bluuebunny/crossref_metadata_2025 huggingface dataset:
Subtle Differences in Virus Composition Affect Disinfection Kinetics and Mechanisms
Authors: Sigstam Thérèse , Gannon Greg , Cascella Michele , Pecson Brian M. , Wigginton Krista Rule , Kohn Tamar
Published: March 2013

Viral disinfection kinetics have been studied in depth, but the molecular-level inactivation mechanisms are not understood. Consequently, it is difficult to predict the disinfection behavior of nonculturable viruses, even when related, culturable viruses are available. The objective of this work was to determine how small differences in the composition of the viral genome and proteins impact disinfection. To this end, we investigated the inactivation of three related bacteriophages (MS2, fr, and GA) by UV
254
, singlet oxygen (
1
O
2
), free chlorine (FC), and chlorine dioxide (ClO
2
). Genome damage was quantified by PCR, and protein damage was assessed by quantitative matrix-assisted laser desorption ionization (MALDI) mass spectrometry. ClO
2
caused great variability in the inactivation kinetics between viruses and was the only treatment that did not induce genome damage. The inactivation kinetics were similar for all viruses when treated with disinfectants possessing a genome-damaging component (FC,
1
O
2
, and UV
254
). On the protein level, UV
254
subtly damaged MS2 and fr capsid proteins, whereas GA's capsid remained intact.
1
O
2
oxidized a methionine residue in MS2 but did not affect the other two viruses. In contrast, FC and ClO
2
rapidly degraded the capsid proteins of all three viruses. Protein composition alone could not explain the observed degradation trends; instead, molecular dynamics simulations indicated that degradation is dictated by the solvent-accessible surface area of individual amino acids. Finally, despite the similarities of the three viruses investigated, their mode of inactivation by a single disinfectant varied. This explains why closely related viruses can exhibit drastically different inactivation kinetics.
Phenotype Overlap in Xylella fastidiosa Is Controlled by the Cyclic Di-GMP Phosphodiesterase Eal in Response to Antibiotic Exposure and Diffusible Signal Factor-Mediated Cell-Cell Signaling
Authors: de Souza Alessandra A. , Ionescu Michael , Baccari Clelia , da Silva Aline M. , Lindow Steven E.
Published: March 2013

Eal is an EAL domain protein in
Xylella fastidiosa
homologous to one involved in resistance to tobramycin in
Pseudomonas aeruginosa
. EAL and HD-GYP domain proteins are implicated in the hydrolysis of the secondary messenger bis-(3′-5′)-cyclic dimeric GMP (cyclic di-GMP). Cell density-dependent communication mediated by a Diffusible Signal Factor (DSF) also modulates cyclic di-GMP levels in
X. fastidiosa
, thereby controlling the expression of virulence genes and genes involved in insect transmission. The possible linkage of Eal to both extrinsic factors such as antibiotics and intrinsic factors such as quorum sensing, and whether both affect virulence, was thus addressed. Expression of
eal
was induced by subinhibitory concentrations of tobramycin, and an
eal
deletion mutant was more susceptible to this antibiotic than the wild-type strain and exhibited phenotypes similar to those of an
rpfF
deletion mutant blocked in DSF production, such as hypermotility, reduced biofilm formation, and hypervirulence to grape. Consistent with that, the
rpfF
mutant was more susceptible than the wild-type strain to tobramycin. Therefore, we propose that cell-cell communication and antibiotic stress can apparently lead to similar modulations of cyclic di-GMP in
X. fastidiosa
, resulting in similar phenotypes. However, the effect of cell density is dominant compared to that of antibiotic stress, since
eal
is suppressed by RpfF, which may prevent inappropriate behavioral changes in response to antibiotic stress when DSF accumulates.
An Expanded Genetic Code in Candida albicans To Study Protein-Protein Interactions
In Vivo
Authors: Palzer Silke , Bantel Yannick , Kazenwadel Franziska , Berg Michael , Rupp Steffen , Sohn Kai
Published: March 2013

For novel insights into the pathogenicity of
Candida albicans
, studies on molecular interactions of central virulence factors are crucial. Since methods for the analysis of direct molecular interactions of proteins
in vivo
are scarce, we expanded the genetic code of
C. albicans
with the synthetic photo-cross-linking amino acid
p
-azido-
l
-phenylalanine (AzF). Interacting molecules in close proximity of this unnatural amino acid can be covalently linked by UV-induced photo-cross-link, which makes unknown interacting molecules available for downstream identification. Therefore, we applied an aminoacyl-tRNA synthetase and a suppressor tRNA pair (
Ec
TyrtRNA
CUA
) derived from
Escherichia coli
, which was previously reported to be orthogonal in
Saccharomyces cerevisiae
. We further optimized the aminoacyl-tRNA synthetase for AzF (AzF-RS) and
Ec
TyrtRNA
CUA
for
C. albicans
and identified one AzF-RS with highest charging efficiency. Accordingly, incorporation of AzF into selected model proteins such as Tsa1p or Tup1p could be considerably enhanced. Immunologic detection of C-terminally tagged Tsa1p and Tup1p upon UV irradiation in a strain background containing suppressor tRNA and optimized AzF-RS revealed not only the mutant monomeric forms of these proteins but also higher-molecular-weight complexes, strictly depending on the specific position of incorporated AzF and UV excitation. By Western blotting and tandem mass spectrometry, we could identify these higher-molecular-weight complexes as homodimers consisting of one mutant monomer and a differently tagged, wild-type version of Tsa1p or Tup1p, respectively, demonstrating that expanding the genetic code of
C. albicans
with the unnatural photo-cross-linker amino acid AzF and applying it for
in vivo
binary protein interaction analyses is feasible.
Central Carbon Metabolism and Electron Transport in Chlamydomonas reinhardtii: Metabolic Constraints for Carbon Partitioning between Oil and Starch
Authors: Johnson Xenie , Alric Jean
Published: March 2013

