bluuebunny/crossref_metadata_2025_split huggingface dataset:
A retrospective analysis of post‐operative outcomes in a series of 108 labial gland biopsies
Authors: Ali S. , Patel N. , Challacombe S. 
Published: February 2014

AbstractAimHistopathological assessment of labial salivary glands has long been a core part of the diagnostic criteria for Sjogren's Syndrome. Biopsy of labial salivary glands is technique sensitive and has post‐operative complications which can affect the patient's quality of life. Varying techniques for labial gland biopsy and associated complications are described in the literature. This article gives a step‐by‐step account of an effective technique for labial gland biopsy as described by Daniels in 1984 and provides a retrospective analysis of the post‐operative complications in a series of 108 labial gland biopsies.Materials and methodsA retrospective, post‐operative telephone survey was carried out to study the post‐operative complications of labial gland biopsies performed by a single operator. All consecutive patients (180) who had labial gland biopsies between October 2010 and August 2012 at the Department of Oral Medicine at Guy's Hospital were called, and 108 surveys were successfully completed. The telephone questionnaires aimed to find out medium and long‐term complications of labial gland biopsies to include subjective measures of post‐operative pain, swelling and paraesthesia.ResultsOne patient out of 108 patients (0.9%) reported pain that lasted ≥ 6 months, and six patients (5.5%) reported swelling that lasted > 2 weeks. Three patients (2.8%) reported paraesthesia lasting ≥ 6 months with a median bother score of 0. All biopsies provided sufficient glands to allow for histopathological diagnosis.ConclusionsThis article describes a safe and effective technique for labial gland biopsy. Despite a low complication rate, informed consent is essential.
An unusual complication of melaena on a warfarinised patient following a routine dental extraction: a case report
Authors: Campbell N. , Patel K. 
Published: February 2014

AbstractA case report of a 79‐year‐old man who was on warfarin for atrial fibrillation and developed melaena following a dental extraction is presented here.To give the reader an appreciation of:
Warfarin as an anticoagulant
Complications following dental extractions of warfarinised patients
A new complication, faecal blood, following a dental extraction
Knowing the Answer to a Loaded Question
Authors: Steglich‐Petersen Asbjørn 
Published: February 2014

AbstractMany epistemologists have been attracted to the view that knowledge‐whcan be reduced to knowledge‐that. An important challenge to this, presented byJonathanSchaffer, is the problem of “convergent knowledge”: reductive accounts imply that any two knowledge‐whascriptions with identical true answers to the questions embedded in theirwh‐clauses are materially equivalent, but according toSchaffer, there are counterexamples to this equivalence. Parallel to this,Schaffer has presented a very similar argument against binary accounts of knowledge, and thereby in favour of his alternative contrastive account, relying on similar examples of apparently inequivalent knowledge ascriptions, which binary accounts treat as equivalent. In this article, I develop a unified diagnosis and solution to these problems for the reductive and binary accounts, based on a general theory of knowledge ascriptions that embed presuppositional expressions. All ofSchaffer's apparent counterexamples embed presuppositional expressions, and once the effect of these is taken into account, it becomes apparent that the counterexamples depend on an illicit equivocation of contexts. Since epistemologists often rely on knowledge ascriptions that embed presuppositional expressions, the general theory of them presented here will have ramifications beyond defusingSchaffer's argument.
Gastrointestinal hormones and the dialogue between gut and brain
Authors: Dockray Graham J. 
Published: February 2014

AbstractThe landmark discovery by Bayliss and Starling in 1902 of the first hormone, secretin, emerged from earlier observations that a response (pancreatic secretion) following a stimulus (intestinal acidification) occurred after section of the relevant afferent nerve pathway. Nearly 80 years elapsed before it became clear that visceral afferent neurons could themselves also be targets for gut and other hormones. The action of gut hormones on vagal afferent neurons is now recognised to be an early step in controlling nutrient delivery to the intestine by regulating food intake and gastric emptying. Interest in these mechanisms has grown rapidly in view of the alarming global increase in obesity. Several of the gut hormones (cholecystokinin (CCK); peptide YY3–36 (PYY3–36); glucagon‐like peptide‐1 (GLP‐1)) excite vagal afferent neurons to activate an ascending pathway leading to inhibition of food intake. Conversely others, e.g. ghrelin, that are released in the inter‐digestive period, inhibit vagal afferent neurons leading to increased food intake. Nutrient status determines the neurochemical phenotype of vagal afferent neurons by regulating a switch between states that promote orexigenic or anorexigenic signalling through mechanisms mediated, at least partly, by CCK. Gut–brain signalling is also influenced by leptin, by gut inflammation and by shifts in the gut microbiota including those that occur in obesity. Moreover, there is emerging evidence that diet‐induced obesity locks the phenotype of vagal afferent neurons in a state similar to that normally occurring during fasting. Vagal afferent neurons are therefore early integrators of peripheral signals underling homeostatic mechanisms controlling nutrient intake. They may also provide new targets in developing treatments for obesity and feeding disorders.
Activities of Fluconazole, Caspofungin, Anidulafungin, and Amphotericin B on Planktonic and Biofilm Candida Species Determined by Microcalorimetry
Authors: Maiolo Elena Maryka , Furustrand Tafin Ulrika , Borens Olivier , Trampuz Andrej 
Published: February 2014

