The Pd3(dppm)3(CO)n Clusters (n = 1-,2-); Rare Cases of Anionic Palladium Species

Dalton Transactions (Cambridge, England : 2003). Oct, 2010  |  Pubmed ID: 20820619

Two novel anionic palladium clusters, Pd(3)(dppm)(3)(CO)(n-) (Pd(3)(n); n = 1-,2-) were electrochemically generated from the dicationic cluster Pd(3)(2+) in 0.2 M THF/Bu(4)NPF(6)via two first consecutive reversible 1-electron reductions (Pd(3)(2+) + 1 e(-) ⇌ Pd(3)(+), -0.210, and Pd(3)(+) + 1 e(-) ⇌ Pd(3)(0), -0.470 V vs. SCE) followed by two others at -2.350 (Pd(3)(0) + 1 e(-) ⇌ Pd(3)(1-), reversible) and at -2.690 V vs. SCE (Pd(3)(1-) + 1 e(-) ⇌ Pd(3)(2-), irreversible). The chemical stability and instability, respectively, of the Pd(3)(dppm)(3)(CO)(n-) clusters (Pd(3)(n); n = 1-,2-) at the time scale of the electrochemical experiments were addressed by DFT computations. Indeed, geometry optimisations (B3LYP) indicate expected Pd-Pd, Pd-P, Pd-C bond length variations, but severe structure distortions are noted for the anions Pd(3)(1-) and Pd(3)(2-), including large deviations from the planarity of the Pd(3)P(6) core and for the triangular frame of the Pd(3) center. Space filling models indicate that this skeleton distortion places the phenyl-dppm groups above the unsaturated site of the M(3) frame hence protecting it from any interactions with substrates, and hence explaining the stability of the Pd(3)(1-) species. The computed gas phase total energy shows a decrease going from Pd(3)(2+) to Pd(3)(1+) to Pd(3)(0) and to Pd(3)(1-), but increases going to Pd(3)(2-) hence corroborating the relative stability of these species and the observed chemical reversibility of the CV waves. Large steps in energy stabilisation going from Pd(3)(2+) to Pd(3)(1+) to Pd(3)(0) is totally consistent with the low reduction potentials associated with these species, but the much smaller steps going from Pd(3)(0) to Pd(3)(1-) and to Pd(3)(2-) corroborates their much larger reduction potentials. The host-guest behaviour of Pd(3)(1-) and Pd(3)(2-) in the presence of the neutral substrate EtO(2)C-CC-CO(2)Et (L) and CF(3)CO(2)(-) (X(-)) was examined by CV. From the shifts of the reduction waves, it was possible to demonstrate that Pd(3)(2+) and Pd(3)(+) act as host for X(-) but not Pd(3)(0), Pd(3)(1-) and Pd(3)(2-), whereas Pd(3)(2+), Pd(3)(+), Pd(3)(0), bind L but Pd(3)(1-) and Pd(3)(2-) do not, corroborating evidence for stability but non-reactivity at the same time, particularly for the Pd(3)(1-) cluster. All in all, these anionic clusters exhibit the lowest oxidation state for palladium species ever investigated.

Effect of Aluminum on Cellular Division and Photosynthetic Electron Transport in Euglena Gracilis and Chlamydomonas Acidophila

Environmental Toxicology and Chemistry / SETAC. Apr, 2010  |  Pubmed ID: 20821518

The present study investigated aluminum's effect on cellular division and the photosynthetic processes in Euglena gracilis and Chlamydomonas acidophila at pH 3.0, at which Al is present mostly as Al(3+), AlSO(4) (+), and Al(SO(4))(2) (-). These algal species were exposed to 100, 188, and 740 microM Al, and after 24 h cell-bound Al was significantly different from control only for the highest concentration tested. However, very different effects of Al on algal cellular division, biomass per cell, and photosynthetic activity were found. Aluminum stimulated cell division but decreased at some level biomass per cell in C. acidophila. Primary photochemistry of photosynthesis, as Photosystem II quantum yield, and energy dissipation via nonphotochemical activity were slightly affected. However, for E. gracilis, under the same conditions, Al did not show a stimulating effect on cellular division or photosynthetic activity. Primary photochemical activity was diminished, and energy dissipation via nonphotochemical pathways was strongly increased. Therefore, when Al is highly available in aquatic ecosystems, these effects may indicate very different response mechanisms that are dependent on algal species.

Simplified Sample Preparation Procedure for Measuring Isotope-enriched Methylmercury by Gas Chromatography and Inductively Coupled Plasma Mass Spectrometry

Environmental Toxicology and Chemistry / SETAC. Jun, 2010  |  Pubmed ID: 20821567

Many procedures have been developed to measure the concentration of monomethylmercury (MeHg) from different sample matrices, and the use of stable isotopes of mercury now provides opportunities to determine its formation and degradation rates. Here, a modified procedure for measuring mercury isotopes in sediment samples that uses acid leaching-ion exchange-thiosulfate extraction (TSE) to isolate and purify the methylated mercury from the matrix is proposed. The latter is followed by aqueous-phase ethylation, purge and trap on Tenax, gas chromatography separation of ethylated mercury compounds, and inductively coupled plasma mass spectrometry detection. The new TSE procedure bridges together two well-known methods, the acid-leaching and distillation-derivatization procedures, offering the advantages of artifact-free formation of the first, and low detection limits and the possibility of quantification of individual isotopes of mercury of the second. The modified procedure retains the derivatization, purge and trap, and gas chromatography and inductively coupled plasma mass spectrometry (GC-ICP-MS) detection steps from the distillation-derivatization procedure, and eliminates the distillation step, which is not only laborious but also expensive, due to the high cost of installation and time-consuming cleaning process. Major advantages of the TSE procedure proposed include the extraction and analysis of a large number of samples in a short time, excellent analyte recoveries, and the lack of artifact formation. Sediment certified reference materials (CRMs), BCR 580 and IAEA 405, were used to test the TSE procedure accuracy. Recoveries between 94 to 106% and 95 to 96% were obtained for CRMs and spiked samples (Milli-Q(R) water), respectively. Comparisons among thiosulfate extraction, distillation, and acid-leaching procedures have shown good agreement of methylmercury values.

Vascular Smooth Muscle Contractility Assays for Inflammatory and Immunological Mediators

International Immunopharmacology. Nov, 2010  |  Pubmed ID: 20831918

The blood vessels are one of the important target tissues for the mediators of inflammation and allergy; further cytokines affect them in a number of ways. We review the use of the isolated blood vessel mounted in organ baths as an important source of pharmacological information. While its use in the bioassay of vasoactive substances tends to be replaced with modern analytical techniques, contractility assays are effective to evaluate novel synthetic drugs, generating robust potency and selectivity data about agonists, partial agonists and competitive or insurmountable antagonists. For instance, the human umbilical vein has been used extensively to characterize ligands of the bradykinin B(2) receptors. Isolated vascular segments are live tissues that are intensely reactive, notably with the regulated expression of gene products relevant for inflammation (e.g., the kinin B(1) receptor and inducible nitric oxide synthase). Further, isolated vessels can be adapted as assays of unconventional proteins (cytokines such as interleukin-1, proteases of physiopathological importance, complement-derived anaphylatoxins and recombinant hemoglobin) and to the gene knockout technology. The well known cross-talks between different cell types, e.g., endothelium-muscle and nerve terminal-muscle, can be extended (smooth muscle cell interaction with resident or infiltrating leukocytes and tumor cells). Drug metabolism and distribution problems can be modeled in a useful manner using the organ bath technology, which, for all these reasons, opens a window on an intermediate level of complexity relative to cellular and molecular pharmacology on one hand, and in vivo studies on the other.

Two Naturally Occurring Mutations in the Type 1 Melanin-concentrating Hormone Receptor Abolish Agonist-induced Signaling

The Journal of Pharmacology and Experimental Therapeutics. Dec, 2010  |  Pubmed ID: 20833795

The melanin-concentrating hormone (MCH) receptor type 1 (MCHR1) is a seven-transmembrane domain protein that modulates orexigenic activity of MCH, the corresponding endogenous peptide agonist. MCH antagonists are being explored as a potential treatment for obesity. In the current study, we examined the pharmacological impact of 11 naturally occurring mutations in the human MCHR1. Wild-type and mutant receptors were transiently expressed in human embryonic kidney 293 cells. MCHR1-mediated, Gα(i)-dependent signaling was monitored by using luciferase reporter gene assays. Two mutants, R210H and P377S, failed to respond to MCH. Five other variants showed significant alterations in MCH efficacy, ranging from 44 to 142% of the wild-type value. At each of the MCH-responsive mutants, agonist potency and inhibition by (S)-methyl 3-((3-(4-(3-acetamidophenyl)piperidin-1-yl)propyl)carbamoyl)-4-(3,4-difluorophenyl)-6-(methoxymethyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (SNAP-7941), an established MCHR1 small-molecule antagonist, were similar to wild type. To explore the basis for inactivity of the R210H and P377S mutants, we examined expression levels of these receptors. Assessment by enzyme-linked immunosorbent assay revealed that cell surface expression of both nonfunctional receptors was comparable with wild type. Overnight treatment with SNAP-7941, followed by washout of antagonist, enhanced MCH induced signaling by the wild-type receptor and restored MCH responsiveness of the P377S but not the R210H variant. It is of note that the two loss-of-function mutants were identified in markedly underweight individuals, raising the possibility that a lean phenotype may be linked to deficient MCHR1 signaling. Formal association studies with larger cohorts are needed to explore the extent to which signaling-deficient MCHR1 variants influence the maintenance of body weight.

Evaluation of Two Noninvasive Repositioning Systems for Computer-assisted Oral Implant Surgery in Oral Cancer Patients

The International Journal of Prosthodontics. Sep-Oct, 2010  |  Pubmed ID: 20859564

Reconstructive surgery in oral cancer patients uses thick flaps, which may render the placement of miniscrews for stabilizing radiosurgical templates difficult. The realization of noninvasive systems for the repositioning of surgical templates has been proposed. The present study aimed to assess the clinical usefulness of these noninvasive repositioning systems.

Tolerance to Agricultural Pesticides of Strains Belonging to Four Genera of Rhizobiaceae

Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes. Nov, 2010  |  Pubmed ID: 20936564

In order to determine their tolerance to pesticides, 122 strains of rhizobia isolated from different geographical regions, and belonging to the genera Rhizobium, Mesorhizobium, Sinorhizobium and Bradyrhizobium were tested against eight herbicides, four fungicides and five insecticides. Sensitivity to the pesticides was measured by using the filter paper disk method at four concentrations, 0.45, 4.5, 45 and 450 μg per disk. When the pesticides were used at 0.45 μg per disk, a concentration similar to that found when pesticides are applied under field conditions, no inhibition was observed. Strains growth was affected at concentrations of 45 and 450 μg pesticide per disk. These higher concentrations can be encountered when seeds are treated with pesticides. Pesticides tolerance level was correlated to pesticide function, i.e rhizobial strains were more tolerant to insecticides, followed by herbicides and then fungicides. Two fungicides, captan and mancozeb, inhibited the highest number of strains. Only one insecticide, carbaryl, affected the growth of some rhizobial strains. Strains isolated from the arctic (Mesorhizobium spp. and R. leguminosarum bv. viciae), a putative pesticides-free environment, were either less or equally affected by pesticides compared to strains isolated from agricultural regions.

Morchella Tomentosa: a Unique Belowground Structure and a New Clade of Morels

Mycologia. Sep-Oct, 2010  |  Pubmed ID: 20943507

Mechanisms involved in post-fire morel fructification remain unclear. A new undescribed belowground vegetative structure of Morchella tomentosa in a burned boreal forest was investigated north of Fairbanks, Alaska. The name "radiscisclerotium" is proposed to define this peculiar and elaborate below-ground vegetative structure of M. tomentosa. Bayesian and maximum parsimony analyses based on ITS rRNA regions and nLSU gene strongly supported a new clade composed of M. tomentosa within the genus Morchella.

ASK1-P38 Pathway is Important for Anoikis Induced by Microtubule-targeting Aryl Chloroethylureas

Journal of Pharmacy & Pharmaceutical Sciences : a Publication of the Canadian Society for Pharmaceutical Sciences, Société Canadienne Des Sciences Pharmaceutiques. 2010  |  Pubmed ID: 20816004

We investigated the involvement of MAPK signaling in the cell death mechanisms of classical microtubule interfering agents (MIA) and aryl-3-(2-chloroethyl)ureas (CEU) acting as antimitotics, along with CEU that don't affect directly microtubules (non-MIA CEU).

[Alzheimer's and Related Diseases: Toward Earlier and More Accurate Diagnosis]

La Revue De Médecine Interne / Fondée ... Par La Société Nationale Francaise De Médecine Interne. Dec, 2010  |  Pubmed ID: 20952104

Because of population ageing, the prevalence of Alzheimer's disease (AD), the most common cause of dementia, increases progressively. This condition is now considered as a public health priority. New disease modifying therapeutic strategies could be available in the next few years that would necessitate an accurate and early diagnosis of the disease. Recently developed diagnostic tools are being assessed. Development of structural brain imaging allows to measure the hippocampus volume. Metabolic imaging can assess a broad range of functional parameters such as cerebral blood flow and dopaminergic activity with single photon emission computed tomography, cerebral glucose metabolism and cerebral amyloid burden with positron emission tomography. Those imaging methods are under evaluation to appreciate cerebral abnormalities that may occur earlier than structural ones. Cerebrospinal fluid biomarkers, in particular amyloid and tau peptides, allow us to look at in vivo biochemical cerebral changes related to AD, before possible serum biomarkers. Studies are under way to confirm the relevance of these new diagnostic tools. It will help us to improve evaluation of patients with AD or related diseases.

Ethnocultural Community Leaders' Views and Perceptions on Biobanks and Population Specific Genomic Research: a Qualitative Research Study

Public Understanding of Science (Bristol, England). Jul, 2010  |  Pubmed ID: 20977184

Substantial investments were made in population based biobanks over the past decade. Ethnocultural community members are both sponsors and beneficiaries of biobanks. In addition, the success of biobank projects depends on community support and participation. Yet there are few empirical data on views, perceptions and interests of ethnocultural communities on biobanks. This silent gap in genomics, ethics and policy literatures has to be addressed. We conducted a qualitative research study with in-depth interviews of ethnocultural community leaders (e.g., members of the Canadian Parliament, school commissioners) on their perspectives concerning population specific genomics research and biobanks. An equal partnership model where public is not only informed, but also involved in decision-making processes was perceived as an essential democratic requisite. These empirical data on ethnocultural community leaders' views, interests and perceptions identify several key socio-cultural and ethical factors that can be decisive for effective and sustainable community involvement in biobanks.

Strong Donor-acceptor Couplings in a Special Pair-antenna Model

Chemical Communications (Cambridge, England). Dec, 2010  |  Pubmed ID: 21049124

A special pair model composed of two cofacial zinc porphyrins (acceptor) linked to a free base (donor) acts as an energy transfer dyad. Despite the absence of conjugation, ππ*/charge transfer excited states and ultrafast energy transfer (∼5 ps) are noted.

Nurses Joining Family Doctors in Primary Care Practices: Perceptions of Patients with Multimorbidity

BMC Family Practice. 2010  |  Pubmed ID: 21050443

Among the strategies used to reform primary care, the participation of nurses in primary care practices appears to offer a promising avenue to better meet the needs of vulnerable patients. The present study explores the perceptions and expectations of patients with multimorbidity regarding nurses' presence in primary care practices.

First Halogen Anion-bridged (MMX)(n)-type One-dimensional Coordination Polymer Built Upon D(10)-d(10) Dimers

Inorganic Chemistry. Dec, 2010  |  Pubmed ID: 21067213

The complex [Ag(2)(PhPPy(2))(2)(NCCH(3))(2)](ClO(4))(2) [PhPPy(2) = bis(2-pyridyl)phenylphosphine] reacts with NH(4)Cl to form an insoluble one-dimensional polymer of the type (MMX)(n), {[Ag(2)(PhPPy(2))(2)Cl](ClO(4))}(n). The binuclear unit, Ag(2)(PhPPy(2))(2)(2+), exhibits two PhPPy(2) tridentate ligands bridging the two Ag atoms in a head-to-tail fashion with C(2h) symmetry, and the Ag···Ag distance [3.0942(11) Å, X-ray] suggests argentophilic interactions. Each Ag center adopts a distorted trigonal-bipyramidal geometry, coordinated by one P atom and two pyridyl arms at the equatorial positions and interacting with one Cl ion and one Ag ion at the axial positions. The short Ag-Cl bond length [2.5791(7) Å] indicates the presence of some covalent character. The solid-state absorption bands spread all the way to 600 nm have been interpreted by means of density functional theory (DFT) and time-dependent DFT (B3LYP), and the lowest-energy excited states are assigned to metal/halide-to-pyridyl charge transfer, consistent with the d(10) electronic configuration of Ag. The calculated oscillator strengths are low because of the poor molecular orbital overlaps in the charge-transfer components. The novel material exhibits a luminescence band centered at about ∼520 nm.

Human Albumin for Intradialytic Hypotension in Haemodialysis Patients

Cochrane Database of Systematic Reviews (Online). 2010  |  Pubmed ID: 21069691

Intradialytic hypotension (IDH) occurs in 20% to 55% of haemodialysis sessions and is more frequent among patients on long-term haemodialysis. Symptomatic IDH is generally defined as a decrease in systolic blood pressure (BP) of at least 10 mm Hg or a systolic BP less than 100 mm Hg, with symptoms such as cramps, nausea, vomiting, and dizziness. IDH is managed acutely by volume expansion through the intravenous administration of fluids.

Chloroethyl Urea Derivatives Block Tumour Growth and Thioredoxin-1 Nuclear Translocation

Canadian Journal of Physiology and Pharmacology. Nov, 2010  |  Pubmed ID: 21076498

Aryl chloroethyl ureas (CEUs) are new protein alkylating agents exhibiting anticancer activity both in vitro and in vivo. We report herein that 14C-labeled CEU derivatives, designated CEU-025 and CEU-027, covalently bind to thioredoxin-1 (TRX1). Covalent binding of these molecules slightly decreases the disulfide-reducing activity of recombinant TRX1, when compared with the effect of strong thioalkylating agents such as N-ethylmaleimide. Moreover, site-directed mutagenesis and diamide competition assays demonstrated that TRX1 cysteinyl residues are not the prime targets of CEUs. CEU-025 abrogates the nuclear translocation of TRX1 in human cancer cells. In addition, we show that CEU-025 can block TRX1 nuclear translocation induced by cisplatin. Unexpectedly, pretreatment with sublethal CEU-025 concentrations that block TRX1 nuclear translocation protected the cells against cisplatin cytotoxicity. Overexpression of TRX1 in HT1080 fibrosarcoma cells attenuated CEU-025 cytotoxicity, while its suppression using TRX1-specific siRNA increased the effects of CEU-025, suggesting that loss of function of TRX1 is involved, at least in part, in the cytotoxic activity of CEU-025. These results suggest that CEU-025 and CEU-027 exhibit anticancer activity through a novel, unique mechanism of action. The importance of TRX1 and the dependence of the cytotoxicity of CEU-025 and CEU-027 on TRX1 intracellular localization are also discussed.

Genetic Factors Determining the Functional Organization of Neural Circuits Controlling Rhythmic Movements the Murine Embryonic Parafacial Rhythm Generator

Progress in Brain Research. 2010  |  Pubmed ID: 21111199

In mammals, fetal movements governed by central pattern generators are essential for the development of adaptive behaviors such as breathing, walking, and chewing, which are vital after birth. Combining targeted mutations and genetic fate mapping can help to define the molecular determinants that control the development of these central pattern generators. In this chapter, recent results are presented on the embryonic parafacial (e-pF) rhythm generator, one of the two oscillators involved in controlling the breathing behavior and chemosensitive responsiveness.

What Makes Primary Care Effective for People in Poverty Living with Multiple Chronic Conditions?: Study Protocol

BMC Health Services Research. 2010  |  Pubmed ID: 21118560

The inverse care law persists: people living in poverty have the greatest needs and face considerable challenges in getting the care they need. Evidence reveals that GPs encounter difficulties in delivering care to poor patients, while many of those patients feel stigmatized by healthcare professionals. Patients living in poverty report negative healthcare experiences and unmet healthcare needs. Indeed, there is a growing recognition in primary care research of the importance of addressing the capabilities and social conditions of the poor when delivering care. Few studies have looked at the factors contributing to effective and "socially responsive" care for people living in poverty.

How to Recognize and Diagnose Abusive Head Trauma in Infants

Annals of Physical and Rehabilitation Medicine. Dec, 2010  |  Pubmed ID: 21123129

Abusive head trauma (AHT) is complex to define for establishing proper diagnosis criteria. This observation complicates greatly the diagnosis process when faced with an infant in consultation.

What Are the Factors That Predict Outcome at Relapse After Previous Esophagectomy and Adjuvant Therapy in High-risk Esophageal Cancer?

Current Oncology (Toronto, Ont.). Nov, 2010  |  Pubmed ID: 21151409

The present study investigated factors affecting outcome at relapse after previous surgery and adjuvant chemoradiation (crt) in high-risk esophageal cancer patients.

Evaluation of a Preemptive Strategy for BK Polyomavirus-associated Nephropathy Based on Prospective Monitoring of BK Viremia: a Kidney Transplantation Center Experience

Transplantation Proceedings. Dec, 2010  |  Pubmed ID: 21168633

BK polyomavirus-associated nephropathy (BKPVAN) is a major cause of renal failure early after kidney transplantation. The present study reports the preliminary results of prospective monitoring including a preemptive strategy for BKPVAN during the first year after kidney transplantation.

Safety and Efficacy of Gamma Knife Surgery for Brain Metastases in Eloquent Locations

Journal of Neurosurgery. Dec, 2010  |  Pubmed ID: 21218534

Brain metastases are the most frequently occurring cerebral tumors. Tumors that are located in eloquent cerebral parenchyma can cause considerable morbidity and may pose a significant challenge during surgery. Gamma Knife surgery (GKS) is a recognized treatment modality for brain metastases. This study was undertaken to assess the safety and efficacy of GKS, specifically for brain metastases in eloquent locations.

Emergence of Skew Distributions in Controlled Growth Processes

Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics. Dec, 2010  |  Pubmed ID: 21230652

Starting from a master equation, we derive the evolution equation for the size distribution of elements in an evolving system, where each element can grow, divide into two, and produce new elements. We then probe general solutions of the evolution equation, to obtain such skew distributions as power-law, log-normal, and Weibull distributions, depending on the growth or division and production. Specifically, repeated production of elements of uniform size leads to power-law distributions, whereas production of elements with the size distributed according to the current distribution as well as no production of new elements results in log-normal distributions. Finally, division into two, or binary fission, bears Weibull distributions. Numerical simulations are also carried out, confirming the validity of the obtained solutions.

Search for New Particles in Two-jet Final States in 7 TeV Proton-proton Collisions with the ATLAS Detector at the LHC

Physical Review Letters. Oct, 2010  |  Pubmed ID: 21230962

A search for new heavy particles manifested as resonances in two-jet final states is presented. The data were produced in 7 TeV proton-proton collisions by the LHC and correspond to an integrated luminosity of 315  nb⁻¹ collected by the ATLAS detector. No resonances were observed. Upper limits were set on the product of cross section and signal acceptance for excited-quark (q*) production as a function of q* mass. These exclude at the 95% C.L. the q* mass interval 0.30

Observation of a Centrality-dependent Dijet Asymmetry in Lead-lead Collisions at Sqrt[S(NN)] =2.76 TeV with the ATLAS Detector at the LHC

Physical Review Letters. Dec, 2010  |  Pubmed ID: 21231581

By using the ATLAS detector, observations have been made of a centrality-dependent dijet asymmetry in the collisions of lead ions at the Large Hadron Collider. In a sample of lead-lead events with a per-nucleon center of mass energy of 2.76 TeV, selected with a minimum bias trigger, jets are reconstructed in fine-grained, longitudinally segmented electromagnetic and hadronic calorimeters. The transverse energies of dijets in opposite hemispheres are observed to become systematically more unbalanced with increasing event centrality leading to a large number of events which contain highly asymmetric dijets. This is the first observation of an enhancement of events with such large dijet asymmetries, not observed in proton-proton collisions, which may point to an interpretation in terms of strong jet energy loss in a hot, dense medium.

