bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sepsis‐associated liver injury: Incidence, classification and the clinical significance
Authors: Kobashi Haruhiko , Toshimori Junichi , Yamamoto Kazuhide 
Published: September 2012

Aim:  Although it is a common complication of sepsis, sepsis‐associated liver injury has not been substantially recognized, because its diagnostic criteria and clinical implications are unclear. We aimed to elucidate the incidence, manifestation, disease type classification and prognosis of sepsis‐associated liver injury.Methods:  The subjects were 588 patients admitted to our hospital for sepsis between 2001 and 2010. They were classified into “normal liver function”, “sepsis‐associated liver injury” and “sepsis‐not‐associated liver injury” groups. Sepsis‐associated liver injury was classified as either “cholestatic”, “hepatocellular” or “shock liver.” Each of these three subgroups was further classified into “with jaundice” or “without jaundice”. The primary end‐point was the “poor prognosis ratio”, defined as the proportion of patients whose prognosis was “unchanged”, “worsened” or “died”.Results:  Among the 449 subjects except for sepsis‐not‐associated liver injury (n = 139), the incidence of sepsis‐associated liver injury was 34.7% (156/449), including 75 cholestatic (48.1%), 34 hepatocellular (21.8%) and 47 shock liver (30.1%) cases. Jaundice was a complication in 25 (33%), six (17.6%) and four (8.5%) patients in each group, respectively. The poor prognosis ratio was higher in males (37.5%) and in the elderly (47.7%); it was 48.0%, 38.2% and 62.8% in the cholestatic, hepatocellular and shock liver groups, respectively, and higher than the normal liver function (18.4%) group (P < 0.0001). It was also higher in patients with jaundice (68.6%) than in those without (45.5%) (P < 0.0001).Conclusion:  Sepsis‐associated liver injury, especially with jaundice, is a significant predictive sign of poor prognosis in patients with sepsis.
Association between an IL‐28B genetic polymorphism and the efficacy of the response‐guided pegylated interferon therapy in children with chronic hepatic C infection
Authors: Komatsu Haruki , Inui Ayano , Tsunoda Tomoyuki , Sogo Tsuyoshi , Fujisawa Tomoo 
Published: September 2012

AimThe relation between interleukin‐28B (IL‐28B) genotypes and treatment‐induced hepatitis C virus (HCV) clearance in children is unknown. This was a retrospective study to evaluate the association between an IL‐28B genotype (rs8099917) and pegylated (PEG) interferon (IFN) response.MethodsSixty‐three children (median age, 7 years; range, 3–17 years; 22 with HCV genotype 1 and 41 with genotype non‐1) with chronic HCV infection who were treated with response‐guided PEG IFN on the basis of viral load were evaluated.ResultsThe duration of treatment with PEG IFN was 24 weeks in one child (2%), 36 weeks in eight children (13%), 48 weeks in 36 children (57%), 60 weeks in 11 children (17%) and 72 weeks in seven children (11%). Of the total 63 children, 54 (86%) were initially treated with PEG IFN‐α‐2a monotherapy. The remaining nine (14%) received PEG IFN plus ribavirin as the initial therapy. Of the 54 children initially treated with monotherapy, 35 (65%) continued receiving monotherapy until the end of treatment. In the remaining 19 (35%), monotherapy was changed to PEG IFN plus ribavirin at 12 or 24 weeks of treatment. Of the total 63 children, 54 (86%) achieved a sustained virological response (SVR). In univariate analysis, rs8099917 genotype TT (P = 0.075) showed a weak association with SVR. However, the multivariate analysis revealed no predictive factors which had a significant association with SVR.ConclusionThe IL‐28B genotype was not a strong pretreatment predictor for SVR in a mixed genotype cohort of children treated with response‐guided PEG IFN therapy.
Floriculture du Suroît inc.*
Authors: Martel Louise , Paul Diane 
Published: September 2012

RésuméFloriculture du Suroît inc. est une PME dans le domaine de l'horticulture. Elle cultive et vend des géraniums et, par l'entremise de sa filiale, Les Roses de Caroline, elle vient de démarrer la culture des roses. Floriculture vient d'obtenir une subvention gouvernementale. Pour respecter les conditions imposées par l'organisme subventionnaire, la société devra produire pour la première fois des états financiers préparés selon les PCGR et certifiés par un auditeur externe. Les deux propriétaires‐dirigeants auront donc à choisir entre deux référentiels comptables, soit les normes internationales d'information financière (IFRS) et les normes canadiennes pour les entreprises à capital fermé (NCECF). Non seulement de nombreuses différences existent entre ces deux référentiels, en particulier les normes IFRS propres à l'agriculture et aux immeubles de placement, mais les NCECF offrent également des choix à analyser avant de prendre une décision. Les propriétaires étant des néophytes en matière comptable, ils ont besoin de conseils avisés.
Locally delivered 0.5% clarithromycin, as an adjunct to nonsurgical treatment in chronic periodontitis with well‐controlled type 2 diabetes: a randomized controlled clinical trial
Authors: Bajaj Pavan , Pradeep A R , Agarwal Esha , Kumari Minal , Naik Savitha B. 
Published: September 2012

