bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro
Drug Combination Studies of Letermovir (AIC246, MK-8228) with Approved Anti-Human Cytomegalovirus (HCMV) and Anti-HIV Compounds in Inhibition of HCMV and HIV Replication
Authors: Wildum Steffen , Zimmermann Holger , Lischka Peter
Published: March 2015

Despite modern prevention and treatment strategies, human cytomegalovirus (HCMV) remains a common opportunistic pathogen associated with serious morbidity and mortality in immunocompromised individuals, such as transplant recipients and AIDS patients. All drugs currently licensed for the treatment of HCMV infection target the viral DNA polymerase and are associated with severe toxicity issues and the emergence of drug resistance. Letermovir (AIC246, MK-8228) is a new anti-HCMV agent in clinical development that acts via a novel mode of action and has demonstrated anti-HCMV activity
in vitro
and
in vivo
. For the future, drug combination therapies, including letermovir, might be indicated under special medical conditions, such as the emergence of multidrug-resistant virus strains in transplant recipients or in HCMV-HIV-coinfected patients. Accordingly, knowledge of the compatibility of letermovir with other HCMV or HIV antivirals is of medical importance. Here, we evaluated the inhibition of HCMV replication by letermovir in combination with all currently approved HCMV antivirals using cell culture checkerboard assays. In addition, the effects of letermovir on the antiviral activities of selected HIV drugs, and vice versa, were analyzed. Using two different mathematical techniques to analyze the experimental data, (i) additive effects were observed for the combination of letermovir with anti-HCMV drugs and (ii) no interaction was found between letermovir and anti-HIV drugs. Since none of the tested drug combinations significantly antagonized letermovir efficacy (or vice versa), our findings suggest that letermovir may offer the potential for combination therapy with the tested HCMV and HIV drugs.
The New Macrolide-Lincosamide-Streptogramin B Resistance Gene
erm
(45) Is Located within a Genomic Island in Staphylococcus fleurettii
Authors: Wipf Juliette R. K. , Schwendener Sybille , Nielsen Jesper Boye , Westh Henrik , Perreten Vincent
Published: March 2015

Genome alignment of a macrolide, lincosamide, and streptogramin B (MLS
B
)-resistant
Staphylococcus fleurettii
strain with an MLS
B
-susceptible
S. fleurettii
strain revealed a novel 11,513-bp genomic island carrying the new erythromycin resistance methylase gene
erm
(45). This gene was shown to confer inducible MLS
B
resistance when cloned into
Staphylococcus aureus
. The
erm
(45)-containing island was integrated into the housekeeping gene
guaA
in
S. fleurettii
and was able to form a circular intermediate but was not transmissible to
S. aureus
.
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

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

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

TheEscherichia 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

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

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

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

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

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

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

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

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

To 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.
Acupuncture-Induced Haemothorax: A Rare Iatrogenic Complication of Acupuncture
Authors: Karavis Miltiades Y , Argyra Erifili , Segredos Venieris , Yiallouroy Aneza , Giokas Georgios , Theodosopoulos Thedosios
Published: March 2015

This paper reports a rare iatrogenic complication of acupuncture-induced haemothorax and comments on the importance and need for special education of physicians and physiotherapists in order to apply safe and effective acupuncture treatment. A 37-year-old healthy woman had a session of acupuncture treatments for neck and right upper thoracic non-specific musculoskeletal pain, after which she gradually developed dyspnoea and chest discomfort. After some delay while trying other treatment, she was eventually transferred to the emergency department where a chest X-ray revealed a right pneumothorax and fluid collection. She was admitted to hospital and a chest tube inserted into the right hemithorax (under ultrasound guidance) drained 800 mL of bloody fluid (haematocrit (Hct) 17.8%) in 24 h and 1200 mL over the following 3 days. Her blood Hct fell from 39.0% to 30.8% and haemoglobin from 12.7 to 10.3 g/dL. The patient recovered completely and was discharged after 9 days of hospitalisation. When dyspnoea, chest pain and discomfort occur during or after an acupuncture treatment, the possibility of secondary (traumatic) pneumo- or haemopneumothorax should be considered and the patient should remain under careful observation (watchful waiting) for at least 48 h. To maximise the safety of acupuncture, specific training should be given for the safe use of acupuncture points of the anterior and posterior thoracic wall using dry needling, trigger point acupuncture or other advanced acupuncture techniques.
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

Aims

Acetone 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).

Methods

320 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.

Results

LN 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.

Conclusions

AC 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 purpose

Endovascular recanalization in ischemic stroke is often performed under general anesthesia. Some studies have shown a detrimental effect of general anesthesia. The reasons are unknown.

