Cellular response to rare earth mixtures (La and Gd) as components of degradable Mg alloys for medical applications

Rare earth (RE) elements have been proposed to improve the corrosion resistance of degradable Mg alloys for medical applications. However, good biocompatibility of the elements released by Mg alloys during degradation is essential for their use in implants. Most studies are focused on material science and engineering aspects, but the effects of ions released at the biological interface are not frequently addressed. The aim of this study was to contribute to the knowledge of in vitro toxicological effects of two RE Mg-alloying elements, La and Gd, as individual ions and in mixtures with and without Mg ions. Different combinations (Mg + Gd, Mg + La, and Mg + Gd + La) were used to evaluate their possible synergistic effects on CHO-K1 cells. Two sets of experiments were designed to assess (1) the cyto-genotoxic effect of La and Gd ions by neutral red (NR) technique, Reduction of tetrazolium salt (MTT), Viability with Acridine Orange staining, Clonogenic test, and Comet assay; and, (2) the possible synergistic toxicological effect of La and Gd ions in mixtures, and the influence of osmolarity increase on cellular response. Cytotoxic effects of RE were found at concentrations ≥200 μM RE while DNA damage was detected for doses ≥1500 μM and ≥1600 μM for La and Gd, respectively. When mixtures of ions were evaluated, neither synergistic cytotoxic effects nor biological damage related to osmolarity increase were detected.Fil: Grillo, Claudia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Alvarez, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Fernandez Lorenzo, Monica Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. Universidad Nacional de La Plata. Facultad de Ingenieria; Argentin

Detection of carvacrol in essential oils by electrochemical polymerization

Carvacrol (Carv) and thymol (TOH), components of essential oils, are known by their antimicrobial and antioxidant activity. However, Carv but not TOH seems to be the responsible of anti-inflammatory and inhibition of Cu corrosion properties. Since Carv and TOH are positional isomers, their identification is tricky and GC-MS is usually required. To find simple and inexpensive methods that allow the detection of Carv in presence of TOH (e.g. essential oils), cyclic voltammetry and chronoamperometry tests using Pt and Cu as electrodes in TOH and Carv containing mixtures and essential oils were made. Electrochemical and ATR-FTIR results show that pure phytocompounds and mixtures lead to the formation of polymeric layers on both metallic surfaces. Results show that only Cu is suitable for Carv detection. Potentiostatic and potentiodynamic detection is simple and conclusive in Carv + TOH mixtures and in essential oils due to the formation of a homogeneous blocking Carv electropolymeric layer on Cu.Fil: Bertuola, Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Fagali, Natalia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Fernandez Lorenzo, Monica Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. Universidad Nacional de La Plata. Facultad de Ingeniería; Argentin

Nanofilms of adsorbed thymol formed on titanium surfaces for biomedical applications. Antimicrobial activity and biocompatibility

Titanium (Ti) and its alloys are widely used in the construction of permanent orthopedic and cardiovascular implants. However, one of the most frequent causes of failures are bacterial infections by Staphylococcus aureus. This is aggravated by the abusive use of antibiotics that generate microbial resistance to conventional therapies. As a consequence, new antimicrobial nanotechnologies (AMN) emerge as promising alternatives to prevent prosthetic infections. The aim of this work was to evaluate the antimicrobial effect of an innovative AMN: thymol (TOH, phenolic phytocompound) nanofilms adsorbed on Ti (NPTOH-Ti) against S. aureus. The biocompatibility was also determined using preosteoblast cells (MC3T3-E1). To that end, 1 cm diameter grade 2 Ti discs were used and TOH was adsorbed onto their surface by 2 h immersion in 0.1 M TOH acid solution. NPTOH-Ti was detected by infrared spectroscopy (FTIR-ATR). The antibiofilm activity of NPTOH-Ti and Ti (control) was determined by immersing the metal discs in a suspension of S. aureus (108 bacteria/ml) for 3 h. Subsequently, the number of bacteria adhered on the discs was caunted after sonication by colony forming unit (CFU). In addition, Live/Dead (Invitrogen) staining was used to determine if the adhered bacteria were alive or dead. Finally, biocompatibility of NPTOH-Ti and Ti was assessed by staining the preosteoblast cells with acridine orange. The results showed that NPTOH-Ti has effective anti-biofilm properties. On the one hand, viable bacteria were not observed by the plating count method and Live/Dead staining exhibited only dead (red) bacteria on the surface. On the other hand, control Ti revealed 4 ± 0.5 x105 adhered bacteria that were mostly (95 %) alive (green). In addition, NPTOH-Ti and Ti showed similar cell adhesion and growth (107 ± 12 and 100 ± 16 % respectively; p>0.05). It was concluded that NPTOH-Ti are biocompatible and have anti-biofilm properties which make them promising to prevent prosthetic infections.Fil: Gonzalez, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Miñan, Alejandro Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Grillo, Claudia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schilardi, Patricia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Fernandez Lorenzo, Monica Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaLXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioSociedad Argentina de ProtozoologíaThe Histochemical Societ