Emission Properties of Tb3+ Ions in LYSO: Evidence of a Cross Relaxation Mechanism Explained by a Kinetic Model

Journal of Physics. Condensed Matter : an Institute of Physics Journal. Sep, 2010  |  Pubmed ID: 21403256

The optical properties of Tb(3+) ions in oxyorthosilicates of lutetium and yttrium (LYSO) are reported. The introduction of a small number of terbium ions (nominal content 10 ppm) generates, in the otherwise transparent absorption spectrum of the matrix, an ultraviolet absorption band peaked at about 240 nm. By exciting within the reported UV band, line shaped emissions in the 350-600 nm range are detected. These transitions are related to the (5)D(3) and (5)D(4) levels of the Tb(3+) ions and are characterized by decay times in the millisecond time domain. Analysis of the decay time measurements allows us to individuate a cross relaxation mechanism among terbium ions even at the low dopant concentration investigated. We propose a three-level kinetic model which is able to successfully reproduce the experimental data, allowing us to discriminate among the radiative and non-radiative contributions to the observed emissions.

Comparison of the Mantel Test and Alternative Approaches for Detecting Complex Multivariate Relationships in the Spatial Analysis of Genetic Data

Molecular Ecology Resources. Sep, 2010  |  Pubmed ID: 21565094

The Mantel test is widely used to test the linear or monotonic independence of the elements in two distance matrices. It is one of the few appropriate tests when the hypothesis under study can only be formulated in terms of distances; this is often the case with genetic data. In particular, the Mantel test has been widely used to test for spatial relationship between genetic data and spatial layout of the sampling locations. We describe the domain of application of the Mantel test and derived forms. Formula development demonstrates that the sum-of-squares (SS) partitioned in Mantel tests and regression on distance matrices differs from the SS partitioned in linear correlation, regression and canonical analysis. Numerical simulations show that in tests of significance of the relationship between simple variables and multivariate data tables, the power of linear correlation, regression and canonical analysis is far greater than that of the Mantel test and derived forms, meaning that the former methods are much more likely than the latter to detect a relationship when one is present in the data. Examples of difference in power are given for the detection of spatial gradients. Furthermore, the Mantel test does not correctly estimate the proportion of the original data variation explained by spatial structures. The Mantel test should not be used as a general method for the investigation of linear relationships or spatial structures in univariate or multivariate data. Its use should be restricted to tests of hypotheses that can only be formulated in terms of distances.

Spectroscopic Characterization of Ti-doped α-ZnAl2S4 Spinel-type Single Crystals

Journal of Physics. Condensed Matter : an Institute of Physics Journal. Feb, 2010  |  Pubmed ID: 21386352

The spectroscopic characteristics of the α-ZnAl(2)S(4) wide bandgap semiconductor doped with Ti ions are investigated. It is shown, that the ZnAl(2)S(4):Ti spinel-type crystals exhibit luminescence in the IR spectral range 0.8-1.4 µm. The observed spectroscopic characteristics are assigned to the emission bands arising from the ligand -Ti(4+) charge transfer for octahedral sites of titanium that is in agreement with the experimental evidence for the absence of the EPR signal from Ti ions. A qualitative explanation of the experimental data is given.

Measuring Patients' Perceptions of Patient-centered Care: a Systematic Review of Tools for Family Medicine

Annals of Family Medicine. Mar-Apr, 2011  |  Pubmed ID: 21403143

Patient-centered care is widely acknowledged as a core value in family medicine. In this systematic review, we aimed to identify and compare instruments, subscales, or items assessing patients' perceptions of patient-centered care in family medicine.

Enhanced Luminescent Iridium(III) Complexes Bearing Aryltriazole Cyclometallated Ligands

Inorganic Chemistry. Nov, 2011  |  Pubmed ID: 21961698

Herein we report the synthesis of 4-aryl-1-benzyl-1H-1,2,3-triazoles (atl), made via "Click chemistry" and their incorporation as cyclometallating ligands into new heteroleptic iridium(III) complexes containing diimine (N(^)N) ancillary ligands 2,2'-bipyridine (bpy) and 4,4'-di-tert-butyl-2,2'-bipyridine (dtBubpy). Depending on decoration, these complexes emit from the yellow to sky blue in acetonitrile (ACN) solution at room temperature (RT). Their emission energies are slightly blue-shifted and their photoluminescent quantum efficiencies are markedly higher (between 25 and 80%) than analogous (C(^)N)(2)Ir(N(^)N)(+) type complexes, where C(^)N is a decorated 2-phenylpyridinato ligand. This increased brilliance is in part due to the presence of the benzyl groups, which act to sterically shield the iridium metal center. X-ray crystallographic analyses of two of the atl complexes corroborate this assertion. Their electrochemistry is reversible, thus making these complexes amenable for inclusion in light-emitting electrochemical cells (LEECs). A parallel computational investigation supports the experimental findings and demonstrates that for all complexes included in this study, the highest occupied molecular orbital (HOMO) is located on both the aryl fragment of the atl ligands and the iridium metal while the lowest unoccupied molecular orbital (LUMO) is located essentially exclusively on the ancillary ligand.

Discovery of Dual-action Membrane-anchored Modulators of Incretin Receptors

PloS One. 2011  |  Pubmed ID: 21935440

The glucose-dependent insulinotropic polypeptide (GIP) and the glucagon-like peptide-1 (GLP-1) receptors are considered complementary therapeutic targets for type 2 diabetes. Using recombinant membrane-tethered ligand (MTL) technology, the present study focused on defining optimized modulators of these receptors, as well as exploring how local anchoring influences soluble peptide function.

Two-dimensional Wavelet Analysis of Spruce Budworm Host Basal Area in the Border Lakes Landscape

Ecological Applications : a Publication of the Ecological Society of America. Sep, 2011  |  Pubmed ID: 21939054

Increases in the extent and severity of spruce budworm (Choristoneura fumiferana Clem.) outbreaks over the last century are thought to be the result of changes in forest structure due to forest management. A corollary of this hypothesis is that manipulations of forest structure and composition can be used to reduce future forest vulnerability. However, to what extent historical forest management has influenced current spatial patterns of spruce budworm host species is unknown. To identify landscape-scale spatial legacies of forest management in patterns of spruce budworm host species (i.e., Abies balsamea and Picea spp.), we analyzed remotely sensed forest data from the Border Lakes landscape of northern Minnesota and northwestern Ontario. Our study area contains three regions with different management histories: (1) fine-scale logging patterns in Minnesota, (2) coarse-scale logging patterns in Ontario, and (3) very limited logging history in the Boundary Waters Canoe Area and adjacent Quetico Provincial Park. We analyzed forest basal-area data using wavelets and null models to identify: (1) at which scales forest basal area is structured, (2) where those scales of pattern are significantly present, and (3) whether regions of local significance correspond to regional boundaries that separate the study area. Results indicate that spatial patterns in host basal area are created by nonstationary processes and that these processes are further constrained by lakes and wetlands. Wavelet analysis combined with significance testing revealed a bimodal distribution of scale-specific wavelet variance and separate zones of host species basal area that partially correspond with regional boundaries, particularly between Minnesota and the Wilderness region. This research represents one of the first comparisons of forest spatial structure in this region across an international border and presents a novel method of two-dimensional wavelet analysis that can be used to identify significant scale-specific structure in spatial data.

Practices and Plans for Knowledge Translation at NeuroDevNet

Seminars in Pediatric Neurology. Mar, 2011  |  Pubmed ID: 21575838

Knowledge translation at NeuroDevNet, a new Canadian Network of Centres of Excellence focused on brain development, is a core service that spans its 3 demonstration projects: research programs in cerebral palsy, autism spectrum disorder and fetal alcohol spectrum disorder, and integrated as a network-wide activity. This article describes the results of an environmental scan of NeuroDevNet members using a survey of their existing practices and needs completed by 30% of NeuroDevNet's members (n = 36/120) and key informant interviews with 14 members. Results suggest that most members are somewhat engaged in a number of knowledge translation activities although they tend to be traditional ones, such as attending conferences and giving presentations to other researchers. There is very little in the way of public engagement or consumer-focused activities. It also describes activities underway at the Cerebral Palsy Demonstration Project. This scan is helping members of NeuroDevNet's knowledge translation core plan and prioritize services and activities within NeuroDevNet.

Design, Synthesis, Biological Evaluation, and Structure-activity Relationships of Substituted Phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates As New Tubulin Inhibitors Mimicking Combretastatin A-4

Journal of Medicinal Chemistry. Jul, 2011  |  Pubmed ID: 21604746

Sixty-one phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates (PIB-SOs) and 13 of their tetrahydro-2-oxopyrimidin-1(2H)-yl analogues (PPB-SOs) were prepared and biologically evaluated. The antiproliferative activities of PIB-SOs on 16 cancer cell lines are in the nanomolar range and unaffected in cancer cells resistant to colchicine, paclitaxel, and vinblastine or overexpressing the P-glycoprotein. None of the PPB-SOs exhibit significant antiproliferative activity. PIB-SOs block the cell cycle progression in the G(2)/M phase and bind to the colchicine-binding site on β-tubulin leading to cytoskeleton disruption and cell death. Chick chorioallantoic membrane tumor assays show that compounds 36, 44, and 45 efficiently block angiogenesis and tumor growth at least at similar levels as combretastatin A-4 (CA-4) and exhibit low to very low toxicity on the chick embryos. PIB-SOs were subjected to CoMFA and CoMSIA analyses to establish quantitative structure-activity relationships.

Engineering Light-regulated Ion Channels

Cold Spring Harbor Protocols. Jun, 2011  |  Pubmed ID: 21632787

Measurement of Dijet Azimuthal Decorrelations in Pp Collisions at Sqrt(s)=7  TeV

Physical Review Letters. Apr, 2011  |  Pubmed ID: 21635030

Azimuthal decorrelations between the two central jets with the largest transverse momenta are sensitive to the dynamics of events with multiple jets. We present a measurement of the normalized differential cross section based on the full data set (∫Ldt=36  pb(-1)) acquired by the ATLAS detector during the 2010 sqrt(s)=7  TeV proton-proton run of the LHC. The measured distributions include jets with transverse momenta up to 1.3 TeV, probing perturbative QCD in a high-energy regime.

Modulating the Interference Effect in Timing with Varying Stimulus Onset Asynchrony

Canadian Journal of Experimental Psychology = Revue Canadienne De Psychologie Expérimentale. Sep, 2011  |  Pubmed ID: 21639613

The interference effect on time judgments, when subjects are also required to perform a concurrent nontemporal task, is one of the most reliable findings in the time perception literature. In the present study, the interference between a time discrimination task (short or long tone) and a digit classification task (even or odd digit) was analysed using the overlapping tasks paradigm. Reaction times in the digit task were shorter at longer values of stimulus onset asynchrony (SOA) in Experiment 1, showing a clear modulation of interference with varying the relative position of the tasks. Using longer tone durations in Experiment 2, reaction times in the digit task were affected not only by the overlap between the tasks but also by the temporal proximity of responses in the timing and digit tasks. In Experiment 3, the effect of varying the SOA on performance on the digit task was abolished when the auditory tone was irrelevant, thus eliminating an interpretation in terms of distraction from the tone offset. We conclude that the interference effect in concurrent time discrimination and digit classification may be modulated by the degree of overlap between the tasks as well as by the overlap between late processing stages related to decision and response components in the 2 tasks.

Detection of Low Pathogenic Avian Influenza Viruses in Wild Ducks from Canada: Comparison of Two Sampling Methods

Journal of Wildlife Diseases. Apr, 2011  |  Pubmed ID: 21441201

Surveillance for avian influenza viruses in wild birds was initiated in Canada in 2005. In 2006, in order to maximize detection of highly pathogenic avian influenza viruses, the sampling protocol used in Canada's Inter-agency Wild Bird Influenza Survey was changed. Instead of collecting a single cloacal swab, as previously done in 2005, cloacal and oropharyngeal swabs were combined in a single vial at collection. In order to compare the two sampling methods, duplicate samples were collected from 798 wild dabbling ducks (tribe Anatini) in Canada between 24 July and 7 September 2006. Low pathogenic avian influenza viruses were detected significantly more often (P<0.0001) in combined oropharyngeal and cloacal samples (261/798, 33%) than in cloacal swabs alone (205/798, 26%). Compared to traditional single cloacal samples, combined samples improved virus detection at minimal additional cost.

A Reaction-based Chromogenic and Fluorescent Chemodosimeter for Fluoride Anions

Chemical Communications (Cambridge, England). May, 2011  |  Pubmed ID: 21461422

An innovative trihexylsilylacetylene-containing BODIPY dye was designed and proved to be a highly selective, sensitive, and fast chromogenic and fluorescent chemodosimeter for fluorides.

A Class IA PI3K Controls Inflammatory Cytokine Production in Human Neutrophils

European Journal of Immunology. Jun, 2011  |  Pubmed ID: 21469098

Neutrophils are generally the first leukocytes to arrive at sites of inflammation or injury, where they release a variety of inflammatory mediators, which contribute to shaping the ensuing immune response. Here, we show that in neutrophils exposed to physiological stimuli (i.e. LPS and TNF-α), inhibition of the PI3K signaling pathway impairs the synthesis and secretion of IL-8, Mip-1α, and Mip-1β. Further investigation showed that Mip-1α and Mip-1β gene transcription was similarly decreased, whereas IL-8 transcription and steady-state mRNA levels were unaffected. Accordingly, PI3K inhibition had no impact on NF-κB or C/EBP activation, which are essential for IL-8 transcription, but the basis for this selective inhibition of chemokine transcription remains elusive. We nevertheless identified translational targets of the PI3K pathway (S6, S6 kinase, 4E-BP1). Inhibitor studies and overexpression experiments further established that the various effects of PI3K on chemokine production can be ascribed to p85α and p110δ subunits. Finally, we show that in LPS- and TNF-activated neutrophils, PI3K acts downstream of the kinases p38 MAPK and TAK1. Given the importance of neutrophils and their products in numerous chronic inflammatory disorders, the PI3K pathway could represent an attractive therapeutic target.

Panoramic Images Versus Three-Dimensional Planning Software for Oral Implant Planning in Atrophied Posterior Maxillary: A Clinical Radiological Study

Clinical Implant Dentistry and Related Research. Apr, 2011  |  Pubmed ID: 21477064

Purpose: The objectives of this radiographic study were to determine to what degree the available residual bone area for implant placement was underestimated on panoramic radiographs (by comparison with multislice computed tomography CT/cone beam CT images combined with planning software) and to what degree the rate of severely resorbed posterior maxillae requiring sinus lift was overestimated on panoramic radiographs (by comparison with planning software in combination with strategic implant placement). Materials and Methods: During a 2-year period, every patient who presented for the placement of implants in the posterior maxilla was examined by three practitioners to discuss the treatment plan. When two to three practitioners indicated a sinus lift with creation of a lateral window, a CT scan was performed and examined using dedicated three-dimensional software by a clinician familiar with the Computer Assisted Design/ Computer Assisted Manufacturing (CAD/CAM) implant placement protocol. For each tooth to be replaced, the presence of anatomical features such as anterior or posterior wall, palatal curvature, and septa were examined in view of the placement of an 8-mm or longer implant. Results: One hundred one patients were studied in this case series for the treatment of 135 edentulous spans accounting for 301 missing teeth. After examination of the CT data on the three-dimensional software, 202 teeth (67.1%) could be replaced using a CAD/CAM procedure; 60.7% of the edentulous spans could be completely repaired by a crown or bridge supported by implants. In addition, 67.3% of edentulism with no teeth posterior to the span could be completely repaired using a fixed prosthesis supported by implants. Conclusion: This radiological study demonstrates that the use of a panoramic exam for oral implant planning in severely resorbed maxillae overestimates the need for a sinus augmentation procedure when compared with the use of both three-dimensional planning software and strategic implant placement on small remaining bone volume.

Fraternal Twin Iridium Hemicage Chelates

Dalton Transactions (Cambridge, England : 2003). Nov, 2011  |  Pubmed ID: 21993539

The synthesis and complete photophysical characterization of rigidified neutral hemicage iridium complexes are presented. The hemicage ligands were obtained via a modular synthesis, which will facilitate the expansion of future hemicage syntheses. Slight variations in structure between the two iridium hemicage podates reveal subtle differences in photophysical behavior, which will aid in the design of functional materials. A parallel computational investigation corroborates the experimental findings. The insight gleaned from this study will have an impact for the design of iridium-based luminophores for OLED-type applications.

Narcotic Analgesic Utilization Amongst Injured Workers: Using Concept Mapping to Understand Current Issues from the Perspectives of Physicians and Pharmacists

BMC Health Services Research. 2011  |  Pubmed ID: 22014008

Work-related injuries result in considerable morbidity, as well as social and economic costs. Pain associated with these injuries is a complex, contested topic, and narcotic analgesics (NA) remain important treatment options. Factors contributing to NA utilization patterns are poorly understood. This qualitative study sought to characterize the factors contributing to NA utilization amongst injured workers from the perspectives of physicians and pharmacists.

Singlet and Triplet Energy Transfers in Tetra-(meso-truxene)zinc(II)- and Tetra-(meso-tritruxene)zinc(II) Porphyrin and Porphyrin-free Base Dendrimers

Inorganic Chemistry. Nov, 2011  |  Pubmed ID: 22017417

The synthesis, optical properties, and energy transfer features of four dendrimers composed of meso-tetrasubstituted zinc(II) porphyrin (ZnP) or a free base (P) central core, where the substituents are four truxene (Tru) or four tritruxene dendrons (TriTru), TruP, TriTruP, TruZnP, and TriTruZnP, are reported. Selective excitation of the truxene donors results in a photoinduced singlet energy transfer from the truxenes to the porphyrin acceptor. The rates for singlet energy transfer (k(ET)), evaluated from the change in the fluorescence lifetime of the donors (Tru and TriTru) in the presence and absence of the acceptor (P or ZnP) for TruP, TruZnP, TriTruP, and TriTruZnP, are 5.9, 1.2, 0.87, and 0.74 (ns)(-1) at 298 K and 2.6, 2.6, 2.7, and 1.2 (ns)(-1) at 77 K, respectively. A slow triplet-triplet energy transfer from truxene to porphyrin cores in glassy 2MeTHF at 77 K is also reported with rates of 1.3 × 10(3) and 0.10 × 10(2) s(-1) for TruZnP and TriTruZnP, respectively. If the Dexter mechanism for the triplet energy transfers is considered, these slow rates are easily explained by a poor orbital overlap between the truxene and porphyrin π systems. The fluorescence quantum yields (Φ(F)) are 0.20 and 0.16 for TruP and TriTruP and 0.08 and 0.10 for TruZnP and TriTruZnP, respectively at 298 K. At 298 K, a phosphorescence from TruZnP at 795 nm was also observed and is associated with the ZnP chromophore.

Pain Sensitivity and Vasopressin Analgesia Are Mediated by a Gene-sex-environment Interaction

Nature Neuroscience. Dec, 2011  |  Pubmed ID: 22019732

Quantitative trait locus mapping of chemical/inflammatory pain in the mouse identified the Avpr1a gene, which encodes the vasopressin-1A receptor (V1AR), as being responsible for strain-dependent pain sensitivity to formalin and capsaicin. A genetic association study in humans revealed the influence of a single nucleotide polymorphism (rs10877969) in AVPR1A on capsaicin pain levels, but only in male subjects reporting stress at the time of testing. The analgesic efficacy of the vasopressin analog desmopressin revealed a similar interaction between the drug and acute stress, as desmopressin inhibition of capsaicin pain was only observed in nonstressed subjects. Additional experiments in mice confirmed the male-specific interaction of V1AR and stress, leading to the conclusion that vasopressin activates endogenous analgesia mechanisms unless they have already been activated by stress. These findings represent, to the best of our knowledge, the first explicit demonstration of analgesic efficacy depending on the emotional state of the recipient, and illustrate the heuristic power of a bench-to-bedside-to-bench translational strategy.

Resveratrol Improves Survival, Hemodynamics and Energetics in a Rat Model of Hypertension Leading to Heart Failure

PloS One. 2011  |  Pubmed ID: 22028869

Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001), and prevented the 25% reduction in body weight in HS-NT (P<0.001). Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening -34% in HS-NT) as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF.

Who Should Travel in Kidney Exchange Programs: the Donor, or the Organ?

Open Medicine : a Peer-reviewed, Independent, Open-access Journal. 2011  |  Pubmed ID: 22046215

Fluoride Glass Raman Fiber Laser at 2185 Nm

Optics Letters. Nov, 2011  |  Pubmed ID: 22048348

We report on the first Raman laser based on a fluoride glass optical fiber. The Raman fiber laser was pumped by a 9.6 WTm3+:silica CW fiber laser operating at a wavelength of 1940 nm. A maximum output power of 580 mW was measured at 2185.1 nm, corresponding to a frequency shift of 579 cm(-1) (17.37 THz). We observed a threshold power of 3.8 W and a low power slope efficiency of 29% with respect to the launched pump power. Using those results and the known fiber parameters, we estimated a Raman gain peak value of 3.52*10(-14) m/W, which is lower than the previously reported values.

Assessment of Exposure to Plasmodium Falciparum Transmission in a Low Endemicity Area by Using Multiplex Fluorescent Microsphere-based Serological Assays

Parasites & Vectors. 2011  |  Pubmed ID: 22059951

The evaluation of malaria transmission intensity is a crucial indicator for estimating the burden of malarial disease. In this respect, entomological and parasitological methods present limitations, especially in low transmission areas. The present study used a sensitive multiplex assay to assess the exposure to Plasmodium falciparum infection in children living in an area of low endemicity. In three Senegalese villages, specific antibody (IgG) responses to 13 pre-erythrocytic P. falciparum peptides derived from Lsa1, Lsa3, Glurp, Salsa, Trap, Starp, Csp and Pf11.1 proteins were simultaneously evaluated before (June), at the peak (September) and after (December) the period of malaria transmission, in children aged from 1 to 8 years.

Head Injury Secondary to Suspected Child Maltreatment: Results of a Prospective Canadian National Surveillance Program

Child Abuse & Neglect. Nov, 2011  |  Pubmed ID: 22099143

We sought to determine the incidence, clinical features, and demographic profile of head injury secondary to suspected child maltreatment (abuse or neglect) in Canada to help inform the development and evaluation of prevention programs for abusive head injuries.

A Cocoon of Freshly Accelerated Cosmic Rays Detected by Fermi in the Cygnus Superbubble

Science (New York, N.Y.). Nov, 2011  |  Pubmed ID: 22116880

The origin of Galactic cosmic rays is a century-long puzzle. Indirect evidence points to their acceleration by supernova shockwaves, but we know little of their escape from the shock and their evolution through the turbulent medium surrounding massive stars. Gamma rays can probe their spreading through the ambient gas and radiation fields. The Fermi Large Area Telescope (LAT) has observed the star-forming region of Cygnus X. The 1- to 100-gigaelectronvolt images reveal a 50-parsec-wide cocoon of freshly accelerated cosmic rays that flood the cavities carved by the stellar winds and ionization fronts from young stellar clusters. It provides an example to study the youth of cosmic rays in a superbubble environment before they merge into the older Galactic population.

A Public Hearing. "Shaken Baby Syndrome: Guidelines on Establishing a Robust Diagnosis and the Procedures to Be Adopted by Healthcare and Social Services Staff". Scoping Report

Annals of Physical and Rehabilitation Medicine. Dec, 2011  |  Pubmed ID: 22118913

A Public Hearing "Shaken Baby Syndrome: Guidelines on Establishing a Robust Diagnosis and the Procedures to Be Adopted by Healthcare and Social Services Staff". Guidelines Issued by the Hearing Commission

Annals of Physical and Rehabilitation Medicine. Dec, 2011  |  Pubmed ID: 22118914

Peripheral Neuropathy in Patients with Systemic Lupus Erythematosus

Seminars in Arthritis and Rheumatism. Oct, 2011  |  Pubmed ID: 21641018

In patients with systemic lupus erythematosus (SLE), to determine 1) the prevalence and clinical features of peripheral neuropathies (PN) and whether they were SLE related, 2) whether there are associations between other SLE features and PN.

Novel Inactivating Mutations in the GH Secretagogue Receptor Gene in Patients with Constitutional Delay of Growth and Puberty

European Journal of Endocrinology / European Federation of Endocrine Societies. Aug, 2011  |  Pubmed ID: 21646290

A limited number of mutations in the GH secretagogue receptor gene (GHSR) have been described in patients with short stature. Objective To analyze GHSR in idiopathic short stature (ISS) children including a subgroup of constitutional delay of growth and puberty (CDGP) patients.