Methods

This 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).

Results

In 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.

Conclusions

In 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.
Chrysanthemum Promotes Adipocyte Differentiation, Adiponectin Secretion and Glucose Uptake
Authors: Yamamoto Junpei , Yamane Takumi , Oishi Yuichi , Shimizu Makoto , Tadaishi Miki , Kobayashi-Hattori Kazuo
Published: March 2015

The adipose tissue is an endocrine organ, and its endocrine function is closely related to type 2 diabetes. Edible Chrysanthemum morifolium Ramat. (ECM) possesses several biological properties; however, its effect on adipocytes remains unclear. We investigated the effect of the hot water extract of ECM (HW-ECM) on 3T3-L1 adipocytes. HW-ECM enhanced adipocyte differentiation, adiponectin secretion, and glucose uptake in 3T3-L1 cells. It also increased the mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ), a regulator of adipocyte differentiation, adiponectin transcription, and GLUT4 expression. In addition, HW-ECM increased the mRNA levels of CCAAT/enhancer-binding protein-delta (C/EBPδ), which induces PPARγ expression, but not C/EBPβ, during early adipocyte differentiation. These results suggest that HW-ECM enhances adipocyte differentiation, adiponectin secretion, and glucose uptake through C/EBPδ-induced PPARγ expression. These effects of HW-ECM on adipocytes suggest that HW-ECM is potentially beneficial for type 2 diabetes.
Kaempferol Induces DNA Damage and Inhibits DNA Repair Associated Protein Expressions in Human Promyelocytic Leukemia HL-60 Cells
Authors: Wu Lung-Yuan , Lu Hsu-Feng , Chou Yu-Cheng , Shih Yung-Luen , Bau Da-Tian , Chen Jaw-Chyun , Hsu Shu-Chun , Chung Jing-Gung
Published: March 2015

Numerous evidences have shown that plant flavonoids (naturally occurring substances) have been reported to have chemopreventive activities and protect against experimental carcinogenesis. Kaempferol, one of the flavonoids, is widely distributed in fruits and vegetables, and may have cancer chemopreventive properties. However, the precise underlying mechanism regarding induced DNA damage and suppressed DNA repair system are poorly understood. In this study, we investigated whether kaempferol induced DNA damage and affected DNA repair associated protein expression in human leukemia HL-60 cells in vitro. Percentages of viable cells were measured via a flow cytometry assay. DNA damage was examined by Comet assay and DAPI staining. DNA fragmentation (ladder) was examined by DNA gel electrophoresis. The changes of protein levels associated with DNA repair were examined by Western blotting. Results showed that kaempferol dose-dependently decreased the viable cells. Comet assay indicated that kaempferol induced DNA damage (Comet tail) in a dose-dependent manner and DAPI staining also showed increased doses of kaempferol which led to increased DNA condensation, these effects are all of dose-dependent manners. Western blotting indicated that kaempferol-decreased protein expression associated with DNA repair system, such as phosphate-ataxia-telangiectasia mutated (p-ATM), phosphate-ataxia-telangiectasia and Rad3-related (p-ATR), 14-3-3 proteins sigma (14-3-3σ), DNA-dependent serine/threonine protein kinase (DNA-PK), O6-methylguanine-DNA methyltransferase (MGMT), p53 and MDC1 protein expressions, but increased the protein expression of p-p53 and p-H2AX. Protein translocation was examined by confocal laser microscopy, and we found that kaempferol increased the levels of p-H2AX and p-p53 in HL-60 cells. Taken together, in the present study, we found that kaempferol induced DNA damage and suppressed DNA repair and inhibited DNA repair associated protein expression in HL-60 cells, which may be the factors for kaempferol induced cell death in vitro.
Nonlinear Vibration of Nonlocal Piezoelectric Nanoplates
Authors: Liu Chen , Ke Liao-Liang , Wang Yue-Sheng , Yang Jie
Published: March 2015

This paper presents an analytical study on the nonlinear vibration of rectangular piezoelectric nanoplates resting on the Winkler foundation. The piezoelectric nanoplate is assumed to be simply supported on all four edges and is subjected to an external electric voltage and a uniform temperature rise. Based on von Karman nonlinear strain–displacement relations and the nonlocal constitutive relations, the nonlinear governing equations and corresponding boundary conditions are derived by employing Hamilton's principle. The Galerkin method is used to obtain the nonlinear ordinary equation, which is then solved by the direct integration method. An extensive parametric study is conducted to examine the effects of the nonlocal parameter, external electric voltage, temperature rise and Winkler parameter on the nonlinear vibration characteristics of piezoelectric nanoplates.
Generalized Differential Transform Method for Solving Discrete Complex Cubic Ginzburg–Landau Equation
Authors: Aminikhah H. , Dehghan P.
Published: March 2015

