bluuebunny/crossref_metadata_2025 huggingface dataset:
Tpeak – Tend and Tpeak – Tend/QT Ratio as Markers of Ventricular Arrhythmia Risk in Cardiac Resynchronization Therapy Patients
Authors: BARBHAIYA CHIRAG , PO JOSE RICARDO F. , HANON SAM , SCHWEITZER PAUL
Published: October 2012

Background

Cardiac resynchronization therapy (CRT) increases transmural dispersion of repolarization (TDR) and can be pro‐arrhythmic. However, overall arrhythmia risk was not increased in large‐scale CRT clinical trials. Increased TDR as measured by Tpeak –Tend (TpTe) was associated with arrhythmia risk in CRT in a single‐center study. This study investigates whether QT interval, TpTe, and TpTe/QT ratio are associated with ventricular arrhythmias in patients with CRT‐defibrillator (CRT–D).

Methods

Post‐CRT–D implant electrocardiograms of 128 patients (age 71.3 years ± 10.3) with at least 2 months of follow‐up at our institution's device clinic (mean follow‐up of 28.5 months ± 17) were analyzed for QT interval, TpTe, and TpTe/QT ratio. Incidence of ventricular arrhythmias was determined based on routine and directed device interrogations.

Results

Appropriate implantable cardioverter‐defibrillator therapy for sustained ventricular tachycardia or ventricular fibrillation was delivered in 18 patients (14%), and nonsustained ventricular tachycardia (NSVT) was detected but did not require therapy in 58 patients (45%). Patients who received appropriate defibrillator therapy had increased TpTe/QT ratio (0.24 ± 0.03 ms vs 0.20 ± 0.04, P = 0.0002) and increased TpTe (105.56 ± 20.36 vs 87.82 ± 22.32 ms, P = 0.002), and patients with NSVT had increased TpTe/QT ratio (0.22 ± 0.04 vs 0.20 ± 0.04, P = 0.016). Increased QT interval was not associated with risk of ventricular arrhythmia. The relative risk for appropriate defibrillator therapy of TpTe /QT ratio ≥ 0.25 was 3.24 (P = 0.016).

Conclusion

Increased TpTe and increased TpTe/QT ratio are associated with increased incidence of ventricular arrhythmias in CRT–D. The utility of TpTe interval and TpTe/QT ratio as potentially modifiable risk factors for ventricular arrhythmias in CRT requires further study.

(PACE 2013; 36:103–108)
‘Slicing the Value Chain’ Internationally: Empirical Evidence on the Offshoring Strategy by French Firms
Authors: Jabbour Liza
Published: October 2012

This study analyses firms’ offshoring strategy from an empirical perspective. It focuses on market thickness, firm heterogeneity and the relative costs of organisation modes. This study focuses on a set of theoretical predictions and creates a set of suitable variables to test their validity. This analysis is based on a data set from French manufacturing firms that provides detailed information on their offshoring strategy. The choice of offshoring modes is investigated through the estimation of a multinomial logit model and related to a set of explanatory variables at firm, industry and country level. The results emphasise the role of firm heterogeneity, asset specificity and of market thickness.
Bradycardic effects mediated by activation of G protein‐coupled estrogen receptor in rat nucleus ambiguus
Authors: Brailoiu G. Cristina , Arterburn Jeffrey B. , Oprea Tudor I. , Chitravanshi Vineet C. , Brailoiu Eugen
Published: October 2012

New Findings

What is the central question of this study?

Clinical and experimental studies indicate that estrogen increases cardiac vagal tone. The role of the G protein‐coupled estrogen receptor in autonomic cardiac control is not known.

What is the main finding and its importance?

Using calcium imaging, electrophysiological techniques and in vivo studies of microinjection into the nucleus ambiguus and measurement of cardiovascular responses, we show that activation of the G protein‐coupled estrogen receptor in cardiac vagal neurons of the nucleus ambiguus increases cytosolic Ca2+ and depolarizes these neurons, leading to a decrease in heart rate. Our findings suggest a novel role for the G protein‐coupled estrogen receptor in modulation of cardiac vagal tone.

The G protein‐coupled estrogen receptor (GPER) has been identified in several brain regions, including cholinergic neurons of the nucleus ambiguus, which are critical for parasympathetic cardiac regulation. Using calcium imaging and electrophysiological techniques, microinjection into the nucleus ambiguus and blood pressure measurement, we examined the in vitro and in vivo effects of GPER activation in nucleus ambiguus neurons. A GPER selective agonist, G‐1, produced a sustained increase in cytosolic Ca2+ concentration in a concentration‐dependent manner in retrogradely labelled cardiac vagal neurons of nucleus ambiguus. The increase in cytosolic Ca2+ produced by G‐1 was abolished by pretreatment with G36, a GPER antagonist. G‐1 depolarized cultured cardiac vagal neurons of the nucleus ambiguus. The excitatory effect of G‐1 was also identified by whole‐cell visual patch‐clamp recordings in nucleus ambiguus neurons, in medullary slices. To validate the physiological relevance of our in vitro studies, we carried out in vivo experiments. Microinjection of G‐1 into the nucleus ambiguus elicited a decrease in heart rate; the effect was blocked by prior microinjection of G36. Systemic injection of G‐1, in addition to a previously reported decrease in blood pressure, also reduced the heart rate. The G‐1‐induced bradycardia was prevented by systemic injection of atropine, a muscarinic antagonist, or by bilateral microinjection of G36 into the nucleus ambiguus. Our results indicate that GPER‐mediated bradycardia occurs via activation of cardiac parasympathetic neurons of the nucleus ambiguus and support the involvement of the GPER in the modulation of cardiac vagal tone.
Dopamine infusion for postresuscitation blood pressure support after profound asphyxia in near‐term fetal sheep
Authors: Drury Paul P. , Booth Lindsea C. , Bennet Laura , Davidson Joanne O. , Wibbens Bert , Gunn Alistair Jan
Published: October 2012

New Findings

What is the central question of this study?

