bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pelger–Huët Anomaly in a cat
Authors: Deshuillers Pierre , Raskin Rose , Messick Joanne 
Published: August 2014

AbstractA 14‐year‐old, spayed female Domestic Shorthair cat was referred to the Purdue University Veterinary Teaching Hospital (PUVTH) for iodine 131 treatment of hyperthyroidism. Upon arrival, a biochemistry profile and a CBC were performed. Approximately 50% of the neutrophils and all the eosinophils observed were hyposegmented with a mature, condensed chromatin pattern. Nuclei had a band to “dumbbell” shape, and rarely a round shape, suggesting a Pelger–Huët anomaly or a pseudo Pelger–Huët. Based on both a negative FeLV and FIV tests, the absence of any clinical signs to support an inflammatory process, and the persistence of this granulocytic morphology 6 months after its previous admission to the PUVTH, a diagnosis of Pelger–Huët anomaly was established in this cat.
Effects of Sprint Training With or Without Ball Carry in Elite Rugby Players
Authors: Seitz Laurent B. , Barr Matt , Haff G. Gregory 
Published: August 2014

Purpose:To compare the effects of sprint training with or without ball carry on the sprint performance of elite rugby league players.Methods:Twenty-four elite rugby league players were divided into a ball-carry group (BC; n = 12) and a no-ball-carry group (NBC; n = 12). The players of the BC group were required to catch and carry the ball under 1 arm during each sprint, whereas the NBC group performed sprints without carrying a ball. The 8-wk training intervention took place during the precompetitive phase of the season and consisted of 2 sessions/wk. Sprint performance was measured before and after the training intervention with 40-m linear sprints performed under 2 conditions: with and without ball carry. Split times of 10, 20, and 40 m were recorded for further analysis. A 3-way (group × time × condition) factorial ANOVA was performed to compare changes in sprint performance with and without the ball, before and after the training intervention for both BC and NBC training groups.Results:The BC and NBC groups experienced similar improvements in 10-, 20-, and 40-m sprint times and accelerations, regardless of the condition under which the sprint tests were performed (P = .19).Conclusions:Sprint training while carrying a rugby ball is as effective as sprint training without carrying a rugby ball for improving the sprint performance of elite rugby league players.
Monitoring Neuromuscular Fatigue in Team-Sport Athletes Using a Cycle-Ergometer Test
Authors: Wehbe George , Gabbett Tim , Dwyer Dan , McLellan Christopher , Coad Sam 
Published: August 2014

Purpose:To compare a novel sprint test on a cycle ergometer with a countermovement-jump (CMJ) test for monitoring neuromuscular fatigue after Australian rules football match play.Methods:Twelve elite under-18 Australian rules football players (mean ± SD age 17.5 ± 0.6 y, stature 184.7 ± 8.8 cm, body mass 75.3 ± 7.8 kg) from an Australian Football League club’s Academy program performed a short sprint test on a cycle ergometer along with a single CMJ test 1 h prematch and 1, 24, and 48 h postmatch. The cycle-ergometer sprint test involved a standardized warm-up, a maximal 6-s sprint, a 1-min active recovery, and a 2nd maximal 6-s sprint, with the highest power output of the 2 sprints recorded as peak power (PP).Results:There were small to moderate differences between postmatch changes in cycle-ergometer PP and CMJ PP at 1 (ES = 0.49), 24 (ES = –0.85), and 48 h postmatch (ES = 0.44). There was a substantial reduction in cycle-ergometer PP at 24 h postmatch (ES = –0.40) compared with 1 h prematch.Conclusions:The cycle-ergometer sprint test described in this study offers a novel method of neuromuscular-fatigue monitoring in team-sport athletes and specifically quantifies the concentric component of the fatigue-induced decrement of force production in muscle, which may be overlooked by a CMJ test.
The Effect of Ankle Taping to Restrict Plantar Flexion on Ball and Foot Velocity During an Instep Kick in Soccer
Authors: Sasadai Junpei , Urabe Yukio , Maeda Noriaki , Shinohara Hiroshi , Fujii Eri 
Published: August 2014

