bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cavitary Penetration of Levofloxacin among Patients with Multidrug-Resistant Tuberculosis
Authors: Kempker Russell R. , Barth Aline B. , Vashakidze Sergo , Nikolaishvili Ketino , Sabulua Irina , Tukvadze Nestani , Bablishvili Nino , Gogishvili Shota , Singh Ravi Shankar P. , Guarner Jeannette , Derendorf Hartmut , Peloquin Charles A. , Blumberg Henry M. 
Published: March 2015

ABSTRACT

A better understanding of second-line drug (SLD) pharmacokinetics, including cavitary penetration, may help optimize SLD dosing. Patients with pulmonary multidrug-resistant tuberculosis (MDR-TB) undergoing adjunctive surgery were enrolled in Tbilisi, Georgia. Serum was obtained at 0, 1, 4, and 8 h and at the time of cavitary removal to measure levofloxacin concentrations. After surgery, microdialysis was performed using the
ex vivo
cavity, and levofloxacin concentrations in the collected dialysate fluid were measured. Noncompartmental analysis was performed, and a cavitary-to-serum levofloxacin concentration ratio was calculated. Twelve patients received levofloxacin for a median of 373 days before surgery (median dose, 11.8 mg/kg). The median levofloxacin concentration in serum (
C
max
) was 6.5 μg/ml, and it was <2 μg/ml in 3 (25%) patients. Among 11 patients with complete data, the median cavitary concentration of levofloxacin was 4.36 μg/ml (range, 0.46 to 8.82). The median cavitary/serum levofloxacin ratio was 1.33 (range, 0.63 to 2.36), and 7 patients (64%) had a ratio of >1. There was a significant correlation between serum and cavitary concentrations (
r
= 0.71;
P
= 0.01). Levofloxacin had excellent penetration into chronic cavitary TB lesions, and there was a good correlation between serum and cavitary concentrations. Optimizing serum concentrations will help ensure optimal cavitary concentrations of levofloxacin, which may enhance treatment outcomes.
Limited Transmission of
bla
CTX-M-9
-Type-Positive Escherichia coli between Humans and Poultry in Vietnam
Authors: Ueda Shuhei , Ngan Bui Thi Kim , Huong Bui Thi Mai , Hirai Itaru , Tuyen Le Danh , Yamamoto Yoshimasa 
Published: March 2015

ABSTRACT

We examined whether
Escherichia coli
isolates that produce CTX-M-9-type extended-spectrum β-lactamases (ESBL) are transferred between humans and chickens in a Vietnamese community. The phylogenetic group compositions, sequence types, antimicrobial resistance profiles, the prevalence of plasmid antibiotic resistance genes, and the plasmid replicon types generally differed between the human and chicken
E. coli
isolates. Our results suggest that transmission of the
bla
CTX-M-9
-positive
E. coli
between humans and poultry was limited.
Bactericidal Monoclonal Antibodies Specific to the Lipopolysaccharide O Antigen from Multidrug-Resistant Escherichia coli Clone ST131-O25b:H4 Elicit Protection in Mice
Authors: Szijártó Valéria , Guachalla Luis M. , Visram Zehra C. , Hartl Katharina , Varga Cecília , Mirkina Irina , Zmajkovic Jakub , Badarau Adriana , Zauner Gerhild , Pleban Clara , Magyarics Zoltán , Nagy Eszter , Nagy Gábor 
Published: March 2015

ABSTRACTTheEscherichia colisequence type 131 (ST131)-O25b:H4 clone has spread worldwide and become responsible for a significant proportion of multidrug-resistant extraintestinal infections. We generated humanized monoclonal antibodies (MAbs) that target the lipopolysaccharide O25b antigen conserved within this lineage. These MAbs bound to the surface of live bacterial cells irrespective of the capsular type expressed. In a serum bactericidal assayin vitro, MAbs induced >95% bacterial killing in the presence of human serum as the complement source. Protective efficacy at low antibody doses was observed in a murine model of bacteremia. The mode of actionin vivowas investigated by using aglycosylated derivatives of the protective MAbs. The significant binding to liveE. colicells and thein vitroandin vivoefficacy were corroborated in assays using bacteria grown in human serum to mimic relevant clinical conditions. Given the dry pipeline of novel antibiotics against multidrug-resistant Gram-negative pathogens, passive immunization with bactericidal antibodies offers a therapeutic alternative to control infections caused byE. coliST131-O25b:H4.
Longitudinal Study of Extended-Spectrum-β-Lactamase- and AmpC-Producing Enterobacteriaceae in Household Dogs
Authors: Baede Valérie O. , Wagenaar Jaap A. , Broens Els M. , Duim Birgitta , Dohmen Wietske , Nijsse Rolf , Timmerman Arjen J. , Hordijk Joost 
Published: March 2015

