Glucagon Amyloid-like Fibril Morphology Is Selected via Morphology-Dependent Growth Inhibition

DEFF Research Database (Denmark)

Andersen, C.B.; Otzen, D.; Christiansen, Gunna

2007-01-01

Protein Structure and Biophysics, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Malov, Denmark, Centre for Insoluble Protein Structures (inSPIN), Department of Life Sciences, Aalborg University, Sohngaardsholmsvej 49, DK-9000 Aalborg, Denmark, and Institute of Medical Microbiology and Immunology...... twisted fibril seeds cannot grow at high concentrations. We conclude that there exists a morphology-dependent mechanism for inhibition of glucagon fibril growth. Light scattering experiments indicate that glucagon is mainly monomeric below 1 mg/mL and increasingly trimeric above this concentration. We...

The changing face of glucagon fibrillation: Structural polymorphism and conformational imprinting

DEFF Research Database (Denmark)

Pedersen, J.S.; Dikov, D.; Flink, J.L.

2006-01-01

is not the result of the global energy minimization, but rather kinetically controlled by solvent conditions and seed-imprinting. Fibrillar polymorphism, which is being reported for an increasing number of proteins, probably reflects that fibrils have not been under evolutionary constraints to retain a single...

The C-terminus hot spot region helps in the fibril formation of bacteriophage-associated hyaluronate lyase (HylP2).

Science.gov (United States)

Shukla, Harish; Singh, Sudhir Kumar; Singh, Amit Kumar; Mitra, Kalyan; Akhtar, Md Sohail

2015-09-23

The bacteriophage encoded hyaluronate lyases (HylP and HylP2) degrade hyaluronan and other glycosaminoglycans. HylP2 forms a functional fibril under acidic conditions in which its N-terminus is proposed to form the fibrillar core, leading to nucleation and acceleration of fibril formation. Here we report the presence of a hot spot region (A144GVVVY149) towards the carboxy terminus of HylP2, essential for the acceleration of fibril formation. The 'hot spot' is observed to be inherently mutated for valines (A178AMVMY183) in case of HylP. The N- terminal swapped chimeras between these phage HLs ((N)HylP2(C)HylP and (N)HylP(C)HylP2) or HylP did not form fibrils at acidic pH. However, seeding of prefibrils of HylP2 recompensed nucleation and led to fibrillation in (N)HylP(C)HylP2. The V147A mutation in the 'hot spot' region abolished fibril formation in HylP2. The M179V and M181V double mutations in the 'hot spot' region of HylP led to fibrillation with the seeding of prefibrils. It appears that fibrillation in HylP2 even though is initiated by the N-terminus, is accelerated by the conserved 'hot spot' region in the C-terminus. A collagenous (Gly-X-Y)10 motif in the N-terminus and a mutated 'hot spot' region in the C-terminus of HylP affect fibrillar nucleation and acceleration respectively.

Opposed Effects of Dityrosine Formation in Soluble and Aggregated α-Synuclein on Fibril Growth.

Science.gov (United States)

Wördehoff, Michael M; Shaykhalishahi, Hamed; Groß, Luca; Gremer, Lothar; Stoldt, Matthias; Buell, Alexander K; Willbold, Dieter; Hoyer, Wolfgang

2017-10-13

Parkinson's disease is the second most common neurodegenerative disease. It is characterized by aggregation of the protein α-synuclein (α-syn) in Lewy bodies, mitochondrial dysfunction, and increased oxidative stress in the substantia nigra. Oxidative stress leads to several modifications of biomolecules including dityrosine (DiY) crosslinking in proteins, which has recently been detected in α-syn in Lewy bodies from Parkinson's disease patients. Here we report that α-syn is highly susceptible to ultraviolet-induced DiY formation. We investigated DiY formation of α-syn and nine tyrosine-to-alanine mutants and monitored its effect on α-syn fibril formation in vitro. Ultraviolet irradiation of intrinsically disordered α-syn generates DiY-modified monomers and dimers, which inhibit fibril formation of unmodified α-syn by interfering with fibril elongation. The inhibition depends on both the DiY group and its integration into α-syn. When preformed α-syn fibrils are crosslinked by DiY formation, they gain increased resistance to denaturation. DiY-stabilized α-syn fibrils retain their high seeding efficiency even after being exposed to denaturant concentrations that completely depolymerize non-crosslinked seeds. Oxidative stress-associated DiY crosslinking of α-syn therefore entails two opposing effects: (i) inhibition of aggregation by DiY-modified monomers and dimers, and (ii) stabilization of fibrillar aggregates against potential degradation mechanisms, which can lead to promotion of aggregation, especially in the presence of secondary nucleation. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

End-to-end Structural Restriction of α-Synuclein and Its Influence on Amyloid Fibril Formation

International Nuclear Information System (INIS)

Hong, Chul Suk; Park, Jae Hyung; Choe, Young Jun; Paik, Seung R.

2014-01-01

Relationship between molecular freedom of amyloidogenic protein and its self-assembly into amyloid fibrils has been evaluated with α-synuclein, an intrinsically unfolded protein related to Parkinson's disease, by restricting its structural plasticity through an end-to-end disulfide bond formation between two newly introduced cysteine residues on the N- and C-termini. Although the resulting circular form of α-synuclein exhibited an impaired fibrillation propensity, the restriction did not completely block the protein's interactive core since co-incubation with wild-type α-synuclein dramatically facilitated the fibrillation by producing distinctive forms of amyloid fibrils. The suppressed fibrillation propensity was instantly restored as the structural restriction was unleashed with β-mercaptoethanol. Conformational flexibility of the accreting amyloidogenic protein to pre-existing seeds has been demonstrated to be critical for fibrillar extension process by exerting structural adjustment to a complementary structure for the assembly

End-to-end Structural Restriction of α-Synuclein and Its Influence on Amyloid Fibril Formation

Energy Technology Data Exchange (ETDEWEB)

Hong, Chul Suk; Park, Jae Hyung; Choe, Young Jun; Paik, Seung R. [Seoul National University, Seoul (Korea, Republic of)

2014-09-15

Relationship between molecular freedom of amyloidogenic protein and its self-assembly into amyloid fibrils has been evaluated with α-synuclein, an intrinsically unfolded protein related to Parkinson's disease, by restricting its structural plasticity through an end-to-end disulfide bond formation between two newly introduced cysteine residues on the N- and C-termini. Although the resulting circular form of α-synuclein exhibited an impaired fibrillation propensity, the restriction did not completely block the protein's interactive core since co-incubation with wild-type α-synuclein dramatically facilitated the fibrillation by producing distinctive forms of amyloid fibrils. The suppressed fibrillation propensity was instantly restored as the structural restriction was unleashed with β-mercaptoethanol. Conformational flexibility of the accreting amyloidogenic protein to pre-existing seeds has been demonstrated to be critical for fibrillar extension process by exerting structural adjustment to a complementary structure for the assembly.

The core of Ure2p prion fibrils is formed by the N-terminal segment in a parallel cross-β structure: evidence from solid-state NMR.

Science.gov (United States)

Kryndushkin, Dmitry S; Wickner, Reed B; Tycko, Robert

2011-06-03

Intracellular fibril formation by Ure2p produces the non-Mendelian genetic element [URE3] in Saccharomyces cerevisiae, making Ure2p a prion protein. We show that solid-state NMR spectra of full-length Ure2p fibrils, seeded with infectious prions from a specific [URE3] strain and labeled with uniformly (15)N-(13)C-enriched Ile, include strong, sharp signals from Ile residues in the globular C-terminal domain (CTD) with both helical and nonhelical (13)C chemical shifts. Treatment with proteinase K eliminates these CTD signals, leaving only nonhelical signals from the Gln-rich and Asn-rich N-terminal segment, which are also observed in the solid-state NMR spectra of Ile-labeled fibrils formed by residues 1-89 of Ure2p. Thus, the N-terminal segment, or "prion domain" (PD), forms the fibril core, while CTD units are located outside the core. We additionally show that, after proteinase K treatment, Ile-labeled Ure2p fibrils formed without prion seeding exhibit a broader set of solid-state NMR signals than do prion-seeded fibrils, consistent with the idea that structural variations within the PD core account for prion strains. Measurements of (13)C-(13)C magnetic dipole-dipole couplings among (13)C-labeled Ile carbonyl sites in full-length Ure2p fibrils support an in-register parallel β-sheet structure for the PD core of Ure2p fibrils. Finally, we show that a model in which CTD units are attached rigidly to the parallel β-sheet core is consistent with steric constraints. Published by Elsevier Ltd.

A beta2-microglobulin cleavage variant fibrillates at near-physiological pH

DEFF Research Database (Denmark)

Corlin, Dorthe B; Johnsen, Christina K; Nissen, Mogens H

2009-01-01

Beta2-microglobulin (beta2m) deposits as amyloid in dialysis-related amyloidosis (DRA), predominantly in joints. The molecular mechanisms underlying the amyloidogenicity of beta2m are still largely unknown. In vitro, acidic conditions, pH ... several days. Here, we show that amyloid fibrils are generated in less than an hour when a cleavage variant of beta2m--found in the circulation of many dialysis patients--is exposed to pH levels (pH 6.6) occurring in joints during inflammation. Aggregation and fibrillation, including seeding effects...... with intact, native beta2m were studied by Thioflavin T fluorescence spectroscopy, turbidimetry, capillary electrophoresis, and electron microscopy. We conclude that a biologically relevant variant of beta2m is amyloidogenic at slightly acidic pH. Also, only a very small amount of preformed fibrils...

Atrial fibrillation associated with chocolate intake abuse and chronic salbutamol inhalation abuse.

Science.gov (United States)

Patanè, Salvatore; Marte, Filippo; La Rosa, Felice Carmelo; Rocca, Roberto La

2010-11-19

The use of substances as the substrate for atrial fibrillation is not frequently recognized. Chocolate is derived from the roasted seeds of the plant theobroma cacao and its components are the methylxanthine alkaloids theobromine and caffeine. Caffeine is a methylxanthine whose primary biological effect is the competitive antagonism of the adenosine receptor. Normal consumption of caffeine was not associated with risk of atrial fibrillation or flutter. Sympathomimetic effects, due to circulating catecholamines cause the cardiac manifestations of caffeine overdose toxicity, produce tachyarrhythmias such as supraventricular tachycardia, atrial fibrillation, ventricular tachycardia, and ventricular fibrillation.The commonly used doses of inhaled or nebulized salbutamol induced no acute myocardial ischaemia, arrhythmias or changes in heart rate variability in patients with coronary artery disease and clinically stable asthma or chronic obstructive pulmonary disease. Two-week salbutamol treatment shifts the cardiovascular autonomic regulation to a new level characterized by greater sympathetic responsiveness and slight beta2-receptor tolerance. We present a case of atrial fibrillation associated with chocolate intake abuse in a 19-year-old Italian woman with chronic salbutamol inhalation abuse. This case focuses attention on chocolate intake abuse associated with chronic salbutamol abuse as the substrate for atrial fibrillation. Copyright © 2008 Elsevier Ireland Ltd. All rights reserved.

Comparative analysis of adherence, viability, proliferation and morphology of umbilical cord tissue-derived mesenchymal stem cells seeded on different titanium-coated expanded polytetrafluoroethylene scaffolds

International Nuclear Information System (INIS)

Hollweck, Trixi; Marschmann, Michaela; Hartmann, Isabel; Akra, Bassil; Meiser, Bruno; Reichart, Bruno; Eissner, Guenther; Eblenkamp, Markus; Wintermantel, Erich

2010-01-01

Umbilical cord tissue comprises an attractive new source for mesenchymal stem cells. Umbilical cord tissue-derived mesenchymal stem cells (UCMSC) exhibit self-renewal, multipotency and immunological naivity, and they can be obtained without medical intervention. The transfer of UCMSC to the ischemic region of the heart may have a favorable impact on tissue regeneration. Benefit from typical cell delivery by injection to the infarcted area is often limited due to poor cell retention and survival. Another route of administration is to use populated scaffolds implanted into the infarcted zone. In this paper, the seeding efficiency of UCMSC on uncoated and titanium-coated expanded polytetrafluoroethylene (ePTFE) scaffolds with different surface structures was determined. Dualmesh (registered) (DM) offers a corduroy-like surface in contrast to the comparatively planar surface of cardiovascular patch (CVP). The investigation of adherence, viability and proliferation of UCMSC demonstrates that titanium-coated scaffolds are superior to uncoated scaffolds, independent of the surface structure. Microscopic images reveal spherical UCMSC seeded on uncoated scaffolds. In contrast, UCMSC on titanium-coated scaffolds display their characteristic spindle-shaped morphology and a homogeneous coverage of CVP. In summary, titanium coating of clinically approved CVP enhances the retention of UCMSC and thus offers a potential cell delivery system for the repair of the damaged myocardium.

Comparative analysis of adherence, viability, proliferation and morphology of umbilical cord tissue-derived mesenchymal stem cells seeded on different titanium-coated expanded polytetrafluoroethylene scaffolds

Energy Technology Data Exchange (ETDEWEB)

Hollweck, Trixi; Marschmann, Michaela; Hartmann, Isabel; Akra, Bassil; Meiser, Bruno; Reichart, Bruno; Eissner, Guenther [Department of Cardiac Surgery, University of Munich, Marchioninistrasse 15, 81377 Munich (Germany); Eblenkamp, Markus; Wintermantel, Erich, E-mail: Guenther.Eissner@med.uni-muenchen.d [Chair of Medical Engineering, Technische Universitaet Muenchen, Boltzmannstrasse 15, 85748 Garching (Germany)

2010-12-15

Umbilical cord tissue comprises an attractive new source for mesenchymal stem cells. Umbilical cord tissue-derived mesenchymal stem cells (UCMSC) exhibit self-renewal, multipotency and immunological naivity, and they can be obtained without medical intervention. The transfer of UCMSC to the ischemic region of the heart may have a favorable impact on tissue regeneration. Benefit from typical cell delivery by injection to the infarcted area is often limited due to poor cell retention and survival. Another route of administration is to use populated scaffolds implanted into the infarcted zone. In this paper, the seeding efficiency of UCMSC on uncoated and titanium-coated expanded polytetrafluoroethylene (ePTFE) scaffolds with different surface structures was determined. Dualmesh (registered) (DM) offers a corduroy-like surface in contrast to the comparatively planar surface of cardiovascular patch (CVP). The investigation of adherence, viability and proliferation of UCMSC demonstrates that titanium-coated scaffolds are superior to uncoated scaffolds, independent of the surface structure. Microscopic images reveal spherical UCMSC seeded on uncoated scaffolds. In contrast, UCMSC on titanium-coated scaffolds display their characteristic spindle-shaped morphology and a homogeneous coverage of CVP. In summary, titanium coating of clinically approved CVP enhances the retention of UCMSC and thus offers a potential cell delivery system for the repair of the damaged myocardium.

Glycosaminoglycans enhance the fibrillation propensity of the ß2-microglobulin cleavage variant--¿K58-ß2m

DEFF Research Database (Denmark)

Corlin, Dorthe B; Johnsen, Christina K; Nissen, Mogens H

2010-01-01

when heparan sulfate is present have increased length and diameter, and possess enhanced stability and seeding properties. However, when copper ions are present the fibrils are short, thin and less stable, and form at a slower rate. We suggest that heparan sulfate stabilizes the cleaved monomers...... in the early aggregates, hereby promoting the assembly of these into fibrils, whereas the copper ions appear to have a destabilizing effect on the monomers. This keeps them in a structure forming amorphous aggregates for a longer period of time, leading to the formation of spherical bodies followed...... by the assembly of fibrils. Hence, the in vivo formation of amyloid fibrils in DRA could be initiated by the generation of ¿K58-ß2m which spontaneously aggregate and form fibrils. The fibrillogenesis is enhanced by the involvement of GAGs and/or metal ions, and results in amyloid-like fibrils able to promote...

Preformed template fluctuations promote fibril formation: Insights from lattice and all-atom models

Energy Technology Data Exchange (ETDEWEB)

Kouza, Maksim, E-mail: mkouza@chem.uw.edu.pl; Kolinski, Andrzej [Faculty of Chemistry, University of Warsaw, ul. Pasteura 1, 02-093 Warszaw (Poland); Co, Nguyen Truong [Department of Physics, Institute of Technology, National University of HCM City, 268 Ly Thuong Kiet Street, District 10, Ho Chi Minh City (Viet Nam); Institute for Computational Science and Technology, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City (Viet Nam); Nguyen, Phuong H. [Laboratoire de Biochimie Theorique, UPR 9080 CNRS, IBPC, Universite Paris 7, 13 rue Pierre et Marie Curie, 75005 Paris (France); Li, Mai Suan, E-mail: masli@ifpan.edu.pl [Institute of Physics, Polish Academy of Sciences, Al. Lotnikow 32/46, 02-668 Warsaw (Poland)

2015-04-14

Fibril formation resulting from protein misfolding and aggregation is a hallmark of several neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Despite the fact that the fibril formation process is very slow and thus poses a significant challenge for theoretical and experimental studies, a number of alternative pictures of molecular mechanisms of amyloid fibril formation have been recently proposed. What seems to be common for the majority of the proposed models is that fibril elongation involves the formation of pre-nucleus seeds prior to the creation of a critical nucleus. Once the size of the pre-nucleus seed reaches the critical nucleus size, its thermal fluctuations are expected to be small and the resulting nucleus provides a template for sequential (one-by-one) accommodation of added monomers. The effect of template fluctuations on fibril formation rates has not been explored either experimentally or theoretically so far. In this paper, we make the first attempt at solving this problem by two sets of simulations. To mimic small template fluctuations, in one set, monomers of the preformed template are kept fixed, while in the other set they are allowed to fluctuate. The kinetics of addition of a new peptide onto the template is explored using all-atom simulations with explicit water and the GROMOS96 43a1 force field and simple lattice models. Our result demonstrates that preformed template fluctuations can modulate protein aggregation rates and pathways. The association of a nascent monomer with the template obeys the kinetics partitioning mechanism where the intermediate state occurs in a fraction of routes to the protofibril. It was shown that template immobility greatly increases the time of incorporating a new peptide into the preformed template compared to the fluctuating template case. This observation has also been confirmed by simulation using lattice models and may be invoked to understand the role of template fluctuations in

A β2-microglobulin cleavage variant fibrillates at near-physiological pH

International Nuclear Information System (INIS)

Corlin, Dorthe B.; Johnsen, Christina K.; Nissen, Mogens H.; Heegaard, Niels H.H.

2009-01-01

β 2 -microglobulin (β 2 m) deposits as amyloid in dialysis-related amyloidosis (DRA), predominantly in joints. The molecular mechanisms underlying the amyloidogenicity of β 2 m are still largely unknown. In vitro, acidic conditions, pH 2 m within several days. Here, we show that amyloid fibrils are generated in less than an hour when a cleavage variant of β 2 m-found in the circulation of many dialysis patients-is exposed to pH levels (pH 6.6) occurring in joints during inflammation. Aggregation and fibrillation, including seeding effects with intact, native β 2 m were studied by Thioflavin T fluorescence spectroscopy, turbidimetry, capillary electrophoresis, and electron microscopy. We conclude that a biologically relevant variant of β 2 m is amyloidogenic at slightly acidic pH. Also, only a very small amount of preformed fibrils of this variant is required to induce fibrillation of native β 2 m. This may explain the apparent lack of detectable amounts of the variant β 2 m in extracts of amyloid from DRA patients.

Albumin fibrillization induces apoptosis via integrin/FAK/Akt pathway

Directory of Open Access Journals (Sweden)

Liang Chi-Ming

2009-01-01

Full Text Available Abstract Background Numerous proteins can be converted to amyloid-like fibrils to increase cytotoxicity and induce apoptosis, but the methods generally require a high concentration of protein, vigorous shaking, or fibril seed. As well, the detailed mechanism of the cytotoxic effects is not well characterized. In this study, we have developed a novel process to convert native proteins into the fibrillar form. We used globular bovine serum albumin (BSA as a model protein to verify the properties of the fibrillar protein, investigated its cellular effects and studied the signaling cascade induced by the fibrillar protein. Results We induced BSA, a non-cytotoxic globular protein, to become fibril by a novel process involving Superdex-200 column chromatography in the presence of anionic or zwittergenic detergent(s. The column pore size was more important than column matrix composite in fibril formation. The fibrillar BSA induced apoptosis in BHK-21 cell as well as breast cancer cell line T47D. Pre-treating cells with anti-integrin antibodies blocked the apoptotic effect. Fibrillar BSA, but not globular BSA, bound to integrin, dephosphorylated focal adhesion kinase (FAK, Akt and glycogen synthase kinase-3β (GSK-3β. Conclusion We report on a novel process for converting globular proteins into fibrillar form to cause apoptosis by modulating the integrin/FAK/Akt/GSK-3β/caspase-3 signaling pathway. Our findings may be useful for understanding the pathogenesis of amyloid-like fibrils and applicable for the development of better therapeutic agents that target the underlying mechanism(s of the etiologic agents.

Atrial Fibrillation: Diagnosis

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... of this page please turn JavaScript on. Feature: Atrial Fibrillation Atrial Fibrillation: Diagnosis Past Issues / Winter 2015 Table of Contents ... of your body's cells and organs. Read More "Atrial Fibrillation" Articles Atrial Fibrillation / Who Is at Risk for ...

“Sticky invasion” – the physical properties of Plantago lanceolata L. seed mucilage

Directory of Open Access Journals (Sweden)

Agnieszka Kreitschitz

2016-12-01

Full Text Available The mucilage envelope of seeds has various functions including the provision of different ways for the dispersal of diaspores. Chemical composition and water content of the mucilage yield particular adhesive and frictional properties in the envelope that also influence the dispersal of seeds. To determine the physical properties of Plantago lanceolata seed mucilage we studied (1 composition, (2 desiccation, (3 adhesion, and (4 friction properties of the mucilage under different hydration conditions. We revealed the presence of cellulose fibrils in the mucilage, which are responsible for a continuous and even distribution of the mucilaginous layer on the seed surface. The measured values of adhesive and frictional properties differed significantly in comparison to the previously studied pectic mucilage of Linum usitatissimum. Also, the water loss from the cellulose mucilage was more rapid. The obtained different values can result from the presence of cellulose fibrils and their interaction with pectins in the mucilage. Because of this feature the mucilage of P. lanceolata may represent a more regularly ordered and stabile system than the pectic mucilage of flax, which lacks cellulose. In spite of the fact that P. lanceolata mucilage revealed different adhesive and frictional properties than the pectic mucilage, it still demonstrates an effective system promoting zoochoric seed dispersal. Cellulose may additionally prevent the mucilage against loss from the seed surface.

Spinal cord injury is associated with an increased risk of atrial fibrillation: A population-based cohort study.

Science.gov (United States)

Wang, Chun-Cheng; Chang, Chiz-Tzung; Lin, Cheng-Li; Huang, Bor-Ren; Kao, Chia-Hung

2016-02-01

Spinal cord injury (SCI) can result in substantial sensorimotor and autonomic dysfunctions and an adverse prognosis. Cardiovascular disease is the leading cause of death in patients with chronic SCI. We conducted a retrospective cohort study to investigate the association between atrial fibrillation (AF) and SCI. Using the National Health Insurance Research Database, we identified 41,691 patients without a history of AF who were newly hospitalized for SCI between 2000 and 2011. The comparison group included 166,724 patients without AF or SCI who were matched to the SCI group according to age, sex, and index year at a ratio of 4:1. Both cohorts were followed up until the end of 2011, and the cumulative incidence of AF was calculated. Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier curve analysis were used to compare differences in the cumulative incidence of AF between the 2 groups. During the mean follow-up periods of 5.69 years for the SCI group and 6.17 years for the non-SCI group, the overall incidence rates were 2.70 and 1.99 cases per 1000 person-years, respectively (crude hazard ratio 1.36; 95% confidence interval 1.24-1.48). After adjusting for age, sex, and all comorbidities, the risk of AF remained significantly higher in the SCI group than in the non-SCI group (adjusted hazard ratio 1.28; 95% confidence interval 1.17-1.40). SCI is associated with an increased risk of AF in a long-term follow-up period. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Atrial Fibrillation: Treatment

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... of this page please turn JavaScript on. Feature: Atrial Fibrillation Atrial Fibrillation: Treatment Past Issues / Winter 2015 Table of Contents Treatment for atrial fibrillation depends on how often you have symptoms, how ...

Encapsulated sensory corpuscle in the mucosa of human vocal cord: an electron microscope study.

Science.gov (United States)

Nagai, T

1982-05-01

Encapsulated sensory corpuscles of the Krause type were found in the mucosa of surgically removed human vocal cords. The corpuscles were ellipsoidal structures of about 30 to 50 micrometers and were located beneath the free edge in the mid-region along the intermembranous part. They contained a number of varicose nerve endings and lamellar cells. The lamellar cells had thin cytoplasmic lamellae which contained numerous cytoplasmic filaments and were interposed between the nerve endings. Attachment devices were frequently noted between the cytoplasmic lamellae and between the lamellae and nerve endings. Half-desmosomes were also noted along the plasma membrane of the lamellar cells. The intercellular space was filled with amorphous electron lucent material and contained a few collagen fibrils. Ladder-like filamentous structures were frequently encountered in the intercellular space. The location of the corpuscles at the free edge of the vocal cords suggests that the endings may receive the bilateral touch of the vibrating part of the cords in order to give sensory information for the control of the movement of the cords in phonation.

Atrial Fibrillation: Complications

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... of this page please turn JavaScript on. Feature: Atrial Fibrillation Atrial Fibrillation: Complications Past Issues / Winter 2015 Table of Contents ... has two major complications—stroke and heart failure. Atrial Fibrillation and Stroke Click to enlarge image This illustration ...

The Japanese Mutant Aβ (ΔE22-Aβ1–39) Forms Fibrils Instantaneously, with Low-Thioflavin T Fluorescence: Seeding of Wild-Type Aβ1-40 into Atypical Fibrils by ΔE22-Aβ1-39

Science.gov (United States)

Cloe, Adam L.; Orgel, Joseph P.R.O.; Sachleben, Joseph R.; Tycko, Robert; Meredith, Stephen C.

2012-01-01

The ΔE693 (Japanese) mutation of the β-amyloid precursor protein leads to production of ΔE22-Aβ peptides such as ΔE22-Aβ1–39. Despite reports that these peptides do not form fibrils, here we show that, on the contrary, the peptide forms fibrils essentially instantaneously. The fibrils are typical amyloid fibrils in all respects except that they cause only low levels of thioflavin T (ThT) fluorescence, which, however, develops with no lag phase. The fibrils bind ThT, but with a lower affinity and a smaller number of binding sites than wild-type (WT) Aβ1–40. Fluorescence depolarization confirms extremely rapid aggregation of ΔE22-Aβ1–39. Size exclusion chromatography (SEC) indicates very low concentrations of soluble monomer and oligomer, but only in the presence of some organic solvent, e.g., 2% (v/v) DMSO. The critical concentration is approximately 1 order of magnitude lower for ΔE22-Aβ1–39 than for WTAβ1–40. Several lines of evidence point to an altered structure for ΔE22-Aβ1–39 compared to that of WT Aβ1–40 fibrils. In addition to differences in ThT binding and fluorescence, PITHIRDS-CT solid-state nuclear magnetic resonance (NMR) measurements of ΔE22-Aβ1–39 are not compatible with the parallel in-register β-sheet generally observed for WT Aβ1–40 fibrils. X-ray fibril diffraction showed different D spacings: 4.7 and 10.4 Å for WT Aβ1–40 and 4.7 and 9.6 Å for ΔE22-Aβ1–39. Equimolar mixtures of ΔE22-Aβ1–39 and WT Aβ1–40 also produced fibrils extremely rapidly, and by the criteria of ThT fluorescence and electron microscopic appearance, they were the same as fibrils made from pure ΔE22-Aβ1–39. X-ray diffraction of fibrils formed from 1:1 molar mixtures of ΔE22-Aβ1–39 and WT Aβ1–40 showed the same D spacings as fibrils of the pure mutant peptide, not the wild-type peptide. These findings are consistent with extremely rapid nucleation by ΔE22-Aβ1–39, followed by fibril extension by WT Aβ1–40, and

Thermal Stimulation Alters Cervical Spinal Cord Functional Connectivity in Humans.

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Weber, Kenneth A; Sentis, Amy I; Bernadel-Huey, Olivia N; Chen, Yufen; Wang, Xue; Parrish, Todd B; Mackey, Sean

2018-01-15

The spinal cord has an active role in the modulation and transmission of the neural signals traveling between the body and the brain. Recent advancements in functional magnetic resonance imaging (fMRI) have made the in vivo examination of spinal cord function in humans now possible. This technology has been recently extended to the investigation of resting state functional networks in the spinal cord, leading to the identification of distinct patterns of spinal cord functional connectivity. In this study, we expand on the previous work and further investigate resting state cervical spinal cord functional connectivity in healthy participants (n = 15) using high resolution imaging coupled with both seed-based functional connectivity analyses and graph theory-based metrics. Within spinal cord segment functional connectivity was present between the left and right ventral horns (bilateral motor network), left and right dorsal horns (bilateral sensory network), and the ipsilateral ventral and dorsal horns (unilateral sensory-motor network). Functional connectivity between the spinal cord segments was less apparent with the connectivity centered at the region of interest and spanning spinal cord functional network was demonstrated to be state-dependent as thermal stimulation of the right ventrolateral forearm resulted in significant disruption of the bilateral sensory network, increased network global efficiency, and decreased network modularity. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Synthesis and characterization of chitosan-alginate scaffolds for seeding human umbilical cord derived mesenchymal stem cells.

Science.gov (United States)

Kumbhar, Sneha G; Pawar, S H

2016-01-01

Chitosan and alginate are two natural and accessible polymers that are known to be biocompatible, biodegradable and possesses good antimicrobial activity. When combined, they exhibit desirable characteristics and can be created into a scaffold for cell culture. In this study interaction of chitosan-alginate scaffolds with mesenchymal stem cells are studied. Mesenchymal stem cells were derived from human umbilical cord tissues, characterized by flow cytometry and other growth parameters studied as well. Proliferation and viability of cultured cells were studied by MTT Assay and Trypan Blue dye exclusion assay. Besides chitosan-alginate scaffold was prepared by freeze-drying method and characterized by FTIR, SEM and Rheological properties. The obtained 3D porous structure allowed very efficient seeding of hUMSCs that are able to inhabit the whole volume of the scaffold, showing good adhesion and proliferation. These materials showed desirable rheological properties for facile injection as tissue scaffolds. The results of this study demonstrated that chitosan-alginate scaffold may be promising biomaterial in the field of tissue engineering, which is currently under a great deal of examination for the development and/or restoration of tissue and organs. It combines the stem cell therapy and biomaterials.

Atrial fibrillation and hyperthyroidism: A literature review.

Science.gov (United States)

Reddy, Vivek; Taha, Wael; Kundumadam, Shanker; Khan, Mazhar

Atrial fibrillation is the most common arrhythmia worldwide with increasing frequency noted with age. Hyperthyroidism is a well-known cause of atrial fibrillation with a 16%-60% prevalence of atrial fibrillation in patients with known hyperthyroidism Ross et al. (2016). While hyperthyroidism as a causative factor of atrial fibrillation is well established, this literature review aims to answer several questions on this topic including: 1. The relationship of atrial fibrillation to hyperthyroidism 2. Atrial fibrillation as a predictor of hyperthyroidism 3. The pathophysiology of thyrotoxic atrial fibrillation 4. Subclinical hyperthyroidism and the relationship with atrial fibrillation 5. Cardioversion and Catheter ablation of hyperthyroid patients with atrial fibrillation 6. Thrombotic risk of hyperthyroid patients with atrial fibrillation 7. Management of Thyrotoxic Atrial fibrillation 8. Pharmacological rhythm control in patients with hyperthyroidism and atrial fibrillation 9. Treatment of Hyperthyroidism to prevent atrial fibrillation 10. Clinical Implications of Hyperthyroidism and Atrial Fibrillation. Copyright © 2017 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Stop-and-go kinetics in amyloid fibrillation

DEFF Research Database (Denmark)

Ferkinghoff-Borg, Jesper; Fonslet, Jesper; Andersen, Christian Beyschau

2010-01-01

Many human diseases are associated with protein aggregation and fibrillation. We present experiments on in vitro glucagon fibrillation using total internal reflection fluorescence microscopy, providing real-time measurements of single-fibril growth. We find that amyloid fibrils grow in an intermi......Many human diseases are associated with protein aggregation and fibrillation. We present experiments on in vitro glucagon fibrillation using total internal reflection fluorescence microscopy, providing real-time measurements of single-fibril growth. We find that amyloid fibrils grow...

Atrial fibrillation and delayed gastric emptying.

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Isadora C Botwinick

Full Text Available BACKGROUND: Atrial fibrillation and delayed gastric emptying (DGE are common after pancreaticoduodenectomy. Our aim was to investigate a potential relationship between atrial fibrillation and DGE, which we defined as failure to tolerate a regular diet by the 7(th postoperative day. METHODS: We performed a retrospective chart review of 249 patients who underwent pancreaticoduodenectomy at our institution between 2000 and 2009. Data was analyzed with Fisher exact test for categorical variables and Mann-Whitney U or unpaired T-test for continuous variables. RESULTS: Approximately 5% of the 249 patients included in the analysis experienced at least one episode of postoperative atrial fibrillation. Median age of patients with atrial fibrillation was 74 years, compared with 66 years in patients without atrial fibrillation (p = 0.0005. Patients with atrial fibrillation were more likely to have a history of atrial fibrillation (p = 0.03. 92% of the patients with atrial fibrillation suffered from DGE, compared to 46% of patients without atrial fibrillation (p = 0.0007. This association held true when controlling for age. CONCLUSION: Patients with postoperative atrial fibrillation are more likely to experience delayed gastric emptying. Interventions to manage delayed gastric function might be prudent in patients at high risk for postoperative atrial fibrillation.

Surgery for atrial fibrillation.

Science.gov (United States)

Viganò, M; Graffigna, A; Ressia, L; Minzioni, G; Pagani, F; Aiello, M; Gazzoli, F

1996-01-01

The mechanisms of atrial fibrillation arc multiple reentry circuits spinning around the atrial surface, and these baffle any attempt to direct surgical interruption. The purpose of this article is to report the surgical experience in the treatment of isolated and concomitant atrial fibrillation at the Cardiac Surgical Institute of the University of Pavia. In cases of atrial fibrillation secondary to mitral/valve disease, surgical isolation of the left atrium at the time of mitral valve surgery can prevent atrial fibrillation from involving the right atrium, which can exert its diastolic pump function on the right ventricle. Left atrial isolation was performed on 205 patients at the time of mitral valve surgery. Atrial partitioning ("maze operation") creates straight and blind atrial alleys so that non-recentry circuits can take place. Five patients underwent this procedure. In eight-cases of atrial fibrillation secondary to atrial septal defect, the adult patients with atrial septal defect and chronic or paroxysmal atrial fibrillation underwent surgical isolation of the right atrium associated which surgical correction of the defect, in order to let sinus rhythm govern the left atrium and the ventricles. "Lone" atrial fibrillation occurs in hearts with no detectable organic disease. Bi-atrial isolation with creation of an atrial septal internodal "corridor" was performed on 14 patients. In cases of atrial fibrillation secondary to mitral valve disease, left atrial isolation was performed on 205 patients at the time of mitral valve surgery with an overall sinus rhythm recovery of 44%. In the same period, sinus rhythm was recovered and persisted in only 19% of 252 patients who underwent mitral valve replacement along (P < 0.001). Sinus rhythm was less likely to recover in patients with right atriomegaly requiring tricuspid valve annuloplasty: 59% vs 84% (P < 0.001). Restoration of the right atrial function raised the cardiac index from 2.25 +/- 0.55 1/min per m2

Atrial fibrillation - discharge

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... this page: //medlineplus.gov/ency/patientinstructions/000237.htm Atrial fibrillation - discharge To use the sharing features on this ... have been in the hospital because you have atrial fibrillation . This condition occurs when your heart beats faster ...

Is early cord clamping, delayed cord clamping or cord milking best?

Science.gov (United States)

Vatansever, Binay; Demirel, Gamze; Ciler Eren, Elif; Erel, Ozcan; Neselioglu, Salim; Karavar, Hande Nur; Gundogdu, Semra; Ulfer, Gozde; Bahadir, Selcen; Tastekin, Ayhan

2018-04-01

To compare the antioxidant status of three cord clamping procedures (early clamping, delayed clamping and milking) by analyzing the thiol-disulfide balance. This randomized controlled study enrolled 189 term infants who were divided into three groups according to the cord clamping procedure: early clamping, delayed clamping and milking. Blood samples were collected from the umbilical arteries immediately after clamping, and the thiol/disulfide homeostasis was analyzed. The native and total thiol levels were significantly (p total thiol ratio was significantly (p = .026) lower in the delayed cord clamping and milking groups compared with the early clamping groups. Early cord clamping causes the production of more disulfide bonds and lower thiol levels, indicating that oxidation reactions are increased in the early cord clamping procedure compared with the delayed cord clamping and milking procedures. The oxidant capacity is greater with early cord clamping than with delayed clamping or cord milking. Delayed cord clamping or milking are beneficial in neonatal care, and we suggest that they be performed routinely in all deliveries.

α-Synuclein aggregation, seeding and inhibition by scyllo-inositol

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Ibrahim, Tarek [Biological Sciences, Sunnybrook Research Institute (Canada); Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M4N 3M5, ON (Canada); McLaurin, JoAnne, E-mail: jmclaurin@sri.utoronto.ca [Biological Sciences, Sunnybrook Research Institute (Canada); Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M4N 3M5, ON (Canada)

2016-01-15

Recent literature demonstrates the accelerated aggregation of α-synuclein, a protein implicated in the pathogenesis of Parkinson's disease (PD), by the presence of preformed fibrillar conformers in vitro. Furthermore, these preformed fibrillar seeds are suggested to accelerate pathological induction in vivo when injected into the brains of mice. Variation in the results of in vivo studies is proposed to be caused by α-synuclein conformational variants. To investigate the impact of amino acid sequence on seeding efficiency, human and mouse α-synuclein seeds, which vary at 7 amino acid residues, were generated and cross-seeding kinetics studied. Using transmission electron microscopy (TEM), we confirmed that mouse α-synuclein aggregated more rapidly than human α-synuclein. Subsequently, we determined that seeding of human and mouse α-synuclein was more rapid in the presence of seeds generated from the same species. In addition, an established amyloid inhibitor, scyllo-inositol, was examined for potential inhibitory effects on α-synuclein aggregation. TEM analysis of protein:inhibitor assays demonstrated that scyllo-inositol inhibits the aggregation of α-synuclein, suggesting the therapeutic potential of the small molecule in PD. - Highlights: • Mouse α-syn fibrillizes in a significantly shorter timeframe than human α-syn. • Seeding of monomers is more efficient when seeds originate from the same species. • scyllo-Inositol has anti-aggregation effects on mouse and human α-syn.

Nanomechanical properties of single amyloid fibrils

International Nuclear Information System (INIS)

Sweers, K K M; Bennink, M L; Subramaniam, V

2012-01-01

Amyloid fibrils are traditionally associated with neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease or Creutzfeldt-Jakob disease. However, the ability to form amyloid fibrils appears to be a more generic property of proteins. While disease-related, or pathological, amyloid fibrils are relevant for understanding the pathology and course of the disease, functional amyloids are involved, for example, in the exceptionally strong adhesive properties of natural adhesives. Amyloid fibrils are thus becoming increasingly interesting as versatile nanobiomaterials for applications in biotechnology. In the last decade a number of studies have reported on the intriguing mechanical characteristics of amyloid fibrils. In most of these studies atomic force microscopy (AFM) and atomic force spectroscopy play a central role. AFM techniques make it possible to probe, at nanometer length scales, and with exquisite control over the applied forces, biological samples in different environmental conditions. In this review we describe the different AFM techniques used for probing mechanical properties of single amyloid fibrils on the nanoscale. An overview is given of the existing mechanical studies on amyloid. We discuss the difficulties encountered with respect to the small fibril sizes and polymorphic behavior of amyloid fibrils. In particular, the different conformational packing of monomers within the fibrils leads to a heterogeneity in mechanical properties. We conclude with a brief outlook on how our knowledge of these mechanical properties of the amyloid fibrils can be exploited in the construction of nanomaterials from amyloid fibrils. (topical review)

Curcumin Protects β-Lactoglobulin Fibril Formation and Fibril-Induced Neurotoxicity in PC12 Cells.

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Mansooreh Mazaheri

Full Text Available In this study the β-lactoglobulin fibrillation, in the presence or absence of lead ions, aflatoxin M1 and curcumin, was evaluated using ThT fluorescence, Circular dichroism spectroscopy and atomic force microscopy. To investigate the toxicity of the different form of β-Lg fibrils, in the presence or absence of above toxins and curcumin, we monitored changes in the level of reactive oxygen species and morphology of the differentiated neuron-like PC12 cells. The cell viability, cell body area, average neurite length, neurite width, number of primary neurites, percent of bipolar cells and node/primary neurite ratios were used to assess the growth and complexity of PC12 cells exposed to different form of β-Lg fibrils. Incubation of β-Lg with curcumin resulted in a significant decrease in ROS levels even in the presence of lead ions and aflatoxin M1. The β-Lg fibrils formed in the presence of lead ions and aflatoxin M1 attenuated the growth and complexity of PC12 cells compared with other form of β-Lg fibrils. However, the adverse effects of these toxins and protein fibrils were negated in the presence of curcumin. Furthermore, the antioxidant and inhibitory effects of curcumin protected PC12 cells against fibril neurotoxicity and enhanced their survival. Thus, curcumin may provide a protective effect toward β-Lg, and perhaps other protein, fibrils mediated neurotoxicity.

Toward understanding insulin fibrillation.

Science.gov (United States)

Brange, J; Andersen, L; Laursen, E D; Meyn, G; Rasmussen, E

1997-05-01

Formation of insulin fibrils is a physical process by which partially unfolded insulin molecules interact with each other to form linear aggregates. Shielding of hydrophobic domains is the main driving force for this process, but formation of intermolecular beta-sheet may further stabilize the fibrillar structure. Conformational displacement of the B-chain C-terminal with exposure of nonpolar, aliphatic core residues, including A2, A3, B11, and B15, plays a crucial role in the fibrillation process. Recent crystal analyses and molecular modeling studies have suggested that when insulin fibrillates this exposed domain interacts with a hydrophobic surface domain formed by the aliphatic residues A13, B6, B14, B17, and B18, normally buried when three insulin dimers form a hexamer. In rabbit immunization experiments, insulin fibrils did not elicit an increased immune response with respect to formation of IgG insulin antibodies when compared with native insulin. In contrast, the IgE response increased with increasing content of insulin in fibrillar form. Strategies and practical approaches to prevent insulin from forming fibrils are reviewed. Stabilization of the insulin hexameric structure and blockage of hydrophobic interfaces by addition of surfactants are the most effective means of counteracting insulin fibrillation.

Uniform spatial distribution of collagen fibril radii within tendon implies local activation of pC-collagen at individual fibrils

Science.gov (United States)

Rutenberg, Andrew D.; Brown, Aidan I.; Kreplak, Laurent

2016-08-01

Collagen fibril cross-sectional radii show no systematic variation between the interior and the periphery of fibril bundles, indicating an effectively constant rate of collagen incorporation into fibrils throughout the bundle. Such spatially homogeneous incorporation constrains the extracellular diffusion of collagen precursors from sources at the bundle boundary to sinks at the growing fibrils. With a coarse-grained diffusion equation we determine stringent bounds, using parameters extracted from published experimental measurements of tendon development. From the lack of new fibril formation after birth, we further require that the concentration of diffusing precursors stays below the critical concentration for fibril nucleation. We find that the combination of the diffusive bound, which requires larger concentrations to ensure homogeneous fibril radii, and lack of nucleation, which requires lower concentrations, is only marginally consistent with fully processed collagen using conservative bounds. More realistic bounds may leave no consistent concentrations. Therefore, we propose that unprocessed pC-collagen diffuses from the bundle periphery followed by local C-proteinase activity and subsequent collagen incorporation at each fibril. We suggest that C-proteinase is localized within bundles, at fibril surfaces, during radial fibrillar growth. The much greater critical concentration of pC-collagen, as compared to fully processed collagen, then provides broad consistency between homogeneous fibril radii and the lack of fibril nucleation during fibril growth.

Sucrose modulates insulin amyloid-like fibril formation: effect on the aggregation mechanism and fibril morphology

DEFF Research Database (Denmark)

Marasini, Carlotta; Foderà, Vito; Vestergaard, Bente

2017-01-01

the protein self-assembly pathways. Using a combination of fluorescence spectroscopy, synchrotron radiation circular dichroism and transmission electron microscopy, we study the kinetics of formation and structural properties of human insulin fibrils in the presence of sucrose. The presence of sucrose results...... in a delay of the onset of fibrillation. Moreover, it leads to a dramatic change in both the morphology and overall amount of fibrils. Our results emphasize that the detailed composition of protein surroundings likely influences not only the fibrillation kinetics but also the balance between different...

Atrial fibrillation or flutter

Science.gov (United States)

... this page: //medlineplus.gov/ency/article/000184.htm Atrial fibrillation or flutter To use the sharing features on this page, please enable JavaScript. Atrial fibrillation or flutter is a common type of abnormal ...

Hypothermia with Extreme Bradycardia following Spinal Cord Infarction of Septic Origin

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Philippe Hantson

2017-01-01

Full Text Available Among other autonomic dysfunctions complicating acute spinal cord injury, deep hypothermia is rare but may induce serious cardiovascular complications. There are few pharmacological options to influence hypothermia. A 66-year-old woman was transferred to the intensive care unit (ICU for serious cardiac arrhythmias (atrial fibrillation and asystole in the context of a deep hypothermia (axillary temperature below 32°C. She had been admitted to the hospital two months before for an acute L4-L5 infectious spondylodiscitis without any initial neurological deficit. After surgery for epidural abscess drainage, she became paraplegic due to spinal cord infarction (from C7 to T6 levels in the upper territory of the anterior spinal artery. In the ICU, the patient experienced several episodes of asystole and hypotension associated with a core body temperature below 35°C. Common causes of hypothermia (drugs, hypothyroidism, etc. were excluded. A definitive pacemaker had to be inserted, but hypotension persisted. The prescription of oral progesterone (200 mg·d−1 helped to maintain a core temperature higher than 35°C, with a withdrawal of vasopressors. This case report illustrates that patients with incomplete spinal cord injury may present with delayed and deep hypothermia leading to serious cardiovascular complications. Progesterone could be able to influence positively central and peripheral thermal regulation.

[Atrial fibrillation].

Science.gov (United States)

Spinar, J; Vítovec, J

2003-09-01

Atrial fibrilation is the most frequent arrhythmia, the occurrence increasing with age and associated diseases. The incidence at the age below 60 years is markedly lower than one per cent, whereas in persons above 80 years of age it exceeds six per cent. The occurrence in patients with heart failure is from 10% (NYHA II) up to 50% (NYHA IV). Atrial fibrillation is classified into that observed for the first time and permanent, respectively, while transient forms include paroxyzmal and persistent atrial fibrillation. The diagnosis is based on ECG recording, while echocardiography is most significant. The therapy includes two basic questions--anticoagulant or anti-aggregation treatment and the control of rhythm or frequency. The anticoagulant therapy should be introduced in all patients, where contraindications are not present, being necessary before every cardioversion, provided atrial fibrillation lasts more than two days. In patients without any heart disease and with a physiological echocardiogram it is possible to administer only anti-aggregation treatment. Cardioversion (the control of rhythm) is recommended to all symptomatic patients, in other cases and especially in older persons the control of frequency is safer and of more advantage. Electrical cardioversion is more effective that a pharmacological treatment, the sinus rhythm is preferably controlled by dofetilid, ibutilid, propafenon and amiodaron. For the control of heart rate beta-blockers, diltiazem, verapamil and digitalis are recommended.

Genetics Home Reference: familial atrial fibrillation

Science.gov (United States)

... Twitter Home Health Conditions Familial atrial fibrillation Familial atrial fibrillation Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Familial atrial fibrillation is an inherited abnormality of the heart's normal ...

Atrial Fibrillation - Multiple Languages

Science.gov (United States)

... Are Here: Home → Multiple Languages → All Health Topics → Atrial Fibrillation URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Atrial Fibrillation - Multiple Languages To use the sharing features on ...

Transmission electron microscopy of amyloid fibrils.

Science.gov (United States)

Gras, Sally L; Waddington, Lynne J; Goldie, Kenneth N

2011-01-01

Transmission Electron Microscopy of negatively stained and cryo-prepared specimens allows amyloid fibrils to be visualised at high resolution in a dried or a hydrated state, and is an essential method for characterising the morphology of fibrils and pre-fibrillar species. We outline the key steps involved in the preparation and observation of samples using negative staining and cryo-electron preservation. We also discuss methods to measure fibril characteristics, such as fibril width, from electron micrographs.

Biofabrication enables efficient interrogation and optimization of sequential culture of endothelial cells, fibroblasts and cardiomyocytes for formation of vascular cords in cardiac tissue engineering

International Nuclear Information System (INIS)

Iyer, Rohin K; Radisic, Milica; Chiu, Loraine L Y; Vunjak-Novakovic, Gordana

2012-01-01

We previously reported that preculture of fibroblasts (FBs) and endothelial cells (ECs) prior to cardiomyocytes (CMs) improved the structural and functional properties of engineered cardiac tissue compared to culture of CMs alone or co-culture of all three cell types. However, these approaches did not result in formation of capillary-like cords, which are precursors to vascularization in vivo. Here we hypothesized that seeding the ECs first on Matrigel and then FBs 24 h later to stabilize the endothelial network (sequential preculture) would enhance cord formation in engineered cardiac organoids. Three sequential preculture groups were tested by seeding ECs (D4T line) at 8%, 15% and 31% of the total cell number on Matrigel-coated microchannels and incubating for 24 h. Cardiac FBs were then seeded (32%, 25% and 9% of the total cell number, respectively) and incubated an additional 24 h. Finally, neonatal rat CMs (60% of the total cell number) were added and the organoids were cultivated for seven days. Within 24 h, the 8% EC group formed elongated cords which eventually developed into beating cylindrical organoids, while the 15% and 31% EC groups proliferated into flat EC monolayers with poor viability. Excitation threshold (ET) in the 8% EC group (3.4 ± 1.2 V cm −1 ) was comparable to that of the CM group (3.3 ± 1.4 V cm −1 ). The ET worsened with increasing EC seeding density (15% EC: 4.4 ± 1.5 V cm −1 ; 31% EC: 4.9 ± 1.5 V cm −1 ). Thus, sequential preculture promoted vascular cord formation and enhanced architecture and function of engineered heart tissues. (paper)

Kinetics and mechanical stability of the fibril state control fibril formation time of polypeptide chains: A computational study

Science.gov (United States)

Kouza, Maksim; Co, Nguyen Truong; Li, Mai Suan; Kmiecik, Sebastian; Kolinski, Andrzej; Kloczkowski, Andrzej; Buhimschi, Irina Alexandra

2018-06-01

Fibril formation resulting from protein misfolding and aggregation is a hallmark of several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Despite much progress in the understanding of the protein aggregation process, the factors governing fibril formation rates and fibril stability have not been fully understood. Using lattice models, we have shown that the fibril formation time is controlled by the kinetic stability of the fibril state but not by its energy. Having performed all-atom explicit solvent molecular dynamics simulations with the GROMOS43a1 force field for full-length amyloid beta peptides Aβ40 and Aβ42 and truncated peptides, we demonstrated that kinetic stability can be accessed via mechanical stability in such a way that the higher the mechanical stability or the kinetic stability, the faster the fibril formation. This result opens up a new way for predicting fibril formation rates based on mechanical stability that may be easily estimated by steered molecular dynamics.

Effect of age on stroke prevention therapy in patients with atrial fibrillation: the atrial fibrillation investigators

DEFF Research Database (Denmark)

van Walraven, Carl; Hart, Robert G; Connolly, Stuart

2009-01-01

contains patient level-data from randomized trials of stroke prevention in atrial fibrillation. We used Cox regression models with age as a continuous variable that controlled for sex, year of randomization, and history of cerebrovascular disease, diabetes, hypertension, and congestive heart failure......BACKGROUND AND PURPOSE: Stroke risk increases with age in patients who have nonvalvular atrial fibrillation. It is uncertain whether the efficacy of stroke prevention therapies in atrial fibrillation changes as patients age. The objective of this study was to determine the effect of age...... on the relative efficacy of oral anticoagulants (OAC) and antiplatelet (AP) therapy (including acetylsalicylic acid and triflusal) on ischemic stroke, serious bleeding, and vascular events in patients with atrial fibrillation. METHODS: This is an analysis of the Atrial Fibrillation Investigators database, which...

Fixed cord

International Nuclear Information System (INIS)

Levy, L.M.; DiChiro, G.; DeSouza, B.; McCullough, D.C.; McVeigh, E.; Hefffez, D.

1989-01-01

Pulsatile longitudinal motion of the spinal cord was examined with MR phase imaging in healthy subjects and in cases involving cord tethering and compression. Asymptomatic patients with a low conus medullaris demonstrated normal cord motion. Clinical improvement was associated with improved cord motion after surgical untethering, provided permanent neurologic damage had not occurred. Decreased and unchanged cord motion was associated with unchanged neurologic deficits. In cases of normal cord motion and possible retethering versus syringomyelia, clinical improvement occurred after shunting only. MR imaging of pulsatile cord motion can be clinically useful in the evaluation of diseases restricting motion of the neuraxis

Alginate-Collagen Fibril Composite Hydrogel

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Mahmoud Baniasadi

2015-02-01

Full Text Available We report on the synthesis and the mechanical characterization of an alginate-collagen fibril composite hydrogel. Native type I collagen fibrils were used to synthesize the fibrous composite hydrogel. We characterized the mechanical properties of the fabricated fibrous hydrogel using tensile testing; rheometry and atomic force microscope (AFM-based nanoindentation experiments. The results show that addition of type I collagen fibrils improves the rheological and indentation properties of the hydrogel.

Chondroitin Sulfate Perlecan Enhances Collagen Fibril Formation

DEFF Research Database (Denmark)

Kvist, A. J.; Johnson, A. E.; Mörgelin, M.

2006-01-01

in collagen type II fibril assembly by perlecan-null chondrocytes. Cartilage perlecan is a heparin sulfate or a mixed heparan sulfate/chondroitin sulfate proteoglycan. The latter form binds collagen and accelerates fibril formation in vitro, with more defined fibril morphology and increased fibril diameters...... produced in the presence of perlecan. Interestingly, the enhancement of collagen fibril formation is independent on the core protein and is mimicked by chondroitin sulfate E but neither by chondroitin sulfate D nor dextran sulfate. Furthermore, perlecan chondroitin sulfate contains the 4,6-disulfated...... disaccharides typical for chondroitin sulfate E. Indeed, purified glycosaminoglycans from perlecan-enriched fractions of cartilage extracts contain elevated levels of 4,6-disulfated chondroitin sulfate disaccharides and enhance collagen fibril formation. The effect on collagen assembly is proportional...

Spinal cord stimulation suppresses bradycardias and atrial tachyarrhythmias induced by mediastinal nerve stimulation in dogs.

Science.gov (United States)

Cardinal, René; Pagé, Pierre; Vermeulen, Michel; Bouchard, Caroline; Ardell, Jeffrey L; Foreman, Robert D; Armour, J Andrew

2006-11-01

Spinal cord stimulation (SCS) applied to the dorsal aspect of the cranial thoracic cord imparts cardioprotection under conditions of neuronally dependent cardiac stress. This study investigated whether neuronally induced atrial arrhythmias can be modulated by SCS. In 16 anesthetized dogs with intact stellate ganglia and in five with bilateral stellectomy, trains of five electrical stimuli were delivered during the atrial refractory period to right- or left-sided mediastinal nerves for up to 20 s before and after SCS (20 min). Recordings were obtained from 191 biatrial epicardial sites. Before SCS (11 animals), mediastinal nerve stimulation initiated bradycardia alone (12 nerve sites), bradycardia followed by tachyarrhythmia/fibrillation (50 sites), as well as tachyarrhythmia/fibrillation without a preceding bradycardia (21 sites). After SCS, the number of responsive sites inducing bradycardia was reduced by 25% (62 to 47 sites), and the cycle length prolongation in residual bradycardias was reduced. The number of responsive sites inducing tachyarrhythmia was reduced by 60% (71 to 29 sites). Once elicited, residual tachyarrhythmias arose from similar epicardial foci, displaying similar dynamics (cycle length) as in control states. In the absence of SCS, bradycardias and tachyarrhythmias induced by repeat nerve stimulation were reproducible (five additional animals). After bilateral stellectomy, SCS no longer influenced neuronal induction of bradycardia and atrial tachyarrhythmias. These data indicate that SCS obtunds the induction of atrial arrhythmias resulting from excessive activation of intrinsic cardiac neurons and that such protective effects depend on the integrity of nerves coursing via the subclavian ansae and stellate ganglia.

