bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging and Analysis of Pseudomonas aeruginosa Swarming and Rhamnolipid Production
Authors: Morris Joshua D. , Hewitt Jessica L. , Wolfe Lawrence G. , Kamatkar Nachiket G. , Chapman Sarah M. , Diener Justin M. , Courtney Andrew J. , Leevy W. Matthew , Shrout Joshua D.
Published: October 2011

Many bacteria spread over surfaces by “swarming” in groups. A problem for scientists who study swarming is the acquisition of statistically significant data that distinguish two observations or detail the temporal patterns and two-dimensional heterogeneities that occur. It is currently difficult to quantify differences between observed swarm phenotypes. Here, we present a method for acquisition of temporal surface motility data using time-lapse fluorescence and bioluminescence imaging. We specifically demonstrate three applications of our technique with the bacterium
Pseudomonas aeruginosa
. First, we quantify the temporal distribution of
P. aeruginosa
cells tagged with green fluorescent protein (GFP) and the surfactant rhamnolipid stained with the lipid dye Nile red. Second, we distinguish swarming of
P. aeruginosa
and
Salmonella enterica
serovar Typhimurium in a coswarming experiment. Lastly, we quantify differences in swarming and rhamnolipid production of several
P. aeruginosa
strains. While the best swarming strains produced the most rhamnolipid on surfaces, planktonic culture rhamnolipid production did not correlate with surface growth rhamnolipid production.
Inhibition of Staphylococcus aureus by Lysostaphin-Expressing Lactobacillus plantarum WCFS1 in a Modified Genital Tract Secretion Medium
Authors: Liu Huanli , Gao Yuan , Yu Li-Rong , Jones Richard C. , Elkins Christopher A. , Hart Mark E.
Published: October 2011

Lactobacillusspecies are a predominant member of the vaginal microflora and are critical in maintaining an acidic vaginal environment thought to contribute to the prevention of a number of urogenital diseases. However, during menstruation the pH of the vaginal environment increases to neutrality, a pH conducive forStaphylococcus aureusproliferation and the production of toxic shock syndrome toxin 1 (TSST-1) in susceptible women. In order to generateLactobacillusspecies capable of expressing lysostaphin (an endopeptidase that cleaves the cell wall ofS. aureus) in a modified genital tract secretion medium (mGTS) under neutral-pH conditions, six prominent proteins fromLactobacillus plantarumWCFS1 spent medium were identified by mass spectrometry. Sequences for promoters, signal peptides, and mature lysostaphin were used to construct plasmids that were subsequently transformed intoL. plantarumWCFS1. The promoter and signal sequences of Lp_3014 (putatively identified as a transglycosylase) or the promoter sequence of Lp_0789 (putatively identified as glyceraldehyde 3-phosphate dehydrogenase) with the signal sequence of Lp_3014 exhibited lysostaphin activity on buffered medium containing heat-killedS. aureus. The cassettes were integrated into the chromosome ofL. plantarumWCFS1, but only the cassette containing the promoter and signal sequence from Lp_3014 had integrated into the appropriate site. Coculture assays using buffered mGTS showed that lysostaphin expressed fromL. plantarumWCFS1 reduced the growth of TSST-1-producing strains ofS. aureusunder neutral-pH conditions. This study provides the basis for determining whether lysostaphin-producingLactobacillusstrains could potentially be used as a means to inhibit the growth ofS. aureusduring menstruation.
AccD6, a Key Carboxyltransferase Essential for Mycolic Acid Synthesis in Mycobacterium tuberculosis, Is Dispensable in a Nonpathogenic Strain
Authors: Pawelczyk Jakub , Brzostek Anna , Kremer Laurent , Dziadek Bozena , Rumijowska-Galewicz Anna , Fiolka Marta , Dziadek Jaroslaw
Published: October 2011

Acetyl coenzyme A carboxylase (ACC) is a key enzyme providing a substrate for mycolic acid biosynthesis. Althoughin vitrostudies have demonstrated that the protein encoded byaccD6(Rv2247) may be a functional carboxyltransferase subunit of ACC inMycobacterium tuberculosis, thein vivofunction and regulation ofaccD6in slow- and fast-growing mycobacteria remain elusive. Here, directed mutagenesis demonstrated that althoughaccD6is essential forM. tuberculosis, it can be deleted inMycobacterium smegmatiswithout affecting its cell envelope integrity. Moreover, we showed that although it is part of the type II fatty acid synthase operon, theaccD6gene ofM. tuberculosis, but not that ofM. smegmatis, possesses its own additional promoter (Pacc). The expression level ofaccD6Mtbplaced only under the control of Paccis 10-fold lower than that in wild-typeM. tuberculosisbut is sufficient to sustain cell viability. Importantly, this limited expression level affects growth, mycolic acid content, and cell morphology. These results provide the firstin vivoevidence for AccD6 as a key player in the mycolate biosynthesis ofM. tuberculosis, implicating AccD6 as the essential ACC subunit in pathogenic mycobacteria and an excellent target for new antitubercular compounds. Our findings also highlight important differences in the mechanism of acetyl carboxylation between pathogenic and nonpathogenic mycobacterial species.
Hydrogen Peroxide-Dependent DNA Release and Transfer of Antibiotic Resistance Genes in Streptococcus gordonii
Authors: Itzek Andreas , Zheng Lanyan , Chen Zhiyun , Merritt Justin , Kreth Jens
Published: October 2011

