bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy of surface registration compared to conventional volumetric registration in patient positioning for head‐and‐neck radiotherapy: A simulation study using patient data
Authors: Kim Youngjun , Li Ruijiang , Na Yong Hum , Lee Rena , Xing Lei
Published: November 2014

Purpose:

3D optical surface imaging has been applied to patient positioning in radiation therapy (RT). The optical patient positioning system is advantageous over conventional method using cone‐beam computed tomography (CBCT) in that it is radiation free, frameless, and is capable of real‐time monitoring. While the conventional radiographic method uses volumetric registration, the optical system uses surface matching for patient alignment. The relative accuracy of these two methods has not yet been sufficiently investigated. This study aims to investigate the theoretical accuracy of the surface registration based on a simulation study using patient data.

Methods:

This study compares the relative accuracy of surface and volumetric registration in head‐and‐neck RT. The authors examined 26 patient data sets, each consisting of planning CT data acquired before treatment and patient setup CBCT data acquired at the time of treatment. As input data of surface registration, patient's skin surfaces were created by contouring patient skin from planning CT and treatment CBCT. Surface registration was performed using the iterative closest points algorithm by point–plane closest, which minimizes the normal distance between source points and target surfaces. Six degrees of freedom (three translations and three rotations) were used in both surface and volumetric registrations and the results were compared. The accuracy of each method was estimated by digital phantom tests.

Results:

Based on the results of 26 patients, the authors found that the average and maximum root‐mean‐square translation deviation between the surface and volumetric registrations were 2.7 and 5.2 mm, respectively. The residual error of the surface registration was calculated to have an average of 0.9 mm and a maximum of 1.7 mm.

Conclusions:

Surface registration may lead to results different from those of the conventional volumetric registration. Only limited accuracy can be achieved for patient positioning with an approach based solely on surface information.
Progressive, Site-Specific Loss of Muscle Mass in Older, Frail Nursing Home Residents
Authors: Takeshima Nobuo , Shimada Keizo , Islam Mohammod M. , Kanehisa Hiroaki , Ishida Yoshie , Brechue William F.
Published: November 2014

To clarify the progression of muscle loss in nursing home residents, frail women (n = 16; age: 85 ± 9 years; residence time: 764 days) were assessed for physical activity, caloric intake, and site-specific muscle thickness (MTH) and subcutaneous fat thickness (SFT) using B-mode ultrasound at nine anatomical sites at four intervals over one year. Height, body weight, and BMI did not change. Physical activity (246 steps/day) and nutritional intake (1,441 kcal, 60.3 g protein/day) were unaltered throughout the study. Subjects experienced a significant, progressive loss of muscle indicated by decrements in anterior upper arm (20%), posterior upper arm (25%), abdomen (20%), subscapular (33%), anterior thigh (15%), posterior thigh (22%), anterior lower leg (11%), posterior lower leg (13%), and forearm (15%) MTH. At study inception, prevalence of sarcopenia was related to muscle loss in the upper leg, while upper body muscle wasting contributed to sarcopenia later and was unrelated to physical activity, nutritional input, or duration of residence.
How Sedentary Are Older People? A Systematic Review of the Amount of Sedentary Behavior
Authors: Harvey Juliet A. , Chastin Sebastien F.M. , Skelton Dawn A.
Published: November 2014

Background/objectives:

Sedentary behavior (SB), defined as sitting (nonexercising), reclining, and lying down (posture), or by low energy expenditure, is a public health risk independent to physical activity. The objective of this systematic literature review was to synthesize the available evidence on amount of SB reported by and measured in older adults.

Data source:

Studies published between 1981 and 2014 were identified from electronic databases and manual searching. Large-scale population studies/surveys reporting the amount of SB (objective/subjective) in older adults aged ≥ 60 years of age were included. Appraisal and synthesis was completed using MOOSE guidelines.

Results:

349,698 adults aged ≥ 60 within 22 studies (10 countries and 1 EU-wide) were included. Objective measurement of SB shows that older adults spend an average of 9.4 hr a day sedentary, equating to 65–80% of their waking day. Self-report of SB is lower, with average weighted self-reports being 5.3 hr daily. Within specific domains of SB, older adults report 3.3 hr in leisure sitting time and 3.3 hr watching TV. There is an association with more time spent in SB as age advances and a trend for older men to spend more time in SB than women.

Conclusion/implications:

Time spent sedentary ranges from 5.3–9.4 hr per waking day in older adults. With recent studies suggesting a link between SB, health, and well-being, independent of physical activity, this is an area important for successful aging.

Limitations:

Different methodologies of measurement and different reporting methods of SB made synthesis difficult. Estimated SB time from self-report is half of that measured objectively; suggesting that most self-report surveys of SB will vastly underestimate the actual time spent in SB.
Type I interferon signaling contributes to the bias that Toll-like receptor 4 exhibits for signaling mediated by the adaptor protein TRIF
Authors: Kolb Joseph P. , Casella Carolyn R. , SenGupta Shuvasree , Chilton Paula M. , Mitchell Thomas C.
Published: November 2014

The selective use by Toll-like receptor 4 of an adaptor protein may aid in the development of safer vaccine adjuvants.
Resistance to dual blockade of the kinases PI3K and mTOR in
KRAS
-mutant colorectal cancer models results in combined sensitivity to inhibition of the receptor tyrosine kinase EGFR
Authors: Belmont Peter J. , Jiang Ping , McKee Trevor D. , Xie Tao , Isaacson Jason , Baryla Nicole E. , Roper Jatin , Sinnamon Mark J. , Lee Nathan V. , Kan Julie L. C. , Guicherit Oivin , Wouters Bradly G. , O’Brien Catherine A. , Shields David , Olson Peter , VanArsdale Todd , Weinrich Scott L. , Rejto Paul , Christensen James G. , Fantin Valeria R. , Hung Kenneth E. , Martin Eric S.
Published: November 2014