ABSTRACT

A longitudinal study was performed to (i) investigate the continuity of shedding of extended-spectrum-beta-lactamase (ESBL)-producing
Enterobacteriaceae
in dogs without clinical signs, (ii) identify dominant plasmid-mediated ESBL genes, and (iii) quantify ESBL-producing
Enterobacteriaceae
in feces. Fecal samples from 38 dogs were collected monthly for 6 months. Additional samples were collected from 7 included dogs on a weekly basis for 6 weeks. Numbers of CFU per gram of feces for non-wild-type
Enterobacteriaceae
were determined by using MacConkey agar supplemented with 1 mg/liter cefotaxime (MCC), and those for total
Enterobacteriaceae
were determined by using MacConkey agar. Cefotaxime-resistant isolates were screened by PCR and sequence analysis for the presence of
bla
CTX-M
,
bla
CMY
,
bla
SHV
,
bla
OXA
, and
bla
TEM
gene families. Bacterial species were identified by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) analysis. PCR-negative isolates were tested by a double-disk synergy test for enhanced AmpC expression. A total of 259 samples were screened, and 126 samples were culture positive on MCC, resulting in 352 isolates, 327 of which were
Escherichia coli
. Nine dogs were continuously positive during this study, and 6 dogs were continuously negative. Monthly or weekly shifts in fecal shedding were observed for 23 dogs. Genotyping showed a large variety of ESBL genes and gene combinations at single and multiple consecutive sampling moments. The ESBL genes
bla
CTX-M-1
,
bla
CTX-M-14
,
bla
CTX-M-15
,
bla
SHV-12
, and
bla
CMY-2
were most frequently found. The mean number of CFU of non-wild-type
Enterobacteriaceae
was 6.11 × 10
8
CFU/g feces. This study showed an abundance of ESBL-producing
Enterobacteriaceae
in dogs in the Netherlands, mostly in high concentrations. Fecal shedding was shown to be highly dynamic over time, which is important to consider when studying ESBL epidemiology.
A Novel Gene Amplification Causes Upregulation of the PatAB ABC Transporter and Fluoroquinolone Resistance in Streptococcus pneumoniae
Authors: Baylay Alison J. , Ivens Alasdair , Piddock Laura J. V. 
Published: March 2015

ABSTRACT

Overexpression of the ABC transporter genes
patA
and
patB
confers efflux-mediated fluoroquinolone resistance in
Streptococcus pneumoniae
and is also linked to pneumococcal stress responses. Although upregulation of
patAB
has been observed in many laboratory mutants and clinical isolates, the regulatory mechanisms controlling expression of these genes are unknown. In this study, we aimed to identify the cause of high-level constitutive overexpression of
patAB
in M184, a multidrug-resistant mutant of S.
pneumoniae
R6. Using a whole-genome transformation and sequencing approach, we identified a novel duplication of a 9.2-kb region of the M184 genome which included the
patAB
genes. This duplication did not affect growth and was semistable with a low segregation rate. The expression levels of
patAB
in M184 were much higher than those that could be fully explained by doubling of the gene dosage alone, and inactivation of the first copy of
patA
had no effect on multidrug resistance. Using a green fluorescent protein reporter system, increased
patAB
expression was ascribed to transcriptional read-through from a tRNA gene upstream of the second copy of
patAB
. This is the first report of a large genomic duplication causing antibiotic resistance in
S. pneumoniae
and also of a genomic duplication causing antibiotic resistance by a promoter switching mechanism.
Implication of Candida parapsilosis FKS1 and
FKS2
Mutations in Reduced Echinocandin Susceptibility
Authors: Martí-Carrizosa M. , Sánchez-Reus F. , March F. , Cantón E. , Coll P. 
Published: March 2015

