bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Structure of Enterococcus faecium-Originated
ermB
-Positive Tn
1546
-Like Element in Staphylococcus aureus
Authors: Wan Tsai-Wen , Hung Wei-Chun , Tsai Jui-Chang , Lin Yu-Tzu , Lee Hao , Hsueh Po-Ren , Lee Tai-Fen , Teng Lee-Jene 
Published: August 2016

ABSTRACT

We determined the resistance determinants in 274 erythromycin-resistant methicillin-susceptible
Staphylococcus aureus
(MSSA) isolates during a 13-year period, 2000 to 2012. The resistance phenotypes, inducible macrolide-lincosamide-streptogramin (iMLS), constitutive MLS (cMLS), and macrolide-streptogramin (MS) resistance phenotypes, were examined by a double-disk diffusion D test. The
ermB
gene was more frequent (35%; 97/274) than
ermC
(27%; 75/274) or
ermA
(21%; 58/274). All 97
ermB
-positive isolates harbored Tn
551
and IS
1216V
. The majority (89/97) of
ermB
-positive isolates displayed the cMLS phenotype and carried mobile element structure (MES)-like structures, which has been previously reported in sequence type 59 (ST59) methicillin-resistant
S. aureus
(MRSA). The remaining 8
ermB
-carrying isolates, belonging to ST7 (
n
= 4), ST5 (
n
= 3), and ST59 (
n
= 1), were
sasK
intact and did not carry MES-like structures. Unlike a MES-like structure that was located on the chromosome, the
ermB
elements on
sasK
-intact isolates were located on plasmids by S1 nuclease pulsed-field gel electrophoresis (PFGE) analysis and conjugation tests. Sequence data for the
ermB
-containing region (14,566 bp) from ST59 NTUH_3874 revealed that the best match was a Tn
1546
-like element in plasmid pMCCL2 DNA (GenBank accession number
AP009486
) of
Macrococcus caseolyticus
. Tn
1546
is recognized as an enterococcal transposon and was known from the vancomycin resistance gene cluster in vancomycin-resistant
Enterococcus
(VRE). So far, acquisitions of Tn
1546
in
S. aureus
have occurred in clonal complex 5 (CC5) MRSA, but not in MSSA. This is the first report that MSSA harbors an
Enterococcus faecium
-originated
ermB
-positive Tn
1546
-like element located on a plasmid.
In Vitro
and
In Vivo
Drug Interaction Study of Two Lead Combinations, Oxantel Pamoate plus Albendazole and Albendazole plus Mebendazole, for the Treatment of Soil-Transmitted Helminthiasis
Authors: Cowan Noemi , Vargas Mireille , Keiser Jennifer 
Published: August 2016

ABSTRACT

The current treatments against
Trichuris trichiura
, albendazole and mebendazole, are only poorly efficacious. Therefore, combination chemotherapy was recommended for treating soil-transmitted helminthiasis. Albendazole-mebendazole and albendazole-oxantel pamoate have shown promising results in clinical trials. However,
in vitro
and
in vivo
drug interaction studies should be performed before their simultaneous treatment can be recommended. Inhibition of human recombinant cytochromes P450 (CYPs) CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 was tested by exposure to albendazole, albendazole sulfoxide, mebendazole, and oxantel pamoate, as well as albendazole-mebendazole, albendazole sulfoxide-mebendazole, albendazole-oxantel pamoate, and albendazole sulfoxide-oxantel pamoate. A high-pressure liquid chromatography (HPLC)-UV/visible spectroscopy method was developed and validated for simultaneous quantification of albendazole sulfoxide, albendazole sulfone, mebendazole, and oxantel pamoate in plasma. Albendazole, mebendazole, oxantel pamoate, albendazole-mebendazole, and albendazole-oxantel pamoate were orally applied to rats (100 mg/kg) and pharmacokinetic parameters calculated. CYP1A2 showed a 2.6-fold increased inhibition by albendazole-oxantel pamoate (50% inhibitory concentration [IC
50
] = 3.1 μM) and a 3.9-fold increased inhibition by albendazole sulfoxide-mebendazole (IC
50
= 3.8 μM) compared to the single drugs. In rats, mebendazole's area under the concentration-time curve (AUC) and maximal plasma concentration (
C
max
) were augmented 3.5- and 2.8-fold, respectively (
P
= 0.02 for both) when coadministered with albendazole compared to mebendazole alone. Albendazole sulfone was slightly affected by albendazole-mebendazole, displaying a 1.3-fold-elevated AUC compared to albendazole alone. Oxantel pamoate could not be quantified, translating to a bioavailability below 0.025% in rats. Elevated plasma levels of albendazole sulfoxide, albendazole sulfone, and mebendazole in coadministrations are probably not mediated by CYP-based drug-drug interaction. Even though this study indicates that it is safe to coadminister albendazole-oxantel pamoate and albendazole-mebendazole, human pharmacokinetic studies are recommended.
Tyrphostin AG1478 Inhibits Encephalomyocarditis Virus and Hepatitis C Virus by Targeting Phosphatidylinositol 4-Kinase IIIα
Authors: Dorobantu Cristina M. , Harak Christian , Klein Rahel , van der Linden Lonneke , Strating Jeroen R. P. M. , van der Schaar Hilde M. , Lohmann Volker , van Kuppeveld Frank J. M. 
Published: August 2016

