bluuebunny/crossref_metadata_2025_split huggingface dataset:
Open access support groups for people experiencing personality disorders: Do group members' experiences reflect the theoretical foundations of the SUN project?
Authors: Gillard Steve , White Rachel , Miller Steve , Turner Kati 
Published: May 2014

ObjectivesThe SUN Project is an innovative, open access support group, based in the community, for people experiencing personality disorders, developed in response to UK Department of Health policy advocating improvements in personality disorders services. The aim of this article is to critically explore where and how the theoretically informed model underpinning the SUN Project is reflected in the view and experiences of people attending the project.DesignThis article reports an in‐depth, qualitative interview‐based study employing a critical realist approach.MethodsAs part of a larger study about self‐care and mental health, in‐depth qualitative interviews were held with 38 people new to the SUN Project, and again 9 months later. Data were extracted that were relevant to core components of the project model and were subjected to thematic analysis. The critical realist approach was used to move back and forth between empirical data and theory underpinning the SUN project, providing critical insight into the model.ResultsParticipant accounts were broadly concordant with core components of the SUN Project's underlying model: Open access and self‐referral; group therapeutic processes; community‐based support; service users as staff. There were some tensions between interviewee accounts and theoretical aspects of the model, notably around the challenges that group processes presented for some individuals.ConclusionsThe model underlying the SUN Project is useful in informing good practice in therapeutic, community‐based peer support groups for people experiencing personality disorders. Careful consideration should be given to a limited multi‐modal approach, providing focused one‐to‐one support for vulnerable individuals who find it hard to engage in group processes.Practitioner points

Facilitated peer support groups based in the community may act as a powerful therapeutic resource for people experiencing personality disorders.

Promoting open access and self‐referral to support groups may increase feelings of empowerment and engagement for people experiencing personality disorders.

Some individuals experiencing personality disorders who could potentially benefit from therapeutic groups may need focused one‐to‐one support to do so.
Genetic Analysis of Dobrava–Belgrade Virus from Western Serbia – A Newly Detected Focus in the Balkan Peninsula
Authors: Stamenković G. , Nikolić V. , Blagojević J. , Bugarski‐Stanojević V. , Adnađević T. , Stanojević M. , Vujošević M. 
Published: May 2014

SummaryDobrava–Belgrade virus (DOBV) is a hantavirus species that causes the most severe form of haemorrhagic fever with renal syndrome (HFRS) in Europe. DOBV has been detected in three Apodemus rodents: A. flavicollis, A. agrarius and A. ponticus. These emerging viruses appear throughout the Balkan Peninsula including Serbia as its central part. In this study, we examined the seroprevalence, molecular epidemiology and phylogenetics of DOBV from A. flavicollis captured at six Serbian localities. Furthermore, we applied microsatellite typing of host animal genome to analyse the role of host kinship in DOBV animal transmission. The overall IgG seropositivity rate over 3 years (2008–2010) was 11.9% (22/185). All seropositive samples were subjected to RT‐PCR and DNA sequencing for S and L genome segments (pos. 291–1079 nt and 2999–3316 nt, respectively). DOBV was genetically detected in three samples from mountain Tara in western Serbia, a newly detected DOBV focus in the Balkans. No sequence data from human cases from Serbia are available for the studied period. However, collected DOBV isolates in this work phylogenetically clustered together with isolates from Serbian human cases dating from 2002, with 1.9% nucleotide divergence. We determined the level of kinship between seropositive and seronegative animal groups and found no significant difference, suggesting that horizontal virus transmission in the studied population was the same within and among the hatches. Our findings are the first genetic detection of DOBV in rodents in Serbia. We confirm wide and continuous hantavirus presence in the examined parts of the Balkans, underlying the necessity of continual monitoring of hantavirus circulation in A. flavicollis.
The general low-frequency prediction for asymptotically nonlinear material functions in oscillatory shear
Authors: Bharadwaj N. Ashwin , Ewoldt Randy H. 
Published: May 2014