ABSTRACT

We evaluated
FKS1
and
FKS2
mutations in
Candida parapsilosis
bloodstream isolates and correlated them with the echinocandin MIC values determined by guidelines in CLSI document M27-A3 and the YeastOne panel. All mutations detected were outside hot spot (HS) regions. The F1386S mutation detected in an isolate that was resistant by the YeastOne panel but not by the M27-A3 guidelines might be implicated in echinocandin resistance. Further studies are needed to confirm the implication of the F1386S mutation and to elucidate the capability of the M27-A3 guidelines to detect echinocandin resistance.
agr
Dysfunction Affects Staphylococcal Cassette Chromosome
mec
Type-Dependent Clinical Outcomes in Methicillin-Resistant Staphylococcus aureus Bacteremia
Authors: Kang Chang Kyung , Cho Jeong Eun , Choi Yoon Jeong , Jung Younghee , Kim Nak-Hyun , Kim Chung-Jong , Kim Taek Soo , Song Kyoung-Ho , Choe Pyoeng Gyun , Park Wan Beom , Bang Ji-Hwan , Kim Eu Suk , Park Kyoung Un , Park Sang Won , Kim Nam-Joong , Oh Myoung-don , Kim Hong Bin 
Published: March 2015

ABSTRACT

Staphylococcal cassette chromosome
mec
element (SCC
mec
) type-dependent clinical outcomes may vary due to geographical variation in the presence of virulence determinants. We compared the microbiological factors and mortality attributed to methicillin-resistant
Staphylococcus aureus
(MRSA) bacteremia between SCC
mec
types II/III and type IV. All episodes of MRSA bacteremia in a tertiary-care hospital (South Korea) over a 4.5-year period were reviewed. We studied the microbiological factors associated with all blood MRSA isolates, including
spa
type,
agr
type,
agr
dysfunction, and the genes for Panton-Valentine leukocidin (PVL) and phenol-soluble modulin (PSM)-mec, in addition to SCC
mec
type. Of 195 cases, 137 involved SCC
mec
types II/III, and 58 involved type IV. The mortality attributed to MRSA bacteremia was less frequent among the SCC
mec
type IV (5/58) than that among types II/III (39/137,
P
= 0.002). This difference remained significant when adjusted for clinical factors (adjusted odds ratio [aOR], 0.14; 95% confidence interval [CI], 0.04 to 0.49;
P
= 0.002). Of the microbiological factors tested,
agr
dysfunction was the only significant factor that showed different positivity between the SCC
mec
types, and it was independently associated with MRSA bacteremia-attributed mortality (aOR, 4.71; 95% CI, 1.72 to 12.92;
P
= 0.003). SCC
mec
type IV is associated with lower MRSA bacteremia-attributed mortality than are types II/III, which might be explained by the high rate of
agr
dysfunction in SCC
mec
types II/III in South Korea.
Draft Genome Sequence of Lactococcus lactis subsp. lactis JCM 5805
T
, a Strain That Induces Plasmacytoid Dendritic Cell Activation
Authors: Fujii Toshio , Tomita Yasuyuki , Ikushima Shigehito , Horie Akira , Fujiwara Daisuke 
Published: March 2015

ABSTRACT

Lactococcus lactis
subsp. lactis JCM 5805
T
is a dairy lactic acid bacterium that induces plasmacytoid dendritic cell (pDC) activation. Here, we report the 2.55-Mb draft genome and annotation of
Lactococcus lactis
JCM 5805
T
. This genome information will provide further insights into the mechanisms underlying the immunomodulatory function of this strain.
Genome Sequence of Bacillus anthracis Isolated from an Anthrax Burial Site in Pollino National Park, Basilicata Region (Southern Italy)
Authors: Fasanella Antonio , Braun Peter , Grass Gregor , Hanczaruk Matthias , Aceti Angela , Serrecchia Luigina , Leonzio Giuseppe , Tolve Francesco , Georgi Enrico , Antwerpen Markus 
Published: March 2015

