bluuebunny/crossref_metadata_2025 huggingface dataset:
Active Stabilization of Multistage Axial-Compressor Aerodynamic System Instabilities
Authors: Hosny W. M. , Leventhal L. , Steenken W. G.
Published: March 2015

Active control of multistage axial-compressor aerodynamic instabilities has been studied analytically using a blade-row by blade-row compression system model. The instabilities considered are those which result from a global system instability. The control approach taken is to suppress the instability by actively changing the system damping characteristics. This was accomplished by varying dynamically the compressor stage characteristics to extend the region of the compression system operation. Specifically, the stator row of a compressor stage is actively dithered based on its inlet or exit pressure fluctuation measurement such that the stage characteristics are modified in such a way to improve the overall system stability.

The analytical model and the results of the stator dither study are presented in this paper. The results indicated a slight gain in the compressor stability limit line when the compressor stages are well matched. With increased interstage bleed, resulting in a mismatch between the front and the rear blocks of the compressor, the stabilization results indicated a significant gain in the stability limit line. In addition, the stator selection studies showed the importance of locating the active action near to and upstream of the stage where the system instability initiates.
Modeling flow-induced crystallization in isotactic polypropylene at high shear rates
Authors: Roozemond Peter C. , van Drongelen Martin , Ma Zhe , Hulsen Martien A. , Peters Gerrit W. M.
Published: March 2015

A model is presented to describe flow-induced crystallization in isotactic polypropylene at high shear rates. This model incorporates nonlinear viscoelasticity, compressibility, and nonisothermal process conditions due to shear heating and heat release due to crystallization. Flow-induced nucleation occurs with a rate coupled to the chain backbone stretch associated with the longest mode relaxation time of the polymer melt, obtained from a viscoelastic constitutive model. Flow-induced nuclei propagate in flow direction with a speed related to shear rate, thus forming shish, which increase the viscosity of the material. The viscosity change with formation of oriented fibrillar crystals (known as “shish”) is implemented in a phenomenological manner; shish act as a suspension of fibers with radius equivalent to the radius of the shish plus the attached entangled molecules? The model is implemented in a 2D finite element code and validated with experimental data obtained in a channel flow geometry. Quantitative agreement is observed in terms of pressure drop, apparent crystallinity, parent/daughter ratio, Hermans' orientation, and shear layer thickness. Moreover, simulations for lower flow rates are performed and the results are compared, in a qualitative sense, to experiments from literature.
Relationships Between Propulsion and Anthropometry in Paralympic Swimmers
Authors: Dingley Andrew A. , Pyne David B. , Burkett Brendan
Published: March 2015

Purpose:

To characterize relationships between propulsion, anthropometry, and performance in Paralympic swimming.

Methods:

A cross-sectional study of swimmers (13 male, 15 female) age 20.5 ± 4.4 y was conducted. Subject locomotor categorizations were no physical disability (n = 8, classes S13–S14) and low-severity (n = 11, classes S9–S10) or midseverity disability (n = 9, classes S6–S8). Full anthropometric profiles estimated muscle mass and body fat, a bilateral swim-bench ergometer quantified upper-body power production, and 100-m time trials quantified swimming performance.

Results:

Correlations between ergometer mean power and swimming performance increased with degree of physical disability (low-severity male r = .65, ±0.56, and female r = .68, ±0.64; midseverity, r = .87, ±0.41, and r = .79, ±0.75). The female midseverity group showed nearperfect (positive) relationships for taller swimmers’ (with a greater muscle mass and longer arm span) swimming faster, while for female no- and low-severity-disability groups, greater muscle mass was associated with slower velocity (r = .78, ±0.43, and r = .65, ±0.66). This was supported with lighter females (with less frontal surface area) in the low-severity group being faster (r = .94, ±0.24). In a gender contrast, low-severity males with less muscle mass (r = -.64, ±0.56), high skinfolds (r = .78, ±0.43), a longer arm span (r = .58, ±0.60) or smaller frontal surface area (r = -.93, ±0.19) were detrimental to swimming-velocity production.

Conclusion:

Low-severity male and midseverity female Paralympic swimmers should be encouraged to develop muscle mass and upper-body power to enhance swimming performance. The generalized anthropometric measures appear to be a secondary consideration for coaches.
Variability of PlayerLoad, Bowling Velocity, and Performance Execution in Fast Bowlers Across Repeated Bowling Spells
Authors: McNamara Dean J. , Gabbett Tim J. , Chapman Paul , Naughton Geraldine , Farhart Patrick
Published: March 2015

Purpose:

The use of wearable microtechnology to monitor the external load of fast bowling is challenged by the inherent variability of bowling techniques between bowlers. This study assessed the between-bowlers variability in PlayerLoad, bowling velocity, and performance execution across repeated bowling spells.

Methods:

Seven national-level fast bowlers completed two 6-over bowling spells at a batter during a competitive training session. Key dependent variables were PlayerLoad calculated with a MinimaxX microtechnology unit, ball velocity, and bowling execution based on a predetermined bowling strategy for each ball bowled. The between-bowlers coefficient of variation (CV), repeated-measures ANOVA, and smallest worthwhile change were calculated over the 2 repeated 6-over bowling spells and explored across 12-over, 6-over, and 3-over bowling segments.

Results:

From the sum of 6 consecutive balls, the between-bowlers CV for relative peak PlayerLoad was 1.2% over the 12-over bowling spell (P = .15). During this 12-over period, bowling-execution (P = .43) scores and ball-velocity (P = .31) CVs were calculated as 46.0% and 0.4%, respectively.