Dopamine is commonly used for blood pressure support in the neonate, but there is limited empirical evidence that it prevents hypotension or improves survival after asphyxia.

What is the main finding and its importance?

Dopamine infusion delayed but did not prevent terminal hypotension after severe asphyxia in near‐term fetal sheep. We also demonstrate that hypotension is directly associated with exacerbated brain swelling, strongly supporting the concept that better ways of protecting the brain from hypotension during recovery from asphyxia are essential.

Dopamine is commonly used for blood pressure support in the neonate, but has limited empirical evidence to support its use. We tested the hypothesis that after near‐terminal asphyxia in utero, dopamine infusions would prevent secondary hypotension. Fetal sheep (122–129 days of gestation; term is 147 days) received umbilical cord occlusion for 15 min or sham occlusion (n = 5). If the mean arterial blood pressure fell below 90% of baseline within 6 h after occlusion, fetuses were randomized to either dopamine infusion starting at 4 μg kg−1 min−1 and titrated according to mean arterial blood pressure up to a maximum of 40 μg kg−1 min−1 (n = 5) or to the same volume of normal saline (n = 5). Dopamine infusion, initiated at a median of 180 min after occlusion (range 96–280 min), was associated with a marked but transient increase in mean arterial blood pressure and fall in femoral blood flow compared with saline. Terminal hypotension developed later in four of the five fetuses that received maximal dopamine infusions than in five of five receiving saline infusion [517 (range 240–715) versus 106 min (range 23–497) after the start of infusions, P < 0.05]. In conclusion, dopamine infusion delayed but did not prevent terminal hypotension after severe asphyxia.
Geometrically Nonlinear Free Vibration of Laminated Composite Plate Embedded With Piezoelectric Layers Having Uncertain Material Properties
Authors: Dash Padmanav , Singh B. N.
Published: October 2012

In this paper, the nonlinear free vibration stochastic characteristic of a smart laminated composite plate having random system properties is presented. The transverse shear effects have been included in the system equation in the frame work of higher order shear deformation theory. The analysis uses the Green-Lagrange nonlinear strain displacement relationship to model geometric nonlinearity. The direct iteration approach is used to handle deterministic geometric nonlinearity, and the perturbation approach is employed to handle the randomness in the system properties. Mean and variance of the random natural frequencies have been obtained by employing a C0 isoparametric nonlinear finite element model. Comparisons with the published results show the accuracy of the proposed procedure. A few results covering various features have been presented for a laminated composite plate with different boundary conditions.
Analytical Modeling of Non-Darcy Flow-Induced Conductivity Damage in Propped Hydraulic Fractures
Authors: Rahman M. K. , Salim M. M. , Rahman M. M.
Published: October 2012

This paper presents a simple analytical method to model the non-Darcy flow effect on the production performance of hydraulically fractured wells by modifying the fracture conductivity. The method is suitable to conveniently incorporate the non-Darcy flow effect in a production prediction model usually used for fracture treatment design and optimization. The method is validated against published information of field productivity and production prediction by other complex methods. The method is then used to demonstrate that the non-Darcy effect is one of the major sources for the loss of fracture conductivity, even at a low flow rate well, and hence the source for discrepancy between the predicted and actual productivities. Finally, the implication of neglecting the non-Darcy effect in fracture treatment optimization is also investigated, emphasizing the need to incorporate this effect even for low flow rate wells.
A Global Pattern of Thermal Adaptation in Marine Phytoplankton
Authors: Thomas Mridul K. , Kremer Colin T. , Klausmeier Christopher A. , Litchman Elena
Published: October 2012

Local Optima for Plankton

Recent ocean warming has changed the seasonality and composition of the marine phytoplankton.

Thomas
et al.

(p.
1085
, published online 25 October) investigated the direct effect of temperature on phytoplankton. By fitting published data to reaction temperature norms for 194 phytoplankton strains isolated from a wide latitudinal range, the resultant temperature-related traits (maximum growth rate, temperature optimum, and thermal niche width) reveal latitudinal trends in temperature optima and diversity. Biogeographical differences indicate an increased susceptibility of tropical strains to further warming, and modeling predicts poleward shifts of tropical strains and a loss of phytoplankton diversity in the tropics within the next hundred years.
The
Legionella
Effector RavZ Inhibits Host Autophagy Through Irreversible Atg8 Deconjugation
Authors: Choy Augustine , Dancourt Julia , Mugo Brian , O’Connor Tamara J. , Isberg Ralph R. , Melia Thomas J. , Roy Craig R.
Published: October 2012

Axing Autophagy

When intracellular pathogens like
Legionella pneumophila
take up residence in mammalian host cells, they must combat the efforts of the host cell to attack them. Autophagy is a process by which cells digest their own constituents, often involved in response to starvation or pathogen attack.

Choy
et al.