Risk Factors for Hospitalization and Severe Outcomes of 2009 Pandemic H1N1 Influenza in Quebec, Canada

Influenza and Other Respiratory Viruses. Jul, 2011  |  Pubmed ID: 21651735

BACKGROUND/ OBJECTIVE: This case-control study was carried out to estimate risk factors associated with hospitalizations and severe outcomes [intensive care unit (ICU) admission or death] among patients with illness because of laboratory-confirmed 2009 pandemic A/H1N1 virus (pH1N1) during the first wave of pH1N1 activity in the province of Quebec, Canada. PATIENTS/ METHODS: We collected epidemiologic information by phone using a standardized questionnaire from patients with laboratory-confirmed pH1N1 illness during the first spring/summer pandemic wave in Quebec, Canada. Risk factors associated with hospitalization were assessed by comparing hospitalized to community cases and for ICU admission or death through comparison with hospitalized cases. RESULTS: Cases (321 hospitalized patients including 47 ICU admissions and 15 deaths) were compared to controls (395 non-hospitalized patients) by using multivariable logistic regression adjusted for gender, age, education, being a health care worker, smoking, seasonal influenza vaccination, delay to consultation, antiviral use before admission, pregnancy, underlying medical conditions, and obesity. Age <5 years, underlying medical conditions (neuromuscular, cardiac, pulmonary, and renal conditions, diabetes, asthma, and other), and delayed consultation were associated with hospitalization. The strongest association with hospitalization was observed for neuromuscular disorders. Antiviral medication before hospital admission protected against severe disease. Association of obesity with hospitalization was not significant after adjustment in multivariable analysis. Among hospitalized patients, age ≥60 years and immune suppression were associated with death. CONCLUSIONS: Previously identified risk factors for seasonal influenza were also associated with increased risk of severe pH1N1 outcomes. The independent role of obesity needs to be further defined.

Connectivity for Conservation: a Framework to Classify Network Measures

Ecology. Apr, 2011  |  Pubmed ID: 21661548

Graph theory, network theory, and circuit theory are increasingly being used to quantify multiple aspects of habitat connectivity and protected areas. There has been an explosive proliferation of network (connectivity) measures, resulting in over 60 measures for ecologists to now choose from. Conceptual clarification on the ecological meaning of these network measures and their interrelationships is overdue. We present a framework that categorizes network measures based on the connectivity property that they quantify (i.e., route-specific flux, route redundancy, route vulnerability, and connected habitat area) and the structural level of the habitat network to which they apply. The framework reveals a lack of network measures in the categories of "route-specific flux among neighboring habitat patches" and "route redundancy at the level of network components." We propose that network motif and path redundancy measures can be developed to fill the gaps in these categories. The value of this framework lies in its ability to inform the selection and application of network measures. Ultimately, it will allow a better comparison among graph, network, and circuit analyses, which will improve the design and management of connected landscapes.

Structural Modulation of Dendritic Spines During Synaptic Plasticity

The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry. Jun, 2011  |  Pubmed ID: 21670426

The majority of excitatory synaptic input in the brain is received by small bulbous actin-rich protrusions residing on the dendrites of glutamatergic neurons. These dendritic spines are the major sites of information processing in the brain. This conclusion is reinforced by the observation that many higher cognitive disorders, such as mental retardation, Rett syndrome, and autism, are associated with aberrant spine morphology. Mechanisms that regulate the maturation and plasticity of dendritic spines are therefore fundamental to understanding higher brain functions including learning and memory. It is well known that activity-driven changes in synaptic efficacy modulate spine morphology due to alterations in the underlying actin cytoskeleton. Recent studies have elucidated numerous molecular regulators that directly alter actin dynamics within dendritic spines. This review will emphasize activity-dependent changes in spine morphology and highlight likely roles of these actin-binding proteins.

Exercise Training Reverses Adiponectin Resistance in Skeletal Muscle of Patients with Chronic Heart Failure

Heart (British Cardiac Society). Sep, 2011  |  Pubmed ID: 21685184

Resistance to the insulin-sensitising adipocytokine, adiponectin, has been described at the level of the skeletal muscle in patients with chronic heart failure (CHF).

Peripheral and Central GLP-1 Receptor Populations Mediate the Anorectic Effects of Peripherally Administered GLP-1 Receptor Agonists, Liraglutide and Exendin-4

Endocrinology. Aug, 2011  |  Pubmed ID: 21693680

The long-acting glucagon-like peptide-1 receptor (GLP-1R) agonists, exendin-4 and liraglutide, suppress food intake and body weight. The mediating site(s) of action for the anorectic effects produced by peripheral administration of these GLP-1R agonists are not known. Experiments addressed whether food intake suppression after i.p. delivery of exendin-4 and liraglutide is mediated exclusively by peripheral GLP-1R or also involves direct central nervous system (CNS) GLP-1R activation. Results showed that CNS delivery [third intracerebroventricular (3(rd) ICV)] of the GLP-1R antagonist exendin-(9-39) (100 μg), attenuated the intake suppression by i.p. liraglutide (10 μg) and exendin-4 (3 μg), particularly at 6 h and 24 h. Control experiments show that these findings appear to be based neither on the GLP-1R antagonist acting as a nonspecific competing orexigenic signal nor on blockade of peripheral GLP-1R via efflux of exendin-(9-39) to the periphery. To assess the contribution of GLP-1R expressed on subdiaphragmatic vagal afferents to the anorectic effects of liraglutide and exendin-4, food intake was compared in rats with complete subdiaphragmatic vagal deafferentation and surgical controls after i.p. delivery of the agonists. Both liraglutide and exendin-4 suppressed food intake at 3 h, 6 h, and 24 h for controls; for subdiaphragmatic vagal deafferentation rats higher doses of the GLP-1R agonists were needed for significant food intake suppression, which was observed at 6 h and 24 h after liraglutide and at 24 h after exendin-4. Conclusion: Food intake suppression after peripheral administration of exendin-4 and liraglutide is mediated by activation of GLP-1R expressed on vagal afferents as well as direct CNS GLP-1R activation.

Impact of Agglomeration on the Relaxometric Properties of Paramagnetic Ultra-small Gadolinium Oxide Nanoparticles

Nanotechnology. Jul, 2011  |  Pubmed ID: 21693804

Ultra-small gadolinium oxide nanoparticles (US-Gd(2)O(3)) are used to provide 'positive' contrast effects in magnetic resonance imaging (MRI), and are being considered for molecular and cellular imaging applications. However, these nanoparticles can aggregate over time in aqueous medium, as well as when internalized into cells. This study is aimed at measuring in vitro, in aqueous medium, the impact of aggregation on the relaxometric properties of paramagnetic US-Gd(2)O(3) particles. First, the nanoparticle core size as well as aggregation behaviour was assessed by HRTEM. DLS (hydrodynamic diameter) was used to measure the hydrodynamic diameter of nanoparticles and nanoaggregates. The relaxometric properties were measured by NMRD profiling, as well as with (1)H NMR relaxometers. Then, the positive contrast enhancement effect was assessed by using magnetic resonance scanners (at 1.5 and 7 T). At every magnetic field, the longitudinal relaxivity (r(1)) decreased upon agglomeration, while remaining high enough to provide positive contrast. On the other hand, the transverse relaxivity (r(2)) slightly decreased at 0.47 and 1.41 T, but it was enhanced at higher fields (7 and 11.7 T) upon agglomeration. All NMRD profiles revealed a characteristic relaxivity peak in the range 60-100 MHz, suggesting the possibility to use US-Gd(2)O(3) as an efficient 'positive-T(1)' contrast agent at clinical magnetic fields (1-3 T), in spite of aggregation.

ACTs for the Treatment of Schistosomiasis

The Lancet Infectious Diseases. Jul, 2011  |  Pubmed ID: 21700239

[The FAQ Self-report is a Valid Instrument to Characterize Endophenotypes of the Autistic Spectrum in Parents of Children with Autism]

L'Encéphale. Jun, 2011  |  Pubmed ID: 21703434

We have previously developed the FAQ self-report, an adaptation of the Baron-Cohen's Autism Quotient self-report, in order to detect traits of the autistic spectrum in the parents and siblings of children with autism. We have previously shown that parents of children with autism show significant differences in their global scores and in their social functioning scores according to their answers to the FAQ self-report.

Current Concepts in the Management of Esophageal Perforations: a Twenty-seven Year Canadian Experience

The Annals of Thoracic Surgery. Jul, 2011  |  Pubmed ID: 21718846

Perforation of the esophagus remains a challenging clinical problem.

The Patient Enablement Instrument-French Version in a Family Practice Setting: a Reliability Study

BMC Family Practice. 2011  |  Pubmed ID: 21736729

Patient enablement can be defined as the extent to which a patient is capable of understanding and coping with his or her health issues. This concept is linked to a number of health outcomes such as self-management of chronic diseases and quality of life. The Patient Enablement Instrument (PEI) was designed to measure this concept after a medical consultation. The instrument, in its original form and its translations into several languages, has proven to be reliable and valid. The purpose of this study was to evaluate the reliability of the French version of the PEI (PEI-Fv) in a family practice setting.

Aerial Measurement of Radioxenon Concentration off the West Coast of Vancouver Island Following the Fukushima Reactor Accident

Journal of Environmental Radioactivity. Nov, 2011  |  Pubmed ID: 21745702

In response to the Fukushima nuclear reactor accident, on March 20th, 2011, Natural Resources Canada conducted aerial radiation surveys over water just off the west coast of Vancouver Island. Dose-rate levels were found to be consistent with background radiation, however a clear signal due to (133)Xe was observed. Methods to extract (133)Xe count rates from the measured spectra, and to determine the corresponding (133)Xe activity concentration, were developed. The measurements indicate that (133)Xe concentrations on average lie in the range of 30-70 Bq/m(3).

Canadian Guidelines for Clinical Practice: an Analysis of Their Quality and Relevance to the Care of Adults with Comorbidity

BMC Family Practice. 2011  |  Pubmed ID: 21752267

Clinical guidelines have been the subject of much criticism in primary care literature partly due to potential conflicts in their implementation among patients with multiple chronic conditions. We assessed the relevance of selected Canadian clinical guidelines on chronic diseases for patients with comorbidity and examined their quality.

Search for a Heavy Particle Decaying into an Electron and a Muon with the ATLAS Detector in Sqrt[s] = 7 TeV Pp Collisions at the LHC

Physical Review Letters. Jun, 2011  |  Pubmed ID: 21770629

This Letter presents the first search for a heavy particle decaying into an e ± μ(-/+) final state in sqrt[s] = 7 TeV pp collisions at the LHC. The data were recorded by the ATLAS detector during 2010 and correspond to a total integrated luminosity of 35 pb(-1). No excess above the standard model background expectation is observed. Exclusions at 95% confidence level are placed on two representative models. In an R-parity violating supersymmetric model, tau sneutrinos with a mass below 0.75 TeV are excluded, assuming all R-parity violating couplings are zero except λ(311)' = 0.11 and λ312 = 0.07. In a lepton flavor violating model, a Z'-like vector boson with masses of 0.70-1.00 TeV and corresponding cross sections times branching ratios of 0.175-0.183 pb is excluded. These results extend to higher mass R-parity violating sneutrinos and lepton flavor violating Z's than previous constraints from the Tevatron.

Prevalence of Anaerobic Ammonium-oxidizing Bacteria in Contaminated Groundwater

Environmental Science & Technology. Sep, 2011  |  Pubmed ID: 21786759

Anaerobic ammonium-oxidizing (anammox) bacteria perform an important step in the global nitrogen cycle: anaerobic oxidation of ammonium and reduction of nitrite to form dinitrogen gas (N(2)). Anammox organisms appear to be widely distributed in natural and artificial environments. However, their roles in groundwater ammonium attenuation remain unclear and only limited biomarker-based data confirmed their presence prior to this study. We used complementary molecular and isotope-based methods to assess anammox diversity and activity occurring at three ammonium-contaminated groundwater sites: quantitative PCR, denaturing gradient gel electrophoresis, sequencing of 16S rRNA genes, and (15)N-tracer incubations. Here we show that anammox performing organisms were abundant bacterial community members. Although all sites were dominated by Candidatus Brocadia-like sequences, the community at one site was particularly diverse, possessing four of five known genera of anammox bacteria. Isotope data showed that anammox produced up to 18 and 36% of N(2) at these sites. By combining molecular and isotopic results we have demonstrated the diversity, abundance, and activity of these autotrophic bacteria. Our results provide strong evidence for their important biogeochemical role in attenuating groundwater ammonium contamination.

Impact of a Multipronged Education Strategy on Antibiotic Prescribing in Quebec, Canada

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Sep, 2011  |  Pubmed ID: 21791439

Antibiotic overuse and resistance have become a major threat in the last 2 decades. Many programs tried to optimize antibiotic consumption in the inpatient setting, but the outpatient environment that represents the bulk of antibiotic use has been challenging. Following a significant rise of Clostridium difficile infections, all the health care stakeholders in the province of Quebec, Canada initiated a global education program targeting physicians and pharmacists.

Towards a Functional Organization of Episodic Memory in the Medial Temporal Lobe

Neuroscience and Biobehavioral Reviews. Jul, 2011  |  Pubmed ID: 21810443

Here we describe a model of medial temporal lobe organization in which parallel "what" and "where" processing streams converge within the hippocampus to represent events in the spatio-temporal context in which they occurred; this circuitry also mediates the retrieval of context from event cues and vice versa, which are prototypes of episodic recall. Evidence from studies in animals are reviewed in support of this model, including experiments that distinguish characteristics of episodic recollection from familiarity, neuropsychological and recording studies that have identified a key role for the hippocampus in recollection and in associating events with the context in which they occurred, and distinct roles for parahippocampal region areas in separate "what" and "where" information processing that contributes to recollective and episodic memory.

19,20-EpDPE, a Bioactive CYP450 Metabolite of DHA Monoacyglyceride, Decreases Ca²⁺ Sensitivity in Human Pulmonary Arteries

American Journal of Physiology. Heart and Circulatory Physiology. Oct, 2011  |  Pubmed ID: 21821782

The aim of this study was to investigate the effect of docosahexaenoic acid monoacylglyceride (MAG-DHA) on human pulmonary arterial tone. Tension measurements on pulmonary arterial tissues demonstrated that MAG-DHA reduced U-46619-induced tone, which is highly sensitive to the H-1152 inhibitor. Results also showed that MAG-DHA treatments decreased RhoA activity levels, which in turn inactivated the Rho-kinase pathway, leading to a reduction in U-46619-induced Ca(2+) sensitivity of permeabilized pulmonary artery smooth muscle cells. According to the mechanical responses assessing U-46619-induced Ca(2+) sensitivity in the absence or presence of 3 μM MAG-DHA, MAG-DHA plus 1 μM N-methylsulfonyl-6-(2-propargyloxyphenyl) hexanamide (MS-PPOH, a cytochrome P-450 epoxygenase inhibitor) and 300 nM 19,20-epoxydocosapentaenoic acid (a cytochrome P-450 epoxygenase-dependent DHA metabolite), our data suggest that the MAG-DHA is metabolized in a bioactive epoxymetabolite. This epoxyeicosanoid in turn decreases active tone and Ca(2+) sensitivity of smooth muscles cells through an inhibition of the Rho-kinase pathway. Together, these data provide primary evidence regarding the mode of action of MAG-DHA in human pulmonary arteries and suggest that this compound may be of pharmacological interest in patients with pulmonary hypertension to generate intracellular bioactive metabolites.

Mechanisms of Functional Connectivity: the Case of Free-ranging Bison in a Forest Landscape

Ecological Applications : a Publication of the Ecological Society of America. Jul, 2011  |  Pubmed ID: 21830725

Functional connectivity is a key determinant of animal distributions in heterogeneous landscapes. Patch connectivity depends on both patch preference and accessibility, but few studies have integrated habitat selection and movement analyses to gain a general understanding of functional connectivity. In this paper, we define functional connectivity by identifying which factors influence the choice of the patch that is visited next, the location from which animals leave the current patch, and the inter-patch trajectory. Our study provides tools to anticipate movement trajectories and, therefore, animal distribution in patchy landscapes. We followed 23 radio-collared bison across the meadow network of Prince Albert National Park between 2005 and 2008. Selection of the next meadow visited over available meadows was assessed by comparing their characteristics and land cover composition of the area separating them from the departure meadow. Additionally, we used 196 bison trails originating from 29 meadows to evaluate movement rules during inter-patch travels. Bison preferred to travel in deciduous rather than in conifer stands during summer and fall but displayed no preference during winter and spring. They also selected meadows offering higher plant biomass in winter than in other seasons. Throughout the year, meadow proximity was an important determinant of meadow selection. Inter-patch trajectory was influenced by directional persistence, as well as movement biases toward the next meadow and toward canopy gaps. Unlike the choices individuals made in selecting their next meadow, bison displayed no preference between forest stands during inter-meadow travel, indicating that functional connectivity involves hierarchical movement decisions. We showed that the behavioral determinants of functional connectivity varied over spatiotemporal scales. First, forest stand composition between meadows influenced the next target, but not the trajectory during inter-meadow travels. Second, meadow selection varied among seasons. Therefore, although structural connectivity may be immutable to these behaviorally induced changes in inter-patch movements, functional connectivity would adequately account for such modifications in animal spatial dynamics.

Effect of Light Intensity on the Relative Dominance of Toxigenic and Nontoxigenic Strains of Microcystis Aeruginosa

Applied and Environmental Microbiology. Oct, 2011  |  Pubmed ID: 21841026

In aquatic ecosystems, the factors that regulate the dominance of toxin-producing cyanobacteria over non-toxin-producing strains of the same species are largely unknown. One possible hypothesis is that limiting resources lead to the dominance of the latter because of the metabolic costs associated with toxin production. In this study, we tested the effect of light intensity on the performance of a microcystin-producing strain of Microcystis aeruginosa (UTCC 300) when grown in mixed cultures with non-microcystin-producing strains with similar intrinsic growth rates (UTCC 632 and UTCC 633). The endpoints measured included culture growth rates, microcystin concentrations and composition, and mcyD gene copy numbers determined using quantitative PCR (Q-PCR). In contrast to the predicted results, under conditions of low light intensity (20 μmol·m(-2)·s(-1)), the toxigenic strain became dominant in both of the mixed cultures based on gene copy numbers and microcystin concentrations. When grown under conditions of high light intensity (80 μmol·m(-2)·s(-1)), the toxigenic strain still appeared to dominate over nontoxigenic strain UTCC 632 but less so over strain UTCC 633. Microcystins may not be so costly to produce that toxigenic cyanobacteria are at a disadvantage in competition for limiting resources.

Children's Appraisals As Mediators of the Relationship Between Domestic Violence and Child Adjustment

Violence and Victims. 2011  |  Pubmed ID: 21846024

This study examines the relationships among variables that were likely to mediate the effects of exposure to domestic violence on children's internalizing problems (i.e., children's appraisals of domestic violence and their perceptions of family relationships). The study was conducted with 79 children exposed to domestic violence, including 41 boys and 38 girls, aged between 9 and 12 years old. Indicators used for children's appraisals of violence were attribution of blame and perceived threat. Children's perceptions of family relationships were based on their levels of parentification and the degree of their loyalty conflicts. A path analysis was used to verify the predictive model's pathways and to test the multiple mediator effects. Findings confirm the contribution of mediating variables and also reflect the association between self-blame and children's parentification. The results stress the relevance of evaluating the combined role of different potential mediators to provide a better understanding of the impact of domestic violence on children.

The Common Hepatic Branch of the Vagus is Not Required to Mediate the Glycemic and Food Intake Suppressive Effects of Glucagon-like-peptide-1

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. Nov, 2011  |  Pubmed ID: 21849636

The incretin and food intake suppressive effects of intraperitoneally administered glucagon-like peptide-1 (GLP-1) involve activation of GLP-1 receptors (GLP-1R) expressed on vagal afferent fiber terminals. Central nervous system processing of GLP-1R-driven vagal afferents results in satiation signaling and enhanced insulin secretion from pancreatic-projecting vagal efferents. As the vast majority of endogenous GLP-1 is released from intestinal l-cells following ingestion, it stands to reason that paracrine GLP-1 signaling, activating adjacent GLP-1R expressed on vagal afferent fibers of gastrointestinal origin, contributes to glycemic and food intake control. However, systemic GLP-1R-mediated control of glycemia is currently attributed to endocrine action involving GLP-1R expressed in the hepatoportal bed on terminals of the common hepatic branch of the vagus (CHB). Here, we examine the hypothesis that activation of GLP-1R expressed on the CHB is not required for GLP-1's glycemic and intake suppressive effects, but rather paracrine signaling on non-CHB vagal afferents is required to mediate GLP-1's effects. Selective CHB ablation (CHBX), complete subdiaphragmatic vagal deafferentation (SDA), and surgical control rats received an oral glucose tolerance test (2.0 g glucose/kg) 10 min after an intraperitoneal injection of the GLP-1R antagonist, exendin-(9-39) (Ex-9; 0.5 mg/kg) or vehicle. CHBX and control rats showed comparable increases in blood glucose following blockade of GLP-1R by Ex-9, whereas SDA rats failed to show a GLP-1R-mediated incretin response. Furthermore, GLP-1(7-36) (0.5 mg/kg ip) produced a comparable suppression of 1-h 25% glucose intake in both CHBX and control rats, whereas intake suppression in SDA rats was blunted. These findings support the hypothesis that systemic GLP-1R mediation of glycemic control and food intake suppression involves paracrine-like signaling on GLP-1R expressed on vagal afferent fibers of gastrointestinal origin but does not require the CHB.

Ultra-small Gadolinium Oxide Nanoparticles to Image Brain Cancer Cells in Vivo with MRI

Contrast Media & Molecular Imaging. Jul-Aug, 2011  |  Pubmed ID: 21861281

The majority of contrast agents used in magnetic resonance imaging (MRI) is based on the rare-earth element gadolinium. Gadolinium-based nanoparticles could find promising applications in pre-clinical diagnostic procedures of certain types of cancer, such as glioblastoma multiforme. This is one of the most malignant, lethal and poorly accessible forms of cancer. Recent advances in colloidal nanocrystal synthesis have led to the development of ultra-small crystals of gadolinium oxide (US-Gd(2)O(3), 2-3 nm diameter). As of today, this is the smallest and the densest of all Gd-containing nanoparticles. Cancer cells labeled with a sufficient quantity of this compound appear bright in T(1)-weighted MRI images. Here we demonstrate that US-Gd(2)O(3) can be used to label GL-261 glioblastoma multiforme cells, followed by localization and visualization in vivo using MRI. Very high amounts of Gd are efficiently internalized and retained in cells, as confirmed with TEM and ICP-MS. Labeled cells were visualized in vivo at 1.5 T using the chicken embryo model. This is one more step toward the development of "positively contrasted" cell tracking procedures with MRI.

Measurement of the W+ W- Cross Section in Sqrt(s) = 7  TeV Pp Collisions with ATLAS

Physical Review Letters. Jul, 2011  |  Pubmed ID: 21866993

This Letter presents a measurement of the W+ W- production cross section in sqrt(s) = 7  TeV pp collisions by the ATLAS experiment, using 34  pb(-1) of integrated luminosity produced by the Large Hadron Collider at CERN. Selecting events with two isolated leptons, each either an electron or a muon, 8 candidate events are observed with an expected background of 1.7 ± 0.6 events. The measured cross section is 41(-16)(+20)(stat) ± 5(syst)±1(lumi)  pb, which is consistent with the standard model prediction of 44 ± 3  pb calculated at next-to-leading order in QCD.

Posterior Reversible Encephalopathy Syndrome: an Emerging Disease Manifestation in Systemic Lupus Erythematosus

Seminars in Arthritis and Rheumatism. Dec, 2011  |  Pubmed ID: 21868061

Posterior reversible encephalopathy syndrome (PRES) is a rare feature of systemic lupus erythematosus (SLE) that can present with seizures, visual disturbance, and/or hypertension. We describe 7 new cases of PRES in SLE patients that highlight some of the diagnostic and treatment dilemmas of this condition.