Combination therapy with EGFR inhibitors may overcome acquired resistance to PI3K pathway inhibitors in some colorectal cancer patients.
Contribution of Clinically Derived Mutations in
ERG11
to Azole Resistance in Candida albicans
Authors: Flowers Stephanie A. , Colón Brendan , Whaley Sarah G. , Schuler Mary A. , Rogers P. David
Published: November 2014

In
Candida albicans
, the
ERG11
gene encodes lanosterol demethylase, the target of the azole antifungals. Mutations in
ERG11
that result in an amino acid substitution alter the abilities of the azoles to bind to and inhibit Erg11, resulting in resistance. Although
ERG11
mutations have been observed in clinical isolates, the specific contributions of individual
ERG11
mutations to azole resistance in
C. albicans
have not been widely explored. We sequenced
ERG11
in 63 fluconazole (FLC)-resistant clinical isolates. Fifty-five isolates carried at least one mutation in
ERG11
, and we observed 26 distinct positions in which amino acid substitutions occurred. We mapped the 26 distinct variant positions in these alleles to four regions in the predicted structure for Erg11, including its predicted catalytic site, extended fungus-specific external loop, proximal surface, and proximal surface-to-heme region. In total, 31 distinct
ERG11
alleles were recovered, with 10
ERG11
alleles containing a single amino acid substitution. We then characterized 19 distinct
ERG11
alleles by introducing them into the wild-type azole-susceptible
C. albicans
SC5314 strain and testing them for susceptibilities to FLC, itraconazole (ITC), and voriconazole (VRC). The strains that were homozygous for the single amino acid substitutions Y132F, K143R, F145L, S405F, D446E, G448E, F449V, G450E, and G464S had a ≥4-fold increase in FLC MIC. The strains that were homozygous for several double amino acid substitutions had decreased azole susceptibilities beyond those conferred by any single amino acid substitution. These findings indicate that mutations in
ERG11
are prevalent among azole-resistant clinical isolates and that most mutations result in appreciable changes in FLC and VRC susceptibilities.
Effect of the Hepatitis C Virus Protease Inhibitor Faldaprevir on the Pharmacokinetics of an Oral Contraceptive Containing Ethinylestradiol and Levonorgestrel in Healthy Female Volunteers
Authors: Sabo John P. , Lang Benjamin , Elgadi Mabrouk , Huang Fenglei
Published: November 2014

Faldaprevir is a potent hepatitis C virus (HCV) NS3/4A protease inhibitor. Faldaprevir is known to inhibit P-glycoprotein, CYP3A4, and UDP-glucuronosyltransferase 1A1. This study evaluated the effect of steady-state 240 mg faldaprevir on the pharmacokinetics (PK) of an oral contraceptive containing ethinylestradiol (EE) and levonorgestrel (LNG) in healthy premenopausal women. In period 1, subjects received EE/LNG once daily (QD) for 14 days. Blood samples were taken on days 1, 11, and 12, with intensive PK blood sampling for EE and LNG on day 13. In period 2, subjects received EE-LNG QD and 240 mg faldaprevir QD on days 14 to 21 (240 mg faldaprevir twice daily on day 14). Blood samples were taken on days 14, 19, and 20, with PK profiling samples obtained for EE and LNG on day 21. A total of 15/16 subjects completed the study. Overall, EE and LNG exposure (assessed by the area under the curve) was approximately 1.4-fold higher when EE and LNG were coadministered with faldaprevir than when administered alone. Median
t
1/2
(terminal half-life in plasma at steady state) values were prolonged for both EE (2.4 h longer) and LNG (4.7 h longer) when EE and LNG were coadministered with faldaprevir. The mean oral clearance and apparent volume of distribution of both EE and LNG were lower (∼30%) when EE and LNG were coadministered with faldaprevir. Coadministration of faldaprevir and an oral contraceptive resulted in a moderate increase in exposure to both EE and LNG. However, this increase was not considered clinically meaningful, and no dose adjustment of oral contraceptives was deemed necessary. (This study has been registered at ClinicalTrials.gov under registration number NCT01570244.)
Pharmacokinetic Interactions between Primaquine and Pyronaridine-Artesunate in Healthy Adult Thai Subjects
Authors: Jittamala Podjanee , Pukrittayakamee Sasithon , Ashley Elizabeth A. , Nosten François , Hanboonkunupakarn Borimas , Lee Sue J. , Thana Praiya , Chairat Kalayanee , Blessborn Daniel , Panapipat Salwaluk , White Nicholas J. , Day Nicholas P. J. , Tarning Joel
Published: November 2014