In this paper, generalized differential transform method (GDTM) is applied to solve discrete complex cubic Ginzburg–Landau (DCCGL) equation which is a famous nonlinear difference-differential equation (NDDE). GDTM approximate solutions for various discrete soliton solutions of DCCGL such as discrete bright soliton, discrete dark soliton, and discrete alternating soliton are obtained. Also this method is successfully employed to obtain approximate solution for dark solitary wave solution of integrable discrete nonlinear Schrödinger (IDNS) equation. Numerical results compared with their corresponding numerical and analytical solutions to show the efficiency and high accuracy of the considered method.
Effects of heme modification on oxygen affinity and cooperativity of human adult hemoglobin
Authors: Shibata Tomokazu , Furuichi Eisuke , Imai Kiyohiro , Suzuki Akihiro , Yamamoto Yasuhiko
Published: March 2015

We substituted strongly electron-withdrawing trifluoromethyl ( CF3) group(s) as heme side chain(s) of human adult hemoglobin (Hb) to achieve large alterations of the heme electronic structure, in order to elucidate the relationship between the oxygen ( O2) binding properties of Hb and the electronic properties of heme peripheral side chains. The obtained results were compared with those of similar studies performed on myoglobin (Mb), e.g. (Nishimura R, Matsumoto D, Shibata T, Yanagisawa S, Ogura T, Tai H, Matsuo T, Hirota S, Neya S, Suzuki A, and Yamamoto Y. Inorg. Chem. 2014; 53: 9156–9165). These two proteins shared the common feature of a decrease in O2affinity upon the CF3substitution(s). Using the P50value, which is the partial pressure of O2required for 50% oxygenation of a protein, and the equilibrium constant ( p Ka) of the "acid-alkaline transition" in the met form of a protein as measures of the O2affinity and the electron density of heme Fe atom of the protein, respectively, a linear p Ka- log (1/P50) relationship was demonstrated for the Hb and Mb systems. The native Hb, however, deviated from the p Ka- log (1/P50) relationship, while the native Mb followed it. These results highlighted the significance of the vinyl side chains of the heme cofactor in the functional control of Hb through tertiary and quaternary structural changes upon the oxygenation of the protein.
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。
China's Asian Infrastructure Investment Bank: East Asian Responses
Authors: LAM Peng Er
Published: March 2015

Beijing's Asian Infrastructure Investment Bank appears to be a “game changer” in the political economy of East Asia. In an era when the US superpower and Japan are facing fiscal problems, China has ample funds to woo Asian states seeking economic development. Notwithstanding its maritime disputes in the South China Sea with some ASEAN states, Beijing has offered the carrot of development as a means to serve its geopolitical ends.
Digital Signal Processing Using Stream High Performance Computing
Authors: Kocz J. , Greenhill L. J. , Barsdell B. R. , Price D. , Bernardi G. , Bourke S. , Clark M. A. , Craig J. , Dexter M. , Dowell J. , Eftekhari T. , Ellingson S. , Hallinan G. , Hartman J. , Jameson A. , MacMahon D. , Taylor G. , Schinzel F. , Werthimer D.
Published: March 2015

A “large-N” correlator that makes use of Field Programmable Gate Arrays and Graphics Processing Units has been deployed as the digital signal processing system for the Long Wavelength Array station at Owens Valley Radio Observatory (LWA-OV), to enable the Large Aperture Experiment to Detect the Dark Ages (LEDA). The system samples a [Formula: see text][Formula: see text]MHz baseband and processes signals from 512 antennas (256 dual polarization) over a [Formula: see text][Formula: see text]MHz instantaneous sub-band, achieving 16.8[Formula: see text]Tops[Formula: see text]s[Formula: see text] and 0.236 Tbit[Formula: see text]s[Formula: see text] throughput in a 9[Formula: see text]kW envelope and single rack footprint. The output data rate is 260 MB[Formula: see text]s[Formula: see text] for 9-s time averaging of cross-power and 1[Formula: see text]s averaging of total power data. At deployment, the LWA-OV correlator was the largest in production in terms of N and is the third largest in terms of complex multiply accumulations, after the Very Large Array and Atacama Large Millimeter Array. The correlator’s comparatively fast development time and low cost establish a practical foundation for the scalability of a modular, heterogeneous, computing architecture.
"Universal" vitrification of cells by ultra-fast cooling
Authors: Heo Yun Seok , Nagrath Sunitha , Moore Alessandra L. , Zeinali Mahnaz , Irimia Daniel , Stott Shannon L. , Toth Thomas L. , Toner Mehmet
Published: March 2015