Certain oral streptococci produce H2O2under aerobic growth conditions to inhibit competing species likeStreptococcus mutans. Additionally, H2O2production causes the release of extracellular DNA (eDNA). eDNA can participate in several important functions: biofilm formation and cell-cell aggregation are supported by eDNA, while eDNA can serve as a nutrient and as an antimicrobial agent by chelating essential cations. eDNA contains DNA fragments of a size that has the potential to transfer genomic information. By usingStreptococcus gordoniias a model organism for streptococcal H2O2production, H2O2-dependent eDNA release was further investigated. Under defined growth conditions, the eDNA release process was shown to be entirely dependent on H2O2. Chromosomal DNA damage seems to be the intrinsic signal for the release, although only actively growing cells were proficient eDNA donors. Interestingly, the process of eDNA production was found to be coupled with the induction of theS. gordoniinatural competence system. Consequently, the production of H2O2triggered the transfer of antibiotic resistance genes. These results suggest that H2O2is potentially much more than a simple toxic metabolic by-product; rather, its production could serve as an important environmental signal that facilitates species evolution by transfer of genetic information and an increase in the mutation rate.
Regulation of the Competence Pathway as a Novel Role Associated with a Streptococcal Bacteriocin
Authors: Dufour Delphine , Cordova Martha , Cvitkovitch Dennis G. , Lévesque Céline M.
Published: October 2011

The oral biofilm organism
Streptococcus mutans
must face numerous environmental stresses to survive in its natural habitat. Under specific stresses,
S. mutans
expresses the competence-stimulating peptide (CSP) pheromone known to induce autolysis and facilitate the uptake and incorporation of exogenous DNA, a process called DNA transformation. We have previously demonstrated that the CSP-induced CipB bacteriocin (mutacin V) is a major factor involved in both cellular processes. Our objective in this work was to characterize the role of CipB bacteriocin during DNA transformation. Although other bacteriocin mutants were impaired in their ability to acquire DNA under CSP-induced conditions, the Δ
cipB
mutant was the only mutant showing a sharp decrease in transformation efficiency. The autolysis function of CipB bacteriocin does not participate in the DNA transformation process, as factors released via lysis of a subpopulation of cells did not contribute to the development of genetic competence in the surviving population. Moreover, CipB does not seem to participate in membrane depolarization to assist passage of DNA. Microarray-based expression profiling showed that under CSP-induced conditions, CipB regulated ∼130 genes, among which are the
comDE
locus and
comR
and
comX
genes, encoding critical factors that influence competency development in
S. mutans
. We also discovered that the CipI protein conferring immunity to CipB-induced autolysis also prevented the transcriptional regulatory activity of CipB. Our data suggest that besides its role in cell lysis, the
S. mutans
CipB bacteriocin also functions as a peptide regulator for the transcriptional control of the competence regulon.
Production of Multiple Bacteriocins from a Single Locus by Gastrointestinal Strains of Lactobacillus salivarius
Authors: O'Shea Eileen F. , O'Connor Paula M. , Raftis Emma J. , O'Toole Paul W. , Stanton Catherine , Cotter Paul D. , Ross R. Paul , Hill Colin
Published: October 2011

Bacteriocins produced by
Lactobacillus salivarius
isolates derived from a gastrointestinal origin have previously demonstrated efficacy for
in vivo
protection against
Listeria monocytogenes
infection. In this study, comparative genomic analysis was employed to investigate the intraspecies diversity of seven
L. salivarius
isolates of human and porcine intestinal origin, based on the genome of the well-characterized bacteriocin-producing strain
L. salivarius
UCC118. This revealed a highly conserved megaplasmid-borne gene cluster in these strains involved in the regulation and secretion of two-component class IIb bacteriocins. However, considerable intraspecific variation was observed in the structural genes encoding the bacteriocin peptides. They ranged from close relatives of abp118, such as salivaricin P, which differs by 2 amino acids, to completely novel bacteriocins, such as salivaricin T, which is characterized in this study. Salivaricin T inhibits closely related lactobacilli and bears little homology to previously characterized salivaricins. Interestingly, the two peptides responsible for salivaricin T activity, SalTα and SalTβ, share considerable identity with the component peptides of thermophilin 13, a bacteriocin produced by
Streptococcus thermophilus
. Furthermore, the salivaricin locus of strain DPC6488 also encodes an additional novel one-component class IId anti-listerial bacteriocin, salivaricin L. These findings suggest a high level of redundancy in the bacteriocins that can be produced by intestinal
L. salivarius
isolates using the same enzymatic production and export machinery. Such diversity may contribute to their ability to dominate and compete within the complex microbiota of the mammalian gut.
Covered stents safely utilized to prevent catastrophic hemorrhage in patients with advanced head and neck malignancy
Authors: Miller Todd , Burns Judah , Farinhas Joaquim , Pasquale David , Haboosheh Amit , Bello Jacqueline A , Brook Allan
Published: October 2011

Purpose

The purpose of this study was to review the use of covered stents in patients with squamous cell carcinoma of the head and neck threatening bilateral neurovascular structures.

Methods

The radiology information system was searched for all patients with bilateral head and neck carcinoma treated with covered stents in the carotid vasculature from 2006 through 2009. Five patients (one woman) of mean age 60.5 years (range 45–69) were identified. All had carotid blowout syndrome after treatment for primary squamous cell carcinoma of the head and neck with subsequent tumor recurrence or metastases immediately threatening bilateral carotid vasculature. Covered stents were placed. Long-term follow-up included clinical progress, verification of stent patency and detection of tumor progression via ultrasound or contrast-enhanced CT after the first month and then every 3–6 months. All patients were maintained on antiplatelet medication after treatment.