Pyronaridine-artesunate is a newly introduced artemisinin-based combination treatment which may be deployed together with primaquine. A single-dose, randomized, three-sequence crossover study was conducted in healthy Thai volunteers to characterize potential pharmacokinetic interactions between these drugs. Seventeen healthy adults received a single oral dose of primaquine alone (30 mg base) and were then randomized to receive pyronaridine-artesunate alone (540−180 mg) or pyronaridine-artesunate plus primaquine in combination, with intervening washout periods between all treatments. The pharmacokinetic properties of primaquine, its metabolite carboxyprimaquine, artesunate, its metabolite dihydroartemisinin, and pyronaridine were assessed in 15 subjects using a noncompartmental approach followed by a bioequivalence evaluation. All drugs were well tolerated. The single oral dose of primaquine did not result in any clinically relevant pharmacokinetic alterations to pyronaridine, artesunate, or dihydroartemisinin exposures. There were significantly higher primaquine maximum plasma drug concentrations (geometric mean ratio, 30%; 90% confidence interval [CI], 17% to 46%) and total exposures (15%; 6.4% to 24%) during coadministration with pyronaridine-artesunate than when primaquine was given alone. Pyronaridine, like chloroquine and piperaquine, increases plasma primaquine concentrations. (This study has been registered at ClinicalTrials.gov under registration no. NCT01552330.)
Lycopene Attenuates Colistin-Induced Nephrotoxicity in Mice via Activation of the Nrf2/HO-1 Pathway
Authors: Dai Chongshan , Tang Shusheng , Deng Sijun , Zhang Shen , Zhou Yan , Velkov Tony , Li Jian , Xiao Xilong
Published: November 2014

Nephrotoxicity is the major dose-limiting factor for the clinical use of colistin against multidrug-resistant (MDR) Gram-negative bacteria. This study aimed to investigate the protective effect of lycopene on colistin-induced nephrotoxicity in a mouse model. Fifty mice were randomly divided into 5 groups: the control group (saline solution), the lycopene group (20 mg/kg of body weight/day administered orally), the colistin group (15 mg/kg/day administered intravenously), the colistin (15 mg/kg/day) plus lycopene (5 mg/kg/day) group, and the colistin (15 mg/kg/day) plus lycopene (20 mg/kg/day) group; all mice were treated for 7 days. At 12 h after the last dose, blood was collected for measurements of blood urea nitrogen (BUN) and serum creatinine levels. The kidney tissue samples were obtained for examination of biomarkers of oxidative stress and apoptosis, histopathological assessment, and quantitative reverse transcription-PCR (qRT-PCR) analysis. Colistin treatment significantly increased concentrations of BUN and serum creatinine, tubular apoptosis/necrosis, lipid peroxidation, and heme oxygenase 1 (HO-1) activity, while the treatment decreased the levels of endogenous antioxidant biomarkers glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Notably, the changes in the levels of all biomarkers were attenuated in the kidneys of mice treated with colistin by lycopene (5 or 20 mg/kg). Lycopene treatment, especially in the colistin plus lycopene (20 mg/kg) group, significantly downregulated the expression of NF-κB mRNA (
P
< 0.01) but upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 mRNA (both
P
< 0.01) in the kidney compared with the results seen with the colistin group. Our data demonstrated that coadministration of 20 mg/kg/day lycopene can protect against colistin-induced nephrotoxicity in mice. This effect may be attributed to the antioxidative property of lycopene and its ability to activate the Nrf2/HO-1 pathway.
Lead Clinical and Preclinical Antimalarial Drugs Can Significantly Reduce Sporozoite Transmission to Vertebrate Populations
Authors: Upton L. M. , Brock P. M. , Churcher T. S. , Ghani A. C. , Gething P. W. , Delves M. J. , Sala K. A. , Leroy D. , Sinden R. E. , Blagborough A. M.
Published: November 2014

To achieve malarial elimination, we must employ interventions that reduce the exposure of human populations to infectious mosquitoes. To this end, numerous antimalarial drugs are under assessment in a variety of transmission-blocking assays which fail to measure the single crucial criteria of a successful intervention, namely impact on case incidence within a vertebrate population (reduction in reproductive number/effect size). Consequently, any reduction in new infections due to drug treatment (and how this may be influenced by differing transmission settings) is not currently examined, limiting the translation of any findings. We describe the use of a laboratory population model to assess how individual antimalarial drugs can impact the number of secondary
Plasmodium berghei
infections over a cycle of transmission. We examine the impact of multiple clinical and preclinical drugs on both insect and vertebrate populations at multiple transmission settings. Both primaquine (>6 mg/kg of body weight) and NITD609 (8.1 mg/kg) have significant impacts across multiple transmission settings, but artemether and lumefantrine (57 and 11.8 mg/kg), OZ439 (6.5 mg/kg), and primaquine (<1.25 mg/kg) demonstrated potent efficacy only at lower-transmission settings. While directly demonstrating the impact of antimalarial drug treatment on vertebrate populations, we additionally calculate effect size for each treatment, allowing for head-to-head comparison of the potential impact of individual drugs within epidemiologically relevant settings, supporting their usage within elimination campaigns.
Lack of Neuropathological Changes in Rats Administered Tedizolid Phosphate for Nine Months
Authors: Schlosser Michael J. , Hosako Hiromi , Radovsky Ann , Butt Mark T. , Draganov Dragomir , Vija Jenifer , Oleson Frederick
Published: November 2014

