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https://www.readbyqxmd.com/read/27791160/optogenetic-activation-of-dopamine-neurons-in-the-ventral-tegmental-area-induces-reanimation-from-general-anesthesia
#1
Norman E Taylor, Christa J Van Dort, Jonathan D Kenny, JunZhu Pei, Jennifer A Guidera, Ksenia Y Vlasov, Justin T Lee, Edward S Boyden, Emery N Brown, Ken Solt
Dopamine (DA) promotes wakefulness, and DA transporter inhibitors such as dextroamphetamine and methylphenidate are effective for increasing arousal and inducing reanimation, or active emergence from general anesthesia. DA neurons in the ventral tegmental area (VTA) are involved in reward processing, motivation, emotion, reinforcement, and cognition, but their role in regulating wakefulness is less clear. The current study was performed to test the hypothesis that selective optogenetic activation of VTA DA neurons is sufficient to induce arousal from an unconscious, anesthetized state...
October 24, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27745744/effect-of-itraconazole-and-rifampin-on-the-pharmacokinetics-of-olaparib-in-patients-with-advanced-solid-tumors-results-of-two-phase-i-open-label-studies
#2
Luc Dirix, Helen Swaisland, Henk M W Verheul, Sylvie Rottey, Karin Leunen, Guy Jerusalem, Christian Rolfo, Dorte Nielsen, L Rhoda Molife, Rebecca Kristeleit, Judith de Vos-Geelen, Morten Mau-Sørensen, Patricia Soetekouw, Carla van Herpen, Anitra Fielding, Karen So, Wendy Bannister, Ruth Plummer
PURPOSE: The metabolism of olaparib, a potent inhibitor of poly(ADP-ribose) polymerase (PARP) with demonstrated efficacy in patients with BRCA-mutated ovarian cancer, is mediated by cytochrome P450 (CYP) enzymes (predominantly CYP3A4/5). We assessed the potential of a CYP3A4 inhibitor (itraconazole) and inducer (rifampin) to alter the pharmacokinetic (PK) profile of olaparib following single oral tablet doses. METHODS: Two Phase I, open-label, non-randomized trials were conducted in patients with advanced solid tumors...
October 10, 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27729618/antibody-based-pet-of-upa-upar-signaling-with-broad-applicability-for-cancer-imaging
#3
Dongzhi Yang, Gregory W Severin, Casey A Dougherty, Rachel Lombardi, Daiqin Chen, Marcian E Van Dort, Todd E Barnhart, Brian D Ross, Andrew P Mazar, Hao Hong
Mounting evidence suggests that the urokinase plasminogen activator (uPA) and its receptor (uPAR) play a central role in tumor progression. The goal of this study was to develop an 89Zr-labeled, antibody-based positron emission tomography (PET) tracer for quantitative imaging of the uPA/uPAR system. An anti-uPA monoclonal antibody (ATN-291) was conjugated with a deferoxamine (Df) derivative and subsequently labeled with 89Zr. Flow cytometry, microscopy studies, and competitive binding assays were conducted to validate the binding specificity of Df-ATN-291 against uPA...
October 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27712078/the-extracellular-proteome-and-citrullinome-of-the-oral-pathogen-porphyromonas-gingivalis
#4
Tim Stobernack, Corinna Glasner, Sabryna Junker, Giorgio Gabarrini, Menke de Smit, Anne de Jong, Andreas Otto, Dörte Becher, Arie Jan van Winkelhoff, Jan Maarten van Dijl
Porphyromonas gingivalis is an oral pathogen associated with the inflammatory disease periodontitis. Periodontitis and P. gingivalis¬ have been associated with rheumatoid arthritis. One of the hallmarks of rheumatoid arthritis is the loss of tolerance against citrullinated proteins. Citrullination is a post-translational modification of arginine residues, leading to a change in structure and function of the respective protein. This modification, which is catalysed by peptidylarginine deiminases (PAD), plays a role in several physiological processes in the human body...
