bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of Isavuconazole Susceptibility of Aspergillus and Candida Species by the EUCAST Method
Authors: Howard Susan J. , Lass-Flörl Cornelia , Cuenca-Estrella Manuel , Gomez-Lopez Alicia , Arendrup Maiken C. 
Published: August 2013

ABSTRACT

Isavuconazole is a novel expanded-spectrum triazole, which has recently been approved by the FDA as an orphan drug to treat invasive aspergillosis and is currently being studied in phase III clinical trials for invasive candidiasis. The susceptibility of relatively few clinical isolates has been reported. In this study, the isavuconazole susceptibilities of 1,237
Aspergillus
and 2,010
Candida
geographically diverse clinical isolates were determined by EUCAST methodology at four European mycology laboratories, producing the largest multicenter data set thus far for this compound. In addition, a blinded collection of 30
cyp51A
mutant
Aspergillus fumigatus
clinical isolates and 10 wild-type isolates was tested. From these two data sets, the following preliminary epidemiological cutoff (ECOFF) values were suggested: 2 mg/liter for
Aspergillus fumigatus
,
Aspergillus terreus
, and
Aspergillus flavus
; 4 mg/liter for
Aspergillus niger
; 0.25 mg/liter for
Aspergillus nidulans
; and 0.03 mg/liter for
Candida albicans
,
Candida parapsilosis
, and
Candida tropicalis
. Unfortunately, ECOFFs could not be determined for
Candida glabrata
or
Candida krusei
due to an unexplained interlaboratory MIC variation. For the blinded collection of
A. fumigatus
isolates, all MICs were ≤2 mg/liter for wild-type isolates. Differential isavuconazole MICs were observed for triazole-resistant
A. fumigatus
isolates with different
cyp51A
alterations: TR
34
/L98H mutants had elevated isavuconazole MICs, whereas isolates with G54 and M220 alterations had MICs in the wild-type range, suggesting that the efficacy of isavuconazole may not be affected by these alterations. This study will be an aid in interpreting isavuconazole MICs for clinical care and an important step in the future process of setting official clinical breakpoints.
In Vitro
Efficacies and Resistance Profiles of Rifampin-Based Combination Regimens for Biofilm-Embedded Methicillin-Resistant Staphylococcus aureus
Authors: Tang Hung-Jen , Chen Chi-Chung , Cheng Kuo-Chen , Wu Kuan-Ying , Lin Yi-Chung , Zhang Chun-Cheng , Weng Tzu-Chieh , Yu Wen-Liang , Chiu Yu-Hsin , Toh Han-Siong , Chiang Shyh-Ren , Su Bo An , Ko Wen-Chien , Chuang Yin-Ching 
Published: August 2013

ABSTRACT

To compare the
in vitro
antibacterial efficacies and resistance profiles of rifampin-based combinations against methicillin-resistant
Staphylococcus aureus
(MRSA) in a biofilm model, the antibacterial activities of vancomycin, teicoplanin, daptomycin, minocycline, linezolid, fusidic acid, fosfomycin, and tigecycline alone or in combination with rifampin against biofilm-embedded MRSA were measured. The rifampin-resistant mutation frequencies were evaluated. Of the rifampin-based combinations, rifampin enhances the antibacterial activities of and even synergizes with fusidic acid, tigecycline, and, to a lesser extent, linezolid, fosfomycin, and minocycline against biofilm-embedded MRSA. Such combinations with weaker rifampin resistance induction activities may provide a therapeutic advantage in MRSA biofilm-related infections.
Menaquinone Analogs Inhibit Growth of Bacterial Pathogens
Authors: Schlievert Patrick M. , Merriman Joseph A. , Salgado-Pabón Wilmara , Mueller Elizabeth A. , Spaulding Adam R. , Vu Bao G. , Chuang-Smith Olivia N. , Kohler Petra L. , Kirby John R. 
Published: August 2013

