bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activities of Fosfomycin and Rifampin on Planktonic and Adherent Enterococcus faecalis Strains in an Experimental Foreign-Body Infection Model
Authors: Oliva Alessandra , Furustrand Tafin Ulrika , Maiolo Elena Maryka , Jeddari Safaa , Bétrisey Bertrand , Trampuz Andrej 
Published: October 2013

ABSTRACT

Enterococcal implant-associated infections are difficult to treat because antibiotics generally lack activity against enterococcal biofilms. We investigated fosfomycin, rifampin, and their combinations against planktonic and adherent
Enterococcus faecalis
(ATCC 19433)
in vitro
and in a foreign-body infection model. The MIC/MBC
log
values were 32/>512 μg/ml for fosfomycin, 4/>64 μg/ml for rifampin, 1/2 μg/ml for ampicillin, 2/>256 μg/ml for linezolid, 16/32 μg/ml for gentamicin, 1/>64 μg/ml for vancomycin, and 1/5 μg/ml for daptomycin. In time-kill studies, fosfomycin was bactericidal at 8× and 16× MIC, but regrowth of resistant strains occurred after 24 h. With the exception of gentamicin, no complete inhibition of growth-related heat production was observed with other antimicrobials on early (3 h) or mature (24 h) biofilms. In the animal model, fosfomycin alone or in combination with daptomycin reduced planktonic counts by ≈4 log
10
CFU/ml below the levels before treatment. Fosfomycin cleared planktonic bacteria from 74% of cage fluids (i.e., no growth in aspirated fluid) and eradicated biofilm bacteria from 43% of cages (i.e., no growth from removed cages). In combination with gentamicin, fosfomycin cleared 77% and cured 58% of cages; in combination with vancomycin, fosfomycin cleared 33% and cured 18% of cages; in combination with daptomycin, fosfomycin cleared 75% and cured 17% of cages. Rifampin showed no activity on planktonic or adherent
E. faecalis
, whereas in combination with daptomycin it cured 17% and with fosfomycin it cured 25% of cages. Emergence of fosfomycin resistance was not observed
in vivo
. In conclusion, fosfomycin showed activity against planktonic and adherent
E. faecalis
. Its role against enterococcal biofilms should be further investigated, especially in combination with rifampin and/or daptomycin treatment.
Real-time Liquid Biopsy in Cancer Patients: Fact or Fiction?
Authors: Pantel Klaus , Alix-Panabières Catherine 
Published: October 2013

Abstract
Distant metastases harbor unique genomic characteristics not detectable in the corresponding primary tumor of the same patient and metastases located at different sites show a considerable intrapatient heterogeneity. Thus, the mere analysis of the resected primary tumor alone (current standard practice in oncology) or, if possible, even reevaluation of tumor characteristics based on the biopsy of the most accessible metastasis may not reveal sufficient information for treatment decisions. Here, we propose that this dilemma can be solved by a new diagnostic concept: liquid biopsy, that is, analysis of therapeutic targets and drug resistance–conferring gene mutations on circulating tumor cells (CTC) and cell-free circulating tumor DNA (ctDNA) released into the peripheral blood from metastatic deposits. We discuss the current challenges and future perspectives of CTCs and ctDNA as biomarkers in clinical oncology. Both CTCs and ctDNA are interesting complementary technologies that can be used in parallel in future trials assessing new drugs or drug combinations. We postulate that the liquid biopsy concept will contribute to a better understanding and clinical management of drug resistance in patients with cancer. Cancer Res; 73(21); 6384–8. ©2013 AACR.
Prostaglandin E
2
Inhibits Elastogenesis in the Ductus Arteriosus via EP4 Signaling
Authors: Yokoyama Utako , Minamisawa Susumu , Shioda Aki , Ishiwata Ryo , Jin Mei-Hua , Masuda Munetaka , Asou Toshihide , Sugimoto Yukihiko , Aoki Hiroki , Nakamura Tomoyuki , Ishikawa Yoshihiro 
Published: October 2013

Background—
Elastic fiber formation begins in mid-gestation and increases dramatically during the last trimester in the great arteries, providing elasticity and thus preventing vascular wall structure collapse. However, the ductus arteriosus (DA), a fetal bypass artery between the aorta and pulmonary artery, exhibits lower levels of elastic fiber formation, which promotes vascular collapse and subsequent closure of the DA after birth. The molecular mechanisms for this inhibited elastogenesis in the DA, which is necessary for the establishment of adult circulation, remain largely unknown.

