bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rifampin Induces Hydroxyl Radical Formation in Mycobacterium tuberculosis
Authors: Piccaro Giovanni , Pietraforte Donatella , Giannoni Federico , Mustazzolu Alessandro , Fattorini Lanfranco 
Published: October 2014

ABSTRACT

The antituberculosis (anti-TB) drug rifampin (RIF) binds to the beta subunit of the RNA polymerase (RpoB) of
Mycobacterium tuberculosis
, but the bactericidal responses triggered after target interaction are not known. To evaluate whether RIF induced an oxidative burst, lysates of RIF-treated
M. tuberculosis
were tested for determination of reactive oxygen species (ROS) by the electron paramagnetic resonance (EPR) technique using 1-hydroxy-3-carboxy-pyrrolidine (CPH) and 5,5-dimethyl-1-pyrrolidine-
N
-oxide (DMPO) as spin traps.
M. tuberculosis
killing by RIF stimulated an increase in the rate of formation of the CPH radical (CP·). Lysate pretreatment with the O
2
·
−
and ·OH scavengers superoxide dismutase (SOD) and thiourea (THIO), respectively, or with the metal chelator diethylene triamine pentaacetic acid (DTPA) inhibited CP· formation, arguing in favor of a metal-catalyzed ROS response. Formation of CP· did not increase following treatment of RIF-resistant strains with RIF, indicating that the ROS were induced after RpoB binding. To identify the ROS formed, lysates of RIF-treated bacilli were incubated with DMPO, a spin trap specific for ·OH and O
2
·
−
, with or without pretreatment with SOD, catalase, THIO, or DTPA. Superoxide dismutase, catalase, and THIO decreased formation of the DMPO-OH adduct, and SOD plus DTPA completely suppressed it, suggesting that RIF activated metal-dependent O
2
·
−
-mediated mechanisms producing ·OH inside tubercle bacilli. The finding that the metal chelator DTPA reduced the bactericidal activity of RIF supported the possibility that ·OH was generated through these mechanisms and that it participated at least in part in
M. tuberculosis
killing by the drug.
Heterogeneity of
mprF
Sequences in Methicillin-Resistant Staphylococcus aureus Clinical Isolates: Role in Cross-Resistance between Daptomycin and Host Defense Antimicrobial Peptides
Authors: Bayer Arnold S. , Mishra Nagendra N. , Sakoulas George , Nonejuie Poochit , Nast Cynthia C. , Pogliano Joseph , Chen Kuan-Tsen , Ellison Steven N. , Yeaman Michael R. , Yang Soo-Jin 
Published: October 2014

ABSTRACT

Over the past several years, single-nucleotide polymorphisms (SNPs) within the
mprF
open reading frame (ORF) have been proposed to be associated with a gain-of-function phenotype in terms of daptomycin (DAP) nonsusceptibility (referred to as daptomycin resistance [DAP-R] herein for ease of presentation) in
Staphylococcus aureus
. We investigated the frequencies of SNPs within the
mprF
ORF and the relationships of such SNPs to cross-resistance between DAP and cationic host defense peptides (HDPs). Thirty-five well-characterized, unique DAP-susceptible (DAP-S) and DAP-R methicillin-resistant
S. aureus
(MRSA) isolates of the clonal complex 5 genotype were used. In addition to
mprF
SNPs and DAP-HDP cross-resistance, several other key genotypic and phenotypic metrics often associated with DAP-R were delineated, as follows: (i)
mprF
expression, (ii) membrane phospholipid content, (iii) positive surface charge, (iv) DAP binding, and (v) cell wall thickness profiles. A number of DAP-S strains (MICs of ≤1 μg/ml) exhibited
mprF
SNPs, occasionally with high-level
mprF
sequence variation from the genotype reference strain. However, none of these SNPs were localized to well-chronicled
mprF
hot spot locations associated with DAP-R in
S. aureus
. In contrast, all 8 DAP-R isolates demonstrated SNPs within such known
mprF
hot spots. Moreover, only the DAP-R strains showed MprF gain-of-function phenotypes, enhanced
mprF
expression, higher survival against two prototypical HDPs, and reduced DAP binding. Although a heterogenous array of
mprF
SNPs were often found in DAP-S strains, only selected hot spot SNPs, combined with concurrent
mprF
dysregulation, were associated with the DAP-R phenotype.
Triazole-Based Compound as a Candidate To Develop Novel Medicines To Treat Toxoplasmosis
Authors: Dzitko Katarzyna , Paneth Agata , Plech Tomasz , Pawełczyk Jakub , Węglińska Lidia , Paneth Piotr 
Published: October 2014

ABSTRACT

This article reports anti-
Toxoplasma gondii
activity of 3-(thiophen-2-yl)-1,2,4-triazole-5-thione. The compound displayed significant and reproducible antiparasitic effects at nontoxic concentrations for the host cells, with an experimentally determined 50% inhibitory concentration (IC
50
) at least 30 times better than that of the known chemotherapeutic agent sulfadiazine. Purine nucleoside phosphorylase was defined as the probable target for anti-
Toxoplasma
activity of the tested compound. These results provide the foundation for future work to develop a new class of medicines to better treat toxoplasmosis.
Antibacterial Properties of Magnesium
In Vitro
and in an
In Vivo
Model of Implant-Associated Methicillin-Resistant Staphylococcus aureus Infection
Authors: Li Yang , Liu Guangwang , Zhai Zanjing , Liu Lina , Li Haowei , Yang Ke , Tan Lili , Wan Peng , Liu Xuqiang , Ouyang Zhengxiao , Yu Zhifeng , Tang Tingting , Zhu Zhenan , Qu Xinhua , Dai Kerong 
Published: October 2014

ABSTRACT

Periprosthetic infection remains a challenging clinical complication. We investigated the antibacterial properties of pure (99.9%) magnesium (Mg)
in vitro
and in an
in vivo
rat model of implant-related infection. Mg was highly effective against methicillin-resistant
Staphylococcus aureus
-induced osteomyelitis and improved new peri-implant bone formation. Bacterial
icaA
and
agr
RNAIII transcription levels were also assessed to characterize the mechanism underlying the antibacterial properties of the Mg implant.
Mycoplasma pneumoniae Modulates STAT3-STAT6/EGFR-FOXA2 Signaling To Induce Overexpression of Airway Mucins
Authors: Hao Yonghua , Kuang Zhizhou , Jing Jia , Miao Jinfeng , Mei Li Yu , Lee Ryan J. , Kim Susie , Choe Shawn , Krause Duncan C. , Lau Gee W. 
Published: October 2014

ABSTRACT

Aberrant mucin secretion and accumulation in the airway lumen are clinical hallmarks associated with various lung diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis.
Mycoplasma pneumoniae
, long appreciated as one of the triggers of acute exacerbations of chronic pulmonary diseases, has recently been reported to promote excessive mucus secretion. However, the mechanism of mucin overproduction induced by
M. pneumoniae
remains unclear. This study aimed to determine the mechanism by which
M. pneumoniae
induces mucus hypersecretion by using
M. pneumoniae
infection of mouse lungs, human primary bronchial epithelial (NHBE) cells cultured at the air-liquid interface, and the conventionally cultured airway epithelial NCI-H292 cell line. We demonstrated that
M. pneumoniae
induced the expression of mucins MUC5AC and MUC5B by activating the STAT6-STAT3 and epidermal growth factor receptor (EGFR) signal pathways, which in turn downregulated FOXA2, a transcriptional repressor of mucin biosynthesis. The upstream stimuli of these pathways, including interleukin-4 (IL-4), IL-6, and IL-13, increased dramatically upon exposure to
M. pneumoniae
. Inhibition of the STAT6, STAT3, and EGFR signaling pathways significantly restored the expression of FOXA2 and attenuated the expression of airway mucins MUC5AC and MUC5B. Collectively, these studies demonstrated that
M. pneumoniae
induces airway mucus hypersecretion by modulating the STAT/EGFR-FOXA2 signaling pathways.
Contribution of the Interaction of Streptococcus mutans Serotype
k
Strains with Fibrinogen to the Pathogenicity of Infective Endocarditis
Authors: Nomura Ryota , Otsugu Masatoshi , Naka Shuhei , Teramoto Noboru , Kojima Ayuchi , Muranaka Yoshinori , Matsumoto-Nakano Michiyo , Ooshima Takashi , Nakano Kazuhiko 
Published: October 2014