Results

Covered stents were safely deployed in all patients. Mean survival was 5 months with one outlier surviving for 3 years. There were no subsequent uncontrollable hemorrhages.

Conclusion

The use of covered stents for avoidance of catastrophic hemorrhage following treatment in patients with head and neck tumors with bilaterally threatened carotid arteries was successful.
Use of web based systems to support postgraduate medical education
Authors: Tochel C , Beggs K , Haig A , Roberts J , Scott H , Walker K , Watson M
Published: October 2011

Background

To meet the demands of delivering the Foundation programme across a geographically diverse country, two web based systems (ePortfolio and eLearning) were developed to promote accessibility to training material and assessment tools on standardised platforms. This study evaluated the use of both tools throughout an entire academic year.

Methods

All Scottish Foundation trainees' online learning and assessment data in 2007/08 were analysed, providing a national breakdown of post specialty, completion rates of mandatory assessments (including summary analysis of anonymised scores), and trainees' use of non-mandatory learning tools. Independent verification of competence data was sought from Deaneries.

Results

There were high levels of engagement with both the ePortfolio (75–97% assessment completion) and eLearning systems (89–98% induction course completion), and the majority of trainees completed all required elements. There was extensive use of ePortfolio beyond mandatory levels for recording of learning events, including almost 20 000 personal learning records submitted by second year trainees. There was evidence that ePortfolio was used to record achievement of clinical competence rather than to track improvements towards competence (median workplace based assessment scores were ‘high’ or ‘very high’). Online learning modules received positive feedback and its flexible format suited the trainees' working environment. External verification of formal assessment data revealed good correlation with locally stored outcomes, both indicating approximately 99% programme completion rates.

Conclusions

Core components of the Foundation programme have been delivered successfully to thousands of trainees across Scotland using web based systems to deliver and support education and assessment. There is great potential for further exploration of this carefully managed, rich dataset at individual, regional, and national levels to inform the future of medical education.
Effects of changing work patterns on general surgical training over the last decade
Authors: Blencowe N S , Parsons B A , Hollowood A D
Published: October 2011

Background

There is concern across all medical specialties that shift patterns and reduced working hours are detrimental to training, and that craft specialties have been most affected. This study aimed to examine the effects of these changes to training on the quantity of operating performed by surgical trainees in a UK teaching hospital.

Methods

This retrospective study of prospectively collected computerised theatre data examined elective and emergency general surgical operations performed over four time periods: 1996 (Calman), 2001 (New Deal), 2004 and 2009 (European Working Time Directive). Procedures were analysed according to grade of surgeon and time of day.

Results

In 1996, most appendicectomies (72.2%) were performed by senior house officers (SHOs), compared with 3.8% in 2009. By 2009, SHOs did not perform any emergency procedures other than abscess drainage and appendicectomy. The proportion of emergency operating performed by specialist registrar (SpRs) has remained constant, but elective operating has reduced from 34.6% (1996) to 15.7% (2009). Supervision of both SHOs and SpRs has increased between 1996 and 2009 in both elective and emergency work.

Conclusions

The proportion of operating performed by SpRs and SHOs has fallen over the last decade, coinciding with implementation of structural changes to training, the advent of minimally invasive techniques, and the drive for a consultant led health service. Trainees may therefore require increased supervision as well as protected theatre sessions to balance operative training with ward based duties. Education must be integrated into working practice in order for trainees to achieve expected competencies and ultimately produce adequately experienced consultants.
Improved measures of racial mixing among men who have sex with men using Newman's assortativity coefficient
Authors: Bohl Daniel D , McFarland Willi , Raymond H Fisher
Published: October 2011

Objective

To measure sexual mixing among racial groups of men who have sex with men (MSM).

Methods

The authors explore its potential impacts, making two methodological advancements over previous work. First, the authors pioneer the use of Newman's assortativity coefficient to characterise mixing among MSM. Second, the authors examine mixing at the level of primary ties and at the level of secondary ties.

Results

Results from the 1142-participant sample suggest that MSM are highly assortative by all races at the secondary level.

Conclusions

Networks of MSM may be more tightly contracted around racial groupings than previously supposed. These groupings may lead to increased HIV transmission in certain racial groups.
Emerging characterization of the role of SIRT3-mediated mitochondrial protein deacetylation in the heart
Authors: Sack Michael N.
Published: October 2011

Studies to quantify the protein acetylome show that lysine-residue acetylation rivals phosphorylation in prevalence as a posttranslational modification. Interesting, this posttranslational modification is modified by nutrient flux and by redox stress and targets the vast majority of metabolic pathway proteins in the mitochondria. Furthermore, the mitochondrial deacetylase enzyme SIRT3 appears to be regulated by exercise in skeletal muscle and in response to pressure overload in the heart. The alteration of protein lysine residues by acetylation and the enzymes controlling deacetylation are beginning to be explored as important regulatory events in the control of mitochondrial function and homeostasis. This review focuses on the mitochondrial targets of SIRT3 that are functionally implicated in heart biology and pathology and on the direct cardiac consequences of the genetic manipulation of SIRT3. As therapeutic modulators of other SIRT isoforms have been identified, the longer-term objective of our understanding of this biology would be to identify SIRT3 modulators as putative cardiac therapeutic agents.
Coronary microvascular dysfunction in a porcine model of early atherosclerosis and diabetes
Authors: van den Heuvel Mieke , Sorop Oana , Koopmans Sietse-Jan , Dekker Ruud , de Vries René , van Beusekom Heleen M. M. , Eringa Etto C. , Duncker Dirk J. , Danser A. H. Jan , van der Giessen Willem J.
Published: October 2011