We use a fourth-order fluid expansion to make general predictions for asymptotically nonlinear material functions in oscillatory shear, a characterization protocol sometimes known as medium-amplitude oscillatory shear. The calculation applies to any viscoelastic fluid in the terminal regime defined by the limit of Deborah number much less than one. Two viscous nonlinearities appear at third order, with shear stress scaling as ω3, and are interrelated by a constant multiplicative factor. Two elastic nonlinearities appear at fourth order, with shear stress scaling as ω4, and are also interrelated by a constant multiplicative factor. These nonlinear measures are decoupled from the linear material functions G′ and G″ because they depend on different expansion coefficients. Experimental measurements are presented for all four asymptotic shear material functions using a linear and well-entangled homopolymer of polyisoprene. The experimental observations are consistent with both the predicted frequency scaling and the predicted interrelations in the terminal regime. Signs and magnitudes cannot be universally predicted, leaving these as free parameters that depend on the specifics of the material microstructure or constitutive model. These general results explain previous observations involving different materials and constitutive models, and provide an important reference for future experiments, analytical results, and numerical computations of these rheological fingerprints.
Carbapenem-Resistant Klebsiella pneumoniae Strains Exhibit Diversity in Aminoglycoside-Modifying Enzymes, Which Exert Differing Effects on Plazomicin and Other Agents
Authors: Almaghrabi Reem , Clancy Cornelius J. , Doi Yohei , Hao Binghua , Chen Liang , Shields Ryan K. , Press Ellen G. , Iovine Nicole M. , Townsend Bethany M. , Wagener Marilyn M. , Kreiswirth Barry , Nguyen M. Hong 
Published: May 2014

ABSTRACT

We measured
in vitro
activity of plazomicin, a next-generation aminoglycoside, and other aminoglycosides against 50 carbapenem-resistant
Klebsiella pneumoniae
strains from two centers and correlated the results with the presence of various aminoglycoside-modifying enzymes (AMEs). Ninety-four percent of strains were sequence type 258 (ST258) clones, which exhibited 5
ompK36
genotypes; 80% and 10% of strains produced
Klebsiella pneumoniae
carbapenemase 2 (KPC-2) and KPC-3, respectively. Ninety-eight percent of strains possessed AMEs, including AAC(6′)-Ib (98%), APH(3′)-Ia (56%), AAC(3)-IV (38%), and ANT(2″)-Ia (2%). Gentamicin, tobramycin, and amikacin nonsusceptibility rates were 40, 98, and 16%, respectively. Plazomicin MICs ranged from 0.25 to 1 μg/ml. Tobramycin and plazomicin MICs correlated with gentamicin MICs (
r
= 0.75 and 0.57, respectively). Plazomicin exerted bactericidal activity against 17% (1× MIC) and 94% (4× MIC) of strains. All strains with AAC(6′)-Ib were tobramycin-resistant; 16% were nonsusceptible to amikacin. AAC(6′)-Ib combined with another AME was associated with higher gentamicin, tobramycin, and plazomicin MICs than AAC(6′)-Ib alone (
P
= 0.01, 0.0008, and 0.046, respectively). The presence of AAC(3)-IV in a strain was also associated with higher gentamicin, tobramycin, and plazomicin MICs (
P
= 0.0006,
P
< 0.0001, and
P
= 0.01, respectively). The combination of AAC(6′)-Ib and another AME, the presence of AAC(3)-IV, and the presence of APH(3′)-Ia were each associated with gentamicin resistance (
P
= 0.0002, 0.003, and 0.01, respectively). In conclusion, carbapenem-resistant
K. pneumoniae
strains (including ST258 clones) exhibit highly diverse antimicrobial resistance genotypes and phenotypes. Plazomicin may offer a treatment option against strains resistant to other aminoglycosides. The development of molecular assays that predict antimicrobial responses among carbapenem-resistant
K. pneumoniae
strains should be a research priority.
Alternative Strategies for Proof-of-Principle Studies of Antibacterial Agents
Authors: Dalhoff Axel , Weintraub Andrej , Nord Carl Erik 
Published: May 2014

ABSTRACT

The proof that a new antibacterial agent is not only active
in vitro
but also effective
in vivo
under clinically relevant conditions is currently provided (i) by using appropriate nonclinical models of infection and pharmacokinetic-pharmacodynamic (PK-PD) analysis providing evidence of the likelihood of clinical efficacy and (ii) by examining the study drug in exploratory clinical trials, as well as dose and schedule finding during phase II of clinical development. This approach is both time-consuming and costly. Furthermore, PK-PD targets for any novel antibacterial agent cannot be derived from studies with experimental animals. Therefore, alternative strategies have to be identified to prove the principle that a novel antibacterial agent is active under clinically relevant conditions. This review summarizes evidence that the quantitative analysis of shifts in the viable counts of pathogens in infected patients or the evaluation of the PD effect of an investigational agent on indicator organisms of the human resident microflora or colonizers of healthy volunteers, if paralleled with PK monitoring of serum and the target site, provides an alternative to a classical proof-of-principle study in the course of a phase II study program.
Antifungal Resistance to Fluconazole and Echinocandins Is Not Emerging in Yeast Isolates Causing Fungemia in a Spanish Tertiary Care Center
Authors: Marcos-Zambrano Laura Judith , Escribano Pilar , Sánchez Carlos , Muñoz Patricia , Bouza Emilio , Guinea Jesús 
Published: May 2014