ABSTRACT

Streptococcus mutans
, a pathogen responsible for dental caries, is occasionally isolated from the blood of patients with bacteremia and infective endocarditis (IE). Our previous study demonstrated that serotype
k
-specific bacterial DNA is frequently detected in
S. mutans
-positive heart valve specimens extirpated from IE patients. However, the reason for this frequent detection remains unknown. In the present study, we analyzed the virulence of IE from
S. mutans
strains, focusing on the characterization of serotype
k
strains, most of which are positive for the 120-kDa cell surface collagen-binding protein Cbm and negative for the 190-kDa protein antigen (PA) known as SpaP, P1, antigen I/II, and other designations. Fibrinogen-binding assays were performed with 85 clinical strains classified by Cbm and PA expression levels. The Cbm
+
/PA
−
group strains had significantly higher fibrinogen-binding rates than the other groups. Analysis of platelet aggregation revealed that SA31, a Cbm
+
/PA
−
strain, induced an increased level of aggregation in the presence of fibrinogen, while negligible aggregation was induced by the Cbm-defective isogenic mutant SA31CBD. A rat IE model with an artificial impairment of the aortic valve created using a catheter showed that extirpated heart valves in the SA31 group displayed a prominent vegetation mass not seen in those in the SA31CBD group. These findings could explain why Cbm
+
/PA
−
strains are highly virulent and are related to the development of IE, and the findings could also explain the frequent detection of serotype
k
DNA in
S. mutans
-positive heart valve clinical specimens.
Anaplasma marginale Superinfection Attributable to Pathogen Strains with Distinct Genomic Backgrounds
Authors: Vallejo Esquerra Eduardo , Herndon David R. , Alpirez Mendoza Francisco , Mosqueda Juan , Palmer Guy H. 
Published: October 2014

ABSTRACT

Strain superinfection occurs when a second pathogen strain infects a host already infected with a primary strain. The selective pressures that drive strain divergence, which underlies superinfection, and allow penetration of a new strain into a host population are critical knowledge gaps relevant to shifts in infectious disease epidemiology. In regions of endemicity with a high prevalence of infection, broad population immunity develops against
Anaplasma marginale
, a highly antigenically variant rickettsial pathogen, and creates strong selective pressure for emergence of and superinfection with strains that differ in their Msp2 variant repertoires. The strains may emerge either by
msp2
locus duplication and allelic divergence on an existing genomic background or by introduction of a strain with a different
msp2
allelic repertoire on a distinct genomic background. To answer this question, we developed a multilocus typing assay based on high-throughput sequencing of non-
msp2
target loci to distinguish among strains with different genomic backgrounds. The technical error level was statistically defined based on the percentage of perfect sequence matches of clones of each target locus and validated using experimental single strains and strain pairs. Testing of
A. marginale
-positive samples from tropical regions where
A. marginale
infection is endemic identified individual infections that contained unique alleles for all five targeted loci. The data revealed a highly significant difference in the number of strains per animal in the tropical regions compared to infections in temperate regions and strongly supported the hypothesis that transmission of genomically distinct
A. marginale
strains predominates in high-prevalence areas of endemicity.
Plasmid-Encoded Pgp3 Is a Major Virulence Factor for Chlamydia muridarum To Induce Hydrosalpinx in Mice
Authors: Liu Yuanjun , Huang Yumeng , Yang Zhangsheng , Sun Yina , Gong Siqi , Hou Shuping , Chen Chaoqun , Li Zhongyu , Liu Quanzhong , Wu Yimou , Baseman Joel , Zhong Guangming 
Published: October 2014

ABSTRACT

Hydrosalpinx induction in mice by
Chlamydia muridarum
infection, a model that has been used to study
C. trachomatis
pathogenesis in women, is known to depend on the cryptic plasmid that encodes eight genes designated
pgp1
to
pgp8
. To identify the plasmid-encoded pathogenic determinants, we evaluated
C. muridarum
transformants deficient in the plasmid-borne gene
pgp3
, -
4
, or -
7
for induction of hydrosalpinx.
C. muridarum
transformants with an in-frame deletion of either
pgp3
or -
4
but not -
7
failed to induce hydrosalpinx. The deletion mutant phenotype was reproduced by using transformants with premature termination codon insertions in the corresponding
pgp
genes (to minimize polar effects inherent in the deletion mutants). Pgp4 is known to regulate
pgp3
expression, while lack of Pgp3 does not significantly affect Pgp4 function. Thus, we conclude that Pgp3 is an effector virulence factor and that lack of Pgp3 may be responsible for the attenuation in
C. muridarum
pathogenicity described above. This attenuated pathogenicity was further correlated with a rapid decrease in chlamydial survival in the lower genital tract and reduced ascension to the upper genital tract in mice infected with
C. muridarum
deficient in Pgp3 but not Pgp7. The Pgp3-deficient
C. muridarum
organisms were also less invasive when delivered directly to the oviduct on day 7 after inoculation. These observations demonstrate that plasmid-encoded Pgp3 is required for
C. muridarum
survival in the mouse genital tract and represents a major virulence factor in
C. muridarum
pathogenesis in mice.
Development and validation of a questionnaire (FASH—Functional Assessment Scale for Acute Hamstring Injuries): to measure the severity and impact of symptoms on function and sports ability in patients with acute hamstring injuries
Authors: Malliaropoulos Nikos , Korakakis Vasileios , Christodoulou Dimitris , Padhiar Nat , Pyne Debasish , Giakas Giannis , Nauck Tanja , Malliaras Peter , Lohrer Heinz 
Published: October 2014