(p.
1072
, published online 25 October) now describe how
L. pneumophila
can inhibit the autophagy pathway in eukaryotic cells, and provide a detailed description of the biochemical mechanism. A
Legionella
effector protein, RavZ, acts as a very potent enzyme that specifically deconjugates a key autophagy protein, Atg8, from autophagosomal membranes, thus blocking autophagy.
A Bipolar Spindle of Antiparallel ParM Filaments Drives Bacterial Plasmid Segregation
Authors: Gayathri P. , Fujii T. , Møller-Jensen J. , van den Ent F. , Namba K. , Löwe J.
Published: October 2012

Plasmid Partitioning

Bacterial plasmids need to be able to partition faithfully into daughter cells. Combining structural data and advanced microscopy,

Gayathri
et al.

(p.
1334
, published online 25 October; see the cover) describe how actin-like ParM filaments form a bipolar spindle for the faithful segregation of low-copy-number plasmids to the two cell poles of
Escherichia coli
, despite being polar, with two distinct ends. ParM filaments are elongated by a small adaptor protein ParR that physically links the filament end(s) to a centromere-like region on the plasmid. Antiparallel filament bundling and sliding appear to produce a bipolar spindle made of filaments that elongate unidirectionally so that all the plasmids are segregated together in one large bundle.
Identification of Methanoculleus spp. as Active Methanogens during Anoxic Incubations of Swine Manure Storage Tank Samples
Authors: Barret Maialen , Gagnon Nathalie , Kalmokoff Martin L. , Topp Edward , Verastegui Yris , Brooks Stephen P. J. , Matias Fernando , Neufeld Josh D. , Talbot Guylaine
Published: October 2012

Methane emissions represent a major environmental concern associated with manure management in the livestock industry. A more thorough understanding of how microbial communities function in manure storage tanks is a prerequisite for mitigating methane emissions. Identifying the microorganisms that are metabolically active is an important first step. Methanogenic archaea are major contributors to methanogenesis in stored swine manure, and we investigated active methanogenic populations by DNA stable isotope probing (DNA-SIP). Following a preincubation of manure samples under anoxic conditions to induce substrate starvation, [U-13C]acetate was added as a labeled substrate. Fingerprint analysis of density-fractionated DNA, using length-heterogeneity analysis of PCR-amplifiedmcrAgenes (encoding the alpha subunit of methyl coenzyme M reductase), showed that the incorporation of13C into DNA was detectable atin situacetate concentrations (∼7 g/liter). Fingerprints of DNA retrieved from heavy fractions of the13C treatment were primarily enriched in a 483-bp amplicon and, to a lesser extent, in a 481-bp amplicon. Analyses based on clone libraries of themcrAand 16S rRNA genes revealed that both of these heavy DNA amplicons corresponded toMethanoculleusspp. Our results demonstrate that uncultivated methanogenic archaea related toMethanoculleusspp. were major contributors to acetate-C assimilation during the anoxic incubation of swine manure storage tank samples. Carbon assimilation and dissimilation rate estimations suggested thatMethanoculleusspp. were also major contributors to methane emissions and that the hydrogenotrophic pathway predominated during methanogenesis.
Seasonal Methane Oxidation Potential in Manure Crusts
Authors: Nielsen Daniel A. , Schramm Andreas , Nielsen Lars P. , Revsbech Niels P.
Published: October 2012

Organic crusts on liquid manure storage tanks harbor ammonia- and nitrite-resistant methane oxidizers and may significantly reduce methane emissions. Methane oxidation potential (0.6 mol CH4m−2day−1) peaked during fall and winter, after 4 months of crust development. Consequences for methane mitigation potential of crusts are discussed.
The Salmonella Transcriptome in Lettuce and Cilantro Soft Rot Reveals a Niche Overlap with the Animal Host Intestine
Authors: Goudeau Danielle M. , Parker Craig T. , Zhou Yaguang , Sela Shlomo , Kroupitski Yulia , Brandl Maria T.
Published: October 2012

Fresh vegetables have been recurrently associated with salmonellosis outbreaks, and
Salmonella
contamination of retail produce has been correlated positively with the presence of soft rot disease. We observed that population sizes of
Salmonella enterica
serovar Typhimurium SL1344 increased 56-fold when inoculated alone onto cilantro leaves, versus 2,884-fold when coinoculated with
Dickeya dadantii
, a prevalent pathogen that macerates plant tissue. A similar trend in
S. enterica
populations was observed for soft-rotted lettuce leaves. Transcriptome analysis of
S. enterica
cells that colonized
D. dadantii
-infected lettuce and cilantro leaves revealed a clear shift toward anaerobic metabolism and catabolism of substrates that are available due to the degradation of plant cells by the pectinolytic pathogen. Twenty-nine percent of the genes that were upregulated in cilantro macerates were also previously observed to have increased expression levels in the chicken intestine. Furthermore, multiple genes induced in soft rot lesions are also involved in the colonization of mouse, pig, and bovine models of host infection. Among those genes, the operons for ethanolamine and propanediol utilization as well as for the synthesis of cobalamin, a cofactor in these pathways, were the most highly upregulated genes in lettuce and cilantro lesions. In
S
. Typhimurium strain LT2, population sizes of mutants deficient in propanediol utilization or cobalamin synthesis were 10- and 3-fold lower, respectively, than those of the wild-type strain in macerated cilantro (
P
< 0.0002); in strain SL1344, such mutants behaved similarly to the parental strain. Anaerobic conditions and the utilization of nutrients in macerated plant tissue that are also present in the animal intestine indicate a niche overlap that may explain the high level of adaptation of
S. enterica
to soft rot lesions, a common postharvest plant disease.
Environmental Transcription of
mmoX
by Methane-Oxidizing Proteobacteria in a Subarctic Palsa Peatland
Authors: Liebner Susanne , Svenning Mette M.
Published: October 2012

