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Lauren Walker, Kirsty E McAleese, Daniel Erskine, Johannes Attems
This chapter describes the main neuropathological features of the most common age associated neurodegenerative diseases including Alzheimer's disease, Lewy body diseases, vascular dementia and the various types of frontotemporal lobar degeneration. In addition, the more recent concepts of primary age-related tauopathy and ageing-related tau astrogliopathy as well as chronic traumatic encephalopathy are briefly described. One section is dedicated to cerebral multi-morbidity as it is becoming increasingly clear that the old brain is characterised by the presence of multiple pathologies (to varying extent) rather than by one single, disease specific pathology alone...
2019: Sub-cellular Biochemistry
Shaunak N Amin, Justin R Shinn, Alice Tang, James S Lewis, Kyle Mannion
Although early complications of microvascular free flaps and regional pedicled flaps of the head and neck are well described in the literature, there is relatively limited knowledge regarding their long-term complications. We describe the case of a 62-year-old gentleman who underwent primary resection and adjuvant radiation therapy for supraglottic squamous cell carcinoma who subsequently underwent salvage total laryngectomy with pectoralis major muscle flap reconstruction. During a later esophageal dilation for complaints of dysphagia, a new exophytic lesion of the hypopharynx was biopsied on endoscopy...
March 19, 2019: Head and Neck Pathology
Jinxing Chen, Liang Huang, Qingqing Wang, Weiwei Wu, He Zhang, Youxing Fang, Shaojun Dong
Nanozymes provide comparative advantages over natural enzymes and conventional artificial enzymes for catalytic reactions. However, nanozymes are only suitable for limited types of reactions, whose catalytic principles are not yet fully revealed. Herein, a new nanozyme based on a bionic zeolitic imidazolate framework is proposed. Zeolitic imidazolate framework-8 (ZIF-8) possesses a similar geometric structure to that of the active center of human carbonic anhydrase II (hCAII) and exhibits catalytic performance analogous to that of the hCAII...
March 19, 2019: Nanoscale
Axel Schulz, Kevin Bläsing, Jonas Bresien, Rene Labbow, Dirk Michalik, Max Thomas, Alexander Villinger
The reaction of HN3 with the strong Lewis acid B(C6F5)3 led to the formation of a very labile HN3·B(C6F5)3 adduct, which decomposed to an aminoborane, H(C6F5)NB(C6F5)2, above -20°C with the release of molecular nitrogen and simultaneous migration of a C6F5 group from boron to nitrogen. Hydrolysis of the aminoborane provided C6F5-substituted amine, HN(R)(C6F5), in good yields. The intermediate formation of an azide-borane adduct in the reaction with B(C6F5)3 was also demonstrated for a series of different organic azides, R-N3 (R = Me3Si = TMS, Ph, 3,5-(CF3)2C6H3 = Btp), as well as their Staudinger-like decomposition along with C6F5-group migration...
March 19, 2019: Angewandte Chemie
Kylee Lewis, Ruth Ann Marrie, Charles N Bernstein, Lesley A Graff, Scott B Patten, Jitender Sareen, John D Fisk, James M Bolton
BACKGROUND: Inflammatory bowel disease (IBD) is associated with a high prevalence of comorbid depressive and anxiety disorders. A significant proportion of IBD patients with comorbid psychiatric disorders remain undiagnosed and untreated, but factors associated with diagnosis are unknown. We evaluated the prevalence of undiagnosed depression and anxiety in an IBD cohort, along with the associated demographic and clinical characteristics. METHODS: We obtained data from the enrollment visit of a cohort study of psychiatric comorbidity in immune-mediated diseases including IBD...