Conclusions:

PlayerLoad was found to be stable across the repeated bowling spells in the fast-bowling cohort. Measures of variability and change across the repeated bowling spells were consistent with the performance measure of ball velocity. The stability of PlayerLoad improved when assessed relative to the individual’s peak PlayerLoad. Only bowling-execution measures were found to have high variability across the repeated bowling spells. PlayerLoad provides a stable measure of external workload between fast bowlers.
Threats to Internal Validity in Exercise Science: A Review of Overlooked Confounding Variables
Authors: Halperin Israel , Pyne David B. , Martin David T.
Published: March 2015

Internal validity refers to the degree of control exerted over potential confounding variables to reduce alternative explanations for the effects of various treatments. In exercise and sports-science research and routine testing, internal validity is commonly achieved by controlling variables such as exercise and warm-up protocols, prior training, nutritional intake before testing, ambient temperature, time of testing, hours of sleep, age, and gender. However, a number of other potential confounding variables often do not receive adequate attention in sports physiology and performance research. These confounding variables include instructions on how to perform the test, volume and frequency of verbal encouragement, knowledge of exercise endpoint, number and gender of observers in the room, influence of music played before and during testing, and the effects of mental fatigue on performance. In this review the authors discuss these variables in relation to common testing environments in exercise and sports science and present some recommendations with the goal of reducing possible threats to internal validity.
Toll receptors wire the olfactory circuit
Authors: Ferrarelli Leslie K.
Published: March 2015

Toll-family receptors Toll-6 and Toll-7 instruct neuron wiring specificity in the olfactory circuit in flies.
Complete Sequence of a
bla
KPC
-Harboring Cointegrate Plasmid Isolated from Escherichia coli
Authors: Chavda Kalyan D. , Chen Liang , Jacobs Michael R. , Rojtman Albert D. , Bonomo Robert A. , Kreiswirth Barry N.
Published: March 2015

Horizontal transfer of
bla
KPC
-harboring plasmids contributes significantly to the inter- and intraspecies spread of
Klebsiella pneumoniae
carbapenemase (KPC). Here we report the complete nucleotide sequence of a
bla
KPC
-harboring IncFIA plasmid, pBK32533, from
Escherichia coli
. pBK32533 is a cointegrate plasmid comprising of a 72-kb sequence identical to that of the nonconjugative pBK30661 plasmid plus an additional 170-kb element that harbors the genes for plasmid transfer. pBK32533 demonstrates how
bla
KPC
can be spread from a nonconjugative plasmid through cointegration.
β-Lactams Enhance Daptomycin Activity against Vancomycin-Resistant Enterococcus faecalis and Enterococcus faecium in
In Vitro
Pharmacokinetic/Pharmacodynamic Models
Authors: Smith Jordan R. , Barber Katie E. , Raut Animesh , Rybak Michael J.
Published: March 2015

Enterococcus faecalis
and
Enterococcus faecium
are frequently resistant to vancomycin and β-lactams. In enterococcal infections with reduced glycopeptide susceptibility, combination therapy is often administered. Our objective was to conduct pharmacokinetic/pharmacodynamic (PK/PD) models to evaluate β-lactam synergy with daptomycin (DAP) against resistant enterococci. One
E. faecalis
strain (R6981) and two
E. faecium
strains (R6370 and 8019) were evaluated. DAP MICs were obtained. All strains were evaluated for response to LL37, an antimicrobial peptide, in the presence and absence of ceftaroline (CPT), ertapenem (ERT), and ampicillin (AMP). After 96 h,
in vitro
models were run simulating 10 mg DAP/kg body weight/day, 600 mg CPT every 8 h (q8h), 2 g AMP q4h, and 1 g ERT q24h, both alone and in combination against all strains. DAP MICs were 2, 4, and 4 μg/ml for strains R6981, R6370, and 8019, respectively. PK/PD models demonstrated bactericidal activity with DAP-CPT, DAP-AMP, and DAP-ERT combinations against strain 8019 (
P
< 0.001 and log
10
CFU/ml reduction of >2 compared to any single agent). Against strains R6981 and R6370, the DAP-AMP combination demonstrated enhancement against R6370 but not R6981, while the combinations of DAP-CPT and DAP-ERT were bactericidal, demonstrated enhancement, and were statistically superior to all other regimens at 96 h (
P
< 0.001) against both strains. CPT, ERT, and AMP similarly augmented LL37 killing against strain 8019. In strains R6981 and R6370, CPT and ERT aided LL37 more than AMP (
P
< 0.001). Compared to DAP alone, combination regimens provide better killing and prevent resistance. Clinical research involving DAP combinations is warranted.
A Putative Cro-Like Repressor Contributes to Arylomycin Resistance in Staphylococcus aureus
Authors: Craney Arryn , Romesberg Floyd E.
Published: March 2015