ABSTRACT

We investigated the activities of fluconazole, caspofungin, anidulafungin, and amphotericin B against
Candida
species in planktonic form and biofilms using a highly sensitive assay measuring growth-related heat production (microcalorimetry).
C. albicans
,
C. glabrata
,
C. krusei
, and
C. parapsilosis
were tested, and MICs were determined by the broth microdilution method. The antifungal activities were determined by isothermal microcalorimetry at 37°C in RPMI 1640. For planktonic
Candida
, heat flow was measured in the presence of antifungal dilutions for 24 h.
Candida
biofilm was formed on porous glass beads for 24 h and exposed to serial dilutions of antifungals for 24 h, and heat flow was measured for 48 h. The minimum heat inhibitory concentration (MHIC) was defined as the lowest antifungal concentration reducing the heat flow peak by ≥50% (≥90% for amphotericin B) at 24 h for planktonic
Candida
and at 48 h for
Candida
biofilms (measured also at 24 h). Fluconazole (planktonic MHICs, 0.25 to >512 μg/ml) and amphotericin B (planktonic MHICs, 0.25 to 1 μg/ml) showed higher MHICs than anidulafungin (planktonic MHICs, 0.015 to 0.5 μg/ml) and caspofungin (planktonic MHICs, 0.125 to 0.5 μg/ml). Against
Candida
species in biofilms, fluconazole's activity was reduced by >1,000-fold compared to its activity against the planktonic counterparts, whereas echinocandins and amphotericin B mainly preserved their activities. Fluconazole induced growth of planktonic
C. krusei
at sub-MICs. At high concentrations of caspofungin (>4 μg/ml), paradoxical growth of planktonic
C. albicans
and
C. glabrata
was observed. Microcalorimetry enabled real-time evaluation of antifungal activities against planktonic and biofilm
Candida
organisms. It can be used in the future to evaluate new antifungals and antifungal combinations and to study resistant strains.
Fluoroquinolone-Resistant Escherichia coli Sequence Type 131 Isolates Causing Bloodstream Infections in a Canadian Region with a Centralized Laboratory System: Rapid Emergence of the
H
30-Rx Sublineage
Authors: Peirano Gisele , Pitout Johann D. D. 
Published: February 2014

ABSTRACT

A population-based surveillance study was designed to describe the clinical features and characteristics of sequence type 131 (ST131) and its
H
30 and
H
30-Rx sublineages among fluoroquinolone-resistant (FQ-R)
Escherichia coli
isolates that caused bloodstream infections (BSIs) in a Canadian region with a centralized laboratory system over an 11-year period (2000 to 2010). Nonrepeat isolates from true incident cases were included. Established PCR methods were used to define ST131, its
H
30 and
H
30-Rx sublineages, extended-spectrum β-lactamase and AmpC production, and plasmid-mediated quinolone resistance determinants. A total of 677 Calgary residents with incident BSIs due to FQ-R
E. coli
were identified; the majority presented with health care-associated upper urinary tract infections (UTIs). There was a rise in FQ-R over the 11-year period because of an increase in ST131 toward the end of the study period (2008 to 2010) that was due to a rapid influx of the
H
30-Rx sublineage. We identified the association of
H
30-Rx with primary sepsis, upper UTIs as a complication of prostate biopsies, multidrug resistance, and the presence of
bla
CTX-M-15
and
aac
(
6
′)-
lb-cr. E. coli
ST131
H
30-Rx has established itself as a major drug-resistant sublineage in Calgary, posing an important new public health threat within our region. We urgently need well-designed epidemiological and molecular studies to further understand the dynamics of transmission, risk factors, and reservoirs of
H
30-Rx.
Doripenem, Gentamicin, and Colistin, Alone and in Combinations, against Gentamicin-Susceptible, KPC-Producing Klebsiella pneumoniae Strains with Various
ompK36
Genotypes
Authors: Clancy Cornelius J. , Hao Binghua , Shields Ryan K. , Chen Liang , Perlin David S. , Kreiswirth Barry N. , Nguyen M. Hong 
Published: February 2014

