bluuebunny/crossref_metadata_2025_split huggingface dataset:
Descriptive results from a longitudinal study of airway inflammation in British National Hunt racehorses
Authors: CARDWELL J. M. , WOOD J. L. N. , SMITH K. C. , NEWTON J. R. 
Published: March 2011

SummaryReasons for performing study:Rates of airway inflammation in young racehorses decrease with time but it is not clear whether this is associated with increasing age or time exposed to the training environment. The structure of the British National Hunt (NH) population allowed closer examination of this relationship.Objectives:To compare rates of inflammatory airway disease diagnosed by tracheal sampling (trIAD), and its components, in NH racehorses by age and training history and with published rates in young racehorses.Methods:A prospective, longitudinal study was conducted on 5 NH yards over 2 years. Period sample prevalences of nasal discharge,tracheal mucus, airway neutrophilia and trIAD (defined by a combination of tracheal mucus and airway neutrophilia) were estimated and compared between horses with different ages and time in training.Results:Horses new to training had twice the odds of visible tracheal mucus as ex‐flat trained horses (OR 2.0; 95% CI: 1.4–2.8; P<0.001) but no significantly increased odds of airway neutrophilia (OR 1.3; 95% CI: 0.8–1.9; P = 0.3) and inconclusive evidence of increased odds of trIAD (OR 1.8; CI: 0.9–3.5; P = 0.08). However, a lower median time in training was significantly associated with the presence of visible mucus (P<0.001), increased mucus (P = 0.005) and trIAD (P = 0.03). No disease measure varied significantly with age.Conclusions:Tracheal mucus and trIAD, but not neutrophilia detected in tracheal wash samples, were less prevalent in horses that had been exposed to the training environment for longer, explaining previously reported associations with age.Potential relevance:Neutrophil proportion in tracheal wash samples is not as useful a clinical tool as measures of visible tracheal mucus for identifying horses requiring treatment or changes in management. The inclusion of tracheal wash neutrophils in the assessment of equine airways, or at least their relative weighting in definitions of trIAD, should be re‐evaluated.
Enhanced IL‐6 transcriptional response to adenosine receptor ligands in horses with lower airway inflammation
Authors: ZHANG L. , FRANCHINI M. , WEHRLI ESER M. , DIP R. 
Published: March 2011

SummaryReasons for performing study: Accumulation of extracellular adenosine has been closely associated with human asthmatic responses. However, the relevance of adenosine signalling in equine airways has not previously been investigated.Objectives: To determine the expression of adenosine receptors (AR) in bronchoalveolar lavage (BAL) cells and assess the reactivity of these cells to AR ligands ex vivo, employing IL‐6 as readout of adenosinergic inflammatory signalling.Methods: Eight horses with varying degrees of lower airway inflammation and 10 healthy controls were analysed. Expression of AR‐subtypes in each BAL sample was determined by quantitative RT‐PCR and compared to that in 13 other tissues. Bronchoalveolar lavage cells were stimulated either with the adenosine analogue NECA, CGS‐21680 (A2AAR selective agonist) or with a combination of NECA and SCH‐58261 (A2AAR antagonist) and IL‐6 expression assessed.Results: Bronchoalveolar lavage cells predominantly expressed A2BAR, with lower A2AAR levels and marginal A3AR expression; A1AR was not detected. This pattern was similar to that of PBMCs but different from the other tissues tested. No significant differences in AR expression in BAL cells from both groups were detected, although a trend for decreased A2BAR in airway‐compromised horses was observed. Treatment of BAL cells with the nonselective agonist NECA upregulated IL‐6 expression in cells from airway‐compromised horses, but levels remained unchanged in control animals. Furthermore, blockage of A2AAR with SCH‐58261 enhanced IL‐6 mRNA induction by NECA in both groups, with higher levels in airway‐compromised horses; the amplitude of this response correlated with neutrophil count.Conclusions: These results demonstrate the presence of an adenosine/IL‐6 inflammatory axis in the bronchoalveolar milieu of airway‐compromised horses. While A2BAR is the predominant proinflammatory AR subtype expressed, A2AAR appears to modulate inflammatory signalling (IL‐6 expression) by adenosine.Potential relevance: This study supports selective AR targeting as a potential therapeutic approach for the modulation of inflammation in the equine lower respiratory tract.
Early maladaptive schemas and child and adult attachment: A 15‐year longitudinal study
Authors: Simard Valérie , Moss Ellen , Pascuzzo Katherine 
Published: March 2011

