bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced Chance of Hearing Loss Associated with Therapeutic Drug Monitoring of Aminoglycosides in the Treatment of Multidrug-Resistant Tuberculosis
Authors: van Altena R. , Dijkstra J. A. , van der Meer M. E. , Borjas Howard J. F. , Kosterink J. G. W. , van Soolingen D. , van der Werf T. S. , Alffenaar J. W. C. 
Published: January 2017

ABSTRACT

Hearing loss and nephrotoxicity are associated with prolonged treatment duration and higher dosage of amikacin and kanamycin. In our tuberculosis center, we used therapeutic drug monitoring (TDM) targeting preset pharmacokinetic/pharmacodynamic (PK/PD) surrogate endpoints in an attempt to maintain efficacy while preventing (oto)toxicity. To evaluate this strategy, we retrospectively evaluated medical charts of tuberculosis (TB) patients treated with amikacin or kanamycin in the period from 2000 to 2012. Patients with culture-confirmed multiresistant or extensively drug-resistant tuberculosis (MDR/XDR-TB) receiving amikacin or kanamycin as part of their TB treatment for at least 3 days were eligible for inclusion in this retrospective study. Clinical data, including maximum concentration (
C
max
),
C
min
, and audiometry data, were extracted from the patients' medical charts. A total of 80 patients met the inclusion criteria. The mean weighted
C
max
/MIC ratios obtained from 57 patients were 31.2 for amikacin and 12.3 for kanamycin. The extent of hearing loss was limited and correlated with the cumulative drug dose per kg of body weight during daily administration. At follow-up, 35 (67.3%) of all patients had successful outcome; there were no relapses. At a median dose of 6.5 mg/kg, a correlation was found between the dose per kg of body weight during daily dosing and the extent of hearing loss in dB at 8,000 Hz. These findings suggest that the efficacy at this lower dosage is maintained with limited toxicity. A randomized controlled trial should provide final proof of the safety and efficacy of TDM-guided use of aminoglycosides in MDR-TB treatment.
Evidence To Support Continuation of Statin Therapy in Patients with Staphylococcus aureus Bacteremia
Authors: Caffrey Aisling R. , Timbrook Tristan T. , Noh Eunsun , Sakoulas George , Opal Steven M. , Nizet Victor , LaPlante Kerry L. 
Published: January 2017

ABSTRACT

In addition to cholesterol-lowering capabilities, statins possess anti-inflammatory and immunomodulatory effects. We sought to quantify the real-world impact of different statin exposure patterns on clinical outcomes in
Staphylococcus aureus
bacteremia. We conducted a retrospective cohort study among hospitalized patients with positive
S. aureus
blood cultures receiving appropriate antibiotics within 48 h of culture collection (Veterans Affairs hospitals, 2002 to 2013). Three statin exposure groups were compared to nonusers: pretreated statin users initiating therapy in the 30 days prior to culture and either (i) continuing statin therapy after culture or (ii) not continuing after culture, and (iii)
de novo
users initiating at culture. Nonusers included patients without statins in the year prior to culture through discharge. Propensity score-matched Cox proportional hazards regression models were developed. We were able to balance significantly different baseline characteristics using propensity score matching for pretreated without continuation (
n
= 331), pretreated with continuation (
n
= 141), and
de novo
(
n
= 177) statin users compared to nonusers. We observed a significantly lower 30-day mortality rate (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.25 to 0.84; number needed to treat [NNT], 10) among pretreated and continued statin users, while protective effects were not observed in
de novo
(HR, 1.04; 95% CI, 0.60 to 1.82; NNT, undefined) or pretreated but not continued (HR, 0.92; 95% CI, 0.64 to 1.32; NNT, 47) users. In our national cohort study among patients with
S. aureus
bacteremia, continuation of statin therapy among incident statin users was associated with significant beneficial effects on mortality, including a 54% lower 30-day mortality rate.
High Incidence of Escherichia coli Strains Coharboring
mcr-1
and
bla
NDM
from Chickens
Authors: Liu Bao-Tao , Song Feng-Jing , Zou Ming , Zhang Qi-Di , Shan Hu 
Published: January 2017