Methane-oxidizing bacteria (MOB) that possess the soluble form of methane monooxygenase (sMMO) are present in various environments, but unlike the prevalent particulate methane monooxygenase (pMMO), the
in situ
activity of sMMO has not been documented. Here we report on the environmental transcription of a gene (
mmoX
) for this enzyme, which was attributed mainly to MOB lacking a pMMO. Our study indicates that the sMMO is an active enzyme in acidic peat ecosystems, but its importance for the mitigation of methane releases remains unknown.
Gut and Root Microbiota Commonalities
Authors: Ramírez-Puebla Shamayim T. , Servín-Garcidueñas Luis E. , Jiménez-Marín Berenice , Bolaños Luis M. , Rosenblueth Mónica , Martínez Julio , Rogel Marco Antonio , Ormeño-Orrillo Ernesto , Martínez-Romero Esperanza
Published: October 2012

Animal guts and plant roots have absorption roles for nutrient uptake and converge in harboring large, complex, and dynamic groups of microbes that participate in degradation or modification of nutrients and other substances. Gut and root bacteria regulate host gene expression, provide metabolic capabilities, essential nutrients, and protection against pathogens, and seem to share evolutionary trends.
Bartonella Infections in Deer Keds (Lipoptena cervi) and Moose (Alces alces) in Norway
Authors: Duodu Samuel , Madslien Knut , Hjelm Eva , Molin Ylva , Paziewska-Harris Anna , Harris Philip D. , Colquhoun Duncan J. , Ytrehus Bjørnar
Published: October 2012

Infections withBartonellaspp. have been recognized as emerging zoonotic diseases in humans. Large knowledge gaps exist, however, relating to reservoirs, vectors, and transmission of these bacteria. We describe identification by culture, PCR, and housekeeping gene sequencing ofBartonellaspp. in fed, wingless deer keds (Lipoptena cervi), deer ked pupae, and blood samples collected from moose,Alces alces, sampled within the deer ked distribution range in Norway. Direct sequencing from moose blood sampled in a deer ked-free area also indicatedBartonellainfection but at a much lower prevalence. The sequencing data suggested the presence of mixed infections involving two species ofBartonellawithin the deer ked range, while moose outside the range appeared to be infected with a single species.Bartonellawere not detected or cultured from unfed winged deer keds. The results may indicate that long-term bacteremia in the moose represents a reservoir of infection and thatL. cerviacts as a vector for the spread of infection ofBartonellaspp. Further research is needed to evaluate the role ofL. cerviin the transmission ofBartonellato animals and humans and the possible pathogenicity of these bacteria for humans and animals.
Autotransporter Protein-Encoding Genes of Diarrheagenic Escherichia coli Are Found in both Typical and Atypical Enteropathogenic E. coli Strains
Authors: Abreu Afonso G. , Bueris Vanessa , Porangaba Tatiane M. , Sircili Marcelo P. , Navarro-Garcia Fernando , Elias Waldir P.
Published: October 2012

Autotransporter (AT) protein-encoding genes of diarrheagenic
Escherichia coli
(DEC) pathotypes (
cah
,
eatA
,
ehaABCDJ
,
espC
,
espI
,
espP
,
pet
,
pic
,
sat
, and
tibA
) were detected in typical and atypical enteropathogenic
E. coli
(EPEC) in frequencies between 0.8% and 39.3%. Although these ATs have been described in particular DEC pathotypes, their presence in EPEC indicates that they should not be considered specific virulence markers.
Quantitative Microbial Risk Assessment of Pathogenic Vibrios in Marine Recreational Waters of Southern California
Authors: Dickinson Gregory , Lim Keah-ying , Jiang Sunny C.
Published: October 2012

This study investigated the occurrence of three types of vibrios in Southern California recreational beach waters during the peak marine bathing season in 2007. Over 160 water samples were concentrated and enriched for the detection of vibrios. Four sets of PCR primers, specific for
Vibrio cholerae
,
V. parahaemolyticus
, and
V. vulnificus
species and the
V. parahaemolyticus
toxin gene, respectively, were used for the amplification of bacterial genomic DNA. Of 66 samples from Doheny State Beach, CA, 40.1% were positive for
V. cholerae
and 27.3% were positive for
V. parahaemolyticus
, and 1 sample (1.5%) was positive for the
V. parahaemolyticus
toxin gene. Of the 96 samples from Avalon Harbor, CA, 18.7% were positive for
V. cholerae
, 69.8% were positive for
V. parahaemolyticus
, and 5.2% were positive for the
V. parahaemolyticus
toxin gene. The detection of the
V. cholerae
genetic marker was significantly more frequent at Doheny State Beach, while the detection of the
V. parahaemolyticus
genetic marker was significantly more frequent at Avalon Harbor. A probability-of-illness model for
V. parahaemolyticus
was applied to the data. The risk for bathers exposed to recreational waters at two beaches was evaluated through Monte Carlo simulation techniques. The results suggest that the microbial risk from vibrios during beach recreation was below the illness benchmark set by the U.S. EPA. However, the risk varied with location and the type of water recreation activities. Surfers and children were exposed to a higher risk of vibrio diseases. Microbial risk assessment can serve as a useful tool for the management of risk related to opportunistic marine pathogens.
Phylogenetic, Metabolic, and Taxonomic Diversities Shape Mediterranean Fruit Fly Microbiotas during Ontogeny
Authors: Aharon Yael , Pasternak Zohar , Ben Yosef Michael , Behar Adi , Lauzon Carol , Yuval Boaz , Jurkevitch Edouard
Published: October 2012

