636 research outputs found
Adalimumab efficacy in enteropathic spondyloarthritis: A 12-mo observational multidisciplinary study
AIM To report adalimumab (Ada) efficacy on articulargastrointestinal disease and health-related quality of life (HRQoL) in patients with enteropathic spondyloarthritis (ES). METHODS A cohort of 52 patients with ES was evaluated in the departments of gastroenterology and internal medicine. At baseline, all patients underwent assessment by an integrated gastro-rheumatologic evaluation of articular and gastrointestinal activity, as well patient reported outcomes (PROs) of the HRQoL questionnaires. After this integrated evaluation and following a specific working flowchart, the Ada anti-tumor necrosis factor (TNF)-inhibitor was assigned to a cohort of 30 patients and its clinical efficacy was evaluated at baseline and after 6-mo and 12-mo treatment by the following tests: (1) Ankylosing Spondylitis Disease Activity Score- C-Reactive Protein (ASDAS-CRP); Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) for articular activity; (2) Inflammatory Bowel Disease Questionnaire (IBDQ), Crohn's Disease Activity Index (CDAI) and partial Mayo (pMayo) score for gastrointestinal symptoms and activity; and (3) Health Assessment Questionnaire (HAQ), Patient Global Assessment (PGA) and Short Form-36 health survey (SF-36) questionnaires for PROs of the HRQoL. RESULTS Integrated evaluation and management of the patients affected by ES, carried out simultaneously by a gastroenterologist and a rheumatologist, allowed clinicians to choose the optimal therapeutic strategy. In a cohort of 30 ES patients affected by active articular and gastrointestinal disease, or axial active articular inflammation, Ada led to fast and sustained improvement of both articular and gastrointestinal disease activities. In fact, all the clinimetric evaluation tests exploring articular or gastrointestinal activity, as well as all the HRQoL scores, showed a significant improvement having been achieved at the earliest (6-mo) assessment. This important clinical improvement was maintained at the 12-mo follow-up. Importantly, global and gastrointestinal quality of life significantly correlated with articular disease activity, providing evidence to support that the integrated evaluation is the best option to manage patients with ES. CONCLUSION Ada treatment, upon multidisciplinary (gastrorheumatologic) evaluation, significantly improves both articular and gastrointestinal inflammation, thereby improving the HRQoL in patients affected by ES
Libri novi
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43270/1/11046_2005_Article_BF02089882.pd
Compaction of Rods: Relaxation and Ordering in Vibrated, Anisotropic Granular Material
We report on experiments to measure the temporal and spatial evolution of
packing arrangements of anisotropic, cylindrical granular material, using
high-resolution capacitive monitoring. In these experiments, the particle
configurations start from an initially disordered, low-packing-fraction state
and under vertical vibrations evolve to a dense, highly ordered, nematic state
in which the long particle axes align with the vertical tube walls. We find
that the orientational ordering process is reflected in a characteristic, steep
rise in the local packing fraction. At any given height inside the packing, the
ordering is initiated at the container walls and proceeds inward. We explore
the evolution of the local as well as the height-averaged packing fraction as a
function of vibration parameters and compare our results to relaxation
experiments conducted on spherically shaped granular materials.Comment: 9 pages incl. 7 figure
Shear-Modulus Investigations of Monohydroxy Alcohols: Evidence for a Short-Chain-Polymer Rheological Response
In addition to the ubiquitous structural relaxation of viscous supercooled
liquids, monohydroxy alcohols and several other hydrogen-bonded systems display
a strong single-exponential electrical low-frequency absorption. So far, this
so-called Debye process could be observed only using dielectric techniques.
Exploiting a combination of broad-band and high-resolution rheology experiments
for three isomeric octanols, unambiguous mechanical evidence for the Debye
process is found. Its spectral signature is similar to the viscoelastic
fingerprint of small-chain polymers, enabling us to estimate the effective
molecular weight for the supramolecular structure formed by the studied
monohydroxy alcohols. This finding opens the venue for the application of
further non-dielectric techniques directed at unraveling the microscopic nature
of the Debye process and for an understanding of this phenomenon in terms of
polymer concepts.Comment: 12 pages, 4 figure
Self-assembly in solution of a reversible comb-shaped supramolecular polymer
We report a single step synthesis of a polyisobutene with a bis-urea moiety
in the middle of the chain. In low polarity solvents, this polymer
self-assembles by hydrogen bonding to form a combshaped polymer with a central
hydrogen bonded backbone and polyisobutene arms. The comb backbone can be
reversibly broken, and consequently, its length can be tuned by changing the
solvent, the concentration or the temperature. Moreover, we have proved that
the bulkiness of the side-chains have a strong influence on both the
self-assembly pattern and the length of the backbone. Finally, the density of
arms can be reduced, by simply mixing with a low molar mass bis-urea
Random, blocky and alternating ordering in supramolecular polymers of chemically bidisperse monomers
As a first step to understanding the role of molecular or chemical
polydispersity in self-assembly, we put forward a coarse-grained model that
describes the spontaneous formation of quasi-linear polymers in solutions
containing two self-assembling species. Our theoretical framework is based on a
two-component self-assembled Ising model in which the bidispersity is
parameterized in terms of the strengths of the binding free energies that
depend on the monomer species involved in the pairing interaction. Depending
upon the relative values of the binding free energies involved, different
morphologies of assemblies that include both components are formed, exhibiting
paramagnetic-, ferromagnetic- or anti ferromagnetic-like order,i.e., random,
blocky or alternating ordering of the two components in the assemblies.