ABSTRACT

This study investigated the characteristics of
Escherichia coli
isolates carrying
mcr-1-bla
NDM
from a chicken farm in China. Of the 78
E. coli
isolates, 21 clonally unrelated isolates carried
mcr-1-bla
NDM
. Diverse IncI2 plasmids disseminated
mcr-1
, while the dissemination of
bla
NDM
was mediated by diverse IncB/O plasmids. More striking was the colocalization of resistance genes
mcr-1
and
bla
NDM-4
in an IncHI2/ST3 plasmid, which might pose a great challenge for public health.
Characterization of BRP
MBL
, the Bleomycin Resistance Protein Associated with the Carbapenemase NDM
Authors: Dortet Laurent , Girlich Delphine , Virlouvet Anne-Laure , Poirel Laurent , Nordmann Patrice , Iorga Bogdan I. , Naas Thierry 
Published: January 2017

ABSTRACT

The metallo-β-lactamase NDM-1 is among the most worrisome resistance determinants and is spreading worldwide among Gram-negative bacilli. A bleomycin resistance gene,
ble
MBL
, downstream of the
bla
NDM-1
gene has been associated with resistance almost systematically. Here, we characterized the corresponding protein, BRP
MBL
, conferring resistance to bleomycin, an antitumoral glycopeptide molecule. We have determined whether the expression of the
bla
NDM-1
-
ble
MBL
operon is inducible in the presence of carbapenems and/or bleomycin-like molecules using quantitative reverse transcription-PCR (qRT-PCR), determination of imipenem and zeocin MICs, and carbapenemase-specific activity assays. We showed that the
bla
NDM-1
-
ble
MBL
operon is constitutively expressed. Using electrophoretic mobility shift and DNA protection assays performed with purified glutathione
S
-transferase (GST)-BRP
MBL
, we demonstrated that BRP
MBL
is able to bind and sequester bleomycin-like molecules, thus preventing bleomycin-dependent DNA degradation.
In silico
modeling confirmed that the mechanism of action required the dimerization of the BRP
MBL
protein in order to sequester bleomycin and prevent DNA damage. BRP
MBL
acts specifically on bleomycin-like molecules since cloning and expression of
ble
MBL
in
Staphyloccoccus aureus
did not confer cross-resistance to any other antimicrobial glycopeptides such as vancomycin and teicoplanin.
Interaction of the CD43 Sialomucin with the Mycobacterium tuberculosis Cpn60.2 Chaperonin Leads to Tumor Necrosis Factor Alpha Production
Authors: Torres-Huerta Alvaro , Villaseñor Tomás , Flores-Alcantar Angel , Parada Cristina , Alemán-Navarro Estefanía , Espitia Clara , Pedraza-Alva Gustavo , Rosenstein Yvonne 
Published: January 2017

ABSTRACTMycobacterium tuberculosisis the causal agent of tuberculosis. Tumor necrosis factor alpha (TNF-α), transforming growth factor β (TGF-β), and gamma interferon (IFN-γ) secreted by activated macrophages and lymphocytes are considered essential to containMycobacterium tuberculosisinfection. The CD43 sialomucin has been reported to act as a receptor for bacilli through its interaction with the chaperonin Cpn60.2, facilitating mycobacterium-macrophage contact. We report here that Cpn60.2 induces both human THP-1 cells and mouse-derived bone marrow-derived macrophages (BMMs) to produce TNF-α and that this production is CD43 dependent. In addition, we present evidence that the signaling pathway leading to TNF-α production upon interaction with Cpn60.2 requires active Src family kinases, phospholipase C-γ (PLC-γ), phosphatidylinositol 3-kinase (PI3K), p38, and Jun N-terminal protein kinase (JNK), both in BMMs and in THP-1 cells. Our data highlight the role of CD43 and Cpn60.2 in TNF-α production and underscore an important role for CD43 in the host-mycobacterium interaction.
Quorum Sensing Regulators Are Required for Metabolic Fitness in Vibrio parahaemolyticus
Authors: Kalburge Sai Siddarth , Carpenter Megan R. , Rozovsky Sharon , Boyd E. Fidelma 
Published: January 2017