Cord Blood

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Saeed Abroun

2014-05-01

Full Text Available   Stem cells are naïve or master cells. This means they can transform into special 200 cell types as needed by body, and each of these cells has just one function. Stem cells are found in many parts of the human body, although some sources have richer concentrations than others. Some excellent sources of stem cells, such as bone marrow, peripheral blood, cord blood, other tissue stem cells and human embryos, which last one are controversial and their use can be illegal in some countries. Cord blood is a sample of blood taken from a newborn baby's umbilical cord. It is a rich source of stem cells, umbilical cord blood and tissue are collected from material that normally has no use following a child’s birth. Umbilical cord blood and tissue cells are rich sources of stem cells, which have been used in the treatment of over 80 diseases including leukemia, lymphoma and anemia as bone marrow stem cell potency.  The most common disease category has been leukemia. The next largest group is inherited diseases. Patients with lymphoma, myelodysplasia and severe aplastic anemia have also been successfully transplanted with cord blood. Cord blood is obtained by syringing out the placenta through the umbilical cord at the time of childbirth, after the cord has been detached from the newborn. Collecting stem cells from umbilical blood and tissue is ethical, pain-free, safe and simple. When they are needed to treat your child later in life, there will be no rejection or incompatibility issues, as the procedure will be using their own cells. In contrast, stem cells from donors do have these potential problems. By consider about cord blood potency, cord blood banks (familial or public were established. In IRAN, four cord blood banks has activity, Shariati BMT center cord blood bank, Royan familial cord blood banks, Royan public cord blood banks and Iranian Blood Transfusion Organ cord blood banks. Despite 50,000 sample which storage in these banks, but the

Atrial fibrillation and survival in colorectal cancer

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Justin Timothy A

2004-11-01

Full Text Available Abstract Background Survival in colorectal cancer may correlate with the degree of systemic inflammatory response to the tumour. Atrial fibrillation may be regarded as an inflammatory complication. We aimed to determine if atrial fibrillation is a prognostic factor in colorectal cancer. Patients and methods A prospective colorectal cancer patient database was cross-referenced with the hospital clinical-coding database to identify patients who had underwent colorectal cancer surgery and were in atrial fibrillation pre- or postoperatively. Results A total of 175 patients underwent surgery for colorectal cancer over a two-year period. Of these, 13 patients had atrial fibrillation pre- or postoperatively. Atrial fibrillation correlated with worse two-year survival (p = 0.04; log-rank test. However, in a Cox regression analysis, atrial fibrillation was not significantly associated with survival. Conclusion The presence or development of atrial fibrillation in patients undergoing surgery for colorectal cancer is associated with worse overall survival, however it was not found to be an independent factor in multivariate analysis.

Interaction of magnetic nanoparticles with lysozyme amyloid fibrils

Energy Technology Data Exchange (ETDEWEB)

Gdovinová, Veronika [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Košice (Slovakia); Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Joliot-Curie 6, 141980 Dubna, Moscow Region (Russian Federation); Tomašovičová, Natália, E-mail: nhudak@saske.sk [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Košice (Slovakia); Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Joliot-Curie 6, 141980 Dubna, Moscow Region (Russian Federation); Batko, Ivan; Batková, Marianna; Balejčíková, Lucia [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Košice (Slovakia); Garamus, Vasyl M. [Helmholtz-Zentrum Geesthacht: Zentrum fr Material, und Kstenforschung GmbH, Max-Plank-Strae 1, Geesthacht 216502 (Germany); Petrenko, Viktor I. [Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Joliot-Curie 6, 141980 Dubna, Moscow Region (Russian Federation); Physics Department, Taras Shevchenko Kyiv National University, Volodymyrska Street 64, 01601 Kyiv (Ukraine); Avdeev, Mikhail V. [Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Joliot-Curie 6, 141980 Dubna, Moscow Region (Russian Federation); Kopčanský, Peter [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Košice (Slovakia)

2017-06-01

This work is devoted to the structural study of complex solutions of magnetic nanoparticles with lysozyme amyloid fibrils due to possible ordering of such system by applying the external magnetic field. The interaction of magnetic nanoparticles with amyloid fibrils has been followed by atomic force microscopy and small-angle X-ray scattering. It has been observed that magnetic nanoparticles (MNPs) adsorb to lysozyme amyloid fibrils. It was found that MNPs alter amyloids structures, namely the diameter of lysozyme amyloid fibrils is increased whereas the length of fibrils is decreased. In the same time MNPs do not change the helical pitch significantly. - Highlights: • Solution of MNPs with lysozyme amyloid fibrils was characterized by AFM and SAXS. • MNPs adsorb to lysozyme amyloid fibrils. • Diameter and size of lysozyme amyloid fibrils change due to doping with MNPs.

Intrinsic Resting-State Functional Connectivity in the Human Spinal Cord at 3.0 T.

Science.gov (United States)

San Emeterio Nateras, Oscar; Yu, Fang; Muir, Eric R; Bazan, Carlos; Franklin, Crystal G; Li, Wei; Li, Jinqi; Lancaster, Jack L; Duong, Timothy Q

2016-04-01

To apply resting-state functional magnetic resonance (MR) imaging to map functional connectivity of the human spinal cord. Studies were performed in nine self-declared healthy volunteers with informed consent and institutional review board approval. Resting-state functional MR imaging was performed to map functional connectivity of the human cervical spinal cord from C1 to C4 at 1 × 1 × 3-mm resolution with a 3.0-T clinical MR imaging unit. Independent component analysis (ICA) was performed to derive resting-state functional MR imaging z-score maps rendered on two-dimensional and three-dimensional images. Seed-based analysis was performed for cross validation with ICA networks by using Pearson correlation. Reproducibility analysis of resting-state functional MR imaging maps from four repeated trials in a single participant yielded a mean z score of 6 ± 1 (P 3, P 3.0-T clinical MR imaging unit and standard MR imaging protocols and hardware reveals prominent functional connectivity patterns within the spinal cord gray matter, consistent with known functional and anatomic layouts of the spinal cord.

Risk of atrial fibrillation in diabetes mellitus

DEFF Research Database (Denmark)

Pallisgaard, Jannik L; Schjerning, Anne-Marie; Lindhardt, Tommi B

2016-01-01

AIM: Diabetes has been associated with atrial fibrillation but the current evidence is conflicting. In particular knowledge regarding young diabetes patients and the risk of developing atrial fibrillation is sparse. The aim of our study was to investigate the risk of atrial fibrillation in patients...... with diabetes compared to the background population in Denmark. METHODS AND RESULTS: Through Danish nationwide registries we included persons above 18 years of age and without prior atrial fibrillation and/or diabetes from 1996 to 2012. The study cohort was divided into a background population without diabetes...... and a diabetes group. The absolute risk of developing atrial fibrillation was calculated and Poisson regression models adjusted for sex, age and comorbidities were used to calculate incidence rate ratios of atrial fibrillation. The total study cohort included 5,081,087 persons, 4,827,713 (95%) in the background...

Relevance of Electrical Remodeling in Human Atrial Fibrillation Results of the Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial Mechanisms of Atrial Fibrillation Study

NARCIS (Netherlands)

Healey, Jeff S.; Israel, Carsten W.; Connolly, Stuart J.; Hohnloser, Stefan H.; Nair, Girish M.; Divakaramenon, Syamkumar; Capucci, Alessandro; Van Gelder, Isabelle C.; Lau, Chu-Pak; Gold, Michael R.; Carlson, Mark; Themeles, Ellison; Morillo, Carlos A.

Background-In animal models of atrial fibrillation (AF), changes in atrial electrophysiological properties are associated with the development of AF. Their relevance to human AF is unclear. Methods and Results-The Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the

Pharmacological Treatment for Atrial Fibrillation

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Kaoru Sugi, MD PhD

2005-01-01

Full Text Available Pharmacological treatment for atrial fibrillation has a variety of purposes, such as pharmacological defibrillation, maintenance of sinus rhythm, heart rate control to prevent congestive heart failure and prevention of both cerebral infarction and atrial remodeling. Sodium channel blockers are superior to potassium channel blockers for atrial defibrillation, while both sodium and potassium channel blockers are effective in the maintenance of sinus rhythm. In general, digitalis or Ca antagonists are used to control heart rate during atrial fibrillation to prevent congestive heart failure, while amiodarone or bepridil also reduce heart rates during atrial fibrillation. Anticoagulant therapy with warfarin is recommended to prevent cerebral infarction and angiotensin converting enzyme antagonists or angiotensin II receptor blockers are also used to prevent atrial remodeling. One should select appropriate drugs for treatment of atrial fibrillation according to the patient's condition.

Fracture mechanics of collagen fibrils

DEFF Research Database (Denmark)

Svensson, Rene B; Mulder, Hindrik; Kovanen, Vuokko

2013-01-01

Tendons are important load-bearing structures, which are frequently injured in both sports and work. Type I collagen fibrils are the primary components of tendons and carry most of the mechanical loads experienced by the tissue, however, knowledge of how load is transmitted between and within...... fibrils is limited. The presence of covalent enzymatic cross-links between collagen molecules is an important factor that has been shown to influence mechanical behavior of the tendons. To improve our understanding of how molecular bonds translate into tendon mechanics, we used an atomic force microscopy...... technique to measure the mechanical behavior of individual collagen fibrils loaded to failure. Fibrils from human patellar tendons, rat-tail tendons (RTTs), NaBH₄ reduced RTTs, and tail tendons of Zucker diabetic fat rats were tested. We found a characteristic three-phase stress-strain behavior in the human...

Atrial fibrillation in the elderly

Science.gov (United States)

Franken, Roberto A.; Rosa, Ronaldo F.; Santos, Silvio CM

2012-01-01

This review discusses atrial fibrillation according to the guidelines of Brazilian Society of Cardiac Arrhythmias and the Brazilian Cardiogeriatrics Guidelines. We stress the thromboembolic burden of atrial fibrillation and discuss how to prevent it as well as the best way to conduct cases of atrial fibrillatios in the elderly, reverting the arrhythmia to sinus rhythm, or the option of heart rate control. The new methods to treat atrial fibrillation, such as radiofrequency ablation, new oral direct thrombin inhibitors and Xa factor inhibitors, as well as new antiarrhythmic drugs, are depicted. PMID:22916053

Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers

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Rasool Suhail

2007-09-01

Full Text Available Abstract Background Amyloid-related degenerative diseases are associated with the accumulation of misfolded proteins as amyloid fibrils in tissue. In Alzheimer disease (AD, amyloid accumulates in several distinct types of insoluble plaque deposits, intracellular Aβ and as soluble oligomers and the relationships between these deposits and their pathological significance remains unclear. Conformation dependent antibodies have been reported that specifically recognize distinct assembly states of amyloids, including prefibrillar oligomers and fibrils. Results We immunized rabbits with a morphologically homogeneous population of Aβ42 fibrils. The resulting immune serum (OC specifically recognizes fibrils, but not random coil monomer or prefibrillar oligomers, indicating fibrils display a distinct conformation dependent epitope that is absent in prefibrillar oligomers. The fibril epitope is also displayed by fibrils of other types of amyloids, indicating that the epitope is a generic feature of the polypeptide backbone. The fibril specific antibody also recognizes 100,000 × G soluble fibrillar oligomers ranging in size from dimer to greater than 250 kDa on western blots. The fibrillar oligomers recognized by OC are immunologically distinct from prefibrillar oligomers recognized by A11, even though their sizes overlap broadly, indicating that size is not a reliable indicator of oligomer conformation. The immune response to prefibrillar oligomers and fibrils is not sequence specific and antisera of the same specificity are produced in response to immunization with islet amyloid polypeptide prefibrillar oligomer mimics and fibrils. The fibril specific antibodies stain all types of amyloid deposits in human AD brain. Diffuse amyloid deposits stain intensely with anti-fibril antibody although they are thioflavin S negative, suggesting that they are indeed fibrillar in conformation. OC also stains islet amyloid deposits in transgenic mouse models of type

On the role of fibril mechanics in the work of separation of fibrillating interfaces

NARCIS (Netherlands)

Vossen, B.G.; Sluis, van der O.; Schreurs, P.J.G.; Geers, M.G.D.; Neggers, J.; Hoefnagels, J.P.M.

2015-01-01

High values for the work of separation have been reported in peel tests on fibrillating interfacial systems. The exact origin of these high values is not properly understood, since it remains unclear which dissipative mechanisms related to fibrillation cause a significant increase in the work of

Heterologous amyloid seeding: revisiting the role of acetylcholinesterase in Alzheimer's disease.

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Létitia Jean

2007-07-01

Full Text Available Neurodegenerative diseases associated with abnormal protein folding and ordered aggregation require an initial trigger which may be infectious, inherited, post-inflammatory or idiopathic. Proteolytic cleavage to generate vulnerable precursors, such as amyloid-beta peptide (Abeta production via beta and gamma secretases in Alzheimer's Disease (AD, is one such trigger, but the proteolytic removal of these fragments is also aetiologically important. The levels of Abeta in the central nervous system are regulated by several catabolic proteases, including insulysin (IDE and neprilysin (NEP. The known association of human acetylcholinesterase (hAChE with pathological aggregates in AD together with its ability to increase Abeta fibrilization prompted us to search for proteolytic triggers that could enhance this process. The hAChE C-terminal domain (T40, AChE(575-614 is an exposed amphiphilic alpha-helix involved in enzyme oligomerisation, but it also contains a conformational switch region (CSR with high propensity for conversion to non-native (hidden beta-strand, a property associated with amyloidogenicity. A synthetic peptide (AChE(586-599 encompassing the CSR region shares homology with Abeta and forms beta-sheet amyloid fibrils. We investigated the influence of IDE and NEP proteolysis on the formation and degradation of relevant hAChE beta-sheet species. By combining reverse-phase HPLC and mass spectrometry, we established that the enzyme digestion profiles on T40 versus AChE(586-599, or versus Abeta, differed. Moreover, IDE digestion of T40 triggered the conformational switch from alpha- to beta-structures, resulting in surfactant CSR species that self-assembled into amyloid fibril precursors (oligomers. Crucially, these CSR species significantly increased Abeta fibril formation both by seeding the energetically unfavorable formation of amyloid nuclei and by enhancing the rate of amyloid elongation. Hence, these results may offer an explanation

Spectral of electrocardiographic RR intervals to indicate atrial fibrillation

Science.gov (United States)

Nuryani, Nuryani; Satrio Nugroho, Anto

2017-11-01

Atrial fibrillation is a serious heart diseases, which is associated on the risk of death, and thus an early detection of atrial fibrillation is necessary. We have investigated spectral pattern of electrocardiogram in relation to atrial fibrillation. The utilized feature of electrocardiogram is RR interval. RR interval is the time interval between a two-consecutive R peaks. A series of RR intervals in a time segment is converted to a signal with a frequency domain. The frequency components are investigated to find the components which significantly associate to atrial fibrillation. A segment is defined as atrial fibrillation or normal segments by considering a defined number of atrial fibrillation RR in the segment. Using clinical data of 23 patients with atrial fibrillation, we find that the frequency components could be used to indicate atrial fibrillation.

Atrial natriuretic peptide in patients with heart failure and chronic atrial fibrillation : Role of duration of at atrial fibrillation

NARCIS (Netherlands)

Van Den Berg, MP; Crijns, HJGM; Van Veldhuisen, DJ; Van Gelder, IC; De Kam, PJ; Lie, KI

The purpose of this study was to analyze the determinants of atrial natriuretic peptide level in patients with congestive heart failure and atrial fibrillation. In particular, the duration of atrial fibrillation was analyzed because atrial fibrillation per se might have a specific effect on atrial

Atrial fibrillation and vascular disease-a bad combination

DEFF Research Database (Denmark)

Bjerring Olesen, Jonas; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian

2012-01-01

This article provides an overview of (i) the risk of stroke associated with vascular disease (acute coronary syndromes and peripheral artery disease) in patients with atrial fibrillation, (ii) the frequent coexistence of vascular disease in patients with atrial fibrillation and, (iii...... fibrillation. Indeed, patients with atrial fibrillation often had coexisting vascular disease (around 18%), and the combination of the two diseases substantially increases the risk of future cardiovascular events. The increased risk associated with peripheral artery disease in atrial fibrillation is even more...... pronounced. Patients with atrial fibrillation and stable vascular disease should be treated with oral anticoagulation only, although when these patients present with acute coronary syndrome and/or undergo coronary stenting, concomitant treatment with antiplatelet drugs is indicated. To guide antithrombotic...

Evaluation of the expansion of umbilical cord blood derived from CD133+ cells on biocompatible microwells

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Mina Soufizomorrod

2016-05-01

Full Text Available Background: Hematopoietic stem cell transplantation (HSCT is a therapeutic approach for treatment of hematological malignancies and incompatibility of Bone marrow. Umbilical cord blood (UCB has known as an alternative for hematopoietic stem/progenitor cells (HPSC in allogeneic transplantation. The low volume of collected samples is the main hindrance in application of HPSC derived from umbilical cord blood. So, ex vivo expansion of HPSCs is the useful approach to overcome this restriction. The goal of using this system is to produce appropriate amount of hematopoietic stem cells, which have the ability of transplantation and long term haematopoiesis. Material & Methods: In current study CD133+ cells were isolated from cord blood (CB. Isolated cells were seeded on microwells. Then expanded cells proliferation rate and ability in colony formation were assessed and finally were compared with 2 Dimensional (2D culture systems. Results: Our findings demonstrated that CD133+ cells derived from UCB which were cultivated on microwells had significantly higher rate of proliferation in compared with routine cell culture systems. Conclusion: In Current study, it was shown that CD133+ cells’ proliferations which were seeded on PDMS microwells coated with collagen significantly increased. We hope that 3 dimensional (3D microenvironment which mimics the 3D structure of bone marrow can solve the problem of using UCB as an alternative source of bone marrow.

Spinal cord contusion.

Science.gov (United States)

Ju, Gong; Wang, Jian; Wang, Yazhou; Zhao, Xianghui

2014-04-15

Spinal cord injury is a major cause of disability with devastating neurological outcomes and limited therapeutic opportunities, even though there are thousands of publications on spinal cord injury annually. There are two major types of spinal cord injury, transaction of the spinal cord and spinal cord contusion. Both can theoretically be treated, but there is no well documented treatment in human being. As for spinal cord contusion, we have developed an operation with fabulous result.

Modulation of α-synuclein fibrillization by ring-fused 2-pyridones: templation and inhibition involve oligomers with different structure.

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Horvath, Istvan; Sellstedt, Magnus; Weise, Christoph; Nordvall, Lina-Maria; Krishna Prasad, G; Olofsson, Anders; Larsson, Göran; Almqvist, Fredrik; Wittung-Stafshede, Pernilla

2013-04-15

In a recent study we discovered that a ring-fused 2-pyridone compound triggered fibrillization of a key protein in Parkinson's disease, α-synuclein. To reveal how variations in compound structure affect protein aggregation, we now prepared a number of strategic analogs and tested their effects on α-synuclein amyloid fiber formation in vitro. We find that, in contrast to the earlier templating effect, some analogs inhibit α-synuclein fibrillization. For both templating and inhibiting compounds, the key species formed in the reactions are α-synuclein oligomers that contain compound. Despite similar macroscopic appearance, the templating and inhibiting oligomers are distinctly different in secondary structure content. When the inhibitory oligomers are added in seed amounts, they inhibit fresh α-synuclein aggregation reactions. Our study demonstrates that small chemical changes to the same central fragment can result in opposite effects on protein aggregation. Copyright © 2013 Elsevier Inc. All rights reserved.

Simultaneous isolation of vascular endothelial cells and mesenchymal stem cells from the human umbilical cord.

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Kadam, Sachin S; Tiwari, Shubha; Bhonde, Ramesh R

2009-01-01

The umbilical cord represents the link between mother and fetus during pregnancy. This cord is usually discarded as a biological waste after the child's birth; however, its importance as a "store house" of stem cells has been explored recently. We developed a method of simultaneous isolation of endothelial cells (ECs) from the vein and mesenchymal stem cells from umbilical cord Wharton's jelly of the same cord. The isolation protocol has been simplified, modified, and improvised with respect to choice of enzyme and enzyme mixture, digestion time, cell yield, cell growth, and culture medium. Isolated human umbilical vascular ECs (hUVECs) were positive for von-Willibrand factor, a classical endothelial marker, and could form capillary-like structures when seeded on Matrigel, thus proving their functionality. The isolated human umbilical cord mesenchymal stem cells (hUCMSCs) were found positive for CD44, CD90, CD 73, and CD117 and were found negative for CD33, CD34, CD45, and CD105 surface markers; they were also positive for cytoskeleton markers of smooth muscle actin and vimentin. The hUCMSCs showed multilineage differentiation potential and differentiated into adipogenic, chondrogenic, osteogenic, and neuronal lineages under influence of lineage specific differentiation medium. Thus, isolating endothelial cells as well as mesenchymal cells from the same umbilical cord could lead to complete utilization of the available tissue for the tissue engineering and cell therapy.

Genetic basis of atrial fibrillation

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Oscar Campuzano

2016-12-01

Full Text Available Atrial fibrillation is the most common sustained arrhythmia and remains as one of main challenges in current clinical practice. The disease may be induced secondary to other diseases such as hypertension, valvular heart disease, and heart failure, conferring an increased risk of stroke and sudden death. Epidemiological studies have provided evidence that genetic factors play an important role and up to 30% of clinically diagnosed patients may have a family history of atrial fibrillation. To date, several rare variants have been identified in a wide range of genes associated with ionic channels, calcium handling protein, fibrosis, conduction and inflammation. Important advances in clinical, genetic and molecular basis have been performed over the last decade, improving diagnosis and treatment. However, the genetics of atrial fibrillation is complex and pathophysiological data remains still unraveling. A better understanding of the genetic basis will induce accurate risk stratification and personalized clinical treatment. In this review, we have focused on current genetics basis of atrial fibrillation.

Thyrotoxic atrial fibrillation.

Science.gov (United States)

Parmar, Malvinder S

2005-01-04

Atrial fibrillation is the most common cardiac complication of hyperthyroidism and occurs in 15% of patients with hyperthyroidism. It is associated with a higher risk of thromboembolism that often involves the central nervous system. Oral anticoagulation is important in the majority of these patients to prevent thromboembolic complications. These patients require adjustment in the dose of various rate-controlling agents because of increased clearance associated with hyperthyroidism and a decrease in warfarin dosage because of increased clearance of vitamin K-dependent clotting factors. The management of thyrotoxic atrial fibrillation is summarized in this clinical review.

Viologen-Phosphorus Dendrimers Inhibit α-Synuclein Fibrillation.

Science.gov (United States)

Milowska, Katarzyna; Grochowina, Justyna; Katir, Nadia; El Kadib, Abdelkrim; Majoral, Jean-Pierre; Bryszewska, Maria; Gabryelak, Teresa

2013-03-04

Inhibition of α-synuclein (ASN) fibril formation is a potential therapeutic strategy in Parkinson's disease and other synucleinopathies. The aim of this study was to examine the role of viologen-phosphorus dendrimers in the α-synuclein fibrillation process and to assess the structural changes in α-synuclein under the influence of dendrimers. ASN interactions with phosphonate and pegylated surface-reactive viologen-phosphorus dendrimers were examined by measuring the zeta potential, which allowed determining the number of dendrimer molecules that bind to the ASN molecule. The fibrillation kinetics and the structural changes were examined using ThT fluorescence and CD spectroscopy. Depending on the concentration of the used dendrimer and the nature of the reactive groups located on the surface, ASN fibrillation kinetics can be significantly reduced, and even, in the specific case of phosphonate dendrimers, the fibrillation can be totally inhibited at low concentrations. The presented results indicate that viologen-phosphorus dendrimers are able to inhibit ASN fibril formation and may be used as fibrillar regulating agents in neurodegenerative disorders.

The role of protonation in protein fibrillation

DEFF Research Database (Denmark)

Jeppesen, Martin D; Westh, Peter; Otzen, Daniel E

2010-01-01

Many proteins fibrillate at low pH despite a high population of charged side chains. Therefore exchange of protons between the fibrillating peptide and its surroundings may play an important role in fibrillation. Here, we use isothermal titration calorimetry to measure exchange of protons between...... buffer and the peptide hormone glucagon during fibrillation. Glucagon absorbs or releases protons to an extent which allows it to attain a net charge of zero in the fibrillar state, both at acidic and basic pH. Similar results are obtained for lysozyme. This suggests that side chain pKa values change...

RR-Interval variance of electrocardiogram for atrial fibrillation detection

Science.gov (United States)

Nuryani, N.; Solikhah, M.; Nugoho, A. S.; Afdala, A.; Anzihory, E.

2016-11-01

Atrial fibrillation is a serious heart problem originated from the upper chamber of the heart. The common indication of atrial fibrillation is irregularity of R peak-to-R-peak time interval, which is shortly called RR interval. The irregularity could be represented using variance or spread of RR interval. This article presents a system to detect atrial fibrillation using variances. Using clinical data of patients with atrial fibrillation attack, it is shown that the variance of electrocardiographic RR interval are higher during atrial fibrillation, compared to the normal one. Utilizing a simple detection technique and variances of RR intervals, we find a good performance of atrial fibrillation detection.

Synaptic Plasticity in Cardiac Innervation and Its Potential Role in Atrial Fibrillation

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Jesse L. Ashton

2018-03-01

Full Text Available Synaptic plasticity is defined as the ability of synapses to change their strength of transmission. Plasticity of synaptic connections in the brain is a major focus of neuroscience research, as it is the primary mechanism underpinning learning and memory. Beyond the brain however, plasticity in peripheral neurons is less well understood, particularly in the neurons innervating the heart. The atria receive rich innervation from the autonomic branch of the peripheral nervous system. Sympathetic neurons are clustered in stellate and cervical ganglia alongside the spinal cord and extend fibers to the heart directly innervating the myocardium. These neurons are major drivers of hyperactive sympathetic activity observed in heart disease, ventricular arrhythmias, and sudden cardiac death. Both pre- and postsynaptic changes have been observed to occur at synapses formed by sympathetic ganglion neurons, suggesting that plasticity at sympathetic neuro-cardiac synapses is a major contributor to arrhythmias. Less is known about the plasticity in parasympathetic neurons located in clusters on the heart surface. These neuronal clusters, termed ganglionated plexi, or “little brains,” can independently modulate neural control of the heart and stimulation that enhances their excitability can induce arrhythmia such as atrial fibrillation. The ability of these neurons to alter parasympathetic activity suggests that plasticity may indeed occur at the synapses formed on and by ganglionated plexi neurons. Such changes may not only fine-tune autonomic innervation of the heart, but could also be a source of maladaptive plasticity during atrial fibrillation.

Acute Thoracolumbar Spinal Cord Injury: Relationship of Cord Compression to Neurological Outcome.

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Skeers, Peta; Battistuzzo, Camila R; Clark, Jillian M; Bernard, Stephen; Freeman, Brian J C; Batchelor, Peter E

2018-02-21

Spinal cord injury in the cervical spine is commonly accompanied by cord compression and urgent surgical decompression may improve neurological recovery. However, the extent of spinal cord compression and its relationship to neurological recovery following traumatic thoracolumbar spinal cord injury is unclear. The purpose of this study was to quantify maximum cord compression following thoracolumbar spinal cord injury and to assess the relationship among cord compression, cord swelling, and eventual clinical outcome. The medical records of patients who were 15 to 70 years of age, were admitted with a traumatic thoracolumbar spinal cord injury (T1 to L1), and underwent a spinal surgical procedure were examined. Patients with penetrating injuries and multitrauma were excluded. Maximal osseous canal compromise and maximal spinal cord compression were measured on preoperative mid-sagittal computed tomography (CT) scans and T2-weighted magnetic resonance imaging (MRI) by observers blinded to patient outcome. The American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades from acute hospital admission (≤24 hours of injury) and rehabilitation discharge were used to measure clinical outcome. Relationships among spinal cord compression, canal compromise, and initial and final AIS grades were assessed via univariate and multivariate analyses. Fifty-three patients with thoracolumbar spinal cord injury were included in this study. The overall mean maximal spinal cord compression (and standard deviation) was 40% ± 21%. There was a significant relationship between median spinal cord compression and final AIS grade, with grade-A patients (complete injury) exhibiting greater compression than grade-C and D patients (incomplete injury) (p compression as independently influencing the likelihood of complete spinal cord injury (p compression. Greater cord compression is associated with an increased likelihood of severe neurological deficits (complete injury) following

Evidence of structurally continuous collagen fibrils in tendon

DEFF Research Database (Denmark)

Svensson, Rene B; Herchenhan, Andreas; Starborg, Tobias

2017-01-01

favor continuity. This study initially set out to trace the full length of individual fibrils in adult human tendons, using serial block face-scanning electron microscopy. But even with this advanced technique the required length could not be covered. Instead a statistical approach was used on a large...... volume of fibrils in shorter image stacks. Only a single end was observed after tracking 67.5 mm of combined fibril lengths, in support of fibril continuity. To shed more light on this observation, the full length of a short tendon (mouse stapedius, 125 μm) was investigated and continuity of individual...... fibrils was confirmed. In light of these results, possible mechanisms that could reconcile the opposing findings on fibril continuity are discussed. STATEMENT OF SIGNIFICANCE: Connective tissues hold all parts of the body together and are mostly constructed from thin threads of the protein collagen...

Chirality and chiroptical properties of amyloid fibrils.

Science.gov (United States)

Dzwolak, Wojciech

2014-09-01

Chirality of amyloid fibrils-linear beta-sheet-rich aggregates of misfolded protein chains-often manifests in morphological traits such as helical twist visible in atomic force microscopy and in chiroptical properties accessible to vibrational circular dichroism (VCD). According to recent studies the relationship between molecular chirality of polypeptide building blocks and superstructural chirality of amyloid fibrils may be more intricate and less deterministic than previously assumed. Several puzzling experimental findings have put into question earlier intuitive ideas on: 1) the bottom-up chirality transfer upon amyloidogenic self-assembly, and 2) the structural origins of chiroptical properties of protein aggregates. For example, removal of a single amino acid residue from an amyloidogenic all-L peptide was shown to reverse handedness of fibrils. On the other hand, certain types of amyloid aggregates revealed surprisingly strong VCD spectra with the sign and shape dependent on the conditions of fibrillation. Hence, microscopic and chiroptical studies have highlighted chirality as one more aspect of polymorphism of amyloid fibrils. This brief review is intended to outline the current state of research on amyloid-like fibrils from the perspective of their structural and superstructural chirality and chiroptical properties. © 2014 Wiley Periodicals, Inc.

Modeling generic aspects of ideal fibril formation

Energy Technology Data Exchange (ETDEWEB)

Michel, D., E-mail: denis.michel@live.fr [Universite de Rennes1-IRSET, Campus de Beaulieu Bat. 13, 35042 Rennes (France)

2016-01-21

Many different proteins self-aggregate into insoluble fibrils growing apically by reversible addition of elementary building blocks. But beyond this common principle, the modalities of fibril formation are very disparate, with various intermediate forms which can be reshuffled by minor modifications of physico-chemical conditions or amino-acid sequences. To bypass this complexity, the multifaceted phenomenon of fibril formation is reduced here to its most elementary principles defined for a linear prototype of fibril. Selected generic features, including nucleation, elongation, and conformational recruitment, are modeled using minimalist hypotheses and tools, by separating equilibrium from kinetic aspects and in vitro from in vivo conditions. These reductionist approaches allow to bring out known and new rudiments, including the kinetic and equilibrium effects of nucleation, the dual influence of elongation on nucleation, the kinetic limitations on nucleation and fibril numbers, and the accumulation of complexes in vivo by rescue from degradation. Overlooked aspects of these processes are also pointed: the exponential distribution of fibril lengths can be recovered using various models because it is attributable to randomness only. It is also suggested that the same term “critical concentration” is used for different things, involved in either nucleation or elongation.

Proinsulin C-peptide interferes with insulin fibril formation

International Nuclear Information System (INIS)

Landreh, Michael; Stukenborg, Jan-Bernd; Willander, Hanna; Söder, Olle; Johansson, Jan; Jörnvall, Hans

2012-01-01

Highlights: ► Insulin and C-peptide can interact under insulin fibril forming conditions. ► C-peptide is incorporated into insulin aggregates and alters aggregation lag time. ► C-peptide changes insulin fibril morphology and affects backbone accessibility. ► C-peptide may be a regulator of fibril formation by β-cell granule proteins. -- Abstract: Insulin aggregation can prevent rapid insulin uptake and cause localized amyloidosis in the treatment of type-1 diabetes. In this study, we investigated the effect of C-peptide, the 31-residue peptide cleaved from proinsulin, on insulin fibrillation at optimal conditions for fibrillation. This is at low pH and high concentration, when the fibrils formed are regular and extended. We report that C-peptide then modulates the insulin aggregation lag time and profoundly changes the fibril appearance, to rounded clumps of short fibrils, which, however, still are Thioflavine T-positive. Electrospray ionization mass spectrometry also indicates that C-peptide interacts with aggregating insulin and is incorporated into the aggregates. Hydrogen/deuterium exchange mass spectrometry further reveals reduced backbone accessibility in insulin aggregates formed in the presence of C-peptide. Combined, these effects are similar to those of C-peptide on islet amyloid polypeptide fibrillation and suggest that C-peptide has a general ability to interact with amyloidogenic proteins from pancreatic β-cell granules. Considering the concentrations, these peptide interactions should be relevant also during physiological secretion, and even so at special sites post-secretory or under insulin treatment conditions in vivo.

Proinsulin C-peptide interferes with insulin fibril formation

Energy Technology Data Exchange (ETDEWEB)

Landreh, Michael [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm (Sweden); Stukenborg, Jan-Bernd [Department of Women' s and Children' s Health, Astrid Lindgren Children' s Hospital, Pediatric Endocrinology Unit, Karolinska Institutet and University Hospital, S-17176 Stockholm (Sweden); Willander, Hanna [KI-Alzheimer' s Disease Research Center, NVS Department, Karolinska Institutet, S-141 86 Stockholm (Sweden); Soeder, Olle [Department of Women' s and Children' s Health, Astrid Lindgren Children' s Hospital, Pediatric Endocrinology Unit, Karolinska Institutet and University Hospital, S-17176 Stockholm (Sweden); Johansson, Jan [KI-Alzheimer' s Disease Research Center, NVS Department, Karolinska Institutet, S-141 86 Stockholm (Sweden); Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, S-751 23 Uppsala (Sweden); Joernvall, Hans, E-mail: Hans.Jornvall@ki.se [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm (Sweden)

2012-02-17

Highlights: Black-Right-Pointing-Pointer Insulin and C-peptide can interact under insulin fibril forming conditions. Black-Right-Pointing-Pointer C-peptide is incorporated into insulin aggregates and alters aggregation lag time. Black-Right-Pointing-Pointer C-peptide changes insulin fibril morphology and affects backbone accessibility. Black-Right-Pointing-Pointer C-peptide may be a regulator of fibril formation by {beta}-cell granule proteins. -- Abstract: Insulin aggregation can prevent rapid insulin uptake and cause localized amyloidosis in the treatment of type-1 diabetes. In this study, we investigated the effect of C-peptide, the 31-residue peptide cleaved from proinsulin, on insulin fibrillation at optimal conditions for fibrillation. This is at low pH and high concentration, when the fibrils formed are regular and extended. We report that C-peptide then modulates the insulin aggregation lag time and profoundly changes the fibril appearance, to rounded clumps of short fibrils, which, however, still are Thioflavine T-positive. Electrospray ionization mass spectrometry also indicates that C-peptide interacts with aggregating insulin and is incorporated into the aggregates. Hydrogen/deuterium exchange mass spectrometry further reveals reduced backbone accessibility in insulin aggregates formed in the presence of C-peptide. Combined, these effects are similar to those of C-peptide on islet amyloid polypeptide fibrillation and suggest that C-peptide has a general ability to interact with amyloidogenic proteins from pancreatic {beta}-cell granules. Considering the concentrations, these peptide interactions should be relevant also during physiological secretion, and even so at special sites post-secretory or under insulin treatment conditions in vivo.

Protein Polymerization into Fibrils from the Viewpoint of Nucleation Theory.

Science.gov (United States)

Kashchiev, Dimo

2015-11-17

The assembly of various proteins into fibrillar aggregates is an important phenomenon with wide implications ranging from human disease to nanoscience. Using general kinetic results of nucleation theory, we analyze the polymerization of protein into linear or helical fibrils in the framework of the Oosawa-Kasai (OK) model. We show that while within the original OK model of linear polymerization the process does not involve nucleation, within a modified OK model it is nucleation-mediated. Expressions are derived for the size of the fibril nucleus, the work for fibril formation, the nucleation barrier, the equilibrium and stationary fibril size distributions, and the stationary fibril nucleation rate. Under otherwise equal conditions, this rate decreases considerably when the short (subnucleus) fibrils lose monomers much more frequently than the long (supernucleus) fibrils, a feature that should be born in mind when designing a strategy for stymying or stimulating fibril nucleation. The obtained dependence of the nucleation rate on the concentration of monomeric protein is convenient for experimental verification and for use in rate equations accounting for nucleation-mediated fibril formation. The analysis and the results obtained for linear fibrils are fully applicable to helical fibrils whose formation is describable by a simplified OK model. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Artificial atrial fibrillation in the dog. An artifact?

NARCIS (Netherlands)

Strackee, J.; Hoelen, A.J.; Zimmerman, A.N.E.; Meijler, F.L.

R-R interval sequences during artificial atrial fibrillation in dogs were studied in the same way as in patients in a previous study and compared with results obtained in dogs with spontaneous atrial fibrillation. Artificial atrial fibrillation was effected by right atrial stimulation in three

Metastable Amyloid Phases and their Conversion to Mature Fibrils

Science.gov (United States)

Muschol, Martin; Miti, Tatiana; Mulaj, Mentor; Schmit, Jeremy

Self-assembly of proteins into amyloid fibrils plays a key role in both functional biological responses and pathogenic disorders which include Alzheimer's disease and type II diabetes. Amyloid fibril assembly frequently generates compact oligomeric and curvilinear polymeric intermediates which are implicated to be toxic to cells. Yet, the relation between these early-stage oligomeric aggregates and late-stage rigid fibrils, which are the hallmark structure of amyloid plaques, has remained unclear. Our measurements indicate that lysozyme amyloid oligomers and their curvilinear fibrils only form after crossing a salt and protein concentration dependent threshold. These oligomeric aggregates are structurally distinct from rigid fibrils and are metastable against nucleation and growth of rigid fibrils. Our experimental transition boundaries match well with colloidal model predictions accounting for salt-modulated charge repulsion. We also report our preliminary findings on the mechanism by which these metastable oligomeric phases are converted into stable amyloid fibrils.

Rising rates of hospital admissions for atrial fibrillation

DEFF Research Database (Denmark)

Friberg, Jens; Buch, Nina Pernille Gardshodn; Scharling, Henrik

2003-01-01

Atrial fibrillation is a common arrhythmia associated with excess morbidity and mortality. We studied temporal changes in hospital admission rates for atrial fibrillation using data from a prospective population-based cohort study spanning 2 decades (the Copenhagen City Heart Study).......Atrial fibrillation is a common arrhythmia associated with excess morbidity and mortality. We studied temporal changes in hospital admission rates for atrial fibrillation using data from a prospective population-based cohort study spanning 2 decades (the Copenhagen City Heart Study)....

HYPERTHYROIDISM AND ATRIAL FIBRILLATION

Directory of Open Access Journals (Sweden)

I. M. Marusenko

2017-01-01

Full Text Available Review on a problem of the development of atrial fibrillation in patients with thyrotoxicosis is presented. Thyrotoxicosis is one of the most frequent endocrine diseases, conceding only to a diabetes mellitus. The most frequent reasons of hyperthyroidism are Graves’ disease and functional thyroid autonomy. The authors give an analysis of data on the cardiac effects of thyrotoxicosis, features of heart remodeling under the influence of thyroid hyperfunction, prevalence of atrial fibrillation in thyrotoxicosis, depending on age, as well as the possibility of restoring sinus rhythm in the combination of these diseases. Particular attention is paid to the effect on the heart of subclinical thyrotoxicosis, which is defined as a dysfunction of the thyroid gland, characterized by low serum concentration of thyrotropin, normal values of free thyroxine and free triiodothyronine. Subclinical hyperthyroidism is also capable of causing heart remodeling and diastolic dysfunction.Prevalence of thyrotoxicosis in elderly people is higher in areas of iodine deficiency; it is relevant for our country due to the large territory of iodine deficiency. In elderly patients, the cardiac effects of thyrotoxicosis prevail in the clinical picture, that makes it difficult to diagnose endocrine disorders, and correction of thyrotoxicosis is critically important for the successful control of the heart rhythm. The article also discusses the problem of thyrotoxic cardiomyopathy, caused by the toxic effect of excess thyroid hormones: features of this heart disorder, factors affecting its formation, clinical significance and contribution to the development of rhythm disturbances. The greatest significance is the development of atrial fibrillation as a result of thyrotox-icosis in older patients who already have various cardiovascular diseases.Atrial fibrillation is the most frequent heart rhythm disorder in thyrotoxicosis. The main cause of arrhythmia in hyperthyroidism is the

Atrial Fibrillation and Hyperthyroidism

Directory of Open Access Journals (Sweden)

Jayaprasad N

2005-10-01

Full Text Available Atrial fibrillation occurs in 10 – 15% of patients with hyperthyroidism. Low serum thyrotropin concentration is an independent risk factor for atrial fibrillation. Thyroid hormone contributes to arrythmogenic activity by altering the electrophysiological characteristics of atrial myocytes by shortening the action potential duration, enhancing automaticity and triggered activity in the pulmonary vein cardio myocytes. Hyperthyroidism results in excess mortality from increased incidence of circulatory diseases and dysrhythmias. Incidence of cerebral embolism is more in hyperthyroid patients with atrial fibrillation, especially in the elderly and anti-coagulation is indicated in them. Treatment of hyperthyroidism results in conversion to sinus rhythm in up to two-third of patients. Beta-blockers reduce left ventricular hypertrophy and atrial and ventricular arrhythmias in patients with hyperthyroidism. Treatment of sub clinical hyperthyroidism is controversial. Optimizing dose of thyroxine treatment in those with replacement therapy and beta-blockers is useful in exogenous subclinical hyperthyroidism.

Ultrafast Hydrogen-Bonding Dynamics in Amyloid Fibrils.

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Pazos, Ileana M; Ma, Jianqiang; Mukherjee, Debopreeti; Gai, Feng

2018-06-08

While there are many studies on the subject of hydrogen bonding dynamics in biological systems, few, if any, have investigated this fundamental process in amyloid fibrils. Herein, we seek to add insight into this topic by assessing the dynamics of a hydrogen bond buried in the dry interface of amyloid fibrils. To prepare a suitable model peptide system for this purpose, we introduce two mutations into the amyloid-forming Aβ(16-22) peptide. The first one is a lysine analog at position 19, which is used to help form structurally homogeneous fibrils, and the second one is an aspartic acid derivative (DM) at position 17, which is intended (1) to be used as a site-specific infrared probe and (2) to serve as a hydrogen-bond acceptor to lysine so that an inter-β-sheet hydrogen bond can be formed in the fibrils. Using both infrared spectroscopy and atomic force microscopy, we show that (1) this mutant peptide indeed forms well defined fibrils, (2) when bulk solvent is removed, there is no detectable water present in the fibrils, (3) infrared results obtained with the DM probe are consistent with a protofibril structure that is composed of two antiparallel β-sheets stacked in a parallel fashion, leading to formation of the expected hydrogen bond. Using two-dimensional infrared spectroscopy, we further show that the dynamics of this hydrogen bond occur on a timescale of ~2.3 ps, which is attributed to the rapid rotation of the -NH3+ group of lysine around its Cε-Nζ bond. Taken together, these results suggest that (1) DM is a useful infrared marker in facilitating structure determination of amyloid fibrils and (2) even in the tightly packed core of amyloid fibrils certain amino acid sidechains can undergo ultrafast motions, hence contributing to the thermodynamic stability of the system.

Embolic Risk in Atrial Fibrillation that Arises from Hyperthyroidism

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Traube, Elie; Coplan, Neil L.

2011-01-01

Atrial fibrillation, the most common cardiac complication of hyperthyroidism, occurs in an estimated 10% to 25% of overtly hyperthyroid patients. The prevalence of atrial fibrillation increases with age in the general population and in thyrotoxic patients. Other risk factors for atrial fibrillation in thyrotoxic patients include male sex, ischemic or valvular heart disease, and congestive heart failure. The incidence of arterial embolism or stroke in thyrotoxic atrial fibrillation is less clear. There are many reports of arterial thromboembolism associated with hyperthyroidism, including cases of young adults without coexisting risk factors other than thyrotoxic atrial fibrillation. The use of anticoagulative agents to prevent thromboembolic sequelae of thyrotoxic atrial fibrillation is controversial: national organizations provide conflicting recommendations in their practice guidelines. Herein, we review the medical literature and examine the evidence behind the recommendations in order to determine the best approach to thromboembolic prophylaxis in patients who have atrial fibrillation that is associated with hyperthyroidism. PMID:21720457

Cord Blood and Transplants

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... donate their baby’s umbilical cord blood to a public cord blood bank. We have more than 249,000 cord blood ... stored as a cord blood unit at a public cord blood bank for future use. It can then be listed ...

Atrial fibrillation

African Journals Online (AJOL)

ABEOLUGBENGAS

Mean blood pressures were 126.03± ... optimal. Keywords: Atrial fibrillation, thrombosis, CHADS2 Score, stroke risk, hypertensive heart disease, ... general population and the average age group ... Appendix 1) to stratify the stroke risk and we.

Collagen Fibrils: Nature's Highly Tunable Nonlinear Springs.

Science.gov (United States)

Andriotis, Orestis G; Desissaire, Sylvia; Thurner, Philipp J

2018-03-21

Tissue hydration is well known to influence tissue mechanics and can be tuned via osmotic pressure. Collagen fibrils are nature's nanoscale building blocks to achieve biomechanical function in a broad range of biological tissues and across many species. Intrafibrillar covalent cross-links have long been thought to play a pivotal role in collagen fibril elasticity, but predominantly at large, far from physiological, strains. Performing nanotensile experiments of collagen fibrils at varying hydration levels by adjusting osmotic pressure in situ during atomic force microscopy experiments, we show the power the intrafibrillar noncovalent interactions have for defining collagen fibril tensile elasticity at low fibril strains. Nanomechanical tensile tests reveal that osmotic pressure increases collagen fibril stiffness up to 24-fold in transverse (nanoindentation) and up to 6-fold in the longitudinal direction (tension), compared to physiological saline in a reversible fashion. We attribute the stiffening to the density and strength of weak intermolecular forces tuned by hydration and hence collagen packing density. This reversible mechanism may be employed by cells to alter their mechanical microenvironment in a reversible manner. The mechanism could also be translated to tissue engineering approaches for customizing scaffold mechanics in spatially resolved fashion, and it may help explain local mechanical changes during development of diseases and inflammation.

Conformational Compatibility Is Essential for Heterologous Aggregation of α-Synuclein

NARCIS (Netherlands)

Sidhu, Arshdeep; Segers-Nolten, Ine; Subramaniam, Vinod

2016-01-01

Under aggregation-prone conditions, soluble amyloidogenic protein monomers can self-assemble into fibrils or they can fibrillize on preformed fibrillar seeds (seeded aggregation). Seeded aggregations are known to propagate the morphology of the seeds in the event of cross-seeding. However, not all

Kinetically controlled thermal response of beta2-microglobulin amyloid fibrils.

Science.gov (United States)

Sasahara, Kenji; Naiki, Hironobu; Goto, Yuji

2005-09-23

Calorimetric measurements were carried out using a differential scanning calorimeter in the temperature range from 10 to 120 degrees C for characterizing the thermal response of beta2-microglobulin amyloid fibrils. The thermograms of amyloid fibril solution showed a remarkably large decrease in heat capacity that was essentially released upon the thermal unfolding of the fibrils, in which the magnitude of negative heat capacity change was not explicable in terms of the current accessible surface area model of protein structural thermodynamics. The heat capacity-temperature curve of amyloid fibrils prior to the fibril unfolding exhibited an unusual dependence on the fibril concentration and the heating rate. Particularly, the heat needed to induce the thermal response was found to be linearly dependent on the heating rate, indicating that its thermal response is under a kinetic control and precluding the interpretation in terms of equilibrium thermodynamics. Furthermore, amyloid fibrils of amyloid beta peptides also exhibited a heating rate-dependent exothermic process before the fibril unfolding, indicating that the kinetically controlled thermal response may be a common phenomenon to amyloid fibrils. We suggest that the heating rate-dependent negative change in heat capacity is coupled to the association of amyloid fibrils with characteristic hydration pattern.

Normal and reversed supramolecular chirality of insulin fibrils probed by vibrational circular dichroism at the protofilament level of fibril structure.

Science.gov (United States)

Kurouski, Dmitry; Dukor, Rina K; Lu, Xuefang; Nafie, Laurence A; Lednev, Igor K

2012-08-08

Fibrils are β-sheet-rich aggregates that are generally composed of several protofibrils and may adopt variable morphologies, such as twisted ribbons or flat-like sheets. This polymorphism is observed for many different amyloid associated proteins and polypeptides. In a previous study we proposed the existence of another level of amyloid polymorphism, namely, that associated with fibril supramolecular chirality. Two chiral polymorphs of insulin, which can be controllably grown by means of small pH variations, exhibit opposite signs of vibrational circular dichroism (VCD) spectra. Herein, using atomic force microscopy (AFM) and scanning electron microscopy (SEM), we demonstrate that indeed VCD supramolecular chirality is correlated not only by the apparent fibril handedness but also by the sense of supramolecular chirality from a deeper level of chiral organization at the protofilament level of fibril structure. Our microscopic examination indicates that normal VCD fibrils have a left-handed twist, whereas reversed VCD fibrils are flat-like aggregates with no obvious helical twist as imaged by atomic force microscopy or scanning electron microscopy. A scheme is proposed consistent with observed data that features a dynamic equilibrium controlled by pH at the protofilament level between left- and right-twist fibril structures with distinctly different aggregation pathways for left- and right-twisted protofilaments. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

[Relations between FANS, PPI and atrial fibrillation].

Science.gov (United States)

Ricci, Fabrizio; De Caterina, Raffaele

2013-05-01

Recent evidence supports the existence of an association between the use of non-steroidal anti-inflammatory drugs and the risk of atrial fibrillation. Anti-inflammatory drugs are widely used for the treatment of systemic inflammatory disorders, and chronic inflammation is a well-known risk factor for the development of myocardial fibrosis. The latter accounts for atrial inhomogeneities of conduction, thus triggering and perpetuating atrial fibrillation. Atrial inflammatory remodeling may therefore be responsible for the higher incidence of atrial fibrillation among patients assuming steroidal and non-steroidal anti-inflammatory drugs because of an underlying inflammatory disorders. Alternative theories contemplate gastroesophageal reflux, which is extremely common during the use of non-steroidal anti-inflammatory drugs and may trigger atrial fibrillation, as mediating the above-mentioned association.

How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin*

Science.gov (United States)

Malmos, Kirsten Gade; Bjerring, Morten; Jessen, Christian Moestrup; Nielsen, Erik Holm Toustrup; Poulsen, Ebbe T.; Christiansen, Gunna; Vosegaard, Thomas; Skrydstrup, Troels; Enghild, Jan J.; Pedersen, Jan Skov; Otzen, Daniel E.

2016-01-01

Glycosaminoglycans (GAGs) bind all known amyloid plaques and help store protein hormones in (acidic) granular vesicles, but the molecular mechanisms underlying these important effects are unclear. Here we investigate GAG interactions with the peptide hormone salmon calcitonin (sCT). GAGs induce fast sCT fibrillation at acidic pH and only bind monomeric sCT at acidic pH, inducing sCT helicity. Increasing GAG sulfation expands the pH range for binding. Heparin, the most highly sulfated GAG, binds sCT in the pH interval 3–7. Small angle x-ray scattering indicates that sCT monomers densely decorate and pack single heparin chains, possibly via hydrophobic patches on helical sCT. sCT fibrillates without GAGs, but heparin binding accelerates the process by decreasing the otherwise long fibrillation lag times at low pH and accelerates fibril growth rates at neutral pH. sCT·heparin complexes form β-sheet-rich heparin-covered fibrils. Solid-state NMR reveals that heparin does not alter the sCT fibrillary core around Lys11 but makes changes to Val8 on the exterior side of the β-strand, possibly through contacts to Lys18. Thus GAGs significantly modulate sCT fibrillation in a pH-dependent manner by interacting with both monomeric and aggregated sCT. PMID:27281819

Cryoballoon Ablation for Atrial Fibrillation

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Jason G. Andrade, MD

2012-03-01

Full Text Available Focal point-by-point radiofrequency catheter ablation has shown considerable success in the treatment of paroxysmal atrial fibrillation. However, it is not without limitations. Recent clinical and preclinical studies have demonstrated that cryothermal ablation using a balloon catheter (Artic Front©, Medtronic CryoCath LP provides an effective alternative strategy to treating atrial fibrillation. The objective of this article is to review efficacy and safety data surrounding cryoballoon ablation for paroxysmal and persistent atrial fibrillation. In addition, a practical step-by-step approach to cryoballoon ablation is presented, while highlighting relevant literature regarding: 1 the rationale for adjunctive imaging, 2 selection of an appropriate cryoballoon size, 3 predictors of efficacy, 4 advanced trouble-shooting techniques, and 5 strategies to reduce procedural complications, such as phrenic nerve palsy.

Fibril assembly in whey protein mixtures

NARCIS (Netherlands)

Bolder, S.G.

2007-01-01

The objective of this thesis was to study fibril assembly in mixtures of whey proteins. The effect of the composition of the protein mixture on the structures and the resulting phase behaviour was investigated. The current work has shown that beta-lactoglobulin is responsible for the fibril assembly

Sequence dependent aggregation of peptides and fibril formation

Science.gov (United States)

Hung, Nguyen Ba; Le, Duy-Manh; Hoang, Trinh X.

2017-09-01

Deciphering the links between amino acid sequence and amyloid fibril formation is key for understanding protein misfolding diseases. Here we use Monte Carlo simulations to study the aggregation of short peptides in a coarse-grained model with hydrophobic-polar (HP) amino acid sequences and correlated side chain orientations for hydrophobic contacts. A significant heterogeneity is observed in the aggregate structures and in the thermodynamics of aggregation for systems of different HP sequences and different numbers of peptides. Fibril-like ordered aggregates are found for several sequences that contain the common HPH pattern, while other sequences may form helix bundles or disordered aggregates. A wide variation of the aggregation transition temperatures among sequences, even among those of the same hydrophobic fraction, indicates that not all sequences undergo aggregation at a presumable physiological temperature. The transition is found to be the most cooperative for sequences forming fibril-like structures. For a fibril-prone sequence, it is shown that fibril formation follows the nucleation and growth mechanism. Interestingly, a binary mixture of peptides of an aggregation-prone and a non-aggregation-prone sequence shows the association and conversion of the latter to the fibrillar structure. Our study highlights the role of a sequence in selecting fibril-like aggregates and also the impact of a structural template on fibril formation by peptides of unrelated sequences.

Regulated viral BDNF delivery in combination with Schwann cells promotes axonal regeneration through capillary alginate hydrogels after spinal cord injury.

Science.gov (United States)

Liu, Shengwen; Sandner, Beatrice; Schackel, Thomas; Nicholson, LaShae; Chtarto, Abdelwahed; Tenenbaum, Liliane; Puttagunta, Radhika; Müller, Rainer; Weidner, Norbert; Blesch, Armin

2017-09-15

Grafting of cell-seeded alginate capillary hydrogels into a spinal cord lesion site provides an axonal bridge while physically directing regenerating axonal growth in a linear pattern. However, without an additional growth stimulus, bridging axons fail to extend into the distal host spinal cord. Here we examined whether a combinatory strategy would support regeneration of descending axons across a cervical (C5) lateral hemisection lesion in the rat spinal cord. Following spinal cord transections, Schwann cell (SC)-seeded alginate hydrogels were grafted to the lesion site and AAV5 expressing brain-derived neurotrophic factor (BDNF) under control of a tetracycline-regulated promoter was injected caudally. In addition, we examined whether SC injection into the caudal spinal parenchyma would further enhance regeneration of descending axons to re-enter the host spinal cord. Our data show that both serotonergic and descending axons traced by biotinylated dextran amine (BDA) extend throughout the scaffolds. The number of regenerating axons is significantly increased when caudal BDNF expression is activated and transient BDNF delivery is able to sustain axons after gene expression is switched off. Descending axons are confined to the caudal graft/host interface even with continuous BDNF expression for 8weeks. Only with a caudal injection of SCs, a pathway facilitating axonal regeneration through the host/graft interface is generated allowing axons to successfully re-enter the caudal spinal cord. Recovery from spinal cord injury is poor due to the limited regeneration observed in the adult mammalian central nervous system. Biomaterials, cell transplantation and growth factors that can guide axons across a lesion site, provide a cellular substrate, stimulate axon growth and have shown some promise in increasing the growth distance of regenerating axons. In the present study, we combined an alginate biomaterial with linear channels with transplantation of Schwann cells within

Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes.