ABSTRACT

Encephalomyocarditis virus (EMCV), like hepatitis C virus (HCV), requires phosphatidylinositol 4-kinase IIIα (PI4KA) for genome replication. Here, we demonstrate that tyrphostin AG1478, a known epidermal growth factor receptor (EGFR) inhibitor, also inhibits PI4KA activity, both
in vitro
and in cells. AG1478 impaired replication of EMCV and HCV but not that of an EMCV mutant previously shown to escape PI4KA inhibition. This work uncovers novel cellular and antiviral properties of AG1478, a compound previously regarded only as a cancer chemotherapy agent.
Secretion Chaperones PrsA2 and HtrA Are Required for Listeria monocytogenes Replication following Intracellular Induction of Virulence Factor Secretion
Authors: Ahmed Jana K. , Freitag Nancy E. 
Published: August 2016

ABSTRACT

The Gram-positive bacterium
Listeria monocytogenes
transitions from an environmental organism to an intracellular pathogen following its ingestion by susceptible mammalian hosts. Bacterial replication within the cytosol of infected cells requires activation of the central virulence regulator PrfA followed by a PrfA-dependent induction of secreted virulence factors. The PrfA-induced secreted chaperone PrsA2 and the chaperone/protease HtrA contribute to the folding and stability of select proteins translocated across the bacterial membrane.
L. monocytogenes
strains that lack both
prsA2
and
htrA
exhibit near-normal patterns of growth in broth culture but are severely attenuated
in vivo
. We hypothesized that, in the absence of PrsA2 and HtrA, the increase in PrfA-dependent protein secretion that occurs following bacterial entry into the cytosol results in misfolded proteins accumulating at the bacterial membrane with a subsequent reduction in intracellular bacterial viability. Consistent with this hypothesis, the introduction of a constitutively activated allele of
prfA
(
prfA*
) into Δ
prsA2
Δ
htrA
strains was found to essentially inhibit bacterial growth at 37°C in broth culture. Δ
prsA2
Δ
htrA
strains were additionally found to be defective for cell invasion and vacuole escape in selected cell types, steps that precede full PrfA activation. These data establish the essential requirement for PrsA2 and HtrA in maintaining bacterial growth under conditions of PrfA activation. In addition, chaperone function is required for efficient bacterial invasion and rapid vacuole lysis within select host cell types, indicating roles for PrsA2/HtrA prior to cytosolic PrfA activation and the subsequent induction of virulence factor secretion.
A Zebrafish Model of Cryptococcal Infection Reveals Roles for Macrophages, Endothelial Cells, and Neutrophils in the Establishment and Control of Sustained Fungemia
Authors: Davis J. Muse , Huang Mingwei , Botts Michael R. , Hull Christina M. , Huttenlocher Anna 
Published: August 2016