Immune Reconstitution Inflammatory Syndrome Following Cryptosporidial Cholangitis

AIDS (London, England). Sep, 2011  |  Pubmed ID: 21876390

Enhanced Sucrose and Cocaine Self-administration and Cue-induced Drug Seeking After Loss of VGLUT2 in Midbrain Dopamine Neurons in Mice

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Aug, 2011  |  Pubmed ID: 21880920

The mesostriatal dopamine (DA) system contributes to several aspects of responses to rewarding substances and is implicated in conditions such as drug addiction and eating disorders. A subset of DA neurons has been shown to express the type 2 Vesicular glutamate transporter (Vglut2) and may therefore corelease glutamate. In the present study, we analyzed mice with a conditional deletion of Vglut2 in DA neurons (Vglut2(f/f;DAT-Cre)) to address the functional significance of the glutamate-DA cophenotype for responses to cocaine and food reinforcement. Biochemical parameters of striatal DA function were also examined by using DA receptor autoradiography, immediate-early gene quantitative in situ hybridization after cocaine challenge, and DA-selective in vivo chronoamperometry. Mice in which Vglut2 expression had been abrogated in DA neurons displayed enhanced operant self-administration of both high-sucrose food and intravenous cocaine. Furthermore, cocaine seeking maintained by drug-paired cues was increased by 76%, showing that reward-dependent plasticity is perturbed in these mice. In addition, several lines of evidence suggest that adaptive changes occurred in both the ventral and dorsal striatum in the absence of VGLUT2: DA receptor binding was increased, and basal mRNA levels of the DA-induced early genes Nur77 and c-fos were elevated as after cocaine induction. Furthermore, in vivo challenge of the DA system by potassium-evoked depolarization revealed less DA release in both striatal areas. This study demonstrates that absence of VGLUT2 in DA neurons leads to perturbations of reward consumption as well as reward-associated memory, features of particular relevance for addictive-like behavior.

Autoantibodies As Biomarkers for the Prediction of Neuropsychiatric Events in Systemic Lupus Erythematosus

Annals of the Rheumatic Diseases. Oct, 2011  |  Pubmed ID: 21893582

Neuropsychiatric events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. This study examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrolment predicted subsequent neuropsychiatric events.

Fostering Health: Health Care for Children and Youth in Foster Care

Medicine and Health, Rhode Island. Jul, 2011  |  Pubmed ID: 21894848

[Category-specific Deficits in Semantic Dementia: Links Between Perception and Semantic Knowledge]

Gériatrie Et Psychologie Neuropsychiatrie Du Vieillissement. Sep, 2011  |  Pubmed ID: 21896435

The nature of knowledge and its relationship with the perceptual processes are among the most central issues in the study of human cognition. Should knowledge be abstract, then semantic memory and perception should be relatively independent. On the contrary, if knowledge is sensory-dependent, then memory and perception should be very close. The first view is supported by the multiple system approach of memory, whereas the second view is supported by the single-store memory theories. One way to study these links is through the category-specific impairment and the sensory-functional theory (SFT). Category-specific impairment is generally observed for living items compared to artefacts. The SFT explains this deficit by defining living items as essentially based on perception. In the abstract view of knowledge, a living deficit should be related to a deficit in processing sensory knowledge. On the opposite, the sensory-dependent view states that this deficit results from perception impairment. This article focuses on the relations between knowledge and perception in semantic dementia (SD). SD is characterized by a progressive loss of semantic knowledge, making it particularly interesting to study. This article first focuses on the SFT, to explain the category-specific impairment. The issue of perceptual processing in SD is then reviewed from the lowest level (senses) to the highest level of perception (multimodal integration). The data demonstrated normal perception for these patients. However, visual integration appeared to be impaired for existing knowledge. This result is discussed in relation with a possible involvement of the anterior temporal lobes. These regions are known to be the most vulnerable in SD. Recently these regions have also been shown to be involved in the multimodal integration. Taken together, these data suggest that perception and knowledge could be linked and partially explained by the SFT. Finally, the data support the sensory-dependent approaches of memory.

Incorporation of Zinc(II) Porphyrins in Polyaniline in Its Perigraniline Form Leading to Polymers with the Lowest Band Gap

Chemical Communications (Cambridge, England). Oct, 2011  |  Pubmed ID: 21897981

Conjugated copolymers built upon quinone diimine-zinc(II) porphyrin units exhibit a very low lying charge transfer band at 800 nm and are strongly emissive from the S(2) and T(2) states.

Breathing Without CO(2) Chemosensitivity in Conditional Phox2b Mutants

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Sep, 2011  |  Pubmed ID: 21900566

Breathing is a spontaneous, rhythmic motor behavior critical for maintaining O(2), CO(2), and pH homeostasis. In mammals, it is generated by a neuronal network in the lower brainstem, the respiratory rhythm generator (Feldman et al., 2003). A century-old tenet in respiratory physiology posits that the respiratory chemoreflex, the stimulation of breathing by an increase in partial pressure of CO(2) in the blood, is indispensable for rhythmic breathing. Here we have revisited this postulate with the help of mouse genetics. We have engineered a conditional mouse mutant in which the toxic PHOX2B(27Ala) mutation that causes congenital central hypoventilation syndrome in man is targeted to the retrotrapezoid nucleus, a site essential for central chemosensitivity. The mutants lack a retrotrapezoid nucleus and their breathing is not stimulated by elevated CO(2) at least up to postnatal day 9 and they barely respond as juveniles, but nevertheless survive, breathe normally beyond the first days after birth, and maintain blood PCO(2) within the normal range. Input from peripheral chemoreceptors that sense PO(2) in the blood appears to compensate for the missing CO(2) response since silencing them by high O(2) abolishes rhythmic breathing. CO(2) chemosensitivity partially recovered in adulthood. Hence, during the early life of rodents, the excitatory input normally afforded by elevated CO(2) is dispensable for life-sustaining breathing and maintaining CO(2) homeostasis in the blood.

Toxicity Report of Once Weekly Radiation Therapy for Low-risk Prostate Adenocarcinoma: Preliminary Results of a Phase I/II Trial

Radiation Oncology (London, England). 2011  |  Pubmed ID: 21906281

Increasing clinical data supports a low α/β ratio for prostate adenocarcinoma, potentially lower than that of surrounding normal tissues. A hypofractionated, weekly radiation therapy (RT) schedule should result in improved tumour control, reduced acute toxicity, and similar or decreased late effects. We report the toxicity profile of such treatment.

The Challenges of Implementing a "patient-oriented" Telepathology Network; the Eastern Québec Telepathology Project Experience

Analytical Cellular Pathology (Amsterdam). Sep, 2011  |  Pubmed ID: 21908908

Background: The aim of the Eastern Québec telepathology project is to provide uniform diagnostic telepathology services across a huge geographic region with a low population density. This project is intended to provide surgeons and pathologists with frozen section and second opinion services anywhere and at any time across the entire region in order to avoid unnecessary patient transfer. Methods: The project has been implemented in 21 sites, each equipped with a whole slide scanner, a macroscopy station, two videoconferencing devices and a viewer/case management and collaboration solution. Of the 21 sites, 6 are devoid of a pathology laboratory. Of the remaining 15 sites, two have no pathologists, 6 have one and 7 have two or more. Results: The project has been successful and most appreciated by pathologists and surgeons. We report a number of challenges related to change management that we had to take into account in the course of implementation of this network. The challenges underscore the need for regular visits and active support to participating centers by the project team. Conclusion: The Eastern Québec telepathology network is successful and improves medical care in this region. In the course of implementation, we encountered a number of challenges which required innovative solutions.

Substituted Phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonamides As Antimitotics. Antiproliferative, Antiangiogenic and Antitumoral Activity, and Quantitative Structure-activity Relationships

European Journal of Medicinal Chemistry. Nov, 2011  |  Pubmed ID: 21920638

The importance of the bridge linking the two phenyl moieties of substituted phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates (PIB-SOs) was assessed using a sulfonamide group, which is a bioisostere of sulfonate and ethenyl groups. Forty one phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonamide (PIB-SA) derivatives were prepared and biologically evaluated. PIB-SAs exhibit antiproliferative activities at the nanomolar level against sixteen cancer cell lines, block the cell cycle progression in G(2)/M phase, leading to cytoskeleton disruption and anoikis. These results were subjected to CoMFA and CoMSIA analyses to establish quantitative structure-activity relationships. These results evidence that the sulfonate and sulfonamide moieties are reciprocal bioisosteres and that phenylimidazolidin-2-one could mimic the trimethoxyphenyl moiety found in the structure of numerous potent antimicrotubule agents. Finally, compounds 16 and 17 exhibited potent antitumor and antiangiogenic activities on HT-1080 fibrosarcoma cells grafted onto chick chorioallantoic membrane similar to CA-4 without significant toxicity for the chick embryos, making this class of compounds a promising class of anticancer agents.

Impact of Intensive Land-based Fish Culture in Qingdao, China, on the Bacterial Communities in Surrounding Marine Waters and Sediments

Evidence-based Complementary and Alternative Medicine : ECAM. 2011  |  Pubmed ID: 21922024

The impact of intensive land-based fish culture in Qingdao, China, on the bacterial communities in surrounding marine environment was analyzed. Culture-based studies showed that the highest counts of heterotrophic, ammonium-oxidizing, nitrifying, and nitrate-reducing bacteria were found in fish ponds and the effluent channel, with lower counts in the adjacent marine area and the lowest counts in the samples taken from 500 m off the effluent channel. Denaturing gradient gel electrophoresis (DGGE) analysis was used to assess total bacterial diversity. Fewer bands were observed from the samples taken from near the effluent channel compared with more distant sediment samples, suggesting that excess nutrients from the aquaculture facility may be reducing the diversity of bacterial communities in nearby sediments. Phylogenetic analysis of the sequenced DGGE bands indicated that the bacteria community of fish-culture-associated environments was mainly composed of Flavobacteriaceae, gamma- and deltaproteobacteria, including genera Gelidibacter, Psychroserpen, Lacinutrix, and Croceimarina.

From Glutamate Co-release to Vesicular Synergy: Vesicular Glutamate Transporters

Nature Reviews. Neuroscience. Apr, 2011  |  Pubmed ID: 21415847

Recent data indicate that 'classical' neurotransmitters can also act as co-transmitters. This notion has been strengthened by the demonstration that three vesicular glutamate transporters (vesicular glutamate transporter 1 (VGLUT1), VGLUT2 and VGLUT3) are present in central monoamine, acetylcholine and GABA neurons, as well as in primarily glutamatergic neurons. Thus, intriguing questions are raised about the morphological and functional organization of neuronal systems endowed with such a dual signalling capacity. In addition to glutamate co-release, vesicular synergy - a process leading to enhanced packaging of the 'primary' transmitter - is increasingly recognized as a major property of the glutamatergic co-phenotype. The behavioural relevance of this co-phenotype is presently the focus of considerable interest.

British HIV Association and Children's HIV Association Position Statement on Infant Feeding in the UK 2011

HIV Medicine. Aug, 2011  |  Pubmed ID: 21418503

To prevent the transmission of HIV infection during the postpartum period, the British HIV Association and Children's HIV Association (BHIVA/CHIVA) continue to recommend the complete avoidance of breast feeding for infants born to HIV-infected mothers, regardless of maternal disease status, viral load or treatment.

L-Carnitine and Intestinal Inflammation

Vitamins and Hormones. 2011  |  Pubmed ID: 21419279

The intestinal barrier is one of the most dynamic surfaces of the body. It is here where a single layer of epithelial cells mediates the intricate encounters that occur between the host's immune system and a multitude of potential threats present in the intestinal lumen. Several key factors play an important role in the final outcome of this interaction, including the state of oxidative stress, the level of activation of the immune cells, and the integrity of the epithelial barrier. This chapter describes the main evidence demonstrating the impact that l-carnitine has on each of these factors. These findings, combined with the demonstrated safety profile of l-carnitine, underscore the potential therapeutic value of l-carnitine supplementation in humans suffering from intestinal inflammation and highlight the functional data supporting an association between Crohn's disease and mutations in the l-carnitine transporter genes.

Hydrogen Cyanide Poisoning in a Prison Environment: a Case Report

Journal of Correctional Health Care : the Official Journal of the National Commission on Correctional Health Care. Jan, 2011  |  Pubmed ID: 21278317

Cyanide poisoning is an important source of morbidity and mortality from smoke exposure in structural fires. This case involved administration of a cyanide antidote to a prisoner (male, 23 years) in France, discovered in cardiorespiratory arrest after about 30 minutes exposure to smoke from a burning mattress during an apparent suicide attempt. Smoke exposure, circulatory failure during initial resuscitation, and elevated blood cyanide and lactate led to the diagnosis of cyanide poisoning. Hydroxocobalamin (Cyanokit®), 5 g intravenous) was given immediately and on arrival at the hospital. Cardiopulmonary resuscitation restored cardiovascular function after 33 minutes. There were no neurological or other sequelae. Timely hydroxocobalamin administration contributed to full recovery from cardiorespiratory arrest secondary to cyanide poisoning from smoke inhalation. Hydroxocobalamin should be available to emergency medical teams attending fire scenes.

Supporting Work Practices Through Telehealth: Impact on Nurses in Peripheral Regions

BMC Health Services Research. 2011  |  Pubmed ID: 21294882

In Canada, workforce shortages in the health care sector constrain the ability of the health care system to meet the needs of its population and of its health care professionals. This issue is of particular importance in peripheral regions of Quebec, where significant inequalities in workforce distribution between regions has lead to acute nursing shortages and increased workloads. Information and communication technologies (ICTs) are innovative solutions that can be used to develop strategies to optimise the use of available resources and to design new nursing work practices. However, current knowledge is still limited about the real impact of ICTs on nursing recruitment and retention. Our aim is to better understand how work practice reorganization, supported by ICTs, and particularly by telehealth, may influence professional, educational, and organizational factors relating to Quebec nurses, notably those working in peripheral regions.

A Multi-scale Comparison of Trait Linkages to Environmental and Spatial Variables in Fish Communities Across a Large Freshwater Lake

Oecologia. Jul, 2011  |  Pubmed ID: 21305321

Species present in communities are affected by the prevailing environmental conditions, and the traits that these species display may be sensitive indicators of community responses to environmental change. However, interpretation of community responses may be confounded by environmental variation at different spatial scales. Using a hierarchical approach, we assessed the spatial and temporal variation of traits in coastal fish communities in Lake Huron over a 5-year time period (2001-2005) in response to biotic and abiotic environmental factors. The association of environmental and spatial variables with trophic, life-history, and thermal traits at two spatial scales (regional basin-scale, local site-scale) was quantified using multivariate statistics and variation partitioning. We defined these two scales (regional, local) on which to measure variation and then applied this measurement framework identically in all 5 study years. With this framework, we found that there was no change in the spatial scales of fish community traits over the course of the study, although there were small inter-annual shifts in the importance of regional basin- and local site-scale variables in determining community trait composition (e.g., life-history, trophic, and thermal). The overriding effects of regional-scale variables may be related to inter-annual variation in average summer temperature. Additionally, drivers of fish community traits were highly variable among study years, with some years dominated by environmental variation and others dominated by spatially structured variation. The influence of spatial factors on trait composition was dynamic, which suggests that spatial patterns in fish communities over large landscapes are transient. Air temperature and vegetation were significant variables in most years, underscoring the importance of future climate change and shoreline development as drivers of fish community structure. Overall, a trait-based hierarchical framework may be a useful conservation tool, as it highlights the multi-scaled interactive effect of variables over a large landscape.

Association of Autoantibodies to Heat-shock Protein 60 with Arterial Vascular Events in Patients with Antiphospholipid Antibodies

Arthritis and Rheumatism. Aug, 2011  |  Pubmed ID: 21506099

Anti-heat shock protein 60 autoantibodies (anti-Hsp60) are associated with cardiovascular disease and are known to affect endothelial cells in vitro, and we have recently shown that anti-Hsp60 promote thrombosis in a murine model of arterial injury. Based on those findings, we undertook the present study to investigate the hypothesis that the presence of anti-Hsp60, alone or in combination with other thrombogenic risk factors, is associated with an elevated risk of vascular events.

Search for Diphoton Events with Large Missing Transverse Energy in 7 TeV Proton-proton Collisions with the ATLAS Detector

Physical Review Letters. Mar, 2011  |  Pubmed ID: 21517301

A search for diphoton events with large missing transverse energy is presented. The data were collected with the ATLAS detector in proton-proton collisions at √s=7 TeV at the CERN Large Hadron Collider and correspond to an integrated luminosity of 3.1 pb⁻¹. No excess of such events is observed above the standard model background prediction. In the context of a specific model with one universal extra dimension with compactification radius R and gravity-induced decays, values of 1/R<729 GeV are excluded at 95% C. L., providing the most sensitive limit on this model to date.

Search for Supersymmetry Using Final States with One Lepton, Jets, and Missing Transverse Momentum with the ATLAS Detector in ˆ�s=7 TeV Pp Collisions

Physical Review Letters. Apr, 2011  |  Pubmed ID: 21517374

This Letter presents the first search for supersymmetry in final states containing one isolated electron or muon, jets, and missing transverse momentum from √s=7  TeV proton-proton collisions at the LHC. The data were recorded by the ATLAS experiment during 2010 and correspond to a total integrated luminosity of 35  pb(-1). No excess above the standard model background expectation is observed. Limits are set on the parameters of the minimal supergravity framework, extending previous limits. Within this framework, for A(0)=0 GeV, tanβ=3, and μ>0 and for equal squark and gluino masses, gluino masses below 700 GeV are excluded at 95% confidence level.

Weibull-type Limiting Distribution for Replicative Systems

Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics. Mar, 2011  |  Pubmed ID: 21517470

The Weibull function is widely used to describe skew distributions observed in nature. However, the origin of this ubiquity is not always obvious to explain. In the present paper, we consider the well-known Galton-Watson branching process describing simple replicative systems. The shape of the resulting distribution, about which little has been known, is found essentially indistinguishable from the Weibull form in a wide range of the branching parameter; this can be seen from the exact series expansion for the cumulative distribution, which takes a universal form. We also find that the branching process can be mapped into a process of aggregation of clusters. In the branching and aggregation process, the number of events considered for branching and aggregation grows cumulatively in time, whereas, for the binomial distribution, an independent event occurs at each time with a given success probability.

Safety and Feasibility of Motexafin Gadolinium Administration with Whole Brain Radiation Therapy and Stereotactic Radiosurgery Boost in the Treatment of ‰� 6 Brain Metastases: a Multi-institutional Phase II Trial

Journal of Neuro-oncology. Nov, 2011  |  Pubmed ID: 21523486

To determine the safety, tolerability, and report on secondary efficacy endpoints of motexafin gadolinium (MGd) in combination with whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) for patients with ≤ 6 brain metastases. We conducted an international study of WBRT (37.5 Gy in 15 fractions) and SRS (15-21 Gy) with the addition of MGd (5 mg/kg preceding each fraction beginning week 2). The primary endpoint was to evaluate the rate of irreversible grade 3 or any grade ≥ 4 neurotoxicity and establish feasibility in preparation for a phase III trial. Sixty-five patients were enrolled from 14 institutions, of which 45 (69%) received SRS with MGd as intended and were available for evaluation. Grade ≥ 3 neurotoxicity attributable to radiation therapy within 3 months of SRS was seen in 2 patients (4.4%), including generalized weakness and radionecrosis requiring surgical management. Immediately following the course of MGd plus WBRT, new brain metastases were detected in 11 patients (24.4%) at the time of the SRS treatment planning MRI. The actuarial incidence of neurologic progression at 6 months and 1 year was 17 and 20%, respectively. The median investigator-determined neurologic progression free survival and overall survival times were 8 (95% CI: 5-14) and 9 months (95% CI: 6-not reached), respectively. We observed a low rate of neurotoxicity, demonstrating that the addition of MGd does not increase the incidence or severity of neurologic complications from WBRT with SRS boost.

IRF8 Mutations and Human Dendritic-cell Immunodeficiency

The New England Journal of Medicine. Jul, 2011  |  Pubmed ID: 21524210

The genetic analysis of human primary immunodeficiencies has defined the contribution of specific cell populations and molecular pathways in the host defense against infection. Disseminated infection caused by bacille Calmette-Guérin (BCG) vaccines is an early manifestation of primary immunodeficiencies, such as severe combined immunodeficiency. In many affected persons, the cause of disseminated BCG disease is unexplained.

Optogenetic Photochemical Control of Designer K+ Channels in Mammalian Neurons

Journal of Neurophysiology. Jul, 2011  |  Pubmed ID: 21525363

Currently available optogenetic tools, including microbial light-activated ion channels and transporters, are transforming systems neuroscience by enabling precise remote control of neuronal firing, but they tell us little about the role of indigenous ion channels in controlling neuronal function. Here, we employ a chemical-genetic strategy to engineer light sensitivity into several mammalian K(+) channels that have different gating and modulation properties. These channels provide the means for photoregulating diverse electrophysiological functions. Photosensitivity is conferred on a channel by a tethered ligand photoswitch that contains a cysteine-reactive maleimide (M), a photoisomerizable azobenzene (A), and a quaternary ammonium (Q), a K(+) channel pore blocker. Using mutagenesis, we identify the optimal extracellular cysteine attachment site where MAQ conjugation results in pore blockade when the azobenzene moiety is in the trans but not cis configuration. With this strategy, we have conferred photosensitivity on channels containing Kv1.3 subunits (which control axonal action potential repolarization), Kv3.1 subunits (which contribute to rapid-firing properties of brain neurons), Kv7.2 subunits (which underlie "M-current"), and SK2 subunits (which are Ca(2+)-activated K(+) channels that contribute to synaptic responses). These light-regulated channels may be overexpressed in genetically targeted neurons or substituted for native channels with gene knockin technology to enable precise optopharmacological manipulation of channel function.

Prenatal Development of Central Rhythm Generation

Respiratory Physiology & Neurobiology. Aug, 2011  |  Pubmed ID: 21527363

Foetal breathing in mice results from prenatal activity of the two coupled hindbrain oscillators considered to be responsible for respiratory rhythm generation after birth: the pre-Bötzinger complex (preBötC) is active shortly before the onset of foetal breathing; the parafacial respiratory group (e-pF in embryo) starts activity one day earlier. Transcription factors have been identified that are essential to specify neural progenitors and lineages forming each of these oscillators during early development of the neural tube: Hoxa1, Egr2 (Krox20), Phox2b, Lbx1 and Atoh1 for the e-pF; Dbx1 and Evx1 for the preBötC which eventually grow contralateral axons requiring expression of Robo3. Inactivation of the genes encoding these factors leads to mis-specification of these neurons and distinct breathing abnormalities: apneic patterns and loss of central chemosensitivity for the e-pF (central congenital hypoventilation syndrome, CCHS, in humans), complete loss of breathing for the preBötC, right-left desynchronized breathing in Robo3 mutants. Mutations affecting development in more rostral (pontine) respiratory territories change the shape of the inspiratory drive without affecting the rhythm. Other (primordial) embryonic oscillators start in the mouse three days before the e-pF, to generate low frequency (LF) rhythms that are probably required for activity-dependent development of neurones at embryonic stages; in the foetus, however, they are actively silenced to avoid detrimental interaction with the on-going respiratory rhythm. Altogether, these observations provide a strong support to the previously proposed hypothesis that the functional organization of the respiratory generator is specified at early stages of development and is dual in nature, comprising two serially non-homologous oscillators.

Feasibility of Internal Mammary Vessel Use in Breast Reconstruction Versus Coronary Artery Bypass Surgery: an Anatomic, Cadaveric Evaluation

Plastic and Reconstructive Surgery. May, 2011  |  Pubmed ID: 21532407

Autologous free flap breast reconstruction using the internal mammary artery is common; however, its use may compromise treatment of occult coronary artery disease. The authors investigated whether internal mammary artery harvest for breast reconstruction is compatible with future use for coronary bypass.

Infections in the Lupus Patient: Perspectives on Prevention

Current Opinion in Rheumatology. Jul, 2011  |  Pubmed ID: 21532484

Infections are one of the most common causes of morbidity, hospitalization and death in patients with systemic lupus erythematosus (SLE). The aim of the review is to describe an approach to screening and prevention of infections in patients with SLE based on recent evidence.

Comparison of Bayesian Clustering and Edge Detection Methods for Inferring Boundaries in Landscape Genetics

International Journal of Molecular Sciences. 2011  |  Pubmed ID: 21541031

Recently, techniques available for identifying clusters of individuals or boundaries between clusters using genetic data from natural populations have expanded rapidly. Consequently, there is a need to evaluate these different techniques. We used spatially-explicit simulation models to compare three spatial Bayesian clustering programs and two edge detection methods. Spatially-structured populations were simulated where a continuous population was subdivided by barriers. We evaluated the ability of each method to correctly identify boundary locations while varying: (i) time after divergence, (ii) strength of isolation by distance, (iii) level of genetic diversity, and (iv) amount of gene flow across barriers. To further evaluate the methods' effectiveness to detect genetic clusters in natural populations, we used previously published data on North American pumas and a European shrub. Our results show that with simulated and empirical data, the Bayesian spatial clustering algorithms outperformed direct edge detection methods. All methods incorrectly detected boundaries in the presence of strong patterns of isolation by distance. Based on this finding, we support the application of Bayesian spatial clustering algorithms for boundary detection in empirical datasets, with necessary tests for the influence of isolation by distance.