Directory of Open Access Journals (Sweden)

Helen P McWilliams-Koeppen

Full Text Available Light chain (AL amyloidosis is the most common form of systemic amyloid disease, and cardiomyopathy is a dire consequence, resulting in an extremely poor prognosis. AL is characterized by the production of monoclonal free light chains that deposit as amyloid fibrils principally in the heart, liver, and kidneys causing organ dysfunction. We have studied the effects of amyloid fibrils, produced from recombinant λ6 light chain variable domains, on metabolic activity of human cardiomyocytes. The data indicate that fibrils at 0.1 μM, but not monomer, significantly decrease the enzymatic activity of cellular NAD(PH-dependent oxidoreductase, without causing significant cell death. The presence of amyloid fibrils did not affect ATP levels; however, oxygen consumption was increased and reactive oxygen species were detected. Confocal fluorescence microscopy showed that fibrils bound to and remained at the cell surface with little fibril internalization. These data indicate that AL amyloid fibrils severely impair cardiomyocyte metabolism in a dose dependent manner. These data suggest that effective therapeutic intervention for these patients should include methods for removing potentially toxic amyloid fibrils.

Spinal Cord Injury 101

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Spinal Cord Injury 101

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Spinal Cord Injury 101

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Spinal Cord Injury 101

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Spinal Cord Injury 101

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Spinal Cord Diseases

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Your spinal cord is a bundle of nerves that runs down the middle of your back. It carries signals back ... of the spine, this can also injure the spinal cord. Other spinal cord problems include Tumors Infections such ...

Spinal Cord Injury 101

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Full Text Available menu Understanding Spinal Cord Injury What is a Spinal Cord Injury Levels of Injury and What They Mean Animated Spinal Cord Injury Chart Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal ...

Differentiation of human umbilical cord mesenchymal stem cells into dermal fibroblasts in vitro

Energy Technology Data Exchange (ETDEWEB)

Han, Yanfu [Department of Burn and Plastic Surgery, Burns Institute, First Hospital Affiliated to General Hospital of PLA, Beijing (China); Chai, Jiake, E-mail: cjk304@126.com [Department of Burn and Plastic Surgery, Burns Institute, First Hospital Affiliated to General Hospital of PLA, Beijing (China); Sun, Tianjun; Li, Dongjie; Tao, Ran [Department of Burn and Plastic Surgery, Burns Institute, First Hospital Affiliated to General Hospital of PLA, Beijing (China)

2011-10-07

Highlights: {yields} Mesenchymal stem cells (MSCs) are potential seed cells for tissue-engineered skin. {yields} Tissue-derived umbilical cord MSCs (UCMSCs) can readily be isolated in vitro. {yields} We induce UCMSCs to differentiate into dermal fibroblasts via conditioned medium. {yields} Collagen type I and collagen type III mRNA level was higher in differentiated cells. {yields} UCMSCs-derived fibroblast-like cells strongly express fibroblast-specific protein. -- Abstract: Tissue-derived umbilical cord mesenchymal stem cells (UCMSCs) can be readily obtained, avoid ethical or moral constraints, and show excellent pluripotency and proliferation potential. UCMSCs are considered to be a promising source of stem cells in regenerative medicine. In this study, we collected newborn umbilical cord tissue under sterile conditions and isolated UCMSCs through a tissue attachment method. UCMSC cell surface markers were examined using flow cytometry. On the third passage, UCMSCs were induced to differentiate into dermal fibroblasts in conditioned induction media. The induction results were detected using immunofluorescence with a fibroblast-specific monoclonal antibody and real time PCR for type I and type III collagen. UCMSCs exhibited a fibroblast-like morphology and reached 90% confluency 14 to 18 days after primary culture. Cultured UCMSCs showed strong positive staining for CD73, CD29, CD44, CD105, and HLA-I, but not CD34, CD45, CD31, or HLA-DR. After differentiation, immunostaining for collagen type I, type III, fibroblast-specific protein, vimentin, and desmin were all strongly positive in induced cells, and staining was weak or negative in non-induced cells; total transcript production of collagen type I and collagen type III mRNA was higher in induced cells than in non-induced cells. These results demonstrate that UCMSCs can be induced to differentiate into fibroblasts with conditioned induction media and, in turn, could be used as seed cells for tissue

Differentiation of human umbilical cord mesenchymal stem cells into dermal fibroblasts in vitro

International Nuclear Information System (INIS)

Han, Yanfu; Chai, Jiake; Sun, Tianjun; Li, Dongjie; Tao, Ran

2011-01-01

Highlights: → Mesenchymal stem cells (MSCs) are potential seed cells for tissue-engineered skin. → Tissue-derived umbilical cord MSCs (UCMSCs) can readily be isolated in vitro. → We induce UCMSCs to differentiate into dermal fibroblasts via conditioned medium. → Collagen type I and collagen type III mRNA level was higher in differentiated cells. → UCMSCs-derived fibroblast-like cells strongly express fibroblast-specific protein. -- Abstract: Tissue-derived umbilical cord mesenchymal stem cells (UCMSCs) can be readily obtained, avoid ethical or moral constraints, and show excellent pluripotency and proliferation potential. UCMSCs are considered to be a promising source of stem cells in regenerative medicine. In this study, we collected newborn umbilical cord tissue under sterile conditions and isolated UCMSCs through a tissue attachment method. UCMSC cell surface markers were examined using flow cytometry. On the third passage, UCMSCs were induced to differentiate into dermal fibroblasts in conditioned induction media. The induction results were detected using immunofluorescence with a fibroblast-specific monoclonal antibody and real time PCR for type I and type III collagen. UCMSCs exhibited a fibroblast-like morphology and reached 90% confluency 14 to 18 days after primary culture. Cultured UCMSCs showed strong positive staining for CD73, CD29, CD44, CD105, and HLA-I, but not CD34, CD45, CD31, or HLA-DR. After differentiation, immunostaining for collagen type I, type III, fibroblast-specific protein, vimentin, and desmin were all strongly positive in induced cells, and staining was weak or negative in non-induced cells; total transcript production of collagen type I and collagen type III mRNA was higher in induced cells than in non-induced cells. These results demonstrate that UCMSCs can be induced to differentiate into fibroblasts with conditioned induction media and, in turn, could be used as seed cells for tissue-engineered dermis.

The inhalation toxicology of p-aramid fibrils.

Science.gov (United States)

Donaldson, Ken

2009-01-01

The pandemic of lung disease caused by asbestos has cast suspicion on any industrial fibrous material that can become airborne in respirable form in workplaces, such that the respirable fibres might be inhaled. Fibre toxicology arose as a sub-specialty of particle toxicology to address the specialised nature of fibre effects and has evolved substantially in the last 25 years. It has yielded valuable information on the dosimetry, structure-activity relationships, and mechanism involved in toxicological effects of a range of fibrous materials, including asbestos, other naturally occurring fibrous materials, and synthetic vitreous fibres. A robust structure/activity paradigm has emerged from this research that highlights fibre length, thinness, and biopersistence as major factors in determining the pathogenicity of a fibre. p-Aramid is a manufactured fibre composed of synthetic polyamide (poly paraphenylene terephthalamide) manufactured on a commercial scale since 1970 by polymerisation and spinning steps. It is used as an advanced composite and in fabrics, body armour, friction materials, etc. Respirable fibrils of p-aramid can be released from the fibres during working and can become airborne. A considerable body of research has been carried out into the hazard posed by inhaled p-aramid fibrils, and this review considers this body of literature and summarises the state-of-the-science in the toxicology of p-aramid fibrils in the light of the existing overarching fibre toxicology paradigm. The peer-reviewed studies demonstrate that p-aramid fibrils can be long and thin but that the fibrils are not biopersistent. Residence in the milieu of the lungs leads to fibre shortening, allowing efficient and complete phagocytosis and effective clearance. Subsequently the p-aramid hazard is low, and this is confirmed in animal studies. The mechanism of shortening of p-aramid fibrils is not well-understood, but may involve the action of macrophages on the fibrils following

Polymorphism complexity and handedness inversion in serum albumin amyloid fibrils.

Science.gov (United States)

Usov, Ivan; Adamcik, Jozef; Mezzenga, Raffaele

2013-12-23

Protein-based amyloid fibrils can show a great variety of polymorphic structures within the same protein precursor, although the origins of these structural homologues remain poorly understood. In this work we investigate the fibrillation of bovine serum albumin--a model globular protein--and we follow the polymorphic evolution by a statistical analysis of high-resolution atomic force microscopy images, complemented, at larger length scales, by concepts based on polymer physics formalism. We identify six distinct classes of coexisting amyloid fibrils, including flexible left-handed twisted ribbons, rigid right-handed helical ribbons and nanotubes. We show that the rigid fibrils originate from flexible fibrils through two diverse polymorphic transitions, first, via a single-fibril transformation when the flexible left-handed twisted ribbons turn into the helical left-handed ribbons, to finally evolve into nanotube-like structures, and second, via a double-fibril transformation when two flexible left-handed twisted ribbons wind together resulting in a right-handed twisted ribbon, followed by a rigid right-handed helical ribbon polymorphic conformation. Hence, the change in handedness occurs with an increase in the level of the fibril's structural organization.

Elasticity in Physically Cross-Linked Amyloid Fibril Networks

Science.gov (United States)

Cao, Yiping; Bolisetty, Sreenath; Adamcik, Jozef; Mezzenga, Raffaele

2018-04-01

We provide a constitutive model of semiflexible and rigid amyloid fibril networks by combining the affine thermal model of network elasticity with the Derjaguin-Landau-Vervey-Overbeek (DLVO) theory of electrostatically charged colloids. When compared to rheological experiments on β -lactoglobulin and lysozyme amyloid networks, this approach provides the correct scaling of elasticity versus both concentration (G ˜c2.2 and G ˜c2.5 for semiflexible and rigid fibrils, respectively) and ionic strength (G ˜I4.4 and G ˜I3.8 for β -lactoglobulin and lysozyme, independent from fibril flexibility). The pivotal role played by the screening salt is to reduce the electrostatic barrier among amyloid fibrils, converting labile physical entanglements into long-lived cross-links. This gives a power-law behavior of G with I having exponents significantly larger than in other semiflexible polymer networks (e.g., actin) and carrying DLVO traits specific to the individual amyloid fibrils.

Spinal Cord Injuries

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... forth between your body and your brain. A spinal cord injury disrupts the signals. Spinal cord injuries usually begin with a blow that fractures or ... down on the nerve parts that carry signals. Spinal cord injuries can be complete or incomplete. With a complete ...

[A Case of Transverse Colon Cancer Metastasized to the Spermatic Cord after Resection of Peritoneal Dissemination].

Science.gov (United States)

Kikuchi, Isao; Kimura, Tomoaki; Azuma, Saya; Shimbo, Tomonori; Wakabayashi, Toshiki; Ota, Sakae; Sato, Tsutomu; Itoh, Seiji; Ishida, Toshiya; Sageshima, Masato

2017-11-01

We report a rare case of spermatic cord metastasis from colon cancer. A man in his 50s underwent extended right hemicolectomy for transverse colon cancer followed by resection of a peritoneal recurrence. After receiving adjuvant chemotherapy for 6 months, he became aware of a right inguinal mass. A spermatic cord tumor was noted on computed tomography(CT) and FDG/PET-CT. He underwent radical orchiectomy. The resected tumor was histologically compatible with the colon cancer. Although he received additional chemotherapy, right inguinal recurrence was resected 6 months after orchiectomy. Colon cancer is the second most common origin, after gastric cancer, of metastatic spermatic tumor. As several metastatic routes have been reported, peritoneal seeding is mostly suspected in this case.

Torakal Ventral Cord Herniation

Directory of Open Access Journals (Sweden)

Sermin Tok

2015-11-01

Full Text Available  Ventral cord herniation is a rare cause of focal myelopathy due to herniation of the thoracic cord through a dural defect.It is also known by a variety of other terms such as spontaneous thoracic cord herniation or idiopathic spinal cord herniation.The key feature is focal distortion and rotation of the cord with no CSF seen between it and the ventral theca.

Does in-hospital ventricular fibrillation affect prognosis after myocardial infarction?

DEFF Research Database (Denmark)

Jensen, G V; Torp-Pedersen, C; Hildebrandt, P

1997-01-01

with ventricular fibrillation in time intervals, indicated that the importance of ventricular fibrillation for risk of death was exhausted during the initial 60 days after infarction. CONCLUSION: Ventricular fibrillation is associated with an independent increased risk of death within 0-60 days after infarction......AIM: The aim of this study was to estimate the prognostic information to be gained from ventricular fibrillation in patients with myocardial infarction. METHODS AND RESULTS: We studied 4259 consecutive patients with myocardial infarction admitted to one centre in 1977-1988. Five hundred and twenty......-eight (12.4%) of the patients had ventricular fibrillation in hospital. The following risk factors were included in multivariate models to estimate their importance for 30-day and long-term (median 7 year) prognosis: age, gender, ventricular fibrillation, congestive heart failure, pulmonary oedema...

Atrial fibrillation

DEFF Research Database (Denmark)

Olesen, Morten S; Nielsen, Morten W; Haunsø, Stig

2014-01-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting 1-2% of the general population. A number of studies have demonstrated that AF, and in particular lone AF, has a substantial genetic component. Monogenic mutations in lone and familial AF, although rare, have been recognized...

Essential Oils May Lead α-Synuclein towards Toxic Fibrils Formation

Directory of Open Access Journals (Sweden)

Dina Morshedi

2016-01-01

Full Text Available α-Synuclein (α-Syn fibrillation links with Parkinson’s disease (PD and several related syndromes. It is believed that exposure to the factors which promote fibrillation may induce and progress such neurodegenerative diseases (NDs. Herein, the effects of some wildly used essential oils including Myrtus communis (M. communis on α-Syn fibrillation were examined. M. communis particularly increased α-Syn fibrillation in a concentration dependent manner. Given that applications of M. communis are very extensive in Asian societies, especially Zoroastrians, this study was extended towards its role on α-Syn fibrillation/cytotoxicity. By using a unilamellar vesicle, it was shown that the aggregated species with tendency to perturb membrane were increased in the presence of M. communis. In this regard, the cytotoxicity of α-Syn on SH-SH5Y cells was also increased significantly. Inappropriately, the effects of fibrillation inhibitors, baicalein and cuminaldehyde, were modulated in the presence of M. communis. However, major components of M. communis did not induce fibrillation and also the effect of M. communis was limited on other fibrinogenic proteins. Assuming that essential oils have the ability to pass through the blood brain barrier (BBB along with the popular attention on aromatherapy for the incurable ND, these findings suggest an implementation of fibrillation tests for essential oils.

Dronedarone in high-risk permanent atrial fibrillation

DEFF Research Database (Denmark)

Connolly, Stuart J; Camm, A John; Halperin, Jonathan L

2011-01-01

Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events...... in high-risk permanent atrial fibrillation....

Newer Anticoagulants for Non-Valvular Atrial Fibrillation

Directory of Open Access Journals (Sweden)

Joseph M. Harburger

2012-05-01

Full Text Available Non-valvular atrial fibrillation is a recognized risk factor for stroke and systemic embolism. It has been clearly established that warfarin reduces the risk of stroke and systemic embolism in persons with atrial fibrillation and additional risk factors for stroke. The use of warfarin, however, requires frequent monitoring, and there is great variability in patient response to warfarin. Warfarin interacts with several medications and foods. In addition, warfarin use portends a significant risk of bleeding. For these reasons, warfarin is frequently not prescribed to persons for whom the drug would provide a clear benefit. Over the past decade, attempts have been made to develop drugs that are at least as safe and effective as warfarin for the treatment of atrial fibrillation that do not require monitoring nor have as many interactions. Initial studies of compounds in this regard ultimately failed due to safety concerns, but over the past two years two novel agents have been approved by the United States Food and Drug Association for anticoagulation in non-valvular atrial fibrillation, another drug is under review, and additional compounds are being studied. This article will review the use of warfarin and these new agents in the treatment of non-valvular atrial fibrillation.

Cervical Cord-Canal Mismatch: A New Method for Identifying Predisposition to Spinal Cord Injury.

Science.gov (United States)

Nouri, Aria; Montejo, Julio; Sun, Xin; Virojanapa, Justin; Kolb, Luis E; Abbed, Khalid M; Cheng, Joseph S

2017-12-01

The risk for spinal cord injuries (SCIs) ranging from devastating traumatic injuries, compression because of degenerative pathology, and neurapraxia is increased in patients with congenital spinal stenosis. Classical diagnostic criteria include an absolute anteroposterior diameter of spinal cord, which varies across patients, independent of canal size. Recent large magnetic resonance imaging studies of population cohorts have allowed newer methods to emerge that account for both cord and canal size by measuring a spinal cord occupation ratio (SCOR). A SCOR defined as ≥70% on midsagittal imaging or ≥80% on axial imaging appears to be an effective method of identifying cord-canal mismatch, but requires further validation. Cord-canal size mismatch predisposes patients to SCI because of 1) less space within the canal lowering the amount of degenerative changes needed for cord compression, and 2) less cerebrospinal fluid surrounding the spinal cord decreasing the ability to absorb kinetic forces directed at the spine. Patients with cord-canal mismatch have been reported to be at a substantially higher risk of traumatic SCI, and present with degenerative cervical myelopathy at a younger age than patients without cord-canal mismatch. However, neurologic outcome after SCI has occurred does not appear to be different in patients with or without a cord-canal mismatch. Recognition that canal and cord size are both factors which predispose to SCI supports that cord-canal size mismatch rather than a narrow cervical canal in isolation should be viewed as the underlying mechanism predisposing to SCI. Copyright © 2017. Published by Elsevier Inc.

Probing the mechanism of insulin fibril formation with insulin mutants.

Science.gov (United States)

Nielsen, L; Frokjaer, S; Brange, J; Uversky, V N; Fink, A L

2001-07-27

The molecular basis of insulin fibril formation was investigated by studying the structural properties and kinetics of fibril formation of 20 different human insulin mutants at both low pH (conditions favoring monomer/dimer) and at pH 7.4 (conditions favoring tetramer/hexamer). Small-angle X-ray scattering showed insulin to be monomeric in 20% acetic acid, 0.1 M NaCl, pH 2. The secondary structure of the mutants was assessed using far-UV circular dichroism, and the tertiary structure was determined using near-UV circular dichroism, quenching of intrinsic fluorescence by acrylamide and interactions with the hydrophobic probe 1-anilino-8-naphthalene-sulfonic acid (ANS). The kinetics of fibril formation were monitored with the fluorescent dye, Thioflavin T. The results indicate that the monomer is the state from which fibrils arise, thus under some conditions dissociation of hexamers may be rate limiting or partially rate limiting. The insulin mutants were found to retain substantial nativelike secondary and tertiary structure under all conditions studied. The results suggest that fibril formation of the insulin mutants is controlled by specific molecular interactions that are sensitive to variations in the primary structure. The observed effects of several mutations on the rate of fibril formation are inconsistent with a previously suggested model for fibrillation [Brange, J., Whittingham, J., Edwards, D., Youshang, Z., Wollmer, A., Brandenburg, D., Dodson, G., and Finch, J. (1997) Curr. Sci. 72, 470-476]. Two surfaces on the insulin monomer are identified as potential interacting sites in insulin fibrils, one consisting of the residues B10, B16, and B17 and the other consisting of at least the residues A8 and B25. The marked increase in the lag time for fibril formation with mutations to more polar residues, as well as mutations to charged residues, demonstrates the importance of both hydrophobic and electrostatic interactions in the initial stages of fibrillation

Fibril formation from pea protein and subsequent gel formation.

Science.gov (United States)

Munialo, Claire Darizu; Martin, Anneke H; van der Linden, Erik; de Jongh, Harmen H J

2014-03-19

The objective of this study was to characterize fibrillar aggregates made using pea proteins, to assemble formed fibrils into protein-based gels, and to study the rheological behavior of these gels. Micrometer-long fibrillar aggregates were observed after pea protein solutions had been heated for 20 h at pH 2.0. Following heating of pea proteins, it was observed that all of the proteins were hydrolyzed into peptides and that 50% of these peptides were assembled into fibrils. Changes on a structural level in pea proteins were studied using circular dichroism, transmission electron microscopy, and particle size analysis. During the fibril assembly process, an increase in aggregate size was observed, which coincided with an increase in thioflavin T binding, indicating the presence of β-sheet aggregates. Fibrils made using pea proteins were more branched and curly. Gel formation of preformed fibrils was induced by slow acidification from pH 7.0 to a final pH of around pH 5.0. The ability of pea protein-based fibrillar gels to fracture during an amplitude sweep was comparable to those of soy protein and whey protein-based fibrillar gels, although gels prepared from fibrils made using pea protein and soy protein were weaker than those of whey protein. The findings show that fibrils can be prepared from pea protein, which can be incorporated into protein-based fibrillar gels.

Spinal Cord Independence Measure, version III: applicability to the UK spinal cord injured population.

Science.gov (United States)

Glass, Clive A; Tesio, Luigi; Itzkovich, Malka; Soni, Bakul M; Silva, Pedro; Mecci, Munawar; Chadwick, Raymond; el Masry, Waghi; Osman, Aheed; Savic, Gordana; Gardner, Brian; Bergström, Ebba; Catz, Amiram

2009-09-01

To examine the validity, reliability and usefulness of the Spinal Cord Independence Measure for the UK spinal cord injury population. Multi-centre cohort study. Four UK regional spinal cord injury centres. Eighty-six people with spinal cord injury. Spinal Cord Independence Measure and Functional Independence Measure on admission analysed using inferential statistics, and Rasch analysis of Spinal Cord Independence Measure. Internal consistency, inter-rater reliability, discriminant validity; Spinal Cord Independence Measure subscale match between distribution of item difficulty and patient ability measurements; reliability of patient ability measures; fit of data to Rasch model; unidimensionality of subscales; hierarchical ordering of categories within items; differential item functioning across patient groups. Scale reliability (kappa coefficients range 0.491-0.835; (p Spinal Cord Independence Measure subscales compatible with stringent Rasch requirements; mean infit indices high; distinct strata of abilities identified; most thresholds ordered; item hierarchy stable across clinical groups and centres. Misfit and differences in item hierarchy identified. Difficulties assessing central cord injuries highlighted. Conventional statistical and Rasch analyses justify the use of the Spinal Cord Independence Measure in clinical practice and research in the UK. Cross-cultural validity may be further improved.

Treatment Guidelines of Atrial Fibrillation (AFib or AF)

Science.gov (United States)

... Artery Disease Venous Thromboembolism Aortic Aneurysm More Treatment Guidelines of Atrial Fibrillation (AFib or AF) Updated:Jun 28,2017 What are the treatment guidelines for atrial fibrillation? Medical guidelines are written by ...

Iowa Mutant Apolipoprotein A-I (ApoA-IIowa) Fibrils Target Lysosomes.

Science.gov (United States)

Kameyama, Hirokazu; Nakajima, Hiroyuki; Nishitsuji, Kazuchika; Mikawa, Shiho; Uchimura, Kenji; Kobayashi, Norihiro; Okuhira, Keiichiro; Saito, Hiroyuki; Sakashita, Naomi

2016-07-28

The single amino acid mutation G26R in human apolipoprotein A-I (apoA-IIowa) is the first mutation that was associated with familial AApoA1 amyloidosis. The N-terminal fragments (amino acid residues 1-83) of apoA-I containing this mutation deposit as amyloid fibrils in patients' tissues and organs, but the mechanisms of cellular degradation and cytotoxicity have not yet been clarified. In this study, we demonstrated degradation of apoA-IIowa fibrils via the autophagy-lysosomal pathway in human embryonic kidney 293 cells. ApoA-IIowa fibrils induced an increase in lysosomal pH and the cytosolic release of the toxic lysosomal protease cathepsin B. The mitochondrial dysfunction caused by apoA-IIowa fibrils depended on cathepsin B and was ameliorated by increasing the degradation of apoA-IIowa fibrils. Thus, although apoA-IIowa fibril transport to lysosomes and fibril degradation in lysosomes may have occurred, the presence of an excess number of apoA-IIowa fibrils, more than the lysosomes could degrade, may be detrimental to cells. Our results thus provide evidence that the target of apoA-IIowa fibrils is lysosomes, and we thereby gained a novel insight into the mechanism of AApoA1 amyloidosis.

Microdialysis to optimize cord perfusion and drug delivery in spinal cord injury.

OpenAIRE

Phang, I; Zoumprouli, A; Papadopoulos, MC; Saadoun, S

2016-01-01

OBJECTIVE: There is lack of monitoring from the injury site to guide management of patients with acute traumatic spinal cord injury. Here we describe a bedside microdialysis monitoring technique for optimizing spinal cord perfusion and drug delivery at the injury site. METHODS: 14 patients were recruited within 72 hours of severe spinal cord injury. We inserted intradurally at the injury site a pressure probe, to monitor continuously spinal cord perfusion pressure, and a microdialysis cathete...

Spinal Cord Injury 101

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Full Text Available ... Topic Resources Peer Counseling Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury 101 Adult Injuries Spinal Cord Injury 101 ...

Meta-analysis identifies six new susceptibility loci for atrial fibrillation

NARCIS (Netherlands)

Ellinor, Patrick T; Lunetta, Kathryn L; Albert, Christine M; Glazer, Nicole L; Ritchie, Marylyn D; Smith, Albert V; Arking, Dan E; Müller-Nurasyid, Martina; Krijthe, Bouwe P; Lubitz, Steven A; Bis, Joshua C; Chung, Mina K; Dörr, Marcus; Ozaki, Kouichi; Roberts, Jason D; Smith, J Gustav; Pfeufer, Arne; Sinner, Moritz F; Lohman, Kurt; Ding, Jingzhong; Smith, Nicholas L; Smith, Jonathan D; Rienstra, Michiel; Rice, Kenneth M; Van Wagoner, David R; Magnani, Jared W; Wakili, Reza; Clauss, Sebastian; Rotter, Jerome I; Steinbeck, Gerhard; Launer, Lenore J; Davies, Robert W; Borkovich, Matthew; Harris, Tamara B; Lin, Honghuang; Völker, Uwe; Völzke, Henry; Milan, David J; Hofman, Albert; Boerwinkle, Eric; Chen, Lin Y; Soliman, Elsayed Z; Voight, Benjamin F; Li, Guo; Chakravarti, Aravinda; Kubo, Michiaki; Tedrow, Usha B; Rose, Lynda M; Ridker, Paul M; Conen, David; Tsunoda, Tatsuhiko; Furukawa, Tetsushi; Sotoodehnia, Nona; Xu, Siyan; Kamatani, Naoyuki; Levy, Daniel; Nakamura, Yusuke; Parvez, Babar; Mahida, Saagar; Furie, Karen L; Rosand, Jonathan; Muhammad, Raafia; Psaty, Bruce M; Meitinger, Thomas; Perz, Siegfried; Wichmann, H-Erich; Witteman, Jacqueline C M; Kao, W H Linda; Kathiresan, Sekar; Roden, Dan M; Uitterlinden, Andre G; Rivadeneira, Fernando; McKnight, Barbara; Sjögren, Marketa; Newman, Anne B; Liu, Yongmei; Gollob, Michael H; Melander, Olle; Tanaka, Toshihiro; Stricker, Bruno H Ch; Felix, Stephan B; Alonso, Alvaro; Darbar, Dawood; Barnard, John; Chasman, Daniel I; Heckbert, Susan R; Benjamin, Emelia J; Gudnason, Vilmundur; Kääb, Stefan

Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death. We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation

Analysis of brain natriuretic peptide in 30 patients with atrial fibrillation

International Nuclear Information System (INIS)

Jin Qiang; Lu Jianghui; Li Weipeng; Yuan Yuan; Sun Weili

2009-01-01

To investigate the relationship between atrial fibrillation and brain natriuretic peptide (BNP), plasma levels of BNP in 30 patients with atrial fibrillation and 30 health controls were assayed and compared. The results showed that plasma levels of BNP in patients with atrial fibrillation were significantly higher than those of health controls (P<0.05). When the patients with atrial fibrillation were restored sinus rhythm, the concentration of BNP decreased significantly (P<0.05). BNP was a sensitive marker of cardiac dysfunction, and BNP was positively correlated with atrial fibrillation. (authors)

Viscoelastic behavior of discrete human collagen fibrils

DEFF Research Database (Denmark)

Svensson, Rene; Hassenkam, Tue; P, Hansen

2010-01-01

Whole tendon and fibril bundles display viscoelastic behavior, but to the best of our knowledge this property has not been directly measured in single human tendon fibrils. In the present work an atomic force microscopy (AFM) approach was used for tensile testing of two human patellar tendon fibr...

Spinal Cord Injury 101

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Full Text Available ... Topic Resources Peer Counseling Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury 101 Adult Injuries Spinal Cord Injury 101 David ...

Personalized management of atrial fibrillation

DEFF Research Database (Denmark)

Kirchhof, Paulus; Breithardt, Günter; Aliot, Etienne

2013-01-01

The management of atrial fibrillation (AF) has seen marked changes in past years, with the introduction of new oral anticoagulants, new antiarrhythmic drugs, and the emergence of catheter ablation as a common intervention for rhythm control. Furthermore, new technologies enhance our ability......, and hospitalizations. During the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association (AFNET/EHRA) consensus conference, we identified the following opportunities to personalize management of AF in a better manner with a view to improve outcomes by integrating atrial morphology and damage...

Exercise-based cardiac rehabilitation for adults with atrial fibrillation

DEFF Research Database (Denmark)

Risom, Signe Stelling; Zwisler, Ann-Dorthe; Johansen, Pernille Palm

2017-01-01

BACKGROUND: Exercise-based cardiac rehabilitation may benefit adults with atrial fibrillation or those who had been treated for atrial fibrillation. Atrial fibrillation is caused by multiple micro re-entry circuits within the atrial tissue, which result in chaotic rapid activity in the atria....... OBJECTIVES: To assess the benefits and harms of exercise-based rehabilitation programmes, alone or with another intervention, compared with no-exercise training controls in adults who currently have AF, or have been treated for AF. SEARCH METHODS: We searched the following electronic databases; CENTRAL...... the benefits and harms of exercise-based cardiac rehabilitation for adults with atrial fibrillation on patient-relevant outcomes....

Spinal Cord Injury 101

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Full Text Available ... Cord Injury Diane M. Rowles, MS, NP How Family Life Changes After Spinal Cord Injury Nancy Rosenberg, ... Children with Spinal Cord Injury Patricia Mucia, RN Family Life After Pediatric Spinal Injury Dawn Sheaffer, MSW ...

Spinal Cord Injury 101

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Full Text Available ... spinal cord injury? play_arrow What kind of surgery is common after a spinal cord injury? play_ ... How soon after a spinal cord injury should surgery be performed? play_arrow Is it common to ...

Spinal Cord Injury 101

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Full Text Available ... Counseling Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury ... Jennifer Piatt, PhD David Chen, MD Read Bio Medical Director, Spinal Cord Injury Rehabilitation Program, Rehabilitation Institute ...

Spinal Cord Injury 101

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Full Text Available ... L Sarah Harrison, OT Anne Bryden, OT The Role of the Social Worker after Spinal Cord Injury ... a spinal cord injury important? play_arrow What role does “compression” play in a spinal cord injury? ...

Spinal Cord Injury 101

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Full Text Available ... Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury 101 ... arrow What is the “Spinal Cord Injury Model Systems” program? play_arrow What are the most promising ...

The contrasting effect of macromolecular crowding on amyloid fibril formation.

Directory of Open Access Journals (Sweden)

Qian Ma

Full Text Available Amyloid fibrils associated with neurodegenerative diseases can be considered biologically relevant failures of cellular quality control mechanisms. It is known that in vivo human Tau protein, human prion protein, and human copper, zinc superoxide dismutase (SOD1 have the tendency to form fibril deposits in a variety of tissues and they are associated with different neurodegenerative diseases, while rabbit prion protein and hen egg white lysozyme do not readily form fibrils and are unlikely to cause neurodegenerative diseases. In this study, we have investigated the contrasting effect of macromolecular crowding on fibril formation of different proteins.As revealed by assays based on thioflavin T binding and turbidity, human Tau fragments, when phosphorylated by glycogen synthase kinase-3β, do not form filaments in the absence of a crowding agent but do form fibrils in the presence of a crowding agent, and the presence of a strong crowding agent dramatically promotes amyloid fibril formation of human prion protein and its two pathogenic mutants E196K and D178N. Such an enhancing effect of macromolecular crowding on fibril formation is also observed for a pathological human SOD1 mutant A4V. On the other hand, rabbit prion protein and hen lysozyme do not form amyloid fibrils when a crowding agent at 300 g/l is used but do form fibrils in the absence of a crowding agent. Furthermore, aggregation of these two proteins is remarkably inhibited by Ficoll 70 and dextran 70 at 200 g/l.We suggest that proteins associated with neurodegenerative diseases are more likely to form amyloid fibrils under crowded conditions than in dilute solutions. By contrast, some of the proteins that are not neurodegenerative disease-associated are unlikely to misfold in crowded physiological environments. A possible explanation for the contrasting effect of macromolecular crowding on these two sets of proteins (amyloidogenic proteins and non-amyloidogenic proteins has been

Mechanical properties of amyloid-like fibrils defined by secondary structures

Science.gov (United States)

Bortolini, C.; Jones, N. C.; Hoffmann, S. V.; Wang, C.; Besenbacher, F.; Dong, M.

2015-04-01

Amyloid and amyloid-like fibrils represent a generic class of highly ordered nanostructures that are implicated in some of the most fatal neurodegenerative diseases. On the other hand, amyloids, by possessing outstanding mechanical robustness, have also been successfully employed as functional biomaterials. For these reasons, physical and chemical factors driving fibril self-assembly and morphology are extensively studied - among these parameters, the secondary structures and the pH have been revealed to be crucial, since a variation in pH changes the fibril morphology and net chirality during protein aggregation. It is important to quantify the mechanical properties of these fibrils in order to help the design of effective strategies for treating diseases related to the presence of amyloid fibrils. In this work, we show that by changing pH the mechanical properties of amyloid-like fibrils vary as well. In particular, we reveal that these mechanical properties are strongly related to the content of secondary structures. We analysed and estimated the Young's modulus (E) by comparing the persistence length (Lp) - measured from the observation of TEM images by using statistical mechanics arguments - with the mechanical information provided by peak force quantitative nanomechanical property mapping (PF-QNM). The secondary structure content and the chirality are investigated by means of synchrotron radiation circular dichroism (SR-CD). Results arising from this study could be fruitfully used as a protocol to investigate other medical or engineering relevant peptide fibrils.Amyloid and amyloid-like fibrils represent a generic class of highly ordered nanostructures that are implicated in some of the most fatal neurodegenerative diseases. On the other hand, amyloids, by possessing outstanding mechanical robustness, have also been successfully employed as functional biomaterials. For these reasons, physical and chemical factors driving fibril self-assembly and morphology

In vitro fibrillization of Alzheimer’s amyloid-β peptide (1-42)

Energy Technology Data Exchange (ETDEWEB)

Tiiman, Ann [Department of Gene Technology, Tallinn University of Technology, Tallinn 12618 (Estonia); Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, 106 91 (Sweden); Krishtal, Jekaterina; Palumaa, Peep; Tõugu, Vello, E-mail: vello.tougu@ttu.ee [Department of Gene Technology, Tallinn University of Technology, Tallinn 12618 (Estonia)

2015-09-15

The amyloid deposition in the form of extracellular fibrillar aggregates of amyloid-β (Aβ) peptide is a critical pathological event in Alzheimer’s disease. Here, we report a systematic investigation of the effects of environmental factors on the kinetics of Aβ fibrillization in vitro. The effects of Aβ42 peptide concentration, temperature, pH, added solvents and the ratio of Aβ40 and Aβ42 on the peptide fibrillization under agitated conditions was studied. The analysis show that the rate of fibril growth by monomer addition is not limited by diffusion but by rearrangement in the monomer structure, which is enhanced by low concentrations of fluorinated alcohols and characterized by the activation energy of 12 kcal/mol. Fibrillization rate decreases at pH values below 7.0 where simultaneous protonation of His 13 and 14 inhibits fibril formation. The lag period for Aβ42 was only twofold shorter and the fibril growth rate twofold faster than those of Aβ40. Lag period was shortened and the fibrillization rate was increased only at 90% content of Aβ42.

Aspects epidemiologiques et etiologiques de la fibrillation ...

African Journals Online (AJOL)

Conclusion : La fibrillation auriculaire est fréquente chez l'adulte noir togolais. Ses étiologies sont dominées par l'hypertension artérielle et les cardiomyopathies dilatées. complications and stoke. Aim: Our aim was to study epidemiologic and etiologic aspects of atrial fibrillation in black togolese in hospital circle. Material ...

Risk of atrial fibrillation and stroke in rheumatoid arthritis

DEFF Research Database (Denmark)

Lindhardsen, Jesper; Ahlehoff, Ole; Gislason, Gunnar Hilmar

2012-01-01

To determine if patients with rheumatoid arthritis have increased risk of atrial fibrillation and stroke.......To determine if patients with rheumatoid arthritis have increased risk of atrial fibrillation and stroke....

Structural and functional characteristics of myocard in patients with different forms of atrial fibrillation

Directory of Open Access Journals (Sweden)

L. I. Vasilyeva

2015-02-01

Full Text Available Aim. To study structural and functional characteristics of myocard in patients with different forms of atrial fibrillation. Atrial fibrillation is the most prevalent arrhythmia in clinical practice. Atrial fibrillation is a progressive disease: the duration of paroxysms increases over time and paroxysmal atrial fibrillation transforms to persistent, the last one becomes refractory to pharmacological and electrical cardioversion in time and transforms to permanent. So assessment of myocardial remodeling in patients with persistent and permanent atrial fibrillation is very actual. Methods and results. According to the aim of the study 133 patients with persistent atrial fibrillation and 100 patients with permanent atrial fibrillation were included into the study. Echocardiographic parameters of left and right atria function were studied. Conclusion. It was found that patients with persistent and permanent atrial fibrillation are characterized with both left and right atrias remodeling. Remodeling of the atrias is less pronounced in patients with permanent atrial fibrillation in comparison with persistent atrial fibrillation patients and arrhythmia recurrence.

Spinal Cord Injury 101

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Spinal Cord Injury 101

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Full Text Available ... Abuse and Spinal Cord Injury Allen Heinemann, PhD How Peer Counseling Works Julie Gassaway, MS, RN Pediatric Injuries Pediatric Spinal ... What is a spinal cord injury? play_arrow How does the spinal cord work? play_arrow Why is the level of a ...

The atrial fibrillation ablation pilot study

DEFF Research Database (Denmark)

Arbelo, Elena; Brugada, Josep; Hindricks, Gerhard

2014-01-01

AIMS: The Atrial Fibrillation Ablation Pilot Study is a prospective registry designed to describe the clinical epidemiology of patients undergoing an atrial fibrillation (AFib) ablation, and the diagnostic/therapeutic processes applied across Europe. The aims of the 1-year follow-up were to analyse...... was achieved in 40.7% of patients (43.7% in paroxysmal AF; 30.2% in persistent AF; 36.7% in long-lasting persistent AF). A second ablation was required in 18% of the cases and 43.4% were under antiarrhythmic treatment. Thirty-three patients (2.5%) suffered an adverse event, 272 (21%) experienced a left atrial...... tachycardia, and 4 patients died (1 haemorrhagic stroke, 1 ventricular fibrillation in a patient with ischaemic heart disease, 1 cancer, and 1 of unknown cause). CONCLUSION: The AFib Ablation Pilot Study provided crucial information on the epidemiology, management, and outcomes of catheter ablation of AFib...

Replica Exchange Simulations of the Thermodynamics of Aβ Fibril Growth

Science.gov (United States)

Takeda, Takako; Klimov, Dmitri K.

2009-01-01

Abstract Replica exchange molecular dynamics and an all-atom implicit solvent model are used to probe the thermodynamics of deposition of Alzheimer's Aβ monomers on preformed amyloid fibrils. Consistent with the experiments, two deposition stages have been identified. The docking stage occurs over a wide temperature range, starting with the formation of the first peptide-fibril interactions at 500 K. Docking is completed when a peptide fully adsorbs on the fibril edge at the temperature of 380 K. The docking transition appears to be continuous, and occurs without free energy barriers or intermediates. During docking, incoming Aβ monomer adopts a disordered structure on the fibril edge. The locking stage occurs at the temperature of ≈360 K and is characterized by the rugged free energy landscape. Locking takes place when incoming Aβ peptide forms a parallel β-sheet structure on the fibril edge. Because the β-sheets formed by locked Aβ peptides are typically off-registry, the structure of the locked phase differs from the structure of the fibril interior. The study also reports that binding affinities of two distinct fibril edges with respect to incoming Aβ peptides are different. The peptides bound to the concave edge have significantly lower free energy compared to those bound on the convex edge. Comparison with the available experimental data is discussed. PMID:19167295

Heart failure and atrial fibrillation: current concepts and controversies.

Science.gov (United States)

Van den Berg, M. P.; Tuinenburg, A. E.; Crijns, H. J.; Van Gelder, I. C.; Gosselink, A. T.; Lie, K. I.

1997-01-01

Heart failure and atrial fibrillation are very common, particularly in the elderly. Owing to common risk factors both disorders are often present in the same patient. In addition, there is increasing evidence of a complex, reciprocal relation between heart failure and atrial fibrillation. Thus heart failure may cause atrial fibrillation, with electromechanical feedback and neurohumoral activation playing an important mediating role. In addition, atrial fibrillation may promote heart failure; in particular, when there is an uncontrolled ventricular rate, tachycardiomyopathy may develop and thereby heart failure. Eventually, a vicious circle between heart failure and atrial fibrillation may form, in which neurohumoral activation and subtle derangement of rate control are involved. Treatment should aim at unloading of the heart, adequate control of ventricular rate, and correction of neurohumoral activation. Angiotensin converting enzyme inhibitors may help to achieve these goals. Treatment should also include an attempt to restore sinus rhythm through electrical cardioversion, though appropriate timing of cardioversion is difficult. His bundle ablation may be used to achieve adequate rate control in drug refractory cases. PMID:9155607

Structural evaluation of an amyloid fibril model using small-angle x-ray scattering

Science.gov (United States)

Dahal, Eshan; Choi, Mina; Alam, Nadia; Bhirde, Ashwinkumar A.; Beaucage, Serge L.; Badano, Aldo

2017-08-01

Amyloid fibrils are highly structured protein aggregates associated with a wide range of diseases including Alzheimer’s and Parkinson’s. We report a structural investigation of an amyloid fibril model prepared from a commonly used plasma protein (bovine serum albumin (BSA)) using small-angle x-ray scattering (SAXS) technique. As a reference, the size estimates from SAXS are compared to dynamic light scattering (DLS) data and the presence of amyloid-like fibrils is confirmed using Congo red absorbance assay. Our SAXS results consistently show the structural transformation of BSA from spheroid to rod-like elongated structures during the fibril formation process. We observe the elongation of fibrils over two months with fibril length growing from 35.9  ±  3.0 nm to 51.5  ±  2.1 nm. Structurally metastable fibrils with distinct SAXS profiles have been identified. As proof of concept, we demonstrate the use of such distinct SAXS profiles to detect fibrils in the mixture solutions of two species by estimating their volume fractions. This easily detectable and well-characterized amyloid fibril model from BSA can be readily used as a control or standard reference to further investigate SAXS applications in the detection of structurally diverse amyloid fibrils associated with protein aggregation diseases.

77 FR 11121 - Scientific Information Request on Treatment of Atrial Fibrillation

Science.gov (United States)

2012-02-24

... Information Request on Treatment of Atrial Fibrillation AGENCY: Agency for Healthcare Research and Quality... Review of the Treatment of Atrial Fibrillation, which is currently being conducted by the Evidence-based... the treatment of atrial fibrillation. The EHC Program is dedicated to identifying as many studies as...

Nanomechanical mapping of hydrated rat tail tendon collagen I fibrils.

Science.gov (United States)

Baldwin, Samuel J; Quigley, Andrew S; Clegg, Charlotte; Kreplak, Laurent

2014-10-21

Collagen fibrils play an important role in the human body, providing tensile strength to connective tissues. These fibrils are characterized by a banding pattern with a D-period of 67 nm. The proposed origin of the D-period is the internal staggering of tropocollagen molecules within the fibril, leading to gap and overlap regions and a corresponding periodic density fluctuation. Using an atomic force microscope high-resolution modulus maps of collagen fibril segments, up to 80 μm in length, were acquired at indentation speeds around 10(5) nm/s. The maps revealed a periodic modulation corresponding to the D-period as well as previously undocumented micrometer scale fluctuations. Further analysis revealed a 4/5, gap/overlap, ratio in the measured modulus providing further support for the quarter-staggered model of collagen fibril axial structure. The modulus values obtained at indentation speeds around 10(5) nm/s are significantly larger than those previously reported. Probing the effect of indentation speed over four decades reveals two distinct logarithmic regimes of the measured modulus and point to the existence of a characteristic molecular relaxation time around 0.1 ms. Furthermore, collagen fibrils exposed to temperatures between 50 and 62°C and cooled back to room temperature show a sharp decrease in modulus and a sharp increase in fibril diameter. This is also associated with a disappearance of the D-period and the appearance of twisted subfibrils with a pitch in the micrometer range. Based on all these data and a similar behavior observed for cross-linked polymer networks below the glass transition temperature, we propose that collagen I fibrils may be in a glassy state while hydrated.

Spinal Cord Injury 101

Medline Plus

Full Text Available ... the spinal cord work? play_arrow Why is the level of a spinal cord injury important? play_arrow What role does “compression” play in a spinal cord injury? play_arrow Why are high-dose steroids often used right after an injury? play_arrow What is meant ...

Synergistic Inhibition of Protein Fibrillation by Proline and Sorbitol: Biophysical Investigations.

Directory of Open Access Journals (Sweden)

Sinjan Choudhary

Full Text Available We report here interesting synergistic effects of proline and sorbitol, two well-known chemical chaperones, in the inhibition of fibrillation of two proteins, insulin and lysozyme. A combination of many biophysical techniques has been used to understand the structural morphology and modes of interaction of the chaperones with the proteins during fibrillation. Both the chaperones establish stronger polar interactions in the elongation and saturation stages of fibrillation compared to that in the native stage. However, when presented as a mixture, we also see contribution of hydrophobic interactions. Thus, a co-operative adjustment of polar and hydrophobic interactions between the chaperones and the protein surface seems to drive the synergistic effects in the fibrillation process. In insulin, this synergy is quantitatively similar in all the stages of the fibrillation process. These observations would have significant implications for understanding protein folding concepts, in general, and for designing combination therapies against protein fibrillation, in particular.

Synergistic Inhibition of Protein Fibrillation by Proline and Sorbitol: Biophysical Investigations.

Science.gov (United States)

Choudhary, Sinjan; Save, Shreyada N; Kishore, Nand; Hosur, Ramakrishna V

2016-01-01

We report here interesting synergistic effects of proline and sorbitol, two well-known chemical chaperones, in the inhibition of fibrillation of two proteins, insulin and lysozyme. A combination of many biophysical techniques has been used to understand the structural morphology and modes of interaction of the chaperones with the proteins during fibrillation. Both the chaperones establish stronger polar interactions in the elongation and saturation stages of fibrillation compared to that in the native stage. However, when presented as a mixture, we also see contribution of hydrophobic interactions. Thus, a co-operative adjustment of polar and hydrophobic interactions between the chaperones and the protein surface seems to drive the synergistic effects in the fibrillation process. In insulin, this synergy is quantitatively similar in all the stages of the fibrillation process. These observations would have significant implications for understanding protein folding concepts, in general, and for designing combination therapies against protein fibrillation, in particular.

From Fibril Formation to Fibril Properties and Rheology of Food Materials

NARCIS (Netherlands)

Linden, van der E.; Venema, P.

2013-01-01

For control and design of food properties it is important to understand how molecules and their interactions give rise to formation of microstructures and resulting rheological properties. This will be illustrated by discussing the formation and properties of fibrils in aqueous and non-aqueous

Spinal cord stimulation

Science.gov (United States)

... this page: //medlineplus.gov/ency/article/007560.htm Spinal cord stimulation To use the sharing features on this page, please enable JavaScript. Spinal cord stimulation is a treatment for pain that uses ...

Visualisation of collagen fibrils in joint cartilage using STIM

International Nuclear Information System (INIS)

Reinert, T.; Reibetanz, U.; Vogt, J.; Butz, T.; Werner, A.; Gruender, W.

2001-01-01

The scanning transmission ion microscopy (STIM) method was used to investigate the collagen network structure of the articular cartilage from a pig's knee in comparison with high resolution nuclear magnetic resonance imaging (microscopic NMR-tomography) and polarised light microscopy (PLM). Single collagen fibrils down to 200 nm in diameter were visualised. It was proved that the cartilage collagen network consists partly of zones of oriented fibrils as suggested by NMR measurements. Radially oriented fibrils were found in the zone near the calcified zone (hypertrophic zone) of both tibia and femur, and in the tibial radial zone. Tangentially oriented fibrils were found in the femoral and tibial superficial zone and in a second zone of the femoral cartilage. Polarisation light microscopy reveals broader zones of orientation than it was found with STIM

Insulin fibrillation: The influence and coordination of Zn2+

DEFF Research Database (Denmark)

Frankær, Christian Grundahl; Sønderby, Pernille; Bang, Maria Blanner

2017-01-01

fibrils has been debated for some years. We have therefore investigated the influence and binding geometry of zinc in fibrillated insulin using extended X-ray absorption fine-structure and X-ray absorption near-edge structure spectroscopy. The results were validated with fibre diffraction, Transmission...... Electron Microscopy and Thioflavin T fluorescence measurements. It is well-known that Zn2+ ions coordinate and stabilize the hexameric forms of insulin. However, this study is the first to show that zinc indeed binds to the insulin fibrils. Furthermore, zinc influences the kinetics and the morphology...... of the fibrils. It also shows that zinc coordinates to histidine residues in an environment, which is similar to the coordination seen in the insulin R6 hexamers, where three histidine residues and a chloride ion is coordinating the zinc....

Nearly reversible conformational change of amyloid fibrils as revealed by pH-jump experiments.

Science.gov (United States)

Yamaguchi, Kei-ichi; Kamatari, Yuji O; Fukuoka, Mayuko; Miyaji, Reiji; Kuwata, Kazuo

2013-10-01

pH-jump induced conformational transitions between substates of preformed amyloid fibrils made by a fragmented peptide of helix 2 (H2 peptide) of MoPrP were detected, and their kinetics were analyzed using a novel pH-jump apparatus specially designed for observing amyloids. Previously, we reported that H2 peptide formed ordered fibrils with a minimum at 207 nm on CD spectra at pH 2.9 (named pH 2.9 fibrils), but formed aggregate-like fibrils with a minimum at 220 nm at pH 7.5 (named pH 7.5 fibrils). When pH-jump from 2.9 to 7.5 was performed, the CD spectrum changed instantly, but the finally observed ellipticities were clearly distinct from those of pH 7.5 fibrils. Thus, the finally observed state is termed 'pH 7.5-like fibrils'. However, pH 7.5-like fibrils reverted to the conformation very similar to that of the pH 2.9 fibrils when the pH of the solution was restored to 2.9. Then, we examined the kinetics of the nearly reversible conformational changes between pH 2.9 fibrils and pH 7.5-like fibrils using ANS fluorescence stopped-flow, and we observed relatively fast phases (0.7-18 s(-1)). In contrast, the conversion between pH 7.5-like fibrils and pH 7.5 fibrils never occurred (<0.2 day(-1)). Thus, H2 fibrils can be switched readily between distinct conformations separated by a low energy barrier, while a large energy barrier clearly separated the different conformations. These conformational varieties of amyloid fibrils may explain the physical basis of the diversity in prion.

Polymorphism, metastable species and interconversion: the many states of glucagon fibrils

DEFF Research Database (Denmark)

Ghodke, Shirin D; Jensen, Grethe Vestergaard; Svane, Anna Sigrid P.

2014-01-01

physicochemical conditions such as high temperature, pressure, mechanical and chemical stress. Factors such as peptide concentration, accessible surface area, surface hydration of the glucagon molecular state, contact surface, temperature and ionic strength all contribute to fibrillar structure and stability...... fibril upon incubation at elevated temperatures (but not vice versa), indicating that fibrils are fundamentally malleable if they have not attained the most stable fibrillar state. While the effect of pressure on glucagon is complex (accelerating fibrillation at intermediate pressures and decelerating...... it at higher pressures), the thermal expansion coefficients obtained from these studies agree well with our previous calorimetric studies to reveal reduced or increased hydration of fibrils (leading to reduced or increased stability) depending on fibrillation conditions. Finally, we report...

NONPOTENTIALITY OF CHROMOSPHERIC FIBRILS IN NOAA ACTIVE REGIONS 11092 AND 9661

International Nuclear Information System (INIS)

Jing Ju; Yuan Yuan; Xu Yan; Wang Haimin; Reardon, Kevin; Wiegelmann, Thomas

2011-01-01

In this paper, we present a method to automatically segment chromospheric fibrils from Hα observations and further identify their orientation. We assume that chromospheric fibrils are aligned with the magnetic field. By comparing the orientation of the fibrils with the azimuth of the embedding chromospheric magnetic field extrapolated from a potential field model, the shear angle, a measure of nonpotentiality, along the fibrils is readily deduced. Following this approach, we make a quantitative assessment of the nonpotentiality of fibrils in two NOAA active regions (ARs): (1) the relatively simple AR 11092, observed with very high resolution by Interferometric Bidimensional Spectrometer, and (2) a β-γ-δ AR 9661, observed with median resolution by Big Bear Solar Observatory before and after an X1.6 flare.

Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen

Science.gov (United States)

Usmani, Shariq M.; Zirafi, Onofrio; Müller, Janis; Sandi-Monroy, Nathallie; Yadav, Jay K.; Meier, Christoph; Weil, Tanja; Roan, Nadia R.; Greene, Warner C.; Walther, Paul; Nilsson, K. Peter R.; Hammarström, Per; Wetzel, Ronald; Pilcher, Christopher D.; Gagsteiger, Friedrich; Fändrich, Marcus; Kirchhoff, Frank; Münch, Jan

2014-01-01

Naturally occurring fragments of the abundant semen proteins prostatic acid phosphatase (PAP) and semenogelins form amyloid fibrils in vitro. These fibrils boost HIV infection and may play a key role in the spread of the AIDS pandemic. However, the presence of amyloid fibrils in semen remained to be demonstrated. Here, we use state of the art confocal and electron microscopy techniques for direct imaging of amyloid fibrils in human ejaculates. We detect amyloid aggregates in all semen samples and find that they partially consist of PAP fragments, interact with HIV particles and increase viral infectivity. Our results establish semen as a body fluid that naturally contains amyloid fibrils that are exploited by HIV to promote its sexual transmission. PMID:24691351

Spinal Cord Injury 101

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Full Text Available ... injury? play_arrow How does the spinal cord work? play_arrow Why is the level of a spinal cord injury important? play_arrow What role does “compression” play in a spinal cord injury? play_arrow Why are high-dose steroids often used right after an injury? play_arrow What is meant ...

What Is Atrial Fibrillation?

Science.gov (United States)

ANSWERS by heart Cardiovascular Conditions What Is Atrial Fibrillation? Your heart has a natural pacemaker, called the “sinus node,” that makes electrical signals. These signals cause the heart to contract and pump ...

Antihypertensive treatment and risk of atrial fibrillation

DEFF Research Database (Denmark)

Marott, Sarah C W; Nielsen, Sune F; Benn, Marianne

2014-01-01

AIMS: To examine the associations between antihypertensive treatment with angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs), β-blockers, diuretics, or calcium-antagonists, and risk of atrial fibrillation. We examined these associations using the entire Danish...... population from 1995 through 2010. METHODS AND RESULTS: Excluding medication used in atrial fibrillation, we matched individuals on ACEi monotherapy 1:1 with individuals on β-blocker (n = 48 658), diuretic (n = 69 630), calcium-antagonist (n = 57 646), and ARB monotherapy (n = 20 158). Likewise, individuals...... on ARB monotherapy were matched 1:1 with individuals on β-blocker (n = 20 566), diuretic (n = 20 832), calcium-antagonist (n = 20 232), and ACEi monotherapy (n = 20 158). All were free of atrial fibrillation and of predisposing diseases like heart failure, ischaemic heart disease, diabetes mellitus...