The Mediterranean fruit fly (medfly) (Ceratitis capitata) lays eggs in fruits, where larvae subsequently develop, causing large-scale agricultural damage. Within its digestive tract, the fly supports an extended bacterial community that is composed of multiple strains of a variety of enterobacterial species. Most of these bacteria appear to be functionally redundant, with most strains sustaining diazotrophy and/or pectinolysis. At least some of these bacteria were shown to be vertically inherited, but colonization, structural, and metabolic aspects of the community's dynamics have not been investigated. We used fluorescentin situhybridization, metabolic profiling, plate cultures, and pyrosequencing to show that an initial, egg-borne, diverse community expands throughout the fly's life cycle. While keeping “core” diazotrophic and pectinolytic functions, it also harbors diverse and fluctuating populations that express varied metabolic capabilities. We suggest that the metabolic and compositional plasticity of the fly's microbiota provides potential adaptive advantages to the medfly host and that its acquisition and dynamics are affected by mixed processes that include stochastic effects, host behavior, and molecular barriers.
Use of Proteomic Analysis To Elucidate the Role of Calcium in Acetone-Butanol-Ethanol Fermentation by Clostridium beijerinckii NCIMB 8052
Authors: Han Bei , Ujor Victor , Lai Lien B. , Gopalan Venkat , Ezeji Thaddeus Chukwuemeka
Published: October 2012

Calcium carbonate increases growth, substrate utilization, and acetone-butanol-ethanol (ABE) fermentation byClostridium beijerinckiiNCIMB 8052. Toward an understanding of the basis for these pleiotropic effects, we profiled changes in theC. beijerinckiiNCIMB 8052 proteome that occur in response to the addition of CaCO3. We observed increases in the levels of different heat shock proteins (GrpE and DnaK), sugar transporters, and proteins involved in DNA synthesis, repair, recombination, and replication. We also noted significant decreases in the levels of proteins involved in metabolism, nucleic acid stabilization, sporulation, oxidative and antibiotic stress responses, and signal transduction. We determined that CaCO3enhances ABE fermentation due to both its buffering effects and its ability to influence key cellular processes, such as sugar transport, butanol tolerance, and solventogenesis. Moreover, activity assaysin vitrofor select solventogenic enzymes revealed that part of the underpinning for the CaCO3-mediated increase in the level of ABE fermentation stems from the enhanced activity of these catalysts in the presence of Ca2+. Collectively, these proteomic and biochemical studies provide new insights into the multifactorial basis for the stimulation of ABE fermentation and butanol tolerance in the presence of CaCO3.
Mitochondrial Porin Por1 and Its Homolog Por2 Contribute to the Positive Control of Snf1 Protein Kinase in Saccharomyces cerevisiae
Authors: Strogolova Vera , Orlova Marianna , Shevade Aishwarya , Kuchin Sergei
Published: October 2012

Saccharomyces cerevisiae
Snf1 is a member of the conserved Snf1/AMP-activated protein kinase (Snf1/AMPK) family involved in regulating responses to energy limitation, which is detected by mechanisms that include sensing adenine nucleotides. Mitochondrial voltage-dependent anion channel (VDAC) proteins, also known as mitochondrial porins, are conserved in eukaryotes from yeast to humans and play key roles in mediating mitochondrial outer membrane permeability to small metabolites, including ATP, ADP, and AMP. We previously recovered the yeast mitochondrial porin Por1 (yVDAC1) from a two-hybrid screen for Snf1-interacting proteins. Here, we present evidence that Snf1 interacts with Por1 and its homolog Por2 (yVDAC2). Cells lacking Por1 and Por2, but not respiratory-deficient
rho
0
cells lacking the mitochondrial genome, exhibit reduced Snf1 activation loop phosphorylation in response to glucose limitation. Thus, Por1 and Por2 contribute to the positive control of Snf1 protein kinase. Physical proximity to the VDAC proteins and mitochondrial surface could facilitate Snf1's ability to sense energy limitation.
Physiologic Expression of the Candida albicans Pescadillo Homolog Is Required for Virulence in a Murine Model of Hematogenously Disseminated Candidiasis
Authors: Uppuluri Priya , Chaturvedi Ashok K. , Jani Niketa , Pukkila-Worley Read , Monteagudo Carlos , Mylonakis Eleftherios , Köhler Julia R. , Lopez Ribot Jose L.
Published: October 2012

Morphogenetic conversions contribute to the pathogenesis of
Candida albicans
invasive infections. Many studies to date have convincingly demonstrated a link between filamentation and virulence; however, relatively little is known regarding the role of the filament-to-yeast transition during the pathogenesis of invasive candidiasis. We previously identified the
C. albicans
pescadillo homolog (
PES1
) as essential during yeast growth and growth of lateral yeast on hyphae but not during hyphal growth. Furthermore, we demonstrated that
PES1
is required for virulence
in vivo
in a
Galleria mellonella
larva model of candidiasis. Here, we have used a regulatable
tetO-PES1
/
pes1
strain to assess the contribution of
C. albicans
PES1
to pathogenesis in the commonly used and clinically relevant murine model of hematogenously disseminated candidiasis. Our results indicate that a physiologically controlled level of
PES1
expression is required for full virulence in this animal model, with virulence defects observed both when
PES1
is overexpressed and and when it is depleted. The pathogenetic defect of cells depleted of
PES1
is not due to a general growth defect, as demonstrated by the fact that
PES1
-depleted cells still kill
Caenorhabditis elegans
as efficiently as the wild type due to hyphal outgrowth through worm tissues. Our results suggest a critical role of lateral yeast growth in the ability of
C. albicans
to normally proliferate within tissues, as well as a pivotal role for Pes1 in the normal developmental cycle of
C. albicans
within the mammalian host during infection.
Dsc Orthologs Are Required for Hypoxia Adaptation, Triazole Drug Responses, and Fungal Virulence in Aspergillus fumigatus
Authors: Willger Sven D. , Cornish E. Jean , Chung Dawoon , Fleming Brittany A. , Lehmann Margaret M. , Puttikamonkul Srisombat , Cramer Robert A.
Published: October 2012