Analyzing the model for the case of ferromagnetic ordering, which is of most
practical interest, we find that the transition from conditions of minimal
assembly to those characterized by strong polymerization can be described by a
critical concentration that depends on the concentration ratio of the two
species. Interestingly, the distribution of monomers in the assemblies is
different from that in the original distribution, i.e., the ratio of the
concentrations of the two components put into the system. The monomers with a
smaller binding free energy are more abundant in short assemblies and monomers
with a larger binding affinity are more abundant in longer assemblies. Under
certain conditions the two components congregate into separate supramolecular
polymeric species and in that sense phase separate. We find strong deviations
from the expected growth law for supramolecular polymers even for modest
amounts of a second component, provided it is chemically sufficiently distinct
from the main one.Comment: Submitted to Macromolecules, 6 figures. arXiv admin note: substantial
text overlap with arXiv:1111.176
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Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab.
Cluster of differentiation 20 (CD20) is a B cell membrane protein that is targeted by monoclonal antibodies for the treatment of malignancies and autoimmune disorders but whose structure and function are unknown. Rituximab (RTX) has been in clinical use for two decades, but how it activates complement to kill B cells remains poorly understood. We obtained a structure of CD20 in complex with RTX, revealing CD20 as a compact double-barrel dimer bound by two RTX antigen-binding fragments (Fabs), each of which engages a composite epitope and an extensive homotypic Fab:Fab interface. Our data suggest that RTX cross-links CD20 into circular assemblies and lead to a structural model for complement recruitment. Our results further highlight the potential relevance of homotypic Fab:Fab interactions in targeting oligomeric cell-surface markers
Structural basis for HCMV Pentamer receptor recognition and antibody neutralization
Human cytomegalovirus (HCMV) represents the viral leading cause of congenital birth defects and uses the gH/
gL/UL128-130-131A complex (Pentamer) to enter different cell types, including epithelial and endothelial cells.
Upon infection, Pentamer elicits the most potent neutralizing response against HCMV, representing a key vaccine
candidate. Despite its relevance, the structural basis for Pentamer receptor recognition and antibody neutralization
is largely unknown. Here, we determine the structures of Pentamer bound to neuropilin 2 (NRP2) and a set of
potent neutralizing antibodies against HCMV. Moreover, we identify thrombomodulin (THBD) as a functional
HCMV receptor and determine the structures of the Pentamer-THBD complex. Unexpectedly, both NRP2 and
THBD also promote dimerization of Pentamer. Our results provide a framework for understanding HCMV receptor
engagement, cell entry, antibody neutralization, and outline strategies for antiviral therapies against HCMV
A strategy to obtain axenic cultures of Arthrospira spp. cyanobacteria
A strategy to obtain axenic cultures of the cyanobacterium Arthrospira sp. (âplatensisâ) Lefevre 1963/M-132-1 strain, consisting of a series of physical and chemical procedures, and the application of an optimized pool of antibiotics, is described in this paper. This strategy, which is an inexpensive and fast way to obtain axenic cultures, can be applied to Arthrospira spp. from culture collections or samples from their natural habitats to eliminate a wide spectrum of contaminants. A high alkaline treatment (pH 12, using KOH) of 72Â h is a determinant initial procedure applied to eliminate protozoa and Microcystis sp. Bacteria were eliminated by an optimal antibiotic pool treatment, and Chroococcus sp. residuals were discarded by serial dilution. Optimal concentrations of the antibiotics composing the pool were obtained by a 24 factorial central composite rotatable design (CCRD) and Response Surface Methodology (RSM), resulting in: ampicillin 61.6Â ÎŒg/ml, penicillin 85.8Â ÎŒg/ml, cefoxitin 76.9Â ÎŒg/ml, and meropenem 38.9Â ÎŒg/ml. The results also indicate that cefoxitin was the most effective antibiotic of this pool. After obtaining the axenic culture, identification of Lefevre 1963/M-132-1 strain was performed using amplification and sequencing of the ITS region (including part of 16S rRNA, tRNA Ile, ITS, tRNA Ala and part of 23S rRNA region) and fatty acid composition data. Data base comparison revealed that Lefevre strain is closely related to A. platensis species (99% identity), while fatty acid composition data suggested A. maxima. These seemingly contradictory results are discussed
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