Digoxin for atrial fibrillation and atrial flutter

DEFF Research Database (Denmark)

Sethi, Naqash J; Nielsen, Emil E; Safi, Sanam

2018-01-01

BACKGROUND: During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the results of these reviews suggested that digoxin seems to increase the risk of all-cause mortality regardless...... of concomitant heart failure. Our objective was to assess the benefits and harms of digoxin for atrial fibrillation and atrial flutter based on randomized clinical trials. METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, BIOSIS for eligible trials comparing digoxin versus placebo......, no intervention, or other medical interventions in patients with atrial fibrillation or atrial flutter in October 2016. Our primary outcomes were all-cause mortality, serious adverse events, and quality of life. Our secondary outcomes were heart failure, stroke, heart rate control, and conversion to sinus rhythm...

Genetics of Atrial Fibrillation and Possible Implications for Ischemic Stroke

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Robin Lemmens

2011-01-01

Full Text Available Atrial fibrillation is the most common cardiac arrhythmia mainly caused by valvular, ischemic, hypertensive, and myopathic heart disease. Atrial fibrillation can occur in families suggesting a genetic background especially in younger subjects. Additionally recent studies have identified common genetic variants to be associated with atrial fibrillation in the general population. This cardiac arrhythmia has important public health implications because of its main complications: congestive heart failure and ischemic stroke. Since atrial fibrillation can result in ischemic stroke, one might assume that genetic determinants of this cardiac arrhythmia are also implicated in cerebrovascular disease. Ischemic stroke is a multifactorial, complex disease where multiple environmental and genetic factors interact. Whether genetic variants associated with a risk factor for ischemic stroke also increase the risk of a particular vascular endpoint still needs to be confirmed in many cases. Here we review the current knowledge on the genetic background of atrial fibrillation and the consequences for cerebrovascular disease.

Stabilization and anomalous hydration of collagen fibril under heating.

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Sasun G Gevorkian

Full Text Available BACKGROUND: Type I collagen is the most common protein among higher vertebrates. It forms the basis of fibrous connective tissues (tendon, chord, skin, bones and ensures mechanical stability and strength of these tissues. It is known, however, that separate triple-helical collagen macromolecules are unstable at physiological temperatures. We want to understand the mechanism of collagen stability at the intermolecular level. To this end, we study the collagen fibril, an intermediate level in the collagen hierarchy between triple-helical macromolecule and tendon. METHODOLOGY/PRINCIPAL FINDING: When heating a native fibril sample, its Young's modulus decreases in temperature range 20-58°C due to partial denaturation of triple-helices, but it is approximately constant at 58-75°C, because of stabilization by inter-molecular interactions. The stabilization temperature range 58-75°C has two further important features: here the fibril absorbs water under heating and the internal friction displays a peak. We relate these experimental findings to restructuring of collagen triple-helices in fibril. A theoretical description of the experimental results is provided via a generalization of the standard Zimm-Bragg model for the helix-coil transition. It takes into account intermolecular interactions of collagen triple-helices in fibril and describes water adsorption via the Langmuir mechanism. CONCLUSION/SIGNIFICANCE: We uncovered an inter-molecular mechanism that stabilizes the fibril made of unstable collagen macromolecules. This mechanism can be relevant for explaining stability of collagen.

Cost of illness of atrial fibrillation: a nationwide study of societal impact.

Science.gov (United States)

Johnsen, Søren Paaske; Dalby, Lene Worsaae; Täckström, Tomas; Olsen, Jens; Fraschke, Anina

2017-11-10

The prevalence of atrial fibrillation is increasing rapidly; however, to date, population-based data are lacking on the attributable cost of illness of atrial fibrillation from a societal perspective, including both direct and indirect costs. The study was an incidence-based cost-of-illness study based on national registries covering the entire population of Denmark. We identified all patients with a first-time hospital diagnosis of atrial fibrillation between 2001 and 2012. For every atrial fibrillation patient, we identified three age- and sex-matched controls from the general population. Both the total and the attributable costs of atrial fibrillation were estimated based on individual level information on hospital care (in- and out-patient contacts), primary sector care, use of prescription drugs and productivity loss. Average 3-year societal costs per patient attributable to atrial fibrillation were estimated to be €20,403-26,544 during the study period. The costs were highest during the first year after diagnosis of atrial fibrillation. Admission costs constituted the largest cost component, whereas primary sector costs and medicine costs only constituted minor components. The attributable costs were more than two-fold higher among patients experiencing a stroke. The total 3-year cost attributable to atrial fibrillation in Denmark was estimated to be €219-295 million. The societal costs attributable to atrial fibrillation are significant. Reducing the need for hospitalizations, in particular from stroke, is a key factor in controlling the costs.

Analysis of amyloid fibrils in the cheetah (Acinonyx jubatus).

Science.gov (United States)

Bergström, Joakim; Ueda, Mitsuharu; Une, Yumi; Sun, Xuguo; Misumi, Shogo; Shoji, Shozo; Ando, Yukio

2006-06-01

Recently, a high prevalence of amyloid A (AA) amyloidosis has been documented among captive cheetahs worldwide. Biochemical analysis of amyloid fibrils extracted from the liver of a Japanese captive cheetah unequivocally showed that protein AA was the main fibril constituent. Further characterization of the AA fibril components by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis revealed three main protein AA bands with approximate molecular weights of 8, 10 and 12 kDa. Mass spectrometry analysis of the 12-kDa component observed in SDS-PAGE and Western blotting confirmed the molecular weight of a 12,381-Da peak. Our finding of a 12-kDa protein AA component provides evidence that the cheetah SAA sequence is longer than the previously reported 90 amino acid residues (approximately 10 kDa), and hence SAA is part of the amyloid fibril.

La fibrillation auriculaire chez le noir Africain: Aspects ...

African Journals Online (AJOL)

In this retrospective work realized during two years (1st january 2002 to 31 december 2003), relative to 300 cases hospitalized at the Cardiology Institute of Abidjan, the authors have studied the epidemiologic, etiologic and prognosis factors of black african atrial fibrillation in hospital cercle. The atrial fibrillation was the most ...

Analysis of XFEL serial diffraction data from individual crystalline fibrils

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David H. Wojtas

2017-11-01

Full Text Available Serial diffraction data collected at the Linac Coherent Light Source from crystalline amyloid fibrils delivered in a liquid jet show that the fibrils are well oriented in the jet. At low fibril concentrations, diffraction patterns are recorded from single fibrils; these patterns are weak and contain only a few reflections. Methods are developed for determining the orientation of patterns in reciprocal space and merging them in three dimensions. This allows the individual structure amplitudes to be calculated, thus overcoming the limitations of orientation and cylindrical averaging in conventional fibre diffraction analysis. The advantages of this technique should allow structural studies of fibrous systems in biology that are inaccessible using existing techniques.

Formation of Calcium Carbonate Deposition in the Cotyledons during he Germination of Justicia procumbens L. (Acanthaceae Seeds

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Miao-Ling Lin

2004-12-01

Full Text Available During seed germination of Justicia procumbens, the formation of lithocysts, trichomes and diacytic stomata in the epidermis of cotyledons was following a specific distribution pattern. During the first 1-3 days, many young stomata and trichome initial cells were formed sporadically in the adaxial and abaxial epidermis, but no lithocyst was found. Three to five days after seed sawing, two cotyledons were exposed to light and then opened. In the meantime, some lithocysts were recognized on both adaxial and abaxial epidermises. The lithocysts on the adaxial epidermis occurred in the radially arranged cells located between the central area and the margin. However on the abaxial epidermis, they were found only in the marginal cell layer and their axes were along the margin of cotyledons. The total number of lithocysts in a cotyledon at this stage was 32.2 ± 4.3 and the cystolith inside the lithocyst was spindle in shape and 48.2 ± 21.1 μm in length. Three weeks after seed sowing, the cotyledons were mature and the total number of lithocysts in a cotyledon was 112.2 ± 10.1 and the cystolith in the lithocyst was enlarged to be 119.8 ± 27.8 μm in length. The cystolith was extracellularly formed in the cell wall of lithocyst. Its surface was with many protuberances and surrounded by a cystolith sheath connecting to cytoplasmic strands. The core of cystolith was surrounded by concentrically stratified fibrils and the calcium carbonate was concentrically accumulated. The waved stratified fibrils were also deposited in the protuberances. The EDX spectra showed that the main mineral elemental compositions of cystoliths were Ca and P. Ca was deposited more in the central part of cystolith than in the marginal area.

Cord Blood Chimerism And Relapse After Haplo-Cord Transplantation

Science.gov (United States)

van Besien, Koen; Koshy, Nebu; Gergis, Usama; Mayer, Sebastian; Cushing, Melissa; Rennert, Hannah; Slotky, Ronit; Mark, Tomer; Pearse, Roger; Rossi, Adriana; Phillips, Adrienne; Vasovic, Liljana; Ferrante, Rosanna; Hsu, Michael; Shore, Tsiporah

2018-01-01

Haplo-cord stem cell transplantation combines the infusion of CD34 selected hematopoietic progenitors from a haplo-identical donor with an umbilical cord blood graft from an unrelated donor and allows faster count recovery, with low rates of disease recurrence and chronic GVHD. But the contribution of the umbilical cord blood graft to long-term transplant outcome remains unclear. We analyzed 39 recipients of haplo-cord transplants with AML and MDS, engrafted and in remission at 2 months. Median age was 66 (18-72) and all had intermediate, high, or very high risk disease. Less than 20% UCB chimerism in the CD33 lineage was associated with an increased rate of disease recurrence (54% vs 11% Pdisease recurrence (46% vs 12%, P=0.007) Persistent haplo-chimerism in the CD3 lineage was associated with an increased rate of disease recurrence (40% vs 15%, P=0.009) Chimerism did not predict for treatment related mortality. The cumulative incidence of acute GVHD by day 100 was 43%. The cumulative incidence of moderate/severe chronic GVHD was only 5%. Engraftment of the umbilical cord blood grafts provides powerful GVL effects which protect against disease recurrence and is associated with low risk of chronic GVHD. Engraftment of CD34 selected haplo-identical cells can lead to rapid development of circulating T-cells, but when these cells dominate, GVL-effects are limited and rates of disease recurrence are high. PMID:27333804

Fixed cord in spinal stenosis

International Nuclear Information System (INIS)

Levy, L.M.; Wang, H.; Francomano, C.; Hurko, O.; Carson, B.; Heffez, D.S.; DiChiro, G.; Bryan, R.N.

1990-01-01

This paper evaluates patients with cervical spinal canal compromise due to congenital anomalies (achondroplasia, Chiari malformation) and degenerative diseases using MR cord motion and cerebrospinal fluid (CSF) flow studies. Pulsatile longitudinal motion of the cervical cord was determined by means of cardiac-gated velocity phase contrast methods, including cine. Pathology included dwarfism (n = 15), Chiari malformation (n = 10), spondylosis (n = 10), and acute cord compression (n = 9). Symptomatic cases of congenital cervical stenosis had decreased cord motion, although CSF flow was not always significantly compromised. Postoperative cases demonstrated good cord and CSF motion, unless compression or obstruction was present

Atrial Fibrillation: When the heart is not in rhythm | NIH MedlinePlus the Magazine

Science.gov (United States)

... of this page please turn JavaScript on. Feature: Atrial Fibrillation Atrial Fibrillation: When the heart is not in rhythm Past ... show, Deal With It . Photo: TBS/Deal Understanding Atrial Fibrillation Atrial fibrillation (AFib) is the most common type ...

Ultra-sensitive detection of prion protein fibrils by flow cytometry in blood from cattle affected with bovine spongiform encephalopathy

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Maas Elke

2005-10-01

Full Text Available Abstract Background The definite diagnosis of prion diseases such as Creutzfeldt-Jakob disease (CJD in humans or bovine spongiform encephalopathy (BSE in cattle currently relies on the post mortem detection of the pathological form of the prion protein (PrPSc in brain tissue. Infectivity studies indicate that PrPSc may also be present in body fluids, even at presymptomatic stages of the disease, albeit at concentrations well below the detection limits of currently available analytical methods. Results We developed a highly sensitive method for detecting prion protein aggregates that takes advantage of kinetic differences between seeded and unseeded polymerization of prion protein monomers. Detection of the aggregates was carried out by flow cytometry. In the presence of prion seeds, the association of labelled recombinant PrP monomers in plasma and serum proceeds much more efficiently than in the absence of seeds. In a diagnostic model system, synthetic PrP aggregates were detected down to a concentration of approximately 10-8 nM [0.24 fg/ml]. A specific signal was detected in six out of six available serum samples from BSE-positive cattle. Conclusion We have developed a method based on seed-dependent PrP fibril formation that shows promising results in differentiating a small number of BSE-positive serum samples from healthy controls. This method may provide the basis for an ante mortem diagnostic test for prion diseases.

The safety of flecainide treatment of atrial fibrillation

DEFF Research Database (Denmark)

Almroth, H; Andersson, Torben Bech; Fengsrud, E

2011-01-01

To assess the safety of long-term treatment with flecainide in patients with atrial fibrillation (AF), particularly with regard to sudden cardiac death (SCD) and proarrhythmic events.......To assess the safety of long-term treatment with flecainide in patients with atrial fibrillation (AF), particularly with regard to sudden cardiac death (SCD) and proarrhythmic events....

Surgical Ablation of Atrial Fibrillation Using Energy Sources.

Science.gov (United States)

Brick, Alexandre Visconti; Braile, Domingo Marcolino

2015-01-01

Surgical ablation, concomitant with other operations, is an option for treatment in patients with chronic atrial fibrillation. The aim of this study is to present a literature review on surgical ablation of atrial fibrillation in patients undergoing cardiac surgery, considering energy sources and return to sinus rhythm. A comprehensive survey was performed in the literature on surgical ablation of atrial fibrillation considering energy sources, sample size, study type, outcome (early and late), and return to sinus rhythm. Analyzing studies with immediate results (n=5), the percentage of return to sinus rhythm ranged from 73% to 96%, while those with long-term results (n=20) (from 12 months on) ranged from 62% to 97.7%. In both of them, there was subsequent clinical improvement of patients who underwent ablation, regardless of the energy source used. Surgical ablation of atrial fibrillation is essential for the treatment of this arrhythmia. With current technology, it may be minimally invasive, making it mandatory to perform a procedure in an attempt to revert to sinus rhythm in patients requiring heart surgery.

Anterior spinal cord syndrome of unknown etiology

OpenAIRE

Klakeel, Merrine; Thompson, Justin; Srinivasan, Rajashree; McDonald, Frank

2015-01-01

A spinal cord injury encompasses a physical insult to the spinal cord. In the case of anterior spinal cord syndrome, the insult is a vascular lesion at the anterior spinal artery. We present the cases of two 13-year-old boys with anterior spinal cord syndrome, along with a review of the anatomy and vasculature of the spinal cord and an explanation of how a lesion in the cord corresponds to anterior spinal cord syndrome.

Seed quality in informal seed systems

NARCIS (Netherlands)

Biemond, P.C.

2013-01-01

Keywords: informal seed systems, seed recycling, seed quality, germination, seed pathology, seed health, seed-borne diseases, mycotoxigenic fungi, Fusarium verticillioides, mycotoxins, Vigna unguiculata, Zea mays, Nigeria.

Seed is a crucial input for agricultural production.

Changes in plasma atrial natriuretic factor in patients with idiopathic atrial fibrillation

International Nuclear Information System (INIS)

Du Tongxin; Xia Xiaojie; Qu Wei; Wang Shukui; Sun Junjiang

2002-01-01

To observe the changes in plasma atrial natriuretic factor (AFN) in patients with idiopathic atrial fibrillation and investigate its mechanism, plasma ANF, platelet count and hematocrit were detected in 21 cases with transient idiopathic atrial fibrillation (group A, A1 representing attack, while A2 termination), 28 with persistent idiopathic atrial fibrillation (group B), 27 suffered from rheumatic heart disease with mitral stenosis and persistent atrial fibrillation (group C), 32 with transient supraventricular tachycardia (group D) and 20 normal controls (group E). It was found that the level of ANF was significantly higher in patients with attacking transient idiopathic atrial fibrillation than that in group A2, D and E (P 0.05), while there was significant difference in hematocrit in group A1 compared with group A2, D, E (P < 0.01). It suggested that ANF and hematocrit play an important role in the attack of idiopathic atrial fibrillation

Alcohol consumption and risk of atrial fibrillation

DEFF Research Database (Denmark)

Tolstrup, Janne Schurmann; Wium-Andersen, Marie Kim; Ørsted, David Dynnes

2016-01-01

BACKGROUND: The aim of this study was to test the hypothesis that alcohol consumption, both observational (self-reported) and estimated by genetic instruments, is associated with a risk of atrial fibrillation and to determine whether people with high cardiovascular risk are more sensitive towards...... alcohol than people with low risk. METHODS: We used data for a total of 88,782 men and women from the Copenhagen City Heart Study 1991-1994 and 2001-2003 and the Copenhagen General Population Study 2003-2010. Information on incident cases of atrial fibrillation was obtained from a validated nationwide...... register. As a measure of alcohol exposure, both self-reported consumption and genetic variations in alcohol metabolizing genes (ADH1B/ADH1C) were used as instrumental variables. The endpoint was admission to hospital for atrial fibrillation as recorded in a validated hospital register. RESULTS: A total...

Women Sex Importance in Stroke Patients with Atrial Fibrillation

Directory of Open Access Journals (Sweden)

Cemile Handan Mısırlı

2014-08-01

Full Text Available OBJECTIVE: It was shown the differences in age, risk factors and treatment between women and men in stroke patients with atrial fibrillation METHODS: The stroke patients with atrial fibrillation who were hospitalized in our department at the last 2 years were seperated into 2 groups of aged above 75 and below 75, investigated with CHADS2 and CHA2DS2VASc scores and looked at the sex differences of women and men. RESULTS: Stroke ratio according to sex was statistically meaningful especially in women above the age of 75. Risc factors also were founded in elderly women and CHA2DS2VASc scores were higher in women than men so more anticoagulan treatment were begun. No differences were shown between sexes at lone atrial fibrillation and no treatment were begun. CONCLUSION: Women with atrial fibrillation had more risk factors, higher stroke rate and higher anticoagulation treatment.

Mouse senile amyloid fibrils deposited in skeletal muscle exhibit amyloidosis-enhancing activity.

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Jinze Qian

2010-05-01

Full Text Available Amyloidosis describes a group of protein folding diseases in which amyloid proteins are abnormally deposited in organs and/or tissues as fine fibrils. Mouse senile amyloidosis is a disorder in which apolipoprotein A-II (apoA-II deposits as amyloid fibrils (AApoAII and can be transmitted from one animal to another both by the feces and milk excreted by mice with amyloidosis. Thus, mouse AApoAII amyloidosis has been demonstrated to be a "transmissible disease". In this study, to further characterize the transmissibility of amyloidosis, AApoAII amyloid fibrils were injected into transgenic Apoa2(cTg(+/- and normal R1.P1-Apoa2(c mice to induce AApoAII systemic amyloidosis. Two months later, AApoAII amyloid deposits were found in the skeletal muscles of amyloid-affected mice, primarily in the blood vessels and in the interstitial tissues surrounding muscle fibers. When amyloid fibrils extracted from the skeletal muscles were subjected to Western blot analysis, apoA-II was detected. Amyloid fibril fractions isolated from the muscles not only demonstrated the structure of amyloid fibrils but could also induce amyloidosis in young mice depending on its fibril conformation. These findings present a possible pathogenesis of amyloidosis: transmission of amyloid fibril conformation through muscle, and shed new light on the etiology involved in amyloid disorders.

Atrial Fibrillation and Gastro-Oesophageal Reflux Disease - Controversies and Challenges.

Science.gov (United States)

Floria, Mariana; Barboi, Oana; Rezus, Ciprian; Ambarus, Valentin; Cijevschi-Prelipcean, Cristina; Balan, Gheorghe; Drug, Vasile Liviu

2015-01-01

Atrial fibrillation and gastro-oesophageal reflux are common manifestations in daily practice. The atria and the oesophagus are closely located and have similar nerve innervations. Over the last years, it has been observed that atrial fibrillation development and reflux disease could be related. Atrial fibrillation occurrence could be due to vagal nerve overstimulation. This, in association with vagal nerve-mediated parasympathetic stimulation, has also been observed in patients with gastro-oesophageal reflux. These mechanisms, in addition to inflammation, seem to be implicated in the pathophysiology of both diseases. Despite these associations supported by clinical and experimental studies, this relationship is still considered controversial. This review summarizes critical data regarding the association of gastro-oesophageal reflux and atrial fibrillation as well as their clinical implications.

Spinal cord injury with central cord syndrome from surfing.

Science.gov (United States)

Steinfeld, Yaniv; Keren, Yaniv; Haddad, Elias

2018-01-01

Central cord syndrome (CCS) is an injury to the center of the spinal cord. It is well known as a hyperextension injury, but it has never been described as a surfing injury. Our report describes this injury in detail. A 35-year-old male novice surfer presented to the emergency department with acute tetraplegia following falling off his surfboard and hitting sea floor at a shallow beach break. He was rescued by a fellow surfer while floating in the sea and unable to raise his head above sea level. Upon arrival at the hospital, tetraplegia and sensory deficits were noted. Radiological investigations showed advanced spinal stenosis at C4-6 levels. T2 magnetic resonance imaging (MRI) demonstrated myelopathy at C5-C6 level. He was diagnosed as having central cord syndrome, treated conservatively, and regained near full neurologic recovery after a month of rehabilitation. Unique sport activities lead to unique injuries. It is important to accurately describe these injuries in order to create protective measures against them. Neurologic injuries in surfers are uncommon. With low-energy trauma, surfer's myelopathy is still the most common diagnosis, but central cord syndrome should be in the differential diagnosis.

Risk of atrial fibrillation in diabetes mellitus: A nationwide cohort study.

Science.gov (United States)

Pallisgaard, Jannik L; Schjerning, Anne-Marie; Lindhardt, Tommi B; Procida, Kristina; Hansen, Morten L; Torp-Pedersen, Christian; Gislason, Gunnar H

2016-04-01

Diabetes has been associated with atrial fibrillation but the current evidence is conflicting. In particular knowledge regarding young diabetes patients and the risk of developing atrial fibrillation is sparse. The aim of our study was to investigate the risk of atrial fibrillation in patients with diabetes compared to the background population in Denmark. Through Danish nationwide registries we included persons above 18 years of age and without prior atrial fibrillation and/or diabetes from 1996 to 2012. The study cohort was divided into a background population without diabetes and a diabetes group. The absolute risk of developing atrial fibrillation was calculated and Poisson regression models adjusted for sex, age and comorbidities were used to calculate incidence rate ratios of atrial fibrillation. The total study cohort included 5,081,087 persons, 4,827,713 (95%) in the background population and 253,374 (5%) in the diabetes group. Incidence rates of atrial fibrillation per 1000 person years were stratified in four age groups from 18 to 39, 40 to 64, 65 to 74 and 75 to 100 years giving incidence rates (95% confidence intervals) of 0.02 (0.02-0.02), 0.99 (0.98-1.01), 8.89 (8.81-8.98) and 20.0 (19.9-20.2) in the background population and 0.13 (0.09-0.20), 2.10 (2.00-2.20), 8.41 (8.10-8.74) and 20.1 (19.4-20.8) in the diabetes group, respectively. The adjusted incidence rate ratios in the diabetes group with the background population as reference were 2.34 (1.52-3.60), 1.52 (1.47-1.56), 1.20 (1.18-1.23) and 0.99 (0.97-1.01) in the four age groups, respectively. Diabetes is an independent risk factor for developing atrial fibrillation/flutter, most pronounced in young diabetes patients. Routine screening for atrial fibrillation/flutter in diabetes patients might be beneficial and have therapeutic implications, especially in younger diabetes patients. Diabetes increases the risk of developing atrial fibrillation and especially young diabetes patients have a high

Optimal method for collection of umbilical cord blood: an Egyptian trial for a public cord blood bank.

Science.gov (United States)

Bassiouny, M R; El-Chennawi, F; Mansour, A K; Yahia, S; Darwish, A

2015-06-01

Umbilical cord blood (UCB) contains stem cells and can be used as an alternative to bone marrow transplantation. Engraftment is dependent on the total nucleated cell (TNC) and CD34+ cell counts of the cord blood units. This study was designed to evaluate the effect of the method of collection of the UCB on the yield of the cord blood units. Informed consent was obtained from 100 eligible mothers for donation of cord blood. Both in utero and ex utero methods were used for collection. The cord blood volume was measured. The TNC and the CD34+ cell counts were enumerated. We have found that in utero collection gave significantly larger volumes of cord blood and higher TNC counts than ex utero collection. There was no significant difference between both methods regarding the CD34+ cell counts. This study revealed a significant correlation between the volume of the collected cord blood and both TNC and CD34+ cell counts. It is better to collect cord blood in utero before placental delivery to optimize the quality of the cord blood unit. © 2015 AABB.

MAK33 antibody light chain amyloid fibrils are similar to oligomeric precursors.

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Manuel Hora

Full Text Available Little structural information is available so far on amyloid fibrils consisting of immunoglobulin light chains. It is not understood which features of the primary sequence of the protein result in fibril formation. We report here MAS solid-state NMR studies to identify the structured core of κ-type variable domain light chain fibrils. The core contains residues of the CDR2 and the β-strands D, E, F and G of the native immunoglobulin fold. The assigned core region of the fibril is distinct in comparison to the core identified in a previous solid-state NMR study on AL-09 by Piehl at. al, suggesting that VL fibrils can adopt different topologies. In addition, we investigated a soluble oligomeric intermediate state, previously termed the alternatively folded state (AFS, using NMR and FTIR spectroscopy. The NMR oligomer spectra display a high degree of similarity when compared to the fibril spectra, indicating a high structural similarity of the two aggregation states. Based on comparison to the native state NMR chemical shifts, we suggest that fibril formation via domain-swapping seems unlikely. Moreover, we used our results to test the quality of different amyloid prediction algorithms.

New risk factors for atrial fibrillation : causes of 'not-so-lone atrial fibrillation'

NARCIS (Netherlands)

Schoonderwoerd, Bas A.; Smit, Marcelle D.; Pen, Lucas; Van Gelder, Isabelle C.

Atrial fibrillation (AF) is a prevalent arrhythmia in patients with cardiovascular disease. The classical risk factors for developing AF include hypertension, valvular disease, (ischaemic) cardiomyopathy, diabetes mellitus, and thyroid disease. In some patients with AF, no underlying

Observation of the efficacy of radiofrequency catheter ablation on patients with different forms of atrial fibrillation.

Science.gov (United States)

Zhao, R-C; Han, W; Han, J; Yu, J; Guo, J; Fu, J-L; Li, Z; Zhao, R-Z

2016-10-01

To study the efficacy and safety of radiofrequency catheter ablation (RFCA) in patients with different forms of atrial fibrillation. By retrospective analysis, we summarize 720 cases, where patients diagnosed with atrial fibrillation in our hospital were treated with RFCA from February 2010 to October 2014. Among the cases, 425 were diagnosed with paroxysmal atrial fibrillation and 295 with non-paroxysmal atrial fibrillation (including persistent atrial fibrillation and permanent atrial fibrillation). All patients were followed up until June 2015 to compare and analyze the differences in operation success rates, complications and recurrence rates. 395 cases (92.9%) of paroxysmal atrial fibrillation and 253 cases (85.8%) with non-paroxysmal atrial fibrillation were subject to surgery and followed up. The age of onset, disease course, underlying diseases, left atrial diameter and combined anti-arrhythmics of patients with paroxysmal atrial fibrillation were lower than those of patients with non-paroxysmal atrial fibrillation, and the differences were statistically significant (p success rate of the first ablation was higher than that of non-paroxysmal atrial fibrillation. Procedure time, procedure method, complications and recurrence rate of patients with paroxysmal atrial fibrillation were lower than those of non-paroxysmal atrial fibrillation group, and the differences were statistically significant (p failure caused by atrial fibrillation in the two groups, the difference was not statistically significant (Apoplexy: p = 0.186; Heart failure: p = 0.170). The individual ablation success rate was higher for paroxysmal atrial fibrillation, and long-term follow-up showed that the occurrence of apoplexy and heart failure was not different from the non-paroxysmal atrial fibrillation group.

Assembly of α-synuclein fibrils in nanoscale studied by peptide truncation and AFM

International Nuclear Information System (INIS)

Zhang Feng; Lin Xiaojing; Ji Lina; Du Haining; Tang Lin; He Jianhua; Hu Jun; Hu Hongyu

2008-01-01

α-Synuclein (α-Syn) fibrils are the major component of Lewy bodies that are closely associated with the pathogenesis of Parkinson's disease, but the mechanism for the fibril assembly remains poorly understood. Here we report using a combination of peptide truncation and atomic force microscopy (AFM) to elucidate the self-assembly and morphology of the α-Syn fibrils. The results show that protease K significantly slims the fibrils from the mean height of ∼6.6 to ∼4.7 nm, whereas chaotropic denaturant urea completely breaks down the fibrils into small particles. The in situ enzymatic digestion also results in thinning of the fibrils, giving rise to some nicks on the fibrils. Moreover, N- or C-terminally truncated α-Syn fragments assemble into thinner filaments with the heights depending on the peptide lengths. A nine-residue peptide corresponding to the homologous GAV-motif sequence can form very thin (∼2.2 nm) but long (>1 μm) filaments. Thus, the central sequence of α-Syn forms a fibrillar core by cross-β-structure that is flanked by two flexible termini, and the orientation of the fibril growth is perpendicular to the β-sheet structures

Determination of collagen fibril structure and orientation in connective tissues by X-ray diffraction

Science.gov (United States)

Wilkinson, S. J.; Hukins, D. W. L.

1999-08-01

Elastic scattering of X-rays can provide the following information on the fibrous protein collagen: its molecular structure, the axial arrangement of rod-like collagen molecules in a fibril, the lateral arrangement of molecules within a fibril, and the orientation of fibrils within a biological tissue. The first part of the paper reviews the principles involved in deducing this information. The second part describes a new computer program for measuring the equatorial intensity distribution, that provides information on the lateral arrangement of molecules within a fibril, and the angular distribution of the equatorial peaks that provides information on the orientation of fibrils. Orientation of fibrils within a tissue is quantified by the orientation distribution function, g( φ), which represents the probability of finding a fibril oriented between φ and φ+ δφ. The application of the program is illustrated by measurement of g( φ) for the collagen fibrils in demineralised cortical bone from cow tibia.

Decision-making interventions to stop the global atrial fibrillation-related stroke tsunami.

Science.gov (United States)

Cerasuolo, Joshua O; Montero-Odasso, Manuel; Ibañez, Agustin; Doocy, Shannon; Lip, Gregory Yh; Sposato, Luciano A

2017-04-01

Atrial fibrillation affects 33.5 million people worldwide and its prevalence is expected to double by 2050 because of the aging population. Atrial fibrillation confers a 5-fold higher risk of ischemic stroke compared to sinus rhythm. We present our view of the role of shared medical decision-making to combat global underutilization of oral anticoagulation for stroke prevention in atrial fibrillation patients. Oral anticoagulation underuse is widespread as it is present within atrial fibrillation patients of all risk strata and in countries across all income levels. Reasons for oral anticoagulation underuse include but are probably not limited to poor risk stratification, over-interpretation of contraindications, and discordance between physician prescription preferences and actual administration. By comparing a catastrophic event to the consequences of atrial fibrillation related strokes, it may help physicians and patients understand the negative outcomes associated with oral anticoagulation under-utilization and the magnitude to which oral anticoagulations neutralize atrial fibrillation burden.

Role of sequence and structural polymorphism on the mechanical properties of amyloid fibrils.

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Gwonchan Yoon

Full Text Available Amyloid fibrils playing a critical role in disease expression, have recently been found to exhibit the excellent mechanical properties such as elastic modulus in the order of 10 GPa, which is comparable to that of other mechanical proteins such as microtubule, actin filament, and spider silk. These remarkable mechanical properties of amyloid fibrils are correlated with their functional role in disease expression. This suggests the importance in understanding how these excellent mechanical properties are originated through self-assembly process that may depend on the amino acid sequence. However, the sequence-structure-property relationship of amyloid fibrils has not been fully understood yet. In this work, we characterize the mechanical properties of human islet amyloid polypeptide (hIAPP fibrils with respect to their molecular structures as well as their amino acid sequence by using all-atom explicit water molecular dynamics (MD simulation. The simulation result suggests that the remarkable bending rigidity of amyloid fibrils can be achieved through a specific self-aggregation pattern such as antiparallel stacking of β strands (peptide chain. Moreover, we have shown that a single point mutation of hIAPP chain constituting a hIAPP fibril significantly affects the thermodynamic stability of hIAPP fibril formed by parallel stacking of peptide chain, and that a single point mutation results in a significant change in the bending rigidity of hIAPP fibrils formed by antiparallel stacking of β strands. This clearly elucidates the role of amino acid sequence on not only the equilibrium conformations of amyloid fibrils but also their mechanical properties. Our study sheds light on sequence-structure-property relationships of amyloid fibrils, which suggests that the mechanical properties of amyloid fibrils are encoded in their sequence-dependent molecular architecture.

How does domain replacement affect fibril formation of the rabbit/human prion proteins.

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Xu Yan

Full Text Available It is known that in vivo human prion protein (PrP have the tendency to form fibril deposits and are associated with infectious fatal prion diseases, while the rabbit PrP does not readily form fibrils and is unlikely to cause prion diseases. Although we have previously demonstrated that amyloid fibrils formed by the rabbit PrP and the human PrP have different secondary structures and macromolecular crowding has different effects on fibril formation of the rabbit/human PrPs, we do not know which domains of PrPs cause such differences. In this study, we have constructed two PrP chimeras, rabbit chimera and human chimera, and investigated how domain replacement affects fibril formation of the rabbit/human PrPs.As revealed by thioflavin T binding assays and Sarkosyl-soluble SDS-PAGE, the presence of a strong crowding agent dramatically promotes fibril formation of both chimeras. As evidenced by circular dichroism, Fourier transform infrared spectroscopy, and proteinase K digestion assays, amyloid fibrils formed by human chimera have secondary structures and proteinase K-resistant features similar to those formed by the human PrP. However, amyloid fibrils formed by rabbit chimera have proteinase K-resistant features and secondary structures in crowded physiological environments different from those formed by the rabbit PrP, and secondary structures in dilute solutions similar to the rabbit PrP. The results from transmission electron microscopy show that macromolecular crowding caused human chimera but not rabbit chimera to form short fibrils and non-fibrillar particles.We demonstrate for the first time that the domains beyond PrP-H2H3 (β-strand 1, α-helix 1, and β-strand 2 have a remarkable effect on fibrillization of the rabbit PrP but almost no effect on the human PrP. Our findings can help to explain why amyloid fibrils formed by the rabbit PrP and the human PrP have different secondary structures and why macromolecular crowding has different

Screening for Atrial Fibrillation

DEFF Research Database (Denmark)

Freedman, Ben; Camm, John; Calkins, Hugh

2017-01-01

Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed...

Michler’s Hydrol Blue: A Sensitive Probe for Amyloid Fibril Detection

KAUST Repository

Kitts, Catherine C.

2011-05-03

Michler\\'s hydrol blue (MHB) is investigated with respect to photophysical properties in varied solvent environment and when bound to insulin and lysozyme fibrils. The MHB chromophore is shown to act like a molecular rotor and bind well to amyloid fibrils, where it exhibits a characteristic red-shift in its excitation spectrum and an increase in the emission quantum yield upon binding. MHB is more sensitive to environmental changes than Thioflavin T (ThT) and furthermore, in contrast to the latter amyloid probe, can differentiate between insulin and lysozyme fibrils by a more red-shifted excitation spectrum for insulin fibrils. To support the experimental observations, time-dependent density functional theory (TDDFT) calculations were performed on MHB at several levels of theory. The predicted changes of spectral properties as a function of the environment are in good agreement with the experimental results. Linear dichroism (LD) is used to determine the orientation of the MHB within the fibrils. It was shown through LD and molecular modeling that MHB aligns itself preferentially parallel with the amyloid fiber at an angle of 14°-22° to the fibril axis and along the grooves of the β-sheet. © 2011 American Chemical Society.

Conjugated Quantum Dots Inhibit the Amyloid β (1–42 Fibrillation Process

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Garima Thakur

2011-01-01

Full Text Available Nanoparticles have enormous potential in diagnostic and therapeutic studies. We have demonstrated that the amyloid beta mixed with and conjugated to dihydrolipoic acid- (DHLA capped CdSe/ZnS quantum dots (QDs of size approximately 2.5 nm can be used to reduce the fibrillation process. Transmission electron microscopy (TEM and atomic force microscopy (AFM were used as tools for analysis of fibrillation. There is a significant change in morphology of fibrils when amyloid β (1–42 (Aβ (1–42 is mixed or conjugated to the QDs. The length and the width of the fibrils vary under modified conditions. Thioflavin T (ThT fluorescence supports the decrease in fibril formation in presence of DHLA-capped QDs.

Salbutamol Abuse is Associated with Ventricular Fibrillation

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Emin UYSAL

2015-06-01

Full Text Available SUMMARY: Salbutamol-induced cardiac complications are well-established. Herein, we describe a case of a 24-year female who was admitted to the emergency department because of a suicide attempt with salbutamol (76 mg. Salbutamol abuse induced the development of supraventricular tachycardia and ventricular fibrillation. Regular sinus rhythm was restored with defibrillation. The hypokalemic patient who stayed in the intensive care unit was discharged after 48 hours of hospitalization. Key words: Salbutamol, suicide, ventricular fibrillation

Evidence for novel beta-sheet structures in Iowa mutant beta-amyloid fibrils.

Science.gov (United States)

Tycko, Robert; Sciarretta, Kimberly L; Orgel, Joseph P R O; Meredith, Stephen C

2009-07-07

Asp23-to-Asn mutation within the coding sequence of beta-amyloid, called the Iowa mutation, is associated with early onset, familial Alzheimer's disease and cerebral amyloid angiopathy, in which patients develop neuritic plaques and massive vascular deposition predominantly of the mutant peptide. We examined the mutant peptide, D23N-Abeta40, by electron microscopy, X-ray diffraction, and solid-state NMR spectroscopy. D23N-Abeta40 forms fibrils considerably faster than the wild-type peptide (k = 3.77 x 10(-3) min(-1) and 1.07 x 10(-4) min(-1) for D23N-Abeta40 and the wild-type peptide WT-Abeta40, respectively) and without a lag phase. Electron microscopy shows that D23N-Abeta40 forms fibrils with multiple morphologies. X-ray fiber diffraction shows a cross-beta pattern, with a sharp reflection at 4.7 A and a broad reflection at 9.4 A, which is notably smaller than the value for WT-Abeta40 fibrils (10.4 A). Solid-state NMR measurements indicate molecular level polymorphism of the fibrils, with only a minority of D23N-Abeta40 fibrils containing the in-register, parallel beta-sheet structure commonly found in WT-Abeta40 fibrils and most other amyloid fibrils. Antiparallel beta-sheet structures in the majority of fibrils are indicated by measurements of intermolecular distances through (13)C-(13)C and (15)N-(13)C dipole-dipole couplings. An intriguing possibility exists that there is a relationship between the aberrant structure of D23N-Abeta40 fibrils and the unusual vasculotropic clinical picture in these patients.

[Atrial fibrillation as consequence and cause of structural changes of atria].

Science.gov (United States)

Aparina, O P; Chikhireva, L N; Stukalova, O V; Mironova, N A; Kashtanova, S Iu; Ternovoĭ, S K; Golitsyn, S P

2014-01-01

Changes of atrial structure and function are the contributors of atrial fibrillation clinical course, complications and treatment effectiveness. Effects of inflammation and mechanical stretch on atrial structural remodeling leading to atrial fibrillation are reviewed in the article. Contemporary invasive and non-invasive methods of evaluation (including late gadolinium enhancement magnetic resonance imaging) of patients with atrial structural remodeling in atrial fibrillation are also described.

Arterial Blood Supply to the Spinal Cord in Animal Models of Spinal Cord Injury. A Review.

Science.gov (United States)

Mazensky, David; Flesarova, Slavka; Sulla, Igor

2017-12-01

Animal models are used to examine the results of experimental spinal cord injury. Alterations in spinal cord blood supply caused by complex spinal cord injuries contribute significantly to the diversity and severity of the spinal cord damage, particularly ischemic changes. However, the literature has not completely clarified our knowledge of anatomy of the complex three-dimensional arterial system of the spinal cord in experimental animals, which can impede the translation of experimental results to human clinical applications. As the literary sources dealing with the spinal cord arterial blood supply in experimental animals are limited and scattered, the authors performed a review of the anatomy of the arterial blood supply to the spinal cord in several experimental animals, including pigs, dogs, cats, rabbits, guinea pigs, rats, and mice and created a coherent format discussing the interspecies differences. This provides researchers with a valuable tool for the selection of the most suitable animal model for their experiments in the study of spinal cord ischemia and provides clinicians with a basis for the appropriate translation of research work to their clinical applications. Anat Rec, 300:2091-2106, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

SDS-Induced Fibrillation of α-Synuclein

DEFF Research Database (Denmark)

Giehm, L.; Oliveira, Cristiano Luis Pinto De; Pedersen, J.S.

2010-01-01

. In this fibrillogenic complex, 4 αSN molecules initially associate with 40-50 SDS molecules to form a shared micelle that gradually grows in size. The complex initially exhibits a mixture of random coil and α-helix, but incubation results in a structural conversion into β-sheet structure and concomitant formation......-stabilized micelles. Thus, fibrillation in this case occurs by a process of continuous accretion rather than by the rate-limiting accumulation of a distinct nucleus. The morphology of the SDS-induced fibrils does not exhibit the classical rod-like structures formed by αSN when aggregated by agitation in the absence...

Atrial fibrillation and risk of stroke

DEFF Research Database (Denmark)

Christiansen, Christine Benn; Gerds, Thomas A.; Olesen, Jonas Bjerring

2016-01-01

AIM: Although the relation between stroke risk factors and stroke in patients with atrial fibrillation (AF) has been extensively examined, only few studies have explored the association of AF and the risk of ischaemic stroke/systemic thromboembolism/transient ischaemic attack (stroke.......5-10.6), and 15.4% (14.5-16.4), respectively. CONCLUSIONS: Stroke/TE/TIA risk was particularly increased when prior stroke/TE/TIA was present. Atrial fibrillation is associated with an increase in risk of stroke/TE/TIA in the absence of other risk factors but only a moderate increase in risk when other risk...

Initiation of anticoagulation in atrial fibrillation

DEFF Research Database (Denmark)

Gundlund, A.; Staerk, L.; Fosbøl, E. L.

2017-01-01

Background: The use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prophylaxis in atrial fibrillation (AF) is increasing rapidly. We compared characteristics of AF patients initiated on NOACs versus vitamin K antagonists (VKAs). Methods: Using Danish nationwide registry data, we...... compared with a VKA [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.28–1.43]. By contrast, patients with a history of myocardial infarction were less likely to be initiated on a NOAC compared with a VKA (OR 0.72, 95% CI 0.67–0.77). Conclusions: Atrial fibrillation patients who were initiated...

A biomechanical model for fibril recruitment: Evaluation in tendons and arteries.

Science.gov (United States)

Bevan, Tim; Merabet, Nadege; Hornsby, Jack; Watton, Paul N; Thompson, Mark S

2018-06-06

Simulations of soft tissue mechanobiological behaviour are increasingly important for clinical prediction of aneurysm, tendinopathy and other disorders. Mechanical behaviour at low stretches is governed by fibril straightening, transitioning into load-bearing at recruitment stretch, resulting in a tissue stiffening effect. Previous investigations have suggested theoretical relationships between stress-stretch measurements and recruitment probability density function (PDF) but not derived these rigorously nor evaluated these experimentally. Other work has proposed image-based methods for measurement of recruitment but made use of arbitrary fibril critical straightness parameters. The aim of this work was to provide a sound theoretical basis for estimating recruitment PDF from stress-stretch measurements and to evaluate this relationship using image-based methods, clearly motivating the choice of fibril critical straightness parameter in rat tail tendon and porcine artery. Rigorous derivation showed that the recruitment PDF may be estimated from the second stretch derivative of the first Piola-Kirchoff tissue stress. Image-based fibril recruitment identified the fibril straightness parameter that maximised Pearson correlation coefficients (PCC) with estimated PDFs. Using these critical straightness parameters the new method for estimating recruitment PDF showed a PCC with image-based measures of 0.915 and 0.933 for tendons and arteries respectively. This method may be used for accurate estimation of fibril recruitment PDF in mechanobiological simulation where fibril-level mechanical parameters are important for predicting cell behaviour. Copyright © 2018 Elsevier Ltd. All rights reserved.

Seed regulations and local seed systems

NARCIS (Netherlands)

Louwaars, N.

2000-01-01

Seed regulations have been introduced in most countries based on the development of formal seed production. Concerns about seed quality and about the varietal identity of the seeds have commonly led to seed laws. However, formal regulations are often inappropriate for informal seed systems, which

Fibril morphology and tendon mechanical properties in patellar tendinopathy: effects of heavy slow resistance training

DEFF Research Database (Denmark)

Kongsgaard, Mads; Qvortrup, Klaus; Larsen, Jytte Overgaard

2010-01-01

BACKGROUND: Patellar tendinopathy is characterized by pathologic abnormalities. Heavy slow resistance training (HSR) is effective in the management of patellar tendinopathy, but the underlying functional mechanisms remain elusive. PURPOSE: To investigate fibril morphology and mechanical properties...... assessed symptoms/function and maximal tendon pain during activity. Tendon biopsy samples were analyzed for fibril density, volume fraction, and mean fibril area. Tendon mechanical properties were assessed using force and ultrasonography samplings. RESULTS: Patients improved in symptoms/function (P = .02...... area decreased (-26% +/- 21%, P = .04) in tendinopathic tendons after HSR. CONCLUSION: Fibril morphology is abnormal in tendinopathy, but tendon mechanical properties are not. Clinical improvements after HSR were associated with changes in fibril morphology toward normal fibril density and mean fibril...

SPINAL CORD- A CADAVERIC STUDY

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Vijayamma K. N

2018-01-01

Full Text Available BACKGROUND Spinal cord is situated within the vertebral canal extending from the lower end of the medulla oblongata at the upper border of first cervical vertebra. In early foetal life, it extends throughout the length of the vertebral canal, and at the time of birth, it reaches the level of third lumbar vertebra. In adult, it ends at the lower border of first lumbar vertebra and thereafter continued as filum terminale, which gets attached to tip of coccyx. Spinal cord is covered by three protective membranes called spinal meninges, diameter, arachnoid and pia mater. The diameter and arachnoid mater extent up to second sacral vertebra and the pia mater forms filum terminale and extend at the tip of coccyx. MATERIALS AND METHODS Forty spinal cord cadaveric specimen were studied by dissection method after exposing the vertebral canal. The roots of spinal nerve were sectioned on both sides and the cord is released along with its coverings. The dura and arachnoid mater were incised longitudinally and the subarachnoid space, blood vessels, nerve roots, ligament denticulata, cervical and lumbar enlargements were observed. The blood vessels including radicular arteries were also studied photographed. RESULTS The spinal cord is a highly vascular structure situated within the vertebral canal, covered by diameter, arachnoid mater and pia mater. Spinal dura is thicker anteriorly than posteriorly. The pia mater forms linea splendens, which extend along the whole length of the cord in front of the anterior median fissure. The average length of the cord is 38 cm. The length and breadth of cervical enlargement was more compared to lumbar enlargement. The number of rootlets in both dorsal and ventral roots accounts more in cervical compared to other regions of the cord. The ligament denticulata is a thin transparent bands of pia mater attached on either sides of the cord between the dorsal and ventral roots of spinal nerves. The tooth like extensions are well

Is Supramolecular Filament Chirality the Underlying Cause of Major Morphology Differences in Amyloid Fibrils?

Science.gov (United States)

2015-01-01

The unique enhanced sensitivity of vibrational circular dichroism (VCD) to the formation and development of amyloid fibrils in solution is extended to four additional fibril-forming proteins or peptides where it is shown that the sign of the fibril VCD pattern correlates with the sense of supramolecular filament chirality and, without exception, to the dominant fibril morphology as observed in AFM or SEM images. Previously for insulin, it has been demonstrated that the sign of the VCD band pattern from filament chirality can be controlled by adjusting the pH of the incubating solution, above pH 2 for “normal” left-hand-helical filaments and below pH 2 for “reversed” right-hand-helical filaments. From AFM or SEM images, left-helical filaments form multifilament braids of left-twisted fibrils while the right-helical filaments form parallel filament rows of fibrils with a flat tape-like morphology, the two major classes of fibril morphology that from deep UV resonance Raman scattering exhibit the same cross-β-core secondary structure. Here we investigate whether fibril supramolecular chirality is the underlying cause of the major morphology differences in all amyloid fibrils by showing that the morphology (twisted versus flat) of fibrils of lysozyme, apo-α-lactalbumin, HET-s (218–289) prion, and a short polypeptide fragment of transthyretin, TTR (105–115), directly correlates to their supramolecular chirality as revealed by VCD. The result is strong evidence that the chiral supramolecular organization of filaments is the principal underlying cause of the morphological heterogeneity of amyloid fibrils. Because fibril morphology is linked to cell toxicity, the chirality of amyloid aggregates should be explored in the widely used in vitro models of amyloid-associated diseases. PMID:24484302

Is supramolecular filament chirality the underlying cause of major morphology differences in amyloid fibrils?

Science.gov (United States)

Kurouski, Dmitry; Lu, Xuefang; Popova, Ludmila; Wan, William; Shanmugasundaram, Maruda; Stubbs, Gerald; Dukor, Rina K; Lednev, Igor K; Nafie, Laurence A

2014-02-12

The unique enhanced sensitivity of vibrational circular dichroism (VCD) to the formation and development of amyloid fibrils in solution is extended to four additional fibril-forming proteins or peptides where it is shown that the sign of the fibril VCD pattern correlates with the sense of supramolecular filament chirality and, without exception, to the dominant fibril morphology as observed in AFM or SEM images. Previously for insulin, it has been demonstrated that the sign of the VCD band pattern from filament chirality can be controlled by adjusting the pH of the incubating solution, above pH 2 for "normal" left-hand-helical filaments and below pH 2 for "reversed" right-hand-helical filaments. From AFM or SEM images, left-helical filaments form multifilament braids of left-twisted fibrils while the right-helical filaments form parallel filament rows of fibrils with a flat tape-like morphology, the two major classes of fibril morphology that from deep UV resonance Raman scattering exhibit the same cross-β-core secondary structure. Here we investigate whether fibril supramolecular chirality is the underlying cause of the major morphology differences in all amyloid fibrils by showing that the morphology (twisted versus flat) of fibrils of lysozyme, apo-α-lactalbumin, HET-s (218-289) prion, and a short polypeptide fragment of transthyretin, TTR (105-115), directly correlates to their supramolecular chirality as revealed by VCD. The result is strong evidence that the chiral supramolecular organization of filaments is the principal underlying cause of the morphological heterogeneity of amyloid fibrils. Because fibril morphology is linked to cell toxicity, the chirality of amyloid aggregates should be explored in the widely used in vitro models of amyloid-associated diseases.

Optogenetics of the Spinal Cord: Use of Channelrhodopsin Proteins for Interrogation of Spinal Cord Circuits.

Science.gov (United States)

Rahman, Habibur; Nam, Youngpyo; Kim, Jae-Hong; Lee, Won-Ha; Suk, Kyoungho

2017-12-29

Spinal cord circuits play a key role in receiving and transmitting somatosensory information from the body and the brain. They also contribute to the timing and coordination of complex patterns of movement. Under disease conditions, such as spinal cord injury and neuropathic pain, spinal cord circuits receive pain signals from peripheral nerves, and are involved in pain development via neurotransmitters and inflammatory mediators released from neurons and glial cells. Despite the importance of spinal cord circuits in sensory and motor functions, many questions remain regarding the relationship between activation of specific cells and behavioral responses. Optogenetics offers the possibility of understanding the complex cellular activity and mechanisms of spinal cord circuits, as well as having therapeutic potential for addressing spinal cord-related disorders. In this review, we discuss recent findings in optogenetic research employing the channelrhodopsin protein to assess the function of specific neurons and glia in spinal cord circuits ex vivo and in vivo. We also explore the possibilities and challenges of employing optogenetics technology in future therapeutic strategies for the treatment of spinal disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Vocal cord dysfunction in children.

Science.gov (United States)

Noyes, Blakeslee E; Kemp, James S

2007-06-01

Vocal cord dysfunction is characterised by paradoxical vocal cord adduction that occurs during inspiration, resulting in symptoms of dyspnoea, wheeze, chest or throat tightness and cough. Although the condition is well described in children and adults, confusion with asthma often triggers the use of an aggressive treatment regimen directed against asthma. The laryngoscopic demonstration of vocal cord adduction during inspiration has been considered the gold standard for the diagnosis of vocal cord dysfunction, but historical factors and pulmonary function findings may provide adequate clues to the correct diagnosis. Speech therapy, and in some cases psychological counselling, is often beneficial in this disorder. The natural course and prognosis of vocal cord dysfunction are still not well described in adults or children.

Banking on cord blood stem cells.

Science.gov (United States)

Sullivan, Michael J

2008-07-01

Umbilical cord blood gifted to non-profit public cord blood banks is now routinely used as an alternative source of haematopoietic stem cells for allogeneic transplantation for children and adults with cancer, bone marrow failure syndromes, haemoglobinopathies and many genetic metabolic disorders. Because of the success and outcomes of public cord banking, many companies now provide private cord banking services. However, in the absence of any published transplant evidence to support autologous and non-directed family banking, commercial cord banks currently offer a superfluous service.

Spinal Cord Dysfunction (SCD)

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Department of Veterans Affairs — The Spinal Cord Dysfunction (SCD) module supports the maintenance of local and national registries for the tracking of patients with spinal cord injury and disease...

Picosecond dissociation of amyloid fibrils with infrared laser: A nonequilibrium simulation study

Energy Technology Data Exchange (ETDEWEB)

Hoang Viet, Man; Roland, Christopher, E-mail: cmroland@ncsu.edu; Sagui, Celeste, E-mail: sagui@ncsu.edu [Department of Physics, North Carolina State University, Raleigh, North Carolina 27695-8202 (United States); Derreumaux, Philippe; Nguyen, Phuong H., E-mail: phuong.nguyen@ibpc.fr [Laboratoire de Biochimie Théorique, UPR 9080, CNRS Université Denis Diderot, Sorbonne Paris Cité IBPC, 13 rue Pierre et Marie Curie, 75005 Paris (France); Li, Mai Suan [Institute of Physics, Polish Academy of Sciences, Al. Lotnikow 32/46, 02-668 Warsaw (Poland); Institute for Computational Science and Technology, SBI Building, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City (Viet Nam)

2015-10-21

Recently, mid-infrared free-electron laser technology has been developed to dissociate amyloid fibrils. Here, we present a theoretical framework for this type of experiment based on laser-induced nonequilibrium all-atom molecular dynamics simulations. We show that the fibril is destroyed due to the strong resonance between its amide I vibrational modes and the laser field. The effects of laser irradiation are determined by a balance between fibril formation and dissociation. While the overall rearrangements of the fibril finish over short time scales, the interaction between the peptides and the solvent continues over much longer times indicating that the waters play an important role in the dissociation process. Our results thus provide new insights into amyloid fibril dissociation by laser techniques and open up new venues to investigate the complex phenomena associated with amyloidogenesis.

Intracellular Calcium Dynamics and Autonomic Stimulation in Atrial Fibrillation: Mechanisms and Implications

Directory of Open Access Journals (Sweden)

Chung-Chuan Chou, MD

2008-01-01

Full Text Available While atrial fibrillation is characterized by the co-existence of multiple activation waves within the atria, rapid activations in the pulmonary veins play an important role for the initiation and maintenance of atrial fibrillation. In addition to reentry, non-reentrant mechanisms resulting from abnormal intracellular calcium handling and intracellular calcium overload can also be responsible for these rapid activations in the pulmonary veins. Meanwhile, alterations of autonomic tone, involving both the sympathetic and parasympathetic nervous system, have been implicated in initiating paroxysmal atrial fibrillation. But the effectiveness of autonomic modulation as an adjunctive therapeutic strategy to catheter ablation of atrial fibrillation has been inconsistent. The interactions between the autonomic nervous system and atrial fibrillation are more complex than currently understood and further mechanistic and clinical studies are warranted.

