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Pavel Silvestrov, Sarah J Maier, Michelle Fang, G Andrés Cisneros
Functioning DNA repair capabilities are vital for organisms to ensure that the biological information is preserved and correctly propagated. Disruptions in DNA repair pathways can result in the accumulation of DNA mutations, which may lead to onset of complex disease such as cancer. The discovery and characterization of cancer-related biomarkers may allow early diagnosis and targeted treatment, which could significantly contribute to the survival rates of cancer patients. To this end, we have applied a hypothesis driven bioinformatics approach to identify biomarkers related to 25 different DNA repair enzymes, in combination with structural analysis of six selected missense mutations of newly discovered SNPs that are associated with cancer phenotypes...
July 31, 2018: DNA Repair
Yukiko Karita, Yuka Kimura, Shizuka Sasaki, Taisuke Nitobe, Eiichi Tsuda, Yasuyuki Ishibashi
INTRODUCTION: Axillary artery and brachial plexus injuries have been reported to be associated with proximal humeral fractures. In this report, we present two cases of axillary artery and brachial plexus injury secondary to proximal humeral fracture. PRESENTATION OF CASES: Case 1: An 88-year-old woman with cognitive impairment slipped and fell at home. The diagnosis was left proximal humeral fracture. The second day, paralysis of left upper arm due to left axillary artery occlusion appeared...
July 25, 2018: International Journal of Surgery Case Reports
Dimithree Kahanda, Naveen Singh, David A Boothman, Jason D Slinker
There is a great need to track the selectivity of anticancer drug activity and to understand the mechanisms of associated biological activity. Here we focus our studies on the specific NQO1 bioactivatable drug, ß-lapachone, which is in several Phase I clinical trials to treat human non-small cell lung, pancreatic and breast cancers. Multi-electrode chips with electrochemically-active DNA monolayers are used to track anticancer drug activity in cellular lysates and correlate cell death activity with DNA damage...
July 30, 2018: Biosensors & Bioelectronics
Igri Kolaj, S Imindu Liyanage, Donald F Weaver
Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by progressive dementia, neuroinflammation and the accumulation of intracellular neurofibrillary tangles and extracellular plaques. The etiology of AD is unclear, but is generally attributed to four leading hypotheses: (i) abnormal folding and aggregation of amyloid-β (Aβ)/tau proteins (ii) activation of the innate immune system, (iii) mitochondrial dysfunction, and (iv) oxidative stress. To date, therapeutic strategies have largely focused on Aβ-centric targets; however, the repeated failure of clinical trials and the continued lack of a disease-modifying therapy demand novel, multifaceted approaches...
August 8, 2018: Neurochemistry International
Alessandro Arrigo, Emanuela Aragona, Luigi Capone, Luisa Pierro, Francesco Romano, Francesco Bandello, Maurizio Battaglia Parodi
PURPOSE: To analyze optical coherence tomography angiography (OCTA) quantitative features in patients affected by new-onset choroidal neovascularization (CNV) in one eye and early/intermediate age-related macular degeneration (AMD) in the fellow eye. DESIGN: Case-control study. SETTINGS: Clinical Practice. STUDY POPULATION: Thirty patients and thirty age-matched controls. OBSERVATION PROCEDURES: Both cohorts underwent complete ophthalmologic examination, including best corrected visual acuity (BCVA) measurement, biomicroscopy, fluorescein angiography (FA) and indocyanine green angiography (ICGA) examination (Spectralis HRA; Heidelberg Engineering, Germany), OCT and OCTA scans (DRI OCT Triton; Topcon Corporation, Japan)...
August 8, 2018: American Journal of Ophthalmology
Atalie C Thompson, M Tariq Bhatti, Sidney M Gospe
PURPOSE: To use spectral domain-optical coherence tomography (SD-OCT) to assess whether epipapillary vitreous traction from evolving posterior vitreous detachment (PVD) is mechanistically involved in the pathogenesis of non-arteritic anterior ischemic optic neuropathy (NAION). DESIGN: Retrospective cohort study. METHODS: <AbstractText Label="SETTING" NlmCategory="METHODS">Single academic center. PATIENT OR STUDY POPULATION: Eighty eyes in 74 subjects presenting within 2 weeks of symptom onset of NAION...
August 8, 2018: American Journal of Ophthalmology
Dmiry V Chistyakov, Alina A Astakhova, Marina G Sergeeva
Relationship between mood disorders and inflammation is now well-documented, although molecular mechanisms are not understood. Previously mostly pro-inflammatory cytokines of immune system (IL-6, TNF, etc.) were taken into account. However, recent understanding of resolution of inflammation as an active process drew attention to mediators of resolution, which include both proteins and ω-3 and ω-6 polyunsaturated fatty acids derivatives (resolvins, cyclopentenone prostaglandins, etc.). This review takes into account new data on resolution of inflammation and action of mediators of resolution in models of depression...
