Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Biological characterization of Trypanosoma cruzi zymodemes: In vitro differentiation of epimastigotes and infectivity of culture metacyclic trypomastigotes to mice

Thirty-one Trypanosoma cruzi isolates from Chile, Peru, and Bolivia were studied in their capacity to differentiate in vitro from epimastigotes to metacyclic trypomastigotes on TAU-3AAG medium. Zymodeme 1 parasites displayed the best level of differentiation, which ranges from 60 to 90% depending on the isolate. Zymodeme 2 parasites exhibited highly heterogeneous differentiation rates. This differentiation method permits the obtention of large amounts of metacyclic trypomastigotes from zymodeme 1 parasites. Metacyclic trypomastigotes obtained in vitro were infective to nude Balb/c hybrid mice. Zymodeme 1 parasites produced high parasitemias in this murine model; in contrast, zymodeme 2 parasites displayed lower parasitemias. Of a total of 27 T. cruzi isolates, 20 proved to be infective to mice, 12 gave enough parasites for further studies, and 8 of these were used for biological characterization. Results are compared with the infective clone Dm28 and Tulahuén strains maintained since

Electronic interactions in a new pi-extended tetrathiafulvalene dimer.

The first π-extended tetrathiafulvalene (exTTF) dimer in which the two exTTF units are covalently connected by 1,3-dithiole rings has been obtained in a multistep synthetic procedure involving the Ullmann cross-coupling reaction by using copper(i) thiophene-2-carboxylate (CuTC). The electronic spectrum reveals a significant electronic interaction between the exTTF units. The electrochemical study carried out by cyclic voltammetry in solution and in thin-layer conditions, and the electrochemical simulation and spectroelectrochemical (SEC) measurements confirm the electronic communication and show that the oxidation of dimer 14 occurs as two consecutive 2 e− processes D0–D0[RIGHTWARDS ARROW]D2+–D0[RIGHTWARDS ARROW]D2+–D2+. Theoretical calculations, performed at the B3P86/6-31G* level, confirm the experimental findings and predict that 142+ exists as a delocalized D.+–D.+ species in the gas phase and as a localized D2+–D0 species in solution (CH3CN or CH2Cl2). Oxidation of 142+ forms the tetracation 144+ which is constituted by two aromatic anthracene units bearing four aromatic, almost orthogonal 1,3-dithiolium cations

Enfermedad de Wegener diagnóstico y tratamiento

Granulomatosis with polyangiitis (GPA) or also known as Wegener's Granolomatosis, is a type of systemic vasculitis that affects small vessels, most commonly affecting the respiratory tract and kidneys. Diagnosis is based on clinical criteria, laboratory tests, images, and histology. Ninety percent are ANCA (anti-neutrophil cytoplasmic antibodies) positive. Histolo-gy demonstrates granulomatous inflammation, necrosis, and vasculitis, while imaging studies are vital for initial evaluation and follow-up. Thus, computed tomography (CT) is the method of choice for evaluating the upper airway and lungs, due to its high sensitivity to detect abnormalities of the paranasal sinuses, the bronchial tree, and the lungs. In addition to this, magnetic resonance imaging is indicated for the evaluation of the central nervous system and the heart, however, PET / CT positron emission tomography has high sensitivity for thoracic and abdominal diseases, it is useful to detect lesions that are not seen with other imaging techniques and for monitoring. Renal involvement, very common in GPA, is usually undetectable on imaging, but can be seen on PET / CT in cases of marked glomerulonephritis. However, plain radiographs should not be used to assess GPA due to their poor diagnostic performance. The patients are treated with corticosteroids and immunosuppressants and should be followed long-term, since relapses are generally frequent.Granulomatose com poliangiíte (GPA) ou também conhecida como Granolomatose de Wegener, é um tipo de vasculite sistêmica que afeta pequenos vasos, afetando mais comumente o trato respiratório e os rins. O diagnóstico é baseado em critérios clínicos, exames laboratoriais, imagens e histologia. Noventa por cento são ANCA (anticorpos citoplasmáticos anti-neutrófilos) positivos. A histologia demonstra inflamação granulomatosa, necrose e vasculite, enquanto os estudos de imagem são vitais para avaliação inicial e acompanhamento. Assim, a tomografia computadorizada (TC) é o método de escolha para avaliação das vias aéreas superiores e dos pulmões, devido à sua alta sensibilidade para detectar anormali-dades dos seios paranasais, árvore brônquica e pulmões. Além disso, a ressonância magnética é indicada para avaliação do sistema nervoso central e do coração, porém a tomografia por emissão de pósitrons PET / CT tem alta sensibilidade para doenças torácicas e abdominais, é útil para detectar lesões que não são observadas com outras técnicas de imagem e para monitoramento. O envolvimento renal, muito comum no GPA, geralmente é indetectável na imagem, mas pode ser observado na PET / TC em casos de glomerulonefrite acentuada. No entanto, radiografias simples não devem ser usadas para avaliar GPA devido ao seu baixo desempenho diagnóstico. Os pacientes são tratados com corticosteroides e imu-nossupressores e devem ser acompanhados por longo prazo, pois as recidivas geralmente são frequentes.La granulomatosis con poliangítis (GPA) o también conocida como Granolomatosis de Wegener, es un tipo de vasculitis sistémica que afecta los vasos pequeños, más comúnmente afectando el tracto respiratorio y los riñones. El diagnóstico se basa en criterios clínicos, pruebas de laboratorio, imágenes e histología. El noventa por ciento son ANCA (anticuerpos anticitoplasma de neutrofílico) positivos. La histología demuestra inflamación granulomatosa, necrosis y vasculitis, mientras que, los estudios de imágenes son vitales para la evaluación inicial y el seguimiento. De tal manera, la tomografía computarizada (TC) es el método de elección para la evaluación de la vía aérea superior y los pulmones, debido a su alta sensibilidad para detectar anomalías de los senos paranasales, el árbol bronquial y los pulmones. Aunado a ello, la resonancia magnética está indicada para la evaluación del sistema nervioso central y el corazón, sin embargo, la tomografía por emisión de positrones PET/TC tiene alta sensibilidad para enfermedades torácicas y abdominales, es útil para detectar lesiones que no se ven con otras técnicas de imagen y para el seguimiento. La afectación renal, muy frecuente en la GPA, suele ser indetectable en las imágenes, pero puede verse en la PET/TC en casos de glomerulonefritis marcada. No obstante, las radiografías simples no deben usarse para evaluar el GPA debido a su bajo rendimiento diagnóstico. Los pacientes son tratados con corticosteroides e inmunosupresores y deben llevar un seguimiento a largo plazo, ya que, generalmente las recaídas son frecuentes

