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Petr Vodicka, Kathryn Chase, Maria Iuliano, Adelaide Tousley, Dana T Valentine, Ellen Sapp, Kimberly B Kegel-Gleason, Miguel Sena-Esteves, Neil Aronin, Marian DiFiglia
BACKGROUND: Mutant huntingtin (mHTT) is encoded by the Huntington's disease (HD) gene and its accumulation in the brain contributes to HD pathogenesis. Reducing mHTT levels through activation of the autophagosome-lysosomal pathway may have therapeutic benefit. Transcription factor EB (TFEB) regulates lysosome biogenesis and autophagy. OBJECTIVE: To examine if increasing TFEB protein levels in HD mouse striatum induces autophagy and influences mHTT levels. METHODS: We introduced cDNA encoding TFEB with an HA tag (TFEB-HA) under the control of neuron specific synapsin 1 promoter into the striatum of 3 month old HDQ175/Q7 mice using adeno-associated virus AAV2/9...
October 1, 2016: Journal of Huntington's Disease
D S K Sihono, C Weiss, L Vogel, S Kegel, J Thölking, F Wenz, H Wertz, F Lohr, J Boda-Heggemann
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Tatiana C A Pinto, Fabíola C O Kegele, Cícero A G Dias, Rosana R Barros, José M Peralta, Vânia L C Merquior, Maria da Gloria Carvalho, Sopio Chochua, Paulina Hawkins, Lesley McGee, Lucia M Teixeira
Antimicrobial resistant pneumococcal strains have been detected worldwide since the 1960's. In Brazil, the first penicillin non-susceptible pneumococci (PNSP) were reported in the 1980's, and their emergence and dissemination have been mainly attributed to serogroup 9 and serotype 14 strains, especially those highly related to recognized international clones. In the present study, antimicrobial susceptibility testing and Multilocus Sequence Typing (MLST) were performed on 315 pneumococcal isolates belonging to serogroup 9 (n=99) or serotype 14 (n=216), recovered from patients or asymptomatic carriers between 1988 and 2011 in Brazil, in order to trace changes in antimicrobial resistance and genotypes prior to the full introduction of the pneumococcal conjugate vaccine in the country...
August 29, 2016: Antimicrobial Agents and Chemotherapy
Leen Maes, Alexandra De Kegel, Hilde Van Waelvelde, Els De Leenheer, Helen Van Hoecke, Julie Goderis, Ingeborg Dhooge
OBJECTIVES: Hearing-impaired children are at risk for vestibular damage and delayed motor development. Two major causes of congenital hearing loss are cytomegalovirus (CMV) infection and connexin (Cx) 26 mutations. Comparison of the motor performance and vestibular function between these specific groups is still underexplored. The objective of this study was to investigate the impact of congenital (c)CMV and Cx26 on the motor performance and vestibular function in 6 months old infants...
August 8, 2016: Ear and Hearing
Andres Maiorana, Susan Kegeles, Ximena Salazar, Kelika Konda, Alfonso Silva-Santisteban, Carlos Cáceres
We used qualitative, quantitative, and observational methods to assess the feasibility, acceptability, and potential efficacy of Proyecto Orgullo (PO), a pilot community mobilisation intervention to decrease sexual risk, promote health-seeking behaviours, and facilitate personal and community empowerment among gay men (GM) and transgender women (TW) in Peru. PO was adapted from Mpowerment and Hermanos de Luna y Sol, two US interventions. PO included six interrelated core elements: (1) Self-reflection Small Group sessions; (2) Supporting peers in HIV prevention; (3) Mobilisation Activities addressing HIV, GM/TW issues, and community empowerment; (4) A Core Group (staff + GM/TW volunteers) designing/implementing those activities; (5) A Project Space; (6) Publicity...
August 2016: Global Public Health
Adelaide Tousley, Kimberly B Kegel-Gleason
Induced pluripotent stem cells (iPSCs) derived from controls and patients can act as a starting point for in vitro differentiation into human brain cells for discovery of novel targets and treatments for human disease without the same ethical limitations posed by embryonic stem cells. Numerous groups have successfully produced and characterized Huntington's disease (HD) iPSCs with different CAG repeat lengths, including cells from patients with one or two HD alleles. HD iPSCs and the neural cell types derived from them recapitulate some disease phenotypes found in both human patients and animal models...
June 28, 2016: Journal of Huntington's Disease
Lutz Wartberg, Levente Kriston, Katharina Kegel, Rainer Thomasius
Background and aims The surge of problematic Internet use in adolescents is a continuously growing problem across the globe. To our knowledge, to date valid questionnaire-based measurement of problematic Internet use is possible only by self-assessment. The objective for the present study was to adapt an established instrument for a parental assessment of adolescent problematic Internet use and to evaluate the psychometric properties of this questionnaire. Methods Data were collected from a representative German sample of 1,000 parents of adolescents aged between 12 and 17 years using a standardized questionnaire...