Objectives. To examine the relation between early maladaptive schemas (EMS), as defined in schema therapy, and both child and adult attachment.Design. A 15‐year longitudinal design in which child attachment groups (secure, avoidant, ambivalent, and disorganized) were compared in early adulthood on their profile of scores across EMS domains. A similar strategy was used to examine EMS profiles as a function of adult attachment groups (secure, preoccupied, and fearful).Methods. Sixty participants, recruited from Montreal day‐care centres, were assessed at 6 (Time 1) and 21 years of age (Time 2). Time 1 attachment was assessed using a separation–reunion procedure and Time 2 attachment, using the Experiences in Close Relationships questionnaire. EMS were evaluated with the Young Schema Questionnaire (Time 2).Results. There were more signs of EMS among young adults with either an insecure ambivalent child attachment, or an insecure preoccupied adult attachment style, compared to their secure peers. These differences were not specific to one domain of EMS; they were reported for various EMS.Conclusions. The results suggest that specific elements of representational models are more likely to be related to the development of EMS: high anxiety over abandonment, negative self‐view, and explicit manifestations of personal distress. Unmet childhood needs for secure attachment may lead to a large variety of EMS as defined in schema therapy.
Susceptibility of 186 Nocardia sp. Isolates to 20 Antimicrobial Agents
Authors: Larruskain Julián , Idigoras Pedro , Marimón José M. , Pérez-Trallero Emilio 
Published: March 2011

ABSTRACT

This study determined the antimicrobial susceptibilities of 186 clinical isolates of
Nocardia
spp. isolated in Gipuzkoa, northern Spain, between 1998 and 2009. Most isolates were recovered from respiratory samples,
Nocardia nova
,
N. farcinica
,
N. cyriacigeorgica
,
N. abscessus
, and
N. carnea
being the species most frequently isolated. Linezolid and amikacin were the only two antimicrobials to which all isolates were susceptible. The majority of
N. flavorosea
,
N. carnea
, and
N. farcinica
isolates were trimethoprim-sulfamethoxazole resistant.
The HIV Protease Inhibitor Nelfinavir Inhibits Kaposi's Sarcoma-Associated Herpesvirus Replication In Vitro
Authors: Gantt Soren , Carlsson Jacquelyn , Ikoma Minako , Gachelet Eliora , Gray Matthew , Geballe Adam P. , Corey Lawrence , Casper Corey , Lagunoff Michael , Vieira Jeffrey 
Published: March 2011

ABSTRACT

Kaposi's sarcoma (KS) is the most common HIV-associated cancer worldwide and is associated with high levels of morbidity and mortality in some regions. Antiretroviral (ARV) combination regimens have had mixed results for KS progression and resolution. Anecdotal case reports suggest that protease inhibitors (PIs) may have effects against KS that are independent of their effect on HIV infection. As such, we evaluated whether PIs or other ARVs directly inhibit replication of Kaposi's sarcoma-associated herpesvirus (KSHV), the gammaherpesvirus that causes KS. Among a broad panel of ARVs tested, only the PI nelfinavir consistently displayed potent inhibitory activity against KSHV
in vitro
as demonstrated by an efficient quantitative assay for infectious KSHV using a recombinant virus, rKSHV.294, which expresses the secreted alkaline phosphatase. This inhibitory activity of nelfinavir against KSHV replication was confirmed using virus derived from a second primary effusion lymphoma cell line. Nelfinavir was similarly found to inhibit
in vitro
replication of an alphaherpesvirus (herpes simplex virus) and a betaherpesvirus (human cytomegalovirus). No activity was observed with nelfinavir against vaccinia virus or adenovirus. Nelfinavir may provide unique benefits for the prevention or treatment of HIV-associated KS and potentially other human herpesviruses by direct inhibition of replication.
Systemic Absorption of Rifamycin SV MMX Administered as Modified-Release Tablets in Healthy Volunteers
Authors: Di Stefano A. F. D. , Rusca A. , Loprete L. , Dröge M. J. , Moro L. , Assandri A. 
Published: March 2011