Tedizolid, a novel oxazolidinone antibacterial, was administered to Long Evans rats by oral gavage once daily for up to 9 months at doses near the maximum tolerated dose (MTD) to evaluate for potential neurotoxicity. Mean plasma exposures of tedizolid at the low-, medium-, and high-dose levels (7.5, 15, and 30 mg/kg of body weight/day for males; 2.5, 5, and 10 mg/kg/day for females) were similar between males and females and were 1.8-, 3.9-, and 8.0-fold greater than exposures in patients at the therapeutic dose (200 mg once daily). Evaluated endpoints included survival, clinical observations, body weight, and food consumption. At 1, 3, 6, and 9 months, ophthalmic examinations, functional observational batteries, and locomotor activity measures were conducted, brain weights/sizes were recorded, and perfusion-fixed tissues were collected from 12 rats/sex/group/time point. A detailed morphological assessment was conducted on brain, eyes, optic nerve/tract, spinal cord, peripheral nerves (includes sciatic, sural, tibial, peroneal, trigeminal), and skeletal muscle. At the end of 9 months, less body weight gain was seen in high-dose males (−6.7%) and females (−5.8%) compared with that seen in controls. There were no tedizolid-related adverse neurobehavioral effects or tedizolid-related histopathologic changes in the central/peripheral nervous systems, including the optic nerve. Results of this study indicate that tedizolid was not neurotoxic when administered long term to pigmented rats at doses near the MTD, which were up to 8-fold higher than the human therapeutic exposure.
Genomic and Transcriptomic Analyses of Colistin-Resistant Clinical Isolates of Klebsiella pneumoniae Reveal Multiple Pathways of Resistance
Authors: Wright Meredith S. , Suzuki Yo , Jones Marcus B. , Marshall Steven H. , Rudin Susan D. , van Duin David , Kaye Keith , Jacobs Michael R. , Bonomo Robert A. , Adams Mark D.
Published: November 2014

The emergence of multidrug-resistant (MDR)
Klebsiella pneumoniae
has resulted in a more frequent reliance on treatment using colistin. However, resistance to colistin (Col
r
) is increasingly reported from clinical settings. The genetic mechanisms that lead to Col
r
in
K. pneumoniae
are not fully characterized. Using a combination of genome sequencing and transcriptional profiling by RNA sequencing (RNA-Seq) analysis, distinct genetic mechanisms were found among nine Col
r
clinical isolates. Col
r
was related to mutations in three different genes in
K. pneumoniae
strains, with distinct impacts on gene expression. Upregulation of the
pmrH
operon encoding 4-amino-4-deoxy-
l
-arabinose (Ara4N) modification of lipid A was found in all Col
r
strains. Alteration of the
mgrB
gene was observed in six strains. One strain had a mutation in
phoQ
. Common among these seven strains was elevated expression of
phoPQ
and unaltered expression of
pmrCAB
, which is involved in phosphoethanolamine addition to lipopolysaccharide (LPS). In two strains, separate mutations were found in a previously uncharacterized histidine kinase gene that is part of a two-component regulatory system (TCRS) now designated
crrAB
. In these strains, expression of
pmrCAB
,
crrAB
, and an adjacent glycosyltransferase gene, but not that of
phoPQ
, was elevated. Complementation with the wild-type allele restored colistin susceptibility in both strains. The
crrAB
genes are present in most
K. pneumoniae
genomes, but not in
Escherichia coli
. Additional upregulated genes in all strains include those involved in cation transport and maintenance of membrane integrity. Because the
crrAB
genes are present in only some strains, Col
r
mechanisms may be dependent on the genetic background.
In Vitro
Antibacterial Activity of AZD0914, a New Spiropyrimidinetrione DNA Gyrase/Topoisomerase Inhibitor with Potent Activity against Gram-Positive, Fastidious Gram-Negative, and Atypical Bacteria
Authors: Huband Michael D. , Bradford Patricia A. , Otterson Linda G. , Basarab Gregory S. , Kutschke Amy C. , Giacobbe Robert A. , Patey Sara A. , Alm Richard A. , Johnstone Michele R. , Potter Marie E. , Miller Paul F. , Mueller John P.
Published: November 2014

AZD0914 is a new spiropyrimidinetrione bacterial DNA gyrase/topoisomerase inhibitor with potent
in vitro
antibacterial activity against key Gram-positive (
Staphylococcus aureus
,
Staphylococcus epidermidis
,
Streptococcus pneumoniae
,
Streptococcus pyogenes
, and
Streptococcus agalactiae
), fastidious Gram-negative (
Haemophilus influenzae
and
Neisseria gonorrhoeae
), atypical (
Legionella pneumophila
), and anaerobic (
Clostridium difficile
) bacterial species, including isolates with known resistance to fluoroquinolones. AZD0914 works via inhibition of DNA biosynthesis and accumulation of double-strand cleavages; this mechanism of inhibition differs from those of other marketed antibacterial compounds. AZD0914 stabilizes and arrests the cleaved covalent complex of gyrase with double-strand broken DNA under permissive conditions and thus blocks religation of the double-strand cleaved DNA to form fused circular DNA. Whereas this mechanism is similar to that seen with fluoroquinolones, it is mechanistically distinct. AZD0914 exhibited low frequencies of spontaneous resistance in
S. aureus
, and if mutants were obtained, the mutations mapped to
gyrB
. Additionally, no cross-resistance was observed for AZD0914 against recent bacterial clinical isolates demonstrating resistance to fluoroquinolones or other drug classes, including macrolides, β-lactams, glycopeptides, and oxazolidinones. AZD0914 was bactericidal in both minimum bactericidal concentration and
in vitro
time-kill studies. In
in vitro
checkerboard/synergy testing with 17 comparator antibacterials, only additivity/indifference was observed. The potent
in vitro
antibacterial activity (including activity against fluoroquinolone-resistant isolates), low frequency of resistance, lack of cross-resistance, and bactericidal activity of AZD0914 support its continued development.
Antibody Response Specific to the Capsular Polysaccharide Is Impaired in Streptococcus suis Serotype 2-Infected Animals
Authors: Calzas Cynthia , Lemire Paul , Auray Gael , Gerdts Volker , Gottschalk Marcelo , Segura Mariela
Published: November 2014