The metabolism of microalgae is so flexible that it is not an easy task to give a comprehensive description of the interplay between the various metabolic pathways. There are, however, constraints that govern central carbon metabolism in
Chlamydomonas reinhardtii
that are revealed by the compartmentalization and regulation of the pathways and their relation to key cellular processes such as cell motility, division, carbon uptake and partitioning, external and internal rhythms, and nutrient stress. Both photosynthetic and mitochondrial electron transfer provide energy for metabolic processes and how energy transfer impacts metabolism and vice versa is a means of exploring the regulation and function of these pathways. A key example is the specific chloroplast localization of glycolysis/gluconeogenesis and how it impacts the redox poise and ATP budget of the plastid in the dark. To compare starch and lipids as carbon reserves, their value can be calculated in terms of NAD(P)H and ATP. As microalgae are now considered a potential renewable feedstock, we examine current work on the subject and also explore the possibility of rerouting metabolism toward lipid production.
Posttranslational Modification of Flagellin FlaB in Shewanella oneidensis
Authors: Sun Linlin , Jin Miao , Ding Wen , Yuan Jie , Kelly John , Gao Haichun
Published: March 2013

Shewanella oneidensis
is a highly motile organism by virtue of a polar, glycosylated flagellum composed of flagellins FlaA and FlaB. In this study, the functional flagellin FlaB was isolated and analyzed with nano-liquid chromatography-mass spectrometry (MS) and tandem MS. In combination with the mutational analysis, we propose that the FlaB flagellin protein from
S. oneidensis
is modified at five serine residues with a series of novel
O
-linked posttranslational modifications (PTMs) that differ from each other by 14 Da. These PTMs are composed in part of a 274-Da sugar residue that bears a resemblance to the nonulosonic acids. The remainder appears to be composed of a second residue whose mass varies by 14 Da depending on the PTM. Further investigation revealed that synthesis of the glycans initiates with PseB and PseC, the first two enzymes of the Pse pathway. In addition, a number of lysine residues are found to be methylated by SO4160, an analogue of the lysine methyltransferase of
Salmonella enterica
serovar
Typhimurium
.
The Rcs Stress Response and Accessory Envelope Proteins Are Required for
De Novo
Generation of Cell Shape in Escherichia coli
Authors: Ranjit Dev K. , Young Kevin D.
Published: March 2013

Interactions with immune responses or exposure to certain antibiotics can remove the peptidoglycan wall of many Gram-negative bacteria. Though the spheroplasts thus created usually lyse, some may survive by resynthesizing their walls and shapes. Normally, bacterial morphology is generated by synthetic complexes directed by FtsZ and MreBCD or their homologues, but whether these classic systems can recreate morphology in the absence of a preexisting template is unknown. To address this question, we treated
Escherichia coli
with lysozyme to remove the peptidoglycan wall while leaving intact the inner and outer membranes and periplasm. The resulting lysozyme-induced (LI) spheroplasts recovered a rod shape after four to six generations. Recovery proceeded via a series of cell divisions that produced misshapen and branched intermediates before later progeny assumed a normal rod shape. Importantly, mutants defective in mounting the Rcs stress response and those lacking penicillin binding protein 1B (PBP1B) or LpoB could not divide or recover their cell shape but instead enlarged until they lysed. LI spheroplasts from mutants lacking the Lpp lipoprotein or PBP6 produced spherical daughter cells that did not recover a normal rod shape or that did so only after a significant delay. Thus, to regenerate normal morphology
de novo
,
E. coli
must supplement the classic FtsZ- and MreBCD-directed cell wall systems with activities that are otherwise dispensable for growth under normal laboratory conditions. The existence of these auxiliary mechanisms implies that they may be required for survival in natural environments, where bacterial walls can be damaged extensively or removed altogether.
The Clostridium difficile
cpr
Locus Is Regulated by a Noncontiguous Two-Component System in Response to Type A and B Lantibiotics
Authors: Suárez Jose M. , Edwards Adrianne N. , McBride Shonna M.
Published: March 2013

The intestinal pathogen
Clostridium difficile
is known to grow only within the intestines of mammals, yet little is known about how the bacterium subsists in this environment. In the intestine,
C. difficile
must contend with innate defenses within the host, such as cationic antimicrobial peptides (CAMPs) produced by the host and the indigenous microbiota. In this study, we investigated the mechanism of activation and regulation of the CprABC transporter system, which provides resistance to multiple CAMPs and shows homology to the immunity systems of bacterial antimicrobial peptide producers. The CprABC system proved to be controlled by a noncontiguous two-component system consisting of the CprK sensor kinase and an orphan response regulator (CD3320; CprR). The CprK-CprR regulators were shown to activate
cprABCK
transcription in a manner similar to that by lantibiotic regulatory systems. Unlike lantibiotic producer regulation, regulation by CprK-CprR was activated by multiple lantibiotics produced by diverse Gram-positive bacteria. We identified a motif within these lantibiotics that is likely required for activation of
cpr
. Based on the similarities between the Cpr system and lantibiotic systems, we propose that the CprABC transporter and its regulators are relatives of lantibiotic systems that evolved to recognize multiple substrates to defend against toxins made by the intestinal microbiota.
The δ Subunit of RNA Polymerase Is Required for Rapid Changes in Gene Expression and Competitive Fitness of the Cell
Authors: Rabatinová Alžbeta , Šanderová Hana , Jirát Matějčková Jitka , Korelusová Jana , Sojka Luděk , Barvík Ivan , Papoušková Veronika , Sklenář Vladimír , Žídek Lukáš , Krásný Libor
Published: March 2013