ABSTRACT
Cryptococcal meningoencephalitis is a fungal infection that predominantly affects immunocompromised patients and is uniformly fatal if left untreated. Timely diagnosis is difficult, and screening or prophylactic measures have generally not been successful. Thus, we need a better understanding of early, asymptomatic pathogenesis. Inhaled cryptococci must survive the host immune response, escape the lung, and persist within the bloodstream in order to reach and invade the brain. Here we took advantage of the zebrafish larval infection model to assess the process of cryptococcal infection and disease development sequentially in a single host. Using yeast or spores as infecting particles, we discovered that both cell types survived and replicated intracellularly and that both ultimately established a sustained, low-level fungemia. We propose that the establishment and maintenance of this sustained fungemia is an important stage of disease progression that has been difficult to study in other model systems. Our data suggest that sustained fungemia resulted from a pattern of repeated escape from, and reuptake by, macrophages, but endothelial cells were also seen to play a role as a niche for cryptococcal survival. Circulating yeast collected preferentially in the brain vasculature and eventually invaded the central nervous system (CNS). As suggested previously in a mouse model, we show here that neutrophils can play a valuable role in limiting the sustained fungemia, which can lead to meningoencephalitis. This early stage of pathogenesis—a balanced interaction between cryptococcal cells, macrophages, endothelial cells, and neutrophils—could represent a window for timely detection and intervention strategies for cryptococcal meningoencephalitis.
Patient and carer experience of hospital-based rehabilitation from intensive care to hospital discharge: mixed methods process evaluation of the RECOVER randomised clinical trial
Authors: Ramsay Pam , Huby Guro , Merriweather Judith , Salisbury Lisa , Rattray Janice , Griffith David , Walsh Timothy 
Published: August 2016

ObjectivesTo explore and compare patient/carer experiences of rehabilitation in the intervention and usual care arms of the RECOVER trial (ISRCTN09412438); a randomised controlled trial of a complex intervention of post-intensive care unit (ICU) acute hospital-based rehabilitation following critical illness.DesignMixed methods process evaluation including comparison of patients' and carers' experience of usual care versus the complex intervention. We integrated and compared quantitative data from a patient experience questionnaire (PEQ) with qualitative data from focus groups with patients and carers.SettingTwo university-affiliated hospitals in Scotland.Participants240 patients discharged from ICU who required ≥48 hours of mechanical ventilation were randomised into the trial (120 per trial arm). Exclusion criteria comprised: primary neurologic diagnosis, palliative care, current/planned home ventilation and age <18 years. 182 patients completed the PEQ at 3 months postrandomisation. 22 participants (14 patients and 8 carers) took part in focus groups (2 per trial group) at >3 months postrandomisation.InterventionsA complex intervention of post-ICU acute hospital rehabilitation, comprising enhanced physiotherapy, nutritional care and information provision, case-managed by dedicated rehabilitation assistants (RAs) working within existing ward-based clinical teams, delivered between ICU discharge and hospital discharge. Comparator was usual care.Outcome measuresA novel PEQ capturing patient-reported aspects of quality care.ResultsThe PEQ revealed statistically significant between-group differences across 4 key intervention components: physiotherapy (p=0.039), nutritional care (p=0.038), case management (p=0.045) and information provision (p<0.001), suggesting greater patient satisfaction in the intervention group. Focus group data strongly supported and helped explain these findings. Specifically, case management by dedicated RAs facilitated greater access to physiotherapy, nutritional care and information that cut across disciplinary boundaries and staffing constraints. Patients highly valued its individualisation according to their needs, abilities and preferences.ConclusionsCase management by dedicated RAs improves patients' experiences of post-ICU hospital-based rehabilitation and increases perceived quality of care.Trial registration numberISRCTN09412438.
Risk stratification for major adverse cardiac events and ventricular tachyarrhythmias by cardiac MRI in patients with cardiac sarcoidosis
Authors: Yasuda Masakazu , Iwanaga Yoshitaka , Kato Takao , Izumi Toshiaki , Inuzuka Yasutaka , Nakamura Takashi , Miyaji Yuki , Kawamura Takayuki , Ikeguchi Shigeru , Inoko Moriaki , Kurita Takashi , Miyazaki Shunichi 
Published: August 2016

BackgroundThe presence of myocardial fibrosis by cardiac MRI has prognostic value in cardiac sarcoidosis, and localisation may be equally relevant to clinical outcomes.ObjectiveWe aimed to analyse cardiac damage and function in detail and explore the relationship with clinical outcomes in patients with cardiac sarcoidosis using cardiac MRI.MethodsWe included 81 consecutive patients with cardiac sarcoidosis undergoing cardiac MR. Left ventricular mass and fibrosis mass were calculated, and localisation was analysed using a 17-segment model. Participants underwent follow-up through 2015, and the development of major adverse cardiac events including ventricular tachyarrhythmias was recorded.ResultsIncreased left ventricular fibrosis mass was associated with increased prevalence of ventricular tachyarrhythmias (p<0.001). When localisation was defined as the sum of late gadolinium enhancement in the left ventricular basal anterior and basal anteroseptal areas, or the right ventricular area, it was associated with ventricular tachyarrhythmias (p<0.001). Kaplan-Meier analysis during a median follow-up of 22.1 months showed that both the mass and localisation groupings for fibrosis were significantly associated with major adverse cardiac events or ventricular tachyarrhythmias and that when combined, the risk stratification was better than for each variable alone (p<0.001, respectively). By Cox-proportional hazard risk analysis, the localisation grouping was an independent predictor for the both.ConclusionsIn patients with cardiac sarcoidosis, both fibrosis mass and its localisation to the basal anterior/anteroseptal left ventricle, or right ventricle was associated with the development of major adverse cardiac events or ventricular tachyarrhythmias. Cardiac MR with late gadolinium enhancement may be useful for improving risk stratification in patients with cardiac sarcoidosis.
Visualization of Clusters in an Educational Data Set Based on Convex-Hull Shape Preservation Algorithm
Authors: Albertini Marcelo Keese , Backes André Ricardo 
Published: August 2016