Efecto de las micropartículas de mg con y sin tratamiento con kf en células osteoblásticas y macrófagos

Los materiales biodegradables a base de Mg tienen importantes aplicaciones en medicina debido a su baja densidad y a sus propiedades mecánicas similares al hueso [1]. Entre sus productos de biodegradación in vivo se encuentran las micropartículas (pMg) que se liberan al medio y podrían afectar a las células vecinas. El objetivo del presente trabajo es estudiar el efecto de las pMg sobre las células próximas al biomaterial. Con ese propósito se realizaron estudios sobre el efecto citotóxico de las mismas sobre tres líneas celulares de mamífero, simulando la situación aledaña al implante. Los resultados mostraron una disminución de la viabilidad celular a partir de 1000 μg/ml de pMg, presentando mayor efecto a mayores concentraciones. También se observó una importante interacción de los macrófagos con las pMg. Además, las células expuestas durante una hora a pMg tratadas con KF mostraron efectos citotóxicos menores que las expuestas a pMg sin tratar.Mg-based materials are promising for medical applications due to their low density and mechanical properties close to those of human bone. Degradation products like Mg ions and debris particles may affect the surrounding cells. The aim of this work is to study the effect of pMg on cells in the vicinity of the biomaterial. For this purpose, studies on the cytotoxic effect on mammalian cell lines, simulating the in vivo situation close to the implant, were made. The results revealed a decrease in cell viability from 1000 µg/ml pMg, showing greater effect at higher concentrations. There was also a significant interaction of macrophages with pMg. Additionally, cells exposed for one hour to pMg treated with KF showed lower cytotoxic effects than those exposed to untreated particlesFil: Alvarez, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Lozano Puerto, Rosa. Consejo Superior de Investigaciones Cientificas; EspañaFil: Perez Maceda, Blanca. Consejo Superior de Investigaciones Cientificas; EspañaFil: Grillo, Claudia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Schilardi, Patricia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Fernandez Lorenzo, Monica Alicia. Universidad Nacional de la Plata. Facultad de Ingenieria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentin

Synergistic effect of carboxypterin and methylene blue applied to antimicrobial photodynamic therapy against mature biofilm of Klebsiella pneumoniae

The control of multidrug-resistant (MDR) bacteria is a growing public health problem, and new strategies are urgently needed for the control of the infections caused by these microorganisms. Notoriously, some MDR microorganisms generate complex structures or biofilms, which adhere to surfaces and confer extraordinary resistance properties that are fundamental challenges to control infections. One of the promising strategies for the control of MDR bacteria is antimicrobial photodynamic therapy (aPDT), which takes advantage of suitable photosensitizers (PS), oxygen and radiation to eradicate microorganisms by the generation of highly reactive species, including reactive oxygen species (ROS) that cause cytotoxic damage and cell death. Habitual aPDT treatments use only methylene blue (MB), but MDR microorganism eradication is not completely achieved. The key result of this study revealed that a combination of two known PSs, 6-carboxypterin (Cap, 100 μM) and MB (2.5–10 μM) exposed to ultraviolet and visible radiation, presents a synergistic effect on the eradication of a MDR Klebsiella pneumoniae strain. Similar effect was observed when the treatment was performed either with planktonic or biofilm growing cells. Moreover, it was found that after treatment the killing action continues in the absence of irradiation leading to the eradication of the microorganisms growing in biofilm. Therefore, the combined aPDT represents a promising strategy for the management of clinical contact surfaces, disinfection of surgical instruments, biofouling and even antimicrobial wastewater treatment.Fil: Gaspar Tosato, Maira. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Schilardi, Patricia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Fernandez Lorenzo, Monica Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Thomas, Andrés Héctor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Lorente, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Miñan, Alejandro Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentin

Comparative study of transdermal drug delivery systems of resveratrol: High efficiency of deformable liposomes

Trans-resveratrol (3, 5, 4′ trihydroxystilbene, RSV) is a natural compound that shows antioxidant, cardioprotective, anti-inflammatory and anticancer properties. The transdermal, painless application of RSV is an attractive option to other administration routes owing to its several advantages like avoiding gastrointestinalproblems and first pass metabolism. However, its therapeutic potential is limited by its low solubility and lowstability in water and the reduced permeability of stratum corneum. To overcome these inconveniences theencapsulation of this compound in a drug delivery system is proposed here. In order to find the best carrier fortransdermal application of RSV various liposomal nanoparticulate carriers like conventional liposomes (L-RSV),deformable liposomes (LD-RSV), ultradeformable liposomes (LUD-RSV) and ethosomes (Etho-RSV) were assayed. Transmission electron microscopic (TEM) and dynamic light scattering (DLS) studies were performed toanalyze the surface morphology of these carriers. Structural characterization for these formulations was performed by confocal Raman spectroscopy. The spectroscopic results were analysed in conjunction with calorimetric data to identify the conformational changes and stability of formulations in the different nanoparticlesinduced by the presence of RSV.Comparison of the results obtained with the different carrier systems (L-RSV, LD-RSV, LUD-RSV and EthoRSV) revealed that the best RSV carrier was LD-RSV. The increase in the fluidity of the bilayers in the region ofthe hydrophobic chains of the phospholipid by ethanol probably facilitates the accommodation of the RSV in thebilayer and contributes to the improved encapsulation of RSV without affecting the mobility of this carrier.Fil: Gaspar Tosato, Maira. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Maya Giron, Julie Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Abrahao Martin, Airton. Universidade Federal Do Piauí; BrasilFil: Krishna Tippavajhala, Vamshi. Manipal University; IndiaFil: Fernandez Lorenzo, Monica Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Dicelio, Lelia Elina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentin

Self-sterilizing ormosils surfaces based on photo-synzthesized silver nanoparticles

Medical device-related infections represent a major healthcare complication, resulting in potential risksfor the patient. Antimicrobial materials comprise an attractive strategy against bacterial colonizationand biofilm proliferation. However, in most cases these materials are only bacteriostatic or bactericidal,and consequently they must be used in combination with other antimicrobials in order to reach theeradication condition (no viable microorganisms). In this study, a straightforward and robust antibac-terial coating based on Phosphotungstate Ormosil doped with core-shell (SiO2@TiO2) was developedusing sol-gel process, chemical tempering, and Ag nanoparticle photoassisted synthesis (POrs-CS-Ag).The coating was characterized by X-ray Fluorescence Spectroscopy (XRF), Field Emission ScanningElectron Microscopy (FE-SEM), Atomic Force Microscopy (AFM) and X-ray Photoelectron Microscopy(XPS). The silver free coating displays low antibacterial activity against Staphylococcus aureus and Pseu-domonas aeruginosa, in opposition to the silver loaded ones, which are able to completely eradicate thesestrains. Moreover, the antimicrobial activity of these substrates remains high until three reutilizationcycles, which make them a promising strategy to develop self-sterilizing materials, such as POrs-CS-Ag-impregnated fabric, POrs-CS-Ag coated indwelling metals and polymers, among other materials.Fil: Gonçalves, Lidiane Patrícia. Universidade de Sao Paulo; BrasilFil: Miñan, Alejandro Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Benítez, Guillermo Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Fernandez Lorenzo, Monica Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Vela, Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Schilardi, Patricia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Ferreira Neto, Elias Paiva. Universidade de Sao Paulo; BrasilFil: Noveletto, Júlia Cristina. Universidade de Sao Paulo; BrasilFil: Correr, Wagner Rafael. Universidade de Sao Paulo; BrasilFil: Rodrigues Filho, Ubirajara Pereira. Universidade de Sao Paulo; Brasi

Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care : a pragmatic, randomised, non-inferiority clinical trial (OB12)

The trial was financed by Ministerio de Sanidad y Consumo Español through their call for independent clinical research, Orden Ministerial SAS/2377, 2010 (EC10-115, EC10-116, EC10-117, EC10-119, EC10-122); CAIBER—Spanish Clinical Research Network, Instituto de Salud Carlos III (ISCIII) (CAI08/010044); and Gerencia Asistencial de Atención Primaria de Madrid. This study is also supported by the Spanish Clinical Research Network (SCReN), funded by ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, project number PT13/0002/0007, within the National Research Program I+D+I 2013-2016 and co-funded with European Union ERDF funds (European Regional Development Fund). This project received a grant for the translation and publication of this article from the Foundation for Biomedical Research and Innovation in Primary Care (FIIBAP) Call 2017 for grants to promote research programs.Objectives To compare the effectiveness of oral versus intramuscular (IM) vitamin B12 (VB12) in patients aged ≥65 years with VB12 deficiency. Design Pragmatic, randomised, non-inferiority, multicentre trial in 22 primary healthcare centres in Madrid (Spain). Participants 283 patients ≥65 years with VB12 deficiency were randomly assigned to oral (n=140) or IM (n=143) treatment arm. Interventions The IM arm received 1 mg VB12 on alternate days in weeks 1–2, 1 mg/week in weeks 3–8 and 1 mg/month in weeks 9–52. The oral arm received 1 mg/day in weeks 1–8 and 1 mg/week in weeks 9–52. Main outcomes Serum VB12 concentration normalisation (≥211 pg/mL) at 8, 26 and 52 weeks. Non-inferiority would be declared if the difference between arms is 10% or less. Secondary outcomes included symptoms, adverse events, adherence to treatment, quality of life, patient preferences and satisfaction. Results The follow-up period (52 weeks) was completed by 229 patients (80.9%). At week 8, the percentage of patients in each arm who achieved normal B12 levels was well above 90%; the differences in this percentage between the oral and IM arm were −0.7% (133 out of 135 vs 129 out of 130; 95% CI: −3.2 to 1.8; p>0.999) by per-protocol (PPT) analysis and 4.8% (133 out of 140 vs 129 out of 143; 95% CI: −1.3 to 10.9; p=0.124) by intention-to-treat (ITT) analysis. At week 52, the percentage of patients who achieved normal B12 levels was 73.6% in the oral arm and 80.4% in the IM arm; these differences were −6.3% (103 out of 112 vs 115 out of 117; 95% CI: −11.9 to −0.1; p=0.025) and −6.8% (103 out of 140 vs 115 out of 143; 95% CI: −16.6 to 2.9; p=0.171), respectively. Factors affecting the success rate at week 52 were age, OR=0.95 (95% CI: 0.91 to 0.99) and having reached VB12 levels ≥281 pg/mL at week 8, OR=8.1 (95% CI: 2.4 to 27.3). Under a Bayesian framework, non-inferiority probabilities (Δ>−10%) at week 52 were 0.036 (PPT) and 0.060 (ITT). Quality of life and adverse effects were comparable across groups. 83.4% of patients preferred the oral route. Conclusions Oral administration was no less effective than IM administration at 8 weeks. Although differences were found between administration routes at week 52, the probability that the differences were below the non-inferiority threshold was very low.Publisher PDFPeer reviewe

Comparison of seven prognostic tools to identify low-risk pulmonary embolism in patients aged <50 years

publishersversionPeer reviewe

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio