bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of a Multimodal Rehabilitation Program on Symptoms and Ground-Reaction Forces in Runners With Patellofemoral Pain Syndrome
Authors: Esculier Jean-Francois , Bouyer Laurent J. , Roy Jean-Sébastien 
Published: March 2015

Context:Patellofemoral pain (PFP) is one of the most frequent running-related injuries. However, few interventions taking into consideration the specificity of running have been shown to be effective in runners with PFP.Objective:To evaluate the effects of a multimodal rehabilitation program including lower-limb-strengthening/motor-control exercises, advice on running biomechanics, and symptoms management on symptoms, strength, and ground-reaction forces in runners with PFP.Design:Pre- to post- quasi-experimental.Setting:Gait-analysis laboratory and private physical therapy clinic.Participants:21 runners with PFP (34.1 ± 6.0 y old, symptoms duration 38.1 ± 45.5 mo).Intervention:An 8-wk multimodal rehabilitation program including lower-limb- and core-strengthening and motor-control exercises, as well as advice on running gait and symptoms management.Main Outcome Measures:The Activities of Daily Living Scale of the Knee Outcome Survey (KOS-ADLS) questionnaire and visual analog scales for usual pain (VAS-U), worst pain (VAS-W), and pain during running (VAS-R) were used to assess changes in symptoms and function. Vertical ground-reaction forces (VGRF) during running and lower-limb isometric strength were also measured.Results:Statistically and clinically significant improvements (P < .001) were reported on KOS-ADLS (+17.8 pts), VAS-U (−19.2 pts), VAS-W (−28.7 pts), and VAS-R (−32.2 pts) after the intervention. No significant changes in isometric strength were observed. The instantaneous vertical loading rate was decreased after the intervention (P = .002), and this reduction was correlated with changes in KOS-ADLS scores (P = .028).Conclusion:This multimodal intervention was successful in reducing pain and improving function of runners with PFP. However, no significant changes in lower-limb strength were observed. It appears that changes in VGRF combined with appropriate training advice could explain the clinical outcomes.
Inhibition of Protein Synthesis and Malaria Parasite Development by Drug Targeting of Methionyl-tRNA Synthetases
Authors: Hussain Tahir , Yogavel Manickam , Sharma Amit 
Published: March 2015

ABSTRACT

Aminoacyl-tRNA synthetases (aaRSs) are housekeeping enzymes that couple cognate tRNAs with amino acids to transmit genomic information for protein translation. The
Plasmodium falciparum
nuclear genome encodes two
P. falciparum
methionyl-tRNA synthetases (PfMRS), termed PfMRS
cyt
and PfMRS
api
. Phylogenetic analyses revealed that the two proteins are of primitive origin and are related to heterokonts (PfMRS
cyt
) or proteobacteria/primitive bacteria (PfMRS
api
). We show that PfMRS
cyt
localizes in parasite cytoplasm, while PfMRS
api
localizes to apicoplasts in asexual stages of malaria parasites. Two known bacterial MRS inhibitors, REP3123 and REP8839, hampered
Plasmodium
growth very effectively in the early and late stages of parasite development. Small-molecule drug-like libraries were screened against modeled PfMRS structures, and several “hit” compounds showed significant effects on parasite growth. We then tested the effects of the hit compounds on protein translation by labeling nascent proteins with
35
S-labeled cysteine and methionine. Three of the tested compounds reduced protein synthesis and also blocked parasite growth progression from the ring stage to the trophozoite stage. Drug docking studies suggested distinct modes of binding for the three compounds, compared with the enzyme product methionyl adenylate. Therefore, this study provides new targets (PfMRSs) and hit compounds that can be explored for development as antimalarial drugs.
Moraxella catarrhalis AcrAB-OprM Efflux Pump Contributes to Antimicrobial Resistance and Is Enhanced during Cold Shock Response
Authors: Spaniol Violeta , Bernhard Sara , Aebi Christoph 
Published: March 2015