ABSTRACT
The new oral 200-mg rifamycin SV MMX modified-release tablets, designed to deliver rifamycin SV directly into the colonic lumen, offer considerable advantages over the existing immediate-release antidiarrheic formulations. In two pharmacokinetics studies of healthy volunteers, the absorption, urinary excretion, and fecal elimination of rifamycin SV after single- and multiple-dose regimens of the new formulation were investigated. Concentrations in plasma of >2 ng/ml were infrequently and randomly quantifiable after single and multiple oral doses. The systemic exposure to rifamycin SV after single and multiple oral doses of MMX tablets under fasting and fed conditions or following a four-times-a-day (q.i.d.) or a twice-a-day (b.i.d.) regimen could be considered negligible. With both oral regimens, the drug was confirmed to be very poorly absorbable systemically. The amount of systemically absorbed antibiotic excreted by the renal route is far lower than 0.01% of the administered dose after both the single- and multiple-dose regimens. The absolute bioavailability, calculated as the mean percent ratio between total urinary excretion amounts (ΣXu) after a single intravenous injection and after a single oral dose under fasting conditions, was 0.0410 ± 0.0617. The total elimination of the unchanged rifamycin SV with feces was 87% of the administered oral dose. No significant effect of rifamycin SV on vital signs, electrocardiograms, or laboratory parameters was observed.
Antimicrobial Susceptibilities and Serotypes of Streptococcus pneumoniae Isolates from Elderly Patients with Pneumonia and Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Authors: Pérez-Trallero Emilio , Marimón José M. , Larruskain Julián , Alonso Marta , Ercibengoa María 
Published: March 2011

ABSTRACT

In the elderly,
Streptococcus pneumoniae
is the most common cause of pneumonia and one of the most frequently isolated pathogens in cases of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study was conducted to compare the pneumococcal isolates obtained during episodes of AECOPD and pneumonia in patients of ≥65 years old and to analyze whether in patients with AECOPD and pneumonia within a short interval, the same isolate caused both episodes. This laboratory-based study was performed between 2005 and 2008. Pneumococcal isolates from episodes of pneumonia (
n
= 401) and AECOPD (
n
= 398), matched one-to-one by date of isolation, were characterized. The serotypes and genotypes of other pneumococcal isolates causing pneumonia and AECOPD in the same patient were compared. In patients with pneumonia, COPD as an underlying disease was not associated with more-drug-resistant pneumococci. In contrast, isolates causing AECOPD showed higher rates of resistance than those causing pneumonia. Serotypes 1, 3, and 7F were more frequent in pneumonia. The same pneumococcus was involved in 25.7% (9/35 patients) of patients with two consecutive AECOPD episodes but in only 6.3% (2/32 patients) of COPD patients with pneumonia and exacerbation (Fisher's exact test;
P
= 0.047). Less invasive serotypes were isolated more often in AECOPD and were more resistant to antimicrobials. The presence of a specific pneumococcal serotype in AECOPD does not predict the etiology of subsequent pneumonia.
Pharmacokinetics of Anidulafungin in Pleural Fluid during the Treatment of a Patient with Candida Empyema
Authors: Moriyama Brad , Ditullio Marisa , Wilson Eleanor , Henning Stacey A. , Penzak Scott R. , Danner Robert L. , Pennick Gennethel , Rinaldi Michael G. , Zelazny Adrian M. , Gea-Banacloche Juan , Barrett A. John , Walsh Thomas J. 
Published: March 2011

ABSTRACT

Candida
empyema is a serious complication of disseminated candidiasis. However, little is known about the intrapleural pharmacokinetics of echinocandins. We report the penetration of anidulafungin into the pleural fluid of a patient with
Candida tropicalis
empyema. The anidulafungin ratio for the area under the concentration-time curve from 0 h to the last measurement between pleural fluid and serum values was only 0.125 (12.5%), with pleural fluid concentrations ranging between 0.67 and 0.88 μg/ml.
PME-1, an Extended-Spectrum β-Lactamase Identified in Pseudomonas aeruginosa
Authors: Tian Guo-Bao , Adams-Haduch Jennifer M. , Bogdanovich Tatiana , Wang Hong-Ning , Doi Yohei 
Published: March 2011

ABSTRACT

A novel extended-spectrum β-lactamase (ESBL) was identified in a
Pseudomonas aeruginosa
clinical isolate obtained from a patient admitted to a hospital in Pennsylvania in 2008. The patient had a prolonged hospitalization in a hospital in Dubai, United Arab Emirates, before being transferred to the United States. The novel ESBL, designated PME-1 (

