bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro
Screening Test Using Leishmania Promastigotes Stably Expressing mCherry Protein
Authors: Vacchina Paola , Morales Miguel A. 
Published: January 2014

ABSTRACT

Transgenic
Leishmania major
and
Leishmania donovani
axenic promastigotes constitutively expressing mCherry were used for
in vitro
antileishmanial drug screening. This method requires minimal sample manipulation and can be easily adapted to automatic drug tests, allowing primary high-throughput screenings without the need for expensive and sophisticated instruments.
Identification of a Key Lysine Residue in Heat Shock Protein 90 Required for Azole and Echinocandin Resistance in Aspergillus fumigatus
Authors: Lamoth Frédéric , Juvvadi Praveen R. , Soderblom Erik J. , Moseley M. Arthur , Asfaw Yohannes G. , Steinbach William J. 
Published: January 2014

ABSTRACT

Heat shock protein 90 (Hsp90) is an essential chaperone involved in the fungal stress response that can be harnessed as a novel antifungal target for the treatment of invasive aspergillosis. We previously showed that genetic repression of Hsp90 reduced
Aspergillus fumigatus
virulence and potentiated the effect of the echinocandin caspofungin. In this study, we sought to identify sites of posttranslational modifications (phosphorylation or acetylation) that are important for Hsp90 function in
A. fumigatus
. Phosphopeptide enrichment and tandem mass spectrometry revealed phosphorylation of three residues in Hsp90 (S49, S288, and T681), but their mutation did not compromise Hsp90 function. Acetylation of lysine residues of Hsp90 was recovered after treatment with deacetylase inhibitors, and acetylation-mimetic mutations (K27A and K271A) resulted in reduced virulence in a murine model of invasive aspergillosis, supporting their role in Hsp90 function. A single deletion of lysine K27 or an acetylation-mimetic mutation (K27A) resulted in increased susceptibility to voriconazole and caspofungin. This effect was attenuated following a deacetylation-mimetic mutation (K27R), suggesting that this site is crucial and should be deacetylated for proper Hsp90 function in antifungal resistance pathways. In contrast to previous reports in
Candida albicans
, the lysine deacetylase inhibitor trichostatin A (TSA) was active alone against
A. fumigatus
and potentiated the effect of caspofungin against both the wild type and an echinocandin-resistant strain. Our results indicate that the Hsp90 K27 residue is required for azole and echinocandin resistance in
A. fumigatus
and that deacetylase inhibition may represent an adjunctive anti-
Aspergillus
strategy.
Mechanism of Resistance to an Antitubercular 2-Thiopyridine Derivative That Is Also Active against Burkholderia cenocepacia
Authors: Scoffone Viola C. , Spadaro Francesca , Udine Claudia , Makarov Vadim , Fondi Marco , Fani Renato , De Rossi Edda , Riccardi Giovanna , Buroni Silvia 
Published: January 2014

ABSTRACT

The discovery of new compounds that are able to inhibit the growth of
Burkholderia cenocepacia
is of primary importance for cystic fibrosis patients. Here, the mechanism of resistance to a new pyridine derivative already shown to be effective against
Mycobacterium tuberculosis
and to have good activity toward
B. cenocepacia
was investigated. Increased expression of a resistance-nodulation-cell division (RND) efflux system was detected in the resistant mutants, thus confirming their important roles in
B. cenocepacia
antibiotic resistance.
Prior Exposure to Lamivudine Increases Entecavir Resistance Risk in Chronic Hepatitis B Patients without Detectable Lamivudine Resistance
Authors: Lee Jeong-Hoon , Cho Yuri , Lee Dong Hyeon , Lee Minjong , Yoo Jeong-ju , Choi Won-mook , Cho Young Youn , Lee Yun Bin , Yu Su Jong , Yoon Jung-Hwan , Lee Hyo-Suk , Kim Yoon Jun 
Published: January 2014