Streptococcus suis
serotype 2 is an extracellular encapsulated bacterium that causes severe septicemia and meningitis in swine and humans. Albeit crucial in the fight against encapsulated bacteria, the nature of the capsular polysaccharide (CPS)-specific antibody (Ab) response during
S. suis
type 2 infection is unknown. We compared for the first time the features of CPS-specific versus protein-specific Ab responses during experimental infections with live virulent
S. suis
type 2 in mice. The primary protein-specific Ab response was dominated by both type 1 and 2 IgG subclasses, whereas IgM titers were more modest. The secondary protein-specific Ab response showed all of the features of a memory response with faster kinetics and boosted the titers of all Ig isotypes. In contrast, the primary CPS-specific Ab response was either inexistent or had titers only slightly higher than those in noninfected animals and was essentially composed of IgM. A poor CPS-specific memory response was observed, with only a moderate boost in IgM titers and no IgG. Both protein- and CPS-specific Ab responses were Toll-like receptor 2 independent. By using
S. suis
type 2 strains of European or North American origin, the poor CPS-specific Ab response was demonstrated to be independent of the genotypic/phenotypic diversity of the strain within serotype 2. Finally, the CPS-specific Ab response was also impaired and lacked isotype switching in
S. suis
-infected pigs, the natural host of the bacterium. The better resistance of preinfected animals to reinfection with the same strain of
S. suis
type 2 might thus more likely be related to the development of a protein rather than CPS Ab response.
Role of Dendritic Cells in the Pathogenesis of Whipple's Disease
Authors: Schinnerling Katina , Geelhaar-Karsch Anika , Allers Kristina , Friebel Julian , Conrad Kristina , Loddenkemper Christoph , Kühl Anja A. , Erben Ulrike , Ignatius Ralf , Moos Verena , Schneider Thomas
Published: November 2014

Accumulation of
Tropheryma whipplei
-stuffed macrophages in the duodenum, impaired
T. whipplei
-specific Th1 responses, and weak secretion of interleukin-12 (IL-12) are hallmarks of classical Whipple's disease (CWD). This study addresses dendritic cell (DC) functionality during CWD. We documented composition, distribution, and functionality of DC
ex vivo
or after
in vitro
maturation by fluorescence-activated cell sorting (FACS) and by immunohistochemistry
in situ
. A decrease in peripheral DC of untreated CWD patients compared to healthy donors was due to reduced CD11c
high
myeloid DC (M-DC). Decreased maturation markers CD83, CD86, and CCR7, as well as low IL-12 production in response to stimulation, disclosed an immature M-DC phenotype.
In vitro
-generated monocyte-derived DC from CWD patients showed normal maturation and T cell-stimulatory capacity under proinflammatory conditions but produced less IL-12 and failed to activate
T. whipplei
-specific Th1 cells. In duodenal and lymphoid tissues,
T. whipplei
was found within immature DC-SIGN
+
DC. DC and proliferating lymphocytes were reduced in lymph nodes of CWD patients compared to levels in controls. Our results indicate that dysfunctional IL-12 production by DC provides suboptimal conditions for priming of
T. whipplei
-specific T cells during CWD and that immature DC carrying
T. whipplei
contribute to the dissemination of the bacterium.
The Polyamine
N
-Acetyltransferase-Like Enzyme PmvE Plays a Role in the Virulence of Enterococcus faecalis
Authors: Martini Cecilia , Michaux Charlotte , Bugli Francesca , Arcovito Alessandro , Iavarone Federica , Cacaci Margherita , Sterbini Francesco Paroni , Hartke Axel , Sauvageot Nicolas , Sanguinetti Maurizio , Posteraro Brunella , Giard Jean-Christophe
Published: November 2014

We previously showed that the mutant strain of
Enterococcus faecalis
lacking the transcriptional regulator SlyA is more virulent than the parental strain. We hypothesized that this phenotype was due to overexpression of the second gene of the
slyA
operon,
ef_3001
, renamed
pmvE
(for
p
olyamine
m
etabolism and
v
irulence of
E. faecalis
). PmvE shares strong homologies with
N

1

-spermidine/spermine acetyltransferase enzymes involved in the metabolism of polyamines. In this study, we used an
E. faecalis
strain carrying the recombinant plasmid pMSP3535-
pmvE
(V19/p3535-
pmvE
), which allows the induction of
pmvE
by addition of nisin. Thereby, we showed that the overexpression of PmvE increased the virulence of
E. faecalis
in the
Galleria mellonella
infection model, as well as the persistence within peritoneal macrophages. We were also able to show a direct interaction between the His-tagged recombinant PmvE (rPmvE) protein and putrescine by the surface plasmon resonance (SPR) technique on a Biacore instrument. Moreover, biochemical assays showed that PmvE possesses an
N
-acetyltransferase activity toward polyamine substrates. Our results suggest that PmvE contributes to the virulence of
E. faecalis
, likely through its involvement in the polyamine metabolism.
Pseudomonas aeruginosa LysR PA4203 Regulator NmoR Acts as a Repressor of the PA4202
nmoA
Gene, Encoding a Nitronate Monooxygenase
Authors: Vercammen Ken , Wei Qing , Charlier Daniel , Dötsch Andreas , Haüssler Susanne , Schulz Sebastian , Salvi Francesca , Gadda Giovanni , Spain Jim , Rybtke Morten Levin , Tolker-Nielsen Tim , Dingemans Jozef , Ye Lumeng , Cornelis Pierre
Published: November 2014