ObjectiveTo develop a condition-specific patient-reported outcome measure, the Functional Assessment Scale for Acute Hamstring Injuries (FASH), de novo in three languages, following distinct and rigorous methodology for content generation, analysis and validation and to assess its psychometric properties.BackgroundTo our knowledge, there is no patient-reported functional scale specific for acute hamstring injuries.MethodsThe development of the scale followed specific guidelines, as well as de novo construction in three languages (Greek, English and German). Item generation was accomplished by selecting three different sources of items: literature review, focus group and key informant interviews. Content analysis was conducted by an expert committee. The 21 items selected as appropriate were tested through a structured content analytic method and item-content validity coefficient, and 10 were retained for the FASH. The validation and assessment of its psychometric properties followed theConsensus-based Standards for the selection of health status Measurement Instruments (COSMIN) recommendations to ensure quality, in a convenience sample of 140 participants.ResultsThe face validity was adequate and tested by expert committees, authors and participants. Content validity was characterised as well addressed and conducted independently by experts and through specific content validation procedures. The dimensionality analysis indicated a one-factor solution explaining the 95.8% of total variance. Known group validity was demonstrated by significant differences between patients and controls (p<0.001). The FASH exhibited very good test–retest reliability (intraclass correlation coefficient=0.9, p<0.001), internal consistency (α=0.98) and responsiveness (3.81 and 5.23 using baseline and pooled SD, respectively; standardised response mean (SRD)=4.68).ConclusionThis study provides initial evidence for psychometric properties of the first scale assessing hamstring injuries.
Bayesian estimation of cardiovascular autonomic neuropathy diagnostic test based on short-term heart rate variability without a gold standard
Authors: Tang Zi-Hui , Wang Lin , Zeng Fangfang , Li Zhongtao , Yu Xiaoling , Zhang Keqin , Zhou Linuo 
Published: October 2014

ObjectiveTo evaluate the reference values for short-term heart rate variability (HRV), estimate the performance of cardiovascular autonomic neuropathy (CAN) diagnostic tests in the absence of a gold standard, and assess CAN prevalence in our dataset.SettingCommunity and hospital health centre.ParticipantsOf 2092 subjects available for data analysis, 371 healthy subjects were selected so the reference values for the short-term HRV test could be evaluated. An external dataset contained 88 subjects who completed both the short-term HRV test and Ewing's test.InterventionCollection of information on clinical outcome.Primary and second outcome measuresCardiovascular autonomic function evaluated by using the short-term HRV test and/or Ewing's test.ResultsCut-off points of 356.13, 55.45 and 36.64 ms2were set for total power, low frequency and high frequency (HF), respectively. The diagnostic test for CAN based on the mentioned reference value was created. The HRV test had a high sensitivity (80.01–85.09%) and specificity (82.30–85.20%) for CAN. In addition, the non-inferiority test rejected the null hypothesis that the performance of the HRV test was inferior to that of Ewing's test (p<0.05). The estimated CAN prevalence was 14.92% and 29.17% in the total sample and patients with diabetes, respectively.ConclusionsOur findings provided reference values for short-term HRV, which were used for the CAN diagnostic test with high sensitivity and specificity. The estimated CAN prevalence was high in the Chinese population.
Pain and pressure pain thresholds in adolescents with chronic fatigue syndrome and healthy controls: a cross-sectional study
Authors: Winger Anette , Kvarstein Gunnvald , Wyller Vegard Bruun , Sulheim Dag , Fagermoen Even , Småstuen Milada Cvancarova , Helseth Sølvi 
Published: October 2014