AbstractObjectiveSeveral epidemiologic studies have identified a greater incidence of periodontitis in patients with type 2 diabetes. Recent developments suggest that local delivery of antimicrobials into periodontal pockets improve periodontal health. The present study was designed to investigate the adjunctive effects of subgingivally delivered clarithromycin (CLM) (0.5% concentration) as an adjunct to scaling and root planing for treating chronic periodontitis in patients with well‐controlled type 2 diabetes.MethodsSixty‐three patients were categorized into two treatment groups: Group 1, scaling and root planing (SRP) plus 0.5% CLM; Group 2, SRP plus placebo gel. Clinical parameters were recorded at baseline, 1, 2, and 3 months; which included gingival index (GI), sulcus bleeding index (SBI), plaque index (PI), probing depth (PD), and periodontal attachment level (PAL).ResultsBoth therapies resulted in significant improvements. Using a subject‐based analysis, patients in Group 1 treated with SRP + CLM showed enhanced reductions in PI, GI, SBI, and PD, and gains in PAL (P < 0.001) over a period of 6 months as compared to Group 2.ConclusionAlthough both treatment strategies seemed to benefit the patients, the adjunctive use of 0.5% CLM as a controlled drug delivery system enhanced the clinical outcome.
Study of drug supersaturation for rational early formulation screening of surfactant/co-solvent drug delivery systems
Authors: Stillhart Cordula , Cavegn Martin , Kuentz Martin 
Published: September 2012

Abstract

Objectives
To advance in vitro screening of surfactant/co-solvent formulations in early development by considering drug supersaturation and the mechanism of solubilization upon aqueous dilution.

Methods
Two surfactant/co-solvent model systems were studied at practically relevant aqueous dilution ratios. Precipitation of the model drug fenofibrate was characterized by focused beam reflectance measurement, X-ray diffraction, and Raman spectroscopy. We calculated drug supersaturation in diluted systems and introduced a theoretical model to study the role of excipient interaction in the process of drug solubilization. Finally, vehicle phase changes upon dilution were examined using dynamic light scattering and ultrasound analysis.

Key Findings
Phase changes occurred at low dilution levels, while more extensive dilution barely led to further structural changes. In undiluted formulations, ethanol–surfactant domains were responsible for fenofibrate solubilization. In dispersed formulations, however, the co-solvent partitioned out of the surfactant microstructure, leading to drug solubilization by independent micellization and co-solvency. This loss of excipient interaction caused formulation-specific supersaturation, which was indicative for the risk of drug precipitation.

Conclusions
Experimental protocols of in vitro formulation screening should include both low and high dilution levels of physiological relevance. The study of excipient interaction and estimation of supersaturation allows the identification of formulations that are prone to drug precipitation.
Expression of Bak and Bak/Mcl‐1 ratio can predict photodynamic therapy outcome for oral verrucous hyperplasia and leukoplakia
Authors: Yu Chuan‐Hang , Chen Hsin‐Ming , Lin Hung‐Pin , Chiang Chun‐Pin 
Published: September 2012

BackgroundOur previous studies showed that topical 5‐aminolevulinic acid‐mediated photodynamic therapy (ALA‐PDT) is very effective for oral verrucous hyperplasia (OVH) and relatively less effective for oral leukoplakia (OL) lesions. Nevertheless, there has been no report on the association of the expression of apoptosis‐related proteins in OVH and OL biopsy tissues prior to PDT with PDT treatment outcomes.MethodsThis study used immunohistochemistry to evaluate whether the expression of Bak, Mcl‐1, caspase‐3, caspase‐8, caspase‐9, p53, p21, or PCNA protein in biopsy specimens of OVH and OL lesions could be used to predict the clinical outcomes of 18 OVH and 40 OL lesions treated with topical ALA‐PDT. The marker labeling score (LS) was defined as labeling index (positive cells/total cells) multiplied by staining intensity. The lesions after ALA‐PDT treatment were divided into complete response (CR) group and partial or no response (PR/NR) group.ResultsThe mean Bak LS and the mean Bak/Mcl‐1 LS ratio were significantly higher in the CR group than in the PR/NR group. However, there was no significant difference in the Mcl‐1, caspase‐3, caspase‐8, caspase‐9, p53, p21, or PCNA protein LS between the CR and PR/NR groups.ConclusionWe conclude that the Bak LS or Bak/Mcl‐1 LS ratio may be a useful biomarker to predict the clinical outcomes of OVH and OL lesions treated with topical ALA‐PDT. Pre‐PDT epithelial cell levels of Mcl‐1, caspase‐3, caspase‐8, caspase‐9, p53, p21, and PCNA may not have a significant influence on the clinical outcome of OVH and OL lesions treated with topical ALA‐PDT.
Salivary markers of oxidative stress are related to age and oral health in adult non‐smokers
Authors: Celecová Viera , Kamodyová Natália , Tóthová Ľubomíra , Kúdela Matúš , Celec Peter 
Published: September 2012