Hypoxia is an environmental stress encountered by
Aspergillus fumigatus
during invasive pulmonary aspergillosis (IPA). The ability of this mold to adapt to hypoxia is important for fungal virulence and genetically regulated in part by the sterol regulatory element binding protein (SREBP) SrbA. SrbA is required for fungal growth in the murine lung and to ultimately cause lethal disease in murine models of IPA. Here we identified and partially characterized four genes (
dscA
,
dscB
,
dscC
, and
dscD
, here referred to as
dscA-D
) with previously unknown functions in
A. fumigatus
that are orthologs of the
Schizosaccharomyces pombe
genes
dsc1
,
dsc2
,
dsc3
, and
dsc4
(
dsc1-4
), which encode a Golgi E3 ligase complex critical for SREBP activation by proteolytic cleavage.
A. fumigatus
null
dscA-D
mutants displayed remarkable defects in hypoxic growth and increased susceptibility to triazole antifungal drugs. Consistent with the confirmed role of these genes in
S. pombe
, both Δ
dscA
and Δ
dscC
resulted in reduced cleavage of the SrbA precursor protein in
A. fumigatus
. Inoculation of corticosteroid immunosuppressed mice with Δ
dscA
and Δ
dscC
strains revealed that these genes are critical for
A. fumigatus
virulence. Reintroduction of SrbA amino acids 1 to 425, encompassing the N terminus DNA binding domain, into the Δ
dscA
strain was able to partially restore virulence, further supporting a mechanistic link between DscA and SrbA function. Thus, we have shown for the first time the importance of a previously uncharacterized group of genes in
A. fumigatus
that mediate hypoxia adaptation, fungal virulence, and triazole drug susceptibility and that are likely linked to regulation of SrbA function.
Characterization of a
mazEF
Toxin-Antitoxin Homologue from Staphylococcus equorum
Authors: Schuster Christopher F. , Park Jung-Ho , Prax Marcel , Herbig Alexander , Nieselt Kay , Rosenstein Ralf , Inouye Masayori , Bertram Ralph
Published: October 2012

Toxin-antitoxin (TA) systems encoded in prokaryotic genomes fall into five types, typically composed of two distinct small molecules, an endotoxic protein and a
cis
-encoded antitoxin of ribonucleic or proteinaceous nature.
In silico
analysis revealed seven putative type I and three putative type II TA systems in the genome of the nonpathogenic species strain
Staphylococcus equorum
SE3. Among these, a MazEF system orthologue termed MazEF
seq
was further characterized. 5′ rapid amplification of cDNA ends (RACE) revealed the expression and the transcriptional start site of

mazE
seq

, indicating an immediately upstream promoter. Heterologous expression of the putative toxin-encoding

mazF
seq

gene imposed growth cessation but not cell death on
Escherichia coli
.
In vivo
and
in vitro
, MazF
seq
was shown to cleave at UACAU motifs, which are remarkably abundant in a number of putative metabolic and regulatory
S. equorum
gene transcripts. Specific interaction between MazF
seq
and the putative cognate antitoxin MazE
seq
was demonstrated by bacterial two-hybrid analyses. These data strongly suggest that MazEF
seq
represents the first characterized TA system in a nonpathogenic
Staphylococcus
species and indicate that MazEF modules in staphylococci may also control processes beyond pathogenicity.
Use of Acupuncture in Hospices and Palliative Care Services in the Uk
Authors: Leng Graham
Published: October 2012

Purpose

The aim of the present work was to evaluate the availability of acupuncture in UK hospices and specialist palliative care services and to identify any barriers to the use of acupuncture in these settings, to determine the characteristics of available acupuncture services and of practitioners providing acupuncture, and to determine awareness of the evidence base for the use of acupuncture in palliative care.

Methods

An online questionnaire with an invitation to participate was circulated by email to 263 hospices and specialist palliative care services in the UK.

Results

A response rate of 54% was obtained. Acupuncture was provided by 59% of services that responded. In general, small numbers of patients receive acupuncture as part of their palliative care treatment as inpatients, day patients or outpatients. Most practitioners were regulated health professionals who had received a Western-style training in acupuncture and used a Western-style medical acupuncture approach. Where acupuncture was not available the commonest reason given was the lack of a suitable practitioner. Most agreed that if funding and a suitable practitioner were available, acupuncture would be a useful addition to their service. The level of awareness of specific types of evidence supporting the use of acupuncture in palliative care was low, but most respondents were aware that some evidence existed.