Antibiotic-resistant bacteria are a significant public health concern and motivate efforts to develop new classes of antibiotics. One such class of antibiotics is the arylomycins, which target type I signal peptidase (SPase), the enzyme responsible for the release of secreted proteins from their N-terminal leader sequences. Despite the essentiality, conservation, and relative accessibility of SPase, the activity of the arylomycins is limited against some bacteria, including the important human pathogen
Staphylococcus aureus
. To understand the origins of the limited activity against
S. aureus
, we characterized the susceptibility of a panel of strains to two arylomycin derivatives, arylomycin A-C
16
and its more potent analog arylomycin M131. We observed a wide range of susceptibilities to the two arylomycins and found that resistant strains were sensitized by cotreatment with tunicamycin, which inhibits the first step of wall teichoic acid synthesis. To further understand how
S. aureus
responds to the arylomycins, we profiled the transcriptional response of
S. aureus
NCTC 8325 to growth-inhibitory concentrations of arylomycin M131 and found that it upregulates the cell wall stress stimulon (CWSS) and an operon consisting of a putative transcriptional regulator and three hypothetical proteins. Interestingly, we found that mutations in the putative transcriptional regulator are correlated with resistance, and selection for resistance
ex vivo
demonstrated that mutations in this gene are sufficient for resistance. The results begin to elucidate how
S. aureus
copes with secretion stress and how it evolves resistance to the inhibition of SPase.
Fungal β-1,3-Glucan Increases Ofloxacin Tolerance of Escherichia coli in a Polymicrobial E. coli/Candida albicans Biofilm
Authors: De Brucker Katrijn , Tan Yulong , Vints Katlijn , De Cremer Kaat , Braem Annabel , Verstraeten Natalie , Michiels Jan , Vleugels Jef , Cammue Bruno P. A. , Thevissen Karin
Published: March 2015

In the past, biofilm-related research has focused mainly on axenic biofilms. However, in nature, biofilms are often composed of multiple species, and the resulting polymicrobial interactions influence industrially and clinically relevant outcomes such as performance and drug resistance. In this study, we show that
Escherichia coli
does not affect
Candida albicans
tolerance to amphotericin or caspofungin in an
E. coli/C. albicans
biofilm. In contrast, ofloxacin tolerance of
E. coli
is significantly increased in a polymicrobial
E. coli
/
C. albicans
biofilm compared to its tolerance in an axenic
E. coli
biofilm. The increased ofloxacin tolerance of
E. coli
is mainly biofilm specific, as ofloxacin tolerance of
E. coli
is less pronounced in polymicrobial
E. coli/C. albicans
planktonic cultures. Moreover, we found that ofloxacin tolerance of
E. coli
decreased significantly when
E. coli/C. albicans
biofilms were treated with matrix-degrading enzymes such as the β-1,3-glucan-degrading enzyme lyticase. In line with a role for β-1,3-glucan in mediating ofloxacin tolerance of
E. coli
in a biofilm, we found that ofloxacin tolerance of
E. coli
increased even more in
E. coli/C. albicans
biofilms consisting of a high-β-1,3-glucan-producing
C. albicans
mutant. In addition, exogenous addition of laminarin, a polysaccharide composed mainly of poly-β-1,3-glucan, to an
E. coli
biofilm also resulted in increased ofloxacin tolerance. All these data indicate that β-1,3-glucan from
C. albicans
increases ofloxacin tolerance of
E. coli
in an
E. coli/C. albicans
biofilm.
Complete Nucleotide Sequences of
bla
CTX-M
-Harboring IncF Plasmids from Community-Associated Escherichia coli Strains in the United States
Authors: Li Jun-Jie , Spychala Caressa N. , Hu Fupin , Sheng Ji-Fang , Doi Yohei
Published: March 2015

Community-associated infections due to
Escherichia coli
producing CTX-M-type extended-spectrum β-lactamases are increasingly recognized in the United States. The
bla
CTX-M
genes are frequently carried on IncF group plasmids. In this study,
bla
CTX-M-15
-harboring plasmids pCA14 (sequence type 131 [ST131]) and pCA28 (ST44) and
bla
CTX-M-14
-harboring plasmid pCA08 (ST131) were sequenced and characterized. The three plasmids were closely related to other IncFII plasmids from continents outside the United States in the conserved backbone region and multiresistance regions (MRRs). Each of the
bla
CTX-M-15
-carrying plasmids pCA14 and pCA28 belonged to F31:A4:B1 (FAB [FII, FIA, FIB] formula) and showed a high level of similarity (92% coverage of pCA14 and 99% to 100% nucleotide identity), suggesting a possible common origin. The
bla
CTX-M-14
-carrying plasmid pCA08 belonged to F2:A2:B20 and was highly similar to pKF3-140 from China (88% coverage of pCA08 and 99% to 100% nucleotide identity). All three plasmids carried multiple antimicrobial resistance genes and modules associated with virulence and biochemical pathways, which likely confer selective advantages for their host strains. The
bla
CTX-M
-carrying IncFII-IA-IB plasmids implicated in community-associated infections in the United States shared key structural features with those identified from other continents, underscoring the global nature of this plasmid epidemic.
Efficacy of the Investigational Echinocandin ASP9726 in a Guinea Pig Model of Invasive Pulmonary Aspergillosis
Authors: Wiederhold Nathan P. , Najvar Laura K. , Matsumoto Satoru , Bocanegra Rosie A. , Herrera Monica L. , Wickes Brian L. , Kirkpatrick William R. , Patterson Thomas F.
Published: March 2015