Detailed evaluation of coronary function early in diabetes mellitus (DM)-associated coronary artery disease (CAD) development is difficult in patients. Therefore, we investigated coronary conduit and small artery function in a preatherosclerotic DM porcine model with type 2 characteristics. Streptozotocin-induced DM pigs on a saturated fat/cholesterol (SFC) diet (SFC + DM) were compared with control pigs on SFC and standard (control) diets. SFC + DM pigs showed DM-associated metabolic alterations and early atherosclerosis development in the aorta. Endothelium-dependent vasodilation to bradykinin (BK), with or without blockade of nitric oxide (NO) synthase, endothelium-independent vasodilation to an exogenous NO-donor ( S-nitroso- N-acetylpenicillamine), and vasoconstriction to endothelin (ET)-1 with blockade of receptor subtypes, were assessed in vitro. Small coronary arteries, but not conduit vessels, showed functional alterations including impaired BK-induced vasodilatation due to loss of NO ( P < 0.01 vs. SFC and control) and reduced vasoconstriction to ET-1 ( P < 0.01 vs. SFC and control), due to a decreased ETA receptor dominance. Other vasomotor responses were unaltered. In conclusion, this model demonstrates specific coronary microvascular alterations with regard to NO and ET-1 systems in the process of early atherosclerosis in DM. In particular, the altered ET-1 system correlated with hyperglycemia in atherogenic conditions, emphasizing the importance of this system in DM-associated CAD development.
Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: cross-talk among cytokines, Mg2+, NF-κB, and de novo ceramide
Authors: Altura Burton M. , Shah Nilank C. , Shah Gatha , Zhang Aimin , Li Wenyan , Zheng Tao , Perez-Albela Jose Luis , Altura Bella T.
Published: October 2011

The present study tested the hypotheses that 1) short-term dietary deficiency (MgD) of magnesium (21 days) would result in the upregulation of ceramide synthase (CS) in left ventricular (LV), right ventricular, atrial, and aortic smooth muscle, as well as induce a synthesis/release of select cytokines and chemokines into the LV and aortic smooth muscle and serum; 2) exposure of primary cultured vascular smooth muscle cells (VSMCs) to low extracellular Mg concentration would lead to the synthesis/release of select cytokines/chemokines, activation of N-SMase, and the de novo synthesis of ceramide; and 3) inhibition of CS by fumonisin B1 (FB1) or inhibition of neutral sphingomyelinase (N-SMase) by scyphostatin (SCY) in VSMCs exposed to low Mg would result in reductions in the levels of the cytokines/chemokines and lowered levels of ceramide concomitant with inhibition of NF-κB activation. The data indicated that short-term MgD (10% normal dietary intake) resulted in the upregulation of CS in ventricular, atrial, and aortic smooth muscles coupled to the synthesis/release of 12 different cytokines/chemokines, as well as activation of NF-κB in the LV and aortic smooth muscle and sera; even very low levels of water-borne Mg (e.g., 15 mg·l−1·day−1) either prevented or ameliorated the upregulation and synthesis of the cytokines/chemokines. Our experiments also showed that VSMCs exposed to low extracellular Mg resulted in the synthesis of 5 different cytokines and chemokines concomitant with synthesis/release of ceramide. However, inhibition of the synthesis and release of ceramide by either FB1 or SCY attenuated, markedly , the generation of ceramide, release of the cytokines/chemokines, and activation of NF-κB (as measured by activated p65 and cRel).
Erythropoietin protects against doxorubicin-induced heart failure
Authors: Ammar Hania Ibrahim , Saba Soliman , Ammar Rasha Ibrahim , Elsayed Laila Ahmed , Ghaly Wael Botros Abu-Alyamin , Dhingra Sanjiv
Published: October 2011

The hormone erythropoietin (EPO) has been demonstrated to have cardioprotective properties. The present study investigates the role of EPO to prevent heart failure following cancer treatment with doxorubicin [adriamycin (AD)]. Male Wistar rats (150 ± 10 g) were treated with saline (vehicle control group); with EPO, subcutaneously at 1,000 IU/kg body wt, three times per week for 4 wk (EPO group); with adriamycin, intraperitoneally at 2.5 mg/kg body wt, three times per week for 2 wk (AD group); and with adriamycin and EPO (EPO-AD group). Echocardiographic measurements showed that EPO-AD treatment prevented the AD-induced decline in cardiac function. Each of the hearts was then exposed to ischemia and reperfusion during Langendorff perfusion. The percentage of recovery after ischemia-reperfusion was significantly greater in EPO-AD than the AD-treated group for left ventricular developed pressure, maximal increase in pressure, and rate pressure product. The level of oxidative stress was significantly higher in AD (5 μM for 24 h)-exposed isolated cardiomyocytes; EPO (5 U/ml for 48 h) treatment prevented this. EPO treatment also decreased AD-induced cardiomyocyte apoptosis, which was associated with the decrease in the Bax-to-Bcl2 ratio and caspase-3 activation. Immunostaining of myocardial tissue for CD31 showed a significant decrease in the number of capillaries in AD-treated animals. EPO-AD treatment restored the number of capillaries. In conclusion, EPO treatment effectively prevented AD-induced heart failure. The protective effect of EPO was associated with a decreased level of oxidative stress and apoptosis in cardiomyocytes as well as improved myocardial angiogenesis.
Hyperoxia-induced activation of the integrated stress response in the newborn rat lung
Authors: Konsavage Wesley M. , Zhang Lianqin , Wu Yuchieh , Shenberger Jeffrey S.
Published: October 2011