August 8, 2018: Experimental and Molecular Pathology
Cecilia Mancini, Elisa Giorgio, Anna Rubegni, Luca Pradotto, Silvia Bagnoli, Elisa Rubino, Paolo Prontera, Simona Cavalieri, Eleonora Di Gregorio, Marta Ferrero, Elisa Pozzi, Evelise Riberi, Patrizia Ferrero, Pasquale Nigro, Alessandro Mauro, Maurizio Zibetti, Alessandra Tessa, Melissa Barghigiani, Antonella Antenora, Fabio Sirchia, Silvia Piacentini, Gabriella Silvestri, Giuseppe De Michele, Alessandro Filla, Laura Orsi, Filippo Maria Santorelli, Alfredo Brusco
BACKGROUND: Hereditary Ataxias are heterogeneous groups of neurodegenerative disorders, characterized by cerebellar syndrome associated with dysarthria, oculomotor and corticospinal signs, neuropathy and cognitive impairment. Recent reports suggested mutations in the SPG7 gene, causing the most common form of autosomal recessive spastic paraplegia (MIM#607259), as a main cause of ataxias. The majority of described patients, were homozygotes or compound heterozygotes for the c.1529C>T (p...
August 11, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Rachel Waller, Mark Murphy, Claire J Garwood, Luke Jennings, Paul R Heath, Annabelle Chambers, Fiona E Matthews, Carol Brayne, Paul G Ince, Stephen B Wharton, Julie E Simpson
Oxidative stress and oxidative DNA damage are early features of mild cognitive impairment and Alzheimer's disease (AD), occurring before the formation of classical AD neuropathology, and resulting from an imbalance between pro- and anti-oxidants. Astrocytes play a major neuroprotective role, producing high levels of anti-oxidants including metallothionein-I and -II (MT-I/II). In the present study we characterized the immunoreactive profile of MT-I/II in the temporal cortex of the Cognitive Function and Ageing Study (CFAS) aging population-representative neuropathology cohort, and examined H2 O2 -modulation of MT transcription by human astrocytes...
August 10, 2018: Glia
Vittorio Calabrese, Aurelia Santoro, Angela Trovato Salinaro, Sergio Modafferi, Maria Scuto, Ferdaous Albouchi, Daniela Monti, James Giordano, Mario Zappia, Claudio Franceschi, Edward J Calabrese
Age-related changes in the brain reflect a dynamic interaction of genetic, epigenetic, phenotypic, and environmental factors that can be temporally restricted or more longitudinally present throughout the lifespan. Fundamental to these mechanisms is the capacity for physiological adaptation through modulation of diverse molecular and biochemical signaling occurring from the intracellular to the network-systemic level throughout the brain. A number of agents that affect the onset and progression of Parkinson's disease (PD)-like effects in experimental models exhibit temporal features, and mechanisms of hormetic dose responses...
August 11, 2018: Journal of Neuroscience Research
François Montastruc, Justine Benevent, Vanessa Rousseau, Geneviève Durrieu, Agnès Sommet, Jean-Louis Montastruc
In contrast to statins, the risk of diabetes with fibrates was not clearly studied. The present study investigates a putative signal of diabetes associated with the use of fibrates using the World Health Organization (WHO) global individual case safety reports database, VigiBase® . We included all reports registered until the 31st December 2017 in VigiBase® to measure the risk of reporting "hyperglycemia or new onset of diabetes" (SMQ term) compared with all other reports [as a Reporting Odds Ratio (ROR 95%CI)] for fibrates, statins and the combination fibrates + statins...
August 11, 2018: Fundamental & Clinical Pharmacology
Otavio Berwanger, Magdy Abdelhamid, Thomas Alexander, Abdulmajeed Alzubaidi, Oleg Averkov, Philip Aylward, Eduardo Contreras Zúñiga, Sigrun Halvorsen, Ricardo Iglesias, Muhamad A Sk Abdul Kader, Mohammad Zubaid, Khalid F AlHabib
Primary percutaneous coronary intervention (PCI) is the preferred reperfusion method in patients with ST-segment elevation myocardial infarction (STEMI). In patients with STEMI who cannot undergo timely primary PCI, pharmacoinvasive treatment is recommended, comprising immediate fibrinolytic therapy with subsequent coronary angiography and rescue PCI if needed. Improving clinical outcomes following fibrinolysis remains of great importance for the many patients globally for whom rapid treatment with primary PCI is not possible...
August 11, 2018: Clinical Cardiology
M Kajta, A Wnuk, J Rzemieniec, W Lason, M Mackowiak, E Chwastek, M Staniszewska, I Nehring, A K Wojtowicz
Triclocarban is a phenyl ether that has recently been classified as a contaminant of emerging concern. Evidence shows that triclocarban is present in human tissues, but little is known about the impact of triclocarban on the nervous system, particularly at early developmental stages. This study demonstrated that triclocarban that was used at environmentally relevant concentrations induced apoptosis in mouse embryonic neurons, inhibited sumoylation, and changed the epigenetic status, as evidenced by impaired activities of HDAC, sirtuins, and DNMT, global DNA hypomethylation, and alterations of methylation levels of bax, bcl2, Ahr, and Car genes...
