bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total 25(OH) vitamin D, free 25(OH) vitamin D and markers of bone turnover in cirrhotics with and without synthetic dysfunction
Authors: Lai Jennifer C. , Bikle Daniel D. , Lizaola Blanca , Hayssen Hilary , Terrault Norah A. , Schwartz Janice B. 
Published: March 2015

AbstractBackground & AimsCurrent clinical assays for total 25‐hydroxy (OH) vitamin D measure vitamin D bound to vitamin D‐binding protein (DBP) and albumin plus unbound (‘free’) D. We investigated the relationship between total and free 25(OH)D with bone metabolism markers in normal (>3.5 g/dl) vs. low (≤3.5 g/dl) albumin cirrhotics.MethodsEighty‐two cirrhotics underwent measurement of free and total 25(OH)D by immunoassay, DBP and markers of bone metabolism [intact parathyroid hormone (iPTH), C‐telopeptide (CTX), bone‐specific alkaline phosphatase (BSAP), osteocalcin, amino‐terminal pro‐peptide of type 1‐collagen (P1NP)]. Pearson's coefficients assessed relevant associations.ResultsCirrhotics with low (n = 54) vs. normal (n = 28) albumin had lower total 25(OH)D (12.1 vs. 21.7 ng/ml), free 25(OH)D (6.2vs.8.6 pg/ml) and DBP(91.4 vs. 140.3 μg/ml) [P < 0.01 for each]. iPTH was similar in low and normal albumin groups (33 vs. 28 pg/ml; P = 0.38), although serum CTX(0.46vs.0.28 ng/ml) and BSAP(31.7 vs. 24.8 μg/L) were increased (P < 0.01). An inverse relationship was observed between total 25(OH)D and iPTH in normal (r = −0.47, P = 0.01) but not low albumin cirrhotics (r = 0.07, P = 0.62). Similar associations were seen between free 25(OH)D and iPTH(Normal: r = −0.46, P = 0.01; Low: r = −0.03, P = 0.84). BSAP, osteocalcin and P1NP were elevated above the normal range in all cirrhotics but not consistently associated with total or free 25(OH)D.ConclusionsCirrhotics with low vs. normal albumin have lower levels of DBP, total and free 25(OH)D. The expected relationship between total or free 25(OH)D with iPTH was observed in normal but not in low albumin cirrhotics, demonstrating that total 25(OH)D is not an accurate marker of bioactive vitamin D status in cirrhotics with synthetic dysfunction. Additional investigation into the role of vitamin D supplementation and its impact on bone mineral homoeostasis in this population is needed.
Culicoides monitoring in Belgium in 2011: analysis of spatiotemporal abundance, species diversity and Schmallenberg virus detection
Authors: DE REGGE N. , DE DEKEN R. , FASSOTTE C. , LOSSON B. , DEBLAUWE I. , MADDER M. , VANTIEGHEM P. , TOMME M. , SMEETS F. , CAY A. B. 
Published: March 2015

AbstractIn 2011, Culicoides (Diptera: Ceratopogonidae) were collected at 16 locations covering four regions of Belgium with Onderstepoort Veterinary Institute (OVI) traps and at two locations with Rothamsted suction traps (RSTs). Quantification of the collections and morphological identification showed important variations in abundance and species diversity between individual collection sites, even for sites located in the same region. However, consistently higher numbers of Culicoides midges were collected at some sites compared with others. When species abundance and diversity were analysed at regional level, between‐site variation disappeared. Overall, species belonging to the subgenus Avaritia together with Culicoides pulicaris (subgenus Culicoides) were the most abundant, accounting for 80% and 96% of all midges collected with RSTs and OVI traps, respectively. Culicoides were present during most of the year, with Culicoides obsoletus complex midges found from 9 February until 27 December. Real‐time reverse‐transcription polymerase chain reaction screening for Schmallenberg virus in the heads of collected midges resulted in the first detection of the virus in August 2011 and identified C. obsoletus complex, Culicoides chiopterus and Culicoides dewulfi midges as putative vector species. At Libramont in the south of Belgium, no positive pools were identified.
Glutathione attenuates nitric oxide‐induced retinal lipid and protein changes
Authors: Siu Andrew W. , Shan Sze Wan , Li King Kit , Lam Hiu Yan , Fung Man Yee , Li Ka Ki , To Chi Ho , Do Chi Wai 
Published: March 2015