ABSTRACT

The efficacy of entecavir (ETV) treatment in chronic hepatitis B (CHB) patients who were exposed to lamivudine (LAM) but had no detectable LAM resistance (LAM-R) is not well evaluated. In this study, we aimed to evaluate whether the probability of developing genotypic resistance to ETV in LAM-exposed patients with or without LAM-R is comparable to that in antiviral-naive patients. This retrospective cohort study included 500 consecutive patients with CHB who started ETV monotherapy at a single tertiary hospital in Korea. The patients were divided into three groups: nucleos(t)ide analogue (NA)-naive patients (group 1,
n
= 142), patients who were previously exposed to LAM and had no currently or previously detected LAM-R (group 2,
n
= 233), and patients with LAM-R when starting ETV (group 3,
n
= 125). The overall median ETV treatment duration was 48.7 months. The probabilities of virologic breakthrough were significantly increased not only in group 3 (hazard ratio [HR] = 14.4,
P
< 0.001) but also in group 2 (HR = 5.0,
P
< 0.001) compared to group 1. Genotypic ETV resistance (ETV-R) developed more frequently in group 2 (HR = 13.0,
P
= 0.013) as well as group 3 (HR = 43.9,
P
< 0.001) than in group 1: the probabilities of developing ETV-R in groups 1, 2, and 3 were <1.0%, 8.0%, and 28.2%, respectively, at month 48. The results of this study indicate that ETV-R occurred more frequently in LAM-exposed patients, even though they had no detectable LAM-R, than in NA-naive patients. Therefore, LAM-exposed CHB patients, regardless of the presence or absence of LAM-R, should be monitored more cautiously for the development of ETV-R during ETV monotherapy.
Complete Sequence of a KPC-Producing IncN Multidrug-Resistant Plasmid from an Epidemic Escherichia coli Sequence Type 131 Strain in China
Authors: Chen Liang , Hu Hongyan , Chavda Kalyan D. , Zhao Shulong , Liu Renkun , Liang Hui , Zhang Wei , Wang Xiumei , Jacobs Michael R. , Bonomo Robert A. , Kreiswirth Barry N. 
Published: January 2014

ABSTRACT

We report here the nucleotide sequence of a novel
bla
KPC-2
-harboring incompatibility group N (IncN) plasmid, pECN580, from a multidrug-resistant
Escherichia coli
sequence type 131 (ST131) isolate recovered from Beijing, China. pECN580 harbors β-lactam resistance genes
bla
KPC-2
,
bla
CTX-M-3
, and
bla
TEM-1
; aminoglycoside acetyltransferase gene
aac
(
6
′)-
Ib-cr
; quinolone resistance gene
qnrS1
; rifampin resistance gene
arr-3
; and trimethoprim resistance gene
dfrA14
. The emergence of a
bla
KPC-2
-harboring multidrug-resistant plasmid in an epidemic
E. coli
ST131 clone poses a significant potential threat in community and hospital settings.
Herbal medicine (Gan Mai Da Zao decoction) for depression: a systematic review protocol
Authors: Jun Ji Hee , Lee Ju Ah , Choi Tae-Young , Yun Kyung-Jin , Lim Hyun-Ja , Lee Myeong Soo 
Published: January 2014

IntroductionThe aim of this systematic review is to analyse trial data on the effectiveness of a herbal medicine (Gan Mai Da Zao (GMDZ) decoction) in treating depression.Methods and analysis12 databases will be searched from their inception: PubMed, EMBASE, AMED, the Cochrane Library, five Korean medical databases (KoreaMed, DBpia, OASIS, the Research Information Service System (RISS) and the Korean Studies Information Service System (KISS)) and three Chinese medical databases (China National Knowledge Infrastructure (CNKI), the Wanfang Database and the Chinese Scientific Journals Database (VIP)). Randomised clinical trials (RCTs) or quasi-RCTs using a GMDZ decoction for any type of depression will be considered. The selection of the studies, data abstraction and validations will be performed independently by two researchers.DisseminationThe findings will be disseminated to appropriate audiences via peer-reviewed publication and conference presentations.Trial registration numberPROSPERO 2013:CRD42013005100.
Intravenous paracetamol versus dexketoprofen in acute migraine attack in the emergency department: a randomised clinical trial
Authors: Turkcuer Ibrahim , Serinken Mustafa , Eken Cenker , Yilmaz Atakan , Akdag Ömer , Uyanık Emrah , Kiray Cihan , Elicabuk Hayri 
Published: January 2014