RNA polymerase (RNAP) is an extensively studied multisubunit enzyme required for transcription of DNA into RNA, yet the δ subunit of RNAP remains an enigmatic protein whose physiological roles have not been fully elucidated. Here, we identify a novel, so far unrecognized function of δ from
Bacillus subtilis
. We demonstrate that δ affects the regulation of RNAP by the concentration of the initiating nucleoside triphosphate ([iNTP]), an important mechanism crucial for rapid changes in gene expression in response to environmental changes. Consequently, we demonstrate that δ is essential for cell survival when facing a competing strain in a changing environment. Hence, although δ is not essential
per se
, it is vital for the cell's ability to rapidly adapt and survive in nature. Finally, we show that two other proteins, GreA and YdeB, previously implicated to affect regulation of RNAP by [iNTP] in other organisms, do not have this function in
B. subtilis
.
Competence for Natural Genetic Transformation in the Streptococcus bovis Group Streptococci S. infantarius and S. macedonicus
Authors: Morrison Donald A. , Guédon Eric , Renault Pierre
Published: March 2013

Natural genetic transformation is common among many species of the genus
Streptococcus
, but it has never, or rarely, been reported for the
Streptococcus pyogenes
and
S. bovis
groups of species, even though many streptococcal competence genes and the competence regulators SigX, ComR, and ComS are well conserved in both groups. To explore the incidence of competence in the
S. bovis
group, 25 isolates of
S. infantarius
and
S. macedonicus
were surveyed by employing culture in chemically defined media devoid of peptide nutrients and treatment with synthetic candidate pheromone peptides predicted from the sequence of the gene
comS
. Approximately half of strains examined were transformable, many transforming at high rates comparable to those for the well-characterized streptococcal natural transformation systems. In
S. infantarius
, nanomolar amounts of the synthetic pheromone LTAWWGL induced robust but transient competence in high-density cultures, but mutation of the ComRS locus abolished transformation. We conclude that at least these two species of the
S. bovis
group retain a robust system of natural transformation regulated by a ComRS pheromone circuit and the alternative sigma factor SigX and infer that transformation is even more common among the streptococci than has been recognized. The tools presented here will facilitate targeted genetic manipulation in this group of streptococci.
Activity and Regulation of Various Forms of CwlJ, SleB, and YpeB Proteins in Degrading Cortex Peptidoglycan of Spores of Bacillus Species
In Vitro
and during Spore Germination
Authors: Li Yunfeng , Butzin Xuan Y. , Davis Andrew , Setlow Barbara , Korza George , Üstok Fatma Işik , Christie Graham , Setlow Peter , Hao Bing
Published: March 2013

Germination of
Bacillus
spores requires degradation of a modified layer of peptidoglycan (PG) termed the spore cortex by two redundant cortex-lytic enzymes (CLEs), CwlJ and SleB, plus SleB's partner protein, YpeB. In this study,
in vitro
and
in vivo
analyses have been used to clarify the roles of individual SleB and YpeB domains in PG degradation. Purified mature
Bacillus cereus
SleB without its signal sequence (SleB
M
) and the SleB C-terminal catalytic domain (SleB
C
) efficiently triggered germination of decoated
Bacillus megaterium
and
Bacillus subtilis
spores lacking endogenous CLEs; previously, SleB's N-terminal domain (SleB
N
) was shown to bind PG but have no enzymatic activity. YpeB lacking its putative membrane anchoring sequence (YpeB
M
) or its N- and C-terminal domains (YpeB
N
and YpeB
C
) alone did not exhibit degradative activity, but YpeB
N
inhibited SleB
M
and SleB
C
activity
in vitro
. The severe germination defect of
B. subtilis
c
wlJ sleB
or
cwlJ sleB ypeB
spores was complemented by ectopic expression of full-length
sleB
[
sleB
(FL)] and
ypeB
[
ypeB
(FL)], but normal levels of SleB
FL
in spores required normal spore levels of YpeB
FL
and vice versa.
sleB
(FL) or
ypeB
(FL) alone,
sleB
(FL) plus
ypeB
(C) or
ypeB
(N), and
sleB
(C) or
sleB
(N) plus
ypeB
(FL) did not complement the cortex degradation defect in
cwlJ sleB ypeB
spores. In addition, ectopic expression of
sleB
(FL) or
cwlJ
(FL) with a Glu-to-Gln mutation in a predicted active-site residue failed to restore the germination of
cwlJ sleB
spores, supporting the role of this invariant glutamate as the key catalytic residue in SleB and CwlJ.
Maltose Uptake by the Novel ABC Transport System MusEFGK
2
I Causes Increased Expression of
ptsG
in Corynebacterium glutamicum
Authors: Henrich Alexander , Kuhlmann Nora , Eck Alexander W. , Krämer Reinhard , Seibold Gerd M.
Published: March 2013