ABSTRACT

Moraxella catarrhalis
is a common pathogen of the human respiratory tract. Multidrug efflux pumps play a major role in antibiotic resistance and virulence in many Gram-negative organisms. In the present study, the role of the AcrAB-OprM efflux pump in antibiotic resistance was investigated by constructing mutants that lack the
acrA
,
acrB
, and
oprM
genes in
M. catarrhalis
strain O35E. We observed a moderate (1.5-fold) decrease in the MICs of amoxicillin and cefotaxime and a marked (4.7-fold) decrease in the MICs of clarithromycin for
acrA
,
acrB
, and
oprM
mutants in comparison with the wild-type O35E strain. Exposure of the
M. catarrhalis
strains O35E and 300 to amoxicillin triggered an increased transcription of all AcrAB-OprM pump genes, and exposure of strains O35E, 300, and 415 to clarithromycin enhanced the expression of
acrA
and
oprM
mRNA. Inactivation of the AcrAB-OprM efflux pump genes demonstrated a decreased ability to invade epithelial cells compared to the parental strain, suggesting that
acrA
,
acrB
, and
oprM
are required for efficient invasion of human pharyngeal epithelial cells. Cold shock increases the expression of AcrAB-OprM efflux pump genes in all three
M. catarrhalis
strains tested. Increased expression of AcrAB-OprM pump genes after cold shock leads to a lower accumulation of Hoechst 33342 (H33342), a substrate of AcrAB-OprM efflux pumps, indicating that cold shock results in increased efflux activity. In conclusion, the AcrAB-OprM efflux pump appears to play a role in the antibiotic resistance and virulence of
M. catarrhalis
and is involved in the cold shock response.
Epoxy-α-Lapachone Has
In Vitro
and
In Vivo
Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite
Authors: Souza-Silva Franklin , Bourguignon Saulo Cabral , Pereira Bernardo Acácio Santini , Côrtes Luzia Monteiro de Castro , de Oliveira Luiz Filipe Gonçalves , Henriques-Pons Andrea , Finkelstein Lea Cysne , Ferreira Vitor Francisco , Carneiro Paula Fernandes , de Pinho Rosa Teixeira , Caffarena Ernesto Raul , Alves Carlos Roberto 
Published: March 2015

ABSTRACT

Leishmania
(
Leishmania
)
amazonensis
is a protozoan that causes infections with a broad spectrum of clinical manifestations. The currently available chemotherapeutic treatments present many problems, such as several adverse side effects and the development of resistant strains. Natural compounds have been investigated as potential antileishmanial agents, and the effects of epoxy-α-lapachone on
L
. (
L
.)
amazonensis
were analyzed in the present study. This compound was able to cause measurable effects on promastigote and amastigote forms of the parasite, affecting plasma membrane organization and leading to death after 3 h of exposure. This compound also had an effect in experimentally infected BALB/c mice, causing reductions in paw lesions 6 weeks after treatment with 0.44 mM epoxy-α-lapachone (mean lesion area, 24.9 ± 2.0 mm
2
), compared to untreated animals (mean lesion area, 30.8 ± 2.6 mm
2
) or animals treated with Glucantime (mean lesion area, 28.3 ± 1.5 mm
2
). In addition, the effects of this compound on the serine proteinase activities of the parasite were evaluated. Serine proteinase-enriched fractions were extracted from both promastigotes and amastigotes and were shown to act on specific serine proteinase substrates and to be sensitive to classic serine proteinase inhibitors (phenylmethylsulfonyl fluoride, aprotinin, and antipain). These fractions were also affected by epoxy-α-lapachone. Furthermore,
in silico
simulations indicated that epoxy-α-lapachone can bind to oligopeptidase B (OPB) of
L
. (
L
.)
amazonensis
, a serine proteinase, in a manner similar to that of antipain, interacting with an S1 binding site. This evidence suggests that OPB may be a potential target for epoxy-α-lapachone and, as such, may be related to the compound's effects on the parasite.
Impact of Extended-Spectrum β-Lactamase Production on Treatment Outcomes of Acute Pyelonephritis Caused by Escherichia coli in Patients without Health Care-Associated Risk Factors
Authors: Park Sun Hee , Choi Su-Mi , Lee Dong-Gun , Cho Sung-Yeon , Lee Hyo-Jin , Choi Jae-ki , Choi Jung-Hyun , Yoo Jin-Hong 
Published: March 2015