The PA4203 gene encodes a LysR regulator and lies between the
ppgL
gene (PA4204), which encodes a periplasmic gluconolactonase, and, in the opposite orientation, the PA4202 (
nmoA
) gene, coding for a nitronate monooxygenase, and
ddlA
(PA4201), encoding a
d
-alanine alanine ligase. The intergenic regions between PA4203 and
ppgL
and between PA4203 and
nmoA
are very short (79 and 107 nucleotides, respectively). Here we show that PA4203 (
nmoR
) represses its own transcription and the expression of
nmoA
. A chromatin immunoprecipitation analysis showed the presence of a single NmoR binding site between
nmoA
and
nmoR
, which was confirmed by electrophoretic mobility shift assays (EMSAs) with the purified NmoR protein. Despite this observation, a transcriptome analysis revealed more genes to be affected in an
nmoR
mutant, including genes known to be part of the MexT LysR activator regulon. The PA1225 gene, encoding a quinone oxidoreductase, was the most highly upregulated gene in the
nmoR
deletion mutant, independently of MexT. Finally, deletion of the
nmoA
gene resulted in an increased sensitivity of the cells to 3-nitropropionic acid (3-NPA), confirming the role of the nitronate monooxygenase protein in the detoxification of nitronate.
Lactococcus lactis Metabolism and Gene Expression during Growth on Plant Tissues
Authors: Golomb Benjamin L. , Marco Maria L.
Published: November 2014

Lactic acid bacteria have been isolated from living, harvested, and fermented plant materials; however, the adaptations these bacteria possess for growth on plant tissues are largely unknown. In this study, we investigated plant habitat-specific traits ofLactococcus lactisduring growth in anArabidopsis thalianaleaf tissue lysate (ATL).L. lactisKF147, a strain originally isolated from plants, exhibited a higher growth rate and reached 7.9-fold-greater cell densities during growth in ATL than the dairy-associated strainL. lactisIL1403. Transcriptome profiling (RNA-seq) of KF147 identified 853 induced and 264 repressed genes during growth in ATL compared to that in GM17 laboratory culture medium. Genes induced in ATL included those involved in the arginine deiminase pathway and a total of 140 carbohydrate transport and metabolism genes, many of which are involved in xylose, arabinose, cellobiose, and hemicellulose metabolism. The induction of those genes corresponded withL. lactisKF147 nutrient consumption and production of metabolic end products in ATL as measured by gas chromatography-time of flight mass spectrometry (GC-TOF/MS) untargeted metabolomic profiling. To assess the importance of specific plant-inducible genes forL. lactisgrowth in ATL, xylose metabolism was targeted for gene knockout mutagenesis. Wild-typeL. lactisstrain KF147 but not anxylAdeletion mutant was able to grow using xylose as the sole carbon source. However, both strains grew to similarly high levels in ATL, indicating redundancy inL. lactiscarbohydrate metabolism on plant tissues. These findings show that certain strains ofL. lactisare well adapted for growth on plants and possess specific traits relevant for plant-based food, fuel, and feed fermentations.
Aortoduodenal syndrome in a patient receiving maintenance haemodialysis
Authors: Saigusa Susumu , Ohi Masaki , Imaoka Hiroki , Inoue Yasuhiro
Published: November 2014

An 83-year-old man receiving maintenance haemodialysis presented with abdominal pain, fever and emesis. He was initially diagnosed with acute cholecystitis. His pain and fever improved with fasting and antibiotics, but he continued to suffer from anorexia and emesis. Enhanced abdominal CT scan showed evidence of superior mesenteric artery (SMA) syndrome versus obstruction of the third part of the duodenum caused by abdominal aortic aneurysm (AAA), the so-called aortoduodenal syndrome. An upper gastrointestinal contrast study revealed duodenal dilation and blockage of the third part of the duodenum. The AAA continued to enlarge over the subsequent 3 months and the intra-abdominal visceral fat volume decreased over 1 month. The aortomesentric angle and distance remained within normal ranges. Ultimately, the patient was diagnosed with aortoduodenal syndrome. In the present case, a duodenal obstruction was caused by the combination of an enlarged AAA and reduced intra-abdominal visceral fat in a patient receiving maintenance haemodialysis.
Depression, adherence and attrition from care in HIV-infected adults receiving antiretroviral therapy
Authors: Krumme Alexis A , Kaigamba Felix , Binagwaho Agnes , Murray Megan B , Rich Michael L , Franke Molly F
Published: November 2014

Background

A better understanding of the relationship between depression and HIV-related outcomes, particularly as it relates to adherence to treatment, is critical to guide effective support and treatment of individuals with HIV and depression. We examined whether depression was associated with attrition from care in a cohort of 610 HIV-infected adults in rural Rwanda and whether this relationship was mediated through suboptimal adherence to treatment.

Methods

The association between depression and attrition from care was evaluated with a Cox proportional hazard model and with mediation methods that calculate the direct and indirect effects of depression on attrition and are able to account for interactions between depression and suboptimal adherence. Depression was assessed with the Hopkins Symptom Checklist-15; attrition was defined as death, treatment default, or loss to follow-up.

Results

Baseline depression was significantly associated with time to attrition after adjustment for receipt of community-based accompaniment, physical functioning quality of life score, and CD4 cell count (HR=2.40, 95% CI 1.27 to 4.52, p=0.005). In multivariable mediation analysis, we found no evidence that the association between depression and attrition after 3 months was mediated by suboptimal adherence (direct effect of depression on attrition: OR=3.90 (1.26 to 12.04), p=0.02; indirect effect: OR=1.07 (0.92 to 1.25), p=0.38).