Hippocampal Leptin Signaling Reduces Food Intake and Modulates Food-related Memory Processing

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. Aug, 2011  |  Pubmed ID: 21544068

The increase in obesity prevalence highlights the need for a more comprehensive understanding of the neural systems controlling food intake; one that extends beyond food intake driven by metabolic need and considers that driven by higher-order cognitive factors. The hippocampus, a brain structure involved in learning and memory function, has recently been linked with food intake control. Here we examine whether administration of the adiposity hormone leptin to the dorsal and ventral sub-regions of the hippocampus influences food intake and memory for food. Leptin (0.1 μg) delivered bilaterally to the ventral hippocampus suppressed food intake and body weight measured 24 h after administration; a higher dose (0.4 μg) was needed to suppress intake following dorsal hippocampal delivery. Leptin administration to the ventral but not dorsal hippocampus blocked the expression of a conditioned place preference for food and increased the latency to run for food in an operant runway paradigm. Additionally, ventral but not dorsal hippocampal leptin delivery suppressed memory consolidation for the spatial location of food, whereas hippocampal leptin delivery had no effect on memory consolidation in a non-spatial appetitive response paradigm. Collectively these findings indicate that ventral hippocampal leptin signaling contributes to the inhibition of food-related memories elicited by contextual stimuli. To conclude, the results support a role for hippocampal leptin signaling in the control of food intake and food-related memory processing.

Energy Gains Predict the Distribution of Plains Bison Across Populations and Ecosystems

Ecology. Jan, 2011  |  Pubmed ID: 21560694

Developing tools that help predict animal distribution in the face of environmental change is central to understanding ecosystem function, but it remains a significant ecological challenge. We tested whether a single foraging currency could explain bison (Bison bison) distribution in dissimilar environments: a largely forested environment in Prince Albert National Park (Saskatchewan, Canada) and a prairie environment in Grasslands National Park (Saskatchewan, Canada). We blended extensive behavioral observations, relocations of radio-collared bison, vegetation surveys, and laboratory analyses to spatially link bison distribution in the two parks and expected gains for different nutritional currencies. In Prince Albert National Park, bison were more closely associated with the distribution of plants that maximized their instantaneous energy intake rate (IDE) than their daily intake of digestible energy. This result reflected both bison's intensity of use of individual meadows and their selection of foraging sites within meadows. On this basis, we tested whether IDE could explain the spatial dynamics of bison reintroduced to Grasslands National Park. As predicted, bison distribution in this park best matched spatial patterns of plants offering rapid IDE rather than rapid sodium intake, phosphorus intake, or daily intake of digestible energy. Because the two study areas have very different plant communities, a phenomenological model of resource selection developed in one area could not be used to predict animal distribution in the other. We were able, however, to successfully infer the distribution of bison from their foraging objective. This consistency in foraging currency across ecosystems and populations provides a strong basis for forecasting animal distributions in novel and dynamic environments.

Increased Expression of B Cell Activation Factor Supports the Abnormal Expansion of Transitional B Cells in Systemic Lupus Erythematosus

The Journal of Rheumatology. Apr, 2011  |  Pubmed ID: 21239754

To examine the relationship between interferon-α (IFN-α) and dysregulation of B cell activation factor (BAFF) and specific B cell phenotypes in systemic lupus erythematosus (SLE).

Persistent Proteinuria and Dyslipidemia Increase the Risk of Progressive Chronic Kidney Disease in Lupus Erythematosus

Kidney International. Apr, 2011  |  Pubmed ID: 21248713

Advances in immunotherapy have improved survival of patients with systemic lupus erythematosus who now face an increasing burden of chronic diseases including that of the kidney. As systemic inflammation is also thought to contribute directly to the progression of chronic kidney disease (CKD), we assessed this risk in patients with lupus, with and without a diagnosis of nephritis, and also identified modifiable risk factors. Accordingly, we enrolled 631 patients (predominantly Caucasian), of whom 504 were diagnosed with lupus within the first year and followed them an average of 11 years. Despite the presence of a chronic inflammatory disease, the rate of decline in renal function of 238 patients without nephritis was similar to that described for non-lupus patient cohorts. Progressive loss of kidney function developed exclusively in patients with lupus nephritis who had persistent proteinuria and dyslipidemia, although only six required dialysis or transplantation. The mortality rate was 16% with half of the deaths attributable to sepsis or cancer. Thus, despite the presence of a systemic inflammatory disease, the risk of progressive CKD in this lupus cohort was relatively low in the absence of nephritis. Hence, as in idiopathic glomerular disease, persistent proteinuria and dyslipidemia (modifiable risks) are the major factors for CKD progression in lupus patients with renal involvement.

Surveillance Provinciale Des Infections Nosocomiales (SPIN) Program: Implementation of a Mandatory Surveillance Program for Central Line-associated Bloodstream Infections

American Journal of Infection Control. May, 2011  |  Pubmed ID: 21255873

In 2003, the Surveillance Provinciale des Infections Nosocomiales (SPIN) program was launched to gather data on incidence rates of central line-associated bloodstream infections (CLABSIs) in intensive care units (ICUs) in the Province of Quebec. To improve the generalizability of SPIN benchmarks, in 2007 participation in SPIN became mandatory for all ICUs with ≥10 beds.

Concurrency Benefits in the Attentional Blink: Attentional Flexibility and Shifts of Decision Criteria

Attention, Perception & Psychophysics. Feb, 2011  |  Pubmed ID: 21264730

Fundamental limitations in performing multiple tasks concurrently are well illustrated by the attentional blink (AB) deficit, which refers to the difficulty in reporting a second target (T2) when it is presented shortly after a first target (T1). Surprisingly, recent studies have shown that the AB, which is often thought of as a manifestation of capacity limitations in central processing, can be reduced when the AB task is performed simultaneously with concurrent distracting activities. In the present study, we sought to investigate whether such concurrency benefits would also be observed when the AB task was performed concurrently with a central demanding timing task. The AB was reduced under concurrent-task conditions, as compared with single-AB-task conditions, even though T1 performance was unaffected by the concurrent task. Moreover, shifts in decision criteria were found to be associated with the concurrency benefit effect.

Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index-50: a Reliable Index for Measuring Improvement in Disease Activity

The Journal of Rheumatology. May, 2011  |  Pubmed ID: 21324961

To test the interrater and intrarater reliability of the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Responder Index (SRI-50), an index designed to measure ≥ 50% improvement in disease activity between visits in patients with systemic lupus erythematosus.

Effects of Anticholinergic Drugs on Verbal Episodic Memory Function in the Elderly: a Retrospective, Cross-sectional Study

Drugs & Aging. Mar, 2011  |  Pubmed ID: 21329401

An increasing number of medications that are frequently prescribed to elderly patients have been identified as having weak but definite anticholinergic properties. Few epidemiological studies have evaluated the impact of these drugs on verbal episodic memory using sensitive and specific neuropsychological testing in an elderly population presenting with cognitive impairment.

SF-36 Summary and Subscale Scores Are Reliable Outcomes of Neuropsychiatric Events in Systemic Lupus Erythematosus

Annals of the Rheumatic Diseases. Jun, 2011  |  Pubmed ID: 21342917

To examine change in health-related quality of life in association with clinical outcomes of neuropsychiatric events in systemic lupus erythematosus (SLE).

The Fetal Safety of Hydrocortisone-pramoxine (Proctofoam-HC) for the Treatment of Hemorrhoids in Late Pregnancy

Journal of Obstetrics and Gynaecology Canada : JOGC = Journal D'obstétrique Et Gynécologie Du Canada : JOGC. Feb, 2011  |  Pubmed ID: 21352635

Fetal safety has never been studied for any drug used in the treatment of hemorrhoids. Proctofoam-HC is a combination of a corticosteroid and a local anaesthetic that is proven effective for the treatment of hemorrhoids. The objective of this study was to assess prospectively the fetal safety of third trimester exposure to Proctofoam-HC.

Molecular Markers of Injury in Kidney Biopsy Specimens of Patients with Lupus Nephritis

The Journal of Molecular Diagnostics : JMD. Mar, 2011  |  Pubmed ID: 21354048

Prediction of prognosis in patients who have lupus nephritis is inadequate, limiting individualization of potentially toxic therapy. Advances in tissue molecular techniques offer new approaches to study mechanisms underlying kidney injury, and add to prognostic information gleaned from biopsy specimens. Analysis of mRNA expression in formalin-fixed, paraffin-embedded renal biopsy specimens is limited by both quantity and quality of RNA, requiring RNA pre-amplification, which can introduce bias. Accordingly, we developed a new technique for RNA extraction from human kidney formalin fixed paraffin embedded biopsy specimens, and used Taqman low-density arrays Applied Biosystems, Carlsbad, CA to simultaneously measure 48 mRNAs in duplicate, in a single biopsy. We extracted mRNA from more than 150 blocks to determine the quantity and vintage of biopsy tissue suitable for analysis using this protocol. We then used Taqman low-density arrays to identify suitable housekeeping genes in lupus nephritis. Finally, we measured expression of 48 mRNA transcripts in archived lupus biopsy specimens (n = 54). We identified that the mRNA levels of three transcripts (MMP7, EGF, COL1A1) relate to pathological indices of kidney injury and kidney function at the time of biopsy; these were associated with parallel changes in expression of these proteins. This new method for measurement of kidney biopsy mRNA expression has enabled us to identify tissue biomarkers of kidney damage and function, and potentially can increase the information yielded from diagnostic kidney biopsy specimens to improve tailoring of therapy.

Autoantibodies in Systemic Lupus Erythematosus: Comparison of Historical and Current Assessment of Seropositivity

Lupus. Mar, 2011  |  Pubmed ID: 21362750

Systemic lupus erythematosus (SLE) is characterized by multiple autoantibodies and complement activation. Recent studies have suggested that anti-nuclear antibody (ANA) positivity may disappear over time in some SLE patients. Anti-double-stranded DNA (dsDNA) antibody titers and complement levels may vary with time and immunosuppressive treatment, while the behavior of anti-extractable nuclear antigen (ENA) over time is less well understood. This study sought to determine the correlation between historical autoantibody tests and current testing in patients with SLE. Three hundred and two SLE patients from the ACR Reclassification of SLE (AROSE) database with both historical and current laboratory data were selected for analysis. The historical laboratory data were compared with the current autoantibody tests done at the reference laboratory and tested for agreement using percent agreement and Kappa statistic. Serologic tests included ANA, anti-dsDNA, anti-Smith, anti-ribonucleoprotein (RNP), anti-Ro, anti-La, rheumatoid factor (RF), C3 and C4. Among those historically negative for immunologic markers, a current assessment of the markers by the reference laboratory generally yielded a low percentage of additional positives (3-13%). However, 6/11 (55%) of those historically negative for ANA were positive by the reference laboratory, and the reference laboratory test also identified 20% more patients with anti-RNP and 18% more with RF. Among those historically positive for immunologic markers, the reference laboratory results were generally positive on the same laboratory test (range 57% to 97%). However, among those with a history of low C3 or C4, the current reference laboratory results indicated low C3 or C4 a low percentage of the time (18% and 39%, respectively). ANA positivity remained positive over time, in contrast to previous studies. Anti-Ro, La, RNP, Smith and anti-dsDNA antibodies had substantial agreement over time, while complement had less agreement. This variation could partially be explained by variability of the historical assays, which were done by local laboratories over varying periods of time. Variation in the results for complement, however, is more likely to be explained by response to treatment. These findings deserve consideration in the context of diagnosis and enrolment in clinical trials.

Thrombovascular Events Affect Quality of Life in Patients with Systemic Lupus Erythematosus

The Journal of Rheumatology. Jun, 2011  |  Pubmed ID: 21362766

To compare health-related quality of life (HRQOL) of patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) with and without previous thrombovascular events (TE).

Clonal Analysis by Distinct Viral Vectors Identifies Bona Fide Neural Stem Cells in the Adult Zebrafish Telencephalon and Characterizes Their Division Properties and Fate

Development (Cambridge, England). Apr, 2011  |  Pubmed ID: 21367818

Neurogenesis is widespread in the zebrafish adult brain through the maintenance of active germinal niches. To characterize which progenitor properties correlate with this extensive neurogenic potential, we set up a method that allows progenitor cell transduction and tracing in the adult zebrafish brain using GFP-encoding retro- and lentiviruses. The telencephalic germinal zone of the zebrafish comprises quiescent radial glial progenitors and actively dividing neuroblasts. Making use of the power of clonal viral vector-based analysis, we demonstrate that these progenitors follow different division modes and fates: neuroblasts primarily undergo a limited amplification phase followed by symmetric neurogenic divisions; by contrast, radial glia are capable at the single cell level of both self-renewing and generating different cell types, and hence exhibit bona fide neural stem cell (NSC) properties in vivo. We also show that radial glial cells predominantly undergo symmetric gliogenic divisions, which amplify this NSC pool and may account for its long-lasting maintenance. We further demonstrate that blocking Notch signaling results in a significant increase in proliferating cells and in the numbers of clones, but does not affect clone composition, demonstrating that Notch primarily controls proliferation rather than cell fate. Finally, through long-term tracing, we illustrate the functional integration of newborn neurons in forebrain adult circuitries. These results characterize fundamental aspects of adult progenitor cells and neurogenesis, and open the way to using virus-based technologies for stable genetic manipulations and clonal analyses in the zebrafish adult brain.

Intramolecular Cyclization of N-phenyl N'(2-chloroethyl)ureas Leads to Active N-phenyl-4,5-dihydrooxazol-2-amines Alkylating β-tubulin Glu198 and Prohibitin Asp40

Biochemical Pharmacology. May, 2011  |  Pubmed ID: 21371445

The cyclization of anticancer drugs into active intermediates has been reported mainly for DNA alkylating molecules including nitrosoureas. We previously defined the original cytotoxic mechanism of anticancerous N-phenyl-N'-(2-chloroethyl)ureas (CEUs) that involves their reactivity towards cellular proteins and not against DNA; two CEU subsets have been shown to alkylate β-tubulin and prohibitin leading to inhibition of cell proliferation by G₂/M or G₁/S cell cycle arrest. In this study, we demonstrated that cyclic derivatives of CEUs, N-phenyl-4,5-dihydrooxazol-2-amines (Oxas) are two- to threefold more active than CEUs and share the same cytotoxic properties in B16F0 melanoma cells. Moreover, the CEU original covalent binding by an ester linkage on β-tubulin Glu198 and prohibitin Asp40 was maintained with Oxas. Surprisingly, we observed that Oxas were spontaneously formed from CEUs in the cell culture medium and were also detected within the cells. Our results suggest that the intramolecular cyclization of CEUs leads to active Oxas that should then be considered as the key intermediates for protein alkylation. These results will be useful for the design of new prodrugs for cancer chemotherapy.

Alterations in Circulating Fatty Acid Composition in Patients with Systemic Lupus Erythematosus: a Pilot Study

JPEN. Journal of Parenteral and Enteral Nutrition. Mar, 2011  |  Pubmed ID: 21378249

Circulating fatty acids (FAs) may play a role in the disease pathogenesis of patients with systemic lupus erythematosus (SLE).

Biogeochemical Factors Influencing Net Mercury Methylation in Contaminated Freshwater Sediments from the St. Lawrence River in Cornwall, Ontario, Canada

The Science of the Total Environment. Feb, 2011  |  Pubmed ID: 21176945

The activity of various anaerobic microbes, including sulfate reducers (SRB), iron reducers (FeRP) and methanogens (MPA) has been linked to mercury methylation in aquatic systems, although the relative importance of each microbial group in the overall process is poorly understood in natural sediments. The present study focused on the biogeochemical factors (i.e. the relative importance of various groups of anaerobic microbes (FeRP, SRB, and MPA) that affect net monomethylmercury (MMHg) formation in contaminated sediments of the St. Lawrence River (SRL) near Cornwall (Zone 1), Ontario, Canada. Methylation and demethylation potentials were measured separately by using isotope-enriched mercury species ((200)Hg(2+) and MM(199)Hg(+)) in sediment microcosms treated with specific microbial inhibitors. Sediments were sampled and incubated in the dark at room temperature in an anaerobic chamber for 96h. The potential methylation rate constants (K(m)) and demethylation rates (K(d)) were found to differ significantly between microcosms. The MPA-inhibited microcosm had the highest potential methylation rate constant (0.016d(-1)), whereas the two SRB-inhibited microcosms had comparable potential methylation rate constants (0.003d(-1) and 0.002d(-1), respectively). The inhibition of methanogens stimulated net methylation by inhibiting demethylationand by stimulating methylation along with SRB activity. The inhibition of both methanogens and SRB was found to enhance the iron reduction rates but did not completely stop MMHg production. The strong positive correlation between K(m) and Sulfate Reduction Rates (SRR) and between K(d) and Methane Production Rates (MPR) supports the involvement of SRB in Hg methylation and MPA in MMHg demethylation in the sediments. In contrast, the strong negative correlation between K(d) and Iron Reduction Rates (FeRR) shows that the increase in FeRR corresponds to a decrease in demethylation, indicating that iron reduction may influence net methylation in the SLR sediments by decreasing demethylation rather than favouring methylation.

Littoral Diatoms As Indicators of Recent Water and Sediment Contamination by Metals in Lakes

Journal of Environmental Monitoring : JEM. Mar, 2011  |  Pubmed ID: 21184001

We studied the response of benthic diatoms to recent metal contamination in littoral cores collected at 25 sites in 11 lakes situated at different distances from a smelter in the Rouyn-Noranda mining region (Quebec). Diatom response was described in terms of density, diversity, and taxonomic composition of the entire assemblages and as abundance of individual indicator taxa. Metal concentrations were measured in sediment and in the overlying water (as total dissolved and as free-ions). Sediment metal contamination was significantly higher in lakes located <10 km from the smelters than in lakes farther away. Such difference was not significant when metal concentrations in the overlying water were considered. Metal contamination did not affect diatom density, which indeed was highest in the most contaminated lake. Diversity (either measured as number of taxa or as Shannon and evenness indices) was instead significantly higher in lakes close to the smelter than elsewhere. Redundancy analysis indicated that diatom composition changed along a gradient in alkalinity (CO₃) and one in sediment metal contamination (Cd, Hg, Cu). We identified three diatom taxa (Fragilaria construens var. venter, F. construens var. pumila, and Brachysira vitrea) that increased in relative and absolute abundance with metal contamination. Benthic diatom responses at the community (density, diversity, assemblage composition) and population levels (abundance of selected benthic taxa) were stronger to the sediment metal contamination than to the contamination of overlying water. Comparisons with available literature indicated that, for monitoring recent sediment contamination, diatoms in littoral sediments are preferable to invertebrates that mostly respond to overlying water. Diatoms in littoral cores are therefore unique as tools for monitoring recent contamination of lake sediments.

Immunogenicity and Tolerability of an Inactivated and Adjuvanted Pandemic H1N1 Influenza Vaccine, in HIV-1-infected Patients

Vaccine. Feb, 2011  |  Pubmed ID: 21185423

We evaluated the efficacy and tolerability of a single dose of the split virion AS03-adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in 84 HIV-1 infected individuals. Antibody titers were determined by hemagglutination inhibition assay and by microneutralization. Vaccine was well tolerated. At 21 days post vaccination, 56 (67%) patients had seroconverted. There was no correlation between baseline CD4 cell count (p=0.539) or HIV viral load (p=0.381) and immune response. Other vaccine strategies should be evaluated in this HIV population, to improve response rates.

Gamma-ray Flares from the Crab Nebula

Science (New York, N.Y.). Feb, 2011  |  Pubmed ID: 21212321

A young and energetic pulsar powers the well-known Crab Nebula. Here, we describe two separate gamma-ray (photon energy greater than 100 mega-electron volts) flares from this source detected by the Large Area Telescope on board the Fermi Gamma-ray Space Telescope. The first flare occurred in February 2009 and lasted approximately 16 days. The second flare was detected in September 2010 and lasted approximately 4 days. During these outbursts, the gamma-ray flux from the nebula increased by factors of four and six, respectively. The brevity of the flares implies that the gamma rays were emitted via synchrotron radiation from peta-electron-volt (10(15) electron volts) electrons in a region smaller than 1.4 × 10(-2) parsecs. These are the highest-energy particles that can be associated with a discrete astronomical source, and they pose challenges to particle acceleration theory.

Glomerular Filtration Rate Predicts Arterial Events in Women with Systemic Lupus Erythematosus

Rheumatology (Oxford, England). Apr, 2011  |  Pubmed ID: 21156670

To determine whether renal function predicts the development of cardiovascular disease and other arterial vascular events in patients with SLE.

Healthcare Cost and Loss of Productivity in a Canadian Population of Patients with and Without Lupus Nephritis

The Journal of Rheumatology. Apr, 2011  |  Pubmed ID: 21159829

To compare the healthcare cost and loss of productivity in patients with systemic lupus erythematosus (SLE) with (LN) and without lupus nephritis (lupus nephritis-negative, LNN).

International Consensus for a Definition of Disease Flare in Lupus

Lupus. Apr, 2011  |  Pubmed ID: 21148601

The Lupus Foundation of America (LFA) convened an international working group to obtain a consensus definition of disease flare in lupus. With help from the Paediatric Rheumatology International Trials Organization (PRINTO), two web-based Delphi surveys of physicians were conducted. Subsequently, the LFA held a second consensus conference followed by a third Delphi survey to reach a community-wide agreement for flare definition. Sixty-nine of the 120 (57.5%) polled physicians responded to the first survey. Fifty-nine of the responses were available to draft 12 preliminary statements, which were circulated in the second survey. Eighty-seven of 118 (74%) physicians completed the second survey, with an agreement of 70% for 9/12 (75%) statements. During the second conference, three alternative flare definitions were consolidated and sent back to the international community. One hundred and sixteen of 146 (79.5%) responded, with agreement by 71/116 (61%) for the following definition: "A flare is a measurable increase in disease activity in one or more organ systems involving new or worse clinical signs and symptoms and/or laboratory measurements. It must be considered clinically significant by the assessor and usually there would be at least consideration of a change or an increase in treatment." The LFA proposes this definition for lupus flare on the basis of its high face validity.

Assessment of a Motivational Interviewing Curriculum for Year 3 Medical Students Using a Standardized Patient Case

Patient Education and Counseling. Jul, 2011  |  Pubmed ID: 21123019

We sought to evaluate a year 3 motivational interviewing (MI) curriculum using a standardized patient case.

Host Resistance to Malaria: Using Mouse Models to Explore the Host Response

Mammalian Genome : Official Journal of the International Mammalian Genome Society. Feb, 2011  |  Pubmed ID: 21116636

Malaria is a disease that infects over 500 million people, causing at least 1 million deaths every year, with the majority occurring in developing countries. The current antimalarial arsenal is becoming dulled due to the rapid rate of resistance of the parasite. However, in populations living in malaria-endemic regions there are many examples of genetic-based resistance to the severe effects of the parasite Plasmodium. Defining the genetic factors behind host resistance has been an area of great scientific interest over the last few decades; this review summarizes the current knowledge of the genetic loci involved. Perhaps the lessons learned from the natural variation in both the human populations and experimental mouse models of infection may pave the way for novel resistance-proof antimalarials.

Medication Use in Systemic Lupus Erythematosus

The Journal of Rheumatology. Feb, 2011  |  Pubmed ID: 21078722

To evaluate factors affecting therapeutic approaches used in clinical practice for the management of systemic lupus erythematosus (SLE), in a multicenter cohort.

Blood-brain Barrier Disruption in the Treatment of Brain Tumors

Methods in Molecular Biology (Clifton, N.J.). 2011  |  Pubmed ID: 21082387

Standard chemotherapy administered systemically has a limited efficacy in the treatment of brain tumors. One of the major obstacles in the treatment of brain neoplasias is the impediment to delivery across the intact blood-brain barrier (BBB). Many innovative approaches have been developed to circumvent this obstacle. One such strategy is BBB disruption (BBBD), which successfully increases the delivery of antineoplastic agents to the central nervous system (CNS). This chapter describes the application of the BBBD technique in rats. Different methods to evaluate and measure BBB permeability following hyperosmolar mannitol infusion including Evans blue staining, albumin immunohistochemistry, and dynamic magnetic resonance imaging are also described.