Antibacterial activity of fresh pomegranate juice against clinical strains of Staphylococcus epidermidis

Background: Polyphenols have received a great deal of attention due to their biological functions. Pomegranate (Punica granatum L.) is a polyphenol-rich fruit. In the past decade, studies testing the antimicrobial activity of pomegranates almost exclusively used solvent extracts instead of fresh pomegranate juice (FPJ). The use of FPJ instead of solvent extracts would reduce toxicity issues while increasing patient acceptance. We established a model to test FPJ as a natural antimicrobial agent. Objective: To evaluate the antimicrobial activity of FPJ on clinical isolates of multidrug-resistant Staphylococcus epidermidis strains. Design: Sixty strains of S. epidermidis isolated from ocular infections were grown in the presence of FPJ, and minimum inhibitory concentration (MIC) was determined by broth and agar dilution methods. Results: FPJ at 20% had a MIC equal to 100% (MIC100%) on all 60 strains tested. This inhibition of FPJ was confirmed by the growth kinetics of a multidrug-resistant strain exposed to different concentrations of FPJ. Additionally, the antimicrobial activity of FPJ was compared against commercial beverages containing pomegranate: Ocean Spray® had a MIC100% at 20%, followed by Del Valle® with a MIC15% at 20% concentration only. The beverages Jumex® and Sonrisa® did not have any antimicrobial activity. FPJ had the highest polyphenol content and antioxidant capacity. Conclusions: Overall, FPJ had antimicrobial activity, which might be attributed to its high polyphenol content and antioxidant capacity

Energy deposit by electron excitation in C_nN⁺ projectiles (n=1-3) colliding at in termediate velocity with He atoms : semi-empirical estimates and calculations

International audienceSynopsis Using measured dissociation branching ratios and theoretical dissociation energies, we extracted semi-empirical estimates of the energy deposit due to electron excitation in CnN+-He collisions at v=2.2 a.u. We compared these estimates to calculations based on the IAE (Independent Atom and Electron) model where the atom(ion)-atom excitation is treated within the Classical Trajectory Monte Carlo (CTMC) approach. A good agreement has been found. This atomic approach is also able to reproduce the experimental Kinetic Energy Release (KER) in CN+ dissociation measured in 3.5 a.u CN+-He collision.</jats:p

Probing charge separation in structurally different C-60/exTTF ensembles

The scope of the present work is to highlight the effects stemming from different C-60/exTTF linkages (exTTF = 9,10-bis(1,3-dithiol-2-ylidene)-9,10-dihydroanthracene)-either via an anthracene unit or a dithiole ring. Particular emphasis is placed on photoinduced electron-transfer features. Therefore, we devised a new series Of C-60-exTTF ensembles, synthesized via 1,3-dipolar cycloaddition. and Diels-Alder cycloaddition reactions, in which exTTF units are separated from C-60 by two single bonds (3a-c, 4), one vinylene unit (5a), or two vinylene units (5b). The cyclic voltammetry reveals an amphoteric redox behavior with remarkably strong electron-donor ability of the trimethyl-substituted exTTF moiety in 4 and 5a,b. Steady-state and time-resolved photolytic techniques show that the fullerene singlet excited state in (3a-c, 4, and 5a,b) is subject to a rapid electron-transfer quenching. The resulting charge-separated states, that is C-60(.-)-exTTF(.+), were identified by transient absorption spectroscopy. We determined radical pair lifetimes of the order of 200 ns in benzonitrile. This suggests (i) that the positive charge of the exTTF(.+) is delocalized over the entire donor rather than localized on one of the 1,3-dithiole rings and (ii) that linking exTTF via the anthracene or 1,3-dithiole ring has no appreciable influence. Increasing the donor-acceptor separation via implementing one or two vinylene units as spacers led to improved radical pair lifetimes (5a: tau = 725 ns; 5b: tau = 1465 ns)