ASP9726 is an investigational echinocandin with
in vitro
activity against
Aspergillus
species. We evaluated the pharmacokinetics and efficacy of this agent in an established guinea pig model of invasive pulmonary aspergillosis. ASP9726 plasma concentrations were measured in guinea pigs administered either a single dose or multiple doses of this agent at 2.5, 5, and 10 mg/kg of body weight/day by subcutaneous injection. Immunosuppressed guinea pigs were inoculated with
A. fumigatus
AF293, and ASP9726 (2.5, 5, and 10 mg/kg/day), voriconazole (10 mg/kg by oral gavage twice daily), or caspofungin (3 mg/kg/day by intraperitoneal injection) was administered for 8 days. Changes in fungal burden were measured by enumerating CFU and by quantitative PCR of specimens from within the lungs, as well as by analysis of serum (1→3)-β-
d
-glucan and galactomannan. Lung histopathology was also evaluated. ASP9726 plasma concentrations increased in a dose-proportional manner, and the drug was well tolerated at each dose. Each dose of ASP9726, voriconazole, and caspofungin significantly reduced pulmonary fungal burden as measured by quantitative PCR and by determining (1→3)-β-
d
-glucan and galactomannan levels, but only voriconazole significantly reduced numbers of CFU. ASP9726 at 5 mg/kg also significantly improved survival. Histopathology demonstrated morphological changes in hyphae in animals exposed to ASP9726 and caspofungin, consistent with the activities of the echinocandins. These results suggest that ASP9726 may be efficacious for the treatment of invasive pulmonary aspergillosis.
Potential of Novel Antimicrobial Peptide P3 from Bovine Erythrocytes and Its Analogs To Disrupt Bacterial Membranes
In Vitro
and Display Activity against Drug-Resistant Bacteria in a Mouse Model
Authors: Zhang Qinghua , Xu Yanzhao , Wang Qing , Hang Bolin , Sun Yawei , Wei Xiaoxiao , Hu Jianhe
Published: March 2015

With the emergence of many antibiotic-resistant strains worldwide, antimicrobial peptides (AMPs) are being evaluated as promising alternatives to conventional antibiotics. P3, a novel hemoglobin peptide derived from bovine erythrocytes, exhibited modest antimicrobial activity
in vitro
. We evaluated the antimicrobial activities of P3 and an analog, JH-3, both
in vitro
and
in vivo
. The MICs of P3 and JH-3 ranged from 3.125 μg/ml to 50 μg/ml when a wide spectrum of bacteria was tested, including multidrug-resistant strains. P3 killed bacteria within 30 min by disrupting the bacterial cytoplasmic membrane and disturbing the intracellular calcium balance. Circular dichroism (CD) spectrometry showed that P3 assumed an α-helical conformation in bacterial lipid membranes, which was indispensable for antimicrobial activity. Importantly, the 50% lethal dose (LD
50
) of JH-3 was 180 mg/kg of mouse body weight after intraperitoneal (i.p.) injection, and no death was observed at any dose up to 240 mg/kg body weight following subcutaneous (s.c.) injection. Furthermore, JH-3 significantly decreased the bacterial count and rescued infected mice in a model of mouse bacteremia. In conclusion, P3 and an analog exhibited potent antimicrobial activities and relatively low toxicities in a mouse model, indicating that they may be useful for treating infections caused by drug-resistant bacteria.
Photochemotherapeutic Strategy against Acanthamoeba Infections
Authors: Aqeel Yousuf , Siddiqui Ruqaiyyah , Anwar Ayaz , Shah Muhammad Raza , Khoja Shahrukh , Khan Naveed Ahmed
Published: March 2015

Acanthamoeba
is a protist pathogen that can cause serious human infections, including blinding keratitis and a granulomatous amoebic encephalitis that almost always results in death. The current treatment for these infections includes a mixture of drugs, and even then, a recurrence can occur. Photochemotherapy has shown promise in the treatment of
Acanthamoeba
infections; however, the selective targeting of pathogenic
Acanthamoeba
has remained a major concern. The mannose-binding protein is an important adhesin expressed on the surface membranes of pathogenic
Acanthamoeba
organisms. To specifically target
Acanthamoeba
, the overall aim of this study was to synthesize a photosensitizing compound (porphyrin) conjugated with mannose and test its efficacy
in vitro
. The synthesis of mannose-conjugated porphyrin was achieved by mixing benzaldehyde and pyrrole, yielding tetraphenylporphyrin. Tetraphenylporphyrin was then converted into mono-nitrophenylporphyrin by selectively nitrating the
para
position of the phenyl rings, as confirmed by nuclear magnetic resonance (NMR) spectroscopy. The mono-nitrophenylporphyrin was reduced to mono-aminophenylporphyrin in the presence of tin dichloride and confirmed by a peak at
m/z
629. Finally, mono-aminoporphyrin was conjugated with mannose, resulting in the formation of an imine bond. Mannose-conjugated porphyrin was confirmed through spectroscopic analysis and showed that it absorbed light of wavelengths ranging from 425 to 475 nm. To determine the antiacanthamoebic effects of the derived product, amoebae were incubated with mannose-conjugated porphyrin for 1 h and washed 3 times to remove extracellular compound. Next, the amoebae were exposed to light of the appropriate wavelength for 1 h. The results revealed that mannose-conjugated porphyrin produced potent trophicidal effects and blocked excystation. In contrast,
Acanthamoeba castellanii
incubated with mannose alone and porphyrin alone did not exhibit an antiamoebic effect. Consistently, pretreatment with mannose-conjugated porphyrin reduced the
A. castellanii
-mediated host cell cytotoxicity from 97% to 4.9%. In contrast, treatment with porphyrin, mannose, or solvent alone had no protective effects on the host cells. These data suggest that mannose-conjugated porphyrin has application for the targeted photodynamic therapy of
Acanthamoeba
infections and may serve as a model in the development of therapeutic interventions against other eukaryotic infections.
Trypanosoma cruzitrans-Sialidase Prevents Elicitation of Th1 Cell Response via Interleukin 10 and Downregulates Th1 Effector Cells
Authors: Ruiz Díaz Pablo , Mucci Juan , Meira María Ana , Bogliotti Yanina , Musikant Daniel , Leguizamón María Susana , Campetella Oscar
Published: March 2015