ABSTRACT

Gram-positive bacteria cause serious human illnesses through combinations of cell surface and secreted virulence factors. We initiated studies with four of these organisms to develop novel topical antibacterial agents that interfere with growth and exotoxin production, focusing on menaquinone analogs. Menadione, 1,4-naphthoquinone, and coenzymes Q1 to Q3 but not menaquinone, phylloquinone, or coenzyme Q10 inhibited the growth and to a greater extent exotoxin production of
Staphylococcus aureus
,
Bacillus anthracis
,
Streptococcus pyogenes
, and
Streptococcus agalactiae
at concentrations of 10 to 200 μg/ml. Coenzyme Q1 reduced the ability of
S. aureus
to cause toxic shock syndrome in a rabbit model, inhibited the growth of four Gram-negative bacteria, and synergized with another antimicrobial agent, glycerol monolaurate, to inhibit
S. aureus
growth. The staphylococcal two-component system SrrA/B was shown to be an antibacterial target of coenzyme Q1. We hypothesize that menaquinone analogs both induce toxic reactive oxygen species and affect bacterial plasma membranes and biosynthetic machinery to interfere with two-component systems, respiration, and macromolecular synthesis. These compounds represent a novel class of potential topical therapeutic agents.
Human and Animal Isolates of Yersinia enterocolitica Show Significant Serotype-Specific Colonization and Host-Specific Immune Defense Properties
Authors: Schaake Julia , Kronshage Malte , Uliczka Frank , Rohde Manfred , Knuuti Tobias , Strauch Eckhard , Fruth Angelika , Wos-Oxley Melissa , Dersch Petra 
Published: August 2013

ABSTRACT

Yersinia enterocolitica
is a human pathogen that is ubiquitous in livestock, especially pigs. The bacteria are able to colonize the intestinal tract of a variety of mammalian hosts, but the severity of induced gut-associated diseases (yersiniosis) differs significantly between hosts. To gain more information about the individual virulence determinants that contribute to colonization and induction of immune responses in different hosts, we analyzed and compared the interactions of different human- and animal-derived isolates of serotypes O:3, O:5,27, O:8, and O:9 with murine, porcine, and human intestinal cells and macrophages. The examined strains exhibited significant serotype-specific cell binding and entry characteristics, but adhesion and uptake into different host cells were not host specific and were independent of the source of the isolate. In contrast, survival and replication within macrophages and the induced proinflammatory response differed between murine, porcine, and human macrophages, suggesting a host-specific immune response. In fact, similar levels of the proinflammatory cytokine macrophage inflammatory protein 2 (MIP-2) were secreted by murine bone marrow-derived macrophages with all tested isolates, but the equivalent interleukin-8 (IL-8) response of porcine bone marrow-derived macrophages was strongly serotype specific and considerably lower in O:3 than in O:8 strains. In addition, all tested
Y. enterocolitica
strains caused a considerably higher level of secretion of the anti-inflammatory cytokine IL-10 by porcine than by murine macrophages. This could contribute to limiting the severity of the infection (in particular of serotype O:3 strains) in pigs, which are the primary reservoir of
Y. enterocolitica
strains pathogenic to humans.
IglE Is an Outer Membrane-Associated Lipoprotein Essential for Intracellular Survival and Murine Virulence of Type A Francisella tularensis
Authors: Robertson Gregory T. , Child Robert , Ingle Christine , Celli Jean , Norgard Michael V. 
Published: August 2013

ABSTRACT

IglE is a small, hypothetical protein encoded by the duplicated
Francisella
pathogenicity island (FPI). Inactivation of both copies of
iglE
rendered
Francisella tularensis
subsp.
tularensis
Schu S4 avirulent and incapable of intracellular replication, owing to an inability to escape the phagosome. This defect was fully reversed following single-copy expression of
iglE
in
trans
from
att
Tn
7
under the control of the
Francisella rpsL
promoter, thereby establishing that the loss of
iglE
, and not polar effects on downstream
vgrG
gene expression, was responsible for the defect. IglE is exported to the
Francisella
outer membrane as an ∼13.9-kDa lipoprotein, determined on the basis of a combination of selective Triton X-114 solubilization, radiolabeling with [
3
H]palmitic acid, and sucrose density gradient membrane partitioning studies. Lastly, a genetic screen using the
iglE
-null live vaccine strain resulted in the identification of key regions in the carboxyl terminus of IglE that are required for intracellular replication of
Francisella tularensis
in J774A.1 macrophages. Thus, IglE is essential for
Francisella tularensis
virulence. Our data support a model that likely includes protein-protein interactions at or near the bacterial cell surface that are unknown at present.
Delayed onset of vastii muscle activity in response to rapid postural perturbations following eccentric exercise: a mechanism that underpins knee pain after eccentric exercise?
Authors: Hedayatpour Nosratollah , Falla Deborah 
Published: August 2013