Diverse environmental stresses stimulate eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, leading to a stress-resistant state characterized by global attenuation of protein synthesis and induction of cytoprotective genes. The signal transduction network culminating in these effects is referred to as the integrated stress response (ISR) or, when initiated by misfolded proteins within the endoplasmic reticulum (ER), the unfolded protein response (UPR). Given that we previously reported that exposure of 4-day-old Sprague-Dawley rats to 95% O2 (Ox) diminishes global pulmonary protein synthesis and increases eIF2α phosphorylation, we conducted the current study to determine whether Ox activates the ISR or UPR. We found that Ox-induced alterations in ER morphology of alveolar type II cells and interstitial fibroblasts were not associated with activation of the UPR sensors PERK or activating transcription factor (ATF) 6 or with X-box binding protein-1 mRNA splicing in whole lung extracts. Exposure to Ox enhanced ATF4 immunoreactivity and nuclear protein content, followed by a 2- and 5-fold increase in ATF3 protein and mRNA expression, respectively. The accumulation of nuclear ATF4 protein coincided with induction of glutamate-cysteine ligase catalytic subunit, an ISR-responsive gene. Immunohistochemistry revealed that changes in ATF3/4 expression were prominent in the alveolus, whereas primary cell culture implicated epithelial and endothelial cells as targets. Finally, induction of ISR intermediates in the intact lung occurred in the absence of the phosphorylation of PKR, JNK, ERK1/2, and p38 MAPK. These findings demonstrate that Ox activates the ISR within the newborn lung and highlight regional and cell-specific alterations in the expression ISR transcription factors that regulate redox balance.
Cigarette smoke causes lung vascular barrier dysfunction via oxidative stress-mediated inhibition of RhoA and focal adhesion kinase
Authors: Lu Qing , Sakhatskyy Pavlo , Grinnell Katie , Newton Julie , Ortiz Melanie , Wang Yulian , Sanchez-Esteban Juan , Harrington Elizabeth O. , Rounds Sharon
Published: October 2011

Cigarette smoke (CS) is a major cause of chronic lung and cardiovascular diseases. Recent studies indicate that tobacco use is also a risk factor for acute lung injury (ALI) associated with blunt trauma. Increased endothelial cell (EC) permeability is a hallmark of ALI. CS increases EC permeability in vitro and in vivo; however, the underlying mechanism is not well understood. In this study, we found that only 6 h of exposure to CS impaired endothelial barrier function in vivo, an effect associated with increased oxidative stress in the lungs and attenuated by the antioxidant N-acetylcysteine (NAC). CS also exacerbated lipopolysaccharide (LPS)-induced increase in vascular permeability in vivo. Similar additive effects were also seen in cultured lung EC exposed to cigarette smoke extract (CSE) and LPS. We further demonstrated that CSE caused disruption of focal adhesion complexes (FAC), F-actin fibers, and adherens junctions (AJ) and decreased activities of RhoA and focal adhesion kinase (FAK) in cultured lung EC. CSE-induced inhibition of RhoA and FAK, endothelial barrier dysfunction, and disassembly of FAC, F-actin, and AJ were prevented by NAC. In addition, the deleterious effects of CSE on FAC, F-actin fibers, and AJ were blunted by overexpression of constitutively active RhoA and of FAK. Our data indicate that CS causes endothelial barrier dysfunction via oxidative stress-mediated inhibition of RhoA and FAK.
Lung endothelial cell platelet-activating factor production and inflammatory cell adherence are increased in response to cigarette smoke component exposure
Authors: Sharma Janhavi , Young Dawn M. , Marentette John O. , Rastogi Prerna , Turk John , McHowat Jane
Published: October 2011

An early event in the pathogenesis of emphysema is the development of inflammation associated with accumulation of polymorphonuclear leukocytes (PMN) in small airways, and inflammatory cell recruitment from the circulation involves migration across endothelial and epithelial cell barriers. Platelet-activating factor (PAF) promotes transendothelial migration in several vascular beds, and we postulated that increased PAF production in the airways of smokers might enhance inflammatory cell recruitment and exacerbate inflammation. To examine this possibility, we incubated human lung microvascular endothelial cells (HMVEC-L) with cigarette smoke extract (CSE) and found that CSE inhibits PAF-acetylhydrolase (PAF-AH) activity. This enhances HMVEC-L PAF production and PMN adherence, and adherence is blocked by PAF receptor antagonists (CV3988 or ginkgolide B). CSE also inhibited PAF-AH activity of lung endothelial cells isolated from wild-type (WT) and iPLA2β knockout mice, and with WT cells, CSE enhanced PAF production and RAW 264.7 cell adherence. In contrast, CSE did not affect PAF production or RAW 264.7 cell adherence to iPLA2β-null cells, suggesting that iPLA2β plays an important role in PAF production by lung endothelial cells. These findings suggest that inhibition of PAF-AH by components of cigarette smoke may initiate or exacerbate inflammatory lung disease by enhancing PAF production and promoting accumulation of inflammatory cells in small airways. In addition, iPLA2β is identified as a potential target for therapeutic interventions to reduce airway inflammation and the progression of chronic lung disease.
Weight Cycling and Cancer: Weighing the Evidence of Intermittent Caloric Restriction and Cancer Risk
Authors: Thompson Henry J. , McTiernan Anne
Published: October 2011