Thetrans-sialidases (TSs) fromTrypanosoma cruzi, the agent of Chagas disease, are virulence factors shed to the bloodstream that induce strong alterations in the immune system. Here, we report that both enzymatically active TS (aTS) and its lectinlike isoform (iTS) disturb CD4 T cell physiology, inducing downregulation of Th1 cell functionality andin vivocell expansion. By using ovalbumin-specific DO11.10 cells as tracers of clones developing the Th1 phenotype, we found that the infection induced significant amounts of gamma interferon (IFN-γ) but low levels of interleukin 2 (IL-2) and increased IL-4 productionin vivo, in agreement with a mixed T helper response. The production of cytokines associated with the Th2 phenotype was prevented by passive transfer of anti-TS neutralizing antibodies. TSs also reduced the T cell receptor signaling as assayed by Zap-70 phosphorylation. TSs also reduced IL-2 and IFN-γ secretion, with a concomitant increase in IL-4 production and then an unbalancing of the CD4 T cell response toward the Th2 phenotype. This effect was prevented by using anti-IL-10 neutralizing antibodies or IL-10−/−antigen-presenting cells, supporting the subversion of this regulatory pathway. In support, TSs stimulated IL-10 secretion by antigen-presenting cells during their interaction with CD4 T cells. When polarized cells were stimulated in the presence of TSs, the secretion of IL-2 and IFN-γ was strongly downregulated in Th1 cells, while IL-2 production was upregulated in Th2 cells. Although the Th1 response is associated with host survival, it may simultaneously induce extensive damage to infected tissues. Thus, by delaying the elicitation of the Th1 response and limiting its effector properties, TSs restrain the cell response, supportingT. cruzicolonization and persistence while favoring host survival.
Superantigenic Yersinia pseudotuberculosis Induces the Expression of Granzymes and Perforin by CD4+T Cells
Authors: Goubard Agathe , Loïez Caroline , Abe Jun , Fichel Caroline , Herwegh Stéphanie , Faveeuw Christelle , Porte Rémi , Cayet Delphine , Sebbane Florent , Penet Sylvie , Foligné Benoit , Desreumaux Pierre , Saito Hirohisa , Sirard Jean-Claude , Simonet Michel , Carnoy Christophe
Published: March 2015

Bacterial superantigens (SAgs) are immunostimulatory toxins that induce acute diseases mainly through the massive release of inflammatory cytokines.Yersinia pseudotuberculosisis the only Gram-negative bacterium known to produce a SAg (Y. pseudotuberculosis-derived mitogen [YPM]). This SAg binds major histocompatibility complex class II molecules on antigen-presenting cells and T cell receptors (TcR) bearing the variable region Vβ3, Vβ9, Vβ13.1, or Vβ13.2 (in humans) and Vβ7 or Vβ8 (in mice). We have previously shown that YPM exacerbates the virulence ofY. pseudotuberculosisin mice. With a view to understanding the mechanism of YPM's toxicity, we compared the immune response in BALB/c mice infected with a YPM-producingY. pseudotuberculosisor the corresponding isogenic, SAg-deficient mutant. Five days after infection, we observed strong CD4+Vβ7+T cell expansion and marked interleukin-4 (IL-4) production in mice inoculated with SAg-producingY. pseudotuberculosis. These phenomena were correlated with the activation ofypmgene transcription in liver and spleen. A transcriptomic analysis revealed that the presence of YPM also increased expression of granzyme and perforin genes in the host's liver and spleen. This expression was attributed to a CD4+T cell subset, rather than to natural killer T (NKT) cells that display a TcR with a Vβ region that is potentially recognized by YPM. Increased production of cytotoxic molecules was correlated with hepatotoxicity, as demonstrated by an increase in plasma alanine aminotransferase activity. Our results demonstrate that YPM activates a potentially hepatotoxic CD4+T cell population.
High-Throughput, Signature-Tagged Mutagenic Approach To Identify Novel Virulence Factors of Yersinia pestis CO92 in a Mouse Model of Infection
Authors: Ponnusamy Duraisamy , Fitts Eric C. , Sha Jian , Erova Tatiana E. , Kozlova Elena V. , Kirtley Michelle L. , Tiner Bethany L. , Andersson Jourdan A. , Chopra Ashok K.
Published: March 2015

The identification of new virulence factors in
Yersinia pestis
and understanding their molecular mechanisms during an infection process are necessary in designing a better vaccine or to formulate an appropriate therapeutic intervention. By using a high-throughput, signature-tagged mutagenic approach, we created 5,088 mutants of
Y. pestis
strain CO92 and screened them in a mouse model of pneumonic plague at a dose equivalent to 5 50% lethal doses (LD
50
) of wild-type (WT) CO92. From this screen, we obtained 118 clones showing impairment in disseminating to the spleen, based on hybridization of input versus output DNA from mutant pools with 53 unique signature tags. In the subsequent screen, 20/118 mutants exhibited attenuation at 8 LD
50
when tested in a mouse model of bubonic plague, with infection by 10/20 of the aforementioned mutants resulting in 40% or higher survival rates at an infectious dose of 40 LD
50
. Upon sequencing, six of the attenuated mutants were found to carry interruptions in genes encoding hypothetical proteins or proteins with putative functions. Mutants with in-frame deletion mutations of two of the genes identified from the screen, namely,
rbsA
, which codes for a putative sugar transport system ATP-binding protein, and
vasK
, a component of the type VI secretion system, were also found to exhibit some attenuation at 11 or 12 LD
50
in a mouse model of pneumonic plague. Likewise, among the remaining 18 signature-tagged mutants, 9 were also attenuated (40 to 100%) at 12 LD
50
in a pneumonic plague mouse model. Previously, we found that deleting genes encoding Braun lipoprotein (Lpp) and acyltransferase (MsbB), the latter of which modifies lipopolysaccharide function, reduced the virulence of
Y. pestis
CO92 in mouse models of bubonic and pneumonic plague. Deletion of
rbsA
and
vasK
genes from either the Δ
lpp
single or the Δ
lpp
Δ
msbB
double mutant augmented the attenuation to provide 90 to 100% survivability to mice in a pneumonic plague model at 20 to 50 LD
50
. The mice infected with the Δ
lpp
Δ
msbB
Δ
rbsA
triple mutant at 50 LD
50
were 90% protected upon subsequent challenge with 12 LD
50
of WT CO92, suggesting that this mutant or others carrying combinational deletions of genes identified through our screen could potentially be further tested and developed into a live attenuated plague vaccine(s).
Protein Energy Malnutrition during Vaccination Has Limited Influence on Vaccine Efficacy but Abolishes Immunity if Administered during Mycobacterium tuberculosis Infection
Authors: Hoang Truc , Agger Else Marie , Cassidy Joseph P. , Christensen Jan P. , Andersen Peter
Published: March 2015