BackgroundSalivary concentrations of thiobarbituric acid‐reacting substances (TBARS) are associated with the periodontal status assessed as papillary bleeding index (PBI). Whether this association is age independent is currently unclear. Salivary concentrations of advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEs) have not been assessed in relation to age or oral health yet. The aim of our study was to analyse salivary markers of oxidative stress in dental patients in relation to age, gender and oral health.MethodsConsecutive adult non‐smoking dental patients were enrolled (n = 204; aged 19–83 years).PBIand the caries index (CI) were assessed. Markers of oxidative stress, such asTBARS,AOPPs andAGEs, and the total antioxidant capacity (TAC) were measured in saliva samples taken before clinical examination.ResultsLinear regression showed that salivaryTBARS,AGEs andTACsignificantly increase with age (rsquared = 5.3%, 2.1% and 5%, respectively).PBIis an independent predictor of salivaryTBARS(rsquared = 5.5%), and theCInegatively affectedAOPPs (r = 3.2%) and positively affectedTBARS(r = 2.5%). Gender did not affect any of the analysed parameters.ConclusionsAge as a significant contributor to the variance should be taken into account in studies focusing on salivary markers of oxidative stress. The relationship betweenPBIand salivaryTBARSconfirms results from previous studies. In addition, our results show that the association is age independent. Negative association between theCIandAOPPs might be related to recent findings thatAOPPmight be actually a marker of non‐enzymatic antioxidant status.
Effect of bone morphogenetic protein‐2, demineralized bone matrix and systemic parathyroid hormone (1‐34) on local bone formation in a rat calvaria critical‐size defect model
Authors: Stancoven B. W. , Lee J. , Dixon D. R. , McPherson J.C. , Bisch F. C. , Wikesjö U. M. E. , Susin C. 
Published: September 2012

AimTo determine the potential of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) soak‐loaded on to an absorbable collagen sponge (ACS) to induce local bone formation compared with the clinical reference demineralized bone matrix (DBM) and to investigate potential additive/synergistic effects of exogenous parathyroid hormone (PTH).MethodsCritical‐size (8 mm), through‐through calvaria osteotomy defects in 160 adult male Sprague–Dawley rats were randomized to receive one of eight interventions: rhBMP‐2/ACS, DBM, ACS, or serve as controls (empty defects) combined or not with systemic PTH. Ten animals from each group were followed for 4 and 8 wks for radiographic and histometric analysis. Multivariable analysis was used to assess the effect of experimental intervention and healing time on local bone formation.ResultsIn the multivariable analysis, rhBMP‐2/ACS exhibited significantly greater histologic bone formation than control (β ± SE: 54.76 ± 5.85, p < 0.001) and ACS (β ± SE: 9.14 ± 3.31, p = 0.007) whereas DBM showed significantly less bone formation than control (β ± SE: −32.32 ± 8.23, p < 0.001). Overall, PTH did not show a significant effect on bone formation (β ± SE: 2.72 ± 6.91, p = 0.70). No significant differences in histological defect closure were observed between 4 and 8 wks for all but the control group without PTH.ConclusionrhBMP‐2/ACS significantly stimulates local bone formation whereas bone formation appears significantly limited by DBM. Systemic application of PTH provided no discernible additive/synergistic effects on local bone formation.
Structure of WbdD: a bifunctional kinase and methyltransferase that regulates the chain length of the O antigen in Escherichia coliO9a
Authors: Hagelueken Gregor , Huang Hexian , Clarke Bradley R. , Lebl Tomas , Whitfield Chris , Naismith James H. 
Published: September 2012