Methods and Results—

Stimulation of the prostaglandin E
2
(PGE
2
) receptor EP4 significantly inhibited elastogenesis and decreased lysyl oxidase (LOX) protein, which catalyzes elastin cross-links in DA smooth muscle cells (SMCs), but not in aortic SMCs. Aortic SMCs expressed much less EP4 than DASMCs. Adenovirus-mediated overexpression of LOX restored the EP4-mediated inhibition of elastogenesis in DASMCs. In EP4-knockout mice, electron microscopic examination showed that the DA acquired an elastic phenotype that was similar to the neighboring aorta. More importantly, human DA and aorta tissues from 7 patients showed a negative correlation between elastic fiber formation and EP4 expression, as well as between EP4 and LOX expression. The PGE
2
-EP4-c-Src-phospholipase C (PLC)γ–signaling pathway most likely promoted the lysosomal degradation of LOX.

Conclusions—

Our data suggest that PGE
2
signaling inhibits elastogenesis in the DA, but not in the aorta, through degrading LOX protein. Elastogenesis is spatially regulated by PGE
2
-EP4 signaling in the DA.
Quantification of clusterin in paired cerebrospinal fluid and plasma samples
Authors: Jongbloed Wesley , Herrebout Maaike AC , Blankenstein Marinus A , Veerhuis Robert 
Published: October 2013

Background Clusterin (ApoJ) is an amyloid-associated protein and plays an important role in Alzheimer’s disease (AD) pathology. Recent genome-wide association studies have indicated that certain genetic variants increase the risk of developing AD. To determine if the expression of clusterin is different in AD patients, both systemically and locally in the brain, differs between (subgroups of) AD patients and non-AD cases, an assay available that detects clusterin in both plasma and cerebrospinal fluid (CSF) with equal sensitivity would be helpful. Methods We compared four different commercially available antibodies in their ability to detect recombinant clusterin and immune-purified human clusterin. Specificity was tested on western blot and in ELISA systems, and selection was based on the ability to detect clusterin in CSF and plasma. A sandwich ELISA was developed and validated with monoclonal antibody G7 as capture, and rabbit polyclonal (Alexis) antibodies for detection. Results Our ELISA measured clusterin concentrations in plasma and CSF with dynamic ranges of 2–70 mg/L and 0.5–40 mg/L, respectively. The assays showed 99.8% recovery in CSF and 97% recovery in plasma. Intra-assay coefficient of variation was 1.4% and inter-assay 8.8%. The assay shows no cross-reactivity with related apolipoproteins. Clusterin quantification is dependent on the type of storage for plasma samples. A single freeze/thaw cycle caused fluctuations of clusterin concentrations in plasma, while clusterin in CSF is stable for up to five cycles. Conclusions We have successfully developed a clusterin ELISA that reliably measures CSF and plasma clusterin concentrations. In a pilot study, all samples gave results that were well within the dynamic range of the assay, with low variations. Freshly stored plasma samples are crucial for accurate clusterin quantification.
Patterns of stigma toward schizophrenia among the general population: A latent profile analysis
Authors: Loch Alexandre A , Wang Yuan-Pang , Guarniero Francisco B , Lawson Fabio L , Hengartner Michael P , Rössler Wulf , Gattaz Wagner F 
Published: October 2013

Objective: Our purpose was to assess stigma toward schizophrenia in a representative sample of the Brazilian general population. Methods: The sample consisted of 1015 individuals interviewed by telephone. A vignette describing someone with schizophrenia was read, and four stigma aspects regarding this hypothetical individual were assessed: stereotypes, restrictions, perceived prejudice and social distance. Latent profile analysis searched for stigma profiles among the sample. Multinomial logistic regression was used to find correlates of each class. Results: Four stigma profiles were found; ‘no stigma’ individuals ( n = 251) mostly displayed positive opinions. ‘Labelers’ ( n = 222) scored high on social distance; they more often had familial contact with mental illness and more often labeled the vignette’s disorder as schizophrenia. ‘Discriminators’, the group with the majority of individuals ( n = 302), showed high levels of stigmatizing beliefs in all dimensions; discriminators were significantly older. ‘Unobtrusive stigma’ individuals ( n = 240) seemed to demonstrate uncertainty or low commitment since they mostly answered items with the middle/impartial option. Conclusion: Some findings from the international literature were replicated; however, familial contact increased stigma, possibly denoting a locally modulated determinant. Hereby, our study also adds important cross-cultural data by showing that stigma toward schizophrenia is high in a Latin-American setting. We highlight the importance of analyzing the general population as a heterogeneous group, aiming to better elaborate anti-stigma campaigns.
Surgical informed consent in Iran—how much is it informed?
Authors: Faghanipour Somayeh , Joolaee Soodabeh , Sobhani Marzieh 
Published: October 2013