Conclusions

Even in the context of high antiretroviral therapy adherence, depression may adversely influence HIV outcomes through a pathway other than suboptimal adherence. Treatment of depression is critical to achieving good mental health and retention in HIV-infected individuals with depression.
Cervical cancer screening (Pap testing) behaviours and acceptability of human papillomavirus self-testing among lesbian and bisexual women aged 21–26 years in the USA
Authors: Reiter Paul L , McRee Annie-Laurie
Published: November 2014

Objective

Lesbian and bisexual women are at risk for human papillomavirus (HPV) infection and cervical disease. We examined cervical cancer screening (Pap testing) behaviours among these women and their acceptability of HPV self-testing at home, a potential cervical cancer screening strategy.

Methods

We analysed data from a national sample of lesbian and bisexual women aged 21–26 years (n=418) who completed our online survey in Autumn 2013. Logistic regression identified correlates of (1) having had a Pap test in the last 3 years and (2) willingness to use an HPV self-test at home.

Results

About 70% of women had undergone a Pap test in the last 3 years. Pap testing was more common among women who had disclosed their sexual orientation to their health care provider [odds ratio (OR)=2.01, 95% confidence interval (CI) 1.02–3.95] and less common among women who self-identified as lesbian (OR=0.48, 95% CI 0.25–0.93). Just over half the women (51%) were willing to use an HPV self-test at home. Women were more willing to use an HPV self-test at home if they were older (OR=1.16, 95% CI 1.03–1.30) or reported higher levels of worry about getting an HPV-related disease (OR=1.28, 95% CI 1.01–1.63). The most common concerns about HPV self-testing at home were using the test incorrectly (70%) and test accuracy (64%).

Conclusions

Many young lesbian and bisexual women have not had a recent Pap test. HPV self-testing at home may be a promising future strategy for reaching and screening these women. Findings highlight beliefs and concerns that could be addressed by self-test programmes.
Effect of antiplatelet therapy and platelet function testing on hemorrhagic and thrombotic complications in patients with cerebral aneurysms treated with the pipeline embolization device: a review and meta-analysis
Authors: Skukalek Susana L , Winkler Anne M , Kang Jian , Dion Jacques E , Cawley C Michael , Webb Adam , Dannenbaum Mark J , Schuette Albert J , Asbury Bill , Tong Frank C
Published: November 2014

Purpose

The pipeline embolization device (PED) necessitates dual antiplatelet therapy (APT) to decrease thrombotic complications while possibly increasing bleeding risks. The role of APT dose, duration, and response in patients with hemorrhagic and thromboembolic events warrants further analysis.

Methods

A PubMed and Google Scholar search from 2009 to 2014 was performed using the following search terms individually or in combination: pipeline embolization device, aneurysm(s), and flow diversion, excluding other flow diverters. Review of the bibliographies of the retrieved articles yielded 19 single and multicenter studies. A statistical meta-analysis between aspirin (ASA) dose (low dose ≤160 mg, high dose ≥300 mg), loading doses of APT agents, post-PED APT regimens, and platelet function testing (PFT) with hemorrhagic or thrombotic complications was performed.

Results

ASA therapy for ≤6 months post-PED was associated with increased hemorrhagic events. High dose ASA ≤6 months post-PED was associated with fewer thrombotic events compared with low dose ASA. Post-PED clopidogrel for ≤6 months demonstrated an increased incidence of symptomatic thrombotic events. Loading doses of ASA plus clopidogrel demonstrated a decreased incidence of permanent symptomatic hemorrhagic events. PFT did not show a statistically significant relationship with symptomatic hemorrhagic or thrombotic complications.

Conclusions

High dose ASA >6 months is associated with fewer permanent thrombotic and hemorrhagic events. Clopidogrel therapy ≤6 months is associated with higher rates of thrombotic events. Loading doses of ASA and clopidogrel were associated with a decreased incidence of hemorrhagic events. PFT did not have any significant association with symptomatic events.
Influence of specimen height-to-width ratio on the strainburst characteristics of Tianhu granite under true-triaxial unloading conditions
Authors: Zhao X.G. , Cai M.
Published: November 2014

Strainbursts occur frequently near excavation boundaries, posing a significant threat to the safety of workers and stability of underground structures. A better understanding of the strainburst phenomenon is important for safe underground construction and risk management. This paper presents the results of an experimental study on strainburst behaviours of Tianhu granite with four specimen height-to-width (H/W) ratios. A series of tests under unloading conditions were conducted using a true-triaxial strainburst test system that was equipped with an acoustic emission (AE) monitoring system. A high-speed camera was used to capture the instantaneous strainburst process of the specimens on the unloading surface. The experimental results indicate that regardless of the H/W ratio, strainbursts occurred in all specimens but strainburst characteristics depend on the H/W ratio. When the H/W ratio changes from 2.5 to 1.0, the dynamic failure process of the unloading surface transforms from local rock ejection to full-face burst. The strainburst is more violent when the H/W ratio is small. Analysis of the cumulative AE energy revealed that the cumulative AE energy is not sensitive to the H/W ratio for ratios lower than 1.5. When the H/W ratio is greater than 1.5, the cumulative AE energy shows a decreasing trend during rock failure.
Improving Human Activity Recognition and its Application in Early Stroke Diagnosis
Authors: Villar José R. , González Silvia , Sedano Javier , Chira Camelia , Trejo-Gabriel-Galan Jose M.
Published: November 2014

The development of efficient stroke-detection methods is of significant importance in today's society due to the effects and impact of stroke on health and economy worldwide. This study focuses on Human Activity Recognition (HAR), which is a key component in developing an early stroke-diagnosis tool. An overview of the proposed global approach able to discriminate normal resting from stroke-related paralysis is detailed. The main contributions include an extension of the Genetic Fuzzy Finite State Machine (GFFSM) method and a new hybrid feature selection (FS) algorithm involving Principal Component Analysis (PCA) and a voting scheme putting the cross-validation results together. Experimental results show that the proposed approach is a well-performing HAR tool that can be successfully embedded in devices.
Central soft production of hadrons in pp collisions
Authors: Donnachie A. , Landshoff P. V.
Published: November 2014