October 7, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27600137/comparisons-of-serum-infliximab-and-antibodies-to-infliximab-tests-used-in-inflammatory-bowel-disease-clinical-trials-of-remicade%C3%A2
#5
Joseph C Marini, Jocelyn Sendecki, Freddy Cornillie, John W Popp, Shawn Black, Marion Blank, Ann Gils, Thomas Van Stappen, Dörte Hamann, Theo Rispens, Lina Thérien, Kelly Chun, Gopi Shankar
Monitoring infliximab (IFX) concentrations and antibodies-to-IFX (ATI) titers during inflammatory bowel disease treatment may allow more informed decisions in assessing exposure/response and determining appropriate dosing. To aid in interpreting results from different commercial tests in the context of Janssen's published Remicade® results, the reliability of Janssen's IFX and ATI assays was compared with commercial assays from KU Leuven, Sanquin, Dynacare, and LabCorp. Test results were independently reported to Janssen...
September 6, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27581168/the-fundamental-role-of-ecological-feedback-mechanisms-for-the-adaptive-management-of-seagrass-ecosystems%C3%A2-%C3%A2-a-review
#6
Paul S Maxwell, Johan S Eklöf, Marieke M van Katwijk, Katherine R O'Brien, Maricela de la Torre-Castro, Christoffer Boström, Tjeerd J Bouma, Dorte Krause-Jensen, Richard K F Unsworth, Brigitta I van Tussenbroek, Tjisse van der Heide
Seagrass meadows are vital ecosystems in coastal zones worldwide, but are also under global threat. One of the major hurdles restricting the success of seagrass conservation and restoration is our limited understanding of ecological feedback mechanisms. In these ecosystems, multiple, self-reinforcing feedbacks can undermine conservation efforts by masking environmental impacts until the decline is precipitous, or alternatively they can inhibit seagrass recovery in spite of restoration efforts. However, no clear framework yet exists for identifying or dealing with feedbacks to improve the management of seagrass ecosystems...
September 1, 2016: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/27169904/cross-cultural-validation-of-the-turkish-four-dimensional-symptom-questionnaire-4dsq-using-differential-item-and-test-functioning-dif-and-dtf-analysis
#7
Berend Terluin, Pemra C Unalan, Nurver Turfaner Sipahioğlu, Seda Arslan Özkul, Harm W J van Marwijk
BACKGROUND: The Four-Dimensional Symptom Questionnaire (4DSQ) is originally a Dutch 50 item questionnaire developed in primary care to assess distress, depression, anxiety and somatization. We aimed to develop and validate a Turkish translation of the 4DSQ. METHODS: The questionnaire was translated using forward and backward translation, and pilot testing. Turkish 4DSQ-data were collected in 352 consecutive adult primary care patients. For comparison, gender and age matched Dutch reference data were drawn from a larger existing dataset...
2016: BMC Family Practice
https://www.readbyqxmd.com/read/27157582/customized-recommendations-for-production-management-clusters-of-north-american-automatic-milking-systems
#8
Marlène Tremblay, Justin P Hess, Brock M Christenson, Kolby K McIntyre, Ben Smink, Arjen J van der Kamp, Lisanne G de Jong, Dörte Döpfer
Automatic milking systems (AMS) are implemented in a variety of situations and environments. Consequently, there is a need to characterize individual farming practices and regional challenges to streamline management advice and objectives for producers. Benchmarking is often used in the dairy industry to compare farms by computing percentile ranks of the production values of groups of farms. Grouping for conventional benchmarking is commonly limited to the use of a few factors such as farms' geographic region or breed of cattle...