ObjectivesAlthough pain is a significant symptom in chronic fatigue syndrome (CFS), pain is poorly understood in adolescents with CFS. The aim of this study was to explore pain distribution and prevalence, pain intensity and its functional interference in everyday life, as well as pressure pain thresholds (PPT) in adolescents with CFS and compare this with a control group of healthy adolescents (HC).MethodsThis is a case–control, cross-sectional study on pain including 120 adolescents with CFS and 39 HCs, aged 12–18 years. We measured pain frequency, pain severity and pain interference using self-reporting questionnaires. PPT was measured using pressure algometry. Data were collected from March 2010 until October 2012 as part of the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial.ResultsAdolescents with CFS had significantly lower PPTs compared with HCs (p<0.001). The Pain Severity Score and the Pain Interference Score were significantly higher in adolescents with CFS compared with HCs (p<0.001). Almost all adolescents with CFS experienced headache, abdominal pain and/or pain in muscles and joints. Moreover, in all sites, the pain intensity levels were significantly higher than in HCs (p<0.001).ConclusionsWe found a higher prevalence of severe pain among adolescents with CFS and lowered pain thresholds compared with HCs. The mechanisms, however, are still obscure. Large longitudinal population surveys are warranted measuring pain thresholds prior to the onset of CFS.Trial registration numberClinical Trials,NCT01040429; The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL)http://www.clinicaltrials.gov.
LYTIC LESIONS OF DISTAL RADIUS IN CHILDREN: A RARE TUBERCULAR PRESENTATION
Authors: Agarwal Anil , Kant Kumar Shashi , Kumar Anubrat , Shaharyar Abbas , Verma Indreshwar , Suri Tarun 
Published: October 2014

Introduction: We report the presentation, management, and outcome in five children with osteoarticular tuberculosis of distal radius. Patients: Patients were recruited in a prospective study. All patients underwent an open biopsy, curettage and diagnosis confirmed by histopathological/microbiological examination. In cavitary lytic lesions, bone grafting was also undertaken. The multidrug anti-tubercular chemotherapy was given for one year. Observations: Five patients were included in the study. The average follow-up post-completion chemotherapy was 34.8 months. Bony lesions presented as a poorly defined radiolucent lytic area in metaphysis, cavitary lytic lesions with or without sequestrum or spanned the physeal plate. At final follow-up, except for one case, a full pain free range of movements was achieved in all cases. Fibular graft was used in two cases with cavitary lesions and incorporated well in both cases. Conclusions: Tuberculosis can involve the adjacent physis and can be multifocal. The presentation is usually lytic with minimal sclerosis. For smaller ill defined lesions, curettage and multidrug anti-tubercular chemotherapy results in excellent outcome. Cavitary lytic lesions should be bone grafted as there is a risk of pathological fractures.
Optimal Priority Assignment to Control Tasks
Authors: Mancuso Giulio M. , Bini Enrico , Pannocchia Gabriele 
Published: October 2014

In embedded real-time systems, task priorities are often assigned to meet deadlines. However, in control tasks, a late completion of a task has no catastrophic consequence; rather, it has a quantifiable impact in the control performance achieved by the task.
In this article, we address the problem of determining the optimal assignment of priorities and periods of sampled-data control tasks that run over a shared computation unit. We show that the minimization of the overall cost can be performed efficiently using a branch and bound algorithm that can be further speeded up by allowing for a small degree of suboptimality. Detailed numerical simulations are presented to show the advantages of various branching alternatives, the overall algorithm effectiveness, and its scalability with the number of tasks.
Lichenoid Dermatitis in Three Patients with Metastatic Melanoma Treated with Anti–PD-1 Therapy
Authors: Joseph Richard W. , Cappel Mark , Goedjen Brent , Gordon Matthew , Kirsch Brandon , Gilstrap Cheryl , Bagaria Sanjay , Jambusaria-Pahlajani Anokhi 
Published: October 2014

Abstract
Therapies that activate the immune system through blocking the binding of programmed death ligand 1 (PD-L1) present on tumors and PD-1 (programmed death 1) present on activated immune cells are revolutionizing the care for patients with cancer. These therapies work by inhibiting negative regulators of the immune system, thereby decreasing a tumor's ability to evade the immune system. The side effects of anti–PD-1/PD-L1 therapies are generally mild and as expected are related to autoimmune reactions. Two of the most common side effects of anti–PD-1/PD-L1 therapies are rash and pruritus occurring in approximately 20% of patients. Although the rash is generally recognized to be immune mediated, the exact mechanisms of the rash remain unclear. Herein, we report three cases of lichenoid dermatitis in three patients treated with MK-3475 (anti–PD-1) that were characterized with marked T-cell infiltrates with few PD-1–positive cells. The rashes in all three patients were relatively mild, allowing treatment to continue despite the rashes. Cancer Immunol Res; 3(1); 18–22. ©2014 AACR.