We study the problem of visualization of clusters in an educational data set based on convex-hull shape preservation algorithm. This problem considers multidimensional data with pre-established classes with the requirement of elements of different classes must be presented at distinctive regions. Such problem is commonly found on economic and social data, where visualization is important to understand a phenomenon before further analysis. In this paper, we propose an algorithm that uses a nonlinear transformation to preserve some data distance properties and display in a convenient format to interpretation. The proposed visualization algorithm is a partition-conforming projection, as defined by Kleinberg [An impossibility theorem for clustering, Adv. Neural Inform. Processing Syst. 15: Proc. 2002 Conf., 2003, The MIT Press, p. 463.], and completely separates the convex hull of data classes by applying locally linear operations. We applied this algorithm to visualize data from an important exam applied for over four million students of the Brazilian educational system Exame Nacional do Ensino Médio (ENEM). Results show that the proposed algorithm successfully separates unintelligible data and presents it more accessible to further visual analysis.
Acute cardiopulmonary repercussions in the correct use of the dry-powder inhalers
Authors: Martinelli Bruno , Pinto Karina S. , Besse Carolina R. , Barrile Silvia R. , Rosa Deborah M. C. , Pessoa Bruna V. 
Published: August 2016

Study model: It is a cross-over, clinical and comparative study. Objective: To evaluate the acute respiratory and cardiac respercussions in correct use of the dry powder inhalers (DPI) in patients with asthma. Methodology: Seventeen adult patients with asthma using DPI (Formoterol and Budesonide) were evaluated in two moments. The mensuared variables, before and after use of DPI, were: anthropometric, cognitive, muscle strength, vital signs, periferic oxygen saturation, respiratory pressures and peak expiratory flow. In the first moment (M1) was evaluated and monitored the usual performance before and immediately after using DPI and delivered an explicative leaflet about the correct use. In the second moment (M2), 30 days after M1, there was the same evaluation, however, with correct use of the DPI. Results: In the M2 there were increases to inspiratory pressure of 64,2±2,03 to 74,1±31,7 (cmH2O); expiratory pressure of 71,05±33,8 to 80±31,4 (cmH2O); vital capacity of 3,3±0,9 to 3,9±0,9 (l) and reductions in the pulse frequence of 80,3±10,7 to 72,2±9,4 (bm) and double product of 10001±1693 to 8846±1416 (paired t test, p<0,05). Conclusions: The correct use of the DPI promoves the positive respiratory and cardiac repercussions, improving respiratory conditions and reducing cardiac work><0,05). Conclusions: The correct use of the DPI promoves the positive respiratory and cardiac repercussions, improving respiratory conditions and reducing cardiac work
Soluble ST2 for Prediction of Heart Failure and Cardiovascular Death in an Elderly, Community‐Dwelling Population
Authors: Parikh Ravi H. , Seliger Stephen L. , Christenson Robert , Gottdiener John S. , Psaty Bruce M. , deFilippi Christopher R. 
Published: August 2016

Background

Soluble
ST
2 (
sST
2), a marker of myocyte stretch and fibrosis, has prognostic value in many cardiovascular diseases. We hypothesized that
sST
2 levels are associated with incident heart failure (HF), including subtypes of preserved (
HF
p
EF
) and reduced (
HF
r
EF
) ejection fraction, and cardiovascular death.