ABSTRACT

Extended-spectrum β-lactamase-producing
Escherichia coli
(ESBL-EC) is increasingly identified as a cause of acute pyelonephritis (APN) among patients without recent health care contact, i.e., community-associated APN. This case-control study compared 75 cases of community-associated ESBL-EC APN (CA-ESBL) to 225 controls of community-associated non-ESBL-EC APN (CA-non-ESBL) to identify the risk factors for ESBL-EC acquisition and investigate the impact of ESBL on the treatment outcomes of community-associated APN (CA-APN) caused by
E. coli
at a Korean hospital during 2007 to 2013. The baseline characteristics were similar between the cases and controls; the risk factors for ESBL-EC were age (>55 years), antibiotic use within the previous year, and diabetes with recurrent APN. The severity of illness did not differ between CA-ESBL and CA-non-ESBL (Acute Physiology and Chronic Health Evaluation [APACHE] II scores [mean ± standard deviation], 7.7 ± 5.9 versus 6.4 ± 5.3;
P
= 0.071). The proportions of clinical (odds ratio [OR], 1.76; 95% confidence interval [CI], 0.57 to 5.38;
P
= 0.323) and microbiological (OR, 1.16; 95% CI, 0.51 to 2.65;
P
= 0.730) cures were similar, although the CA-ESBL APN patients were less likely to receive appropriate antibiotics within 48 h. A multivariable Cox proportional hazards analysis of the prognostic factors for CA-APN caused by
E. coli
showed that ESBL production was not a significant factor for clinical (hazard ratio [HR], 0.39; 95% CI, 0.12 to 1.30;
P
= 0.126) or microbiological (HR, 0.49; 95% CI, 0.21 to 1.12;
P
= 0.091) failure. The estimates did not change after incorporating weights calculated using propensity scores for acquiring ESBL-EC. Therefore, ESBL production did not negatively affect treatment outcomes among patients with community-associated
E. coli
APN.
Bacterial Secretions of Nonpathogenic Escherichia coli Elicit Inflammatory Pathways: a Closer Investigation of Interkingdom Signaling
Authors: Zargar Amin , Quan David N. , Carter Karen K. , Guo Min , Sintim Herman O. , Payne Gregory F. , Bentley William E. 
Published: March 2015

ABSTRACT

There have been many studies on the relationship between nonpathogenic bacteria and human epithelial cells; however, the bidirectional effects of the secretomes (secreted substances in which there is no direct bacterium-cell contact) have yet to be fully investigated. In this study, we use a transwell model to explore the transcriptomic effects of bacterial secretions from two different nonpathogenic
Escherichia coli
strains on the human colonic cell line HCT-8 using next-generation transcriptome sequencing (RNA-Seq).
E. coli
BL21 and W3110, while genetically very similar (99.1% homology), exhibit key phenotypic differences, including differences in their production of macromolecular structures (e.g., flagella and lipopolysaccharide) and in their secretion of metabolic byproducts (e.g., acetate) and signaling molecules (e.g., quorum-sensing autoinducer 2 [AI-2]). After analysis of differential epithelial responses to the respective secretomes, this study shows for the first time that a nonpathogenic bacterial secretome activates the NF-κB-mediated cytokine-cytokine receptor pathways while also upregulating negative-feedback components, including the NOD-like signaling pathway. Because of AI-2's relevance as a bacterium-bacterium signaling molecule and the differences in its secretion rates between these strains, we investigated its role in HCT-8 cells. We found that the expression of the inflammatory cytokine interleukin 8 (IL-8) responded to AI-2 with a pattern of rapid upregulation before subsequent downregulation after 24 h. Collectively, these data demonstrate that secreted products from nonpathogenic bacteria stimulate the transcription of immune-related biological pathways, followed by the upregulation of negative-feedback elements that may serve to temper the inflammatory response.

IMPORTANCE
The symbiotic relationship between the microbiome and the host is important in the maintenance of human health. There is a growing need to further understand the nature of these relationships to aid in the development of homeostatic probiotics and also in the design of novel antimicrobial therapeutics. To our knowledge, this is the first global-transcriptome study of bacteria cocultured with human epithelial cells in a model to determine the transcriptional effects of epithelial cells in which epithelial and bacterial cells are allowed to “communicate” with each other only through diffusible small molecules and proteins. By beginning to demarcate the direct and indirect effects of bacteria on the gastrointestinal (GI) tract, two-way interkingdom communication can potentially be mediated between host and microbe.
Regulation of Plasmodium yoelii Oocyst Development by Strain- and Stage-Specific Small-Subunit rRNA
Authors: Qi Yanwei , Zhu Feng , Eastman Richard T. , Fu Young , Zilversmit Martine , Pattaradilokrat Sittiporn , Hong Lingxian , Liu Shengfa , McCutchan Thomas F. , Pan Weiqing , Xu Wenyue , Li Jian , Huang Fusheng , Su Xin-zhuan 
Published: March 2015