Overweight and obese individuals frequently restrict caloric intake to lose weight. The resultant weight loss, however, typically is followed by an equal or greater weight gain, a phenomenon called weight cycling. Most attention to weight cycling has focused on identifying its detrimental effects, but preclinical experiments indicating that intermittent caloric restriction or fasting can reduce cancer risk have raised interest in potential benefits of weight cycling. Although hypothesized adverse effects of weight cycling on energy metabolism remain largely unsubstantiated, there is also a lack of epidemiologic evidence that intentional weight loss followed by regain of weight affects chronic-disease risk. In the limited studies of weight cycling and cancer, no independent effect on postmenopausal breast cancer but a modest enhancement of risk for renal cell carcinoma, endometrial cancer, and non-Hodgkin's lymphoma have been reported. An effect of either intermittent caloric restriction or fasting in protecting against cancer is not supported by the majority of rodent carcinogenesis experiments. Collectively, the data argue against weight cycling and indicate that the objective of energy balance–based approaches to reduce cancer risk should be to strive to prevent adult weight gain and maintain body weight within the normal range defined by body mass index. Cancer Prev Res; 4(11); 1736–42. ©2011 AACR.
Inflammatory Marker Changes in a Yearlong Randomized Exercise Intervention Trial among Postmenopausal Women
Authors: Friedenreich Christine M. , Neilson Heather K. , Woolcott Christy G. , Wang Qinggang , Stanczyk Frank Z. , McTiernan Anne , Jones Charlotte A. , Irwin Melinda L. , Yasui Yutaka , Courneya Kerry S.
Published: October 2011

Chronic low-grade inflammation is a possible risk factor for cancer that may be modifiable with long-term exercise. Very few randomized controlled trials (RCT) have studied the isolated effects of exercise on low-grade inflammation exclusively in postmenopausal women. The Alberta Physical Activity and Breast Cancer Prevention Trial, a 2-armed RCT in healthy postmenopausal women, examined how 1 year of moderate to vigorous aerobic exercise, compared with usual inactivity, influenced circulating inflammatory markers. Baseline, 6-month, and 12-month serum was analyzed by direct chemiluminescent immunoassays to measure high sensitivity C-reactive protein (CRP) and ELISAs to measure interleukin 6 (IL-6) and TNF-α. Intention to treat analyses were conducted with linear mixed models. Statistically significant differences in CRP were observed over 12 months for exercisers versus controls (treatment effect ratio = 0.87, 95% CI = 0.79–0.96, P = 0.005), but not in IL-6 or TNF-α. A statistically significant trend (Ptrend = 0.021) of decreasing CRP with increasing exercise adherence and stronger intervention effects on CRP in women with higher baseline physical fitness (Pheterogeneity = 0.040) was found. The intervention effect on CRP became statistically nonsignificant with adjustment for dietary fiber intake change and seemed to be mediated by fat loss. Low-grade inflammation may be lowered with exercise, but confounding by dietary intake occurred and should be considered in future studies. Further trials are needed to corroborate our findings about the optimal dose of exercise required to lower CRP levels and effect modification of CRP changes by levels of body fatness and fitness. Cancer Prev Res; 5(1); 98–108. ©2011 AACR.
Transcoronary Ethanol Ablation for Recurrent Ventricular Tachycardia After Failed Catheter Ablation
Authors: Tokuda Michifumi , Sobieszczyk Piotr , Eisenhauer Andrew C. , Kojodjojo Pipin , Inada Keiichi , Koplan Bruce A. , Michaud Gregory F. , John Roy M. , Epstein Laurence M. , Sacher Frédéric , Stevenson William G. , Tedrow Usha B.
Published: October 2011

Background—

Despite substantial progress, radiofrequency catheter ablation (RFCA) fails in some patients. After encouraging results with transcoronary ethanol ablation (TCEA), we began offering TCEA routinely when endocardial and epicardial RFCA failed or a deep intramural substrate was likely.

Methods and Results—

Among 274 consecutive patients who underwent 408 ventricular tachycardia (VT) ablation procedures, 27 patients (21 men; age, 63±13 years; left ventricular ejection fraction, 30±11%; ischemic cardiomyopathy, 14) had 29 TCEA procedures attempted. In 5 patients, TCEA was abandoned because of unfavorable anatomy. In 22 patients, a mean of 1.3±0.6 arteries (range, 1–3 arteries) were targeted for TCEA. After ablation, the targeted VT was no longer inducible in 18 of 22 (82%) patients. Complete heart block occurred in 5 patients, and 3 patients with advanced heart failure died within 30 days of the procedure. After the last TCEA procedure, a VT recurred in 64% of patients, and overall, 32% of patients died. Of 11 patients with prior VT storm, 9 were free of VT storm. At repeat study in 8 patients who had a recurrence, 7 had a new QRS morphology of VT originating from the same general substrate region as the prior VT.

Conclusions—

In patients with difficult-to-control VT in whom RFCA fails, TCEA prevents all VT recurrences in 36% and improves arrhythmia control in an additional 27%. Inadequate target vessels, collaterals, and recurrence of modified VTs limit efficacy, but TCEA continues to play an important role for difficult VTs in these high-risk patients.
Genomic Risk Variants at 1p13.3, 1q41, and 3q22.3 Are Associated With Subsequent Cardiovascular Outcomes in Healthy Controls and in Established Coronary Artery Disease
Authors: Ellis Katrina L. , Frampton Chris M. , Pilbrow Anna P. , Troughton Richard W. , Doughty Rob N. , Whalley Gillian A. , Ellis Chris J. , Skelton Lorraine , Thomson Judith , Yandle Tim G. , Richards A. Mark , Cameron Vicky A.
Published: October 2011

Background—

Genome-wide association studies have identified gene variants associated with coronary artery disease risk; however, whether they affect disease progression is largely unknown. This study investigated associations between polymorphisms at 1p13.3 (rs599839), 1q41 (rs17465637), and 3q22.3 (rs9818870) and cardiovascular outcomes in healthy volunteers and in patients with established heart disease.

