bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of a Dose–Response Model to Study Temporal Trends in Spatial Exposure to Coxiella burnetii: Analysis of a Multiyear Outbreak of Q Fever
Authors: Brooke R. J. , Teunis P. F. M. , Kretzschmar M. E. E. , Wielders C. C. H. , Schneeberger P. M. , Waller L. A. 
Published: August 2016

SummaryThe Netherlands underwent a large Q fever outbreak between 2007 and 2009. In this paper, we study spatial and temporal Coxiella burnetii exposure trends during this large outbreak as well as validate outcomes against other published studies and provide evidence to support hypotheses on the causes of the outbreak. To achieve this, we develop a framework using a dose–response model to translate acute Q fever case incidence into exposure estimates. More specifically, we incorporate a geostatistical model that accounts for spatial and temporal correlation of exposure estimates from a human Q fever dose–response model to quantify exposure trends during the outbreak. The 2051 cases, with the corresponding age, gender and residential addresses, reside in the region with the highest attack rates during the outbreak in the Netherlands between 2006 and 2009. We conclude that the multiyear outbreak in the Netherlands is caused by sustained release of infectious bacteria from the same sources, which suggests that earlier implementation of interventions may have prevented many of the cases. The model predicts the risk of infection and acute symptomatic Q fever from multiple exposure sources during a multiple‐year outbreak providing a robust, evidence‐based methodology to support decision‐making and intervention design.
Influence of On‐farm pig Salmonella status on Salmonella Shedding at Slaughter
Authors: Casanova‐Higes A. , Andrés‐Barranco S. , Mainar‐Jaime R. C. 
Published: August 2016

SummaryThe risk of Salmonella shedding among pigs at slaughter with regard to their previous on‐farm Salmonella status was assessed in a group of pigs from a farm from NE of Spain. A total of 202 pigs that had been serologically monitored monthly during the fattening period and from which mesenteric lymph nodes (MLN) and faecal (SFEC) samples were collected at slaughter for Salmonella isolation were included. A repeated‐measures anova was used to assess the relationship between mean OD% values during the fattening period and sampling time and bacteriology on MLN and SFEC. Pigs were also grouped into four groups, that is pigs seronegative during the fattening period and Salmonella negative in MLN (group A; n = 69); pigs seronegative during the fattening period but Salmonella positive in MLN (B; n = 36); pigs seropositive at least once and Salmonella positive in MLN (C; n = 50); and pigs seropositive at least once but Salmonella negative in (D; n = 47). Pigs shedding at slaughter seroconverted much earlier and showed much higher mean OD% values than non‐shedders pigs. The proportion of Salmonella shedders in groups A and D was high and similar (26.1% and 29.8%, respectively), but significantly lower than that for groups B and C. The odds of shedding Salmonella for groups B and C were 4.8 (95% CI = 1.5–15.5) and 20.9 (3.7–118) times higher, respectively, when compared to A. It was concluded that a large proportion of Salmonella seronegative pigs may shed Salmonella at slaughter, which would be likely associated to previous exposure with contaminated environments (i.e. transport and lairage). For pigs already infected at farm, the likelihood of shedding Salmonella was much higher and may depend on whether the bacterium has colonized the MLN or not. The odds of shedding Salmonella spp. were always much higher for pigs in which Salmonella was isolated from MLN.
Modulation of the Substitution Pattern of 5-Aryl-2-Aminoimidazoles Allows Fine-Tuning of Their Antibiofilm Activity Spectrum and Toxicity
Authors: Peeters Elien , Hooyberghs Geert , Robijns Stijn , Waldrant Kai , De Weerdt Ami , Delattin Nicolas , Liebens Veerle , Kucharíková Soňa , Tournu Hélène , Verstraeten Natalie , Dovgan Barbara , Girandon Lenart , Fröhlich Mirjam , De Brucker Katrijn , Van Dijck Patrick , Michiels Jan , Cammue Bruno P. A. , Thevissen Karin , Vanderleyden Jozef , Van der Eycken Erik , Steenackers Hans P. 
Published: August 2016