Conclusions

There is a need to increase training in acupuncture for healthcare professionals working in palliative care. There is also a need to raise awareness of the potential benefits to patients and the evidence base supporting the use of acupuncture in palliative care.
Health service use in adults 20–64 years with traumatic brain injury, spinal cord injury or pelvic fracture. A cohort study with 9-year follow-up
Authors: Laursen Bjarne , Helweg-Larsen Karin
Published: October 2012

Objectives

To estimate the health service use over 9 years after the injury year for patients with traumatic brain injury (TBI), spinal cord injury (SCI) and pelvic fracture (PF), and compare with non-injured.

Design

A register-based cohort design with a 9-year follow-up period.

Setting

The Danish population.

Participants

The study included 434, 100 and 278 hospital-treated incident patients with TBI, SCI and PF, respectively, among 20-year-olds to 64-year-olds identified using the National Patient Register. Controls for each patient group were drawn from the population register, matched by age, sex and health service use during 1995. All were followed during 1996–2005 by linkage to national health registers. The observations were excluded when the patients left Denmark or died.

Outcome measures

The use of hospital treatments, contacts with general practitioners and the use of physiotherapy.

Results

Compared to the controls, more patients with TBI and SCI were hospital admitted all 9 years after the injury year, on average 0.36 and 0.50 times annually, respectively. For patients with PF hospital admissions returned to baseline year 2 after the injury year. For patients with SCI the use of general practitioner services remained at an increased level year 9 after the injury year, while it returned to baseline level year 4 after the injury year for patients with TBI and year 2 for patients with PF. For patients with SCI physiotherapy use remained increased over 9 years after the injury year, while it returned to baseline the fifth year for patients with TBI and the third year after for patients with PF.

Conclusions

TBI and SCI increase the use of health services over 9 years after the injury year, while most health service use after PF returned to baseline 2 years after the injury year.
Evaluation of the self-inflating bag-valve-mask and non-rebreather mask as preoxygenation devices in volunteers
Authors: Robinson Amelia , Ercole Ari
Published: October 2012

Objective

To evaluate and compare the effectiveness and tolerability of preoxygenation with the self-inflating bag-valve-mask (BVM) and non-rebreather mask (NRM) as are used before emergency anaesthesia.

Design

Device performance evaluation.

Setting

Experimental study.

Participants

12 male and 12 female healthy volunteers (age range 24–47) with no history of clinically significant respiratory disease.

Interventions

End-expiration oxygen measurements (FEO2) after 3 min of preoxygenation with BVM (without mechanical assistance) and NRM devices. Mask pressures were measured and subjective difficulty of breathing was also assessed with a visual analogue score (VAS).

Primary and secondary outcome measures

The final FEO2achieved was 58.0% (SD 7.3%) for the NRM compared to 53.1% (SD 13.4%) for the BVM (p=0.072). Preoxygenation was associated with small increases in FECO2that were greater for the BVM (0.50%; 95% CI 0.48 to 0.52) than the NRM (0.29%; 95% CI 0.31 to 0.28); this difference was statistically significant (p=0.028). Both devices were well tolerated on VAS assessment of difficulty of breathing although this was higher for the BVM than the NRM (median VAS 1.85/10 compared to 1.1/10; p=0.041). Inspiratory and expiratory mask pressures were higher for the BVM.

Conclusions

In healthy volunteers, the NRM performs comparably to the BVM in terms of the degree of denitrogenation achieved although neither performed well. Although it was well tolerated, the BVM was subjectively more difficult to breathe through and was associated with greater mask pressures and a small increase in FECO2consistent with hypoventilation or rebreathing. Our results suggest that preoxygenation with the NRM may be a preferable approach in spontaneously breathing patients.
The impact of drug eluting stents availability on the treatment choice among medical therapy, percutaneous or surgical revascularisation and on 4-year clinical outcome in patients with coronary artery disease: a cohort study
Authors: Olivari Zoran , Stritoni Paolo , Burelli Claudio , Scalia Domenico , Brocco Stefano , Fedeli Ugo , Avossa Francesco , Ferlin Dario , Reimers Bernhard , Grassi Giuseppe , Fontanelli Alessandro , Valfrè Carlo
Published: October 2012

Objective

To investigate the influence of the availability of drug eluting stents (DES) on treatment choice (TC) among medical therapy (MT), coronary by-pass surgery (CABG) or percutaneous coronary interventions (PCI) and the consequent clinical outcomes in patients hospitalised because of coronary artery disease (CAD).

Design

Observational study comparing two cohorts hospitalised immediately before, and 3 years after DES availability.

Setting

Thirteen hospitals with cardiology facilities.

Patients

2131 consecutive patients with at least one coronary stenosis >50% at coronary angiography (CA) after exclusion of those with acute myocardial infarction or previous CABG or associated relevant valvular disease.

Main outcome measures

Treatment choice after CA and 4-year clinical outcomes.

Results

TC among MT (27% vs 29.2%), PCI (58.6% vs 55.5%) and CABG (14.5% vs 15.3%) was similar in the DES and bare metal stent (BMS) periods (p = 0.51). At least one DES was implanted in 57% of patients treated with PCI in 2005. After 4 years, no difference in mortality (13.8% vs 13.2%, p = 0.72), hospital admissions for myocardial infarction (6.6% vs 5.2%, p = 0.26), stroke (2.2% vs 1.7%, p = 0.49) and further revascularisations (22.3% vs 19.7%, p = 0.25) were observed in patients enrolled in the DES and BMS periods. Only in patients with Syntax score 23–32 a significant change of TC (p = 0.0002) occurred in the DES versus BMS period: MT in 17.4% vs 31%, PCI in 62.2% vs 35.8%, CABG in 20.3% vs 33.2%, with similar 4-year combined end-point of mortality, stroke, myocardial infarction and further revascularisations (45.3% vs 34.2%, p = 0.087).