ABSTRACT

Quorum sensing (QS) is a process by which bacteria alter gene expression in response to cell density changes. In
Vibrio
species, at low cell density, the sigma 54-dependent response regulator LuxO is active and regulates the two QS master regulators AphA, which is induced, and OpaR, which is repressed. At high cell density the opposite occurs: LuxO is inactive, and therefore OpaR is induced while AphA is repressed. In
Vibrio parahaemolyticus
, a significant enteric pathogen of humans, the roles of these regulators in pathogenesis are less known. We examined deletion mutants of
luxO
,
opaR
, and
aphA
for
in vivo
fitness using an adult mouse model. We found that the
luxO
and
aphA
mutants were defective in colonization compared to levels in the wild type. The
opaR
mutant did not show any defect
in vivo
. Colonization was restored to wild-type levels in a
luxO opaR
double mutant and was also increased in an
opaR aphA
double mutant. These data suggest that AphA is important and that overexpression of
opaR
is detrimental to
in vivo
fitness. Transcriptome sequencing (RNA-Seq) analysis of the wild type and
luxO
mutant grown in mouse intestinal mucus showed that 60% of the genes that were downregulated in the
luxO
mutant were involved in amino acid and sugar transport and metabolism. These data suggest that the
luxO
mutant has a metabolic disadvantage, which was confirmed by growth pattern analysis using phenotype microarrays. Bioinformatics analysis revealed OpaR binding sites in the regulatory region of 55 carbon transporter and metabolism genes. Biochemical analysis of five representatives of these regulatory regions demonstrated direct binding of OpaR in all five tested. These data demonstrate the role of OpaR in carbon utilization and metabolic fitness, an overlooked role in the QS regulon.
The origin of contractional structures in extensional gneiss domes
Authors: Rey P.F. , Mondy L. , Duclaux G. , Teyssier C. , Whitney D.L. , Bocher M. , Prigent C. 
Published: January 2017

Abstract
The juxtaposition of domains of shortening and extension at different scales in orogens has fueled many debates about driving forces and tectonic interpretations, including timing of deformation. At the orogen scale, gravitational collapse and mass transfer from orogenic plateaux to forelands explain some of these juxtapositions. At a regional scale, structures in gneiss domes are commonly contractional yet are coeval with regional extension and denudation. Here we use three-dimensional numerical experiments to show that crustal flow in orogenic domains does not necessarily conform to plate motion. We document contractional crustal flow associated with the formation of a gneiss dome in an orogenic pull-apart setting where localized extension and crustal thinning focus the exhumation of deep crust. We show that the flow field results in a complex strain pattern in which an extensional strain regime that is collinear with the direction of plate motion is partitioned into the shallow crust, whereas contractional structures and fabrics at a high angle to the direction of imposed transport develop in the deep crust. Advective mass transfer across regions of contrasting yet coeval strain regimes leads to a polyphase tectonic history. We observe structural features remarkably similar to those documented in some natural gneiss domes such as the Montagne Noire, which developed in a dextral pull-apart domain at the southern margin of the French Massif Central.
What sets the size of current ripples?
Authors: Lapotre Mathieu G.A. , Lamb Michael P. , McElroy Brandon 
Published: January 2017

Abstract
Water flowing over sand in fluvial and marine settings often results in the formation of current ripples. Found in modern and ancient deposits on Earth and Mars, ripple stratification records flow directions and fluid properties that are crucial to interpreting sedimentary records. Despite decades of observations of current ripples, there is no universal scaling relation to predict their size or to distinguish them from dunes. Here we use dimensional analysis and a new data compilation to develop a scaling relation that collapses data for equilibrium wavelengths of ripples forming under unidirectional flows. Results show that ripples are larger with more viscous fluids, coarser grains, smaller bed shear stresses, and smaller specific gravity of sediment. The scaling relation also segregates ripples from dunes, highlighting a narrow regime of transitional bedforms that have morphologic properties and sediment transport conditions that overlap with both ripples and dunes. Our analysis shows that previous absolute size–based definitions of ripples and dunes only hold for certain conditions, such as water flows transporting siliciclastic grains on Earth. The new theory allows estimates of ripple sizes in foreign fluids and on other planets, including meter-scale ripples in methane flows on Titan or in viscous brines on Mars.
Ultrafast magmatic buildup and diversification to produce continental crust during subduction
Authors: Ducea Mihai N. , Bergantz George W. , Crowley James L. , Otamendi Juan 
Published: January 2017