The Gram-positive
Corynebacterium glutamicum
efficiently metabolizes maltose by a pathway involving maltodextrin and glucose formation by 4-α-glucanotransferase, glucose phosphorylation by glucose kinases, and maltodextrin degradation via maltodextrin phosphorylase and α-phosphoglucomutase. However, maltose uptake in
C. glutamicum
has not been investigated. Interestingly, the presence of maltose in the medium causes increased expression of
ptsG
in
C. glutamicum
by an unknown mechanism, although the
ptsG
-encoded glucose-specific EII permease of the phosphotransferase system itself is not required for maltose utilization. We identified the maltose uptake system as an ABC transporter encoded by
musK
(
cg2708
; ATPase subunit),
musE
(
cg2705
; substrate binding protein),
musF
(
cg2704
; permease), and
musG
(
cg2703
; permease) by combination of data obtained from characterization of maltose uptake and reanalyses of transcriptome data. Deletion of the
mus
gene cluster in
C. glutamicum
Δ
mus
abolished maltose uptake and utilization. Northern blotting and reverse transcription-PCR experiments revealed that
musK
and
musE
are transcribed monocistronically, whereas
musF
and
musG
are part of an operon together with
cg2701
(
musI
), which encodes a membrane protein of unknown function with no homologies to characterized proteins. Characterization of growth and [
14
C]maltose uptake in the
musI
insertion strain
C. glutamicum
IM
cg2701
showed that
musI
encodes a novel essential component of the maltose ABC transporter of
C. glutamicum
. Finally,
ptsG
expression during cultivation on different carbon sources was analyzed in the maltose uptake-deficient strain
C. glutamicum
Δ
mus
. Indeed, maltose uptake by the novel ABC transport system MusEFGK
2
I is required for the positive effect of maltose on
ptsG
expression in
C. glutamicum
.
Relaxed Cleavage Specificity within the RelE Toxin Family
Authors: Goeders Nathalie , Drèze Pierre-Luc , Van Melderen Laurence
Published: March 2013

Bacterial type II toxin-antitoxin systems are widespread in bacteria. Among them, the RelE toxin family is one of the most abundant. The RelE
K-12
toxin of
Escherichia coli
K-12 represents the paradigm for this family and has been extensively studied, both
in vivo
and
in vitro
. RelE
K-12
is an endoribonuclease that cleaves mRNAs that are translated by the ribosome machinery as these transcripts enter the A site. Earlier
in vivo
reports showed that RelE
K-12
cleaves preferentially in the 5′-end coding region of the transcripts in a codon-independent manner. To investigate whether the molecular activity as well as the cleavage pattern are conserved within the members of this toxin family, RelE-like sequences were selected in
Proteobacteria
,
Cyanobacteria
,
Actinobacteria
, and
Spirochaetes
and tested in
E. coli
. Our results show that these RelE-like sequences are part of toxin-antitoxin gene pairs, and that they inhibit translation in
E. coli
by cleaving transcripts that are being translated. Primer extension analyses show that these toxins exhibit specific cleavage patterns
in vivo
, both in terms of frequency and location of cleavage sites. We did not observe codon-dependent cleavage but rather a trend to cleave upstream purines and between the second and third positions of codons, except for the actinobacterial toxin. Our results suggest that RelE-like toxins have evolved to rapidly and efficiently shut down translation in a large spectrum of bacterial species, which correlates with the observation that toxin-antitoxin systems are spreading by horizontal gene transfer.
A Critical Role for the
cccA
Gene Product, Cytochrome
c
2
, in Diverting Electrons from Aerobic Respiration to Denitrification in Neisseria gonorrhoeae
Authors: Hopper Amanda C. , Li Ying , Cole Jeffrey A.
Published: March 2013

Neisseria gonorrhoeae
is a microaerophile that, when oxygen availability is limited, supplements aerobic respiration with a truncated denitrification pathway, nitrite reduction to nitrous oxide. We demonstrate that the
cccA
gene of
Neisseria gonorrhoeae
strain F62 (accession number
NG0292
) is expressed, but the product, cytochrome
c
2
, accumulates to only low levels. Nevertheless, a
cccA
mutant reduced nitrite at about half the rate of the parent strain. We previously reported that cytochromes
c
4
and
c
5
transfer electrons to cytochrome oxidase
cbb
3
by two independent pathways and that the CcoP subunit of cytochrome oxidase
cbb
3
transfers electrons to nitrite. We show that mutants defective in either cytochrome
c
4
or
c
5
also reduce nitrite more slowly than the parent. By combining mutations in
cccA
(Δ
c
2
),
cycA
(Δ
c
4
),
cycB
(Δ
c
5
), and
ccoP
(
ccoP
-C368A), we demonstrate that cytochrome
c
2
is required for electron transfer from cytochrome
c
4
via the third heme group of CcoP to the nitrite reductase, AniA, and that cytochrome
c
5
transfers electrons to nitrite reductase by an independent pathway. We propose that cytochrome
c
2
forms a complex with cytochrome oxidase. If so, the redox state of cytochrome
c
2
might regulate electron transfer to nitrite or oxygen. However, our data are more consistent with a mechanism in which cytochrome
c
2
and the CcoQ subunit of cytochrome oxidase form alternative complexes that preferentially catalyze nitrite and oxygen reduction, respectively. Comparison with the much simpler electron transfer pathway for nitrite reduction in the meningococcus provides fascinating insights into niche adaptation within the pathogenic neisseriae.
The Effect of Electroacupuncture on Osteotomy Gap Healing in a Rat Fibula Model
Authors: Inoue Motohiro , Nakajima Miwa , Hojo Tatsuya , Itoi Megumi , Kitakoji Hiroshi
Published: March 2013

Objective

To examine the effect of electroacupuncture (EA) on osteotomy gap healing in a rat fibula model.