ABSTRACT

Gentamicin doses of 2 and 10 μg/ml were bactericidal against 64% and 100%, respectively, of gentamicin-susceptible KPC-2-producing
Klebsiella pneumoniae
strains. Treatment with the combination of doripenem (8 μg/ml) plus colistin (2 μg/ml) was inferior to treatment with gentamicin (2 μg/ml), doripenem-gentamicin, gentamicin-colistin, and doripenem-gentamicin-colistin against strains with glycine and aspartic acid insertions in OpmK36 porin at amino acid (aa) positions 134 and 135 (
n
= 9). Doripenem-colistin was comparable to other 2- or 3-drug regimens and superior to single drugs against wild-type/minor
ompK36
mutants (
n
= 5). An algorithm incorporating
ompK36
genotypes and susceptibility to gentamicin and doripenem may predict antimicrobial activity against KPC-producing
K. pneumoniae
.
N
-Acylated Derivatives of Sulfamethoxazole and Sulfafurazole Inhibit Intracellular Growth of Chlamydia trachomatis
Authors: Marwaha Sania , Uvell Hanna , Salin Olli , Lindgren Anders E. G. , Silver Jim , Elofsson Mikael , Gylfe Åsa 
Published: February 2014

ABSTRACT

Antibacterial compounds with novel modes of action are needed for management of bacterial infections. Here we describe a high-content screen of 9,800 compounds identifying acylated sulfonamides as novel growth inhibitors of the sexually transmitted pathogen
Chlamydia trachomatis
. The effect was bactericidal and distinct from that of sulfonamide antibiotics, as para-aminobenzoic acid did not reduce efficacy. Chemical inhibitors play an important role in
Chlamydia
research as probes of potential targets and as drug development starting points.
Agp2p, the Plasma Membrane Transregulator of Polyamine Uptake, Regulates the Antifungal Activities of the Plant Defensin NaD1 and Other Cationic Peptides
Authors: Bleackley Mark R. , Wiltshire Jennifer L. , Perrine-Walker Francine , Vasa Shaily , Burns Rhiannon L. , van der Weerden Nicole L. , Anderson Marilyn A. 
Published: February 2014

ABSTRACT

Cationic antifungal peptides (AFPs) act through a variety of mechanisms but share the common feature of interacting with the fungal cell surface. NaD1, a defensin from
Nicotiana alata
, has potent antifungal activity against a variety of fungi of both hyphal and yeast morphologies. The mechanism of action of NaD1 occurs via three steps: binding to the fungal cell surface, permeabilization of the plasma membrane, and internalization and interaction with intracellular targets to induce fungal cell death. The targets at each of these three stages have yet to be defined. In this study, the screening of a
Saccharomyces cerevisiae
deletion collection led to the identification of Agp2p as a regulator of the potency of NaD1. Agp2p is a plasma membrane protein that regulates the transport of polyamines and other molecules, many of which carry a positive charge. Cells lacking the
agp2
gene were more resistant to NaD1, and this resistance was accompanied by a decreased uptake of defensin. Agp2p senses and regulates the uptake of the polyamine spermidine, and competitive inhibition of the antifungal activity of NaD1 by spermidine was observed in both
S. cerevisiae
and the plant pathogen
Fusarium oxysporum
. The resistance of
agp2
Δ cells to other cationic antifungal peptides and decreased binding of the cationic protein cytochrome
c
to
agp2
Δ cells compared to that of wild-type cells have led to a proposed mechanism of resistance whereby the deletion of
agp2
leads to an increase in positively charged molecules at the cell surface that repels cationic antifungal peptides.
Complete Nucleotide Sequences of Two
bla
KPC-2
-Bearing IncN Plasmids Isolated from Sequence Type 442 Klebsiella pneumoniae Clinical Strains Four Years Apart
Authors: Pérez-Chaparro Paula Juliana , Cerdeira Louise Teixeira , Queiroz Maíse Gomes , de Lima Clayton Pereira Silva , Levy Carlos Emílio , Pavez Mónica , Lincopan Nilton , Gonçalves Evonnildo Costa , Mamizuka Elsa Masae , Sampaio Jorge Luiz Mello , Nunes Marcio Roberto Teixeira , McCulloch John Anthony 
Published: February 2014