Context:Posterior ankle impingement syndrome is a common disorder in soccer players and ballet dancers. In soccer players, it is caused by the repetitive stress of ankle plantar flexion due to instep kicking. Protective ankle dorsiflexion taping is recommended with the belief that it prevents posterior ankle impingement. However, the relationship between ankle taping and ball-kicking performance remains unclear.Objective:To demonstrate the relationship between the restrictions of ankle taping and performance of an instep kick in soccer.Design:Laboratory-based repeated-measures.Setting:University laboratory.Participants:11 male university soccer players.Intervention:The subjects’ ankle plantar flexion was limited by taping. Four angles of planter flexion (0°, 15°, 30°, and without taping) were formed by gradation limitation. The subjects performed maximal instep kicks at each angle.Main Outcome Measures:The movements of the kicking legs and the ball were captured using 3 high-speed cameras at 200 Hz. The direct linear-transformation method was used to obtain 3-dimensional coordinates using a digitizing system. Passive ankle plantar-flexion angle, maximal plantar-flexion angle at ball impact, ball velocity, and foot velocity were measured. The data were compared among 4 conditions using repeated-measures ANOVA, and the correlations between ball velocity and foot velocity and between ball velocity and toe velocity were calculated.Results:Ankle dorsiflexion taping could gradually limit both passive plantar flexion and plantar flexion at the impact. Furthermore, limitation of 0° and 15° reduced the ball velocity generated by instep kicks.Conclusion:Plantar-flexion-limiting taping at 30° has a potential to prevent posterior ankle impingement without decreasing the ball velocity generated by soccer instep kicks.
Resistome Analysis of Enterobacter cloacae CY01, an Extensively Drug-Resistant Strain Producing VIM-1 Metallo-β-Lactamase from China
Authors: Yang Ling , Wu Ai-Wu , Su Dan-Hong , Lin Yong-Ping , Chen Ding-Qiang , Qiu Yu-Rong 
Published: August 2014

ABSTRACT

Resistome analysis of clinical VIM-1-producing
Enterobacter cloacae
strain CY01 from China revealed the presence of multiple resistance determinants. Two resistance plasmids were identified in CY01. The pCY-VIM plasmid was 14 kb in size and possessed a replicase gene (
repA
), a gene cluster encoding the partitioning function (
parABC
), and a carbapenemase gene (
bla
VIM-1
). Another 5.9-kb plasmid, pCY-MdT, with an
aac
(
6
′)-
Ib
gene, was very closely related (13 nucleotide differences) to pMdT1, a ColE1 plasmid carrying
aac
(
6
′)-
Ib-cr4
.
Impact of Lopinavir-Ritonavir or Nevirapine on Bedaquiline Exposures and Potential Implications for Patients with Tuberculosis-HIV Coinfection
Authors: Svensson Elin M. , Dooley Kelly E. , Karlsson Mats O. 
Published: August 2014