ABSTRACT

Accurate knowledge of fungemia epidemiology requires identification of strains to the molecular level. Various studies have shown that the rate of resistance to fluconazole ranges from 2.5% to 9% in
Candida
spp. isolated from blood samples. However, trends in antifungal resistance have received little attention and have been studied only using CLSI M27-A3 methodology. We assessed the fungemia epidemiology in a large tertiary care institution in Madrid, Spain, by identifying isolates to the molecular level and performing antifungal susceptibility testing according to the updated breakpoints of European Committee for Antimicrobial Susceptibility Testing (EUCAST) definitive document (EDef) 7.2. We studied 613 isolates causing 598 episodes of fungemia in 544 patients admitted to our hospital (January 2007 to December 2013). Strains were identified after amplification and sequencing of the ITS1-5.8S-ITS2 region and further tested for
in vitro
susceptibility to amphotericin B, fluconazole, posaconazole, voriconazole, micafungin, and anidulafungin. Resistance was defined using EUCAST species-specific breakpoints, and epidemiological cutoff values (ECOFFs) were applied as tentative breakpoints. Most episodes were caused by
Candida albicans
(46%),
Candida parapsilosis
(28.7%),
Candida glabrata
(9.8%), and
Candida tropicalis
(8%). Molecular identification enabled us to better detect cryptic species of
Candida guilliermondii
and
C. parapsilosis
complexes and episodes of polyfungal fungemia. The overall percentage of fluconazole-resistant isolates was 5%, although it was higher in
C. glabrata
(8.6%) and non-
Candida
yeast isolates (47.4%). The rate of resistance to echinocandins was 4.4% and was mainly due to the presence of intrinsically resistant non-
Candida
species. Resistance mainly affected non-
Candida
yeasts. The rate of resistance to fluconazole and echinocandins did not change considerably during the study period.
Whole-Genome Analyses of Enterococcus faecium Isolates with Diverse Daptomycin MICs
Authors: Diaz Lorena , Tran Truc T. , Munita Jose M. , Miller William R. , Rincon Sandra , Carvajal Lina P. , Wollam Aye , Reyes Jinnethe , Panesso Diana , Rojas Natalia L. , Shamoo Yousif , Murray Barbara E. , Weinstock George M. , Arias Cesar A. 
Published: May 2014

ABSTRACT

Daptomycin (DAP) is a lipopeptide antibiotic frequently used as a “last-resort” antibiotic against vancomycin-resistant
Enterococcus faecium
(VRE). However, an important limitation for DAP therapy against VRE is the emergence of resistance during therapy. Mutations in regulatory systems involved in cell envelope homeostasis are postulated to be important mediators of DAP resistance in
E. faecium
. Thus, in order to gain insights into the genetic bases of DAP resistance in
E. faecium
, we investigated the presence of changes in 43 predicted proteins previously associated with DAP resistance in enterococci and staphylococci using the genomes of 19
E. faecium
with different DAP MICs (range, 3 to 48 μg/ml). Bodipy-DAP (BDP-DAP) binding to the cell membrane assays and time-kill curves (DAP alone and with ampicillin) were performed. Genetic changes involving two major pathways were identified: (i) LiaFSR, a regulatory system associated with the cell envelope stress response, and (ii) YycFGHIJ, a system involved in the regulation of cell wall homeostasis. Thr120→Ala and Trp73→Cys substitutions in LiaS and LiaR, respectively, were the most common changes identified. DAP bactericidal activity was abolished in the presence of
liaFSR
or
yycFGHIJ
mutations regardless of the DAP MIC and was restored in the presence of ampicillin, but only in representatives of the LiaFSR pathway. Reduced binding of BDP-DAP to the cell surface was the predominant finding correlating with resistance in isolates with DAP MICs above the susceptibility breakpoint. Our findings suggest that genotypic information may be crucial to predict response to DAP plus β-lactam combinations and continue to question the DAP breakpoint of 4 μg/ml.
In Vitro
and
In Vivo
Assessment of Dermatophyte Acquired Resistance to Efinaconazole, a Novel Triazole Antifungal
Authors: Iwata Atsushi , Watanabe Yoko , Kumagai Naomichi , Katafuchi-Nagashima Maria , Sugiura Keita , Pillai Radhakrishnan , Tatsumi Yoshiyuki 
Published: May 2014