March 19, 2019: Inflammatory Bowel Diseases
Lewis E Johnson, Jason S Kingsbury, Delwin L Elder, Rose Ann Cattolico, Luke N Latimer, William Hardin, Evelien De Meulenaere, Chloe Deodato, Griet Depotter, Sowmya Madabushi, Nicholas W Bigelow, Brittany A Smolarski, Trevor K Hougen, Werner Kaminsky, Koen Clays, Bruce H Robinson
Dyes with nonlinear optical (NLO) properties enable new imaging techniques and photonic systems. We have developed a dye (DANPY-1) for photonics applications in biological substrates such as nucleic acids; however, the design specification also enables it to be used for visualizing biomolecules. It is a prototype dye demonstrating a water-soluble, NLO-active fluorophore with high photostability, a large Stokes shift, and a favorable toxicity profile. A practical and scalable synthetic route to DANPY salts has been optimized featuring: (1) convergent Pd-catalyzed Suzuki coupling with pyridine 4-boronic acid, (2) site-selective pyridyl N-methylation, and (3) direct recovery of crystalline intermediates without chromatography...
March 19, 2019: Organic & Biomolecular Chemistry
Marcos Ucha, Santiago M Coria, Adrián E Núñez, Raquel Santos-Toscano, David Roura-Martínez, Javier Fernández-Ruiz, Alejandro Higuera-Matas, Emilio Ambrosio
BACKGROUND: Addiction is a chronic disorder with a high risk of relapse. The neural mechanisms mediating addictions require protein synthesis, which could be relevant for the development of more effective treatments. The mTOR signaling pathway regulates protein synthesis processes that have recently been linked to the development of drug addiction. AIMS: To assess the effects of morphine self-administration and its subsequent extinction on the expression of several genes that act in this pathway, and on the levels of specific phosphoproteins (Akt, Gsk3α/β, mTOR, PDK1 and p70 S6 kinase) in the amygdala, nucleus accumbens, and the prefrontal cortex...
March 19, 2019: Journal of Psychopharmacology
Emmanuel Canet, Sobia Amjad, Raymond Robbins, Jane Lewis, Michelle Matalanis, Daryl Jones, Rinaldo Bellomo
BACKGROUND: Delirium is common in hospitalized patients but its epidemiology remains poorly characterized. AIMS: To test the hypothesis that patient demographics, clinical phenotype, management, and outcomes of patient with delirium in hospital ward patients differ from ICU patients. METHODS: Retrospective cohort of patients admitted to an Australian university-affiliated hospital between March 2013 and April 2017 and coded for delirium at discharge using the ICD-10 criteria...
March 19, 2019: Internal Medicine Journal
Sven Halbedel, Richard J Lewis
DivIVA proteins and their GpsB homologues are late cell division proteins found in Gram-positive bacteria. DivIVA/GpsB proteins associate with the inner leaflet of the cytosolic membrane and act as scaffolds for other proteins required for cell growth and division. DivIVA/GpsB proteins comprise an N-terminal lipid-binding domain for membrane association fused to C-terminal domains supporting oligomerization. Despite sharing the same domain organisation, DivIVA and GpsB serve different cellular functions: DivIVA plays diverse roles in division site selection, chromosome segregation and controlling peptidoglycan homeostasis, whereas GpsB contributes to the spatiotemporal control of penicillin binding protein activity...
March 18, 2019: Molecular Microbiology
James M Shine, Peter T Bell, Elie Matar, Russell A Poldrack, Simon J G Lewis, Glenda M Halliday, Claire O'Callaghan
Parkinson's disease is primarily characterized by diminished dopaminergic function; however, the impact of these impairments on large-scale brain dynamics remains unclear. It has been difficult to disentangle the direct effects of Parkinson's disease from compensatory changes that reconfigure the functional signature of the whole brain network. To examine the causal role of dopamine depletion in network-level topology, we investigated time-varying network structure in 37 individuals with idiopathic Parkinson's disease, both ON and OFF dopamine replacement therapy, along with 50 age-matched, healthy control subjects using resting state functional MRI...