ABSTRACT

A
Bacillus anthracis
strain was isolated from a burial-site in Pollino National Park where a bovine died of anthrax and was buried in 2004. We report the first genome sequence of
B. anthracis
isolated in the Basilicata region (southern Italy), which is the highest risk area of anthrax infection in Italy.
A Genomic Virulence Reference Map of Enterococcus faecalis Reveals an Important Contribution of Phage03-Like Elements in Nosocomial Genetic Lineages to Pathogenicity in a Caenorhabditis elegans Infection Model
Authors: La Rosa Sabina Leanti , Snipen Lars-Gustav , Murray Barbara E. , Willems Rob J. L. , Gilmore Michael S. , Diep Dzung B. , Nes Ingolf F. , Brede Dag Anders 
Published: March 2015

ABSTRACT

In the present study, the commensal and pathogenic host-microbe interaction of
Enterococcus faecalis
was explored using a
Caenorhabditis elegans
model system. The virulence of 28
E. faecalis
isolates representing 24 multilocus sequence types (MLSTs), including human commensal and clinical isolates as well as isolates from animals and of insect origin, was investigated using
C. elegans
strain
glp-4
(
bn2ts
);
sek-1
(
km4
). This revealed that 6
E. faecalis
isolates behaved in a commensal manner with no nematocidal effect, while the remaining strains showed a time to 50% lethality ranging from 47 to 120 h. Principal component analysis showed that the difference in nematocidal activity explained 94% of the variance in the data. Assessment of known virulence traits revealed that gelatinase and cytolysin production accounted for 40.8% and 36.5% of the observed pathogenicity, respectively. However, coproduction of gelatinase and cytolysin did not increase virulence additively, accounting for 50.6% of the pathogenicity and therefore indicating a significant (26.7%) saturation effect. We employed a comparative genomic analysis approach using the 28 isolates comprising a collection of 82,356 annotated coding sequences (CDS) to identify 2,325 patterns of presence or absence among the investigated strains. Univariate statistical analysis of variance (ANOVA) established that individual patterns positively correlated (
n
= 61) with virulence. The patterns were investigated to identify potential new virulence traits, among which we found five patterns consisting of the phage03-like gene clusters. Strains harboring phage03 showed, on average, 17% higher killing of
C. elegans
(
P
= 4.4e
−6
). The phage03 gene cluster was also present in gelatinase-and-cytolysin-negative strain
E. faecalis
JH2-2. Deletion of this phage element from the JH2-2 clinical strain rendered the mutant apathogenic in
C. elegans
, and a similar mutant of the nosocomial V583 isolate showed significantly attenuated virulence. Bioinformatics investigation indicated that, unlike other
E. faecalis
virulence traits, phage03-like elements were found at a higher frequency among nosocomial isolates. In conclusion, our report provides a valuable virulence map that explains enhancement in
E. faecalis
virulence and contributes to a deeper comprehension of the genetic mechanism leading to the transition from commensalism to a pathogenic lifestyle.
Molecular Dissection of a Borrelia burgdorferi
In Vivo
Essential Purine Transport System
Authors: Jain Sunny , Showman Adrienne C. , Jewett Mollie W. 
Published: March 2015