ABSTRACT

Efinaconazole is a novel triazole antifungal drug for the topical treatment of onychomycosis, a nail infection caused mainly by dermatophytes. We assessed the potential of efinaconazole to induce resistance in dermatophytes by continuous exposure of
Trichophyton rubrum
strains to efinaconazole
in vitro
(12 passages) and in a guinea pig onychomycosis model (8 weeks). There was no evidence of efinaconazole resistance development in the tested strains under the experimental conditions used.
Different Interaction Profiles of Direct-Acting Anti-Hepatitis C Virus Agents with Human Organic Anion Transporting Polypeptides
Authors: Furihata Tomomi , Matsumoto Shogo , Fu Zhongguo , Tsubota Akihito , Sun Yuchen , Matsumoto Sayaka , Kobayashi Kaoru , Chiba Kan 
Published: May 2014

ABSTRACT
Simeprevir (SMV), asunaprevir (ASV), daclatasvir (DCV), and sofosbuvir (SFV), which are newly developed direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection, are among the key components of anti-HCV regimens. Preclinical studies have identified inhibitory properties for some of these DAAs against organic anion transporting polypeptide 1B (OATP1B) functions. However, their details remain mostly uncharacterized. Because OATP1B1 and OATP1B3 play determinant roles in the pharmacokinetics of various drugs via their uptake into human hepatocytes, it is plausible that the inhibition of these OATP1Bs by a DAA would create a potential risk of drug-drug interaction, which has been an emerging concern in anti-HCV therapy. Accordingly, in the present study, we intended to clarify the inhibitory characteristics of newly developed DAAs toward OATP1B1 and -1B3 functions. The results of our coincubation inhibition assays have shown that all tested DAAs could inhibit OATP1B1 functions and that SMV, ASV, and DCV (to a lesser extent), but not SFV, exhibited long-lasting preincubation inhibitory effects on OATP1B1 functions. It was also found that the preincubation inhibitory effects of SMV and ASV could augment their coincubation inhibition potency. Furthermore, significant, but differential, inhibitory effects of the DAAs on the OATP1B3 function were identified. To summarize, our results clearly show that the newly developed DAAs are newly identified OATP1B1 and OATP1B3 inhibitors with distinctive interaction properties. It is believed that these inhibition profiles will provide essential information to all concerned parties with respect to the clinical significance of DAA-mediated inhibition of OATP1Bs in anti-HCV therapy.
Effects of the W153L Substitution in HIV Reverse Transcriptase on Viral Replication and Drug Resistance to Multiple Categories of Reverse Transcriptase Inhibitors
Authors: Xu Hong-Tao , Colby-Germinario Susan P. , Oliveira Maureen , Rajotte Daniel , Bethell Richard , Wainberg Mark A. 
Published: May 2014

ABSTRACTA W153L substitution in HIV-1 reverse transcriptase (RT) was recently identified by selection with a novel nucleotide-competing RT inhibitor (NcRTI) termed compound A that is a member of the benzo[4,5]furo[3,2,d]pyrimidin-2-one NcRTI family of drugs. To investigate the impact of W153L, alone or in combination with the clinically relevant RT resistance substitutions K65R (change of Lys to Arg at position 65), M184I, K101E, K103N, E138K, and Y181C, on HIV-1 phenotypic susceptibility, viral replication, and RT enzymatic function, we generated recombinant RT enzymes and viruses containing each of these substitutions or various combinations of them. We found that W153L-containing viruses were impaired in viral replicative capacity and were hypersusceptible to tenofovir (TFV) while retaining susceptibility to most nonnucleoside RT inhibitors. The nucleoside 3TC retained potency against W153L-containing viruses but not when the M184I substitution was also present. W153L was also able to reverse the effects of the K65R substitution on resistance to TFV, and K65R conferred hypersusceptibility to compound A. Biochemical assays demonstrated that W153L alone or in combination with K65R, M184I, K101E, K103N, E138K, and Y181C impaired enzyme processivity and polymerization efficiency but did not diminish RNase H activity, providing mechanistic insights into the low replicative fitness associated with these substitutions. We show that the mechanism of the TFV hypersusceptibility conferred by W153L is mainly due to increased efficiency of TFV-diphosphate incorporation. These results demonstrate that compound A and/or derivatives thereof have the potential to be important antiretroviral agents that may be combined with tenofovir to achieve synergistic results.
SAMHD1 Has Differential Impact on the Efficacies of HIV Nucleoside Reverse Transcriptase Inhibitors
Authors: Huber Andrew D. , Michailidis Eleftherios , Schultz Megan L. , Ong Yee T. , Bloch Nicolin , Puray-Chavez Maritza N. , Leslie Maxwell D. , Ji Juan , Lucas Anthony D. , Kirby Karen A. , Landau Nathaniel R. , Sarafianos Stefan G. 
Published: May 2014