ObjectiveMigraine is a common form of headache that is a major burden for patients who often seek emergency care. The goal of this study was to compare the effectiveness of intravenous non-steroidal anti-inflammatory medication (dexketoprofen) with paracetamol (acetaminophen) in the treatment of an acute migraine attack.Materials and methodsThis prospective, randomised, double blind, controlled study was conducted in a tertiary care emergency unit. Study patients were randomised into two groups to receive either 50 mg of dexketoprofen trometamol or 1000 mg of paracetamol intravenously by rapid infusion in 150 mL of normal saline. Pain reduction was measured at baseline, and after 15 and 30 min, using a Visual Analogue Scale (VAS)) as the primary outcome. VAS is a measurement tool ranging from 0 (no pain) to 100 mm (worst pain).Results200 patients were included in the final analysis. Mean (SD) age of the study subjects was 30.1±11 years and 81% (n=162) were women. Median reduction in VAS score at 30 min was 56 (IQR 30–78.5) for the paracetamol group and 55 (IQR 34–75) for the dexketoprofen group, with a difference of 1 mm (95% CI −7 to 10) between the two groups.ConclusionsIntravenous paracetamol and dexketoprofen appear to produce equivalent pain relief for migraine in the emergency department.ClinicalTrials.gov NoNCT01730326.
Clinicians’ views on low-lying intrauterine devices or systems
Authors: Golightly Ellen , Gebbie Ailsa E 
Published: January 2014

BackgroundThere is a lack of consensus and very little published guidance on the management of a low-lying or malpositioned intrauterine contraceptive device (IUD) or system (IUS).Methods and resultsA short e-mail questionnaire sent to senior medical staff working in contraceptive services confirmed the variation in views and management of this clinical area. Almost all respondents would replace an IUD/IUS lying either totally or partially in the cervical canal. The nearer the device was to the fundus the more likely respondents were to leave itin situand there was less concern if the device was an IUS, presumably in view of the hormonal action. In the presence of abnormal bleeding or pain, most respondents would look for other causes rather than assume that the low-lying device was to blame. Respondents expressed uncertainty as to whether low-lying devices were more likely to fail or not and around half the respondents felt that low-lying devices could migrate upwards within the cavity.ConclusionThis survey highlighted the need for accurate evidence-based guidance to assist in this area of clinical contraceptive practice.
Final results of the multicenter, prospective Axium MicroFX for Endovascular Repair of IntraCranial Aneurysm Study (AMERICA)
Authors: Fargen Kyle M , Blackburn Spiros , Deshaies Eric M , Carpenter Jeffrey S , Jabbour Pascal , Mack William J , Rai Ansaar T , Siddiqui Adnan H , Turner Raymond D , Mocco J 
Published: January 2014

BackgroundWe previously performed a multicenter prospective single-arm trial of 100 patients treated with Axium MicroFX Coils (ev3; Plymouth, Minnesota, USA), AMERICA: Axium MicroFX for Endovascular Repair of IntraCranial Aneurysm study. Initial angiographic and clinical outcomes were excellent. The final results are presented herein.MethodsAMERICA is a multicenter, prospective single-arm trial evaluating the safety and efficacy of the ev3 Axium MicroFX coil system in 100 separate aneurysms between April 2010 and October 2012. Trial endpoints were 3–6 month angiographic occlusion and clinical status, as reported by treatment center.ResultsMean follow-up was 157.9 days (median 153.5, range 1–445, SEM 9.3 days). At last follow-up imaging, 90.6% of all aneurysms, 90% of unruptured aneurysms, and 93.3% of ruptured aneurysms had Raymond grade I or II occlusion. Progression to further occlusion (lower Raymond occlusion grade) occurred in 29/85 aneurysms (34.1%). Aneurysm recurrence occurred in 11/85 aneurysms (12.9%). Ninety-nine per cent of patients treated electively and 68.7% of ruptured patients had a modified Rankin score of 0–2. Delayed adverse events (AEs), occurring after discharge and during the follow-up period, occurred in 10% of patients. In total, two AEs (one severe and one moderate) were potentially related to the device, thereby providing a 2% device-related AE rate.ConclusionsIn this prospective, multicenter series of 100 aneurysms treated with Axium MicroFX PGLA (polyglycolic/polylactic acid) coils, 3–6 month angiographic occlusion and clinical outcomes were excellent. This study suggests that Axium MicroFX PGLA coils are safe and effective in the treatment of intracranial aneurysms.
Mechanistic Relationship Between Membrane Type-1 Matrix Metalloproteinase and the Myocardial Response to Pressure Overload
Authors: Zile Michael R. , Baicu Catalin F. , Stroud Robert E. , Van Laer An O. , Jones Jeffrey A. , Patel Risha , Mukherjee Rupak , Spinale Francis G. 
Published: January 2014

Background—
Although matrix metalloproteinases (MMPs) were initially thought to result primarily in extracellular matrix degradation, certain MMP types, such as membrane type-1 (MT1) MMP, may also be involved in profibrotic cascades through hydrolysis of latency-associated transforming growth factor–binding protein (LTBP-1) and activation of transforming growth factor–dependent profibrotic signaling. The present study tested the hypothesis that MT1-MMP plays a direct role in the matrix remodeling response to a left ventricular (LV) pressure overload (PO) stimulus.