Methods and Results—

Canterbury Healthy Volunteer study (HV) (n=1649), Coronary Disease Cohort Study (CDCS) (n=1797), and Post-Myocardial Infarction study (PMI) (n=906) participants (New Zealand), were genotyped for rs599839, rs9818870, and rs17465637. Associations between genotype and anthropometric characteristics, neurohormonal analysis, echocardiography, and clinical outcomes over medium-long-term follow-up (median HV, 5.9 years; CDCS, 3.7 years; PMI, 11.3 years) were tested. At 1p13.3, HV and CDCS participants carrying 1 or more rs599839 G allele had a lower prevalence of dyslipidemia (
P
≤0.005) or lower levels of low-density lipoprotein (
P
=0.031) and total (
P
=0.004) cholesterol and/or less history of myocardial infarction (
P
≤0.04) compared with AA participants. Moreover, CDCS and PMI AG/GG participants had better cardiac function as indicated by echocardiography (
P
≤0.026), and fewer CDCS AG/GG participants were readmitted for a non-ST-segment elevation MI (
P
=0.012) during follow-up. The polymorphism at 1q41 (rs17465637) was associated with better cardiovascular outcomes in the HV (
P
=0.028) and PMI (
P
=0.008) cohorts, and 3q22.3 (rs9818870) was a predictor of death/admission in the HV cohort (
P
=0.045).

Conclusions—

These data suggest that coronary artery disease genomic risk variants at 1p13.3 and 1q41 are associated with subsequent clinical outcome in heart patients and confirm rs9818870 at 3q22.3 as a predictor of cardiovascular risk in individuals free of overt heart disease.
Walking in Unfamiliar Territory
Authors: Onguko Brown Bully , Abdalla Mohamed , Webber Charles F.
Published: October 2011

Purpose: The purpose of this study is to describe the preappointment experiences of early-career headteachers in Tanzania and to discuss implications for postsecondary institutions and ministries of education in East Africa. Research Design: Seven novice headteachers in a suburb of Dar es Salaam, Tanzania, completed questionnaires and participated in face-to-face interviews about their preappointment professional and academic experiences germane to their school leadership roles. Themes within the data from the seven case studies were analyzed and are presented. Findings: There are very limited opportunities for formal preparation programs for headteachers. Preparation experiences typically follow an ad hoc apprenticeship model in which aspiring headteachers learn from their current headteachers. Inadequate preparation is reflected in the limited roles of headteachers in schools. Opportunities for collaborative headteacher preparation are emerging across East African countries but are dependent on support from the private sector and political leaders. Recommendations for further research are presented.
Advancing a disability rights agenda in a context of war: Challenges and opportunities
Authors: Wehbi Samantha
Published: October 2011

This article reports on a qualitative analysis of 28 interviews with activists from a disability rights organization in Lebanon about their experiences organizing during war-time. Findings reveal challenges as well as opportunities for advancing a disability rights agenda within the context of war. Implications for social work are discussed.
Evaluation of strength-controlling defects in paper by stress concentration analyses
Authors: Considine John M , Vahey David W , Evans James W , Turner Kevin T , Rowlands Robert E
Published: October 2011

Cellulosic webs, such as paper materials, are composed of an interwoven, bonded network of cellulose fibers. Strength-controlling parameters in these webs are influenced by constituent fibers and method of processing and manufacture. Instead of estimating the effect on tensile strength of each processing/manufacturing variable, this study modifies and compares the point stress criteria and average stress criteria models used to estimate defect-free (i.e., maximum possible) tensile strength and the inherent size of the cumulative effect of strength-limiting defects. The two major modifications to these models were to assume that defect-free tensile strength was unknown and that unnotched tensile strength was reduced by the presence of inherent defects. These modifications allow the calculation of inherent defect size and defect-free tensile strength by characterizing the tensile strength of the web in the presence of stress concentrations associated with holes of different radius. The models were applied to seven paper materials including lightweight, commercial papers, linerboards, and cylinder boards; estimated inherent defect sizes ranged from 0.1 to 1.5 mm. For most materials considered, defect size was larger in the 2-direction than the 1-direction. Actual measured tensile strengths ranged from 59% to over 95% of the estimated defect-free tensile strengths, σu.
Dental Arch Relationships following Palatoplasty for Cleft Lip and Palate Repair
Authors: Fudalej P. , Katsaros C. , Dudkiewicz Z. , Offert B. , Piwowar W. , Kuijpers M. , Kuijpers-Jagtman A.M.
Published: October 2011