ABSTRACT

We previously synthesized several series of compounds, based on the 5-aryl-2-aminoimidazole scaffold, that showed activity preventing the formation of
Salmonella enterica
serovar Typhimurium and
Pseudomonas aeruginosa
biofilms. Here, we further studied the activity spectrum of a number of the most active
N
1- and 2
N
-substituted 5-aryl-2-aminoimidazoles against a broad panel of biofilms formed by monospecies and mixed species of bacteria and fungi. An
N
1-substituted compound showed very strong activity against the biofilms formed by Gram-negative and Gram-positive bacteria and the fungus
Candida albicans
but was previously shown to be toxic against various eukaryotic cell lines. In contrast, 2
N
-substituted compounds were nontoxic and active against biofilms formed by Gram-negative bacteria and
C. albicans
but had reduced activity against biofilms formed by Gram-positive bacteria. In an attempt to develop nontoxic compounds with potent activity against biofilms formed by Gram-positive bacteria for application in antibiofilm coatings for medical implants, we synthesized novel compounds with substituents at both the
N
1 and 2
N
positions and tested these compounds for antibiofilm activity and toxicity. Interestingly, most of these
N
1-,2
N
-disubstituted 5-aryl-2-aminoimidazoles showed very strong activity against biofilms formed by Gram-positive bacteria and
C. albicans
in various setups with biofilms formed by monospecies and mixed species but lost activity against biofilms formed by Gram-negative bacteria. In light of application of these compounds as anti-infective coatings on orthopedic implants, toxicity against two bone cell lines and the functionality of these cells were tested. The
N
1-,2
N
-disubstituted 5-aryl-2-aminoimidazoles in general did not affect the viability of bone cells and even induced calcium deposition. This indicates that modulating the substitution pattern on positions
N
1 and 2
N
of the 5-aryl-2-aminoimidazole scaffold allows fine-tuning of both the antibiofilm activity spectrum and toxicity.
Open-Label Study of Absorption and Clearance of 1% Voriconazole Eye Drops
Authors: Neoh Chin Fen , Leung Lok , Chan Elsie , Al-Badriyeh Daoud , Fullinfaw Robert O. , Jhanji Vishal , Vajpayee Rasik B. , Davies Geoffrey E. , Stewart Kay , Kong David C. M. 
Published: August 2016

ABSTRACT

Twenty participants undergoing elective cataract surgery received 1% voriconazole eye drops (1 drop per eye) either 20, 40, 60, or 80 min before surgery. Median voriconazole concentrations of 1.9 to 3.2 mg/liter in aqueous humor samples were attained over the first 80 min, which were higher than
in vitro
MIC
90
values for typical fungi that cause keratitis.
In Vitro
Bactericidal Activity of Trimethoprim-Sulfamethoxazole Alone and in Combination with Colistin against Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates
Authors: Nepka Martha , Perivolioti Efstathia , Kraniotaki Eleni , Politi Lida , Tsakris Athanasios , Pournaras Spyros 
Published: August 2016

ABSTRACT

Trimethoprim-sulfamethoxazole alone and combined with colistin was tested
in vitro
against six carbapenem-resistant
Acinetobacter baumannii
(CRAB) clinical strains. After 24 h, at achievable serum concentrations, trimethoprim-sulfamethoxazole effectively killed all strains, while colistin killed only one strain. Trimethoprim-sulfamethoxazole plus colistin rapidly killed all strains after 6 h and for up to 24 h. Trimethoprim-sulfamethoxazole, one of the few remaining antimicrobials that still has a degree of activity, particularly combined with colistin, might represent an effective therapy for severe CRAB infections.
Effect of Obesity on the Population Pharmacokinetics of Fluconazole in Critically Ill Patients
Authors: Alobaid Abdulaziz S. , Wallis Steven C. , Jarrett Paul , Starr Therese , Stuart Janine , Lassig-Smith Melissa , Mejia Jenny Lisette Ordóñez , Roberts Michael S. , Sinnollareddy Mahipal G. , Roger Claire , Lipman Jeffrey , Roberts Jason A. 
Published: August 2016