ABSTRACT

We sequenced the oldest
bla
KPC-2
-bearing plasmid isolated in Brazil and another plasmid also carried by a
Klebsiella pneumoniae
strain of sequence type 442 (ST442), isolated 52 months later. Both plasmids present an IncN backbone and few acquired regions. Because the 2005 plasmid presented deletions and a truncated gene within Tn
4401b
compared to the 2009 plasmid, we can thus infer that IncN
bla
KPC-2
-bearing plasmids pFCF1305 and pFCF3SP had a common ancestor circulating in Brazil prior to May 2005.
Identification of CMY-2-Type Cephalosporinases in Clinical Isolates of Enterobacteriaceae by MALDI-TOF MS
Authors: Papagiannitsis C. C. , Kotsakis S. D. , Tuma Z. , Gniadkowski M. , Miriagou V. , Hrabak J. 
Published: February 2014

ABSTRACT

This study exploited the possibility to detect
Citrobacter freundii
-derived CMY-2-like cephalosporinases in
Enterobacteriaceae
clinical isolates using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). Periplasmic proteins were prepared using a modified sucrose method and analyzed by MALDI-TOF MS. A ca. 39,850-
m
/
z
peak, confirmed to represent a
C. freundii
-like β-lactamase by in-gel tryptic digestion followed by MALDI-TOF/TOF MS, was observed only in CMY-producing isolates. We have also shown the potential of the assay to detect ACC- and DHA-like AmpC-type β-lactamases.
Fitness Costs for Influenza B Viruses Carrying Neuraminidase Inhibitor-Resistant Substitutions: Underscoring the Importance of E119A and H274Y
Authors: Burnham Andrew J. , Baranovich Tatiana , Marathe Bindumadhav M. , Armstrong Jianling , Webster Robert G. , Govorkova Elena A. 
Published: February 2014

ABSTRACT

Influenza B viruses cause annual outbreaks of respiratory illness in humans and are increasingly recognized as a major cause of influenza-associated pediatric mortality. Neuraminidase (NA) inhibitors (NAIs) are the only available therapy for patients infected with influenza B viruses, and the potential emergence of NAI-resistant viruses is a public health concern. The NA substitutions located within the enzyme active site could not only reduce NAI susceptibility of influenza B virus but also affect virus fitness. In this study, we investigated the effect of single NA substitutions on the fitness of influenza B/Yamanashi/166/1998 viruses (Yamagata lineage). We generated recombinant viruses containing either wild-type (WT) NA or NA with a substitution in the catalytic (R371K) or framework (E119A, D198E, D198Y, I222T, H274Y, and N294S) residues. We assessed NAI susceptibility, NA biochemical properties, NA protein expression, and virus replication
in vitro
and in differentiated normal human bronchial epithelial (NHBE) cells. Our results showed that four NA substitutions (D198E, I222T, H274Y, and N294S) conferred reduced inhibition by oseltamivir and three (E119A, D198Y, and R371K) conferred highly reduced inhibition by oseltamivir, zanamivir, and peramivir. All NA substitutions, except for D198Y and R371K, were genetically stable after seven passages in MDCK cells. Cell surface NA protein expression was significantly increased by H274Y and N294S substitutions. Viruses with the E119A, I222T, H274Y, or N294S substitution were not attenuated in replication efficiency
in vitro
or in NHBE cells. Overall, viruses with the E119A or H274Y NA substitution possess fitness comparable to NAI-susceptible virus, and the acquisition of these substitutions by influenza B viruses should be closely monitored.
Novel Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Detection of Anti-HIV Drugs Lopinavir, Ritonavir, and Tenofovir in Plasma
Authors: Koehn Josefin , Ho Rodney J. Y. 
Published: February 2014

ABSTRACT

For HIV infection, anti-HIV drug combinations are typically used as highly active antiretroviral therapy (HAART), intended to maximize viral suppression. Three drugs used frequently in combination are the protease inhibitors lopinavir and ritonavir and the nucleotide reverse transcriptase inhibitor tenofovir. We have successfully developed a simple, efficient, and sensitive method to simultaneously extract and determine the concentrations of lopinavir, ritonavir, and tenofovir in plasma samples. The plasma extractions were performed using a liquid-liquid extraction followed by protein precipitation of the remaining aqueous layer. The collected fractions were combined, dried, and reconstituted in the mobile phase. The drugs were quantified using liquid chromatography coupled with tandem mass spectrometry. The assay was applied to a study of plasma drug levels in two primates (
Macaca nemestrina
). The bioanalytical assay was optimized and validated to exhibit a high extraction efficiency and good sensitivity and reproducibility. When the assay was applied in a primate study, all three drugs could be detected in plasma within minutes of subcutaneous dosing. This validated assay will be useful for evaluation of drug concentrations in an efficient, selective, and sensitive manner.
An
ethA-ethR
-Deficient Mycobacterium bovis BCG Mutant Displays Increased Adherence to Mammalian Cells and Greater Persistence
In Vivo
, Which Correlate with Altered Mycolic Acid Composition
Authors: Ang Michelle Lay Teng , Siti Zarina Zainul Rahim , Shui Guanghou , Dianišková Petronela , Madacki Jan , Lin Wenwei , Koh Vanessa Hui Qi , Martinez Gomez Julia Maria , Sudarkodi Sukumar , Bendt Anne , Wenk Markus , Mikušová Katarína , Korduláková Jana , Pethe Kevin , Alonso Sylvie 
Published: February 2014