Palatal scarring is assumed to be a primary cause of facial growth derangement in cleft lip and palate. Evidence supporting this hypothesis is confounded by the clinical involvement of various surgeons, and therefore definitive conclusions are not possible. In this study, we investigated the dental arch relationship in two groups, Exposed (47 children; 11.2 yrs) and Unexposed (61 children; 11.2 yrs), with a unilateral cleft lip and palate operated on by the same surgeon. The technique of hard palate repair differed between the two groups. In the Exposed group, palatal bone of the non-cleft side only was left denuded, inducing scar formation. In the Unexposed group, a vomerplasty with tight closure of the soft tissues was applied. Three raters graded the dental arch relationship and palatal morphology using the EUROCRAN Index. The dental arch relationship in the Exposed group was less favorable than in the Unexposed group (p = 0.009). Palatal morphology in both groups was comparable (p = 0.323). This study demonstrates that reduction of denuded bony areas on the palate after palatal repair with a vomer flap had a favorable effect on the dental arch relationship. For palatal morphology, no effect of the type of palatal repair was found.
Nested saturation control for overhead crane systems
Authors: Liu Rongjie , Li Shihua , Ding Shihong
Published: October 2011

This paper presents a new control strategy for overhead crane systems. First, by utilizing a coordinate change, the underactuated overhead crane dynamical model can be transformed into an upper-triangular form. Second, a finite-time controller is designed based on the nonlinear nested saturation and adding a power integrator technique. Rigorous proof shows that the controller can guarantee finite-time stability of the closed-loop system. Simulations show the effectiveness of the proposed method.
The Growth of Unproductive Activities, the Rate of Profit, and the Phase-Change of the U.S. Economy
Authors: Paitaridis Dimitris , Tsoulfidis Lefteris
Published: October 2011

This paper by using the categories of productive and unproductive labor and by extending and further elaborating the data series utilized in Shaikh and Tonak (1994) reveals a sharp expansion of the unproductive activities in the U.S. economy during the period 1964-2007. The combination of growing productivity and the stagnant or even falling real wages of productive workers increased the rate of surplus value in the recent decades to unprecedented highs. As a consequence, the general rate of profit from the early 1980s onwards was also rising until the last years of our analysis; meanwhile the net rate of profit remained at levels much lower than those of the 1960s and the slightly rising trend during the post-1980s has been already reversed. The patterns of these crucial variables reveal startling similarities with the onset of the slowdown that started in the mid- to late 1960s.

JEL classification: B5, E1, O51
Balancing Eldercare and Employment
Authors: Kim Jeungkun , Ingersoll-Dayton Berit , Kwak Minyoung
Published: October 2011

This study investigates pathways by which employed caregivers’ stress is related to their work performance appraisal, with particular attention to work interruptions and supportive employers. Based on a nationally representative sample from the 2004 National Long-Term Care Survey (NLTCS), the study focuses on caregivers to older adults who are currently participating in paid employment ( N = 652). Results from structural equation modeling indicate that work interruptions mediate the relationship between caregivers’ stress and their work performance appraisal. In addition, the support of employers moderates the relationship between employed caregivers’ stress and their work interruptions as well as the relationship between their work interruptions and work performance appraisal. These results point to the need for training supervisors and helping them to understand the potential dual effects of their support on employed caregivers’ work interruptions and performance.
Toxic impact of two organophosphate insecticides on biochemical parameters of a food fish and assessment of recovery response
Authors: Narra Madhusudan Reddy , Begum Ghousia , Rajender Kodimyala , Rao J Venkateswara
Published: October 2011

Sublethal effects of chlorpyrifos (CPF) and monocrotophos (MCP) on fish biochemical constituents were investigated along with the assessment of recovery response after cessation of intoxication. The fish, Clarias batrachus were exposed to 1.656 mg–l and 2.114 mg–l of CPF and MCP for 28 days. After 28 days, they were released in freshwater and allowed to recover for 21 days. The CPF exposure resulted in the decrease of carbohydrate and glycogen content, whereas MCP intoxication caused mixed response. Pyruvate and lactate contents were altered under the stress of CPF and MCP. Recovery of these alterations was observed after the cessation of toxicity. Exposure of C. batrachus to CPF and MCP resulted in decreased activity of lactate dehydrogenase in the kidney, liver and muscle but its activity increased in the gills. The CPF caused inhibition of succinate dehydrogenase enzyme in all tissues. Induction in the activity of malate dehydrogenase was caused by both insecticides. Glycogen phosphorylase a was induced in all tissues, whereas glycogen phosphorylase ab showed both induction and inhibition. Of the two insecticides, CPF was more toxic and the recovery response was less. These results are important in the assessment of the risk caused by organophosphate insecticides on nontarget organisms, especially the food fish.
Acute toxicity bioassay of mercury and silver on Capoeta fusca (black fish)
Authors: Mansouri Borhan , Baramaki Rahimeh , Ebrahimpour Mohammad
Published: October 2011

Since toxicity is based on the effect that a toxicant produces at a target site within an organism, establishing the relationship between the concentration of substance at the target site and the subsequent toxic effect can provide a tool for predicting toxicity. The behavior of a single toxicant could not be fully understood without the knowledge of the fact the physical and biochemical properties of substances that can change. To understand this, the acute toxicity of mercury (as HgSO4) and silver (as AgSO4) to Capoeta fusca (6 treatments in triplicate) was determined. During September 2009, C. fusca belonging to the family Cyprinidae, weighing 2.95 (±0.55) g, were obtained from qanats in Birjand, East of Iran. The fish were maintained in an aquarium system at a holding temperature of 21 (±0.2) and were allowed to adjust to lab conditions for 1 week before experimentation. The lethal concentration 50 (LC50) values for HgSO4 at 24, 48, 72, and 96 h of exposure were 0.32, 0.28, 0.26, and 0.24 mg L–1, respectively. Also, the LC50 values for AgSO4 at 24, 48, 72, and 96 h of exposure were 0.014, 0.013, 0.013, and 0.013 mg L–1, respectively. Results of this study showed that C. fusca was very sensitive to AgSO4.