The high-energy behavior of soft scattering observables such as total cross-sections, elastic scattering at small momentum transfer, diffractive dissociation and central production have been described successfully in the context of Regge theory, with the same basic structure holding as energies have increased. For elastic scattering and diffraction dissociation the defining energies were those of the ISR, the [Formula: see text] collider and the Tevatron. The elastic scattering data from the LHC demonstrate the continuing applicability of Regge theory. Preliminary data on diffraction dissociation promise to add to our understanding and now, for the first time, we can expect to test fully these concepts in central production. Although the latter is the principal objective of this discussion, understanding the first two is an essential prerequisite as they define the formalism and establish parameters.
Trigonometric identities and volumes of the hyperbolic twist knot cone-manifolds
Authors: Ham Ji-Young , Mednykh Alexander , Petrov Vladimir
Published: November 2014

We calculate the volumes of the hyperbolic twist knot cone-manifolds using the Schläfli formula. Even though general ideas for calculating the volumes of cone-manifolds are around, since there is no concrete calculation written, we present here the concrete calculations. We express the length of the singular locus in terms of the distance between the two axes fixed by two generators. In this way the calculation becomes easier than using the singular locus directly. The volumes of the hyperbolic twist knot cone-manifolds simpler than Stevedore's knot are known. As an application, we give the volumes of the cyclic coverings over the hyperbolic twist knots.
Solution of Faddeev integral equations in configuration space using the hyperspherical harmonics expansion method
Authors: Kovalchuk Valery I.
Published: November 2014

In this paper, a method has been developed to solve three-particle Faddeev equations in the configuration space making use of a series expansion in hyperspherical harmonics. The following parameters of the bound state of triton and helium-3 nuclei have been calculated: the binding energies, the weights of symmetric and mixed-symmetry components of the wave function, the magnetic moments, and the charge radii.
Core–crust transition properties of neutron stars within systematically varied extended relativistic mean-field model
Authors: Sulaksono A. , Alam Naosad , Agrawal B. K.
Published: November 2014

The model dependence and the symmetry energy dependence of the core–crust transition properties for the neutron stars (NS) are studied using three different families of systematically varied extended relativistic mean field model. Several forces within each of the families are so considered that they yield wide variations in the values of the nuclear symmetry energy a sym and its slope parameter L at the saturation density. The core–crust transition density is calculated using a method based on random-phase-approximation. The core–crust transition density is strongly correlated, in a model independent manner, with the symmetry energy slope parameter evaluated at the saturation density. The pressure at the transition point does not show any meaningful correlations with the symmetry energy parameters at the saturation density. At best, pressure at the transition point is correlated with the symmetry energy parameters and their linear combination evaluated at the some sub-saturation density. Yet, such correlations might not be model independent. The correlations of core–crust transition properties with the symmetry energy parameter are also studied by varying the symmetry energy within a single model. The pressure at the transition point is correlated once again with the symmetry energy parameter at the sub-saturation density.
Bottom-strange mesons in hyperonic matter
Authors: Pathak Divakar , Mishra Amruta
Published: November 2014

The in-medium behavior of bottom-strange pseudoscalar mesons in hot, isospin asymmetric and dense hadronic environment is studied using a chiral effective model. The same was recently generalized to the heavy quark sector and employed to study the behavior of open-charm and open-bottom mesons. The heavy quark (anti-quark) is treated as frozen and all medium modifications of these bottom-strange mesons are due to their strange anti-quark (quark) content. We observe a pronounced dependence of their medium mass on baryonic density and strangeness content of the medium. Certain aspects of these in-medium interactions are similar to those observed for the strange-charmed mesons in a preceding investigation, such as the lifting of mass-degeneracy of [Formula: see text] and [Formula: see text] mesons in hyperonic matter, while the same is respected in vacuum as well as in nuclear matter. In general, however, there is a remarkable distinction between the two species, even though the formalism predicts a completely analogous in-medium interaction Lagrangian density. We discuss in detail the reason for different in-medium behavior of these bottom-strange mesons as compared to charmed-strange mesons, despite the dynamics of the heavy quark being treated as frozen in both cases.
Mechanism Study of Gene Delivery and Expression in PK-15 Cells Using Magnetic Iron Oxide Nanoparticles as Gene Carriers
Authors: Wang Yan , Cui Haixin , Yang Yongguang , Zhao Xiang , Sun Changjiao , Chen Wenjie , Du Wei , Cui Jinhui
Published: November 2014

The mechanism of gene delivery and expression is one of the most important concerns raised by the development of gene delivery methods. Limited investigation is performed on how magnetic nanoparticles combine with DNA and deliver gene into mammalian cells. In this context, polyethyleneimine (PEI) coated iron oxide magnetic nanoparticles (MNPs) were used as gene carriers for binding and condensing with plasmid DNA expressing enhanced green fluorescent protein (EGFP). The morphology and structure of MNP–DNA complexes were characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM). We evidenced that large amounts of DNA wrapped around the surface of MNPs and that the MNPs were physically entrapped by the DNA arranged both horizontally and vertically. EGFP gene was successfully expressed under mediation of an external magnetic field which is necessary to efficiently target EGFP gene to the cells. Fluorescence from EGFP was separately detected in the cell cytoplasm and cell nucleus.