Introduction: Informed consent constitutes one of the most important legal, professional, and ethical principles of a surgical operation. Consent obtained from a patient is only valid when the patient has received enough information regarding the proposed treatment option. This study aims to determine how much the patients are informed before undergoing surgery, as well as the factors influencing it in hospitals affiliated with Tehran University of Medical Sciences. Method: This is a cross-sectional, descriptive–analytic study of 300 patients undergoing surgery in 7 teaching hospitals affiliated with Tehran University of Medical Sciences. The patients were recruited through clustered sampling. Data were collected using a questionnaire completed by interview. Data were analyzed on SPSS software using descriptive and inferential statistics. Result: The mean score of data provision for patients was 27.09 out of 60, indicating the level of information provided as unacceptable. Among 12 questions dealing with data provision, patients had received an intermediate level of information about nature of the disease, type of surgery, benefits and importance of the surgery, and complications of rejecting the recommended therapy. On the contrary, they had not received enough information about the surgical procedure, type of anesthesia, potential complications of surgery, potential risks of surgery, other therapy options instead of surgery, length of hospital stay for surgery, postsurgical follow-up, and expenses of the surgery. In the majority (85%) of cases, the surgeon was reported to be the information provider. Among the variables studied, level of information received was directly related to the patient’s education level. Discussion: The findings of this study indicate that during the process of obtaining an informed consent for surgery, patients do not receive sufficient information, and it is necessary to provide the essential information in an understandable manner adjusted for the patient’s level of education.
Reduced axonal motor protein expression in non-lesional grey matter in multiple sclerosis
Authors: Hares K , Kemp K , Rice C , Gray E , Scolding N , Wilkins A 
Published: October 2013

Background: Multiple sclerosis (MS) is a neurological disease characterised by central nervous system inflammation, demyelination, axonal degeneration and neuronal injury. Preventing neuronal and axon damage is of paramount importance in attempts to prevent disease progression. Intact axonal transport mechanisms are crucial to axonal integrity and evidence suggests these mechanisms are disrupted in MS. Anterograde axonal transport is mediated to a large extent through the kinesin superfamily proteins. Recently, certain kinesin superfamily proteins (KIF5A, KIF1B and KIF21B) were implicated in MS pathology. Objectives: To investigate the expression of KIF5A, KIF21B and KIF1B in MS and control post-mortem grey matter. Methods: Using both quantitative real-time polymerase chain reaction (PCR) and Immunodot-blots assays, we analysed the expression of kinesin superfamily proteins in 27 MS cases and 13 control cases not linked to neurological disease. Results: We have shown significant reductions in KIF5A, KIF21B and KIF1B messenger ribonucleic acid (mRNA) expression and also KIF5A protein expression in MS grey matter, as compared to control grey matter. Conclusion: We have shown significant reductions in mRNA and protein levels of axonal motor proteins in the grey matter of MS cases, which may have important implications for the pathogenesis of neuronal/axonal injury in the disease.
HLA-E restricted CD8+ T cell subsets are phenotypically altered in multiple sclerosis patients
Authors: Pannemans Kim , Broux Bieke , Goris An , Dubois Bénédicte , Broekmans Tom , Van Wijmeersch Bart , Geraghty Daniel , Stinissen Piet , Hellings Niels 
Published: October 2013

Background: The importance of Qa-1 restricted CD8+ T cells in regulating autoreactive T cell responses has been demonstrated in animal models for autoimmune disorders, including multiple sclerosis (MS). Objective: We hypothesize that their human variant, HLA-E restricted CD8+ T cells, fulfills a similar regulatory role in man and that these cells are of importance in MS. Methods: A large cohort of MS patients and healthy controls was genotyped for the two known HLA-E polymorphisms. Flow cytometry was used to determine HLA-E expression kinetics and to phenotype HLA-E restricted CD8+ T cells. Immunohistochemistry was performed to investigate HLA-E expression in the central nervous system (CNS) of MS patients. Results: HLA-E is upregulated on immune cells upon in vitro activation and this upregulation is polymorphism-dependent for T and B cells. T and B cells in lesions of MS patients show enhanced HLA-E expression. Furthermore, NKG2C+CD8+ T cells of MS patients have a significantly lower Foxp3 expression, while NKG2A+CD8+ T cells of MS patients produce higher levels of pro-inflammatory cytokines compared to those of healthy individuals. Conclusion: Our study indicates that the HLA-E system is altered in MS and could play a regulatory role in disease.
Serological markers in psoriatic arthritis: promising tools
Authors: Ramonda Roberta , Modesti Valentina , Ortolan Augusta , Scanu Anna , Bassi Nicola , Oliviero Francesca , Punzi Leonardo 
Published: October 2013