Methods and Results—
Wild-type (WT) and transgenic mice with cardiac-restricted MT1-MMP overexpression or MT1-MMP reduced expression underwent PO for 4 weeks. PO resulted in a 57% increase in LV mass (no change in LV end diastolic volume, resulting in an increase in the LV mass/volume ratio consistent with concentric remodeling), a 60% increase in MT1-MMP–mediated LTBP-1 hydrolysis and a 190% increase in collagen content in WT mice. Although LV mass was similar among WT, MT1-MMP overexpression, and MT1-MMP reduced expression after PO, significant differences in LV function, MT1-MMP–mediated LTBP-1 hydrolysis, and collagen content occurred. PO in MT1-MMP overexpression increased LTBP-1 hydrolysis (18%), collagen content (60%), and left atrial dimension (19%; indicative of LV diastolic dysfunction) when compared with WT. PO in MT1-MMP reduced expression reduced left atrial dimension (19%), LTBP-1 hydrolysis (40%), and collagen content (32%) when compared with both WT.

Conclusions—
Despite an equivalent PO stimulus and magnitude of LV myocardial growth, altering MT1-MMP levels caused specific matrix-dependent changes in remodeling, thereby demonstrating a mechanistic role in the development of the maladaptive remodeling and myocardial fibrotic response to PO.
Histone Deacetylase Inhibition Blunts Ischemia/Reperfusion Injury by Inducing Cardiomyocyte Autophagy
Authors: Xie Min , Kong Yongli , Tan Wei , May Herman , Battiprolu Pavan K. , Pedrozo Zully , Wang Zhao V. , Morales Cyndi , Luo Xiang , Cho Geoffrey , Jiang Nan , Jessen Michael E. , Warner John J. , Lavandero Sergio , Gillette Thomas G. , Turer Aslan T. , Hill Joseph A. 
Published: January 2014

Background—
Reperfusion accounts for a substantial fraction of the myocardial injury occurring with ischemic heart disease. Yet, no standard therapies are available targeting reperfusion injury. Here, we tested the hypothesis that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor approved for cancer treatment by the US Food and Drug Administration, will blunt reperfusion injury.

Methods and Results—
Twenty-one rabbits were randomly assigned to 3 groups: (1) vehicle control, (2) SAHA pretreatment (1 day before and at surgery), and (3) SAHA treatment at the time of reperfusion only. Each arm was subjected to ischemia/reperfusion surgery (30 minutes coronary ligation, 24 hours reperfusion). In addition, cultured neonatal and adult rat ventricular cardiomyocytes were subjected to simulated ischemia/reperfusion to probe mechanism. SAHA reduced infarct size and partially rescued systolic function when administered either before surgery (pretreatment) or solely at the time of reperfusion. SAHA plasma concentrations were similar to those achieved in patients with cancer. In the infarct border zone, SAHA increased autophagic flux, assayed in both rabbit myocardium and in mice harboring an RFP-GFP-LC3 transgene. In cultured myocytes subjected to simulated ischemia/reperfusion, SAHA pretreatment reduced cell death by 40%. This reduction in cell death correlated with increased autophagic activity in SAHA-treated cells. RNAi-mediated knockdown of ATG7 and ATG5, essential autophagy proteins, abolished SAHA’s cardioprotective effects.

Conclusions—
The US Food and Drug Administration–approved anticancer histone deacetylase inhibitor, SAHA, reduces myocardial infarct size in a large animal model, even when delivered in the clinically relevant context of reperfusion. The cardioprotective effects of SAHA during ischemia/reperfusion occur, at least in part, through the induction of autophagic flux.
Advances in motor neurone disease
Authors: Bäumer Dirk , Talbot Kevin , Turner Martin R 
Published: January 2014