SummaryThe Escherichia coli serotype O9a O‐antigen polysaccharide (O‐PS) is a model for glycan biosynthesis and export by the ATP‐binding cassette transporter‐dependent pathway. The polymannose O9a O‐PS is synthesized as a polyprenol‐linked glycan by mannosyltransferase enzymes located at the cytoplasmic membrane. The chain length of the O9a O‐PS is tightly regulated by the WbdD enzyme. WbdD first phosphorylates the terminal non‐reducing mannose of the O‐PS and then methylates the phosphate, stopping polymerization. The 2.2 Å resolution structure of WbdD reveals a bacterial methyltransferase domain joined to a eukaryotic kinase domain. The kinase domain is again fused to an extended C‐terminal coiled‐coil domain reminiscent of eukaryotic DMPK (Myotonic Dystrophy Protein Kinase) family kinases such as Rho‐associated protein kinase (ROCK). WbdD phosphorylates 2‐α‐d‐mannosyl‐d‐mannose (2α‐MB), a short mimic of the O9a polymer. Mutagenesis identifies those residues important in catalysis and substrate recognition and the in vivo phenotypes of these mutants are used to dissect the termination reaction. We have determined the structures of co‐complexes of WbdD with two known eukaryotic protein kinase inhibitors. Although these are potent inhibitors in vitro, they do not show any in vivo activity. The structures reveal new insight into O‐PS chain‐length regulation in this important model system.
Mycoredoxin‐1 is one of the missing links in the oxidative stress defence mechanism of Mycobacteria
Authors: Van Laer Koen , Buts Lieven , Foloppe Nicolas , Vertommen Didier , Van Belle Karolien , Wahni Khadija , Roos Goedele , Nilsson Lennart , Mateos Luis M. , Rawat Mamta , van Nuland Nico A. J. , Messens Joris 
Published: September 2012

SummaryTo survive hostile conditions, the bacterial pathogen Mycobacterium tuberculosis produces millimolar concentrations of mycothiol as a redox buffer against oxidative stress. The reductases that couple the reducing power of mycothiol to redox active proteins in the cell are not known. We report a novel mycothiol‐dependent reductase (mycoredoxin‐1) with a CGYC catalytic motif. With mycoredoxin‐1 and mycothiol deletion strains of Mycobacterium smegmatis, we show that mycoredoxin‐1 and mycothiol are involved in the protection against oxidative stress. Mycoredoxin‐1 acts as an oxidoreductase exclusively linked to the mycothiol electron transfer pathway and it can reduce S‐mycothiolated mixed disulphides. Moreover, we solved the solution structures of oxidized and reduced mycoredoxin‐1, revealing a thioredoxin fold with a putative mycothiol‐binding site. With HSQC snapshots during electron transport, we visualize the reduction of oxidized mycoredoxin‐1 as a function of time and find that mycoredoxin‐1 gets S‐mycothiolated on its N‐terminal nucleophilic cysteine. Mycoredoxin‐1 has a redox potential of −218 mV and hydrogen bonding with neighbouring residues lowers the pKa of its N‐terminal nucleophilic cysteine. Determination of the oxidized and reduced structures of mycoredoxin‐1, better understanding of mycothiol‐dependent reactions in general, will likely give new insights in how M. tuberculosis survives oxidative stress in human macrophages.
West Nile Virus in North‐Eastern Italy, 2011: Entomological and Equine IgM‐Based Surveillance to Detect Active Virus Circulation
Authors: Mulatti Paolo , Bonfanti Lebana , Capelli Gioia , Capello Katia , Lorenzetto Monica , Terregino Calogero , Monaco Federica , Ferri Gaetana , Marangon Stefano 
Published: September 2012

SummarySince 2008, West Nile Virus (WNV) has expanded its range in several Italian regions, and its yearly recurrence suggests the virus may have become endemic in some areas. In 2011, a new plan based also on the detection of IgM antibodies was implemented in the north‐eastern Italian regions of Veneto and Friuli Venezia Giulia, aiming to early detect WNV infections in areas where the virus had already circulated during the previous summers, and in adjacent zones. From July to November 2011, 1880 sera from 521 equine premises were screened by a commercial IgM capture ELISA. Mosquitoes were captured by CDC‐CO2 traps at 61 locations in the two regions. Collected mosquitoes were identified, pooled by species/date/location and examined by real‐time RT‐PCR and sequencing. Passive surveillance was carried out on clinically affected horses and non‐migratory wild birds found dead. IgM sero‐positive equines were detected in 19 holdings, five in the area with WNV circulation (AWC) and 14 in the surveillance area (SA); 10 more horse premises tested positive to further serological controls within 4 km of the positive holdings. A total of 85 398 mosquitoes of 15 species were collected and 2732 pools examined. Five Culex pipiens pools tested positive for the presence of WNV. Passive surveillance on non‐migratory wild birds allowed detection of the virus only in one found dead collared dove (Streptopelia decaocto), of 82 birds sampled. The WNV belonged to the lineage 2, which had been isolated for the first time in Italy earlier in 2011. By the first week of October, nine human cases had been confirmed in the same area. The implementation of a protocol combining IgM screening of horses with surveillance on mosquito vectors proved to be valuable for early detecting WNV circulation.
Motion mitigation in intensity modulated particle therapy by internal target volumes covering range changes
Authors: Graeff Christian , Durante Marco , Bert Christoph 
Published: September 2012