ABSTRACT

One unique feature of malaria parasites is the differential transcription of structurally distinct rRNA (rRNA) genes at different developmental stages: the A-type genes are transcribed mainly in asexual stages, whereas the S-type genes are expressed mostly in sexual or mosquito stages. Conclusive functional evidence of different rRNAs in regulating stage-specific parasite development, however, is still absent. Here we performed genetic crosses of
Plasmodium yoelii
parasites with one parent having an oocyst development defect (ODD) phenotype and another producing normal oocysts to identify the gene(s) contributing to the ODD. The parent with ODD—characterized as having small oocysts and lacking infective sporozoites—was obtained after introduction of a plasmid with a green fluorescent protein gene into the parasite genome and subsequent passages in mice. Quantitative trait locus analysis of genome-wide microsatellite genotypes of 48 progeny from the crosses linked an ~200-kb segment on chromosome 6 containing one of the S-type genes (D-type small subunit rRNA gene [
D-ssu
]) to the ODD. Fine mapping of the plasmid integration site, gene expression pattern, and gene knockout experiments demonstrated that disruption of the
D-ssu
gene caused the ODD phenotype. Interestingly, introduction of the
D-ssu
gene into the same parasite strain (self), but not into a different subspecies, significantly affected or completely ablated oocyst development, suggesting a stage- and subspecies (strain)-specific regulation of oocyst development by
D-ssu
. This study demonstrates that
P. yoelii
D-ssu
is essential for normal oocyst and sporozoite development and that variation in the
D-ssu
sequence can have dramatic effects on parasite development.

IMPORTANCE
Malaria parasites are the only known organisms that express structurally distinct rRNA genes at different developmental stages. The differential expression of these genes suggests that they play unique roles during the complex life cycle of the parasites. Conclusive functional proof of different rRNAs in regulating parasite development, however, is still absent or controversial. Here we functionally demonstrate for the first time that a stage-specifically expressed D-type small-subunit rRNA gene (
D-ssu
) is essential for oocyst development of the malaria parasite
Plasmodium yoelii
in the mosquito. This study also shows that variations in
D-ssu
sequence and/or the timing of transcription may have profound effects on parasite oocyst development. The results show that in addition to protein translation, rRNAs of malaria parasites also regulate parasite development and differentiation in a strain-specific manner, which can be explored for controlling parasite transmission.
New Method for the Orthogonal Labeling and Purification of Toxoplasma gondii Proteins While Inside the Host Cell
Authors: Wier Gregory M. , McGreevy Erica M. , Brown Mark J. , Boyle Jon P. 
Published: March 2015

ABSTRACT

Toxoplasma gondii
is an obligate intracellular protozoan parasite that is capable of causing severe disease in immunocompromised humans. How T. gondii is able to modulate the host cell to support itself is still poorly understood. Knowledge pertaining to the host-parasite interaction could be bolstered by developing a system to specifically label parasite proteins while the parasite grows inside the host cell. For this purpose, we have created a strain of T. gondii that expresses a mutant Escherichia coli methionyl-tRNA synthetase (MetRS
NLL
) that allows methionine tRNA to be loaded with the azide-containing methionine analog azidonorleucine (Anl). Anl-containing proteins are susceptible to a copper-catalyzed “click” reaction to attach affinity tags for purification or fluorescent tags for visualization. The MetRS
NLL
-Anl system labels nascent T. gondii proteins in an orthogonal fashion, labeling proteins only in MetRS
NLL
-expressing parasites. This system should be useful for nonradioactive pulse-chase studies and purification of nascently translated proteins. Although this approach allows labeling of a diverse array of parasite proteins, secreted parasite proteins appear to be only minimally labeled in MetRS
NLL
-expressing T. gondii. The minimal labeling of secreted proteins is likely a consequence of the selective charging of the initiator tRNA (and not the elongator methionine tRNA) by the heterologously expressed bacterial MetRS.

IMPORTANCE
Studying how T. gondii modifies the host cell to permit its survival is complicated by the complex protein environment of the host cell. The approach presented in this article provides the first method for specific labeling of T. gondii proteins while the parasite grows inside the host cell. We show that this approach is useful for pulse-chase labeling of parasite proteins during
in vitro
growth. It should also be applicable during
in vivo
infections and in other apicomplexan parasites, including Plasmodium spp.
Cervical cancer screening and HPV vaccine acceptability among rural and urban women in Kilimanjaro Region, Tanzania
Authors: Cunningham Melissa S , Skrastins Emily , Fitzpatrick Ryan , Jindal Priya , Oneko Olola , Yeates Karen , Booth Christopher M , Carpenter Jennifer , Aronson Kristan J 
Published: March 2015