Abstract
The processes and fluxes that produce the distinct compositional structure of Earth’s continental crust by subduction remain controversial. The rates of oceanic crust production, in contrast, are well quantified and are generally believed to be faster than those responsible for building magmatic systems in subduction settings. Here we show that a recently recognized crustal section, the 30-km-thick Ordovician Sierra Valle Fértil–Sierra Famatina complex in Argentina, was built magmatically within only ∼4 m.y. More than half of the crustal section represents additions from the mantle, and is preserved as mafic igneous rocks and mafic-ultramafic cumulates; the remainder is tonalite to granodiorite with evidence for widespread assimilation from highly melted metasedimentary units. U-Pb zircon geochronology reveals that the construction of the arc was not a simple bottom-up construction process. This continuous exposure of the arc crust allows the quantification of field constrained magmatic addition rates of 300–400 km3 km–1 m.y.–1. These rates are similar to those determined for modern slow-spreading mid-ocean ridges and are of the same magnitude as magmatic addition rates required to build certain large segments of the continental masses such as the Arabian-Nubian shield, among others. The implication is that significant convective removal of arc roots is required over time in order to build the modern continental crust via subduction-related magmatism.
Pyritized in situ trilobite eggs from the Ordovician of New York (Lorraine Group): Implications for trilobite reproductive biology
Authors: Hegna Thomas A. , Martin Markus J. , Darroch Simon A.F. 
Published: January 2017

Abstract
Despite a plethora of exceptionally preserved trilobites, trilobite reproduction has remained a mystery. No previously described trilobite has unambiguous eggs or genitalia preserved. This study reports the first occurrence of in situ preserved eggs belonging to Triarthrus eatoni (Hall, 1838) trilobites from the Lorraine Group in upstate New York, USA. Like other exceptionally preserved trilobites from the Lorraine Group, the complete exoskeletons are replaced with pyrite. The eggs are spherical to elliptical in shape, nearly 200 µm in size, and are clustered in the genal area of the cephalon. The fact that the eggs are smaller than the earliest-known trilobite ontogenetic (protaspis) stage suggests that trilobites may have had an unmineralized preliminary stage in their ontogeny, and that the protaspis shield formed only after hatching. The eggs are only visible ventrally with no dorsal brood pouch or recognized sexual dimorphism. The location of the eggs is consistent with where modern female horseshoe crabs release their unfertilized eggs from the ovarian network within their head. Trilobites likely released their gametes (eggs and sperm) through a genital pore of as-yet unknown location (likely near the posterior boundary of the head). If the T. eatoni reproductive biology is representative of other trilobites, they spawned with external fertilization, possibly the ancestral mode of reproduction for early arthropods. Because pyritization preferentially preserves the external rather than internal features of fossils, it is suggested that there is likely a bias in the fossil record toward the preservation of arthropods that brood eggs externally: arthropods that brood their eggs internally are unlikely to preserve any evidence of their mode of reproduction.
Prenatal exposure to antiepileptic drugs and use of primary healthcare during childhood: a population-based cohort study in Denmark
Authors: Würtz Anne Mette , Rytter Dorte , Vestergaard Claus Høstrup , Christensen Jakob , Vestergaard Mogens , Bech Bodil Hammer 
Published: January 2017

ObjectivePrenatal exposure to antiepileptic drugs (AEDs) has been associated with adverse outcomes in the offspring such as congenital malformations and neuropsychiatric disorders. The objective of this study was to investigate whether prenatal exposure to AEDs is also associated with more frequent use of primary healthcare during childhood.DesignPopulation-based cohort study.SettingNationwide national registers in Denmark.ParticipantsAll live-born singletons in Denmark during 1997–2012 identified in the Danish National Patient Register and followed until 31 December 2013 (n=963 010). Information on prenatal exposure to AEDs for maternal indication of epilepsy and other neurological conditions was obtained from the Danish Register of Medicinal Product Statistics.Main outcome measuresThe primary outcome measure was the number and type of contacts with the general practitioner (GP), excluding routine well-child visits and vaccinations. The secondary outcome measure was specific services provided at the GP contact. The association between prenatal exposure to AEDs and contacts with the GP was estimated by using negative binomial regression adjusting for sex and date of birth of the child, maternal age, cohabitation status, income, education, substance abuse, depression, severe psychiatric disorders and use of antipsychotics, antidepressants and insulin.ResultsChildren exposed prenatally to AEDs (n=4478) had 3% (95% CI 0 to 5%) more GP contacts during the study period than unexposed children. This was primarily accounted for by the number of phone contacts. Within each year of follow-up, exposed children tended to have more contacts than unexposed children, but the differences were small. We found no difference between exposed and unexposed children with regard to specific services provided at the GP contact. For the individual AEDs, we found that exposure to valproate or oxcarbazepine was associated with more GP contacts.ConclusionsWe found only minor differences between prenatally AED-exposed and unexposed children in the number of GP contacts.
Epidemiological survey of the feasibility of broadband ultrasound attenuation measured using calcaneal quantitative ultrasound to predict the incidence of falls in the middle aged and elderly
Authors: Ou Ling-Chun , Chang Yin-Fan , Chang Chin-Sung , Chiu Ching-Ju , Chao Ting-Hsing , Sun Zih-Jie , Lin Ruey-Mo , Wu Chih-Hsing 
Published: January 2017

