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Menuka Pallebage-Gamarallage, Sean Foxley, Ricarda A L Menke, Istvan N Huszar, Mark Jenkinson, Benjamin C Tendler, Chaoyue Wang, Saad Jbabdi, Martin R Turner, Karla L Miller, Olaf Ansorge
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a clinically and histopathologically heterogeneous neurodegenerative disorder, in which therapy is hindered by the rapid progression of disease and lack of biomarkers. Magnetic resonance imaging (MRI) has demonstrated its potential for detecting the pathological signature and tracking disease progression in ALS. However, the microstructural and molecular pathological substrate is poorly understood and generally defined histologically...
March 13, 2018: BMC Neuroscience
Nora Maria Raschle, Willeke Martine Menks, Lynn Valérie Fehlbaum, Martin Steppan, Areti Smaragdi, Karen Gonzalez-Madruga, Jack Rogers, Roberta Clanton, Gregor Kohls, Anne Martinelli, Anka Bernhard, Kerstin Konrad, Beate Herpertz-Dahlmann, Christine M Freitag, Graeme Fairchild, Stephane A De Brito, Christina Stadler
Callous-unemotional traits are characterized by a lack of empathy, a disregard for others' feelings and shallow or deficient affect, such as a lack of remorse or guilt. Neuroanatomical correlates of callous-unemotional traits have been demonstrated in clinical samples (i.e., adolescents with disruptive behavior disorders). However, it is unknown whether callous-unemotional traits are associated with neuroanatomical correlates within normative populations without clinical levels of aggression or antisocial behavior...
2018: NeuroImage: Clinical
Deborah Gleeson, David B Menkes
There is growing international concern about the risks posed by direct-to-consumer advertising (DTCA) of prescription pharmaceuticals, including via the internet. Recent trade agreements negotiated by the United States, however, incorporate provisions that may constrain national regulation of DTCA. Some provisions explicitly mention DTCA; others enable foreign investors to seek compensation if new regulations are seen to harm their investments. These provisions may thus prevent countries from restricting DTCA or put them at risk of expensive legal action from companies seeking damages due to restrictions on advertising...
October 16, 2017: International Journal of Health Policy and Management
Oliver Hailes, Rhys Jones, David Menkes, Joshua Freeman, Erik Monasterio
No abstract text is available yet for this article.
March 9, 2018: New Zealand Medical Journal
Shankar Revu, Jing Wu, Matthew Henkel, Natalie Rittenhouse, Ashley Menk, Greg M Delgoffe, Amanda C Poholek, Mandy J McGeachy
Th17 cells drive autoimmune disease but also control commensal microbes. A common link among antigens from self-proteins or commensal microbiota is relatively low activation of T cell receptor (TCR) and costimulation signaling. Indeed, strong TCR/CD28 stimulation suppressed Th17 cell differentiation from human naive T cells, but not effector/memory cells. CD28 suppressed the classical Th17 transcriptional program, while inducing known Th17 regulators, and acted through an Akt-dependent mechanism. Th17 cells differentiated without CD28 were not anergic: they showed robust proliferation and maintained Th17 cytokine production following restimulation...
March 6, 2018: Cell Reports
Marilena Crescente, Laura Menke, Melissa V Chan, Paul C Armstrong, Timothy D Warner
Platelets are important players in thrombosis and haemostasis with their function being modulated by mediators in the blood and the vascular wall. Among these, eicosanoids can both stimulate or inhibit platelet reactivity. Platelet cyclooxygenase (COX)-1 generated thromboxane (TX) A2 is the primary prostanoid that stimulates platelet aggregation; its action is counter-balanced by prostaglandin (PG)I2 (prostacyclin), a product of vascular COX. PGD2 , PGE2 , 12- hydroxyeicosatraenoic acid (HETE) or 15-HETE, are other prostanoid modulators of platelet activity, but some also play a role in carcinogenesis...
March 7, 2018: British Journal of Pharmacology
Ashley V Menk, Nicole E Scharping, Dayana B Rivadeneira, Michael J Calderon, McLane J Watson, Deanna Dunstane, Simon C Watkins, Greg M Delgoffe
Despite remarkable responses to cancer immunotherapy in a subset of patients, many patients remain resistant to these therapies. The tumor microenvironment can impose metabolic restrictions on T cell function, creating a resistance mechanism to immunotherapy. We have previously shown tumor-infiltrating T cells succumb to progressive loss of metabolic sufficiency, characterized by repression of mitochondrial activity that cannot be rescued by PD-1 blockade. 4-1BB, a costimulatory molecule highly expressed on exhausted T cells, has been shown to influence metabolic function...