AbstractBackgroundElevated levels of nitric oxide (NO•), a pro‐oxidant that has been associated with numerous retinal diseases, have been implicated in experimental glaucoma models. This study investigated the oxidative effects of sodium nitroprusside (SNP), a nitric oxide donor, on the retinal lipids and proteins and evaluated the potential protective effects of glutathione (GSH).MethodsPorcine retinal homogenates were incubated with 0, 1, 2, 3, 4 and 5 μm SNP. Malondialdehyde (MDA) levels were assayed spectrophotometrically to quantify lipid peroxidation. Differential protein expressions of 3 μm SNP‐treated retinal homogenates were compared with controls after the conduction of two‐dimensional gel electrophoresis. Mass spectrometric data was used to identify proteins in NCBInr database. Furthermore, GSH was co‐incubated with 3 μm SNP‐treated retinal homogenates. MDA levels and protein expressions were compared with SNP‐treated controls.ResultsSNP significantly increased retinal‐MDA levels (p = 0.0002). 2‐D gel electrophoresis images displayed a significant change in 13 protein spot expressions (p < 0.05). GSH suppressed SNP‐induced MDA elevation (p < 0.0001) and selected protein changes (p < 0.05). SNP down‐regulated paraoxonase/arylesterase 2 precursor (PON2), β‐actin and β‐tubulin; however, these effects were prevented by a co‐incubation with GSH, as confirmed by Western blots.ConclusionsNitric oxide induced lipid and protein changes in retinal tissues. The effects were partially reversed by co‐incubation with GSH. Data from this study suggests that nitric oxide‐induced retinal oxidative stress induces specific molecular changes. This may enable us to better understand the pathogenesis of glaucoma. Further studies are indicated to explore potential pharmacological applications of GSH in nitric oxide‐related retinal diseases.
Measuring the Impacts of Health Conditions on Work Incapacity – Evidence from the British Household Panel Survey
Authors: Whittaker William , Sutton Matt 
Published: March 2015

AbstractThe UK has experienced substantial increases in both the number of claimants of work incapacity benefit and the proportion of claims for mental health reasons. However, identifying causality between experiencing mental health problems and claiming benefits is complex as claiming disability benefits may be the instigator or result of having a mental health problem. We use longitudinal data from the British Household Panel Survey (1991–2008) to disentangle the relationship between claiming benefits and mental health problems. We model the probability of claiming disability benefits using a dynamic random‐effects probit model, which reduces the endogeneity bias in modelling the effects of health on claiming disability benefits. Mental health has the largest effect of all health conditions modelled on the probability of disability benefit claiming. We find that the causal effect of mental health on claiming disability benefits is substantially over‐estimated by cross‐sectional associations. The effect decreases in magnitude from 12.5 to 0.5 percentage points for males and 8 to 0.7 percentage points for females. Policymakers should pay attention to other important influences on claiming disability benefits as well as interventions to improve the health of the working‐age population.
Large scale validation of the M5L lung CAD on heterogeneous CT datasets
Authors: Lopez Torres E. , Fiorina E. , Pennazio F. , Peroni C. , Saletta M. , Camarlinghi N. , Fantacci M. E. , Cerello P. 
Published: March 2015

Purpose:M5L, a fully automated computer‐aided detection (CAD) system for the detection and segmentation of lung nodules in thoracic computed tomography (CT), is presented and validated on several image datasets.Methods:M5L is the combination of two independent subsystems, based on the Channeler Ant Model as a segmentation tool [lung channeler ant model (lungCAM)] and on the voxel‐based neural approach. The lungCAM was upgraded with a scan equalization module and a new procedure to recover the nodules connected to other lung structures; its classification module, which makes use of a feed‐forward neural network, is based of a small number of features (13), so as to minimize the risk of lacking generalization, which could be possible given the large difference between the size of the training and testing datasets, which contain 94 and 1019 CTs, respectively. The lungCAM (standalone) and M5L (combined) performance was extensively tested on 1043 CT scans from three independent datasets, including a detailed analysis of the full Lung Image Database Consortium/Image Database Resource Initiative database, which is not yet found in literature.Results:The lungCAM and M5L performance is consistent across the databases, with a sensitivity of about 70% and 80%, respectively, at eight false positive findings per scan, despite the variable annotation criteria and acquisition and reconstruction conditions. A reduced sensitivity is found for subtle nodules and ground glass opacities (GGO) structures. A comparison with other CAD systems is also presented.Conclusions:The M5L performance on a large and heterogeneous dataset is stable and satisfactory, although the development of a dedicated module for GGOs detection could further improve it, as well as an iterative optimization of the training procedure. The main aim of the present study was accomplished: M5L results do not deteriorate when increasing the dataset size, making it a candidate for supporting radiologists on large scale screenings and clinical programs.
Quadratic Association Between Corticomotor and Spinal-Reflexive Excitability and Self-Reported Disability in Participants With Chronic Ankle Instability
Authors: Harkey Matthew , McLeod Michelle M. , Terada Masafumi , Gribble Phillip A. , Pietrosimone Brian G. 
Published: March 2015