July 2016: Journal of Dairy Science
https://www.readbyqxmd.com/read/27113605/multicentre-comparison-of-a-diagnostic-assay-aquaporin-4-antibodies-in-neuromyelitis-optica
#9
Patrick Waters, Markus Reindl, Albert Saiz, Kathrin Schanda, Friederike Tuller, Vlastimil Kral, Petra Nytrova, Ondrej Sobek, Helle Hvilsted Nielsen, Torben Barington, Søren T Lillevang, Zsolt Illes, Kristin Rentzsch, Achim Berthele, Tímea Berki, Letizia Granieri, Antonio Bertolotto, Bruno Giometto, Luigi Zuliani, Dörte Hamann, E Daniëlle van Pelt, Rogier Hintzen, Romana Höftberger, Carme Costa, Manuel Comabella, Xavier Montalban, Mar Tintoré, Aksel Siva, Ayse Altintas, Günnur Deniz, Mark Woodhall, Jacqueline Palace, Friedemann Paul, Hans-Peter Hartung, Orhan Aktas, Sven Jarius, Brigitte Wildemann, Christian Vedeler, Anne Ruiz, M Isabel Leite, Peter Trillenberg, Monika Probst, Sandra Saschenbrecker, Angela Vincent, Romain Marignier
OBJECTIVE: Antibodies to cell surface central nervous system proteins help to diagnose conditions which often respond to immunotherapies. The assessment of antibody assays needs to reflect their clinical utility. We report the results of a multicentre study of aquaporin (AQP) 4 antibody (AQP4-Ab) assays in neuromyelitis optica spectrum disorders (NMOSD). METHODS: Coded samples from patients with neuromyelitis optica (NMO) or NMOSD (101) and controls (92) were tested at 15 European diagnostic centres using 21 assays including live (n=3) or fixed cell-based assays (n=10), flow cytometry (n=4), immunohistochemistry (n=3) and ELISA (n=1)...
September 2016: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/26996810/global-analysis-of-the-impact-of-linezolid-onto-virulence-factor-production-in-s-aureus-usa300
#10
Florian Bonn, Jan Pané-Farré, Rabea Schlüter, Marc Schaffer, Stephan Fuchs, Jörg Bernhardt, Katharina Riedel, Andreas Otto, Uwe Völker, Jan Maarten van Dijl, Michael Hecker, Ulrike Mäder, Dörte Becher
The translation inhibitor linezolid is an antibiotic of last resort against Gram-positive pathogens including methicillin resistant strains of the nosocomial pathogen Staphylococcus aureus. Linezolid is reported to inhibit production of extracellular virulence factors, but the molecular cause is unknown. To elucidate the physiological response of S. aureus to linezolid in general and the inhibition of virulence factor synthesis in particular a holistic study was performed. Linezolid was added to exponentially growing S...
May 2016: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/26991753/physostigmine-and-methylphenidate-induce-distinct-arousal-states-during-isoflurane-general-anesthesia-in-rats
#11
Jonathan D Kenny, Jessica J Chemali, Joseph F Cotten, Christa J Van Dort, Seong-Eun Kim, Demba Ba, Norman E Taylor, Emery N Brown, Ken Solt
BACKGROUND: Although emergence from general anesthesia is clinically treated as a passive process driven by the pharmacokinetics of drug clearance, agents that hasten recovery from general anesthesia may be useful for treating delayed emergence, emergence delirium, and postoperative cognitive dysfunction. Activation of central monoaminergic neurotransmission with methylphenidate has been shown to induce reanimation (active emergence) from general anesthesia. Cholinergic neurons in the brainstem and basal forebrain are also known to promote arousal...
November 2016: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/26988203/an-exploratory-study-on-speech-and-hearing-outcomes-in-children-with-cleft-lip-and-palate
#12
H Mohd Ibrahim, F H Mohamed Yusoff, K Ahmad, S Van Dort
INTRODUCTION: Little is known about the treatment outcomes of children with cleft lip and/or palate (CLP) receiving surgical care for primary lip and palate closure in Malaysia. OBJECTIVES: This study examined the speech and hearing status of Malay-speaking children with CLP residing in Kuala Lumpur. METHODS: Parents whose children were between the age of 5 and 7 years were recruited via the Cleft Lip and Palate Association of Malaysia (CLAPAM) registry...