BackgroundAppropriate timing of activity of the vastus medialis obliqus (VMO) and vastus lateralis (VL) muscles is a key factor for proper tracking of the patella in the trochlear groove during knee extension. This study investigates the relative timing of activation of the VMO and VL muscles during unexpected perturbations performed before and after eccentric exercise.MethodsSurface electromyography signals were recorded from the VMO and VL muscles of the right leg in 11 healthy men during rapid postural perturbations performed at baseline, immediately after eccentric exercise of the quadriceps, and at 24 and 48 h after exercise. Participants stood on a moveable platform during which eight randomised postural perturbations were performed (4 repetitions of 2 perturbation types: 8 cm forward slides, 8 cm backward slides).ResultsBefore the eccentric exercise, the onset of VMO activity was significantly earlier than the VL muscle (average for both forward and backward perturbations: VMO 39.0±7.1 ms; VL 43.7±7.9 ms). However, the onset of VMO activity was significantly later compared with VL muscle immediately after eccentric exercise and this remained 24 and 48 h after eccentric exercise (average across all postexercise sessions and perturbation directions: VMO 72.3±11.1 ms; VL 56.0±8.2 ms; p<0.05).ConclusionsThe onset of VMO–VL activity in response to rapid destabilising perturbations is altered immediately after eccentric exercise and during eccentric exercise-induced muscle soreness up to 48 h later. These observations may help explain the high prevalence of knee disorders after high intensity eccentric exercise.
Trends in ischaemic heart disease hospitalisation and case fatality in the Hong Kong Chinese population 2000–2009: a secondary analysis
Authors: Chau P H , Wong M , Woo J 
Published: August 2013

ObjectivesThis study examines the recent trends in ischaemic heart disease (IHD) incidence and case fatality in Hong Kong and explores the possible risk factors.DesignRetrospective observational study.SettingAll public hospitals in Hong Kong.Outcome measuresIncidence rate was defined as the number of IHD inpatient episodes divided by the size of the corresponding population. Short-term and long-term case fatality rate was defined as deaths from all causes occurring within 30 and 31–365 days, respectively, divided by the number of IHD inpatient episodes among the corresponding population.MethodsPoisson and logistic regression models were used to examine the IHD incidence and short-term/long-term case fatality trends, respectively, for different age and sex groups.ResultsIHD incidence was stable in most age groups. However, the incidence in men aged 15–24, 35–44 and ≥85 years showed increasing trends, whereas the incidence in men aged 55–64 years and women aged 35–74 years showed decreasing trends. Overall, the short-term/long-term case fatality rates were unchanged over time for both sexes. Short-term case fatality showed increasing trends in women aged 65–74 and ≥85 years, while long-term case fatality in men aged 55–64 and 75–84 years and women aged ≥75 years showed increasing trends.ConclusionsHong Kong trends resembled those in the USA, England and Wales, showing stable or slow decline in the IHD rates, while increasing trends were observed for some age groups, particularly young adults. Public health promotion efforts should focus on reducing cardiovascular risk factors, such as hypertension prevalence.
Surgical Intensive Care Unit Optimal Mobilisation Score (SOMS) trial: a protocol for an international, multicentre, randomised controlled trial focused on goal-directed early mobilisation of surgical ICU patients
Authors: Meyer Matthew J , Stanislaus Anne B , Lee Jarone , Waak Karen , Ryan Cheryl , Saxena Richa , Ball Stephanie , Schmidt Ulrich , Poon Trudy , Piva Simone , Walz Matthias , Talmor Daniel S , Blobner Manfred , Latronico Nicola , Eikermann Matthias 
Published: August 2013

IntroductionImmobilisation in the intensive care unit (ICU) leads to muscle weakness and is associated with increased costs and long-term functional disability. Previous studies showed early mobilisation of medical ICU patients improves clinical outcomes. The Surgical ICU Optimal Mobilisation Score (SOMS) trial aims to test whether a budget-neutral intervention to facilitate goal-directed early mobilisation in the surgical ICU improves participant mobilisation and associated clinical outcomes.Methods and analysisThe SOMS trial is an international, multicentre, randomised clinical study being conducted in the USA and Europe. We are targeting 200 patients. The primary outcome is average daily SOMS level and key secondary outcomes are ICU length of stay until discharge readiness and ‘mini’ modified Functional Independence Measure (mmFIM) at hospital discharge. Additional secondary outcomes include quality of life assessed at 3 months after hospital discharge and global muscle strength at ICU discharge. Exploratory outcomes will include: ventilator-free days, ICU and hospital length of stay and 3-month mortality. We will explore genetic influences on the effectiveness of early mobilisation and centre-specific effects of early mobilisation on outcomes.Ethics and disseminationFollowing Institutional Review Board (IRB) approval in three institutions, we started study recruitment and plan to expand to additional centres in Germany and Italy. Safety monitoring will be the domain of the Data and Safety Monitoring Board (DSMB). The SOMS trial will also explore the feasibility of a transcontinental study on early mobilisation in the surgical ICU.ResultsThe results of this study, along with those of ancillary studies, will be made available in the form of manuscripts and presentations at national and international meetings.RegistrationThis study has been registered at clinicaltrials.gov (NCT01363102).
Protocol for a qualitative study of knowledge translation in a participatory research project
Authors: Lillehagen Ida , Vøllestad Nina , Heggen Kristin , Engebretsen Eivind 
Published: August 2013