Context:Spinal-reflexive and corticomotor excitability may have a critical role in altering muscle function needed to stabilize the ankle in people with chronic ankle instability (CAI).Objective:To determine the association between self-reported disability and both spinal-reflexive and corticomotor excitability in people with CAI.Design:Descriptive laboratory study.Setting:Research laboratory.Participants:30 participants with CAI.Main Outcome Measures:Soleus spinal-reflexive excitability was measured with normalized Hoffmann reflexes (H:M ratio), and corticomotor excitability was measured with transcranial magnetic stimulation and quantified by normalized motor-evoked-potential (MEP) amplitudes at 120% of active motor threshold (120%MEP). Self-reported disability was quantified with the activities-of-daily-living and sport subscales of the Foot and Ankle Ability Measure (FAAM-ADL and FAAM-S). Separate linear Pearson product–moment correlations and nonlinear quadratic correlations were used to determine associations between the neural-excitability and disability variables.Results:Thirty participants were included in the spinal-reflexive-excitability analysis, while only 19 were included in the corticomotor analysis. There was a significant, weak linear association between H:M ratio and FAAM-ADL (R = .39, P = .03) and a nonsignificant, weak linear association between H:M ratio and FAAM-S (R = .36, P = .06). There were significant, moderate quadratic associations between H:M ratio and both FAAM-ADL (R = .48, P = .03) and FAAM-S (R = .50, P = .02). There was a significant, moderate linear association between 120%MEP and FAAM-ADL (R = –.48, P = .04) and a nonsignificant, moderate negative linear association between FAAM-S (R = –.42, P = .07). There was a significant, moderate quadratic association between 120%MEP and FAAM-ADL (R = .57, P = .046) and a significant, strong quadratic correlation between 120%MEP and FAAM-S (R = .71, P = .004).Conclusions:There are significant quadratic associations between self-reported disability and both spinal-reflexive and corticomotor excitability of the soleus. CAI participants with low or high neural excitability present with lower function.
SQ109, a New Drug Lead for Chagas Disease
Authors: Veiga-Santos Phercyles , Li Kai , Lameira Lilianne , de Carvalho Tecia Maria Ulisses , Huang Guozhong , Galizzi Melina , Shang Na , Li Qian , Gonzalez-Pacanowska Dolores , Hernandez-Rodriguez Vanessa , Benaim Gustavo , Guo Rey-Ting , Urbina Julio A. , Docampo Roberto , de Souza Wanderley , Oldfield Eric 
Published: March 2015

ABSTRACT

We tested the antituberculosis drug SQ109, which is currently in advanced clinical trials for the treatment of drug-susceptible and drug-resistant tuberculosis, for its
in vitro
activity against the trypanosomatid parasite
Trypanosoma cruzi
, the causative agent of Chagas disease. SQ109 was found to be a potent inhibitor of the trypomastigote form of the parasite, with a 50% inhibitory concentration (IC
50
) for cell killing of 50 ± 8 nM, but it had little effect (50% effective concentration [EC
50
], ∼80 μM) in a red blood cell hemolysis assay. It also inhibited extracellular epimastigotes (IC
50
, 4.6 ± 1 μM) and the clinically relevant intracellular amastigotes (IC
50
, ∼0.5 to 1 μM), with a selectivity index of ∼10 to 20. SQ109 caused major ultrastructural changes in all three life cycle forms, as observed by light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). It rapidly collapsed the inner mitochondrial membrane potential (Δψ
m
) in succinate-energized mitochondria, acting in the same manner as the uncoupler FCCP [carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone], and it caused the alkalinization of internal acidic compartments, effects that are likely to make major contributions to its mechanism of action. The compound also had activity against squalene synthase, binding to its active site; it inhibited sterol side-chain reduction and, in the amastigote assay, acted synergistically with the antifungal drug posaconazole, with a fractional inhibitory concentration index (FICI) of 0.48, but these effects are unlikely to account for the rapid effects seen on cell morphology and cell killing. SQ109 thus most likely acts, at least in part, by collapsing Δψ/ΔpH, one of the major mechanisms demonstrated previously for its action against
Mycobacterium tuberculosis
. Overall, the results suggest that SQ109, which is currently in advanced clinical trials for the treatment of drug-susceptible and drug-resistant tuberculosis, may also have potential as a drug lead against Chagas disease.
Missense Mutations in PBP2A Affecting Ceftaroline Susceptibility Detected in Epidemic Hospital-Acquired Methicillin-Resistant Staphylococcus aureus Clonotypes ST228 and ST247 in Western Switzerland Archived since 1998
Authors: Kelley William L. , Jousselin Ambre , Barras Christine , Lelong Emmanuelle , Renzoni Adriana 
Published: March 2015