Long-term preservation of live cells is critical for a broad range of clinical and research applications. With the increasing diversity of cells that need to be preserved (e.g. oocytes, stem and other primary cells, genetically modified cells), careful optimization of preservation protocols becomes tedious and poses significant limitations for all but the most expert users. To address the challenge of long-term storage of critical, heterogeneous cell types, we propose a universal protocol for cell vitrification that is independent of cell phenotype and uses only low concentrations of cryoprotectant (1.5 M PROH and 0.5 M trehalose). We employed industrial grade microcapillaries made of highly conductive fused silica, which are commonly used for analytical chemistry applications. The minimal mass and thermal inertia of the microcapillaries enabled us to achieve ultrafast cooling rates up to 4,000 K/s. Using the same low, non-toxic concentration of cryoprotectant, we demonstrate high recovery and viability rates after vitrification for human mammary epithelial cells, rat hepatocytes, tumor cells from pleural effusions, and multiple cancer cell lines.
Regulatory hypothesis and bank dividend payouts: Empirical evidence from Italian banking sector
Authors: Ashraf Badar Nadeem , Arshad Sidra , Rahman Mohammad Morshedur , Kamal Muhammad Abdul , Khan Khalid
Published: March 2015

This study examines the regulatory hypothesis for bank dividend payouts using a panel dataset of 229 Italian banks over the period 2005–2012. Regulatory hypothesis suggests that undercapitalized banks face more regulatory pressure for increasing capital levels by paying lower amount of dividends. Empirical results support the regulatory hypothesis by finding that the Italian banks having lower equity to total assets ratios or lower regulatory capital ratios retain more profits and pay lower amount of dividends. Results also suggest that dividend payer banks try to maintain dividends at previous level by not skipping or reducing dividends. Results further support that Fama and French (2001)'s three characteristics of dividend payers are also applicable to banks. That is, big-in-size, more profitable and low growth Italian banks pay higher amount of dividends. Findings of this study have important implications for recent regulatory proposals that suggest a direct regulation of dividends. A direct regulation of dividends, on one hand, and regulatory pressure on dividend payout decisions through capital requirements, on the other hand, may have unintended consequences for dividends as signaling and agency cost reducing tools.
Special Issue on Foundations of Social Computing
Authors: Kourtellis Nicolas , Blackburn Jeremy , Borcea Cristian , Iamnitchi Adriana
Published: March 2015

An unprecedented information wealth produced by online social networks, further augmented by location/collocation data, is currently fragmented across different proprietary services. Combined, it can accurately represent the social world and enable novel socially aware applications. We present Prometheus, a socially aware peer-to-peer service that collects social information from multiple sources into a multigraph managed in a decentralized fashion on user-contributed nodes, and exposes it through an interface implementing nontrivial social inferences while complying with user-defined access policies. Simulations and experiments on PlanetLab with emulated application workloads show the system exhibits good end-to-end response time, low communication overhead, and resilience to malicious attacks.
Integrated Intrusion Detection and Tolerance in Homogeneous Clustered Sensor Networks
Authors: Al-Hamadi Hamid , Chen Ing Ray
Published: March 2015

In this article, we propose and analyze dynamic redundancy management of integrated intrusion detection and tolerance for lifetime maximization of homogeneous clustered wireless sensor networks (WSNs). We take a holistic approach of integrating multisource and multipath routing for intrusion tolerance with majority voting for intrusion detection in our redundancy management protocol design. By dynamically controlling the redundancy level for both multisource multipath routing and voting-based intrusion detection with energy consideration, we identify the optimal redundancy level to be applied to maximize the WSN lifetime in response to changing environment conditions including node density, radio range, and node capture rate. We demonstrate the effectiveness of our integrated redundancy management protocol by a comparative analysis with a multisource multipath routing algorithm called AFTQC that considers only fault/intrusion tolerance.
Prevalence and Associated Factors of Nonexclusive Breastfeeding to Infants within the First 6 Months in Gondar Town, Northwest Ethiopia, 2014
Authors: Berhanu Mengistu , Zemene Workie , Mekonnen Mengistu
Published: March 2015