Methods

A total of 40 12-week-old male Wistar rats underwent unilateral open osteotomy of the fibula to create a 2 mm gap. The rats were randomly assigned to an EA group (n=20) and a control group (n=20). In the EA group, a cathodal electrode was connected to an acupuncture needle percutaneously at the surgery site, while another acupuncture needle inserted 15 mm proximal to the surgery site was used as an anodal electrode. EA was performed 5 days a week for 6 weeks. The control group received no treatment. Some rats were killed at 3 days and 1 week after surgery and the cut end of the distal part of the fibula was surgically removed and histologically assessed. Haematoxylin and eosin (H&E) staining was used to measure total cell count and immunohistochemical staining to assess the increase in the bone morphogenetic protein 2 (BMP-2)-positive cells. The healing process was also assessed weekly after surgery via x-ray examinations.

Results

At each time point, total cell count showed a marked increase in the EA group (p<0.05), while BMP-2 expression showed a tendency to increase in the EA group. Radiological examination showed a marked reduction in the distance between the cut ends of the fibula in the EA group.

Conclusions

There was a marked increase in cell count and expression of growth factor in the EA group. These results indicate direct current EA could be useful for promoting bone healing.
Partial claviculectomy after non-union of proximal clavicle fracture
Authors: Teng Hsiu-Gwo , Liu Andy Li-Jen
Published: March 2013

Non-union of a proximal clavicle fracture is rare. When it does occur, it poses a difficult problem causing severe pain and shoulder impairment that must be dealt with surgically. We report a 29-year-old woman who suffered a proximal clavicle fracture and received plate and screws fixation. Six months later, after constant pain and a diminished range of shoulder motion, she sought help at our clinic and was diagnosed with symptomatic non-union. Reconstruction with bone graft and interosseous sutures was performed in vain as pain persisted and follow-up radiograph showed no healing. A salvage procedure with partial claviculectomy was then carried out. The patient has been pain free after 3.5 years of follow-up, a full range of motion and is quite satisfied with the cosmetics. This outcome demonstrates that claviculectomy can be used successfully in a clinical situation where restoration of clavicular non-union fails.
Injury patterns in Swedish elite athletics: annual incidence, injury types and risk factors
Authors: Jacobsson Jenny , Timpka Toomas , Kowalski Jan , Nilsson Sverker , Ekberg Joakim , Dahlström Örjan , Renström Per A
Published: March 2013

Objective

To estimate the incidence, type and severity of musculoskeletal injuries in youth and adult elite athletics athletes and to explore risk factors for sustaining injuries.

Design

Prospective cohort study conducted during a 52-week period.

Setting

Male and female youth and adult athletics athletes ranked in the top 10 in Sweden (n=292).

Results

199 (68%) athletes reported an injury during the study season. Ninety-six per cent of the reported injuries were non-traumatic (associated with overuse). Most injuries (51%) were severe, causing a period of absence from normal training exceeding 3 weeks. Log-rank tests revealed risk differences with regard to athlete category (p=0.046), recent previous injury (>3 weeks time-loss; p=0.039) and training load rank index (TLRI; p=0.019). Cox proportional hazards regression analyses showed that athletes in the third (HR 1.79; 95% CI 1.54 to 2.78) and fourth TLRI quartiles (HR 1.79; 95% CI 1.16 to 2.74) had almost a twofold increased risk of injury compared with their peers in the first quartile and interaction effects between athlete category and previous injury; youth male athletes with a previous serious injury had more than a fourfold increased risk of injury (HR=4.39; 95% CI 2.20 to 8.77) compared with youth females with no previous injury.

Conclusions

The injury incidence among both youth and adult elite athletics athletes is high. A training load index combing hours and intensity and a history of severe injury the previous year were predictors for injury. Further studies on measures to quantify training content and protocols for safe return to athletics are warranted.
Parent perceptions of children's hospital safety climate
Authors: Cox Elizabeth D , Carayon Pascale , Hansen Kristofer W , Rajamanickam Victoria P , Brown Roger L , Rathouz Paul J , DuBenske Lori L , Kelly Michelle M , Buel Linda A
Published: March 2013

Background

Because patients are at the frontline of care where safety climate is closely tied to safety events, understanding patient perceptions of safety climate is crucial. We sought to develop and evaluate a parent-reported version of the Agency for Healthcare Research and Quality Hospital Survey on Patient Safety Culture and to relate parent-reported responses to parental need to watch over their child's care to ensure mistakes are not made.

Methods

Parents (n=172) were surveyed about perceptions of hospital safety climate (14 items representing four domains—overall perceptions of safety, openness of staff and parent communication, and handoffs and transitions) and perceived need to watch over their child's care. Confirmatory factor analysis (CFA) was used to validate safety climate domain measures. Logistic regression was used to relate need to watch over care to safety climate domains.

Results

CFA indices suggested good model fit for safety climate domains. Thirty-nine per cent of parents agreed or strongly agreed they needed to watch over care. In adjusted models, need to watch over care was significantly related to overall perceptions of safety (OR 0.20, 95% CI 0.11 to 0.37) and to handoffs and transitions (0.25, 0.14 to 0.46), but not to openness of staff (0.67, 0.40 to 1.12) or parent (0.83, 0.48 to 1.45) communication.

Conclusions

Findings suggest parents can provide valuable data on specific safety climate domains. Opportunities exist to improve our safety climate's impact on parent burden to watch over their child's care, such as targeting overall perceptions of safety as well as handoffs and transitions.
A prospective observational study of techniques to remove corneal foreign body in the emergency department
Authors: Quirke Michael , Mullarkey Caitriona , Askoorum Shakti , Coffey Norma , Binchy James
Published: March 2013

Introduction

Patients  with corneal foreign bodies (CFBs) often present to the emergency department (ED). However, removal techniques vary among emergency physicians (EPs). A prospective, single-blinded, observational study was performed to compare slit-lamp-aided (SLA) versus non-slit-lamp-aided (NSLA) CFB removal by EPs.