The aim of this study was to identify specific biomarkers that could be used to screen for psoriatic arthritis (PsA), as well as to assess disease activity and treatment outcome in affected patients. Forty-three outpatients considered eligible for anti-TNF-α treatment (etanercept 50 mg/week) were enrolled. Serum samples of vascular endothelial growth factor (VEGF), metalloproteinase-3 (MMP3), pentraxin 3 (PTX3), and high-sensitive C-reactive protein (hs-CRP) were collected at baseline (t0) and after 6 (t6), 12 (t12), and 24 months (t24) of treatment. Baseline values were compared with those of a group of healthy controls matched for age and sex. Disease activity scores and functional tests (DAS28, BASDAI, PASI, BASFI, HAQ, VAS pain, and VAS patient global disease activity) after treatment were found to be significantly different from baseline values. At baseline, MMP3, hs-CRP and VEGF values in the PsA-patients were found to be significantly higher with respect to levels in the controls. There were no differences in the PTX3 values. MMP3 was significantly lower at t6 ( P < 0.0001), t12 ( P < 0.0001) and t24 ( P < 0.0001). hs-CRP and VEGF were significantly lower, respectively, at t12 ( P < 0.01; P < 0.05) and t24 ( P < 0.05; P < 0.01). PTX3 was significantly higher at t24 ( P < 0.05). A correlation was found between MMP3 and hs-CRP (r = 0.45, P = 0.0005). MMP3, hs-CRP, and VEGF appear to be useful for the early detection of PsA and to monitor disease progression. The rise in PTX3 did not appear to be linked to the inflammatory state of the disease but might be an expression of the atherosclerotic process frequently observed in PsA.
Clinical, genomic, and imaging predictors of myeloma progression from asymptomatic monoclonal gammopathies (SWOG S0120)
Authors: Dhodapkar Madhav V. , Sexton Rachael , Waheed Sarah , Usmani Saad , Papanikolaou Xenofon , Nair Bijay , Petty Nathan , Shaughnessy John D. , Hoering Antje , Crowley John , Orlowski Robert Z. , Barlogie Bart 
Published: October 2013

Key PointsFirst prospective US cooperative trial group in preneoplastic gammopathies. Prospective demonstration that genomic features of preneoplastic cells predict disease risk.
Association of frailty and physical function in patients with non-dialysis CKD: a systematic review
Authors: Walker Simon R , Gill Kamalpreet , Macdonald Kerry , Komenda Paul , Rigatto Claudio , Sood Manish M , Bohm Clara J , Storsley Leroy J , Tangri Navdeep 
Published: October 2013

Abstract

Background
Frailty is a condition characterized by a decline in physical function and functional capacity. Common symptoms of frailty, such as weakness and exhaustion, are prevalent in patients with chronic kidney disease (CKD). The increased vulnerability of frail patients with coexisting CKD may place them at a heightened risk of encountering additional health complications. The purpose of this systematic review was to explore the link between frailty, CKD and clinical outcomes.

Methods
We searched for cross sectional and prospective studies in the general population and in the CKD population indexed in EMBASE, Pubmed, Web of Science, CINAHL, Cochrane and Ageline examining the association between frailty and CKD and those relating frailty in patients with CKD to clinical outcomes.

Results
We screened 5,066 abstracts and retrieved 108 studies for full text review. We identified 7 studies associating frailty or physical function to CKD. From the 7 studies, we identified only two studies that related frailty in patients with CKD to a clinical outcome. CKD was consistently associated with increasing frailty or reduced physical function [odds ratios (OR) 1.30 to 3.12]. In patients with CKD, frailty was associated with a greater than two-fold higher risk of dialysis and/or death [OR from 2.0 to 5.88].