Spinal cord swelling and candidiasis

International Nuclear Information System (INIS)

Ho, K.; Gronseth, G.; Aldrich, M.; Williams, A.

1982-01-01

Fusiform swelling of the spinal cord was noted myelographically in a patient with Hodgkin's disease. Autopsy revealed that the swelling was cauused by Candida infection of the spinal cord. It is suggested that fungal infection be included in the differential diagnosis of spinal cord swelling in the immunsupporessed cancer patient. (orig.)

Spinal Cord Injury 101

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Increased amount of atrial fibrosis in patients with atrial fibrillation secondary to mitral valve disease

NARCIS (Netherlands)

Geuzebroek, Guillaume S. C.; van Amersfoorth, Shirley C. M.; Hoogendijk, Mark G.; Kelder, Johannes C.; van Hemel, Norbert M.; de Bakker, Jacques M. T.; Coronel, Ruben

2012-01-01

Objective: Atrial fibrosis is related to atrial fibrillation but may differ in patients with mitral valve disease or lone atrial fibrillation. Therefore, we studied atrial fibrosis in patients with atrial fibrillation + mitral valve disease or with lone atrial fibrillation and compared it with

MR imaging and spinal cord injury

International Nuclear Information System (INIS)

Azar-Kia, B.; Fine, M.; Naheedy, M.; Elias, D.

1987-01-01

MR imaging has significantly improved diagnostic capability of spinal cord injuries. Other available diagnostic modalities such as plain films, myelography, CT, and post-CT myelography have failed to consistently show the secific evidence of spinal cord injuries and their true extent. The authors are presenting our experiences with MR imaging in spinal column injury. They have found MR imaging to be the procedure of choice for prognostic evaluation of spinal cord trauma. They are showing examples of recent and old spinal cord injury such as hematomyelia, myelomalacia, transection, spinal cord edema, and cavitation

Spinal cord swelling and candidiasis

Energy Technology Data Exchange (ETDEWEB)

Ho, K.; Gronseth, G.; Aldrich, M.; Williams, A.

1982-11-01

Fusiform swelling of the spinal cord was noted myelographically in a patient with Hodgkin's disease. Autopsy revealed that the swelling was caused by Candida infection of the spinal cord. It is suggested that fungal infection be included in the differential diagnosis of spinal cord swelling in the immunosuppressed cancer patient.

Spinal-cord swelling in acute multiple sclerosis

International Nuclear Information System (INIS)

Kikuchi, Seiji; Tashiro, Kunio; Naganuma, Mutsuo; Hida, Kazutoshi; Iwasaki, Yoshinobu; Abe, Hiroshi; Miyasaka, Kazuo

1986-01-01

Despite the frequent involvement of the spinal cord by multiple sclerosis, reports concerning neuroradiological findings regarding these lesions have been limited; most of them have demonstrated a normal or small spinal cord. Two cases of acute paraparesis showed evidence of spinal-cord swelling on myelography and CT myelography, initially suggesting the diagnosis of an intramedullary tumor. Spinal-cord swelling was demonstrated more clearly on CT myelography than on conventional myelography. The diagnosis of multiple sclerosis was made with the aid of the CSF findings, the clinical course, and the contracting-cord sign. The ''contracting-cord sign'' means the diminution of the spinal-cord diameter in the chronic stage. Since acute multiple sclerosis may produce spinal-cord swelling simulating a tumor, careful investigations are necessary to avoid unwarranted surgical interventions. (author)

Does Myocardial Infarction Beget Atrial Fibrillation and Atrial Fibrillation Beget Myocardial Infarction?

NARCIS (Netherlands)

Vermond, Rob A.; Van Gelder, Isabelle C.; Crijns, Harry J.; Rienstra, Michiel

2015-01-01

Atrial fibrillation (AF) affects millions of people worldwide.(1) It is already known several decades that AF is not a benign condition, and it's associated with a 5-fold increased risk of stroke, 3-fold increased risk of heart failure, and doubling of risk of dementia and death.(2-4) Myocardial

Focal Anterior Displacement of the Thoracic Spinal Cord without Evidence of Spinal Cord Herniation or an Intradural Mass

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Lee, Jong Yoon; Lee, Joon Woo; Lee, Guen Young; Kang, Heung Sik [Department of Radiology, Seoul National University Bundang Hospital, Seongnam 463-707 (Korea, Republic of)

2014-07-01

We report magnetic resonance imaging (MRI) findings on focal anterior displacement of the thoracic spinal cord in asymptomatic patients without a spinal cord herniation or intradural mass. We identified 12 patients (male:female = 6:6; mean age, 51.7; range, 15-83 years) between 2007 and 2011, with focal anterior displacement of the spinal cord and without evidence of an intradural mass or spinal cord herniation. Two radiologists retrospectively reviewed the MRI findings in consensus. An asymmetric spinal cord deformity with a focal dented appearance was seen on the posterior surface of the spinal cord in all patients, and it involved a length of 1 or 2 vertebral segments in the upper thoracic spine (thoracic vertebrae 1-6). Moreover, a focal widening of the posterior subarachnoid space was also observed in all cases. None of the patients had myelopathy symptoms, and they showed no focal T2-hyperintensity in the spinal cord with the exception of one patient. In addition, cerebrospinal fluid (CSF) flow artifacts were seen in the posterior subarachnoid space of the affected spinal cord level. Computed tomography myelography revealed preserved CSF flow in the two available patients. Focal anterior spinal cord indentation can be found in the upper thoracic level of asymptomatic patients without a spinal cord herniation or intradural mass.

Focal Anterior Displacement of the Thoracic Spinal Cord without Evidence of Spinal Cord Herniation or an Intradural Mass

International Nuclear Information System (INIS)

Lee, Jong Yoon; Lee, Joon Woo; Lee, Guen Young; Kang, Heung Sik

2014-01-01

We report magnetic resonance imaging (MRI) findings on focal anterior displacement of the thoracic spinal cord in asymptomatic patients without a spinal cord herniation or intradural mass. We identified 12 patients (male:female = 6:6; mean age, 51.7; range, 15-83 years) between 2007 and 2011, with focal anterior displacement of the spinal cord and without evidence of an intradural mass or spinal cord herniation. Two radiologists retrospectively reviewed the MRI findings in consensus. An asymmetric spinal cord deformity with a focal dented appearance was seen on the posterior surface of the spinal cord in all patients, and it involved a length of 1 or 2 vertebral segments in the upper thoracic spine (thoracic vertebrae 1-6). Moreover, a focal widening of the posterior subarachnoid space was also observed in all cases. None of the patients had myelopathy symptoms, and they showed no focal T2-hyperintensity in the spinal cord with the exception of one patient. In addition, cerebrospinal fluid (CSF) flow artifacts were seen in the posterior subarachnoid space of the affected spinal cord level. Computed tomography myelography revealed preserved CSF flow in the two available patients. Focal anterior spinal cord indentation can be found in the upper thoracic level of asymptomatic patients without a spinal cord herniation or intradural mass

Spinal Cord Injury 101

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Management of atrial fibrillation in the setting of heart failure

NARCIS (Netherlands)

Crijns, HJGM; VandenBerg, MP; VanGelder, IC; VanVeldhuisen, DJ

Heart failure is often complicated by atrial fibrillation. Once atrial fibrillation has started it further enhances heart failure due to uncontrolled rate with shortened filling time and provocation of tachycardiomyopathy. Absent atrial kick and irregularity of the ventricular rhythm also

Embolic risk in atrial fibrillation that arises from hyperthyroidism: review of the medical literature.

Science.gov (United States)

Traube, Elie; Coplan, Neil L

2011-01-01

Atrial fibrillation, the most common cardiac complication of hyperthyroidism, occurs in an estimated 10% to 25% of overtly hyperthyroid patients. The prevalence of atrial fibrillation increases with age in the general population and in thyrotoxic patients. Other risk factors for atrial fibrillation in thyrotoxic patients include male sex, ischemic or valvular heart disease, and congestive heart failure. The incidence of arterial embolism or stroke in thyrotoxic atrial fibrillation is less clear. There are many reports of arterial thromboembolism associated with hyperthyroidism, including cases of young adults without coexisting risk factors other than thyrotoxic atrial fibrillation. The use of anticoagulative agents to prevent thromboembolic sequelae of thyrotoxic atrial fibrillation is controversial: National organizations provide conflicting recommendations in their practice guidelines. Herein, we review the medical literature and examine the evidence behind the recommendations in order to determine the best approach to thromboembolic prophylaxis in patients who have atrial fibrillation that is associated with hyperthyroidism.

Spinal Cord Injury 101

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Modulation of atrial fibrillation

NARCIS (Netherlands)

Geuzebroek, G.S.C.

2013-01-01

In this thesis we investigate the results of various surgical procedures for atrial fibrillation which have been performed in the last 2 decades in the Sint Antonius Hospital, Nieuwegein, The Netherlands. In the 1990s the classical Maze III procedure was the main surgical technique for

Longitudinal and concurrent dimensional changes of cellulose aggregate fibrils during sorption stages

International Nuclear Information System (INIS)

Lee, Jung Myoung; Pawlak, Joel J.; Heitmann, John A.

2010-01-01

Atomic force microscopy (AFM) studies of the dimensional changes of cellulose microfibril materials, called cellulose aggregate fibrils (approx. 100 μm x 3 μm x 300 nm), exposed to two distinct relative humidities of 80% and 23% for 24 h and then suddenly subjected to 50% RH and 23 deg. C show that the fibrils are responsive to the surrounding environments in a nonspecific fashion. AFM images (10 μm x 10 μm) of the individual straight cellulose aggregate fibrils were taken as a function of elapsed time during both desorption and adsorption of moisture. The longitudinal distance between discrete natural defects observed on the cellulose aggregate fibrils as well as the width, cross-sectional area, and height of the cellulose aggregate fibril were measured from the AFM images. The length of the cellulose aggregate fibrils was found to have reduced after exposure to either high or low relative humidity, and then placement in ambient conditions. Over time in ambient conditions, the cellulose aggregate fibrils progressively relaxed to their original length during both desorption and adsorption of moisture. However, the relaxation rate during adsorption was faster than that during desorption. The possible explanations for this phenomenon are discussed including the sample preparation method, volume conservation, entropy elasticity, and free volume theory. The changes in the width, height, and cross-sectional area are also discussed.

The architecture of amyloid-like peptide fibrils revealed by X-ray scattering, diffraction and electron microscopy

DEFF Research Database (Denmark)

Langkilde, Annette Eva; Morris, Kyle L; Serpell, Louise C

2015-01-01

Structural analysis of protein fibrillation is inherently challenging. Given the crucial role of fibrils in amyloid diseases, method advancement is urgently needed. A hybrid modelling approach is presented enabling detailed analysis of a highly ordered and hierarchically organized fibril of the G......Structural analysis of protein fibrillation is inherently challenging. Given the crucial role of fibrils in amyloid diseases, method advancement is urgently needed. A hybrid modelling approach is presented enabling detailed analysis of a highly ordered and hierarchically organized fibril...

Cryoballoon Catheter Ablation in Atrial Fibrillation

Directory of Open Access Journals (Sweden)

Cevher Ozcan

2011-01-01

Full Text Available Pulmonary vein isolation with catheter ablation is an effective treatment in patients with symptomatic atrial fibrillation refractory or intolerant to antiarrhythmic medications. The cryoballoon catheter was recently approved for this procedure. In this paper, the basics of cryothermal energy ablation are reviewed including its ability of creating homogenous lesion formation, minimal destruction to surrounding vasculature, preserved tissue integrity, and lower risk of thrombus formation. Also summarized here are the publications describing the clinical experience with the cryoballoon catheter ablation in both paroxysmal and persistent atrial fibrillation, its safety and efficacy, and discussions on the technical aspect of the cryoballoon ablation procedure.

Spinal Cord Injury 101

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Full Text Available ... About Media Donate Spinal Cord Injury Medical Expert Videos ... Home Kim Eberhardt Muir, MS Coping with a New Injury Robin Dorman, PsyD Sex and Fertility After Spinal Cord Injury Diane M. ...

Ebstein's anomaly as a cause of paroxysmal atrial fibrillation

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Damjanović Miodrag R.

2008-01-01

Full Text Available Background. Ebstein's anomaly is characterized by a displacement of the tricuspid valve toward apex, because of anomalous attachment of the tricuspid leaflets. There are type B of Wolff-Parkinson-White (WPW syndrome and paroxysmal arrhythmias in more than a half of all patients. Case report. We presented a female, 32-year old, with frequent paroxysms of atrial fibrillation. After conversion of rhythm an ECG showed WPW syndrome. Echocardiographic examination discovered normal size of the left cardiac chambers with paradoxical ventricular septal motion. The right ventricle was very small because of its atrialization. The origin of the tricuspid valve was 20 mm closer to apex of the right ventricle than the origin of the mitral valve. Electrophysiological examination showed a posterolateral right accesorial pathway. Atrial fibrillation was induced very easily in electrophysiological laboratory and a successful ablation of accessorial pathway was made. There were no WPW syndrome and paroxysms of atrial fibrillation after that. Conclusion. Ebstein's anomaly is one of the reasons of paroxysmal atrial fibrillation, especially in young persons with WPW syndrome.

Ultrastructural study of myelinating cells and sub-pial astrocytes in developing rat spinal cord.

Science.gov (United States)

Nagashima, K

1979-12-01

The anterior funiculus of the spinal cervical cord of post-natal rats was examined ultrastructurally. The myelinating cells found one day after brith contained a large amount of evenly distributed ribosomes up to the outer tongue of mesaxons, representing the cytoplasmic density. These cells were separated by astrocytic processes from the pial basement membrane, even when they were located on the pial surface. Astrocytes contained glial fibrils from one day onwards and often attached their processes to the pial basement membrane. Although the cytoplasmic processes of astrocytes occasionally wrapped axons, they were never shown to form the initial layer of myelin sheaths. However, the tenuous processes of the sub-pial astrocytes were occasionally rolled in myelin lamellae, as if a part of the myelin sheaths was constructed by astrocytic processes. The interpretation for this finding is discussed in relation to function and potency of the astrocytes, and variations and anomalies of nervous ontogeny.

Surface characterization of insulin protofilaments and fibril polymorphs using tip-enhanced Raman spectroscopy (TERS).

Science.gov (United States)

Kurouski, Dmitry; Deckert-Gaudig, Tanja; Deckert, Volker; Lednev, Igor K

2014-01-07

Amyloid fibrils are β-sheet-rich protein aggregates that are strongly associated with a variety of neurodegenerative maladies, such as Alzheimer's and Parkinson's diseases. Even if the secondary structure of such fibrils is well characterized, a thorough understanding of their surface organization still remains elusive. Tip-enhanced Raman spectroscopy (TERS) is one of a few techniques that allow the direct characterization of the amino acid composition and the protein secondary structure of the amyloid fibril surface. Herein, we investigated the surfaces of two insulin fibril polymorphs with flat (flat) and left-twisted (twisted) morphology. It was found that the two differ substantially in both amino acid composition and protein secondary structure. For example, the amounts of Tyr, Pro, and His differ, as does the number of carboxyl groups on the respective surfaces, whereas the amounts of Phe and of positively charged amino and imino groups remain similar. In addition, the surface of protofilaments, the precursors of the mature flat and twisted fibrils, was investigated using TERS. The results show substantial differences with respect to the mature fibrils. A correlation of amino acid frequencies and protein secondary structures on the surface of protofilaments and on flat and twisted fibrils allowed us to propose a hypothetical mechanism for the propagation to specific fibril polymorphs. This knowledge can shed a light on the toxicity of amyloids and define the key factors responsible for fibril polymorphism. Finally, this work demonstrates the potential of TERS for the surface characterization of amyloid fibril polymorphs. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation.

Science.gov (United States)

Dou, John; Schmidt, Rebecca J; Benke, Kelly S; Newschaffer, Craig; Hertz-Picciotto, Irva; Croen, Lisa A; Iosif, Ana-Maria; LaSalle, Janine M; Fallin, M Daniele; Bakulski, Kelly M

2018-01-01

Cord blood DNA methylation is associated with numerous health outcomes and environmental exposures. Whole cord blood DNA reflects all nucleated blood cell types, while centrifuging whole blood separates red blood cells, generating a white blood cell buffy coat. Both sample types are used in DNA methylation studies. Cell types have unique methylation patterns and processing can impact cell distributions, which may influence comparability. We evaluated differences in cell composition and DNA methylation between cord blood buffy coat and whole cord blood samples. Cord blood DNA methylation was measured with the Infinium EPIC BeadChip (Illumina) in eight individuals, each contributing buffy coat and whole blood samples. We analyzed principal components (PC) of methylation, performed hierarchical clustering, and computed correlations of mean-centered methylation between pairs. We conducted moderated t-tests on single sites and estimated cell composition. DNA methylation PCs were associated with individual (P PC1 = 1.4 × 10 -9 ; P PC2 = 2.9 × 10 -5 ; P PC3 = 3.8 × 10 -5 ; P PC4 = 4.2 × 10 -6 ; P PC5 = 9.9 × 10 -13 , P PC6 = 1.3 × 10 -11 ) and not with sample type (P PC1-6 >0.7). Samples hierarchically clustered by individual. Pearson correlations of mean-centered methylation between paired samples ranged from r = 0.66 to r = 0.87. No individual site significantly differed between buffy coat and whole cord blood when adjusting for multiple comparisons (five sites had unadjusted Pcoat and whole cord blood are much lower than inter-individual variation, demonstrating that both sample preparation types can be analytically combined and compared.

Atrial fibrillation and bleeding complication - risk factors and risk marker

NARCIS (Netherlands)

Breithardt, G.; Ravens, U.; Kirchhof, P.; van Gelder, I. C.

2012-01-01

The development of atrial fibrillation (AF) is closely linked to risk factors like hypertension and heart failure, diabetes mellitus, myocardial infarction and valvular heart disease. These factors partly overlap with those which determine the progression of atrial fibrillation and the incidence of

Experimental spinal cord trauma: a review of mechanically induced spinal cord injury in rat models.

Science.gov (United States)

Abdullahi, Dauda; Annuar, Azlina Ahmad; Mohamad, Masro; Aziz, Izzuddin; Sanusi, Junedah

2017-01-01

It has been shown that animal spinal cord compression (using methods such as clips, balloons, spinal cord strapping, or calibrated forceps) mimics the persistent spinal canal occlusion that is common in human spinal cord injury (SCI). These methods can be used to investigate the effects of compression or to know the optimal timing of decompression (as duration of compression can affect the outcome of pathology) in acute SCI. Compression models involve prolonged cord compression and are distinct from contusion models, which apply only transient force to inflict an acute injury to the spinal cord. While the use of forceps to compress the spinal cord is a common choice due to it being inexpensive, it has not been critically assessed against the other methods to determine whether it is the best method to use. To date, there is no available review specifically focused on the current compression methods of inducing SCI in rats; thus, we performed a systematic and comprehensive publication search to identify studies on experimental spinalization in rat models, and this review discusses the advantages and limitations of each method.

Long working hours as a risk factor for atrial fibrillation

DEFF Research Database (Denmark)

Kivimäki, Mika; Nyberg, Solja T.; Batty, G. David

2017-01-01

long hours (≤55 per week) and those working standard 35-40 h/week. Methods and results In this prospective multi-cohort study from the Individual-Participant-Data Meta-Analysis in Working Populations (IPD-Work) Consortium, the study population was 85 494 working men and women (mean age 43.4 years...... of atrial fibrillation (10-year cumulative incidence 12.4 per 1000). After adjustment for age, sex and socioeconomic status, individuals working long hours had a 1.4-fold increased risk of atrial fibrillation compared with those working standard hours (hazard ratio = 1.42, 95% CI= 1.13-1.80, P= 0......Aims Studies suggest that people who work long hours are at increased risk of stroke, but the association of long working hours with atrial fibrillation, the most common cardiac arrhythmia and a risk factor for stroke, is unknown. We examined the risk of atrial fibrillation in individuals working...

Imaging of Spinal Cord Injury: Acute Cervical Spinal Cord Injury, Cervical Spondylotic Myelopathy, and Cord Herniation.

Science.gov (United States)

Talekar, Kiran; Poplawski, Michael; Hegde, Rahul; Cox, Mougnyan; Flanders, Adam

2016-10-01

We review the pathophysiology and imaging findings of acute traumatic spinal cord injury (SCI), cervical spondylotic myelopathy, and briefly review the much less common cord herniation as a unique cause of myelopathy. Acute traumatic SCI is devastating to the patient and the costs to society are staggering. There are currently no "cures" for SCI and the only accepted pharmacologic treatment regimen for traumatic SCI is currently being questioned. Evaluation and prognostication of SCI is a demanding area with significant deficiencies, including lack of biomarkers. Accurate classification of SCI is heavily dependent on a good clinical examination, the results of which can vary substantially based upon the patient׳s condition or comorbidities and the skills of the examiner. Moreover, the full extent of a patients׳ neurologic injury may not become apparent for days after injury; by then, therapeutic response may be limited. Although magnetic resonance imaging (MRI) is the best imaging modality for the evaluation of spinal cord parenchyma, conventional MR techniques do not appear to differentiate edema from axonal injury. Recently, it is proposed that in addition to characterizing the anatomic extent of injury, metrics derived from conventional MRI and diffusion tensor imaging, in conjunction with the neurological examination, can serve as a reliable objective biomarker for determination of the extent of neurologic injury and early identification of patients who would benefit from treatment. Cervical spondylosis is a common disorder affecting predominantly the elderly with a potential to narrow the spinal canal and thereby impinge or compress upon the neural elements leading to cervical spondylotic myelopathy and radiculopathy. It is the commonest nontraumatic cause of spinal cord disorder in adults. Imaging plays an important role in grading the severity of spondylosis and detecting cord abnormalities suggesting myelopathy. Copyright © 2016 Elsevier Inc. All rights

[Panic disorder and atrial fibrillation].

Science.gov (United States)

Olazabal Eizaguirre, N; Chavez, R; González-Torres, M A; Gaviria, M

2013-10-01

This paper studies the relationship between atrial fibrillation and panic disorder. There are often doubts on the differential diagnosis in emergency services and general medical settings. Panic disorder prevalence rates have been found to be high in patients suffering from atrial fibrillation. Various studies have observed that patients diagnosed with anxiety disorders frequently have higher cardiovascular disease rates compared to the general population. Usually, patients suffering from panic disorder exhibit somatic complaints suggesting coronary disease, such as chest pain or palpitations. The aim is to make the correct diagnosis and treatment for these different illnesses, and to decrease the costs due to misdiagnosis. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Spinal Cord Injury 101

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Spinal Cord Injury 101

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Spinal Cord Injury 101

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Systematic examination of polymorphism in amyloid fibrils by molecular-dynamics simulation.

Science.gov (United States)

Berryman, Joshua T; Radford, Sheena E; Harris, Sarah A

2011-05-04

Amyloid fibrils often exhibit polymorphism. Polymorphs are formed when proteins or peptides with identical sequences self-assemble into fibrils containing substantially different arrangements of the β-strands. We used atomistic molecular-dynamics simulation to examine the thermodynamic stability of a amyloid fibrils in different polymorphic forms by performing a systematic investigation of sequence and symmetry space for a series of peptides with a range of physicochemical properties. We show that the stability of fibrils depends on both sequence and the symmetry because these factors determine the availability of favorable interactions between the peptide strands within a sheet and in intersheet packing. By performing a detailed analysis of these interactions as a function of symmetry, we obtained a series of simple design rules that can be used to determine which polymorphs of a given sequence are most likely to form thermodynamically stable fibrils. These rules can potentially be employed to design peptide sequences that aggregate into a preferred polymorphic form for nanotechnological purposes. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The Impact of Age on the Epidemiology of Atrial Fibrillation Hospitalizations

Science.gov (United States)

Naderi, Sahar; Wang, Yun; Miller, Amy L.; Rodriguez, Fátima; Chung, Mina K.; Radford, Martha J.; Foody, JoAnne M.

2015-01-01

Background Given 4 million individuals in the United States suffer from atrial fibrillation, understanding the epidemiology of this disease is crucial. We sought to identify and characterize the impact of age on national atrial fibrillation hospitalization patterns. Methods The study sample was drawn from the 2009–2010 Nationwide Inpatient Sample (NIS). Patients hospitalized with a principal ICD9 discharge diagnosis of atrial fibrillation were included. Patients were categorized as “older” (65 and older) or “younger” (under 65 years) for the purposes of analysis. The outcomes measured included hospitalization rate, length of stay, in-hospital mortality, and discharge status. Results We identified 192,846 atrial fibrillation hospitalizations. There was significant geographic variation in hospitalizations for both younger and older age groups. States with high hospitalizations differed from those states known to have high stroke mortality. Younger patients (33% of the sample) were more likely to be obese (21% versus 8%, patrial fibrillation hospitalizations in contemporary practice. Younger patients are healthier, with a different distribution of risk factors, than older patients who have higher associated morbidity and mortality. PMID:24332722

Patients with atrial fibrillation and permanent pacemaker

DEFF Research Database (Denmark)

Dalgaard, Frederik; Ruwald, Martin H; Lindhardt, Tommi Bo

2018-01-01

BACKGROUND: The management of patients with non-valvular atrial fibrillation (NVAF) with rate-lowering or anti-arrhythmic drugs has markedly changed over the last decade, but it is unknown how these changes have affected patients with NVAF with a permanent pacemaker (PPM). METHODS: Through Danish......,261. Thus, the proportional amount of NVAF patients with a PPM decreased from 1.3% to 1.1% (p = 0.015). Overall 45.9% had atrial fibrillation (AF) duration less than one year and the proportion declined from 55.5% to 42.4% (p

Integrating new approaches to atrial fibrillation management

DEFF Research Database (Denmark)

Kotecha, Dipak; Breithardt, Günter; Camm, A John

2018-01-01

There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse...... of the Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association (EHRA), held at the European Society of Cardiology Heart House in Sophia Antipolis, France, 17-19 January 2017. Sixty-two global specialists in AF and 13 industry partners met to develop innovative solutions based on new...

Viscoelastic behavior of discrete human collagen fibrils

DEFF Research Database (Denmark)

Svensson, René; Hassenkam, Tue; Hansen, Philip

2010-01-01

Whole tendon and fibril bundles display viscoelastic behavior, but to the best of our knowledge this property has not been directly measured in single human tendon fibrils. In the present work an atomic force microscopy (AFM) approach was used for tensile testing of two human patellar tendon...... saline, cyclic testing was performed in the pre-yield region at different strain rates, and the elastic response was determined by a stepwise stress relaxation test. The elastic stress-strain response corresponded to a second-order polynomial fit, while the viscous response showed a linear dependence...

Spinal Cord Injury 101

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Full Text Available ... Cord Injury Allen Heinemann, PhD How Peer Counseling Works Julie Gassaway, MS, RN Pediatric Injuries Pediatric Spinal ... injury? play_arrow How does the spinal cord work? play_arrow Why is the level of a ...

Spinal Cord Injury 101

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Full Text Available ... spinal cord injuries? play_arrow What is “Braingate” research? play_arrow How would stem-cell therapies work ... cord injuries? play_arrow What does stem-cell research on animals tell us? play_arrow When can ...

Spinal Cord Injury 101

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Full Text Available ... Spinal Cord Injury Guy W. Fried, MD Substance Abuse and Spinal Cord Injury Allen Heinemann, PhD How ... arrow Why are high-dose steroids often used right after an injury? play_arrow What is meant ...

Spinal Cord Injury 101

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Full Text Available ... RN Pediatric Injuries Pediatric Spinal Cord Injury 101 Lawrence Vogel, MD The Basics of Pediatric SCI Rehabilitation ... Rogers, PT Recreational Therapy after Spinal Cord Injury Jennifer Piatt, PhD David Chen, MD Read Bio Medical ...

Tethered Spinal Cord Syndrome

Science.gov (United States)

... cord over time and may be exacerbated during sports or pregnancy, or may be due to narrowing of the ... cord over time and may be exacerbated during sports or pregnancy, or may be due to narrowing of the ...

Michler’s Hydrol Blue: A Sensitive Probe for Amyloid Fibril Detection

KAUST Repository

Kitts, Catherine C.; Beke-Somfai, Tamás; Nordén, Bengt

2011-01-01

amyloid probe, can differentiate between insulin and lysozyme fibrils by a more red-shifted excitation spectrum for insulin fibrils. To support the experimental observations, time-dependent density functional theory (TDDFT) calculations were performed

Spinal Cord Injury 101

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Full Text Available ... Disabilities Photography by Rona Talcott Website by Mobile Marketing LLC Understanding Spinal Cord Injury About Us Expert Videos Contact Us Personal Experience Videos Blog Videos By Topic Media Resources Donate to support families facing spinal cord ...

Spinal Cord Injury 101

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Full Text Available ... Spinal Cord Injury 101 Lawrence Vogel, MD The Basics of Pediatric SCI Rehabilitation Sara Klaas, MSW Transitions for Children with Spinal Cord Injury Patricia Mucia, RN Family Life After Pediatric Spinal Injury Dawn Sheaffer, MSW Rehabilitation ...

A carboxylated Zn-phthalocyanine inhibits fibril formation of Alzheimer's amyloid β peptide.

Science.gov (United States)

Tabassum, Shatera; Sheikh, Abdullah M; Yano, Shozo; Ikeue, Takafumi; Handa, Makoto; Nagai, Atsushi

2015-02-01

Amyloid β (Aβ), a 39-42 amino acid peptide derived from amyloid precursor protein, is deposited as fibrils in Alzheimer's disease brains, and is considered to play a major role in the pathogenesis of the disease. We have investigated the effects of a water-soluble Zn-phthalocyanine, ZnPc(COONa)₈, a macrocyclic compound with near-infrared optical properties, on Aβ fibril formation in vitro. A thioflavin T fluorescence assay showed that ZnPc(COONa)₈ significantly inhibited Aβ fibril formation, increasing the lag time and dose-dependently decreasing the plateau level of fibril formation. Moreover, it destabilized pre-formed Aβ fibrils, resulting in an increase in low-molecular-weight species. After fibril formation in the presence of ZnPc(COONa)₈, immunoprecipitation of Aβ₁₋₄₂ using Aβ-specific antibody followed by near-infrared scanning demonstrated binding of ZnPc(COONa)₈ to Aβ₁₋₄₂. A study using the hydrophobic fluorescent probe 8-anilino-1-naphthalenesulfonic acid showed that ZnPc(COONa)8 decreased the hydrophobicity during Aβ₁₋₄₂ fibril formation. CD spectroscopy showed an increase in the α helix structure and a decrease in the β sheet structure of Aβ₁₋₄₀ in fibril-forming buffer containing ZnPc(COONa)₈. SDS/PAGE and a dot-blot immunoassay showed that ZnPc(COONa)₈ delayed the disappearance of low-molecular-weight species and the appearance of higher-molecular-weight oligomeric species of Aβ₁₋₄₂. A cell viability assay showed that ZnPc(COONa)₈ was not toxic to a neuronal cell line (A1), but instead protected A1 cells against Aβ₁₋₄₂-induced toxicity. Overall, our results indicate that ZnPc(COONa)₈ binds to Aβ and decreases the hydrophobicity, and this change is unfavorable for Aβ oligomerization and fibril formation. © 2014 FEBS.

Spinal Cord Injury Disrupts Resting-State Networks in the Human Brain.

Science.gov (United States)

Hawasli, Ammar H; Rutlin, Jerrel; Roland, Jarod L; Murphy, Rory K J; Song, Sheng-Kwei; Leuthardt, Eric C; Shimony, Joshua S; Ray, Wilson Z

2018-03-15

Despite 253,000 spinal cord injury (SCI) patients in the United States, little is known about how SCI affects brain networks. Spinal MRI provides only structural information with no insight into functional connectivity. Resting-state functional MRI (RS-fMRI) quantifies network connectivity through the identification of resting-state networks (RSNs) and allows detection of functionally relevant changes during disease. Given the robust network of spinal cord afferents to the brain, we hypothesized that SCI produces meaningful changes in brain RSNs. RS-fMRIs and functional assessments were performed on 10 SCI subjects. Blood oxygen-dependent RS-fMRI sequences were acquired. Seed-based correlation mapping was performed using five RSNs: default-mode (DMN), dorsal-attention (DAN), salience (SAL), control (CON), and somatomotor (SMN). RSNs were compared with normal control subjects using false-discovery rate-corrected two way t tests. SCI reduced brain network connectivity within the SAL, SMN, and DMN and disrupted anti-correlated connectivity between CON and SMN. When divided into separate cohorts, complete but not incomplete SCI disrupted connectivity within SAL, DAN, SMN and DMN and between CON and SMN. Finally, connectivity changed over time after SCI: the primary motor cortex decreased connectivity with the primary somatosensory cortex, the visual cortex decreased connectivity with the primary motor cortex, and the visual cortex decreased connectivity with the sensory parietal cortex. These unique findings demonstrate the functional network plasticity that occurs in the brain as a result of injury to the spinal cord. Connectivity changes after SCI may serve as biomarkers to predict functional recovery following an SCI and guide future therapy.

Pericytes Make Spinal Cord Breathless after Injury.

Science.gov (United States)

Almeida, Viviani M; Paiva, Ana E; Sena, Isadora F G; Mintz, Akiva; Magno, Luiz Alexandre V; Birbrair, Alexander

2017-09-01

Traumatic spinal cord injury is a devastating condition that leads to significant neurological deficits and reduced quality of life. Therapeutic interventions after spinal cord lesions are designed to address multiple aspects of the secondary damage. However, the lack of detailed knowledge about the cellular and molecular changes that occur after spinal cord injury restricts the design of effective treatments. Li and colleagues using a rat model of spinal cord injury and in vivo microscopy reveal that pericytes play a key role in the regulation of capillary tone and blood flow in the spinal cord below the site of the lesion. Strikingly, inhibition of specific proteins expressed by pericytes after spinal cord injury diminished hypoxia and improved motor function and locomotion of the injured rats. This work highlights a novel central cellular population that might be pharmacologically targeted in patients with spinal cord trauma. The emerging knowledge from this research may provide new approaches for the treatment of spinal cord injury.

Ventricular fibrillation development following atrial fibrillation after the ingestion of sildenaphil in a patient with Wolff-Parkinson-White syndrome.

Science.gov (United States)

Inci, Sinan; Izgu, Ibrahim; Aktas, Halil; Dogan, Pinar; Dogan, Ali

2015-08-01

Complications in the accessory pathway in Wolff-Parkinson-White (WPW) syndrome could cause different clinical conditions by inducing different arrhythmias. Atrial fibrillation (AF) is one of these arrhythmias and is important as it causes life-threatening arrhythmias. It is known that some drugs, underlying cardiac diseases, and the number of accessory pathways, cause a predisposition to this condition. In the current report, we presented a patient with WPW who was admitted to the emergency department with AF, wide QRS and a rapid ventricular response that progressed to ventricular fibrillation.

Cord Blood Banking for Potential Future Transplantation.

Science.gov (United States)

Shearer, William T; Lubin, Bertram H; Cairo, Mitchell S; Notarangelo, Luigi D

2017-11-01

This policy statement is intended to provide information to guide pediatricians, obstetricians, and other medical specialists and health care providers in responding to parents' questions about cord blood donation and banking as well as the types (public versus private) and quality of cord blood banks. Cord blood is an excellent source of stem cells for hematopoietic stem cell transplantation in children with some fatal diseases. Cord blood transplantation offers another method of definitive therapy for infants, children, and adults with certain hematologic malignancies, hemoglobinopathies, severe forms of T-lymphocyte and other immunodeficiencies, and metabolic diseases. The development of universal screening for severe immunodeficiency assay in a growing number of states is likely to increase the number of cord blood transplants. Both public and private cord blood banks worldwide hold hundreds of thousands of cord blood units designated for the treatment of fatal or debilitating illnesses. The procurement, characterization, and cryopreservation of cord blood is free for families who choose public banking. However, the family cost for private banking is significant and not covered by insurance, and the unit may never be used. Quality-assessment reviews by several national and international accrediting bodies show private cord blood banks to be underused for treatment, less regulated for quality control, and more expensive for the family than public cord blood banks. There is an unquestionable need to study the use of cord blood banking to make new and important alternative means of reconstituting the hematopoietic blood system in patients with malignancies and blood disorders and possibly regenerating tissue systems in the future. Recommendations regarding appropriate ethical and operational standards (including informed consent policies, financial disclosures, and conflict-of-interest policies) are provided for physicians, institutions, and organizations that

Spinal Cord Injury 101

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Full Text Available ... arrow What are the latest developments in the use of electrical stimulation for spinal cord injuries? play_arrow What is “Braingate” research? play_arrow How would stem-cell therapies work in the treatment of spinal cord ...

Aggregation properties of a short peptide that mediates amyloid fibril ...

Indian Academy of Sciences (India)

Short peptides have been identified from amyloidogenic proteins that form amyloid fibrils in isolation. The ... proteins. These peptide fibrils have the conformational features of β-structure that .... water and immediately deposited on freshly cleaved surface of mica .... with the peptide via electrostatic interactions. NaCl would.

Management of Newly Diagnosed Atrial Fibrillation in an Outpatient Clinic Setting

DEFF Research Database (Denmark)

Thrysoee, Lars; Strömberg, Anna; Brandes, Axel

2018-01-01

fibrillation is not a fatal disease in itself was very important for patients. At the same time, visiting the clinic was overwhelming, information was difficult to understand, and patients found it difficult to be involved in decision-making. CONCLUSIONS: This study indicates that patients were uncertain......AIMS: To gain in-depth knowledge of patients' experiences of the consultation processes at a multidisciplinary atrial fibrillation outpatient clinic in a university hospital in Denmark. BACKGROUND: Atrial fibrillation is the most common cardiac arrhythmia associated with morbidity and mortality...... if not diagnosed and treated as recommended. Patients with newly diagnosed atrial fibrillation preferably should be managed in an outpatient setting which includes medical examination, patient education and decision making on medical therapy. DESIGN: This is a qualitative study of 14 patients newly diagnosed...

Structure–mechanics relationships of collagen fibrils in the osteogenesis imperfecta mouse model

Science.gov (United States)

Andriotis, O. G.; Chang, S. W.; Vanleene, M.; Howarth, P. H.; Davies, D. E.; Shefelbine, S. J.; Buehler, M. J.; Thurner, P. J.

2015-01-01

The collagen molecule, which is the building block of collagen fibrils, is a triple helix of two α1(I) chains and one α2(I) chain. However, in the severe mouse model of osteogenesis imperfecta (OIM), deletion of the COL1A2 gene results in the substitution of the α2(I) chain by one α1(I) chain. As this substitution severely impairs the structure and mechanics of collagen-rich tissues at the tissue and organ level, the main aim of this study was to investigate how the structure and mechanics are altered in OIM collagen fibrils. Comparing results from atomic force microscopy imaging and cantilever-based nanoindentation on collagen fibrils from OIM and wild-type (WT) animals, we found a 33% lower indentation modulus in OIM when air-dried (bound water present) and an almost fivefold higher indentation modulus in OIM collagen fibrils when fully hydrated (bound and unbound water present) in phosphate-buffered saline solution (PBS) compared with WT collagen fibrils. These mechanical changes were accompanied by an impaired swelling upon hydration within PBS. Our experimental and atomistic simulation results show how the structure and mechanics are altered at the individual collagen fibril level as a result of collagen gene mutation in OIM. We envisage that the combination of experimental and modelling approaches could allow mechanical phenotyping at the collagen fibril level of virtually any alteration of collagen structure or chemistry. PMID:26468064

Stroke prevention in hospitalized patients with atrial fibrillation: a population-based study.

Science.gov (United States)

Nagpal, Seema; Anderson, David; Putnam, Wayne; Flowerdew, Gordon; Gardner, Martin; Cox, Jafna

2003-01-01

Oral anticoagulants reduce the incidence of stroke by 68%, yet suboptimal use has been documented in surveys of patients with atrial fibrillation. The present study examined current patterns of anticoagulant use for patients hospitalized with atrial fibrillation across an entire health care system. Improving Cardiovascular Outcomes in Nova Scotia (ICONS) is a prospective cohort study involving all patients hospitalized in Nova Scotia with atrial fibrillation, among other conditions. Consecutive inpatients with atrial fibrillation from October 15, 1997 to October 14, 1998 were studied. Detailed demographic and clinical data were collected and the proportion of patients using antithrombotic therapy was tabulated by risk category. Multivariate logistic regression was used to assess the relationship of various demographic and clinical factors with the use of antithrombotic agents. There were 2202 patients hospitalized with atrial fibrillation; 644 admitted specifically for this condition. Only 21% of patients admitted with atrial fibrillation were on warfarin sodium at admission and this increased by time of discharge. Diabetes was negatively correlated with warfarin sodium use. Histories of prosthetic valve replacement, stroke/transient ischemic attack, and heart failure were positively associated with anticoagulant use on admission. Patients with prosthetic valve replacement, heart failure, or hyperlipidemia were most likely to receive anticoagulants at discharge. Antithrombotic agents remain underused by patients with atrial fibrillation. While higher risk patients are generally targeted, this is not invariably the case; thus, diabetics remain under treated. Further work is needed to explain such anomalous practice and promote optimal antithrombotic therapy use.

Optimizing cellulose fibrillation for the production of cellulose nanofibrils by a disk grinder

Science.gov (United States)

Chuanshuang Hu; Yu Zhao; Kecheng Li; J.Y. Zhu; Roland Gleisner

2015-01-01

The fibrillation of a bleached kraft eucalyptus pulp was investigated by means of a laboratory-scale disk grinder for the production of cellulose nanofibrils (CNF), while the parameters disk rotating speed, solid loading, and fibrillation duration were varied. The cumulative energy consumption was monitored during fibrillation. The degree of polymerization (DP) and...

Phosphate and HEPES buffers potently affect the fibrillation and oligomerization mechanism of Alzheimer's Aβ peptide

International Nuclear Information System (INIS)

Garvey, Megan; Tepper, Katharina; Haupt, Caroline; Knuepfer, Uwe; Klement, Karolin; Meinhardt, Jessica; Horn, Uwe; Balbach, Jochen; Faendrich, Marcus

2011-01-01

Highlights: → Sodium phosphate buffer accelerated Aβ(1-40) nucleation relative to HEPES. → Aβ(1-40) fibrils formed in the two buffers show only minor structural differences. → NMR revealed that Aβ(1-40) histidine residues mediate buffer dependent changes. -- Abstract: The oligomerization of Aβ peptide into amyloid fibrils is a hallmark of Alzheimer's disease. Due to its biological relevance, phosphate is the most commonly used buffer system for studying the formation of Aβ and other amyloid fibrils. Investigation into the characteristics and formation of amyloid fibrils frequently relies upon material formed in vitro, predominantly in phosphate buffers. Herein, we examine the effects on the fibrillation and oligomerization mechanism of Aβ peptide that occur due solely to the influence of phosphate buffer. We reveal that significant differences in amyloid fibrillation are observed due to fibrillation being initiated in phosphate or HEPES buffer (at physiological pH and temperature). Except for the differing buffer ions, all experimental parameters were kept constant. Fibril formation was assessed using fluorescently monitored kinetic studies, microscopy, X-ray fiber diffraction and infrared and nuclear magnetic resonance spectroscopies. Based on this set up, we herein reveal profound effects on the mechanism and speed of Aβ fibrillation. The three histidine residues at positions 6, 13 and 14 of Aβ(1-40) are instrumental in these mechanistic changes. We conclude that buffer plays a more significant role in fibril formation than has been generally acknowledged.

CT-myelography of cervical cord injury

International Nuclear Information System (INIS)

Koyanagi, Izumi; Isu, Toyohiko; Iwasaki, Yoshinobu

1986-01-01

We reported seven cases of acute cervical cord injuries who were examined by CT-Myelography (CTM) within 7 days after trauma. The presence or absence of spinal cord enlargement, the initial neurological status and the neurological prognosis of these patients were studied. The neurological status of each patient was graded by the method of Frankel who defined five grades from A to E according to the severity of neurological deficits. Seven patients were all males. The youngest was 18 and the oldest was 73 years old, with a mean age of 40.7 years. Follows up periods ranged from 7 to 23 months. Result: CTM revealed the enlargement of spinal cord in two cases, who had severe neurological deficits and were graded to A. No neurological improvements were obtained in these cases. Five cases without cord enlargement were graded to A in one patient, B in one patient and C in three patients. Four of these five patients improved neurologically. One grade C patient remained grade C. Complete block of subarachnoid space was observed in two out of seven cases. Cord enlargement was present in one of them. Another case of complete block improved from C to D. Conclusion: We consider the presence of cord enlargement which can be demonstrated by CTM well correlates the severity of the cord damage and presume poor neurological prognosis. Internal decompression, such as posterior longitudinal myelotomy may be recommended to the case of cord enlargement. When the cord enlargement is absent, improvement of neurological grade is expected although the initial neurological status shows severe deficits. (author)

Use of Vitamins K antagonists in non-valvular atrial fibrillation ...

African Journals Online (AJOL)

Introduction: atrial fibrillation is the commonest cardiac rythm disorder. Thromboembolic accidents are common complications that should be prevented by anticoagulant treatment. The aim of our study is to assess the use of vitamins K antagonists in the prevention of thromboembolic risk in atrial fibrillation. Methods: it was a ...

Clinical characteristics, management, and control of permanent vs. nonpermanent atrial fibrillation: insights from the RealiseAF survey.

LENUS (Irish Health Repository)

Murin, Jan

2014-01-01

Atrial fibrillation can be categorized into nonpermanent and permanent atrial fibrillation. There is less information on permanent than on nonpermanent atrial fibrillation patients. This analysis aimed to describe the characteristics and current management, including the proportion of patients with successful atrial fibrillation control, of these atrial fibrillation subsets in a large, geographically diverse contemporary sample.

Twiddler's syndrome in spinal cord stimulation.

Science.gov (United States)

Al-Mahfoudh, Rafid; Chan, Yuen; Chong, Hsu Pheen; Farah, Jibril Osman

2016-01-01

The aims are to present a case series of Twiddler's syndrome in spinal cord stimulators with analysis of the possible mechanism of this syndrome and discuss how this phenomenon can be prevented. Data were collected retrospectively between 2007 and 2013 for all patients presenting with failure of spinal cord stimulators. The diagnostic criterion for Twiddler's syndrome is radiological evidence of twisting of wires in the presence of failure of spinal cord stimulation. Our unit implants on average 110 spinal cord stimulators a year. Over the 5-year study period, all consecutive cases of spinal cord stimulation failure were studied. Three patients with Twiddler's syndrome were identified. Presentation ranged from 4 to 228 weeks after implantation. Imaging revealed repeated rotations and twisting of the wires of the spinal cord stimulators leading to hardware failure. To the best of our knowledge this is the first reported series of Twiddler's syndrome with implantable pulse generators (IPGs) for spinal cord stimulation. Hardware failure is not uncommon in spinal cord stimulation. Awareness and identification of Twiddler's syndrome may help prevent its occurrence and further revisions. This may be achieved by implanting the IPG in the lumbar region subcutaneously above the belt line. Psychological intervention may have a preventative role for those who are deemed at high risk of Twiddler's syndrome from initial psychological screening.

Failure of antiarrhythmic drugs to prevent experimental reperfusion ventricular fibrillation.

Science.gov (United States)

Naito, M; Michelson, E L; Kmetzo, J J; Kaplinsky, E; Dreifus, L S

1981-01-01

Ninety-nine adult mongrel dogs underwent acute ligation of the proximal left anterior descending coronary artery. Thirty minutes later, the occlusion was released to evaluate the effectiveness of five antiarrhythmic protocols in eliminating reperfusion ventricular fibrillation. The five protocols included: protocol 1 --i.v. lidocaine, preligation and prerelease (n = 19); protocol 2 -- i.v. lidocaine, prereperfusion only (n = 22); protocol 3 -- chronic, oral, daily amiodarone for 2 weeks preligation (n = 19); protocol 4 -- i.v. procainamide, preligation and prereperfusion (n = 21); and protocol 5 -- i.v. verapamil, prereperfusion (n = 18). Each regimen was evaluated with respect to the incidence of reperfusion ventricular fibrillation in dogs that survived to reperfusion, and the results were compared to 77 control dogs that underwent identical coronary artery occlusion and release procedures without drug therapy. The incidence of reperfusion ventricular fibrillation was as follows: protocol 1 -- seven of 15 dogs (47%); protocol 2 -- six of 18 (33%); protocol 3 -- 11 of 16 dogs (69%); protocol 4 -- eight of 17 dogs (47%); and protocol 5 -- 10 of 17 dogs (59%), compared with 36 of 60 (60%) in control dogs. Using chi-square analysis, protocol 2 was beneficial (p antecedent coronary artery ligation periods, and predictive risk indexes for the occurrence of reperfusion ventricular fibrillation were developed. the Mantel-Haenszel method of statistical analysis revealed that none of these protocols resulted in a statistically significant reduction in the incidence of reperfusion ventricular fibrillation. Thus, use of these predictive indexes plus appropriate statistical methods has revealed, unexpectedly, limitations in the efficacy of a spectrum of antiarrhythmic agents in preventing reperfusion ventricular fibrillation.

Spectroscopic study of Alzheimer's amyloid fibrils using terahertz time domain spectroscopy

International Nuclear Information System (INIS)

Jung, Euna; Kim, Jeonghoi; Han, Younho; Moon, Kiwon; Lim, Meehyun; Han, Haewook; Park, Joonhyuck; Kim, Sungjee

2008-01-01

Alzheimer's disease, one of the most common neurodegenerative diseases, is characterized by extensive amyloid deposition. Amyloid deposits contain the abundant fibrils formed by amyloid β protein (Aβ). Because amyloid fibrils are associated with amyloid diseases, including Alzheimer's disease, type 2 diabetes, prion disease, Parkinson's disease, senile systemic amyloidosis and Huntington's disease, there has been considerable interest within the biomedical and biochemical research communities. In transmission electron microscopic (TEM)images, amyloid firils are 0.1∼10μm long and approximately 10nm wide. Amyloid fibrils commonly exhibit self assembled filaments, often described as twisted or parallel assemblies of finer protofilaments. They are formed by the spontaneous aggregation of a wide variety of peptides and proteins. Structural studies of amyloid fibrils have revealed that the common structural motif of virtually all amyloid fibrils consists of cross β sheets in which the peptide strands are arranged perpendicular to the long axis of the fiber. But little was known until recently about the molecular level structures of amyloid fibils. Therefore, spectroscopic investigation of both amyloid fibrils and Aβ at the molecular level can provide the significant evidence for the molecular understanding of amyloidogenesis and for the development of innovative therapeutic and diagnostic approaches. We used terahertz time domain spectroscopy (THz TDS)to investigate both Aβ and amyloid fibril. THz TDS, developed over the last two decades, is a powerful tool to extract the properties of biomaterials and provides unique spectral signatures of biomolecules within 0.1∼10THz, which exists between microwave and infrared frequency range. Current interest in THz radiation arises from its capability of probing the delocalized collective vibrational modes in proteins. Studying the collective modes of proteins in THz frequency range can play an important role in

Morphology and mechanical properties of multi-stranded amyloid fibrils probed by atomistic and coarse-grained simulations

International Nuclear Information System (INIS)

Yoon, Gwonchan; Lee, Myeongsang; Kim, Kyungwoo; In Kim, Jae; Joon Chang, Hyun; Baek, Inchul; Na, Sungsoo; Eom, Kilho

2015-01-01

Amyloid fibrils are responsible for pathogenesis of various diseases and exhibit the structural feature of an ordered, hierarchical structure such as multi-stranded helical structure. As the multi-strandedness of amyloid fibrils has recently been found to be highly correlated with their toxicity and infectivity, it is necessary to study how the hierarchical (i.e. multi-stranded) structure of amyloid fibril is formed. Moreover, although it has recently been reported that the nanomechanics of amyloid proteins plays a key role on the amyloid-induced pathogenesis, a critical role that the multi-stranded helical structure of the fibrils plays in their nanomechanical properties has not fully characterized. In this work, we characterize the morphology and mechanical properties of multi-stranded amyloid fibrils by using equilibrium molecular dynamics simulation and elastic network model. It is shown that the helical pitch of multi-stranded amyloid fibril is linearly proportional to the number of filaments comprising the amyloid fibril, and that multi-strandedness gives rise to improving the bending rigidity of the fibril. Moreover, we have also studied the morphology and mechanical properties of a single protofilament (filament) in order to understand the effect of cross-β structure and mutation on the structures and mechanical properties of amyloid fibrils. Our study sheds light on the underlying design principles showing how the multi-stranded amyloid fibril is formed and how the structure of amyloid fibrils governs their nanomechanical properties. (paper)

Diagnosis and surgical treatment of terminal syringomyelia within spinal cord combined with tethered cord syndrome

Directory of Open Access Journals (Sweden)

Jing-cheng XIE

2016-04-01

Full Text Available Objective To summarize the clinical manifestations, imaging characteristics and experience of surgical treatment of spinal cord terminal syringomyelia with tethered cord syndrome (TCS.  Methods and Results Clinical data of 10 patients with spinal cord syringomyelia combined with TCS surgically treated under microscope from January 1999 to March 2014 in our hospital were retrospectively analyzed. There were 3 males and 7 females with average age of 15.06 years old (ranged from 2 to 35 years old. The course of disease ranged from 3 months to 20 years (average 42.17 months. Among those patients, one patient presented hydromyelia, 8 patients suffered from meningeal cyst within the sacral canal, and one patient were concurrent with sacral dermal sinus. The weakness of lower extremities, especially distal limbs, was the main clinical manifestation. Five patients were accompanied with bowel and bladder dysfunction and 5 patients with sensory disturbance below the level of syringomyelia, especially hypesthesia. Preoperative MRI showed conus medullaris disappeared at the end of spinal cord, and there was fluid signal in the lower spinal cord with hypo-intensity signal in T1WI and hyper-intensity signal in T2WI without enhancement. All patients underwent surgical procedures. Under microscope, filum terminale was cut off, drainage was performed, meningeal cyst within the sacral canal was removed, and tethered cord was released. The success rate of operations was 100%. The duration of surgery ranged from 1.52 to 3.07 h (average 2.15 h, with average intraoperative blood loss 220 ml (ranged from 100 to 410 ml. The tethering filum had been totally resected and histological examination showed typical filum tissue in all cases. No operative complication was found. Visual Analogue Scale (VAS score was decreased, and the lower limbs weakness as well as bowel and bladder dysfunction was gradually relieved after operation. The period of follow-up was ranged from 6

Susceptibility tensor imaging and tractography of collagen fibrils in the articular cartilage.

Science.gov (United States)

Wei, Hongjiang; Gibbs, Eric; Zhao, Peida; Wang, Nian; Cofer, Gary P; Zhang, Yuyao; Johnson, G Allan; Liu, Chunlei

2017-11-01

To investigate the B 0 orientation-dependent magnetic susceptibility of collagen fibrils within the articular cartilage and to determine whether susceptibility tensor imaging (STI) can detect the 3D collagen network within cartilage. Multiecho gradient echo datasets (100-μm isotropic resolution) were acquired from fixed porcine articular cartilage specimens at 9.4 T. The susceptibility tensor was calculated using phase images acquired at 12 or 15 different orientations relative to B 0 . The susceptibility anisotropy of the collagen fibril was quantified and diffusion tensor imaging (DTI) was compared against STI. 3D tractography was performed to visualize and track the collagen fibrils with DTI and STI. STI experiments showed the distinct and significant anisotropic magnetic susceptibility of collagen fibrils within the articular cartilage. STI can be used to measure and quantify susceptibility anisotropy maps. Furthermore, STI provides orientation information of the underlying collagen network via 3D tractography. The findings of this study demonstrate that STI can characterize the orientation variation of collagen fibrils where diffusion anisotropy fails. We believe that STI could serve as a sensitive and noninvasive marker to study the collagen fibrils microstructure. Magn Reson Med 78:1683-1690, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

The Protective Effect of Spinal Cord Stimulation Postconditioning Against Spinal Cord Ischemia/Reperfusion Injury in Rabbits.