Introduction. Nonexclusive breastfeeding (NEBF) is giving infants other foods or fluids in addition to the breast milk within the first six months of age. According to Ethiopian Demographic and Health Survey 2011, prevalence of NEBF was found to be 48%; this has a great impact on the health and development of the child.Objectives. To assess the prevalence and associated factors of NEBF to infants within the first six months.Methods. Community based cross-sectional study design was employed from March 1 to 31, 2014, among 828 mothers with infants 6 to 12 months old. Systematic random sampling technique was used to select study subjects. Logistic regression analysis with 95% CI was computed to identify predictor variables.Result. A total of 828 mothers with infants aged between 6 and 12 months were interviewed with 100% response rate. Prevalence of NEBF was 47.5%. Mothers who completed primary school (AOR=0.46[95% CI: 0.30, 0.71]) were less likely practicing NEBF compared to mothers with no formal education. Governmental employees (AOR=2.55[95% CI: 1.45, 4.46]) were more likely practicing NEBF.Conclusion. NEBF was practiced by 47% of mothers. Maternal educational status, occupation, and knowledge of initiation of complementary feeding were factors significantly associated with NEBF.
A Multisource Heterogeneous Data Fusion Method for Pedestrian Tracking
Authors: Shi Zhenlian , Sun Yanfeng , Xiong Linxin , Hu Yongli , Yin Baocai
Published: March 2015

Traditional visual pedestrian tracking methods perform poorly when faced with problems such as occlusion, illumination changes, and complex backgrounds. In principle, collecting more sensing information should resolve these issues. However, it is extremely challenging to properly fuse different sensing information to achieve accurate tracking results. In this study, we develop a pedestrian tracking method for fusing multisource heterogeneous sensing information, including video, RGB-D sequences, and inertial sensor data. In our method, a RGB-D sequence is used to position the target locally by fusing the texture and depth features. The local position is then used to eliminate the cumulative error resulting from the inertial sensor positioning. A camera calibration process is used to map the inertial sensor position onto the video image plane, where the visual tracking position and the mapped position are fused using a similarity feature to obtain accurate tracking results. Experiments using real scenarios show that the developed method outperforms the existing tracking method, which uses only a single sensing dataset, and is robust to target occlusion, illumination changes, and interference from similar textures or complex backgrounds.
Vascular Effects of Advanced Glycation End-Products: Content of Immunohistochemically Detected AGEs in Radial Artery Samples as a Predictor for Arterial Calcification and Cardiovascular Risk in Asymptomatic Patients with Chronic Kidney Disease
Authors: Janda Katarzyna , Krzanowski Marcin , Gajda Mariusz , Dumnicka Paulina , Jasek Ewa , Fedak Danuta , Pietrzycka Agata , Kuźniewski Marek , Litwin Jan A. , Sułowicz Władysław
Published: March 2015

Objectives.Our aim was to determine whether vascular deposition of advanced glycation end-products (AGEs) is associated with arterial calcification and cardiovascular mortality in chronic kidney disease (CKD) patients and to assess the relationships between vascular content of AGEs and selected clinical and biochemical parameters.Materials and Methods.The study comprised 54 CKD patients (33 hemodialyzed, 21 predialyzed). Examined parameters included BMI, incidence of diabetes, plasma fasting glucose, AGEs, soluble receptor for AGEs and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, serum C-reactive protein (hsCRP), plasminogen activator inhibitor-1 (PAI-1), and fetuin-A. Fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications using alizarin red. AGEs deposits were identified immunohistochemically and their relative content was quantified.Results.Vascular content of AGEs was positively correlated with BMI, hsCRP, fetuin-A, PAI-1, and DPPH scavenging in simple regression; only fetuin-A was an independent predictor in multiple regression. There was a significant positive trend in the intensity of AGEs immunostaining among patients with grades 1, 2, and 3 calcifications. AGEs immunostaining intensity predicted 3-year cardiovascular mortality irrespective of patient’s age.Conclusions.The present study demonstrates an involvement of AGEs in the development of medial arterial calcification and the impact of arterial AGE deposition on cardiovascular mortality in CKD patients.
Treatment for Retinopathy of Prematurity in an Infant with Adenoviral Conjunctivitis
Authors: Gunay Murat , Celik Gokhan , Con Rahim
Published: March 2015

Retinopathy of prematurity (ROP) has been a major problematic disorder during childhood. Laser photocoagulation (LPC) has been proven to be effective in most of the ROP cases. Adenoviral conjunctivitis (AVC) is responsible for epidemics among adult and pediatric population. It has also been reported to be a cause of outbreaks in neonatal intensive care units (NICU) several times. We herein demonstrate a case with AVC who underwent LPC for ROP. And we discuss the treatment methodology in such cases.