P

seudo

m

onas aeruginosa
E
SBL 1), is a molecular class A, Bush-Jacoby-Medeiros group 2be enzyme and shared 50, 43, and 41% amino acid identity with the L2 β-lactamase of
Stenotrophomonas maltophilia
, CTX-M-9, and KPC-2, respectively. PME-1 conferred clinically relevant resistance to ceftazidime, cefotaxime, cefepime, and aztreonam in
P. aeruginosa
PAO1 but not to carbapenems. Purified PME-1 showed good hydrolytic activity against ceftazidime, cefotaxime, and aztreonam, while activity against carbapenems and cefepime could not be measured. PME-1 was inhibited well by β-lactamase inhibitors, including clavulanic acid, sulbactam, and tazobactam. The
bla
PME-1
gene was carried by an approximately 9-kb plasmid and flanked by tandem IS
CR24
elements.
Use of a Selective Inhibitor To Define the Chemotherapeutic Potential of the Plasmodial Hexose Transporter in Different Stages of the Parasite's Life Cycle
Authors: Slavic Ksenija , Delves Michael J. , Prudêncio Miguel , Talman Arthur M. , Straschil Ursula , Derbyshire Elvira T. , Xu Zhengyao , Sinden Robert E. , Mota Maria M. , Morin Christophe , Tewari Rita , Krishna Sanjeev , Staines Henry M. 
Published: March 2011

ABSTRACT

During blood infection, malarial parasites use
d
-glucose as their main energy source. The
Plasmodium falciparum
hexose transporter (PfHT), which mediates the uptake of
d
-glucose into parasites, is essential for survival of asexual blood-stage parasites. Recently, genetic studies in the rodent malaria model,
Plasmodium berghei
, found that the orthologous hexose transporter (PbHT) is expressed throughout the parasite's development within the mosquito vector, in addition to being essential during intraerythrocytic development. Here, using a
d
-glucose-derived specific inhibitor of plasmodial hexose transporters, compound 3361, we have investigated the importance of
d
-glucose uptake during liver and transmission stages of
P. berghei
. Initially, we confirmed the expression of PbHT during liver stage development, using a green fluorescent protein (GFP) tagging strategy. Compound 3361 inhibited liver-stage parasite development, with a 50% inhibitory concentration (IC
50
) of 11 μM. This process was insensitive to the external
d
-glucose concentration. In addition, compound 3361 inhibited ookinete development and microgametogenesis, with IC
50
s in the region of 250 μM (the latter in a
d
-glucose-sensitive manner). Consistent with our findings for the effect of compound 3361 on vector parasite stages, 1 mM compound 3361 demonstrated transmission blocking activity. These data indicate that novel chemotherapeutic interventions that target PfHT may be active against liver and, to a lesser extent, transmission stages, in addition to blood stages.
Priming of Protective Anti-Listeria monocytogenes Memory CD8+T Cells Requires a Functional SecA2 Secretion System
Authors: Rahmoun Massilva , Gros Marilyn , Campisi Laura , Bassand Delphine , Lazzari Anne , Massiera Christophe , Narni-Mancinelli Emilie , Gounon Pierre , Lauvau Grégoire 
Published: March 2011

ABSTRACTThe SecA2 auxiliary secretion system of Gram-positive bacteria promotes the export of virulence proteins essential for colonization of the host in the case of bothMycobacterium tuberculosisandListeria monocytogenes, two intracellular bacteria causing diseases in humans. We and others have demonstrated that this secretion system is also linked to the onset of long-term CD8+T cell-mediated protective immunity in mice. In the case ofL. monocytogenes, expression of SecA2 inside the cytosol of infected cells correlates with the generation of CCL3-secreting memory CD8+T cells that are required for protection against secondary challenge with wild-type (wt)L. monocytogenes.Since the SecA2 ATPase is well conserved among Gram-positive pathogenic bacteria, we hypothesized that SecA2 itself bears evolutionarily conserved motifs recognized by cytosolic pattern recognition receptors, leading to signaling events promoting the differentiation of CCL3+memory CD8+T cells. To test this possibility, we generated a stableL. monocytogeneschromosomal mutant that expressed a SecA2 ATPase bearing a mutated nucleotide binding site (NBS). Similarly to a SecA2 deletion mutant, the NBS mutant exhibited rough colonies, a bacterial chaining phenotype, an impaired protein secretion profile, andin vivovirulence in comparison to wtL. monocytogenes. Importantly, mice immunized with the SecA2 NBS mutant were not protected against secondary infection with wtL. monocytogenesand did not develop CCL3+memory CD8+T cells. NBS mutant and wt SecA2 proteins were expressed to comparable extents by bacteria, suggesting that SecA2 itself is unlikely to promote the induction of these cells. Rather, one or several of the SecA2 substrate proteins released inside the cytosol of infected cells may be involved.
Role of the Accessory Gene Regulator
agr
in Community-Associated Methicillin-Resistant Staphylococcus aureus Pathogenesis
Authors: Cheung Gordon Y. C. , Wang Rong , Khan Burhan A. , Sturdevant Daniel E. , Otto Michael 
Published: March 2011