ABSTRACTOur objective was to describe the population pharmacokinetics of fluconazole in a cohort of critically ill nonobese, obese, and morbidly obese patients. Critically ill patients prescribed fluconazole were recruited into three body mass index (BMI) cohorts, nonobese (18.5 to 29.9 kg/m2), obese (30.0 to 39.9 kg/m2), and morbidly obese (≥40 kg/m2). Serial fluconazole concentrations were determined using a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Twenty-one critically ill patients (11 male) were enrolled, including obese (n= 6) and morbidly obese (n= 4) patients. The patients mean ± standard deviation (SD) age, weight, and BMI were 54 ± 15 years, 90 ± 24 kg, and 31 ± 9 kg/m2, respectively. A two-compartment linear model described the data adequately. The mean ± SD population pharmacokinetic parameter estimates were clearance (CL) of 0.95 ± 0.48 liter/h, volume of distribution of the central compartment (Vc) of 15.10 ± 11.78 liter, intercompartmental clearance from the central to peripheral compartment of 5.41 ± 2.28 liter/h, and intercompartmental clearance from the peripheral to central compartment of 2.92 ± 4.95 liter/h. A fluconazole dose of 200 mg daily was insufficient to achieve an area under the concentration-time curve for the free, unbound drug fraction/MIC ratio of 100 for pathogens with MICs of ≥2 mg/liter in patients with BMI of >30 kg/m2. A fluconazole loading dose of 12 mg/kg and maintenance dose of 6 mg/kg/day achieved pharmacodynamic targets for higher MICs. A weight-based loading dose of 12 mg/kg followed by a daily maintenance dose of 6 mg/kg, according to renal function, is required in critically ill patients for pathogens with a MIC of 2 mg/liter.
Sequence Type 48 Escherichia coli Carrying the
bla
CTX-M-1
IncI1/ST3 Plasmid in Drinking Water in France
Authors: Madec Jean-Yves , Haenni Marisa , Ponsin Cécile , Kieffer Nicolas , Rion Emmanuelle , Gassilloud Benoit 
Published: August 2016

ABSTRACT

Drinking water has rarely been recognized as a source of antimicrobial resistance for humans, and only in low-income countries. Here, a sequence type 48
Escherichia coli
isolate carrying the
bla
CTX-M-1
IncI1/ST3 plasmid was recovered from drinking water in France. This plasmid was similar to other
bla
CTX-M-1
IncI1/ST3 plasmids found previously in animals and humans. Our findings highlight the possible human transfer of extended-spectrum β-lactamase (ESBL) genes through drinking water in high-income countries.
Inhibitory Interaction Potential of 22 Antituberculosis Drugs on Organic Anion and Cation Transporters of the SLC22A Family
Authors: Parvez M. Masud , Kaisar Nazia , Shin Ho Jung , Jung Jin Ah , Shin Jae-Gook 
Published: August 2016

ABSTRACT

Twenty-two currently marketed antituberculosis drugs were comprehensively evaluated for their inhibitory effect on organic anionic transporter (OAT)- and organic cation transporter (OCT)-mediated uptake using stably transfected HEK293 cells
in vitro
. We observed moderate to strong inhibitory effects on OAT1- and OAT3-mediated
para
-aminohippurate (PAH) uptake and OCT1- and OCT2-mediated
N
-methyl-4-phenylpylidinium acetate (MPP
+
) uptake. Ciprofloxacin, linezolid,
para
-aminosalicylic acid (PAS), and rifampin were observed to have strong inhibitory effects, with the concentrations for a 50% inhibitory effect (IC
50
s) being 35.1, 31.1, 37.6, and 48.1 μM, respectively, for OAT1 and >100, 21.9, 24.6, and 30.2 μM, respectively, for OAT3. Similarly, pyrazinamide, rifabutin, and levofloxacin were observed to have inhibitory effects, with IC
50
values being 36.5, 42.7, and 30.3 μM, respectively, for OCT1 and with the IC
50
value for PAS being 94.2 μM for OCT2. In addition, we used zidovudine and metformin as clinically prescribed substrates of OATs and OCTs, respectively, and zidovudine and metformin uptake was also strongly inhibited by the antituberculosis drugs. Among the tested drugs, the highest drug-drug interaction (DDI) indexes were found for PAS, which were 9.3 to 13.9 for OAT1 and 12.0 to 17.7 for OAT3, and linezolid, which were 1.18 to 2.15 for OAT1 and 1.7 to 3.01 for OAT3. Similarly, the DDI indexes of pyrazinamide and levofloxacin were 0.57 and 0.30, respectively, for OCT1, and the DDI index of PAS was 3.8 for OCT2, suggesting a stronger possibility (DDI index value cutoff, >0.1) of
in vivo
DDIs. This is the first comprehensive report of the inhibitory potential of anti-TB drugs on OAT- and OCT-mediated uptake of prototype and clinically prescribed substrate drugs
in vitro
, providing an ability to predict DDIs between anti-TB drugs and other coprescribed drugs in clinical studies
in vivo
.
Early Bactericidal Activity of AZD5847 in Patients with Pulmonary Tuberculosis
Authors: Furin Jennifer J. , Du Bois Jeannine , van Brakel Elana , Chheng Phalkun , Venter Amour , Peloquin Charles A. , Alsultan Abdullah , Thiel Bonnie A. , Debanne Sara M. , Boom W. Henry , Diacon Andreas H. , Johnson John L. 
Published: August 2016