March 6, 2018: Journal of Experimental Medicine
Cheri M Ackerman, Peter K Weber, Tong Xiao, Bao Thai, Tiffani J Kuo, Emily Zhang, Jennifer Pett-Ridge, Christopher J Chang
Copper is essential for eukaryotic life, and animals must acquire this nutrient through the diet and distribute it to cells and organelles for proper function of biological targets. Indeed, mutations in the central copper exporter ATP7A contribute to a spectrum of diseases, including Menkes disease, with symptoms ranging from neurodegeneration to lax connective tissue. As such, a better understanding of the fundamental impacts of ATP7A mutations on in vivo copper distributions is of relevance to those affected by these diseases...
March 6, 2018: Metallomics: Integrated Biometal Science
Sean B Menke, Philip S Ward, David A Holway
The ecological effects of species introductions can change in magnitude over time, but an understanding of how and why they do so remains incompletely understood. Clarifying this issue requires consideration of how temporal variation in invader traits affects invasion impacts (e.g., through differential effects on the diversity and composition of native species assemblages). We examine the temporal dynamics of Argentine ant invasions in northern California by resurveying 202 sites first sampled 30-40 years ago...
March 5, 2018: Ecology
Rudolf A Werner, Ryohei Kobayashi, Mehrbod Som Javadi, Zoe Koeck, Hiroshi Wakabayashi, Stefan Unterecker, Kenichi Nakajima, Constantin Lapa, Andreas Menke, Takahiro Higuchi
Background: 123 I-metaiodobenzylguanidine (mIBG) provides independent prognostic value for risk stratification among heart failure patients, but the use of concomitant medication should not impact its quantitative information. We aimed to evaluate the four most-prescribed antidepressants currently used as a first‑line treatment for patients with major depressive disorder (MDD) and their potential on altering mIBG imaging results. Methods: The inhibition effect of four different types of antidepressants (desipramine, escitalopram, venlafaxine and bupropion) for MDD treatment on131 I-mIBG uptake was assessed by in-vitro cell uptake assays using human neuroblastoma SK-N-SH cells...
March 1, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Kalpana Thammineni, Jeffrey M Vinocur, Brian Harvey, Jeremiah S Menk, Michael Scott Kelleman, Anna-Maria Korakiti, Amanda S Thomas, James H Moller, James D St Louis, Lazaros K Kochilas
OBJECTIVE: Surgical coronary revascularisation in children with congenital heart disease (CHD) is a rare event for which limited information is available. In this study, we review the indications and outcomes of surgical coronary revascularisation from the Pediatric Cardiac Care Consortium, a large US-based multicentre registry of interventions for CHD. METHODS: This is a retrospective cohort study of children (<18 years old) with CHD who underwent surgical coronary revascularisation between 1982 and 2011...
February 22, 2018: Heart: Official Journal of the British Cardiac Society
Leonie A Menke, Thatjana Gardeitchik, Peter Hammond, Ketil R Heimdal, Gunnar Houge, Sophia B Hufnagel, Jianling Ji, Stefan Johansson, Sarina G Kant, Esther Kinning, Eyby L Leon, Ruth Newbury-Ecob, Stefano Paolacci, Rolph Pfundt, Nicola K Ragge, Tuula Rinne, Claudia Ruivenkamp, Sulagna C Saitta, Yu Sun, Marco Tartaglia, Paulien A Terhal, Anthony J van Essen, Magnus D Vigeland, Bing Xiao, Raoul C Hennekam
In 2016, we described that missense variants in parts of exons 30 and 31 of CREBBP can cause a phenotype that differs from Rubinstein-Taybi syndrome (RSTS). Here we report on another 11 patients with variants in this region of CREBBP (between bp 5,128 and 5,614) and two with variants in the homologous region of EP300. None of the patients show characteristics typical for RSTS. The variants were detected by exome sequencing using a panel for intellectual disability in all but one individual, in whom Sanger sequencing was performed upon clinical recognition of the entity...
February 20, 2018: American Journal of Medical Genetics. Part A
Bernadette Gillick, Tonya Rich, Samuel Nemanich, Chao-Ying Chen, Jeremiah Menk, Bryon Mueller, Mo Chen, Marcie Ward, Gregg Meekins, Tim Feyma, Linda Krach, Kyle Rudser
We investigated the safety, feasibility, and efficacy of transcranial direct current stimulation (tDCS) combined with constraint-induced movement therapy (CIMT) in children and young adults with unilateral cerebral palsy. Twenty participants were randomized to receive active or sham tDCS. The intervention consisted of 10 consecutive weekday sessions of tDCS applied to the non-lesioned hemisphere (20 min) concurrently with CIMT (120 min). Participants, caregivers, and interventionists were blinded to group assignment...
February 11, 2018: European Journal of Paediatric Neurology: EJPN
Carolin Leistner, Andreas Menke
Stress is a state of derailed homeostasis and a main environmental risk factor for psychiatric diseases. Chronic or uncontrollable stress may lead to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which is a common feature of stress-related psychiatric disorders. One of the key mechanisms underlying a disturbed HPA axis is an impaired function of the glucocorticoid receptor (GR) with an enhanced or reduced feedback sensitivity for glucocorticoids and subsequently altered concentrations of peripheral cortisol...