December 2015: Medical Journal of Malaysia
https://www.readbyqxmd.com/read/26971629/electrical-stimulation-of-the-parabrachial-nucleus-induces-reanimation-from-isoflurane-general-anesthesia
#13
Fanuel Muindi, Jonathan D Kenny, Norman E Taylor, Ken Solt, Matthew A Wilson, Emery N Brown, Christa J Van Dort
Clinically, emergence from general anesthesia is viewed as a passive process where anesthetics are discontinued at the end of surgery and anesthesiologists wait for the drugs to wear off. The mechanisms involved in emergence are not well understood and there are currently no drugs that can actively reverse the state of general anesthesia. An emerging hypothesis states that brain regions that control arousal become active during emergence and are a key part of the return to wakefulness. In this study, we tested the hypothesis that electrical activation of the glutamatergic parabrachial nucleus (PBN) in the brainstem is sufficient to induce reanimation (active emergence) during continuous isoflurane general anesthesia...
June 1, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/26955830/trajectories-of-body-mass-index-before-the-diagnosis-of-cardiovascular-disease-a-latent-class-trajectory-analysis
#14
Klodian Dhana, Joost van Rosmalen, Dorte Vistisen, M Arfan Ikram, Albert Hofman, Oscar H Franco, Maryam Kavousi
Patients with cardiovascular disease (CVD) are a heterogeneous group regarding their body mass index (BMI) levels at the time of diagnosis. To address the heterogeneity of CVD, we examined the trajectories of change in body mass index (BMI) and in other cardio-metabolic risk factors before CVD diagnosis. The study included 6126 participants from the prospective population-based Rotterdam Study, followed over 22 years with clinical examinations every 4 years. Latent class trajectory analysis and mixed-effect models were used to develop trajectories of BMI and other cardio-metabolic risk factors respectively...
June 2016: European Journal of Epidemiology
https://www.readbyqxmd.com/read/26945896/hla-c-and-kir-combined-genotype-as-new-response-marker-for-hbeag-positive-chronic-hepatitis-b-patients-treated-with-interferon-based-combination-therapy
#15
F Stelma, L Jansen, M J Sinnige, K A van Dort, R B Takkenberg, H L A Janssen, H W Reesink, N A Kootstra
Current treatment for chronic hepatitis B infection (CHB) consists of interferon-based therapy. However, for unknown reasons, a large proportion of patients with CHB do not respond to this treatment. Hence, there is a pressing need to establish response markers to select patients who will benefit from therapy and to spare potential nonresponders from unnecessary side effects of antiviral therapy. Here, we assessed whether HLA-C and KIR genotypes were associated with treatment outcome for CHB. Twelve SNPs in or near the HLA-C gene were genotyped in 86 CHB patients (41 HBeAg positive; 45 HBeAg negative) treated with peginterferon alfa-2a + adefovir...
August 2016: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/26943489/discovery-of-bifunctional-oncogenic-target-inhibitors-against-allosteric-mitogen-activated-protein-kinase-mek1-and-phosphatidylinositol-3-kinase-pi3k
#16
Marcian E Van Dort, Hao Hong, Hanxiao Wang, Charles A Nino, Rachel L Lombardi, Avery E Blanks, Stefanie Galbán, Brian D Ross
The synthesis of a series of single entity, bifunctional MEK1/PI3K inhibitors achieved by covalent linking of structural analogs of the ATP-competitive PI3K inhibitor ZSTK474 and the ATP-noncompetitive MEK inhibitor PD0325901 is described. Inhibitors displayed potent in vitro inhibition of MEK1 (0.015 < IC50 (nM) < 56.7) and PI3K (54 < IC50 (nM) < 341) in enzymatic inhibition assays. Concurrent MEK1 and PI3K inhibition was demonstrated with inhibitors 9 and 14 in two tumor cell lines (A549, D54)...