IntroductionIn this article, we present a methodological design for qualitative investigation of knowledge translation (KT) between participants in a participatory research project. In spite of a vast expansion of conceptual models and frameworks for conducting KT between research and practice, few models emphasisehowKTs come about. Better understanding of the actions and activities involved in a KT process is important for promoting diffusion of knowledge and improving patient care. The purpose of this article is to describe a methodological design for investigating how KTs come about in participatory research.Methods and analysisThe article presents an ethnographic study which investigates meetings between participants in a participatory research project. The participants are researchers and primary healthcare clinicians. Data are collected through observation, interviews and document studies. The material is analysed using the analytical concepts of knowledge objects, knowledge forms and knowledge positions. These concepts represent an analytical framework enabling us to observe knowledge and how it is translated between participants. The main expected outcome of our study is to develop a typology of KT practices relevant to participatory research.Ethics and disseminationThe project has been evaluated and approved by the Norwegian Social Science Data Services. Informed consent was obtained for all participants. The findings from this study will be disseminated through peer-reviewed publications and national and international conference presentations.
Design of an instrument to measure alcohol-related psychosocial influences in the development of norms among 13-year-old to 17-year-old adolescents
Authors: Hildebrand Janina , Maycock Bruce , Burns Sharyn , Zhao Yun , Allsop Steve , Howat Peter , Lobo Roanna 
Published: August 2013

IntroductionHarmful drinking among young people is common in Australia and many other countries. Social norms and their influence on adolescents’ alcohol consumption behaviours have received much research attention in recent years. However, there is limited understanding of how social norms related to alcohol are developed and transmitted across social networks and a specific tool that measures these constructs has yet to be developed. This paper outlines the rationale and protocol for the design and validation of a multidimensional survey instrument which measures the development and transmission pathways of alcohol-related norms among adolescents. A longer term aim is to apply the instrument in a respondent-driven sampling study with a large adolescent cohort.Methods and analysisSocial Cognitive Theory (SCT) and relevant literature will guide the design of the online survey instrument. Feedback from a practitioner-based stakeholder committee, academic expert panel reviews, focus groups and interviews with adolescents aged 13–17 years in Perth, Western Australia (WA) will serve to ascertain content and face validity. A test–retest will be conducted using a purposive sample of students (n=400) at secondary schools in Perth. The instrument's psychometric properties will be analysed, including exploratory factor analyses, discriminant validity, internal consistency and test–retest reliability.Ethics and disseminationThe results of this research will provide public health researchers and practitioners with a comprehensive standardised instrument to explore the characteristics of individual-level and community-level social influences and norms associated with use of alcohol by adolescents and the routes through which these norms are transmitted. The data collected by the instrument is anticipated to inform the design of youth specific interventions with the potential to reduce alcohol-related harms. The Study findings will be disseminated widely through peer-reviewed publications and conference presentations. The study has received approval from the Curtin University Human Research Ethics Committee.
Using the Clinical Research Network for psychosocial cancer research: lessons learned from two observational studies
Authors: Wright Penny , Fenlon Deborah , Jones Helen , Foster Claire , Ashley Laura , Seymour Kim Chivers , Velikova Galina , Okamoto Ikumi , Brown Julia 
Published: August 2013