ObjectiveTo determine cervical cancer screening coverage and the knowledge, attitudes and barriers toward screening tests among women in rural and urban areas of Tanzania, as well as explore how they view the acceptability of the HPV vaccine and potential barriers to vaccination.SettingA cross-sectional study using interview-administered questionnaires was conducted using multistage random sampling within urban and rural areas in Kilimanjaro Region, Tanzania.ParticipantsWomen aged 18–55 were asked to participate in the survey. The overall response rate was 97.5%, with a final sample of 303 rural and 272 urban dwelling women.Primary and secondary outcome measuresDescriptive and simple test statistics were used to compare across rural and urban strata. Multivariate logistic regression models were used to estimate ORs and 95% CIs.ResultsMost women (82%) reported they had heard of cervical cancer, while self-reported cervical cancer screening among women was very low (6%). In urban areas, factors associated with screening were: older age (OR=4.14, 95% CI 1.86 to 9.24 for ages 40–49, and OR=8.38, 95% CI 2.10 to 33.4 for >50 years), having health insurance (OR=4.15, 95% CI 1.52 to 11.4), and having knowledge about cervical cancer (OR=5.81, 95% CI 1.58 to 21.4). In contrast, among women residing in rural areas, only condom use (OR=6.44, 95% CI 1.12 to 37.1) was associated with screening. Women from both rural and urban areas had low vaccine-related knowledge; however, most indicated they would be highly accepting if it were readily available (93%).ConclusionsThe current proportion of women screened for cervical cancer is very low in Kilimanjaro Region, and our study has identified several modifiable factors that could be addressed to increase screening rates. Although best implemented concurrently, the availability of prophylactic vaccination for girls may provide an effective means of prevention if they are unable to access screening in the future.
VAlidation of an 8-item-questionnaire predictive for a positive caLprotectin tEst and Real-life implemenTation in primary care to reduce diagnostic delay in inflammatory bowel disease (ALERT): protocol for a prospective diagnostic study
Authors: Hasler Susann , Zahnd Nadine , Müller Salomé , Vavricka Stephan , Rogler Gerhard , Tandjung Ryan , Rosemann Thomas 
Published: March 2015

IntroductionDiagnosis of inflammatory bowel disease (IBD) in primary healthcare is challenging and often associated with a considerable diagnostic delay. This delay is associated with worse disease progression and outcomes. Although testing for faecal calprotectin is a useful screening tool to identify patients who need endoscopy for IBD, the widespread use may not be appropriate due to the low prevalence of patients with IBD among all patients attending a general practitioner (GP) with gastrointestinal symptoms. To increase the appropriate application of the faecal calprotectin test, an 8-item questionnaire, the CalproQuest, has been developed to increase pretest probability for a positive test result.Methods and analysisThis is a prospective diagnostic trial. The study consists of two independent and consecutive parts A and B, conducted by gastroenterologists (A) and GPs (B), respectively. Patients included in part A are referred to the gastroenterologist for any endoscopic evaluation. Patients included in part B present at their GP because of ongoing unspecific gastrointestinal symptoms (abdominal pain, bloating, stool irregularities, diarrhoea) for at least 2 weeks. CalproQuest consists of four main and four secondary questions specific for IBD; it is considered positive if ≥2 main criteria are answered positively or one main criterion and two secondary criteria are answered positively. In part A, the sensitivity and specificity of CalproQuest for stool calprotectin levels ≥50 μg/g faeces and for positive IBD diagnosis will be investigated. In part B, the feasibility of CalproQuest in daily primary healthcare practice will be assessed.Ethics and disseminationThe study protocol was approved by the Ethics Committee of the Kanton Zurich (reference KEK-ZH-number 2013-0516). The results will be published in a peer-reviewed journal and shared with the worldwide medical community.Trial registration numberISRCTN66310845.
Predicting subseismic fracture density and orientation in the Gorm Field, Danish North Sea
Authors: Freeman Brett , Quinn David J. , Dillon Cathal G. , Arnhild Michael , Jaarsma Bastiaan 
Published: March 2015

Abstract
The chalk reservoir of the Gorm Field, southern North Sea is dome-shaped and faulted owing to a combination of salt diapirism and regional east–west extension. Fractures developed in the structure considerably enhance permeability. The dataset discussed here records fractures in horizontal wells from more than 10 km of image logs and provides a special opportunity to test theoretical models of fracture development with quantitative observations. In an effort to forecast fracture density and fracture orientation, we have estimated the strains in the structure using an elastic dislocation model that incorporates mechanical boundaries in the form of the tectono-stratigraphic interface with salt and tectonic faults. More than 50% of the angular differences between poles to the planes of simulated and observed fractures are less than 30°; 75% are less than 45°. Relative strain magnitude appears to be a useful indicator of fracture density. At the field scale, small strain magnitudes correspond with small non-zero fracture densities and relatively large strain magnitudes correspond with high fracture densities.