Methods

Five EPs enrolled consecutive patients with a CFB over 3 months. One blinded EP reviewed patients after 3 days. The study end points were: change in visual acuity; visual analogue pain scale (VAS) score at 12 and 24 h; satisfaction rating; symptoms at follow-up; and rate of complications.

Results

54 patients were enrolled: 28 had SLA removal and 26 NSLA removal; 52 were male; 22 had undergone previous CFB removal; six were wearing eye protection at the time of injury. Forty-three patients were reviewed: 26 by attendance and 18 by telephone. There was no difference in any end points at review. However, patients in the SLA group had median VAS scores that were 1.5 cm lower after 24 h than patients in the NSLA group (p=0.43, 95% CI −2.0 to 1.0). One patient in the SLA group developed keratitis.

Conclusions

We show that patient satisfaction ratings, complications and visual acuity were similar for the two methods. There was a trend for increased pain in the NSLA group at 12 and 24 h. Slit-lamp biomicroscopy and the use of magnification to remove CFBs remains the gold standard of care, and more intensive training should be given to EPs at the departmental level, particularly in EDs that receive patients with eye injuries.
Vasohibin-1 is a new predictor of disease-free survival in operated patients with renal cell carcinoma
Authors: Kanomata Naoki , Sato Yasufumi , Miyaji Yoshiyuki , Nagai Atsushi , Moriya Takuya
Published: March 2013

Background

Vasohibin-1 (VASH1) is an endothelium-produced angiogenesis inhibitor. Renal cell carcinoma is highly vascularised, but the significance of endogenous VASH1 in renal cell carcinoma has not been defined.

Aims

To identify VASH1 expression and its possible relationship with various clinicopathological factors and prognosis in renal cell carcinoma.

Methods

A retrospective analysis of 122 tumours obtained from 118 consecutive patients with renal cell carcinoma was performed. The expression patterns of VASH1, CD31, vascular endothelial growth factor (VEGF) and VEGF receptor type 2 (VEGFR2) were examined immunohistochemically and their relationships with clinicopathological factors were analysed.

Results

Microvessel density, VASH1 and VEGFR2 expression were significantly higher in clear cell carcinoma than in other subtypes. The VEGF expression pattern differed significantly between clear cell carcinoma and other histological subtypes. VASH1, pT factor and TNM stage were significantly associated with disease-free survival (p=0.030, p = 0.0012 and p = 0.0018, respectively). Cox models of multivariable disease-free survival analyses indicated that VASH1 and stage are independent prognostic factors (p=0.019 and p = 0.024).

Conclusions

VASH1 expression may be useful for estimating the prognosis of renal cell carcinoma. Further studies of the role of VASH1 in renal cell carcinoma involving larger sample sizes are warranted.
Common mental disorders and mortality in the West of Scotland Twenty-07 Study: comparing the General Health Questionnaire and the Hospital Anxiety and Depression Scale
Authors: Hannah Mary Kathleen , Batty G David , Benzeval Michaela
Published: March 2013

Background

While various measures of common mental disorders (CMD) have been found to be associated with mortality, a comparison of how different measures predict mortality may improve our understanding of the association. This paper compares how the Hospital Anxiety and Depression Scale (HADS) and the 30-item General Health Questionnaire (GHQ-30) predict all cause and cause-specific mortality.

Methods

Data on 2547 men and women from two cohorts, aged approximately 39 and 55 years, from the West of Scotland Twenty-07 Study who were followed up for mortality over an average of 18.9 (SD 5.0) years. Scores were calculated for HADS depression (HADS-D), HADS Anxiety (HADS-A) and GHQ-30. Cox Proportional Hazards Models were used to determine how each CMD measure predicted mortality.

Results

After adjusting for serious physical illness, smoking, social class, alcohol, obesity, pulse rate and living alone, HRs (95% CI) per SD increase in score for all-cause mortality were: 1.15 (1.07 to 1.25) for HADS-D; 1.13 (1.04 to 1.23) for GHQ-30 and 1.05 (0.96 to 1.14) for HADS-A. After the same adjustments, cardiovascular disease mortality was also related to HADS-D (HR 1.24 (1.07 to 1.43)), to GHQ-30 (HR 1.24 (1.11 to 1.40)) and to HADS-A (HR 1.15 (1.01 to 1.32)); respiratory mortality to GHQ-30 (HR 1.33 (1.13 to 1.55)) and mortality from other causes, excluding injuries, to HADS-D (HR 1.28 (1.05 to 1.55)).