BackgroundPatient recruitment to psychosocial oncology research has increased but the many studies have been single-site or small-scale. The National Institute for Health Research Clinical Research Network, supports National Institute for Health Research portfolio studies through provision of research staff for recruitment and follow-up. These studies are usually clinical trials of an investigational medicinal product. Psychosocial researchers have little used this resource.ProcessWe report the processes followed and experiences of two psychosocial research teams who recently used the Clinical Research Network, to undertake patient recruitment to two prospective observational studies: electronic Patient-reported Outcomes from Cancer Survivors study (ePOCS) and the ColoREctal Wellbeing study (CREW). Both research groups employed different approaches to using Clinical Research Network support.OutcomesePOCS secured Comprehensive Local Research Networks funding to appoint ePOCS-specific study research nurses. CREW obtained research support through the National Institute for Health Research Cancer Research Network. Recruitment targets were met (ePOCS n=636; CREW n=1055) despite logistical, administrative and bureaucratic challenges in setting up the studies. Research nurses feedback was mainly positive (ePOCS study only). Top tips for establishing and running psychosocial studies with Clinical Research Network staff are provided and suggestions given for advancing multicentre complex psychosocial studies.ConclusionsSome challenges were similar to those in delivery of clinical trials of an investigational medicinal product. The pros and cons of being involved in ePOCS from the research nurse perspective are also described. Overall the approaches used were successful with both studies reaching their recruitment targets.
Tumor Cells Upregulate Normoxic HIF-1α in Response to Doxorubicin
Authors: Cao Yiting , Eble Joseph M. , Moon Ejung , Yuan Hong , Weitzel Douglas H. , Landon Chelsea D. , Yu-Chih Nien Charleen , Hanna Gabi , Rich Jeremy N. , Provenzale James M. , Dewhirst Mark W. 
Published: August 2013

Abstract
Hypoxia-inducible factor 1 (HIF-1) is a master transcription factor that controls cellular homeostasis. Although its activation benefits normal tissue, HIF-1 activation in tumors is a major risk factor for angiogenesis, therapeutic resistance, and poor prognosis. HIF-1 activity is usually suppressed under normoxic conditions because of rapid oxygen-dependent degradation of HIF-1α. Here, we show that, under normoxic conditions, HIF-1α is upregulated in tumor cells in response to doxorubicin, a chemotherapeutic agent used to treat many cancers. In addition, doxorubicin enhanced VEGF secretion by normoxic tumor cells and stimulated tumor angiogenesis. Doxorubicin-induced accumulation of HIF-1α in normoxic cells was caused by increased expression and activation of STAT1, the activation of which stimulated expression of iNOS and its synthesis of nitric oxide (NO) in tumor cells. Mechanistic investigations established that blocking NO synthesis or STAT1 activation was sufficient to attenuate the HIF-1α accumulation induced by doxorubicin in normoxic cancer cells. To our knowledge, this is the first report that a chemotherapeutic drug can induce HIF-1α accumulation in normoxic cells, an efficacy-limiting activity. Our results argue that HIF-1α-targeting strategies may enhance doxorubicin efficacy. More generally, they suggest a broader perspective on the design of combination chemotherapy approaches with immediate clinical impact. Cancer Res; 73(20); 6230–42. ©2013 AACR.
Specific Recruitment of γδ Regulatory T Cells in Human Breast Cancer
Authors: Ye Jian , Ma Chunling , Wang Fang , Hsueh Eddy C. , Toth Karoly , Huang Yi , Mo Wei , Liu Shuai , Han Bing , Varvares Mark A. , Hoft Daniel F. , Peng Guangyong 
Published: August 2013

AbstractUnderstanding the role of different subtypes of tumor-infiltrating lymphocytes (TIL) in the immunosuppressive tumor microenvironment is essential for improving cancer treatment. Enriched γδ1 T-cell populations in TILs suppress T-cell responses and dendritic cell maturation in breast cancer, where their presence is correlated negatively with clinical outcomes. However, mechanism(s) that explain the increase in this class of regulatory T cells (γδ Treg) in patients with breast cancer have yet to be elucidated. In this study, we show that IP-10 secreted by breast cancer cells attracted γδ Tregs. Using neutralizing antibodies against chemokines secreted by breast cancer cells, we found that IP-10 was the only functional chemokine that causes γδ Tregs to migrate toward breast cancer cells. In a humanized NOD-scid IL-2Rγnull (NSG) mouse model, human breast cancer cells attracted γδ Tregs as revealed by a live cell imaging system. IP-10 neutralization in vivo inhibited migration and trafficking of γδ Tregs into breast tumor sites, enhancing tumor immunity mediated by tumor-specific T cells. Together, our studies show how γδ Tregs accumulate in breast tumors, providing a rationale for their immunologic targeting to relieve immunosuppression in the tumor microenvironment. Cancer Res; 73(20); 6137–48. ©2013 AACR.