Docosahexaenoic Acid Derivative Prevents Inflammation and Hyperreactivity in Lung: Implication of PKC-Potentiated Inhibitory Protein for Heterotrimeric Myosin Light Chain Phosphatase of 17 KD in Asthma

American Journal of Respiratory Cell and Molecular Biology. Aug, 2011  |  Pubmed ID: 21057106

The effects of a newly synthesized docosahexaenoic acid (DHA) derivative, CRBM-0244, on lung inflammation and airway hyperresponsiveness were determined in an in vitro model of TNF-α-stimulated human bronchi and in an in vivo model of allergic asthma. Mechanical tension measurements revealed that CRBM-0244 prevented bronchial hyperresponsiveness in TNF-α-pretreated human bronchi. Moreover, treatment with CRBM-0244 resulted in a decrease in NF-κB activation and cyclooxygenase-2 (COX-2) overexpression triggered by TNF-α. The inhibition of peroxisome proliferator-activated receptor-γ with GW9662 abolished the CRBM-0244-mediated anti-inflammatory effects. CRBM-0244 reduced the Ca(2+) sensitivity of bronchial smooth muscle through a decrease in the phosphorylation and expression of the PKC-potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17 kDa (CPI-17). Results also revealed an overexpression of CPI-17 protein in lung biopsies derived from patients with asthma. Furthermore, the presence of specialized enzymes such as 5-lipoxygenase and 15-lipoxygenase in the lung may convert CRBM-0244 into active mediators, leading to the resolution of inflammation. The in vivo anti-inflammatory properties of CRBM-0244 were also investigated in a guinea pig model of allergic asthma. After oral administration of CRBM-0244, airway leukocyte recruitment, airway mucus, ovalbumin-specific IgE, and proinflammatory markers such as TNF-α and COX-2 were markedly reduced. Hence, CRBM-0244 treatment prevents airway hyperresponsiveness, Ca(2+) hypersensitivity, and the overexpression of CPI-17 in lung tissue. Together, these findings provide key evidence regarding the mode of action of CRBM-0244 in the lung, and point to new therapeutic strategies for modulating inflammation in patients with asthma.

Characterization of the Covalent Binding of N-phenyl-N'-(2-chloroethyl)ureas to {beta}-tubulin: Importance of Glu198 in Microtubule Stability

The Journal of Pharmacology and Experimental Therapeutics. Feb, 2011  |  Pubmed ID: 20978170

N-Phenyl-N'-(2-chloroethyl)ureas (CEUs) are antimicrotubule agents interacting covalently with β-tubulin near the colchicine-binding site (C-BS). Glutamyl 198 residue in β-tubulin (Glu198), which is adjacent to the C-BS behind the two potent nucleophilic residues, Cys239 and Cys354, has been shown to covalently react with 1-(2-chloroethyl)-3-(4-iodophenyl)urea (ICEU). By use of mass spectrometry, we have now identified residues in β-tubulin that have become modified irreversibly by 1-(2-chloroethyl)-3-[3-(5-hydroxypentyl)phenyl]urea (HPCEU), 1-[4-(3-hydroxy-4-methoxystyryl)phenyl]-3-(2-chloroethyl)urea (4ZCombCEU), and N,N'-ethylenebis(iodoacetamide) (EBI). The binding of HPCEU and 4ZCombCEU to β-tubulin resulted in the acylation of Glu198, a protein modification of uncommon occurrence in living cells. Prototypical CEUs then were used as molecular probes to assess, in mouse B16F0 and human MDA-MB-231 cells, the role of Glu198 in microtubule stability. For that purpose, we studied the effect of Glu198 modification by ICEU, HPCEU, and 4ZCombCEU on the acetylation of Lys40 on α-tubulin, a key indicator of microtubule stability. We show that modification of Glu198 by prototypical CEUs correlates with a decrease in Lys40 acetylation, as observed also with other microtubule depolymerizing agents. Therefore, CEU affects the stability and the dynamics of microtubule, likewise a E198G mutation, which is unusual for xenobiotics. We demonstrate for the first time that EBI forms an intramolecular cross-link between Cys239 and Cys354 of β-tubulin in living cells. This work establishes a novel basis for the development of future chemotherapeutic agents and provides a framework for the design of molecules useful for studying the role of Asp and Glu residues in the structure/function and the biological activity of several cellular proteins under physiological conditions.

A Targeted Association Study in Systemic Lupus Erythematosus Identifies Multiple Susceptibility Alleles

Genes and Immunity. Jan, 2011  |  Pubmed ID: 20962850

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Multiple genetic and environmental factors contribute to the pathogenesis of this disease. Recent genome-wide association studies have added substantially to the number of genes associated with SLE. To replicate some of these susceptibility loci, single-nucleotide polymorphisms reported to be associated to SLE were evaluated in a cohort of 245 well-phenotyped Canadian SLE trios. Our results replicate previously reported associations to alleles of interferon regulatory factor 5 (IRF5), major histocompatibility complex (MHC), tumor necrosis factor (ligand) superfamily member 4 (TNFSF4), Kell blood group complex subunit-related family member 6 (XKR6), B-cell scaffold protein with ankyrin repeats 1 (BANK1), protein tyrosine phosphatase non-receptor type 22 (PTPN22), ubiquitin-conjugating enzyme E2L 3 (UBE2L3) and islet cell autoantigen 1 (ICA1). We also identify putative associations to cytotoxic T-lymphocyte-associated protein 4 (CTLA4), a gene associated with several autoimmune disorders, and ERBB3, a locus on 12q13 that was previously reported to be associated with type 1 diabetes. This study confirms the existence of multiple genetic risk factors for SLE, and supports the notion that some risk factors for SLE are shared with other inflammatory disorders.

Effect of Simulated Masticatory Loading on the Retention of Stud Attachments for Implant Overdentures

Journal of Oral Rehabilitation. Mar, 2011  |  Pubmed ID: 20819139

This study assessed the effect of simulated mastication on the retention of two stud attachment systems for 2-implants overdentures. Sixteen specimens, each simulating an edentulous ridge with implants and an overdenture were divided into two groups, according to the attachment system: Group I (Nobel Biocare ball-socket attachments) and Group II (Locator attachments). Retention forces were measured before and after 400,000 simulated masticatory loads in a customised device. Data were compared by two-way anova followed by Bonferroni test (α = 0·05). Group I presented significantly lower retention forces (Newtons) than Group II at baseline (10·6 ± 3·6 and 66·4 ± 16·0, respectively). However, differences were not significant after 400,000 loads (7·9 ± 4·3 and 21·6 ± 17·0). The number of cycles did not influence the measurements in Group I, whereas a non-linear descending curve was found for Group II. It was concluded that simulated mastication resulted in minor changes for the ball attachment tested. Nevertheless, it reduced the retention of Locator attachments to 40% of the baseline values, what suggests that mastication is a major factor associated with maintenance needs for this system.

Comparative Oral Bioavailability of Non-fixed and Fixed Combinations of Artesunate and Amodiaquine in Healthy Indian Male Volunteers

European Journal of Clinical Pharmacology. Mar, 2011  |  Pubmed ID: 20949263

The aim of the present study was to compare the pharmacokinetic properties, bioavailability and tolerability of artesunate (AS) and amodiaquine (AQ) administered as a fixed-dose combination (Amonate FDC tablets; Dafra Pharma, Turnhout, Belgium) or as a non-fixed dose combination of separate AS tablets (Arsuamoon; Guilin Pharmaceutical Co, Shanghai, China) and AQ tablets (Flavoquine; Sanofi-Aventis, Paris, France).

Fused-core Silica Column Ultra-performance Liquid Chromatography-ion Trap Tandem Mass Spectrometry for Determination of Global DNA Methylation Status

Analytical Biochemistry. Feb, 2011  |  Pubmed ID: 20950581

Epigenetic modifications, such as DNA methylation, play key roles in transcriptional regulation of gene expression. More recently, global DNA methylation levels have been documented to be altered in several diseases, including cancer, and as the result of exposure to environmental toxicants. Based on the potential use of global DNA methylation status as a biomarker of disease status and exposure to environmental toxicants, we sought to develop a rapid, sensitive, and precise analytical method for the quantitative measurement of global DNA methylation status using ultra-performance liquid chromatography with detection by ion trap tandem mass spectrometry. Using a fused-core silica column, 2'-deoxyguanosine (2dG) and 5-methyl-2'-deoxycytidine (5mdC) were resolved in less than 1 min with detection limits of 0.54 and 1.47 fmol for 5mdC and 2dG, respectively. The accuracy of detection was 95% or higher, and the day-to-day coefficient of variation was found to be 3.8%. The method was validated by quantification of global DNA methylation status following treatment of cells with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine, which reduced DNA methylation from 3.1% in control cells to 1.1% in treated cells. The sensitivity and high throughput of this method rend it suitable for large-scale analysis of epidemiological and clinical DNA samples.

An Assessment of Disease Flare in Patients with Systemic Lupus Erythematosus: a Comparison of BILAG 2004 and the Flare Version of SELENA

Annals of the Rheumatic Diseases. Jan, 2011  |  Pubmed ID: 20833737

To compare the British Isles Lupus Assessment Group (BILAG) 2004, the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) flare index (SFI) and physician's global assessment (PGA) in assessing flares of disease activity in patients with systemic lupus erythematosus (SLE).

Search for Dilepton Resonances in Pp Collisions at ˆ�s=7 TeV with the ATLAS Detector

Physical Review Letters. Dec, 2011  |  Pubmed ID: 22243306

This Letter reports on a search for narrow high-mass resonances decaying into dilepton final states. The data were recorded by the ATLAS experiment in pp collisions at √s=7  TeV at the Large Hadron Collider and correspond to a total integrated luminosity of 1.08 (1.21)  fb(-1) in the e(+)e(-) (μ(+)μ(-)) channel. No statistically significant excess above the standard model expectation is observed and upper limits are set at the 95% C.L. on the cross section times branching fraction of Z' resonances and Randall-Sundrum gravitons decaying into dileptons as a function of the resonance mass. A lower mass limit of 1.83 TeV on the sequential standard model Z' boson is set. A Randall-Sundrum graviton with coupling k/M(Pl)=0.1 is excluded at 95% C.L. for masses below 1.63 TeV.

Search for a Standard Model Higgs Boson in the H→ZZ→ℓ(+)ℓ(-)νν Decay Channel with the ATLAS Detector

Physical Review Letters. Nov, 2011  |  Pubmed ID: 22182021

A search for a heavy standard model Higgs boson decaying via H→ZZ→→ℓ(+)ℓ(-)νν, where ℓ=e, μ, is presented. It is based on proton-proton collision data at √s=7 TeV, collected by the ATLAS experiment at the LHC in the first half of 2011 and corresponding to an integrated luminosity of 1.04 fb(-1). The data are compared to the expected standard model backgrounds. The data and the background expectations are found to be in agreement and upper limits are placed on the Higgs boson production cross section over the entire mass window considered; in particular, the production of a standard model Higgs boson is excluded in the region 340

Search for the Higgs Boson in the H→WW→lνjj Decay Channel in Pp Collisions at ˆ�s=7 TeV with the ATLAS Detector

Physical Review Letters. Dec, 2011  |  Pubmed ID: 22182080

A search for a Higgs boson has been performed in the H→WW→ℓνjj channel in 1.04 fb(-1) of pp collision data at √s=7 TeV recorded with the ATLAS detector at the Large Hadron Collider. No significant excess of events is observed over the expected background and limits on the Higgs boson production cross section are derived for a Higgs boson mass in the range 240 GeV

Identification of Loci Controlling Restriction of Parasite Growth in Experimental Taenia Crassiceps Cysticercosis

PLoS Neglected Tropical Diseases. Dec, 2011  |  Pubmed ID: 22206032

Human neurocysticercosis (NC) caused by Taenia solium is a parasitic disease of the central nervous system that is endemic in many developing countries. In this study, a genetic approach using the murine intraperitoneal cysticercosis caused by the related cestode Taenia crassiceps was employed to identify host factors that regulate the establishment and proliferation of the parasite. A/J mice are permissive to T. crassiceps infection while C57BL/6J mice (B6) are comparatively restrictive, with a 10-fold difference in numbers of peritoneal cysticerci recovered 30 days after infection. The genetic basis of this inter-strain difference was explored using 34 AcB/BcA recombinant congenic strains derived from A/J and B6 progenitors, that were phenotyped for T. crassiceps replication. In agreement with their genetic background, most AcB strains (A/J-derived) were found to be permissive to infection while most BcA strains (B6-derived) were restrictive with the exception of a few discordant strains, together suggesting a possible simple genetic control. Initial haplotype association mapping using >1200 informative SNPs pointed to linkages on chromosomes 2 (proximal) and 6 as controlling parasite replication in the AcB/BcA panel. Additional linkage analysis by genome scan in informative [AcB55xDBA/2]F1 and F2 mice (derived from the discordant AcB55 strain), confirmed the effect of chromosome 2 on parasite replication, and further delineated a major locus (LOD = 4.76, p<0.01; peak marker D2Mit295, 29.7 Mb) that we designate Tccr1 (T. crassiceps cysticercosis restrictive locus 1). Resistance alleles at Tccr1 are derived from AcB55 and are inherited in a dominant fashion. Scrutiny of the minimal genetic interval reveals overlap of Tccr1 with other host resistance loci mapped to this region, most notably the defective Hc/C5 allele which segregates both in the AcB/BcA set and in the AcB55xDBA/2 cross. These results strongly suggest that the complement component 5 (C5) plays a critical role in early protective inflammatory response to infection with T. crassiceps.

[In Process Citation]

The Canadian Journal of Hospital Pharmacy. Mar, 2011  |  Pubmed ID: 22479039

Few data are available on the use and consequences of decentralized automated dispensing cabinets (ADCs) in institutional settings.

The Deadly Effects of "nonlethal" Predators

Ecology. Nov, 2011  |  Pubmed ID: 22164828

Nonconsumptive predator effects are widespread and include plasticity as well as general stress responses. Caged predators are often used to estimate nonconsumptive effects, and numerous studies have focused on the larval stages of animals with complex life cycles. However, few of these studies test whether nonconsumptive predator effects, including stress responses, are exclusively sublethal. Nor have they assessed whether these effects extend beyond the larval stage, affecting success during stressful life-history transitions such as metamorphosis. We conducted experiments with larvae of a dragonfly (Leucorrhinia intacta) that exhibits predator-induced plasticity to assess whether the mere presence of predators affects larval survivorship, metamorphosis, and adult body size. Larvae exposed to caged predators with no ability to attack them had higher levels of mortality. In the second experiment, larvae reared with caged predators had higher rates of metamorphic failure, but there was no effect on adult body size. Our results suggest that stress responses induced by exposure to predator cues increase the vulnerability of prey to other mortality factors, and that mere exposure to predators can result in significant increases in mortality.

Prevalence and Risk Factors for Liver Biochemical Abnormalities in Canadian Patients with Systemic Lupus Erythematosus

The Journal of Rheumatology. Feb, 2012  |  Pubmed ID: 22174205

To determine the prevalence of abnormal liver enzymes in patients with systemic lupus erythematosus (SLE) and whether further investigations were done, and the differences in SLE-related and/or metabolic factors in patients with and without liver biochemical abnormalities.

Group Dynamics and Landscape Features Constrain the Exploration of Herds in Fusion-fission Societies: the Case of European Roe Deer

PloS One. 2012  |  Pubmed ID: 22479652

Despite the large number of movement studies, the constraints that grouping imposes on movement decisions remain essentially unexplored, even for highly social species. Such constraints could be key, however, to understanding the dynamics and spatial organisation of species living in group fusion-fission systems. We investigated the winter movements (speed and diffusion coefficient) of groups of free-ranging roe deer (Capreolus capreolus), in an agricultural landscape characterised by a mosaic of food and foodless patches. Most groups were short-lived units that merged and split up frequently during the course of a day. Deer groups decreased their speed and diffusion rate in areas where food patches were abundant, as well as when travelling close to main roads and crest lines and far from forests. While accounting for these behavioural adjustments to habitat features, our study revealed some constraints imposed by group foraging: large groups reached the limit of their diffusion rate faster than small groups. The ability of individuals to move rapidly to new foraging locations following patch depression thus decreases with group size. Our results highlight the importance of considering both habitat heterogeneity and group dynamics when predicting the movements of individuals in group fusion-fission societies. Further, we provide empirical evidence that group cohesion can restrain movement and, therefore, the speed at which group members can explore their environment. When maintaining cohesion reduces foraging gains because of movement constraints, leaving the group may become a fitness-rewarding decision, especially when individuals can join other groups located nearby, which would tend to maintain highly dynamical group fusion-fission systems. Our findings also provide the basis for new hypotheses explaining a broad range of ecological patterns, such as the broader diet and longer residency time reported for larger herbivore groups.

Seizure Disorders in Systemic Lupus Erythematosus Results from an International, Prospective, Inception Cohort Study

Annals of the Rheumatic Diseases. Apr, 2012  |  Pubmed ID: 22492779

OBJECTIVE: The aim of this study was to describe the frequency, attribution, outcome and predictors of seizures in systemic lupus erythematosus (SLE).METHODS: The Systemic Lupus International Collaborating Clinics, or SLICC, performed a prospective inception cohort study. Demographic variables, global SLE disease activity (SLE Disease Activity Index 2000), cumulative organ damage (SLICC/American College of Rheumatology Damage Index (SDI)) and neuropsychiatric events were recorded at enrolment and annually. Lupus anticoagulant, anticardiolipin, anti-β(2) glycoprotein-I, antiribosomal P and anti-NR2 glutamate receptor antibodies were measured at enrolment. Physician outcomes of seizures were recorded. Patient outcomes were derived from the SF-36 (36-Item Short Form Health Survey) mental component summary and physical component summary scores. Statistical analyses included Cox and linear regressions.RESULTS: The cohort was 89.4% female with a mean follow-up of 3.5±2.9 years. Of 1631 patients, 75 (4.6%) had ≥1 seizure, the majority around the time of SLE diagnosis. Multivariate analysis indicated a higher risk of seizures with African race/ethnicity (HR (CI): 1.97 (1.07 to 3.63); p=0.03) and lower education status (1.97 (1.21 to 3.19); p<0.01). Higher damage scores (without neuropsychiatric variables) were associated with an increased risk of subsequent seizures (SDI=1:3.93 (1.46 to 10.55); SDI=2 or 3:1.57 (0.32 to 7.65); SDI≥4:7.86 (0.89 to 69.06); p=0.03). There was an association with disease activity but not with autoantibodies. Seizures attributed to SLE frequently resolved (59/78 (76%)) in the absence of antiseizure drugs. There was no significant impact on the mental component summary or physical component summary scores. Antimalarial drugs in the absence of immunosuppressive agents were associated with reduced seizure risk (0.07 (0.01 to 0.66); p=0.03).CONCLUSION: Seizures occurred close to SLE diagnosis, in patients with African race/ethnicity, lower educational status and cumulative organ damage. Most seizures resolved without a negative impact on health-related quality of life. Antimalarial drugs were associated with a protective effect.

Interventions for Improving Outcomes in Patients with Multimorbidity in Primary Care and Community Settings

Cochrane Database of Systematic Reviews (Online). 2012  |  Pubmed ID: 22513941

Many people with chronic disease have more than one chronic condition, which is referred to as multimorbidity. While this is not a new phenomenon, there is greater recognition of its impact and the importance of improving outcomes for individuals affected. Research in the area to date has focused mainly on descriptive epidemiology and impact assessment. There has been limited exploration of the effectiveness of interventions for multimorbidity.

Regulation of Neuronal MRNA Translation by CaM-Kinase I Phosphorylation of EIF4GII

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Apr, 2012  |  Pubmed ID: 22514323

Ca(2+)/calmodulin-dependent kinases (CaMKs) are essential for neuronal development and plasticity, processes requiring de novo protein synthesis. Roles for CaMKs in modulating gene transcription are well established, but their involvement in mRNA translation is evolving. Here we report that activity-dependent translational initiation in cultured rat hippocampal neurons is enhanced by CaMKI-mediated phosphorylation of Ser1156 in eukaryotic initiation factor eIF4GII (4GII). Treatment with bicuculline or gabazine to enhance neuronal activity promotes recruitment of wild-type 4GII, but not the 4GII S1156A mutant or 4GI, to the heterotrimeric eIF4F (4F) complex that assembles at the 5' cap structure (m(7)GTP) of mRNA to initiate ribosomal scanning. Recruitment of 4GII to 4F is suppressed by pharmacological inhibition (STO-609) of CaM kinase kinase, the upstream activator of CaMKI. Post hoc in vitro CaMKI phosphorylation assays confirm that activity promotes phosphorylation of S1156 in transfected 4GII in neurons. Changes in cap-dependent and cap-independent translation were assessed using a bicistronic luciferase reporter transfected into neurons. Activity upregulates cap-dependent translation, and RNAi knockdown of CaMKIβ and γ isoforms, but not α or δ, led to its attenuation as did blockade of NMDA receptors. Furthermore, RNAi knockdown of 4GII attenuates cap-dependent translation and reduces density of dendritic filopodia and spine formation without effect on dendritic arborization. Together, our results provide a mechanistic link between Ca(2+) influx due to neuronal activity and regulation of cap-dependent RNA translation via CaMKI activation and selective recruitment of phosphorylated 4GII to the 4F complex, which may function to regulate activity-dependent changes in spine density.

Synthesis, Antiproliferative Activity and Estrogen Receptor α Affinity of Novel Estradiol-linked Platinum(II) Complex Analogs to Carboplatin and Oxaliplatin. Potential Vector Complexes to Target Estrogen-dependent Tissues

European Journal of Medicinal Chemistry. Feb, 2012  |  Pubmed ID: 22209414

In the course of efforts to develop 17β-estradiol-linked to anticancer agents targeting estrogen-dependent tissue, we identified three estradiol-linked platinum(II) complex analogs to cisplatin (E-CDDP) derivatives namely: VP-128 (1), CD-38 (2) and JMP-39 (3) that exhibit potent in vitro and in vivo (for derivative VP-128) activity along with interaction with the estrogen receptor α (ERα). In this study, we prepared and biologically evaluated two novel classes of estradiol-linked platinum(II) complex analogs to carboplatin (E-CarboP, 1a-3a) and oxaliplatin (E-OxaP, 1b-3b). E-CarboP and E-OxaP were designed and based on the estradiol-linker scaffold of E-CDDP derivatives previously identified. Consequently, we assessed the importance of the nature of platinum(II) salt on the antiproliferative activity on MCF-7 and MDA-MB-231 human mammary carcinoma cell lines together with affinity for the ERα by replacing the dichloroplatinum(II) moiety by a cyclobutane-1,1-dicarboxylateplatinum(II) or an oxalateplatinum(II) moiety. Except for compound 3b which is inactive at the concentration tested, the antiproliferative activity of all compounds on both human mammary carcinomas cell lines are in micromolar range and are more active than carboplatin and oxaliplatin alone but less active that their E-CDDP counterparts (1-3). In addition, E-CarboP derivatives 1a-3a show very low affinity for ERα whereas E-OxaPs 1b and 2b show higher affinity for ERα than their parents E-CDDPs (1-2), suggesting that the nature of the platinum(II) salt involved in the vector complexes is extremely important to both retain significant antiproliferative activity and selectivity for the ERα and possibility to target estrogen-dependent tissues. Finally, E-OxaPs 1b and 2b are potentially promising alternatives vector complexes to target estrogen-dependent tissues.

Sexual Abuse

Pediatrics in Review / American Academy of Pediatrics. Jan, 2012  |  Pubmed ID: 22210930

Child sexual abuse is a common pediatric problem that concerns all pediatric health care providers. Management of child sexual abuse is multifaceted and multidisciplinary. Specialized health providers can provide consultation, but this availability does not minimize the role of the referring physician who often has ongoing contact with the family. Physicians are mandated to report cases of suspected or confirmed sexual abuse. In the majority of cases, a child’s statement about sexual abuse is the strongest evidence that abuse has occurred. Physical examination is normal in the majority of sexual abuse victims. Accurate, evidence-based interpretation of physical and laboratory findings is essential. Normal examinations, normal variants, and findings indicative of sexual contact must be differentiated. Forensic evidence collection and prophylactic treatments may be indicated when patients present within 72 hours of an abusive episode, and patients should be triaged accordingly. Potentially negative psychosocial outcomes should be addressed for patients and their families on initial evaluation and follow-up.