ABSTRACT

AZD5847 is an oxazolidinone antibiotic with
in vitro
activity against
Mycobacterium tuberculosis
. The objective of this study was to evaluate the antimycobacterial activity, safety, and pharmacokinetics of AZD5847 in patients with pulmonary tuberculosis. Groups of 15 treatment-naive, sputum smear-positive adults with pulmonary tuberculosis were randomly assigned to receive AZD5847 at one of four doses (500 mg once daily, 500 mg twice daily, 1,200 mg once daily, and 800 mg twice daily) or daily standard chemotherapy. The primary efficacy endpoint was the mean daily rate of change in the log
10
number of CFU of
M. tuberculosis
per milliliter of sputum, expressed as the change in log
10
number of CFU per milliliter of sputum per day. The mean 14-day activity of the combination of isoniazid, rifampin, ethambutol, and pyrazinamide (−0.163 log
10
CFU/ml sputum/day; 95% confidence interval [CI], −0.193, −0.133 log
10
CFU/ml sputum/day) was consistent with that found in previous studies. AZD5847 at 500 mg twice daily significantly decreased the number of CFU on solid medium (−0.039; 95% CI, −0.069, −0.009;
P
= 0.0048). No bactericidal activity was detected at doses of AZD5847 of 500 mg once daily (mean early bactericidal activity [EBA], 0.02 [95% CI, −0.01, 0.05]), 1,200 mg once daily (mean EBA, 0.02 [95% CI, −0.01, 0.05]), and 800 mg twice daily (mean EBA, 0.02 [95% CI, −0.01, 0.05]). AZD5847 at doses of both 500 mg and 800 mg twice daily also showed an increase in the time to a positive culture in MGIT liquid culture medium. Two serious adverse events (grade 4 thrombocytopenia and grade 4 hyperbilirubinemia) occurred in patients receiving AZD5847 at higher doses. AZD5847 dosed twice daily kills tubercle bacilli in the sputum of patients with pulmonary tuberculosis and has modest early bactericidal activity. (This study has been registered at ClinicalTrials.gov under registration no. NCT01516203.)
Clarithromycin Suppresses Chloride Channel Accessory 1 and Inhibits Interleukin-13-Induced Goblet Cell Hyperplasia in Human Bronchial Epithelial Cells
Authors: Nagashima Akimichi , Shinkai Masaharu , Shinoda Masahiro , Shimokawaji Tadasuke , Kimura Yasuhiro , Mishina Kei , Sato Takashi , Toda Mariko , Inayama Yoshiaki , Rubin Bruce K. , Kaneko Takeshi 
Published: August 2016