March 18, 2019: Brain: a Journal of Neurology
Vicki Johnson-Lawrence, Sarah Bailey, Patrick E Sanders, Rodlescia Sneed, Ariel Angel-Vincent, Allysoon Brewer, Kent Key, E Yvonne Lewis, Jennifer E Johnson
Chronic disease carries high morbidity and mortality in the United States, with large racial and ethnic disparities observed in chronic disease. Physical activity and healthy food are vital for chronic disease prevention yet challenging to access in economically distressed areas. Public health prevention efforts have become particularly prominent within faith-based organizations over the last three decades. This manuscript describes the protocol of the Church Challenge, a multilevel cluster-randomized controlled nutrition and physical activity trial across 24 churches to reduce blood pressure by 6 mmHg among 576 residents in Flint, MI...
June 2019: Contemporary Clinical Trials Communications
Sarah Howlett, Tadhg Sullivan, Alireza Abdolrasouli, Andrew M Borman, Elizabeth M Johnson, Paul Lewis, Aravindhan Baheerathan, Frances Davies, Frances Sanderson, Nicholas Davies, Victoria Singh-Curry
Cladophialophora bantiana is a neurotropic mould and primary cause of cerebral phaeohyphomycoses, which presents with brain abscesses in both immunocompromised and immunocompetent individuals. It is associated with high mortality due to delay in diagnosis and absence of standardised therapy. We present a case of fatal cerebral phaeohyphomycosis in a 67-year-old Caucasian man. Diagnosis was achieved by histopathological examination of brain tissue followed by conventional culture and molecular identification...
June 2019: Medical Mycology Case Reports
Zahra Jafari, Mohammad Rahim Shahbodaghi, Saman Maroufizadeh, Abdorreza Naser Moghadasi
Background: About one third of patients with multiple sclerosis (MS) experience dysphagia. Dysphagia can cause complications such as malnutrition, lung infections, aspiration pneumonia and dehydration, thus it is very helpful to diagnose dysphagia as soon as possible. The aim in this study was to translate dysphagia in multiple sclerosis (DYMUS) questionnaire into Farsi and and validate it. Methods: Forward-backward method was used to translate original English version of DYMUS into farsi, and then the questionnaire (one for each patient) was filled in through asking questions from 200 patients with MS by a speech and language pathologist...
July 6, 2018: Iranian Journal of Neurology
Craig R White, Dustin J Marshall, Lesley A Alton, Pieter A Arnold, Julian E Beaman, Candice L Bywater, Catriona Condon, Taryn S Crispin, Aidan Janetzki, Elia Pirtle, Hugh S Winwood-Smith, Michael J Angilletta, Stephen F Chenoweth, Craig E Franklin, Lewis G Halsey, Michael R Kearney, Steven J Portugal, Daniel Ortiz-Barrientos
Organisms vary widely in size, from microbes weighing 0.1 pg to trees weighing thousands of megagrams - a 1021 -fold range similar to the difference in mass between an elephant and the Earth. Mass has a pervasive influence on biological processes, but the effect is usually non-proportional; for example, a tenfold increase in mass is typically accompanied by just a four- to sevenfold increase in metabolic rate. Understanding the cause of allometric scaling has been a long-standing problem in biology. Here, we examine the evolution of metabolic allometry in animals by linking microevolutionary processes to macroevolutionary patterns...
March 18, 2019: Nature Ecology & Evolution
Quan Peng, Chang Xu, Daniel Kim, Marcus Lewis, John DiCarlo, Yexun Wang
For specific detection of somatic variants at very low levels, artifacts from the NGS workflow have to be eliminated. Various approaches using unique molecular identifiers (UMI) to analytically remove NGS artifacts have been described. Among them, Duplex-seq was shown to be highly effective, by leveraging the sequence complementarity of two DNA strands. However, all of the published Duplex-seq implementations so far required pair-end sequencing and in the case of combining duplex sequencing with target enrichment, lengthy hybridization enrichment was required...