ABSTRACTConcomitant treatment of tuberculosis (TB) and HIV is recommended and improves outcomes. Bedaquiline is a novel drug for the treatment of multidrug-resistant (MDR) TB; combined use with antiretroviral drugs, nevirapine, or ritonavir-boosted lopinavir (LPV/r) is anticipated, but no clinical data from coinfected patients are available. Plasma concentrations of bedaquiline and its M2 metabolite after single doses were obtained from interaction studies with nevirapine or LPV/r in healthy volunteers. The antiretrovirals' effects on bedaquiline and M2 pharmacokinetics were assessed by nonlinear mixed-effects modeling. Potential dose adjustments were evaluated with simulations. No significant effects of nevirapine on bedaquiline pharmacokinetics were identified. LPV/r decreased bedaquiline and M2 clearances to 35% (relative standard error [RSE], 9.2%) and 58% (RSE, 8.4%), respectively, of those without comedication. As almost 3-fold (bedaquiline) and 2-fold (M2) increases in exposures during chronic treatment with LPV/r are expected, dose adjustments are suggested for evaluation. Efficacious, safe bedaquiline dosing for MDR-TB patients receiving antiretrovirals is important. Modeling results suggest that bedaquiline can be coadministered with nevirapine without dose adjustments. The predicted elevation of bedaquiline and M2 levels during LPV/r coadministration may be a safety concern, and careful monitoring is recommended. Further data are being collected in coinfected patients to determine whether dose adjustments are needed. (These studies have been registered at ClinicalTrials.gov under registration numbers NCT00828529 [study C110] and NCT00910806 [study C117].)
A First-in-Human Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple-Ascending Oral Dose Study of Novel Antimalarial Spiroindolone KAE609 (Cipargamin) To Assess Its Safety, Tolerability, and Pharmacokinetics in Healthy Adult Volunteers
Authors: Leong F. Joel , Li Ruobing , Jain Jay Prakash , Lefèvre Gilbert , Magnusson Baldur , Diagana Thierry T. , Pertel Peter 
Published: August 2014

ABSTRACT

This first-in-human randomized, double-blind, placebo-controlled, ascending-single and -multiple oral dose study was designed to evaluate the safety, tolerability, and pharmacokinetics in healthy volunteers of KAE609 (cipargamin; formerly NITD609), a spiroindolone now in trials for malaria treatment. It was studied in single-dose cohorts (1 to 300 mg, including one 30-mg food effect cohort) with 4 to 10 subjects in each cohort and in multiple-dose cohorts (10 to 150 mg once daily for 3 days) with 8 subjects in each cohort. The follow-up period was 6 to 8 days post-last dose. Safety and pharmacokinetics were assessed at scheduled time points during the study. Systemic exposure in terms of the area under the concentration-time curve from 0 h extrapolated to infinity (AUC
0–∞
) increased in a dose-proportional manner over the dose range of 1 to 300 mg. The AUC from time zero to the time of the last quantifiable concentration (AUC
last
) and the maximum concentration of drug in plasma (
C
max
) also increased in an approximately dose-proportional manner. When administered daily for 3 days, the accumulation ratio on day 3 (the AUC from time zero to 24 h postdosing [AUC
0–24
] on day 3/AUC
0–24
on day 1) was in the range of 1.5 to 2 in the studied dose range (10 to 150 mg) and was consistent with an elimination half-life of around 24 h. Urine analysis for unchanged KAE609 revealed negligible amounts (≤0.01%) were excreted renally. The high fat food intake did not affect the extent of KAE609 absorption (AUC); however, the
C
max
was reduced by around 27%. KAE609 was tolerated in this study, with transient gastrointestinal and genitourinary adverse events of mild to moderate intensity (semen discoloration, diarrhea, nausea and abdominal discomfort, dizziness and headache, catheter site hematoma). Gastrointestinal and genitourinary adverse events increased with rising doses.
Combination of the CCL5-Derived Peptide R4.0 with Different HIV-1 Blockers Reveals Wide Target Compatibility and Synergic Cobinding to CCR5
Authors: Secchi Massimiliano , Vassena Lia , Morin Sébastien , Schols Dominique , Vangelista Luca 
Published: August 2014