June 2016: Journal of Behavioral Addictions
Fernando Caravaggio, Lawrence S Kegeles, Alan A Wilson, Gary Remington, Carol Borlido, David C Mamo, Ariel Graff-Guerrero
Endogenous dopamine (DA) levels at dopamine D2/3 receptors (D2/3 R) have been quantified in the living human brain using the agonist radiotracer [(11) C]-(+)-PHNO. As an agonist radiotracer, [(11) C]-(+)-PHNO is more sensitive to endogenous DA levels than antagonist radiotracers. We sought to determine the proportion of the variance in baseline [(11) C]-(+)-PHNO binding to D2/3 Rs which can be accounted for by variation in endogenous DA levels. This was done by computing the Pearson's coefficient for the correlation between baseline binding potential (BPND ) and the change in BPND after acute DA depletion, using previously published data...
November 2016: Synapse
A Mehnert, J Barth, M Gaspar, B Leibbrand, C-D Kegel, W Bootsveld, M Friedrich, T J Hartung, D Berger, U Koch
This longitudinal study was designed to assess patients' desire for early retirement and investigate which cancer-related and psychosocial characteristics are associated with early retirement. We assessed 750 cancer patients at the beginning (t0 ) and end (t1 ) of, and 12 months after (t2 ) inpatient cancer rehabilitation. At t0 , 22% had a desire to retire early. These patients reported significantly longer sick leave periods, less favourable workplace environments, lower work ability, higher psychological distress and lower quality of life than other patients...
June 23, 2016: European Journal of Cancer Care
Daniela Deharde, Christin Schneider, Thomas Hiller, Nicolas Fischer, Victoria Kegel, Marc Lübberstedt, Nora Freyer, Jan G Hengstler, Tommy B Andersson, Daniel Seehofer, Johann Pratschke, Katrin Zeilinger, Georg Damm
Primary human hepatocytes (PHH) are still considered as gold standard for investigation of in vitro metabolism and hepatotoxicity in pharmaceutical research. It has been shown that the three-dimensional (3D) cultivation of PHH in a sandwich configuration between two layers of extracellular matrix (ECM) enables the hepatocytes to adhere three dimensionally leading to formation of in vivo like cell-cell contacts and cell-matrix interactions. The aim of the present study was to investigate the influence of different ECM compositions on morphology, cellular arrangement and bile canaliculi formation as well as bile excretion processes in PHH sandwich cultures systematically...
October 2016: Archives of Toxicology
Petr Vodicka, Kathryn Chase, Maria Iuliano, Dana T Valentine, Ellen Sapp, Boxun Lu, Kimberly B Kegel-Gleason, Miguel Sena-Esteves, Neil Aronin, Marian DiFiglia
BACKGROUND: Reducing mutant huntingtin (mHTT) in neurons may be a therapy for Huntington's disease (HD). Elevating NUB1 protein reduced mHTT levels in cell and fly models of HD through a proteasome dependent mechanism. OBJECTIVE: To examine the effects of augmenting NUB1 in HD mouse striatum on mHTT levels. METHODS: Striata of HDQ175/Q7 mice were injected at 3 months of age with recombinant AAV2/9 coding for NUB1 or GFP under the control of the neuron specific human synapsin 1 promoter and examined 6 months post-injection for levels of huntingtin, the striatal markers DARPP32 and PDE10A, the astrocyte marker GFAP, and the autophagy and mHTT aggregate marker P62 using immunolabeling of brain sections and Western blot assay of striatal subcellular fractions...
June 13, 2016: Journal of Huntington's Disease
Chris H J Evers, Jurriaan A Luiken, Peter G Bolhuis, Willem K Kegel
Particles with directional interactions are promising building blocks for new functional materials and may serve as models for biological structures. Mutually attractive nanoparticles that are deformable owing to flexible surface groups, for example, may spontaneously order themselves into strings, sheets and large vesicles. Furthermore, anisotropic colloids with attractive patches can self-assemble into open lattices and the colloidal equivalents of molecules and micelles. However, model systems that combine mutual attraction, anisotropy and deformability have not yet been realized...
June 16, 2016: Nature
Jodi J Weinstein, Muhammad O Chohan, Mark Slifstein, Lawrence S Kegeles, Holly Moore, Anissa Abi-Dargham
In light of the clinical evidence implicating dopamine in schizophrenia and the prominent hypotheses put forth regarding alterations in dopaminergic transmission in this disease, molecular imaging has been used to examine multiple aspects of the dopaminergic system. We review the imaging methods used and compare the findings across the different molecular targets. Findings have converged to suggest early dysregulation in the striatum, especially in the rostral caudate, manifesting as excess synthesis and release...