The Role of Nausea in Food Intake and Body Weight Suppression by Peripheral GLP-1 Receptor Agonists, Exendin-4 and Liraglutide

Neuropharmacology. Apr, 2012  |  Pubmed ID: 22227019

The FDA-approved glucagon-like-peptide-1 receptor (GLP-1R) agonists exendin-4 and liraglutide reduce food intake and body weight. Nausea is the most common adverse side effect reported with these GLP-1R agonists. Whether food intake suppression by exendin-4 and liraglutide occurs independently of nausea is unknown. Further, the neurophysiological mechanisms mediating the nausea associated with peripheral GLP-1R agonist use are poorly understood. Using two established rodent models of nausea [conditioned taste avoidance (CTA) and pica (ingestion of nonnutritive substances)], results show that all peripheral doses of exendin-4 that suppress food intake also produce CTA, whereas one dose of liraglutide suppresses intake without producing CTA. Chronic (12 days) daily peripheral administration of exendin-4 produces a progressive increase in pica coupled with stable, sustained food intake and body weight suppression, whereas the pica response and food intake reduction by daily liraglutide are more transient. Results demonstrate that the nausea response accompanying peripheral exendin-4 occurs via a vagal-independent pathway involving GLP-1R activation in the brain as the exendin-4-induced pica response is attenuated with CNS co-administration of the GLP-1R antagonist exendin-(9-39), but not by vagotomy. Direct administration of exendin-4 to the medial subnucleus of the nucleus tractus solitarius (mNTS), but not to the central nucleus of the amygdala, reduced food intake and produced a pica response, establishing the mNTS as a potential GLP-1R-expressing site mediating nausea responses associated with GLP-1R agonists.

The Blood-brain Barrier: Its Influence in the Treatment of Brain Tumors Metastases

Current Cancer Drug Targets. Mar, 2012  |  Pubmed ID: 22229251

Brain metastases represent the most common intracranial tumors in the adults. Its incidence outnumbers that of primary brain tumors by a tenfold factor. Estimated cumulative incidence is between 10 to 20% of all cancer patients, which would represent over 170 000 new cases in the US. Typically, patients with multiple brain metastases are exposed to whole brain radiation therapy, as a palliative measure. Resulting median survival improvement is modest, ranging from 3 to 5 months. This survival has not been altered despite 3 decades of clinical research aiming at improving outcome of these patients. The role of standard chemotherapy in the treatment of brain metastases has always been marginal, as the penetration of chemotherapy beyond the BBB (blood-brain barrier) is considered limited. Whereas the BBB is universally recognized as a physiological entity, its role in the treatment of brain metastases remains controversial. Metastatic lesions often depict a homogeneous intense enhancement on either CT or MRI, thus implying that the brain tumor barrier (BTB) is breached. Although there is no doubt that the BBB and BTB suffer from variable degrees of breach in integrity in the presence of malignant brain tumors, impediment to drug delivery remains, and strategy to optimize delivery must be considered if one is to really impact patient � s outcome in the treatment of these diseases. The intended purpose of this paper is to review current data on the role of the BBB in the treatment of CNS metastatic disease.

The Challenges of Implementing a "patient-oriented" Telepathology Network; the Eastern Québec Telepathology Project Experience

Analytical Cellular Pathology (Amsterdam). 2012  |  Pubmed ID: 22233700

The aim of the Eastern Québec telepathology project is to provide uniform diagnostic telepathology services across a huge geographic region with a low population density. This project is intended to provide surgeons and pathologists with frozen section and second opinion services anywhere and at any time across the entire region in order to avoid unnecessary patient transfer.

Periodic Emission from the Gamma-ray Binary 1FGL J1018.6-5856

Science (New York, N.Y.). Jan, 2012  |  Pubmed ID: 22246769

Gamma-ray binaries are stellar systems containing a neutron star or black hole, with gamma-ray emission produced by an interaction between the components. These systems are rare, even though binary evolution models predict dozens in our Galaxy. A search for gamma-ray binaries with the Fermi Large Area Telescope (LAT) shows that 1FGL J1018.6-5856 exhibits intensity and spectral modulation with a 16.6-day period. We identified a variable x-ray counterpart, which shows a sharp maximum coinciding with maximum gamma-ray emission, as well as an O6V((f)) star optical counterpart and a radio counterpart that is also apparently modulated on the orbital period. 1FGL J1018.6-5856 is thus a gamma-ray binary, and its detection suggests the presence of other fainter binaries in the Galaxy.

Photonics of a Conjugated Organometallic Pt-Ir Polymer and Its Model Compounds Exhibiting Hybrid CT Excited States

Macromolecular Rapid Communications. Apr, 2012  |  Pubmed ID: 22253217

Trans- dichlorobis(tri-n-butylphosphine)platinum(II) reacts with bis(2- phenylpyridinato)-(5,5'-diethynyl-2,2'-bipyridine)iridium(III) hexafluorophosphate to form the luminescent conjugated polymer poly[trans-[(5,5'-ethynyl-2,2'-bipyridine)bis(2- phenylpyridinato)-iridium(III)]bis(tri-n-butylphosphine)platinum(II)] hexafluorophosphate ([Pt]-[Ir])n. Gel permeation chromatography indicates a degree of polymerization of 9 inferring the presence of an oligomer. Comparison of the absorption and emission band positions and their temperature dependence, emission quantum yields, and lifetimes with those for models containing only the [Pt] or the [Ir] units indicates hybrid excited states including features from both chromophores.

[1,2,4]triazol-3-ylsulfanylmethyl)-3-phenyl-[1,2,4]oxadiazoles: Antagonists of the Wnt Pathway That Inhibit Tankyrases 1 and 2 Via Novel Adenosine Pocket Binding

Journal of Medicinal Chemistry. Feb, 2012  |  Pubmed ID: 22260203

The Wnt signaling pathway is critical to the regulation of key cellular processes. When deregulated, it has been shown to play a crucial role in the growth and progression of multiple human cancers. The identification of small molecule modulators of Wnt signaling has proven challenging, largely due to the relative paucity of druggable nodes in this pathway. Several recent publications have identified small molecule inhibitors of the Wnt pathway, and tankyrase (TNKS) inhibition has been demonstrated to antagonize Wnt signaling via axin stabilization. Herein, we report the early hit assessment of a series of compounds previously reported to antagonize Wnt signaling. We report the biophysical, computational characterization, structure-activity relationship, and physicochemical properties of a novel series of [1,2,4]triazol-3-ylsulfanylmethyl)-3-phenyl-[1,2,4]oxadiazole inhibitors of TNKS1 and 2. Furthermore, a cocrystal structure of compound 24 complexed to TNKS1 demonstrates an alternate binding mode for PARP family member proteins that does not involve interactions with the nicotinamide binding pocket.

Reliability of a Quantitative Clinical Posture Assessment Tool Among Persons with Idiopathic Scoliosis

Physiotherapy. Mar, 2012  |  Pubmed ID: 22265387

To determine overall, test-retest and inter-rater reliability of posture indices among persons with idiopathic scoliosis.

Canadian Task Force on Preventive Health Care: We're Back!

Canadian Family Physician Médecin De Famille Canadien. Jan, 2012  |  Pubmed ID: 22267610

A Universal RNA Polymerase II CTD Cycle is Orchestrated by Complex Interplays Between Kinase, Phosphatase, and Isomerase Enzymes Along Genes

Molecular Cell. Jan, 2012  |  Pubmed ID: 22284676

Transcription by RNA polymerase II (RNAPII) is coupled to mRNA processing and chromatin modifications via the C-terminal domain (CTD) of its largest subunit, consisting of multiple repeats of the heptapeptide YSPTSPS. Pioneering studies showed that CTD serines are differentially phosphorylated along genes in a prescribed pattern during the transcription cycle. Genome-wide analyses challenged this idea, suggesting that this cycle is not uniform among different genes. Moreover, the respective role of enzymes responsible for CTD modifications remains controversial. Here, we systematically profiled the location of the RNAPII phosphoisoforms in wild-type cells and mutants for most CTD modifying enzymes. Together with results of in vitro assays, these data reveal a complex interplay between the modifying enzymes, and provide evidence that the CTD cycle is uniform across genes. We also identify Ssu72 as the Ser7 phosphatase and show that proline isomerization is a key regulator of CTD dephosphorylation at the end of genes.

Glioblastoma Treatment: Bypassing the Toxicity of Platinum Compounds by Using Liposomal Formulation and Increasing Treatment Efficiency with Concomitant Radiotherapy

International Journal of Radiation Oncology, Biology, Physics. Jan, 2012  |  Pubmed ID: 22284691

PURPOSE: Treatments of glioblastoma with cisplatin or oxaliplatin only marginally improve the overall survival of patients and cause important side effects. To prevent adverse effects, improve delivery, and optimize the tumor response to treatment in combination with radiotherapy, a potential approach consists of incorporating the platinum agent in a liposome. METHODS AND MATERIALS: In this study, cisplatin, oxaliplatin, carboplatin, Lipoplatin (the liposomal formulation of cisplatin), and Lipoxal (the liposomal formulation of oxaliplatin) were tested on F98 glioma orthotopically implanted in Fischer rats. The platinum compounds were administered by intracarotid infusion and were assessed for the ability to reduce toxicity, improve cancer cell uptake, and increase survival of animals when combined or not combined with radiotherapy. RESULTS: The tumor uptake was 2.4-fold more important for Lipoxal than the liposome-free oxaliplatin. Lipoxal also improved the specificity of oxaliplatin as shown by a higher ratio of tumor to right hemisphere uptake. Surprisingly, Lipoplatin led to lower tumor uptake compared with cisplatin. However, Lipoplatin had the advantage of largely reducing the toxicity of cisplatin and allowed us to capitalize on the anticancer activity of this agent. CONCLUSION: Among the five platinum compounds tested, carboplatin showed the best increase in survival when combined with radiation for treatment of glioma implanted in Fischer rats.

Measurement of Separate Cosmic-ray Electron and Positron Spectra with the Fermi Large Area Telescope

Physical Review Letters. Jan, 2012  |  Pubmed ID: 22304252

We measured separate cosmic-ray electron and positron spectra with the Fermi Large Area Telescope. Because the instrument does not have an onboard magnet, we distinguish the two species by exploiting Earth's shadow, which is offset in opposite directions for opposite charges due to Earth's magnetic field. We estimate and subtract the cosmic-ray proton background using two different methods that produce consistent results. We report the electron-only spectrum, the positron-only spectrum, and the positron fraction between 20 and 200 GeV. We confirm that the fraction rises with energy in the 20-100 GeV range. The three new spectral points between 100 and 200 GeV are consistent with a fraction that is continuing to rise with energy.

Bronchial Inflammation Induced PKCζ Over-expression: Involvement in Mechanical Properties of Airway Smooth Muscle

Canadian Journal of Physiology and Pharmacology. Feb, 2012  |  Pubmed ID: 22324796

Protein kinase C variants (PKCs) have been involved in the control of airway smooth muscle (ASM) tone, and abnormalities in PKC-dependent signaling have been associated with respiratory diseases such as asthma. In this study, the role of atypical PKCζ in airway hyperresponsiveness was investigated, using an in-vitro model of TNFα-treated human bronchi and an in vivo guinea pig model of chronic asthma. Our results demonstrated that PKCζ-specific inhibition produced a significant increase in isoproterenol sensitivity in TNFα-treated bronchi and ovalbumin (OVA)-sensitized guinea pig bronchi. The role of epoxy-eicosanoids, known to exert anti-inflammatory effects in lung, on PKCζ expression and activity in these models was evaluated. An enhanced PKCζ protein expression was delineated in TNFα-treated bronchi when compared with control (untreated) and epoxy-eicosanoid-treated bronchi. Measurements of Ca(2+) sensitivity, performed in TNFα-treated bronchi, demonstrated that treatment with myristoylated (Myr) PKCζ peptide inhibitor resulted in significant reductions of pCa-induced tension. Epoxy-eicosanoid treatments had similar effects on Ca(2+) sensitivity in TNFα-treated bronchi. In control and epoxy-eicosanoid-treated bronchi, the phosphorylated forms of p38MAPK and CPI-17 were significantly decreased compared with the TNFα-treated bronchi. An enhanced expression of PKCζ was ascertained in our in-vivo model of allergic asthma. Hence an increased Ca(2+) sensitivity could be explained by the phosphorylation of p38-MAPK, which in turn leads to phosphorylation and activation of the CPI-17 regulatory protein. This process was reversed upon treatment with the Myr-PKCζ-peptide inhibitor. The present data provide relevant evidence regarding the role of PKCζ in human and rodent models of airways inflammation.

Ultrastructural Characterization of the Mesostriatal Dopamine Innervation in Mice, Including Two Mouse Lines of Conditional VGLUT2 Knockout in Dopamine Neurons

The European Journal of Neuroscience. Feb, 2012  |  Pubmed ID: 22330100

Despite the increasing use of genetically modified mice to investigate the dopamine (DA) system, little is known about the ultrastructural features of the striatal DA innervation in the mouse. This issue is particularly relevant in view of recent evidence for expression of the vesicular glutamate transporter 2 (VGLUT2) by a subset of mesencephalic DA neurons in mouse as well as rat. We used immuno-electron microscopy to characterize tyrosine hydroxylase (TH)-labeled terminals in the core and shell of nucleus accumbens and the neostriatum of two mouse lines in which the Vglut2 gene was selectively disrupted in DA neurons (cKO), their control littermates, and C57BL/6/J wild-type mice, aged P15 or adult. The three regions were also examined in cKO mice and their controls of both ages after dual TH-VGLUT2 immunolabeling. Irrespective of the region, age and genotype, the TH-immunoreactive varicosities appeared similar in size, vesicular content, percentage with mitochondria, and exceedingly low frequency of synaptic membrane specialization. No dually labeled axon terminals were found at either age in control or in cKO mice. Unless TH and VGLUT2 are segregated in different axon terminals of the same neurons, these results favor the view that the glutamatergic cophenotype of mesencephalic DA neurons is more important during the early development of these neurons than for the establishment of their scarce synaptic connectivity. They also suggest that, in mouse even more than rat, the mesostriatal DA system operates mainly through non-targeted release of DA, diffuse transmission and the maintenance of an ambient DA level.

Validation of the Disease Burden Morbidity Assessment by Self-report in a French-speaking Population

BMC Health Services Research. 2012  |  Pubmed ID: 22333434

The Disease Burden Morbidity Assessment (DBMA) is a self-report questionnaire used to estimate the disease burden experienced by patients. The aim of this study was to test and to measure the properties of the French translation of the DBMA (DBMA-Fv).

Patient-centered Care in Chronic Disease Management: A Thematic Analysis of the Literature in Family Medicine

Patient Education and Counseling. Feb, 2012  |  Pubmed ID: 22360841

OBJECTIVE: The objective was to provide a synthesis of the results of the research and discourse lines on main dimensions of patient-centered care in the context of chronic disease management in family medicine, building on Stewart et al.'s model. METHODS: We developed search strategies for the Medline, Embase, and Cochrane databases, from 1980 to April 2009. All articles addressing patient-centered care in the context of chronic disease management in family medicine were included. A thematic analysis was performed using mixed codification, based on Stewart's model of patient-centered care. RESULTS: Thirty-two articles were included. Six major themes emerged: (1) starting from the patient's situation; (2) legitimizing the illness experience; (3) acknowledging the patient's expertise; (4) offering realistic hope; (5) developing an ongoing partnership; (6) providing advocacy for the patient in the health care system. CONCLUSION: The context of chronic disease management brings forward new dimensions of patient-centered care such as legitimizing the illness experience, acknowledging patient expertise, offering hope and providing advocacy. PRACTICE IMPLICATIONS: Chronic disease management calls for the adaptation of the family physician's role to patients' fluctuating needs. Literature also suggests the involvement of the family physician in care transitions as a component of patient-centered care.

Brainstem Respiratory Oscillators Develop Independently of Neuronal Migration Defects in the Wnt/PCP Mouse Mutant Looptail

PloS One. 2012  |  Pubmed ID: 22363567

The proper development and maturation of neuronal circuits require precise migration of component neurons from their birthplace (germinal zone) to their final positions. Little is known about the effects of aberrant neuronal position on the functioning of organized neuronal groups, especially in mammals. Here, we investigated the formation and properties of brainstem respiratory neurons in looptail (Lp) mutant mice in which facial motor neurons closely apposed to some respiratory neurons fail to migrate due to loss of function of the Wnt/Planar Cell Polarity (PCP) protein Vangl2. Using calcium imaging and immunostaining on embryonic hindbrain preparations, we found that respiratory neurons constituting the embryonic parafacial oscillator (e-pF) settled at the ventral surface of the medulla in Vangl2(Lp/+) and Vangl2(Lp/Lp) embryos despite the failure of tangential migration of its normally adjacent facial motor nucleus. Anatomically, the e-pF neurons were displaced medially in Lp/+ embryos and rostro-medially Lp/Lp embryos. Pharmacological treatments showed that the e-pF oscillator exhibited characteristic network properties in both Lp/+ and Lp/Lp embryos. Furthermore, using hindbrain slices, we found that the other respiratory oscillator, the preBötzinger complex, was also anatomically and functionally established in Lp mutants. Importantly, the displaced e-pF oscillator established functional connections with the preBötC oscillator in Lp/+ mutants. Our data highlight the robustness of the developmental processes that assemble the neuronal networks mediating an essential physiological function.

Silver Binding by Humic Acid As Determined by Equilibrium Ion-Exchange and Dialysis

The Journal of Physical Chemistry. A. Mar, 2012  |  Pubmed ID: 22375620

One of the major challenges in environmental analytical chemistry is to develop methods for determining metal speciation in natural waters that contain low metal concentrations and dissolved organic matter (DOM). Because of its complex heterogeneous nature, metal binding to DOM cannot be predicted accurately using equilibrium models. Two independent speciation methods, the equilibrium ion-exchange technique (IET) and equilibrium dialysis (EqD), were used to determine silver binding by standard Suwannee River humic acid. Both approaches gave very similar results, although for a given silver loading, the concentration of free silver obtained by IET was somewhat higher than that determined by EqD. Our results suggest that any high-affinity binding sites present within the humic acid are likely saturated at [Ag(T)] > 10(-9) M. This comparison of free metal ion concentrations with two independent methods provides useful speciation information in the absence of reliable complexation constants for the reaction of silver with humic acid.

The Max B-HLH-LZ Can Transduce into Cells and Inhibit C-Myc Transcriptional Activities

PloS One. 2012  |  Pubmed ID: 22384171

The inhibition of the functions of c-Myc (endogenous and oncogenic) was recently shown to provide a spectacular therapeutic index in cancer mouse models, with complete tumor regression and minimal side-effects in normal tissues. This was achieved by the systemic and conditional expression of omomyc, the cDNA of a designed mutant of the b-HLH-LZ of c-Myc named Omomyc. The overall mode of action of Omomyc consists in the sequestration of Max and the concomitant competition of the Omomyc/Max complex with the endogenous c-Myc/Max heterodimer. This leads to the inhibition of the transactivation of Myc target genes involved in proliferation and metabolism. While this body of work has provided extraordinary insights to guide the future development of new cancer therapies that target c-Myc, Omomyc itself is not a therapeutic agent. In this context, we sought to exploit the use of a b-HLH-LZ to inhibit c-Myc in a cancer cell line in a more direct fashion. We demonstrate that the b-HLH-LZ domain of Max (Max*) behaves as a bona fide protein transduction domain (PTD) that can efficiently transduce across cellular membrane via through endocytosis and translocate to the nucleus. In addition, we show that the treatment of HeLa cells with Max* leads to a reduction of metabolism and proliferation rate. Accordingly, we observe a decrease of the population of HeLa cells in S phase, an accumulation in G1/G0 and the induction of apoptosis. In agreement with these phenotypic changes, we show by q-RT-PCR that the treatment of HeLa cells with Max* leads to the activation of the transcription c-Myc repressed genes as well as the repression of the expression of c-Myc activated genes. In addition to the novel discovery that the Max b-HLH-LZ is a PTD, our findings open up new avenues and strategies for the direct inhibition of c-Myc with b-HLH-LZ analogs.

Measurement of the ZZ Production Cross Section and Limits on Anomalous Neutral Triple Gauge Couplings in Proton-proton Collisions at Sqrt[s] = 7 TeV with the ATLAS Detector

Physical Review Letters. Jan, 2012  |  Pubmed ID: 22400826

A measurement of the ZZ production cross section in proton-proton collisions at sqrt[s] = 7 TeV using data corresponding to an integrated luminosity of 1.02 fb(-1) recorded by the ATLAS experiment at the LHC is presented. Twelve events containing two Z boson candidates decaying to electrons and/or muons are observed, with an expected background of 0.3 ± 0.3(stat)(-0.3)(+0.4)(syst) events. The cross section measured in a phase-space region with good detector acceptance and for dilepton masses within the range 66 to 116 GeV is σ(ZZ → ℓ+ ℓ- ℓ+ ℓ-)(fid) = 19.4(-5.2)(+6.3)(stat)(-0.7)(+0.9)(syst) ± 0.7(lumi) fb. The resulting total cross section for on-shell ZZ production, σ(ZZ)(tot) = 8.5(-2.3)(+2.7)(stat)(-0.3)(+0.4)(syst) ± 0.3(lumi) pb, is consistent with the standard model expectation of 6.5(-0.2)(+0.3) pb calculated at the next-to-leading order in QCD. Limits on anomalous neutral triple gauge boson couplings are derived.

Search for New Phenomena in Tt Events with Large Missing Transverse Momentum in Proton-proton Collisions at Sqrt[s] = 7 TeV with the ATLAS Detector

Physical Review Letters. Jan, 2012  |  Pubmed ID: 22400827

A search for new phenomena in tt events with large missing transverse momentum in proton-proton collisions at a center-of-mass energy of 7 TeV is presented. The measurement is based on 1.04 fb(-1) of data collected with the ATLAS detector at the LHC. Contributions to this final state may arise from a number of standard model extensions. The results are interpreted in terms of a model where new top-quark partners are pair produced and each decay to an on-shell top (or antitop) quark and a long-lived undetected neutral particle. The data are found to be consistent with standard model expectations. A limit at 95% confidence level is set excluding a cross section times branching ratio of 1.1 pb for a top-partner mass of 420 GeV and a neutral particle mass less than 10 GeV. In a model of exotic fourth generation quarks, top-partner masses are excluded up to 420 GeV and neutral particle masses up to 140 GeV.

Quantitative Paraspinal Muscle Measurements: Inter-Software Reliability and Agreement Using OsiriX and ImageJ

Physical Therapy. Apr, 2012  |  Pubmed ID: 22403091

BackgroundVariations in paraspinal muscle cross-sectional area (CSA) and composition, particularly of the multifidus muscle, have been of interest with respect to risk of, and recovery from, low back pain problems. Several investigators have reported on the reliability of such muscle measurements using various protocols and image analysis programs. However, there is no standard protocol for tissue segmentation, nor has there been an investigation of reliability or agreement of measurements using different software.ObjectiveThe purpose of this study was to provide a detailed muscle measurement protocol and determine the reliability and agreement of associated paraspinal muscle composition measurements obtained with 2 commonly used image analysis programs: OsiriX and ImageJ.DesignThis was a measurement reliability study. METHODS:/b>Lumbar magnetic resonance images of 30 individuals were randomly selected from a cohort of patients with various low back conditions. Muscle CSA and composition measurements were acquired from axial T2-weighted magnetic resonance images of the multifidus muscle, the erector spinae muscle, and the 2 muscles combined at L4-L5 and S1 for each participant. All measurements were repeated twice using each software program, at least 5 days apart. The assessor was blinded to all earlier measurements. RESULTS: /b>The intrarater reliability and standard error of measurement (SEM) were comparable for most measurements obtained using OsiriX or ImageJ, with reliability coefficients (intraclass correlation coefficients [ICCs]) varying between .77 and .99 for OsiriX and .78 and .99 for ImageJ. There was similarly excellent agreement between muscle composition measurements using the 2 software applications (inter-software ICCs=.81-.99).LimitationsThe high degree of inter-software measurement reliability may not generalize to protocols using other commercial or custom-made software. CONCLUSION:/b>The proposed method to investigate paraspinal muscle CSA, composition, and side-to-side asymmetry was highly reliable, with excellent agreement between the 2 software programs.