Summary Motor neurone disease (MND), the commonest clinical presentation of which is amyotrophic lateral sclerosis (ALS), is regarded as the most devastating of adult-onset neurodegenerative disorders. The last decade has seen major improvements in patient care, but also rapid scientific advances, so that rational therapies based on key pathogenic mechanisms now seem plausible. ALS is strikingly heterogeneous in both its presentation, with an average one-year delay from first symptoms to diagnosis, and subsequent rate of clinical progression. Although half of patients succumb within 3–4 years of symptom onset, typically through respiratory failure, a significant minority survives into a second decade. Although an apparently sporadic disorder for most patients, without clear environmental triggers, recent genetic studies have identified disease-causing mutations in genes in several seemingly disparate functional pathways, so that motor neuron degeneration may need to be understood as a common final pathway with a number of upstream causes. This apparent aetiological and clinical heterogeneity suggests that therapeutic studies should include detailed biomarker profiling, and consider genetic as well as clinical stratification. The most common mutation, accounting for 10% of all Western hemisphere ALS, is a hexanucleotide repeat expansion in C9orf72. This and several other genes implicate altered RNA processing and protein degradation pathways in the core of ALS pathogenesis. A major gap remains in understanding how such fundamental processes appear to function without obvious deficit in the decades prior to symptom emergence, and the study of pre-symptomatic gene carriers is an important new initiative.
Gender associations with world music instruments by secondary school music students from the USA
Authors: Kelly Steven N. , VanWeelden Kimberly 
Published: January 2014

This article investigated possible gender associations with world music instruments by secondary school-age music students from the USA. Specific questions included: (1) Do the primary instruments played by the students influence gender associations of world music instruments? (2) Does age influence possible gender associations with world music instruments? (3) Does students’ gender affect possible gender associations? (4) Do presentation modes of visual only, instrument timbre, or a combination of visual and timbre influence gender associations? (5) What variables may influence possible gender association with world music instruments? Participants ( N = 455) were band and string students attending a large university-based summer music camp. Participants were randomly divided into three treatment groups: visual only, audio only, and visual/audio combination and exposed to 10 world music instruments that have specific sex-role associations in the culture of which they are a part. Participants completed a survey to indicate their perception of the extent of gender association with each instrument. Results showed that students were influenced by similar variables regarding gender associations with world music instruments as they are with traditional public school instruments typically found in the USA.
Corporatist Ideas in Inter-war Greece: From Theory to Practice (1922–1940)
Authors: Ploumidis Spyridon 
Published: January 2014

The article examines the reception, conception and practical application of corporatist ideas in inter-war Greece. Drawing on Peter Williamson’s terms, this study looks closely at both consensual- and authoritarian-licensed corporatist theories and policies. In the period under consideration, Greece was a fledgling, fast industrializing society that was significantly affected by the economic advantages and misgivings of the ‘gloomy thirties’. High rates of unemployment, which were aggravated by the global economic crisis of 1929, low wages, long working hours and insufficient enforcement of labour law increased the dissatisfaction of the working classes and fanned social unrest. Consensual-licensed corporatist proposals for ‘professional representation’ entered the debate on the (re-)establishment of the Senate in 1928–29. Authoritarian-licensed corporatism found a much broader audience and practical scope during the Kondylis and the Metaxas dictatorships in the period 1935–40. Fascist-like corporatist practices were applied in agriculture and in the bargaining of collective agreements that regulated minimum wages and salaries. In fact, Metaxas had pronounced the transformation of his anti-parliamentary regime into a corporatist ‘new State’. However, the eventual implementation of corporatist ideas was rather limited. For that matter, I argue that interbellum Greece remained, in its European setting, a marginal case of corporatist theories and policies.
Agonist of inward rectifier K+ channels enhances the protection of ischemic postconditioning in isolated rat hearts
Authors: Liao Z , Feng Z , Long C 
Published: January 2014

Background: Selective inhibition of inward rectifier K+ channels could abolish the protection mediated by ischemic preconditioning, but the roles of these channels in ischemic postconditioning have not been well characterized. Our study aims to evaluate the effect of inward rectifier K+ channels on the protection induced by ischemic postconditioning. Methods: Langendorff-perfused rat hearts (n=8 per group) were split into four groups: postconditioning hearts (IPO group); ischemic postconditioning with BaCl2 hearts (PB group); ischemic postconditioning with zacopride hearts (PZ group); and without ischemic postconditioning (CON group). After suffering 30 minutes of global ischemia, groups IPO, PB and PZ went through 10 seconds of ischemic postconditioning with three different perfusates: respectively, Krebs–Henseleit buffer (IPO group); 20 μmol/L BaCl2 (antagonist of the channel, PB group); 1 μmol/L zacopride (agonist of the channel, PZ group). Results: At the end of reperfusion, the myocardial performance was better preserved in the PZ group than the other three groups. The PB group showed no significant differences from the CON group. Conclusions: Our study has shown that the IK1 channel agonist zacopride is associated with the enhancement of ischemic postconditioning.