ABSTRACT
Sterile alpha motif- and histidine/aspartic acid domain-containing protein 1 (SAMHD1) limits HIV-1 replication by hydrolyzing deoxynucleoside triphosphates (dNTPs) necessary for reverse transcription. Nucleoside reverse transcriptase inhibitors (NRTIs) are components of anti-HIV therapies. We report here that SAMHD1 cleaves NRTI triphosphates (TPs) at significantly lower rates than dNTPs and that SAMHD1 depletion from monocytic cells affects the susceptibility of HIV-1 infections to NRTIs in complex ways that depend not only on the relative changes in dNTP and NRTI-TP concentrations but also on the NRTI activation pathways.
Giardia muris Infection in Mice Is Associated with a Protective Interleukin 17A Response and Induction of Peroxisome Proliferator-Activated Receptor Alpha
Authors: Dreesen Leentje , De Bosscher Karolien , Grit Grietje , Staels Bart , Lubberts Erik , Bauge Eric , Geldhof Peter 
Published: May 2014

ABSTRACTThe protozoan parasiteGiardia duodenalis(Giardia lamblia) is one of the most commonly found intestinal pathogens in mammals, including humans. In the current study, aGiardia muris-mouse model was used to analyze cytokine transcription patterns and histological changes in intestinal tissue at different time points during infection in C57BL/6 mice. Since earlier work revealed the upregulation of peroxisome proliferator-activated receptors (PPARs) inGiardia-infected calves, a second aim was to investigate the potential activation of PPARs in the intestines of infected mice. The most important observation in all mice was a strong upregulation ofil17astarting around 1 week postinfection. The significance of interleukin 17A (IL-17A) in orchestrating a protective immune response was further demonstrated in an infection trial or experiment using IL-17 receptor A (IL-17RA) knockout (KO) mice: whereas in wild-type (WT) mice, cyst secretion dropped significantly after 3 weeks of infection, the IL-17RA KO mice were unable to clear the infection. Analysis of the intestinal response further indicated peroxisome proliferator-activated receptor alpha (PPARα) induction soon after the initial contact with the parasite, as characterized by the transcriptional upregulation ofpparaitself and several downstream target genes such aspltpandcpt1. Overall, PPARα did not seem to have any influence on the immune response againstG. muris, since PPARα KO animals expressedil-17aand could clear the infection similar to WT controls. In conclusion, this study shows for the first time the importance of IL-17 production in the clearance of aG. murisinfection together with an early induction of PPARα. The effect of the latter, however, is still unclear.
Development of an
Ex Vivo
Porcine Lung Model for Studying Growth, Virulence, and Signaling of Pseudomonas aeruginosa
Authors: Harrison Freya , Muruli Aneesha , Higgins Steven , Diggle Stephen P. 
Published: May 2014

ABSTRACT

Research into chronic infection by bacterial pathogens, such as
Pseudomonas aeruginosa
, uses various
in vitro
and live host models. While these have increased our understanding of pathogen growth, virulence, and evolution, each model has certain limitations.
In vitro
models cannot recapitulate the complex spatial structure of host organs, while experiments on live hosts are limited in terms of sample size and infection duration for ethical reasons; live mammal models also require specialized facilities which are costly to run. To address this, we have developed an
ex vivo
pig lung (EVPL) model for quantifying
Pseudomonas aeruginosa
growth, quorum sensing (QS), virulence factor production, and tissue damage in an environment that mimics a chronically infected cystic fibrosis (CF) lung. In a first test of our model, we show that
lasR
mutants, which do not respond to 3-oxo-C
12
-homoserine lactone (HSL)-mediated QS, exhibit reduced virulence factor production in EVPL. We also show that
lasR
mutants grow as well as or better than a corresponding wild-type strain in EVPL.
lasR
mutants frequently and repeatedly arise during chronic CF lung infection, but the evolutionary forces governing their appearance and spread are not clear. Our data are not consistent with the hypothesis that
lasR
mutants act as social “cheats” in the lung; rather, our results support the hypothesis that
lasR
mutants are more adapted to the lung environment. More generally, this model will facilitate improved studies of microbial disease, especially studies of how cells of the same and different species interact in polymicrobial infections in a spatially structured environment.