ABSTRACT

The development and maintenance of an arsenal of antibiotics is a major health care challenge. Ceftaroline is a new cephalosporin with activity against methicillin-resistant
Staphylococcus aureus
(MRSA); however, no reports concerning MRSA ceftaroline susceptibility have been reported in Switzerland. We tested the
in vitro
activity of ceftaroline against an archived set of 60 MRSA strains from the University Hospital of Geneva collected from 1994 to 2003. Our results surprisingly revealed ceftaroline-resistant strains (MIC, >1 μg/ml in 40/60 strains; EUCAST breakpoints, susceptible [S], ≤1 μg/ml; resistant [R], >1 μg/ml) were present from 1998 to 2003. The detected resistant strains predominantly belonged to sequence type 228 (ST228) (South German clonotype) but also to ST247 (Iberian clonotype). A sequence analysis of these strains revealed missense mutations in the penicillin-binding protein 2A (PBP2A) allosteric domain (N146K or E239K and N146K-E150K-G246E). The majority of our ST228 PBP2A mutations (N146K or E150K) were distinct from ST228 PBP2A allosteric domain mutations (primarily E239K) recently described for MRSA strains collected in Thailand and Spain during the 2010 Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) global surveillance program. We also found that similar allosteric domain PBP2A mutations (N146K) correlated with ceftaroline resistance in an independent external ST228 MRSA set obtained from the nearby University Hospital of Lausanne, Lausanne, Switzerland, collected from 2003 to 2008. Thus, ceftaroline resistance was observed in our archived strains (including two examples of an MIC of 4 µg/ml for the Iberian ST247 clonotype with the triple mutation N146K/E150K/G246E), at least as far back as 1998, considerably predating the commercial introduction of ceftaroline. Our results reinforce the notion that unknown parameters can potentially exert selective pressure on PBP2A that can subsequently modulate ceftaroline resistance.
In Vitro
Antibiotic Susceptibilities of Yersinia pestis Determined by Broth Microdilution following CLSI Methods
Authors: Heine Henry S. , Hershfield Jeremy , Marchand Charles , Miller Lynda , Halasohoris Stephanie , Purcell Bret K. , Worsham Patricia L. 
Published: March 2015

ABSTRACT

In vitro
susceptibilities to 45 antibiotics were determined for 30 genetically and geographically diverse strains of
Yersinia pestis
by the broth microdilution method at two temperatures, 28°C and 35°C, following Clinical and Laboratory Standards Institute (CLSI) methods. The
Y. pestis
strains demonstrated susceptibility to aminoglycosides, quinolones, tetracyclines, β-lactams, cephalosporins, and carbapenems. Only a 1-well shift was observed for the majority of antibiotics between the two temperatures. Establishing and comparing antibiotic susceptibilities of a diverse but specific set of
Y. pestis
strains by standardized methods and establishing population ranges and MIC
50
and MIC
90
values provide reference information for assessing new antibiotic agents and also provide a baseline for use in monitoring any future emergence of resistance.
Multicenter Evaluation of Candida QuickFISH BC for Identification of Candida Species Directly from Blood Culture Bottles
Authors: Abdelhamed Ayman M. , Zhang Sean X. , Watkins Tonya , Morgan Margie A. , Wu Fann , Buckner Rebecca J. , Fuller DeAnna D. , Davis Thomas E. , Salimnia Hossein , Fairfax Marilynn R. , Lephart Paul R. , Poulter Melinda D. , Regi Sarah B. , Jacobs Michael R. 
Published: March 2015