ABSTRACT

R4.0, a synthetic CCL5/RANTES-derived peptide, exerts potent anti-HIV-1 activity via its nonactivating interaction with CCR5, the major HIV-1 coreceptor. CCR5 chronic activation may promote undesirable inflammatory effects and enhance viral infection; thus, receptor antagonism is a necessary requisite. HIV-1 gp120, CCL5, and maraviroc dock on CCR5 by sharing two receptor sites: the N terminus and the second extracellular loop. In combination studies, R4.0, CCL5, and maraviroc exhibited concomitant interactions with CCR5 and promoted synergic inhibition of HIV-1 in acute-infection assays. Furthermore, various degrees of additive/synergic HIV-1 inhibition were observed when R4.0 was tested in combination with drugs and lead compounds directed toward different viral targets (gp120, gp41, reverse transcriptase, and protease). In combination with tenofovir, R4.0 provides cross-clade synergic inhibition of primary HIV-1 isolates. Remarkably, an
in vitro
-generated maraviroc-resistant R5 HIV-1 strain was inhibited by R4.0 comparably to the wild-type strain, suggesting the presence of viral resistance barriers similar to those reported for CCL5. Overall, R4.0 appears to be a promising lead peptide with potential for combination in anti-HIV-1 therapy and in microbicide development to prevent sexual HIV-1 transmission.
Masking of β(1-3)-Glucan in the Cell Wall of Candida albicans from Detection by Innate Immune Cells Depends on Phosphatidylserine
Authors: Davis Sarah E. , Hopke Alex , Minkin Steven C. , Montedonico Anthony E. , Wheeler Robert T. , Reynolds Todd B. 
Published: August 2014

ABSTRACT

The virulence of
Candida albicans
in a mouse model of invasive candidiasis is dependent on the phospholipids phosphatidylserine (PS) and phosphatidylethanolamine (PE). Disruption of the PS synthase gene
CHO1
(i.e.,
cho1
Δ/Δ) eliminates PS and blocks the
de novo
pathway for PE biosynthesis. In addition, the
cho1
Δ/Δ mutant's ability to cause invasive disease is severely compromised. The
cho1
Δ/Δ mutant also exhibits cell wall defects, and in this study, it was determined that loss of PS results in decreased masking of cell wall β(1-3)-glucan from the immune system. In wild-type
C. albicans
, the outer mannan layer of the wall masks the inner layer of β(1-3)-glucan from exposure and detection by innate immune effector molecules like the C-type signaling lectin Dectin-1, which is found on macrophages, neutrophils, and dendritic cells. The
cho1
Δ/Δ mutant exhibits increases in exposure of β(1-3)-glucan, which leads to greater binding by Dectin-1 in both yeast and hyphal forms. The unmasking of β(1-3)-glucan also results in increased elicitation of TNF-α from macrophages in a Dectin-1-dependent manner. The role of phospholipids in fungal pathogenesis is an emerging field, and this is the first study showing that loss of PS in
C. albicans
results in decreased masking of β(1-3)-glucan, which may contribute to our understanding of fungus-host interactions.
Characterization of a Lipopolysaccharide-Targeted Monoclonal Antibody and Its Variable Fragments as Candidates for Prophylaxis against the Obligate Intracellular Bacterial Pathogen Coxiella burnetii
Authors: Peng Ying , Schoenlaub Laura , Elliott Alexandra , Mitchell William J. , Zhang Guoquan 
Published: August 2014

ABSTRACTOur previous study demonstrated that treatment ofCoxiella burnetiiwith the phase I lipopolysaccharide (PI-LPS)-targeted monoclonal antibody (MAb) 1E4 significantly inhibitedC. burnetiiinfection in mice, suggesting that 1E4 is a protective MAb. To determine whether passive transfer of antibodies (Abs) can provide protection againstC. burnetiinatural infection, we examined if passive transfer of 1E4 would protect SCID mice againstC. burnetiiaerosol infection. The results indicated that 1E4 conferred significant protection against aerosolizedC. burnetii, suggesting that 1E4 may be useful for preventingC. burnetiinatural infection. To further understand the mechanisms of 1E4-mediated protection and to test the possibility of using humanized 1E4 to preventC. burnetiiinfection, we examined whether the Fab fragment of 1E4 (Fab1E4), a recombinant murine single-chain variable fragment (muscFv1E4), and a humanized single-chain variable fragment (huscFv1E4) retained the ability of 1E4 to inhibitC. burnetiiinfection. The results indicated that Fab1E4, muscFv1E4, and huscFv1E4 were able to inhibitC. burnetiiinfection in mice but that their ability to inhibitC. burnetiiinfection was lower than that of 1E4. In addition, treatment ofC. burnetiiwith Fab1E4, muscFv1E4, or huscFv1E4 can blockC. burnetiiinfection of macrophages. Interestingly, treatment ofC. burnetiiwith huscFv1E4 can significantly reduceC. burnetiiinfectivity in human macrophages. This report provides the first evidence to demonstrate that the humanized variable fragments of an LPS-specific MAb can neutralizeC. burnetiiinfection and appears to be a promising step toward the potential use of a humanized MAb as emergency prophylaxis againstC. burnetiiexposure.
Glycosylation and Immunoreactivity of the Histoplasma capsulatum Cfp4 Yeast-Phase Exoantigen
Authors: Holbrook Eric D. , Kemski Megan M. , Richer Sarah M. , Wheat L. Joseph , Rappleye Chad A. 
Published: August 2014

ABSTRACTThe yeast phase ofHistoplasma capsulatumis the virulent form of this thermally dimorphic fungal pathogen. Among the secreted proteome ofHistoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically byHistoplasmayeast cells, suggesting its role in pathogenesis. We have generated three monoclonal antibodies as tools for characterization and detection of Cfp4 and determined the epitope each recognizes. Through site-directed mutagenesis of Cfp4, we identified three asparagines that function as the principal sites of N-linked glycan modification. To test the function of Cfp4 inHistoplasmapathogenesis, we generated Cfp4-deficient strains by insertional mutagenesis and by RNA interference. Cfp4-deficient strains are not attenuated in virulence in human macrophages or during lung infection in a murine model of histoplasmosis. Coinfection of differentially marked Cfp4-producing and Cfp4-deficient strains demonstrates that production of Cfp4 does not confer a fitness advantage toHistoplasmayeasts during murine lung infection. Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. In addition, human immune sera recognize theHistoplasmaCfp4 protein, confirming Cfp4 production during infection of human hosts. These results suggest the potential utility of Cfp4 as a diagnostic exoantigen for histoplasmosis.
The Serine/Threonine Kinase STK11 Promotes Shigella flexneri Dissemination through Establishment of Cell-Cell Contacts Competent for Tyrosine Kinase Signaling
Authors: Dragoi Ana-Maria , Agaisse Hervé 
Published: August 2014

ABSTRACT

Shigella flexneri
is an intracellular pathogen that disseminates in the intestinal epithelium by displaying actin-based motility. We found that although
S. flexneri
displayed comparable actin-based motilities in the cytosols of HeLa229 and HT-29 epithelial cell lines, the overall dissemination process was much more efficient in HT-29 cells. Time-lapse microscopy demonstrated that as motile bacteria reached the cell cortex in HT-29 cells, they formed membrane protrusions that resolved into vacuoles, from which the bacteria escaped and gained access to the cytosol of adjacent cells. In HeLa229 cells,
S. flexneri
also formed membrane protrusions that extended into adjacent cells, but the protrusions rarely resolved into vacuoles. Instead, the formed protrusions collapsed and retracted, bringing the bacteria back to the cytosol of the primary infected cells. Silencing the serine/threonine kinase STK11 (also known as LKB1) in HT-29 cells decreased the efficiency of protrusion resolution into vacuoles. Conversely, expressing STK11 in HeLa229 cells, which lack the STK11 locus, dramatically increased the efficiency of protrusion resolution into vacuoles.
S. flexneri
dissemination in HT-29 cells led to the local phosphorylation of tyrosine residues in protrusions, a signaling event that was not observed in HeLa229 cells but was restored in STK11-expressing HeLa229 cells. Treatment of HT-29 cells with the tyrosine kinase inhibitor imatinib abrogated tyrosine kinase signaling in protrusions, which correlated with a severe decrease in the efficiency of protrusion resolution into vacuoles. We suggest that the formation of STK11-dependent lateral cell-cell contacts competent for tyrosine kinase signaling promotes
S. flexneri
dissemination in epithelial cells.
The Interleukin-1β/CXCL1/2/Neutrophil Axis Mediates Host Protection against Group B Streptococcal Infection
Authors: Biondo C. , Mancuso G. , Midiri A. , Signorino G. , Domina M. , Lanza Cariccio V. , Mohammadi N. , Venza M. , Venza I. , Teti G. , Beninati C. 
Published: August 2014