Conclusions

There were associations between CMD and both all-cause and cause-specific mortality which were broadly similar for GHQ-30 and HADS-D and were still present after adjustment for important confounders and mediators.
Erysipelas in laying hens is associated with housing system
Authors: Eriksson H. , Nyman A.‐K. , Fellström C. , Wallgren P.
Published: March 2013

Following the change from conventional cages to non‐cage housing systems and furnished cages, which in Sweden was finalised by 2005, problems caused by Erysipelothrix rhusiopathiae increased in laying hen flocks. This study aimed to investigate possible associations between housing systems for laying hens and outbreaks of erysipelas. Also, sera from 129 flocks in different housing systems, collected during 2005–2007, were analysed for the presence of antibodies to E rhusiopathia e using an indirect ELISA test. Antibodies were detected in all housing systems. The mean flock absorbance values from free‐range flocks were significantly higher than corresponding values from other housing systems. Data on the Swedish laying hen population were compared with the recorded number of erysipelas outbreaks during 1998–2011. Outbreaks occurred on 15 farms with indoor litter‐based systems (n=87 farms in 2011). No outbreak was diagnosed on farms with flocks in conventional or furnished cages. The results indicate that the risk for an outbreak was higher in free‐range systems than in indoor litter‐based systems, and lowest for flocks housed in cages. Absence of erysipelas in the majority of subsequent flocks on the affected farms suggested that proper measures, including vaccination, were undertaken.
Tempol prevents cardiac oxidative damage and left ventricular dysfunction in the PPAR-α KO mouse
Authors: Guellich Aziz , Damy Thibaud , Conti Marc , Claes Victor , Samuel Jane-Lise , Pineau Thierry , Lecarpentier Yves , Coirault Catherine
Published: March 2013

Peroxisome proliferator-activated receptor (PPAR)-α deletion induces a profound decrease in MnSOD activity, leading to oxidative stress and left ventricular (LV) dysfunction. We tested the hypothesis that treatment of PPAR-α knockout (KO) mice with the SOD mimetic tempol prevents the heart from pathological remodelling and preserves LV function. Twenty PPAR-α KO mice and 20 age-matched wild-type mice were randomly treated for 8 wk with vehicle or tempol in the drinking water. LV contractile parameters were determined both in vivo using echocardiography and ex vivo using papillary muscle mechanics. Translational and posttranslational modifications of myosin heavy chain protein as well as the expression and activity of major antioxidant enzymes were measured. Tempol treatment did not affect LV function in wild-type mice; however, in PPAR-α KO mice, tempol prevented the decrease in LV ejection fraction and restored the contractile parameters of papillary muscle, including maximum shortening velocity, maximum extent of shortening, and total tension. Moreover, compared with untreated PPAR-α KO mice, myosin heavy chain tyrosine nitration and anion superoxide production were markedly reduced in PPAR-α KO mice after treatment. Tempol also significantly increased glutathione peroxidase and glutathione reductase activities (∼ 50%) in PPAR-α KO mice. In conclusion, these findings demonstrate that treatment with the SOD mimetic tempol can prevent cardiac dysfunction in PPAR-α KO mice by reducing the oxidation of contractile proteins. In addition, we show that the beneficial effects of tempol in PPAR-α KO mice involve activation of the glutathione peroxidase/glutathione reductase system.
Muscle metaboreflex activation speeds the recovery of arterial blood pressure following acute hypotension in humans
Authors: Ichinose Masashi , Watanabe Kazuhito , Fujii Naoto , Kondo Narihiko , Nishiyasu Takeshi
Published: March 2013

It has been suggested that the arterial baroreflex and muscle metaboreflex are both activated during heavy exercise and that they interact to modulate primary cardiovascular reflex responses. This proposed interaction and its consequences are not fully understood, however. The purpose of present study was to test our hypothesis that dynamic arterial baroreflex-mediated cardiovascular responses to acute systemic hypotension in humans are augmented when the muscle metaboreflex is active and that this results in a faster recovery of arterial blood pressure. Acute hypotension was induced nonpharmacologically in 12 healthy subjects by releasing bilateral thigh cuffs after 9 min of suprasystolic resting ischemia, with and without muscle metaboreflex activation via postexercise muscle ischemia (PEMI) after 1 min of isometric handgrip exercise at 50% maximum voluntary contraction. The thigh-cuff release evoked rapid reductions in mean arterial pressure (MAP) and increases in heart rate, cardiac output (Doppler), and total vascular conductance (TVC) under control conditions and during PEMI. The reductions in MAP from baseline were greater and the increases in TVC were smaller during PEMI than control. In addition, arterial baroreflex-mediated peripheral vasoconstriction was augmented during PEMI, as evidenced by a near doubling of the rate of recovery of MAP and TVC. These results show that when the muscle metaboreflex is activated in humans, arterial baroreflex-mediated peripheral vasoconstriction elicited in response to acute hypotension is augmented, which halves the time needed for MAP recovery. Such modulation of baroreflex function would be advantageous for maintaining an elevated arterial blood pressure during activation of the muscle metaboreflex.
Impaired mitochondrial function in chronically ischemic human heart
Authors: Stride Nis , Larsen Steen , Hey-Mogensen Martin , Hansen Christina N. , Prats Clara , Steinbrüchel Daniel , Køber Lars , Dela Flemming
Published: March 2013

Chronic ischemic heart disease is associated with myocardial hypoperfusion. The resulting hypoxia potentially inflicts damage upon the mitochondria, leading to a compromised energetic state. Furthermore, ischemic damage may cause excessive production of reactive oxygen species (ROS), producing mitochondrial damage, hereby reinforcing a vicious circle. Ischemic preconditioning has been proven protective in acute ischemia, but the subject of chronic ischemic preconditioning has not been explored in humans. We hypothesized that mitochondrial respiratory capacity would be diminished in chronic ischemic regions of human myocardium but that these mitochondria would be more resistant to ex vivo ischemia and, second, that ROS generation would be higher in ischemic myocardium. The aim of this study was to test mitochondrial respiratory capacity during hyperoxia and hypoxia, to investigate ROS production, and finally to assess myocardial antioxidant levels. Mitochondrial respiration in biopsies from ischemic and nonischemic regions from the left ventricle of the same heart was compared in nine human subjects. Maximal oxidative phosphorylation capacity in fresh muscle fibers was lower in ischemic compared with nonischemic myocardium ( P < 0.05), but the degree of coupling (respiratory control ratio) did not differ ( P > 0.05). The presence of ex vivo hypoxia did not reveal any chronic ischemic preconditioning of the ischemic myocardial regions ( P > 0.05). ROS production was higher in ischemic myocardium ( P < 0.05), and the levels of antioxidant protein expression was lower. Diminished mitochondrial respiration capacity and excessive ROS production demonstrate an impaired mitochondrial function in ischemic human heart muscle. No chronic ischemic preconditioning effect was found.
Allogeneic Hematopoietic Cell Transplantation for Therapy-Related Myeloid Leukemia following Orthotopic Cardiac Transplantation
Authors: Lin Richard J. , Larson Richard A. , van Besien Koen , Rich Elizabeth S.
Published: March 2013