ABSTRACT

The Lyme disease spirochete
Borrelia burgdorferi
is dependent on purine salvage from the host environment for survival. The genes
bbb22
and
bbb23
encode purine permeases that are essential for
B. burgdorferi
mouse infectivity. We now demonstrate the unique contributions of each of these genes to purine transport and murine infection. The affinities of spirochetes carrying
bbb22
alone for hypoxanthine and adenine were similar to those of spirochetes carrying both genes. Spirochetes carrying
bbb22
alone were able to achieve wild-type levels of adenine saturation but not hypoxanthine saturation, suggesting that maximal hypoxanthine uptake requires the presence of
bbb23
. Moreover, the purine transport activity conferred by
bbb22
was dependent on an additional distal transcriptional start site located within the
bbb23
open reading frame. The initial rates of uptake of hypoxanthine and adenine by spirochetes carrying
bbb23
alone were below the level of detection. However, these spirochetes demonstrated a measurable increase in hypoxanthine uptake over a 30-min time course. Our findings indicate that
bbb22
-dependent adenine transport is essential for
B. burgdorferi
survival in mice. The
bbb23
gene was dispensable for
B. burgdorferi
mouse infectivity, yet its presence was required along with that of
bbb22
for
B. burgdorferi
to achieve maximal spirochete loads in infected mouse tissues. These data demonstrate that both genes,
bbb22
and
bbb23
, are critical for
B. burgdorferi
to achieve wild-type infection of mice and that the differences in the capabilities of the two transporters may reflect distinct purine salvage needs that the spirochete encounters throughout its natural infectious cycle.
Impact of Malaria Preexposure on Antiparasite Cellular and Humoral Immune Responses after Controlled Human Malaria Infection
Authors: Obiero Joshua M. , Shekalaghe Seif , Hermsen Cornelus C. , Mpina Maxmillian , Bijker Else M. , Roestenberg Meta , Teelen Karina , Billingsley Peter F. , Sim B. Kim Lee , James Eric R. , Daubenberger Claudia A. , Hoffman Stephen L. , Abdulla Salim , Sauerwein Robert W. , Scholzen Anja 
Published: March 2015

ABSTRACTTo understand the effect of previous malaria exposure on antiparasite immune responses is important for developing successful immunization strategies. Controlled human malaria infections (CHMIs) using cryopreservedPlasmodium falciparumsporozoites provide a unique opportunity to study differences in acquisition or recall of antimalaria immune responses in individuals from different transmission settings and genetic backgrounds. In this study, we compared antiparasite humoral and cellular immune responses in two cohorts of malaria-naive Dutch volunteers and Tanzanians from an area of low malarial endemicity, who were subjected to the identical CHMI protocol by intradermal injection ofP. falciparumsporozoites. Samples from both trials were analyzed in parallel in a single center to ensure direct comparability of immunological outcomes. Within the Tanzanian cohort, we distinguished one group with moderate levels of preexisting antibodies to asexualP. falciparumlysate and another that, based onP. falciparumserology, resembled the malaria-naive Dutch cohort. PositiveP. falciparumserology at baseline was associated with a lower parasite density at first detection by quantitative PCR (qPCR) after CHMI than that for Tanzanian volunteers with negative serology. Post-CHMI, both Tanzanian groups showed a stronger increase in anti-P. falciparumantibody titers than Dutch volunteers, indicating similar levels of B-cell memory independent of serology. In contrast to the Dutch, Tanzanians failed to increaseP. falciparum-specificin vitrorecall gamma interferon (IFN-γ) production after CHMI, and innate IFN-γ responses were lower inP. falciparumlysate-seropositive individuals than in seronegative individuals. In conclusion, positiveP. falciparumlysate serology can be used to identify individuals with better parasite control but weaker IFN-γ responses in circulating lymphocytes, which may help to stratify volunteers in future CHMI trials in areas where malaria is endemic.
Comprehensive lymph node morphometry in rectal cancer using acetone compression
Authors: Scheel Andreas H , Reineke Rebecca A , Sprenger Thilo , Lokka Suvi , Kitz Julia , Ghadimi B Michael , Rüschoff Josef , Liersch Torsten , Middel Peter 
Published: March 2015