March 18, 2019: Scientific Reports
Omar S Akbik, Robert V Starling, Seymur Gahramanov, Yiliang Zhu, Jeremy Lewis
Significant morbidity and mortality is associated with surgical evacuation of acute subdural hematomas (ASDH) in the elderly population. The literature remains mixed on risk factors associated with poor outcomes, specifically preoperative antithrombotic usage and postoperative seizures. Between January 1st 2013 and December 31st 2017 we retrospectively identified 62 patients ≥ 65 years who underwent a craniotomy for evacuation of an ASDH with the primary outcome being GOS at discharge, 3 month, and 6 month follow-up...
March 15, 2019: World Neurosurgery
Frances H Priddy, David J M Lewis, Huub C Gelderblom, Hana Hassanin, Claire Streatfield, Celia LaBranche, Jonathan Hare, Josephine H Cox, Len Dally, Daryl Bendel, David Montefiori, Eddy Sayeed, Jim Ackland, Jill Gilmour, Bruce C Schnepp, J Fraser Wright, Philip Johnson
BACKGROUND: A preventive vaccine for HIV is a crucial public health need; adeno-associated virus (AAV)-mediated antibody gene delivery could be an alternative to immunisation to induce sustained expression of neutralising antibodies to prevent HIV. We assessed safety and tolerability of rAAV1-PG9DP, a recombinant AAV1 vector encoding the gene for PG9, a broadly neutralising antibody against HIV. METHODS: This first-in-human, proof-of-concept, double-blind, phase 1, randomised, placebo-controlled, dose-escalation trial was done at one clinical research centre in the UK...
March 15, 2019: Lancet HIV
Shinya Dohgu, Fuyuko Takata, Junichi Matsumoto, Ikuya Kimura, Atsushi Yamauchi, Yasufumi Kataoka
Blood-brain barrier (BBB) disruption is often mediated by neuroinflammation, and occurs during various neurodegenerative diseases including Parkinson's disease (PD). PD is characterized by loss of dopaminergic neurons and aggregated α-synuclein protein in inclusions known as Lewy bodies. Misfolded α-synuclein has been implicated in neurodegeneration and neuroinflammation through activation of microglia and astrocytes. Pericytes are a key cellular regulator of the BBB, although it is not known if they participate in α-synuclein-associated PD pathology...
March 15, 2019: Microvascular Research
Zibo Li, Yukun Lin, Shuhui Zhang, Lin Zhou, Guixi Yan, Yuehua Wang, Mengdi Zhang, Mengqi Wang, Haihong Lin, Qiaozhen Tong, Yongjian Duan, Gangjun Du
BACKGROUND: Hypercoagulation and neutrophilia are described in several cancers, however, whether they are involved in lung carcinogenesis is currently unknown. Emodin is the main bioactive component from Rheum palmatum and has many medicinal values, such as anti-inflammation and anticancer. This study is to investigate the contributions of neutrophils to the effects of emodin on hypercoagulation and carcinogenesis. METHODS: The effects of emodin on neutrophil phenotypes were assessed by cell proliferation, morphological changes, phagocytosis and autophagy in vitro...
March 18, 2019: Journal of Translational Medicine
Frances Humby, Myles Lewis, Nandhini Ramamoorthi, Jason A Hackney, Michael R Barnes, Michele Bombardieri, A Francesca Setiadi, Stephen Kelly, Fabiola Bene, Maria DiCicco, Sudeh Riahi, Vidalba Rocher, Nora Ng, Ilias Lazarou, Rebecca Hands, Désirée van der Heijde, Robert B M Landewé, Annette van der Helm-van Mil, Alberto Cauli, Iain McInnes, Christopher Dominic Buckley, Ernest H Choy, Peter C Taylor, Michael J Townsend, Costantino Pitzalis
OBJECTIVES: To unravel the hierarchy of cellular/molecular pathways in the disease tissue of early, treatment-naïve rheumatoid arthritis (RA) patients and determine their relationship with clinical phenotypes and treatment response/outcomes longitudinally. METHODS: 144 consecutive treatment-naïve early RA patients (<12 months symptoms duration) underwent ultrasound-guided synovial biopsy before and 6 months after disease-modifying antirheumatic drug (DMARD) initiation...
March 16, 2019: Annals of the Rheumatic Diseases
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