Conclusions
CKD is associated with a higher risk of frailty or diminished physical function. Furthermore, the presence of frailty in patients with CKD may lead to a higher risk of mortality. Further research must be conducted to understand the mechanisms of frailty in CKD and to confirm its association with clinical outcomes.
Using intervention mapping for the development of a targeted secure web-based outreach strategy named SafeFriend, for Chlamydia trachomatis testing in young people at risk
Authors: Theunissen Kevin ATM , Hoebe Christian JPA , Crutzen Rik , Kara-Zaïtri Chakib , de Vries Nanne K , van Bergen Jan EAM , van der Sande Marianne AB , Dukers-Muijrers Nicole HTM 
Published: October 2013

AbstractBackgroundMany young people at high risk for Chlamydia trachomatis (Ct) are not reached by current sexual health care systems, such as general practitioners and public sexual health care centres (sexually transmitted infection clinics).Ct is the most frequently diagnosed bacterial sexually transmitted infection (STI) among sexually active people and in particular young heterosexuals. Innovative screening strategies are needed to interrupt the transmission of Ct among young people and connect the hidden cases to care.MethodsIntervention Mapping (IM), a systematic approach to develop theory- and evidence-based interventions, was used to develop a strategy to target Ct testing towards young people who are currently hidden to care in The Netherlands. Both clinical users (i.e. sexual health care nurses) and public users (i.e., young people at risk for Ct) were closely involved in the IM process. A needs assessment study was carried out using semi-structured interviews among users (N = 21), a literature search and by taking lessons learned from existing screening programmes. Theoretical methods and practical applications to reach high risk young people and influence testing were selected and translated into specific programme components.ResultsThe IM approach resulted in the development of a secure and web-based outreach Ct screening strategy, named SafeFriend. It is developed to target groups of high-risk young people who are currently hidden to care. Key methods include web-based Respondent Driven Sampling, starting from young Ct positive sexual health care centre clients, to reach and motivate peers (i.e., sex partners and friends) to get tested for Ct. Testing and the motivation of peers were proposed as the desired behavioural outcomes and the Precaution Adoption Process Model was chosen as theoretical framework. End users, i.e., young people and sexual health care nurses were interviewed and included in the development process to increase the success of implementation.ConclusionsIM proved useful to develop an intervention for targeted Ct testing among young people. We believe this to be the first web-based outreach screening strategy which combines chain referral sampling with the delivery of targeted Ct testing to high risk young people within their sexual and social networks.
Psychological Impact of Prostate Biopsy: Physical Symptoms, Anxiety, and Depression
Authors: Wade Julia , Rosario Derek J. , Macefield Rhiannon C. , Avery Kerry N.L. , Salter C. Elizabeth , Goodwin M. Louise , Blazeby Jane M. , Lane J. Athene , Metcalfe Chris , Neal David E. , Hamdy Freddie C. , Donovan Jenny L. 
Published: October 2013

Purpose To investigate the psychological impact of prostate biopsy, including relationships between physical biopsy-related symptoms and anxiety and depression. Patients and Methods A prospective cohort of 1,147 men, nested within the Prostate Testing for Cancer and Treatment trial and recommended to receive prostate biopsy, completed questionnaires assessing physical and psychological harms after biopsy in the Prostate Biopsy Effects study. Psychological impact was measured using the Hospital Anxiety and Depression Scale, and scores were compared according to experiences of biopsy-related symptoms at biopsy, and at 7 and 35 days afterward, and in relation to biopsy results. Results A total of 1,144 men (99.7%) returned questionnaires at biopsy, with 1,090 (95.0%) and 1,016 (88.6%) responding at 7 and 35 days postbiopsy. Most men experienced biopsy-related symptoms as no problem or a minor problem, and overall levels of anxiety and depression were low and similar to normative levels. Of men receiving a negative biopsy result (n = 471), anxiety was greater in those experiencing problematic biopsy-related symptoms compared with those experiencing nonproblematic symptoms at 7 days for the following symptoms: pain (P < .001), shivers, (P = .020), hematuria (P < .001), hematochezia (P < .001), and hemoejaculate (P < .001). Anxiety was reduced, although symptoms were not, after 35 days. Overall levels of anxiety were low across all time points except at the 35-day assessment among men who had received a cancer diagnosis. Conclusion Problematic postbiopsy symptoms can lead to increased anxiety, distinct from distress related to diagnosis of prostate cancer. Men and doctors need to consider these additional potential harms of biopsy when deciding whether to initiate prostate-specific antigen testing.