ABSTRACTPrevious studies have indicated that group B streptococcus (GBS), a frequent human pathogen, potently induces the release of interleukin-1β (IL-1β), an important mediator of inflammatory responses. Since little is known about the role of this cytokine in GBS disease, we analyzed the outcome of infection in IL-1β-deficient mice. These animals were markedly sensitive to GBS infection, with most of them dying under challenge conditions that caused no deaths in wild-type control mice. Lethality was due to the inability of the IL-1β-deficient mice to control local GBS replication and dissemination to target organs, such as the brain and the kidneys. Moreover, in a model of inflammation induced by the intraperitoneal injection of killed GBS, a lack of IL-1β was associated with selective impairment in the production of the neutrophil chemokines CXCL1 and CXCL2 and in neutrophil recruitment to the peritoneal cavity. Decreased blood neutrophil counts and impaired neutrophil recruitment to the brain and kidneys were also observed during GBS infection in IL-1β-deficient mice concomitantly with a reduction in CXCL1 and CXCL2 tissue levels. Notably, the hypersusceptibility to GBS infection observed in the immune-deficient animals was recapitulated by neutrophil depletion with anti-Gr1 antibodies. Collectively, our data identify a cytokine circuit that involves IL-1β-induced production of CXCL1 and CXCL2 and leads the recruitment of neutrophils to GBS infection sites. Moreover, our data point to an essential role of these cells in controlling the progression and outcome of GBS disease.
Blockade of Indoleamine 2,3-Dioxygenase Reduces Mortality from Peritonitis and Sepsis in Mice by Regulating Functions of CD11b+Peritoneal Cells
Authors: Hoshi Masato , Osawa Yosuke , Ito Hiroyasu , Ohtaki Hirofumi , Ando Tatsuya , Takamatsu Manabu , Hara Akira , Saito Kuniaki , Seishima Mitsuru 
Published: August 2014

ABSTRACTIndoleamine 2,3-dioxygenase-1 (Ido), which catalyzes the first and limiting step of tryptophan catabolism, has been implicated in immune tolerance. However, the roles of Ido in systemic bacterial infection are complicated and remain controversial. To explore this issue, we examined the roles of Ido in bacterial peritonitis and sepsis after cecal ligation and puncture (CLP) in mice by using the Ido inhibitor 1-methyl-d,l-tryptophan (1-MT), by comparing Ido+/+and Ido−/−mice, or by using chimeric mice in which Ido in the bone marrow-derived cells was deficient. Ido expression in the peritoneal CD11b+cells and its metabolitel-kynurenine in the serum were increased after CLP. 1-MT treatment or Ido deficiency, especially in bone marrow-derived cells, reduced mortality after CLP. Compared to Ido+/+mice, Ido−/−mice showed increased recruitment of neutrophils and mononuclear cells into the peritoneal cavity and a decreased bacterial count in the blood accompanied by increased CXCL-2 and CXCL-1 mRNA in the peritoneal cells. Ido has an inhibitory effect on LPS-induced CXCL-2 and CXCL-1 production in cultured peritoneal cells. These findings indicate that inhibition of Ido reduces mortality from peritonitis and sepsis after CLP via recruitment of neutrophils and mononuclear cells by chemokine production in peritoneal CD11b+cells. Thus, blockade of Ido plays a beneficial role in host protection during bacterial peritonitis and sepsis.