ABSTRACT

The molecular basis underlying the pathogenic success of community-associated methicillin-resistant
Staphylococcus aureus
(CA-MRSA) is not completely understood, but differential gene expression has been suggested to account at least in part for the high virulence of CA-MRSA strains. Here, we show that the
agr
gene regulatory system has a crucial role in the development of skin infections in the most prevalent CA-MRSA strain USA300. Importantly, our data indicate that this is due to discrepancies between the
agr
regulon of CA-MRSA and those of hospital-associated MRSA and laboratory strains. In particular,
agr
regulation in strain USA300 led to exceptionally strong expression of toxins and exoenzymes, upregulation of fibrinogen-binding proteins, increased capacity to bind fibrinogen, and increased expression of methicillin resistance genes. Our findings demonstrate that
agr
functionality is critical for CA-MRSA disease and indicate that an adaptation of the
agr
regulon contributed to the evolution of highly pathogenic CA-MRSA.
Essential Role for Neutrophils in Pathogenesis and Adaptive Immunity in Chlamydia caviae Ocular Infections
Authors: Lacy H. Marie , Bowlin Anne K. , Hennings Leah , Scurlock Amy M. , Nagarajan Uma M. , Rank Roger G. 
Published: March 2011

ABSTRACT

Trachoma, the world's leading cause of preventable blindness, is produced by chronic ocular infection with
Chlamydia trachomatis
, an obligate intracellular bacterium. While many studies have focused on immune mechanisms for trachoma during chronic stages of infection, less research has targeted immune mechanisms in primary ocular infections, events that could impact chronic responses. The goal of this study was to investigate the function of neutrophils during primary chlamydial ocular infection by using the guinea pig model of
Chlamydia caviae
inclusion conjunctivitis. We hypothesized that neutrophils help modulate the adaptive response and promote host tissue damage. To test these hypotheses, guinea pigs with primary
C. caviae
ocular infections were depleted of neutrophils by using rabbit antineutrophil antiserum, and immune responses and immunopathology were evaluated during the first 7 days of infection. Results showed that neutrophil depletion dramatically decreased ocular pathology, both clinically and histologically. The adaptive response was also altered, with increased
C. caviae
-specific IgA titers in tears and serum and decreased numbers of CD4
+
and CD8
+
T cells in infected conjunctivae. Additionally, there were changes in conjunctival chemokines and cytokines, such as increased expression of IgA-promoting interleukin-5 and anti-inflammatory transforming growth factor β, along with decreased expression of T cell-recruiting CCL5 (RANTES). This study, the first to investigate the role of neutrophils in primary chlamydial ocular infection, indicates a previously unappreciated role for neutrophils in modulating the adaptive response and suggests a prominent role for neutrophils in chlamydia-associated ocular pathology.
"Equation missing" -Functions on Quasimetric Spaces and Fixed Points for Multivalued Maps
Authors: Marín J , Romaguera S , Tirado P 
Published: March 2011

AbstractWe discuss several properties of "Equation missing"-functions in the sense of Al-Homidan et al.. In particular, we prove that the partial metric induced by any "Equation missing" weighted quasipseudometric space is a "Equation missing"-function and show that both the Sorgenfrey line and the Kofner plane provide significant examples of quasimetric spaces for which the associated supremum metric is a "Equation missing"-function. In this context we also obtain some fixed point results for multivalued maps by using Bianchini-Grandolfi gauge functions.