Science.gov (United States)

Li, Huixian; Dong, Xiuhua; Jin, Mu; Cheng, Weiping

2018-01-18

Delayed paraplegia due to spinal cord ischemia/reperfusion injury (IRI) remains one of the most severe complications of thoracoabdominal aneurysm surgery, for which effective prevention and treatment is still lacking. The current study investigates whether spinal cord stimulation (SCS) postconditioning has neuroprotective effects against spinal cord IRI. Ninety-six New Zealand white male rabbits were randomly divided into four groups as follows: a sham group and three experimental groups (C group, 2 Hz group, and 50 Hz group) n = 24/group. Spinal cord ischemia was induced by transient infrarenal aortic balloon occlusion for 28 min, after which rabbits in group C underwent no additional intervention, while rabbits in the other two experimental groups underwent 2 Hz or 50 Hz epidural SCS for 30 min at the onset of reperfusion and then daily until sacrifice. Hind limb neurologic function of rabbits was assessed using Jacob scale. Lumbar spinal cords were harvested immediately after sacrifice for histological examination and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The number of viable α-motor neurons in ventral horn was counted and TUNEL-positive rate of α-motor neurons was calculated. Spinal cord IRI was caused by transient infrarenal aorta occlusion for 28 min. Both 2 Hz and 50 Hz SCS postconditioning had neuroprotective effects, particularly the 2 Hz SCS postconditioning. Comparing to C group and 50 Hz group, rabbits in the 2 Hz group demonstrated better hind limb motor function and a lower rate of TUNEL-positive α-motor neuron after eight hours, one day, three days, and seven days of spinal cord reperfusion. More viable α-motor neurons were preserved after one and three days of spinal cord reperfusion in 2 Hz group rabbits than in C group and 50 Hz group rabbits. SCS postconditioning at 2 Hz protected the spinal cord from IRI. © 2018 International Neuromodulation Society.

Atrial Fibrillation

DEFF Research Database (Denmark)

Staerk, Laila; Sherer, Jason A; Ko, Darae

2017-01-01

The past 3 decades have been characterized by an exponential growth in knowledge and advances in the clinical treatment of atrial fibrillation (AF). It is now known that AF genesis requires a vulnerable atrial substrate and that the formation and composition of this substrate may vary depending...... on comorbid conditions, genetics, sex, and other factors. Population-based studies have identified numerous factors that modify the atrial substrate and increase AF susceptibility. To date, genetic studies have reported 17 independent signals for AF at 14 genomic regions. Studies have established...

The economics of atrial fibrillation: a time for review and prioritization.

Science.gov (United States)

Cadilhac, Dominique A

2012-08-01

Stroke associated with atrial fibrillation may occur in up to one third of people who experience an ischemic event, and results in greater stroke severity and poorer health outcomes. The ageing population in developed and developing countries will lead to an increase in the prevalence of atrial fibrillation in society. Detecting people who have atrial fibrillation and ensuring optimal prevention management is essential for reducing the burden of stroke worldwide. There is evidence that use of anticoagulants is inadequate in primary and secondary prevention of stroke. New anticoagulants that have fewer side effects and population screening tools are available. However, there is little information available about the cost-effectiveness of these new options for atrial fibrillation detection and stroke prevention management over current practice. Since resources for spending in health are limited, it is essential that formal economic analyses are undertaken to ensure there are informed and evidence-based decisions on where to best invest stroke prevention resources. It is essential that renewed efforts in the area of atrial fibrillation and options for stroke prevention are undertaken within the public health research community. © 2012 The Author. International Journal of Stroke © 2012 World Stroke Organization.

Influence of dendrimer's structure on its activity against amyloid fibril formation

International Nuclear Information System (INIS)

Klajnert, B.; Cortijo-Arellano, M.; Cladera, J.; Bryszewska, M.

2006-01-01

Inhibition of fibril assembly is a potential therapeutic strategy in neurodegenerative disorders such as prion and Alzheimer's diseases. Highly branched, globular polymers-dendrimers-are novel promising inhibitors of fibril formation. In this study, the effect of polyamidoamine (PAMAM) dendrimers (generations 3rd, 4th, and 5th) on amyloid aggregation of the prion peptide PrP 185-208 and the Alzheimer's peptide Aβ 1-28 was examined. Amyloid fibrils were produced in vitro and their formation was monitored using the dye thioflavin T (ThT). Fluorescence studies were complemented with electron microscopy. The results show that the higher the dendrimer generation, the larger the degree of inhibition of the amyloid aggregation process and the more effective are dendrimers in disrupting the already existing fibrils. A hypothesis on dendrimer-peptide interaction mechanism is presented based on the dendrimers' molecular structure

Characterization of fibrillation process of α-synuclein at the initial stage

International Nuclear Information System (INIS)

Tashiro, Mitsuru; Kojima, Masaki; Kihara, Hiroshi; Kasai, Kouki; Kamiyoshihara, Tomoaki; Ueda, Kenji; Shimotakahara, Sakurako

2008-01-01

α-Synuclein is the major component of the filamentous Lewy bodies and Lewy-related neurites, neuropathological hallmarks of Parkinson's disease. Although numerous studies on α-synuclein fibrillation have been reported, the molecular mechanisms of aggregation and fibrillation at the initial stage are still unclear. In the present study, structural properties and propensities to form fibrils of α-synuclein at the initial stage were investigated using 2D 1 H- 15 N NMR spectroscopy, electron microscope, and small angle X-ray scattering (SAXS). Observation of the 2D 1 H- 15 N HSQC spectra indicated significant attenuation of many cross peak intensities in the regions of KTKEGV-type repeats and the non-Aβ component of Alzheimer's disease amyloid (NAC), suggesting that these regions contributed fibril formation. Oligomerization comprising heptamer was successfully monitored at the initial stage using the time-dependent SAXS measurements

Fibrillation of Aspen by Alkaline Cold Pre-treatment and Vibration Milling

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Kärt KÄRNER

2016-09-01

Full Text Available In this article an attempt to fibrillate aspen bleached chemi-thermo mechanical pulp (BCTMP fibre in an environmentally friendly way is reported. The effects of various NaOH, KOH, urea and ethanol aqueous solutions at lowered temperature were tested for pre-treatment. The pre-treatment was followed by vibration milling aiming to peel off outer cell wall layers and to fibrillate S2 layer of the aspen wood fibre. The effects of the treatments were evaluated by scanning electron microscopy (SEM. The results show that it is possible to fibrillate BCTMP aspen fibres by using alkaline aqueous solutions at low temperatures followed by a mechanical treatment. A strong dependence on fibrillation of cellulose on temperature, time and alkali concentration was established.DOI: http://dx.doi.org/10.5755/j01.ms.22.3.7412

Influence of Aluminium and EGCG on Fibrillation and Aggregation of Human Islet Amyloid Polypeptide

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Zhi-Xue Xu

2016-01-01

Full Text Available The abnormal fibrillation of human islet amyloid polypeptide (hIAPP has been implicated in the development of type II diabetes. Aluminum is known to trigger the structural transformation of many amyloid proteins and induce the formation of toxic aggregate species. The (−-epigallocatechin gallate (EGCG is considered capable of binding both metal ions and amyloid proteins with inhibitory effect on the fibrillation of amyloid proteins. However, the effect of Al(III/EGCG complex on hIAPP fibrillation is unclear. In the present work, we sought to view insight into the structures and properties of Al(III and EGCG complex by using spectroscopic experiments and quantum chemical calculations and also investigated the influence of Al(III and EGCG on hIAPP fibrillation and aggregation as well as their combined interference on this process. Our studies demonstrated that Al(III could promote fibrillation and aggregation of hIAPP, while EGCG could inhibit the fibrillation of hIAPP and lead to the formation of hIAPP amorphous aggregates instead of the ordered fibrils. Furthermore, we proved that the Al(III/EGCG complex in molar ratio of 1 : 1 as Al(EGCG(H2O2 could inhibit the hIAPP fibrillation more effectively than EGCG alone. The results provide the invaluable reference for the new drug development to treat type II diabetes.

Atrial fibrillation and the 4P medicine.

Science.gov (United States)

Censi, Federica; Cianfrocca, Cinzia; Purificato, Ivana

2013-01-01

Although the paradigm of the 4P medicine - Predictive, Personalized, Preemptive, and Participatory - has been suggested several years ago, its application to atrial fibrillation is still far away. Given the increasing prevalence and incidence of this pathology it is the time to promote preventive strategies, by identifying the risk factors associated to life style and by incentivizing innovative diagnostic technologies. The promotion of the correct life style and of the use of diagnostic devices based on innovative and reliable technologies, represent a first step towards the full realization of the revolution of 4P medicine in atrial fibrillation.

Atrial fibrillation and the 4P medicine

Directory of Open Access Journals (Sweden)

Federica Censi

2013-09-01

Full Text Available Although the paradigm of the 4P medicine - Predictive, Personalized, Preemptive, and Participatory - has been suggested several years ago, its application to atrial fibrillation is still far away. Given the increasing prevalence and incidence of this pathology it is the time to promote preventive strategies, by identifying the risk factors associated to life style and by incentivizing innovative diagnostic technologies. The promotion of the correct life style and of the use of diagnostic devices based on innovative and reliable technologies, represent a first step towards the full realization of the revolution of 4P medicine in atrial fibrillation.

Reliable and fast volumetry of the lumbar spinal cord using cord image analyser (Cordial).

Science.gov (United States)

Tsagkas, Charidimos; Altermatt, Anna; Bonati, Ulrike; Pezold, Simon; Reinhard, Julia; Amann, Michael; Cattin, Philippe; Wuerfel, Jens; Fischer, Dirk; Parmar, Katrin; Fischmann, Arne

2018-04-30

To validate the precision and accuracy of the semi-automated cord image analyser (Cordial) for lumbar spinal cord (SC) volumetry in 3D T1w MRI data of healthy controls (HC). 40 3D T1w images of 10 HC (w/m: 6/4; age range: 18-41 years) were acquired at one 3T-scanner in two MRI sessions (time interval 14.9±6.1 days). Each subject was scanned twice per session, allowing determination of test-retest reliability both in back-to-back (intra-session) and scan-rescan images (inter-session). Cordial was applied for lumbar cord segmentation twice per image by two raters, allowing for assessment of intra- and inter-rater reliability, and compared to a manual gold standard. While manually segmented volumes were larger (mean: 2028±245 mm 3 vs. Cordial: 1636±300 mm 3 , p<0.001), accuracy assessments between manually and semi-automatically segmented images showed a mean Dice-coefficient of 0.88±0.05. Calculation of within-subject coefficients of variation (COV) demonstrated high intra-session (1.22-1.86%), inter-session (1.26-1.84%), as well as intra-rater (1.73-1.83%) reproducibility. No significant difference was shown between intra- and inter-session reproducibility or between intra-rater reliabilities. Although inter-rater reproducibility (COV: 2.87%) was slightly lower compared to all other reproducibility measures, between rater consistency was very strong (intraclass correlation coefficient: 0.974). While under-estimating the lumbar SCV, Cordial still provides excellent inter- and intra-session reproducibility showing high potential for application in longitudinal trials. • Lumbar spinal cord segmentation using the semi-automated cord image analyser (Cordial) is feasible. • Lumbar spinal cord is 40-mm cord segment 60 mm above conus medullaris. • Cordial provides excellent inter- and intra-session reproducibility in lumbar spinal cord region. • Cordial shows high potential for application in longitudinal trials.

Risk Factors for Atrial Fibrillation

NARCIS (Netherlands)

B.P. Krijthe (Bouwe)

2013-01-01

textabstractAtrial fibrillation is a common cardiac arrhythmia that is characterized by rapid disorganized atrial electrical activity resulting in absence of atrial contractions. It is diagnosed on the basis of typical findings on an electrocardiogram (ECG). The characteristic ECG findings are

Umbilical Cord Blood: Counselling, Collection, and Banking.

Science.gov (United States)

Armson, B Anthony; Allan, David S; Casper, Robert F

2015-09-01

To review current evidence regarding umbilical cord blood counselling, collection, and banking and to provide guidelines for Canadian health care professionals regarding patient education, informed consent, procedural aspects, and options for cord blood banking in Canada. Selective or routine collection and banking of umbilical cord blood for future stem cell transplantation for autologous (self) or allogeneic (related or unrelated) treatment of malignant and non-malignant disorders in children and adults. Cord blood can be collected using in utero or ex utero techniques. Umbilical cord blood counselling, collection, and banking, education of health care professionals, indications for cord blood collection, short- and long-term risk and benefits, maternal and perinatal morbidity, parental satisfaction, and health care costs. Published literature was retrieved through searches of Medline and PubMed beginning in September 2013 using appropriate controlled MeSH vocabulary (fetal blood, pregnancy, transplantation, ethics) and key words (umbilical cord blood, banking, collection, pregnancy, transplantation, ethics, public, private). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date limits, but results were limited to English or French language materials. Searches were updated on a regular basis and incorporated in the guideline to September 2014. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Umbilical cord blood is a readily available source of hematopoetic stem cells used with increasing frequency as an alternative to

Clinical Differences between Subtypes of Atrial Fibrillation and Flutter: Cross-Sectional Registry of 407 Patients

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Eduardo Dytz Almeida

2015-01-01

Full Text Available Introduction: Atrial fibrillation and atrial flutter account for one third of hospitalizations due to arrhythmias, determining great social and economic impacts. In Brazil, data on hospital care of these patients is scarce. Objective: To investigate the arrhythmia subtype of atrial fibrillation and flutter patients in the emergency setting and compare the clinical profile, thromboembolic risk and anticoagulants use. Methods: Cross-sectional retrospective study, with data collection from medical records of every patient treated for atrial fibrillation and flutter in the emergency department of Instituto de Cardiologia do Rio Grande do Sul during the first trimester of 2012. Results: We included 407 patients (356 had atrial fibrillation and 51 had flutter. Patients with paroxysmal atrial fibrillation were in average 5 years younger than those with persistent atrial fibrillation. Compared to paroxysmal atrial fibrillation patients, those with persistent atrial fibrillation and flutter had larger atrial diameter (48.6 ± 7.2 vs. 47.2 ± 6.2 vs. 42.3 ± 6.4; p < 0.01 and lower left ventricular ejection fraction (66.8 ± 11 vs. 53.9 ± 17 vs. 57.4 ± 16; p < 0.01. The prevalence of stroke and heart failure was higher in persistent atrial fibrillation and flutter patients. Those with paroxysmal atrial fibrillation and flutter had higher prevalence of CHADS2 score of zero when compared to those with persistent atrial fibrillation (27.8% vs. 18% vs. 4.9%; p < 0.01. The prevalence of anticoagulation in patients with CHA2DS2-Vasc ≤ 2 was 40%. Conclusions: The population in our registry was similar in its comorbidities and demographic profile to those of North American and European registries. Despite the high thromboembolic risk, the use of anticoagulants was low, revealing difficulties for incorporating guideline recommendations. Public health strategies should be adopted in order to improve these rates.

Human Islet Amyloid Polypeptide Fibril Binding to Catalase: A Transmission Electron Microscopy and Microplate Study

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Nathaniel G. N. Milton

2010-01-01

Full Text Available The diabetes-associated human islet amyloid polypeptide (IAPP is a 37-amino-acid peptide that forms fibrils in vitro and in vivo. Human IAPP fibrils are toxic in a similar manner to Alzheimer's amyloid-β (Aβ and prion protein (PrP fibrils. Previous studies have shown that catalase binds to Aβ fibrils and appears to recognize a region containing the Gly-Ala-Ile-Ile sequence that is similar to the Gly-Ala-Ile-Leu sequence found in human IAPP residues 24-27. This study presents a transmission electron microscopy (TEM—based analysis of fibril formation and the binding of human erythrocyte catalase to IAPP fibrils. The results show that human IAPP 1-37, 8-37, and 20-29 peptides form fibrils with diverse and polymorphic structures. All three forms of IAPP bound catalase, and complexes of IAPP 1-37 or 8-37 with catalase were identified by immunoassay. The binding of biotinylated IAPP to catalase was high affinity with a KD of 0.77nM, and could be inhibited by either human or rat IAPP 1-37 and 8-37 forms. Fibrils formed by the PrP 118-135 peptide with a Gly-Ala-Val-Val sequence also bound catalase. These results suggest that catalase recognizes a Gly-Ala-Ile-Leu—like sequence in amyloid fibril-forming peptides. For IAPP 1-37 and 8-37, the catalase binding was primarily directed towards fibrillar rather than ribbon-like structures, suggesting differences in the accessibility of the human IAPP 24-27 Gly-Ala-Ile-Leu region. This suggests that catalase may be able to discriminate between different structural forms of IAPP fibrils. The ability of catalase to bind IAPP, Aβ, and PrP fibrils demonstrates the presence of similar accessible structural motifs that may be targets for antiamyloid therapeutic development.

Prednisone prevents atrial fibrillation promotion by atrial tachycardia remodeling in dogs

NARCIS (Netherlands)

Shiroshita-Takeshita, A; Brundel, BJJM; Lavoie, J; Nattel, S

2006-01-01

Background: There is evidence suggesting involvement of oxidative stress, inflammation, and calcineurin/nuclear factor of activated T cell pathways in atrial fibrillation. This study evaluated the efficacy of anti-inflammatory and calcineurin-inhibitory drugs on promotion of atrial fibrillation by

Distribution of elements in human spinal cord

International Nuclear Information System (INIS)

Yukawa, Masae; Kobayashi, T.; Qiu, Y.; Kameda, N.; Ito, Y.; Otomo, E.

1992-01-01

The distribution of elements in human spinal cord was investigated on unfixed frozen cord material using PIXE technique. Distribution of Cu, Zn and Fe were not uniform in the cross section of the spinal cord and concentrations of these elements were higher in the anterior gray horn than in the other areas, while K and Cl distributed uniformly. The content of K changed along the spinal cord from the cervical to the lumbar level. These findings are discussed in relation to current understanding of the physiology of the spinal cord. (author)

Radiation treatment of spinal cord neoplasms

International Nuclear Information System (INIS)

Smirnov, R.V.

1982-01-01

Results of radiation treatment of spinal cord neoplasms are presented. The results of combined (surgical and radiation) treatment of tumors are studied. On the whole it is noted that radiation treatment of initial spinal cord tumours is not practised on a large scale because of low radiostability of spinal cord

Spinal cord involvement in tuberculous meningitis.

Science.gov (United States)

Garg, R K; Malhotra, H S; Gupta, R

2015-09-01

To summarize the incidence and spectrum of spinal cord-related complications in patients of tuberculous meningitis. Reports from multiple countries were included. An extensive review of the literature, published in English, was carried out using Scopus, PubMed and Google Scholar databases. Tuberculous meningitis frequently affects the spinal cord and nerve roots. Initial evidence of spinal cord involvement came from post-mortem examination. Subsequent advancement in neuroimaging like conventional lumbar myelography, computed tomographic myelography and gadolinium-enhanced magnetic resonance-myelography have contributed immensely. Spinal involvement manifests in several forms, like tuberculous radiculomyelitis, spinal tuberculoma, myelitis, syringomyelia, vertebral tuberculosis and very rarely spinal tuberculous abscess. Frequently, tuberculous spinal arachnoiditis develops paradoxically. Infrequently, spinal cord involvement may even be asymptomatic. Spinal cord and spinal nerve involvement is demonstrated by diffuse enhancement of cord parenchyma, nerve roots and meninges on contrast-enhanced magnetic resonance imaging. High cerebrospinal fluid protein content is often a risk factor for arachnoiditis. The most important differential diagnosis of tuberculous arachnoiditis is meningeal carcinomatosis. Anti-tuberculosis therapy is the main stay of treatment for tuberculous meningitis. Higher doses of corticosteroids have been found effective. Surgery should be considered only when pathological confirmation is needed or there is significant spinal cord compression. The outcome in these patients has been unpredictable. Some reports observed excellent recovery and some reported unfavorable outcomes after surgical decompression and debridement. Tuberculous meningitis is frequently associated with disabling spinal cord and radicular complications. Available treatment options are far from satisfactory.

Quantification of anaesthetic effects on atrial fibrillation rate by partial least-squares

International Nuclear Information System (INIS)

Cervigón, R; Moreno, J; Pérez-Villacastín, J; Reilly, R B; Castells, F

2012-01-01

The mechanism underlying atrial fibrillation (AF) remains poorly understood. Multiple wandering propagation wavelets drifting through both atria under hierarchical models are not understood. Some pharmacological drugs, known as antiarrhythmics, modify the cardiac ionic currents supporting the fibrillation process within the atria and may modify the AF propagation dynamics terminating the fibrillation process. Other medications, theoretically non-antiarrhythmic, may slightly affect the fibrillation process in non-defined mechanisms. We evaluated whether the most commonly used anaesthetic agent, propofol, affects AF patterns. Partial least-squares (PLS) analysis was performed to reduce significant noise into the main latent variables to find the differences between groups. The final results showed an excellent discrimination between groups with slow atrial activity during the propofol infusion. (paper)

Stroke prevention in atrial fibrillation

DEFF Research Database (Denmark)

Fanaroff, Alexander C; Steffel, Jan; Alexander, John H

2018-01-01

of anticoagulation for atrial fibrillation (AF). Observational studies employing RWD are useful for describing how oral anticoagulants are used in clinical practice, but generally cannot be used to make claims regarding comparative treatment effects. Questions regarding treatment effect generally are best answered...

Clinical application of low energy intracardiac cardioversion of atrial fibrillation

International Nuclear Information System (INIS)

Wu Liqun; Gu Gang; Su Kan; Su Renying; Shen Yongchu; Shen Weifeng

2002-01-01

Objective: To evaluate the efficacy and safety of low energy intracardiac cardioversion in persistent atria fibrillation. Methods: Low energy intracardiac cardioversion was performed by delivering R wave-synchronized biphasic shocks in 7 patients (4 men, 3 women) with persistent atrial fibrillation. Prior to the procedure, all patients underwent transesophageal echocardiographic examinations to rule out the presence of intracardiac thrombus and received subcutaneous injection of low molecular weight heparin for 3-5 days. Two custom-made 6 Fr catheters (Rhythm Technologies of Getz, USA) were used for de-fibrillation shock delivery. One catheter was positioned in the lower right atrium so that the majority of the catheter electrodes had firm contact with the right atrial free wall. The second catheter was placed randomly either in coronary sinus through right internal jugular vein or in the left pulmonary artery through femoral vein. In addition, a standard diagnostic 6-F quadrupolar catheter was placed at the right ventricular apex for ventricular synchronization and postshock ventricular pacing. Shocks were delivered by Implant Support Device (Model 4510, Teleceronics). After conversion, all patients were treated with intravenous amiodarone in the first 24 hours followed by oral administration. Results: In all 7 patients cardioversion of atrial fibrillation to sinus rhythm was successfully obtained. A mean of 2 ± 1 shocks per patient has been delivered with a total amount of 13 shocks. The average delivered energy was 7.8 ± 2.2 Joules. No complication occurred. At a mean follow-up of 18 ± 9 months, 4 of the 7 patients treated successfully showed sinus rhythm there after. Atrial fibrillation recurred in 3 patients at the second, fifth day and eighth month after cardioversion. Conclusions: Low energy intracardiac cardioversion is effective and safe, and can be easily performed in patients without general anesthesia. It offers a new option for restoring sinus

Therapeutic approaches for spinal cord injury

Directory of Open Access Journals (Sweden)

Alexandre Fogaça Cristante

2012-10-01

Full Text Available This study reviews the literature concerning possible therapeutic approaches for spinal cord injury. Spinal cord injury is a disabling and irreversible condition that has high economic and social costs. There are both primary and secondary mechanisms of damage to the spinal cord. The primary lesion is the mechanical injury itself. The secondary lesion results from one or more biochemical and cellular processes that are triggered by the primary lesion. The frustration of health professionals in treating a severe spinal cord injury was described in 1700 BC in an Egyptian surgical papyrus that was translated by Edwin Smith; the papyrus reported spinal fractures as a ''disease that should not be treated.'' Over the last biological or pharmacological treatment method. Science is unraveling the mechanisms of cell protection and neuroregeneration, but clinically, we only provide supportive care for patients with spinal cord injuries. By combining these treatments, researchers attempt to enhance the functional recovery of patients with spinal cord injuries. Advances in the last decade have allowed us to encourage the development of experimental studies in the field of spinal cord regeneration. The combination of several therapeutic strategies should, at minimum, allow for partial functional recoveries for these patients, which could improve their quality of life.

Umbilical cord blood for unrelated bone marrow replacement; Asia bank and Japan cord blood bank network update.

Science.gov (United States)

Mugishima, Hideo; Takahashi, Tuneo; Nagamura, Tokiko; Asano, Sigetaka; Saito, Hidehiko

2002-08-01

Cord blood offers many advantages including a high concentration of hematopoietic stem cells, a large number of potential donors, and ease of harvest. Furthermore, since there is no risk for either the mother or baby, few people refuse to donate. There is thought to be a low risk for virus contamination and also probably a low incidence and severity of GVHD. Cord blood can be obtained quickly without the assistance of a coordinator and one or 2 locus-mismatched HLA is usually acceptable. In Japan, there are 10 cord blood banks supported by the government. Between 1996 and June 2002, 9,500 units were registered with the Japan cord blood bank network (JCBBN). 630 units were delivered and most of these were transplanted. The status of registered cord blood units worldwide is shown. 59,081 units have been registered by NETCORD. The Japan cord blood bank network accounts for 13% of these units. I will discuss the Tokyo cord blood tank (TCBB). The bank at Tokyo, to which we belong, is one of the largest banks in Japan. We helped to establish Asia CORD in 2000 and have held annual conferences and meetings in Tokyo to exchange information. So far, China, Korea, Taiwan, Thailand, Viet Nam and Japan have participated. We accepted three trainees from the Ho Chi Minh City Blood Transfusion and Hematology Center for training in cord blood transplantation in May 2001. In January 2002, a patient with ALL received cord blood and was successfully engrafted at Ho Chi Minh City Blood Transfusion and Hematology Center. We present here the clinical outcome of these patients through Tokyo cord blood bank and Japan cord blood bank network. First, the number of CB units stored and registered at JCBBN and TCBB has increased rapidly over the past two years. Second, the survival rate of acute leukemia patients in release was significantly lower than that in patients in CR. Third, the engraftment rate in patients with metabolic disease (50%) was lower than that in patients with leukemia

Amyloid Fibril Polymorphism: Almost Identical on the Atomic Level, Mesoscopically Very Different.

Science.gov (United States)

Seuring, Carolin; Verasdonck, Joeri; Ringler, Philippe; Cadalbert, Riccardo; Stahlberg, Henning; Böckmann, Anja; Meier, Beat H; Riek, Roland

2017-03-02

Amyloid polymorphism of twisted and straight β-endorphin fibrils was studied by negative-stain transmission electron microscopy, scanning transmission electron microscopy, and solid-state nuclear magnetic resonance spectroscopy. Whereas fibrils assembled in the presence of salt formed flat, striated ribbons, in the absence of salt they formed mainly twisted filaments. To get insights into their structural differences at the atomic level, 3D solid-state NMR spectra of both fibril types were acquired, allowing the detection of the differences in chemical shifts of 13 C and 15 N atoms in both preparations. The spectral fingerprints and therefore the chemical shifts are very similar for both fibril types. This indicates that the monomer structure and the molecular interfaces are almost the same but that these small differences do propagate to produce flat and twisted morphologies at the mesoscopic scale. This finding is in agreement with both experimental and theoretical considerations on the assembly of polymers (including amyloids) under different salt conditions, which attribute the mesoscopic difference of flat versus twisted fibrils to electrostatic intermolecular repulsions.

Trauma: Spinal Cord Injury.

Science.gov (United States)

Eckert, Matthew J; Martin, Matthew J

2017-10-01

Injuries to the spinal column and spinal cord frequently occur after high-energy mechanisms of injury, or with lower-energy mechanisms, in select patient populations like the elderly. A focused yet complete neurologic examination during the initial evaluation will guide subsequent diagnostic procedures and early supportive measures to help prevent further injury. For patients with injury to bone and/or ligaments, the initial focus should be spinal immobilization and prevention of inducing injury to the spinal cord. Spinal cord injury is associated with numerous life-threatening complications during the acute and long-term phases of care that all acute care surgeons must recognize. Published by Elsevier Inc.

Umbilical cord cell banking-implications for the future

International Nuclear Information System (INIS)

Gunning, Jennifer

2005-01-01

The first successful cord cell transplant to a sibling with Fanconi's anaemia took place 15 years ago. This proven utility of cord blood led to the establishment of cord blood banks both private and public and there are now nearly 100 cord blood banks worldwide. It is estimated that over 200,000 cord blood units (CBU) are held by the private sector and over 160,000 CBU are registered with the largest public cord blood registry. There is a tension between private cord blood banks, which store CBU for autologous or family use, and public banks, which store CBU for unrelated use and the ethics of private cord blood storage has been questioned. But more general ethical questions also arise regarding ownership, consent, confidentiality, costs and quality standards and patenting. In looking at these ethical issues one also needs to look at potential future use of cord blood stem cells. Up until now cord cells have principally been used in the treatment of paediatric blood and immune disorders. Improvements in cell expansion technology will make CBU more appropriate also for treating adults with such disorders. However, it has also been demonstrated that cord blood stem cells have the capacity to differentiate into other types of cells, neuronal, bone, epithelial and muscle which would have a future role to play in cell therapy and regenerative medicine

Apixaban in patients at risk of stroke undergoing atrial fibrillation ablation

DEFF Research Database (Denmark)

Kirchhof, Paulus; Haeusler, Karl Georg; Blank, Benjamin

2018-01-01

Aims: It is recommended to perform atrial fibrillation ablation with continuous anticoagulation. Continuous apixaban has not been tested. Methods and results: We compared continuous apixaban (5 mg b.i.d.) to vitamin K antagonists (VKA, international normalized ratio 2-3) in atrial fibrillation pa...

Cardiovascular exercise and burden of arrhythmia in patients with atrial fibrillation

DEFF Research Database (Denmark)

Skielboe, Ane Katrine; Bandholm, Thomas Quaade; Hakmann, Stine

2017-01-01

BACKGROUND: Physical activity at moderate-high intensity is recommended to prevent lifestyle diseases. Patients with atrial fibrillation are at risk of a sedentary lifestyle due to fear of exercise-induced episodes of atrial fibrillation. The burden of arrhythmia can be reduced by physical exercise...

Insulin fibrillation: The influence and coordination of Zn²⁺

DEFF Research Database (Denmark)

Frankær, Christian Grundahl; Sønderby, Pernille; Bang, Maria Blanner

2017-01-01

fibrils has been debated for some years. We have therefore investigated the influence and binding geometry of zinc in fibrillated insulin using extended X-ray absorption fine-structure and X-ray absorption near-edge structure spectroscopy. The results were validated with fibre diffraction, Transmission...

Irradiation effect on the seed vigor, SOD activity and MDA content in germinating seeds of yellow-seeded and black-seeded rape seed (Brassica napus L.)

International Nuclear Information System (INIS)

Han Jixiang; Hu Danhong; Liu Houli

1993-01-01

Seeds of a set of near-isogenic lines (Brassica napus L.) with different seed coat color from yellow to black were irradiated by 60 Co γ-rays of 150 krad. Seed vigor, superoxide dismutase (SOD) and malondialdehyde (MDA) in germinating seeds were analysed. In these characters, no significant difference between yellow-seeded lines (YLs) and black-seeded lines (BLs) showed before irradiation. But after irradiation, SOD activity in YLs was lower than that in BLs. While MDA content in YLs was obviously higher that that in DLs. As a result of irradiation, seed vigor of YLs was lower than that in BLs. these results indicated that the irradiation resistance of rape seed was related to the level of SOD as well as protective structure or substances in seed coat and that the radiosensitivity of YLs was higher than that of DLs

The architecture of amyloid-like peptide fibrils revealed by X-ray scattering, diffraction and electron microscopy

Energy Technology Data Exchange (ETDEWEB)

Langkilde, Annette E., E-mail: annette.langkilde@sund.ku.dk [University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen (Denmark); Morris, Kyle L.; Serpell, Louise C. [University of Sussex, Falmer, Brighton (United Kingdom); Svergun, Dmitri I. [European Molecular Biology Laboratory, Hamburg Outstation, 22607 Hamburg (Germany); Vestergaard, Bente [University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen (Denmark)

2015-04-01

The aggregation process and the fibril state of an amyloidogenic peptide suggest monomer addition to be the prevailing mechanism of elongation and a model of the peptide packing in the fibrils has been obtained. Structural analysis of protein fibrillation is inherently challenging. Given the crucial role of fibrils in amyloid diseases, method advancement is urgently needed. A hybrid modelling approach is presented enabling detailed analysis of a highly ordered and hierarchically organized fibril of the GNNQQNY peptide fragment of a yeast prion protein. Data from small-angle X-ray solution scattering, fibre diffraction and electron microscopy are combined with existing high-resolution X-ray crystallographic structures to investigate the fibrillation process and the hierarchical fibril structure of the peptide fragment. The elongation of these fibrils proceeds without the accumulation of any detectable amount of intermediate oligomeric species, as is otherwise reported for, for example, glucagon, insulin and α-synuclein. Ribbons constituted of linearly arranged protofilaments are formed. An additional hierarchical layer is generated via the pairing of ribbons during fibril maturation. Based on the complementary data, a quasi-atomic resolution model of the protofilament peptide arrangement is suggested. The peptide structure appears in a β-sheet arrangement reminiscent of the β-zipper structures evident from high-resolution crystal structures, with specific differences in the relative peptide orientation. The complexity of protein fibrillation and structure emphasizes the need to use multiple complementary methods.

Atrial fibrillation pearls and perils of management.

Science.gov (United States)

Kudenchuk, P J

1996-01-01

Atrial fibrillation, a common arrhythmia, is responsible for considerable cardiovascular morbidity. Its management demands more than antiarrhythmic therapy alone, but must address the causes and consequences of the arrhythmia. Although remediable causes are infrequently found, a thorough search for associated heart disease or its risk factors results in better-informed patient management. Controlling the ventricular response and protecting from thromboembolic complications are important initial goals of therapy and may include the administration of aspirin in younger, low-risk patients. Older patients and those with risk factors for systemic embolism are not adequately protected from stroke complications by aspirin therapy alone. It remains controversial whether all high-risk patients should receive warfarin and at what intensity. Whether and how sinus rhythm should be restored and maintained poses the greatest therapeutic controversy for atrial fibrillation. The mortal risk of antiarrhythmic therapy is substantially greater in patients with evidence of heart failure. In such persons, the risks and benefits of maintaining normal sinus rhythm with antiarrhythmic medications should be weighted carefully. A definitive cure for atrial fibrillation remains elusive, but promising surgical and catheter ablation therapies are being developed. PMID:8686300

Dronedarone: a novel antiarrhythmic agent for the treatment of atrial fibrillation.

Science.gov (United States)

Duray, Gabor Z; Ehrlich, Joachim R; Hohnloser, Stefan H

2010-01-01

To describe the electrophysiological profile and the clinical portfolio of dronedarone, a new multichannel-blocking antiarrhythmic drug developed for the treatment of atrial fibrillation. Dronedarone is a derivative of amiodarone that is free of iodine and less lipophilic. The drug has - as its predecessor - multichannel-blocking efficacy and in addition vasodilating effects. It reduces the incidence of ventricular fibrillation in several experimental models. Dronedarone has undergone thorough clinical evaluation in various patient populations. In two large trials, the drug was shown to postpone the recurrence of atrial fibrillation after cardioversion relative to placebo. In a trial in unstable heart failure patients, there was excess mortality in the dronedarone arm. This trial was stopped prematurely and prompted the conduct of a large outcome study. The ATHENA trial demonstrated a significant reduction in cardiovascular hospitalizations and death in atrial fibrillation patients randomly assigned to receive dronedarone or placebo. This large trial in more than 4600 patients revealed no signs of excess mortality or morbidity in patients receiving dronedarone. On the basis of the results of five international, multicenter, randomized clinical trials involving nearly 6300 patients, dronedarone was approved by the FDA for treatment of nonpermanent atrial fibrillation to reduce the risk of cardiovascular hospitalization.

Signal analysis of ventricular fibrillation

NARCIS (Netherlands)

Herbschleb, J.N.; Heethaar, R.M.; Tweel, L.H. van der; Zimmerman, A.N.E.; Meijler, F.L.

Signal analysis of electro(cardio)grams during ventricular fibrillation (VF) in dogs and human patients indicates more organization and regularity than the official WHO definition suggests. The majority of the signal is characterized by a power spectrum with narrow, equidistant peaks. In a further

Molecular Mechanisms and New Treatment Paradigm for Atrial Fibrillation.

Science.gov (United States)

Sirish, Padmini; Li, Ning; Timofeyev, Valeriy; Zhang, Xiao-Dong; Wang, Lianguo; Yang, Jun; Lee, Kin Sing Stephen; Bettaieb, Ahmed; Ma, Sin Mei; Lee, Jeong Han; Su, Demetria; Lau, Victor C; Myers, Richard E; Lieu, Deborah K; López, Javier E; Young, J Nilas; Yamoah, Ebenezer N; Haj, Fawaz; Ripplinger, Crystal M; Hammock, Bruce D; Chiamvimonvat, Nipavan

2016-05-01

Atrial fibrillation represents the most common arrhythmia leading to increased morbidity and mortality, yet, current treatment strategies have proven inadequate. Conventional treatment with antiarrhythmic drugs carries a high risk for proarrhythmias. The soluble epoxide hydrolase enzyme catalyzes the hydrolysis of anti-inflammatory epoxy fatty acids, including epoxyeicosatrienoic acids from arachidonic acid to the corresponding proinflammatory diols. Therefore, the goal of the study is to directly test the hypotheses that inhibition of the soluble epoxide hydrolase enzyme can result in an increase in the levels of epoxyeicosatrienoic acids, leading to the attenuation of atrial structural and electric remodeling and the prevention of atrial fibrillation. For the first time, we report findings that inhibition of soluble epoxide hydrolase reduces inflammation, oxidative stress, atrial structural, and electric remodeling. Treatment with soluble epoxide hydrolase inhibitor significantly reduces the activation of key inflammatory signaling molecules, including the transcription factor nuclear factor κ-light-chain-enhancer, mitogen-activated protein kinase, and transforming growth factor-β. This study provides insights into the underlying molecular mechanisms leading to atrial fibrillation by inflammation and represents a paradigm shift from conventional antiarrhythmic drugs, which block downstream events to a novel upstream therapeutic target by counteracting the inflammatory processes in atrial fibrillation. © 2016 American Heart Association, Inc.

Atrial fibrillation: Therapeutic potential of atrial K+ channel blockers.

Science.gov (United States)

Ravens, Ursula; Odening, Katja E

2017-08-01

Despite the epidemiological scale of atrial fibrillation, current treatment strategies are of limited efficacy and safety. Ideally, novel drugs should specifically correct the pathophysiological mechanisms responsible for atrial fibrillation with no other cardiac or extracardiac actions. Atrial-selective drugs are directed toward cellular targets with sufficiently different characteristics in atria and ventricles to modify only atrial function. Several potassium (K + ) channels with either predominant expression in atria or distinct electrophysiological properties in atria and ventricles can serve as atrial-selective drug targets. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting I Kur , the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting I K,ACh , the Ca 2+ -activated K + channels of small conductance (SK) conducting I SK , and the two pore domain K + (K2P) channels TWIK-1, TASK-1 and TASK-3 that are responsible for voltage-independent background currents I TWIK-1 , I TASK-1 , and I TASK-3 . Here, we briefly review the characteristics of these K + channels and their roles in atrial fibrillation. The antiarrhythmic potential of drugs targeting the described channels is discussed as well as their putative value in treatment of atrial fibrillation. Copyright © 2016 Elsevier Inc. All rights reserved.

Studies of the structure of insulin fibrils by Fourier transform infrared (FTIR) spectroscopy and electron microscopy.

Science.gov (United States)

Nielsen, L; Frokjaer, S; Carpenter, J F; Brange, J

2001-01-01

Fibril formation (aggregation) of insulin was investigated in acid media by visual inspection, transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy. Insulin fibrillated faster in hydrochloric acid than in acetic acid at elevated temperatures, whereas the fibrillation tendencies were reversed at ambient temperatures. Electron micrographs showed that bovine insulin fibrils consisted of long fibers with a diameter of 5 to 10 nm and lengths of several microns. The fibrils appeared either as helical filaments (in hydrochloric acid) or arranged laterally in bundles (in acetic acid, NaCl). Freeze-thawing cycles broke the fibrils into shorter segments. FTIR spectroscopy showed that the native secondary structure of insulin was identical in hydrochloric acid and acetic acid, whereas the secondary structure of fibrils formed in hydrochloric acid was different from that formed in acetic acid. Fibrils of bovine insulin prepared by heating or agitating an acid solution of insulin showed an increased content of beta-sheet (mostly intermolecular) and a decrease in the intensity of the alpha-helix band. In hydrochloric acid, the frequencies of the beta-sheet bands depended on whether the fibrillation was induced by heating or agitation. This difference was not seen in acetic acid. Freeze-thawing cycles of the fibrils in hydrochloric acid caused an increase in the intensity of the band at 1635 cm(-1) concomitant with reduction of the band at 1622 cm(-1). The results showed that the structure of insulin fibrils is highly dependent on the composition of the acid media and on the treatment. Copyright 2001 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 90: 29-37, 2001

Family-directed umbilical cord blood banking.

Science.gov (United States)

Gluckman, Eliane; Ruggeri, Annalisa; Rocha, Vanderson; Baudoux, Etienne; Boo, Michael; Kurtzberg, Joanne; Welte, Kathy; Navarrete, Cristina; van Walraven, Suzanna M

2011-11-01

Umbilical cord blood transplantation from HLA-identical siblings provides good results in children. These results support targeted efforts to bank family cord blood units that can be used for a sibling diagnosed with a disease which can be cured by allogeneic hematopoietic stem cell transplantation or for research that investigates the use of allogeneic or autologous cord blood cells. Over 500 patients transplanted with related cord blood units have been reported to the Eurocord registry with a 4-year overall survival of 91% for patients with non-malignant diseases and 56% for patients with malignant diseases. Main hematologic indications in children are leukemia, hemoglobinopathies or inherited hematologic, immunological or metabolic disorders. However, family-directed cord blood banking is not widely promoted; many cord blood units used in sibling transplantation have been obtained from private banks that do not meet the necessary criteria required to store these units. Marketing by private banks who predominantly store autologous cord blood units has created public confusion. There are very few current validated indications for autologous storage but some new indications might appear in the future. Little effort is devoted to provide unbiased information and to educate the public as to the distinction between the different types of banking, economic models and standards involved in such programs. In order to provide a better service for families in need, directed-family cord blood banking activities should be encouraged and closely monitored with common standards, and better information on current and future indications should be made available.

Risk of atrial fibrillation as a function of the electrocardiographic PR interval

DEFF Research Database (Denmark)

Nielsen, Jonas Bille; Pietersen, Adrian; Graff, Claus

2013-01-01

Prolongation of the PR interval has been associated with an increased risk of incident atrial fibrillation (AF).......Prolongation of the PR interval has been associated with an increased risk of incident atrial fibrillation (AF)....

The oblique cord of the forearm in man.

Science.gov (United States)

Tubbs, R Shane; O'Neil, James T; Key, Christopher D; Zarzour, Jessica G; Fulghum, Sarah B; Kim, Eugenia J; Lyerly, Michael J; Shoja, Mohammadali M; George Salter, E; Jerry Oakes, W

2007-05-01

There is minimal and often conflicting data in the literature regarding the oblique cord of the forearm. The current study seeks to elucidate further the anatomy of this structure of the upper extremity. In adult cadavers, the oblique cord was observed for and, when found, measurements were made of it. Ranges of motion were carried out while observation of the oblique cord was made. An oblique cord was found on 52.6% of sides. Gantzer's muscle was found on 55% of sides and, when present, had attachment into the oblique cord on five sides. The oblique cord was present on 13 sides with a Gantzer's muscle. Of the 20 sides with an oblique cord, no Gantzer's muscle was found on 10. The mean length of the oblique cord was 3.4 cm. In the majority of specimens, this cord tapered from proximal to distal. The proximal, middle, and distal widths of this structure had means 9, 7, and 4 mm, respectively. The oblique cord was found to travel approximately 45 degrees from a line drawn through the ulna and more or less traveled perpendicular to the insertion site of the bicipital tendon. This ligament was lax in the neutral position and with pronation became lax in all specimens. The oblique cord progressively became taut with increased supination from the neutral position and was maximally taut with the forearm fully supinated. Tautness of this cord was also found with distal distraction of the radius. Following the transection of the oblique cord, no discernable difference was observed in regard to maximal supination of the forearm or distal distraction of the radius. No obvious instability of the proximal forearm was found following transection of the oblique cord. Functionally, although the oblique cord may resist supination, it is unlikely that this structure affords significant stability to the proximal forearm, as it was often absent, of a very small caliber, and based on our observations, following its transection, the amount of supination of the forearm did not increase

SAFETY OF AMIODARONE USAGE IN PATIENTS WITH WOLFF-PARKINSON-WHITE SYNDROME AND ATRIAL FIBRILLATION

Directory of Open Access Journals (Sweden)

D. A. Kuzhel

2010-01-01

Full Text Available Amiodarone is one of the basic antiarrhytmic drugs for atrial fibrillation treatment. However application of amiodarone in patients with atrial fibrillation and Wolff-Parkinson-White syndrome can induce ventricular fibrillation. Amiodarone usage in these patients should be accompanied by readiness for performance of resuscitation. This is confirmed by clinical case presentation.

Pregnancy Complications: Umbilical Cord Abnormalities

Science.gov (United States)

... Umbilical cord abnormalities Umbilical cord abnormalities Now playing: E-mail to a friend Please fill in all fields. ... blood supply) to the baby. The two arteries transport waste from the baby to the placenta (where ...

78 FR 11207 - Clinical Study Designs for Surgical Ablation Devices for Treatment of Atrial Fibrillation...

Science.gov (United States)

2013-02-15

...] Clinical Study Designs for Surgical Ablation Devices for Treatment of Atrial Fibrillation; Guidance for... devices intended for the treatment of atrial fibrillation. DATES: Submit either electronic or written... Study Designs for Surgical Ablation Devices for Treatment of Atrial Fibrillation'' to the Division of...

Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)

OpenAIRE

Antonenko, Kateryna; Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Becattini, Cecilia; Marcheselli, Simona; Rueckert, Christina; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Csiba, Laszló; Szabó, Lilla; Sohn, Sung-Il; Tassinari, Tiziana; Abdul-Rahim, Azmil H

2016-01-01

Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes.\\ud Methods Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibril...

Fibril deformation under load of the rabbit Achilles tendon and medial collateral ligament femoral entheses.

Science.gov (United States)

Sevick, Johnathan L; Abusara, Ziad; Andrews, Stephen H; Xu, Minjia; Khurshid, Saad; Chatha, Jansher; Hart, David A; Shrive, Nigel G

2018-04-10

Microscopic visualization under load of the region connecting ligaments/tendons to bone, the enthesis, has been performed previously; however, specific investigation of individual fibril deformation may add insight to such studies. Detailed visualization of fibril deformation would inform on the mechanical strategies employed by this tissue in connecting two mechanically disparate materials. Clinically, an improved understanding of enthesis mechanics may help guide future restorative efforts for torn or injured ligaments/tendons, where the enthesis is often a point of weakness. In this study, a custom ligament/tendon enthesis loading device was designed and built, a unique method of sample preparation was devised, and second harmonic and two-photon fluorescence microscopy were used to capture the fibril-level load response of the rabbit Achilles tendon and medial collateral ligament femoral entheses. A focus was given to investigation of the mechanical problem of fibril embedment. Resultant images indicate a rapid (occurring over approximately 60 μm) change in fibril orientation at the interface of ligament/tendon and calcified fibrocartilage early in the loading regime, before becoming relatively constant. Such a change in fibril angle helps confirm the materially graded region demonstrated by others, while, in this case, providing additional insight into fibril bending. We speculate that the scale of the mechanical problem (i.e., fibril diameters being on the order of 250 nm) allows fibrils to bend over the small (relative to the imaging field of view, but large relative to fibril diameter) distances observed; thus, potentially lessening required embedment lengths. Nevertheless, this behavior merits further investigation to be confirmed. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Imaging β-amyloid fibrils in Alzheimer's disease: a critical analysis through simulation of amyloid fibril polymerization

International Nuclear Information System (INIS)

Shoghi-Jadid, Kooresh; Barrio, Jorge R.; Kepe, Vladimir; Wu, H.-M.; Small, Gary W.; Phelps, Michael E.; Huang, S.-C.

2005-01-01

The polymerization of β-amyloid (Aβ) peptides into fibrillary plaques is implicated, in part, in the pathogenesis of Alzheimer's disease. Aβ molecular imaging probes (Aβ-MIPs) have been introduced in an effort to quantify amyloid burden or load, in subjects afflicted with AD by invoking the classic PET receptor model for the quantitation of neuronal receptor density. In this communication, we explore conceptual differences between imaging the density of amyloid fibril polymers and neuronal receptors. We formulate a mathematical model for the polymerization of Aβ with parameters that are mapped to biological modulators of fibrillogenesis and introduce a universal measure for amyloid load to accommodate various interactions of Aβ-MIPs with fibrils. Subsequently, we hypothesize four Aβ-MIPs and utilize the fibrillogenesis model to simulate PET tissue time activity curves (TACs). Given the unique nature of polymer growth and resulting PET TAC, the four probes report differing amyloid burdens for a given brain pathology, thus complicating the interpretation of PET images. In addition, we introduce the notion of an MIP's resolution, apparent maximal binding site concentration, optimal kinetic topology and its resolving power in characterizing the pathological progression of AD and the effectiveness of drug therapy. The concepts introduced in this work call for a new paradigm that goes beyond the classic parameters B max and K D to include binding characteristics to polymeric peptide aggregates such as amyloid fibrils, neurofibrillary tangles and prions

Diffusion tensor imaging in spinal cord injury

International Nuclear Information System (INIS)

Kamble, Ravindra B; Venkataramana, Neelam K; Naik, Arun L; Rao, Shailesh V

2011-01-01

To assess the feasibility of spinal tractography in patients of spinal cord injury vs a control group and to compare fractional anisotropy (FA) values between the groups. Diffusion tensor imaging (DTI) was performed in the spinal cord of 29 patients (18 patients and 11 controls). DTI was done in the cervical region if the cord injury was at the dorsal or lumbar region and in the conus region if cord injury was in the cervical or dorsal region. FA was calculated for the patients and the controls and the values were compared. The mean FA value was 0.550±0.09 in the control group and 0.367±0.14 in the patients; this difference was statistically significant (P=0.001). Spinal tractography is a feasible technique to assess the extent of spinal cord injury by FA, which is reduced in patients of spinal cord injury, suggesting possible Wallerian degeneration. In future, this technique may become a useful tool for assessing cord injury patients after stem cell therapy, with improvement in FA values indicating axonal regeneration

Protein disulfide isomerase interacts with tau protein and inhibits its fibrillization.

Directory of Open Access Journals (Sweden)

Li-Rong Xu

Full Text Available BACKGROUND: Tau protein is implicated in the pathogenesis of neurodegenerative disorders such as tauopathies including Alzheimer disease, and Tau fibrillization is thought to be related to neuronal toxicity. Physiological inhibitors of Tau fibrillization hold promise for developing new strategies for treatment of Alzheimer disease. Because protein disulfide isomerase (PDI is both an enzyme and a chaperone, and implicated in neuroprotection against Alzheimer disease, we want to know whether PDI can prevent Tau fibrillization. In this study, we have investigated the interaction between PDI and Tau protein and the effect of PDI on Tau fibrillization. METHODOLOGY/PRINCIPAL FINDINGS: As evidenced by co-immunoprecipitation and confocal laser scanning microscopy, human PDI interacts and co-locates with some endogenous human Tau on the endoplasmic reticulum of undifferentiated SH-SY5Y neuroblastoma cells. The results from isothermal titration calorimetry show that one full-length human PDI binds to one full-length human Tau (or human Tau fragment Tau244-372 monomer with moderate, micromolar affinity at physiological pH and near physiological ionic strength. As revealed by thioflavin T binding assays, Sarkosyl-insoluble SDS-PAGE, and transmission electron microscopy, full-length human PDI remarkably inhibits both steps of nucleation and elongation of Tau244-372 fibrillization in a concentration-dependent manner. Furthermore, we find that two molecules of the a-domain of human PDI interact with one Tau244-372 molecule with sub-micromolar affinity, and inhibit both steps of nucleation and elongation of Tau244-372 fibrillization more strongly than full-length human PDI. CONCLUSIONS/SIGNIFICANCE: We demonstrate for the first time that human PDI binds to Tau protein mainly through its thioredoxin-like catalytic domain a, forming a 1∶1 complex and preventing Tau misfolding. Our findings suggest that PDI could act as a physiological inhibitor of Tau

Alterations in Cortical Sensorimotor Connectivity following Complete Cervical Spinal Cord Injury: A Prospective Resting-State fMRI Study.

Directory of Open Access Journals (Sweden)

Akinwunmi Oni-Orisan

Full Text Available Functional magnetic resonance imaging (fMRI studies have demonstrated alterations during task-induced brain activation in spinal cord injury (SCI patients. The interruption to structural integrity of the spinal cord and the resultant disrupted flow of bidirectional communication between the brain and the spinal cord might contribute to the observed dynamic reorganization (neural plasticity. However, the effect of SCI on brain resting-state connectivity patterns remains unclear. We undertook a prospective resting-state fMRI (rs-fMRI study to explore changes to cortical activation patterns following SCI. With institutional review board approval, rs-fMRI data was obtained in eleven patients with complete cervical SCI (>2 years post injury and nine age-matched controls. The data was processed using the Analysis of Functional Neuroimages software. Region of interest (ROI based analysis was performed to study changes in the sensorimotor network using pre- and post-central gyri as seed regions. Two-sampled t-test was carried out to check for significant differences between the two groups. SCI patients showed decreased functional connectivity in motor and sensory cortical regions when compared to controls. The decrease was noted in ipsilateral, contralateral, and interhemispheric regions for left and right precentral ROIs. Additionally, the left postcentral ROI demonstrated increased connectivity with the thalamus bilaterally in SCI patients. Our results suggest that cortical activation patterns in the sensorimotor network undergo dynamic reorganization following SCI. The presence of these changes in chronic spinal cord injury patients is suggestive of the inherent neural plasticity within the central nervous system.

Smartphone electrographic monitoring for atrial fibrillation in acute ischemic stroke and transient ischemic attack.

Science.gov (United States)

Tu, Hans T; Chen, Ziyuan; Swift, Corey; Churilov, Leonid; Guo, Ruibing; Liu, Xinfeng; Jannes, Jim; Mok, Vincent; Freedman, Ben; Davis, Stephen M; Yan, Bernard

2017-10-01

Rationale Paroxysmal atrial fibrillation is a common and preventable cause of devastating strokes. However, currently available monitoring methods, including Holter monitoring, cardiac telemetry and event loop recorders, have drawbacks that restrict their application in the general stroke population. AliveCor™ heart monitor, a novel device that embeds miniaturized electrocardiography (ECG) in a smartphone case coupled with an application to record and diagnose the ECG, has recently been shown to provide an accurate and sensitive single lead ECG diagnosis of atrial fibrillation. This device could be used by nurses to record a 30-s ECG instead of manual pulse taking and automatically provide a diagnosis of atrial fibrillation. Aims To compare the proportion of patients with paroxysmal atrial fibrillation detected by AliveCor™ ECG monitoring with current standard practice. Sample size 296 Patients. Design Consecutive ischemic stroke and transient ischemic attack patients presenting to participating stroke units without known atrial fibrillation will undergo intermittent AliveCor™ ECG monitoring administered by nursing staff at the same frequency as the vital observations of pulse and blood pressure until discharge, in addition to the standard testing paradigm of each participating stroke unit to detect paroxysmal atrial fibrillation. Study outcome Proportion of patients with paroxysmal atrial fibrillation detected by AliveCor™ ECG monitoring compared to 12-lead ECG, 24-h Holter monitoring and cardiac telemetry. Discussion Use of AliveCor™ heart monitor as part of routine stroke unit nursing observation has the potential to be an inexpensive non-invasive method to increase paroxysmal atrial fibrillation detection, leading to improvement in stroke secondary prevention.

Directly measuring spinal cord blood flow and spinal cord perfusion pressure via the collateral network: correlations with changes in systemic blood pressure.