Therapy-related myeloid neoplasm (t-MN) is a subtype of acute myeloid leukemia with adverse cytogenetics and poor overall prognosis despite intensive induction chemotherapy and allogeneic hematopoietic cell transplantation (allo-HCT). It is increasingly recognized as a late complication of chronic immunosuppression in patients who have received solid organ transplantation. In this paper, we describe a case of t-MN following orthotopic cardiac transplantation and its treatment with allo-HCT. We discuss molecular and biological challenges and considerations in double solid organ and bone marrow transplantation and review similar cases at our institution. Our experience suggests general feasibility and safety of allo-HCT in patients who have received solid organ transplantation.
Bleeding in a 43 Year Old Female: A Rare Disease
Authors: Nwankwo Nwabundo , Akinola Olayinka , Mirrakhimov Aibek E. , Iroegbu Nkemakolam A.
Published: March 2013

A 43-year-old gravida 2 para 2 Caucasian female with a past medical history of menorrhagia secondary to uterine fibroids and thyroid disease presented to the emergency department with complaints of bruising in her oral mucosa and vaginal bleeding. One week prior to this presentation, she was transfused with two units of packed red blood cells because of symptomatic anemia secondary to menorrhagia. Physical examination was normal, except for petechiae on the abdomen and the lower extremities as well as purpuric lesions on the buccal mucosa. Blood work revealed thrombocytopenia. Posttransfusion thrombocytopenia was suspected. The patient was transfused with washed and leukoreduced platelets and treated with steroids and intravenous immunoglobulins. Laboratory studies demonstrated that she was homozygous for the HPA-Ib/1b platelet gene and positive antibodies against class 1 HLA and platelet glycoproteins. The patient responded well to treatment, with normalization of her platelet count.
An Unusual Case of Mammary Paget’s Disease Diagnosed Using Dynamic Contrast-Enhanced MRI
Authors: Gaspari Eleonora , Ricci Aurora , Liberto Valeria , Scarano Angela Lia , Fornari Maria , Simonetti Giovanni
Published: March 2013

Mammary Paget’s disease is a rare presentation of breast cancer. At clinical examination, it is characterized by skin lesions of the nipple-areola complex, almost always a sign of malignancy. In fact, it is often associated with an underlying mammary ductal carcinoma in situ (DCIS) or invasive carcinoma. An underlying carcinoma is also common in women with negative mammography and ultrasound (US); in these cases, magnetic resonance imaging (MRI) is a diagnostic tool useful in the detection of occult cancer. We described an unusual case of mammary Paget’s disease with underlying DCIS, in a patient without nipple-areola complex alterations and/or palpable lump. On suspicion of Paget’s disease, the patient underwent MRI examination that proved useful for an accurate diagnosis. Biopsy confirmed dynamic MRI findings.
Acute Zonal Occult Outer Retinopathy: Vision Loss in an Active Duty Soldier
Authors: Crawford Courtney M. , Rivers Bruce A. , Nelson Mark
Published: March 2013

Objective. To describe a case of acute zonal occult outer retinopathy (AZOOR) in an active duty patient.Methods. In this paper we studied fundus photographs, optical coherence tomograph, Humphrey visual field 30-2, fundus autofluorescence images, fluorescein angiograms, and electroretinography.Results. Exam findings on presentation: a 34-year-old American Indian female presented with bilateral photopsias, early RPE irregularity, and an early temporal visual field defect. Progression RPE damage and visual field defect along with ERG findings support final diagnosis of AZOOR.Conclusion. AZOOR may initially be identified as a broader category of disease called the “AZOOR complex of disorders”. Specific visual field defects, ERG results, and clinical exam findings will help distinguish AZOOR from other similar disorders.
On Some Symmetric Systems of Difference Equations
Authors: Diblík Josef , Iričanin Bratislav , Stević Stevo , Šmarda Zdeněk
Published: March 2013

Here we show that the main results in the papers by Yalcinkaya (2008), Yalcinkaya and Cinar (2010), and Yalcinkaya, Cinar, and Simsek (2008), as well as a conjecture from the last mentioned paper, follow from a slight modification of a result by G. Papaschinopoulos and C. J. Schinas. We also give some generalizations of these results.
Stability and Boundedness of Stochastic Volterra Integrodifferential Equations with Infinite Delay
Authors: Zhang Chunmei , Li Wenxue , Wang Ke
Published: March 2013

We make the first attempt to discuss stability and boundedness of solutions to stochastic Volterra integrodifferential equations with infinite delay (IDSVIDEs). By the Lyapunov-Krasovskii functional approach, we get kinds of sufficient criteria for stability and boundedness of solutions to IDSVIDEs. The main innovation here is that stochastic systems with infinite delay can retain stability and boundedness of corresponding deterministic systems under some conditions.