Purpose:Particle therapy offers benefits over conventional photon therapy but also introduces sensitivity to changes in the water‐equivalent path length (WEPL) in case of target motion, e.g., breathing. Target motion can be addressed by the internal target volume (ITV) approach, defined as the CTV plus target movement. In photon therapy, the ITV can be constructed as the geometric union of CTVs in all motion states (GEO‐ITV) of a 4D‐CT, but this does not account for WEPL‐changes. An ITV including WEPL‐changes can be defined as the union of all CTVs transformed to a WEPL‐equivalent axis along beamˈs eye view. The resulting WEPL‐ITV is field‐specific and thus unsuitable for intensity modulated particle therapy (IMPT). The purpose of this study was an IMPT‐compatible ITV by splitting geometrical motion and field‐specific WEPL changes, following ICRU 78 recommendations.Methods:For all fields, the GEO‐ITV was used as a common target. This identical geometry for all fields was mapped to an enlarged WEPL extent with a field‐specific transformation. As the dose distribution is determined by the WEPL, this is sufficient to achieve equivalent dose coverage as for a geometrically enlarged target volume. The WEPL enlargement is only visible to the specific field and therefore does not increase the target volume of other fields. This avoids unnecessary lateral field extensions, reducing the dose to normal tissue. Homogeneous dose coverage in IMPT is achieved only if the inhomogeneous doses from the individual fields match up during delivery. As the course of the WEPL within each motion phase differs, this cannot be guaranteed by optimizing the fields only in the reference phase. The WEPL‐ITV for the reference phase can be amended by CTVs from a subset of motion phases (4D‐WEPL‐ITV). Here, end‐exhale as the reference phase was combined with end‐inhale to cover the whole motion range. The GEO‐ITV, WEPL‐ITV, and 4D‐WEPL‐ITV were applied in an IMPT simulation of a lung cancer patient case using a four‐field geometry and the heart as an OAR. A static plan of the CTV in end‐exhale was computed for reference. The CTV was moving approximately 20 mm in SI and was partly overlapping the heart. For a single fraction a target dose of 17.7 GyE was prescribed, with a 50% maximum dose for the heart.Results:With 21 rescans to counter interplay, the homogeneity (D5‐D95) was 17.0%, 9.0%, 6.0%, and 3.5% for the GEO‐ITV, WEPL‐ITV, 4D‐WEPL‐ITV, and a 3D CTV plan computed for reference, respectively. Due to the overlap, the 50% maximum dose was violated by all plans, with V50 of 3.8%, 3.5%, 3.7%, and 2.0% for the four plans.Conclusions:A 4D‐WEPL‐ITV method was developed that is suitable for IMPT, covers range changes, and drastically improves dose homogeneity in the target without increasing the OAR dose.
Modeling the Growth of Listeria monocytogenes in Soft Blue-White Cheese
Authors: Rosshaug Per Sand , Detmer Ann , Ingmer Hanne , Larsen Marianne Halberg 
Published: September 2012

ABSTRACT

The aim of this study was to develop a predictive model simulating growth over time of the pathogenic bacterium
Listeria monocytogenes
in a soft blue-white cheese. The physicochemical properties in a matrix such as cheese are essential controlling factors influencing the growth of
L. monocytogenes
. We developed a predictive tertiary model of the bacterial growth of
L. monocytogenes
as a function of temperature, pH, NaCl, and lactic acid. We measured the variations over time of the physicochemical properties in the cheese. Our predictive model was developed based on broth data produced in previous studies. New growth data sets were produced to independently calibrate and validate the developed model. A characteristic of this tertiary model is that it handles dynamic growth conditions described in time series of temperature, pH, NaCl, and lactic acid. Supplying the model with realistic production and retail conditions showed that the number of
L. monocytogenes
cells increases 3 to 3.5 log within the shelf life of the cheese.