Down-regulation of OPA1 Alters Mouse Mitochondrial Morphology, PTP Function, and Cardiac Adaptation to Pressure Overload

Cardiovascular Research. Apr, 2012  |  Pubmed ID: 22406748

AIMS: The optic atrophy 1 (OPA1) protein is an essential protein involved in the fusion of the mitochondrial inner membrane. Despite its high level of expression, the role of OPA1 in the heart is largely unknown. We investigated the role of this protein in Opa1(+/-) mice, having a 50% reduction in OPA1 protein expression in cardiac tissue. METHODS AND RESULTS: In mutant mice, cardiac function assessed by echocardiography was not significantly different from that of the Opa1(+/+). Electron and fluorescence microscopy revealed altered morphology of the Opa1(+/-) mice mitochondrial network; unexpectedly, mitochondria were larger with the presence of clusters of fused mitochondria and altered cristae. In permeabilized mutant ventricular fibres, mitochondrial functional properties were maintained, but direct energy channelling between mitochondria and myofilaments was weakened. Importantly, the mitochondrial permeability transition pore (PTP) opening in isolated permeabilized cardiomyocytes and in isolated mitochondria was significantly less sensitive to mitochondrial calcium accumulation. Finally, 6 weeks after transversal aortic constriction, Opa1(+/-) hearts demonstrated hypertrophy almost two-fold higher (P< 0.01) than in wild-type mice with altered ejection fraction (decrease in 43 vs. 22% in Opa1(+/+) mice, P< 0.05). CONCLUSIONS: These results suggest that, in adult cardiomyocytes, OPA1 plays an important role in mitochondrial morphology and PTP functioning. These properties may be critical for cardiac function under conditions of chronic pressure overload.

A Systematic Review of Prevalence Studies on Multimorbidity: Toward a More Uniform Methodology

Annals of Family Medicine. Mar-Apr, 2012  |  Pubmed ID: 22412006

We sought to identify and compare studies reporting the prevalence of multimorbidity and to suggest methodologic aspects to be considered in the conduct of such studies.

Evaluation of Clinical Outcomes and Renal Vascular Pathology Among Patients with Lupus

Clinical Journal of the American Society of Nephrology : CJASN. Mar, 2012  |  Pubmed ID: 22442181

Background and objectivesThe objective of this study was to determine the clinical significance of renal vascular lesions in lupus nephritis.Design, setting, participants, & measurementsRenal vascular lesions defined as thrombotic microangiopathy, lupus vasculopathy, uncomplicated vascular immune deposits, and arterial sclerosis were evaluated in relation to renal and vascular morbidity and overall mortality.ResultsBiopsies from 161 patients revealed thrombotic microangiopathy (13), lupus vasculopathy (5), and arterial sclerosis (93). No renal vascular lesions were found in 24.8% of patients. At the time of biopsy, arterial sclerosis or lupus vasculopathy patients were older (arterial sclerosis=37.9±13.0 and lupus vasculopathy=44.4±8.9 versus controls=33.1±8.9 years, P<0.05), and the mean arterial pressure was higher in all groups compared with controls. Nephritis subtype, activity indices, and proteinuria were similar between groups, estimated GFR was lower in arterial sclerosis (70.5±33.3 versus 84.5±26.6 ml/min per 1.73 m(2), P=0.03), and chronicity index (thrombotic microangiopathy=3.5, lupus vasculopathy=4.5, and arterial sclerosis=2.5) was higher in all renal vascular lesions subgroups versus controls (1.0, P<0.05). In 133 patients with similar follow-up, the association between renal vascular lesions and vascular events was significant (Fisher exact test, P=0.002) and remained so after multivariate analysis (exact conditional scores test, P=0.04), where the difference between arterial sclerosis and uncomplicated vascular immune deposits was most noticeable (odds ratio [95% confidence interval]=8.35[0.98, 83.12], P=0.05). The associations between renal vascular lesions, renal outcomes, and death were not significant, likely because of insufficient power.ConclusionsRenal vascular lesions are common in SLE patients with nephritis and may be associated with arterial vascular events.

A Mine of Information: Benthic Algal Communities As Biomonitors of Metal Contamination from Abandoned Tailings

The Science of the Total Environment. Mar, 2012  |  Pubmed ID: 22459883

Various biomonitoring approaches were tested in the field to assess the response of natural periphythic algal communities to chronic metal contamination downstream from an abandoned mine tailings site. The accumulation of cadmium (Cd), copper (Cu), lead (Pb) and zinc (Zn) as well as the production of phytochelatins, the presence of diatom taxa known to tolerate high metal concentrations, diatom diversity and the presence of teratologies were determined. We observed highly significant relationships between intracellular metal and calculated free metal ion concentrations. Such relationships are often observed in laboratory studies but have been rarely validated in field studies. These results suggest that the concentration of metal inside the field-collected periphyton, regardless of its species composition, is a good indicator of exposure and is an interesting proxy for bioavailable metal concentrations in natural waters. The presence of teratologies and metal-tolerant taxa at our contaminated sites provided a clear indication that diatom communities were responding to this metal stress. A multi-metric approach integrating various bioassessment methods could be used for the field monitoring of metal contamination and the quantification of its effects.

Longitudinal Evolution of Risk of Coronary Heart Disease in Systemic Lupus Erythematosus

The Journal of Rheumatology. Apr, 2012  |  Pubmed ID: 22467935

OBJECTIVE: To produce evidence on the longitudinal evolution of risk factors for coronary heart disease (CHD) in patients with systemic lupus erythematosus (SLE). METHODS: Based on data for 115 patients from the Montreal General Hospital Lupus Clinic (1971-2003) and for 4367 control subjects from the Framingham Offspring Study (1971-1994), we investigated the temporal evolution of total serum cholesterol, systolic blood pressure (SBP), body mass index (BMI), blood glucose, and estimated risk for CHD (reflecting the balance of changes in different risk factors). In analyses limited to patients with SLE, we assessed the effect of SLE duration on each risk factor, adjusting for age, calendar time, sex, baseline level of the risk factor, and medication use. Next, we assessed how the adjusted difference in the values of the risk factors between SLE and controls changes over time. RESULTS: Among patients with SLE, longer disease duration was independently associated with higher SBP and blood glucose levels. Compared with controls, these patients appeared to have accelerated rates of increase in total cholesterol, blood glucose, and overall estimated CHD risk. The rate of increase in BMI was lower in patients with SLE than in controls. CONCLUSION: Elevated CHD risk in patients with SLE appears to be at least partially mediated by accelerated increases in some CHD risk factors, longitudinal trajectories of which increasingly diverge over time from those of population controls.

Healthcare-associated Bloodstream Infections Secondary to a Urinary Focus: the Québec Provincial Surveillance Results

Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. May, 2012  |  Pubmed ID: 22476271

Objective. Urinary tract infections (UTIs) are an important source of secondary healthcare-associated bloodstream infections (BSIs), where a potential for prevention exists. This study describes the epidemiology of BSIs secondary to a urinary source (U-BSIs) in the province of Québec and predictors of mortality. Design. Dynamic cohort of 9,377,830 patient-days followed through a provincial voluntary surveillance program targeting all episodes of healthcare-associated BSIs occurring in acute care hospitals. Setting. Sixty-one hospitals in Québec, followed between April 1, 2007, and March 31, 2010. Participants. Patients admitted to participating hospitals for 48 hours or longer. Methods. Descriptive statistics were used to summarize characteristics of U-BSIs and microorganisms involved. Wilcoxon and χ(2) tests were used to compare U-BSI episodes with other BSIs. Negative binomial regression was used to identify hospital characteristics associated with higher rates. We explored determinants of mortality using logistic regression. Results. Of the 7,217 reported BSIs, 1,510 were U-BSIs (21%), with an annual rate of 1.4 U-BSIs per 10,000 patient-days. A urinary device was used in 71% of U-BSI episodes. Identified institutional risk factors were average length of stay, teaching status, and hospital size. Increasing hospital size was influential only in nonteaching hospitals. Age, nonhematogenous neoplasia, Staphylococcus aureus, and Foley catheters were associated with mortality at 30 days. Conclusion. U-BSI characteristics suggest that urinary catheters may remain in patients for ease of care or because practitioners forget to remove them. Ongoing surveillance will enable hospitals to monitor trends in U-BSIs and impacts of process surveillance that will be implemented shortly.

Simultaneous Integrated Boost Using Intensity-modulated Radiotherapy Compared with Conventional Radiotherapy in Patients Treated with Concurrent Carboplatin and 5-fluorouracil for Locally Advanced Oropharyngeal Carcinoma

International Journal of Radiation Oncology, Biology, Physics. Feb, 2012  |  Pubmed ID: 21277695

To compare, in a retrospective study, the toxicity and efficacy of simultaneous integrated boost using intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) in patients treated with concomitant carboplatin and 5-fluorouracil for locally advanced oropharyngeal cancer.

The Role of Computed Tomography in the Management of the Neck After Chemoradiotherapy in Patients with Head-and-neck Cancer

International Journal of Radiation Oncology, Biology, Physics. Feb, 2012  |  Pubmed ID: 21310545

The aim of this study was to describe the outcome in patients with head-and neck-squamous cell carcinoma (HNSCC) followed up without neck dissection (ND) after concomitant chemoradiotherapy (CRT) based on computed tomography (CT) response. The second objective was to establish CT characteristics that can predict which patients can safely avoid ND.

Factors Associated with Weight Loss During Radiotherapy in Patients with Stage I or II Head and Neck Cancer

Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. Mar, 2012  |  Pubmed ID: 21424341

The purpose of the study was to identify factors associated with weight loss during radiotherapy (RT) in patients with stage I or II head and neck (HN) cancer.

Recognition Memory for Social and Non-social Odors: Differential Effects of Neurotoxic Lesions to the Hippocampus and Perirhinal Cortex

Neurobiology of Learning and Memory. Jan, 2012  |  Pubmed ID: 21930227

The contributions of the hippocampus (HC) and perirhinal cortex (PER) to recognition memory are currently topics of debate in neuroscience. Here we used a rapidly-learned (seconds) spontaneous novel odor recognition paradigm to assess the effects of pre-training N-methyl-D-aspartate lesions to the HC or PER on odor recognition memory. We tested memory for both social and non-social odor stimuli. Social odors were acquired from conspecifics, while non-social odors were household spices. Conspecific odor stimuli are ethologically-relevant and have a high degree of overlapping features compared to non-social household spices. Various retention intervals (5 min, 20 min, 1h, 24h, or 48 h) were used between study and test phases, each with a unique odor pair, to assess changes in novelty preference over time. Consistent with findings in other paradigms, modalities, and species, we found that HC lesions yielded no significant recognition memory deficits. In contrast, PER lesions caused significant deficits for social odor recognition memory at long retention intervals, demonstrating a critical role for PER in long-term memory for social odors. PER lesions had no effect on memory for non-social odors. The results are consistent with a general role for PER in long-term recognition memory for stimuli that have a high degree of overlapping features, which must be distinguished by conjunctive representations.

Epidemiology of Central Line-associated Bloodstream Infections in Quebec Intensive Care Units: A 6-year Review

American Journal of Infection Control. Apr, 2012  |  Pubmed ID: 21824682

The burden of central line-associated bloodstream infections (CLABSI) in Canadian intensive care units (ICUs) is not well established. The present study aimed to describe CLABSI epidemiology in Quebec ICUs during 2003-2009.

Hybrid Charged Heterometallic Pt-Ir Complexes: Tailoring Excited States by Taking the Best of Both Worlds

Chemical Communications (Cambridge, England). Jan, 2012  |  Pubmed ID: 22158686

The C≡C-linkage of Pt(PR(3))(2)(C≡CAr)(2) with (C^N)(2)Ir(N^N)(+) (C^N = 2-phenylpyridine; N^N = bipyridyl) leads to hetero-bi- and trimetallic species exhibiting photophysical properties reminiscent of both [Pt]- and [Ir]-containing moieties through the generation of a [Pt] → [Ir] charge transfer excited state.

Catecholamine-induced Cardiac Mitochondrial Dysfunction and MPTP Opening: Protective Effect of Curcumin

American Journal of Physiology. Heart and Circulatory Physiology. Feb, 2012  |  Pubmed ID: 22101527

The present study was designed to characterize the mitochondrial dysfunction induced by catecholamines and to investigate whether curcumin, a natural antioxidant, induces cardioprotective effects against catecholamine-induced cardiotoxicity by preserving mitochondrial function. Because mitochondria play a central role in ischemia and oxidative stress, we hypothesized that mitochondrial dysfunction is involved in catecholamine toxicity and in the potential protective effects of curcumin. Male Wistar rats received subcutaneous injection of 150 mg·kg(-1)·day(-1) isoprenaline (ISO) for two consecutive days with or without pretreatment with 60 mg·kg(-1)·day(-1) curcumin. Twenty four hours after, cardiac tissues were examined for apoptosis and oxidative stress. Expression of proteins involved in mitochondrial biogenesis and function were measured by real-time RT-PCR. Isolated mitochondria and permeabilized cardiac fibers were used for swelling and mitochondrial function experiments, respectively. Mitochondrial morphology and permeability transition pore (mPTP) opening were assessed by fluorescence in isolated cardiomyocytes. ISO treatment induced cell damage, oxidative stress, and apoptosis that were prevented by curcumin. Moreover, mitochondria seem to play an important role in these effects as respiration and mitochondrial swelling were increased following ISO treatment, these effects being again prevented by curcumin. Importantly, curcumin completely prevented the ISO-induced increase in mPTP calcium susceptibility in isolated cardiomyocytes without affecting mitochondrial biogenesis and mitochondrial network dynamic. The results unravel the importance of mitochondrial dysfunction in isoprenaline-induced cardiotoxicity as well as a new cardioprotective effect of curcumin through prevention of mitochondrial damage and mPTP opening.

Ionizing Radiation-induced Expression of INK4a/ARF in Murine Bone Marrow-derived Stromal Cell Populations Interferes with Bone Marrow Homeostasis

Blood. Jan, 2012  |  Pubmed ID: 22101896

Alterations of the BM microenvironment have been shown to occur after chemoradiotherapy, during aging, and after genetic manipulations of telomere length. Nevertheless, whether BM stromal cells adopt senescent features in response to these events is unknown. In the present study, we provide evidence that exposure to ionizing radiation (IR) leads murine stromal BM cells to express senescence markers, namely senescence-associated β-galactosidase and increased p16(INK4a)/p19(ARF) expression. Long (8 weeks) after exposure of mice to IR, we observed a reduction in the number of stromal cells derived from BM aspirates, an effect that we found to be absent in irradiated Ink4a/arf-knockout mice and to be mostly independent of the CFU potential of the stroma. Such a reduction in the number of BM stromal cells was specific, because stromal cells isolated from collagenase-treated bones were not reduced after IR. Surprisingly, we found that exposure to IR leads to a cellular nonautonomous and Ink4a/arf-dependent effect on lymphopoiesis. Overall, our results reveal the distinct sensitivity of BM stromal cell populations to IR and suggest that long-term residual damage to the BM microenvironment can influence hematopoiesis in an Ink4a/arf-dependent manner.

Seasonal Variations in Clostridium Difficile Infections Are Associated with Influenza and Respiratory Syncytial Virus Activity Independently of Antibiotic Prescriptions: a Time Series Analysis in Quebec, Canada

Antimicrobial Agents and Chemotherapy. Feb, 2012  |  Pubmed ID: 22106208

Seasonal variations in Clostridium difficile-associated diarrhea (CDAD), with a higher incidence occurring during winter months, have been reported. Although winter epidemics of respiratory viruses may be temporally associated with an increase in CDAD morbidity, we hypothesized that this association is mainly due to increased antibiotic use for respiratory infections. The objective of this study was to evaluate the effect of the two most frequent respiratory viruses (influenza virus and respiratory syncytial virus [RSV]) and antibiotics prescribed for respiratory infections (fluoroquinolones and macrolides) on the CDAD incidence in hospitals in the province of Québec, Canada. A multivariable Box-Jenkins transfer function model was built to relate monthly CDAD incidence to the monthly percentage of positive tests for influenza virus and RSV and monthly fluoroquinolone and macrolide prescriptions over a 4-year period (January 2005 to December 2008). Analysis showed that temporal variations in CDAD incidence followed temporal variations for influenza virus (P = 0.043), RSV (P = 0.004), and macrolide prescription (P = 0.05) time series with an average delay of 1 month and fluoroquinolone prescription time series with an average delay of 2 months (P = 0.01). We conclude that influenza virus and RSV circulation is independently associated with CDAD incidence after controlling for fluoroquinolone and macrolide use. This association was observed at an aggregated level and may be indicative of other phenomena occurring during wintertime.

Increased Lead Biomarker Levels Are Associated with Changes in Hormonal Response to Stress in Occupationally Exposed Male Participants

Environmental Health Perspectives. Feb, 2012  |  Pubmed ID: 22112310

Lead (Pb) exposure has been associated with a host of pathological conditions in humans. In rodents Pb exposure has been shown to alter the hypothalamic-pituitary-adrenal (HPA) axis function.Objective: We investigated the effects of lead on responses of the HPA axis to a psychosocial laboratory stressor administered to Pb-exposed workers.

Enrichment of Sulfate-reducing Bacteria and Resulting Mineral Formation in Media Mimicking Pore Water Metal Ion Concentrations and PH Conditions of Acidic Pit Lakes

FEMS Microbiology Ecology. Jan, 2012  |  Pubmed ID: 22066948

Acid mine drainage sites are extreme environments with high acidity and metal ion concentrations. Under anoxic conditions, microbial sulfate reduction may trigger the formation of secondary minerals as a result of H2S production and pH increase. This process was studied in batch experiments with enrichment cultures from acidic sediments of a pit lake using growth media set at different pH values and containing elevated concentrations of Fe²⁺ and Al³⁺. At initial pH values of 5 and 6, sulfate reduction occurred shortly after inoculation. Sulfate- reducing bacteria affiliated to the genus Desulfosporosinus predominated the microbial communities as shown by 16S rRNA gene analysis performed at the end of the incubation. At initial pH values of 3 and 4, sulfate reduction and cell growth occurred only after an extended lag phase, however, at a higher rate than in the less acidic assays. At the end of the growth phase, enrichments were dominated by Thermodesulfobium spp. suggesting that these sulfate reducers were better adapted to acidic conditions. Iron sulfides in the bulk phase were common in all assays, but specific aluminum precipitates formed in close association with cell surfaces and may function as a detoxification mechanism of dissolved Al species at low pH.

Women's Preferences for Pain Control During First-trimester Surgical Abortion: a Qualitative Study

Contraception. Apr, 2012  |  Pubmed ID: 22067751

To explore women's preferences for pain control during first-trimester surgical abortion.

Can Women Accurately Assess the Outcome of Medical Abortion Based on Symptoms Alone?

Contraception. Feb, 2012  |  Pubmed ID: 22067786

The primary purpose of this study was to evaluate whether women undergoing medical abortion can accurately assess abortion outcome based on symptoms alone. Our secondary aim was to identify predictors of medical abortion failure.

Development of a French-canadian Version of the Oswestry Disability Index: Cross-cultural Adaptation and Validation

Spine. Apr, 2012  |  Pubmed ID: 22037523

STUDY DESIGN.: Cross-cultural translation and psychometric testing. OBJECTIVE.: To translate, culturally adapt, and validate the Oswestry Disability Index (ODI) version 2.0 for the French-Canadian population. SUMMARY OF BACKGROUND DATA.: Many authors have recommended the administration of standardized instruments, rather than the creation of new scales, and advocate the adaptation of validated questionnaires in other languages. The application of these scales in different countries and by cultural groups necessitates cross-cultural adaptation. Many scales evaluate the functional incapacity resulting from low back pain. The ODI is among the most commonly used for this purpose. METHODS.: The French-Canadian ODI (ODI-FC) was developed by cross-cultural adaptation following internationally recommended methodology: forward translation, back translation, expert committee revision, and clinical evaluation of the prefinal version. Psychometric testing was performed on 72 patients with chronic low back pain. The subjects were recruited from a physiatry department in a university hospital and from a private practice physiatry clinic. They came from the Montreal area. The psychometric testing included internal consistency (Cronbach α), test-retest reliability (intraclass correlation coefficient) with a time interval set at 48 hours, and construct validity, comparing the ODI-FC with the Roland-Morris Disability Questionnaire and the Quebec Back Pain Disability Scale (Pearson correlation coefficient). RESULTS.: In 44.4% of the subjects, the average duration of low-back pain varied between 1 and 5 years. Average score for the ODI-FC was 29.2. Good internal consistency was found (Cronbach α = 0.88). Reliability was excellent, with intraclass correlation coefficient = 0.92 (95% confidence interval, 0.87-0.95). Construct validity results revealed excellent correlations between the ODI and the Quebec Back Pain Disability Scale (r = 0.90) and between the ODI and the Roland-Morris Disability Questionnaire (r = 0.84). CONCLUSION.: Cross-cultural translation and adaptation of the ODI-FC were successful. Psychometric testing determined that the instrument was homogeneous, reliable, and valid. It could be employed in future clinical trials in Canada and possibly in other French-speaking countries.

Cervical Lymph Node Metastases from Unknown Primary Cancer: a Single-institution Experience with Intensity-modulated Radiotherapy

International Journal of Radiation Oncology, Biology, Physics. Apr, 2012  |  Pubmed ID: 21497452

To determine the effectiveness and rate of complications of intensity-modulated radiotherapy (IMRT) in the treatment of cervical lymph node metastases from unknown primary cancer.

Predictors of Severe Acute and Late Toxicities in Patients with Localized Head-and-neck Cancer Treated with Radiation Therapy

International Journal of Radiation Oncology, Biology, Physics. Mar, 2012  |  Pubmed ID: 21640495

Radiation therapy (RT) causes acute and late toxicities that affect various organs and functions. In a large cohort of patients treated with RT for localized head and neck cancer (HNC), we prospectively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities.

Evolution of Disease Burden over Five Years in a Multicenter Inception Systemic Lupus Erythematosus Cohort

Arthritis Care & Research. Jan, 2012  |  Pubmed ID: 21954226

We describe disease activity, damage, and the accrual of key autoantibodies in an inception systemic lupus erythematosus (SLE) cohort.

Resorufin Butyrate As a Soluble and Monomeric High-throughput Substrate for a Triglyceride Lipase

Journal of Biomolecular Screening. Feb, 2012  |  Pubmed ID: 21956174

Triglyceride lipases such as lipoprotein lipase, endothelial lipase, and hepatic lipase play key roles in controlling the levels of plasma lipoprotein. Accordingly, small-molecule modulation of these species could alter patient lipid profiles with corresponding health effects. Screening of these enzymes for small-molecule therapeutics has historically involved the use of lipid-based particles to mimic native substrates. However, particle-based artifacts can complicate the discovery of therapeutic molecules. As a simplifying solution, the authors sought to develop an approach involving a soluble and monomeric lipase substrate. Using purified bovine lipoprotein lipase as a model system, they show that the hydrolysis of resorufin butyrate can be fluorescently monitored to give a robust assay (Z' > 0.8). Critically, using parallel approaches, they show that resorufin butyrate is soluble and monomeric under assay conditions. The presented assay should be useful as a simple and inexpensive primary or secondary screen for the discovery of therapeutic lipase modulators.

Surface Modification of Gadolinium Oxide Thin Films and Nanoparticles Using Poly(ethylene Glycol)-phosphate

Langmuir : the ACS Journal of Surfaces and Colloids. Jan, 2012  |  Pubmed ID: 21970413

The performance of nanomaterials for biomedical applications is highly dependent on the nature and the quality of surface coatings. In particular, the development of functionalized nanoparticles for magnetic resonance imaging (MRI) requires the grafting of hydrophilic, nonimmunogenic, and biocompatible polymers such as poly(ethylene glycol) (PEG). Attached at the surface of nanoparticles, this polymer enhances the steric repulsion and therefore the stability of the colloids. In this study, phosphate molecules were used as an alternative to silanes or carboxylic acids, to graft PEG at the surface of ultrasmall gadolinium oxide nanoparticles (US-Gd(2)O(3), 2-3 nm diameter). This emerging, high-sensitivity "positive" contrast agent is used for signal enhancement in T(1)-weighted molecular and cellular MRI. Comparative grafting assays were performed on Gd(2)O(3) thin films, which demonstrated the strong reaction of phosphate with Gd(2)O(3) compared to silane and carboxyl groups. Therefore, PEG-phosphate was preferentially used to coat US-Gd(2)O(3) nanoparticles. The grafting of this polymer on the particles was confirmed by XPS and FTIR. These analyses also demonstrated the strong attachment of PEG-phosphate at the surface of Gd(2)O(3), forming a protective layer on the nanoparticles. The stability in aqueous solution, the relaxometric properties, and the MRI signal of PEG-phosphate-covered Gd(2)O(3) particles were also better than those from non-PEGylated nanoparticles. As a result, reacting PEG-phosphate with Gd(2)O(3) particles is a promising, rapid, one-step procedure to PEGylate US-Gd(2)O(3) nanoparticles, an emerging "positive" contrast agent for preclinical molecular and cellular applications.