Protein energy malnutrition (PEM) increases susceptibility to infectious diseases, including tuberculosis (TB), but it is not clear how PEM influences vaccine-promoted immunity to TB. We demonstrate that PEM during low-level steady-state TB infection in a mouse model results in rapid relapse of
Mycobacterium tuberculosis
, as well as increased pathology, in both
Mycobacterium bovis
BCG-vaccinated and unvaccinated animals. PEM did not change the overall numbers of CD4 T cells in BCG-vaccinated animals but resulted in an almost complete loss of antigen-specific cytokine production. Furthermore, there was a change in cytokine expression characterized by a gradual loss of multifunctional antigen-specific CD4 T cells and an increased proportion of effector cells expressing gamma interferon and tumor necrosis factor alpha (IFN-γ
+
TNF-α
+
and IFN-γ
+
cells). PEM during
M. tuberculosis
infection completely blocked the protection afforded by the H56-CAF01 subunit vaccine, and this was associated with a very substantial loss of the interleukin-2-positive memory CD4 T cells promoted by this vaccine. Similarly, PEM during the vaccination phase markedly reduced the H56-CAF01 vaccine response, influencing all cytokine-producing CD4 T cell subsets, with the exception of CD4 T cells positive for TNF-α only. Importantly, this impairment was reversible and resupplementation of protein during infection rescued both the vaccine-promoted T cell response and the protective effect of the vaccine against
M. tuberculosis
infection.
hfq
Plays Important Roles in Virulence and Stress Adaptation in Cronobacter sakazakii ATCC 29544
Authors: Kim Seongok , Hwang Hyelyeon , Kim Kwang-Pyo , Yoon Hyunjin , Kang Dong-Hyun , Ryu Sangryeol
Published: March 2015

Cronobacter
spp. are opportunistic pathogens that cause neonatal meningitis and sepsis with high mortality in neonates. Despite the peril associated with
Cronobacter
infection, the mechanisms of pathogenesis are still being unraveled. Hfq, which is known as an RNA chaperone, participates in the interaction with bacterial small RNAs (sRNAs) to regulate posttranscriptionally the expression of various genes. Recent studies have demonstrated that Hfq contributes to the pathogenesis of numerous species of bacteria, and its roles are varied between bacterial species. Here, we tried to elucidate the role of Hfq in
C. sakazakii
virulence. In the absence of
hfq
,
C. sakazakii
was highly attenuated in dissemination
in vivo
, showed defects in invasion (3-fold) into animal cells and survival (10
3
-fold) within host cells, and exhibited low resistance to hydrogen peroxide (10
2
-fold). Remarkably, the loss of
hfq
led to hypermotility on soft agar, which is contrary to what has been observed in other pathogenic bacteria. The hyperflagellated bacteria were likely to be attributable to the increased transcription of genes associated with flagellar biosynthesis in a strain lacking
hfq
. Together, these data strongly suggest that
hfq
plays important roles in the virulence of
C. sakazakii
by participating in the regulation of multiple genes.
Acute airway obstruction due to retropharyngeal haematoma caused by a large fish bone in a patient with hypertension caused by a pheochromocytoma
Authors: Wei Yan , Jahreiß Linda , Zhang Zhili , Albers Andreas E
Published: March 2015

Retropharyngeal haematoma (RH) is an extremely rare but potentially life-threatening condition that requires an early diagnosis and immediate management. Acute complications arise from compression and obstruction of the upper airway and oesophagus with the risk of consecutive aspiration. We present the case of a 48-year-old man with formation of a RH after accidental ingestion of a large fish bone with hypertension as comorbidity caused by a so far undiagnosed pheochromocytoma. The patient presented with acute onset of retropharyngeal pain, dysphonia and dysphagia secondary to fish bone foreign body ingestion. His medical history was significant for uncontrolled hypertension. CT showed a large RH extending from the oropharynx to the superior mediastinum. The patient underwent emergency tracheostomy, surgical debridement and removal of the fish bone. Antihypertensive medication was utilised to control his labile blood pressure. The postoperative CT scan revealed an adrenal pheochromocytoma that was subsequently resected.
Renal denervation for severe hypertension in a small child with Turner syndrome: miniaturisation of the procedure and results
Authors: Bonanni Alice , Pasetti Francesco , Ghiggeri Gian Marco , Gandolfo Carlo
Published: March 2015

