottlenecks in the entire workflow. The success of this step determines the success of the entire research, therefore the quality at which annotations are given requires special attention. A variety of tools and resources are available to aid metabolite identification or annotation, offering different and often complementary functionalities. In preparation for this article, almost 50 databases were reviewed, from which 17 were selected for discussion, chosen for their on-line ESI-MS functionality...
April 20, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28425640/profiling-of-the-silica-induced-molecular-events-in-lung-epithelial-cells-using-the-rna-seq-approach
#10
Judy Y W Chan, Joseph C C Tsui, Patrick T W Law, Winnie K W So, Doris Y P Leung, Michael M K Sham, Stephen K W Tsui, Carmen W H Chan
Silicosis is a prolonged, irreversible and incurable occupational disease, and there is a significant number of newly diagnosed cases every year in Hong Kong. Due to the long latency of the disease, the diagnosis can be missed until detailed clinical examination at a later stage. For a better control of this deadly disease, detailing the pro-inflammatory and fibrotic events in the macrophage would be instrumental in understanding the pathogenesis of the disease and essential for the significant biomarkers discovery...
April 20, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28425373/calm-child-programme
#11
Ereny Gobrial, Raghu Raghavan
Children with autism spectrum disorder (ASD) and intellectual disabilities (IDs) are more vulnerable to experiencing anxiety disorders. Parental involvement in intervention is crucial for successful management of the interventions in the population of people with ASDs. This article describes the design and evaluation of parenting programme for anxiety disorders in children and young people with ASD and ID. In phase 1 semi-structured interviews were conducted to explore management strategies for anxiety at home and in school settings...
January 1, 2017: Journal of Intellectual Disabilities: JOID
https://www.readbyqxmd.com/read/28424659/online-measurement-of-microembolic-signal-burden-by-transcranial-doppler-during-catheter-ablation-for-atrial-fibrillation-results-of-a-multicenter-trial
#12
Christian von Bary, Thomas Deneke, Thomas Arentz, Anja Schade, Heiko Lehrmann, Sabine Fredersdorf, Dobri Baldaranov, Lars Maier, Felix Schlachetzki
INTRODUCTION: Left atrial pulmonary vein isolation (PVI) is an accepted treatment option for patients with symptomatic atrial fibrillation (AF). This procedure can be complicated by stroke or silent cerebral embolism. Online measurement of microembolic signals (MESs) by transcranial Doppler (TCD) may be useful for characterizing thromboembolic burden during PVI. In this prospective multicenter trial, we investigated the burden, characteristics, and composition of MES during left atrial catheter ablation using a variety of catheter technologies...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28424273/certainty-of-genuine-treatment-increases-drug-responses-among-intellectually-disabled-patients
#13
Karin B Jensen, Irving Kirsch, Moa Pontén, Annelie Rosén, Kathy Yang, Randy L Gollub, Vincent des Portes, Ted J Kaptchuk, Aurore Curie
OBJECTIVE: To determine the placebo component of treatment responses in patients with intellectual disability (ID). METHODS: A statistical meta-analysis comparing bias-corrected effect sizes (Hedges g) of drug responses in open-label vs placebo-controlled clinical trials was performed, as these trial types represent different certainty of receiving genuine treatment (100% vs 50%). Studies in fragile X, Down, Prader-Willi, and Williams syndrome published before June 2015 were considered...
April 19, 2017: Neurology
https://www.readbyqxmd.com/read/28423213/systemic-tumor-targeted-sodium-iodide-symporter-nis-gene-therapy-of-hepatocellular-carcinoma-mediated-by-b6-peptide-polyplexes
#14
Sarah Urnauer, Kathrin Klutz, Geoffrey K Grünwald, Stephan Morys, Nathalie Schwenk, Christian Zach, Franz-Josef Gildehaus, Wolfgang Roedl, Manfred Ogris, Ernst Wagner, Christine Spitzweg
BACKGROUND: Non-viral polymer-based gene transfer represents an adaptable system for tumor-targeted gene therapy, as various design strategies of shuttle systems together with the mechanistic concept of active tumor targeting lead to improved gene delivery vectors resulting in higher tumor specificity, efficacy and safety. METHODS: Using the sodium iodide symporter (NIS) as theranostic gene, non-viral gene delivery vehicles based on linear polyethylenimine (LPEI), polyethylene glycol (PEG) and coupled with the synthetic peptide B6 (LPEI-PEG-B6), which specifically binds to tumor cells, were investigated in a hepatocellular carcinoma (HCC) xenograft model for tumor-selectivity and transduction efficiency...