ABSTRACT

Candida
species are common causes of bloodstream infections (BSI), with high mortality. Four species cause >90% of
Candida
BSI:
C. albicans
,
C. glabrata
,
C. parapsilosis
, and
C. tropicalis
. Differentiation of
Candida
spp. is important because of differences in virulence and antimicrobial susceptibility.
Candida
QuickFISH BC, a multicolor, qualitative nucleic acid hybridization assay for the identification of
C. albicans
(green fluorescence),
C. glabrata
(red fluorescence), and
C. parapsilosis
(yellow fluorescence), was tested on Bactec and BacT/Alert blood culture bottles which signaled positive on automated blood culture devices and were positive for yeast by Gram stain at seven study sites. The results were compared to conventional identification. A total of 419 yeast-positive blood culture bottles were studied, consisting of 258 clinical samples (89
C. glabrata
, 79
C. albicans
, 23
C. parapsilosis
, 18
C. tropicalis
, and 49 other species) and 161 contrived samples inoculated with clinical isolates (40
C. glabrata
, 46
C. albicans
, 36
C. parapsilosis
, 19
C. tropicalis
, and 20 other species). A total of 415 samples contained a single fungal species, with
C. glabrata
(
n
= 129; 30.8%) being the most common isolate, followed by
C. albicans
(
n
= 125; 29.8%),
C. parapsilosis
(
n
= 59; 14.1%),
C. tropicalis
(
n
= 37; 8.8%), and
C. krusei
(
n
= 17; 4.1%). The overall agreement (with range for the three major
Candida
species) between the two methods was 99.3% (98.3 to 100%), with a sensitivity of 99.7% (98.3 to 100%) and a specificity of 98.0% (99.4 to 100%). This study showed that
Candida
QuickFISH BC is a rapid and accurate method for identifying
C. albicans
,
C. glabrata
, and
C. parapsilosis
, the three most common
Candida
species causing BSI, directly from blood culture bottles.
HIV-1 Nef and Vpu Interfere with L-Selectin (CD62L) Cell Surface Expression To Inhibit Adhesion and Signaling in Infected CD4+T Lymphocytes
Authors: Vassena Lia , Giuliani Erica , Koppensteiner Herwig , Bolduan Sebastian , Schindler Michael , Doria Margherita 
Published: March 2015

ABSTRACTLeukocyte recirculation between blood and lymphoid tissues is required for the generation and maintenance of immune responses against pathogens and is crucially controlled by the L-selectin (CD62L) leukocyte homing receptor. CD62L has adhesion and signaling functions and initiates the capture and rolling on the vascular endothelium of cells entering peripheral lymph nodes. This study reveals that CD62L is strongly downregulated on primary CD4+T lymphocytes upon infection with human immunodeficiency virus type 1 (HIV-1). Reduced cell surface CD62L expression was attributable to the Nef and Vpu viral proteins and not due to increased shedding via matrix metalloproteases. Both Nef and Vpu associated with and sequestered CD62L in perinuclear compartments, thereby impeding CD62L transport to the plasma membrane. In addition, Nef decreased total CD62L protein levels. Importantly, infection with wild-type, but not Nef- and Vpu-deficient, HIV-1 inhibited the capacity of primary CD4+T lymphocytes to adhere to immobilized fibronectin in response to CD62L ligation. Moreover, HIV-1 infection impaired the signaling pathways and costimulatory signals triggered in primary CD4+T cells by CD62L ligation. We propose that HIV-1 dysregulates CD62L expression to interfere with the trafficking and activation of infected T cells. Altogether, this novel HIV-1 function could contribute to virus dissemination and evasion of host immune responses.IMPORTANCEL-selectin (CD62L) is an adhesion molecule that mediates the first steps of leukocyte homing to peripheral lymph nodes, thus crucially controlling the initiation and maintenance of immune responses to pathogens. Here, we report that CD62L is downmodulated on the surfaces of HIV-1-infected T cells through the activities of two viral proteins, Nef and Vpu, that prevent newly synthesized CD62L molecules from reaching the plasma membrane. We provide evidence that CD62L downregulation on HIV-1-infected primary T cells results in impaired adhesion and signaling functions upon CD62L triggering. Removal of cell surface CD62L may predictably keep HIV-1-infected cells away from lymph nodes, the privileged sites of both viral replication and immune response activation, with important consequences, such as systemic viral spread and evasion of host immune surveillance. Altogether, we propose that Nef- and Vpu-mediated subversion of CD62L function could represent a novel determinant of HIV-1 pathogenesis.