Sympathetic nervous system hyperactivity plays a role in development and progression of hypertension. While renal denervation employing radiofrequency devices has been used therapeutically in treating severe hypertension with alternate results in adults, few data are available regarding children. We treated a 6-year-old girl affected by Turner syndrome presenting severe hypertension and an episode of stroke, in spite of treatment with four antihypertensive drugs, with sympathetic ablation. The Simplicity device (Medtronic, Minneapolis, USA) was adapted to the smaller vessels, allowing a tailored approach. After 3 and 6 months of treatment, and β-blocker discontinuation, blood pressure values were set between the 90th and 95th centiles for sex and age, and normalised at 12 months. We confirm that renal denervation can be used to treat severe hypertension in children; miniaturisation of catheter and tailoring the procedure for small vessels allowed a safe approach. Progressive improvement of blood pressure had a satisfactory clinical impact.
Cricket fast bowling workload patterns as risk factors for tendon, muscle, bone and joint injuries
Authors: Orchard John W , Blanch Peter , Paoloni Justin , Kountouris Alex , Sims Kevin , Orchard Jessica J , Brukner Peter
Published: March 2015

Objective

To assess workload-related risk factors for injuries to particular tissue types in cricket fast bowlers.

Design

235 fast bowlers who bowled in 14600 player innings over a period of 15 years were followed in a prospective cohort risk factor study to compare overs bowled in each match (including preceding workload patterns) and injury risk in the 3–4 weeks subsequent to the match. Injuries were categorised according to the affected tissue type as either: bone stress, tendon injuries, muscle strain or joint injuries. Workload risk factors were examined using binomial logistic regression multivariate analysis, with a forward stepwise procedure requiring a significance of <0.05.

Results

High acute match workload and high previous season workload were risk factors for tendon injuries, but high medium term (3-month workload) was protective. For bone stress injuries, high medium term workload and low career workload were risk factors. For joint injuries, high previous season and career workload were risk factors. There was little relationship between muscle injury and workload although high previous season workload was slightly protective.

Conclusions

The level of injury risk for some tissue types varies in response to preceding fast bowling workload, with tendon injuries most affected by workload patterns. Workload planning may need to be individualised, depending on individual susceptibility to various injury types. This study supports the theory that tendons are at lowest risk with consistent workloads and susceptible to injury with sudden upgrades in workload. Gradual upgrades are recommended, particularly at the start of a bowler's career to reduce the risk of bone stress injury.
Protocol for the PREHAB study—Pre-operative Rehabilitation for reduction of Hospitalization After coronary Bypass and valvular surgery: a randomised controlled trial
Authors: Stammers Andrew N , Kehler D Scott , Afilalo Jonathan , Avery Lorraine J , Bagshaw Sean M , Grocott Hilary P , Légaré Jean-Francois , Logsetty Sarvesh , Metge Colleen , Nguyen Thang , Rockwood Kenneth , Sareen Jitender , Sawatzky Jo-Ann , Tangri Navdeep , Giacomantonio Nicholas , Hassan Ansar , Duhamel Todd A , Arora Rakesh C
Published: March 2015

Introduction

Frailty is a geriatric syndrome characterised by reductions in muscle mass, strength, endurance and activity level. The frailty syndrome, prevalent in 25–50% of patients undergoing cardiac surgery, is associated with increased rates of mortality and major morbidity as well as function decline postoperatively. This trial will compare a preoperative, interdisciplinary exercise and health promotion intervention to current standard of care (StanC) for elective coronary artery bypass and valvular surgery patients for the purpose of determining if the intervention improves 3-month and 12-month clinical outcomes among a population of frail patients waiting for elective cardiac surgery.

Methods and analysis

This is a multicentre, randomised, open end point, controlled trial using assessor blinding and intent-to-treat analysis. Two-hundred and forty-four elective cardiac surgical patients will be recruited and randomised to receive either StanC or StanC plus an 8-week exercise and education intervention at a certified medical fitness facility. Patients will attend two weekly sessions and aerobic exercise will be prescribed at 40–60% of heart rate reserve. Data collection will occur at baseline, 1–2 weeks preoperatively, and at 3 and 12 months postoperatively. The primary outcome of the trial will be the proportion of patients requiring a hospital length of stay greater than 7 days.

Potential impact of study

The healthcare team is faced with an increasingly complex older adult patient population. As such, this trial aims to provide novel evidence supporting a health intervention to ensure that frail, older adult patients thrive after undergoing cardiac surgery.

Ethics and dissemination

Trial results will be published in peer-reviewed journals, and presented at national and international scientific meetings. The University of Manitoba Health Research Ethics Board has approved the study protocol V.1.3, dated 11 August 2014 (H2014:208).

Trial registration number

The trial has been registered on ClinicalTrials.gov, a registry and results database of privately and publicly funded clinical studies (NCT02219815).
Female perineal injuries in children and adolescents presenting to a paediatric emergency department
Authors: Roland Damian , Lewis Gareth , Rowlands Rachel , Davidson Emmanuel , Davies Ffion
Published: March 2015

This retrospective case series determined documentation quality and likelihood of safeguarding issues in girls  aged 0–15 years with perineal and genital injuries presenting to a paediatric emergency department (ED). During the period between 2002 and 2010, cases were identified and clinical information was recorded. Cases were cross-referenced against the hospital's safeguarding unit's records up to 2011. In total, 181 case notes were available for review with 76.2% of patients discharged home from the ED. Fewer than 50% of case notes contained clear anatomical description of the injuries. In 51 (28.2%) cases, child safeguarding issues were considered, with specific referrals made to safeguarding services in 20 of these (11.0%). Only one case involved subsequent child safeguarding proceedings. Clear documentation of injury patterns by medical staff was poor, but medical and nursing staff should not be anxious about dealing with this cohort of patients as they are no different from other incidental injuries needing diligent levels of child safeguarding awareness.
Lactate level, aetiology and mortality of adult patients in an emergency department: a cohort study
Authors: Pedersen Mathilde , Brandt Vibeke Schnack , Holler Jon Gitz , Lassen Annmarie Touborg
Published: March 2015

Background

Increased lactate is associated with high mortality among patients with suspected infection or trauma in the emergency department (ED), but the association with patients with other aetiologies is less well described. The aim of this study was to describe the relation between lactate, aetiology and 7-day mortality in adult ED patients.