ABSTRACT

Activation of the interleukin-13 (IL-13) receptor leads to signal transducer and activator of transcription 6 (STAT6) activation and subsequent induction of SAM pointed domain containing ETS transcription factor (SPDEF) and chloride channel accessory 1 (CLCA1), increasing secretion of the gel-forming mucin MUC5AC. Activation of the epidermal growth factor receptor (EGFR) also leads to MUC5AC production via extracellular signal-regulated kinase (ERK1/2). We examined the effect of clarithromycin IL-13 signaling leading to production. Normal human bronchial epithelial (NHBE) cells were grown for 14 days at an air-liquid interface (ALI) with IL-13 and/or clarithromycin. Histochemical analysis was performed using hematoxylin and eosin (HE) staining and MUC5AC immunostaining. MUC5AC, SPDEF, and CLCA1 mRNA expression were evaluated by real-time PCR. Western analysis was used to assess phosphorylation of STAT6 and ERK1/2. Clarithromycin decreased IL-13-induced goblet cell hyperplasia and MUC5AC mRNA expression in a dose-dependent manner. Clarithromycin decreased IL-13-stimulated SPDEF and CLCA1 mRNA expression in a dose-dependent manner, and at 32 μg/ml CLCA1 was profoundly decreased (
P
< 0.001). Although clarithromycin had no effect on STAT6 phosphorylation induced by IL-13, it decreased constitutive phosphorylation of ERK1/2 (
P
< 0.05).
Emergence of NDM-5- and MCR-1-Producing Escherichia coli Clones ST648 and ST156 from a Single Muscovy Duck (Cairina moschata)
Authors: Yang Run-Shi , Feng Youjun , Lv Xiao-Yue , Duan Jia-Hong , Chen Jing , Fang Liang-Xing , Xia Jing , Liao Xiao-Ping , Sun Jian , Liu Ya-Hong 
Published: August 2016

ABSTRACT

Two
Escherichia coli
clones (sequence type 648 [ST648] and ST156) that coproduce NDM-5 and MCR-1 were detected from a single fowl in China. The
bla
NDM-5
gene was found on the two indistinguishable IncX3 plasmids from the two different
E. coli
isolates, whereas the
mcr-1
gene was located on IncHI2 and IncI2 plasmids, respectively, suggesting that
bla
NDM-5
and
mcr-1
have spread in avian intestinal flora. Also, the two strains harbor
bla
TEM-1
,
bla
CTX-M-55
,
fosA3
, and
aac(6
′
)-Ib
. The multiresistant
E. coli
strains (especially the epidemic clone ST648) might raise a potential threat to human health via food chain transmission.
Chalcone Isomerase from Eubacterium ramulus Catalyzes the Ring Contraction of Flavanonols
Authors: Braune Annett , Engst Wolfram , Elsinghorst Paul W. , Furtmann Norbert , Bajorath Jürgen , Gütschow Michael , Blaut Michael 
Published: August 2016

ABSTRACT

The enzyme catalyzing the ring-contracting conversion of the flavanonol taxifolin to the auronol alphitonin in the course of flavonoid degradation by the human intestinal anaerobe
Eubacterium ramulus
was purified and characterized. It stereospecifically catalyzed the isomerization of (+)-taxifolin but not that of (−)-taxifolin. The

K
m

for (+)-taxifolin was 6.4 ± 0.8 μM, and the
V
max
was 108 ± 4 μmol min
−1
(mg protein)
−1
. The enzyme also isomerized (+)-dihydrokaempferol, another flavanonol, to maesopsin. Inspection of the encoding gene revealed its complete identity to that of the gene encoding chalcone isomerase (CHI) from
E. ramulus
. Based on the reported X-ray crystal structure of CHI (M. Gall et al., Angew Chem Int Ed 53:1439–1442, 2014,
http://dx.doi.org/10.1002/anie.201306952
), docking experiments suggest the substrate binding mode of flavanonols and their stereospecific conversion. Mutation of the active-site histidine (His33) to alanine led to a complete loss of flavanonol isomerization by CHI, which indicates that His33 is also essential for this activity. His33 is proposed to mediate the stereospecific abstraction of a proton from the hydroxymethylene carbon of the flavanonol C-ring followed by ring opening and recyclization. A flavanonol-isomerizing enzyme was also identified in the flavonoid-converting bacterium
Flavonifractor plautii
based on its 50% sequence identity to the CHI from
E. ramulus
.