Conclusions

Three years after DES availability, the TC in patients with CAD has not changed significantly as well as the 4-year incidence of death, myocardial infarction, stroke and further revascularisations. In subgroup with Syntax score 23–32, a significant increase of indications to PCI was observed in the DES period, without any improvement of the 4-year clinical outcome.
Applying the RE-AIM framework to the Alberta's Caring for Diabetes Project: a protocol for a comprehensive evaluation of primary care quality improvement interventions
Authors: Wozniak Lisa , Rees Sandra , Soprovich Allison , Al Sayah Fatima , Johnson Steven T , Majumdar Sumit R , Johnson Jeffrey A
Published: October 2012

Introduction

Diabetes represents a major public health and health system burden. As part of the Alberta's Caring for Diabetes (ABCD) Project, two quality-improvement interventions are being piloted in four Primary Care Networks in Alberta. Gaps between health research, policy and practice have been documented and the need to evaluate the impact of public health interventions in real-world settings to inform decision-making and clinical practice is paramount. In this article, we describe the application of the RE-AIM framework to evaluate the interventions beyond effectiveness.

Methods and analysis

Two quality-improvement interventions were implemented, based on previously proven effective models of care and are directed at improving the physical and mental health of patients with type-2 diabetes. Our goal is to adapt and apply the RE-AIM framework, using a mixed-methods approach, to understand the impact of the interventions to inform policy and clinical decision-making. We present the proposed measures, data sources and data management and analysis strategies used to evaluate the interventions by RE-AIM dimension.

Ethics and dissemination

Ethics approval for the ABCD Project has been granted from the Health Research Ethics Board (HREB #PRO00012663) at the University of Alberta. The RE-AIM framework will be used to structure our dissemination activities by dimension.

Results

It will be presented at relevant conferences and prepared for publication in peer-reviewed journals. Various products, such as presentations, briefing reports and webinars, will be developed to inform key stakeholders of the findings. Presentation of findings by RE-AIM dimension will facilitate discussion regarding the public health impact of the two interventions within the primary care context of Alberta and lessons learned to be used in programme planning and care delivery for patients with type-2 diabetes. It will also promote the application of evaluation models to better assess the impact of community-based primary healthcare interventions through our dissemination activities.
Why traditional statistical process control charts for attribute data should be viewed alongside anxmr-chart
Authors: Mohammed Mohammed A , Worthington Peter
Published: October 2012

The use of statistical process control (SPC) charts in healthcare is increasing. The general advice when plotting SPC charts is to begin by selecting the right chart. This advice, in the case of attribute data, may be limiting our insights into the underlying process and consequently be potentially misleading. Given the general lack of awareness that additional insights may be obtained by using more than one SPC chart, there is a need to review this issue and make some recommendations. Under purely common cause variation the control limits on thexmr-chart and traditional attribute charts (eg,p-chart,c-chart,u-chart) will be in close agreement, indicating that the observed variation (xmr-chart) is consistent with the underlying Binomial model (p-chart) or Poisson model (c-chart,u-chart). However, when there is a material difference between the limits from thexmr-chart and the attribute chart then this also constitutes a signal of an underlying systematic special cause of variation. We use one simulation and two case studies to demonstrate these ideas and show the utility of plotting the SPC chart for attribute data alongside anxmr-chart. We conclude that the combined use of attribute charts andxmr-charts, which requires little additional effort, is a useful strategy because it is less likely to mislead us and more likely to give us the insight to do the right thing.
Is CDX2 immunostaining useful for delineating anorectal from penile/vulvar squamous cancer in the setting of squamous cell carcinoma with clinically unknown primary site presenting with histologically confirmed inguinal lymph node metastasis?
Authors: Gunia Sven , Koch Stefan , May Matthias
Published: October 2012

Aims

Penile, vulvar and anal squamous cell carcinomas (SCCs) share histomorphological overlap and are prone to lymphatic dissemination into inguinal nodes. Anal SCCs might derive from the anorectal zone (ARZ), anal transitional zone, squamous zone or from perianal skin. These anatomically distinct zones differ in terms of their embryological development. We sought to investigate the role of caudal-related homeobox 2 (CDX2), a homeobox gene implicated in the development and anterior/posterior pattern specification from duodenum to rectum including the ARZ, in terms of narrowing the possible sites of origin to be considered in the setting of SCC with unknown primary presenting with histologically confirmed inguinal lymph node metastasis.

Methods

By immunohistochemistry (IHC) employing a panel of antibodies directed against CK5/6, CK7, CK20, p63, p16, CEA and CDX2, we compared 89 penile, 11 vulvar and eight anal SCCs with respect to their staining profiles. Moreover, anal SCCs were subjected to in situ hybridisation (ISH) for high-risk human papillomavirus (HPV) subtypes.

Results

By IHC, CDX2 expression was observed in 2/8 anal SCCs (25%) while being absent from all penile and vulvar SCCs examined. High-risk HPV subtypes were detected by ISH in all anal SCCs examined, which were uniformly p16-positive by IHC.

Conclusions

CDX2 might be valuable in terms of narrowing the possible sites of origin to be considered in the setting of SCC with unknown primary presenting with inguinal lymph node metastasis. However, despite its favourable specificity, the diagnostic benefit achieved by this observation is limited by the low sensitivity.