Science.gov (United States)

Kise, Yuya; Kuniyoshi, Yukio; Inafuku, Hitoshi; Nagano, Takaaki; Hirayasu, Tsuneo; Yamashiro, Satoshi

2015-01-01

During thoracoabdominal surgery in which segmental arteries are sacrificed over a large area, blood supply routes from collateral networks have received attention as a means of avoiding spinal cord injury. The aim of this study was to investigate spinal cord blood supply through a collateral network by directly measuring spinal cord blood flow and spinal cord perfusion pressure experimentally. In beagle dogs (n = 8), the thoracoabdominal aorta and segmental arteries L1-L7 were exposed, and a temporary bypass was created for distal perfusion. Next, a laser blood flow meter was placed on the spinal dura mater in the L5 region to measure the spinal cord blood flow. The following were measured simultaneously when the direct blood supply from segmental arteries L2-L7 to the spinal cord was stopped: mean systemic blood pressure, spinal cord perfusion pressure (blood pressure within the aortic clamp site), and spinal cord blood flow supplied via the collateral network. These variables were then investigated for evidence of correlations. Positive correlations were observed between mean systemic blood pressure and spinal cord blood flow during interruption of segmental artery flow both with (r = 0.844, P flow with and without distal perfusion (r = 0.803, P network from outside the interrupted segmental arteries, and high systemic blood pressure (∼1.33-fold higher) was needed to obtain the preclamping spinal cord blood flow, whereas 1.68-fold higher systemic blood pressure was needed when distal perfusion was halted. Spinal cord blood flow is positively correlated with mean systemic blood pressure and spinal cord perfusion pressure under spinal cord ischemia caused by clamping a wide range of segmental arteries. In open and endovascular thoracic and thoracoabdominal surgery, elevating mean systemic blood pressure is a simple and effective means of increasing spinal cord blood flow, and measuring spinal cord perfusion pressure seems to be useful for monitoring

Organic leek seed production - securing seed quality

DEFF Research Database (Denmark)

Deleuran, Lise Christina; Boelt, Birte

2011-01-01

To maintain integrity in organic farming, availability of organically produced GM-free seed of varieties adapted to organic production systems is of vital impor-tance. Despite recent achievements, organic seed supply for a number of vegetable species is insufficient. Still, in many countries...... seeds. Tunnel production is a means of securing seed of high genetic purity and quality, and organic leek (Allium porrum L.) seed production was tested in tunnels in Denmark. The present trial focused on steckling size and in all years large stecklings had a positive effect on both seed yield...

Organic Leek Seed Production - Securing Seed Quality

DEFF Research Database (Denmark)

Deleuran, L C; Boelt, B

2011-01-01

To maintain integrity in organic farming, availability of organically produced GM-free seed of varieties adapted to organic production systems is of vital impor-tance. Despite recent achievements, organic seed supply for a number of vegetable species is insufficient. Still, in many countries...... seeds. Tunnel production is a means of securing seed of high genetic purity and quality, and organic leek (Allium porrum L.) seed production was tested in tunnels in Denmark. The present trial focused on steckling size and in all years large stecklings had a positive effect on both seed yield...

Deposition, clearance, and shortening of Kevlar para-aramid fibrils in acute, subchronic, and chronic inhalation studies in rats.

Science.gov (United States)

Kelly, D P; Merriman, E A; Kennedy, G L; Lee, K P

1993-10-01

The deposition and clearance of lung-deposited Kevlar para-aramid fibrils (subfibers) have been investigated as part of a subchronic and chronic inhalation toxicity testing program. Fibrils recovered from lung tissue in para-aramid-exposed Sprague-Dawley rats were microscopically counted and measured after exposures to airborne fibrils which were about 12 microns median length (ML) and < 0.3 micron median diameter. In each of three studies lung-recovered fibrils were progressively shorter with increasing residence time in the lungs. Twenty-eight days after a single 6-hr exposure at 400 respirable fibrils per cubic centimeter (f/cm3) the ML of recovered fibrils decreased to about 5 microns. Twenty-four months after a 3-week exposure to 25 or 400 f/cm3, fibrils reached about 2 microns ML. After 2 years of continuous exposure at 2.5, 25, or 100 f/cm3 or 1 year exposure plus 1 year recovery at 400 f/cm3, fibril ML approached 4 microns. In the 2-year study, the lung-fiber accumulation rate/exposure concentration was similar for the three highest concentrations and was about 3 x greater than that seen at 2.5 f/cm3, indicating that concentrations of about 25 f/cm3 or more may overwhelm clearance mechanisms. Time required for fibrils to be reduced to < 5 microns in the lung was markedly less at lower exposure concentration and shorter exposure time. The primary shortening mechanism is proposed to be long fibril cutting by enzymatic attack at fibril defects. However, length-selective fibril deposition and clearance may contribute to shortening in the first few days after exposure. The enzymatic cutting hypothesis is supported by measured increases in numbers of short fibers following cessation of exposures, continued shortening of the fibril length distribution up to 2 years following exposure, and in vitro fibril shortening after 3 months in a proteolytic enzyme preparation. The conclusion is that para-aramid fibrils are less durable in the lungs of rats than expected from

Cost-effectiveness of private umbilical cord blood banking.

Science.gov (United States)

Kaimal, Anjali J; Smith, Catherine C; Laros, Russell K; Caughey, Aaron B; Cheng, Yvonne W

2009-10-01

To investigate the cost-effectiveness of private umbilical cord blood banking. A decision-analytic model was designed comparing private umbilical cord blood banking with no umbilical cord blood banking. Baseline assumptions included a cost of $3,620 for umbilical cord blood banking and storage for 20 years, a 0.04% chance of requiring an autologous stem cell transplant, a 0.07% chance of a sibling requiring an allogenic stem cell transplant, and a 50% reduction in risk of graft-versus-host disease if a sibling uses banked umbilical cord blood. Private cord blood banking is not cost-effective because it cost an additional $1,374,246 per life-year gained. In sensitivity analysis, if the cost of umbilical cord blood banking is less than $262 or the likelihood of a child needing a stem cell transplant is greater than 1 in 110, private umbilical cord blood banking becomes cost-effective. Currently, private umbilical cord blood banking is cost-effective only for children with a very high likelihood of needing a stem cell transplant. Patients considering private blood banking should be informed of the remote likelihood that a unit will be used for a child or another family member. III.

Malignant spinal cord compression in cancer patients may be mimicked by a primary spinal cord tumour.

Science.gov (United States)

Mohammadianpanah, M; Vasei, M; Mosalaei, A; Omidvari, S; Ahmadloo, N

2006-12-01

Although it is quite rare, second primary neoplasms in cancer patients may present with the signs and symptoms of malignant spinal cord compression. Primary spinal cord tumours in the cancer patients may be deceptive and considered as the recurrent first cancer. Therefore, it should be precisely differentiated and appropriately managed. We report such a case of intramedullary ependymoma of the cervical spinal cord mimicking metatstatic recurrent lymphoma and causing cord compression. A 50-year-old man developed intramedullary ependymoma of the cervical spinal cord 1.5 years following chemoradiation for Waldeyer's ring lymphoma. He presented with a 2-month history of neck pain, progressive upper- and lower-extremity numbness and weakness, and bowel and bladder dysfunction. Magnetic resonance imaging revealed an intramedullary expansive lesion extending from C4 to C6 levels of the cervical spinal cord. The clinical and radiological findings were suggestive of malignant process. A comprehensive investigation failed to detect another site of disease. He underwent operation, and the tumour was subtotally resected. The patient's neurological deficits improved subsequently. The development of the intramedullary ependymoma following treating lymphoma has not been reported. We describe the clinical, radiological and pathological findings of this case and review the literature.

HPMA-RGD Hydrogels Seeded with Mesenchymal Stem Cells Improve Functional Outcome in Chronic Spinal Cord Injury

Czech Academy of Sciences Publication Activity Database

Hejčl, Aleš; Šedý, Jiří; Kapcalová, Miroslava; Arboleda Toro, David; Amemori, Takashi; Lesný, Petr; Likavčanová, Katarína; Krumbholcová, Eva; Přádný, Martin; Michálek, Jiří; Burian, M.; Hájek, M.; Jendelová, Pavla; Syková, Eva

2010-01-01

Roč. 19, č. 10 (2010), s. 1535-1546 ISSN 1547-3287 R&D Projects: GA MŠk(CZ) LC554; GA AV ČR IAA500390902 Grant - others:GA ČR(CZ) GD309/08/H079; GA MZd(CZ) 1A8697; GA MŠk(CZ) 1M0538; EC FP6 project RESCUE(XE) LSHB-CT-2005-518233 Program:1M Institutional research plan: CEZ:AV0Z50390703; CEZ:AV0Z40500505 Keywords : magnetic-resonance tracking * spinal cord injury * stem cells Subject RIV: FH - Neurology Impact factor: 4.791, year: 2010

Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis.

Science.gov (United States)

Perumal, Shiamalee; Antipova, Olga; Orgel, Joseph P R O

2008-02-26

We describe the molecular structure of the collagen fibril and how it affects collagen proteolysis or "collagenolysis." The fibril-forming collagens are major components of all mammalian connective tissues, providing the structural and organizational framework for skin, blood vessels, bone, tendon, and other tissues. The triple helix of the collagen molecule is resistant to most proteinases, and the matrix metalloproteinases that do proteolyze collagen are affected by the architecture of collagen fibrils, which are notably more resistant to collagenolysis than lone collagen monomers. Until now, there has been no molecular explanation for this. Full or limited proteolysis of the collagen fibril is known to be a key process in normal growth, development, repair, and cell differentiation, and in cancerous tumor progression and heart disease. Peptide fragments generated by collagenolysis, and the conformation of exposed sites on the fibril as a result of limited proteolysis, regulate these processes and that of cellular attachment, but it is not known how or why. Using computational and molecular visualization methods, we found that the arrangement of collagen monomers in the fibril (its architecture) protects areas vulnerable to collagenolysis and strictly governs the process. This in turn affects the accessibility of a cell interaction site located near the cleavage region. Our observations suggest that the C-terminal telopeptide must be proteolyzed before collagenase can gain access to the cleavage site. Collagenase then binds to the substrate's "interaction domain," which facilitates the triple-helix unwinding/dissociation function of the enzyme before collagenolysis.

Empty seeds are not always bad: simultaneous effect of seed emptiness and masting on animal seed predation.

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Ramón Perea

Full Text Available Seed masting and production of empty seeds have often been considered independently as different strategies to reduce seed predation by animals. Here, we integrate both phenomena within the whole assemblage of seed predators (both pre and post-dispersal and in two contrasting microsites (open vs. sheltered to improve our understanding of the factors controlling seed predation in a wind-dispersed tree (Ulmus laevis. In years with larger crop sizes more avian seed predators were attracted with an increase in the proportion of full seeds predated on the ground. However, for abundant crops, the presence of empty seeds decreased the proportion of full seeds predated. Empty seeds remained for a very long period in the tree, making location of full seeds more difficult for pre-dispersal predators and expanding the overall seed drop period at a very low cost (in dry biomass and allocation of C, N and P. Parthenocarpy (non-fertilized seeds was the main cause of seed emptiness whereas seed abortion was produced in low quantity. These aborted seeds fell prematurely and, thus, could not work as deceptive seeds. A proportion of 50% empty seeds significantly reduced ground seed predation by 26%. However, a high rate of parthenocarpy (beyond 50% empty seeds did not significantly reduce seed predation in comparison to 50% empty seeds. We also found a high variability and unpredictability in the production of empty seeds, both at tree and population level, making predator deception more effective. Open areas were especially important to facilitate seed survival since rodents (the main post-dispersal predators consumed seeds mostly under shrub cover. In elm trees parthenocarpy is a common event that might work as an adaptive strategy to reduce seed predation. Masting per se did not apparently reduce the overall proportion of seeds predated in this wind-dispersed tree, but kept great numbers of seeds unconsumed.

Digoxin use and risk of mortality in hypertensive patients with atrial fibrillation

DEFF Research Database (Denmark)

Okin, Peter M; Hille, Darcy A; Wachtell, Kristian

2015-01-01

, diabetes, history of ischemic heart disease, stroke, or heart failure, baseline Cornell product, QRS duration, heart rate, serum glucose, creatinine and high-density lipoprotein cholesterol, and a propensity score for digoxin use entered as standard covariates, and for in-treatment heart rate, pulse...... patients with atrial fibrillation has not been examined. METHODS AND RESULTS: All-cause mortality was examined in relation to in-treatment digoxin use in 937 hypertensive patients with ECG left ventricular hypertrophy in atrial fibrillation at baseline (n = 134) or who developed atrial fibrillation during...... fibrillation, digoxin use is not associated with a significantly increased risk of all-cause mortality after adjusting for other independent predictors of death and for the factors associated with the propensity to use digoxin in this population. These findings suggest that factors other than digoxin use may...

Family history of atrial fibrillation is associated with earlier-onset and more symptomatic atrial fibrillation

DEFF Research Database (Denmark)

Gundlund, Anna; Fosbøl, Emil Loldrup; Kim, Sunghee

2016-01-01

BACKGROUND: We addressed whether patients with a family history of atrial fibrillation (AF) were diagnosed as having AF earlier in life, were more symptomatic, and had worse outcomes compared with those without a family history of AF. METHODS: Using the ORBIT-AF, we compared symptoms and disease...

Cost-effectiveness of a specialized atrial fibrillation clinic vs. usual care in patients with atrial fibrillation

NARCIS (Netherlands)

Hendriks, Jeroen; Tomini, Florian; van Asselt, Thea; Crijns, Harry; Vrijhoef, Hubertus

AIMS: A recent randomized controlled trial demonstrated significant reductions in cardiovascular hospitalizations and deaths with a nurse-led integrated chronic care approach in patients with atrial fibrillation (AF) compared with usual care. The aim of the present study is to assess

Cost-effectiveness of a specialized atrial fibrillation clinic vs. usual care in patients with atrial fibrillation

NARCIS (Netherlands)

Hendriks, J.M.L.; Tomini, F.; van Asselt, A.D.I.; Crijns, H.J.G.M.; Vrijhoef, H.J.M.

2013-01-01

Aims A recent randomized controlled trial demonstrated significant reductions in cardiovascular hospitalizations and deaths with a nurse-led integrated chronic care approach in patients with atrial fibrillation (AF) compared with usual care. The aim of the present study is to assess

Topologically preserving straightening of spinal cord MRI.

Science.gov (United States)

De Leener, Benjamin; Mangeat, Gabriel; Dupont, Sara; Martin, Allan R; Callot, Virginie; Stikov, Nikola; Fehlings, Michael G; Cohen-Adad, Julien

2017-10-01

To propose a robust and accurate method for straightening magnetic resonance (MR) images of the spinal cord, based on spinal cord segmentation, that preserves spinal cord topology and that works for any MRI contrast, in a context of spinal cord template-based analysis. The spinal cord curvature was computed using an iterative Non-Uniform Rational B-Spline (NURBS) approximation. Forward and inverse deformation fields for straightening were computed by solving analytically the straightening equations for each image voxel. Computational speed-up was accomplished by solving all voxel equation systems as one single system. Straightening accuracy (mean and maximum distance from straight line), computational time, and robustness to spinal cord length was evaluated using the proposed and the standard straightening method (label-based spline deformation) on 3T T 2 - and T 1 -weighted images from 57 healthy subjects and 33 patients with spinal cord compression due to degenerative cervical myelopathy (DCM). The proposed algorithm was more accurate, more robust, and faster than the standard method (mean distance = 0.80 vs. 0.83 mm, maximum distance = 1.49 vs. 1.78 mm, time = 71 vs. 174 sec for the healthy population and mean distance = 0.65 vs. 0.68 mm, maximum distance = 1.28 vs. 1.55 mm, time = 32 vs. 60 sec for the DCM population). A novel image straightening method that enables template-based analysis of quantitative spinal cord MRI data is introduced. This algorithm works for any MRI contrast and was validated on healthy and patient populations. The presented method is implemented in the Spinal Cord Toolbox, an open-source software for processing spinal cord MRI data. 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1209-1219. © 2017 International Society for Magnetic Resonance in Medicine.

Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival

Science.gov (United States)

van Besien, Koen; Hari, Parameswaran; Zhang, Mei-Jie; Liu, Hong-Tao; Stock, Wendy; Godley, Lucy; Odenike, Olatoyosi; Larson, Richard; Bishop, Michael; Wickrema, Amittha; Gergis, Usama; Mayer, Sebastian; Shore, Tsiporah; Tsai, Stephanie; Rhodes, Joanna; Cushing, Melissa M.; Korman, Sandra; Artz, Andrew

2016-01-01

Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, Pdisease (HR=0.26, Pdisease (HR=0.06, Pdisease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588. PMID:26869630

Managing atrial fibrillation in the elderly: critical appraisal of dronedarone

Directory of Open Access Journals (Sweden)

Trigo P

2011-12-01

Full Text Available Paula Trigo, Gregory W FischerDepartment of Anesthesiology, Mount Sinai School of Medicine, New York, NY, USAAbstract: Atrial fibrillation is the most commonly seen arrhythmia in the geriatric population and is associated with increased cardiovascular morbidity and mortality. Treatment of the elderly with atrial fibrillation remains challenging for physicians, because this unique subpopulation is characterized by multiple comorbidities requiring chronic use of numerous medications, which can potentially lead to severe drug interactions. Furthermore, age-related changes in the cardiovascular system as well as other physiological changes result in altered drug pharmacokinetics. Dronedarone is a new drug recently approved for the treatment of arrhythmias, such as atrial fibrillation and/or atrial flutter. Dronedarone is a benzofuran amiodarone analog which lacks the iodine moiety and contains a methane sulfonyl group that decreases its lipophilicity. These differences in chemical structure are responsible for making dronedarone less toxic than amiodarone which, in turn, results in fewer side effects. Adverse events for dronedarone include gastrointestinal side effects and rash. No dosage adjustments are required for patients with renal impairment. However, the use of dronedarone is contraindicated in the presence of severe hepatic dysfunction.Keywords: atrial fibrillation, elderly, antiarrhythmic agents, amiodarone, dronedarone

Risk factors in iatrogenic spinal cord injury.

Science.gov (United States)

Montalva-Iborra, A; Alcanyis-Alberola, M; Grao-Castellote, C; Torralba-Collados, F; Giner-Pascual, M

2017-09-01

In the last years, there has been a change in the aetiology of spinal cord injury. There has been an increase in the number of elderly patients with spinal cord injuries caused by diseases or medical procedures. The aim of this study is to investigate the frequency of the occurrence of iatrogenic spinal cord injury in our unit. The secondary aim is to study what variables can be associated with a higher risk of iatrogenesis. A retrospective, descriptive, observational study of patients with acute spinal cord injury admitted from June 2009 to May 2014 was conducted. The information collected included the patient age, aetiology, neurological level and grade of injury when admitted and when discharged, cardiovascular risk factors, a previous history of depression and any prior treatment with anticoagulant or antiplatelet drugs. We applied a logistic regression. The grade of statistical significance was established as Pinjury was the thoracic level (48%). The main aetiology of spinal cord injury caused by iatrogenesis was surgery for degenerative spine disease, in patients under the age of 30 were treated with intrathecal chemotherapy. Iatrogenic spinal cord injury is a frequent complication. A statistically significant association between a patient history of depression and iatrogenic spinal cord injury was found as well as with anticoagulant and antiplatelet drug use prior to iatrogenic spinal cord injury.

Spinal cord injury arising in anaesthesia practice.

Science.gov (United States)

Hewson, D W; Bedforth, N M; Hardman, J G

2018-01-01

Spinal cord injury arising during anaesthetic practice is a rare event, but one that carries a significant burden in terms of morbidity and mortality. In this article, we will review the pathophysiology of spinal cord injury. We will then discuss injuries relating to patient position, spinal cord hypoperfusion and neuraxial techniques. The most serious causes of spinal cord injury - vertebral canal haematoma, spinal epidural abscess, meningitis and adhesive arachnoiditis - will be discussed in turn. For each condition, we draw attention to practical, evidence-based measures clinicians can undertake to reduce their incidence, or mitigate their severity. Finally, we will discuss transient neurological symptoms. Some cases of spinal cord injury during anaesthesia can be ascribed to anaesthesia itself, arising as a direct consequence of its conduct. The injury to a spinal nerve root by inaccurate and/or incautious needling during spinal anaesthesia is an obvious example. But in many cases, spinal cord injury during anaesthesia is not caused by, related to, or even associated with, the conduct of the anaesthetic. Surgical factors, whether direct (e.g. spinal nerve root damage due to incorrect pedicle screw placement) or indirect (e.g. cord ischaemia following aortic surgery) are responsible for a significant proportion of spinal cord injuries that occur concurrently with the delivery of regional or general anaesthesia. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

Cardiac monitoring for detection of atrial fibrillation after TIA: A systematic review and meta-analysis.

Science.gov (United States)

Korompoki, Eleni; Del Giudice, Angela; Hillmann, Steffi; Malzahn, Uwe; Gladstone, David J; Heuschmann, Peter; Veltkamp, Roland

2017-01-01

Background and purpose The detection rate of atrial fibrillation has not been studied specifically in transient ischemic attack (TIA) patients although extrapolation from ischemic stroke may be inadequate. We conducted a systematic review and meta-analysis to determine the rate of newly diagnosed atrial fibrillation using different methods of ECG monitoring in TIA. Methods A comprehensive literature search was performed following a pre-specified protocol the PRISMA statement. Prospective observational studies and randomized controlled trials were considered that included TIA patients who underwent cardiac monitoring for >12 h. Primary outcome was frequency of detection of atrial fibrillation ≥30 s. Analyses of subgroups and of duration and type of monitoring were performed. Results Seventeen studies enrolling 1163 patients were included. The pooled atrial fibrillation detection rate for all methods was 4% (95% CI: 2-7%). Yield of monitoring was higher in selected (higher age, more extensive testing for arrhythmias before enrolment, or presumed cardioembolic/cryptogenic cause) than in unselected cohorts (7% vs 3%). Pooled mean atrial fibrillation detection rates rose with duration of monitoring: 4% (24 h), 5% (24 h to 7 days) and 6% (>7 days), respectively. Yield of non-invasive was significantly lower than that of invasive monitoring (4% vs. 11%). Significant heterogeneity was observed among studies (I 2 =60.61%). Conclusion This first meta-analysis of atrial fibrillation detection in TIA patients finds a lower atrial fibrillation detection rate in TIA than reported for IS and TIA cohorts in previous meta-analyses. Prospective studies are needed to determine actual prevalence of atrial fibrillation and optimal diagnostic procedure for atrial fibrillation detection in TIA.

The Effect of Milk Constituents and Crowding Agents on Amyloid Fibril Formation by κ-Casein.

Science.gov (United States)

Liu, Jihua; Dehle, Francis C; Liu, Yanqin; Bahraminejad, Elmira; Ecroyd, Heath; Thorn, David C; Carver, John A

2016-02-17

When not incorporated into the casein micelle, κ-casein, a major milk protein, rapidly forms amyloid fibrils at physiological pH and temperature. In this study, the effects of milk components (calcium, lactose, lipids, and heparan sulfate) and crowding agents on reduced and carboxymethylated (RCM) κ-casein fibril formation was investigated using far-UV circular dichroism spectroscopy, thioflavin T binding assays, and transmission electron microscopy. Longer-chain phosphatidylcholine lipids, which form the lining of milk ducts and milk fat globules, enhanced RCM κ-casein fibril formation irrespective of whether the lipids were in a monomeric or micellar state, whereas shorter-chain phospholipids and triglycerides had little effect. Heparan sulfate, a component of the milk fat globule membrane and catalyst of amyloid deposition in extracellular tissue, had little effect on the kinetics of RCM κ-casein fibril formation. Major nutritional components such as calcium and lactose also had no significant effect. Macromolecular crowding enhances protein-protein interactions, but in contrast to other fibril-forming species, the extent of RCM κ-casein fibril formation was reduced by the presence of a variety of crowding agents. These data are consistent with a mechanism of κ-casein fibril formation in which the rate-determining step is dissociation from the oligomer to give the highly amyloidogenic monomer. We conclude that the interaction of κ-casein with membrane-associated phospholipids along its secretory pathway may contribute to the development of amyloid deposits in mammary tissue. However, the formation of spherical oligomers such as casein micelles is favored over amyloid fibrils in the crowded environment of milk, within which the occurrence of amyloid fibrils is low.

Dynamic behavior of small heat shock protein inhibition on amyloid fibrillization of a small peptide (SSTSAA) from RNase A

International Nuclear Information System (INIS)

Xi, Dong; Dong, Xiao; Deng, Wei; Lai, Luhua

2011-01-01

Highlights: ► Mechanism of small heat shock protein inhibition on fibril formation was studied. ► Peptide SSTSAA with modified ends was used for amyloid fibril formation. ► FRET signal was followed during the fibril formation. ► Mj HSP16.5 inhibits fibril formation when introduced in the lag phase. ► Mj HSP16.5 slows down fibril formation when introduced after the lag phase. -- Abstract: Small heat shock proteins, a class of molecular chaperones, are reported to inhibit amyloid fibril formation in vitro, while the mechanism of inhibition remains unknown. In the present study, we investigated the mechanism by which Mj HSP16.5 inhibits amyloid fibril formation of a small peptide (SSTSAA) from RNase A. A model peptide (dansyl-SSTSAA-W) was designed by introducing a pair of fluorescence resonance energy transfer (FRET) probes into the peptide, allowing for the monitoring of fibril formation by this experimental model. Mj HSP16.5 completely inhibited fibril formation of the model peptide at a molar ratio of 1:120. The dynamic process of fibril formation, revealed by FRET, circular dichroism, and electron microscopy, showed a lag phase of about 2 h followed by a fast growth period. The effect of Mj HSP16.5 on amyloid fibril formation was investigated by adding it into the incubation solution during different growth phases. Adding Mj HSP16.5 to the incubating peptide before or during the lag phase completely inhibited fibril formation. However, introducing Mj HSP16.5 after the lag phase only slowed down the fibril formation process by adhering to the already formed fibrils. These findings provide insight into the inhibitory roles of small heat shock proteins on amyloid fibril formation at the molecular level.

Dynamic behavior of small heat shock protein inhibition on amyloid fibrillization of a small peptide (SSTSAA) from RNase A

Energy Technology Data Exchange (ETDEWEB)

Xi, Dong [BNLMS, State Key Laboratory of Structural Chemistry for Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 (China); Center for Theoretical Biology, Peking University, Beijing 100871 (China); Dong, Xiao; Deng, Wei [BNLMS, State Key Laboratory of Structural Chemistry for Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 (China); Lai, Luhua, E-mail: lhlai@pku.edu.cn [BNLMS, State Key Laboratory of Structural Chemistry for Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 (China); Center for Theoretical Biology, Peking University, Beijing 100871 (China)

2011-12-09

Highlights: Black-Right-Pointing-Pointer Mechanism of small heat shock protein inhibition on fibril formation was studied. Black-Right-Pointing-Pointer Peptide SSTSAA with modified ends was used for amyloid fibril formation. Black-Right-Pointing-Pointer FRET signal was followed during the fibril formation. Black-Right-Pointing-Pointer Mj HSP16.5 inhibits fibril formation when introduced in the lag phase. Black-Right-Pointing-Pointer Mj HSP16.5 slows down fibril formation when introduced after the lag phase. -- Abstract: Small heat shock proteins, a class of molecular chaperones, are reported to inhibit amyloid fibril formation in vitro, while the mechanism of inhibition remains unknown. In the present study, we investigated the mechanism by which Mj HSP16.5 inhibits amyloid fibril formation of a small peptide (SSTSAA) from RNase A. A model peptide (dansyl-SSTSAA-W) was designed by introducing a pair of fluorescence resonance energy transfer (FRET) probes into the peptide, allowing for the monitoring of fibril formation by this experimental model. Mj HSP16.5 completely inhibited fibril formation of the model peptide at a molar ratio of 1:120. The dynamic process of fibril formation, revealed by FRET, circular dichroism, and electron microscopy, showed a lag phase of about 2 h followed by a fast growth period. The effect of Mj HSP16.5 on amyloid fibril formation was investigated by adding it into the incubation solution during different growth phases. Adding Mj HSP16.5 to the incubating peptide before or during the lag phase completely inhibited fibril formation. However, introducing Mj HSP16.5 after the lag phase only slowed down the fibril formation process by adhering to the already formed fibrils. These findings provide insight into the inhibitory roles of small heat shock proteins on amyloid fibril formation at the molecular level.

Posibilities of cardiac pacemaker use in paroxsysmal atrial fibrilation

Directory of Open Access Journals (Sweden)

Borut Kamenik

2005-12-01

Full Text Available Background: Prevention of atrial fibrillation is a big therapeutic challenge because of all known negative consequences of this the most frequent cardiac arrhythmia. Numerous of clinical studies showed bad control or ineffectiveness of antiarhythmic drugs. Nonfarmakological therapies like surgical treatment, radiofrequency ablation and atrial pacing are being tested. Effectiveness of atrial pacing in prevention of paroxysmal artial fibrillation has been documented in numerous prospective studies and is effective for a long time interval, but only for patients with bradicardic underlying cardiac rhythm. In Normocardic rhythm or normal AV conduction the effective Atrial fibrillation prevention was not proven. The mechanism of action is based on premature atrial complex suppression, reduction of dispersion of refractoriness after short-long cycles and reduction of interatrial conduction delay. The atrial stimulation site or multi-site atrial pacing could be effective in AF prevention when interatrial conduction delay is present; otherwise the difference is not significant.Conclusions: In bradicardic patient who has frequent paroxysms of atrial fibrillation, regardless if bradycardia is due to ineffective antiarrhythmic drug treathement, implantation of DDDR pacemaker with atrial prevention algorhythm is indicated. If the P-wave duration is >120 milliseconds multi-site atrial pacing or septal atrial pacing should be considered. Pacemaker diagnostic tools could be used for adequate start of anticoagulant therapy and control of effectiveness of anthyarhythmic drug therapy.

SCT: Spinal Cord Toolbox, an open-source software for processing spinal cord MRI data.

Science.gov (United States)

De Leener, Benjamin; Lévy, Simon; Dupont, Sara M; Fonov, Vladimir S; Stikov, Nikola; Louis Collins, D; Callot, Virginie; Cohen-Adad, Julien

2017-01-15

For the past 25 years, the field of neuroimaging has witnessed the development of several software packages for processing multi-parametric magnetic resonance imaging (mpMRI) to study the brain. These software packages are now routinely used by researchers and clinicians, and have contributed to important breakthroughs for the understanding of brain anatomy and function. However, no software package exists to process mpMRI data of the spinal cord. Despite the numerous clinical needs for such advanced mpMRI protocols (multiple sclerosis, spinal cord injury, cervical spondylotic myelopathy, etc.), researchers have been developing specific tools that, while necessary, do not provide an integrative framework that is compatible with most usages and that is capable of reaching the community at large. This hinders cross-validation and the possibility to perform multi-center studies. In this study we introduce the Spinal Cord Toolbox (SCT), a comprehensive software dedicated to the processing of spinal cord MRI data. SCT builds on previously-validated methods and includes state-of-the-art MRI templates and atlases of the spinal cord, algorithms to segment and register new data to the templates, and motion correction methods for diffusion and functional time series. SCT is tailored towards standardization and automation of the processing pipeline, versatility, modularity, and it follows guidelines of software development and distribution. Preliminary applications of SCT cover a variety of studies, from cross-sectional area measures in large databases of patients, to the precise quantification of mpMRI metrics in specific spinal pathways. We anticipate that SCT will bring together the spinal cord neuroimaging community by establishing standard templates and analysis procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

Seed-borne pathogens and electrical conductivity of soybean seeds

Directory of Open Access Journals (Sweden)

Adriana Luiza Wain-Tassi

2012-02-01

Full Text Available Adequate procedures to evaluate seed vigor are important. Regarding the electrical conductivity test (EC, the interference in the test results caused by seed-borne pathogens has not been clarified. This research was carried out to study the influence of Phomopsis sojae (Leh. and Colletotrichum dematium (Pers. ex Fr. Grove var. truncata (Schw. Arx. fungi on EC results. Soybean seeds (Glycine max L. were inoculated with those fungi using potato, agar and dextrose (PDA medium with manitol (-1.0 MPa and incubated for 20 h at 25 °C. The colony diameter, index of mycelial growth, seed water content, occurrence of seed-borne pathogens, physiological potential of the seeds, measured by germination and vigor tests (seed germination index, cold test, accelerated aging and electrical conductivity, and seedling field emergence were determined. The contents of K+, Ca2+, and Mg2+ in the seed and in the soaking solution were also determined. A complete 2 × 4 factorial design with two seed sizes (5.5 and 6.5 mm and four treatments (control, seeds incubated without fungi, seeds incubated with Phomopsis and seeds incubated with Colletotrichum were used with eight (5.5 mm large seeds and six (6.5 mm large seeds replications. All seeds submitted to PDA medium had their germination reduced in comparison to the control seeds. This reduction was also observed when seed vigor and leached ions were considered. The presence of Phomopsis sojae fungus in soybean seed samples submitted to the EC test may be the cause of misleading results.

Religious perspectives on umbilical cord blood banking.

Science.gov (United States)

Jordens, Christopher F C; O'Connor, Michelle A C; Kerridge, Ian H; Stewart, Cameron; Cameron, Andrew; Keown, Damien; Lawrence, Rabbi Jeremy; McGarrity, Andrew; Sachedina, Abdulaziz; Tobin, Bernadette

2012-03-01

Umbilical cord blood is a valuable source of haematopoietic stem cells. There is little information about whether religious affiliations have any bearing on attitudes to and decisions about its collection, donation and storage. The authors provided information about umbilical cord blood banking to expert commentators from six major world religions (Catholicism, Anglicanism, Islam, Judaism, Hinduism and Buddhism) and asked them to address a specific set of questions in a commentary. The commentaries suggest there is considerable support for umbilical cord blood banking in these religions. Four commentaries provide moral grounds for favouring public donation over private storage. None attach any particular religious significance to the umbilical cord or to the blood within it, nor place restrictions on the ethnicity or religion of donors and recipients. Views on ownership of umbilical cord blood vary. The authors offer a series of general points for those who seek a better understanding of religious perspectives on umbilical cord blood banking.

Psoriasis is associated with subsequent atrial fibrillation in hypertensive patients with left ventricular hypertrophy

DEFF Research Database (Denmark)

Bang, Casper N; Okin, Peter M; Køber, Lars

2014-01-01

BACKGROUND: Inflammation contributes to the pathogenesis of psoriasis as well as atrial fibrillation. The impact of psoriasis and its association with new-onset atrial fibrillation was assessed in hypertensive patients with left ventricular hypertrophy (LVH). METHODS: The predictive value...... or developed psoriasis and new-onset atrial fibrillation occurred in 506 patients (7.1%) during a mean follow-up of 4.7 ± 1.1 years. At baseline, the psoriasis patients were younger (65 ± 7 vs. 67 ± 7 years) and had less left ventricle hypertrophy by ECG Sokolow-Lyon voltage (27.6 ± 9.7 vs. 30.1 ± 10.4 mm...... of baseline or incident psoriasis for new-onset atrial fibrillation was evaluated in 7099 hypertensive patients with electrocardiographic LVH with no history of atrial fibrillation or other cardiovascular disease, in sinus rhythm on their baseline electrocardiogram. RESULTS: A total of 154 patients (2.2%) had...

Angiotensinogen and ACE gene polymorphisms and risk of atrial fibrillation in the general population

DEFF Research Database (Denmark)

Ravn, Lasse S; Benn, Marianne; Nordestgaard, Børge G

2008-01-01

OBJECTIVES: The renin-angiotensin system may play a role in the pathogenesis of atrial fibrillation, and renin-angiotensin system blockers reduce the risk of atrial fibrillation. We hypothesized that polymorphisms in the angiotensinogen and angiotensin-converting enzyme (ACE) genes encoding...... in the ACE gene; rare allele frequencies were 0.16, 0.40, 0.12, 0.41, and 0.49, respectively. Participants had sinus rhythm at inclusion. During 26 years of follow-up, 968 individuals developed atrial fibrillation. Multifactorially adjusted hazard ratios for atrial fibrillation for a-20c ac and cc versus aa...... proteins in this system predict risk of atrial fibrillation. METHODS AND RESULTS: We genotyped 9235 individuals from the Danish general population, The Copenhagen City Heart Study, for the a-20c, g-6a, T174M, and M235T polymorphisms in the angiotensinogen gene and the insertion/deletion (I/D) polymorphism...

Atrial Fibrillation in Eight New World Camelids.

Science.gov (United States)

Bozorgmanesh, R; Magdesian, K G; Estell, K E; Stern, J A; Swain, E A; Griffiths, L G

2016-01-01

There is limited information on the incidence of clinical signs, concurrent illness and treatment options for atrial fibrillation (AF) in New World Camelids (NWC). Describe clinical signs and outcome of AF in NWC. Eight New World Camelids admitted with AF. A retrospective observational study of camelids diagnosed with AF based on characteristic findings on electrocardiogram (ECG). All animals had an irregularly irregular heart rhythm detected on physical examination and 4 cases had obtunded mentation on admission. Three camelids were diagnosed with AF secondary to oleander intoxication, 3 animals had underlying cardiovascular disease, 1 was diagnosed with lone AF and 1 had AF diagnosed on examination for a urethral obstruction. Five of eight animals survived to discharge and nonsurvivors consisted of animals which died or were euthanized as a result of cardiovascular disease (2/8) or extra-cardiac disease unrelated to the AF (1/8). Atrial fibrillation occurs in NWC in association with cardiovascular disease, extra-cardiac disease or as lone AF. Amiodarone and transthoracic cardioversion were attempted in one llama with lone AF, but were unsuccessful. Atrial fibrillation was recorded in 0.1% of admissions. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Electromechanical vortex filaments during cardiac fibrillation

Science.gov (United States)

Christoph, J.; Chebbok, M.; Richter, C.; Schröder-Schetelig, J.; Bittihn, P.; Stein, S.; Uzelac, I.; Fenton, F. H.; Hasenfuß, G.; Gilmour, R. F., Jr.; Luther, S.

2018-03-01

The self-organized dynamics of vortex-like rotating waves, which are also known as scroll waves, are the basis of the formation of complex spatiotemporal patterns in many excitable chemical and biological systems. In the heart, filament-like phase singularities that are associated with three-dimensional scroll waves are considered to be the organizing centres of life-threatening cardiac arrhythmias. The mechanisms that underlie the onset, maintenance and control of electromechanical turbulence in the heart are inherently three-dimensional phenomena. However, it has not previously been possible to visualize the three-dimensional spatiotemporal dynamics of scroll waves inside cardiac tissues. Here we show that three-dimensional mechanical scroll waves and filament-like phase singularities can be observed deep inside the contracting heart wall using high-resolution four-dimensional ultrasound-based strain imaging. We found that mechanical phase singularities co-exist with electrical phase singularities during cardiac fibrillation. We investigated the dynamics of electrical and mechanical phase singularities by simultaneously measuring the membrane potential, intracellular calcium concentration and mechanical contractions of the heart. We show that cardiac fibrillation can be characterized using the three-dimensional spatiotemporal dynamics of mechanical phase singularities, which arise inside the fibrillating contracting ventricular wall. We demonstrate that electrical and mechanical phase singularities show complex interactions and we characterize their dynamics in terms of trajectories, topological charge and lifetime. We anticipate that our findings will provide novel perspectives for non-invasive diagnostic imaging and therapeutic applications.

[The contribution of inflammatory process in pathogenesis and natural history of atrial fibrillation].

Science.gov (United States)

Zyśko, Dorota; Gajek, Jacek; Mazurek, Walentyna

2005-02-01

The inflammatory process plays important role in pathogenesis of some cardiovascular diseases. Atrial fibrillation is atrial arrhythmia with rapid, asynchronous activation of atrial myocytes. The inflammatory process can be responsible for atrial electrical and anatomical remodeling and therefore shifts towards arrhythmia persistence. The presence of systemic inflammation may be assessed by means of C-reactive protein (CRP) measurement. Maximal concentration of CRP coincidences with the peak of paroxysmal atrial fibrillation occurrence in patients after cardiac surgery. In patients with sinus rhythm the concentration of CRP is a risk factor for this arrhythmia in long-term follow-up. In patients with atrial fibrillation mean CRP concentration is 2-fold higher comparing to control group. CRP concentration is higher in patients with chronic than paroxysmal form of this arrhythmia. High CRP level predicts worse results of direct current cardioversion and more frequent paroxysms of atrial fibrillation during follow-up. Besides of, the patients with echocardiographic signs of thromboembolic risk have higher CRP levels than control subjects. There is no data about the influence of anti-inflammatory therapy on atrial fibrillation or its recurrences.

Advanced age and incidence of atrial fibrillation in the postoperative period of aortic valve replacement

Science.gov (United States)

Pivatto Júnior, Fernando; Teixeira Filho, Guaracy Fernandes; Sant'anna, João Ricardo Michelin; Py, Pablo Mondim; Prates, Paulo Roberto; Nesralla, Ivo Abrahão; Kalil, Renato Abdala Karam

2014-01-01

Objective This study aims to describe the correlation between age and occurrence of atrial fibrillation after aortic stenosis surgery in the elderly as well as evaluate the influence of atrial fibrillation on the incidence of strokes, hospital length of stay, and hospital mortality. Methods Cross-sectional retrospective study of > 70 year-old patients who underwent isolated aortic valve replacement. Results 348 patients were included in the study (mean age 76.8±4.6 years). Overall, post-operative atrial fibrillation was 32.8% (n=114), but it was higher in patients aged 80 years and older (42.9% versus 28.8% in patients aged 70-79 years, P=0.017). There was borderline significance for linear correlation between age and atrial fibrillation (P=0.055). Intensive Care Unit and hospital lengths of stay were significantly increased in atrial fibrillation (Patrial fibrillation. Conclusion Post-operative atrial fibrillation incidence in aortic valve replacement is high and correlates with age in patients aged 70 years and older and significantly more pronounced in patients aged 80 years. There was increased length of stay at Intensive Care Unit and hospital, but there was no increase in mortality or stroke. These data are important for planning prophylaxis and early treatment for this subgroup. PMID:24896162

Clinical Use and Patentability of Cord Blood

Science.gov (United States)

Cavusoglu, Turker; Kilic, Kubilay Dogan; Yigitturk, Gurkan; Tomruk, Canberk; Turgut, Mehmet; Uyanikgil, Yigit

2018-03-14

The blood in the umbilical cord that provides the connection between mother and fetus during pregnancy is called cord blood. The blood of umbilical cord which is usually got rid of following birth, is a very rich stem cell source. Cord blood collection gives no harm to the mother and baby. Besides, its allogeneic and au-tologous usage, the most important disadvantage is that the number of cells is insufficient in adults. Today, it is predominantly used for therapeutic purposes for many diseases. The aim of this review is giving a detailed information about groups of stem cells in cord blood and determining the point of clinical use. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The effect of point mutations on structure and mechanical properties of collagen-like fibril: A molecular dynamics study

International Nuclear Information System (INIS)

Marlowe, Ashley E.; Singh, Abhishek; Yingling, Yaroslava G.

2012-01-01

Understanding sequence dependent mechanical and structural properties of collagen fibrils is important for the development of artificial biomaterials for medical and nanotechnological applications. Moreover, point mutations are behind many collagen associated diseases, including Osteogenesis Imperfecta (OI). We conducted a combination of classical and steered atomistic molecular dynamics simulations to examine the effect of point mutations on structure and mechanical properties of short collagen fibrils which include mutations of glycine to alanine, aspartic acid, cysteine, and serine or mutations of hydroxyproline to arginine, asparagine, glutamine, and lysine. We found that all mutations disrupt structure and reduce strength of the collagen fibrils, which may affect the hierarchical packing of the fibrils. The glycine mutations were more detrimental to mechanical strength of the fibrils (WT > Ala > Ser > Cys > Asp) than that of hydroxyproline (WT > Arg > Gln > Asn > Lys). The clinical outcome for glycine mutations agrees well with the trend in reduction of fibril's tensile strength predicted by our simulations. Overall, our results suggest that the reduction in mechanical properties of collagen fibrils may be used to predict the clinical outcome of mutations. Highlights: ► All mutations disrupt structure and bonding pattern and reduce strength of the collagen fibrils. ► Gly based mutations are worst to mechanical integrity of fibrils than that of Hyp. ► Lys and Arg mutations most dramatically destabilize collagen fibril properties. ► Clinical outcome of mutations may be related to the reduced mechanical properties of fibrils.

Contribution of Electrostatics in the Fibril Stability of a Model Ionic-Complementary Peptide.

Science.gov (United States)

Owczarz, Marta; Casalini, Tommaso; Motta, Anna C; Morbidelli, Massimo; Arosio, Paolo

2015-12-14

In this work we quantified the role of electrostatic interactions in the self-assembly of a model amphiphilic peptide (RADA 16-I) into fibrillar structures by a combination of size exclusion chromatography and molecular simulations. For the peptide under investigation, it is found that a net charge of +0.75 represents the ideal condition to promote the formation of regular amyloid fibrils. Lower net charges favor the formation of amorphous precipitates, while larger net charges destabilize the fibrillar aggregates and promote a reversible dissociation of monomers from the ends of the fibrils. By quantifying the dependence of the equilibrium constant of this reversible reaction on the pH value and the peptide net charge, we show that electrostatic interactions contribute largely to the free energy of fibril formation. The addition of both salt and a charged destabilizer (guanidinium hydrochloride) at moderate concentration (0.3-1 M) shifts the monomer-fibril equilibrium toward the fibrillar state. Whereas the first effect can be explained by charge screening of electrostatic repulsion only, the promotion of fibril formation in the presence of guanidinium hydrochloride is also attributed to modifications of the peptide conformation. The results of this work indicate that the global peptide net charge is a key property that correlates well with the fibril stability, although the peptide conformation and the surface charge distribution also contribute to the aggregation propensity.

Potent inhibition of tau fibrillization with a multivalent ligand

International Nuclear Information System (INIS)

Honson, Nicolette S.; Jensen, Jordan R.; Darby, Michael V.; Kuret, Jeff

2007-01-01

Small-molecule inhibitors of tau fibrillization are under investigation as tools for interrogating the tau aggregation pathway and as potential therapeutic agents for Alzheimer's disease. Established inhibitors include thiacarbocyanine dyes, which can inhibit recombinant tau fibrillization in the presence of anionic surfactant aggregation inducers. In an effort to increase inhibitory potency, a cyclic bis-thiacarbocyanine molecule containing two thiacarbocyanine moieties was synthesized and characterized with respect to tau fibrillization inhibitory activity by electron microscopy and ligand aggregation state by absorbance spectroscopy. Results showed that the inhibitory activity of the bis-thiacarbocyanine was qualitatively similar to a monomeric cyanine dye, but was more potent with 50% inhibition achieved at ∼80 nM concentration. At all concentrations tested in aqueous solution, the bis-thiacarbocyanine collapsed to form a closed clamshell structure. However, the presence of tau protein selectively stabilized the open conformation. These results suggest that the inhibitory activity of bis-thiacarbocyanine results from multivalency, and reveal a route to more potent tau aggregation inhibitors

Ionic Strength Modulation of the Free Energy Landscape of Aβ40 Peptide Fibril Formation.

Science.gov (United States)

Abelein, Axel; Jarvet, Jüri; Barth, Andreas; Gräslund, Astrid; Danielsson, Jens

2016-06-01

Protein misfolding and formation of cross-β structured amyloid fibrils are linked to many neurodegenerative disorders. Although recently developed quantitative approaches have started to reveal the molecular nature of self-assembly and fibril formation of proteins and peptides, it is yet unclear how these self-organization events are precisely modulated by microenvironmental factors, which are known to strongly affect the macroscopic aggregation properties. Here, we characterize the explicit effect of ionic strength on the microscopic aggregation rates of amyloid β peptide (Aβ40) self-association, implicated in Alzheimer's disease. We found that physiological ionic strength accelerates Aβ40 aggregation kinetics by promoting surface-catalyzed secondary nucleation reactions. This promoted catalytic effect can be assigned to shielding of electrostatic repulsion between monomers on the fibril surface or between the fibril surface itself and monomeric peptides. Furthermore, we observe the formation of two different β-structured states with similar but distinct spectroscopic features, which can be assigned to an off-pathway immature state (Fβ*) and a mature stable state (Fβ), where salt favors formation of the Fβ fibril morphology. Addition of salt to preformed Fβ* accelerates transition to Fβ, underlining the dynamic nature of Aβ40 fibrils in solution. On the basis of these results we suggest a model where salt decreases the free-energy barrier for Aβ40 folding to the Fβ state, favoring the buildup of the mature fibril morphology while omitting competing, energetically less favorable structural states.

Stroke and bleeding in atrial fibrillation with chronic kidney disease

DEFF Research Database (Denmark)

Olesen, Jonas Bjerring; Lip, Gregory Y.H.; Kamper, Anne-Lise

2012-01-01

Both atrial fibrillation and chronic kidney disease increase the risk of stroke and systemic thromboembolism. However, these risks, and the effects of antithrombotic treatment, have not been thoroughly investigated in patients with both conditions.......Both atrial fibrillation and chronic kidney disease increase the risk of stroke and systemic thromboembolism. However, these risks, and the effects of antithrombotic treatment, have not been thoroughly investigated in patients with both conditions....

The spectrum of thyroid disease and risk of new onset atrial fibrillation

DEFF Research Database (Denmark)

Selmer, Christian; Olesen, Jonas Bjerring; Hansen, Morten Lock

2012-01-01

To examine the risk of atrial fibrillation in relation to the whole spectrum of thyroid function in a large cohort of patients.......To examine the risk of atrial fibrillation in relation to the whole spectrum of thyroid function in a large cohort of patients....

Familial clustering of atrial fibrillation and comparative longitudinal outcomes of familial and non-familial atrial fibrillation

DEFF Research Database (Denmark)

Gundlund, Anna; Olesen, Jonas B.; Peterson, Eric D.

2017-01-01

Several studies have suggested that family history of atrial fibrillation (AF) is an important risk factor for AF, with several specific genetic regions now implicated through Genome Wide Association Studies. In addition, familial AF is associated with earlier age of onset and affects patients...

Nanoscale characterization of the biomechanical properties of collagen fibrils in the sclera

Energy Technology Data Exchange (ETDEWEB)

Papi, M. [Institute of Physics, Università Cattolica del Sacro Cuore, Largo F.Vito 1, 00168 Rome (Italy); Paoletti, P. [Centre for Engineering Dynamics, School of Engineering, Brownlow Hill, Liverpool, L69 3GH (United Kingdom); Geraghty, B.; Akhtar, R. [Centre for Materials and Structures, School of Engineering, Brownlow Hill, Liverpool, L69 3GH (United Kingdom)

2014-03-10

We apply the PeakForce Quantitative Nanomechanical Property Mapping (PFQNM) atomic force microscopy mode for the investigation of regional variations in the nanomechanical properties of porcine sclera. We examine variations in the collagen fibril diameter, adhesion, elastic modulus and dissipation in the posterior, equatorial and anterior regions of the sclera. The mean fibril diameter, elastic modulus and dissipation increased from the posterior to the anterior region. Collagen fibril diameter correlated linearly with elastic modulus. Our data matches the known macroscopic mechanical behavior of the sclera. We propose that PFQNM has significant potential in ocular biomechanics and biophysics research.

Nanoscale characterization of the biomechanical properties of collagen fibrils in the sclera

International Nuclear Information System (INIS)

Papi, M.; Paoletti, P.; Geraghty, B.; Akhtar, R.

2014-01-01

We apply the PeakForce Quantitative Nanomechanical Property Mapping (PFQNM) atomic force microscopy mode for the investigation of regional variations in the nanomechanical properties of porcine sclera. We examine variations in the collagen fibril diameter, adhesion, elastic modulus and dissipation in the posterior, equatorial and anterior regions of the sclera. The mean fibril diameter, elastic modulus and dissipation increased from the posterior to the anterior region. Collagen fibril diameter correlated linearly with elastic modulus. Our data matches the known macroscopic mechanical behavior of the sclera. We propose that PFQNM has significant potential in ocular biomechanics and biophysics research

AFM-based force spectroscopy measurements of mature amyloid fibrils of the peptide glucagon

DEFF Research Database (Denmark)

Dong, M. D.; Hovgaard, M. B.; Mamdouh, W.

2008-01-01

We report on the mechanical characterization of individual mature amyloid fibrils by atomic force microscopy (AFM) and AFM-based single-molecule force spectroscopy (SMFS). These self-assembling materials, formed from the 29-residue amphiphatic peptide hormone glucagon, were found to display...... a reversible elastic behaviour. Based on AFM morphology and SMFS studies, we suggest that the observed elasticity is due to a force-induced conformational transition which is reversible due to the beta-helical conformation of protofibrils, allowing a high degree of extension. The elastic properties...... of such mature fibrils contribute to their high stability, suggesting that the internal hydrophobic interactions of amyloid fibrils are likely to be of fundamental importance in the assembly of amyloid fibrils and therefore for the understanding of the progression of their associated pathogenic disorders...

Useful clinical features for the selection of ideal patients with strial fibrillation for mapping and catheter ablation

Directory of Open Access Journals (Sweden)

Mehta Niraj

2002-01-01

Full Text Available OBJECTIVE: To identify useful clinical characteristics for selecting patients eligible for mapping and ablation of atrial fibrillation. METHODS: We studied 9 patients with atrial fibrillation, without structural heart disease, associated with: 1 antiarrhythmic drugs, 2 symptoms of low cardiac output, and 3 intention to treat. Seven patients had paroxysmal atrial fibrillation and 2 had recurrent atrial fibrillation. RESULTS: In the 6 patients who underwent mapping (all had paroxysmal atrial fibrillation, catheter ablation was successfully carried out in superior pulmonary veins in 5 patients (the first 3 in the left superior pulmonary vein and the last 2 in the right superior pulmonary vein. One patient experienced a recurrence of atrial fibrillation after 10 days. We observed that patients who had short episodes of atrial fibrillation on 24-hour Holter monitoring before the procedure were those in whom mapping the focus of tachycardia was possible. Tachycardia was successfully suppressed in 4 of 6 patients. The cause of failure was due to the impossibility of maintaining sinus rhythm long enough for efficient mapping. CONCLUSION: Patients experiencing short episodes of atrial fibrillation during 24-hour Holter monitoring were the most eligible for mapping and ablation, with a final success rate of 66%, versus the global success rate of 44%. Patients with persistent atrial fibrillation were not good candidates for focal ablation.

Increasing rate of atrial fibrillation from 2003 to 2011 in patients with ischaemic stroke

DEFF Research Database (Denmark)

Jespersen, S F; Christensen, L. M.; Christensen, A

2015-01-01

BACKGROUND AND PURPOSE: The general awareness of atrial fibrillation is increasing. The key to prevent atrial fibrillation related stroke is oral anticoagulation therapy; however, it has often been proposed that oral anticoagulation therapy is under-utilized despite indication. The aim of the stu...... increase in the use of oral anticoagulation therapy, most probably reflecting an increased awareness and questioning assumed current under-use of oral anticoagulation therapy in secondary stroke prevention.......BACKGROUND AND PURPOSE: The general awareness of atrial fibrillation is increasing. The key to prevent atrial fibrillation related stroke is oral anticoagulation therapy; however, it has often been proposed that oral anticoagulation therapy is under-utilized despite indication. The aim of the study...... was to examine the trends in atrial fibrillation rate in patients after acute ischaemic stroke and to determine whether the use of oral anticoagulation therapy increased from 2003 to 2011. METHODS: In the nationwide Danish Stroke Registry 55 551 patients (≥18 years) admitted with acute ischaemic stroke were...

Traumatic spinal cord injury in MR imaging

International Nuclear Information System (INIS)

Bronarski, J.; Wozniak, E.

1993-01-01

Spinal cord injuries in tetraplegics were briefly discussed on the basis of MR imaging. It was found that severe cervical spine trauma usually results in concussion - the complete transection of the cord is rare. A case of 19 years old male with total cord transection confirmed by MR imaging is described. (author)

Agent-based modeling traction force mediated compaction of cell-populated collagen gels using physically realistic fibril mechanics.