IMPORTANCE
Chalcone isomerase was known to be involved in flavone/flavanone conversion by the human intestinal bacterium
E. ramulus
. Here we demonstrate that this enzyme moreover catalyzes a key step in the breakdown of flavonols/flavanonols. Thus, a single isomerase plays a dual role in the bacterial conversion of dietary bioactive flavonoids. The identification of a corresponding enzyme in the human intestinal bacterium
F. plautii
suggests a more widespread occurrence of this isomerase in flavonoid-degrading bacteria.
Measurement of patient safety: a systematic review of the reliability and validity of adverse event detection with record review
Authors: Hanskamp-Sebregts Mirelle , Zegers Marieke , Vincent Charles , van Gurp Petra J , de Vet Henrica C W , Wollersheim Hub 
Published: August 2016

ObjectivesRecord review is the most used method to quantify patient safety. We systematically reviewed the reliability and validity of adverse event detection with record review.DesignA systematic review of the literature.MethodsWe searched PubMed, EMBASE, CINAHL, PsycINFO and the Cochrane Library and from their inception through February 2015. We included all studies that aimed to describe the reliability and/or validity of record review. Two reviewers conducted data extraction. We pooled κ values (κ) and analysed the differences in subgroups according to number of reviewers, reviewer experience and training level, adjusted for the prevalence of adverse events.ResultsIn 25 studies, the psychometric data of the Global Trigger Tool (GTT) and the Harvard Medical Practice Study (HMPS) were reported and 24 studies were included for statistical pooling. The inter-rater reliability of the GTT and HMPS showed a pooled κ of 0.65 and 0.55, respectively. The inter-rater agreement was statistically significantly higher when the group of reviewers within a study consisted of a maximum five reviewers. We found no studies reporting on the validity of the GTT and HMPS.ConclusionsThe reliability of record review is moderate to substantial and improved when a small group of reviewers carried out record review. The validity of the record review method has never been evaluated, while clinical data registries, autopsy or direct observations of patient care are potential reference methods that can be used to test concurrent validity.
Impact of ASPECT scores and infarct distribution on outcomes among patients undergoing thrombectomy for acute ischemic stroke with the ADAPT technique
Authors: Hungerford John P , Hyer Madison , Turk Aquilla S , Turner Raymond D , Chaudry M Imran , Fargen Kyle M , Spiotta Alejandro M 
Published: August 2016

ObjectiveTo investigate the associations between Alberta Stroke Program Early CT Score (ASPECTS) or distribution and sidedness of acute infarction and clinical outcomes following intervention with a direct aspiration first pass technique (ADAPT).MethodsA review was performed of patients who had undergone thrombectomy with ADAPT for emergent large vessel occlusions of the middle cerebral artery (MCA) between December 2012 and May 2015. Preintervention CT scans were reviewed by a blinded radiologist to calculate ASPECTS and determine the distribution of infarction. Clinical outcomes were compared for subsets of patients depending upon ASPECTS and regional infarction distribution (cortical, subcortical, or both).ResultsOne hundred and fifty-four patients (50% female, mean age 67) underwent thrombectomy using ADAPT for MCA emergent large vessel occlusion. The median presenting National Institute of Health Stroke Scale score was 15. Fifty-five per cent of patients had left-side occlusions. Similar good outcomes were achieved for patients with perfect and non-perfect ASPECTS (modified Rankin Scale (mRS) 0–2: 63% vs 51%, respectively; p=0.20). Similar outcomes were also achieved for patients with ‘poor’ ASPECTS (≤6) compared with those with ASPECTS >6 (mRS 0–2: 52% vs 53%, respectively; p=0.91). Regional distribution and sidedness of core infarction on preintervention CT also did not correlate with worse outcomes.ConclusionsPatients with moderate-sized core infarcts involving various distributions in either hemisphere can potentially achieve similar good outcomes compared with those with no core infarction at presentation. A treatment algorithm for acute ischemic stroke, which employs hardline ASPECTS thresholds or excludes patients with basal ganglia infarcts, might preclude patients who would potentially benefit from mechanical thrombectomy with ADAPT.