Methods

A retrospective cohort study of all adult patients who had a lactate measured within 4 h after arrival to the ED at Odense University Hospital between June 2012 and May 2013. The categorisation of suspected aetiology was based on discharge diagnoses.

Results

5360 patients were included; 51.7% were men, and the median age was 67 years (IQR 50–79). 77.2% had low lactate (0–1.9 mmol/L), 16.2% intermediate lactate (2–3.9 mmol/L), and 6.6% high lactate (≥4 mmol/L). 7-day mortality was 2.9% (95% CI 2.4% to 3.5%) for patients with low lactate, 7.8% (95% CI 6.1% to 9.8%) for patients with intermediate lactate, and 23.9% (95% CI 19.6% to 28.8%) for patients with high lactate. The association between lactate level and mortality varied across different diagnostic groups. Based on Area Under the Curve in receiver operating characteristic analysis, lactate level showed to be useful in patients with infection (0.78, 95% CI 0.73 to 0.84), trauma (0.78, 95% CI 0.65 to 0.92), cardiac diseases (0.83, 95% CI 0.75 to 0.91) and gastrointestinal diseases (0.83, 95% CI 0.68 to 0.98). Lactate level was not useful in neurological (0.58, 95% CI 0.50 to 0.67) and respiratory disease (0.64, 95% CI 0.55 to 0.74), and of uncertain value in the remaining diagnostic groups.

Conclusions

Among adult ED patients, the prognostic value of lactate varies between diagnostic groups.
Age and sex-dependent trends in pulmonary embolism testing and derivation of a clinical decision rule for young patients
Authors: Mongan John , Kline Jeffrey , Smith-Bindman Rebecca
Published: March 2015

Importance

Despite low prevalence of pulmonary embolism (PE) in young adults, they are frequently imaged for PE, which involves radiation exposure and substantial financial cost.

Objective

Determine the use and positive proportions for PE imaging by age, differences in clinical presentation of PE by age and the projected impact of an age-targeted decision rule.

Design

Analysis of two national population-based datasets: the 2009 Nationwide Emergency Department Sample, a 20% sample of US emergency departments (EDs) and the 2003–2006 Pulmonary Embolism Rule-out Criteria (PERC) dataset, a multisite cohort of ED patients with suspected PE from 12 US EDs.

Results

Prevalence of PE was 10 times lower in young patients (18–35 years) than in older patients (>65 years) (0.06% vs 0.60%, p<0.001), but young patients were imaged for PE almost as frequently as older patients (2.3% vs 3.2%). This resulted in a lower proportion of positive examinations in young adults than older adults (2.3% vs 17.4%, p<0.001 in women; 4.0% vs 21.4%, p<0.001 in men). Clinical predictors of PE varied by age. Tachycardia was a significant predictor of PE in older patients (OR: 1.2–1.9, p<0.001), but not young patients. Fever was a significant predictor only in young patients (OR: 1.4–7.2, p<0.01). A modification of the previously described PERC rule to include age-specific risk factors could reduce PE imaging by 51% in young patients, with a missed PE rate of 0.6% in those excluded from imaging.

Conclusions and relevance

Young patients are frequently imaged for PE and have lower positive imaging rates than older patients. After further validation, application of our proposed rule for excluding young patients from PE imaging could reduce imaging, increase the positive rate of imaging and result in a low rate of missed PE among those excluded from imaging.
Mercury in Pacific bluefin tuna (Thunnus orientalis): bioaccumulation and trans-Pacific Ocean migration
Authors: Colman John A. , Nogueira Jacob I. , Pancorbo Oscar C. , Batdorf Carol A. , Block Barbara A.
Published: March 2015

Pacific bluefin tuna (Thunnus orientalis) have the largest home range of any tuna species and are well known for the capacity to make transoceanic migrations. We report the measurement of mercury (Hg) concentrations in wild Pacific bluefin tuna (PBFT), the first reported with known size-of-fish and capture location. The results indicate juvenile PBFT that are recently arrived in the California Current from the western Pacific Ocean have significantly higher Hg concentrations in white muscle (0.51 μg·g–1 wet mass, wm) than PBFT of longer California Current residency (0.41 μg·g–1 wm). These new arrivals are also higher in Hg concentration than PBFT in farm pens (0.43 μg·g–1 wm) that were captured on arrival in the California Current and raised in pens on locally derived feed. Analysis by direct Hg analyzer and attention to Hg by tissue type and location on the fish allowed precise comparisons of mercury among wild and captive fish populations. Analysis of migration and nearshore residency, determined through extensive archival tagging, bioaccumulation models, trophic investigations, and potential coastal sources of methylmercury, indicates Hg bioaccumulation is likely greater for PBFT juvenile habitats in the western Pacific Ocean (East China Sea, Yellow Sea) than in the eastern Pacific Ocean (California Current). Differential bioaccumulation may be a trophic effect or reflect methylmercury availability, with potential sources for coastal China (large hypoxic continental shelf receiving discharge of three large rivers, and island-arc volcanism) different from those for coastal Baja California (small continental shelf, no large rivers, spreading-center volcanism).