February 2, 2018: Psychoneuroendocrinology
Brandon Menke, Alex Walters, John F Payne
An 11-year-old boy presented for central vision blurring in each eye. Visual acuity was 20/80 and examination revealed spoke-wheel foveal schisis and peripheral elevated diaphanous inner retina in each eye. Spectral-domain optical coherence tomography showed inner-retinal, flat-topped cysts in each eye. Electrophysiologic testing was refused, but a clinical diagnosis of X-linked retinoschisis was made. Three months after topical dorzolamide (Trusopt; Santen Pharmaceutical, Osaka, Japan) was started, the macular cysts worsened significantly...
February 1, 2018: Ophthalmic Surgery, Lasers & Imaging Retina
J C Klein, M Rolinski, L Griffanti, K Szewczyk-Krolikowski, F Baig, C Ruffmann, A R Groves, R A L Menke, M T Hu, C Mackay
Magnetic resonance imaging (MRI) studies in early Parkinson's disease (PD) have shown promise in the detection of disease-related brain changes in the white and deep grey matter. We set out to establish whether intrinsic cortical involvement in early PD can be detected with quantitative MRI. We collected a rich, multi-modal dataset, including diffusion MRI, T1 relaxometry and cortical morphometry, in 20 patients with early PD (disease duration, 1.9 ± 0.97 years, Hoehn & Yahr 1-2) and in 19 matched controls...
February 13, 2018: NMR in Biomedicine
Ashley V Menk, Nicole E Scharping, Rebecca S Moreci, Xue Zeng, Cliff Guy, Sonia Salvatore, Heekyong Bae, Jianxin Xie, Howard A Young, Stacy Gelhaus Wendell, Greg M Delgoffe
To fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mitochondria. However, the signaling events that initiate aerobic glycolysis in T cells remain unclear. We show T cell activation rapidly induces glycolysis independent of transcription, translation, CD28, and Akt and not involving increased glucose uptake or activity of glycolytic enzymes. Rather, TCR signaling promotes activation of pyruvate dehydrogenase kinase 1 (PDHK1), inhibiting mitochondrial import of pyruvate and facilitating breakdown into lactate...
February 6, 2018: Cell Reports
Chia-Huei Peng, Chyong-Hsin Hsu, Nien-Lu Wang, Hung-Chang Lee, Shuan-Pei Lin, Wai-Tao Chan, Chun-Yan Yeung, Chuen-Bin Jiang
RATIONALE: Menkes disease (MD), also known as Menkes kinky hair disease, is a fatal neurodegenerative disease caused by a defect in copper metabolism. The symptoms involve multiple organ systems, such as the brain, lung, gastrointestinal tract, urinary tract, connective tissue, and skin. There is currently no cure for this disease entity, and patients with the classic form of MD usually die from complications between 6 months and 3 years of age. Intracranial hemorrhage secondary to tortuous intracranial arteries is a well-known complication of MD, but spontaneous retroperitoneal hemorrhage, to the best of our knowledge, has never been reported in a patient with MD...
February 2018: Medicine (Baltimore)
Sascha Hein, Jonas von Irmer, Markus Gallei, Reinhard Meusinger, Jörg Simon
Dimethylmenaquinone (DMMK), a prevalent menaquinone (MK) derivative of uncertain function, is characteristic for members of the class Coriobacteriia. Such bacteria are frequently present in intestinal microbiomes and comprise several pathogenic species. The coriobacterial model organism Adlercreutzia equolifaciens was used to investigate the enzymology of DMMK biosynthesis. A HemN-like class C radical S-adenosylmethionine methyltransferase (MenK2) from A. equolifaciens was produced in Wolinella succinogenes or Escherichia coli cells and found to methylate MK specifically at position C-7...
February 3, 2018: Biochimica et Biophysica Acta
Stephanie A Zlatic, Alysia Vrailas-Mortimer, Avanti Gokhale, Lucas J Carey, Elizabeth Scott, Reid Burch, Morgan M McCall, Samantha Rudin-Rush, John Bowen Davis, Cortnie Hartwig, Erica Werner, Lian Li, Michael Petris, Victor Faundez
Rare neurological diseases shed light onto universal neurobiological processes. However, molecular mechanisms connecting genetic defects to their disease phenotypes are elusive. Here, we obtain mechanistic information by comparing proteomes of cells from individuals with rare disorders with proteomes from their disease-free consanguineous relatives. We use triple-SILAC mass spectrometry to quantify proteomes from human pedigrees affected by mutations in ATP7A, which cause Menkes disease, a rare neurodegenerative and neurodevelopmental disorder stemming from systemic copper depletion...
January 30, 2018: Cell Systems
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