March 31, 2016: Biological Psychiatry
Dikoma C Shungu, Xiangling Mao, Robyn Gonzales, Tacara N Soones, Jonathan P Dyke, Jan Willem van der Veen, Lawrence S Kegeles
Abnormalities in brain γ-aminobutyric acid (GABA) have been implicated in various neuropsychiatric and neurological disorders. However, in vivo GABA detection by (1) H MRS presents significant challenges arising from the low brain concentration, overlap by much stronger resonances and contamination by mobile macromolecule (MM) signals. This study addresses these impediments to reliable brain GABA detection with the J-editing difference technique on a 3-T MR system in healthy human subjects by: (i) assessing the sensitivity gains attainable with an eight-channel phased-array head coil; (ii) determining the magnitude and anatomic variation of the contamination of GABA by MM; and (iii) estimating the test-retest reliability of the measurement of GABA with this method...
July 2016: NMR in Biomedicine
Lawrence S Kegeles
No abstract text is available yet for this article.
May 1, 2016: American Journal of Psychiatry
Joachim Schmutzhard, Peter Lackner, Raimund Helbok, Helene Verena Hurth, Fabian Cedric Aregger, Veronika Muigg, Josua Kegele, Sebastian Bunk, Lukas Oberhammer, Natalie Fischer, Leyla Pinggera, Allan Otieno, Bernards Ogutu, Tsiri Agbenyega, Daniel Ansong, Ayola A Adegnika, Saadou Issifou, Patrick Zorowka, Sanjeev Krishna, Benjamin Mordmüller, Erich Schmutzhard, Peter Kremsner
No abstract text is available yet for this article.
2016: BMC Medicine
R J Elbin, Jordan Knox, Nathan Kegel, Philip Schatz, Harrison B Lowder, Jonathan French, Scott Burkhart, Michael W Collins, Anthony P Kontos
This study compared post-concussion symptom endorsements on the Post-Concussion Symptom Scale (PCSS) between a clinical open-ended interview, clinician-guided PCSS, parent-report PCSS, and computer-based PCSS in youth athletes with sport-related concussion (SRC). Participants included 54 patients aged 13-17 years (M = 15.19, SD = 1.29, 51.8% male) with a diagnosed SRC seen at a concussion clinic. Participants were administered a computer-based version (COMP) of the PCSS followed by clinical open-ended symptom interview (OPEN) and clinician-guided PCSS (GUIDED)...
October 2016: Applied Neuropsychology. Child
Anthony P Kontos, Alicia Sufrinko, Melissa Womble, Nathan Kegel
Neuropsychological evaluation is one component of a comprehensive and multifaceted assessment following concussion. Although some neuropsychologists use a "hybrid" assessment approach integrating computerized neurocognitive testing batteries with traditional paper and pencil tests, computerized neurocognitive test batteries are the predominant testing modality for assessment of athletes from the youth to professional level. This review summarizes the most recent research supporting the utility of neuropsychological evaluation and highlights the strengths and weaknesses of both computerized and traditional neuropsychological testing approaches...
June 2016: Current Pain and Headache Reports
Victoria Kegel, Daniela Deharde, Elisa Pfeiffer, Katrin Zeilinger, Daniel Seehofer, Georg Damm
Beside parenchymal hepatocytes, the liver consists of non-parenchymal cells (NPC) namely Kupffer cells (KC), liver endothelial cells (LEC) and hepatic Stellate cells (HSC). Two-dimensional (2D) culture of primary human hepatocyte (PHH) is still considered as the "gold standard" for in vitro testing of drug metabolism and hepatotoxicity. It is well-known that the 2D monoculture of PHH suffers from dedifferentiation and loss of function. Recently it was shown that hepatic NPC play a central role in liver (patho-) physiology and the maintenance of PHH functions...
2016: Journal of Visualized Experiments: JoVE
Emina Wild, Ursula Bonifas, Jolanta Klimek, Jan-Hendrik Trösemeier, Beate Krämer, Birgit Kegel, Heike A Behrensdorf-Nicol
Botulinum neurotoxins (BoNTs) are the most potent toxins known. However, the paralytic effect caused by BoNT serotypes A and B is taken advantage of to treat different forms of dystonia and in cosmetic procedures. Due to the increasing areas of application, the demand for BoNTs A and B is rising steadily. Because of the high toxicity, it is mandatory to precisely determine the potency of every produced BoNT batch, which is usually accomplished by performing toxicity testing (LD50 test) in mice. Here we describe an alternative in vitro assay for the potency determination of the BoNT serotype B...
August 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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