ABSTRACT

Tuberculosis remains a major worldwide epidemic because of its sole etiological agent,
Mycobacterium tuberculosis
. Ethionamide (ETH) is one of the major antitubercular drugs used to treat infections with multidrug-resistant
M. tuberculosis
strains. ETH is a prodrug that requires activation within the mycobacterial cell; its bioactivation involves the
ethA-ethR
locus, which encodes the monooxygenase EthA, while EthR is a transcriptional regulator that binds to the intergenic promoter region of the
ethA-ethR
locus. While most studies have focused on the role of EthA-EthR in ETH bioactivation, its physiological role in mycobacteria has remained elusive, although a role in bacterial cell detoxification has been proposed. Moreover, the importance of EthA-EthR
in vivo
has never been reported on. Here we constructed and characterized an EthA-EthR-deficient mutant of
Mycobacterium bovis
BCG. Our results indicate that absence of the
ethA-ethR
locus led to greater persistence of
M. bovis
BCG in the mouse model of mycobacterial infection, which correlated with greater adherence to mammalian cells. Furthermore, analysis of cell wall lipid composition by thin-layer chromatography and mass spectrometry revealed differences between the
ethA-ethR
KO mutant and the parental strain in the relative amounts of α- and keto-mycolates. Therefore, we propose here that
M. bovis
BCG
ethA-ethR
is involved in the cell wall-bound mycolate profile, which impacts mycobacterial adherence properties and
in vivo
persistence. This study thus provides some experimental clues to the possible physiological role of
ethA-ethR
and proposes that this locus is a novel factor involved in the modulation of mycobacterial virulence.
Inflammatory Bone Loss in Experimental Periodontitis Induced by Aggregatibacter actinomycetemcomitans in Interleukin-1 Receptor Antagonist Knockout Mice
Authors: Izawa A. , Ishihara Y. , Mizutani H. , Kobayashi S. , Goto H. , Okabe E. , Takeda H. , Ozawa Y. , Kamiya Y. , Sugita Y. , Kubo K. , Kamei H. , Kikuchi T. , Mitani A. , Hayashi J. , Nishihara T. , Maeda H. , Noguchi T. 
Published: February 2014

ABSTRACT

The interleukin-1 receptor antagonist (IL-1Ra) binds to IL-1 receptors and inhibits IL-1 activity. However, it is not clear whether IL-1Ra plays a protective role in periodontal disease. This study was undertaken to compare experimental periodontitis induced by
Aggregatibacter actinomycetemcomitans
in IL-1Ra knockout (KO) mice and wild-type (WT) mice. Computed tomography (CT) analysis and hematoxylin-and-eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) staining were performed. In addition, osteoblasts were isolated; the mRNA expression of relevant genes was assessed by real-time quantitative PCR (qPCR); and calcification was detected by Alizarin Red staining. Infected IL-1Ra KO mice exhibited elevated (
P
, <0.05) levels of antibody against
A. actinomycetemcomitans
, bone loss in furcation areas, and alveolar fenestrations. Moreover, protein for tumor necrosis factor alpha (TNF-α) and IL-6, mRNA for macrophage colony-stimulating factor (M-CSF), and receptor activator of NF-κB ligand (RANKL) in IL-1Ra KO mouse osteoblasts stimulated with
A. actinomycetemcomitans
were increased (
P
, <0.05) compared to in WT mice. Alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN)/bone gla protein (BGP), and runt-related gene 2 (Runx2) mRNA levels were decreased (
P
, <0.05). IL-1α mRNA expression was increased, and calcification was not observed, in IL-1 Ra KO mouse osteoblasts. In brief, IL-1Ra deficiency promoted the expression of inflammatory cytokines beyond IL-1 and altered the expression of genes involved in bone resorption in
A. actinomycetemcomitans
-infected osteoblasts. Alterations consistent with rapid bone loss in infected IL-Ra KO mice were also observed for genes expressed in bone formation and calcification. In short, these data suggest that IL-1Ra may serve as a potential therapeutic drug for periodontal disease.