March 24, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/26898275/factors-associated-with-increased-milk-production-for-automatic-milking-systems
#17
Marlène Tremblay, Justin P Hess, Brock M Christenson, Kolby K McIntyre, Ben Smink, Arjen J van der Kamp, Lisanne G de Jong, Dörte Döpfer
Automatic milking systems (AMS) are increasingly popular throughout the world. Our objective was to analyze 635 North American dairy farms with AMS for (risk) factors associated with increased milk production per cow per day and milk production per robot per day. We used multivariable generalized mixed linear regressions, which identified several significant risk factors and interactions of risk factors associated with milk production. Free traffic was associated with increased production per cow and per robot per day compared with forced systems, and the presence of a single robot per pen was associated with decreased production per robot per day compared with pens using 2 robots...
May 2016: Journal of Dairy Science
https://www.readbyqxmd.com/read/26885396/beliefs-barriers-and-preferences-of-european-overweight-women-to-adopt-a-healthier-lifestyle-in-pregnancy-to-minimize-risk-of-developing-gestational-diabetes-mellitus-an-explorative-study
#18
Judith G M Jelsma, Karen M van Leeuwen, Nicolette Oostdam, Christopher Bunn, David Simmons, Gernot Desoye, Rosa Corcoy, Juan M Adelantado, Alexandra Kautzky-Willer, Jürgen Harreiter, Frans Andre van Assche, Roland Devlieger, Dirk Timmerman, David Hill, Peter Damm, Elisabeth R Mathiesen, Ewa Wender-Ozegowska, Agnieszka Zawiejska, Pablo Rebollo, Annunziata Lapolla, Maria G Dalfrà, Stefano Del Prato, Alessandra Bertolotto, Fidelma Dunne, Dorte M Jensen, Lise Lotte T Andersen, Frank J Snoek, Mireille N M van Poppel
INTRODUCTION: We explored beliefs, perceived barriers, and preferences regarding lifestyle changes among overweight European pregnant women to help inform the development of future lifestyle interventions in the prevention of gestational diabetes mellitus. METHODS: An explorative mixed methods, two-staged study was conducted to gather information from pregnant European women (BMI ≥ 25 kg/m2). In three European countries 21 interviews were conducted, followed by 71 questionnaires in six other European countries...
2016: Journal of Pregnancy
https://www.readbyqxmd.com/read/26780110/loop-mediated-isothermal-amplification-lamp-for-the-detection-and-subtyping-of-human-papillomaviruses-hpv-in-oropharyngeal-squamous-cell-carcinoma-opscc
#19
D M Livingstone, M Rohatensky, P Mintchev, S C Nakoneshny, D J Demetrick, G van Marle, J C Dort
BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is a growing problem that presents a significant challenge to Otolaryngologist-Head and Neck Surgeons. Knowledge of HPV status yields critical prognostic information, with potential for treatment selection based on tumour HPV status. The current gold standard of diagnosis, PCR, is expensive, demanding and time consuming. Alternatives such as p16 immunohistochemistry are subjective and potentially inaccurate...
February 2016: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/26641855/dyrk1a-controls-hiv-1-replication-at-a-transcriptional-level-in-an-nfat-dependent-manner
#20
Thijs Booiman, Vladimir V Loukachov, Karel A van Dort, Angélique B van 't Wout, Neeltje A Kootstra
BACKGROUND: Transcription of the HIV-1 provirus is regulated by both viral and host proteins and is very important in the context of viral latency. In latently infected cells, viral gene expression is inhibited as a result of the sequestration of host transcription factors and epigenetic modifications. RESULTS: In our present study we analyzed the effect of host factor dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) on HIV-1 replication. We show that DYRK1A controls HIV-1 replication by regulating provirus transcription...
2015: PloS One
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