ObjectivesWe investigated whether calcaneal quantitative ultrasound (QUS-C) is a feasible tool for predicting the incidence of falls.DesignProspective epidemiological cohort study.SettingCommunity-dwelling people sampled in central western Taiwan.ParticipantsA cohort of community-dwelling people who were ≥40 years old (men: 524; women: 676) in 2009–2010. Follow-up questionnaires were completed by 186 men and 257 women in 2012.MethodsStructured questionnaires and broadband ultrasound attenuation (BUA) data were obtained in 2009–2010 using QUS-C, and follow-up surveys were done in a telephone interview in 2012. Using a binary logistic regression model, the risk factors associated with a new fall during follow-up were analysed with all significant variables from the bivariate comparisons and theoretically important variables.Primary outcome measuresThe incidence of falls was determined when the first new fall occurred during the follow-up period. The mean follow-up time was 2.83 years.ResultsThe total incidence of falls was 28.0 per 1000 person-years for the ≥40 year old group (all participants), 23.3 per 1000 person-years for the 40–70 year old group, and 45.6 per 1000 person-years for the ≥70 year old group. Using multiple logistic regression models, the independent factors were current smoking, living alone, psychiatric drug usage and lower BUA (OR 0.93; 95% CI 0.88 to 0.99, p<0.05) in the ≥70 year old group.ConclusionsThe incidence of falls was highest in the ≥70 year old group. Using QUS-C-derived BUA is feasible for predicting the incidence of falls in community-dwelling elderly people aged ≥70 years.
External validation of the Revised Cardiac Risk Index and update of its renal variable to predict 30-day risk of major cardiac complications after non-cardiac surgery: rationale and plan for analyses of the VISION study
Authors: Roshanov Pavel S , Walsh Michael , Devereaux P J , MacNeil S Danielle , Lam Ngan N , Hildebrand Ainslie M , Acedillo Rey R , Mrkobrada Marko , Chow Clara K , Lee Vincent W , Thabane Lehana , Garg Amit X 
Published: January 2017

IntroductionThe Revised Cardiac Risk Index (RCRI) is a popular classification system to estimate patients' risk of postoperative cardiac complications based on preoperative risk factors. Renal impairment, defined as serum creatinine >2.0 mg/dL (177 µmol/L), is a component of the RCRI. The estimated glomerular filtration rate has become accepted as a more accurate indicator of renal function. We will externally validate the RCRI in a modern cohort of patients undergoing non-cardiac surgery and update its renal component.Methods and analysisThe Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation (VISION) study is an international prospective cohort study. In this prespecified secondary analysis of VISION, we will test the risk estimation performance of the RCRI in ∼34 000 participants who underwent elective non-cardiac surgery between 2007 and 2013 from 29 hospitals in 15 countries. Using data from the first 20 000 eligible participants (the derivation set), we will derive an optimal threshold for dichotomising preoperative renal function quantified using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) glomerular filtration rate estimating equation in a manner that preserves the original structure of the RCRI. We will also develop a continuous risk estimating equation integrating age and CKD-Epi with existing RCRI risk factors. In the remaining (approximately) 14 000 participants, we will compare the risk estimation for cardiac complications of the original RCRI to this modified version. Cardiac complications will include 30-day non-fatal myocardial infarction, non-fatal cardiac arrest and death due to cardiac causes. We have examined an early sample to estimate the number of events and the distribution of predictors and missing data, but have not seen the validation data at the time of writing.Ethics and disseminationThe research ethics board at each site approved the VISION protocol prior to recruitment. We will publish our results and make our models available online athttp://www.perioperativerisk.com.Trial registration numberClinicalTrials.govNCT00512109.