August 10, 2018: Molecular Neurobiology
Khwaja Salahuddin Siddiqi, Azamal Husen, Sayed Sartaj Sohrab, Mensur Osman Yassin
Nanomaterials (NMs) are receiving remarkable attention due to their unique properties and structure. They vary from atoms and molecules along with those of bulk materials. They can be engineered to act as drug delivery vehicles to cross blood-brain barriers (BBBs) and utilized with better efficacy and safety to deliver specific molecules into targeted cells as compared to conventional system for neurological disorders. Depending on their properties, various metal chelators, gold nanoparticles (NPs), micelles, quantum dots, polymeric NPs, liposomes, solid lipid NPs, microparticles, carbon nanotubes, and fullerenes have been utilized for various purposes including the improvement of drug delivery system, treatment response assessment, diagnosis at early stage, and management of neurological disorder by using neuro-engineering...
August 10, 2018: Nanoscale Research Letters
Elizabeth George, Ashish Khandelwal, Christopher Potter, Aaron Sodickson, Srinivasan Mukundan, Diego Nunez, Bharti Khurana
Cerebrovascular injury is increasingly identified in patients presenting after blunt trauma due to the implementation of screening criteria and advances in noninvasive angiographic imaging by CT. The variable latent time before onset of secondary stroke presents a window of opportunity for prevention, reinforcing the importance of detection of asymptomatic patients via screening. Furthermore, the high morbidity and mortality associated with secondary stroke makes it imperative that radiologists recognize these challenging injuries...
August 10, 2018: Emergency Radiology
Hari-Mandir K Khalsa, Ross J Baldessarini, Mauricio Tohen, Paola Salvatore
BACKGROUND: Aggression by patients with bipolar I disorder (BD-I) is not uncommon. Identifying potential risk factors early in the illness-course should inform clinical management and reduce risk. METHODS: In a study sample of 216 initially hospitalized, first-psychotic episode subjects diagnosed with DSM-IV-TR BD-I, we identified recent (within 1 month before hospitalization) aggression by ratings on the Brief Psychiatric Rating Scale-Expanded and review of detailed clinical research records...
August 11, 2018: International Journal of Bipolar Disorders
U Maus, J Flechtenmacher, K M Peters
BACKGROUND: Femoral head necrosis is a progressive disease that can progress within a relatively short time. Therefore, an early and clear diagnosis including stage classification and treatment is necessary to prevent or delay the onset of the femoral head and joint destruction. TREATMENT: In addition to the identification of possible risk factors and treatment, the question of the available treatment options arises. The present article deals with conservative treatment options and presents the published results in the sense of the currently available evidence and against the background of the S3 guideline on atraumatic femoral head necrosis...
August 10, 2018: Der Orthopäde
Marija Kojic, Monika Gaik, Bence Kiska, Anna Salerno-Kochan, Sarah Hunt, Angelo Tedoldi, Sergey Mureev, Alun Jones, Belinda Whittle, Laura A Genovesi, Christelle Adolphe, Darren L Brown, Jennifer L Stow, Kirill Alexandrov, Pankaj Sah, Sebastian Glatt, Brandon J Wainwright
Cerebellar ataxias are severe neurodegenerative disorders with an early onset and progressive and inexorable course of the disease. Here, we report a single point mutation in the gene encoding Elongator complex subunit 6 causing Purkinje neuron degeneration and an ataxia-like phenotype in the mutant wobbly mouse. This mutation destabilizes the complex and compromises its function in translation regulation, leading to protein misfolding, proteotoxic stress, and eventual neuronal death. In addition, we show that substantial microgliosis is triggered by the NLRP3 inflammasome pathway in the cerebellum and that blocking NLRP3 function in vivo significantly delays neuronal degeneration and the onset of ataxia in mutant animals...
August 10, 2018: Nature Communications
Susan Mayor
No abstract text is available yet for this article.
August 10, 2018: BMJ: British Medical Journal
Telma Santos, Andreia Carvalho, André Almeida Cunha, Marta Rodrigues, Tiago Gregório, Ludovina Paredes, Henrique Costa, José Mário Roriz, João Pinho, Miguel Veloso, Sérgio Castro, Pedro Barros, Manuel Ribeiro
INTRODUCTION: Recently, the benefit of selecting patients for endovascular treatment (EVT) beyond the 6-hour time window using a tissue-based approach was demonstrated in two randomized trials. The optimal imaging protocol for selecting patients is under debate, and it is still unknown if a simpler and faster protocol may adequately select patients with wake-up stroke (WUS) and late-presenting stroke (LPS) for EVT. OBJECTIVE: To compare outcomes of patients submitted to EVT presenting within 6 hours of symptom onset or 6-24 hours after last seen well, selected using non-contrast computed tomography (NCCT) and CT angiography (CTA)...
August 10, 2018: Journal of Neurointerventional Surgery
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