April 19, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28422131/variants-in-cplx1-in-two-families-with-autosomal-recessive-severe-infantile-myoclonic-epilepsy-and-id
#15
Silke Redler, Tim M Strom, Thomas Wieland, Kirsten Cremer, Hartmut Engels, Felix Distelmaier, Jörg Schaper, Alma Küchler, Johannes R Lemke, Stephanie Jeschke, Nicole Schreyer, Heinrich Sticht, Margarete Koch, Hermann-Josef Lüdecke, Dagmar Wieczorek
For a large number of individuals with intellectual disability (ID), the molecular basis of the disorder is still unknown. However, whole-exome sequencing (WES) is providing more and more insights into the genetic landscape of ID. In the present study, we performed trio-based WES in 311 patients with unsolved ID and additional clinical features, and identified homozygous CPLX1 variants in three patients with ID from two unrelated families. All displayed marked developmental delay and migrating myoclonic epilepsy, and one showed a cerebellar cleft in addition...
April 19, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28421567/early-biomarker-response-and-patient-preferences-to-oral-and-intramuscular-vitamin-b12-substitution-in-primary-care-a-randomised-parallel-group-trial
#16
Corina Metaxas, Deborah Mathis, Cyrill Jeger, Kurt Eduard Hersberger, Isabelle Arnet, Philipp Walter
BACKGROUND: Vitamin B12 (VB12) deficiency can be treated with oral high-dose substitution or intramuscular (i.m.) injection of VB12. Whenever alternative routes of administration exist, patient preferences should be considered when choosing the treatment. We aimed to assess outpatient preferences towards oral or IM VB12 substitution and confirm noninferiority of early biomarker response with oral treatment, in a typical primary care population. METHODS: Prospective randomised nonblinded parallel-group trial...
April 19, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28420419/optimizing-veteran-centered-prostate-cancer-survivorship-care-study-protocol-for-a-randomized-controlled-trial
#17
Ted A Skolarus, Tabitha Metreger, Soohyun Hwang, Hyungjin Myra Kim, Robert L Grubb, Jeffrey R Gingrich, Sarah T Hawley
BACKGROUND: Although prostate cancer is the most common cancer among veterans receiving care in the Veterans Health Administration (VA), more needs to be done to understand and improve survivorship care for this large population. This study, funded by VA Health Services Research & Development (HSR&D), seeks to address the need to improve patient-centered survivorship care for veterans with prostate cancer. METHODS/DESIGN: This is a two-armed randomized controlled trial (RCT) with a target enrollment of up to 325 prostate cancer survivors per study arm (total anticipated n = 600)...
April 18, 2017: Trials
https://www.readbyqxmd.com/read/28420357/in-search-of-quality-indicators-for-down-syndrome-healthcare-a-scoping-review
#18
Francine A van den Driessen Mareeuw, Mirjam I Hollegien, Antonia M W Coppus, Diana M J Delnoij, Esther de Vries
BACKGROUND: The medical care chain around Down syndrome (DS) is complex, with many multidisciplinary challenges. The current quality of care is unknown. Outcome-oriented quality indicators have the potential to improve medical practice and evaluate whether innovations are successful. This is particularly interesting for the evolving care for people with DS and intellectual disabilities (ID). The aim of this study was to identify existing indicators for medical DS care, by reviewing the literature...
April 18, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28420349/grey-literature-in-systematic-reviews-a-cross-sectional-study-of-the-contribution-of-non-english-reports-unpublished-studies-and-dissertations-to-the-results-of-meta-analyses-in-child-relevant-reviews
#19
Lisa Hartling, Robin Featherstone, Megan Nuspl, Kassi Shave, Donna M Dryden, Ben Vandermeer
BACKGROUND: Systematic reviews (SRs) are an important source of information about healthcare interventions. A key component of a well-conducted SR is a comprehensive literature search. There is limited evidence on the contribution of non-English reports, unpublished studies, and dissertations and their impact on results of meta-analyses. METHODS: Our sample included SRs from three Cochrane Review Groups: Acute Respiratory Infections (ARI), Infectious Diseases (ID), Developmental Psychosocial and Learning Problems (DPLP) (n = 129)...
April 19, 2017: BMC Medical Research Methodology
https://www.readbyqxmd.com/read/28419929/-r-and-s-18-f-labeled-2-arylbenzofurans-with-improved-pharmacokinetics-as-%C3%AE-amyloid-imaging-probes
#20
Jia Song, Xiaoyang Zhang, Yunling Zhao, Hui Yang, Jinming Zhang, Xiaojun Zhang, Jiapei Dai, Mengchao Cui
A new class of optical isomers of 2-arylbenzofuran derivatives were synthesized and evaluated as potential β-amyloid plaques imaging agents. Both lipophilicity and signal-to-noise ratio were significantly improved by adding a chiral hydroxyl group to 1-fluoro-3-(oxidanyl)propan-2-ol side chain. These derivatives displayed moderate to high binding affinity towards Aβ1-42 aggregates. Four tracers possessing potent binding affinity (Ki < 30 nM) were chosen for further investigation. In in vitro autoradiography studies, the four selected probes showed effective binding to Aβ plaques in Tg mouse and AD human brain tissue after labeled by (18)F...
April 3, 2017: European Journal of Medicinal Chemistry
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