AimsAcetone compression (AC) is an elution compression technique for the comprehensive pathological examination of fatty tissue. Here AC is combined with digital morphometry to evaluate the impact of preoperative (neoadjuvant) chemoradiotherapy (neoCRT) on lymph node (LN) numbers and morphology in locally advanced rectal cancer. AC is compared with complete embedding of the mesorectal fat (whole mesorectal embedding (WME)) to exclude artificial alterations and to the standard technique, manual dissectioning (MD).Methods320 rectal cancer specimens were subjected to LN morphometry. Neoadjuvant CRT was applied in 204 specimens. LNs were prepared either with AC (n=138), WME (n=51) or MD (n=131). 8523 LNs were assessed including 530 nodes with metastases.ResultsLN prepared by AC and WME showed similar morphologies. AC revealed reduced LN sizes in neoCRT specimens compared with primary resection (2.2; 2.4 mm, p=0.049) while the LN number was comparable (27; 30/specimen). AC yielded 28 LN/specimen on average, MD yielded 22 LN (p<0.001). In neoCRT specimens, MD yielded less LN compared with primary resection (19; 25). MD detected less small LN (<2 mm; MD: 25%; AC: 56%) while 24 of the 135 LN metastases found by AC were ≤2 mm in diameter.ConclusionsAC does not alter LN morphology and is especially suited to retrieve small LN after neoadjuvant CRT of rectal cancer. Neoadjuvant multimodality treatment caused reduced LN sizes while the LN numbers were not affected. When compared with MD, AC proved more reliable in the retrieval of LN from rectal cancer specimens after neoCRT.
Pulmonary and circulatory parameter guided anesthesia in patients with ischemic stroke undergoing endovascular recanalization
Authors: Mundiyanapurath S , Stehr A , Wolf M , Kieser M , Möhlenbruch M , Bendszus M , Hacke W , Bösel J 
Published: March 2015

Background and purposeEndovascular recanalization in ischemic stroke is often performed under general anesthesia. Some studies have shown a detrimental effect of general anesthesia. The reasons are unknown.MethodsThis was an observational study with retrospective and prospective phases. From 2008 to 2010, 60 patients treated by endovascular recanalization due to proximal vessel occlusion were analyzed with regard to ventilation parameters, blood gas values, blood pressure, and clinical parameters (pre-protocol phase). Subsequently, a protocol with target values for end-tidal CO2(Petco2) and systolic blood pressure (SBP) was introduced and prospectively analyzed in 64 patients in 2012 (protocol phase).ResultsIn the pre-protocol phase, significant hypocapnia (<30 mm Hg), a decrease in SBP after intervention (p<0.001), and an increase in SBP after extubation (p<0.001) were observed. After implementing the protocol in 2012, 63% of Petco2values and 55% of SBP values (median) of the duration of intervention were within the predefined range. Severe hypocapnia and hypotension (SBP <100 mm Hg) after the intervention were significantly reduced. Longer duration of Petco2values within 40–45 mm Hg, intracerebral hemorrhage, longer door to needle time, older age, unsuccessful recanalization, longer duration of endovascular treatment, and higher cumulative dose of norepinephrine were associated with an unfavorable outcome (modified Rankin Scale score >2). Intracerebral hemorrhage (OR 0.028, p=0.001), age (OR 0.9, p=0.013), and cumulative dose of norepinephrine (OR 0.142, p=0.003) were independent predictors of an unfavorable outcome.ConclusionsIn patients receiving endovascular stroke treatment under general anesthesia, the cumulative dose of norepinephrine was an independent predictor of an unfavorable outcome. Further studies are needed to evaluate the optimal management of blood pressure in these patients, and whether avoidance of catecholamines could partly explain the improved outcomes for patients treated under conscious sedation in retrospective studies.
正视海外华人研究的重要性，拓展中国历史学的国际视野
Authors: 陈勇  
Published: March 2015

海外华人是中国历史进程中的一个重要篇章，也对世界历史的发展产生着深远的影响。但是长久以来，在美国与中国对中国历史的研究中，海外华人的发展史远远没有得到其应当得到的重视。美国对中国的研究源远流长，近年来更是蓬勃发展。但相比之下，学术界对华人的研究并没有获得足够的重视。在中国，海外华人史通常只是中国史研究的小分支，甚至仅仅被视为中国历史的一个脚注。由于没有得到其应有的重视，海外华人研究还有一个很大的弱点。那就是，无论是在中国还是在美国乃至世界其他地方，它都没成为一个具有高度横向和纵向联系的独立学科。华人研究常常是其他领域，如美国史和中国史的附产品。而且，研究世界不同地区华人的学者很少有互动。 正视海外华人的重要性，不但是了解其对历史发展所作的贡献，加强对于海外华人的研究，也是拓展中国历史学的视野，营造中国历史研究的国际性框架的一个重要契机。所谓的国际性框架指的是一个新的历史研究的方法。它可以帮助我们摆脱传统国别史的窠臼，从而理解历史中跨越国界的和跨文化的联系。