Science.gov (United States)

Reinhardt, James W; Gooch, Keith J

2014-02-01

Agent-based modeling was used to model collagen fibrils, composed of a string of nodes serially connected by links that act as Hookean springs. Bending mechanics are implemented as torsional springs that act upon each set of three serially connected nodes as a linear function of angular deflection about the central node. These fibrils were evaluated under conditions that simulated axial extension, simple three-point bending and an end-loaded cantilever. The deformation of fibrils under axial loading varied <0.001% from the analytical solution for linearly elastic fibrils. For fibrils between 100 μm and 200 μm in length experiencing small deflections, differences between simulated deflections and their analytical solutions were <1% for fibrils experiencing three-point bending and <7% for fibrils experiencing cantilever bending. When these new rules for fibril mechanics were introduced into a model that allowed for cross-linking of fibrils to form a network and the application of cell traction force, the fibrous network underwent macroscopic compaction and aligned between cells. Further, fibril density increased between cells to a greater extent than that observed macroscopically and appeared similar to matrical tracks that have been observed experimentally in cell-populated collagen gels. This behavior is consistent with observations in previous versions of the model that did not allow for the physically realistic simulation of fibril mechanics. The significance of the torsional spring constant value was then explored to determine its impact on remodeling of the simulated fibrous network. Although a stronger torsional spring constant reduced the degree of quantitative remodeling that occurred, the inclusion of torsional springs in the model was not necessary for the model to reproduce key qualitative aspects of remodeling, indicating that the presence of Hookean springs is essential for this behavior. These results suggest that traction force mediated matrix

Insulin amyloid fibrillation studied by terahertz spectroscopy and other biophysical methods

Energy Technology Data Exchange (ETDEWEB)

Liu, Rui [State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); He, Mingxia [College of Precision Instrument and Optoelectronics Engineering, Tianjin University, Tianjin 300072 (China); Su, Rongxin, E-mail: surx@tju.edu.cn [State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Tianjin Key Laboratory of Membrane Science and Desalination Technology, Tianjin University, Tianjin 300072 (China); Yu, Yanjun [State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Qi, Wei; He, Zhimin [State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Tianjin Key Laboratory of Membrane Science and Desalination Technology, Tianjin University, Tianjin 300072 (China)

2010-01-01

Assembly and fibrillation of amyloid proteins are believed to play a key role in the etiology of various human diseases, including Alzheimer's, Parkinson's, Huntington's and type II diabetes. Insights into conformational changes and formation processes during amyloid fibrillation are essential for the clinical diagnosis and drug discovery. To study the changes in secondary, tertiary, quaternary structures, and the alteration in the collective vibrational mode density of states during the amyloid fibrillation, bovine insulin in 20% acetic acid was incubated at 60 {sup o}C, and its multi-level structures were followed by various biophysical techniques, including circular dichroism (CD), thioflavin T fluorescence (ThT), dynamic light scattering (DLS), electron microscopy, and terahertz (THz) absorption spectroscopy. The experimental data demonstrated a transformation of {alpha}-helix into {beta}-sheet starting at 26 h. This was followed by the aggregation of insulin, as shown by ThT binding, with a transition midpoint at 41 h, and by the bulk formation of mature aggregates after about 71 h. THz is a quick and non-invasive technique, which has the advantage of allowing the study of the conformational state of biomolecules and tissues. We first applied THz spectroscopy to study the amyloid fibrillation. At the terahertz frequency range of 0.2-2.0 THz, there was an apparent increase in both the absorbance and refractive index in THz spectra. Thus, THz is expected to provide a new way of looking into amyloid fibrillation.

Surgical Treatment of Atrial Fibrillation in Patients with Rheumatic Valve Disease

Directory of Open Access Journals (Sweden)

Ernesto Koehler Chavez

Full Text Available Abstract Objective: To assess heart rhythm and predictive factors associated with sinus rhythm after one year in patients with rheumatic valve disease undergoing concomitant surgical treatment of atrial fibrillation. Operative mortality, survival and occurrence of stroke after one year were also evaluated. Methods: Retrospective longitudinal observational study of 103 patients undergoing rheumatic mitral valve surgery and ablation of atrial fibrillation using uni- or bipolar radiofrequency between January 2013 and December 2014. Age, gender, functional class (NYHA, type of atrial fibrillation, EuroSCORE, duration of atrial fibrillation, stroke, left atrial size, left ventricular ejection fraction, cardiopulmonary bypass time, myocardial ischemia time and type of radiofrequency were investigated. Results: After one year, 66.3% of patients were in sinus rhythm. Sinus rhythm at hospital discharge, lower left atrial size in the preoperative period and bipolar radiofrequency were associated with a greater chance of sinus rhythm after one year. Operative mortality was 7.7%. Survival rate after one year was 92.3% and occurrence of stroke was 1%. Conclusion: Atrial fibrillation ablation surgery with surgical approach of rheumatic mitral valve resulted in 63.1% patients in sinus rhythm after one year. Discharge from hospital in sinus rhythm was a predictor of maintenance of this rhythm. Increased left atrium and use of unipolar radiofrequency were associated with lower chance of sinus rhythm. Operative mortality rate of 7.7% and survival and stroke-free survival contribute to excellent care results for this approach.

Architecture of polyglutamine-containing fibrils from time-resolved fluorescence decay.

Science.gov (United States)

Röthlein, Christoph; Miettinen, Markus S; Borwankar, Tejas; Bürger, Jörg; Mielke, Thorsten; Kumke, Michael U; Ignatova, Zoya

2014-09-26

The disease risk and age of onset of Huntington disease (HD) and nine other repeat disorders strongly depend on the expansion of CAG repeats encoding consecutive polyglutamines (polyQ) in the corresponding disease protein. PolyQ length-dependent misfolding and aggregation are the hallmarks of CAG pathologies. Despite intense effort, the overall structure of these aggregates remains poorly understood. Here, we used sensitive time-dependent fluorescent decay measurements to assess the architecture of mature fibrils of huntingtin (Htt) exon 1 implicated in HD pathology. Varying the position of the fluorescent labels in the Htt monomer with expanded 51Q (Htt51Q) and using structural models of putative fibril structures, we generated distance distributions between donors and acceptors covering all possible distances between the monomers or monomer dimensions within the polyQ amyloid fibril. Using Monte Carlo simulations, we systematically scanned all possible monomer conformations that fit the experimentally measured decay times. Monomers with four-stranded 51Q stretches organized into five-layered β-sheets with alternating N termini of the monomers perpendicular to the fibril axis gave the best fit to our data. Alternatively, the core structure of the polyQ fibrils might also be a zipper layer with antiparallel four-stranded stretches as this structure showed the next best fit. All other remaining arrangements are clearly excluded by the data. Furthermore, the assessed dimensions of the polyQ stretch of each monomer provide structural evidence for the observed polyQ length threshold in HD pathology. Our approach can be used to validate the effect of pharmacological substances that inhibit or alter amyloid growth and structure. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Lessons from comparative studies of atrial fibrillation in dog, man and horse

NARCIS (Netherlands)

Meijler, F.L.; Tweel, I. van der; Herbschleb, J.N.; Heethaar, R.M.; Borst, C.

1985-01-01

Since its first description in 1903 by Hering, the irregularity of the heart beat has been the most striking characteristic of atrial fibrillation and has been subject of many studies. To quote Selzer, "Atrial fibrillation is the grandfather of cardiac arrhythmias." It is an arrhythmia that 1)

Heat-induced whey protein isolate fibrils: Conversion, hydrolysis, and disulphide bond formation

NARCIS (Netherlands)

Bolder, S.G.; Vasbinder, A.; Sagis, L.M.C.; Linden, van der E.

2007-01-01

Fibril formation of individual pure whey proteins and whey protein isolate (WPI) was studied. The heat-induced conversion of WPI monomers into fibrils at pH 2 and low ionic strength increased with heating time and protein concentration. Previous studies, using a precipitation method, size-exclusion

Time to implement fitness and reduction of fatness in atrial fibrillation therapy

NARCIS (Netherlands)

Van Gelder, Isabelle C.; Hobbelt, Anne H.; Brugemann, Johan; Rienstra, Michiel

This editorial refers to ‘Self-reported physical activity and major adverse events in patients with atrial fibrillation: a report from the EURObservational Research Programme Pilot Survey on Atrial Fibrillation (EORP-AF) General Registry’ by M. Proietti et al. , doi:10.1093/europace/euw150. Atrial

The effect of point mutations on structure and mechanical properties of collagen-like fibril: A molecular dynamics study

Energy Technology Data Exchange (ETDEWEB)

Marlowe, Ashley E.; Singh, Abhishek; Yingling, Yaroslava G., E-mail: yara_yingling@ncsu.edu

2012-12-01

Understanding sequence dependent mechanical and structural properties of collagen fibrils is important for the development of artificial biomaterials for medical and nanotechnological applications. Moreover, point mutations are behind many collagen associated diseases, including Osteogenesis Imperfecta (OI). We conducted a combination of classical and steered atomistic molecular dynamics simulations to examine the effect of point mutations on structure and mechanical properties of short collagen fibrils which include mutations of glycine to alanine, aspartic acid, cysteine, and serine or mutations of hydroxyproline to arginine, asparagine, glutamine, and lysine. We found that all mutations disrupt structure and reduce strength of the collagen fibrils, which may affect the hierarchical packing of the fibrils. The glycine mutations were more detrimental to mechanical strength of the fibrils (WT > Ala > Ser > Cys > Asp) than that of hydroxyproline (WT > Arg > Gln > Asn > Lys). The clinical outcome for glycine mutations agrees well with the trend in reduction of fibril's tensile strength predicted by our simulations. Overall, our results suggest that the reduction in mechanical properties of collagen fibrils may be used to predict the clinical outcome of mutations. Highlights: Black-Right-Pointing-Pointer All mutations disrupt structure and bonding pattern and reduce strength of the collagen fibrils. Black-Right-Pointing-Pointer Gly based mutations are worst to mechanical integrity of fibrils than that of Hyp. Black-Right-Pointing-Pointer Lys and Arg mutations most dramatically destabilize collagen fibril properties. Black-Right-Pointing-Pointer Clinical outcome of mutations may be related to the reduced mechanical properties of fibrils.

Cord lactate, pH, and blood gases from healthy neonates.

Science.gov (United States)

Shirey, T; St Pierre, J; Winkelman, J

1996-01-01

Lactate, pH, pO2, and pCO2 were determined in arterial, venous, and free-flowing mixed umbilical cord blood obtained from deliveries of apparently healthy neonates. The goals of this study were to establish reference ranges for lactate and pH against which results in cases of high-risk labor and delivery could be compared, to see how the gases correlated with these values, and to determine whether easily accessible mixed umbilical cord blood can serve as the sample in lieu of cord arterial or cord venous blood. Arterial and venous cord lactates were 2.98 mmol/l (+/- 1.40) and 2.80 mmol/l (+/- 1.35), respectively, from 85 cords obtained from vaginal and cesarean deliveries. Mixed cord blood lactate, obtained on 48 cords, was 2.72 mmol/l (+/- 1.28) versus 3.14 and 2.97 mmol/l for the arterial and venous samples from those cords, respectively, and correlated quite well with lactate from the venous specimens (r = 0.97). Differences of > 0.5 mmol/l occurred between mixed and arterial cord bloods in 21 patients, and between mixed and venous cord bloods in 6 of the 48 patients, respectively. We conclude that (1) less than 2.5% of deliveries of apparently healthy neonates have arterial, venous, or mixed cord lactates > or = 7.0 mmol/l and pH pO2 nor pCO2 correlate well with cord venous lactate, and (3) readily available mixed cord blood is a satisfactory specimen for the measurement of venous cord latate.

Atrial fibrillation in a healthy adolescent after heavy smoking of contraband cigarettes.

Science.gov (United States)

Ozyilmaz, Isa; Ozyilmaz, Sinem; Tosun, Oyku; Tola, Hasan Tahsin; Saygi, Murat; Ergul, Yakup

2015-08-01

The use of contraband cigarettes is a serious public health problem. We present a case of atrial fibrillation in a healthy adolescent suspected to be caused by smoking contraband cigarettes. A 15-year-old man was admitted to our emergency department experiencing syncope and palpitations. He was a cigarette smoker, but he had never smoked any illicit tobacco products before. He had finished a pack of counterfeit cigarettes (20 pieces) in 1.5 h. His electrocardiogram showed atrial fibrillation with a rapid ventricular response and irregular RR intervals. The patient had no history of alcohol use, surgery, palpitations, hypertension, chronic bronchitis, or any infectious diseases. His atrial fibrillation was converted to a normal sinus rhythm after the cardioversion treatment. Our patient was discharged from the pediatric cardiology service and advised to quit smoking cigarettes, strictly warning against illicit tobacco products. In conclusion, intensive smoking of counterfeit cigarettes may lead to occurrences of atrial fibrillation.

CORD PROLAPSE, ASSOCIATED FACTORS AND FETAL OUTCOME

African Journals Online (AJOL)

Several factors predispose to cord prolapse, amongst which are breech presentation, abnormal lie and presentation, hydramnios and long cord [2-3, 5-7]. Perinatal mortality is the most feared complication and often seen in up to 91% of cases [8-9]. Little is known about the pattern of umbilical cord prolapse in Cameroon as ...

Probability of atrial fibrillation after ablation: Using a parametric nonlinear temporal decomposition mixed effects model.

Science.gov (United States)

Rajeswaran, Jeevanantham; Blackstone, Eugene H; Ehrlinger, John; Li, Liang; Ishwaran, Hemant; Parides, Michael K

2018-01-01

Atrial fibrillation is an arrhythmic disorder where the electrical signals of the heart become irregular. The probability of atrial fibrillation (binary response) is often time varying in a structured fashion, as is the influence of associated risk factors. A generalized nonlinear mixed effects model is presented to estimate the time-related probability of atrial fibrillation using a temporal decomposition approach to reveal the pattern of the probability of atrial fibrillation and their determinants. This methodology generalizes to patient-specific analysis of longitudinal binary data with possibly time-varying effects of covariates and with different patient-specific random effects influencing different temporal phases. The motivation and application of this model is illustrated using longitudinally measured atrial fibrillation data obtained through weekly trans-telephonic monitoring from an NIH sponsored clinical trial being conducted by the Cardiothoracic Surgery Clinical Trials Network.

Spectroscopic study of Alzheimer's amyloid fibrils using terahertz time domain spectroscopy

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Jung, Euna; Kim, Jeonghoi; Han, Younho; Moon, Kiwon; Lim, Meehyun; Han, Haewook; Park, Joonhyuck; Kim, Sungjee [POSTECH, Pohang (Korea, Republic of)

2008-11-15

Alzheimer's disease, one of the most common neurodegenerative diseases, is characterized by extensive amyloid deposition. Amyloid deposits contain the abundant fibrils formed by amyloid β protein (Aβ). Because amyloid fibrils are associated with amyloid diseases, including Alzheimer's disease, type 2 diabetes, prion disease, Parkinson's disease, senile systemic amyloidosis and Huntington's disease, there has been considerable interest within the biomedical and biochemical research communities. In transmission electron microscopic (TEM)images, amyloid firils are 0.1∼10μm long and approximately 10nm wide. Amyloid fibrils commonly exhibit self assembled filaments, often described as twisted or parallel assemblies of finer protofilaments. They are formed by the spontaneous aggregation of a wide variety of peptides and proteins. Structural studies of amyloid fibrils have revealed that the common structural motif of virtually all amyloid fibrils consists of cross β sheets in which the peptide strands are arranged perpendicular to the long axis of the fiber. But little was known until recently about the molecular level structures of amyloid fibils. Therefore, spectroscopic investigation of both amyloid fibrils and Aβ at the molecular level can provide the significant evidence for the molecular understanding of amyloidogenesis and for the development of innovative therapeutic and diagnostic approaches. We used terahertz time domain spectroscopy (THz TDS)to investigate both Aβ and amyloid fibril. THz TDS, developed over the last two decades, is a powerful tool to extract the properties of biomaterials and provides unique spectral signatures of biomolecules within 0.1∼10THz, which exists between microwave and infrared frequency range. Current interest in THz radiation arises from its capability of probing the delocalized collective vibrational modes in proteins. Studying the collective modes of proteins in THz frequency range can play an

Structural fingerprints and their evolution during oligomeric vs. oligomer-free amyloid fibril growth.

Science.gov (United States)

Foley, Joseph; Hill, Shannon E; Miti, Tatiana; Mulaj, Mentor; Ciesla, Marissa; Robeel, Rhonda; Persichilli, Christopher; Raynes, Rachel; Westerheide, Sandy; Muschol, Martin

2013-09-28

Deposits of fibrils formed by disease-specific proteins are the molecular hallmark of such diverse human disorders as Alzheimer's disease, type II diabetes, or rheumatoid arthritis. Amyloid fibril formation by structurally and functionally unrelated proteins exhibits many generic characteristics, most prominently the cross β-sheet structure of their mature fibrils. At the same time, amyloid formation tends to proceed along one of two separate assembly pathways yielding either stiff monomeric filaments or globular oligomers and curvilinear protofibrils. Given the focus on oligomers as major toxic species, the very existence of an oligomer-free assembly pathway is significant. Little is known, though, about the structure of the various intermediates emerging along different pathways and whether the pathways converge towards a common or distinct fibril structures. Using infrared spectroscopy we probed the structural evolution of intermediates and late-stage fibrils formed during in vitro lysozyme amyloid assembly along an oligomeric and oligomer-free pathway. Infrared spectroscopy confirmed that both pathways produced amyloid-specific β-sheet peaks, but at pathway-specific wavenumbers. We further found that the amyloid-specific dye thioflavin T responded to all intermediates along either pathway. The relative amplitudes of thioflavin T fluorescence responses displayed pathway-specific differences and could be utilized for monitoring the structural evolution of intermediates. Pathway-specific structural features obtained from infrared spectroscopy and Thioflavin T responses were identical for fibrils grown at highly acidic or at physiological pH values and showed no discernible effects of protein hydrolysis. Our results suggest that late-stage fibrils formed along either pathway are amyloidogenic in nature, but have distinguishable structural fingerprints. These pathway-specific fingerprints emerge during the earliest aggregation events and persist throughout the

Structural fingerprints and their evolution during oligomeric vs. oligomer-free amyloid fibril growth

Science.gov (United States)

Foley, Joseph; Hill, Shannon E.; Miti, Tatiana; Mulaj, Mentor; Ciesla, Marissa; Robeel, Rhonda; Persichilli, Christopher; Raynes, Rachel; Westerheide, Sandy; Muschol, Martin

2013-09-01

Deposits of fibrils formed by disease-specific proteins are the molecular hallmark of such diverse human disorders as Alzheimer's disease, type II diabetes, or rheumatoid arthritis. Amyloid fibril formation by structurally and functionally unrelated proteins exhibits many generic characteristics, most prominently the cross β-sheet structure of their mature fibrils. At the same time, amyloid formation tends to proceed along one of two separate assembly pathways yielding either stiff monomeric filaments or globular oligomers and curvilinear protofibrils. Given the focus on oligomers as major toxic species, the very existence of an oligomer-free assembly pathway is significant. Little is known, though, about the structure of the various intermediates emerging along different pathways and whether the pathways converge towards a common or distinct fibril structures. Using infrared spectroscopy we probed the structural evolution of intermediates and late-stage fibrils formed during in vitro lysozyme amyloid assembly along an oligomeric and oligomer-free pathway. Infrared spectroscopy confirmed that both pathways produced amyloid-specific β-sheet peaks, but at pathway-specific wavenumbers. We further found that the amyloid-specific dye thioflavin T responded to all intermediates along either pathway. The relative amplitudes of thioflavin T fluorescence responses displayed pathway-specific differences and could be utilized for monitoring the structural evolution of intermediates. Pathway-specific structural features obtained from infrared spectroscopy and Thioflavin T responses were identical for fibrils grown at highly acidic or at physiological pH values and showed no discernible effects of protein hydrolysis. Our results suggest that late-stage fibrils formed along either pathway are amyloidogenic in nature, but have distinguishable structural fingerprints. These pathway-specific fingerprints emerge during the earliest aggregation events and persist throughout the

Amide proton solvent protection in amylin fibrils probed by quenched hydrogen exchange NMR.

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Andrei T Alexandrescu

Full Text Available Amylin is an endocrine hormone that accumulates in amyloid plaques in patients with advanced type 2 diabetes. The amyloid plaques have been implicated in the destruction of pancreatic β-cells, which synthesize amylin and insulin. To better characterize the secondary structure of amylin in amyloid fibrils we assigned the NMR spectrum of the unfolded state in 95% DMSO and used a quenched hydrogen-deuterium exchange technique to look at amide proton solvent protection in the fibrils. In this technique, partially exchanged fibrils are dissolved in 95% DMSO and information about amide proton occupancy in the fibrils is determined from DMSO-denatured monomers. Hydrogen exchange lifetimes at pH 7.6 and 37°C vary between ∼5 h for the unstructured N-terminus to 600 h for amide protons in the two β-strands that form inter-molecular hydrogen bonds between amylin monomers along the length of the fibril. Based on the protection data we conclude that residues A8-H18 and I26-Y37 comprise the two β-strands in amylin fibrils. There is variation in protection within the β-strands, particularly for strand β1 where only residues F15-H18 are strongly protected. Differences in protection appear to be due to restrictions on backbone dynamics imposed by the packing of two-layers of C2-symmetry-related β-hairpins in the protofilament structure, with strand β1 positioned on the surface and β2 in the interior.

Pulmonary vein dimensions and variation of branching pattern in patients with paroxysmal atrial fibrillation using magnetic resonance angiography

International Nuclear Information System (INIS)

Takase, Bonpei; Nagata, Masayoshi; Matsui, Takemi

2004-01-01

Pulmonary veins are the most frequent origin of focal and paroxysmal atrial fibrillation. Although radiofrequency ablation has been attempted for the treatment of focal and paroxysmal atrial fibrillation, the anatomy of the pulmonary vein is still not fully understood. To investigate the dimensions and anatomical variation of the pulmonary vein in patients with paroxysmal atrial fibrillation, we performed breath-hold gadolinium enhanced magnetic resonance (MR) angiography using a 1.5 T cardiac MR imager (GE CV/i) in 32 patients with paroxysmal atrial fibrillation (61±8 years old), 11 patients with chronic atrial fibrillation (64±9 years old), and 26 patients with normal sinus rhythm (55±15 years old). Three-dimensional images of the pulmonary veins were thus obtained, and the diameters of the most proximal portion of the left or right superior pulmonary vein and left or right inferior pulmonary vein were measured. Pulmonary vein branching variations were determined by a visual qualitative analysis by two separate readers' agreements, who were blinded to any clinical information. We focused on the existence of a complex-branching pattern draining into the orifice of four pulmonary veins. Patients with either paroxysmal atrial fibrillation or chronic atrial fibrillation showed larger superior pulmonary veins than those with normal sinus rhythm (mean±SD; in the left superior pulmonary vein, 20±3 mm 23±3 mm vs 16±3 mm, P<0.05; in right superior pulmonary vein, 19±4 mm, 19±2 mm vs 16±2 mm, P<0.05). Complex-branching pattern was frequently observed in inferior pulmonary veins in patients with either paroxysmal atrial fibrillation or chronic atrial fibrillation; 25/32 patients with paroxysmal atrial fibrillation, 11/11 patients with chronic atrial fibrillation, compared to 7/26 patients with normal sinus rhythm. Complex-branching patterns were not observed in superior pulmonary veins in any patients in this cohort. In patients with paroxysmal atrial fibrillation

Elastic properties of woven bone: effect of mineral content and collagen fibrils orientation.

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García-Rodríguez, J; Martínez-Reina, J

2017-02-01

Woven bone is a type of tissue that forms mainly during fracture healing or fetal bone development. Its microstructure can be modeled as a composite with a matrix of mineral (hydroxyapatite) and inclusions of collagen fibrils with a more or less random orientation. In the present study, its elastic properties were estimated as a function of composition (degree of mineralization) and fibril orientation. A self-consistent homogenization scheme considering randomness of inclusions' orientation was used for this purpose. Lacuno-canalicular porosity in the form of periodically distributed void inclusions was also considered. Assuming collagen fibrils to be uniformly oriented in all directions led to an isotropic tissue with a Young's modulus [Formula: see text] GPa, which is of the same order of magnitude as that of woven bone in fracture calluses. By contrast, assuming fibrils to have a preferential orientation resulted in a Young's modulus in the preferential direction of 9-16 GPa depending on the mineral content of the tissue. These results are consistent with experimental evidence for woven bone in foetuses, where collagen fibrils are aligned to a certain extent.

Is there a clinically significant seasonal component to hospital admissions for atrial fibrillation?

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Moineddin Rahim

2004-03-01

Full Text Available Abstract Background Atrial fibrillation is a common cardiac dysrhythmia, particularly in the elderly. Recent studies have indicated a statistically significant seasonal component to atrial fibrillation hospitalizations. Methods We conducted a retrospective population cohort study using time series analysis to evaluate seasonal patterns of atrial fibrillation hospitalizations for the province of Ontario for the years 1988 to 2001. Five different series methods were used to analyze the data, including spectral analysis, X11, R-Squared, autocorrelation function and monthly aggregation. Results This study found evidence of weak seasonality, most apparent at aggregate levels including both ages and sexes. There was dramatic increase in hospitalizations for atrial fibrillation over the years studied and an age dependent increase in rates per 100,000. Overall, the magnitude of seasonal difference between peak and trough months is in the order of 1.4 admissions per 100,000 population. The peaks for hospitalizations were predominantly in April, and the troughs in August. Conclusions Our study confirms statistical evidence of seasonality for atrial fibrillation hospitalizations. This effect is small in absolute terms and likely not significant for policy or etiological research purposes.

High-Pressure-Driven Reversible Dissociation of α-Synuclein Fibrils Reveals Structural Hierarchy.

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Piccirilli, Federica; Plotegher, Nicoletta; Ortore, Maria Grazia; Tessari, Isabella; Brucale, Marco; Spinozzi, Francesco; Beltramini, Mariano; Mariani, Paolo; Militello, Valeria; Lupi, Stefano; Perucchi, Andrea; Bubacco, Luigi

2017-10-17

The analysis of the α-synuclein (aS) aggregation process, which is involved in Parkinson's disease etiopathogenesis, and of the structural feature of the resulting amyloid fibrils may shed light on the relationship between the structure of aS aggregates and their toxicity. This may be considered a paradigm of the ground work needed to tackle the molecular basis of all the protein-aggregation-related diseases. With this aim, we used chemical and physical dissociation methods to explore the structural organization of wild-type aS fibrils. High pressure (in the kbar range) and alkaline pH were used to disassemble fibrils to collect information on the hierarchic pathway by which distinct β-sheets sequentially unfold using the unique possibility offered by high-pressure Fourier transform infrared spectroscopy. The results point toward the formation of kinetic traps in the energy landscape of aS fibril disassembly and the presence of transient partially folded species during the process. Since we found that the dissociation of wild-type aS fibrils by high pressure is reversible upon pressure release, the disassembled molecules likely retain structural information that favors fibril reformation. To deconstruct the role of the different regions of aS sequence in this process, we measured the high-pressure dissociation of amyloids formed by covalent chimeric dimers of aS (syn-syn) and by the aS deletion mutant that lacks the C-terminus, i.e., aS (1-99). The results allowed us to single out the role of dimerization and that of the C-terminus in the complete maturation of fibrillar aS. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Exposure-Based Therapy for Symptom Preoccupation in Atrial Fibrillation

DEFF Research Database (Denmark)

Särnholm, Josefin; Skúladóttir, Helga; Rück, Christian

2017-01-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Patients often experience a range of symptoms resulting in a markedly reduced quality of life, and commonly show symptom preoccupation in terms of avoidance and control behaviors. Cognitive behavior therapy (CBT) has been shown...... with symptomatic paroxysmal (intermittent) atrial fibrillation who were assessed pre- and posttreatment and at 6-month follow-up. The CBT lasted 10 weeks and included exposure to physical sensations similar to AF symptoms, exposure to avoided situations or activities, and behavioral activation. We observed large...

Cord blood banking and transplantation: advances and controversies.

Science.gov (United States)

Yoder, Mervin C

2014-04-01

A review of articles published since January 2012 on the topic of cord blood banking and cord blood stem cell transplantation was conducted for this the 25th anniversary year of the first cord blood transplant performed in a human. Cord blood banking is performed throughout the world. Umbilical cord blood (UCB) transplantation is recognized as an acceptable alternative stem cell source for paediatric and adults requiring a haematopoietic transplant, particularly for patients of racial and ethnic minorities. To further advance the use of UCB, methods to enhance UCB stem cell expansion, engraftment and maintenance may be required. Controversy on the most effective and economically sustainable model for banking and storing an optimal UCB product continues to persist. Cord blood banking and transplantation of cord blood stem cells has advanced rapidly over the initial 25 years, as more than 30 ,000 patients have benefited from the therapy. New concepts on the use of methods to expand UCB stem cells for transplantation and use for nonhaematopoietic indications may increase demand for UCB over the next few decades.

Spinal cord injury reveals multilineage differentiation of ependymal cells.

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Konstantinos Meletis

2008-07-01

Full Text Available Spinal cord injury often results in permanent functional impairment. Neural stem cells present in the adult spinal cord can be expanded in vitro and improve recovery when transplanted to the injured spinal cord, demonstrating the presence of cells that can promote regeneration but that normally fail to do so efficiently. Using genetic fate mapping, we show that close to all in vitro neural stem cell potential in the adult spinal cord resides within the population of ependymal cells lining the central canal. These cells are recruited by spinal cord injury and produce not only scar-forming glial cells, but also, to a lesser degree, oligodendrocytes. Modulating the fate of ependymal progeny after spinal cord injury may offer an alternative to cell transplantation for cell replacement therapies in spinal cord injury.

Prenatal exposure to fenugreek impairs sensorimotor development and the operation of spinal cord networks in mice.

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Loubna Khalki

Full Text Available Fenugreek is a medicinal plant whose seeds are widely used in traditional medicine, mainly for its laxative, galactagogue and antidiabetic effects. However, consumption of fenugreek seeds during pregnancy has been associated with a range of congenital malformations, including hydrocephalus, anencephaly and spina bifida in humans. The present study was conducted to evaluate the effects of prenatal treatment of fenugreek seeds on the development of sensorimotor functions from birth to young adults. Pregnant mice were treated by gavage with 1 g/kg/day of lyophilized fenugreek seeds aqueous extract (FSAE or distilled water during the gestational period. Behavioral tests revealed in prenatally treated mice a significant delay in righting, cliff avoidance, negative geotaxis responses and the swimming development. In addition, extracellular recording of motor output in spinal cord isolated from neonatal mice showed that the frequency of spontaneous activity and fictive locomotion was reduced in FSAE-exposed mice. On the other hand, the cross-correlation coefficient in control mice was significantly more negative than in treated animals indicating that alternating patterns are deteriorated in FSAE-treated animals. At advanced age, prenatally treated mice displayed altered locomotor coordination in the rotarod test and also changes in static and dynamic parameters assessed by the CatWalk automated gait analysis system. We conclude that FSAE impairs sensorimotor and coordination functions not only in neonates but also in adult mice. Moreover, spinal neuronal networks are less excitable in prenatally FSAE-exposed mice suggesting that modifications within the central nervous system are responsible, at least in part, for the motor impairments.

Tensile properties of human collagen fibrils and fascicles are insensitive to environmental salts

DEFF Research Database (Denmark)

Svensson, René B; Hassenkam, Tue; Grant, Colin A

2010-01-01

loading direction of tendon is along its longitudinal axis. Thus, in this study, we focus on the tensile mechanical properties of two hierarchical levels from human patellar tendon, namely: individual collagen fibrils and fascicles. Investigations on collagen fibrils and fascicles were made at pH 7...... was observed at the highest phosphate-buffered saline concentration for both the fibrils and fascicles, indicating a stabilizing effect of ionic screening, but changes were much less than reported for radial compression. Due to the small magnitude of the effects, the tensile mechanical properties of collagen...

Different strategies to improve the use of the umbilical cord and cord blood for hematopoietic and other regenerative cell therapies

NARCIS (Netherlands)

Garde, Mark Paul van der

2016-01-01

The umbilical cord and cord blood contain stem cells that can be used for regenerative cell therapies such as hematopoietic stem cell transplantation. However, the application of cord blood is hindered by the slow engraftment of the cells and delayed immune reconstitution compared to stem cells of

Ventilation onset prior to umbilical cord clamping (physiological-based cord clamping improves systemic and cerebral oxygenation in preterm lambs.

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Graeme R Polglase

Full Text Available As measurement of arterial oxygen saturation (SpO2 is common in the delivery room, target SpO2 ranges allow clinicians to titrate oxygen therapy for preterm infants in order to achieve saturation levels similar to those seen in normal term infants in the first minutes of life. However, the influence of the onset of ventilation and the timing of cord clamping on systemic and cerebral oxygenation is not known.We investigated whether the initiation of ventilation, prior to, or after umbilical cord clamping, altered systemic and cerebral oxygenation in preterm lambs.Systemic and cerebral blood-flows, pressures and peripheral SpO2 and regional cerebral tissue oxygenation (SctO2 were measured continuously in apnoeic preterm lambs (126±1 day gestation. Positive pressure ventilation was initiated either 1 prior to umbilical cord clamping, or 2 after umbilical cord clamping. Lambs were monitored intensively prior to intervention, and for 10 minutes following umbilical cord clamping.Clamping the umbilical cord prior to ventilation resulted in a rapid decrease in SpO2 and SctO2, and an increase in arterial pressure, cerebral blood flow and cerebral oxygen extraction. Ventilation restored oxygenation and haemodynamics by 5-6 minutes. No such disturbances in peripheral or cerebral oxygenation and haemodynamics were observed when ventilation was initiated prior to cord clamping.The establishment of ventilation prior to umbilical cord clamping facilitated a smooth transition to systemic and cerebral oxygenation following birth. SpO2 nomograms may need to be re-evaluated to reflect physiological management of preterm infants in the delivery room.

Utility of MR imaging in pediatric spinal cord injury

International Nuclear Information System (INIS)

Felsberg, G.J.; Tien, R.D.; Osumi, A.K.; Cardenas, C.A.

1995-01-01

We evaluated the utility of MR imaging in pediatric patients with acute and subacute spinal cord injuries. MR imaging of 22 pediatric patients with suspected traumatic spinal cord injuries was reviewed. MR findings were correlated with physical examination and compared to available radiographs and CT examinations performed at time of presentation. Twelve patients had abnormalities on MR imaging. Seven had spinal cord contusions; five contusions were hemorrhagic. Five of seven patients with cord contusion had normal radiographs and CT exams. Six patients with normal radiographs and CT examinations had abnormal MR studies revealing cord contusion, ligamentous injury, disc herniation, and epidural hematoma. MR is useful in initial evaluation of pediatric patients with spinal cord injuries and in prognosis of future neurologic function. In the setting of spinal cord symptomatology and negative radiographic studies, MR imaging should be performed. Surgically correctable causes of cord compression demonstrated by MR imaging include disc herniation, epidural hematoma, and retropulsed fracture fragments. The entity of spinal cord injury without radiographic abnormality is a diagnosis of exclusion which should only be made after radiologic investigation with radiographs, high-resolution thin-section CT, and MR imaging. (orig.)

Circulating microRNA-1a is a biomarker of Graves' disease patients with atrial fibrillation.

Science.gov (United States)

Wang, Fang; Zhang, Sheng-Jie; Yao, Xuan; Tian, Dong-Mei; Zhang, Ke-Qin; She, Dun-Min; Guo, Fei-Fan; Zhai, Qi-Wei; Ying, Hao; Xue, Ying

2017-07-01

It has been increasingly suggested that specific microRNAs expression profiles in the circulation and atrial tissue are associated with the susceptibility to atrial fibrillation. Nonetheless, the role of circulating microRNAs in Graves' disease patients with atrial fibrillation has not yet been well described. The objective of the study was to identify the role of circulating microRNAs as specific biomarkers for the diagnosis of Graves' disease with atrial fibrillation. The expression profiles of eight serum microRNAs, which are found to be critical in the pathogenesis of atrial fibrillation, were determined in patients with Graves' disease with or without atrial fibrillation. MicroRNA expression analysis was performed by real-time PCR in normal control subjects (NC; n = 17), patients with Graves' disease without atrial fibrillation (GD; n = 29), patients with Graves' disease with atrial fibrillation (GD + AF; n = 14), and euthyroid patients with atrial fibrillation (AF; n = 22). Three of the eight serum microRNAs,i.e., miR-1a, miR-26a, and miR-133, had significantly different expression profiles among the four groups. Spearman's correlation analysis showed that the relative expression level of miR-1a was positively correlated with free triiodothyronine (FT3) and free thyroxine (FT4), and negatively related to thyroid stimulating hormone. Spearman's correlations analysis also revealed that the level of miR-1a was negatively correlated with a critical echocardiographic parameter (left atrial diameter), which was dramatically increased in GD + AF group compared to GD group. Furthermore, the receiver-operating characteristic curve analysis indicated that, among the eight microRNAs, miR-1a had the largest area under the receiver-operating characteristic curves not only for discriminating between individuals with and without Graves' disease, but also for predicting the presence of atrial fibrillation in patients with Graves' disease. Our findings

Does the informal seed system threaten cowpea seed health?

NARCIS (Netherlands)

Biemond, P.C.; Oguntade, O.; Lava Kumar, P.; Stomph, T.J.; Termorshuizen, A.J.; Struik, P.C.

2013-01-01

Most smallholder farmers in developing countries depend on an informal Seed System (SS) for their seed. The informal SS is often criticized because farmer-produced seed samples are not tested for seed health, thus accepting the risk of planting infected seeds. Here we aimed at assessing the quality

Lung response to ultrafine Kevlar aramid synthetic fibrils following 2-year inhalation exposure in rats.

Science.gov (United States)

Lee, K P; Kelly, D P; O'Neal, F O; Stadler, J C; Kennedy, G L

1988-07-01

Four groups of 100 male and 100 female rats were exposed to ultrafine Kevlar fibrils at concentrations of 0, 2.5, 25, and 100 fibrils/cc for 6 hr/day, 5 days/week for 2 years. One group was exposed to 400 fibrils/cc for 1 year and allowed to recover for 1 year. At 2.5 fibrils/cc, the lungs had normal alveolar architecture with a few dust-laden macrophages (dust cell response) in the alveolar airspaces. At 25 fibrils/cc, the lungs showed a dust cell response, slight Type II pneumocyte hyperplasia, alveolar bronchiolarization, and a negligible amount of collagenized fibrosis in the alveolar duct region. At 100 fibrils/cc, the same pulmonary responses were seen as at 25 fibrils/cc. In addition, cystic keratinizing squamous cell carcinoma (CKSCC) was found in 4 female rats, but not in male rats. Female rats had more prominent foamy alveolar macrophages, cholesterol granulomas, and alveolar bronchiolarization. These pulmonary lesions were related to the development of CKSCC. The lung tumors were derived from metaplastic squamous cells in areas of alveolar bronchiolarization. At 400 fibrils/cc following 1 year of recovery, the lung dust content, average fiber length, and the pulmonary lesions were markedly reduced, but slight centriacinar emphysema and minimal collagenized fibrosis were found in the alveolar duct region. One male and 6 female rats developed CKSCC. The lung tumors were a unique type of experimentally induced tumors in the rats and have not been seen as spontaneous tumors in man or animals. Therefore, the relevance of this type of lung tumor to the human situation is minimal.

Atrial fibrillation in the Middle East

DEFF Research Database (Denmark)

Al-Shamkhani, Warkaa; Ayetey, Harold; Lip, Gregory Y H

2018-01-01

INTRODUCTION: Atrial fibrillation (AF) is the commonest persistent cardiac arrhythmia with an estimated incidence rate of between 1.5-2% and an important cause of strokes. Few epidemiological studies and clinical trials on the management of AF have been conducted outside Europe and North America...

Amyloid Fibril-Induced Structural and Spectral Modifications in the Thioflavin-T Optical Probe

DEFF Research Database (Denmark)

Murugan, N. Arul; Olsen, Jógvan Magnus Haugaard; Kongsted, Jacob

2013-01-01

Motivated by future possibilities to design target molecules for fibrils with diagnostic or therapeutic capability related to amyloidosis diseases, we investigate in this work the dielectric nature of amyloid fibril microenvironments in different binding sites using an optical probe, thioflavin-T...

Spinal Cord Stimulation

DEFF Research Database (Denmark)

Meier, Kaare

2014-01-01

Spinal cord stimulation (SCS) is a surgical treatment for chronic neuropathic pain that is refractory to other treatment. Originally described by Shealy et al. in 1967(1), it is used to treat a range of conditions such as complex regional pain syndrome (CRPS I)(2), angina pectoris(3), radicular...... pain after failed back surgery syndrome (FBSS)(4), pain due to peripheral nerve injury, stump pain(5), peripheral vascular disease(6) and diabetic neuropathy(7,8); whereas phantom pain(9), postherpetic neuralgia(10), chronic visceral pain(11), and pain after partial spinal cord injury(12) remain more...

Atrial Fibrillation and Coronary Bypass Surgery – What Can Be Risk Factors for its' Appearance?

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Slavenka Štraus

2010-02-01

Full Text Available The main goal of our study was to evalúate possible perioperative risk factors for occurrence of atrial fibrillation in the postoperative period in patients after CABG operations. The study included 140 patients after CABG, divided into two groups - Group I - 64 patients with new onset of POAF and Group II - 76 patients without postoperative atrial fibrillation occurrence. In both groups possible risk factors for atrial fibrillation onset (preoperative and postoperative were analyzed.Results showed that we can predict new onset of atrial fibrillation after CABG if the following preoperative factors are present - low ejection fraction (less than 40%, LAd > 40mm, higher body mass index (BMI over 30, presence of COPD and older age. Important perioperative factors for onset of atrial fibrillation in our study were longer extracorporeal circulation, increased dose/number of inotropic drugs, blood transfusion and elevated WBC count postoperatively.

Comparison of the effect of topical application of human milk and dry cord care on the bacterial colonization of umbilical cord in newborn infants

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Fatemeh Abbaszadeh

2014-04-01

Full Text Available Background: Breast milk contains significant amounts of compounds that act as natural antimicrobial agents. This study was conducted to compare the effect of topical application of human milk and dry cord care on bacterial colonization in the umbilical cord of newborn infants. Methods: This clinical trial study was carried out on 174 infants in Kashan. The newborns were randomized to mother's milk group and dry cord care group from the birth. In group 1, the mother rubbed her own milk on the cord stump every 12 hours from 3 hours after birth to 2 days after the umbilical cord separation. In group 2, the mother was recommended not to use any material on the cord. Then, the cord samples were taken four times; 3hours after birth, at days 3 and 7, and 2 days after the umbilical cord separation. Results: The findings of the culture two days after umbilical cord separation indicated that low percentage of neonates in the breast milk (23.1% and dry cord care (28.8% groups had bacterial colonization. Moreover, no significant difference was found between the two groups in terms of growth of pathogenic organisms and normal flora of the skin (P>0.05. Conclusion: Given the low prevalence of pathogenic microorganisms in the two groups, it seems using breast milk and dry cord care are equally effective methods of taking care of umbilical cord.

Revealing molecular-level surface structure of amyloid fibrils in liquid by means of frequency modulation atomic force microscopy

Energy Technology Data Exchange (ETDEWEB)

Fukuma, Takeshi [Frontier Science Organization, Kanazawa University, Kakuma-machi, Kanazawa 920-1192 (Japan); Mostaert, Anika S; Jarvis, Suzanne P [Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Republic of Ireland (Ireland); Serpell, Louise C [Department of Biochemistry, University of Sussex, John Maynard Building, Falmer BN1 9QG (United Kingdom)], E-mail: fukuma@staff.kanazawa-u.ac.jp, E-mail: Anika.Mostaert@ucd.ie, E-mail: L.C.Serpell@sussex.ac.uk, E-mail: Suzi.Jarvis@ucd.ie

2008-09-24

We have investigated the surface structure of islet amyloid polypeptide (IAPP) fibrils and {alpha}-synuclein protofibrils in liquid by means of frequency modulation atomic force microscopy (FM-AFM). Angstroem-resolution FM-AFM imaging of isolated macromolecules in liquid is demonstrated for the first time. Individual {beta}-strands aligned perpendicular to the fibril axis with a spacing of 0.5 nm are resolved in FM-AFM images, which confirms cross-{beta} structure of IAPP fibrils in real space. FM-AFM images also reveal the existence of 4 nm periodic domains along the axis of IAPP fibrils. Stripe features with 0.5 nm spacing are also found in images of {alpha}-synuclein protofibrils. However, in contrast to the case for IAPP fibrils, the stripes are oriented 30 deg. from the axis, suggesting the possibility of {beta}-strand alignment in protofibrils different from that in mature fibrils or the regular arrangement of thioflavin T molecules present during the fibril preparation aligned at the surface of the protofibrils.

Revealing molecular-level surface structure of amyloid fibrils in liquid by means of frequency modulation atomic force microscopy

International Nuclear Information System (INIS)

Fukuma, Takeshi; Mostaert, Anika S; Jarvis, Suzanne P; Serpell, Louise C

2008-01-01

We have investigated the surface structure of islet amyloid polypeptide (IAPP) fibrils and α-synuclein protofibrils in liquid by means of frequency modulation atomic force microscopy (FM-AFM). Angstroem-resolution FM-AFM imaging of isolated macromolecules in liquid is demonstrated for the first time. Individual β-strands aligned perpendicular to the fibril axis with a spacing of 0.5 nm are resolved in FM-AFM images, which confirms cross-β structure of IAPP fibrils in real space. FM-AFM images also reveal the existence of 4 nm periodic domains along the axis of IAPP fibrils. Stripe features with 0.5 nm spacing are also found in images of α-synuclein protofibrils. However, in contrast to the case for IAPP fibrils, the stripes are oriented 30 deg. from the axis, suggesting the possibility of β-strand alignment in protofibrils different from that in mature fibrils or the regular arrangement of thioflavin T molecules present during the fibril preparation aligned at the surface of the protofibrils

Atrial fibrillation screening in pharmacies using an iPhone ECG: a qualitative review of implementation.

Science.gov (United States)

Lowres, Nicole; Krass, Ines; Neubeck, Lis; Redfern, Julie; McLachlan, Andrew J; Bennett, Alexandra A; Freedman, S Ben

2015-12-01

Atrial fibrillation guidelines advocate screening to identify undiagnosed atrial fibrillation. Community pharmacies may provide an opportunistic venue for such screening. To explore the experience of implementing an atrial fibrillation screening service from the pharmacist's perspective including: the process of study implementation; the perceived benefits; the barriers and enablers; and the challenges for future sustainability of atrial fibrillation screening within pharmacies. Setting Interviews were conducted face-to-face in the pharmacy or via telephone, according to pharmacist preference. The 'SEARCH-AF study' screened 1000 pharmacy customers aged ≥65 years using an iPhone electrocardiogram, identifying 1.5 % with undiagnosed atrial fibrillation. Nine pharmacists took part in semi-structured interviews. Interviews were transcribed in full and thematically analysed. Qualitative analysis of the experience of implementing an AF screening service from the pharmacist's perspective. Four broad themes relating to service provision were identified: (1) interest and engagement in atrial fibrillation screening by pharmacists, customers, and doctors with the novel, easy-to-use electrocardiogram technology serving as an incentive to undergo screening and an education tool for pharmacists to use with customers; (2) perceived benefits to the pharmacist including increased job satisfaction, improvement in customer relations and pharmacy profile by fostering enhanced customer care and the educational role of pharmacists; (3) implementation barriers including managing workflow, and enablers such as personal approaches for recruitment, and allocating time to discuss screening process and fears; and, (4) potential for sustainable future implementation including remuneration linked to government or pharmacy incentives, combined cardiovascular screening, and automating sections of risk-assessments using touch-screen technology. Atrial fibrillation screening in pharmacies is well

Atrial Fibrillation, Atrioventricular Blocks and Bundle Branch Blocks in Hemodialysis Patients

OpenAIRE

Mandic, Ante; Tomic, Monika; Petrov, Bozo; Romic, Zeljko

2012-01-01

Atrial fibrillation is one of the most frequent arrhythmias diagnosed in clinical practice and it is also relatively common in dialysis patients. Atrioventricular and intraventricular conduction disturbances are less investigated in hemodialysis patients and data about their prevalence are insufficient. The objective of this study was to determine the prevalence of atrial fibrillation, atrioventricular blocks and bundle branch blocks in hemodialysis patients and to analyze different clinical ...

Patient-Reported Outcomes for Quality of Life Assessment in Atrial Fibrillation: A Systematic Review of Measurement Properties.

Science.gov (United States)

Kotecha, Dipak; Ahmed, Amar; Calvert, Melanie; Lencioni, Mauro; Terwee, Caroline B; Lane, Deirdre A

2016-01-01

Atrial fibrillation is a large and growing burden across all types of healthcare. Both incidence and prevalence are expected to double in the next 20 years, with huge impact on hospital admissions, costs and patient quality of life. Patient wellbeing determines the management strategy for atrial fibrillation, including the use of rhythm control therapy and the clinical success of heart rate control. Hence, evaluation of quality of life is an emerging and important part of the assessment of patients with atrial fibrillation. Although a number of questionnaires to assess quality of life in atrial fibrillation are available, a comprehensive overview of their measurement properties is lacking. We performed a systematic review of the measurement properties of atrial fibrillation-specific health-related quality of life questionnaires. Methodological quality was assessed using the Consensus based Standards for selection of health Measurement Instruments (COSMIN) checklist, with measurement properties rated for quality against optimal criteria and levels of evidence. We screened 2,216 articles, of which eight articles describing five questionnaires were eligible for inclusion: Atrial Fibrillation 6 (AF6), Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT), Atrial Fibrillation Quality of Life Questionnaire (AFQLQ), Atrial Fibrillation Quality of Life (AFQoL), and Quality of Life in Atrial Fibrillation (QLAF). Good reliability (internal consistency and test-retest reliability) was demonstrated for AF6, AFEQT, AFQLQ and AFQoL. Content, construct and criterion validity were positively rated only in AFEQT. Responsiveness was positively rated only in AFEQT, but with limited evidence. Overall, AFEQT showed strong positive evidence for 2 of 9 measurement properties, compared to one for AFQoL and none for the remaining questionnaires. Given the low ratings for many measurement properties, no single questionnaire can be recommended, although AFEQT performed strongest. Further

Spinal cord magnetic resonance imaging in suspected multiple sclerosis

International Nuclear Information System (INIS)

Lycklama a Nijeholt, G.J.; Bergers, E.; Castelijns, J.A.; Barkhof, F.; Uitdehaag, B.M.J.; Polman, C.H.

2000-01-01

We examined the value of spinal cord magnetic resonance imaging (MRI) in the diagnostic work-up of multiple sclerosis (MS). Forty patients suspected of having MS were examined within 24 months after the start of symptoms. Disability was assessed, and symptoms were categorized as either brain or spinal cord. Work-up further included cerebrospinal fluid analysis and standard proton-density, T2-, and T1-weighted gadolinium-enhanced brain and spinal cord MRI. Patients were categorized as either clinically definite MS (n = 13), laboratory-supported definite MS (n = 14), or clinically probable MS (n = 4); four patients had clinically probable MS, and in nine MS was suspected. Spinal cord abnormalities were found in 35 of 40 patients (87.5 %), consisting of focal lesions in 31, only diffuse abnormalities in two, and both in two. Asymptomatic spinal cord lesions occurred in six patients. All patients with diffuse spinal cord abnormality had clear spinal cord symptoms and a primary progressive disease course. In clinically definite MS, the inclusion of spinal imaging increased the sensitivity of MRI to 100 %. Seven patients without a definite diagnosis had clinically isolated syndromes involving the spinal cord. Brain MRI was inconclusive, while all had focal spinal cord lesions which explained symptoms and ruled out other causes. Two other patients had atypical brain abnormalities suggesting ischemic/vascular disease. No spinal cord abnormalities were found, and during follow-up MS was ruled out. Spinal cord abnormalities are common in suspected MS, and may occur asymptomatic. Although diagnostic classification is seldom changed, spinal cord imaging increases diagnostic sensitivity of MRI in patients with suspected MS. In addition, patients with primary progressive MS may possibly be earlier diagnosed. Finally, differentiation with atypical lesions may be improved. (orig.)

Magnetic resonance imaging of experimental spinal cord injury

International Nuclear Information System (INIS)

Nakamura, Tsutomu; Kumano, Kouichi; Kadoya, Satoru

1989-01-01

Correlation between pathological findings and magnetic resonance imaging (MRI) of experimental cord injury were investigated. Cord injuries were made on ten Wistar rats weighing 80-170 gm by epidural compression of the thoracic cord with a Biemer cerebral vascular clip for 5-20 seconds. Several hours after the procedure animals were examined by spin echo axial MR images with a pulse sequence of TR/TE=1000/36 msec. MR studies were repeated on 4 animals 3-7 days after the initial examination. Immediately after the latest MRI examination animals were sacrificed and fixed with 10% formalin. Three micron thickness paraffin sections stained with hematoxylin and eosin were evaluated under a microscope. The pathological finding was hemorrhagic necrosis with edema of various severity depending on duration of clip application. The hemorrhagic necrosis was observed either unilaterally or bilaterally to the cord. MR findings of the cord were of high intensity in five animals which were severely injured, while central low intensity of the injured cord appeared in three mildly injured animals. Of the remaining two animals which had mild injury, one showed unilateral high intensity, while no definitive change was demonstrated in the other. The high intensity in the MRI suggested edema associated with hemorrhagic necrosis rather than hemorrhage. The central low intensity appearing in the mildly injured cord might be hemorrhage in the gray matter. It is concluded that MRI was useful to diagnose not only the level and severity but also the pathological process in the injured cord, and thus to estimate the prognosis of the cord injuries. (author)

Risk of atrial fibrillation among bisphosphonate users: a multicenter, population-based, Italian study

NARCIS (Netherlands)

L. Herrera (Lizbeth); I. Leal (Ingrid); F. Lapi (Francesco); M.J. Schuemie (Martijn); V. Arcoraci (Vincenzo); F. Cipriani (Francesco); E. Sessa (E.); A. Vaccheri (Alberto); C. Piccinni (C.); T. Staniscia (Tommaso); A. Vestri (Annarita); M. Di Bari (M.); G. Corrao (Giovanni); A. Zambon (A.); D Gregori (Dario); F. Carle (F.); M.C.J.M. Sturkenboom (Miriam); G. Mazzaglia (Giampiero); G. Trifirò (Gianluca)

2015-01-01

textabstractSummary: Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with

Mesenchymal stem cells encapsulated into biomimetic hydrogel scaffold gradually release CCL2 chemokine in situ preserving cytoarchitecture and promoting functional recovery in spinal cord injury.

Science.gov (United States)

Papa, S; Vismara, I; Mariani, A; Barilani, M; Rimondo, S; De Paola, M; Panini, N; Erba, E; Mauri, E; Rossi, F; Forloni, G; Lazzari, L; Veglianese, P

2018-04-03

Spinal cord injury (SCI) is an acute neurodegenerative disorder caused by traumatic damage of the spinal cord. The neuropathological evolution of the primary trauma involves multifactorial processes that exacerbate the pathology, worsening the neurodegeneration and limiting neuroregeneration. This complexity suggests that multi-therapeutic approaches, rather than any single treatment, might be more effective. Encouraging preclinical results indicate that stem cell-based treatments may improve the disease outcome due to their multi-therapeutic ability. Mesenchymal Stem Cells (MSCs) are currently considered one of the most promising approaches. Significant improvement in the behavioral outcome after MSC treatment sustained by hydrogel has been demonstrated. However, it is still not known how hydrogel contribute to the delivery of factors secreted from MSCs and what factors are released in situ. Among different mediators secreted by MSCs after seeding into hydrogel, we have found CCL2 chemokine, which could account for the neuroprotective mechanisms of these cells. CCL2 secreted from human MSCs is delivered efficaciously in the lesioned spinal cord acting not only on recruitment of macrophages, but driving also their conversion to an M2 neuroprotective phenotype. Surprisingly, human CCL2 delivered also plays a key role in preventing motor neuron degeneration in vitro and after spinal cord trauma in vivo, with a significant improvement of the motor performance of the rodent SCI models. Copyright © 2018 Elsevier B.V. All rights reserved.

Spinal cord motion. Influence of respiration and cardiac cycle

Energy Technology Data Exchange (ETDEWEB)

Winklhofer, S. [RWTH Aachen University Hospital (Germany). Dept. of Neuroradiology; University Hospital Zurich (Switzerland). Inst. of Diagnostic and Interventional Radiology; Schoth, F. [RWTH Aachen University Hospital (Germany). Dept. of Diagnostic Radiology; Stolzmann, P. [University Hospital Zurich (Switzerland). Inst. of Diagnostic and Interventional Radiology; Krings, T. [Toronto Western Hospital, ON (Canada). Div. of Neuroradiology; Mull, M.; Wiesmann, M. [RWTH Aachen University Hospital (Germany). Dept. of Neuroradiology; Stracke, C.P. [RWTH Aachen University Hospital (Germany). Dept. of Neuroradiology; Alfried-Krupp-Hospital, Essen (Germany). Dept. of Neuroradiology

2014-11-15

To assess physiological spinal cord motion during the cardiac cycle compared with the influence of respiration based on magnetic resonance imaging (MRI) measurements. Anterior-posterior spinal cord motion within the spinal canal was assessed in 16 healthy volunteers (median age, 25 years) by cardiac-triggered and cardiac-gated gradient echo pulse sequence MRI. Image acquisition was performed during breath-holding, normal breathing, and forced breathing. Normal spinal cord motion values were computed using descriptive statistics. Breathing-dependent differences were assessed using the Wilcoxon signed-rank test and compared with the cardiac-based cord motion. A normal value table was set up for the spinal cord motion of each vertebral cervico-thoracic-lumbar segment. Significant differences in cord motion were found between cardiac-based motion while breath-holding and the two breathing modalities (P < 0.01 each). Spinal cord motion was found to be highest during forced breathing, with a maximum in the lower cervical spinal segments (C5; mean, 2.1 mm ± 1.17). Image acquisition during breath-holding revealed the lowest motion. MRI permits the demonstration and evaluation of cardiac and respiration-dependent spinal cord motion within the spinal canal from the cervical to lumbar segments. Breathing conditions have a considerably greater impact than cardiac activity on spinal cord motion.