Methods and Results

Baseline serum
sST
2 was measured in 3915 older, community‐dwelling subjects from the Cardiovascular Health Study without prevalent HF.
sST
2 levels were associated with older age, male sex, black race, traditional cardiovascular risk factors, other biomarkers of inflammation, cardiac stretch, myocardial injury, and fibrosis, and abnormal echocardiographic parameters. In longitudinal analysis, greater
sST
2 was associated with a higher risk of incident HF and cardiovascular death; however, in multivariate models adjusting for other cardiac risk factors and the cardiac‐specific biomarker, N‐terminal pro–type B natriuretic peptide, these associations were attenuated. In these models, an
sST
2 level above the US Food and Drug Administration–approved cut‐off value (>35 ng/mL) was significantly associated with incident HF (hazard ratio [
HR
], 1.20; 95%
CI
, 1.02–1.43) and cardiovascular death (
HR
, 1.21; 95%
CI
, 1.02–1.44), and greater
sST
2 was continuously associated with cardiovascular death (per 1‐ln increment:
HR
, 1.24; 95%
CI
, 1.02–1.50).
sST
2 was not associated with the
HF
subtypes of
HF
p
EF
and
HF
r
EF
in adjusted analysis. Addition of
sST
2 to existing risk models of HF and cardiovascular death modestly improved discrimination and reclassification into a higher risk.

Conclusions

The predictive value of
sST
2 for HF of all subtypes and cardiovascular death is modest in an elderly population despite strong cross‐sectional associations with risk factors and underlying cardiac pathology.
Interaction of an Upper-Tropospheric Jet with a Squall Line Originating along a Cold Frontal Boundary
Authors: Stechman Daniel M. , Rauber Robert M. , McFarquhar Greg M. , Jewett Brian F. , Jorgensen David P. 
Published: August 2016

AbstractOn 8 June 2003, an expansive squall line along a surface cold frontal boundary was sampled during the Bow Echo and Mesoscale Convective Vortex Experiment. The Naval Research Laboratory P-3 aircraft and the National Oceanic and Atmospheric Administration P-3 aircraft simultaneously sampled the leading and trailing edge of this squall line, respectively, with X-band Doppler radars. Data from these two airborne radar systems have been synthesized to produce a pseudo-quad-Doppler analysis of the squall line, yielding a detailed three-dimensional kinematic analysis of its structure. A simulation of the squall line was carried out using the Weather Research and Forecasting Model to complement the pseudo-quad-Doppler analysis. The simulation employed a 3-km, convection-allowing, nested domain centered over the pseudo-quad-Doppler domain, along with a 9-km parent domain to capture the larger synoptic-scale cyclone.The pseudo-quad-Doppler analysis reveals that the convective line was embedded within the upper-tropospheric jet stream, causing local decelerations and deviations in the jet-level flow. The vertical transport of low momentum air from the boundary layer via convective updrafts is shown to significantly decelerate jet-level flow. Pressure perturbations associated with the intrusion of low momentum air into the jet stream–level flow led to deviation of the jet stream flow around the squall line that resulted in counter-rotating ribbons of vertical vorticity parallel to the squall line. Model results indicate that disturbances in the jet stream structure persisted downwind of the squall line for several hours.
Studying administrative reforms through textual analysis: the case of Italian central government accounting
Authors: Liguori Mariannunziata , Steccolini Ileana , Rota Silvia 
Published: August 2016

This article contributes to the literature on public sector reforms by proposing textual analysis as a useful research strategy to explore how reform archetypes and related ideas are deployed in the parliamentary debate and regulations advancing reforms. Public Administration (PA), New Public Management (NPM) and Public Governance (GOV) can be depicted as three different archetypes providing characteristic administrative ideas and concepts and related tools and practices, which lead reforms. We use textual analysis to look into more than 20 years of Italian central government accounting reforms and investigate how the three administrative archetypes have evolved, intertwined and replaced each other. Textual analysis proves a useful tool through which to investigate reform processes and allows us to show that in neo-Weberian countries, such as Italy, NPM and GOV, far from being revolutionary paradigms, may represent fashionable trends that have not left significant traces in the practice and rhetoric of reforms. Points for practitioners In contexts based on civil law traditions, the introduction of new reforms appears to be slow and difficult, and is often more successful when it respects extant PA systems, which remain well rooted in the public sector. Decision-makers may want to keep this into consideration when proposing or implementing new changes. From an organizational point of view, this underlines the importance of reassuring civil servants and politicians of the consistency of the ‘new’ proposed models with those they have been accustomed to, and of using the traditional language of PA to explain and introduce new ideas and tools and make them more acceptable. However, this has to be balanced by an actual change in the old systems and routines, using continuity to bring about change and avoiding the re-enactment of merely formalistic approaches.